Altruism,” Boger spat, “has no other evolutionarily justified motive but self-interest. Selfless altruism is an oxymoron; it’s impossible. For me, the best motivation for going into AIDS, where motives are just so suspect, is that we think we can make a difference. The science took us there. The opportunity took us there, which I think is more honest than getting in either because we wanted to make a lot of money or because we wanted to save the world. Martyrs are very selfish people. People who do things for grand motives elevate themselves perhaps inordinately high.”

Boger sat game-faced at his desk, deep in fluorescence. It was Februrary 28, 1991, after 8 P.M., long beyond dark at the cusp of Cambridge’s direst months. During the past several hours he had personally edited the scientists’ Pittsburgh abstracts, chosen the fonts for them, photocopied them, tinkered with a balky copier, supervised their mailing—“micromanaged,” as Murcko unreassuredly put it, the company’s coming foray into gladitorial science. Now he was racing to get home to see Amy and the boys before leaving at five the next morning for ten days in Japan.

It had not, in the end, been a hard decision to make AIDS Vertex’s second project. The scientists had. produced encouraging data, the business climate had improved, cathepsin E faded; time had run out. But the choice had required from Boger a 180-degree conversion—an uncommon occurrence. For two years he had sworn, correctly, that Vertex had no place in HIV research. Now he was embarking with equal commitment to sell an AIDS program in Japan, his third “death march” there in twelve months. Packing his slides, rifling through the mounds of paper on his desk, he had the no-nonsense paraintensity of a skilled pilot heading into the teeth of a storm in a small, untested plane.

“We backed into this because we thought we could do it, so our motives are clear,” he said. “This is not cold and calculating, ride-the-bandwagon stuff. This is science.”

If Boger was defensive, it was because of the numerous personal and scientific demons he’d had to exorcise in reversing himself. As Susan Sontag and others have suggested, diseases and the responses to them mirror society. With AIDS, the scientific reaction has been at once strikingly productive and shamelessly self-serving. Boger didn’t have to be an altruist to be alarmed by the “suspect” intentions of many of those he was now joining. AIDS research was rafted with them. Indeed, they had informed much of his earlier resistance.

At first, science had simply been uninterested in AIDS, the search for what was killing young gay men in California and New York suggesting a routine microbe hunt on the fringes of scientific respectability. Forty years after penicillin and streptomycin, new infectious diseases, somewhat justifiably, were considered washed up, passé. Cancer was then science’s scourge of choice. Through the War on Cancer, brokered and then built into a federal powerhouse by Schmidt, researchers had discovered that they could develop and sustain large labs for pursuing their own interests as long as they could demonstrate some connection, however tenuous and remote, to treating the disease. Biomedicine was transfigured by the bonanza. Finding that they were rewarded chiefly for doing science that was visible, researchers concentrated on areas that invited attention, because attention brought money and money, more research. Competition—for money, reagents, credit, priority, and access—became not just the main thing, but everything. The drug industry, following suit, was similarly changed. Cancer research was a great story. Wall Street ate it up. No pharmaceutical portfolio was complete without a major anticancer effort, regardless of what there was to it.

The first rash of AIDS deaths in the United States was reported within weeks of Ronald Reagan’s election as president. Fateful as that was for those with the syndrome, it exonerated even further the new era of scientific self-interest. Dr. Robert Gallo, the government’s chief AIDS researcher, set the tone. Heavily promoted by the White House, which at first simply ignored the disease, he announced triumphantly in April 1984 that he had discovered the virus that caused it, then descended through a nine-year spiral of alleged scientific misconduct and personal disgrace that ended with his conceding that he had gotten the virus from French researchers who’d discovered it first. Loudly and publicly obsessed with winning a Nobel Prize, receiving $100,000 a year in patent royalties on a discovery he didn’t make, Gallo ended up all but quitting science to defend himself from multiple investigations by Congress, NIH, the National Academy of Sciences, the media, and the General Accounting Office.

Willful and paranoid, Gallo became synonymous with the drive for individual credit in AIDS, but the atmosphere in drug research was by 1987, if anything, even more venal. In March, the FDA approved the first drug for treating AIDS—AZT—a twenty-three-year-old compound first designed as an anticancer agent and rescued jointly by researchers at the NIH and at Burroughs Wellcome, a British-owned drug firm best known for making Sudafed, a cold remedy. The molecule was primitive, toxic, and, having first been made under a federal grant and never patented, gathering dust in the public domain. Desperate for input from the drug industry, which still saw little opportunity in AIDS, NIH had pressured Burroughs to submit compounds it thought might slow the replication of the virus, and Burroughs had sent AZT along with several others it had identifed from the scientific literature.

