<http://schema.org/articleBody>
" Read more of the Best and Brightest 2007 ***** His eyes are these ruddy slits. All he can see is a tiny circle of light directly in front of his face, and the rest is haze. If you walk with Bill Jacobs, you have to stick by his side, track his steps exactly, or else you&amp;#039;ll force one of our best microbiologists to stop and whirl and squint like some kind of hunched nocturnal animal. Tunnel vision. It&amp;#039;s genetic. And yet Jacobs moves with speed, even in his &amp;quot;hot&amp;quot; lab. Even in the realm of the bug. The bug&amp;#039;s scientific name is Mycobacterium tuberculosis. TB. It floats. It&amp;#039;s airborne. One lone bug is enough to make you sick, so the hot lab is designed to keep the bugs trapped inside large silver hoods; any escaping bugs get sucked through powerful filters and blasted away from human lungs with pressurized air. This is where Jacobs probes the genetic code of the bug using revolutionary techniques that he invented. He deletes some genes, splices others. It&amp;#039;s where Jacobs is learning how to save us, to cure us. Millions of us.  I watched Jacobs &amp;quot;gown up.&amp;quot; He pulled a white Tyvek suit over his polo shirt and paunch. He covered his red, veiny nose with a surgical mask. I could tell he was grinning underneath his mask. He looked like a square-dance caller about to spray his house for termites. Jacobs opened the inner door. Air whooshed into the hot part of the lab. He walked inside. Then rammed his left shin into a biohazard container brimming with pathogens. This is a story about persistence -- the bug&amp;#039;s and ours and Bill Jacobs&amp;#039;s. Ours is an act of will, an act of choice. But the bug has no will and no choice. Only preferences, only ruthless chemical needs. Humans falter, but the bug cannot. The bug can only live or die. The bug prefers not to die. Bill Jacobs and others like him choose to spend their lives trying to kill it.  The bug is a slosh of proteins in a weird waxy shell. If you could stick your nose into a billion of the bugs, you would smell dirty, musty socks. Soil is the womb. For millions of years, the bug fought other bugs in the soil, in the earth itself, and it won and won and won. The weak strains died, the strong survived. Evolution. Then the bug found a host. Us. Humans. And the bug must have liked its new soil, because it stippled our lungs with lesions and filled our throats with blood, persisting inside our bodies, infiltrating and dividing within the very cells that we sent to kill it, sometimes escaping the lungs to infect our livers and melt our joints and eat our bones from the inside. The bug killed a billion of us in the last two centuries alone, until we learned, through a persistence of our own, to kill it and kill it and kill it. Then we relaxed.  We stopped learning, because the flip side of human persistence is a lazy optimism; because we tend to forget that once a problem is solved with dramatic and heroic action, it doesn&amp;#039;t stay solved without hard and undramatic work.  So the bug persisted. And here in the West, very few of us noticed, until one day a gooberous American lawyer named Andrew Speaker got on an airplane with his hot American wife and a lungful of drug-resistant tuberculosis. Soil is powerful. The bug already knows this, but it&amp;#039;s something Bill Jacobs had to learn. Jacobs loves telling this story because it&amp;#039;s about zebra shit. Nobody expects zebra shit, but then again, neither did Jacobs. As he tells it, he was just hanging out at the Bronx Zoo one day, checking out the lions and the bears, when he got this sudden urge in front of the zebra pit. He reached over the barrier, picked up a clump of dirt and shit, put the clump of dirt and shit in his pants pocket, and took it back to his lab a few miles away at the Albert Einstein College of Medicine.  