Future medical breakthroughs may come from an unexpected industry

Future medical breakthroughs may come from an unexpected industry

The technology industry has entered the field of medicine and aims to eliminate disease itself. It may well succeed because of a convergence of exponentially advancing technologies, such as computing, artificial intelligence, sensors, and genomic sequencing. We’re going to see more medical advances in the next decade than happened in the past century. We already wear devices, such as the Fitbit and Apple Watch, which monitor our physical activities, sleep cycles, and stress and energy levels and upload these data to distributed servers via our smartphones. And those smartphones contain countless applications to keep track of our vitals and gauge our emotional and psychological states. Then there is sequencing of the human genome, first completed in 2001 at a cost of about $3 billion. It’s possible today for about $1,000, with costs falling so fast that, by 2022, genome sequencing may be cheaper than a blood test. Now that it has been mapped into bits that computers can process, the genome has become an information technology. With increasingly large sample sizes and tools such as IBM’s A.I. system, Watson, scientists are gaining an understanding of how our genes affect our health; how the environment, the food we eat, and the medicines we take affect the complex interplay between our genes and our organisms. The next big medical frontier is on the horizon: our microbiomes, the bacterial populations that live inside our bodies. We may think we are just made up of cells, but in reality there are 10 times as many microbes in our body as cells. This is a field that I am most excited about, because it takes us back to looking at the human organism as a whole. The microbiome may be the missing link between environment, genomics, and human health.  Within a few years, our genome, microbiome, behavior and environment will all be mapped and measured, and prescriptive-medicine systems based on artificial intelligence will help us feel better and live longer.   Yes, it will take time for the inventions to get from the lab to people in need, and the technology elite will have these before the rest of us. But this will only be for a short period, because the way the tech industry builds value is by democratizing technology, reducing its cost and enabling it to reach billions. This is why I am so excited that companies such as IBM, Facebook, and Google are taking the mantle from the health-care industry. These companies have a motivation to keep us healthy: so that we download more applications rather than remain hooked on prescription medicines.

Industry stranglehold keeps drug prices high

The Nov. 1 front-page article “For insulin users, price of wellness can be high” highlighted a problem that is not new. Over the years, Congress has held hearings on the outlandish cost of drugs, industry tactics to ensure profitability and the resulting injustice to the American public. Testimony has pointed out that companies typically spend more on advertising than research, a nebulous term that includes “marketing research.” Witnesses in hearings that date to the 1950s have revealed a conflict of interest for the American Medical Association (whose journal received millions of dollars from drug-company advertising), frenzied advertising campaigns by drug companies and the marketing of drugs as breakthrough medications though they were not an improvement over drugs already available. Industry clout is extensive. Besides its largesse lavished on political campaigns, lobbyists may come from the ranks of previous federal officials, who know best how to protect industry interests. Consider the fate of the Medicare Part D prescription drug program, implemented in 2006: Amazingly, it forbids the federal government from negotiating lower prices on behalf of America’s seniors. To change this situation — namely, industry profitability on the backs of the American public — will take a moral imperative on the part of lawmakers. Let us hope that our next president will lead the way. However, in light of industry influence over the past 60 years, I’m not holding my breath. ****Nancy J. Herin** , Silver Spring**

A life-changing genetics breakthrough deserves celebration — and demands caution

THE NEWS that researchers have carried out the first known attempt to create genetically modified human embryos is another signpost in an astounding revolution unfolding before our eyes. This is not the first breakthrough nor will it be the last, but it should serve as a reminder — an unmistakable one — that this realm of scientific inquiry, manipulating the tiny building blocks of life, demands caution as well as enthusiasm and encouragement. The latest effort, led by Shoukhrat Mitalipov of Oregon Health & Science University, with researchers from South Korea, China, the Salk Institute for Biological Studies in California and others, involved editing the DNA of single-cell embryos with CRISPR-Cas9, a tool for genome engineering that is much simpler, faster and cheaper than earlier methods, and which has sparked an explosion of interest in possible applications. According to a report published Wednesday in the journal Nature, the researchers were able to demonstrate that it is possible to safely and efficiently correct defective genes that cause inherited diseases. The embryos they modified were not allowed to develop for more than a few days and were not implanted in a womb. In earlier research in China, the modified DNA was taken up by only some cells, not all, and suffered other setbacks, raising questions about its effectiveness. The latest research team reports it achieved “efficiency, accuracy and safety” with the approach. If so, the research may be yet another step toward what is called germline engineering, or changing the genetic material in reproductive cells, so that any offspring would pass the changes on to future generations. The potential impact is huge; thousands of inherited diseases are caused by mutations in single genes, so editing the germline cells of individuals who carry these mutations could allow them to have children without the risk of passing on the conditions. But the dangers and concerns are also significant. The technique could be used to enhance human traits beyond just eradicating disease, such as creating “designer babies,” or for other malevolent purposes. Genome editing was singled out for concern in a 2016 report  to Congress from the U.S. intelligence community about potential wordwide threats: “Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications.” In a report this year, a panel of the National Academy of Sciences addressed the potential and the risks of germline engineering, concluding that basic research should proceed, closely watched. But the panel also said, “Do not proceed at this time with human genome editing for purposes other than treatment or prevention of disease and disability.” This seems to us to strike a reasonable balance, but one that will require vigilance — transparency, oversight and public awareness — to ensure the fruits of this remarkable revolution are not somehow abused or misused. **Read more here:** Jerry A. Coyne: New gene-editing tool could cure disease. Or customize kids. Or aid bioterrorism. The Post’s View: A way forward in gene editing Jacob Corn: CRISPR will change lives, but not only through genetic engineering

Cancer immunotherapy is moving fast. Here’s what you need to know.

The idea of using the body's immune system to fight cancer has been around for a century, but only in the past half a dozen years have dramatic breakthroughs begun rocking the medical world. "That's when the tsunami came," says Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunology at Johns Hopkins University, and those advances are spawning hundreds of clinical trials nationwide, plus generating intense interest from patients, physicians and investors. Many cancer researchers compare the progress to medical milestones such as the discovery of penicillin or the development of chemotherapy. Over the next decade, the growth in the field will be "exponential," predicts Philip Greenberg, head of the immunology program at the Fred Hutchinson Cancer Research Center. "Making something better is enormously different than making something work that doesn't work." At the same time, researchers remember the past anti-cancer efforts that fizzled after initially showing promise. That explains the consensus sentiment at this week's international immunotherapy conference in New York: Turning science into cures will take years of perseverance against daunting hurdles. Here's a primer about new treatments and how they work:  Immunotherapy is a significantly different approach from conventional treatments such as chemotherapy or radiation. The latter attack the malignancy itself, while immunotherapy aims to empower the immune system to kill it. Because of the immune system's unique power, says the nonprofit Cancer Research Institute, this therapy could prove a formidable weapon against many kinds of cancer and offer long-term protection with reduced side effects.  Two types of immunotherapy are drawing most of the interest: checkpoint inhibitors, which remove "brakes" from the immune system, allowing it to see and go after cancer; and CAR T-cell therapy, which involves a more customized attack. "Checkpoint" inhibitors are designed to block the ability of certain proteins to blunt or weaken the response of the immune system so it can't recognize and go after abnormal cells. In normal times, such checkpoint proteins keep the immune system from being too aggressive and damaging the body. But cancer sometimes hijacks them and uses them to suppress the immune system's response to disease. The Food and Drug Administration has cleared four checkpoint inhibitors for adults: Yervoy, also known as ipilimumab; Keytruda, or pembrolizumab; Opdivo, or nivolumab, and Tecentriq, or atezolizumab. The drugs are approved for malignancies including melanoma and Hodgkin lymphoma, as well as lung, kidney and bladder cancer. The treatments also are being tested in a wide range of other cancers. Former president Jimmy Carter was treated with Keytruda, surgery and radiation for advanced melanoma last year. He announced in December that all signs of his cancer had disappeared. In CAR T-cell therapy, T cells — a key part of the immune system — are removed from a patient, genetically modified in the lab to target a specific cancer and infused back into the person. This treatment, available only in clinical trials, is being tested mainly for leukemia and lymphoma. The Food and Drug Administration is likely to approve the first CAR T-cell treatment next year or in 2018. Of these two immunotherapy approaches, most research and investor interest is focused on checkpoint inhibitors. That's because they are off-the-shelf treatments that are much easier to administer than customized T-cell therapy, said Crystal Mackall, a former National Cancer Institute researcher who's now leading immunotherapy trials for Stanford University School of Medicine.  Among the biggest challenges are increasing the response rate among patients and turning initial responses into long-lasting remissions. CAR T-cell therapy often produces a high remission rate in blood-disorder trials, but a significant percentage of patients relapse. Checkpoint inhibitors induce responses — signaling a tumor has been shrunk or stabilized — in an average of just about 20 percent of patients, said oncologist Elizabeth Jaffee, the deputy director of the Sidney Kimmel Comprehensive Cancer Center at Hopkins. Researchers need to understand why only some cases and some cancers respond. Why, for example, the treatment benefits melanoma but not pancreatic cancer. They think the key to improving effectiveness will be coming up with combination treatments, as happened with AIDS. Jaffee points out that the tide was turned against that disease only after researchers figured out how to use a "cocktail" of medications to keep people with HIV from developing AIDS. Nationwide, combination trials are testing the simultaneous use of two or more checkpoint inhibitors, a checkpoint inhibitor with a CAR T-cell therapy or an immunotherapy plus radiation and chemotherapy. But combining these can increase safety risks. Jill O'Donnell-Tormey, chief executive of the Cancer Research Institute, said researchers also are trying to understand tumors' "micro-environments," which contain cells and other factors that appear to sometimes suppress the immune system's response to cancer. The institute, along with the American Association for Cancer Research and two European groups, sponsored the three-day conference in New York.  By revving up the immune system, immunotherapy can cause sometimes serious damage to healthy tissue and organs. Researchers are working on ways to limit or even reverse the potential toxicity, but much work needs to be done. CAR T-cell therapy poses two types of safety risks. Almost all patients get sick with flu-like symptoms, including high fever and pain, a week or so after the treatment; some end up in intensive care. The treatment also can cause brain swelling that can be fatal. Yet standard treatments have major side effects as well. Chemotherapy and radiation, when used for children with leukemia, can cause long-term problems such as secondary cancers, infertility and heart damage. In many ways, researchers say, immunotherapy is less toxic over the long term and might eventually be a good first-line alternative to chemo and radiation. Immunotherapy can carry higher price tags. For example, Merck's checkpoint inhibitor, Keytruda, costs about $150,000 a year. Once CAR T-cell therapies are approved by the Food and Drug Administration, they may cost hundreds of thousands of dollars a year, according to some analysts. If the treatments are used as directed by the agency, chances are good that insurance will pay for at least some of that.  Immunotherapy in kids is a mixed picture. Checkpoint inhibitors are only now being tested extensively in children, so it will take time to see how well they work. But very early-stage studies suggest that they may not be as effective as in adults. One theory holds that these drugs work better in cancers with many mutations — and pediatric cancers tend to have many fewer mutations. CAR T-cell treatment, on the other hand, is being widely tested in children and has shown impressive effectiveness against acute lymphoblastic leukemia, the most common childhood leukemia.

A changing battlefield in the fight against fat

The nation’s war on obesity, which has included everything from plans to introduce higher prices on airline seats for obese passengers to outright bans on sugary sodas, just took a new turn this week, with the American Medical Association (AMA) clarifying that obesity is now a “disease” rather than a condition or lifestyle choice. That may seem like a semantic to some, but it could have a significant impact on technological innovation as it relates to obesity.    *[WSU]: Wayne State University Let’s start with the biotech industry, which has been agitating for the freedom to create new “fat-busting pills”. The FDA, however, has made it close to impossible to get any obesity drug approved. Many of these pills work by attacking mechanisms in the body thought to control hunger, making weight loss possible. But, like other medications, they can come with unwanted side effects ranging from uncomfortable to life-threatening. Some experts see the AMA re-classification as putting pressure on the FDA to relax some of its stringent approval guidelines. In 2012, the FDA made headlines by sanctioning the first weight-loss pill in over a decade and now there could be more on the way, especially if the big pharmaceutical giants re-start their pipelines for obesity drugs.    *[WSU]: Wayne State University Another area that might see a boost from the new AMA stance on obesity is genetics. Researchers are working hard to find and then isolate the genetic markers thought to code for obesity. By taking genetic tests at an early age, for example, you would have advance notice if your body is genetically inclined towards obesity and start taking corrective steps. In the future, it may even be possible to create gene therapy treatments that result in less weight gain and higher activity levels in patients shown to be genetically- predisposed to obesity.    *[WSU]: Wayne State University Which is not to say that the new classification by the AMA will result in a wave of immediate results. First of all, the AMA classification is not legally binding, so a health insurer would still have the right (theoretically) to reject coverage for a treatment or procedure. Even doctors within the AMA are divided over whether obesity should be considered a disease, with some stating that there’s still no causality that obesity is quite the beast it’s supposed to be. And, there’s the question of whether a flood of new products to the market will do anything to reduce America’s obesity epidemic.    *[WSU]: Wayne State University At the very least, though, the AMA’s changing stance could help get health insurers onboard with the idea of covering medical costs associated with obesity. Now that obesity has been labeled a chronic disease, it will give insurance companies less wiggle room to get out of paying for things such as obesity treatment, counseling and (in extreme cases) surgery. It should also make the cost of research and development of “fat-busting pills” or gene therapy treatments more affordable if insurers help to subsidize their costs.    *[WSU]: Wayne State University Until now, very little has worked to solve America’s obesity problem. Education programs have raised awareness about the long-term health risks of being obese but have done little to reverse the tide, with roughly 1 in 3 Americans affected by obesity. Instead of passing judgment — blaming people and then telling them to eat better and exercise more — we now have another option available to us: taking advantage of rapid advances in biotechnology and genetic research to create innovative solutions to one of this nation’s most far-reaching problems.

‘Exceptional responders’ to cancer drugs draw scrutiny from scientists

BOSTON — Grace Silva and Karen Coakley are both 59, mothers living in the Boston suburbs and patients at Dana-Farber Cancer Institute, where they have spent years wrestling with daunting diagnoses. While they have never met, the two women are connected in a way that goes beyond their similar stories and their struggles with cancer. They share an intimate and uncommon link, the sort of genetic bond possible only in an age of precision medicine. Silva is what researchers call an “exceptional responder,” the rare patient who has a surprising, dramatic response to a drug. Coakley is the unsuspecting beneficiary of what scientists are now learning from these unique patients. In 2010, Silva was diagnosed with anaplastic thyroid cancer, an aggressive and rapidly fatal disease with no effective treatment. Despite surgery, chemotherapy and radiation, the cancer spread to her lungs. As a last resort, she enrolled in a small clinical trial the following year with other patients with the same cancer. “It was a shot in the dark,” said Jochen Lorch, her oncologist. Along with the other patients, Silva got a drug called everolimus, approved for advanced kidney cancer and some types of breast and pancreatic cancer. The other patients died, but Silva’s tumors virtually vanished, to the astonishment of her doctors. Such inexplicable reversals have always existed in medicine, but until recently, outliers such as Silva remained little more than hopeful anecdotes. That could be changing. Silva’s story, and those of other exceptional responders, have led to an intriguing set of questions: Could researchers use technologies such as genetic sequencing to figure out what made Silva’s tumor respond to treatment? Could they mine that data for clues that might help other patients? Could they ultimately find a way to make the exceptional more routine? The quest to answer those questions led them to Coakley, whose ovarian cancer was progressing despite years of treatments, and who found herself wondering whether she was out of options and out of time. In the past, a drug under development probably would be written off as a failure if, for example, 48 out of 50 patients in a clinical trial experienced little or no benefit. But that left unanswered why a handful of patients had “a Lazarus-like, unbelievable response,” said Barry Taylor, a molecular oncologist at New York’s Memorial Sloan Kettering Cancer Center. Maybe the drugs themselves weren’t failures, Taylor and other researchers thought. Maybe they were being given to the wrong patients. If they could figure out which genetic wrinkles caused a Grace Silva to respond so profoundly to a certain drug, they might be able to find others — people whose tumors had the same mutations — who would have the same extraordinary reaction. That would have been difficult, if not impossible, just a few years ago, when it took weeks and cost millions of dollars to decode an individual’s DNA. Today, far more powerful genetic sequencing costs less than $1,000 and can be done in hours. Major cancer hospitals such as Dana-Farber now routinely sequence the tumors of all patients, allowing researchers to create vast databases to study which gene mutations drive certain cancers. The National Cancer Institute in the fall launched a nationwide search for people with a variety of cancers who had unique responses to treatments. It has already identified scores and is hoping to identify many more. “What we’re trying to do with these cancers is find their Achilles’ heel and attack that,” said Barbara Conley, associate director of NCI’s Cancer Diagnosis Program. The goal, she said, is to identify genetic markers that could lead toward better treatments for other patients — involving, perhaps, drugs that were abandoned in early-phase trials because they didn’t work for most participants, or approved medications that might benefit more patients than doctors realized. Conley and others say the strategy, although promising, is not foolproof. While ever-   improving technologies allow researchers to study cancer tumors in unprecedented depth, some tumors contain many mutations, and it can be hard to determine which ones cause a certain reaction to a drug. But sometimes, answers do emerge. Curious about Silva’s remarkable response, investigators from Harvard and the Massachusetts Institute of Technology analyzed samples of her original tumor. They discovered she had a mutation in TSC2, one of two genes that regulate a protein pathway called mTOR, which her cancer relied upon to grow. The drug she had reacted to so strongly, everolimus, inhibits mTOR, probably explaining why Silva had seen such an instant, long-lasting benefit. Even before Silva, a patient at Sloan Kettering with advanced bladder cancer had experienced a similar reaction to the drug. That patient’s bladder cancer had a genetic mutation that was similar to Silva’s thyroid cancer. Nikhil Wagle, a medical oncologist at Dana-Farber, said that suggested to researchers that patients whose cancers have similar mutations “could be extraordinary responders, regardless which kind of cancer they might have. This really spurred our interest.” Doctors at the hospital began searching their database, trying to identify other patients with the same sort of genetic mutation — regardless of where their tumors were — for a small clinical trial of everolimus that would test their theory. They soon turned up dozens of names. One of them was Karen Coakley, a soft-spoken woman who had spent much of the winter on a sofa in her home in Tewksbury, north of Boston. She didn’t know much about the genetic mutations of her cancer, but she did worry she wouldn’t see another winter. “I have to be honest,” Coakley said while sitting in her yellow sunroom on a recent morning. “In September, I didn’t think I would be here today.” Diagnosed in July 2008 with Stage 3 ovarian cancer, Coakley had undergone surgery and chemotherapy, which sent her cancer into remission. But by 2011, it was back, and since then, she had cycled through a dizzying series of drugs. Most would work for a while, but the cancer inevitably would resurface, and her doctor would move on to the next treatment on a list that was growing shorter. “It’s a roller coaster,” Coakley said. In September, she began a leave of absence from her job working in accounts payable at a manufacturing company, unsure she would ever return. She watched the New England snow fall outside her window. She watched daytime TV and worked on puzzles but had energy for little else. In February, her oncologist at Dana-Farber told Coakley she was eligible for a new drug trial. Her tumor was very similar to Silva’s, and doctors suspected Coakley might benefit from everolimus. “I think you need to do this,” the oncologist told Coakley. Coakley began taking the drug in early March, swallowing one pill at her kitchen table each morning. After the first month, a blood test showed a sharp drop in the levels of CA-125, a protein produced by ovarian cancer cells. A month later, when her doctor called to say a scan showed her tumors were shrinking, she burst into tears in her driveway. Coakley returned to work at the end of March. She’s planning a trip to New York soon to see a Broadway show with one of her daughters, and she and her husband are planning to visit their other daughter in Florida in the fall. They never used to look so far ahead on the calendar. “It’s just allowed me more freedom to do things,” Coakley said. “I don’t have this sentence hanging over my head.” Daniel, her husband of three decades who has been her chauffeur, nurse and confidant throughout the seven-year ordeal, said the couple feel “more comfortable now.” Doctors are discovering that even people whose cancers have genetic mutations they think might respond to a certain drug often do not, for reasons that remain largely mysteries. And those who do respond often don’t benefit indefinitely. Precision medicine, for all its promise, is not a panacea. Knowing that, neither Coakley nor her doctors use the word “cure.” None of them know how long everolimus will continue to send her cancer into retreat. Still, Coakley said, she is grateful for Silva and other exceptional responders — none of whom she has met — as well as for the researchers smart enough to pinpoint their key genetic similarities. “I feel like I’ve gotten a reprieve,” she said. “I’ve gotten my life back.” For all her good fortune, Silva faces an uncertain journey. After 18 months, the cancer in her lungs became resistant to everolimus. Since 2013, Silva has tried several therapies aimed at heading off the spread of the disease, with mixed results. Her most recent scans show that the cancer in her lungs has grown, albeit slowly. She is waiting to begin a new trial for a drug that targets the same genetic mutation in her cancer but through a different mechanism. Her doctors hope the new treatment will spark a reaction similar to the one she surprised them with years ago. “Now, I’m actually expecting a response,” said Lorch, her oncologist. “I’d be really disappointed if it didn’t work.” Silva is aware of the ongoing trial at Dana-Farber and is glad that her genetic information and that of other exceptional responders is beginning to benefit people like Coakley. “I told my doctor . . . God has a plan here somewhere; we just don’t understand it. This is happening for a reason, and maybe that reason is to help someone else,” said Silva, who was born in Portugal but raised in Massachusetts. “It’s giving people hope.” She’s also thankful for the time she might not have had, for the blessings each unexpected year has brought. “I’m very grateful God gave me this time,” she said. On a recent Wednesday afternoon, Silva was on the floor of her living room in Dartmouth with the two grandchildren she might never have met — 14-month-old Jaelynn and 2-year-old Maddox — when her phone buzzed with a text. “On my way to the hospital, pretty sure I’m in labor,” read the message from her youngest daughter. Another grandchild was on the way, and once again, Silva would be there to meet him. Later, as Silva loaded the children into her Honda CR-V for the ride to St. Luke’s Hospital, where her daughter was undergoing a Caesarean section, another text arrived: “Healthy beautiful boy.” Soon came a picture of the 7-pound 5-ounce newborn. “He’s got my nose,” Silva said, smiling. In the hospital’s maternity ward, Silva found her daughter in a small recovery room, cradling her newest grandson, Conner, barely an hour old. She leaned over the bed, kissed them both and stroked the boy’s cheek. “My goodness,” she said. “Look at that face.”

Oh My Goodness! What IF???

Some aspects of life get hilariously out of whack. Medicine is one of those areas. We will leave aside the Ebola policy mess, for now. We will just talk about ordinary medicine, and how it increasingly looks like an old guy digging through a box of remote controls, trying to find the one which makes his TV go. Here’s an interesting article that poses what would be a thoughtful question, if it had been asked about a decade ago.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico Just imagine! A service delivered remotely! How nearly breathtaking in its futuristicality! Could there be an upside? What a fascinating theoretical question! Or maybe we would be better off staying with the tried and true model of American medicine that costs vastly more than other advanced economies, for no better outcome. Let’s not get out too far on this internet thing! I mean it was only a couple of years ago we were seriously debating whether digitizing medical records might be a GOOD thing! We have a phenomenal amount of talent and money in medicine. But in terms of how it serves ordinary people on a day-to-day basis, the cutting edge of American healthcare delivery is less like a scalpel and more like a wooden tongue depressor. An ambulance by oxen. I wonder how many of the speeches the drug industry pays doctors to give deal with solving any of this.

Drug companies have always been bad at collaboration. That’s changing.

On Tuesday, the National Institutes of Health announced a partnership of breathtaking scope. Ten drug companies had agreed to collaborate on curing four of the world's most devastating diseases, which will affect millions of people in the coming years and have proven largely resistant to cures: Alzheimer's, Type 2 diabetes, lupus and rheumatoid arthritis.    *[WSU]: Wayne State University It took NIH Director Francis Collins more than two years to wrangle the industry into cooperating. They brought in consultants to structure the $230 million project, which will be jointly funded by companies and the government; several companies and one mental disorder -- schizophrenia -- fell by the wayside in the process. It ended up being a remarkable arrangement for a sector that's long been fiercely competitive, jealously guarding its intellectual property against would-be copycats: All the results they come up with will be open source. At the end of the project, which should lock in a basic understanding of how the diseases work, they'll race to bring new drugs to market as fast as possible. If it works, it'll be a major achievement for Collins. At the same time, however, the industry was already changing in ways that made the effort possible. **1\. Drug companies are now more used to talking about what they're up to**    *[WSU]: Wayne State University Historically, drug development has been top secret. "Unlike many other industries, the pharmaceuticals industry has been extremely insular. They didn't share anything with anybody else," says Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development. About 15 years ago, though, small biotech companies started popping up. Under federal rules, they have to disclose anything that might have a material impact on their operations. Since interruptions to research processes affect small companies more than big companies, they ended up disclosing more of it. "I think that was the major reason why investors started looking at the large companies and saying, 'how come we don't know what you're doing?'" Kaitin says. "Now, you not only know what's going on with the products, but you have a pretty good idea about clinical trials." That also makes it easier to collaborate. And this consortium isn't the first: Others, like Boston-based Enlight Biosciences and TransCelerate Biopharma, have also popped up in recent years. They don't always generate great results, but they at least signify a willingness to try.    *[WSU]: Wayne State University **2\. The industry has gotten poorer**    *[WSU]: Wayne State University With the expiration of a bunch of blockbuster drugs, the pharmaceutical industry's fat profits have slimmed, leaving less money to pour into research and development -- especially when most drug trials ultimately fail, wasting millions of dollars and years of time.    *[WSU]: Wayne State University The new consortium is meant to unravel the biological roots of the disease, so companies know how to make drugs to attack them, and there's no way any one company could do that by itself. BCG's Sarah Cairns-Smith, who helped set up the partnership, compares this "pre-competitive" of the drug discovery process to a giant archaeological dig. "Some people believed that it was okay just to send in the artisans, and the artisans would find the pieces of the pot," she says. "You needed a more systematic approach." Companies put in a comparatively small amount of money for the chance to develop a successful drug at all, knowing that there's no way they can do it without competition.    *[WSU]: Wayne State University **3\. There's less public money for basic science research**    *[WSU]: Wayne State University Compare the funding environment today with the one in which scientists started combating another set of huge diseases: cancer. Resources have been pouring into cancer research for decades; the federal government has a whole Cancer Institute. These days, though, budgets for basic research are slimmer.    *[WSU]: Wayne State University "What's happened is, there hasn't been that much money spent on understanding the mechanisms of these other diseases," Kaitin says. "Companies are saying, we're not going to wait for NIH to provide the funding." So, congratulations to Collins and the participating companies. You probably couldn't have done it ten years ago.

How a fluorescent jellyfish – and federal dollars – helped fight AIDS

The road to Martin Chalfie's Nobel Prize-winning breakthrough began with a curious question: Why do green jellyfish glow in the dark? By itself, the federally-funded research project may have seemed frivolous, particularly when taxpayer dollars were at stake. But the answer to the question ultimately led Chalfie and his collaborators to discover a groundbreaking new substance that allows scientists to observe how HIV, cancer, and other diseases spread in the body. "Research is an investment in the long run. You can't predict what you're going to get," said Chalfie, whose research on "green fluorescent protein" was funded by the National Science Foundation and the National Institute of Health. At a Capitol Hill ceremony on Thursday, Chalfie, Osamu Shimomura and Roger Y. Tsien became the first recipients of the "Golden Goose Awards," which Rep. Jim Cooper (D-Tenn.) created in order to show how seemingly obscure research funded by the government can result in revolutionary, unexpected scientific breakthroughs. Another award recipient was Nobel Prize winner Charles Townes, whose discovery of laser technology in the 1950s began with an odd-sounding quest to amplify microwave radiation. A third group of scientists was honored for discovering a new material for bone grafts by studying the composition of coral. (Here's a video of the winning scientists explaining their research findings and the role of government funding.) It's been a long-standing Washington pasttime to single out similarly odd- sounding projects as a sign of government waste — the "sex life of the screwworm," for instance. But that can lead to big misconceptions about how scientific breakthroughs work, the awardees explained. In Washington, "they like to think they can foresse what's needed. You've got to be open-minded," said Townes. Funding for basic scientific research has retained bipartisan support, and it's so far been shielded from major budget cuts. But Cooper warns that there are still threats on the horizon. "Gridlock means sequestration, which means devastating cuts to science," he said. In such "budgetary emergencies," science needs to be prioritized, Cooper continued. "I'm calling it 'women and children first.'" Cooper was joined by a handful of other House members — including one Republican, Rep. Charlie Dent — at the awards ceremony. But they all had to excuse themselves early. "The anti-science forces have just called for five votes," Cooper explained.

The data innovation revolution

The Aug. 25 Sports article “Moneyball 2.0: Player health” detailed the growing role data analytics play in preventing and predicting sports injuries. It’s worth noting such software-enabled breakthroughs are revolutionizing health care at a phenomenal pace. Yet with these great advances comes greater responsibility. In our increasingly data-reliant world, a huge opportunity exists to craft policies that address patients’ concerns about their data while providing room for the sort of innovation that’s leading to better health worldwide. Such innovation is, in many cases, extending and saving lives. For instance, researchers have developed an algorithm that can predict cardiac arrest a crucial four hours in advance by combining real-time data with patients’ medical histories. Moving from two-dimensional to three-dimensional imagery for mammography is improving breast cancer detection rates. And researchers have shocked doctors with data showing that premature infants with unusually stable vital signs correlated with serious fevers the next day — enabling doctors to take preventive actions. Moving forward with amazing technological progress requires positive policy steps on data as well. Countless people worldwide stand to benefit. ****Victoria Espinel** , Washington** The writer is president and chief executive of BSA: The Software Alliance.

New therapies offer some hope for those facing glioblastoma brain tumors

One day, perhaps in the next five years, I will develop a malignant brain tumor called a glioblastoma that could take just 15 months to kill me. As a former practicing doctor, I know that these tumors are some of the hardest to treat — which is why this short prognosis has remained largely unchanged for the past decade. But radical thinking is starting to yield results. For example, an innovative “anti-cancer hat” has been so successful that trials have been cut short to allow more people to benefit from this approach as quickly as possible. Other unconventional treatments are also moving forward in trials. My medical career ended the day I was diagnosed with a glioma brain tumor, back in 2008. While it was surgically removed several days later, the cancerous growth had already seeded my brain with microscopic deposits, which will help it to return as an angrier and more aggressive glioblastoma. In 2008, I was given a 50 percent chance of making it to 2020, but — who knows? — one of these new options may help me live longer. When a tumor is buried deep within the brain, removing it via traditional surgery risks causing brain damage. Nanotechnology, using a microscopically small scale, is a safer alternative. A technique dubbed NanoTherm involves injecting tiny metallic spheres into tumors. When agitated using a strong alternating magnetic field, these spheres heat up to 176 degrees to cook and cauterize a tumor from the inside. Created by a team at the German firm MagForce, this approach is being tested as a method to boost the power of chemotherapy and radiotherapy for treating glioblastoma tumors. Early trials have been a success, and MagForce’s Hoda Tawfik says that some recipients have lived for nine years after diagnosis. Larger trials are underway. A potential cure for me? Tawfik hedges her bets, explaining that this treatment will work best alongside others. “We do not have a cure,” she says, but adds that the work so far can “offer hope of long-term survival.” In November, Roger Stupp at the University of Zurich proclaimed the birth of “a new standard of care for patients suffering from glioblastoma.” Speaking in Miami, he was describing an anti-cancer hat — the NovoTTF-100A, to give it its official name. Twenty years in development, it doesn’t have the pipes and metalwork I would expect from a cancer-killing machine. It’s more like the sort of thing Apple would design: a white skullcap attached to a battery pack. It is designed to be worn for 18 hours a day while ceramic transducers within the hat pulse alternating electrical fields into the brain. These fields interfere with the protein framework essential for cell division, preventing the replication of malignant tumor cells, which divide far more often than healthy adult cells. An ongoing trial of people receiving chemotherapy while wearing the device has found that they are 50 percent more likely to be alive two years after diagnosis than those receiving standard treatments. These mid-trial results were so impressive — a survival rate of 43 percent vs. 29 percent — that the test is due to end early so that more people can use the device as soon as possible. David Stocker, of the device’s manufacturer, Novocure Europe, says the hat has been too much like science fiction for some, who believe the use of electric fields in medicine has more to do with quackery than science. “Many researchers and academics have a hard time understanding how the system works,” he says. “It is only now that we have the trial results to show beyond any doubt that it does actually work.” The NovoTTF-100A is no silver bullet, though: It usually adds only months to life, effectively slowing but not killing the cancer, although some users have gone on to live for more than 10 years. I would be interested to know if it could be used for people like me, whose tumors have not yet progressed to a highly aggressive glioblastoma. A cheaper alternative might be a personalized vaccine called DCVax. Developed by NorthWest Biotherapeutics in Bethesda, this approach uses a person’s own immune system to attack his cancer. Cancer vaccines have been tried before, but virtually all have failed. Linda Powers of NorthWest Biotherapeutics says most existing attempts are “trying to rehabilitate immune cells that have already been hobbled by the cancer.” Her firm’s solution is to rekindle a person’s exhausted immune system by growing new white blood cells for them. The idea is that bone marrow cells that haven’t yet matured into immune cells are extracted from a person’s blood and nurtured in the lab into dendritic cells — the army generals that organize the rest of the brain’s immune system. Exposing these cells to biomarkers from the person’s tumor primes them to seek and destroy that particular cancer. The finished batch of activated, educated immune cells is then injected into the person’s blood to do their work. Early trials show promise. One trial had an average survival of around three years, and in some tests, a few individuals have survived more than 10 years — eight times the average of 15 months. Applying this technique to an earlier-stage glioma like mine might prevent it from mutating into a glioblastoma. And because it would be my immune system doing the work, there are likely to be relatively few side effects. For now I’m crossing my fingers: Randomized trials are now recruiting, with early results expected later this year. Meanwhile, Dror Harats of Israel-based VBL Therapeutics thinks he may have devised a gene therapy technique that could change my future. His strategy hits cancer cells’ ability to divide by targeting their blood supply and starving them of the fuel they need. As a tumor grows, it releases chemical messengers that trigger new blood vessels to grow toward it, feeding its appetite for oxygen and nutrients. Through 20 years of research, Harats discovered that the cells lining these newly forming capillaries have unique genetic features that can be exploited. His team has genetically engineered harmless adenoviruses to infect the capillaries’ cells and insert a gene that triggers them to self-destruct. In early human trials, this experimental treatment, called VB-111, has fared remarkably well, apart from some flulike symptoms. When tested on 46 people with glioblastoma for whom all other treatments had failed, those who received repeated injections of virus particles alongside standard drugs survived for 18 months — much longer than the average life expectancy for such patients of around six months. If these numbers hold up under repeated testing, VB-111 will be a breakthrough, offering a longer, better quality of life. It wouldn’t work for me yet, but it could be an option once my tumor becomes a glioblastoma. But speaking personally and not as a doctor, I confess I have some irrational hang-ups about a genetically engineered virus coursing through my blood. As a doctor, I am encouraged that these treatments offer serious potential, and as a patient, I’m excited by what they could offer me. I would jump at the chance to get a nanoparticle injection instead of an operation, and the anti-cancer hat could well treat my tumor while I live a normal life, walking the dog or doing the shopping. Although none would count as a cure, each of these treatments boasts a handful of long-term survivors, and over the next five to 10 years, it is possible that combined therapies could turn this terminal condition into a controllable one.

