sottnet--2019-01-13--Scientists confirm elderberry beats the flu prevents colds strengthens immunity

Scientists confirm elderberry beats the flu, prevents colds & strengthens immunity

Scientists have discovered that elderberry has been known to man since the prehistoric era, and elderberry recipes were commonly used as natural medicines in ancient Egypt.Hippocrates, the "father of medicine" from ancient Greece depicted it as his "medicine chest" because of its numerous health benefits.The elderberry juice has been used as hair dye by the Romans, and the wood of the elderberry tree has been used to make combs, toys, pegs for shoemakers, needles for weaving musical instruments, and skewers for butchers. The Native Americans used this plant as a natural cure, body paint, ink, for jewelry and musical instruments, hunting whistles, and much more.During the 1995 Panama flu epidemic, the government used it as a natural way to fight the flu, and it reduced its severity and thus helped to end the epidemic.Elderberry is native to Africa, Europe, and parts of Asia. Sambucus is a genus of flowering plants in the family Adoxaceae, and the berries and flowers are powerful natural medicines. The plant has deciduous leaves, white flowers (elderflowers) and berries that turn from green to red to black as they ripen.Other common names for Sambucus nigra are European elder, European elderberry, black elder, and European black elderberry. The flowers contain 0.3 percent of an essential oil composed of free fatty acids and alkanes, and the fruit contains rutin, quercetin, kaempferol, phenolic acids, and anthocyanins. Elderberry is also high in flavonoids, which are powerful antioxidants that prevent cellular damages, as well as anthocyanidins, chemical compounds which have immunostimulant effects.Elderberries are rich in iron and potassium, vitamins A, C, B6, and other nutrients. The raw berries are made up of 80 percent water, 18 percent carbohydrates, and less than 1 percent each of protein and fat."Elderberry has a long, rich history of use for medicinal benefits by numerous cultures. It fights infections including influenza, herpes, viral infections, and bacterial infections. A study published in the Journal of Alternative and Complementary Medicine concluded that elderberry can be used as a safe treatment for influenza A and B.This is due to its efficacy on all strains of influenza virus that were tested, the clinical results, its low cost and the absence of side effects. Most every part of the elderberry can be used - the flowers, bark, roots, and leaves are often used for their amazing health benefits.", and here are some of its health benefits:Elderberries boost the immune system, due to the presence of chemical compounds known as anthocyanidins, which have potent immunostimulant effects. Elderberry extract is one of the safest and most powerful treatments for both cold and flu symptoms.Scientists have conducted numerous studies which have confirmed the strong effects of the elderberry extract in the treatment and control of influenza symptoms."In one placebo-controlled, double-blind study conducted by Israeli virologist Dr. Madeleine Mumcuoglu, 93.3% of the people taking an elderberry preparation reported significant improvement in influenza symptoms within 2 days of starting it, compared with the 6 days it took for the placebo group to see improvement.In another randomized, double-blind, placebo-controlled study performed in Norway, researchers gave either a placebo syrup or elderberry syrup to patients who reported having flu-like symptoms for less than 48 hours.The results were similar to Dr. Mumcuoglu's results. On average, the patients who received the elderberry syrup saw relief of symptoms 4 days earlier than the group that received the placebo syrup. As an added benefit, the patients in the elderberry syrup group reported taking significantly fewer over-the-counter medications in hopes of symptom relief.The strong anti-inflammatory and antioxidant properties help sinus issues in a natural way. Swiss scientists have evaluated the effects of a proprietary product, Sinupret, which contains elderberry flowers, in the treatment of bacterial sinusitis in a combination with an antibiotic (doxycycline or Vibramycin) and a decongestant, and found that it boosted the effects of the medications.The berry and the flower have been used as a diabetes cure for centuries. The elderflower extract has been found to stimulate glucose metabolism and the secretion of insulin, and thus decreases blood sugar levels.The flowers of the elder plant are a powerful herbal allergy remedy, as this plant fortifies the immune system, and soothes inflammation.This plant has powerful diuretic properties, so it effectively fights water retention.Elderberry fights constipation, since it acts as a natural laxative, and stimulates healthy bowel movements.Elderberry is often added to numerous cosmetic products, as it is rich in antioxidants, vitamin A, and bioflavonoids, that improve the healthy appearance of the skin, prevent premature aging and provide a healthy skin glow.You can buy elderberry online or in the nearest local health store. You can consume it in the form of juice, tea, jelly and jams, wine, in ointments, as powder, syrups, pills, lozenges, sprays, and capsules.The elderberry syrup is the best way to treat the flu, colds, and upper respiratory issues, so here is how to prepare it:In a saucepan, pour the water, and add the elderberries, cinnamon, and ginger. Boil the syrup, lower the heat, and leave to simmer for 45 minutes, covered. Then, remove the saucepan from heat, mash the berries, and strain through a strainer or cheesecloth into a glass bowl. Sweeten with honey, and pour the syrup in a sterilized glass container."This herb can deactivate the flu virus and naturally boost immunity. The flowers and berries of elderberry are said to boost the immune system, treat flu and relieve sinus pain.Elderberry attacks flu viruses and reduces bronchial inflammation. A preliminary study found that when 15 milliliters of elderberry syrup was taken four times daily for a five-day period, it relieved symptoms of influenza an average of four days earlier than those taking a placebo. "You can also drink elderberry tea by adding a tablespoon of dried berries or flowers to eight ounces of water.Note that the ripe, cooked berries of most of the Sambucus species are edible, but do not consume them raw, as they contain a cyanide-inducing chemical.Sometimes, the elderflowers and elderberries cause allergic reactions, so discontinue their use if you notice a mild reaction. You should also not use them if you are pregnant or breastfeeding.People suffering from an autoimmune disease, those with organ transplants, or individuals taking diuretics, diabetes medications, laxatives, immune-suppressing drugs, or undergoing chemotherapy, should not take elderberry.Source: realfarmacy.com


sottnet--2019-03-24--Turns out we didnt understand viruses Plant virus distributes genes into separate cells - all work

Turns out we didn't understand viruses: Plant virus distributes genes into separate cells - all work together