Burroughs had studied AZT’s toxicity, but most early testing of the drug was done at NIH. Still, in 1985, after government researchers determined that the molecule was active against the AIDS virus, the company asked for a patent. When the FDA licensed the compound two years later, AZT instantly became one of the most expensive long-term drugs ever sold, costing each patient about $8000 a year. By the time Burroughs’s patent was issued in 1988, the company held a seventeen-year government-sponsored monopoly on the only approved drug for a disease that was fatal in every case, a drug that analysts were predicting would become a billion-dollar seller by 1992, a drug that the company hadn’t discovered and hadn’t paid for.

Science follows money. As long as there was little spending on AIDS research and the drug market looked relatively small and unpromising, most scientists and drug company executives deemed Gallo’s and Burroughs’s transgressions a sideshow, beneath comment. But the gravity of the contagion and the forced realization by the federal government and the pharmaceutical industry that AIDS was exploding worldwide and would not go away suddenly by 1987 reversed most researchers’ indifference and unleashed a tide of scientific interest. NIH funding for AIDS research began to swell, multiplying more than 600 percent in three years. Researchers who formerly concluded their grant applications with “and its possible application to cancer” now learned to write “and its possible application to AIDS.” The drug industry, witnessing the controversy over AZT with more jealousy than revulsion, but having little success historically with antivirals, tentatively began launching its own protoprojects in AIDS.

Whatever else, AIDS research had become a compelling story, and in the way of all phenomena taken up and amplified by the media, it now became fashionable. Venture capitalists, without a hot new commodity since microchips a few years earlier seized on the disease. Entrepreneurial scientists, dazzled by the sudden new opportunities for money and fame and indulging a taste for business, accommodated them. Together they quickly started new companies—AIDS companies—then just as quickly sold them to Wall Street. By 1987, a frenzy erupted. A British investment firm headed by Lord Rothschild invested in fourteen such companies. A small vaccine company promoting the work of Jonas Salk, who’d steadfastly refused to patent his polio vaccine, attracted so much money that its founders had to send back checks. Scientists became rich and famous without much more than a hopeful-sounding idea and a willingness to speculate on its chances. That few of them had any experience with making drugs or bringing them to market, that more than two-thirds of the companies were doomed to fail, that no one had any idea where the money would come from to keep them going, all were blithely overlooked in the frenzy to position the new firms.

AIDS at last had captured the interest of scientists, but scientific interest itself doesn’t induce progress. The search for the cause of AIDS had been relatively narrow and straightforward—tracking down the right microbe. Curing it, however, would require an extraordinary new understanding not only of the virus and how it works but of the immune system and its complex reaction to it. How was science to proceed? Technically not a disease but a syndrome, AIDS is hydraheaded by nature. It’s riddled with nightmarish features: a highly mutable virus; a long, deceptive latency; cofactors—other agents—that accelerate its timing and spread; multiple diseases rampaging simultaneously through different organs; a devastated, ineffectual immune system. Singular solutions—“magic bullets” like vaccines or one-shot therapies like antibiotics—were unlikely. The manifold challenges before the newly engaged research community were more like those associated with putting out a forest fire than capturing a sociopath. They required a coordinated effort on several fronts and were visualized perhaps better from the air than on the ground. Now that science had been enlisted in AIDS research, how to manage it remained elusive and unclear.

“Science,” says Nobel laureate David Baltimore, “is much better at solving problems of its own devising than those it is asked to solve.” At the time of AIDS’s ascendancy in research, Baltimore was director of the prestigious Whitehead Institute at MIT, a leading scientific policy chief and statesman, and already—though the world would not know about it until later—embroiled in the publication controversy that would eventually force him, after a celebrated congressional fraud investigation that absolved him of misconduct but not misjudgment and arrogance, to resign as president of Rockefeller University. Baltimore, working to some degree in AIDS himself, tried, not uncharacteristically, also to become its tribune. By the time of the run-up in AIDS funding, he’d taken to publicly beseeching other researchers to overcome their aversion to managed research, put aside their obsession with credit, and sublimate their own urgent career choices and business imperatives to “a sense of responding to a national need.” In short, he urged a crash program for AIDS—a Manhattan Project, he called it. The A-bomb project’s biomedical cousin, the wartime pencillin program, perhaps was a more apt precedent, but scientists understood what Baltimore was proposing. Under federal leadership, the nation’s best scientists would put aside competition and join hands in a common cause. Hardly subversive, Baltimore’s notion stemmed from an established wartime practice: the temporary suspension of business as usual.