Jacobs was looking for a weird little creature called a bacteriophage, a virus that eats bacteria. He thought he could use the phage to learn about TB -- and maybe, ultimately, to create a new and better vaccine. But that was like seventy-eight steps away. Anyone staring at a young, thirtyish Jacobs, emptying a pocketful of dirt onto a plate in his lab, would have thought he was crazy. Phages? What the hell did phages have to do with a new vaccine? Phages were an obscurity within an already obscure field. Jacobs didn&amp;#039;t have a grant to look for phages. No tax dollars, no private windfall. Why not? Because science is not some blind dude mining turds from an urban zoo. Okay. But Jacobs had been hearing that ever since he was a kid. What science was, and, more crucially, what a scientist looked like. And he didn&amp;#039;t look like one. He didn&amp;#039;t come from the right place, didn&amp;#039;t go to the right school, couldn&amp;#039;t see for shit, and Jacobs knew it was true. He couldn&amp;#039;t deny it. He could only get pissed off. As a kid, he spoke in gibberish his teachers couldn&amp;#039;t understand a word of; his parents sent him to a speech pathologist, who left Jacobs with a strange, lifelong Southern drawl even though Jacobs grew up near Pittsburgh. His father was a steelworker in West Mifflin, Pennsylvania, where football ruled. Jacobs loved football, but with his bad eyes, he had to settle for cleaning the football team&amp;#039;s jockstraps. At Edinboro State College -- &amp;quot;maybe Playboy said it was one of the top party schools in the country?&amp;quot; -- Jacobs sucked at memorizing things. Probably had ADD. But he fell hard for math; math didn&amp;#039;t require good vision, only his deductive mind. And then Jacobs discovered genetics, which was like useful math -- math that could save the world. Jacobs began to ask simple questions about diseases that no one much wanted to work on. In grad school at the University of Alabama, he started futzing with the bug that causes leprosy, Mycobacterium leprae, a close cousin of M. tuberculosis. Unlike most bugs, M. leprae doesn&amp;#039;t grow on a plate or in a test tube, but in the belly -- this is true -- of a nine-banded armadillo. There are old pictures of Jacobs with Boogie Nights hair and Coke-bottle glasses, clutching armadillos to his chest like human babies. Jacobs moved to the Bronx in 1985, during the first TB epidemic in the U. S. in thirty years. He came young and arrogant, talking smack in an excitable squeal, pronouncing mycobacteria like MIKE-a-back-turr-ya. His new boss was the famous immunologist Barry R. Bloom, now dean of the Harvard School of Public Health. &amp;quot;New York City was full of TB,&amp;quot; says Bloom. &amp;quot;People were terrified, and it was amazing -- there was very little scientific expertise . . . it was like the Cultural Revolution in China. A generation got wiped out. The only ones who knew about TB were these old-time docs who treated it.&amp;quot; Bloom saw Jacobs&amp;#039;s passion and set him loose. It was brutal. TB is a slow wonder. It divides once in twenty-four hours; by contrast, E. coli divides once every twenty minutes. A single TB-vaccine experiment takes at least nine months. A single course of the antibiotics needed to cure TB -- isoniazid, rifampin, pyrazinamide, and ethambutol -- takes six to nine months. The &amp;quot;short course.&amp;quot; It&amp;#039;s a joke. Lots of people can&amp;#039;t even take their strep-throat drugs for a lousy ten days. And yet if you miss one pill, you give the weak bugs a chance to die and the strong ones a chance to divide. Resistance. Evolution. The bug mutates and mutates. And if the bug keeps mutating, you get unkillable strains . . . you get &amp;quot;extensively drug-resistant TB,&amp;quot; or XDR-TB . . . which swept through an African farming village in 2005, killing fifty-two of fifty-three patients, many of them already weakened by HIV . . . killing them in sixteen days flat . . . with the alarming speed of a virus . . . heralding a terrifying new plague, a coepidemic of drug-resistant TB and HIV -- two deadly diseases, one ancient, one modern, teaming up and blazing across the continent . . .  No, you had to stop that. You had to either kill the bug directly with an antibiotic, or help the body kill the bug with a vaccine. Jacobs preferred a vaccine, because he knew that even kids in the poorest countries -- kids with little or no access to antibiotics -- get vaccinated four hours after they&amp;#039;re born. But at the time, there were very few weapons. The last major drug had been introduced in 1967 and the only available vaccine didn&amp;#039;t work so well. And nobody knew why. Nobody even knew how the drugs that did somewhat work actually worked.  