FBNSV needs all of its components, but it doesn't need them in the same place.  It is a truth universally acknowledged among virologists that a single virus, carrying a full set of genes, must be in want of a cell. A virus is just a collection of genes packaged into a capsule. It infiltrates and hijacks a living cell to make extra copies of itself. Those daughter viruses then bust out of their ailing host, and each finds a new cell to infect. Rinse, and repeat. This is how all viruses, from Ebola to influenza, are meant to work.But Stéphane Blanc and his colleagues at the University of Montpellier have shown that one virus breaks all the rules.Faba bean necrotic stunt virus, or FBNSV for short, infects legumes, and is spread through the bites of aphids.And, as Blanc's team has now shown Indeed, this virus never seems to fully come together., its existence spread between capsules and split among different host cells."This is truly a revolutionary result in virology," says Siobain Duffy of Rutgers University, who wasn't involved in the study. "Once again, viruses prove that they've had the evolutionary time to try just about every reproductive strategy, even ones that are hard for scientists to imagine."FBNSV is one of several "multipartite viruses" that split their genes among different capsules. These oddballs were first discovered in the 1940s, and though, they're still rather obscure. Blanc thinks that's because they almost always infect plants and fungi, and only two have been found in animals - one in a moth and one in a mosquito . "I lecture on several virology courses, and even people in Ph.D. programs haven't heard of them," he laments. "They're everywhere, but because they're mainly on plants, no one cares."These viruses, even to virologists who knew about them.Everyone assumed that they could only reproduce if all the segments infected the same host cell. But the risk of losing a piece, and so dooming the others, skyrockets as the number of pieces goes up. In 2012, two researchers calculated that the odds of successfully getting every segment in the same cell become too low with anything more than three or four segments.Its mere existence suggests "that something must be wrong in the conceptual framework of virology."Perhaps, he realized, these viruses don't actually need to unite their segments in the same host cell. "If theory was saying that this is impossible, maybe the viruses just don't do it," he says. "And once we had this stupid idea, testing it was very easy."His colleagues Anne Sicard and Elodie Pirolles labeled pairs of FBNSV's genes with molecules that glowed in different colors - red for one segment, for example, and green for another. Then, they simply looked down a microscope to see whether the colors overlapped in the same cells.When the team first saw that, "we were jumping and running around the lab," Blanc says. "But we were also scared about it being a [mistake]. We took six years to verify it."For example, they showed that the levels of one segment aren't tied to the levels of another, as you would expect if they were replicating in the same host cell. Instead, in any one infected plant, the different segments seem to accumulate at different rates.But that discovery raised another problem.One makes the proteins that copy the virus's DNA once it gets inside its hosts. Another creates the proteins that form the virus's capsules. See the problem? If these segments end up in different cells, the DNA-copying one shouldn't be able to make capsules, the capsule-making gene shouldn't be able to copy itself, and both of them would be stuck.That doesn't happen, the team discovered, because the virus's genes might be stuck in neighboring cells,. The capsule-making protein can get into a cell with the DNA-copying gene, and cover it. The DNA-making protein can get into a cell with the capsule-making gene, and copy it. Think of the eight segments as factories in different cities, shipping assembly robots to one another so that each site can manufacture its own separate product. It is within this expansive trade network that the distributed virus truly exists., but many scientists have found that plant proteins can voyage between cells , even over long distances from root to shoot. Some researchers who study multipartite viruses have even suggested that they could make use of these botanical highways. But Blanc's team has now found clear and unambiguous evidence that they do. Perhaps, he says, "this is why multipartite viruses don't exist so much in animals. Maybe it's harder for our proteins to travel between cells.""The work is very important ... and very carefully done," says Marilyn Roossinck of Pennsylvania State University. For decades, she has been studying a different multipartite virus that affects cucumbers, and though she has seen some of the patterns that Blanc's team did, "these were never published, as their significance wasn't clear," she says.," adds Rodrigo Almeida of the University of California at Berkeley, who studies plant diseases. "I am not aware of any similar example in biology, where genetic information appears to be split among host cells."The closest example I can think of exists in cicadas. These noisy insects rely on a bacterium called Hodgkinia , which lives inside their cells and provides them with nutrients. But this one bacterium has fractured into several daughter species, each of which contains just a few of Hodgkinia's full set of genes. None of these partial microbes can survive on its own;. But these daughter species are all still locked within the same cell, so they're not truly distributed as the virus is. They are also problematic:. Hodgkinia's fragmented existence is a looming disaster - "a slow-motion extinction event," according to John McCutcheon, who described it.By contrast, multipartite viruses are clearly very successful, so their bizarre distributed existence must have some benefit. And Blanc thinks he knows what that might be.His team has shown that when FBNSV infects a plant, the frequency of each segment is very predictable. Some of them are common and others are rare, but, at least within a given species of plant. If the virus infects a different plant species, those proportions change - to a different, but still predictable, pattern. Blanc calls these " genome formulas " - ratios of genes that FBNSV uses for different hosts.The virus's use of these formulas reminds Blanc of the ways in which animals and other complex organisms adapt to different environments by tweaking the numbers of important genes . In very rough terms, the more copies you have, the more effectively that gene can do its thing. But viruses are tiny entities, whose capsules only have room for small genomes. There's not enough space for them to just wantonly double their gene counts.Multipartite viruses don't have to. If they want to emphasize the use of a certain gene, they just need to get the segment carrying it into more host cells. "This lifestyle allows the virus to adjust its gene copy number without mutating," Blanc says.These discoveries could also change our understanding of other more traditional viruses. Influenza's genome is split into eight segments, and unlike FBNSV, all of these are packaged into the same capsule. Researchers typically assume that every capsule contains the full octet, but in 2013, Christopher Brooke of the University of Illinois showed that 90 percent of them are missing at least one segment. Influenza virus "exists primarily as a swarm of complementation-dependent, semi-infectious virions," Brooke wrote.Three years later, a different team showed that the same is true for the virus behind Rift Valley fever : Only a minority contain all three of the virus's gene segments, and most are missing one. "Perhaps the boundary between these viruses and the multipartite ones isn't so clear," Blanc says.Many viruses also produce capsules called " defective interfering particles ," which ... well, the clue's in the name. They're defective because, for some reason, they've lost part of their full genome. They're interfering because, though they're defective, their parent viruses will still make copies of them, flooding the total pool of capsules with noninfective deadbeats. "These things have been known for a century, and they've long been considered as junk," Blanc says. "But they are very efficiently maintained in any viral infection. Maybe they can profit from the system we have identified."