Scientists show their disapproval in an odd way. Something considered promising or important will be challenged vigorously, even harshly. Something deemed uninteresting, thus unworthy of pursuit, is met with a dismissive silence. Crows ostracize each other by cackling raucously; scientists, by turning to whisper something or staring at their shoes. Such was the reaction to Baltimore’s plan. No one supported it. The implicit message was that money alone sufficed to marshal research and that the helter-skelter of the patent fight and the dominance of strong labs over weaker ones was preferable to any coordinated system for determining what science does and how it does it, even in AIDS.

This was the world Boger was now entering: a world of self-selection, secrecy, competition, and greed—none of which Boger abhorred, but which he believed also invited great posing and mendacity. There had, of course, been acts of extraordinary science and great humanity within AIDS research, but charity, Boger thought, was for those who could afford it. “Money-grubbing corporations need to look selfless,” he said starkly in his office, fixing on a slide with his jeweler’s eye. “I think Roy Vagelos and Ed Scolnick think it’s one of the responsibilities of their research wealth that they have to act altruistically.”

Merck’s entry into AIDS research in late 1986 indeed accomplished much of what Baltimore with his appeals to common sacrifice could not. It was the arrival of the cavalry, not the soapbox rantings of a single voice of conscience. By then Merck was both the Arnold Schwarzenegger and Mother Teresa of American businesses. Its stock was in the midst of one of the great sustained surges in history; ultimately it would rise more than 500 percent in five years, twice as fast as the Dow during the greatest market runup of all time. It would soon donate enough avermectin, a veterinary drug, to wipe out African river blindness. Within a year, Merck would be voted America’s Most Admired Corporation by Fortune’s annual poll of executives, displacing perennial over-achiever IBM. (It would eventually win the honor seven years running, hanging banners in Rahway saying America’s Most Admired Corporation and, in later years, using the designation prominently in its want ads.) Brilliantly innovative, spectacularly profitable, yet governed seemingly by a deep humanity and sense of responsibility, Merck had managed to retain much of Tishler’s and George Merck’s heroic altruism while growing at 20 percent a year. Merck and Company remembered World War II if no one else did. “The Miracle Company,” as Business Week described it in a flattering cover story, seemed the perfect antidote to the squalid carnival in AIDS research.

Swaggering, Merck helped redeem the search for AIDS drugs by pushing it to a higher level. CEO Roy Vagelos, a highly competitive M.D. with a penchant for brilliant science and aggressive play—he was always photographed for magazine profiles in a kayak or in tennis garb—announced that he was “damn optimistic” that the company would succeed. Shunning the normal secrecy around research, he encouraged Merck’s scientists to talk openly about their progress and share vital data before publication. AIDS was still considered a small market, and Merck risked losing what little edge it might have by being open, but Vagelos gamely insisted it didn’t matter. Merck was the industry leader. Its rightful place was at the forefront of important science, regardless of the risks.

What Vagelos knew, of course—and what soon drew other big drugmakers into the field—is that the drug industry, and Merck especially, now had cause for confidence, a promising new target. AZT worked by blocking reverse transcriptase, an enzyme common in cancer viruses and a difficult target for drugs. However, in early 1987, a young Harvard-educated molecular biologist at Merck’s West Point labs, Irving Sigal, and his colleagues had been dissecting the virus for alternate drug receptors when they discovered something extremely hopeful, the salient role of an aspartyl protease in HIV’s reproductive cycle. Here—HIV protease—was the key to Vagelos’s optimism. Vagelos, as director of research and then CEO, had made enzyme inhibition Merck’s main scientific area. Largely because of Boger, it had led the field in renin, an exceptionally close relative of the viral protease. Indeed, the company’s next big drug, a prospective billion-dollar seller for treating enlarged prostates, worked by blocking a proteaselike enzyme. Vagelos’s bravado in AIDS was more than generic: The company was strongly in its element.

Sigal championed the project. Two years younger than Boger, he was, if anything, broader than Boger, having been trained as a chemist before making a string of exceptional discoveries in biology. His father, Max, had been director of research at Eli Lilly, and Sigal seemed destined to rise at least as far at Merck. Brilliant, single-minded, passionate, brusque, abrasive, he’d begun acquiring by age thirty-three an extraordinary degree of influence within the company. Indeed, now, as Sigal began assembling his program in AIDS and Boger, his structure-based design effort, the two unavoidably became rivals, heirs apparent to the helm. Not surprising, there was little love lost between them.

Sigal was formidable, a powerhouse. “Irving was the kind of guy who, if he said, ‘I’m going to deliver protein on such and such a day, in such and such a quantity and such and such a purity,’ you could bet on it,” says Navia, whom Sigal had recruited to solve the enzyme’s structure (Boger, who had just invited Navia into his group, “cleared the decks” for the move). “He delivered. He had the right focus. He wasn’t doing this because it was going to be a tour de force for his lab, but because he wanted to go for this disease.”