The reason was simple, fundamental. Genes. Genes define all life. If you don&amp;#039;t know what a bug&amp;#039;s genes do, you&amp;#039;re just guessing about how the bug does what it does. How it kills. How it becomes resistant to drugs. How it defeats the human immune system. How it can act as a time bomb in the body, going to sleep for fifty years, persisting in a mysterious latent state, then bursting to life when the immune system&amp;#039;s weakened by old age or by HIV. To do more than guess, you have to manipulate the bug&amp;#039;s genes. Make mutants. Then compare the mutants with normal bugs and see what&amp;#039;s different. See which genes are essential -- which genes, when deleted, either kill the bug or smash its kneecaps, rendering it kittenish, docile. Find a bug-killing gene and you may have found your antibiotic target. Find a kneecap-smashing gene and you may have found your vaccine. Nice. Except with TB, no one could do it. No one could make mutants. It was the fault of the shell. The freaky armor of the bug. It&amp;#039;s made of wax. A colony of E. coli is glassy, smooth, shiny; everybody&amp;#039;s swimming around all happy. But a colony of TB is like a melted candle that has cooled. No one could move DNA into M. tuberculosis, because no one could penetrate the shell. But Jacobs knew something that could. His phages. They were like little viral trucks that could ram their way into a bacterium and deliver a cargo of DNA. If he could jack into the truck, he could use it to deliver some cargo of his own. First he needed to know how the truck worked. He needed to collect lots of different trucks, take them apart, and study them. So that&amp;#039;s what Jacobs did. He recruited high school students as phage prospectors -- Jacobs&amp;#039;s very own &amp;quot;No Phage Left Behind&amp;quot; program. He found a phage in a rosebush and named it Rosebush; he found one in his own backyard and named it the Bronx Bomber. The one he found in the zebra pit he named Bxz1, for Bronx Zoo 1, followed soon by Bxz2, from the monkey cage. And once he&amp;#039;d gathered all these phages, all these little trucks, and once he&amp;#039;d poked around in their genes, their engines, he knew enough to build a phage, a truck, of his own. A better truck. In biological terms, Jacobs&amp;#039;s invention was a hybrid creature, a chimera. He made it using a genetic-engineering technique similar to the one that has given us pest-resistant crops and zebra fish that glow in the dark. It was able to load up with genetic cargo inside E. coli, and then shuttle that cargo into the TB bug, where it acted like a phage. What this meant was that Jacobs -- and everybody else who cared about TB -- could finally study the bug on its most basic level. They could ask yes-or-no questions and get yes-or-no answers.  Good things followed. Money, for one -- from the National Institutes of Health and the private Howard Hughes Medical Institute, which funds Jacobs&amp;#039;s work in the Bronx from its lavish $16 billion endowment, giving Jacobs added freedom to take risks.  Progress followed, too. And knowledge. And better tools. Jacobs, at age fifty-two, is just hitting his stride. In the past ten years -- often working with his longtime collaborators Graham Hatfull at the University of Pittsburgh and James Sacchettini at Texas A&amp;amp;amp;M -- he has built the &amp;quot;Bronx Box,&amp;quot; a cheap machine that uses a firefly gene to test for drug resistance (resistant bugs light up); helped discover what he believes is the exact chemical target of the drug isoniazid; and learned how the bug can become resistant in the first place. His newest project is a comprehensive library of mutants, each with a single gene deleted.  As for new vaccines, Jacobs&amp;#039;s got eight or ten of them in various stages.  &amp;quot;When we get one that really kills . . . &amp;quot; He trails off, grins. The grin says, I&amp;#039;m close. I think. But hell, who knows? Tuberculosis is scary. But it&amp;#039;s not sexy. It&amp;#039;s not Ebola. Ebola is sexy. A long, slim, lethal black dress of a virus. Can reduce you to oozy sludge in days. Sexy. West Nile -- it&amp;#039;s carried by songbirds, robins, in the heart of New York City. SARS and bird flu, they&amp;#039;re cruising the Strip, looking for a club with a good beat. They all slink past the velvet rope and into the Western media. Doesn&amp;#039;t matter that none of them are as successful -- biologically, sexually -- as TB; doesn&amp;#039;t matter that something like Ebola kills too quickly to do any real damage, whereas TB&amp;#039;s hiding away in the meat of two billion of us, a third of all humans. TB is not sexy -- and that&amp;#039;s the other big reason, aside from its coy shell, why it&amp;#039;s taken so long to get better drugs. Because as smart as these academic guys are, they don&amp;#039;t make drugs. Drug companies make drugs. The drug companies have the money, the people, and, honestly, the kick-ass robots -- robots capable of screening and tweaking and testing millions of chemical compounds at a time. Brute force. What academics offer are new ways of finding drugs -- the more fundamental and creative end of what&amp;#039;s called the drug pipeline. In the 1980s and 1990s, the pipeline was broken. Snapped in two. Academics had ideas but no money. Drug companies had money but no will. They didn&amp;#039;t see a market. For the most part, people rich enough to pay for drugs don&amp;#039;t get TB -- it&amp;#039;s mostly the homeless, the global destitute, and prisoners. Only about 250,000 TB-infected people have hacked and coughed their way into American hospitals since Clinton&amp;#039;s first term -- hardly an epidemic.  But here&amp;#039;s the thing that Andrew Speaker drilled into the American psyche this past spring: If bugs can get to a subway, a bus, or an airport, they don&amp;#039;t care if you&amp;#039;re rich or poor. And if these bugs happen to be the drug-resistant kind, well then, your rich ass is fucked. We may not always believe in curing the poor because it&amp;#039;s the right thing to do -- and it is, always -- but we do at least believe in saving ourselves. And isolated cases of XDR-TB have so far popped up in ten U. S. states. California. New York. Ohio. Texas. So that&amp;#039;s why we&amp;#039;re suddenly freaking out. And very far behind. It&amp;#039;s also why the pipeline&amp;#039;s only now being glued back together with a recent infusion of money and energy from government bodies (the NIH, the European Union) and especially from nonprofits and private foundations like the Bill &amp;amp;amp; Melinda Gates Foundation, Howard Hughes, Partners in Health, and the Global Fund. Even the drug companies have perked up. Now when an academic has an idea, he can call up a guy he knows at Novartis or AstraZeneca or GlaxoSmithKline. All three companies have built new infectious-disease arms in Europe and Asia -- gleaming outposts with the goal of finding new drugs for TB, among others, and getting them to the poor. The poor are not sexy. But look at it this way: TB is here. Now we have a chance to atone for our past sins. Sin is sexy. Redemption is sexy. If we want to have a chance at conquering the superbugs of the future, we have to slay and learn from this one first. Drug-resistant TB is our test run. All praise, then, to the sexy Andrew Speaker and his sexy, sexy wife. &amp;quot;That was great, man,&amp;quot; says Jacobs. &amp;quot;That was great for business. I&amp;#039;m sorry, you know?&amp;quot; When Jacobs created his chimera, he named it after his lab and his hero -- AE, for Albert Einstein -- then gave it away to anyone who asked. Scientists began to make and test mutants . . . slowly. Even by 2001, they could test mutants only in small pools -- fifty or a hundred at a time, max. It was taking forever. Luckily, one of the guys who asked for Jacobs&amp;#039;s chimera got so annoyed at the speed problem that he solved it with one stroke. Eric Rubin is three years Jacobs&amp;#039;s junior, compact, with a nervous, chirpy vibe. He has an office in Cambridge, Massachusetts, at a glassy citadel of genetics research called the Broad Institute, but I talked to Rubin in his Boston office -- the one the size of a closet, full of overflowing piles of manila folders and Scotch bottles his postdocs have brought him from around the world. Rubin is both a doctor and a microbiologist, so in between my questions he took calls about patients sick with infections: a pregnant woman, a man with syphilis. Other days, he gets a lot of HIV calls. &amp;quot;It&amp;#039;s really great,&amp;quot; he said. &amp;quot;Fun. HIV is, like, the best part of infectious disease.