It’s not the Jetsons, but it may be coming soon

Imagine if your coat could wrap itself around you a little bit tighter when the temperature dropped. Or what if your car drove you to work instead of the other way around? Well, don’t expect anything in time for the next snowstorm or morning commute. But some experts predict the technology that could lead to these capabilities is likely to start entering the marketplace within the next five to 10 years. Robots, multidimensional printers, sci-fi-style polymers and other new technologies are beginning to shape the future of manufacturing. Google is testing self-driving cars. Scientists are working on bio-printers that might create usable human tissue. And traditional manufacturing workers are losing jobs as high-tech automated processes replace familiar assembly lines. It’s all part of a new era in manufacturing, with possibilities for expanding what U.S. manufacturers can produce, the role of the worker and the types 0f products consumers can use in their daily lives. A major player in the new world is something called additive manufacturing — better known as 3-D printing, because the process involves putting plastics, metals or some other material into a device that works much like a printer. The device extrudes a thin layer of the material onto a flat surface. Then, it extrudes another layer, then another, until it has built a three-dimensional object. One advantage: The precise addition of substances at any point ideally makes an object stronger or more flexible exactly where it needs to be stronger or more flexible. “I think additive manufacturing in general is going to get bigger and more important,” said Carl Bass, chief executive of Autodesk, a developer of tools for computer-aided design. It might sound futuristic, but 3-D printing is here: Some cutting-edge dentists are printing permanent crowns for damaged teeth. Japanese company FASOTEC is using MRI scans to give expectant mothers a 3-D model — instead of the familiar wedge-shaped ultrasound printout — of their developing fetuses. And doctors can take a patient’s CT scan and create a 3-D model of human bones to better plan the individual’s treatment. As those examples show, a lot of this technology is aimed at the lucrative health-care market. “Looking 10 years out, I do believe that when you start to look at . . . the ultimate machine, it’s the human body,” said Jeff DeGrange, vice president of direct digital manufacturing for Stratasys, which makes 3-D printers and supplies. For now, developers are working on many levels. Autodesk’s flagship product, AutoCAD (CAD for computer-assisted design), is a professional 3-D software application primarily used by engineers to design anything from buildings to wind turbines. But the company also makes hobbyist-friendly software tools, such as 123D Design, which is free to download or use online or on an iPad. Offered in conjunction with 3-D printing, laser-cutting and other creative services, it gives amateur designers an opportunity to have their creations printed or sculpted into being. Three-D printing is exciting enough. But consider the fourth dimension — time. Skylar Tibbits, director of the Self-Assembly Lab at the Massachusetts Institute of Technology and a lecturer in the school’s architecture department, ignited the imagination of technologists and futurists in February when he gave a TED talk on the concept of of “4-D printing” — printing objects that transform over time. Tibbits describes the process as “self- reconfiguration.” The technology seems to come straight out of science fiction. Videos on the MITWeb site show what looks like lumpy strings being submerged in water. At a measured pace, each object changes shape. One string contorts slowly into a cube. Another makes an outline of the letters MIT. There’s no power source, no apparent reason for the material to change. And the process isn’t simply like a sponge expanding: It’s an object taking on a completely different shape. Tibbits has described it as “robotics without wires and motors.” Huh? When explaining the process, Tibbits tends to use technical phrasing such as “geometric code” and “activation energy.” ****But what it seems to be, basically, is this: A black, static material is blended with a white, active material during the 3-D printing process. When put in water, the white material starts to swell — but its activity is controlled by the black material’s pre-programmed range of motion. This is key: The movement and its limits are programmed not into some kind of electronics or motors, but into the material itself. __ Tibbits and his team are exploring other ways to induce self-reconfiguration — through light, heat and pressure. He is collaborating with Stratasys to develop the synthetic polymers used in the process. He’s also collaborating with Autodesk on something called “Project Cyborg,” a cloud-based platform of design tools for programming matter. “Our products, materials and systems that we interact with in the future will adapt to how they are being used and how the environment is continually changing,” Tibbits said. “Rather than traditional 3-D printing, where we print static objects that are fixed materials, this is adding the ability to print smart materials that change shape or change property.” The technology is barely in the embryonic stage, but Tibbits is exploring how it can be used to create materials that could be used to make consumer products. **** “Let’s say for sportswear,” Tibbits said, “you could imagine sweat or heat, or if it’s raining or altitude or how you run versus how you walk” — all factors that could prompt the fabric to change its form in some way. He says he is talking to companies in “the sportswear realm,” although he wouldn’t give details. “I would target ambitiously to have some of these technologies and materials commercially implemented within five years,” he said. Stratasys’s DeGrange envisions a longer timeline. “I think we’re certainly greater than 10 years out on that [consumer] front, but there are some limited applications that could potentially fall in the 4-D space right now,” he said. “And it will be a game-changer, when that time arrives.” Here’s one potential game-changer: Tibbits is working with environmental engineering consulting firmGeosyntec Consultants to develop pipes that are able to bend and flex based on how much water passes through them or how the environment changes around them. This is not anything he had envisioned. “Water infrastructure would not have been the first thing on my mind,” said Tibbits when asked what potential application of his technology surprised him the most. In America, the word “manufacturing” is almost inextricably tied to the automobile. So let us consider the self-driving car, which employs radar, lasers, sensors and on-board computers — at least Google’s cars do. The search giant’s fleet of self-driving vehicles are still being tested, but last September, Google co-founder Sergey Brin said, “You can count on one hand the number of years before people can experience this.” Now imagine a self-driving car that is printed rather than assembled. It is packed for shipment by a robot. It is sent to the consumer in a flat, streamlined form, ideal for packing and shipping. Then, with the addition of water, the car is able to, in a matter of moments, reconfigure itself. Wow. For now, it’s just a fantasy. But as Tibbits says, we’re looking at a future in which “materials can produce solutions that we could have never come up with.”

Gene therapies offer dramatic promise but shocking costs

For most of her life, Allison Corona lived in a world dimmed by bad genetic luck. A disease called Leber’s congenital amaurosis left her legally blind at age 4. She could not navigate the short distance from her driveway to her front door after dusk. Three years ago, Corona, now 23, received an experimental medical treatment aimed at fixing the faulty genes in her eyes. Researchers at the Children’s Hospital of Philadelphia injected viruses carrying a good copy of her errant gene into her right eye and, nine days later, her left eye. The world around her, once dark and austere, soon grew brighter. Her vision is still far from perfect, but for the first time, she sees that paper towels have texture. She marvels at the velvet floral wallpaper that covers her bedroom wall. She takes a college class that gets out at 10:30 p.m. and no longer fears getting stranded in the night. “Things became much more beautiful for me,” Corona said. First tested in patients a quarter-century ago, gene therapy — a risky approach aimed at fixing the malfunctioning genes at the root of some diseases — is finally emerging from its own darkness after weathering high-profile tragedies, including the death of a teenage patient. As it evolves from experimental to applied medicine, gene therapy might soon find itself steeped in a new controversy: soaring drug prices. No therapy is approved yet in the United States, so discussions about price — as well as crucial questions about how much patients will pay directly — are hypothetical. But industry leaders are already talking about ways to get ahead of potentially massive one-time price tags that could make insurers and patients balk. A gene therapy approved in Europe in 2012 costs close to $1 million, and prices are expected to follow suit in the United States. The therapies in the pipeline are mostly for rare genetic diseases: sickle cell, hemophilia or immune deficiency. Their likely high prices stem from the expected value; unlike drugs that a person takes regularly, gene therapies are designed to be given once and have lasting effects. But everyone involved anticipates the potential backlash against a seven-figure price tag, which is leading to radical proposals. Instead of paying for a treatment all at once, insurers and patients could make installment payments as long as the therapy works, similar to a mortgage on a house. Some researchers are adding up the cost of the traditional treatments that a patient will be able to avoid each year to determine a price that, although high, could lead to savings for the health-care system. To Corona, the gift of vision is something approaching a miracle. But how much is that miracle worth in dollars? In the 1980s, a daring idea seized the imagination of scientists and physicians. What if they could design a drug that wouldn’t just treat the symptoms of a disease caused by a mutant gene, but could instead replace the gene with one that worked normally? Gene therapy was technically difficult but conceptually simple. Scientists would modify a virus so that when it infected a cell, it would ferry in the correct version of a broken gene. If the process worked, doctors would have a powerful weapon against rare but devastating maladies such as cystic fibrosis and “bubble boy” disease, which leaves children without immune defenses. As basic research moved forward, excitement about gene therapy soared. But, as with many new biomedical technologies, that initial exuberance would die down as the powerful idea of replacing broken genes collided with the inherent complexity of human biology. For gene therapy, the blip wouldn’t be just a scientific setback fought out on the pages of scientific and medical journals, but an international scandal in which patients were harmed and public faith was shaken. In 1999, an Arizona teenager named Jesse Gelsinger died after he experienced an unexpected, severe immune reaction while participating in a clinical trial of gene therapy led by researcher James M. Wilson at the University of Pennsylvania. “Everybody sort of stepped back and said, ‘Okay, we really have to consider, now that gene therapy has lost its innocence, what are we doing here? And what are the ways in which, if we’re going to do additional experiments, we don’t let this happen again?’ ” Francis Collins, director of the National Institutes of Health, said recently. “It was big; it was very big. I would not be surprised if some young scientists who were thinking of going down this path decided to do something else.” Wilson became the subject of legal action and scathing media coverage. The government restricted his work on human subjects. Lawmakers on Capitol Hill held hearings to probe the lack of oversight and the ethical lapses that had marked some gene-therapy trials. Gelsinger’s father, Paul, told one Senate panel in 2000, “The concern should not be on getting to the finish line first but on making sure no unnecessary risks are taken, no lives filled with potential and promise are lost forever, no more fathers lose their sons.” Also in the early 2000s, a few patients in a French gene-therapy trial developed leukemia. Along with the Gelsinger case, it proved a tipping point. Private investment in the field rapidly dried up, and it entered what Cowen & Co. Managing Director Phil Nadeau calls a “nuclear winter.” Regulators halted dozens of trials. To many, gene therapy seemed close to dead; a field of science that had been on a fast track appeared to have been relegated to little more than an interesting academic pursuit for a small cadre of researchers. With less money, less hype, and much more humility and caution, Wilson and other researchers searched for ways to improve the safety of the viruses used to insert genes. “It was a realization that the technology we had, which was on the shelf when we began the field, was inadequate for this field to move forward in any substantive way,” Wilson recalled. “It was really to go back to the drawing board, for me. That was a complete reorganization of what I was doing, how I was doing it, the kind of people who worked for me. It was a complete reboot.” Gene therapy’s comeback started with a trickle. In 2008, researchers reported that a small number of patients with an inherited form of blindness gained modest improvements in vision with gene therapy. Not long after, gene therapy restored immune function in eight of 10 children with typically lethal “bubble boy” disease. Katherine High, a researcher at the Children’s Hospital of Philadelphia who worked on one of the early blindness trials, started getting cold calls from investors and from pharmaceutical companies, asking if they could partner with her. Then the team of experts she had assembled in Philadelphia began to get job offers. “I remember very clearly, around 2011, I began to think to myself, ‘If we don’t form a company so we can all stay together, I’m going to lose these people,’ ” High said. She co-founded Spark Therapeutics, which went public this year and is sponsoring the trial in which Corona participated. The company is expected to put its blindness therapy before U.S. regulators, likely next year. It’s one of many companies with treatments in the pipeline. UniQure’s drug, Glybera, in 2012 became the first gene therapy approved in Europe, for a rare metabolic disease. Bluebird Bio, a biotechnology company that went public in 2013, is developing a variety of gene therapies, including a treatment for a genetic blood disease. Regenxbio, where Wilson serves as chief scientific adviser, went public in September. “This is only the beginning of what’s going to be a remarkable era in medicine,” Wilson said. “But if it’s the beginning, that suggests there’s significant room for improvement. That means there will be failures and there will be successes.” On the precipice of having a treatment finally make it onto the market, gene therapy faces yet another controversy: price. Although much of the current outrage has been spurred by companies that take old drugs and jack up their prices, the potential sticker shock from a million-dollar drug — even if it’s for a previously incurable disease — is sure to raise some of the same questions from politicians and the public. Nadeau, of Cowen & Co., said his firm has estimated that Spark Therapeutics’ gene therapy will cost $500,000 per eye. A study published last year in the journal Nature Biotechnology examined current health-care spending on hemophilia B and found that a gene therapy could conceivably be priced as a one-time payment of $4 million to $6 million. The authors argued that paying $150,000 a year as long as the drug works could potentially save the health- care system money. Spark Therapeutics chief executive Jeffrey Marrazzo is reluctant to talk about a dollar figure, but he does think it’s time to consider changes in the way the health-care system pays for treatments. The options being discussed include a down-payment model, with annual payments. University of Washington economist Anirban Basu has proposed an alternate health currency, HealthCoin, that insurers pay for when buying a cure and then sell to another insurance plan at a depreciated price if a patient switches insurers or becomes eligible for Medicare. The feasibility of these plans remains uncertain. But gene-therapy executives are arguing that, even at unprecedented prices, their drugs will save the health-care system money — and carry other benefits. “How do we recognize that there’s truly something that’s important and valuable to people, not only to have certain aspects of their vision restored, but . . . to have it done once and then have the ability to go on with their lives?” Marrazzo said. Corona, who excitedly woke up her family in the middle of the night when she read about the possibility of gene therapy years ago, didn’t have to pay for her treatment, because she was part of a clinical trial. But she said her family would have found a way to get her the therapy if it had already been on the market, even if it meant battling an insurance company or taking out a loan. After all, she said, it’s not only about seeing better. She now feels like a happier, more confident person. That part feels priceless.

Investing in the nation’s health at NIH

_Francis S. Collins is director of the National Institutes of Health._ Biomedical research is at a critical juncture — a moment of exceptional opportunities that demand exceptional attention if their promise is to be fully realized. Many of the most exciting possibilities stem from the convergence of several factors: innovative tools and technologies arising from the Human Genome Project; advances in computers and biomedical imaging that are fueling a generation of complex digital data sets known as “big data”; and increased interest by both public and private sectors in finding ways to accelerate the rate at which research findings are turned into treatments and cures. The National Institutes of Health (NIH) is responsible for turning scientific discoveries into better health, but a combination of sequestration-mandated spending cuts and budgets that have not kept pace with biomedical research inflation over the past 10 years has weakened NIH’s ability to carry out its mission. One transformative program that hangs in the balance is the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, part of a focus aimed at revolutionizing understanding of the human brain. By catalyzing development and application of new technologies, researchers plan to produce a dynamic picture of the brain that shows, for the first time, how individual cells and complex neural circuits interact in both time and space. This could mean enormous advances for efforts to treat and possibly even prevent epilepsy, schizophrenia, Alzheimer’s disease, autism, Parkinson’s disease, traumatic brain injury and many other neurological conditions. Another area of great promise is the ability to assemble very large data sets of medical research information. The advent of electronic health records will dramatically accelerate the “big data revolution.” Details can be understood by focusing on one disease: cancer. Taking advantage of breathtaking advances in DNA-sequencing technology, NIH-funded researchers working on the Cancer Genome Atlas have conducted comprehensive analyses of more than 20 different types of cancer and plan to study dozens more. Besides expanding understanding of the molecular roots of different cancers, this pioneering work has opened doors to new therapeutic targets, as well as to new and more precise uses of chemotherapy drugs. Unfortunately, this mountain of data will be of limited use to cancer patients if researchers and clinicians lack the tools necessary to manipulate and mine it effectively. Another fascinating frontier is the microbiome. The human body contains trillions of microbes, outnumbering human cells 10 to 1. So far, work to gather information on the genetic makeup of these microbial communities has yielded important insights into their roles in a wide range of chronic diseases, including obesity, diabetes, allergies, cancer and heart disease. The opportunity to expand and build on that knowledge to develop evidence-based treatments, such as probiotics for obesity, is just one of the exciting possibilities. Vaccine development is also poised for rapid progress, especially in the areas of AIDS and influenza. Some researchers are exploring the production of “broadly neutralizing” antibodies that work against all strains of a virus. In the case of influenza, that could mean an end to the annual flu shot and a vaccine that would profoundly reduce the global risks of the next influenza pandemic. In recent years, researchers have learned how to reprogram human skin cells or white blood cells into induced pluripotent stem cells, which have the amazing ability to develop into different types of cells. This opens the door to unprecedented opportunities for the advancement of basic research into human development, acceleration of drug screening for a host of diseases, and design of new “cell-based” therapies to cure some of medicine’s toughest challenges, such as sickle cell anemia and inherited forms of blindness. Clearly, NIH is not lacking for ideas. And the institutes will continue to support innovative research across the country. But without sustained investment, many high-priority efforts would move at a substantially slower pace, and years of effectively flat funding for biomedical research have left scientists facing the lowest chances in history of having their research funded by NIH. Many young scientists are on the verge of giving up, taking with them the talent needed to make tomorrow’s medical breakthroughs. The budget deal reached last week, however, would give appropriators the chance to provide some much-needed relief for biomedical research. The economic benefits of NIH funding include a return-on-investment of research grants to local economies and cost savings from decreased disease burdens. But beyond that, for the millions of sick people awaiting treatments and cures, the investment in NIH’s mission is priceless. If an investment in hope is not worth supporting, I don’t know what is. **Read more on this issue:** The Post’s View: NIH research weakened by the budget squeeze George Will: The sequester’s a public health hazard Five myths about big data

Why we should believe the dreamers — and not the experts

History is littered with the failed predictions of experts. Yet governments hire high-paid consultants to advise on policy; businesses use them to vet research and development projects; and venture capitalists have them make investment decisions. Experts excel in looking backwards, protecting their turf, and saying what their clients want to hear. Their short-term predictions are sometimes right, but they are almost always wrong in forecasting any more-distant future. Experts are the greatest inhibitors of innovation—the ones who shouldn’t be listened to. Peter Diamandis says it best: “An expert is someone who can tell you exactly how it can’t be done.” Look at some of the most famous historical examples: The problem with experts is that they think they know it all; ignore data that don’t fit their points of view; and extrapolate from the past on a linear basis. If some disruptive technology hasn’t come along in the past, the assumption is that it won’t happen in the future. What’s worse is that experts often try to block technologies that might up-end their roles. After all, if things change too fast, they will no longer be experts. You see these specialists in governments, businesses, and academia. Government experts usually have an agenda. Business experts are typically old-timers trying to protect their jobs. Academics specialize in digging deep into fields that most people would consider arcane or obscure. They gain tenure by writing academic papers and being extremely knowledgeable in a narrow area. They often remain in the same field for decades and can’t see the forest for the trees. Technology is, today, moving faster than ever. Advances that took decades, sometime centuries, such as the development of telephones, airplanes, and the first computers, now happen in years. Witness how smartphones and social media have come out of nowhere in the past seven years and changed the way we interact and communicate. We are always connected to each other and to our employers. Computing power is advancing at exponential rates and causing acceleration in fields such as artificial intelligence, robotics, 3D printing, sensors, and medicine. When advancing technologies converge, they lead to artificial intelligence–based apps that analyze data from medical sensors, with the potential to disrupt the medical industry. Smartphones apps such as Uber and AirBnb are already threatening transportation and lodging. Amazon.com has made bookstores disappear and Apple has changed the music industry. Which experts ever predicted these disruptions?   The experts are becoming more wrong—and irrelevant—than ever.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday Silicon Valley’s most respected venture capitalists can’t see even the near future. Mary Meeker of Kleiner Perkins Caufield & Byers produces a yearly report, Internet Trends, which is the tech industry’s bible. Its May 2013 report analyzed the leading players in social media and made predictions on the future of mobile technologies. It did not even mention WhatsApp—which Facebook acquired for $19 billion in February 2014. This was the largest acquisition in history of a venture-backed company and was not even on Meeker’s radar. As an academic expert in advancing technologies, I may lack the credibility to write this article. When entrepreneurs come to me for advice, I tell them, as I am telling you, to take it for what it’s worth. No one can accurately predict the future of business any more, because too much is happening too fast. At best, you can gain an understanding of the overall trends and the types of opportunities and obstacles that lie ahead. You can look backwards to understand what problems have already been solved, how others overcame hurdles, and what types of business strategies worked best. You can learn what questions to ask. You can realize yourself when your idea is either just plain silly or impractical. I tell entrepreneurs that if they really believe in their gut that they have a world-changing idea, then they should pursue it. They shouldn’t let anyone stop them—no one really knows more than they do. As Peter Diamandis also says “The day before something is a breakthrough, it’s a crazy idea.”

Emerging technologies: A solution to the unemployment puzzle

_Javier Garcia Martinez is vice-chair of theThe Global Agenda Council on Emerging Technologies of The World Economic Forum, Professor at the University of Alicante (Spain) and founder of Rive Technology, an MIT spin-off commercializing nanomaterials for energy applications. Sang Yup Lee is chair of the Emerging Technologies Global Agenda Council of the World Economic Forum, Distinguished Professor and Dean at the Korea Advanced Institute of Science and Technology (KAIST)._ World leaders across the political spectrum insist that innovation is the path to creating more, better-paying jobs. Unfortunately, they are delivering this message even as their countries are cutting back on public financing for research and development. In a recent editorial, the journal Nature argued that Greece, Italy, and Spain – three countries that are drastically reducing their public R&D; funding – could, benefit from doing the exact opposite. Public funding for R&D; often provides the seed money for foundational innovations at the heart of some of the world’s leading companies. After all, Google started with NSF, NASA and DARPA support. The Global Agenda Council on Emerging Technologies of the World Economic Forum, in consultation with the over 700 members of the over 80 councils from a wide range of disciplines, has identified the top ten emerging technologies that have the greatest potential to create new industries and impact existing ones. From nanotechnology to synthetic biology, these technologies are beginning to show their potential in the lab if not already in the market whether in sun block, planes or sports equipment. These innovations could fuel discoveries that fundamentally change our understanding of what is technologically possible, while providing a much needed boost to the global job market. The field of nanotechnology is a particularly good example, since nanomaterials can reveal unique properties that impact a variety of economic sectors, from energy production and storage and the diagnosis and treatment of cancer to water and food consumption. Beyond that, and even more importantly, this new technology will create the need for new factories where materials for other industries such as construction and transportation, will be produced with minimal waste and greater efficiency. Rapid advances in synthetic biology and metabolic engineering are allowing biologists and engineers to tap into the potential of both of these emerging technologies in unprecedented ways. We can now develop new biological processes and organisms designed to serve specific purposes, including the conversion of renewable biomass to chemicals, fuels and materials, producing new therapeutic drugs, or protecting the body against infectious diseases. The biotech industry, already a worldwide job-creator, will greatly benefit from advances in synthetic biology, metabolic engineering, and modelling of complex biological systems. Organizing information in a structured, useful way through advances in computation, data visualization and intuitive communication has the potential to extract knowledge from what was once considered noise in order to create solutions to emerging challenges. Companies will become more efficient, using added-valued information, and information processing and visualization software and hardware will lead to job creation. Emerging technologies play an important role in addressing our major mega-challenges such as energy, water, food and health for the world’s growing population. Integrating these emerging technologies within existing industries presents not only a major challenge but an opportunity. The energy industry, for example, stands to benefit from emerging technologies. Bio-engineering microorganisms is allowing for the enzymatic degradation of cellulose, making possible the transformation of agricultural waste — instead of food — into biofuels. Nanomaterials embedded in polymers are being used in a new generation of flexible, lighter and more efficient solar cells free of costly silicon. These are just a few examples of how a large and fairly traditional industry is already benefiting from disruptive innovations, although some major challenges such as cost, scalability, and reliability remain greatly unsolved. The development of great technologies is not enough. Commercialization is key to creating new jobs. Once a discovery has been made, the first challenge is harnessing the entrepreneurial drive of the discoverer. In too many cases, groundbreaking discoveries with great commercial potential end in a scientific publication or a patent without a product prototype. This happens because entrepreneurship is not top of mind for most world-class scientists. The second challenge, once the technology has been validated and a business plan has been created, is to transition an invention from the lab to the marketplace. The lack of private funding to grow small companies into successful and sustainable ones is a major challenge. This is especially true in the fields of energy and health where massive and sustained funding is needed. Before we can adequately address either of these challenges, however, the appropriate talent needs to be there. Education systems will need to be revised to equip future generations to be able to refine and develop the technologies and make themselves employable in the employment opportunities created. There are no shortcuts on the path from emerging technologies to new industries. In most cases, the best recipe is to promote innovation and entrepreneurship to accelerate the time to failure and favor a Darwinian selection of the “fittest” ideas. Today, the United States is the best ecosystem to start successful companies that commercialize new technologies. However, the world’s emerging economies are becoming well-aware of technology’s job-creating potential, and, as a result, they are investing heavily in education, world-class research and supporting their new high-tech companies. With large populations of highly-motivated young people, it is likely that many of these new industries will begin to flourish in emerging economies that invest in R&D, higher education and entrepreneurship.

Taking magnetic resonance imaging down to the nano scale

Jacob M. Taylor, a young physicist at the National Institute of Standards and Technology (NIST), has made pioneering scientific discoveries that in time could lead to significant advances in health care, communications, computing and technology. As a fellow at NIST since 2009, the 34-year-old Taylor has conceived a number of original theories, including a way to vastly improve magnetic resonance imaging that allow probes down to the cellular and molecular levels. This approach holds the promise of providing detailed information that could lead to far better diagnoses, more targeted medical treatments for patients and rapid turnaround for drug discovery. He is also responsible for a major breakthrough that could eventually permit the routing of greater quantities of information over the Internet than now possible, while using reduced levels of energy. In addition, Taylor has proposed a novel theory that could help advance the elusive drive toward quantum computing, permitting exponentially faster calculations then conceivable on conventional computers. Mihkail Lukin, a Harvard University professor of quantum optics and atomic physics, said scientists around the world are examining how to harness quantum properties of matter to gather information with higher resolution and sensitivity, to process greater quantities of information faster and more securely, and to advance the technology of computing. “Jake has made fundamental contributions in all three of these areas,” said Lukin, Taylor’s former professor and now a colleague. “He is one of the most creative young scientists I have ever seen. He thinks about problems in unusual ways and comes back with new and novel ideas.” William Phillips a NIST fellow and a Nobel Prize winner in physics, said Taylor’s ideas are at “the cutting-edge of theoretical physics.” But Phillips said Taylor does more than come up with novel theories. He said Taylor “thinks about reality and the practical application of his complex work,” and is engaged in a wide array of experiments that could have “great technological importance” for electronics and communications systems used by consumers and industry. One of Taylor’s major accomplishments has been the use for the first time of diamond-tipped sensors that can perform magnetic resonance tests on individual cells or on single molecules, a sort of MRI scanner at the microscopic or nano-scale. No one had previously thought diamond crystals could be used for this purpose and in the way devised by Taylor. The physicist now has patents pending on the unique process and is conducting experiments that have shown success in the laboratory. The work raises the possibility that physicians one day will be able to use the technology to detect diseases at a far earlier stage, and that drug companies may be able to devise more effective medications because of the precise information that will flow from the advanced imaging technology. Without Taylor’s “pioneering” contributions, said Lukin, “this field of experimentation would not exist.” Taylor also is experimenting with another magnetic imaging process that works with increased speed and sensitivity, and could allow patients with pacemakers or individuals with shrapnel embedded in their bodies to obtain scans that now might be too risky. Today, the technology poses dangers to individuals who have magnetic metals in certain sensitive locations in their bodies. Another Taylor innovation centers on the development of technology for the next generation of Internet routers that rely on light as opposed to electrons to communicate information. The information carried by the router would be immune to the environmental noise and defects encountered with currently available technology, representing an advance over today’s telecommunication applications by increasing bandwidth and reliability, and by reducing energy usage and costs. A patent is pending on this process and experiments are underway. In addition, Taylor and colleagues are testing new theories that could help make inroads into much faster computing than now possible, an area of great interest in the world of quantum physics. Taylor said that working at NIST provides him with the resources he needs, a stimulating environment and the freedom to take risks, think boldly and work on issues that can have a big impact for technology and the nation. “It is a thrill to do something that no one has dreamed up or done before,” said Taylor. “The long term implications of some of these projects could be huge. It’s what gets me up in the morning—the feeling I can really change the world, at least in small steps.” _This article was jointly prepared by the Partnership for Public Service, a group seeking to enhance the performance of the federal government, and washingtonpost.com. Go tohttp://washingtonpost.com/wp- srv/politics/fedpage/players/ to read about other federal workers who are making a difference._

A prize for life

LAST WEEK a group of technology titans announced the establishment of the Breakthrough Prize in Life Sciences, a $3 million award for each scientist honored, more than twice the sum of the Nobel Prize. The award comes at a time when the life sciences are in the middle of a scientific revolution no less awe-inspiring than the splitting of the atom. The founders of the prize include Art Levinson, chairman of both Apple and Genentech; Mark Zuckerberg, founder of Facebook; Sergey Brin, co-founder of Google; and Yuri Milner, a Russian Internet tycoon, who previously launched a similar prize for physics. What they share in common are fortunes and empires built on digital innovations such as search, e-mail and social media. What they are celebrating is also a phenomenon of the digital era but in a way not widely appreciated. That is because biology — indeed, the very secrets of life and evolution — is experiencing a period of innovation and discovery that owes much to the power of computation. An organism’s genetic blueprint, or genome, can be turned into millions or billions of bits of digital information in a process known as sequencing. In more than a decade since the end of the Human Genome Project, there has been an explosion of sequencing technology and an enormous acceleration in speed. In addition to humans, the genomes of everything from songbirds to sunflowers, down to the smallest bacteria and viruses, are being sequenced. The makeup of DNA can be recorded and examined in an electronic blueprint, not unlike the pixels in a digital photo. The applications are only gradually coming into view, and there have been disappointments, but the promise is enormous. Diseases might be conquered by examining the genome of various pathogens or cells and modifying them. In 2010, researchers at the J. Craig Venter Institute reported that they used computers to design a synthetic chromosome and then transplanted it into a living cell controlled only by the synthetic material. New techniques are allowing accurate genome sequences to be made from single human cells; according to the journal Nature, this could speed up and reduce the cost of screening embryos for in vitro fertilization, picking the one likely to produce a healthy baby. At Harvard and other places, work is being done to develop artificial organelles that can be incorporated into algae, plants and even human cells and can perform specific and valuable functions. And sequencing is potentially valuable for unlocking new drugs that target specific illnesses, although it is difficult and there have already been plenty of failures. Eleven researchers were named the first winners of the lucrative new prize. Their accomplishments range widely, not only in genomics. The founders hope to shine a light on scientists who often are overlooked in our celebrity-saturated society and to encourage a new generation. That’s good, but the real powerhouse of funding for basic biomedical research is the federal government, and its support must be sustained and expanded. We stand at the intersection of both the digital and life sciences revolutions, a suitable moment to salute explorers peering over the next horizon and to ensure that the potential of these revolutions can be fully realized. **More on this topic:** The Post’s View: Fighting superbugs The Post’s View: Tracking a superbug at the NIH The Post’s View: Protection for science and security

It’s time to get serious about science

_Jim Cooper, a Democrat, represents Tennessee’s Fifth Congressional District in the U.S. House. Alan I. Leshner is chief executive of the American Association for the Advancement of Science and executive publisher of the journal Science._ Some policymakers, including certain senators and members of Congress, cannot resist ridiculing any research project with an unusual title. Their press releases are perhaps already waiting in the drawer, with blanks for the name of the latest scientist being attacked. The hottest topics for ridicule involve sex, exotic animals and bugs. The champion of mocking science was the late William Proxmire, whose Golden Fleece Awards enlivened dull Senate floor proceedings from 1975 until 1988. His monthly awards became a staple of news coverage. He generated good laughs back home by talking about a “wacko” in a lab coat experimenting with something seemingly stupid. Proxmire did not invent the mad-scientist stereotype, but he did much to popularize it. The United States may now risk falling behind in scientific discoveries as other countries increase their science funding. We need to get serious about science. In fact, maybe it’s time for researchers to fight back, to return a comeback for every punch line. Toward that end, we are announcing this week the winners of the first Golden Goose Awards, which recognize the often-surprising benefits of science to society. Charles H. Townes, for example, is hailed as a primary architect of laser technology. Early in his career, though, he was reportedly warned not to waste resources on an obscure technique for amplifying radiation waves into an intense, continuous stream. In 1964, he shared the Nobel Prize in Physics with Nikolay Basov and Alexander Prokhorov. Similarly, research on jellyfish nervous systems by Osamu Shimomura, Martin Chalfie and Roger Y. Tsien unexpectedly led to advances in cancer diagnosis and treatment, increased understanding of brain diseases such as Alzheimer’s, and improved detection of poisons in drinking water. In 2008, the trio received the Nobel Prize in Chemistry for this initially silly-seeming research. Four other Golden Goose Award winners — the late Jon Weber as well as Eugene White, Rodney White and Della Roy — developed special ceramics based on coral’s microstructure that is now used in bone grafts and prosthetic eyes. Across society, we don’t have to look far for examples of basic research that paid off. Larry Page and Sergey Brin, then a National Science Foundation fellow, did not intend to invent the Google search engine. Originally, they were intrigued by a mathematical challenge, so they developed an algorithm to rank Web pages. Today, Google is one of the world’s most highly valued brands, employing more than 30,000 people. It is human nature to chuckle at a study titled “Acoustic Trauma in the Guinea Pig,” yet this research led to a treatment for hearing loss in infants. Similar examples abound. Transformative technologies such as the Internet, fiber optics, the Global Positioning System, magnetic resonance imaging (MRI), computer touch-screens and lithium-ion batteries were all products of federally funded research. Yes, “the sex life of the screwworm” sounds funny. But a $250,000 study of this pest, which is lethal to livestock, has, over time, saved the U.S. cattle industry more than $20 billion. Remember: The United States itself is the product of serendipity: Columbus’s voyage was government-funded. Remember, too, that basic science, the seed corn of innovation, is primarily supported by the federal government — not industry, which is typically more interested in applied research and development. While some policymakers continue to mock these kinds of efforts, researchers have remained focused on improving our quality of life. Scientific know-how, the engine of American prosperity, is especially critical amid intense budgetary pressures. Federal investments in R&D; have fueled half of the nation’s economic growth since World War II. This is why a bipartisan team of U.S. lawmakers joined a coalition of science, business and education leaders to launch the Golden Goose Awards. Federal support for basic science is at risk: We are already investing a smaller share of our economy in science as compared with seven other countries, including Japan, Taiwan and South Korea. Since 1999, the United States has increased R&D; funding, as a percentage of the economy, by 10 percent. Over the same period, the share of R&D; in the economies of Finland, Germany and Israel have grown about twice as fast. In Taiwan, it has grown five times as fast; in South Korea, six times as fast; in China; 10 times. In the United States, meanwhile, additional budget cuts have been proposed to R&D; spending for non-defense areas. If budget-control negotiations fail, drastic across-the-board cuts will take effect in January that could decimate entire scientific fields. Columbus thought he knew where he was going, but he didn’t know what he had found until many years later. He was searching for the Orient, but he discovered something even better: the New World. Let’s honor our modern-day explorers. We need more of them. They deserve the last laugh. **Read more about this debate:** Charles Lane: Electric cars and liberals’ refusal to accept science Matt Cooper and Elizabeth Wiley: Keep the library open after graduation Charles Lane: Congress should cut funding for political science research

Want to catalyze innovation? Look to the gamers.