sottnet--2019-06-19--The secret life of viruses Communication cooperation

The secret life of viruses: Communication, cooperation

Geneticist Rotem Sorek could see that his bacteria were sick - so far, so good. He had deliberately infected them with a virus to test whether each ailing microbe soldiered on alone or communicated with its allies to fight the attack.But when he and his team at the Weizmann Institute of Science in Rehovot, Israel, looked into the contents of their flasks, they saw something completely unexpected: the bacteria were silent, and, passing notes to each other in a molecular language only they could understand.It was an accidental discovery that would fundamentally change scientists' understanding of how viruses behave.Viruses that infect bacteria - spiky lollipop-like creatures known as bacteriophages (or phages) - have. But researchers long thought these processes were; the phages seemed to just sit back and listen in, waiting for bacterial distress signals to reach fever pitch before taking action.Sorek and his colleagues had found phagesdiscussing their choices. They realized that as a phage infects a cell, it releases a tiny protein - a peptide just six amino acids long - that serves as a message to its brethren: "I've taken a victim". As the phages infect more cells, the message gets louder, signalling that uninfected hosts are becoming scarce. Phages then put a halt to lysis - the process of replicating and breaking out of their hosts - instead staying hidden in a sluggish state called lysogeny 1 The viruses, it turns out, did not depend on bacterial cues to make their decisions.. "This finding was a big, important, revolutionary concept in virology," says Wei Cheng, a structural microbiologist at Sichuan University in Chengdu, China.Sorek named this viral peptide 'arbitrium', after the Latin word for decision. It seemed to work much like the communication system used by bacteria - quorum sensing - to share information about cell density and adjust the population accordingly. Yet it was the first time anyone had demonstrated molecular messaging of this kind in viruses. And it fitted into an emerging picture of viruses asVirologists have long studied their subjects in isolation, targeting cells with just a single viral particle. But it's become increasingly clear that many viruses cooperate, teaming up to co-infect hosts and break down antiviral immune defences.The implication is that researchers might have been going about their experiments all wrong.says Sam Díaz-Muñoz, an evolutionary biologist at the University of California, Davis.Learning the language behind these viral interactions could inform the design of new treatments for cancer and nasty superinfections. The social predilections of viruses even help to explain how they evade the bacterial immune system known as CRISPR. "Conceptually, it's really powerful," Díaz-Muñoz says.Scientists first spied viruses mingling in the 1940s, when separate experiments by biophysicist Max Delbrück and bacteriologist Alfred Hershey showed that two viral particles could simultaneously invade the same cell and swap genes. But according to Dale Kaiser, a molecular geneticist at Stanford University in California and a protégé of Delbrück's, these early observations were only really interesting to scientists as an experimental method - they allowed researchers to create a cross between two viral strains. The relevance to basic biology was missed.It wasn't until 1999 that anyone took any notice of what cooperation achieved for the viruses themselves. That year, evolutionary biologists Paul Turner, now at Yale University in New Haven, Connecticut, and Lin Chao, now at the University of California, San Diego, showed that phages play their own version of the prisoner's dilemma strategy game, working in partnership under certain circumstances and acting in their own self-interests in others 2 Other examples of beneficial viral interactions followed, including ones that involved the pathogens responsible for diseases such as hepatitis, polio, measles and influenza. They often took place between different viral strains that had a shared interest in boosting their own reproductive chances. But the molecular basis of those cooperative traits - the method of communication - had largely remained elusive. And as Rafael Sanjuán, an evolutionary geneticist at the University of Valencia in Spain, points out: "The 'how' is really important here."That's why the arbitrium discovery was such a big step forward for the field.Almost immediately after Sorek first described the phenomenon, in 2017, four independent groups - including Cheng's and one led by structural biologist Alberto Marina at the Biomedical Institute of Valencia in Spain - set to work trying to reveal the molecular basis by which arbitrium peptides are made, sensed and acted on by phages.Those technical details, reported in five papers 3 7 over the past nine months, helped to explain exactly how the short peptides Sorek discovered influence viral decision-making. For Marina, however, this is just the start of the story:Marina's suspicion rests on a finding in one of those papers 6 . Working with José Penadés, a microbiologist at the University of Glasgow, UK, Marina showed that the receptor for arbitrium in the phage can interface not only with genes in the bacterium that help the virus to reproduce, but also with other, unrelated stretches of DNA.The researchers are now exploring whether the phage's peptide language alters the activity of key genes in its victim, too. "If true," Marina says, "this would make the picture much bigger and more exciting."Expanding on his own initial discovery, Sorek has found arbitrium peptides popping up everywhere. His team has now found at least 15 different types of phage, all of which can infect soil microbes and use some sort of short peptide to communicate 8 . Notably, says Sorek,. The viral chit-chat thus seems to have evolved to allow communication only between close relatives.Phages might speak only to their own kind, but they can also listen in on other languages. Molecular biologist Bonnie Bassler and her graduate student Justin Silpe have found that 9 . "The phages are eavesdropping, and they're hijacking host information for their own purposes - in this case, to kill the host," Bassler explains.This molecular snooping occurs naturally in phages that infect the bacterium responsible for cholera, Vibrio cholerae. But in their lab at Princeton University in New Jersey, Bassler and Silpe have engineered 'spy' phages that can sense signals unique to other microbes, including Escherichia coli and Salmonella typhimurium, and obliterate them. The viruses in effect became programmable assassins that could be made to kill off any bacterium - at will and on demand.. Two independent groups reported last year that some phages act selflessly to overcome the viral countermeasures of Pseudomonas bacteria 10 The teams - one led by phage biologist Joe Bondy-Denomy at the University of California, San Francisco, the other by CRISPR expert Edze Westra and virologist Stineke van Houte at the University of Exeter, UK - watched as viruses bombarded bacteria with specialized proteins designed to break down the cells' CRISPR-based immune defences. The first wave of viruses attacked the cells, killing themselves but also weakening the bacteria. The initial bombardment paved the way for others to conquer the microbial foe. "Those phages had to be there, and to die, and produce anti-CRISPRs before another phage could come along and succeed," says Bondy-Denomy.In follow-up work, Westra and his postdoc Anne Chevallereau demonstrated how phages lacking these anti-CRISPR proteins 12 . To Westra, that shows the potentially far-reaching consequences of altruistic behaviours among viruses. "There are a lot of emergent properties at the population level," he says. "It's very important to keep the ecology of these phages in mind."These examples of communication and cooperation in phages are, says Lanying Zeng, a biophysicist at Texas A&M University's Center for Phage Technology in College Station. "This is a whole unexplored area." And the same goes for viruses that infect other cell types - including animal and human cells - which employ some social tricks of their own.Take vesicular stomatitis virus (VSV), which mainly infects farm animals, but can cause a flu-like illness in humans, too. Particles of this viral pathogen suppress host immunity at a personal cost but at a benefit to the group, as Sanjuán and his colleagues have shown 13 . No one is sure yet how this cooperative evasion is happening, but the work highlights how crucial altruism can be for the success of VSV. That could help scientists to beat the virus in farm animals, and optimize it for use in vaccines and therapeutics.Other instances of collective action are widespread among disease-causing viruses. In poliovirus, for example, multiple genetically distinct viral strains can clump together to swap gene products and enhance their human-cell-killing potential 14 . And two strains of influenza - one that excels at cell entry, the other at cell exit - grow better when maintained in cell culture together than when kept apart 15 But in a real-world setting, in nasal swabs from people with influenza, the two viral strains didn't seem to coexist 16 . Jesse Bloom at the Fred Hutchinson Cancer Research Center in Seattle, Washington, who led the research, thinks that has to do with some peculiarities of the flu virus' life - its population size swings so wildly that cooperative particles have a slim chance of sticking together. For viruses that don't undergo those kinds of transmission bottlenecks, "cooperation might be more likely to be maintained in real-world settings", he says.That's exactly what microscopist Nihal Altan-Bonnet found when she studied rotavirus transmission between mouse pups. Rotavirus particles can travel together between cells in bubble-like vesicles, sharing resources and hiding from the host's immune system. And, Altan-Bonnet and her colleagues have shown, the particles become more infectious to mice when they are inside these cooperative clusters than when going it alone 17 Many other pathogenic viruses - including those responsible for Zika, hepatitis, chickenpox, norovirus and the common cold - are now known to transmit themselves through these vesicles, too."These viruses are very sneaky," says Altan-Bonnet, who heads the Laboratory of Host-Pathogen Dynamics at the US National Heart, Lung, and Blood Institute in Bethesda, Maryland. "And we have to think of strategies that disrupt this cooperativity and clustering of viruses."That is, unless the destructive power of viruses could be used for good.- and knowing more about how they converse with each other could help to refine such therapies, which have a long history in medicine but are only just starting to be manipulated for therapeutic gain.Last month, for instance, researchers described the first successful clinical use of genetically engineered phages to tackle a drug-resistant bacterial infection 18 . For infections such as this, of course, the ideal solution is to use the virus to annihilate the bacteria entirely. But for conditions that are marked by a microbial imbalance, such as acne, some types of cancer and inflammatory bowel disease, it might be better to deploy a phage that can help to restore the balance without an all-out assault.And for those more subtle applications, knowing exactly how viruses communicate "could be really useful for helping us to engineer phages that could be used for treating disease", says Karen Maxwell, a phage biologist at the University of Toronto in Canada. Tapping into the arbitrium system could thus lead to more tractable, or even reversible, treatments.Learning to speak virus could provide a different kind of therapeutic benefit, too. "This could be an addition to the synthetic-biology toolkit to help fine-tune engineered bacterial gene expression," says Christopher Alteri, a microbiologist at the University of Michigan in Dearborn.Sorek, for example, has taken the arbitrium peptides out of their natural habitat in the phage and plugged them into other organisms, where they act as dimmer switches that dial up or dampen gene activity. In unpublished work, he and his graduate student Zohar Erez inserted the arbitrium machinery into the bacterium Bacillus subtilis, allowing them to manipulate several of its genes at will.What's more, notes Sorek, if arbitrium-like systems turn out to be conserved in human viruses - pathogens such as HIV and herpes simplex virus that, like phages, spend portions of their lives hiding out in cells - thenEvery scientific project that persists gets an '-ology', and the study of sociable viruses is no different. Two years ago, Díaz-Muñoz, Sanjuán and evolutionary biologist Stu West from the University of Oxford, UK, coined 19 a new term - sociovirology - to provide a framework for their line of research. The American Society for Microbiology will host the first-ever workshop dedicated to the topic at its annual meeting this month in San Francisco. "It's an idea whose time has come," Díaz-Muñoz says.In sociovirology, he sees many parallels with the gradual acceptance of similar group behaviours among bacteria in years past: it wasn't until researchers pinpointed the chemicals involved in quorum sensing and put a name to the process that most microbiologists paid the phenomenon any attention."It isn't in the consciousness," Díaz-Muñoz says. But as with all things social and viral, the message is spreading.Nature 570, 290-292 (2019)doi: 10.1038/d41586-019-01880-6


theindependent--2019-01-28--Life-changing gene therapies donapost work for everyone But researchers want to fix that

Life-changing gene therapies don't work for everyone. But researchers want to fix that