&amp;quot; Uh . . . really? &amp;quot;Really. It&amp;#039;s a blast.&amp;quot; To hear Rubin tell it, he&amp;#039;s far from saintly. He became a doctor because he&amp;#039;s a nice Jewish boy from Brockton, Massachusetts, and his father said he had to. He got a Ph.D. because his cool friends were all getting Ph.D.&amp;#039;s, &amp;quot;and I wanted to be cool, too.&amp;quot; He picked TB because &amp;quot;it wasn&amp;#039;t very competitive&amp;quot; and because it was fun to ask basic questions about the bug. Practical things like drug development were &amp;quot;very boring.&amp;quot; Not fun. If this sounds flippant, it&amp;#039;s because TB work is so difficult, so slow, that if you want to save the world, it can help to detach. For Rubin, that means startling self-deprecation and humility. You also have to like the intellectual game. And Rubin likes it. It&amp;#039;s actually his great strength. &amp;quot;I like to find ways of asking questions,&amp;quot; he says. Gradually, as he met the TB guys &amp;quot;who weren&amp;#039;t in it because it was fun . . . but because it was important&amp;quot; -- guys like Paul Farmer, who built from scratch a health-care system in the Haitian mountains that treats more than one million of some of the poorest people in the world -- he began to feel guilty. And inspired. He vowed to do something both useful and fun. That was TraSH. Before TraSH -- Rubin&amp;#039;s typically humble name for his speedy-mutant technique (it stands for Transposon Site Hybridization), which he invented along with colleagues Christopher Sassetti and Dana Boyd -- you couldn&amp;#039;t take advantage of the real power of genetics, which is the power of comprehensiveness. The bug has only four thousand genes. The way Rubin saw it, there ought to be a way to look at the entire genome, all at once, in any environment -- in a human white blood cell, in a mouse, whatever. So in a single test tube, he and his team grew a hundred thousand mutant strains. It took only three weeks, because instead of knocking out specific genes -- which takes six months per gene -- they knocked out random genes using a piece of jumping DNA called a transposon. A transposon wrecks whatever gene it jumps into. Jacobs was the first to use transposons in TB, but Jacobs&amp;#039;s transposon could only jump into a few hundred genes. The Rubin team built a new transposon, based on DNA from a horn fly, that could jump into every gene. By making such a large collection of strains -- a hundred thousand -- they ensured that all four thousand genes would be wrecked. Now here&amp;#039;s the fun part, the key logical leap: Any living bugs had to be the mutants whose wrecked genes weren&amp;#039;t essential for growth. Right? So to find the essential genes, the researchers built special probes to tally up the living mutants. Then they made a list of the missing, the dead. Then they repeated the process in mice. The List. The List was six hundred genes in a test tube, plus two hundred extra genes in a mouse. The List was hope. The List was . . . long. The List unleashed a frantic global hunt to winnow those eight hundred genes to a pulsing and beautiful core. &amp;quot;The bug is smarter than we are,&amp;quot; Rubin says. &amp;quot;So let&amp;#039;s ask the bug what kills it.&amp;quot; There&amp;#039;s only one type of place where you can ask that question, and it&amp;#039;s beyond a card-swipe door and two blue alarm boxes that say, EMERGENCY DOOR RELEASE BREAK GLASS. Two young TB researchers are gowning up: Gyanu Lamichhane, a microbiologist, and Sanjay Jain, a pediatrician. With practiced speed, each makes himself into a nested China doll of plastic -- gown, gloves, booties, helmet, Tyvek suit -- before spacewalking into the Biosafety Level 3 hot lab at Johns Hopkins University. First thing you notice is the bank of giant hoods, in glinting silver, attached to the ceiling with thick vacuum tubes. Then the noise. The place hums. It&amp;#039;s like being inside a huge walk-in fridge.  