I would say, don’t be afraid of failure. Really go for it. I have a bar on my desk that is engraved with the following question: What would you attempt to do if you knew you could not fail? It’s an amazingly powerful question. When you ask it, you begin to understand how the fear of failure limits you — not failure itself, but the fear of it. We have a number of things that we’re investigating and advancing, such as the ability to make vaccines in tobacco plants — perhaps the first healthy use of tobacco plants ever in the history of the world. In tobacco plants, we can make vaccines in weeks and months instead of nearly a year. So, in the event of a pandemic or a biological warfare attack, we can make vaccines much more quickly. The agency’s historical success in breakthrough innovation is based on the focus: big-reach science together with a driving application. We have to break what is now a long-standing impression that big breakthrough innovation happens in a linear fashion. It doesn’t. And it isn’t some ethereal thing. Innovation is a discipline. We use a variety of strategies for catalyzing innovation, and one of them is prize-based competitions. These type of challenges can dramatically increase the number and diversity of people who contribute ideas. When you can do that, you often get breakthroughs that you don’t expect. We have a program — a game — called Foldit. It was originally sponsored at DARPA, and it is essentially the Tetris of protein folding. Understanding the three-dimensional folded structure of a protein is very important for understanding disease and for developing treatments for diseases. A gamer said, “Oh, look, lots of small manipulations, lots of detailed interactions — that’s a game.” And so they built Foldit. Just last September, the three-dimensional protein structure for the retroviral protease that contributes [to] AIDS in rhesus monkeys was solved. For 15 years that problem was unsolved in the scientific community. The gamers solved it in days. I think we have not yet completely harnessed that which we can from large numbers of people contributing to [solving] big problems.

THE PHILADELPHIA CHROMOSOME A Mutant Gene and the Quest to Cure Cancer at the Genetic Level By Jessica Wapner

To tell the story in “The Philadelphia Chromosome,” Jessica Wapner has to go back in time and re-create the laboratory challenges of the 1970s and ’80s. These eras are not so long ago chronologically, but the changes in genetic understanding and laboratory techniques in the intervening years mean that it can be tricky to evoke the magnitude of creative but laborious steps undertaken back when. In 1959, David Hungerford, a scientist examining the chromosomes of a patient with chronic myeloid leukemia (CML), noticed that one of those chromosomes had an abnormally short arm. Something was missing. Remember that this was happening only six years after the structure of DNA had been discovered; the field of modern genetics was just taking shape. CML was a disease without a treatment, a slow-growing cancer of the white blood cells that could lurk for a long time in a person’s bone marrow and eventually develop into a “blast crisis,” in which abnormal white blood cells proliferate, wiping out the bone marrow and eventually killing the patient. This book tells the story of the complex research steps that led scientists from the observation of that abnormal chromosome in CML patients to the understanding of oncogenes, genes that transform normal cells into cancer cells, and then the steps toward the development of a pharmacologic cure. Wapner uses the details of this scientific journey to illuminate many different sides of the story of research and medicine over the past three or four decades: The highs and lows of research in progress, the sociology of organized science, the politics and economics of drug development and drug testing, and the bedside challenge of caring for patients, especially when they are taking part in a clinical trial. The characters in “The Philadelphia Chromosome” include the scientists and the doctors who were drawn into this project following Hungerford’s discovery — in particularBrian Druker, who started his fellowship in oncology in the mid-1980s. “Most of his patients would die, if not shortly after coming under his care, then in the easily foreseeable future,” Wapner writes. “That was what happened with cancer: Almost everyone died from the disease.” Druker started as a lab researcher at a moment when the genetic understanding of cancer was developing rapidly and new therapies were beginning to seem plausible — therapies that might alter those fatal outcomes. The chromosome abnormality had led to the understanding of a genetic deviance, a different stretch of DNA found in the cells of people with CML. But what did that different gene encode? Again, a question that might be answered quickly and easily in today’s world of rapid sequencing took arduous research — which helped elucidate not only the specific protein involved here, an enzyme called a tyrosine kinase, but also some of the mechanisms underlying cancer. The challenge was to use that understanding to create a drug that would interfere with this specific kinase and block this specific cancer. The scientists found a possible compound — a possible treatment. But then a new process of research and investigation had to begin, obedient to a new set of rules and constraints, since this time the goal was to experiment on people. Wapner is particularly good at evoking the promise and tension of the drug trials, as STI-571 is tested in rats, mice and dogs — and the researchers and the drug company have to deal with the news that it causes liver damage in both rats and dogs. But if the book attends carefully to the extraordinary work of the scientists, it also pays attention to that first brave — and lucky — cohort of patients who not only volunteered to test a possibly dangerous drug, but organized themselves to demand a voice in their treatment, creating an online petition to the drug company to produce more of the experimental medication and speed up clinical trials. Or as one patient put it, “There is no way that there is a drug out there that can help me that’s not going to be given to me.” Wapner’s challenge as she turns a close eye on this complex chain of discovery, drug development and medical practice is to link the huge conceptual and experimental jumps to the details of the science. To follow the story, you have to care not only about the scientists and the patients, but also about the compound, which almost becomes a character itself: “From a genetic mutation to its haywire fusion protein, from the fusion protein to the leukemia, a path had been traced for the rational design of this drug. From CGP-57148B to STI-571 and finally to imatinib mesylate and Gleevec, the world’s first drug targeted against a specific mutant protein that stopped cancer in its tracks was ready for wide release.” It’s a model for a more targeted and intelligent way of treating cancer. The most sophisticated lessons of genetic research are applied to a kind of “personalized” drug development in which chemotherapeutic drugs attack very specific cancer cells. All this has happened with CML, though results with other forms of cancer have so far been much more limited. Just as the story of the early research illuminates the byways of genetic research, the story of the development of the drug, Gleevec, involves collaborations between academic doctors and pharmaceutical companies, the fear of liability, even the politics of naming a new drug. Wapner uses her exhaustive research into this bench-to-bedside story to evoke controversies and complexities in science and medicine at every level. This reporting takes in a huge swath of science and research, a landscape that changes dramatically over the course of her story. Wapner’s achievement is to help the reader understand why each development is huge in its time and place — starting with Hungerford peering through his camera at the chromosomes and following scientists through the laboratory stories, through drug development and animal testing, to the triumphant patient treatment when the drug becomes almost routine — a scientific miracle absorbed into the daily lives of a group of patients no longer united by a fatal diagnosis. **Perri Klass** is a professor of journalism and pediatrics and the director of the Arthur L. Carter Journalism Institute at New York University. **THE PHILADELPHIA CHROMOSOME** **A Mutant Gene and the Quest   to Cure Cancer at the Genetic Level ** By Jessica Wapner The Experiment. 303 pp. $25.95

This one step by the government may unlock the untapped speed and power of mobile technology

When you use the LTE connection in your smartphone, that mobile data travels over invisible airwaves that support everything from Google Maps to FaceTime. But not long from now, all sorts of devices will be connected wirelessly to the Internet, from home appliances to automobiles to virtual reality headsets — and they'll all need lots of fast, reliable bandwidth. That's why the government on Monday announced it's looking to open up a huge swath of these airwaves for companies to play with, more than they've ever had before. If it's approved, the result could lead to an array of new apps, services and ways to send and receive information of all kinds. To draw an analogy, it could be to wireless Internet what gigabit fiber meant for wired networks: massive amounts of new capacity that unlocks the next generation of Internet-driven entrepreneurship. Here are the nuts and bolts of the plan, which will be officially circulated by Tom Wheeler, the chairman of the Federal Communications Commission, to his fellow commissioners Thursday. If it's approved, companies will start getting licenses to use the airwaves at extremely high frequencies compared to today. Many of our existing cordless phones and WiFi antennas work in the 2.4 gigahertz range, but the policy change from the FCC would open up channels in the 28 GHz range and higher. "That’s damn important," said Wheeler in a speech Monday, "because it means U.S. companies will be first out of the gate" developing new technologies and standards for 5G, the next in mobile Internet after the current generation of 4G. What's so special about this part of the radio spectrum? Well, at such high frequencies the airwaves don't go through walls or very far; they just tend to bounce around instead of penetrating obstacles. But that may not be a bad thing; it means companies like Verizon or AT&T could set up hyper-local cell sites around a hospital, for example, and the hospital could use all the bandwidth provided by that site without worrying about others clogging the site with demand. Not only will these new channels be higher up in frequency — they'll also be much, much wider, which makes them able to support a lot more wireless traffic. Imagine the difference between a small residential road and extra-wide highways, and that's kind of what we're talking about here. Instead of channels that are 5 or 10 megahertz in size, you'd get 200 MHz-channels, said Wheeler. Under the plan, the government would set aside as much as 14 GHz for unlicensed uses. That's a huge chunk of airwaves not owned or controlled by any corporation and that can be used for Bluetooth, WiFi, garage door openers, hobbyists and tinkerers. Companies in the mobile industry may get access to their own, massive swath of commercial spectrum in what Wheeler called the government's biggest such offering in history. The upshot is that Americans may soon be among the first to start tinkering with 5G mobile Internet and all that follows from it. The FCC is expected to vote on Wheeler's proposal next month.

How the Internet may be shifting innovation away from big cities

Think of the device you're reading this on. It's the culmination of hundreds, maybe thousands, of inventions that all got added together to form a computer, tablet or smartphone. Most of this technology came out of Silicon Valley, one of the world's greatest hubs for innovation. But what is it about that place that makes it such a fruitful breeding ground for ideas? Intuitively, you might imagine that having lots of inventors clustered together would be great for collaboration. One engineer or company can quickly take someone else's idea and build upon it. Now there's research to back that up. A recent study of the entire U.S. patent system — covering millions of patents dating back to 1836 — finds that geographic clustering does, in fact, accelerate the pace of innovation.  Looking at keywords that represent important technological leaps, such as "database," "microprocessor" or "transistor," the researchers examined how quickly those terms made it into other patents soon after the terms first appeared in the U.S. patent system. They found that in places with higher population density, inventors were quicker to pick up on new ideas and incorporate them into their own work. This might sound like an obvious conclusion. But, Packalen and Bhattacharya point out, there's nothing special about geographic clustering that makes innovation inevitable. A big city that's home to a dominant industry could plausibly suppress innovation if the industry in question decides a new invention poses a threat, for instance. So the fact that America's inventors do their best work when they're around other inventors seems like something worth appreciating, and perhaps promoting through public policy. There's just one complication: For whatever reason, the researchers note that the benefits of geographic clustering appeared to drop off beginning in the 1960s and 1970s. What's so interesting about that pattern is that it fits the rise of advanced communications technologies, along with a precipitous fall in the cost of talking to someone over long distances. One of the first examples that comes to mind is the Internet, which the researchers say has "made new ideas available more cheaply to all, regardless of where they were developed." But you also can't forget the rise of satellite communications, fiber optics, the fax machine, the cellphone and all manner of other technologies that shrunk distances and made it easier for inventors in small towns to benefit from advantages enjoyed by inventors in large cities. While the researchers don't provide conclusive evidence for that conclusion, they point to predictions from as far back as 1920 that communications technology would someday lead to a dramatic decrease in the cost of innovation. The economist Alfred Marshall "himself explored the implications of such ‘cheapening of the means of communication,’ and raised the possibility that location might play only a minor role in knowledge production," Packalen and Bhattacharya write. Whether this is actually what we're seeing isn't fully clear. But it does raise questions about whether it's better to cluster innovators together — or whether the Internet has effectively erased the tremendous historical advantages of physical proximity.

Congress is finally investing in health

CONGRESS HAS finally started to boost federal funding for biomedical research. The omnibus spending bill just signed by the president will provide a vital increase for the National Institutes of Health — its budget will go up 6.6 percent, or $2 billion from the current $30.1 billion. This is the largest single increase in more than a decade  and signals a much-needed change of direction. NIH is an engine that drives basic research in biomedicine in the United States, and these are exciting times, offering immense promise for better understanding of how disease occurs and how to treat illness. Just one example of the startling accomplishments of late is the new genetic technique known as CRISPR-Cas9, which gives biologists unprecedented power to edit and repair DNA. It could result in creation of a gene “drive” in which a selected genetic trait can be pushed through a whole population; for example, mosquitoes could be made resistant to the malaria parasite, and the disease could no longer be spread by them. Basic research funded by NIH helped lead to the new technique. NIH Director Francis S. Collins has expressed concern in recent years that with the number of successful grant applications dropping to historic lows, young scientists might abandon the laboratory for other careers or take their research ambitions abroad. From fiscal 1998 to 2003, NIH saw its program-level funding double, but then it went stagnant for more than a decade. To make matters worse, recent sequestrations and shutdowns have created a climate of instability that is deeply disruptive to scientific research, which often unfolds over a long timeline. The fresh injection of money includes $200 million that will allow NIH to launch President Obama’s precision medicine initiative, an approach to disease prevention and treatment that seeks to account for individual variations in genes, environment and lifestyles. The effort will attempt to acquire the scientific evidence needed to move this promising concept into clinical practice. There’s also $350 million in new spending for Alzheimer’s disease research, a major increase, and $85 million for the initiative to gain a better understanding of the human brain. After many years when it was a secondary priority, Congress has also added $100 million for research on antimicrobial resistance, the alarming trend in which bacteria and viruses are evolving to fight back against antibiotics and other drugs that are essential in modern medicine. Progress in all these fields is difficult, and there may not be results right away. Biomedical research must be seen as a long-term investment. Now that Congress has done the right thing for one year, it must continue to provide a sturdy, multi-year funding platform for NIH and avoid going back to the days of slow stagnation. **Read more on this topic:** Francis S. Collins: Investing in the nation’s health at NIH Marcia Angell: Why do drug companies charge so much? Because they can. The Post’s View: NIH research is ailing from the budget squeeze

Gasp-Powered

Real surprises are rare at the movies these days. Even though I see most films before they’re released, it seems I always know something about a movie before I go in — either I’ve seen the trailer or I’ve read the press notes or I’ve seen something on Twitter or I’ve come across a giant tongue-bath of a story on the cover of “Entertainment Weekly” the week before. Some “surprises” aren’t even surprises any more: No one leaves a Marvel comic-book movie before the teaser scene at the very end we all know is coming. I’d seen the trailers for Steven Soderbergh’s “Side Effects,” out Friday, and I’d like to nominate them all for Most Ambiguous Trailers That Are Also Incredibly Misleading. And the marketing team in charge of selling the film should take a lot of pride in that (and I’m not being sarcastic). Walking in, I knew little about what the film is about. Murder! Maybe! And … psychiatric drugs! Possibly! Because the trailers were so nebulous, though — for reasons that are clear once you see the movie — the plot, and all its twists and turns, delivered an unexpected rush that’s rare in a world where God forbid you don’t see “Downton Abbey” live because your Facebook friends will spoil it for you. Unless they acquired season 3 by questionable means, in which case they spoiled it for you months ago. It seems I always knew that it was a really bad idea for Janet Leigh to take a shower and that Darth Vader was Luke’s father. But with “Side Effects,” I got to gasp and drop my jaw for the first time in a long time. It was a pleasure to be surprised by surprises.

‘Revolutionary.’ ‘Game changer.’ ‘Miracle.’ How much are we hyping unproven cancer drugs?

The news stories, one after another, heaped grandiose descriptions on cancer drugs that had not been approved, had shown little ability to extend the lives of patients or otherwise remained unproven. "Breakthrough," the articles said about treatments aimed at harnessing the body's immune system to fight cancer. "Revolutionary," they said about drugs targeted toward certain genetic mutations. The adjectives went on and on: Groundbreaking. Home run. Transformative. Life saver. Marvel. Cure. Undoubtedly, we are living through an exciting time in cancer research. New immune therapy treatments approved in recent years have demonstrated dramatic results in some patients, extending their lives by months or years. Targeted drugs continue to show promise in treating specific cancers with specific genetic profiles. There are breakthroughs happening, and some sure look transformative. And yet, when researchers this summer searched the Web for coverage of the new drugs in the media, they came away concerned that the routine use of superlatives describing the treatments might offer a misleading and overly optimistic view compared to reality. After all, even the best treatments work for only a fraction of patients. _[The 'breakthrough' drug Jimmy Carter is taking to treat his cancer]_    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico "Some of the drugs are actually very excellent drugs. It’s reasonable to feel excited about them … I'm excited about some of those drugs, too," said Vinay Prasad, an assistant professor of medicine at the Oregon Health and Sciences University and a co-author of the study, which appeared Thursday in the journal JAMA Oncology. "But you want to balance that against reasonable expectations. You want hope, but realistic hope. That’s what we all strive for." The experiment the group ran was simple. It involved running a Google news search for stories that appeared between June 21 and 25. They searched the phrase "cancer drug," along with nearly a dozen superlatives, such as "revolutionary" and "miracle." The inquiry turned up 94 articles from 66 separate news outlets, referencing 36 different drugs. Despite the glowing adjectives, half the treatments had not yet been approved by the Food and Drug Administration; a handful of them had not yet even been tested in humans, meaning far more research was needed to know if they might succeed. "These news articles may be important sources of information to patients, the public, and investors -- with a broader reach than medical journal articles," the scientists wrote. "However, omission of medical context or use of inflated descriptors may lead to misunderstandings among readers." _[Cancer trials are changing. That could mean faster access to better drugs.]_    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico Who was responsible for the potentially premature praise? "The majority were journalists (55%), who may not have the expertise to identify the most promising medical therapies, or what magnitude of benefit warrants a superlative," the authors wrote. But journalists weren't the only ones hyping the new treatments. Doctors, pharmaceutical industry experts, patients and even one member of Congress were quoted using one of the superlatives. The researchers noted that one limitation of their study was the brief window of time they examined, which also came not long after the annual conference of the American Society of Clinical Oncology, an event that typically generates a wave of coverage about promising new cancer therapies. Also, it's worth noting that the FDA itself labels some new therapies as "breakthrough" candidates, an official designation that can lead to a speedier review process, and probably one reason that word appears so often in the coverage. Still, the point of Thursday's study remains. "Hot fields" of cancer research, the authors wrote, often garner the most -- and the most glowing -- media coverage. That optimism can be useful, but so can a healthy dose of caution. **Read more:**    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico Cutting sugar from kids’ diets appears to have a beneficial effect in just 10 days    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico Sleep study on modern-day hunter-gatherers dispels notion that we're wired to need 8 hours    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico WHO says hot dogs, bacon cause cancer. Does this mean we should all be vegetarians?    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico There are roughly 480 other things the WHO says might cause cancer.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico SPECIAL REPORT: Billionaire Paul Allen's quest to build an artificial brain    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico _For more health news, you can sign up for our weekly newsletter_ _here_ _._    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico

Cloning advance using stem cells from human adult reopens ethical questions

Scientists have grown stem cells from adults using cloning techniques for the first time — bringing them closer to developing patient-specific lines of cells that can be used to treat a whole host of ailments, from heart disease to blindness. The research, described in Thursday’s online edition of the journal Cell Stem Cell, is a controversial advance likely to reopen the debate over the ethics of human cloning. The scientists’ technique was similar to the one used in the first clone of a mammal, Dolly the sheep, which was created in 1996. They “reprogrammed” an egg cell by removing its DNA and replaced it with that of an adult donor. Scientists then zapped the cell with electricity, which made it divide and multiply. The resulting cells were identical in DNA to the donor. The first success in humans was reported last year by scientists at the Oregon Health & Science University and the Oregon National Primate Research Center. But they used donor cells from infants. In this study, the cells came from two men, a 35-year-old and a 75-year-old. Paul Knoepfler, an associate professor at the University of California at Davis who studies stem cells, called the new research “exciting, important, and technically convincing.” “In theory you could use those stem cells to produce almost any kind of cell and give it back to a person as a therapy,” he said. In their paper, Young Gie Chung from the Research Institute for Stem Cell Research for CHA Health Systems in Los Angeles, Robert Lanza from Advanced Cell Technology in Marlborough, Mass., and their co-authors emphasized the promise of the technology for new therapies. What they didn’t mention but was clear to those working with stem cells was that their work was also an important discovery for human cloning. While the research published Thursday involves cells that are technically an early stage embryo, the intention is not to try to grow them into a fully formed human. However the techniques in theory could be a first step toward creating a baby with the same genetic makeup as a donor. Bioethicists call this the “dual-use dilemma.” Marcy Darnovsky, executive director of the Berkeley, Calif.-based Center for Genetics and Society, explained that many technologies developed for good can be used in ways that the inventor may not have intended and may not like. “This and every technical advance in cloning human tissue raises the possibility that somebody will use it to clone a human being, and that is a prospect everyone is against,” Darnovsky said. The research was conducted in California by a large team that included representatives from both academia and industry and was funded by a private medical foundation and South Korea’s Ministry of Science. From a technical standpoint, the technique — called somatic-cell nuclear transfer — is far from perfect. Chung’s team attempted the cloning 39 times and only two tries produced embryos. At first they couldn’t get the cells to multiply. But it turned out that if the researchers waited two hours — instead of 30 minutes — before trying to coax the cells, it worked. “We have reaffirmed that it is possible to generate patient-specific stem cells using [this] technology,” Chung said. Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health & Science University, developed the method that Chung’s group built upon. He emphasized that the work involves eggs that have not been fertilized. “There will always be opposition to embryonic research, but the potential benefits are huge,” Mitalipov said. Seventeen years ago, news about Dolly’s birth led to impassioned calls for a ban on human cloning for the purpose of producing a baby who is a genetic copy of someone else. Several countries took measures to limit or outlaw such work. But in the United States, the issue became entangled in the politics of abortion, and Congress became deadlocked. Some lawmakers called for a ban on reproductive human cloning, but others refused to support such legislation unless it included a ban on human cloning whether it was for the purposes of reproduction or for the development of new therapies. President George W. Bush brokered a compromise of sorts, restricting federal funding from stem cell research that results in harm to a human embryo. At least 15 states have laws addressing human cloning. About half of them ban both reproductive and therapeutic cloning. Since embryonic stem cell research began to take off 15 years ago, one of the main challenges scientists have faced is getting the material for their experiments. Many had been getting the cells from embryos left over from fertility treatments, but religious groups such as the U.S. Conference of Catholic Bishops vehemently objected to this, arguing that it involves killing a human being because the research involved fertilized eggs. About seven years ago, scientists discovered they could use a different, molecular approach, called induced pluripotent stem cells, that could turn ordinary cells into stem cells without the need for an egg. While this technique did not present the same ethical issues, researchers soon found that some of the new cells had glitches, and there is still debate over how significant the flaws are. The research conducted by Mitalipov and Chung provides a second way of producing those cells through laboratory techniques.

Big pharma depends on immigrants. It kept quiet about Trump’s travel ban.

And among those who work in research and development — the engine of discovery and innovation for the industry — immigrants made up one-third of the labor force, according to the 2014 report. Foreign-born scientists made up 43 percent of medical and life scientists, the study found. “In general, intellectual endeavors in the U.S. -- education, research — they rely on immigrants,” Lowry said. “It’s important to have innovation, and innovation comes from diversity. A difference in perspective allows for a difference in approach.”  Pharmaceutical Research and Manufacturers of America (PhRMA), the trade group that represents the industry and usually speaks on its behalf, said it didn't have a comment about the ban. Neither did Pfizer, one of the world's largest pharmaceutical companies. And those that did have a response to the ban often struck a neutral tone and focused on its employees. “We are working to fully understand the implications of the Executive Order on our business and our employees,” AstraZeneca said in a statement. “Upholding our steadfast commitment to associates of all nationalities and religions is core to our values as we work to address society's most pressing healthcare challenges,” a Novartis statement said, noting that to date there had been no disruption to Novartis employees as a result of the order. Leaders in the biotech industry, on the other hand, were more vocal. “The travel ban is causing confusion among several of my company's associates and I have been told by other biotech CEOs of similar responses across the industry,” Ron Cohen, a chief executive of Acorda Therapeutics, said in an email. “This is a difficult situation for scientists, doctors and other professionals whom we rely on to help invent and develop new treatments and cures for disease. If we restrict travel excessively, they will go elsewhere and their talents will enrich other countries.”  After the meeting at the White House, Merck chief executive Kenneth Frazier answered a reporter's question about the ban. “We have employees from around the world; we have to get the best scientists, the best employees around the world, so having access to those employees and having an environment in our companies that stimulates diversity and inclusion is very important to us,” Frazier said. But the George Mason researchers said that the industry's competitive edge going forward may depend in large part on keeping and attracting its immigrant workforce for a reason none of those leaders brought up. Immigrants tend to come from countries that have fast-growing pharmaceutical markets — places where U.S. companies would like to sell drugs. In other words, if those immigrant workers are deterred, they could easily become part of the competition. “Given that the majority of immigrants within the pharmaceutical industry are from the world’s fastest growing pharmaceutical markets, the U.S. may benefit from the continued encouragement of immigration from those regions,” the authors said. “Failing to do so carries the risk that those individuals will use their skills and talents to build the pharmaceutical industries in the very countries that are emerging as the leading competitors to the U.S. pharmaceutical industry.”

This gadget makes our health-care projections obsolete

Scientists at Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland have developed a minuscule implant that measures various blood chemicals and sends the results, via Bluetooth, to your smart phone. The upside? Your smartphone knows when you're about to have a heart attack. And it can call someone on your behalf. It is, after all ,a smartphone.    *[WSU]: Wayne State University This particular device might prove, for one reason or another, to be bunk. Many seemingly magical inventions do. But it's not alone. The founder of Blackberry is launching a $99 million fund to "to support entrepreneurs developing real-life 'Star Trek'-style blood-test scanning devices." And every major health device company knows there's billions and billions to be made here.    *[WSU]: Wayne State University I've asked experts in health technology whether they believe devices along these lines will be commonplace in 25 years. They invariably do. And they're almost certainly right. Consider how dramatically these devices will change medicine. Right now, the medical industry is fundamentally reactive. Something goes wrong, and we go to them to fix it. This will make medicine fundamentally proactive. They will see something going wrong, and they will intervene to stop it. It's like "Minority Report" for health care. This is why I don't put much stock in projections of health-care spending that run 30 or 50 or 75 years into the future. Will biometric devices in constant communication with the cloud make medicine more or less expensive? Will driverless cars prolong life in a way that saves money or costs it? Will the advances in preventive technology make medicine so effective that we're glad to devote 40 percent of gross domestic product to it? Who knows?

Cancer researchers: It’s time to pay more attention to ‘miracle’ patients

Call it luck — or a medical miracle. During clinical trials for experimental cancer drugs, some patients simply respond better than others. And a tiny fraction of patients see dramatic results, responding so well to treatment that they survive forms of cancers that quickly kill their counterparts. Stories about people like Emily Whitehead, the then-6-year-old who was enrolled in a clinical trial that saved her life, make headlines. But statistically speaking, they’re insignificant, mere outliers. Because they deviate so far from the norm, these “exceptional responders” are often overlooked by researchers. Not so fast, says Eric Perakslis.   Given that over 8 million people die of cancer each year worldwide, Perakslis says it’s time to establish a national exceptional responder network among clinical trial participants that offers free genome sequencing, registers all patients who do unexpectedly well during clinical trials, and makes their data available to qualified researchers. He finds inspiration in the national Undiagnosed Diseases Network, which pools clinical and research resources to solve medical mysteries. If the kind of broad-scale initiative open to patients with the rarest diseases were available to cancer patients, too, he argues, unlocking their secrets could become easier and cheaper — and reveal critical clues faster. “These outliers are really important humans,” Perakslis says. “They can help us fill in the map.” He compares exceptional responders to the outside edge of a puzzle — the part most people must complete before the larger structure becomes clear.  “Thanks to this program, we now know that breast cancer is not breast cancer. It’s really five different diseases,” he says. Because of the insights yielded by exceptional responders’ genes, Zenklusen says, researchers now realize that some cancers share molecular signatures despite the anatomical location of the tumors themselves. Unlike Perakslis’s suggested network and registry model, the Exceptional Responders Initiative runs more like a clinical trial. Patients who have demonstrated an exceptional response to any modality — experimental or no — are welcome, but must fit strict criteria before molecular characterization takes place. So far, says Zenklusen, 57 of the 154 patients who have been accepted into the program have begun to have their genomes analyzed. At first, says Zenklusen, he saw the program as “the definition of a fishing expedition. We were accepting all tissues, all comers, all therapies. Every single case is a world on its own. But we actually are finding a lot.” Out of the approximately 30 cases that have complete molecular characterizations, he says, at least 12 have yielded clear combinations of genes that make it obvious why patients have responded to certain treatments. “It’s the mother of all fishing expeditions,” he adds, “but we have found the whale.” Zenklusen says that it’s premature to pursue a networked registry model like the one Perakslis suggests. “It’s a little too early, but we are not too far away,” he says. “Unfortunately, when we find something that is interesting, we tend to get very excited. Cancer is a horrible disease. But sometimes we communicate the information a little too enthusiastically.” He worries that leaping toward a national registry before it’s been firmly established that exceptional responders really have smoking guns tucked into their genome could mislead the public into thinking that personalized, precision cures for cancer are just around the corner. “No one knows the winning formula here,” admits Perakslis. For him, the challenge is data density — which makes it even more urgent to collect as much data from exceptional responders as possible. Cures may still be far in the future, he says, but that’s no reason not to look hard at patients who respond dramatically to treatment now. “[There are] so many cancers, subtypes, unique patients, potential treatments,” he says. “It is like trying to paint the sky.”

Human-pig hybrids might be unsettling. But they could save lives.

But on balance, the promise of this biotechnology should outweigh our fears and ethical questions. Chimeras could be a game-changer in terms of organ transplants in coming decades, and for that reason, scientists should carefully proceed with the research. More than 100,000 people in the United States currently sit on organ waiting lists, struggling to stay alive long enough to get a new liver or kidney. With few realistic alternatives to the limited supply of cadaver-based transplants, about 22 Americans die each day. Hundreds more die daily at the global level. Our recent renaissance of cutting-edge biotechnologies — particularly based on the utilization of pluripotent stem cells — gives real hope for these people in need of transplants. What exactly is a human chimera? It’s a mixture of a small number of human cells within an otherwise predominantly animal embryo, such as a pig. The hope is that, if allowed to grow, a chimera embryo would develop entirely as animal except for one harvestable organ that is human. It might even be possible for that organ to be produced from the patient’s own stem cells, making it a perfect match. In the past, other researchers have made similar chimeric embryos, mixing human stem cells with mouse cells. But a mouse-size kidney or liver — even if made of human cells — cannot help a human, because these organs would be about the size of a small kidney bean. Pigs, on the other hand, are relatively closer to humans on the evolutionary tree, perhaps bringing us a small step closer to actual clinical use. Even so, there’s a long road ahead. The California researchers found that many of the human-pig chimeric embryos did not grow properly. And even if organs in pig chimeras ended up 100 percent human at a cellular level, they are certain to contain other factors — such as pig proteins — that could spark a patient immune reaction leading to organ rejection. Still, every cutting-edge biomedical technology faces technical obstacles at first, and there is a good chance that researchers might overcome these hurdles in the future. It’s understandable if people imagined full-grown, human-pig creatures when reading about this new research. In reality, though, the chimeras produced were only embryos — just tiny collections of cells. If the technology progresses further, chimeras would have to be taken to term or near-term before full-size organs could be harvested. Inevitably that means there may be large chimeras produced and photographed for the world to see; but remember, these animals wouldn’t look any different from ordinary animals, because only a single organ would be human. Animal rights advocates were quick to raise ethical questions: Should we allow chimeric pigs to be used as a biomedical incubator of sorts and then sacrificed to obtain a human organ? But this ignores the fact that people are eating billions of animals each year. Tougher questions focus on the human side of chimeras and include the dilemma of what makes an animal a human in terms of cells. How many human cells within a chimera overall would make that chimera too close to a human being? How many human brain cells and in particular neurons in a human-pig chimera would be too many? What should we do if a human-pig chimera accidentally ended up with an abundance of human cells in its brain? What if a human-pig chimera made human sperm or eggs? Fortunately, there are some simple technological answers to many of these questions. We could agree, for example, to prevent all chimeras from being born. We could also use animals that are sterile as the basis for making chimeras and closely monitor human cell numbers in chimeras (including in the brain) during early research studies. We could also ban organ production if human-cell levels consistently fall outside acceptable parameters. Overall, though, the global shortage of organs for transplants is too urgent a problem to refuse to explore innovative solutions. We should pursue more human-chimera technology while from the start acknowledging and addressing the important bioethical considerations it faces. We should also carefully plan outreach efforts to the public as the technology advances. Human chimeras not only have potential to address the organ shortage; they also could educate us about unexplored questions of human development. Groundbreaking biomedical technologies might be unnerving, but they have real potential to positively change our world.

Are Musk, Bezos and Branson the Wright brothers of today? Some in Congress think so.

The breakthroughs were right around the corner, they promised. Soon people would be taking regular trips to the cosmos, and the era of commercial spaceflight would finally become reality. And so in 2004, the young space companies lobbied for an extended “learning period’ that would allow them to develop their rockets and space vehicles without all of the burdensome federal regulations that would hamper innovation and prevent the industry from taking off. They got their wish for a regulatory break, but the advances were slower to come by. Now, more than a decade later, the industry says that this time it is really on the verge of that long-awaited breakthrough. And once again, Congress granted the industry an eight-year grace period that supporters say will prevent the Federal Aviation Administration from stunting the growth of an industry that has been largely driven by a class of billionaires with huge ambitions. Industry officials and their backers in Congress hailed the passage of the Space Act this week as an important step that will pave the way for businesses to soon take tourists to space and make the cosmos more accessible and affordable. The bill would also extend operations on the International Space Station through 2024, and allow U.S. companies the rights to resources they mine in space—on asteroids or on the moon, for example. But the heart of the bill grapples with a tough question: how should the government regulate a growing industry that is dangerous but also could open up space to the masses the way airline travel was transformed decades ago? “Everybody is walking into unknown territory, and it’s difficult to regulate something you don’t understand fully,” said Michael Listner, the founder of Space Law and Policy Solutions. Rep. Kevin McCarthy (R-Calif.) the bill’s sponsor, said that today’s industry leaders are pioneers, pushing the boundaries in the spirit of the Wright brothers and Chuck Yeager. The legislation, he said, would “unite law with innovation, allowing the next generation of pioneers to experiment—learn—and succeed without being constrained by premature regulatory action. The legislation would expand “the American experiment and environment that led to not only pioneer railroads, automobiles and planes but to turn these technological advancements into sustainable businesses,” said Eric Stallmer, the president of the Commercial Spaceflight Federation. But others say space travel is extraordinarily dangerous, and risky— an endeavor that requires more oversight, not less. Rep. Eddie Bernice Johnson, (D-Texas) pointed out that the commercial space industry has had three catastrophic failures in the last 13 months—Orbital ATK and SpaceX rockets that were to supply cargo to the International Space Station blew up, and a Virgin Galactic test flight crashed, killing one of the pilots. [Watch a SpaceX rocket almost land on a floating platform.]    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico “With these major accidents as a backdrop, I think it is unconscionable that we are here today moving this bill in its current form,” she said. “When the inevitable accident with significant loss of life occurs—whether it’s a year from now or five years from now—the American public will look back at what we are doing today and ask how we could be so short-sighted.” In the past several years, the commercial space industry has made some major leaps, giving hope that it is finally on the verge of a tipping point. SpaceX, the California company founded by billionaire entrepreneur Elon Musk, has won multi-billion dollar NASA contracts to fly cargo and, eventually, astronauts to the space station. The company is building its own private spaceport in southern Texas for commercial launches, and also appears to be on the verge of winning a lucrative contract to launch a national security satellite for the Pentagon. After years of relative quiet, Blue Origin, the space company founded by Amazon.com’s Jeff Bezos, has also shown some progress. Earlier this year, it launched an unmanned rocket to what’s considered the edge of space in a test flight. And it is reportedly planning another test flight soon. (Bezos owns The Washington Post.) Despite its crash last year, Richard Branson's Virgin Galactic is forging ahead with plans to fly tourists to suborbital space--though it's not clear when that will happen. Meanwhile, SpaceX and Blue Origin have taken over historic launch pads at the Kennedy Space Center and Cape Canaveral, signs that that the commercial sector is emerging into what was once exclusively the government’s domain. [Jeff Bezos' space company to launch from historic pad on Space Coast.]    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico And both have designed their rockets so that the booster stage, the most expensive part of the rocket, would be recovered and reused—instead of getting ditched in the ocean. Once they are able to perfect that—and Musk has come close twice—the cost of space travel would drop dramatically. And that, analysts say, would be a major breakthrough that could change how humans fly to space.