Growing up in Devon in the 1980s, brothers James* and Matt* had to be careful with their antics – a cut or bruise could land them in hospital.  They have haemophilia, a genetic disease where the blood doesn’t clot efficiently due to a lack of a clotting protein. It’s plagued their family for generations. Their granny’s brother died from it, and they, their uncle and a younger cousin have long managed it by injecting the missing protein to prevent bleeds.  While haemophilia can now be managed effectively – in high-income countries at least, where medication is readily available – it can severely limit freedom and quality of life and can even reduce life expectancy. Bleeds can be triggered by minor strains that healthy people barely notice, such as from walking or lifting boxes. Blood then seeps from the capillaries and pools in the joints, causing throbbing pain and lasting damage.  Although the younger of the two at 41, Matt’s joints are the more wrecked; he can’t straighten his right arm due to eroded cartilage in the elbow, while both his ankles and his right knee are in bad shape. For James, 45, it’s worst in his ankles, which swell up and bleed after walking or standing for too long.  So when they heard about a clinical trial for an experimental gene therapy, both brothers were intrigued. Unlike the injections, the therapy might fix their haemophilia for good. It’s a simple idea: if you inherit a faulty gene, then putting a working copy into the body’s cells should fix things.  We might at long last be on the cusp of a new era in which it will be possible to halt certain genetic disorders. In 2012, the EU approved its first therapy targeted at a specific mutated gene, one which causes liver disease; five years later, a genetic treatment for vision loss was approved in the US. There are ongoing clinical trials of gene therapies for dozens of other diseases.  “Gene therapy has the potential to be transformational,” says David Schaffer, whose lab at the University of California, Berkeley, researches gene therapeutics. The best available drugs for diseases like haemophilia have only transient effects, he says, but using DNA as a medicine means that “the field, at least ambitiously, is thinking of a cure”.  For people like Matt and James, these new treatments could be life-changing.  There’s just one problem. For many of us, they won’t work.  Even for siblings, James and Matt’s worlds are alike. They both live in East Anglia, not far from each other, and have friends in common and go to the same pubs. Both are fans of indie music, and have had to endure crippling pain from standing at live gigs. Outside of work, James is the frontman of a local post-punk band, and Matt used to play guitar in another group.  And they both have haemophilia A, caused by a genetic mutation that makes their bodies unable to produce a blood-clotting protein called factor VIII. It affects about 1 in 5,000 men worldwide – it’s much, much rarer in women because the faulty gene is located on the X chromosome and is recessive, meaning its effects are usually masked if the body has another working copy. Women typically have to have a mutated gene on both their X chromosomes to suffer the effects.  “As kids, we played outside a lot,” says James. “The house where we grew up had a massive playing field behind it and an abandoned quarry. I remember us going to hospital a lot because of a bleed or a sore joint, bad cuts, a bash on the head.”  While James accepted his condition and did his best to not get hurt, Matt was more reckless, splitting his head open more than once as he rebelled against having to be careful. “When I was younger, I tried to ignore the disease,” he says. “That’s probably why I have more joint issues.”  When they got hurt, their parents would rush them to the doctor to receive injections of factor VIII, purified from donor blood. It wasn’t until their 20s that prophylactic injections of factor VIII became available to them. Life got easier: spontaneous bleeds could be avoided; joint damage could be controlled.  But they still had to boost their factor VIII every three to four days, meaning the injections would always fall on different days of the week, something that had to be kept track of. And they’d take 30 minutes each – far from ideal.  The gene therapy would instead give their bodies a working gene for them to make their own factor VIII. But transferring a gene into a person is no easy feat. Genes are long strings of DNA that don’t readily get inside cells. So therapies typically rely on viruses, which squirt DNA into cells’ nuclei as a way of life. In this case, a virus, modified so that it doesn’t cause disease, and with the healthy human factor VIII gene added to its DNA, is injected into the body. It then enters the body’s cells to deposit its cargo, leaving it as a separate piece of DNA in the nucleus next to the host cell’s genome. The cells then start using the implanted gene to create factor VIII.  After all those years of being forced to be careful, Matt decided to sign up for the clinical trial. But James was unsure – he didn’t fancy having to undergo lots of follow-up testing. He decided to speak to one of his uncles, who also has haemophilia. “He comes from an era when there was no treatment,” says James. “He said I should just give it a go.”  Part of a larger ongoing trial, it was a small study, with only 15 participants, and by the time James had also decided to enrol, all the spots had filled up. But soon afterwards, he got a call letting him know that a place had become available. A person had dropped out. It was Matt.  A blood test had revealed Matt had antibodies for the adeno-associated virus, or AAV, that the trial was using as the therapy’s carrier. A chance event – a fleeting infection earlier in life – had rendered him immune to the treatment. As Matt withdrew from the study, James took his place.  Matt is not alone. Across the population, it’s thought that immunity to AAV5, the specific type of virus used in this study, could be as high as 50 per cent; for other AAV types it could be higher still – for AAV1 and AAV2, perhaps as much as 70 per cent. But estimates vary, and without a standard way to test for immunity, we don’t really know the scale of the issue. What we do know, says Schaffer, is that pre-existing immunity is the main reason volunteers are excluded from gene therapy trials, and that it will severely restrict who gets to be treated if and when these therapies become widely available.  Luk Vandenberghe, a gene therapy researcher and associate professor of ophthalmology at Harvard Medical School, says that immunity to AAV is gene therapy’s Achilles heel. These are “incredibly potent therapies”, he says, “but they are only going to be relevant to a sliver of the population”.  So why, then, transport genes with such a common family of viruses that so many people have been exposed to?  The truth is that AAV wasn’t originally the leading candidate for gene delivery. It only came to the forefront after a tragic event that would change the field for ever.  The idea that genes could be used as medicine began brewing in the second half of the 20th century, drawing on new insights into the structure of DNA and the way that genes code for proteins.  It was clear early on that gene delivery would be difficult, but the knowledge that viruses embed their genetic material in cells raised the possibility that they could be co-opted as delivery vehicles. The development, in the 1970s, of tools for cutting and stitching together DNA finally made this possible.  The first trials to transfer genes into humans began in the late 1980s and 1990s. Yet the preferred vectors weren’t AAVs but retroviruses and adenoviruses; the latter, despite their similar-sounding name, are very different from AAVs. Adenovirus’s big draw was that it was easy to engineer and grow in the large quantities needed for treatment.  A concern was that a patient’s immune system might react badly. Adenovirus was known to elicit an immune response, but researchers considered this a manageable risk. They were wrong.  On 13 September 1999, Jesse Gelsinger, an 18-year-old from Arizona, received an infusion of adenovirus in a gene therapy trial to treat a urea cycle disorder. He soon developed a fever and other reactions to the virus. Some other trial participants had also reacted to the virus, but none as severely as Jesse. His immune system unleashed an all-out attack that could not be stopped. He slipped into a coma and died of multiple organ failure four days after receiving the treatment.  The trial, led by James Wilson of the University of Pennsylvania, was promptly stopped. A subsequent investigation by the US Food and Drug Administration (FDA) found mistakes in its execution, including patients not meeting eligibility criteria and the researchers failing to inform patients of adverse reactions previously seen in animals. In a wrongful death lawsuit, the Gelsinger family also alleged that Wilson had inadequately disclosed a conflict of interest, as he had a stake in a biotech company that would have profited from the trial’s success. Wilson was banned for five years from sponsoring FDA-regulated clinical trials or participating in research on human subjects, and the legal cases brought by the Gelsinger family and the government against the investigators and university were settled out of court.  Gelsinger’s death cast a long shadow over the fledgling field, and threw considerable doubt over whether adenovirus could be used for these sorts of therapies.  With heightened concern about patient safety, it was AAV’s time to shine.  First discovered in the 1960s as a contaminant of adenovirus, AAV will always remain linked in name to its notorious predecessor. But unlike adenovirus, which is a cause of the common cold, AAV sweeps through the body silently without signs of infection.  Jude Samulski, today the director of the Gene Therapy Centre at the University of North Carolina, isolated the first AAV genome in the early 1980s while a graduate student at the University of Florida. This allowed researchers to start thinking about engineering it into a gene delivery tool.  But it was difficult to grow, and adenovirus remained the popular choice. AAV, says Samulski, “was considered a stepchild”.  By the mid-1990s, though, it had been shown that AAV could safely shuttle genes into lab animals, and that the genes then worked. AAV had become a serious candidate for gene delivery. It was just unfortunate that, at the time of the Gelsinger trial, research with adenovirus was at a more advanced stage.  But after the tragedy, it was clear that a much less obtrusive virus was needed. Gene therapies require pumping massive doses of the carrier virus into people – many times more than you’d see in a natural infection. At such high doses, a virus that doesn’t normally cause an immune response is far less likely to get out of hand and harm the patient.  “With adenovirus, you are taking a pathogenic virus and you’re attempting to turn it into a harmless FedEx truck for the genes,” says Samulski. “AAV was a natural FedEx truck.”  James’s therapy was scheduled for a Monday in April 2016, at a hospital in west London.  The timing wasn’t ideal. He had recently bought a house with his partner, Anna*, and the move ended up falling just three days after his treatment. Frayed and exhausted from packing, the couple took the Sunday afternoon train to London, where they spent the night.  The next morning, James gave himself one last injection. The doctors told him to hold off putting in any outside factor VIII after this, to make it easier to detect if and when his body started making its own. If the treatment failed, his joints would start hurting within a couple of days. But even as his body was about to be genetically altered in a procedure that not long ago belonged to science fiction, James had other worries.  “No one was sure when the gene therapy would start working,” he says. “They just told me to be a bit careful. I was like, ‘Well that’s well and good, but I’ve got to move house later this week.’”  The treatment itself was a mere hour-long IV drip. This is how long it took to inject James’s arm with a cup full of liquid containing over 450 trillion AAV virus particles, each carrying a working copy of the factor VIII gene. Once in the bloodstream, some of the virus would find its way into James’s liver and the cells lining his circulatory system, where factor VIII is normally made, and unload its cargo.  During the next 24 hours, James was not allowed to leave the treatment room, and he was closely watched for any adverse effects. There were none. The room had a chair for Anna to sit on, a TV and a bathroom off to the side, but for James, being confined in a tight space was the worst part of the treatment.  The next day, the couple went home and moved house as planned.  “I could already feel something,” says James. “I remember sitting down at the end of the day after putting all that furniture together, and I did not feel quite so bad. And then the next day we were properly moving and I carried loads of boxes. I was tired but otherwise feeling good.”  