Lamichhane and Jain are both thirty-two, but if you had to guess, you&amp;#039;d say Jain was forty and Lamichhane was twenty. Jain is a tenacious, slightly roly-poly doctor who went to an elite med school in New Delhi, in a country where TB was all around him. He spends about 20 percent of his time treating sick kids, so he speaks with a doctor&amp;#039;s air of calm, gentle authority -- &amp;quot;Don&amp;#039;t touch anything, and if there&amp;#039;s anything wrong, let us know, loud&amp;quot; -- while Lamichhane takes a geeky delight in showing off the lab&amp;#039;s gizmos. He walks to a tray full of flasks hugged by rubber bands. The tray jitters and stirs the TB in the flasks. Beige boogerish stuff. It sticks to the sides, like whole milk. Lamichhane wriggles out a flask and holds it to the light. &amp;quot;Mr. Speaker, he coughs on an airplane? This, you aerosolize this, you have billions and billions of bugs.&amp;quot; He unclenches his right hand, spreads his fingers like a Bond villain. Science humor. In fact, between the air filters, pressure controls, and Tyvek suits, this lab is one of the safest places you can be in Baltimore, disease-wise. As Lamichhane says, &amp;quot;You&amp;#039;re far more likely to get TB riding the bus in the city.&amp;quot; Everything about Lamichhane is angular and sharp: his face, his black hair, his mind, his Eastern accent. Lamichhane&amp;#039;s father was a poor tailor in Nepal, the caste-system equivalent of a janitor. Because Lamichhane was smart, he eventually made it out of Nepal to America -- but not before taking care of his grandfather as he died, slowly, bloodily, of TB. At Wabash College, Lamichhane was drawn to the creativity of architecture. &amp;quot;But then I found that lifeless,&amp;quot; he says. He tried math. Tried chemistry. Lifeless. &amp;quot;I said, Screw this.&amp;quot; Propelled by the images of his dying grandfather, he became a biologist instead, at Hopkins. Lamichhane and Jain are two of ten investigators at the school&amp;#039;s Center for TB Research, a sort of Special Ops squadron of happy warriors who live to kill the bug. Ten people means ten sets of obsessions and ideas and collaborations. Jain gets juiced by zapping animals with PET scanners, trying to find a quicker way to chart how TB spreads in the body. Lamichhane? He&amp;#039;s into mutants. And Hopkins happens to be the world&amp;#039;s preeminent mutant warehouse. Pretty much every day, scientists without BSL3&amp;#039;s equipped for animal testing dribble their mutants into test tubes, seal them in Tupperware enclosed in leak-proof Saf-T-Paks, and FedEx the Paks, plastered with biohazard stickers, to Hopkins, where Lamichhane (or a colleague) walks the mutants to a supercold fridge in the BSL3. The fridge also contains Hopkins&amp;#039;s own mutant library -- four thousand individual strains. Now any of those mutants can travel to the basement, via a card-swipe elevator and two secured doors, to a second BSL3 lab that feels like a Halo level and smells like a barnyard, thanks to the rabbits and the guinea pigs and the thousands of mice piddling away in wall racks of plastic cages. The mice go into a chamber where the mutants aerosolize, infect. Some days later, the mice are &amp;quot;sacrificed,&amp;quot; their organs plucked and ground by hand into liquidy pulps with a mortar and pestle. The liquid is plated, examined, counted; the mutants are sifted into two piles: the living and the dead. This is what it takes to either verify that the genes on Eric Rubin&amp;#039;s List are truly essential, or discover essential genes of your own; so far, Lamichhane and his senior colleague William Bishai have found at least eleven unique essential genes -- that&amp;#039;s at least eleven new targets for drugs. Not bad. Now comes the hard part. As we know, TB can go to sleep for years. It hides in some mysterious place in the body. Maybe attacking these new and unique drug targets will kill the active bugs, but will it kill the sleepy bugs? To know, you have to test the drugs on the sleepy bugs, too. But hold on. For one thing, you can&amp;#039;t find those bugs -- where are they hiding? Lungs? Kidneys? Who knows? Obviously, if you can&amp;#039;t find them, you can&amp;#039;t test them. And even if you could find those sleepy bugs, as soon as you isolate them and grow them inside a test tube, they wake up. And you need them to be sleeping. &amp;quot;To do this,&amp;quot; says Lamichhane, &amp;quot;it&amp;#039;s so difficult, we have banged our heads.