Are risks worth the rewards when nonprofits act like venture capitalists?

By the late 1990s, the Bethesda-based Cystic Fibrosis Foundation had spent decades searching for ways to alter the course of the deadly lung disease. Researchers had identified the genetic cause of the condition a decade earlier, and incremental improvements in care meant that many patients were living into their 30s. But frustrated that no game-changing treatments were in sight, the group’s leaders in 1999 placed what many considered a risky bet, deciding to invest millions of dollars in a small California biotech firm. Robert J. Beall, the foundation’s president, believed that putting money into drug companies directly, rather than merely making grants to academic investigators, might persuade the industry to focus on the disease and turn research into real-world treatments. That initial bet, which over time grew into a $150 million investment, has paid off in a big way. It led to the approval in 2012 of a breakthrough drug — the first that treats the underlying cause of cystic fibrosis rather than the symptoms, in a small subset of patients. On Thursday came another big win: The Food and Drug Administration approved a second drug for the group also helped fund development; that drug eventually could aid roughly half of the 30,000 cystic fibrosis patients in the United States. And last fall, the CF Foundation sold its rights to future royalties from the drugs for $3.3 billion, the largest windfall of its kind for a charitable organization. The pioneering success of Beall and the Cystic Fibrosis Foundation in the practice of “venture philanthropy” is prompting a growing number of nonprofit groups to explore whether they, too, might be able to benefit their patients, and bottom lines, by investing in similar ways. Dozens of organizations, from the Michael J. Fox Foundation to the Multiple Myeloma Research Foundation to the National Multiple Sclerosis Society, have embraced the approach over the past decade. Typically, though not always, groups take an equity stake in a company or negotiate a percentage of future royalties for approved drugs in exchange for their investment. They also have shared their scientific expertise and patient registries, which can be invaluable for companies conducting clinical trials of new medicines. Venture philanthropy has its skeptics, who argue that patient groups risk harming their reputations and their bank accounts by forming partnerships with the drug industry. Some experts worry that the relationships create inherent conflicts of interest and that nonprofits could allow financial motives to undermine their primary mission of putting patients first. For instance, the initial drug that the CF Foundation helped fund, Kalydeco, costs more than $300,000 a year per patient. Orkambi, the drug approved Thursday, will cost $259,000 a year. Critics say such price tags inevitably will place burdens on patients, even as they increased the value of the CF Foundation’s recent royalty deal and create significant revenues for Vertex Pharmaceuticals, the company that developed both drugs. A group of specialists wrote to Vertex after Kalydeco’s approval, calling the price “unconscionable.” _[One company’s battle to stop the wave of high-priced drugs]_ “There’s a reason why corporate America exists, and there’s a reason why philanthropic organizations exist,” said David Cornfield, a professor of pediatric pulmonary medicine at Stanford University. “When that distinction becomes invisible, it becomes very difficult to know where philanthropy ends and venture capital begins.” Proponents counter that venture philanthropy has helped to fill a persistent gap that exists between basic academic research funded largely by the government and later-stage clinical trials typically funded by large pharmaceutical companies — a gap known as the “valley of death.” “It’s where great ideas, unfortunately, go to die,” said Francis Collins, director of the National Institutes of Health, who, as a researcher at the University of Michigan, helped identify the gene for cystic fibrosis in 1989. “If foundations can pitch in there, that’s great. . . . We need as many models to get there as possible.” The Leukemia & Lymphoma Society created a “therapy acceleration program” in 2007, in part after realizing that even the most promising academic research it had funded too often went nowhere. “An academic investigator would write a paper, and nothing would happen,” said the group’s president, Louis J. DeGennaro. “[The projects] basically languished on the shelf.” In recent years, the group has put about $40 million into a variety of companies, trying to help them clear hurdles in the drug-development process. It also has offered medical expertise and the ability to help companies locate potential patients for clinical trials. “We do as deep a due diligence as any venture capital firm might,” DeGennaro said. “When we partner with a company, it’s not a grant, it’s a business alliance. There’s a contract with timelines and milestones. We’re paying for performance.” JDRF, formerly known as the Juvenile Diabetes Research Foundation, now spends roughly 20 percent of its money each year investing in corporations developing treatments for the autoimmune disease. “We ask the question: Will our funding lead to something happening that otherwise wouldn’t happen?” said Derek Rapp, the group’s president. “At the end of the day, that’s our job as an organization — to accelerate therapies that can have a tremendous difference for everyone living with this disease.” Still, venture philanthropy is not always practical — or even realistic. Many organizations don’t have the money to risk significant sums on drug development projects that are more likely to fail than succeed. DeGennaro said he also reminds nonprofits that come seeking advice that the CF Foundation took its leap only after researchers identified the gene behind the condition. “They no longer had to solve the science problem. . . . What they needed was drugs,” he said. “If you need to solve a science problem, venture philanthropy is probably not right for you.” For companies, a kind of partnership that once seemed strange is becoming more common. Paul Negulescu was director of cell biology for Aurora Biosciences in the late 1990s when the CF Foundation asked the company to begin screening for drug compounds that might treat the genetic cause of cystic fibrosis. “It was an unusual, unprecedented request,” recalled Negulescu, now senior vice president of research at Vertex, which later acquired Aurora. “We were used to working with [larger] pharmaceutical companies. . . . This was basically a patient group saying, ‘Can you help us?’ ” He said that logistical and financial support from the foundation over the years made the company’s scientists feel invested and set it on a course it wouldn’t have pursued otherwise. “The scope of the goal definitely motivated people here,” Negulescu said. “For us, as a very small biotech, it put us on the path of drug discovery.” People with cystic fibrosis frequently experience digestive problems and a buildup of sticky mucus in their lungs that can lead to serious infections. Patients often die of respiratory failure in their 30s or 40s, although some live much longer. As recently as the 1950s, few children diagnosed with the disease lived long enough to attend elementary school. Kalydeco, the 2012 breakthrough drug, is approved to treat only about 2,000 patients in the United States who have specific genetic mutations. Orkambi, which combines Kalydeco and another compound called lumacaftor, is targeted toward patients who have two copies of the most common mutation, called F508del. Nearly half of the estimated 30,000 cystic fibrosis patients in the United States fall into that category, though Thursday’s approval of Orkambi applies only to the 8,500 or so who are 12 and older. Vertex has been testing the drug in younger patients, in hopes of eventually broadening its use. Emily Schaller, a 33-year-old cystic fibrosis patient from Detroit, said she is grateful that the CF Foundation took its long-ago gamble that led to the development of the drugs. “I just don’t think [drug companies] would spend time and money on small groups like cystic fibrosis unless there was an incentive,” said Schaller, who has been taking Kalydeco for several years and now runs half-marathons and operates her own nonprofit group. “I’m alive, and I’ve never been more alive because of this drug. . . . I’m now starting a retirement fund, which is something I never thought that I would need.” _[Will I live long enough for someone to give me his seat on the subway?]_ Beall, now in his fourth decade at the CF Foundation and one of the top- earning chief executives in the nonprofit world, is aware of the concerns and criticism prompted by the landmark $3.3 billion deal last fall. Among them: that such a financial bonanza might discourage future contributions from supporters; that the foundation should be sharing its billions more directly with patients; that the group should have pushed harder to lower the price of Kalydeco and subsequent drugs. Beall insists that fundraising has remained steady. He said using the proceeds to pay directly for patient care would be shortsighted and that the group already supports patient assistance programs and accredited care centers around the country. He agrees that the cost of Kalydeco, which he believes could double some patients’ life expectancy, is far too high. But he said his group had no say in the price, and that last year’s royalty deal will allow it to fund competing treatments in the pipeline that he hopes will eventually drive down costs. Beall said the recent deal also has allowed the foundation to “supercharge” the search for its ultimate goal: a cure for all patients. “Now we can start thinking about things that are out 20 or 30 years,” he said. Some bets don’t pay off. The CF Foundation has invested nearly $450 million in several dozen companies over time as part of its venture philanthropy efforts. Some projects have ended in disappointment, and others probably will, too, Beall said. But to him, the risks are worth the potential rewards. “Venture philanthropy is not for the faint of heart,” he said. “There are going to be failures. . . . But you have to take the shots on goal.”

Trump said he wanted more miracle drugs. His budget could make funding them dramatically harder.

“If there’s an interest in innovative medicines, it’s hard to think of a worse idea than cutting NIH,” said Joshua Sharfstein, a professor in the department of health policy and management at Johns Hopkins Bloomberg School of Public Health. “The basic discoveries that fuel clinical advancements happen because of NIH funding, so it’s like you're shutting off the start of the pipeline.”  “It's just a terrible idea. There is substantial evidence that the sources of the most important and transformative pharmaceutical innovation that we have comes from NIH-funded, publicly funded science that occurs in academic settings and government laboratories. Reducing that by 20 percent is the surest way to ensure we don’t have the cures of tomorrow,” said Aaron Kesselheim, an associate professor of medicine at Harvard Medical School.  What they found, generally, was a pattern of innovation that depended critically on exchanges between academic labs that draw on government funding and pharmaceutical companies. A typical origin story of a drug goes like this: Academic scientists, building on ideas and insights that originated in basic, government-funded research, come up with a strategy to fight disease. Those researchers work to show a proof of concept for the approach and develop industry collaborations. Companies eventually use their expertise and resources to do the hard work of drug development, bringing the molecule through extensive testing to make sure it is safe and effective.  “The importance of basic science research by the NIH is that you don’t know what you don’t know. When a pharmaceutical company engages in research and development on a product, they have a pretty good sense that this product could work. But that product originated out of a process of uncertainty, and many times it came from a direction or a set of research that no one would have predicted would have ended up there,” said Anupam Jena, associate professor of health care policy at Harvard Medical School. The announcement, coming a day after Trump announced he wanted to make the United States the “car capital of the world again,” was ironic to Kenneth Kaitin, the director of the Tufts Center for the Study of Drug Development, who noted that the budget move risks eroding American leadership in an industry where it is unequivocally leading. “If you want to ensure the United States is going to be way behind the rest of the world in finding cures for diseases we don’t understand the basic mechanisms of, like Alzheimer's for example, this is the way to do it,” he said.

2016 Nobel Prize in physics awarded for revealing ‘the secrets of exotic matter’

Most matter exists in the states we see every day: gases, liquids and solids. But at extremely low or high temperatures, matter can start to behave strangely. The three laureates have used advanced mathematical modeling to demonstrate some of the strange properties that can arise in unusual states of matter. In cold layers of atoms so flat they can be considered two dimensional, you can find superconductors — materials that electrical current can flow through with no resistance from the particles therein — and superfluids, where frictionless vortexes can spin forever without slowing down. Using topology — the study of changes that occur step-wise, involving properties that remain intact when an object is stretched, twisted or deformed but not if it is torn apart — the three researchers helped reveal the stunningly strange behaviors of these exotic states of matter. From a topological standpoint, a bagel, a cinnamon bun and a pretzel are distinguished only by the number of holes they contain. If an object changes from having one hole to two, it is said to have undergone a topological phase transition.    "This has paved the way for designing new materials with novel properties and there is great hope that this will be important for many future technologies," Mårtensson said. In the early 1970s, Kosterlitz and Thouless modeled the existence of superconductivity and suprafluidity in thin layers, overturning the prevailing theory that such configurations of matter could not exist. They demonstrated that superconductivity could occur at low temperatures and also explained the mechanism, called phase transition, that makes superconductivity disappear at higher temperatures. In the 1980s, Duncan Haldane discovered how topological concepts can be used to understand the properties of chains of small magnets found in some materials. Haldane spoke to the press gathered in Stockholm for Tuesday's announcement, having been reached on the phone around 4:30 a.m. Eastern time. "I was, as everyone else is, very surprised," Haldane said. "And very gratified." "It was a long time ago," he said of his own research, "But it’s only now that lots of tremendous new discoveries based on this original work have extended it in many ways."  The award, which was established by Swedish inventor Alfred Nobel in 1895 and first awarded in 1901, comes with a prize worth 8 million Swedish krona, or about $937,000. According to the Royal Swedish Academy, the prize is being split two ways — Thouless will receive half the 8 million krona, or around $464,000, because he made "crucial contributions" on multiple fronts. Haldane and Kosterlitz will split the remaining $464,000.

Health-care sector vulnerable to hackers, researchers say

As the health-care industry rushed onto the Internet in search of efficiencies and improved care in recent years, it has exposed a wide array of vulnerable hospital computers and medical devices to hacking, according to documents and interviews. Security researchers warn that intruders could exploit known gaps to steal patients’ records for use in identity theft schemes and even launch disruptive attacks that could shut down critical hospital systems. A year-long examination of cybersecurity by The Washington Post has found that health care is among the most vulnerable industries in the country, in part because it lags behind in addressing known problems. “I have never seen an industry with more gaping security holes,” said Avi Rubin, a computer scientist and technical director of the Information Security Institute at Johns Hopkins University. “If our financial industry regarded security the way the health-care sector does, I would stuff my cash in a mattress under my bed.” Compared with financial, corporate and military networks, relatively few hacks have been directed at hospitals and other medical facilities. But in recent months, officials with the Department of Homeland Security have expressed growing fear that health care presents an inviting target to activist hackers, cyberwarriors, criminals and terrorists. “These vulnerabilities may result in possible risks to patient safety and theft or loss of medical information,” a DHS intelligence bulletin said in May. Security researchers are starting to turn up the same kinds of trivial-seeming flaws that earlier opened the way for hackers to penetrate financial services networks, Pentagon systems and computers at firms such as Google. Rubin has documented the routine failure to fix known software flaws in aging technology and a culture in which physicians, nurses and other health-care workers sidestep basic security measures, such as passwords, in favor of convenience. Another researcher found that a system used to operate an electronic medicine cabinet for hospital prescriptions in Oklahoma could be easily taken over by unauthorized users because of weaknesses in the software interface. OpenEMR, an open-source electronic medical records management system that is about to be adopted worldwide by the Peace Corps, has scores of security flaws that make it easy prey for hackers. The University of Chicago medical center operated an unsecure Dropbox site for new residents managing patient care through their iPads, using a single user name and password published in a manual online. After a Post reporter called about the vulnerabilities, officials at the cabinet manufacturer and the medical center took steps to close the gaps. The Peace Corps said it was considering changes. Government oversight and industry practices have not kept pace with the changing technology. The Food and Drug Administration, which is responsible for overseeing medical devices, most recently published guidance on cybersecurity in 2005. The agency has urged hospitals to allow vendors to guide them on security of sophisticated devices. But the vendors sometimes tell hospitals that they cannot update FDA-approved systems, leaving those systems open to potential attacks. In fact, the agency encourages such updates. “A lot of people are very confused about FDA’s position on this,” said John Murray Jr., a software compliance expert at the agency. A Government Accountability Office report in August noted that defibrillators and insulin pumps are vulnerable to hacks. In July, one researcher-hacker was able for the first time to use a specialized search engine called Shodan to discover a medical device, a wireless patient glucose monitor in Wisconsin, linked to the Internet and open to hacking. The Department of Health and Human Services is overseeing the move to electronic health records systems, some of which have documented security vulnerabilities. John Halamka, a physician and Harvard University professor who is co-chairman of the HHS health information technology standards committee, said security in the health-care industry is “not as good” as in other industries. But he added that the industry is aware of the problems and is scrambling to make improvements. “It’s completely headed in the right direction,” he said. But Laurie Williams, a computer scientist at North Carolina State University, said health care remains widely vulnerable. “There are basic, basic, Security 101 vulnerabilities we identified,” said Williams, who was among a team of researchers that identified numerous security flaws in several electronic heath records systems two years ago. “I’m concerned that at some point the hackers are really going to begin exploiting them. And that’s going to be a scary day.” Questions about the cybersecurity of medical systems have been simmering for more than a decade. But the issue has intensified as hospitals embrace wireless devices and electronic records. Some health-care officials assumed that their networks were too obscure, or offered too few financial enticements, to be of interest to hackers. Information technology executive Peter Tippett, the chief medical officer for Verizon, said the threat from cyberspace should not be overstated. Simple theft of laptops and other devices make up the bulk of incidents. “The fact is, there aren’t many attacks,” said Tippett, who oversees ICSA Labs, an independent division of Verizon that tests electronic health records systems and other security products for government certification. “The bad guys so far at least have been looking for money.” Still, Tippett acknowledged that health care ranks near “the bottom of the list” of industries in terms of cybersecurity. “It’s about like retail,” he said. In July, a consortium of hospitals, health plans, pharmacies, drug companies and government agencies called the Health Information Trust Alliance launched a cybersecurity incident response and coordination center to defend against “cyber crime, cyber espionage and cyber activism.” No one knows exactly how many intrusions have occurred, but anecdotes are mounting. Medical devices at Veterans Affairs facilities were infected by malicious viruses at least 181 times from 2009 to 2011, according to the DHS intelligence report that surfaced in May. On March 30, a hacker broke into a network server at the Utah Health Department, gained access to Medicaid data about 780,000 people and stole an undetermined number of records. Authorities traced attackers to computers in Eastern Europe. Utah officials acknowledged the breach and said they are taking extensive measures to protect patients against identity theft. HHS officials said health-care providers must combine cultural, practical and technological solutions to defend against theft and hacking. The officials also said that they have ramped up enforcement efforts against organizations that failed to protect patient information. “While there is always more work to do, we have reached record settlements against companies who violated privacy laws and sent a message to everyone that privacy violations will not be tolerated,” said Leon Rodriguez, director of the HHS Office for Civil Rights. Three years ago, Rubin, the Johns Hopkins researcher, began assessing systems at major hospitals and clinics, making visits to operating rooms and intensive-care units. He found that doctors and medical workers used the same computers to connect to both the Internet and internal networks. Rubin said doctors become “a pipeline for attackers into the sensitive networks.” One nurse told Rubin that she had the job of typing in a physician’s password constantly so that the doctor would not have to, leaving the unattended machine unprotected. “She literally walked around the room logging the doctor into every machine, every hour,” Rubin said. “Unbelievable.” He declined to name the institutions he studied because to do so would violate his research agreements. “The doctors and technicians I spoke with seemed mostly well aware that their systems are vulnerable,” said Rubin, who has previously found security problems in voting machines. He said that health care “is an industry with the least regard, understanding and respect for IT security of any I’ve seen, and they have some of the most personal and sensitive information of anyone.” Another researcher, Tim Elrod, a consultant at FishNet Security, found vulnerabilities in a system that enables care providers using a Web browser to automatically dispense drugs from a secure cabinet produced by Omnicell. Working with Stefan Morris, Elrod discovered that unauthorized users could sidestep the login and password page and gain control of a cabinet at a hospital run by Integris Health, the largest health organization in Oklahoma. They used a well-known hacking technique called a “forced browsing” attack. “At that point, we had full administrative control,” Elrod said. “We could do anything.” After being contacted by The Post, Peter Fisher, vice president of engineering at Omnicell, said he “is launching an immediate investigation into this reported vulnerability.” The same day, the company issued a software fix to customers around the globe. “Omnicell is committed to delivering the highest level of data security to our customers as demonstrated by our regular release of software updates, which include security enhancements,” Fisher said. John Delano, chief information officer for Integris, confirmed the Omnicell flaw and said his company last year disconnected it from any networks that might link to the Internet. “Unfortunately, a lot of times you run into vendors who have poorly coded software,” Delano said. “That’s the case here.” After an inquiry by The Post, a researcher at the University of Florida, Shawn Merdinger, found flaws in the use of wireless iPads by new medical residents at the University of Chicago medical center. Merdinger found a manual for the iPad initiative posted online, publishing a single user name and password for all the residents to use a shared Dropbox account. The idea was to promote collaboration. But the arrangement opened the medical center to “social engineering” attacks, where hackers plant documents, such as PDFs, that are loaded with malicious code. Once the documents are uploaded, the iPads could become infected, handing over control of hospital networks to hackers. After The Post alerted the medical center, officials closed the gap. “This Dropbox account was intended to be used only to share educational material among residents,” Cindy Kitching-Pena, director of the Department of Medicine Education Programs, said in a statement. “Nevertheless, the username and password to the account have been changed, and the account will be terminated.” In February 2009, Congress mandated the widespread adoption of electronic health records (EHR) computer systems as part of the stimulus legislation known as the American Recovery and Reinvestment Act. The law included as much as $36 billion in stimulus funding to promote the “meaningful use” of such systems. It was the Obama administration’s first big step toward health-care reform. Since then, tens of thousands of doctors, hospitals and other health-care operations have received more than $8.1 billion in government payments, and they have begun using the systems to digitize and share millions of patients’ records in ways that proponents say will save billions of dollars and improve care. The law required electronic health records systems to be certified by independent labs to meet an array of standards established by HHS, but those standards include few security provisions, according to documents and interviews. Officials have known for years about vulnerabilities in the systems. In 2007, the eHealth Vulnerability Reporting Program, a group that included senior health-care officials, concluded that “commercial EHR systems are vulnerable to exploitation given existing industry practices” and that the “skill level required to exploit is low.” Two years ago, Williams, the North Carolina State researcher, and her colleagues found common flaws in four systems that would expose users’ login information and enable outsiders to access patients’ records. The group’s report urged rigorous security testing before electronic health record vendors could be certified for stimulus funding. Federal officials have not gone that far, but Farzad Mostashari, the national coordinator for health information technology at HHS, said they “have taken important steps with vendors to make electronic health records more secure,” such as requiring encryption of data on laptops. Among the systems that HHS has certified is OpenEMR, an open-source software developed by a nonprofit charitable group called OEMR. The software can be downloaded for free. Williams’s group — along with several white-hat hackers — has found hundreds of vulnerabilities in the system. OEMR’s leaders acknowledged the flaws but said it would take an experienced hacker to exploit them. Chief technology officer Kevin Yeh said his group fixes problems as soon as it learns about them and that other Web-based systems probably have the same weaknesses. He added that federal certification standards “are not sufficient.” **oharrowr@washpost.com**

Can transfusions of young blood help cure Alzheimer’s in older people?

It sounds like the dark plot of a vampire movie.  Next month, people with Alzheimer’s disease will be given the blood of young people in the hope that it will reverse some of the damage caused by the condition. The scientists behind the experiment have evidence on their side. Work in animals has shown that a transfusion of young mouse blood can improve cognition and the health of several organs in older mice. It may even make those animals look younger. The ramifications for the cosmetics and pharmaceutical industries could be huge if the same thing happens in people. Disregarding vampire legends, the idea of refreshing old blood with new harks back to the 1950s, when Clive McCay of Cornell University in Ithaca, N.Y., stitched together the circulatory systems of an old mouse and a young mouse, a technique called heterochronic parabiosis. He found that the cartilage of the old mouse soon appeared younger than would be expected. It wasn’t until recently, however, that the mechanisms behind this experiment were more clearly understood. In 2005, Thomas Rando at Stanford University and his team found that young blood returned the liver and skeletal stem cells of old mice to a more youthful state during heterochronic parabiosis. The old mice were also able to repair injured muscles as well as younger ones. Spooky things seemed to happen in the opposite direction, too: Young mice that received old blood appeared to age prematurely. In some cases, injured muscles did not heal as fast as would be expected. Several other experiments have shown similar effects. In 2012, Amy Wagers at Harvard University showed that young blood can reverse heart decline in old mice. Her team paired healthy young mice with old mice that had cardiac hypertrophy — a condition that swells the size of the heart — and connected their circulatory systems. After four weeks, the old mouse’s heart had shrunk to the same size as its younger partner. In this experiment, the young mouse was seemingly unaffected by the old blood, its heart not changing in size. Once the researchers had ruled out the effect of reduced blood pressure on the older mice, they identified a protein in the blood plasma called growth differentiation factor 11 (GDF11) that appeared to fall with age. To see if it was linked to the rejuvenating effects, the team gave old mice with enlarged hearts daily injections of GDF11 for 30 days. Their hearts decreased in size almost as much as older hearts had in the parabiosis experiments. A year later, the same team showed in mice that daily injections of GDF11 increases the number of blood vessels and the number of stem cells in the brain; both of these changes are known to improve brain function. A separate team led by Tony Wyss-Coray at Stanford performed similar experiments. His team injected blood plasma from young mice into old mice and showed an improvement in the old mice’s physical endurance and cognitive function. In both mice and humans, GDF11 falls with age. We don’t know why it declines, but we know it is involved in several mechanisms that control growth. It is also thought to mediate some age-related effects on the brain, in part by activation of another protein that is involved in neuronal growth and long-term memory. So the billion-dollar question is: Would a GDF11 boost have the same effect in humans? Wyss-Coray thinks it will, having taken the next step of injecting young human blood plasma into old mice. His preliminary results suggest that human blood has similar rejuvenating benefits for old mice as young mouse blood does. “We saw these astounding effects,” he says. “The human blood had beneficial effects on every organ we’ve studied so far.” Now, the final step — giving young human blood plasma to older people with a medical condition — is about to begin. Getting approval to perform the experiment in humans has been relatively simple, Wyss-Coray says, thanks to the long safety record of blood transfusions. He warns against swapping blood at home because transfusions need to be screened for disease and matched for blood type and because the plasma needs to be separated out. “Certainly you can’t drink the blood,” he says. “Although obviously we haven’t tried that experiment.” So in early October, a team at the Stanford School of Medicine will give a transfusion of blood plasma donated by people younger than 30 to older volunteers with mild to moderate Alzheimer’s disease. Following the impressive results in animal experiments, the team hopes to see immediate improvements in cognition, but Wyss-Coray cautions that the procedure is still very experimental. “We will assess cognitive function immediately before and for several days after the transfusion, as well as tracking each person for a few months to see if any of their family or carers report any positive effects,” he says. “The effects might be transient, but even if it’s just for a day, it is a proof of concept that is worth pursuing.” All researchers involved in the work agree that GDF11 is unlikely to be the only factor that keeps organs youthful. “It’s too optimistic to think there would be just one factor,” says Francesco Loffredo, who studies the effects of young blood in old animals at Harvard. “It’s much more likely to be several factors that exert these effects in combination.” Loffredo says the approach of testing young blood in people with Alzheimer’s is fascinating, but he reckons that in the long term it is best to continue seeking the individual factors causing the rejuvenating effects so that they can be given to humans more easily. “Imagine if you had to be transfused with young blood all the time: It’s hard to imagine as a therapy. Who is going to be donating all this blood?” he asks. Wyss-Coray agrees. “It would be great if we could identify several factors that we could boost in older people,” he says. “Then we might be able to make a drug that does the same thing. We also want to know what organ in the body produces these factors. If we knew that, maybe we could stimulate that tissue in older people.” Alessandro Laviano at the Sapienza University of Rome says that the research on diseases of aging certainly holds promise, but he is more interested in the potential use of young blood in chronic disease. People with cancer who resist muscle loss have better chances of survival, he says. “So I’d like to consider the possibility of using these youthful factors in young blood to reduce the muscle wasting that occurs during chemotherapy.” Before moving to clinical trials in people with cancer, we need to learn more about the dynamics of the beneficial factors in blood, Laviano says, such as when those factors are at their peak: Do they crest at age 5 or age 35? “We just don’t know,” he says. He would also like to investigate what happens when you give “too much” GDF11: Does it result in extra benefit or a negative outcome? Laviano is looking at whether GDF11 inhibits the growth of tumors in animals, but he would also like to start an observational trial in humans. It would be very simple, he says, to find the age of the blood given to people receiving transfusions and test whether its effectiveness varies by how old its donor was. “I certainly think that this therapy might be beneficial in a number of different conditions,” Wyss-Coray says. “Blood might contain the fountain of youth after all. And it is within us all — that’s the crazy thing. It just loses its power as we age.”

Don’t give up: Older people can have creative breakthroughs

Many of this year’s cohort of Nobel laureates achieved their award-winning efforts when they were quite young — a phenomenon detected by decades of research on creativity. J. Michael Kosterlitz, co-recipient of the Nobel in physics, was 31 at the time of his prizewinning discovery, and his collaborator, David J. Thouless, was 39. Bob Dylan, the literature winner, wrote his defining work even earlier, in his 20s. Based on this pattern, one might assume that once you pass this early career stage, your chances of making a breakthrough drops precipitously. Einstein, who developed his theory of special relativity at the tender age of 26, put it bluntly: “A person who has not made his great contribution to science before the age of thirty will never do so.” Yet as we show in a paper recently published in Science, our ability to have a creative breakthrough does not diminish with age. It is our productivity and will to keep trying that decline, not our creative potential. For those who stick with it, success can come at any point in their career, and if they keep trying, it can return over and over again. Our understanding of creativity comes mainly from studies of recognized geniuses. Studies conducted in the 1980s by psychologist Dean Keith Simonton, who inspected the careers of 2,026 notable scientists and inventors from antiquity to the 20th century, found that most of them made their mark on history around the age of 39, bolstering the contention that youth equals creativity. Benjamin Jones, an economist who analyzed 525 Nobel Prizes between 1900 and 2008, saw a slight increase in the age of winners across the years, rooted mainly in the increased schooling as time passed. We took a different tack. The long-standing focus on genius prompted Professor Roberta Sinatra and me to ask: When do bursts of creativity happen in not just extraordinary but also ordinary scientific careers? We thought this would give us better insight into the effect age has on creativity at large, as opposed to just creativity in extreme and unusual careers. We inspected the careers of tens of thousands of scientists in disciplines ranging from physics to math, biology to computer science. Our results confirmed the decades of research on creativity: Most scientists published their defining work within two decades of the start of their scientific career. In other words, geniuses and everyday scientists alike cease to be creative by the third decade of their career. When we asked why, however, we stumbled across something unexpected. First, we found that productivity — the number of papers published by an individual — has the same early peak as creativity. We scientists are not only the most creative in the first two decades of our careers; we are more productive as well. This made Roberta and me suspicious about the roots of our creative success: Is it because we are young, or is it because we simply buy more raffle tickets during those early decades? We next arranged every paper the scientists had published in chronological order, asking if the highest impact paper was among the earliest of each person’s career, somewhere in the middle, or perhaps among the last. In other words, we took age and productivity out of the equation, viewing each paper as another attempt at a breakthrough. And there lay something unexpected. The highest impact papers were rarely the scientists’ earliest ones. Instead, the biggest hits were completely random: They were just as likely to be a first work as a last one, or anywhere in between. Our surprising conclusion: Fresh-faced thinkers disproportionately break through not because youth and creativity are intertwined but because they produce more work early in their career. Indeed, 30 years into a scientific career there is a sixfold drop in productivity compared with productivity at any time within the first 20 years. Hence scientists’ early success has little to do with the vibrant ideas they bring to the stodgy establishment. Rather, undeterred by disinterest or failure, young people try again and again. These results are good news for those of us with graying hair. Sure, success can come early, as it did for Frank G. Wilczek, who received the 2004 Nobel in physics for the very first paper he co-authored as a graduate student. But it can also come later, as it did for this year’s Nobel winner in physiology or medicine, Yoshinori Ohsumi, who was 48 when he made his breakthrough. In fact, it can even come very late, as it did for John B. Fenn, a chemist whose Nobel-winning discovery came after Yale shut down his lab when he turned 70, the mandatory retirement age then. Equally important, our data show that if you were fortunate enough to have had that coveted early-career breakthrough, there may be more to come. Einstein, despite his age-of-30 admonition, was 59 when he published his finding on quantum entanglement, his most cited work today. And our finding is likely not limited to scientists. Steve Jobs, for example, may have founded Apple at 21, but the company’s most commercially successful innovations — the iMac, the iPhone — came only in his 40s and early 50s. So if you missed that early spark, don’t despair: as long as you stay with it, success can still be yours.

Big surprise

Sparking fears of a zombie apocalypse: Controversial study aims to ‘reanimate’ the brain dead

Ever since Ira Pastor declared his company’s intentions to take 20 brain-dead patients and try to “regenerate” their nervous systems, his email box has been overflowing with inquiries from far-flung parts of the world. Skeptical scientists grilling him about the details of the techniques his team is using. Desperate families, who have been paying for years to keep loved ones on life support, wondering how to enroll. Outraged representatives from every major religion telling him why what he’s doing violates the laws of nature. But the most vociferous challenge, says Pastor, chief executive of Philadelphia-based Bioquark, has been from the “zombie contingent.” “You wouldn't believe how many people have said, ‘Please don’t do this. You’re going to start the zombie apocalypse,’” he says. Such confusion, hope and fear are not unexpected given the radical nature of the project. But Pastor explains that any changes due to the treatments will probably be subtle, at the cellular level at first, and detectable only by sophisticated blood and spinal fluid testing and MRI imaging. Such work, he says, may have more applications for treating traumatic brain injury, mental illnesses, spinal cord issues and Alzheimer's in the short term rather than disorders of consciousness. “We are not waking anybody up in this study,” Pastor emphasizes. “It is very preliminary.” Brain death is perhaps the least understood state of the human mind. Most of us — including many scientists — take it for granted that the condition is absolute and final. Pastor argues that’s a mistake. He says he believes it is a potentially curable condition and that given the right combination of stem cells, drugs, electrical currents, magnetic fields or other stimuli we haven’t thought of yet, the mind may yet have the power to reawaken. That idea is controversial for many reasons — moral, religious, scientific, economic. If the project finds even a little bit of success, it has the potential to upend our entire health-care system. Hospitals could be forced to keep brain-dead people on life support indefinitely, bankrupting insurers, and the whole organ-donation system, which relies heavily on the altruism of families of brain-dead patients, could come to a standstill.  But Parnia emphasized that there is a big difference between being able to reanimate some cells and reanimating a whole brain. “It may reverse cell damage in some areas but not other critical brain areas, leading to severe and significant disabilities and injuries in people who would have otherwise died,” he said. “At worst, people who would have died will come back but end up in a vegetative state.” Robert Veatch, a professor emeritus of medical ethics at Georgetown University’s Kennedy Institute of Ethics who has written a forthcoming book about how death is defined, is more skeptical. He points out that in all of medical history there has not been a single documented case of a person who met the criteria for brain death and was then revived in any state. “It is a bizarre stretch of the imagination to think that all of those billions and billions of cells could be somehow fixed,” he said. At any given time, hundreds of thousands of people in the world are estimated to be trapped in the little-understood place between consciousness and nothingness. Some of them are in a vegetative state that occurs when the part of the brain that controls thought no longer functions but they sleep, breathing as normal. Others are in a coma where they cannot be awakened and don’t respond to light, sound or touch. Those most severely impacted are considered to be brain-dead. The formal definition comes from a Harvard Medical School committee report from 1968 that described the condition as “irreversible coma” in which people are unaware of external stimuli, unable to move or breathe on their own and have no eye movement and other reflexes. Following the controversy over the “right to die” case of Karen Ann Quinlan in 1976, a number of state legislatures moved to clarify the protocols for how and when doctors can declare a patient brain-dead and to equate that with being deceased. This is the point at which many patients are disconnected from life support. But science doesn’t always work in that kind of black and white, and over the years situations have cropped up that challenged this definition. Among the most recent was the 2013 case of 13-year-old Jahi McMath, who went into cardiac arrest and was declared brain-dead after what was supposed to be a routine tonsillectomy. After doctors at a hospital in Oakland, Calif., declared her brain-dead and said they would remove life support, her family ended up moving her to New Jersey, where the laws were more flexible about keeping her on life support, and they have gone to court seeking to have her old death certificate voided. In March, the family posted pictures on Facebook showing Jahi, now 15, “as healthy and beautiful as ever” even though she has not awakened during those two years. The more we learn about the brain, the more it has become clear that there’s no on-off switch and that there area between consciousness and unconsciousness is a spectrum. There have, for instance, been cases of patients being given anesthesia who appear to be asleep but are actually conscious of their pain and paralysis. Researchers have also reported the nearly miraculous reawakenings of the near dead after being given, quite paradoxically, the sleep drug Ambien. Then there’s the case of former Israeli prime minister Ariel Sharon. Cared for in a private room at a medical center with an armed guard outside for eight years, the “sleeping giant,” as he was known, never woke up from his coma, but the scientists caring for him found through scans that when they played the sounds of voices of his family, his brain lit up. Research on brain-dead patients who are still on life support, however, is rare. The MD Anderson Cancer Center in Houston published results of a ground-breaking study on brain-dead and nearly brain-dead patients in 2002 that some believed would set the stage for further work. The research involved infusing millions of peptides — strings of amino acids that scientists believed may have the potential to block blood vessels feeding tumors — into the patients and then doing a number of invasive biopsies to see what happened. The results, published in Nature Medicine, yielded “a wealth of data,” according to a write-up that year in Science magazine.  Now, nearly 15 years later, Bioquark and its India-based partner Revita Life Science hope to build on those findings. Recruitment of study subjects started this month in northern India, a location the company chose partly because it’s cheaper but also because the laws surrounding studies of what some call living cadavers are in a gray area. But for a study with such grand ambitions, it is a modest affair — and there is some doubt that the group is in a position to make huge breakthroughs.  According to the Hindu, Bansal claims that he has been working on comatose patients since 2009 and has had some success with two patients. “One patient was brain-dead, but after we started our experiments, she started responding to pain stimulus — meaning her blood pressure would change every time she felt pain,” he said. “But I cannot give you more details due to confidentiality agreements with my patients.” The setting for the study is just as unlikely — the top floor of a three-story medical facility that is flanked by a restaurant on one side and a gym on the other. It is located in Rudrapur, Uttarakhand, a town about 145 miles from New Delhi that the Hindu said is “so inconsequential that it is best known for bad roads.” The researchers are talking to families with loved ones at intensive care units at local hospitals and looking for people who have been declared brain-dead but whose central nervous systems are mostly intact, such as someone who drowned in a pool or flew off a motorcycle with a helmet on. During the six-week trials (patients will be treated individually as their families sign on), the men and women will be given a continuous infusion into an area around the spinal cord of a biochemical cocktail the company developed through its research on previous regenerative medicine. Stem cells will also be administered every two weeks. Pastor said that the researchers spent a lot of time figuring out how to communicate their work and expectations to the families in a way that is sensitive to the fact that they may still be grieving. Part of the protocol of the experiment makes it clear that families can opt to drop out at any time if they change their minds. “We want them to understand this is highly experimental,” Pastor said. “Although it represents a possibility, we don’t want to generate false hope.”