Before, this level of exertion would make his joints flare up with fresh bleeds. But five days after the treatment, blood tests revealed what he had suspected – his body was making its own factor VIII. The therapy was working.  The trial had started with two patients receiving a low dose of the treatment. When this proved safe, six others were given an intermediate dose, and with this proving safe too, a further seven – including James – got a high dose. Nine of these patients were included in the trial’s writeup. It’s what’s known as a dose-escalation study.  The low-dose patients saw no improvements, and the intermediates some, but it was in the high-dose patients where the effects were most pronounced – all bar one went on to produce their own factor VIII at levels seen in healthy people. Their rates of spontaneous bleeds dropped, as did their need for injections.  “When we started seeing these levels, which were essentially normal… it just blew it out of the water. We were completely gobsmacked,” says John Pasi, professor of haemostasis and thrombosis at Barts and the London School of Medicine and Dentistry and the lead investigator of the study, which was funded by BioMarin Pharmaceutical.  “Because it was so painless, it seemed so easy,” adds James. “Do 24 hours in London, and that was it. It changed my life – it’s crazy.”  When he was rejected from the trial, Matt hadn’t been that upset. But seeing the effects on his brother, the significance of it began to hit home. “If I knew how good the outcome would be, I would have been disappointed,” he says. “Obviously I’m disappointed now.”  James took part in an early phase of the trial, to test the therapy’s safety and efficacy. The study has since expanded to test efficacy on a larger number of patients. Following the FDA’s announcement last year that it would streamline its review process for emerging gene therapies, Samulski thinks the first one for haemophilia could become widely available within three years.  Two and a half years after the treatment, James’s factor VIII levels still hover in the normal range. He has not used a syringe since he gave himself that last injection just before the gene therapy. By all accounts, he appears cured.  The Gene Therapy Centre occupies two floors of a modern redbrick building on the western rim of the University of North Carolina campus at Chapel Hill, which is lush with greenery on the May morning that I visit. Exams have just ended and the campus, normally full of students, is empty. Jude Samulski, the director, is walking with a slight limp due to a back injury from a few months before. “I fought the Christmas tree, and I lost,” he says.  During his time there, the Gene Therapy Centre has created myriad AAV vectors, which are being tested for a host of diseases, including ones that affect the muscles, brain and blood.  Samulski himself has continued to perfect gene delivery both in his lab and through startups. One of these – Bamboo Therapeutics – was recently bought by Pfizer, along with an AAV vector that it equipped with a version of a muscle gene called DMD. Pfizer is now testing this vector in people with Duchenne muscular dystrophy, a devastating condition where the muscles degenerate, caused by a lack of dystrophin, the protein DMD codes for.  Another large pharmaceutical company, Novartis, announced in April 2018 that it had acquired AveXis, a startup behind a promising gene therapy for spinal muscular atrophy, a similarly devastating disease that, in its most severe form, is often fatal in early childhood.  That pharmaceutical giants are getting into the field signals that gene therapy, long plagued by the 1999 tragedy, is finally being taken seriously, Samulski says.  But this isn’t helping people like Matt. “The clinical research hasn’t tipped the scales for patients who have been excluded: if you are fortunate, you can get treated; if you are not fortunate, you can’t,” Samulski explains. “The field is now moving towards finding ways to overcome the remaining challenges, including pre-existing immunity.”  And the clues to this lie in the virus itself.  A viral particle is composed of a protein shell, or capsid, with its genetic material tucked inside. What exactly these viral proteins do is a mystery, and one of the many virologists trying to unlock it is Lauriel Freya Earley, a postdoctoral researcher at Samulski’s lab.  Earley has an encyclopedic knowledge of AAV. The capsid, she tells me, consists of three proteins – vp1, vp2 and vp3 – which somehow self-organise into an icosahedral, or 20-faced, structure that is 3,000 times smaller than the width of a human hair.  She hands me a piece of plastic that looks like a starfish, its surface rugged with tiny spikes. It’s a piece of a 3D-printed model of a blown-up AAV capsid. Besides shielding the viral DNA, the capsid also acts like a key to help the virus get inside different organs in the body. Bits of protein material stick out to form a bumpy surface, which – somehow – helps the virus enter cells.  In the 37 years since Samulski cloned the first AAV, which came to be known as AAV2, a number of other types have emerged. There’s estimated to be around a dozen that can infect human cells, and a number of these are being tested as gene therapy vectors for different diseases. The types are distinguished by their different capsids, which allow them to do different things. AAV5 and AAV8, for example, breeze into the liver. AAV9 can access the liver as well, and it can also cross the blood-brain barrier, an obstacle for many molecules, and so could deliver genes to the brain. As well as sending genes to different tissues, the diverse AAVs could also provide a way around the immune system.  The capsids also make viruses draw the fire of the immune system. When someone who has been exposed to a virus develops antibodies to it, it’s these distinctive structures that they target for destruction.  While the majority of people may have already been infected with AAV2 – studies with higher estimates suggest around 70 per cent of people have antibodies – it’s thought that exposure is lower for other AAV types. For people like Matt, who are immune to one, there’s hope they could be treated with another.  Researchers are also creating new variants in the lab. One way to do this is to engineer capsids so that they are no longer recognised by antibodies. This would be straightforward if researchers knew which bits of the capsid antibodies recognise, but that’s another part of AAV biology shrouded in mystery.  An alternative approach is to create many, many mutant capsid variants, and then select those that slide past the immune system unnoticed.  “There’s no reason that we should be at the mercy of whatever viruses nature has thrown over the fence at us,” says David Schaffer of the University of California, Berkeley, who is also a founder of 4D Molecular Therapeutics, a startup for AAV design. He believes we should engineer AAVs, both to optimise them as gene delivery vehicles and to bypass the immune response. “If we make enough changes in the surface coat of proteins, we can evolve the virus so it’s no longer recognised by the pre-existing antibodies.”  A few years ago, Samulski applied this approach to a real-life situation. Six boys with Duchenne muscular dystrophy had taken part in an early-stage trial using a modified form of AAV2 as a vector for gene therapy. The aim had been not to treat them but to test whether this AAV2 was safe and effective at delivering the relevant gene – and it was. But, as a result, the boys had all developed high levels of AAV2 antibodies, which would preclude them from receiving another dose as treatment in the future.  So Samulski’s team collected blood from three of them, exposed a vast collection of mutated AAV2 capsids to the antibodies it contained, and selected any that evaded detection. AAV2 coated with these capsids could, in principle, be used to deliver therapies to these three boys. However, Samulski’s experiment was only an academic exercise to show that the approach worked.  Under current regulations, personalised gene therapy remains unrealistic. Regulatory agencies do not distinguish between naturally arising and artificially created AAV capsids, so each new variant has to go through onerous and costly clinical trials, says Samulski. “But given that thoUSnds of patients are being excluded overall, there has to be some common-sense conversation between regulatory agencies and clinical need.”  However, even if the approval process were to become more streamlined for artificial AAVs, not everyone is on board. James Wilson, who has shifted the focus of his research from adenoviruses to AAVs, is concerned that engineering AAVs too much could turn a harmless virus into something more pernicious. Instead, he’s focused on isolating new natural AAVs from primates.  “These exotic AAVs are sufficiently different not to be recognised by the immune system,” Wilson says. “But are they good vectors? That’s what we’re working on now.”  Samulski, though, is undeterred by criticism of artificially creating viruses.  “You can look for natural viruses, but if you know how to evolve them, then that’s the same. Natural does not mean better. There is no evidence that engineered viruses could be dangerous.”  On a Friday night in April 2018, a few days short of the second anniversary of his treatment, James’s band performed at a pub in Cambridge. Before, he would have had to boost his factor VIII levels to be on top form, but this was no longer necessary.  The constant worries about having to be careful with his body and to remember the injections have disappeared. He and Anna can now plan longer holidays together without having to think about how much medication to bring along, or whether it will be possible to store it in a cool place.  “I feel like a different person,” he says. “I don’t even think about it. It’s weird how very quickly you get used to not doing something you’d done for 43 years.”  The treatment hasn’t caused friction between the brothers, and they remain close. James, though, admits that he feels guilty about the trial’s success, and having something Matt doesn’t. There’s a sadness too for both over a bond no longer there. Throughout the course of their lives, they had tested different medications together and always had each other to talk to about their disease. They still talk about it, but it’s not the same as before.  No one knows for how long James’s new factor VIII gene will work, but an earlier gene therapy trial for haemophilia B offers hope: patients are continuing to produce their own clotting factor eight years later.  But James does worry about his levels dropping. “In the back of my mind, I’ve got the feeling that this might not last for ever, so I’m totally enjoying it while it lasts. I even have totally irrational thoughts, like maybe I should worry about my levels more, instead of taking them for granted – that way they might stay higher.”  If James were to lose his modified cells as they regenerate, he probably wouldn’t be able to repeat the treatment, because it’s likely he too will now be immune to it. And because gene therapy requires giving high doses of the carrier virus, his AAV5 antibodies are far more plentiful than those produced in a natural infection. This might preclude him from treatment with other AAV types.  But in the future, we may not even need viruses for gene therapy. Researchers are looking to develop other delivery methods, from liposomes – fluid-containing fatty molecules that can fuse with the cell’s membrane – to synthetic nanoparticles that won’t be seen by the immune system. Researchers are also investigating gene-editing methods to permanently embed the working gene into the recipient’s genome.  “There’s lots of funding in gene therapy research, so problems will be easier to solve. It’s only a matter of time,” says Samulski.  As it turns out, Matt doesn’t have to wait long. Since he first applied to take part in the trial, BioMarin has changed how it determines immunity. A subsequent test found Matt’s AAV5 antibody levels to be below threshold, making him eligible for the study’s later stages.  It’s a surprising turnaround – and a reminder that, despite its history, the field is still in its infancy, grappling to fully understand the challenge of pre-existing immunity. “If all goes well, I should be starting the trial in about six months, so obviously I’m very pleased,” Matt says.  It also shows, says Samulski, the need to standardise immunity tests – as everyone at the moment is experimenting with different methods. Until we understand exactly what level of immunity hinders treatment, we might be unnecessarily denying people life-changing therapies.  “Gene therapy is in such early days,” he says, “we are still testing what is going to work.”  * Some names have been changed  Mosaic contacted BioMarin for comment, but it said that as it operates under the Association of the British Pharmaceutical Industry code of practice it would be unable to provide specific information about the haemophilia A treatment discussed in this piece until it is licensed and approved  This article was first published by Wellcome on Mosaic and is republished here under a Creative Commons licence. Sign up to the newsletter