&amp;quot; There is a way. It works like a scout team in college football. Let&amp;#039;s say Team A wants to beat Team B. How does the coach of Team A spend his week? He watches tape of Team B&amp;#039;s star players. Then he teaches his own players to mimic Team B&amp;#039;s players on the practice field, in order to learn how best to grind those Team B sonofabitches into the dirt. Lamichhane is a coach on Team A: human beings. In the lab -- his very own practice field -- he constructs a chemical model that replicates Team B: the bug. He finds a way to put the bugs to sleep, artificially. Maybe he starves them of food or oxygen. When the bugs seem to go to sleep, he tests them. But notice what&amp;#039;s going on here. Genetics is exciting because it promises certitude. Exact knowledge. But a model is just that: a model. A guess. A guess can be wrong. And if Team A guesses wrong about Team B -- well, in that case, it&amp;#039;s the sonofabitches from Team A who get ground into the dirt instead. Science can take anything you&amp;#039;ve got to give -- any virtue, any productive vice. Your own cells, your own skin. I talked to one American researcher, a major figure in the field, who creates experimental drugs here in the U. S. and tests them in drug-resistant humans abroad. I asked if he wore a mask when he treated his study patients. Officially, yes, of course, his institution&amp;#039;s policy requires it. Unofficially, no, are you fucking kidding? How can you mumble at a scared, dying human being through a mask? So this man has &amp;quot;converted.&amp;quot; He has taken TB into his lungs, trusting his body to wall off the bugs. He&amp;#039;s not contagious. He has no active infection. He is now one of the two billion humans with latent TB. He gets a yearly chest X-ray to make sure his latent bugs aren&amp;#039;t waking up into something more dangerous. Is he going to die?  No. But still. And he&amp;#039;s not the exception. Among TB guys who do work abroad, he&amp;#039;s the rule. You want motive? Down the hall from the mutant fridge at Hopkins, there&amp;#039;s a French microbiologist. Ask him. Ask Jacques Grosset, a white-haired seventy-eight-year-old. He got a drug-resistant strain of TB as a young man. He went to a sanatorium in the Alps and began to die. His doctor told him, &amp;quot;Your future is behind you.&amp;quot; Eventually, doctors took the drastic step of hacking out a slice of his lung -- the same procedure doctors used this July to treat Andrew Speaker -- and it worked. Grosset was freed. &amp;quot;Now I will have my revenge,&amp;quot; says Grosset. &amp;quot;Now I have infected Eric, who is helping me to keeeel.&amp;quot;  This would be Eric Nuermberger, Grosset&amp;#039;s prot\u00E9g\u00E9. And what he&amp;#039;s infected Nuermberger with is a righteous frustration that the short course of TB therapy remains six months too long, and a righteous belief that science can do better. Grosset and Nuermberger are shortening the short course. Drug companies send their experimental TB drugs to Hopkins, where the two men combine them with other drugs, to create novel drug cocktails. Using the mice in the Hopkins basement, they&amp;#039;ve discovered a cocktail that can cure mice in just ten to twelve weeks. The cocktail won&amp;#039;t be approved for use in humans until 2012, if at all. &amp;quot;But you must realize,&amp;quot; Grosset says, and snorts a snort that is like a clipped, violent laugh, &amp;quot;I am opteeemest, and I have to convince myself that we will win.&amp;quot; That&amp;#039;s the thing about TB guys. They should be pessimists, but they&amp;#039;re not. They may disagree on the merits of vaccines versus antibiotics (Eric Rubin and Grosset are vaccine skeptics -- &amp;quot;Perhaps it is because I am a winner,&amp;quot; says Grosset, &amp;quot;a fighter, I am a keeeeler, you see? It is not my cup of tea&amp;quot;) or on the exact mechanisms of antibiotics (for five years, Jacobs has been feuding, colorfully, sometimes dickishly, with a guy at the NIH concerning the inner workings of isoniazid), but what unites them is a lucid optimism -- an optimism earned, this time around, by persistence and creativity and will. Now we can penetrate the bug. We can make and test mutants. We can systematically identify new targets for drugs. Just twenty years ago, we couldn&amp;#039;t do any of that. Evolution is a bitch, sure. The bug evolves. But not quickly. That&amp;#039;s the upside. Its rate of mutation is slow compared with, say, HIV&amp;#039;s. &amp;quot;It&amp;#039;s trapped,&amp;quot; says Rubin. &amp;quot;Not only do I think it can be controlled, it&amp;#039;s a totally eradicable infection.