Jack Klugman’s secret, lifesaving legacy

The actor Jack Klugman died on Christmas Eve at age 90. Klugman was best known for his roles as the unkempt sportswriter in "The Odd Couple" and as the crusading medical examiner on "Quincy, M.E." the wildly popular 1980s medical drama. Few people remember it today, but he also played an instrumental role in passing critical health-care legislation, the Orphan Drug Act, through Congress in the early 1980s, using "Quincy" and his own celebrity to roll Sen. Orrin Hatch (R), who was blocking the bill. Klugman's unlikely star turn in Washington stemmed from a 1980 hearing by the House Subcommittee on Health and the Environment on the problem of developing treatments for rare diseases. The problem was that many terrible diseases didn't afflict enough people to entice pharmaceutical companies to develop treatments. Hence they were "orphan" diseases. They included Tourette's syndrome, muscular dystrophy, cystic fibrosis, spina bifida, ALS and many more. The situation was especially tragic because scientists who discovered promising treatments often couldn't interest drug makers, who didn't see potential for profit. The issue of orphan diseases was so obscure that only a single newspaper, the Los Angeles Times, sent a reporter to the hearing (and the Times only did so because a local boy suffering from Tourette's testified). But the article caught the eye of a Hollywood writer and producer named Maurice Klugman, who himself suffered from a rare cancer and also happened to be Jack Klugman's brother. Maurice Klugman wrote an episode of "Quincy" about Tourette's and the orphan drug problem. To capitalize on the publicity and build momentum for a bill, Rep. Henry Waxman (D) of California, the subcommittee chairman, invited Jack Klugman to testify before Congress. Nowadays on Capitol Hill, you're as likely to run into Bono or Ben Affleck as your own representative. But at the time, a bona fide celebrity speaking to Congress was a huge deal. The New York Times ran a front-page story on Klugman and orphan diseases. That led to a bill with three big incentives for drug makers: a lighter regulatory burden for developing new orphan drugs, a seven-year monopoly, and a 90-percent tax credit for the cost of clinical trials. It also established an Office of Rare Diseases at the National Institutes of Health. The Orphan Drug Act of 1982 sailed through the House. But it ran into trouble in the Senate. Hatch, whose committee had jurisdiction, amended the bill to include a cancer research and screening center in his home state of Utah. But to protect the bureaucratic turf of his colleagues on the Finance Committee, which oversees tax policy, Hatch stripped the tax credit, neutering the bill, which the Senate then passed unanimously. Waxman and his allies in Congress and the medical community pushed frantically to revive the tax credit, without any luck. In a fit of pique, Jack Klugman hit upon a novel idea. He and his brother wrote a second "Quincy" episode, this one revolving around an orphan drug bill that was being held up by a heartless (fictitious) senator. In the pivotal scene, Quincy confronts the senator in his office and demands that he look out the window. Peering down, the senator sees a huge crowd gathered with signs that read "We Want the Orphan Drug Act" and relents. To shoot the scene, the show's producers hired 500 extras who really did suffer from rare diseases. Hatch, too, finally relented. Thanks to Klugman, the Waxman-Hatch Orphan Drug Act became law in 1983. In an ending Hollywood might have scripted, it has been a remarkable success. The FDA has approved more than 300 orphan drugs, with 1,100 more under development. One of the first developed under the law was AZT, the early AIDS treatment. Two years later, Congress expanded the law to include biological and chemical drugs, which helped spur the biotech industry. Klugman's distant influence continues to live on in the current Congress. It didn't get any attention, of course, but earlier this year, in a rare feat of bipartisan decency, Congress passed the Creating HOPE Act for pediatric cancer research. The law relies on the same model as the Orphan Drug Act, offering pharmaceutical companies various regulatory and marketing incentives to devise new treatments for rare cancers that strike children, but aren't seen as sufficiently profitable for drug makers to pursue on their own. All in all, an impressive addendum to Klugman's acting career. May he rest in peace. _Joshua Green is a national correspondent at Bloomberg Businessweek and a columnist for the Boston Globe. With Henry Waxman, he cowrote "The Waxman Report: How Congress Really Works" (Twelve, 2009). Follow him on Twitter @JoshuaGreen._

What to expect from Apple’s announcement

Apple is planning a press announcement in New York City Thursday, which is expected to unveil the company’s foray into digital publishing for the education market. As The Washington Post’s Cecilia Kang reported, the company is expected to announce partnerships that will make digital textbooks more available to students, possibly hoping for a repeat of the success it saw getting Macs into school 30 years ago. Little has been leaked in terms of the scope of the announcement. There are currently two main camps of speculation about how Apple will jump into the textbook market. One theory is that Apple is planning to completely upend the textbook space by making it easy for educators to create their own textbooks and bypass publishers completely. Apple’s late co-founder Steve Jobs, in comments to biographer Walter Isaacson, said that he was frustrated by the current textbook market. Kang reports that Jobs told Isaacson, “The process by which states certify textbooks is corrupt. . . . But if we can make the textbooks free, and they come with the iPad, then they don’t have to be certified. The crappy economy at the state level will last for a decade, and we can give them an opportunity to circumvent the whole process and save money.” Textbooks are a big industry, and — if this is what Apple is planning — it would taking on publishing giants such as Houghton Mifflin Harcourt. The less revolutionary theory is that the company will simply become a distribution platform — as it has with music — and work with the existing industry to make e-books more common in schools. In an article in Fortune, Philip Elmer-Dewitt promotes this as the more likely outcome of the day’s events, pointing to comments from digital textbook chief executive Matt MacInnis. MacInnis told Fortune that it’s unlikely that Apple will want to get into the content publishing business. “Like the music and movie industries, Apple has instead built a distribution platform as well as hardware to consume it—but Apple isn’t a record label or production studio,” he said. Regardless of the scope of the announcement, it is set to be an influential one for the textbook industry. It’s unlikely, however, to catch too much interest from the average Apple consumer. This is far from the grand product announcements that Apple arranges in Silicon Valley auditoriums, which should pour cold water on any speculation that the company is planning a surprise announcement about the next iPad or iPhone. Related stories: Apple expected to delve into textbooks Apple discloses its suppliers Angry crowd pelts Apple store in Beijing with eggs after company cancels iPhone 4S sale

First gene therapy — ‘a true living drug’ — on the cusp of FDA approval

PHILADELPHIA — When doctors saw the report on Bill Ludwig’s bone-marrow biopsy, they thought it was a mistake and ordered the test repeated. But the results came back the same: His lethal leukemia had been wiped out by an experimental treatment never before used in humans. “We were hoping for a little improvement,” remembered the 72-year-old retired New Jersey corrections officer, who had battled the disease for a decade. He and his oncologist both broke down when she delivered the good news in 2010. “Nobody was hoping for zero cancer.” The pioneering therapy administered to Ludwig and a few other adults at the University of Pennsylvania hospital paved the way for clinical trials with children. Six-year-old Emily Whitehead, who was near death, became the first pediatric recipient in 2012. Like Ludwig, she remains cancer-free. Such results are why the treatment is on track to become the first gene therapy approved by the Food and Drug Administration. An FDA advisory committee will decide Wednesday whether to recommend approval of the approach, which uses patients’ own genetically altered immune cells to fight blood cancers. If the panel gives the nod, the agency probably will follow suit by the end of September. That would open the latest chapter in immunotherapy — “a true living drug,” said Penn scientist Carl June, who led its development. The CAR T-cell treatment, manufactured by the drug company Novartis, initially would be available only for the small number of children and young adults whose leukemia does not respond to standard care. Those patients typically have a grim prognosis, but in the pivotal trial testing the therapy in almost a dozen countries, 83 percent of patients went into remission. A year later, two-thirds remained so. And childhood leukemia is just the start for a field that has attracted intense interest in academia and industry. Kite Pharma of Santa Monica, Calif., has applied for FDA approval to treat aggressive non-Hodgkin’s lymphoma, and a similar Novartis application is close behind. Researchers also are exploring CAR T-cell therapy’s use for multiple myeloma and chronic lymphocytic leukemia, the disease that afflicted Ludwig. They are also tackling a far more difficult challenge — using the therapy for solid tumors in the lungs or brain, for example. The excitement among doctors and researchers is palpable. “We’re saving patients who three or four years ago we were at our wit’s end trying to keep alive,” said Stephen Schuster, the Penn oncologist who is leading a Novartis lymphoma study. That study and a Kite trial have shown that the treatment can put about one-third of adults with advanced disease — those who have exhausted all options — into remission. Yet along with the enthusiasm come pressing questions about safety, cost and the complexity of the procedure. It involves extracting white blood cells called T cells — the foot soldiers of the immune system — from a patient’s blood, freezing them and sending them to Novartis’s sprawling manufacturing plant in Morris Plains, N.J. There, a crippled HIV fragment is used to genetically modify the T cells so they can find and attack the cancer. The cells then are refrozen and sent back to be infused into the patient. Once inside the person’s body, the T-cell army multiplies astronomically. Novartis has not disclosed the price for its therapy, but analysts are predicting $300,000 to $600,000 for a one-time infusion. Brad Loncar, whose investment fund focuses on companies that develop immunotherapy treatments, hopes the cost does not prompt a backlash. “CAR-T is not the EpiPen,” he said. “This is truly pushing the envelope and at the cutting edge of science.” The biggest concerns, however, center on safety. The revved-up immune system becomes a potent cancer-fighting agent but also a dangerous threat to the patient. Serious side effects abound, raising concerns about broad use. “Treating patients safely is the heart of the rollout,” said Stephan Grupp of Children’s Hospital of Philadelphia, who as director of the hospital’s cancer immunotherapy program led early pediatric studies as well as Novartis’s global trial. “The efficacy takes care of itself, but safety takes a lot of attention.” One of the most common side effects is called cytokine release syndrome, which causes high fever and flulike symptoms that in some cases can be so dangerous that the patient ends up in intensive care. The other major worry is neurotoxicity, which can result in temporary confusion or potentially fatal brain swelling. Juno Therapeutics, a biotech firm in Seattle, shut down one of its CAR T-cell programs after five patients died of brain swelling. Novartis has not seen brain swelling in its trials, company officials said. To try to ensure patient safety, Novartis is not planning a typical product rollout, with a drug pushed as widely and aggressively as possible. The company instead will designate 30 to 35 medical centers to administer the treatment. Many of them took part in the clinical trial, and all have gotten extensive training by Grupp and others. Grupp said he and his staff learned about the side effects of CAR T-cell therapy — and what to do about them — through terrifying experiences that began five years ago with Emily Whitehead. The young girl, who had relapsed twice on conventional treatments for acute lymphoblastic leukemia, was in grave condition. Grupp suggested to her parents that she be the first child to get the experimental therapy. “I said, ‘Surely, this has been tried on kids somewhere else in the world,’ ” recalled her father, Thomas Whitehead of Philipsburg, Pa. “But Steve said, ‘Nope, some adults got it, but that was a different kind of leukemia.’ ” After she received the therapy, Emily’s fever soared, her blood pressure plummeted, and she ended up in a coma and on a ventilator for two weeks in the hospital’s intensive care unit. Convinced his patient would not survive another day, a frantic Grupp got rushed lab results that suggested a surge of the protein Interleukin 6 was causing her immune system to relentlessly hammer her body. Doctors decided to give Emily an immunosuppressant drug called tocilizumab. She was dramatically better within hours. She woke up the next day, her seventh birthday. Tests showed her cancer was gone. The approval of CAR T-cell therapy would represent the second big immunotherapy advance in less than a decade. In 2011, the FDA cleared the first agent in a new class of drugs called checkpoint inhibitors. It has approved five more since then. There are big differences between the two approaches. The checkpoint inhibitors are targeted at solid tumors, such as advanced melanoma and lung and bladder cancer, while CAR T-cell therapy has been aimed at blood disorders. And although checkpoint inhibitors are off the shelf, with every patient getting the same drug, CAR T-cell therapy is customized to an individual. Many immunotherapy experts think the greatest progress against cancer will be achieved when researchers figure out how to combine the approaches. For the Penn team, the CAR T-cell story goes back decades, starting at the then-National Naval Medical Center in Bethesda, Md., where June and a postdoctorate fellow named Bruce Levine worked on new HIV treatments. In the process, they figured out a way to turbocharge T cells to make them more powerful and plentiful. The pair moved to Philadelphia in 1999 and dove into cancer research. Two years later, June’s wife died of ovarian cancer, something he has credited as spurring him to work even harder in the field. In the years that followed, researchers across the country, including at the Memorial Sloan Kettering Cancer Center in New York and Fred Hutchinson Cancer Research Center in Seattle, racked up an array of tantalizing discoveries involving T cells. Fast-forward to 2010, when Ludwig, who lives in Bridgeton, N.J., became Penn’s first patient to receive CAR T-cell therapy. Two other men got the treatment not long after. One is still in remission; the other relapsed and died. But after those three patients, the Penn researchers ran out of money for more treatments. To try to raise interest and funding, they decided to publish the results of their work. The article that appeared in the New England Journal of Medicine in August 2011 created a “firestorm,” June said — one that brought them new resources. David Porter, a Penn oncologist working with June, was on vacation in western Maryland and had to stop at a Kohl’s to buy a dress shirt for the immediate TV interviews. The pediatric trial opened the following spring with Emily. Six months later, Penn licensed its technology to Novartis in exchange for financial support, which included a new on-campus cell-manufacturing facility. With FDA approval seeming imminent, the researchers who were so instrumental in the therapy’s development and testing are almost giddy. Grupp is especially pleased that the advance will be available first to children. “Usually everything is developed first for adults,” he noted recently, “and children are an afterthought.”

Drugmakers find breakthroughs in medicine tailored to individuals’ genetic makeups

When the Food and Drug Administration recently approved a promising new lung cancer drug named Zykadia four months ahead of schedule, it heralded the medication as a “breakthrough” therapy. The drug isn’t meant for everyone with the devastating disease, which kills an estimated 160,000 Americans each year. Or even for the majority of patients with its most common form, non-small-cell lung cancer. Rather, Zykadia is designed for a sliver of patients — about 5 percent — who have advanced non-small-cell lung cancer and have a specific gene mutation that causes tumors to become resistant to existing treatment. For them, and only them, the drug has the proven potential to shrink tumors and extend lives. The FDA’s speedy approval of Zykadia offered the latest evidence that the age of “personalized medicine,” while long predicted, is increasingly becoming reality. For reasons scientific and economic, one-size-fits-all blockbuster drugs are giving way to treatments tailored to individuals’ genetic makeups and aimed at narrow subsets of broader diseases. “It’s a new world,” said Wendy Selig, president of the Melanoma Research Alliance, the largest private funder of research on the disease, which this year is expected to kill nearly 10,000 Americans. “We’re segmenting what we thought of as large diseases into smaller populations of patients that are defined by genetic distinctions. . . . The goal is to match the right therapy to the right patient, and to do it with minimal collateral damage.” Since 2011, the FDA has approved numerous new treatments for melanoma patients with certain types of genetic mutations. The agency also has given the green light to many drugs for other specific cancers, and to a revolutionary treatment for a small proportion of people with cystic fibrosis. Companion diagnostic tests often help identify which patients might benefit from the targeted treatments. Pharmaceutical companies have ramped up investment in personalized medicine in recent years, and the number of targeted therapies in the development pipeline reflect that evolution. For example, the FDA said about 80 percent of the nearly 50 drugs it has designated as potential “breakthrough” drugs involve targeted therapies. For patients who benefit, the advantages are striking: Earlier and better diagnoses, more effective treatments and even possible cures, or at least more time, for people who previously had little hope. But the trend toward targeted medicine also is forcing hard questions on regulators, drug makers, insurers and patients alike: Who should pay for the growing number of specialized drugs, which can cost hundreds of thousands of dollars a year? How does society ensure that everyone who might benefit — rich or poor — can receive treatment? What about patients whose specific conditions or mutations have not attracted investment dollars or the attention of researchers, leaving them to watch and hope from the sidelines? “We’re heading for some kind of reckoning,” said Barry Werth, an author and journalist who has spent decades writing about the pharmaceutical industry. “I don’t know that anybody has thought through how that’s going to play out.” Many of the current breakthroughs stem from successful mapping of the human genome, completed in 2003. Armed with an intimate understanding of the human genetic code, scientists have spent the past decade deciphering the underlying causes of certain diseases. As a result, applications for drugs aimed at specific populations of patients — whether for rare diseases or subsets of more common diseases — keep arriving at the FDA. One factor: a lack of blockbuster drugs that once sustained big pharmaceutical companies. Another reason: financial incentives such as accelerated approval and longer exclusivity for drugs deemed especially novel and necessary. “As we unravel these diseases and we have a better understanding of them and the underlying mechanisms that cause them, I think we’re just going to see more and more of this,”said Anne Pariser, associate director for rare diseases at the FDA’s Center for Drug Evaluation and Research. And likely more sky-high price tags. For now, Werth said, the system works for everyone: Federal regulators can tout their role in getting life-saving drugs to market. Makers of specialized drugs reap profits. Patients receive cutting-edge treatments. Private insurers and Medicare generally cover the high drug costs, which currently account for only a fraction of overall health-care spending. But, Werth said, what happens when targeted drugs become the rule rather than the exception? Will insurers refuse to cover some of them? Will the government ponder rationing them? Will only the wealthy be able to afford the best and newest treatments? He pointed to the much-heralded cystic fibrosis drug Kalydeco, which was approved in the United States and Europe in 2012. About 4 percent of the estimated 30,000 U.S. cystic fibrosis patients have the genetic mutation allowing them to benefit from the drug. Given that relatively small number, insurers have largely covered the drug, which runs about $300,000 a year in the United States. Its manufacturer, Vertex, offers it free to patients without insurance and assists many others with out-of-pocket costs. But in some cases, the willingness of insurers and governments to pay for such pricey drugs is beginning to fray. Insurers are publicly rebelling against the price of Sovaldi, a groundbreaking new treatment for hepatitis C that costs $1,000 per pill — or $84,000 for a 12-week treatment. Unlike drugs targeted to small groups of patients, Sovaldi could treat the estimated 3 million Americans infected with hepatitis C, a potential cost that has sent shudders through the insurance industry. The worry is that Sovaldi is the poster child for a “tsunami of expensive medicines” that collectively threaten to bankrupt the health-care system, said John Rother, president of the National Coalition on Health Care, which represents insurers, employers, consumer and religious groups, health-care providers and some drug manufacturers. “We’ve been able to absorb it so far because there are very few of them and because they are consumed by very small numbers of people,” Rother said of specialty drugs. “[But] if they’re all priced at the same level Sovaldi is, we really won’t be able to absorb it in the current system. It’s not sustainable.” Even the head of the cancer division at the FDA, which is not allowed to consider cost in deciding whether new drugs are safe and effective, has acknowledged the angst surrounding soaring price tags for new cancer treatments. “Obviously, we can’t just continue going on with escalating prices of drugs,” Richard Pazdur told Reuters over the weekend at the American Society of Oncology meeting in Chicago. “That’s not a regulatory decision or anything profound from the FDA. It’s just the reality of the situation.” Edward Abrahams, president of the Personalized Medicine Coalition, an advocacy organization that includes drug-makers, medical providers and patient and research groups, said the development of targeted drugs simply does not come cheap. Getting a promising drug to market can take a decade or more and billions of dollars, he said, and unless companies can recoup those costs, research will wither. “As a society, we’re schizophrenic about this,” Abrahams said, adding that everyone wants to cure cancer and other diseases. “But at the other end, you have to be willing to pay for these products. . . . When you develop a drug for a segmented population, the cost of that drug is likely to be higher than if it worked for everybody.” Abrahams said targeted treatments also can save money by cutting down on unnecessary drugs and procedures, a sentiment echoed recently by John Castellani, head of the Pharmaceutical Research and Manufacturers of America, or PhRMA, who called it “penny wise and pound foolish” to focus solely on the price of new medicines. Rather, Castellani blamed “an outdated insurance model that is forcing patients to pay an ever-   growing share of their prescription drug costs.” More than 2,000 miles from the drug debates in Washington, in Coeur d’Alene, Idaho, Kalydeco has transformed life for 6-year-old Brady Schroeder, who has cystic fibrosis. His mother, Rebecca Schroeder, said his lung function has vastly improved. Minor infections no longer send him to the hospital, and he now requires only about 15 minutes of breathing treatments a day to clear his lungs, compared with two hours or more in the past. Schroeder also frets about the high cost of Kalydeco and wonders what her family — and others — would do if they lost their health insurance or the assistance they receive from Vertex. She is convinced that the drug might give her son decades he otherwise would not have. “I would do anything to get Kalydeco — pay any price,” said Schroeder, a chemist. “Watching your child struggle to breathe and slowly suffocate on their own mucous is an indescribable type of torture. Kalydeco took that away. What is that worth?” Schroeder was so grateful for drug that she felt compelled to get a tattoo on her left foot — of the molecular structure of Kalydeco. Above it, she added three words: “Honor the gift.” More from The Washington Post: Sequencing genes can pinpoint rare illnesses New laws give dying patients ‘right to try’ unproven drugs How an $84,000 drug is sparking a new health-care debate

How 3-D imaging could change heart surgery in the future

In the cardiac operating room of the future, a surgeon may repair your damaged heart with personalized parts made to fit your precise anatomy — bypassing donor lists and immune-suppressing drugs. It sounds far-fetched, but in some ways this future is already here. Doctors use 3-D-printed models of organs and tumors regularly to educate patients and plan surgeries. Some printed body parts have even made their way into human bodies as dental implants, prosthetics, skull and facial reconstructions, and more. Researchers are also working to print out cells, blood vessels and other living tissues, and experimental studies have created, among other parts, knee cartilage, bones and an artificial ear. As costs decrease and discoveries accelerate, experts predict that 3-D printers will become routine tools for heart care, too. Optimistic scientists envision customized patches or even full-fledged beating hearts, ready to be implanted, an exact fit for the patient’s body. “I really think the 3-D jet printer is transformative,” says Daniel Jones, chief of minimally invasive surgical services at Harvard Medical School in Boston. “It’s going to change the way doctors talk to patients, how they plan surgeries and how they do surgeries. The sky is the limit in terms of applications.” Around since the 1980s and now available in basic versions for just hundreds of dollars at   office supply stores, 3-D printers work by creating layers of material in skinny slices that stack up to create a three-dimensional shape. The technology has been used to manufacture eyeglasses, car parts, jewelry and more. Medical applications are also wide-ranging. All it takes is an MRI or CT scan or other image to create a three-dimensional blueprint for creating objects of any shape. Colors can be altered to make visualizing easier. Depending on the design and complexity of the machine, objects can be made with a variety of materials, including plastics, metal and rubber. In cardiology, 3-D models are, for now, proving most useful as educational tools. Like fingerprints, every person’s heart is unique, and every heart problem plays out in its own way, says Paul Iaizzo, associate director of the Institute for Engineering in Medicine at the University of Minnesota in Minneapolis. With help from detailed replicas, surgeons can plan more accurately and reduce procedure times. In the last year, Iaizzo says, his team has printed models of 17 children’s hearts with congenital deformations that required surgical repair. A young child’s heart can be as small as a walnut, so the team prints each heart four or five times larger than normal. The surgeons can then study the models, show parents what needs to be done and discuss risks. They usually print out an extra heart for patients to take home. “One of the most critical parts is discussing the whole thing with the family,” Iaizzo says. “It’s powerful and comforting for parents to really understand what the problem is.” The medical device industry makes frequent use of 3-D models to design and test new products, Iaizzo adds. His team has also printed hearts for medical students, surgical residents and physicians to study and even to use in artistic exercises. “Taking time to put a paintbrush in every crevice is really valuable,” he says. “It puts that anatomy in the brain in a three-dimensional way that never could have been done another way.” The technology of 3-D printing is so new that rigorous studies have not yet assessed how using it affects outcomes. But anecdotal evidence is powerful. When Harvard Medical School cardiac anesthesiologist and echocardiographer Feroze Mahmood began printing full-size replicas of patients’ damaged mitral valves, he gained a new appreciation for the complexity of the structure, particularly a Pringles-shaped region called the annulus that was impossible to visualize with two-dimensional images. Insights gained from handling printed valves have helped him and colleagues understand why a common treatment works for some patients but not others. He has now used the technology hundreds of times. “For most people, it is an ‘aha’ moment,” says Mahmood, who is researching the possibility of printing patient-specific valve parts that would be safe to use in surgeries. “What I foresee is that . . . we will be 3-D printing everything we operate on before surgery. Instruments, grafts and materials will all be customized and will be printed on-site.” Someday, surgeons may even be able to print customized patches for repairing hearts damaged by heart attacks, says Adam Feinberg, a biomedical engineer at Carnegie Mellon University in Pittsburgh. His team is working both to grow heart tissue in petri dishes and to use 3-D printers to create soft, living structures by embedding cells inside gels that can be laid down in precise layers. Feinberg’s team uses consumer-level printers, which cost about $1,000 each, far less than commercial versions, priced at $100,000 or more. To encourage other researchers to accelerate advances, the Carnegie Mellon group is also using open-source hardware and software. “The challenge is to print something high-quality that re-creates the function of real human heart muscle,” he says. “It’s easy to make something that doesn’t work well.” Multiple teams of researchers are working on this kind of bioprinting task, which Feinberg says could help as many as 100,000 people a year who need heart transplants but face long waiting lists. He imagines 3-D-printed living heart tissue becoming available in as little as 10 years, although he admits that he could be a decade off. “It’s definitely science-fiction now,” he says. “But at least we’re getting to the point where it’s conceivable that it could happen.” **Read more:** This young boy could have dropped dead on the playing field What’s the difference between heart attack and sudden cardiac arrest? Heart facts that every woman needs to know ‘The night my heart stopped beating’

Supreme Court rules human genes may not be patented

The Supreme Court ruled unanimously Thursday that human genes cannot be patented, a decision that is likely to shape the future of medical and biotech research. Those who challenged the notion that something that occurs naturally in the human body can be “owned” by a company said the decision could open a new era of expanded research and lower costs for genetic testing. At the same time, the ruling held out hope for industry that certain research methods and the creation of synthetic DNA can be protected and thus worth the investment. “Today, the court struck down a major barrier to patient care and medical innovation,” said Sandra Park of the American Civil Liberties Union, which represented doctors, researchers and cancer patients who brought the challenge. “Because of this ruling, patients will have greater access to genetic testing, and scientists can engage in research on these genes without fear of being sued.” The issue received national attention last month when actress Angelina Jolie revealed that she had a double mastectomy because genetic testing showed she carried a defective gene that greatly increased her chance for cancer. The ruling was a split decision for Myriad Genetics Inc., which holds patents on genes that have been linked to breast and ovarian cancer and thus is the only company that offers the genetic tests, which can cost more than $3,000. Justice Clarence Thomas, writing for the court, said that merely isolating those specific genes — BRCA1 and BRCA2 — was not worthy of a patent. The decision was a departure from decades of decisions to the contrary from the U.S. Patent and Trademark Office. “Myriad did not create anything,” Thomas wrote. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.” He added that “groundbreaking, innovative, or even brilliant discovery does not by itself” overcome the fact that “laws of nature, natural phenomena, and abstract ideas” are beyond the domain of patent protection. On the other hand, Thomas wrote, when Myriad and others create a synthetic form of DNA — called cDNA and particularly useful in conducting experiments and tests, such as cancer screening — their work does deserve patent protection. “The lab technician unquestionably creates something new when cDNA is made,” he wrote. Myriad focused on that part of the decision. “We believe the Court appropriately upheld our claims on cDNA, and underscored the patent eligibility of our method claims, ensuring strong intellectual property protection for our BRACAnalysis test moving forward,” Peter D. Meldrum, the company’s president and chief executive, said in a statement. “More than 250,000 patients rely upon our BRACAnalysis test annually, and we remain focused on saving and improving peoples’ lives and lowering overall healthcare costs.” The average American woman has a 12 to 13 percent chance of developing breast cancer, according to the court’s opinion, but mutations in the two genes isolated by Myriad increase the risk to as much as 80 percent for breast cancer and 50 percent for ovarian cancer. Myriad developed tests useful in detecting those mutations. The court’s opinion required the nine justices to confront not only the mysteries of DNA — their struggle was apparent during the case’s complicated oral arguments — but also the purpose of patents. “As we have recognized before, patent protection strikes a delicate balance between creating incentives that lead to creation, invention, and discovery,” Thomas wrote, “and “impeding the flow of information that might permit, indeed spur, invention.” Some experts in the field said the decision provides needed clarity. “The biotechnology industry won today, because they have some certainty,” said Kevin Noonan, a leading biotechnology and intellectual-property lawyer. “The synthetic DNA is patentable. . . . This [particular issue] is off the table. It’s not going to be challenged.” Matthew J. Dowd, a Washington lawyer who filed a brief opposing Myriad’s position on human genes on behalf of James Watson, the scientist who co- discovered the structure of DNA, said the court’s ruling on cDNA was especially important for companies. “The cDNA has the same genetic information as our natural gene, but it’s in a user-friendly form,” Dowd said. “If you think of a human gene as gold still in a gold mine, then cDNA is the gold after it’s been mined and polished.” But not all were happy. Jim Greenwood, president and chief executive of the Biotechnology Industry Organization, said the decision will put U.S. companies at a disadvantage. “The United States is now the only developed country to take such a restrictive view of patent eligibility, signaling an unjustified indifference towards our global economic and scientific leadership in the life sciences,” Greenwood said in a statement. Those who challenged the patents said the ruling will spur research and competition. “The cost of genetic testing should come down considerably,” said Harry Ostrer of the Albert Einstein College of Medicine at Yeshiva University in New York. Ostrer noted that there were about 4,000 gene-related patents that can now be challenged, and he predicted that additional tests for heart conditions and neuromuscular diseases will become available. Companies already are announcing plans to offer genetic screening similar to Myriad’s test. But Ostrer and others said the company, which won the race to locate and isolate the BRCA1 and BRCA2 genes in the early 1990s, remains far ahead of the rest of the field. Even though Noonan noted that Myriad’s patent is scheduled to expire in 2015, he added: “Myriad has a 15-year head start on everybody. They started this. They have all the relationships with everybody. They are still going to be the gold standard.” The court’s opinion does not settle all questions about the issue. For instance, Timothy McCaffrey, director of the division of genomic medicine at George Washington University Faculty Associates, said the emerging practice in his field is to patent a method or process of working with a gene, rather than trying to isolate and patent the gene itself. Thomas’s opinion held out that option. “Had Myriad created an innovative method of manipulating genes while searching for the BRCA1 and BRCA2 genes, it could possibly have sought a method patent,” Thomas wrote. “But the processes used by Myriad to isolate DNA were well understood by geneticists at the time.” While the briefs and opinion in the case often offered theoretical arguments, reaction to the decision was more emotional. Lisbeth Ceriani, one of the plaintiffs represented by the ACLU, said the decision means that a part of the human body is “not being held hostage by a private company anymore.” The ruling was also praised by Rep. Debbie Wasserman Schultz (D-Fla.), chairman of the Democratic National Committee, who underwent a double mastectomy and had her ovaries removed after Myriad’s test showed she carried the gene mutation. Her treatment required seven surgeries, she said. “Because one company had a patent on the BRCA1 and BRCA2 genes, I was unable to get a second opinion,” Schultz said. The case is _Association for Molecular Pathology v. Myriad Genetics Inc_.