thesun--2019-07-03--HIV cure closer than ever as scientists wipe out virus for first time in living animals

HIV cure ‘closer than ever’ as scientists wipe out virus for first time in living animals

SCIENTISTS are "closer than ever" to finding a cure for HIV after discovering a way to wipe out the virus in living animals for the first time.  Researchers say it marks a critical step towards a possible cure for humans - and clinical trials could begin as early as next year.  Current treatment focuses on the use of antiretroviral therapy, known as ART, which suppresses HIV replication, but does not eliminate the virus from the body.  It's not seen as a cure and requires life-long use because if the treatment is stopped, the virus can renew replication and fuel the development of AIDS.  But researchers at Temple University in Philadelphia and the University of Nebraska say they have come up with a revolutionary gene-editing tool.  The team injected mice with human bone barrow to mimic the immune system and say they were able to eliminate HIV in nine of the 21 animals.  Senior investigator Professor Kamel Khalili, an AIDS expert at Temple University, said: "Our study shows treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals."  His team used a technique called CRISPR-Cas9 that can snip faulty DNA with a harmless virus and has been likened to a pair of "molecular scissors".  It combines this with a recently developed therapeutic strategy known as LASER (long-acting slow-effective release) ART.  The technique targets viral "sanctuaries" - maintaining HIV replication at low levels for extended periods of time.  This also reduces the frequency of treatments.  The long-lasting medications were made possible by pharmacological changes in the chemical structure of antiretroviral drugs.  HIV rebound is directly attributed to the ability of the virus to integrate its DNA sequence into the genomes of cells of the immune system, where it lies dormant and beyond the reach of antiretroviral drugs.  In the study, published in Nature Communications, the modified drug was packaged into nanocrystals, which readily distribute to tissues where HIV is likely to be lying dormant.  From there, the nanocrystals, stored within cells for weeks, slowly release the drug.  Dr Khalili explained: "We wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA."  To test their idea, the researchers used mice engineered to produce human T cells susceptible to HIV infection.  Once infection was established, mice were treated with LASER ART and subsequently with CRISPR-Cas9.  At the end of the treatment period, mice were examined and analyses revealed complete elimination of HIV DNA in about one-third of HIV-infected mice.  Dr Khalili said: "The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection.  "We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year."  Just over a generation ago the world was in the grip of AIDS hysteria, but thanks to modern drugs the picture has transformed.  Today it's more akin to a long-term condition than a certain death sentence and the number of new infections are declining in most parts of the world.  Earlier this year health secretary Matt Hancock promised by 2030 there would be no new cases of HIV in England.  Co senior investigator Dr Howard Gendelman, of Nebraska University, who developed LASER ART, said: "This achievement could not have been possible without an extraordinary team effort that included virologists, immunologists, molecular biologists, pharmacologists, and pharmaceutical experts.  "Only by pooling our resources together were we able to make this groundbreaking discovery."  In previous work, Dr Khalili's team used CRISPR-Cas9 technology to develop a novel gene editing and gene therapy delivery system aimed at removing HIV DNA from genomes harbouring the virus.  In rats and mice, they showed that the gene editing system could effectively excise large fragments of HIV DNA from infected cells, significantly impacting viral gene expression.  Similar to ART, however, gene editing cannot completely eliminate HIV on its own. The researchers now believed they have solved the problem.  We pay for your stories! Do you have a story for The Sun Online news team? Email us at tips@the-sun.co.uk or call 0207 782 4368 . You can WhatsApp us on 07810 791 502. We pay for videos too. Click here to upload yours.


upi--2019-12-23--Experimental Zika vaccine protects monkey fetuses in study

An experimental Zika virus vaccine that was given before pregnancy protected monkey fetuses, researchers say.  The Zika DNA vaccine VRC5283 lowered levels of Zika virus in pregnant rhesus macaques and reduced the risk of fetal problems, according to the study published Dec. 18 in the journal Science Translational Medicine.  The vaccine is in early-stage human trials.  This study was the first to test a Zika vaccine given before conception with exposure to the virus during pregnancy, said virologist Dr. Koen Van Rompay, a scientist at the California National Primate Research Center at University of California, Davis.  Fetuses of pregnant women infected with Zika have a high risk of death, microcephaly (a smaller-than-normal head) and other abnormalities. There is no approved vaccine.  This study with monkeys was designed to resemble a real-world situation in which women could receive a Zika vaccination months or years before becoming pregnant, the researchers explained.  They said their findings could help in the development and approval of the VRC5283 vaccine for use in humans. However, results of animal testing are often different in people.  The team vaccinated female monkeys who weren't pregnant. After vaccination, they were housed with males and allowed to mate. Thirteen vaccinated females and 12 unvaccinated control animals got pregnant.  Pregnant females in both groups were exposed to Zika virus at points representing first and second trimesters.  Compared to the control group, vaccinated females had less Zika virus in their blood and it persisted for a shorter time after exposure. Two unvaccinated monkeys miscarried due to Zika infection, but there was no early fetus loss in the vaccinated group.  At the end of pregnancy, researchers examined tissues from the mothers and fetuses for Zika. Eleven of 12 fetuses in unvaccinated monkeys had detectable Zika virus in their RNA, but no Zika virus RNA was detected in the 13 fetuses from the vaccinated monkeys. Researchers said that suggests the vaccine prevented transmission of Zika to the fetus.  Antibodies against Zika in the vaccinated females correlated with protection against the virus.  The researchers are also looking into how Zika affects the development of young monkeys. "In our previous studies, we found microscopic brain lesions in fetuses exposed to Zika virus," Van Rompay said in a university news release. By observing the monkeys long after birth, his team members hope they'll learn more about how Zika affects children long-term.  The World Health Organization has more on Zika.


vaxxter--2019-10-17--Book Review – The Virus and the Vaccine (about polio vaccines)