&amp;quot; In fact, when Rubin gets new grad students, he tells them to &amp;quot;think about learning tools, not learning TB, because who knows, by the time you&amp;#039;re done, TB may not be the problem it is.&amp;quot; Or as Bill Jacobs puts it, &amp;quot;Knowledge. Makes. The difference.&amp;quot; In late September, Jacobs walked from Einstein to his old house on Paulding Avenue in the Bronx, an Italian neighborhood straight out of Scorsese -- brick split-levels, a porch flag every block or so. The sky turned purple. Jacobs stumbled over a paving stone and a concrete ledge bordering somebody&amp;#039;s lawn. He groped toward the front door, keeping his palms outstretched like a victim in a slasher movie. &amp;quot;Is there a gate here?&amp;quot; No. No gate. I put my hand on his shoulder, but he wriggled away. &amp;quot;Just tell me if I&amp;#039;m about to hit, like, a trash can or something.&amp;quot; Ah, lamp. Fence. Duck. And then Jacobs was trespassing in a Bronx backyard. Two white lawn chairs. A grill with a tarp over it. A chain-link fence protecting two squares of sod lined with bricks. &amp;quot;Is there a little garden back here?&amp;quot; He meant the sod. This was it. This was where Jacobs reached into the dirt twenty years ago and found the Bronx Bomber. His original phage. Two weeks earlier, I had called Jacobs on a bad day. One of his vaccine experiments had tanked. Something had gone wrong with the TB culture, it hadn&amp;#039;t grown right, who knows why (&amp;quot;dammit, dammit&amp;quot;), and it meant four months of work down the drain (&amp;quot;I&amp;#039;m sorry, you know?&amp;quot;). But today Jacobs was feeling good again. We went to dinner. Over pasta and chardonnay, he suddenly got this proud pursed-lipped smile. He had something to tell me. Africa. He was making plans to go to Africa. To take his genetic toolbox, twenty years in the making, to the place that needed it most. Soon he hoped to be training African biologists to make mutants, to fight XDR-TB at the source and probe the lethal coepidemic of TB and HIV. &amp;quot;We&amp;#039;re going against a lot there,&amp;quot; he said. &amp;quot;It&amp;#039;s a difficult problem, but by showing that you can deal with this, it gives you confidence that you can deal with other emerging pathogens.&amp;quot; Jacobs is, of course, crazy. A mutant. And here&amp;#039;s the wild story -- wilder than a nine-banded armadillo with leprosy, wilder than a clump of zebra shit -- that proves it. For twenty years, Jacobs has been working on something called a multivalent vaccine: a single vaccine containing genes from all sorts of bugs. Malaria bugs. TB bugs. Even HIV bugs. &amp;quot;You tell me the disease, we&amp;#039;ll add the genes. Flu. Schistosomiasis. Yeah. Let&amp;#039;s just do it.&amp;quot; He shook his head. &amp;quot;If we put all the money we&amp;#039;re puttin&amp;#039; into Iraq into makin&amp;#039; vaccines, even a tenth of it, darn it, we can do it.&amp;quot; Understand what Jacobs is talking about here. Not a vaccine. The Vaccine. The Mutant to End All Mutants. Outlandish American optimism fixing what outlandish American optimism fucked up. &amp;quot;Now, that&amp;#039;ll keep me busy for a few years,&amp;quot; he said, and as he thought of all the difficult work ahead, all his future years tucked away in the Bronx, he got this luminous grin, and the ruddy slits of his eyes curled into something like joy.  Best and Brightest 2007:  Bill Jacobs, 52, professor of microbiology and immunology, Albert Einstein College of Medicine, and investigator, Howard Hughes Medical Institute. Eric Rubin, 49, associate professor of immunology and infectious diseases, Harvard School of Public Health. The Johns Hopkins Center for TB Research. "^^<http://www.w3.org/2001/XMLSchema#string>
<http://www.esquire.com/news-politics/a3918/exterminators1207/>