Oregon scientists get stem cells from cloned human embryos

A team of researchers said Wednesday that it had produced embryonic stem cells — a possible source of disease-fighting spare parts — from a cloned human embryo. Scientists at the Oregon Health and Science University accomplished in humans what has been done over the past 15 years in sheep, mice, cattle and several other species. The achievement is likely to, at least temporarily, reawaken worries about “reproductive cloning” — the production of one-parent duplicate humans. But few experts think that production of stem cells through cloning is likely to be medically useful soon, or possibly ever. “An outstanding issue of whether it would work in humans has been resolved,” said Rudolf Jaenisch, a biologist at MIT’s Whitehead Institute in Cambridge, Mass., who added that he thinks the feat “has no clinical relevance.” “I think part of the significance is technical and part of the significance is historical,” said John Gearhart, head of the Institute for Regenerative Medicine at the University of Pennsylvania. “Many labs attempted it, and no one had ever been able to achieve it.” A far less controversial way to get stem cells is now available. It involves reprogramming mature cells (often ones taken from the skin) so that they return to what amounts to a second childhood from which they can grow into a new and different adulthood. Learning how to make and manipulate those “induced pluripotent stem” (IPS) cells is one of biology’s hottest fields. Stem cells have the capability of maturing into different types of tissue depending on how they are stimulated. Embryonic stem cells (ESCs), plucked from a microscopic embryo, have the greatest potential. With the right molecular nudges, they could theoretically be used to grow new kidneys, lungs and hearts for use by people whose own organs have worn out. Some experts think that “regenerative medicine” will eventually become an approach to healing that is as important as surgery or pharmacology. The Oregon researchers, led by Shoukhrat Mitalipov, produced embryonic stem cells through “somatic cell nuclear transfer,” the technique used in 1996 to make Dolly the sheep the first cloned mammal. The nucleus of a mature cell is transplanted into a human oocyte (egg) whose own nucleus has been removed. After the right stimulation, this new hybrid cell starts to divide and develop just as a sperm-fertilized egg would. When it is at the “blastocyst” stage — about 100 cells — its core contains a small number of embryonic stem cells capable of becoming any type of cell possessed by the human body. But getting the doctored egg to grow even that far is extremely difficult. For some species, hundreds of eggs must be subjected to nuclear transfer before any produce viable embryonic stem cells. The failure of human oocytes to produce them had led some scientists to speculate that the technique simply might not work in people for some reason. Mitalipov and several members of his team work at the Oregon National Primate Research Center and had refined their techniques using rhesus monkeys. They used nuclei from the skin cells of newborns or, in some cases, fetuses. Their stimulants included a pulse of electricity at the time of nuclear transfer and the addition of caffeine to the fluid cells lived in. The tweaks and improvements apparently made all the difference. In one experiment, eight oocytes harvested from one woman produced five blastocysts and four embryonic stem cell lines — a success rate virtually unseen in other animals. The researchers subsequently proved cells were “pluripotent” by coaxing them to become, among other things, beating heart muscle cells. The experiments were reported in a paper published online in the journal Cell. “Where the kudos come is in being able to over time enhance and improve the technology developed in other species to make this amenable to the human oocyte,” Gearhart said. The blastocysts could be implanted in a woman’s uterus. It might develop into a fetus. Most cloned animals, however, turn out to have major health problems and shortened lives. “We just need to make sure it’s clear to the public that no one in their right mind would want to do that. There is no intent to do reproductive cloning. None at all,” Gearhart said. Are these embryonic stem cells more versatile than IPS cells made by reprogramming skin cells? “That’s of interest,” Jaenisch said. But whatever the answer, “the consequence would be to make the IPS cells better.” Given the difficulty of obtaining human oocytes, and the controversial nature of the research, embryonic stem cells aren’t likely to ever be the preferred tool of regenerative medicine, he said.

Medical research cuts cede a U.S. advantage to Asia

The peril to U.S. leadership in world biomedical research, highlighted in the Dec. 5 editorial “Bad medicine,” is all the more pressing in view of developments in Japan, China, Singapore and South Korea, whose governments are maintaining or increasing their national biomedical research budgets. The self-inflicted impoverishment of U.S. biomedical innovation is already contributing to the brain drain of U.S.-trained researchers and clinical scientists to these Asian countries, who will reap this windfall of talent that has benefited from the first-class scientific mentorship and development received at world-class American universities and research institutes. The United States’ future business and scientific prosperity is far too important to be pawns in such poorly played political chess. ****John A. Tessensohn** , Osaka, Japan**

10 bold predictions for 2014

At the beginning of each year, it’s possible to make predictions about the future of the tech sector simply by extrapolating from data in the latest Mary Meeker Internet Trends presentation. It doesn’t require a crystal ball to realize that smartphones and tablets will replace PCs, big data will continue to grow at an exponential rate, and nations such as China will play an ever- greater role in the development of the Internet. Below is an attempt at thinking big, at imagining how a number of emerging trends may combine in unique ways to create disruptive trends in 2014.    *[WSU]: Wayne State University **Google Glass becomes the must-have tech gadget of the year.**    *[WSU]: Wayne State University After flirting with wearable tech in 2012 and 2013, the consumer technology market is finally ready to embrace wearable computing as a full-on trend in 2014. And the biggest entrant in the wearable computing market is almost certain to be Google Glass. There’s been almost as much anti-hype as hype around Google Glass over the past 12 months, but it’s a safe bet that if Google Glass is cool enough for the runway models of DVF and the fashion spreads of Vogue, it’s also cool enough for the mainstream tech consumer who’s looking to move beyond the smartphone.    *[WSU]: Wayne State University Going forward, broad consumer acceptance around wearable computing — whether in the form of the latest Samsung smartwatch, Google Glass or any of the new fitness gadgets — will continue to open the door to radical innovation in the wearable computing segment. At this month’s CES event in Las Vegas, some of the most-hyped products of the year are related to “biometrics” – such as headbands, socks and bras that claim to be able to measure your brain waves, heart rate and level of physical exertion.    *[WSU]: Wayne State University **Your next-door neighbor becomes a venture capitalist.**    *[WSU]: Wayne State University The JOBS Act (aka the Crowdfunding Act) is set to go into full effect by mid-2014, and that could lead to anyone — not just a wealthy accredited investor — having the ability to invest in start-ups, anywhere in the country and in any industry. In short, it will soon be almost as easy to back a hot tech company on a new equity crowdfunding portal as it is to crowdfund a cool artistic project on Kickstarter or Indiegogo.    *[WSU]: Wayne State University In the process, expect to see a lot of “What’s the future of the VC industry?” articles. It’s only natural, since crowdfunding seems to have the potential to disrupt the traditional VC industry by creating an entirely new type of investor. And once it’s your temperamental next-door neighbor, and not a cooly rational Harvard MBA making the decision of where to allocate investment dollars, this could lead to some fantastic innovations being funded in coming years. Consider the example of the Terrafugia flying car concept, which has raised more than $10 million on the crowdfunding site Wefunder.    *[WSU]: Wayne State University **A commercial drone company gets anointed as “the next Apple.”**    *[WSU]: Wayne State University The excitement around the Amazon drones delivery concept is almost certain to inspire a number of copycat imitators. After the Jeff Bezos “60 Minutes” segment at the end of the year, there was a surge in stories about possible uses for commercial drone technology, including the story of quadcopters being used by Deutsche Post. As drones transition from being used to take out terrorist leaders to being used to revolutionize business models, we’ll inevitably hear talk about the first generation of drone start-ups that are “the next Apple” or the “next Google.” One early front-runner is New York- based Flyterra, which is set to start testing drones in upstate New York, making it one of the first commercial drones companies in the nation.    *[WSU]: Wayne State University Six states (including New York and Virginia, both home to huge tech communities) have now been cleared to host drones-testing facilities. If the first rounds of testing go well, we could soon hear talk about other states vying to host their own drones test sites, in order to get a hand in any future economic goodies that come from having a vibrant drone innovation sector. States might begin to woo drone tech companies, the same way they woo tech startups as part of a broader attempt to revitalize their economies.    *[WSU]: Wayne State University **Virtual reality becomes the next big science fiction technology to go mainstream.**    *[WSU]: Wayne State University In many ways, 2013 was the year that science fiction became science fact, with Terminator bots, password pills and missions to Mars. In 2014, the one science fiction technology that is finally showing signs of going mainstream is virtual reality. Much of the innovation for now is being driven by the gaming market, where the Oculus Rift virtual reality headset for 3D Gaming is due to come to market by mid-2014.    *[WSU]: Wayne State University But gaming is just the tip of the iceberg. People are already thinking of ways that virtual reality could change everything from retail experiences to entertainment experiences. Ford automobile designers are even working on ways to use the Oculus Rift to design better cars.    *[WSU]: Wayne State University **Bill Gates amazes us again with another innovation for the developing world.**    *[WSU]: Wayne State University Bill Gates continues to entice us with his vision for changing the future of the developing world, primarily by creating new innovations that can lower mortality rates. In just the past few years, as he reminded us last summer, Bill Gates has turned into a digital age Leonardo Da Vinci. It’s only a matter of time before he amazes us again with a simple, clever innovation for the world’s rising billions that addresses a basic need like clean sanitation.    *[WSU]: Wayne State University As the “developing” world starts to catch up to the “developed” world, it’s only inevitable that nations across Asia, Africa and Latin America will begin to attract more attention from the West’s top innovators. We’ve already started to see this in Africa, where innovations in mobile banking and mobile health are occurring as fast — or faster — than in the United States. In a best-case scenario, there will be a virtuous circle, as innovations in health complement innovations in mobile and Internet.    *[WSU]: Wayne State University **Bitcoin revolutionizes politics.**    *[WSU]: Wayne State University ****Insurgencies and uprisings around the world — especially in the Arab world — have been quick to use new technologies — everything from smartphones for rapidly organizing protests to Twitter for getting their message out to the world. So why not Bitcoin? Couldn’t sovereign states such as the United States use Bitcoin to fund rebel groups — say, the Syrian rebels — so as not to leave behind a paper trail for the media to follow. In other words, Bitcoin could help avoid anotherIran-Contra Affair.    *[WSU]: Wayne State University Bitcoin, or any of the other emerging crypto-currencies, are perfect for insurgents — anonymous, hard-to-track and just as good as cash. For that matter, they are also perfect for mainstream politicians. It’s only a matter of time before politicians are able to accept Bitcoin, and that could lead to an awkward situation where you really don’t know who’s funding a candidate. In Texas, one Senate campaign could feature Bitcoin in 2014. And, if Bitcoin truly is anonymous (and there’s been debate about that), money could be theoretically funneled to mainstream political candidates to circumvent current campaign donation limits.    *[WSU]: Wayne State University **DIY biology becomes the next big tech hobbyist trend, replacing 3D printing.**    *[WSU]: Wayne State University Just as 3D printing captured the public imagination by radically changing our notions of what it is possible to create in the physical world, DIY biology could have the same impact on the way we view the biological world. Thanks to Craig Venter’s pioneering efforts to map the human genome more than a decade ago, the average person now has the potential to understand his or her own genetic destiny, and that’s leading to the arrival of new startups like 23andMe as well as new DIY biology hacker spaces.    *[WSU]: Wayne State University The only question, of course, is how the DIY biologists and geneticists cope with the legal, moral and philosophical questions of their work. As we’ve seen with 23andMe, it’s not always so easy to gain regulatory approval — and that’s even before the hackers get involved. In some futuristic scenarios proposed by Craig Venter, it’s also possible for biologists to hack the genetic code of some microorganisms, leading to radical new mutations and new forms of life. Most likely, in 2014, you’ll start to see more crowdfunding efforts of the type pioneered by the Glowing Plants project in 2013, which raised nearly half a million dollars to make possible genetically modified glow-in-the-dark plants.    *[WSU]: Wayne State University **The world sees the first-ever 3D-printed organ.**    *[WSU]: Wayne State University Organovo, a biotech company in San Diego, recently claimed that it would have a 3D-printed liver ready to go by the end of 2014. So far, organs have been too complex to print, but there have been limited successes with things such as human tissue and bone. It appears to be only a matter of time before 3D-printed organs become a reality, thanks to new high-tech “bioprinters.”    *[WSU]: Wayne State University This growth in 3D-printed organs will lead to a number of debates about a whole range of possible industries that may be possible in the future, such as cosmetic internal surgery, in which you receive brand-new organ transplants. It would be like the scenario in the science fiction film “Elysium,” where the wealthy are never sick because they could presumably simply swap out unhealthy organs whenever needed.    *[WSU]: Wayne State University **The first MOOC is fully taught by a machine rather than a human.**    *[WSU]: Wayne State University If you think about the MOOC (Massive Open Online Course) as just a form of cheap distance education for people who can’t afford “the real thing,” then you’re not thinking far enough out of the box. Thus far, the traditional market leaders – elite universities such as Stanford, Harvard and MIT – have been at the helm of the MOOC movement. That could change in 2014, if the first artificially intelligent machine begins to fully teach a MOOC — lecturing, grading and engaging with students the way a human professor might, thereby opening the door to new educational start-ups to challenge the entrenched incumbents by demolishing the current cost structure of higher education.    *[WSU]: Wayne State University Unlike humans, machines would be willing to complete all the coursework and do all the assignments. Machines could enroll in — or even teach — these MOOCs not just for the knowledge, but to study how humans learn, and to pick up the various nuances of a specific field of knowledge — the same way that IBM’s Watson learns about medicine not just by memorizing a bunch of medical knowledge, but also by analyzing the case work that shows how doctors think. In short, the MOOC may have started as a way to educate humans, but it may end as a way to educate machines. At the very least, once a MOOC can be taught by a machine, it may end up making the delightfully erudite college professor a quaint artifact of the non-digital past.    *[WSU]: Wayne State University **The United States experiences its first big cyber attack.**    *[WSU]: Wayne State University Don’t say we haven’t been warned — people have been warning of a “Cyber Pearl Harbor” on U.S. soil for more than two years. There are clear signs that the Chinese and North Koreans are working on cyberweapons, and it’s only a matter of time before Al-Qaeda or some other rogue terrorist organization uses cyberweapons to shut down part of the U.S. utility grid, or even worse, to unleash a major attack on a U.S. city by doing something like playing around with the computers inside nuclear reactors.    *[WSU]: Wayne State University It’s not for nothing that the Pentagon has begun to fundamentally alter its force posture to emphasize offensive cyberweapons rather than defensive cyber precautions. It’s safe to assume that the good folks at DARPA are already working on next-generation “Plan X” cyberweapons that make Stuxnet look like a toy pop gun. To discourage a foreign entity or rogue terrorist group from initiating an attack on U.S. soil, look for the nation’s top generals to start thinking in terms of cyberweapons with destructive payloads rather than in terms of conventional or nuclear weapons.    *[WSU]: Wayne State University

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

10 bold predictions for 2014

Five innovation predictions for 2013

Last year I predicted that social media would lose its sizzle. Since then, the bubble has burst for companies such as Facebook, Zynga and Groupon. The tablet computer market, on the other hand, is booming, voice recognition is becoming a standard feature in new computing devices, and there have been, as I alluded to in 2012, notable cloud-computing failures and security breaches in the past year. I am glad to have been wrong about LinkedIn. It is a great company with a stellar management team. Also, tablet prices haven’t quite hit the $100 mark in the U.S., as I predicted they would. But I still anticipate they will, and likely very soon. So, what else lies ahead for 2013? There is nothing as spectacular as the Facebook IPO, at least at this point, but expect gradual technology progressions of greater significance than have been seen in years past. The Post’s Hayley Tsukayama has outlined the trends in tech for the coming year — a year I believe will be one of transition for the sector. This year, expect tech innovators to set the stage to solve global problems, since technologies in fields such as medicine, robotics, artificial intelligence, synthetic biology, 3D printing, and nanomaterials are advancing exponentially. Like the processors in our computers, they are becoming increasingly powerful while their price drops precipitously. This will enable startups to take on problems in fields such as energy, health, education, and security that only government and big research labs previously could. Most recently, the big rewards have gone to startups developing relatively simple social media platforms and applications. In the upcoming era of exponential technologies, expect the rewards to go to players that solve big, global problems. Here are the big innovation trends that I believe will gain traction in 2013. **Tablet explosion to computing revolution** The entry price of tablet computers will almost surely drop to under $100 in 2013 — especially if the rumored $99 Acer tablet gains traction this year, as I believe it will, or if the India Aakash tablet finally lives up to its potential. I also anticipate that the tablet price tag will keep dropping until it reaches close to zero over a 2-to-3 year period. We will reach the point where it makes sense for companies to give tablets away just as mobile carriers give phones away in exchange for plan subscriptions. More broadly, we can expect to see tablet computers almost everywhere in this decade—our kitchens, bathrooms, cars, supermarkets, schools and elevators. Apple currently owns the high end of the market, of course, and I don’t expect cheap tablets to put any dent in the company’s sales this year. But, if Apple fails to keep innovating, the company will surely feel the pain in 2014 and beyond as Samsung continues to nip at its heels. The PC laptop vendors — Dell, HP and Lenovo, among others — should worry since tablets will continue to cannibalize their higher-priced products. The biggest winner in this revolution will likely be Google, with its free Android operating system. Unsurprisingly, the loser will probably be Microsoft, which licenses its mobile operating system, Windows RT, for around $80 — more than the hardware will eventually cost. In the long term, expect the billions of new users that come online over the next few years to be doing Google searches and using Google’s applications. **The “quantified self” goes mainstream and creates a new regulatory battlefield** We saw a trickle of sensor-based medical devices in 2012, but these were just the start of the “quantified self” movement. As sensors become smaller, more powerful, and cheaper, we will see many new types of devices that help us monitor our health. These will be embedded in our iPhone cases, bathroom scales, toothbrushes, and even in our jewelry. In 2013, expect to be able to purchase sophisticated new devices like the AliveCor Heart Monitor, which I have been testing and the FDA has approved for use by licensed U.S. medical professionals. If I had a device like this 10 years ago, I may have been able to avoid the heart attack that I had. The device will cost $199 when prescribed by a physician. Today, we need physicians to analyze the data the device provides. But, given the rate at which technology is advancing, computers may be able to do a better job. Witness the way IBM’s Watson defeated Jeopardy champions. It had far more data available to it. Eventually, I foresee cloud-based systems that have access to the latest medical knowledge and to data from hundreds of millions of people analyzing medical data. I would trust these systems more than I trust my cardiologist, and the app to access these will be available anytime and as often as I need it. Even before we reach this stage, consumers should be allowed to purchase these devices off the shelf to see and analyze their own medical data. This is where the battle lines will increasingly be drawn between technologists and regulators. Users will begin to demand greater control of their own data and more ways to monitor it in order to improve their lives. That means, in the coming year, one should expect to see the regulatory battles over these types of technologies become more frequent and heated. **Manufacturing jobs continue to return to the U.S.** Expect advances in robotics, artificial intelligence, and 3D printing to, as I have previously written, change the economics of manufacturing, lead to a renaissance in design and creativity, and bring manufacturing jobs back to the U.S. over the next year. Manufacturing is also destined to become a technology industry. The jobs of the future will be in creating 3D designs and maintaining and operating sophisticated computer machinery. In 2013, expect to see the commercial availability of a new generation of robots like Baxter from Rethink Robotics and the grape-picking Wall-Ye. **From big baloney to big opportunity in big data** Big data was one of the most hyped concepts in the tech industry in 2012 and some are feeling let down. But there is no reason to lose hope—we are just getting started. The amount of data we are creating is increasing exponentially. That data is coming from sources such as cameras, sensors signals, social media, Web browsing trails and Google searches, e-commerce transactions, medical records, and DNA decoding. I expect that in 2013 we will see more success stories like that of Nate Silver, who was able to use big data to out-predict the pollsters. In subsequent years, we will see billion- dollar startups emerge — companies that have mastered the art of using machine-intelligence to harness big data. Google Now, which was named Innovation of the Year by Popular Science, shows what is possible when you combine disparate pieces of information. Google claims it “tells you today’s weather before you start your day, how much traffic to expect before you leave for work, when the next train will arrive as you’re standing on the platform, or your favorite team’s score while they’re playing.” Within a few years, expect to be able to do Google-like searches to learn what diseases those with similar genetics have had and what medications worked for them. Eventually, when researchers combine the medical records of a hundred million people with their genome data, work habits, and other information, such as weather and pollution data based on where they live, they will all but certainly be able to determine the correlation between genome, disease and lifestyle. **New user interface paradigms** I couldn’t agree more with Tsukayama on this topic. Expect the computer keyboard and mouse to become obsolete. The most promising product on the horizon is the Leap Motion controller, which senses hand and finger movements, allowing users to do sophisticated gestures similar to those in the 2002 film _Minority Report_. There was some buzz about the device in 2012, but this year it is expected to retail for $69. I expect similar technologies to be embedded in many computing devices. These advances in voice and gesture recognition mean we will soon have a more natural way of using computers. When Google releases Project Glass—eyeglasses that display words and pictures — in the coming years, I predict we won’t even need the computer screens at all. Don’t be surprised if 2013 is a a dull year for Silicon Valley bloggers looking for the next social media startup and a really exciting year for humanity. _Washington Post Co. Chairman and chief executive Donald E. Graham is a member of Facebook’s board of directors._ Read more news and ideas on Innovations and follow us on Twitter and Facebook.

Robert Samuelson: Of Internet threats and cyberattacks

If I could, I would repeal the Internet. It is the technological marvel of the age, but it is not — as most people imagine — a symbol of progress. Just the opposite. We would be better off without it. I grant its astonishing capabilities: the instant access to vast amounts of information, the pleasures of YouTube and iTunes, the convenience of GPS and much more. But the Internet’s benefits are relatively modest compared with previous transformative technologies, and it brings with it a terrifying danger: cyberwar. Amid the controversy over leaks from the National Security Agency, this looms as an even bigger downside. By cyberwarfare, I mean the capacity of groups — whether nations or not — to attack, disrupt and possibly destroy the institutions and networks that underpin everyday life. These would be power grids, pipelines, communication and financial systems, business record-keeping and supply-chain operations, railroads and airlines, databases of all types (from hospitals to government agencies). The list runs on. So much depends on the Internet that its vulnerability to sabotage invites doomsday visions of the breakdown of order and trust. In a report, the Defense Science Board, an advisory group to the Pentagon, acknowledged “staggering losses” of information involving weapons design and combat methods to hackers (not identified, but probably Chinese). In the future, hackers might disarm military units. “U.S. guns, missiles and bombs may not fire, or may be directed against our own troops,” the report said. It also painted a specter of social chaos from a full-scale cyberassault. There would be “no electricity, money, communications, TV, radio or fuel (electrically pumped). In a short time, food and medicine distribution systems would be ineffective.” I don’t know the odds of this technological Armageddon. I doubt anyone does. The fears may be wildly exaggerated, as Thomas Rid of Kings College London argues in his book “Cyber War Will Not Take Place” (already published in Britain, due out this fall in the United States). In living memory, there are many threats that, with hindsight, seemed hyped: the “missile gap” in 1960; the Y2K phenomenon in 2000 (the date change was allegedly going to disable many computer chips); and, so far, the prophecies of widespread terrorism after 9/11. Still, the Internet creates new avenues for conflict and mayhem. Until now, the motives for hacking — aside from political activists determined to make some point — have mostly involved larceny and business espionage. Among criminals, “the Internet is seen as the easiest, fastest way to make money,” says Richard Bejtlich, chief security officer for Mandiant, a cybersecurity firm. Recently, federal prosecutors alleged that a gang of cyberthieves had stolen $45 million by hacking into databases of prepaid debit cards and then draining cash from ATMs. Stealing trade secrets likely dwarfs ordinary crime. From its clients, Mandiant identifies four industries as receiving the bulk of attacks: aerospace and defense (31 percent); energy, oil and gas (17 percent); pharmaceuticals (15 percent); and finance (11 percent). Mandiant identified one unit of China’s People’s Liberation Army that allegedly has hacked 141 companies and organizations since 2006, removing “technology blueprints, propriety manufacturing processes, test results, business plans.” What’s unclear is how “infrastructure” systems (electricity grids and the like) have been penetrated and, on command, might be compromised. In the mid-1980s, most of these systems were self-contained. They relied on dedicated phone lines and private communications networks. They were hard to infiltrate. Since then, many systems switched to the Internet. “It’s cheaper,” says James Andrew Lewis, an Internet expert at the Center for Strategic and International Studies. The architects of these conversions apparently underestimated the risk of sabotage. As yet, there has been little. One publicized incident occurred in 2012 when hostile software (“malware”) infected an estimated 30,000 computers of Aramco, Saudi Arabia’s oil company. Business operations suffered, but oil production and delivery continued. More powerful was the Stuxnet virus, reportedly developed by the United States and Israel to disrupt Iran’s nuclear program. The future could be more tumultuous. If the United States attacked Iran’s nuclear facilities, Lewis thinks it would retaliate with cyberattacks against banks and electricity networks. Press stories report that Iran has already increased its attacks. There’s a race between cyber offense and defense. All this qualifies our view of the Internet. Granted, it’s relentless. New uses spread rapidly. Already, 56 percent of U.S. adults own smartphones and 34 percent have tablets, says the Pew Internet & American Life Project. But the Internet’s social impact is shallow. Imagine life without it. Would the loss of e-mail, Facebook or Wikipedia inflict fundamental change? Now imagine life without some earlier breakthroughs: electricity, cars, antibiotics. Life would be radically different. The Internet’s virtues are overstated, its vices understated. It’s a mixed blessing — and the mix may be moving against us. **Read more on this topic:** The Post’s View: Taking the mystery out of cyberwar Richard A. Clarke: Cyberwar’s threat does not justify a new policy of nuclear deterrence James Andrew Lewis: Five myths about Chinese hackers Joseph I. Lieberman: The dangers of delaying heightened cybersecurity

A Texan went to the hospital for surgery. She woke up with a startling British accent.

Lisa Alamia had the jaw surgery in December. She underwent the procedure to correct a serious overbite, and it was a success, according to Houston Methodist Sugar Land Hospital. The 33-year-old woke up and had minimal swelling. But then she began to talk. And she sounded … different. Very different. The voice coming out of Alamia’s mouth didn’t sound like it belonged to a Houston-area native. It sounded British.  Alamia said her surgeon thought the voice change was “just a psychical result of the surgery and that it would go away as I healed,” according to the hospital. But months later, she still speaks as if she’s from across the pond. Eventually, she saw neurologist Toby Yaltho at Houston Methodist Sugar Land Neurology Associates, who diagnosed her with a very rare condition: Foreign Accent Syndrome, or FAS. “This is a fascinating and very rare case,” Yaltho said in a release. “Most neurologists work their entire careers and never come across FAS.”   In the case of Alamia, Yaltho conducted MRI scans to see if she had suffered a stroke, seizure or another injury that led to FAS.  The neurological exam also included an electroencephalogram to detect abnormal brain waves. The cause of Alamia’s FAS remains a mystery. “Everything came back normal,” Yaltho said in a release. “There was no evidence of stroke or other abnormalities.” Meanwhile, Alamia was still in Texas, walking around with a voice that sounded like that of a stranger. “Mom” comes out as “mum.” And “kidding” sounds like “kitten,” she told KHOU. The rarity of the condition makes some reluctant to share their diagnoses.  An Indiana woman named Ellen Spencer, who began speaking with a French-sounding accent following a stroke-like episode, recounted the reactions should would get from people following her FAS diagnosis.   The new accent in people with FAS may persist for only months, or years. The condition could also be permanent. Treatment includes speech therapy, which Alamia is undertaking. But there is no known cure for FAS. “The human brain is a complex organ, and we don’t know if we will ever be able to completely understand what causes FAS,” Yaltho said.

Patents for DNA molecules help promote innovation

Regarding Jeffrey A. Rosenfeld and Christopher E. Mason’s April 7 Sunday Opinions commentary, “Who owns your DNA? Not who you think.”: The patents for which Mr. Rosenfeld and Mr. Mason criticized my company were essential to developing diagnostic tools that have been used by more than 1 million women to understand their hereditary risks of breast cancer and ovarian cancer. We did not patent human genes from anyone’s body. Rather, our patents protect synthetic molecules created in the lab. This is no different than thousands of other patents issued in the past 30 years. Were these molecules derived in part from natural material? Sure. But that is true of many patents. Labs routinely turn naturally found molecules into innovative medicines and get patent protection. Simply put, the U.S. patent system made Myriad’s tests possible. Our research cost more than $500 million, and it took 17 years for us to get to the break-even point. Notably, our tests are faster and more reliable than those available in Europe, where patent protection is less robust. Our tests are also accessible; some 95 percent of patients get insurance coverage, and we offer the test for free to those who cannot afford it. Our patents have also promoted additional research; 18,000 scientists have studied the genes, resulting in 10,000 published papers. The issue before the Supreme Court is greater than my company and our patents. If isolated DNA molecules cannot be patented, the consequences for the life sciences — and for innovation — could be devastating. ****Peter D. Meldrum** , Salt Lake City** The writer is president and chief executive of Myriad Genetics.

Parenting in the age of genetic testing, from the author of ‘The Gene Machine’

In the journey to parenthood, genetic testing is becoming increasingly common and complex. It may start with screening before pregnancy, to see if parents carry genes that could cause devastating diseases in their children. It’s usually offered in pregnancy to detect abnormalities in the fetus, and it may be used if our children have health issues, to help decipher the cause and determine potential treatments. There is no question that this technology has brought triumphs for children’s health, but it also raises difficult questions about how much control we should have over our kids’ genetic makeup and whether it’s possible to know too much about their genetic destinies.  We spoke with Rochman about the promise and perils of genetic information and what to consider before you embark on testing.     But this is controversial, because we’re now at a point where if you’re going to have Down syndrome, there’s never been a better time to have that extra copy of a chromosome. There’s more support and research, and life expectancies have increased. So, at the same time that there has been so much progress, you now have this test that people in the Down syndrome community are concerned makes it easier than ever to have an abortion. These issues are very complex, and they cut across disability and abortion — very difficult, complex themes that we grapple with every day in our society.   But the other reason why you might want to do it is simply to be prepared. If you know ahead of time that you’ll be having a baby with Down syndrome, you can choose a hospital with a NICU and specialists in case your baby has problems at delivery. You can have resources in place, seek out other parents of children who have Down syndrome, do some research ahead of time about what you might expect. You can go ahead and process it and not have that shock in the delivery room. You can’t overstate the value of that.   Genetic counselors can help you do this. These tests can reveal so much potentially powerful information that you don’t want to go into them feeling confused or unprepared. I think it’s human nature; a lot of people go into genetic testing thinking, ‘well, I’m just going to do this for peace of mind.’ But not everyone is going to get that peace of mind, so genetic counselors can help you understand what sort of information could be revealed, and is this actually something that you want to do.   I tell the story of one family who went into genetic testing because their son, Daniel, had problems with his newborn hearing test. The testing did not reveal any useful information about why Daniel had minor hearing loss, but it did reveal that he had an unrelated genetic deletion [with unknown consequences]. Daniel’s parents felt completely blindsided. They were then worried about their son and his future, and then the mother found out that she shares the genetic deletion, so she’s worried about herself, when before, her life seemed fine. It harkens back to ‘be careful what you ask for,’ because you might get it, and it might be very different from what you expected.   Let’s acknowledge where we are in this incredible age of access to information through genetic technology, and let’s go into this with our eyes wide open and be very aware of all the ethical components that are connected to this technology. Let’s think about who should be making decisions about what kinds of children are born, and what we should know about our kids.

Four unexpected ways people are using drones

From national security surveillance to your cousin’s summer wedding, drones are being deployed to capture aerial images more frequently than ever before. Serving as a camera in the sky may be their primary value to date, but devotees of the unmanned aircraft see greater potential in the technology. In addition to high-definition cameras, drones can transport a variety of information-gathering hardware, giving them purpose that spans from recreation to health to science. Take a look at some of the unique and unexpected ways drones are being used today — and could be used in the near future.  Tom Davis started a side business that collects aerial images for real estate and entertainment companies using drones, but his company Aerial Anthropology has found a new focus of late. The Cleveland-based firm now uses drones to show people with terminal illness and living in hospice their beloved locations, such as a childhood hometown or favorite vacation spot, one final time. “They’re watching live on a screen while the drone is actually at their location of choice,” Davis said. “They can interact and say let’s go over here, let’s go a little higher, let’s go out on the water.” Davis said patients are grateful for the visual escape, and he now hopes to expand the concept beyond Ohio.      At the University of Nevada at Reno, researchers are developing a drone that monitors the path of blind runners using a pair of cameras and emits sound to guide those runners as they make their way around a track. Eelke Folmer, an associated professor at the university, hopes the drone will allow the visually impaired, a group that suffers from higher rates of obesity, to exercise more easily. But the technology still has room for improvement, Folmer cautions. For one, even the most advanced commercial drones have a flight time of up to 25 minutes and might tire before the athlete. The limited accuracy of GPS technology also restricts the drone’s ability to navigate treacherous or compact spaces with precision. “This is an ambitious project, and we’re doing the baby steps right now,” Folmer said.   Meanwhile, the Woods Hole Oceanographic Institution, a private research facility in Cape Cod, Mass., has used the flying devices to collect photographs and breath samples from humpback whales for scientific research. A drone affixed with petri dishes hovers over the animal’s blowhole as it exhales, then returns to a ship where the sample is immediately frozen, said assistant scientist Amy Apprill. Scientists then study the microbes in each breath sample, and compare them across different species and environments.

Irwin Rose, who shared 2004 Nobel Prize in chemistry, dies at 88

Irwin A. Rose, the Brooklyn-born biochemist who shared a 2004 Nobel Prize for explaining how living cells recycle and dispose of unneeded molecules, a discovery that opened the way for new medical therapies, died June 2 in Deerfield, Mass., at the home of a son. He was 88. His son Robert Rose confirmed the death but did not cite a cause. In the cellular process discovered by Dr. Rose and two Israeli scientists, a molecule called ubiquitin marks unwanted molecules for destruction by latching onto them in what has been described as a molecular “kiss of death.” Ubiquitin, as its name suggests, comes from the same root as ubiquitous, in recognition of its virtual omnipresence within cells. The delineation of the role of ubiquitin was carried out in the early 1980s at the Fox Chase Cancer Center in Philadelphia by Dr. Rose and the two Israelis who were there on sabbaticals, Aaron Ciechanover and Avram Hershko. In the Bible, Ecclesiastes speaks of a time to build up and a time to break down. To a great degree, modern biology has been the story of DNA and its role in building up the proteins required for life. Dr. Rose and colleagues focused their efforts on the other part of the cycle of life: how molecules are broken down. In this, they were recognized in their discipline as boldly swimming against the current. Yet the work seized the scientific imagination, and the dramatic nature of the processes identified could be recognized in the vivid language of the news release issued in 2004 by the Nobel committee. It was in the news release that the clutching of the doomed proteins by the ubiquitin was described as a biochemical “kiss of death.” In another seeming departure from the often staid language of the scientific world, the release went on to say that after being targeted, the unwanted proteins were sent into what were in effect cellular “waste disposers.” These structures, contained within individual cells, are known as proteasomes and, in them, undesired protein molecules are chopped into bits. Not an indiscriminate sweeping out of the cell interior, the destruction process mediated by ubiquitin is highly specific and selective. After embracing the particular protein molecule that is fated for destruction, ubiquitin journeys with it through the cell to the proteasomes. A process of shape recognition prompts proteasome ingestion of the unwanted molecule. Before this occurs, according to scientists’ understanding, the ubiquitin detaches, taking its leave of the soon-to-be consumed protein, to return to the job for which it was created. In itself, the mere elucidation of so subtle and sophisticated a molecular process might seem a milestone of research. To the Nobel Prize winners’ colleagues, it was even more, offering new approaches to the understanding of such basic processes of life as DNA repair, cell division and the operation of the body’s immune system. Specialists in the field have said that a cell’s inability to eliminate unwanted proteins may lead to illness, including types of cancer. Specialists in the field have said that understanding the process by which cells destroy proteins may aid in developing treatments for cystic fibrosis, forms of cancer and other ailments. At the time the Nobel Prize was awarded, Harvard cell biologist Alfred L. Goldberg lauded it as a “particularly insightful” choice. Dr. Rose and the two Israelis, he wrote, were scientists “whose seminal work has altered modern biology.” Since the inception of the Nobel Prize, Americans have won almost half . Many American winners have immigrated from other countries, but Dr. Rose’s first school was P.S. 134 in Brooklyn and all his succeeding work was done in this country. Irwin Allan Rose, who was often called Ernie, was born July 16, 1926, and lived in Brooklyn until the age of 13, when it was decided that dry climate might benefit a younger brother with rheumatic fever. His mother took her two sons to Spokane, Wash., where they had relatives. Dr. Rose’s father stayed in New York to look after his flooring business — an arrangement, the future Nobel laureate later wrote, “that I never understood and felt conflicted about. Father’s visits were few and far between.” His mother did secretarial work in the Navy Supply Depot in Spokane during World War II. In summers, Dr. Rose worked at a local hospital, which ignited his interest in “solving medical problems.” After Navy service as a radio technician during the war, he went to the University of Chicago on the GI Bill and received a bachelor’s degree in 1948 and a doctorate in biochemistry in 1952. Within a few years, he joined the faculty of the Yale University School of Medicine, where he met his future wife, Zelda Budenstein, a graduate student who became a research scientist. In a Nobel Prize biographical sketch, Dr. Rose acknowledged the contributions of his mother-in-law to his wife’s career and his own. Her help with the Roses’ four children helped make time for the couple to pursue their careers in science. In addition to his wife, of Deerfield, survivors include twin sons Frederic Rose of Deerfield and Robert Rose of Raleigh, N.C.; another son, Howard Rose of San Francisco; a brother; and five grandchildren. A daughter, Sarah Rose, died in 2005. Dr. Rose, who became a member of the National Academy of Sciences, left Yale for Fox Chase in 1963 and remained there until his retirement in 1995. He moved to Laguna Woods, Calif., but was restless without a laboratory and, through a friend, continued to conduct research at the nearby University of California at Irvine. He was at Irvine when the Nobel Prize was announced. Colleagues described him as modest, unpretentious and devoted to his work. On the day the Nobel Prize was announced, the California university said, “he tucked two test tubes in his shirt pocket and that night quietly slipped into” a campus building housing a powerful mass spectrometer to analyze the contents.