THE VIRUS AND THE VACCINE, by Debbie Bookchin and Jim Schumacher, is an impeccably researched expose’. Beyond documenting the historical saga of the polio vaccine and SV40, this book has a much larger and more foreboding message.  This book definitively connects the incestuous interrelationships between the federal government, the major governmental health agencies [the Food and Drug Administration (FDA), the National Institutes of Health (NIH), the Centers for Disease Control (CDC) and the National Cancer Institute (NCI)] and the pharmaceutical industry. If there were ever any misgivings as to how deeply enmeshed these groups are, this book removes all doubt. The impeccable research exposes the extensive use of power, coercion and cover up used to maintain the public’s “confidence in vaccines.”  It goes something like this: • A researcher documents a serious problem with a vaccine. • The government publishes a “definitive study” to “set the record straight.” • A flurry of media campaigns and medical journal articles are commenced to ensure support of the conclusions of the “definitive study.” • Upon critical examination, the “definitive study” is found to have serious flaws. Although broadcast via many venues—through government hearings, journal publications, radio broadcasts and over the internet—the rebuttals are barely acknowledged. The “definitive study” becomes “established medical fact.” • Pressure from the public watchdog groups is placed on Congress to force the hand of the government agencies. Hearings are held to give the appearance of concern. But instead of acting decisively, the hallmark of government committee meetings becomes to delay a decision by using the justification, “temporal association does not prove causality.”  In 1959, researcher Dr. Bernice Eddy, from the National Institutes of Health (NIH), the Division of Biological Standards (DBS) was working with Dr. Sarah Stewart from the National Cancer Institute (NCI). Together, the two proved that a mouse virus could cause cancer when it was injected into other small animals. Both researchers received national recognition for their discovery and Stewart’s reward including being put in charge of her own laboratory at the NCI.  Upon returning to the DBS, Eddy began to question if the simian viruses she found in the monkey tissue cultures used to grow polioviruses could possibly do the same thing. Acting on her own, she set up an experiment using cell cultures from monkey tissue. She injected the serum into hamsters and to her surprise, found that 70% of the animals developed tumors. After several more rounds of experiments, she knew that she had discovered a deadly viral contaminant in the monkey tissue cultures. Alarmed, she knew she needed to do something about it. However, when she approached her boss, Dr. Joe Smadel, with her findings, her concerns were less than welcomed.  Smadel was one of the vaccine’s staunchest defenders. At one time, after the Cutter vaccine had caused a polio outbreak, a congressional committee had considered completely withdrawing the Salk vaccine from the market. It was the “persuasiveness of Smadel’s testimony and his stature in the world of virology that convinced the panel not to cancel the vaccine program outright.” (p. 63)  Rather than praising Eddy for her discovery and demanding more NIH funding for further research, Smadel responded with intense anger. The last thing that the NIH, the federal government—and the pharmaceutical houses—wanted to hear from the DBS was information that might scare people away receiving the vaccine. Instead of being rewarded for her efforts, her discovery eventually cost her her laboratory, her staff, her position, and essentially her career as a serious investigator. This sent a chilling message to other investigators: research on the connection between SV40, cancer and the polio vaccine may be dangerous to your future.  This same message is being sent today to researchers investigating the possible connection between vaccines and autism.  Do not blame the vaccine  Dr. Andrew Wakefield was a pediatric gastroenterologist whose research at the Royal Free Hospital in London had received commendations for elegance. In 1997, he received a few calls from parents who reported their child was normal before receiving the MMR vaccine and then had subsequently lost their verbal skills and became autistic. Their symptoms included bloating, pain, diarrhea, and weight loss.  Dr. Wakefield and a team of others developed a hypothesis that perhaps the measles virus in the MMR given in combination with two other live viruses was somehow damaging the gut of certain, susceptible children. Colonoscopies were performed on 12 children who appeared to be suffering from a new form of inflammatory bowel disease, possibly triggered by the MMR vaccine. This information was published in The Lancet in 1998 (Lancet 351:637-641), as merely a case report, suggesting that “further investigations are needed to examine this the syndrome [of ileolymphoid hyperplasia] and the MMR.  From that point forward, Dr. Wakefield has been villainized by the medical world. The Royal Free eventually fired him, and he has been publicly taken to task in medical journals, in media interviews, and within the mainstream press on a regular basis. The heads of the UK Department of Health continue to emphasize the safety of MMR while pouring scorn on the research of anyone who disagrees. Doctors and researchers, who insist on talking off the record with understandable caution state, ”We’ve all seen what happened to Andrew Wakefield, and we don’t want our careers destroyed.”  The “Definitive Study” to prove SV40 doesn’t cause cancer  By 1963, nearly half of the American population had received the Salk polio vaccine and the NIH’s own research had established the carcinogenicity of SV40. Confronted with a potentially disastrous public health crisis, a massive epidemiological study to assess whether SV40 was actually causing cancer in the Salk vaccine recipients needed to be done.  The daunting task fell on the shoulders of a young physician who came to work at the National Cancer Institute (NCI) Epidemiological branch in the summer of 1962. Joseph Fraumeni, MD was preparing for a career in clinical medicine when he received an offer to work for the NCI. He was hired to become the principal investigator for the office of epidemiological studies, yet by his own admission, he stated:  With the help of biostatisticians from the NIH and the NCI, the study was designed to determine if there had been a statistically significant rise in cancer in children 6-8yo who have been vaccinated during the May and June of 1955. Three types of cancer were surveyed. The study, published in The Journal of the American Medical Association in 1963 (JAMA 185(9):713-718) concluded, “no significant alterations in mortality rates for cancer had been found and the cancer mortality rates appeared to be unaffected.” Henceforth, the Fraumeni study became landmark study that, for the next 30 years, would be quoted as conclusively proving that SV40 was a “moot issue” as a cancer-causing agent.  It was many years before the Fraumani study’s flaws were thoroughly examined, although the study’s investigators admitted several at the outset. For example, the children were only followed for four years and certain types of SV40 cancers can take many years to develop. Only cancer deaths—not cancer diagnoses—were included, meaning children diagnosed with cancer but still alive at the time of the study were excluded. Only three types of cancers were surveyed: brain, kidney, and connective tissue. Therefore, other types of cancer associated with SV40—mesothelioma, bone, leukemias, and lymphomas—were not included.  The most glaring flaws had to do with the cohort assignment. The number of children ages 6 to 8 were estimates and an assumption was made that none of the children had moved from state to state. In addition, it was impossible to actually know who got the contaminated vaccines and who did not. Therefore, the cohort assignment, the cornerstone of epidemiological research, was completely flawed. With this segment of the research flawed, the conclusions were not only highly suspect but completely inaccurate.  In spite of these blatant inaccuracies, the Fraumeni Study became “established medical fact,” definitively concluding that exposure to contaminated polio vaccine did not result in cancer. This study was quoted in every article and in every textbook, without question, for more than 30 years.  The Next Generation of SV40 Research  In the 1990s, SV40 research was resumed through the work of Dr. Michele Carbone. A prestigious virologist, Carbone proved the connection between SV40 and mesothelioma, a rare cancer of the lung pleura thought mainly to be caused by asbestos. His research, published in Nature Medicine in July 1997, was the first of many studies published in Italy, Germany, and the USA showing the association between SV40 and human cancers.  As his work progressed, the Viral Epidemiological Branch (VEB), a division within the NCI, published two additional “definitive studies” meant to dissuade all residual concerns about the connection between SV40 and cancer. The first was published by Shah, Daniel, Strickler and Goedert in the Journal of Infectious Diseases (J.Inf.Dis 176:1618-21). The study, published in 1997 and subsequently referred to at the VEB Study, concluded there was “no demonstrable connection between SV40 and human cancers.” This one study became the primary weapon in the federal government’s efforts to cast doubt on the association.  Like the Fraumeni study, an analysis of the research shows that the data is inherently flawed, making the conclusions at best worthless; at worst, deceptive. The public was misled into believing that SV40 is not a health threat. The scientific community was also misled into believing that no further research was necessary. Wanting to form a united front, when one branch of government turns out a study that other branches champion its conclusions.  One of the most hotly contested arguments currently being debated regarding the safety of vaccines is over the presence of thimerosal in vaccines. Thimerosal, a preservative, which is 49.6% ethylmercury, a substance known to have neurotoxic effects implicated in both clinical and epidemiological studies to be associated with the exponential rise in the incidence of autism.  The government’s latest “definitive study” used repeatedly in arguments to dismiss any causality between thimerosal and autism is referred to as The Danish study. This epidemiologically based study was designed to examine “whether discontinuing the use of thimerosal-containing vaccines led to a decrease in the incidence of autism.”  The conclusions of the study state,  Similar to the Fraumeni study, an in-depth analysis revealed three major flaws:  1. Autism counts [in Denmark] were first based on hospitalized, inpatient records and then changed to include outpatient records in the middle of the study.   2. Mercury levels [in the Danish studies] were substantially lower and given later than those scheduled in the U.S. in the 1990s.   3. Between 1970-92, the only childhood vaccine given in Denmark before 5 months of age was the monovalent pertussis vaccine. In the United States in the 1990s, children were exposed to multiple doses of DTP, polio, hepatitis B and Haemophilus influenza B (Hib) vaccines before five months of age, all containing thimerosal. (adapted from an analysis by Mark Blaxill, Director, www.safeminds.org)  In spite of these flaws, which make the analysis of the data inconclusive, the FDA, the CDC, the American Academy of Pediatrics (AAP) and the Institutes of Medicine (IOM) all site the study as the “definitive study” that conclusively proves there is no connection between thimerosal and autism.  Knowing since the 1960s that the vaccine contained a cancer-causing virus, how did the government allow this to happen? Mostly, it revolves around the cavalier attitude within the federal agencies charged with vaccine safety: • Division of Biological Standards in 1961 allowed contaminated lots to pass • Taking two years to implement safety regulations requiring manufacturers to make sure vaccine was SV-40 free before inactivation • Not issuing a recall of known-contaminated vaccine • Not using a safer, cleaner substrate (WI-38) • Softening of regulations to make manufacture less expensive and less time consuming  In 1961, the Technical Committee on the Poliomyelitis Vaccine met to discuss the safety of the existing Salk vaccine. It was concluded that “no untoward effects” had been attributed to the SV40 virus known to be in the vaccine and the virus was “assumed to be harmless.” The committee recommended no change in the current vaccination policy. Vaccinations should continue using the present stocks and until all the contaminated vaccine was used up.  On July 7, 1999, a recommendation was made by the FDA for the immediate reduction or elimination of thimerosal from infant vaccines. This announcement came after a two-year investigation, prompted by the FDA Modernization Act, which found infants may have been exposed to mercury in excess of Federal Safety Guidelines from routinely administered infant vaccines.  All members involved—including American Academy of Pediatrics (AAP), the FDA, the Centers for Disease Control (CDC) and some vaccine manufacturers—stated that they were making the recommendation to “alleviate the possible concerns” regarding thimerosal, but denied that thimerosal had a causal association with autism. The manufacturers were not ordered to remove the products currently on the market that contained thimerosal, only to create future products that were “thimerosal-free.” Therefore, children continued to receive thimerosal-containing vaccines for at least two additional years.  These are a few of the highlights found in The Virus and The Vaccine. This impeccably documented book provides information that unequivocally shows the mechanisms used today by government agencies and committees to ignore, diminish and dismiss concerns about vaccination are long-standing. Is it any wonder that public watchdog groups, vaccine activists, and concerned parents and physicians seem to make little headway when attempting to affect the problems associated with mandatory vaccination?  Because vaccination is a part of routine healthcare for people of all ages, The Virus and The Vaccine is a “must-read” for everyone. Approximately 77,500 children born each week in the US. Every parent, faced with the decision regarding vaccination, assumes that the vaccines have been proven to be safe and the governmental agencies regulating vaccines have their best interest in mind. However, The Vaccine and the Virus documents a different truth.  However, a shift is occurring: More and more people are questioning the safety and efficacy of vaccines. The information provided in this wonderfully researched book should cause everyone—parent and healthcare providers alike—to reevaluate their trust in the vaccines, and their blind confidence in the governmental agencies who control them.