It looks like Trump has enraged yet another American industry

“Though the ban from the Trump administration is aimed at seven countries, our global employees interpret the underlying message as, 'America is no longer welcoming of any immigrants, whatsoever,'" wrote chief executives, venture capitalists, academic leaders and at least one Nobel Prize winner. “If this misguided policy is not reversed, America is at risk of losing its leadership position in one of its most important sectors, one that will shape the world in the twenty-first century.”  “What this letter represents is the voice of the innovative, entrepreneurial biotechnology industry, which places basic human values ahead of economic gain,” said Steven Holtzman, chief executive of Decibel Therapeutics, an early stage company developing drugs for hearing loss based in Cambridge. Biotech is a relatively young industry born from the emerging understanding of genetic science in the 1970s, best known for complex, expensive drugs created by living organisms. As science has advanced, biotech has become an increasingly broad term for the research-driven, startup-heavy wing of the drug industry trying to turn cutting-edge science into new medicines. As the research and development pipelines of traditional drug companies have dried up, biotech has become increasingly important — economically and to the development of new medicines.  “Without those immigrants, cancer treatment today would never be in the kind of position that it is today,” Jeremy Levin, chief executive of Ovid Therapeutics, said. “For me, the core of innovation — the heart of innovation — resides in America. It resides here because of the borders that we’ve opened to these scientists that have come from abroad; it resides here because of the tremendous capital and infrastructure we’ve built.” The letter-writing effort began informally, when late last week half a dozen colleagues, including Holtzman and Levin, decided they needed to say something about Trump's executive order. They drafted the letter collectively and sent it out to colleagues over the weekend to see if any would sign on. It quickly went viral; they accumulated more than 160 signatures over 96 hours. Holtzman said his mother came to the United States from Cuba as a child and his father's family came to escape religious persecution. Neither of his parents graduated high school, and yet Holtzman has been involved in creating new medicines at six biotechnology companies. His current company, a year-old start-up, has about 40 employees — a quarter of whom are either first-generation or foreign born. “Could such a story be told in Trump's America?” Holtzman asked. Levin is both an immigrant and a refugee. His family was expelled from South Africa during apartheid when he was a child. He also feels that he knows the threat terrorism poses more personally than some. As the former chief executive of generic drug company Teva Pharmaceutical Industries, he recalls touring a factory in Israel on the border while rockets were being fired by Hamas. “I believe you hunt down and destroy terrorism,” Levin said. “I know it more than most people who are in my industry, because I experienced it.” What the executives agree is that the executive order could have far-reaching effects on American business and on the health of sick people. “It will harm an industry dominated by smaller companies and start-ups, the very kind of industry the administration has said it wants to support,” the letter states. “It will slow the fight against the many diseases that afflict us, as well as carry negative economic consequences for the United States.”

China’s on track to surpass our investment in science

The science community’s frustration with the new administration is warranted. But a crisis has been building for more than a decade, for nonpartisan reasons. Over the past 15 years, the United States has slowly watched its global leadership in science stagnate. And while we’ve slowed down, China has developed its commitment to science at breakneck speed.  This isn’t to suggest that the United States has lost its leadership role in scientific research. But at the rate China is investing in its scientists, the country seems poised to surpass U.S. research spending in the near future.  And it’s not just spending; it’s publishing, too. The JCI Insight article found that Chinese researchers have consistently increased the number of articles they publish in high-ranking biomedical journals. The United States, on the other hand, has seen the number of articles published solely by American authors decline during the same time. This not only has the potential to affect the prestige of our research institutions; in the long run, it could also even affect their ability to compete as fundraisers. To some extent, this shouldn’t be a shock. China makes up about a fifth of the world population; the United States is less than 5 percent. It’s no surprise that, given China’s incredibly rapid ascent into the developed world, its capabilities in science would rise at extraordinary rates as well. Nonetheless, science fuels our economy. It’s the basis of our industry, investment and jobs. The United States currently serves as the unquestioned center of higher education in the world. What happens to our country when research institutions elsewhere — under authoritarian regimes such as China’s — start attracting the best and the brightest? What happens to our cities and local economies, which are already painfully strained by the shock of new competition from rapidly developing nations?  Still, the administration would be wise to seriously reconsider its investment in research. This simply is not the time for the United States to give up on its commitment to science.

Book review: ‘The Patient Will See You Now,’ on future of medicine, by Eric Topol

_Perri Klass is a professor of journalism and pediatrics and the director of the Arthur L. Carter Journalism Institute at New York University._ By Eric Topol Basic. 364 pp. $28.99 Eric Topol’s heroes include actress Angelina Jolie and entrepreneur Elizabeth Holmes. He celebrates the autonomy with which Jolie evaluated the information about her genetic risk of cancer and made the decision to have a double mastectomy, as well as her impulse to go public with that decision. She chose to use her visibility and Hollywood’s culture of beauty-worship to make her medical story headline news and to encourage other women to learn their genetic risks and make the relevant medical decisions. In publishing her story, Topol says, Jolie “symbolized the new era of medicine, whereby access to critical information about oneself — in this case genomic information — leads to the individual’s empowerment to make a pivotal choice that determines one’s fate.” Holmes, the founder of a company that seeks to revolutionize the technology of blood tests, is another kind of hero — the technological visionary who finds new, digitally based ways to surmount traditional roadblocks to medical testing and get patients their results swiftly. Topol describes the experience of having a droplet of blood taken painlessly from his finger: “Over fifty tests were analyzed . . . and I got the results back in just a matter of minutes.” In “The Patient Will See You Now,” Topol, a cardiologist and a pioneer in genetics and technology, builds on the arguments of his earlier book “The Creative Destruction of Medicine.” He argues that it is critical for people to know as much as possible about their bodies and their health, from their genetic codes to the moment-by-moment information that implanted sensors might transmit about their bloodstreams, their airways and their hearts. All this information in theory could be registered immediately; tracked to each individual’s cellphone; and used to stave off illness, avoid crises and initiate therapies at optimal moments. The book is written in an exhortative, even urgent voice; as the subtitle suggests, “The Future of Medicine Is in Your Hands.” Topol urges readers to make use of technology, digital know-how and entrepreneurial creativity to learn as much as they can about their health, to know it all, own it all and manage it on their personal devices. “For just as Gutenberg democratized reading, so there is the chance that smartphones will democratize medicine. That will ultimately be achieved when each individual has unfettered, direct access to all of their own health data and information.” And the obstacle? What stands most in the way, according to Topol, is an entrenched culture of medical paternalism, which he gleefully traces back to the original Hippocratic Oath. And for the most part, it is this paternalism that he blames for problems large and small, from the long waits for medical appointments (and the long waits in doctors’ waiting rooms), to the barriers that divide people from their own lab results and medical records, to the medical errors that endanger patients in hospitals. The more that patients control their data, the author argues, the safer and more individualized medical care can become. Thus the vital importance of technological advances that allow quick and accurate access to that information and place it literally in the hands — or handhelds — of those seeking medical care, and not just in those of the providers. “The Patient Will See You Now” is full of innovative thinking. Readers learn about devices that can measure body chemistry, organ function or medical risk, integrate that information instantly into a profile of their health, and offer answers to questions they didn’t even realize they ought to be asking. Topol’s argument is that these devices and this kind of patient involvement have the potential to revolutionize the practice of medicine, eliminating many of the abuses of medical paternalism by returning information (and the power that it brings) into the hands of patients. And he presents many intriguing scenarios in which technological creativity offers everything from telehealth — “My (Smartphone) Doctor” — to cheap, fast skin tests for diagnosing malaria. But however exciting the technology, it’s important to keep in mind that devices, tests and therapies are all tools, with no inherent moral valence, and that one of the recurring lessons of medical history is that exciting discoveries and promising therapies can also carry dangers, unexpected outcomes — physical, ethical and social. In addition to the very real issues of entrenched paternalism, many problems that inhibit good patient care reflect the uneasy intersection of market forces and medical practice, from productivity pressures applied to doctors by their institutions (see more patients, spend less time with each one) to paperwork overload (if you want to prescribe a drug that will cost us more, we’re going to make you spend a lot of time filling in forms and waiting on hold on the phone). The market plays a complicated role here, and new products and technologies are not guaranteed to make life easier or more convenient for patients or doctors. Any discussion of increasing, accumulating and analyzing personal medical data raises important questions about privacy and confidentiality. Topol acknowledges this issue, exploring the problems of identity theft and hacking and the question of whether your insurer should have access to all possible medical data. He believes that keeping patient records secure is possible, noting in particular that “anything that will better protect the genomic privacy of an individual should be pursued.” But the questions are huge and complicated, and if the changes that Topol describes are coming as quickly as he hopes, they’re going to require development of new technical and legal protections so that we keep ourselves safe and healthy in every sense. Topol sees a future in which “your smartphone will become central to labs, physical exams, and even medical imaging; and . . . you can have ICU-like [intensive-care unit] monitoring in the safety, reduced expense, and convenience of your home.” This is a book full of technical wizardry and intriguing questions about the nature — and the future — of diagnosing, monitoring and healing.

Scientists embark on unprecedented effort to connect millions of patient medical records

Inside an otherwise ordinary office building in lower Manhattan, government-funded scientists have begun collecting and connecting together terabytes of patient medical records in what may be one of the most radical projects in health care ever attempted. The data — from every patient treated at one of New York’s major hospital centers over the past few years — include some of the most intimate details of a life. Vital signs. Diagnoses and conditions. Results of blood tests, X-rays, MRI scans. Surgeries. Insurance claims. And in some cases, links to genetic samples. The effort is being duplicated at 10 other sites across the country using data from hospitals, academic research centers, community health clinics, insurers and other sources. If all goes well, by September 2015 they will be linked together to create a giant repository of medical information from 26 million to 30 million Americans. Nothing of this scale has been built before, and researchers say the potential of the network to speed up research efforts and to answer questions that have long vexed scientists cannot be overstated. But the creation of the network presents tricky ethical questions about who owns and controls the data, how to protect patient privacy and how research questions will be prioritized. “Both the opportunity and the anxiety are pretty electrifying,” Francis S. Collins, director of the National Institutes of Health, said in an interview. The origins of the patient project lie in an obscure part of the 2010 Affordable Care Act. As part of the nation’s health-care overhaul, Congress created an independent nonprofit group to help patients and their doctors make better-informed decisions about care. Dubbed the Patient-Centered Outcomes Research Institute, or PCORI, and based in the District, the organization’s mandate is to launch, fund and coordinate research on “comparative effectiveness” — to find out which drugs, devices and treatment options are more effective than others. Do certain sets of behavioral interventions work better than others for weight control, for example? Might certain antibiotics work better for cystic fibrosis patients, based on their genetic profile? Such questions have been surprisingly difficult to answer, despite the thousands of clinical trials published every year. Physicians have long grumbled that few studies can be translated into practical advice. Some studies are too small to draw any definitive conclusions. Others include patients diagnosed with a single condition, while most patients are more complicated — they suffer from multiple issues. It isn’t uncommon for studies to contradict each other, and there’s no way for clinicians to know which one is right, because they often use different methodologies. “The whole idea was to create a way to do the kind of research that would inform the real world,” explained Eugene Rich, who researches health-care effectiveness for Mathematica Policy Research, based in Princeton, N.J. The database — an idea that has been talked about for years by everyone from insurance companies to Google but has never been successfully executed — holds the hope that some of those obstacles can be overcome. “We will be able to get answers with a degree of certainty that we’ve never had before,” said Joe V. Selby, PCORI’s executive director, who calls the patient records network “the holy grail” of health-care research. Collins said the value of the network is that it gives scientists the ability to ask an endless number of questions about a massive patient population with great speed and little cost. In the randomized trials that NIH typically supports, “you have to enroll patients from the very beginning, and that’s a big infrastructure-building process that can take quite some time. And once a trial has been conducted, the whole thing has to be taken down again,” Collins said. “It’s a great way to answer one specific question, but it’s not an efficient way to ask lots of questions,” he explained. Before PCORI’s vision can be realized, the project’s leaders must overcome numerous hurdles. The technical challenges of the project are enormous. The specter of the botched launch of HealthCare.gov haunts anyone trying to get large numbers of separate computer systems to talk to each other. But it is the larger questions about governance that have triggered conflict and worry in the nation’s health-care community. How will research questions be prioritized? How should disagreements be resolved? Should pharmaceutical companies and insurers be able to access the records and, if so, under what circumstances? What about the Centers for Disease Control and Prevention? The information could help epidemiologists track outbreaks and clusters of disease in a way they have never done before. And, critically important to the multibillion-dollar pharmaceutical industry, how will the Food and Drug Administration view this type of research when considering applications for new drugs or in recalling old ones? PCORI was never imagined to be the custodian of this kind of data network. It was designed to launch and fund research in a manner similar to NIH and the National Science Foundation. But it did not get nearly the same kind of funding. President Obama’s budget request for fiscal 2015 included $30.4 billion for NIH and nearly $7.3 billion for NSF. But PCORI, which is funded through several streams, gets only about $500 million annually. Large, randomized clinical trials such as the ones NIH does for important questions cost upwards of $150 million, meaning that PCORI has enough to fund only two or three a year. “So about a year ago, PCORI started talking about whether there is another model that is different from the NIH model, which would be more about embedding clinical studies in the fabric of day-to-day care,” said Robert W. Dubois, chief science officer for the National Pharmaceutical Council, a health policy research group funded by the industry. The PCORI network, which is being built at a cost of nearly $100 million, would also be a way to pinpoint patients with certain criteria who could be invited to join a clinical trial. As it stands today, identifying patients eligible for trials is often time-consuming, expensive and hit-or-miss. Researchers must use a variety of tools to get enough participants, including reaching out to a network of doctors who then contact their patients and the old-fashioned method of putting up fliers in places where people with the criteria they are looking for congregate. The new national patient network will comprise 11 sub-networks that include records from New York and Chicago, children’s hospitals, Kaiser Permanente and other groups. Each participating organization retains all the personally identifiable data and would have the right to accept or decline a research proposal. If a research project is greenlighted, each of the smaller networks would analyze its own databases and return an anonymized, aggregated response to the researcher. “The raw data is not what is being shared. That remains with the institution that the patient trusts,” said Devon McGraw, director of the health privacy project for the Center for Democracy and Technology and head of the data privacy task force for PCORI. Privacy experts say the general consent forms that patients sign when they get treatment should allow the use of data already collected in the aggregate. Hospitals and other organizations participating in the project don’t have any plans to explicitly inform patients about this. If researchers wanted doctors to collect additional data as part of a clinical trial, the researchers would clearly have to get a patient’s consent. But what about projects that involve more detailed analysis of individual patient histories? One aspect of the project that was highlighted by researchers involved is that it has included patients at every step. Patient panels have been convened to help suggest research questions, and patients serve on the committees looking at privacy and data security. Rainu Kaushal, a researcher at Weill Cornell Medical College who heads the New York-based part of the project, said patients’ perspectives on studies are often very different than scientists’. “As a provider, I may be interested in how a serum marker changes with a treatment. But patients may be more interested in how it affects how they feel, their ability to exercise and eat,” she said. Brian Currie, vice president for medical research for the Montefiore Medical Center, the university hospital for the Albert Einstein College of Medicine in the Bronx, which is participating in the New York network, said the number of questions are understandable given the historical barriers between different types of institutions that have prevented this research in the past. “It’s pushing all the fronts on how medical institutions do research,” Currie said.

Scientists are growing anxious about genome-editing tools

Every human genome contains the blueprints for building a person, a library of roughly 20,000 genes that encode everything from eye color to cancer risk. Imagine if those genetic instructions could be tweaked at will — with a snip here and a cut there, a gene might be deleted, inserted or replaced by a different piece of DNA. Tools that can do this already exist, but one in particular, called CRISPR/Cas 9, has leapt ahead of other genome-editing tools because it’s cost-effective and simple. Researchers say that human clinical trials to fix genetic diseases — for example, sickle cell anemia — are only a few years away. Last month, a team of Chinese researchers reported that, in a first-of-its-kind event, they had edited the genomes of human embryos. (The embryos, obtained from local fertility clinics, would not have resulted in live births because they contained an extra set of chromosomes.) The scientists’ aim was to modify the gene responsible for a common blood disorder using CRISPR. The majority of embryos developed unintended mutations, and only a small fraction of them had the blood-disorder gene correctly modified — not what you’d call a success. Many experts believe it was too soon for such work to be carried out — both because the technology is not yet perfected and because the ethical, medical and legal implications of the research have not been hashed out. Soon after the results were published — by the open-access journal Protein & Cell — the National Institutes of Health reaffirmed its ban on gene editing of human embryos. In a statement released April 29, NIH Director Francis S. Collins said that genome editing in human embryos is “a line that should not be crossed” due to safety and ethical issues “presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.” Genome editing of a human embryo would affect every cell in the embryo’s resulting fetus, as opposed to altering the DNA of a select type of cells — such as the stem cells that produce blood cells. “You can think about it as a molecular scalpel,” said biochemist Jennifer Doudna of the University of California at Berkeley. “It’s a way for making a really precise change in an organism, such as changing a disease-causing mutation into one that is harmless.” The CRISPR system is a collection of molecules that work together to edit an organism’s DNA. These molecules can be packed into an empty virus and then injected along with a molecule to jump-start the process once the virus encounters a cell. Another approach is to remove cells with undesirable mutations from the body, edit them in a petri dish and insert them back into the body. Such an easy method of genome manipulation has prompted tremendous excitement in the biological sciences community, as a flood of academic labs and start-up companies scramble to take advantage of CRISPR’s capabilities. But with that buzz have come big ethical questions. “No one should be doing anything right now until we figure out what the hell is going on with this technique in animals,” said bioethicist Arthur Caplan of New York University. “That’s how we perfected in vitro fertilization, and that’s how you establish safety — you do it in animals first.” But amid the fears of mad scientists creating designer babies and real-life Jurassic Parks, experts agree on one thing: It is no longer a matter of if but rather of when CRISPR-based genomic surgery will come to a hospital near you. Genomic sequencing is readily and cheaply available, and genetic testing and disease screening have long been underway in clinics across the country. “As much as we worry about premature or ethical use, using these technologies to get rid of genetic disease would be amazing: Tay-Sachs, cystic fibrosis, sickle cell disease, hemophilia,” Caplan said. “We’ve never really wiped out a disease except for smallpox, and these technologies might actually add to the list.” Rumors of the experiment by scientists based at Sun Yat-sen University in Guangdong spurred others, including Doudna, to meet in January to discuss the future of the technology and its responsible use in humans. A particular focus was germline editing, which refers to changing the DNA of fertilized eggs or embryos. Such editing affects all cells in the developing organism and passes those changes down to future generations. The scientists, in a summary of their meeting published by the journal Science in April, strongly discourage their colleagues from attempting any germline editing in humans. However, they remain supportive of basic CRISPR research on animals and non-embryonic human cells to see if human germline gene therapy might be helpful in the future to fix genetic mutations. Doudna is planning to convene a larger, international meeting later this year. “We really need to be getting in front of this conversation,” she said. “The field has just taken off in an unbelievable way, with many hundreds of papers being published in the scientific literature now, not just in human health but other areas as well.” While Doudna and French microbiologist Emmanuelle Charpentier are commonly cited as the inventors of CRISPR/Cas9, we can actually thank modest, single-celled bacteria for this revolutionary genome editing system. “CRISPR” stands for “clustered regularly interspaced palindromic repeats,” first described in 1987 by Japanese researchers who found chunks of oddly repeating DNA sequences in the genome of _E. coli_. It wasn’t until about 15 years later that scientists realized the purpose of CRISPRs: They are a key part of the bacterium’s immune system. Each CRISPR is followed by unique DNA segments of viruses that the bacterium previously encountered: If that type of virus tries to attack the cell again, a CRISPR can recognize and defend against it. CRISPRs have been found in 45 percent of sequenced bacteria genomes and in 84 percent of archaea, a type of single-cell microorganism. Cas9, a scissors-like enzyme, uses the viral DNA segments as an identification system to check for foreign invaders. If the DNA of an incoming suspicious entity is a match, Cas9 proceeds to chop up the intruder’s genetic material by severing both strands of the double helix molecule. In 2012, Doudna and Charpentier published a study in which they adapted parts of the bacterium’s immune system to create a simple two-part genome editing tool: The Cas9 enzyme and the guide sequence — a small piece of single-stranded RNA 20 nucleotides, or “letters,” long — could be used to target any spot in the genome for cutting. From that point on, CRISPR/Cas9 technology exploded. The next year, it was used to edit the genomes of human and mouse cells, followed by frogs, monkeys and such crop plants as rice and wheat. “The range of possible applications is really quite broad, but translating from this very experimental science into real therapeutics — there is a lot of work to be done,” said Katrine Bosley, chief executive of Editas Medicine, a start-up in Cambridge, Mass., that is trying to develop CRISPR/Cas9-based drugs to treat genetic mutations. Perhaps the biggest issue left to solve involves off-target cuts, which occur when Cas9 gets a bit snip-happy and chops the genome in unintended places. These mistakes can cause big problems, including cell toxicity and cancer. “Sometimes Cas9 can recognize sequences that are very similar but not identical to the target sequence,” said biological engineer Feng Zhang of the Massachusetts Institute of Technology, a co-founder of Editas and head of a lab at the Broad Institute, a Harvard-MIT biomedical research collaborative. “Depending on the specific sequence, the off-target effect may be more severe or less of a problem.” Biomedical engineer Gang Bao of Rice University said that scientists cannot answer yet whether, even with some off-target effects, it can be used for humans. In his lab, Bao is analyzing off-target effects for his treatment of the genetic mutation that causes sickle cell disease. The idea is to take blood-cell-producing stem cells from a patient, use CRISPR to correct the mutation and then reinsert the stem cells back into the bone marrow. Every step of the process requires precision, from minimizing off-target cuts to getting the modified stem cells to survive and transform into blood cells. After having initial success using CRISPR therapy with mice, he has moved on to inserting human stem cells into monkeys for his experiments. He hopes to initiate the first human clinical trials in 2018. Editas is taking a different approach, working to neatly package CRISPR/Cas9 into a virus for direct delivery into the patient’s body and letting the genome editing happen there. For certain diseases, such as cystic fibrosis, which affects the lungs and other organs, Editas researchers must figure out how to get the viruses into the right cells while avoiding others. “From the patient’s perspective, [the therapeutic] would be an injection of some sort — maybe an IV, maybe a local injection,” Bosley said. “If you’re working on a genetic disease of the eye, you might do a direct injection into the eye.” Bao and Bosley say they aren’t interested in germline editing and don’t believe that it is necessary for the medical applications they are working on. Their work, which involves modifying somatic, or non-germline, cells, might have unexpected consequences down the line as well. The technology is so new that no one really knows.

High prices make once-neglected ‘orphan’ drugs a booming business

Three decades ago, Congress listened to the plight of Americans sick with diseases so rare many people had never heard of them. They were victims of a pharmaceutical market failure — “orphans” ignored by drug companies because, the thinking went, tiny groups of patients would lead to trifling sales. To make the business viable, Congress — pushed by patients and a popular television show that highlighted rare diseases — passed the Orphan Drug Act. The 1983 law offered drug companies attractive tax credits and monopolies to develop treatments for rare diseases, radically transforming the pipeline of orphan drugs. Now, rare diseases are no longer a neglected niche of the pharmaceutical business; they are a tantalizing moneymaking opportunity. More than 400 treatments have been approved since the law passed. Last year, nearly half of all novel drugs approved were treatments for orphan diseases. But critics and some medical experts are concerned that the Orphan Drug Act may have backfired. Pharmaceutical companies can reap huge profits because of the most important perk offered by the law: a period of market exclusivity that prevents competition for seven years. That has paved the way for drug prices so high that a single year of treatment can cost more than a car or even a house. Since the act passed, the median launch price of orphan drugs for chronic use has doubled every five years, according to an analysis presented in May by a team of Massachusetts researchers. In one way, this is a straightforward success story: Patients with rare and often devastating diseases have the attention of drug companies and a growing trove of treatments. Despite the drugs’ high list prices, patients generally are not on the hook for the full amount, thanks to insurance, secret rebates and assistance programs underwritten by drug companies. As the rare-disease drug business has expanded, though, the high prices could drive up insurance costs for everyone. Spending on orphan drugs is growing twice as fast as the overall drug market, according to the market research firm Evaluate. For example, the orphan drug Soliris has an average annual cost of up to $488,000 per patient for the treatment of paroxysmal nocturnal hemoglobinuria — one of two ultra-rare diseases for which it is approved. It netted $2.59 billion in sales last year. Rituxan, an orphan cancer drug sometimes called “vitamin R” because it has become an important treatment for so many diseases, had worldwide sales of more than $7 billion last year. “We’re seeing the Orphan Drug Act used in ways that we never anticipated when the law was adopted,” said former congressman Henry A. Waxman, the California Democrat who was the principal author of the bill and now works at his son’s lobbying and communications firm, Waxman Strategies. “In the way people use the word ‘orphan status,’ it’s almost becoming a synonym for a monopoly price. Sounds like it’s good to be an orphan.” That wasn’t always true. In the late 1970s, Abbey Meyers was a young mother from Connecticut who had finally found relief. Her son, David, was taking an experimental drug for Tourette’s syndrome, a rare disease that causes motor and vocal tics. The treatment worked. But when the drug failed the main trial for a common illness, the drugmaker stopped supplying it. After testifying at a congressional hearing, Meyers was invited to speak with drug executives. “You have grandchildren — what if it was one of your grandchildren?” Meyers recalled pleading. The problem gained national attention when the popular medical drama “Quincy, M.E.” aired an episode on Tourette’s and actor Jack Klugman, who played the medical examiner at the center of the show, testified before Congress. As written, the law sought to fix a clear market failure: “Because so few individuals are affected by any one rare disease or condition, a pharmaceutical company which develops an orphan drug may reasonably expect . . . to incur a financial loss.” “It gave them the realistic chance of making a profit,” said Meyers, who would go on to found an advocacy group, the National Organization for Rare Disorders. “It was not going to be a great big profit. . . . It was only going to be reasonable profit, because the market was very small.” For drugs treating diseases that affect fewer than 200,000 people in the United States, the law provides tax credits for half the cost of clinical development, seven years free from competition, and waived fees. The debate over profits began not long after the law was adopted. Congress passed an amendment that would have increased competition and revoked exclusivity if the drug’s target population grew to more than 200,000, but President George H.W. Bush refused to sign it into law. Two years later, a proposed amendment would have terminated the exclusivity early if a drug reached $200 million in annual sales. Henri Termeer, then the chief executive of the Massachusetts biotechnology company Genzyme, appeared before Congress to argue against the cap, which was never passed, and defend a $300,000-a-year treatment for a rare metabolic disorder called Gaucher disease. In his testimony, Termeer said the cost of the treatment, Ceredase, would naturally drop “in the affordability range” — without a change to the law — because the dose could be reduced over time. That never happened. Lower doses did not control the disease as hoped, and the next generation of the drug, called Cerezyme, became a blockbuster, hitting a billion dollars in annual revenue. There are now five drugs for Gaucher disease, which has been diagnosed in 10,000 people worldwide. Two are made by Genzyme and are both priced around $310,000 a year. David Meeker, the current head of Sanofi Genzyme, said that the Orphan Drug Act is an important law but that the proof of profitability has been crucial in establishing the industry. “It suddenly created a business model that said you can go after these incredibly rare diseases and survive,” Meeker said. Not every drug is a success, but the appeal of the niche is clear. In 2014, the average annual cost per patient for the 100 top-selling orphan drugs in the United States was nearly $112,000, compared with $23,000 for non-orphans, according to an Evaluate report. And orphan drugs are generally cheaper to develop. The largest, most expensive clinical trials for orphan drugs cost about a quarter as much as those for non-orphan drugs, after the tax credits are factored in, according to the report. Nowhere are the strange economics of drug pricing more difficult to understand than when a drug invented decades earlier is granted orphan status — and an orphan price. Last summer, an old glaucoma drug was reborn as an orphan for a disease called periodic paralysis. Its list price was $50 a bottle in 2002, according to Truven Health Analytics. In 2015, it was relaunched by Taro Pharmaceutical Industries with a new brand name, Keveyis, and a new price: $13,650 a bottle. The relaunch of the drug was first envisioned by a family with unusual connections to periodic paralysis and the pharmaceutical industry. Jacob Levitt, a member of that family, experienced his first attack of paralysis at a karate lesson when he was 12, three decades ago. Jacob sat down on the floor, and when he tried to stand up, he couldn’t. A neighbor slung the boy over his shoulder and drove him home. His father, Barrie Levitt, a physician and then-chairman of Taro, drew blood and raced to his Manhattan medical office in the middle of the night to run tests. By the next day, Jacob Levitt’s scary illness had a name: periodic paralysis, an ultra-rare disorder that causes temporary bouts of immobility and muscle weakness. Patients can wake up paralyzed and go through their days feeling as if they are wearing lead shoes and a 50-pound backpack. Jacob Levitt began taking an old glaucoma treatment that is sometimes used off-label to manage periodic paralysis. It worked, and he was able to continue practicing karate and went on to become a doctor and a vice president at Taro. In the early 2000s, a similar glaucoma drug called Daranide was discontinued by Merck, leaving many periodic-paralysis patients without their best option for controlling their disease. The Levitts wondered whether Taro could help launch it as a generic drug that could be used off-label, like Jacob’s medication. Taro bought Daranide from Merck for less than half a million dollars in 2008, according to the Levitts. Two years later, Taro filed for orphan status. Then in 2010, after a contentious corporate and legal battle, the Levitts were forced out of Taro and the company was taken over by Sun Pharmaceutical Industries, the Indian drugmaking giant. Under the new leadership, Taro got orphan approval in 2015 and priced the drug at more than 270 times its last price. Credit Suisse analysts estimated the drug could bring in $100 million per year for Taro, with a “blue sky” scenario of up to $600 million. In May, however, the company changed its plan and announced the drug would be given away free. Taro said it had made less than $1 million selling Keveyis and spent millions on patient support services, medical education and promoting disease awareness. Experts who track the industry said that the sudden reversal on price is an uncommon move. But it is not uncommon for companies to recycle old drugs as orphans and stamp them with a price hike. For example, a decades-old pregnancy drug received orphan approval in 2011 as a treatment to lower the risk of preterm birth. The drug was previously available from compounding pharmacies for $20, but the list price for the approved drug, Makena, rose to more than $1,400 a dose — although it was halved after public backlash. After receiving orphan designation as an infantile spasm treatment, H.P. Acthar Gel increased in price by more than $20,000 a vial in 2007, though it had been used since the 1950s. Today, its list price is $34,034, not including discounts. In February, dozens of physicians signed a letter in the journal Muscle and Nerve, highlighting concerns about the future price of a treatment for a rare autoimmune disease that had been around for decades, though never approved — now at risk of a hike. “What is particularly troublesome to us is a ‘loophole’ in the Orphan Drug Act that allows companies to receive FDA market exclusivity . . . for older, existing drugs,” the physicians wrote. The high prices of orphan drugs have been detached from the law’s original rationale — that incentives are necessary for companies to recoup the costs of research and development of treatments with tiny markets. Today, some pharmaceutical companies use the word “orphan” to justify a drug’s high price, whether or not that drug is protected by the law’s exclusivity. The market has come to expect high prices for any drug that treats very few patients, and the system lacks any real mechanism to counter the price increases. In a slide deck released to a Senate committee last year, Valeant Pharmaceuticals International outlined its reasoning for a price hike for Syprine, a three-decade-old rare-disease drug that ultimately went from $652 for 100 capsules to $21,267 over a five-year period. The slide explains the reason for the price hike: “Progressive pricing actions to bring in line with comparable Orphan products.” Former pharmaceutical executive Martin Shkreli, who became notorious for hiking the price of an old drug called Daraprim that is used to fight an exceedingly rare infection, called the drug an orphan even though it is not protected by the law. “This drug is priced similarly to other drugs for rare disease, and I think most physicians understand that,” Shkreli told The Washington Post last year. Orphan drugs are isolated from many of the typical pressures that bring down prices. Insurance companies often have so few rare-disease patients on their books that even a very high-priced drug gets little attention. And pharmaceutical companies fund assistance programs that ensure patients do not forgo a treatment because of its price. Drug companies argue that any change to incentives could lead the industry to abandon orphans once more. Patients and their advocates worry about that — but also see how the new market for orphan drugs gives companies virtually unlimited pricing power. In 1979, Joseph Jankovic, a physician at the Baylor College of Medicine, began treating the uncontrollable movements of Huntington’s disease, called chorea, by importing tetrabenazine, a drug not approved in the United States. For years, his efforts to interest a drug company in tetrabenazine were fruitless. The medicine cost about $200 for a 180-pill bottle. Prestwick Pharmaceuticals got U.S. orphan approval for the drug in 2008. The brand-name version, Xenazine, now sold by Lundbeck, carries a list price of $10,622 for a 112-pill bottle. “Obviously, I’m concerned about the cost of the drug, but more importantly, I’m concerned about what is the out-of-pocket cost to the patient,” Jankovic said. Cheaper generic versions entered last year after the drug’s exclusivity expired. But now a chemically altered form of the drug that breaks down slower is being developed by Teva Pharmaceutical Industries as an orphan. “On one hand, I’m encouraged by the data we just published showing that the drug is very effective in reducing chorea, with minimal side effects,” Jankovic said. “On the other hand, I’m concerned that once the drug is approved, it’s going to be perhaps even more expensive.”