activistpost--2019-11-23--FDA Shocking Study: Cells Used In Vaccines Contaminated With Serious Viruses Including Cancer

The U.S. Food and Drug Administration (FDA) has published shocking results which found that cells used in the manufacturing of numerous childhood vaccines are often contaminated with serious viruses including cancer.  The FDA study looked at vaccines that are made from living cells, or replicated cell substrates that some manufacturers are investigating to create. According to research, these cells are oftentimes contaminated with hidden viral fragments which have the potential to cause cancer.  These viruses are dormant, meaning they live “quietly” inside other cells. However, eventually these cells no longer hide and circulate throughout the body in the form of serious disease. As a result, a person injected with a vaccine containing these cancer-causing micro-organisms may not display signs of health complications until long after they have been jabbed sometimes several years later.  An experiment injecting rodents with vaccines yielded surprising results showing that the rats now had tumor cells.  “In some cases the cell lines that are used might be tumorigenic, that is, they form tumors when injected into rodents,” the FDA paper explains.  “Some of these tumor-forming cell lines may contain cancer-causing viruses that are not actively reproducing. Such viruses are hard to detect using standard methods. These latent, or ‘quiet,’ viruses pose a potential threat, since they might become active under vaccine manufacturing conditions.”  The list of tumorigenic or cells that run the risk of causing cancer include MDCK and CHO cells (for influenza virus vaccines), 293 and PER.C6 cells (for adenovirus-vectored HIV-1 and other vaccines), and tumor-derived cells such as HeLa cells (for HIV-1 vaccines) according to the FDA.  Although this author is against the injection of foreign chemicals into his own body, the FDA proceeded with the study for other reasons. The FDA writes they want “to ensure the safety of vaccines, our laboratory is investigating ways to activate latent viruses in cell lines and to detect the activated viruses, as well as other unknown viruses, using new technologies. We will then adapt our findings to detect viruses in the same types of cell substrates that are used to produce vaccines.”  The FDA adds, “These methods will enable FDA scientists to help manufacturers to determine whether their specific cell substrate is safe to use for vaccine production. The methods our laboratory are developing and testing will help to ensure the production of safe and effective vaccines in two ways: 1) FDA will be able to develop testing guidelines for manufacturers who use new cell substrates for producing vaccines; and 2) FDA will publish the new methods it develops in peer-reviewed scientific journals, thus making them readily accessible to all manufacturers.”  The FDA is also evaluating the risk of retrovirus infections in humans such as Simian foamy virus (SFV) which can be transmitted from monkeys to humans. Although, the FDA says “there is no evidence that SFV causes disease.” However, the FDA cautions that the virus can “remain in a lifelong quiet state in the DNA after infection.”  Despite these claims, we know that polio and smallpox vaccines contain monkey, pig, kidney and other foreign cells that are contaminated with SIV, SFV, and various other cancer-causing viruses. Most are also well aware that the Polio vaccine SV40 is documented on record by the CDC themselves (on a now-deleted page) to have cost people their lives and caused cancer. However, you can confirm the web page existed by using Archive.org’s time machine. Also there’s other evidence that SV40 has been detected in some human tumors.  So the claim made by the FDA “there is no evidence that SFV causes disease” is a laughably ill-researched statement.  In other gene sequencing news, recently it has been reported by scientists in a separate study that there are 560 cancer genes in the human gene sequencing for GlaxoSmithKline’s (GSK) combination vaccine for measles, mumps, rubella, and varicella (MMRV).  Cancer genes aren’t the only worry with MMR vaccines or vaccines in general. As Activist Post has previously expressed, mercury and aluminum have long been debated by people like Robert Kennedy Jr. as ingredients (adjuvants) in vaccines that could cause autism. This is for good reason since we know that both aluminum and mercury are neurotoxins that harm the body at high levels.  RFK, Jr. believes “it’s the preservative Thimerosal in the vaccines that causes autism.”  Kennedy expressed his opinion in a weighty now-deleted piece on the CDC whistleblower entitled “CDC’s Latest Tuskegee Experiment African American Autism and Vaccines.” (archive)  Thiomersal isn’t the only ingredient in vaccines; they have admitted to traces of aluminum, which is classified as a neurotoxin to the body and stated that “despite using it for 90 years medical sciences’ understanding about using aluminum as a vaccine adjuvant is remarkably poor.”  In 2017, Activist Post reported a previous separate study that confirmed aluminum in vaccines may cause Autism Spectrum Disorder (ASD), and children who suffer from it have up 10 times more metal in their brains than what is considered a safe amount for adults. Those researchers discovered that aluminum causes the membrane to separate the brain from blood flowing to it, thus affecting its internal temperature, non-neuronal cells and inflammatory cells.  Another previous study in 2012, from the peer-reviewed medical journal Lupus by Lucija Tomljenovic, PhD and Christopher A. Shaw, PhD of the University of British Columbia corroborates those claims, indicating that aluminum toxicity targets the mitochondria. That experiment found evidence that aluminum as an adjuvant can lead to permanent detrimental alterations of the brain and immune system function.  A court ruling in the UK found that the Swine Flu vaccinations had caused brain damage and Guillain-Barre syndrome (GBS) in multiple kids in 2015 who took the jab. Another case in an Italian court in September, 2014, “ruled mercury and aluminum in vaccines cause autism” and awarded a plaintiff’s family compensation for their young boy who developed autism from a six-in-one hexavalent vaccine manufactured by GlaxoSmithKline. GSK even admits INFANRIX Hexa can cause several deadly illnesses, but insists that its risk-benefit profile “continues to be favorable.” In 2013, two kids were awarded millions by the vaccine court, confirming the MMR vaccine causes autism.  There are several additional court cases; although the CDC and pharmaceutical industry would love to have these covered up, I dug them up. One MMR clinical trial’s results were faked by Big Pharma Merck. Merck knowingly falsified its mumps vaccine test results to fabricate a “95% efficacy rate.” In order to do this, Merck “spiked the blood test with animal antibodies to artificially inflate the appearance of immune system antibodies,” as reported by CourthouseNews.com.  In fact, regarding the use of aluminum and other metals in vaccines as an adjuvant, we may all be part of a 90-year-old experiment where we were all the lab rats.  Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science’s understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue. – US National Library of Medicine National Institutes of Health.  The MMR vaccine isn’t the only vaccine under scrutiny. In 2017, the Centers for Disease Control (CDC) announced there might be a link between miscarriages and vaccinations. The researchers found that women who had miscarriages between 2010 and 2012 were more likely to have had back-to-back annual flu shots including the Swine flu vaccine that a UK court ruled caused brain damage and Guillain-Barre syndrome (GBS) in multiple kids in 2015, as Natural Blaze reported.  At this point, the FDA effectively just inadvertently proved that jabbing yourself with a vaccine is the equivalent to trying Chinese research chemicals. Except that these deadly chemical combinations are approved by the FDA. The question on everyone’s minds is, how wasn’t any of this identified long before any of these vaccines were ever approved for use by the masses? Especially, the Polio and Smallpox vaccines which have injured and killed many over the years.  Where at first the problem may have been isolated to metallics (aluminum) used in vaccines that the US National Library of Medicine National Institutes of Health has admitted their understanding of as a main adjuvant in vaccines is “poor.” The new issue is vaccines that are made from living cells, or replicated cell substrates that may cause cancer or other serious diseases. Despite all this evidence, forced vaccinations are occurring in places like BC, Canada where, as Activist Post reported, parents have no choice but to vaccinate children. As this writer previously wrote, vaccines affect individuals differently and can have adverse side effects; now parents need to worry about deadly cells hidden beneath the vaccines that can cause illnesses.  Is it ever really safe to put a foreign substance into your body when each person’s body functions differently and has a different chemical make up? As RFK, Jr. says when it comes to vaccines: “Let the evidence speak for itself.”  Aaron Kesel writes for Activist Post. Support us at Patreon. Follow us on Minds, Steemit, SoMee, BitChute, Facebook and Twitter.    Subscribe to Activist Post for truth, peace, and freedom news. Become an Activist Post Patron for as little as $1 per month at Patreon. Follow us on SoMee, Flote, Minds, Twitter, and Steemit.  Provide, Protect and Profit from what’s coming! 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