In genomics, a need to balance science and privacy

GENOMICS is the study of the whole genetic blueprint of living organisms, and it is turning out to be every bit as surprising and profound as space travel or splitting the atom. A tiny bacterium may have 160,000 base pairs, the chemical bits that make up the strands of DNA and RNA, while a human genome has 3 billion. The ability to map this information, known as genetic sequencing, has raced ahead with new technology, opening vistas on how genes function, how organisms compare with each other, how diseases take hold — and, perhaps, how they can be conquered. The sequencing technology has also produced an avalanche of data. The genetic blueprint can be stored, compared, studied and transmitted as a digital file. In general, in the study of human genomes, it has been common practice for scientists to share sequencing data without the identity of the person from whom it came. But an important announcement from the National Institutes of Health has cast light on the need for more debate and clarity on a subject certain to challenge both science and individual privacy in the future. The announcement concerns Henrietta Lacks, a poor black woman from Baltimore who was being treated in 1951 for cervical cancer at Johns Hopkins Hospital. At the time, doctors removed some of her tumor cells without her knowledge or consent. She died soon after at age 31, but the cells lived on — they showed a remarkable ability to grow endlessly in culture and became a bedrock of biomedical research around the world. However, as author Rebecca Skloot documented in her bestselling book, “The Immortal Life of Henrietta Lacks,” the descendants of Ms. Lacks did not know for many years that her cells had played such an important role in science. In March, researchers in Germany published a scientific paper online that described the genome sequence of the HeLa cell line. The research could, at least in theory, expose possible disease risk among the Lacks family, yet once again its members had not been told or consulted. Six decades ago, when the original cells were taken from the tumor, there was no requirement for Ms. Lacks to give consent. But now that sequencing can expose an intimate genetic blueprint, does the family deserve some privacy or at least a role in deciding how the information will be used? In a significant decision, Francis S. Collins, the NIH director, and Kathy L. Hudson, deputy director for science, outreach and policy, have announced an agreement with the Lacks family that the genome sequence will be used for research only under “controlled access,” in which researchers must agree to terms beforehand and two members of the family will sit on a panel reviewing proposals. The agreement is a smart first step, but the issue will grow only larger in the years ahead. Genetic data can be so revealing that it may not be possible to keep such information totally anonymous. A balance may have to be found between individual rights to privacy and the value of open, shared knowledge in advancing scientific discovery. **Read more on this issue:** She the People: Family of Henrietta Lacks gains some control over her cells and – perhaps – peace

One big myth about medicine: We know how drugs work

Here’s how we think we discover powerful new medicines: Scientists dig deep into biology and zero in on a molecular Achilles’ heel that could disable a devastating disease, be it cancer or an infection. They concoct experimental drugs that hit the target. Then they conduct trials to find one that is safe and effective in people. Here’s how we actually develop a surprising number of treatments: good old-fashioned observation, trial and error, and luck. Detailed scientific understanding of how a drug works often comes, ironically enough, near the end of the process. “It’s sort of a fairy tale,” said Jon Clardy, a professor of biological chemistry and molecular pharmacology at Harvard Medical School, of the idea that drugs are born mostly from reason and not serendipity. “If you think of it as an aspirational goal, it’s fine.” Understanding how drugs are developed matters crucially because the government and companies pour billions of dollars into the endeavor. But the dirty secret of modern medicine may be that the most logically alluring method for solving diseases – steadily accruing knowledge about human biology that we can act on  – hasn’t always been the best way to hit home runs. An older method of just slinging possible drugs at cells, animals -- or in some cases, people -- and watching what works has often been the more productive starting point, with understanding to come later. “We’re not as smart as we look,” said Michael Jordan, a physician in the immunobiology division at Cincinnati Children’s Hospital Medical Center. Knowing why a drug works has historically trailed the treatment, sometimes by decades. Some of the most recognizable drugs -- acetaminophen for pain relief, penicillin for infections, and lithium for bipolar disorder, continue to be scientific mysteries today.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico A study published in the journal Science on Thursday neatly illustrates how understanding can trail success. Eight years ago, Jordan and colleagues in Cincinnati treated a 12-year-old boy who had been sick for years, suffering from a rare genetic disease that caused his immune system to wreak havoc on his lungs and guts. He came to the hospital to be evaluated for a possible bone marrow transplant that would fully replace his immune system, but he was too sick for the procedure. It was a palliative move when the medical team decided to give him abatacept, a drug approved for rheumatoid arthritis. The most attractive feature was that its side effects weren’t likely to make him sicker.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico “We were expecting that he would likely die,”Jordan said. Six months later, the boy and his family came back – much improved. The medicine is far from a cure, but he is still alive today. It's only now that Jordan and colleagues have figured out the scientific rationale for why the drug works. They've published the scientific details this week, and say it could lay the groundwork for a rigorous clinical trial – although nine patients have already been treated with the drug. This is the sort of reverse of what you would expect under the model that is often presented to the public, but it isn't the first time Jordan has personally seen this process work in reverse. In 2013, he published a paper showing why another rare immune disorder, HLH, is successfully treated with a chemotherapy drug called etoposide. Successes with that drug were first reported in the 1980s.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico “My own feeling is that there are many ways to discover drugs, and one of the mistakes we’re making at the  moment is just trying to think there is one way and focusing on that,” Clardy said. “And I think what past certainly and current experience are showing, is drugs can be discovered in a bunch of different ways and you should be open-minded.” Even in the dawning age of precision medicine, where sophisticated understanding of human biology and the genome is supposed to give scientists a leg up on disease, the most rationally designed drug still requires a little human ingenuity. More than a decade ago, a promising lung cancer drug was designed to inhibit a gene thought to be crucial for cancer. It failed, except in a small fraction of patients. That led doctors to study those patients and learn that their cancers were being driven by a mutated version of the gene. Daniel Haber, director of the Massachusetts General Hospital Cancer Center, quotes Louis Pasteur, the scientist who had the insight that germs carry disease: “Fortune favors the prepared mind.” “If you think you're too smart and you only do what is scientifically indicated, there’s always going to be something, 'Oh my God, we never thought of that!'” Haber said. “If you half-know what you're doing, then you're better prepared to understand or appreciate discoveries that are serendipitous in some way." A 2011 study reviewed a decade worth of drug approvals found that of 75 drugs that worked in a completely new way, 28 came from the more old-fashioned method of screening drugs against cells or animals, and 17 were built from detailed understanding of how the disease worked. David Swinney of the Institute for Rare and Neglected Diseases Drug Discovery said that despite the fact that far more resources are devoted to developing drugs by focusing on targets, the older method of screening has been more productive by his analysis.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico A naysayer might question why, in that case, it’s even important to know how medicines work. But that’s because refining drugs and getting more effective or less toxic versions can depend on those insights. That’s what drives Thomas Bernhardt, a Harvard Medical School scientist who last year published a paper in Cell showing how penicillin, the wonder drug of more than a half century ago, works. The traditional understanding has been that the drug interfered with bacteria's cell wall, causing the germs to burst. But Bernhardt found that in fact, the drug also puts the bacteria into a futile cycle of building and tearing down cell wall components that it can't use -- he compares it to throwing a wrench in an engine.    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico That may seem like a scientific curiosity, but there's real utility to unraveling the mechanism of a drug -- eventually. “If we’re trying to develop new antibiotics, as a group of scientist and an industry as well, how can we expect to be as efficient as we can at going about it, when we don’t understand how our old antibiotics work," Bernhardt said. Robert Raffa, a professor of pharmacology at Temple University School of Pharmacy, has spent time trying to figure out how a drug found in most people’s bathroom cabinets works: the medical mystery of Tylenol. “We can eliminate things. It is not obviously morphine-like, it is not obviously aspirin-like, and it seems so we’re beginning to narrow it down," Raffa said. "Here’s why it’s very, very important: It’s because the other options for pain relief are not optimal, by a long shot." Drug discovery does sometimes follow that neat progression, but even when a drug starts with a coherent scientific idea about what the drug is supposed to do, twists in the road can seem like the norm. Erectile dysfunction drugs had their origins in the side effects of a blood pressure drug. Thalidomide was infamously used for morning sickness before being pulled from the market and then rescued to be used as a drug in cancer and leprosy. In an age of ubiquitous biological information, it can seem that insight will lead us to new drugs, but it may be important to keep in mind how much we don't know.

The story of the surgery that made Ben Carson famous — and its complicated aftermath

For months, a team of physicians and nurses had rehearsed for the delicate surgery. For hours they had prepped the two tiny bodies perilously joined at the head. And when it came time on that day in 1987 to put a knife to the large vein connecting them — the most fraught step in the groundbreaking operation to separate infant conjoined twins — Benjamin Solomon Carson, the brilliant young pediatric neurosurgeon who had overseen the babies’ case from the start, offered his scalpel to his boss. It was a sign of deference and respect — and perhaps, a measure of caution. But Donlin Long, head of neurosurgery at Johns Hopkins Hospital, refused the gesture. Carson, he had already decided, should make the crucial cut. “Part of me thought, maybe I should take the knife. If things go badly it would be terrible for the young doctor’s career,” Long recalled this month. “But I also know that if this was a success, if things go well, it would make his reputation, would make him famous, that people would grow up trying to emulate him.” More than any other moment in a dazzling career, the separation of the Binder twins launched the stardom of Ben Carson. The then-35-year-old doctor walked out of the operating room that day and stepped into a spotlight that has never dimmed, from the post-surgery news conference covered worldwide, through his subsequent achievements in his medical career, to publishing deals and a lucrative career as a motivational speaker — all paving the way to his current moment as a leading candidate for the Republican presidential nomination. But while Carson frequently deploys anecdotes from his compelling life story — a hardscrabble childhood in Detroit, his climb to the Ivy League, his journeys through spiritual faith and advanced medicine — he only occasionally cites and never dwells on the story of Benjamin and Patrick Binder. Like many stories from the frontiers of medical science, it’s a hard one to fit into an inspirational narrative — a tale of risk and loss and brutally tough options. And although Carson and his team achieved something unprecedented, with long-term benefits for science, it did not result in a happy ending for the Binders. “In a technological ‘star wars’ sort of way, the operation was a fantastic success,” Carson said in an Associated Press article from 1989. “But as far as having normal children, I don’t think it was all that successful.” When reached for comment this week, Carson said: “The great reward of using your talents to save a child’s life can be a tremendous high, but you often find that there is nothing you can do to stop the pain of a patient’s journey through life. As a doctor, no matter how far we push medical science, we cannot conquer all pain.” Updates on the children were limited after they returned to Germany following the surgery. The German magazine Bunte signed an exclusivity deal with the family until the boys turned 18. A search through its archives, in addition to new interviews conducted with members of the family and Carson’s medical colleagues, shows a more complete and complicated portrait of an event that shaped the lives of those involved. “I will never get over this. . . . Why did I have them separated?” the boys’ mother, Theresia Binder, told the Freizeit Revue, a sister publication of Bunte, in November 1993. “I will feel guilty forever.” **In January 1987** , Theresia Binder was eight months pregnant and suicidal. “I wanted to kill them and myself as well,” she said, according to Carson’s best-selling book “Gifted Hands.” She had just learned that her babies were stuck together and felt as if “a sick, ugly monster” was writhing inside of her. “I saw the babies [and] noticed only a huge head with two faces,” she told Bunte. “I thought: ‘My God, what will they look like, how will they live?’ ” She debated swallowing pills. She considered opening up the window of a tall building and jumping out. Instead, on Feb. 2, 1987, she gave birth to her boys. They weighed a combined 8 pounds and 14 ounces. They shared a head, but Theresia’s fear was replaced with a new emotion. “Not once did we ever not love them,” her husband, Josef, was quoted by Carson as saying in “Gifted Hands.” “They were our sons.” Doctors informed the parents that if the sons remained joined, these pudgy blond babies would never be able to sit, crawl or turn over. Learning to walk was out of the question. But Johns Hopkins in Baltimore was world-renowned for taking on difficult cases. There they would meet a man who had grown up poor in Detroit, made it to Yale, gotten a medical degree at the University of Michigan, and at the age of 33 had become the youngest chief of pediatric neurosurgery in the country. “After studying the available information, I tentatively agreed to do the surgery knowing it would be the riskiest and most demanding thing I had ever done,” Carson wrote. “But I also knew it would give the boys a chance — their only chance — to live normally.” Conjoined twins occur in about one out of every 200,000 births. Almost 60 percent of them die before birth, and an additional 35 percent don’t survive beyond a day. Of all conjoined twins, only about 2 percent are craniophagus, or connected by the head. Which means that few surgeons have had much practice separating them. So at Hopkins, a team of seven pediatric anesthesiologists, five neurosurgeons, two cardiac surgeons, five plastic surgeons and an array of nurses and technicians spent months practicing on dolls joined at the head by Velcro, according to a 1987 account of the surgery in Newsweek. The Binder twins were lucky in that they had two brains. It meant that the surgery was at least feasible. “From the time we started discussing it, we all tried to keep in mind that we wouldn’t proceed with surgery unless we believed we had a good chance of separating the boys without damaging the neurological function of either baby,” Carson wrote in “Gifted Hands.” On Labor Day 1987, the 7-month-old twins — who, according to Newsweek had been “giggling and kicking since entering Hopkins on September 2” — went in for surgery. For four hours, heart surgeons inserted “hair-thin” tubes into their veins and connected them to heart-lung machines that would keep them alive through surgery. Plastic surgeons sliced into their scalp, removing the bone tissue that connected them. The cardiologists then cut open their chests and removed small amounts of tissue from their heart to use later to construct new veins. Doctors dropped the babies’ body temperature down to 68 degrees, stopping their hearts and allowing surgeons to operate without blood flow — the first time anyone had tried such a strategy for this type of surgery. A big clock on the wall counted down from an hour: Every minute without a heartbeat beyond the 60-minute mark threatened to cause irreparable damage to the boys. “When the hour is up, just turn the pumps back on,” Carson told his team, according to his book. “If they bleed to death then they’ll have bled to death, but we’ll know we did the best we could.” After Long gave him back his scalpel at the pivotal moment, Carson severed the primary thin blue vein that connected the twins. The doctors rapidly set about creating new veins from the heart tissue they had removed earlier. One twin was finished in 57 minutes, the other in 63. “It got pretty intense in there,” said Bruce Reitz, director of cardiac surgery, according to a Washington Post article from the time. “We tried not to look at the clock.” Separated for the first time in their lives, Benjamin and Patrick were placed in medically induced comas. The magnitude of this precarious success was lost on no one; a massive media scrum awaited the doctors as they emerged from the operation. “The success in this operation is not just in separating the twins,” said Mark Rogers, the director of the department of anesthesiology, at the news conference. “Success is producing two normal children.” **The Binders’ early recovery** was closely charted in subsequent headlines: “Twins’ Doctors ‘Encouraged’ But Cautious, No Prediction Now For Health of Either,” “Siamese Twins Begin to Wake From Coma And Breathing Alone,” “Twins Face New Crisis,” “Breathing Problems for Twins,” “Fever Slowing Recovery of Separated Twin Boys,” “Separated Twins’ Status Delights Their Doctors; Last 10 Days’ Progress Called Remarkable,” “Separated Twins May Lead Normal Lives, Doctors Say,” “Twins Separated By Surgery Ready to Go Home to Germany.” And they did go home to Germany, seven months later. And then, news of the Binders almost immediately evaporated. Even Carson lost track of them, he would say later in an interview, noting that he had written letters and never heard back. Carson, though, remained very much in the news. In 1992 he published “Gifted Hands” — which became a made-for-TV movie starring Cuba Gooding Jr. — and a series of other books in an inspirational or self-help vein. Carson was appointed to lofty boards and commissions; the NAACP gave him its prestigious Spingarn Medal and the White House gave him a Presidential Medal of Freedom. His fame — in particular for his work with conjoined twins — was such that when the filmmaking Farrelly brothers of “Dumb and Dumber” fame made a comedy, “Stuck on You,” about conjoined twins (played by Matt Damon and Greg Kinnear), they just had to have a Ben Carson cameo — and he signed on, once they agreed to host the movie premiere in Baltimore. He became a wildly popular figure on the speakers’ circuit, his religious faith and social conservatism popular with black churches and red-state audiences. In 2013 he landed on stage at the National Prayer Breakfast, where his dark warnings of an America in decline were seen as a rebuke to President Obama, sitting just a few feet away — and Carson became the new darling of conservative radio hosts and activists. And now he is a presidential candidate, known for announcing at debates that among the field of rivals he’s “the only one to separate Siamese twins.” Meanwhile, Carson’s first conjoined twins kept a lower profile back home in Germany. Their mother would later tell reporters that they came home with the hope, instilled in them by the Johns Hopkins surgeons, that the boys might soon begin crawling, and then hit other milestones. “‘I took it seriously,’’ she told Freizeit Revue in 1989. “But maybe they just wanted to encourage me.’’ It soon became apparent, though, that the boys were hopelessly delayed, according to a 1993 interview with the Revue. Benjamin would moan occasionally, but Patrick remained completely silent; he had had a setback in the Baltimore hospital when he choked on a piece of food, going without oxygen for a short time. Years later, neither boy could get around on his own or feed himself. The doctors say they always knew this outcome was a possibility, that the swelling from the surgery and the time without blood flow left the children very much at risk. They say they hoped that the twins would mature into normal lives, but that it was always just a hope. “We certainly made the risks clear,” Long said. “And we made it clear that it had never been done before.” When Freizeit Revue caught up with Theresia in November 1993, she said her children’s brain damage had destroyed her marriage. “Josef has never been able to cope with this blow of fate,” she said in the little-seen interview written in German and translated into English. She said Josef, who has since died, according to Theresia’s brother, became an alcoholic, lost his job, cheated on her and spent all their money, leaving her and the children to live “from hand to mouth.” “He never touched them,” she said. “He was appalled.” Unable to care for the twins on her own, she brought them to a home for disabled children, where they became wards of the state. “The first thing I think of every morning is ‘today I’m going to get them,’ ” she said in 1993. “But then I can’t.” She said she had lost her faith in God. She remarried and had another child, and in 1993 was pregnant with another. “When we go for a walk with the children in their wheelchair, people look at me, as if I’m a monster,” she said. “I need this child. To heal. I still have to prove to myself that I’m not a monster.” Katharina Korn was a neighbor of Theresia Binder in Ravensburg, a town in southern Germany famous for its picturesque medieval buildings, until Theresia moved away about eight years ago. Korn recalled seeing the toll the twins’ conditions took on Theresia. “She was feeling bad, because her children were severely disabled, much worse than before the operation,” Korn told The Post. “They promised her much more than what the actual outcome was.” Patrick Binder died sometime in the past decade, Theresia’s brother Peter Parlagi said. Benjamin is 28 now and still cannot speak, but according to Parlagi is doing “relatively well.” He’s grown up; his hair is now dark. His younger half-brother, Florian Vosseler, still checks in on him two or three times a year, often with their mother, who declined to be interviewed for this story. They’ll take walks, feed him cake and help him drink coffee, which he prefers with extra milk. “It’s difficult to communicate with him,” Vosseler said. “But you can tell by the way he looks at you that he’s happy to see you.” **At the office for his plastic surgery practice** in Fairfax, Va., Craig Dufresne has hung a framed copy of a 1987 New York Times article trumpeting the 22-hour surgery that he participated in with his longtime friend Carson. As he sees it, the doctors never explicitly promised the Binders anything, though he can understand how they got their hopes up. “We said that if all goes well, they would be completely normal,” said Dufresne, who went on the initial trip to examine the twins in Germany. “And we really thought there was a good chance it would turn out with a happy ending.” Dufresne said the plan was for the twins to return to Hopkins a year later, but that once they left for Germany it was impossible to keep track of the family. When there was no news, he figured there must have been bad news. He and others on the team would have to take the surgery for what it was: a big step forward for medical science, even without the ideal result. “My job as a doctor is to make sick people well, and when I fail to do that, regardless of exactly why, I still failed,” Long, the former head of neurosurgery, said in a phone interview about the Binder surgery. “So in that way, the simple answer is no, I do not think it was a success.” The surgery did prove that it was technically possible for twins conjoined at the head to be separated and for both to survive. It created a blueprint for other doctors to follow in the future. Carson himself would go on to participate in four other similar surgeries — one of which, a 1997 surgery of Zambian twins, left both patients not only alive but neurologically normal. “You can’t go into something like this with a pessimistic attitude,” Carson told Johns Hopkins Magazine after a 2004 separation of twins joined at the head. “A lot of younger guys are learning a lot, pushing on the next border, which is how progress is made. We all act as stepping stones.” Carson would go on to perform hundreds of other difficult and impressive surgeries, including operating on babies inside the womb and removing large chunks of the brains of children plagued by repetitive seizures. But it was the Binder twins who launched Carson onto the national stage he now dominates, barely three years after retiring from surgery. “If I hadn’t given him the knife, he probably wouldn’t be there today,” Long said. “He still would have received a great deal of credit, but it would have been divided. It became the thing that got him everybody’s notice.” David Farenthold contributed to this report.

Lessons from the Ebola outbreak in West Africa

THE OUTBREAK of the Ebola virus in West Africa this year came as a surprise. Perhaps no one could have predicted that such a terrible scenario would unfold. But over the past decade, there have been four major outbreaks of infectious disease caused by a virus: severe acute respiratory syndrome, or SARS; swine flu; Middle East respiratory syndrome; and now Ebola. Each has taken populations by surprise. Next time, the world should not be gobsmacked. It is possible to be better prepared, be more aware of the potential threats and not start from zero every time the alarm goes off. Speed is of the essence. The global response to Ebola was tardy, in part because 24 previous outbreaks of the virus since 1976, mostly in remote locations, were contained, so it was assumed that this one would also be extinguished quickly. But when Doctors Without Borders began to warn in April that something different was unfolding — that Ebola was getting out of control in West Africa, where it had not previously struck — the call was not heeded. The World Health Organization response lagged. The U.N. agency has suffered budget cuts and is poorly structured, with regional offices not easily accountable to its headquarters in Geneva. In this case, the Africa office of the WHO was slow to react, and that put the whole organization behind the curve. Margaret Chan, the WHO director general, first learned of the urgency of the situation in June, according to a WHO timeline disclosed by the Associated Press. No doubt the slow response was also a product of public health agencies that were ill-prepared and overwhelmed in the three hardest- hit countries: Guinea, Sierra Leone and Liberia. It would be smart to begin thinking of a more agile and effective organization or system for responding to such dire threats, one that could bring together a capability for surveillance, early warning and rapid response; and that would be wired into the pharmaceutical industry. Another important lesson is that fighting a disease outbreak is not only a medical challenge but also must take into account economics, politics, culture and traditions. The Ebola response was hampered by deep suspicion among those affected, a failure of responders to build confidence in communities and methods that backfired, such as the containment of a whole section of Monrovia, Liberia, which led to panic and frequent violations of the cordon. The traditional burial methods of touching the deceased and washing the body also spread the disease. Many of these errors were later rectified in an admirable way — special burial teams have been notably effective — but these are lessons that should not have to be learned on the fly. The knock-on effects of the epidemic are still being felt. Half a million people have been classified as “severely food insecure” in the three countries, because of border closures, quarantines, and disruption in food markets and processing chains, according to the United Nations’ Food and Agriculture Organization . Another lesson is the importance of getting the low-tech, simple things right, such as adequate personal protective equipment for first responders, who have suffered a terrible toll. Ebola has demonstrated that disease threats do not stop at passport control and that health security is national security. Stopping the virus in West Africa is an investment in keeping it from U.S. soil. The Obama administration has championed a global health security agenda with this in mind, but it was initially slow in rallying to the challenge of Ebola. The president’s decision to deploy the military in September put the United States in position to lead, but that should have happened sooner. Perhaps the most difficult challenge is to develop biomedical treatments — vaccines and antivirals — for an emergency on the scale of Ebola. It wasn’t a serious threat before, so the pharmaceutical industry did not have the incentives to develop treatments. Someday, it may be possible to dial up a rapid response to a novel disease threat, but science hasn’t found the way yet. More ought to be done jointly by governments and the private sector to improve the ability to swing into action. **Read more about this topic:** Ban Ki-moon: The Ebola fight is far from over Joanne Liu: A concrete response to the Ebola outbreak cannot wait Laurie Garrett: Five myths about Ebola Marc Thiessen: Ebola and Obama’s crisis of competence Dana Milbank: The nasty politicization of Ebola

Martine Rothblatt: Endless supply of modified organs, and their delivery by drone, not far away

“We’ll be able to create an unlimited supply of transplantable organs through the modification of the pig genome so that there will be a supply of hearts, livers, kidneys and lungs that can be tolerated by humans without the need for life-long immunosuppression. “We are on schedule to have our first clinical procedures, which means using these organs in people by the end of this decade. We hope for regulatory approval less than 10 years from now, and I’m pretty confident that by the end of the 2020s there will be literally tens of thousands of people a year receiving organ transplants as a result of xenotransplantation. “When you make a genetically modified organ, it’s like a drug. But unlike medicines for other diseases, this drug has a 24-hour half-life. We all know that you can’t just put an organ on a shelf and keep it waiting there for a year. We can’t ship it to Walgreens. “I know as a technologist that if you can have a drone that drops a pile of books on your front yard today that you’re going to be able to have, within 10 years, a drone that is going to be able to land, very softly, on the hospital heliport and have a person roll the organ out of the drone and to the surgeon’s table, where they’ll take it and implant it. We’ve placed this order for 1,000, what we call manufactured organ transport helicopters, or MOTHs, and these will be delivered within the next 10 to 15 years.”

A Johns Hopkins team designed an Ebola suit so good, it’s going on the market

Youseph Yazdi was surprised by the number of people who jumped in to help design better protective gear for people helping Ebola victims – everyone from freshmen to robotics experts to a wedding-dress maker. But he was even more surprised when the solutions the team came up with at the hackathon at Johns Hopkins University attracted the notice of leading producers of protective clothing. A version of the suit they designed will be manufactured by DuPont and available early next year, the university announced Monday. “It was a bit of a shocker,” said Yazdi, the executive director of the Center for Biomedical Engineering Innovation and Design at Hopkins, “when major companies approached us and said, ‘Wow, you came up with something new, that we’re interested in.’ “You’d think people at companies doing this all their lives,” would have better ideas, a better understanding of the situation. “But if you bring in the right experts, with bright young people who are looking at the problem for the first time, you can get amazing innovations…. “A crucial element of the innovation ecosystem is to have fresh eyes on the problem.” After the U.S. Agency for International Development signaled a need for help — and Ebola’s grim toll in  Africa, and on front-line health-care workers had become frighteningly obvious last winter — scores of people volunteered to help. More than 11,000 people died after outbreaks in Liberia, Guinea and Sierra Leone, and 500 health workers died from Ebola infections. “Hundreds of nurses, midwives, and physicians selflessly responded to the Ebola outbreak and lost their lives trying to save others,” Leslie Mancuso, president and CEO of Jhpiego, a global health affiliate at Hopkins, said in a release. The new protective suit can help health workers respond more safely to any infectious disease. Working with people from Jhpiego, the Hopkins students, faculty and other experts identified several problems with the suits being used. One was complexity; with multiple pieces, there was more possibility for a mistake being made when a health worker took it off, and a mistake could easily be deadly. So they designed a suit that takes just one zip to remove. They also included a clear plastic area near the face, after learning that peoples’ perceptions of aid workers in the villages where people were infected dramatically changed the number of people who got treatment. “We wanted to make it less scary,” Yazdi said, so they redesigned the air flow to ensure that people’s mouths and eyes would be visible. The DuPont-produced suit may include that element. “We look forward to the next step of making this protective apparel solution available where it is needed for both emergency response and preparedness,” Marc Doyle, senior vice president DuPont Safety & Protection said in a release. The suit will be tested in Liberia by Jhpiego. With the Hopkins-DuPont collaboration, people from the university will help evaluate prototype garments and teach people to use them, while the company will handle the commercialization of the product. They expect them to be on the market in 2016. Students were working on the design challenge late into the night, Yazdi said. “They love that they’re having an impact. I had a student say, ‘Up to now this school of engineering has taught me how to be an engineer; this is the first time I get to _be_ an engineer.'”    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico Read more: Johns Hopkins team wins award for Ebola protective suit    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico How a wedding-dress maker is trying to stop the spread of Ebola    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico Student: I want to stop viruses like Ebola. But I can’t afford grad school    *[WSU]: Wayne State University   *[Tue]: Tuesday   *[Wed]: Wednesday   *[UNM]: University of New Mexico

Curbing the costs of high-tech health

Advances in medical technology are a double-edged sword. On the one hand, they have brought huge health gains to millions of Americans. Hip and knee replacements, heart operations, brain surgery, drugs — treating everything from high cholesterol to depression — have become routine when they were once considered exotic or unimaginable. The drawback is that these same breakthroughs have driven health spending upward, because they’re prone to misuse and overuse. Can we curb waste without undermining new technologies? Well, maybe. We now have a study suggesting, optimistically, that proper incentives can concentrate new technologies on the patients who might most benefit. The study involves advanced diagnostic imaging, including CT scans (for computed tomography) and MRIs (for magnetic resonance imaging). From 2000 to 2005, CT and MRI use among Medicare recipients grew 14 percent annually. Now, growth of both Medicare and non-Medicare spending has slowed to estimated annual rates of 1 percent to 3 percent, the study says. Imaging represents one of the great medical achievements since World War II. Until the 1970s, when CT scans appeared, traditional X-rays were the only way doctors could peer inside the body. X-rays’ most conspicuous limitation is that they can’t penetrate deeply into the brain. “The first CT scans were so exciting because you could see the brain much better,” says Yale historian Bettyann Kevles, author of “Naked to the Bone: Medical Imaging in the Twentieth Century.” What CT scans can’t show, MRIs usually can. For example, CT scans are less able to image soft tissue (ligaments, tendons, nerves and blood vessels). “The two of them together give a good picture of the entire body,” says Kevles. Better imaging is a natural ally in diagnosing many diseases and ailments: heart disease, cancer, spinal injuries, strokes and bone and muscle pain. Not surprisingly, costs ballooned. In 2009, Medicare paid $11.7 billion for medical imaging, according to Kaiser Health News. Controlling spending on medical advances isn’t easy, because it’s favored by a three-legged alliance. First, patients want the newest and best care. Second, hospitals’ and doctors’ incomes often depend on using diagnostics and procedures in which they have invested. Finally, device and drug manufacturers want big markets for their products. There are huge pressures to apply medical advances to borderline cases where they might not be helpful. The slowing growth of medical imaging might reflect a natural saturation: Scans are being used in most plausible clinical situations. But the new study, posted on the Web site of the journal Health Affairs, disputes this. It argues that rapid growth was driven partly by powerful non- medical forces: Demanding patients insisted on scans; doctors feared malpractice suits if they refused; and doctors and hospitals wanted to maximize revenues. What explains slower growth is that these incentives weakened, contend economists Frank Levy of the Massachusetts Institute of Technology and David Lee of General Electric. (Note: GE is a major supplier of imaging equipment.) One change was the adoption of prior authorization by many private insurers. Doctors usually had to get permission for advanced imaging and, if patients’ conditions didn’t comply with guidelines, explain why. This may have discouraged referrals, because doctors don’t like being overruled. Patients also became less demanding, because deductibles and co-payments rose. From 2006 to 2010, the share of workers with deductibles exceeding $1,000 grew from 10 percent to 27 percent. “Increased out-of-pocket expenses have made patients and physicians more cost conscious,” write Levy and Lee. Finally, some reimbursement rates fell. In 2005, Congress mandated that Medicare couldn’t pay free-standing imaging centers — often owned by doctors — more than it paid hospitals for outpatient imaging. This “reduced profits for imaging centers and resulted in extensive consolidation in the industry,” the study said. Under complex reimbursement rules, doctors had incentives to establish imaging centers or install scanning devices in their offices, says Levy. And these imaging centers seemed “particularly active in stimulating demand.” Have patients suffered from less imaging? Comprehensive studies haven’t been done, but Levy and Lee provide evidence of limited effects. Data from one insurance group suggested that about half the MRI slowdown involved lower back, elbow and knee pain. These cases often respond to “conservative treatment, including exercise,” they write. “Instead of ordering an MRI at the outset, a physician can prescribe conservative treatment and order a scan if the problem persists.” The larger lesson involves better ways to police new technologies. The question is “how to stop physicians from just going with the flow and thereby breaking the bank,” says Levy. Some combination of prior notification, higher patient co-payments and restrained reimbursements might do the trick. **Read more Opinions** Robert J. Samuelson: The Medicaid albatross Bryan R. Lawrence: Health care — spend less, live longer?

In the rush to deregulate, let’s not forget government’s role in spurring innovation

Our economy does not grow at a consistent rate. Its growth rate expands most dramatically during an industrial wave — meaning a period where a new technology is broadly adopted, changing the fundamental underpinnings of employment, entrepreneurship and capital. Consider intercontinental railroads, automobiles, electrification, radio, television, semiconductors, software, the Internet, wireless communication and mapping the human genome and the effect each had on the creation of commercial opportunities. Each of these technologies fostered industrial waves. The federal government’s role in creating the conditions for industrial waves is demonstrable. For example, the adoption of the intercontinental railroads was driven by a desire for a mechanism to transport federal troops around the nation. The government ensured that standardization of trackbeds occurred, created time zones to keep trains on schedule and adjusted freight rates so they wouldn’t choke farmers and businesses relying on railroads to transport their goods. We can thank the federal government’s breaking up AT&T’s longstanding monopoly in telephony for our rapid adoption of new telecommunications technologies, the growth in consumer alternatives for long distance, and wireless. In fact, the underpinnings of the Internet and mobile that have driven these new alternatives were funded and fostered by research and development from our Department of Defense. Ideas becoming industries are at the heart of disrupting the status quo. Just like an old tree must fall for the sapling to find the sun, incumbent companies must step back so others can rise. However, large companies will not simply cede so others can succeed, and those profiting from the status quo will not merely stand aside to allow the future to emerge. Interestingly, the federal government is often the woodcutter clearing that forest, or the gardener protecting the saplings. Look at current technological ideas that that could emerge as new industrial waves: artificial intelligence, alternative energy and conservation, artificial life or proteomic medicine and see also large established businesses happy with the status quo which are often standing in the way. Sure, we want a market free of government intervention, but we might be creating conditions that inhibit our growth. Sometimes government intervention is both necessary and desirable, and it is our duty to remind the incoming administration of that distinction.

To fight their negative image on prices, drug companies launch a major ad campaign that doesn’t mention them

That strategy has worked many times in the past, but it may be a risky time to rehash this message. The campaign launches as the affordability of health care has become a pressing issue for millions of Americans, as it remains uncertain what will replace the Affordable Care Act. “What does it matter to the average American that there are new and exciting treatments for cancer if there’s no confidence they’ll be able to afford them or access them?” said Jeremy Greene, a historian of medicine at Johns Hopkins University who also practices medicine in a community health center in Baltimore. “When people don’t have insurance, you begin to realize just how much drugs cost at the pharmacy with no insurance.”   Industry observers said that a campaign focused on science and future therapeutic revolutions don't address a core issue that has emerged over the past year and a half: the public perception that the industry is not holding up its part of the social contract to not only develop drugs but also make them accessible. “Just because you have a new breakthrough medicine doesn’t mean I’m going to get access to it,” said Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development. “I think this is the exact wrong time to play around with that issue, because more and more people are going to get concerned — or already are concerned — about the state of their health-care coverage.” Ubl said the campaign will also focus on demonstrating the value of drugs. That, too, isn't new, said Dominique Tobbell, a historian of medicine at the University of Minnesota. Tobbell said in an email that since the late 1950s the pharmaceutical industry has made arguments about its drugs' values, from the reductions in mortality to saving health-care costs through reduced hospitalizations or getting workers back on the job faster. “Consistently, the industry has cast pharmaceuticals as the major reasons for these health-care gains — the role of public-health measures, preventive medicine, and lifestyle changes have been routinely missing or downplayed in its campaigns,” Tobbell said. Greene argues that there are essentially two conversations Americans have about drugs. One is about the frontiers of science and the need for medicines to treat rare and overlooked diseases. Another is about access to medicine and health. These two discussions rarely overlap, he says. For example, in a rare wave of bipartisan support late last year, Congress passed the 21st Century Cures Act aimed at speeding up the development of new drugs. What wasn't part of that legislation was an acknowledgment that patients were frustrated with the price and access to older drugs, an issue that came up at multiple congressional hearings over the past year. Tobbell said that although the strategy of focusing on innovation has been successfully used for decades, consumers have more information about how pricing works that may keep them skeptical about the industry. But if history is a guide, the strategy may simply put off the issue until the next time a pricing controversy flares. “Each time, it seems like prescription drug prices have reached some new high that’s just impossible to bear. The level of prices that we’re talking about when we talk about the unaffordability of prescription drugs — if you were to show them to people having arguments over prescription drug prices in the '80s, it would be incredible,” Greene said. “How many cycles of normalization of high drug prices and reinflation of drug prices can we stand as a society?”