By the summer of 1988, with Sigal driving the project ahead and Boger, unbeknownst to anyone at Merck, edging closer to leaving, Navia and Brian McKeever began the experiments that would lead three months later to their solving the crystal structure of the protease. They were now in competition with a second group at NIH. The period was intense, strenuous, and marked by heated disagreements over strategy. Despite Vagelos’s edict to share information with Merck’s competitors, Navia worried (as he would later at Vertex) about publishing Merck’s crystallization conditions before the structure itself was finished. He and Sigal quarreled bitterly. After one such argument, both of them left, exhausted, for the December holidays.

It was the last time Navia would see Sigal. Returning from Heathrow Airport in London four days before Christmas, he was killed when Pan Am Flight 103 exploded in a fireball over Lockerbie, Scotland, killing all 258 passengers. He was thirty-five.

“I was devastated,” Navia would recall three years later. “I knew that this program was really going to have a problem. The guy who was the soul of it was now gone. These terrorists view these airplanes as being filled with nameless, faceless things. But I know that there was one guy on that airplane who probably more than anybody else could have, by now, significantly affected a disease that has the potential of exterminating the human race.”

Whether Sigal’s death or Boger’s defection two days later had a greater impact on Merck, both came to symbolize the company’s sudden vulnerability. As a martyr of AIDS research, Sigal had not “elevated [himself] . . . inordinately high,” but others had, and now, like Navia, they were bereft. Merck had been able to impose a new discipline and public-mindedness on the field in part by pointing it in a vivid and promising direction. That direction had been promulgated especially by Sigal and Boger, who believed equally that one could stop the virus by tailoring molecules, atom by atom, to block a key piece of it. Now, both of them were gone, and though Vagelos and Scolnick professed no public doubts about the company’s prospects, others did. Eight years into the epidemic, Merck’s AIDS efforts seemed to outsiders to bog down in familiar ground—an inability to make protease blockers that were smaller and less easily metabolized than peptides, which were both bulky and weak. Not quite back where it started, the search for AIDS drugs again seemed daunting, implacable, stalled, demoralized.

Boger’s initial reluctance to go into AIDS at Vertex had reflected this new uncertainty, even though, as Aldrich continually noted, the company had inherited Merck’s “first team”—Boger, Navia, Murcko, and Tung. That, of course, was an exaggeration, but without Sigal, it was also true that perhaps no other group of scientists so embodied the reasons for Vagelos’s original optimism. Now, after reconsidering and after proving that the Abbott and Roche compounds indeed blocked the replication of the virus as effectively as AZT, Boger was becoming as confident as Vagelos had been. When the chemists began synthesizing two classes of novel inhibitors that were equally active, all Boger’s litmus tests were suddenly and irremediably met.

“Now that we’re up and going and can see what’s possible,” he said, “we have a responsibility to make this work. This is possible now. We don’t want to cede this opportunity until the time when big drug companies get around to it.”

But had Vertex, by delaying its decision, been too late? Belated timing was as oxymoronic to Boger as selfless altruism. With sufficient data, there was no being wrong in his world. “When I’m in decision mode, I let events take control. You shouldn’t decide things when you don’t have enough information. Because of my worry about this, I set a very high standard about what had to happen before we could make a firm decision. I waited.”

In fact, Boger’s timing now looked canny. Small companies like Vertex that were chasing AIDS while trying to survive had in the past been forced to sell to corporate partners at the earliest possible moment. The costly, uncertain development gauntlet for experimental drugs demanded it. But AIDS patients, with nothing to lose and no future, had demanded and won a vastly truncated timetable for making new drugs available. In December, Merck announced that it had begun testing a new reverse transcriptase inhibitor in Europe that was found in a natural products screen scarcely six months earlier. The time-value-of-money implications of such a compression for a small, cash-starved company were fathomless, beyond reckoning. Rather than being hopelessly behind, as Vertex had appeared to be as recently as three months ago, the company (Boger could now state confidently), whose compounds had yet to be tested in animals, trailed the industry leaders by less than a financial quarter or two. Vertex had become competitive practically overnight.

Novel inhibitors, Merck’s first team, a greased track for development, record turnaround time—these were the elements of Boger’s story for the Japanese, the elements he had to have. He knew he could sell them. What he didn’t know was whether anyone besides Nissin, the family-run noodlemaker and perennial shopper, was buying. “He’s about to present this cold to more sophisticated companies, shall we say,” enzymologist Dave Livingston, a biotech veteran, observed as he watched Boger prepare. “We haven’t done a reality check on HIV, and now we’re about to do that in a big way.” And unlike with Chugai, there would be no Benno Schmidt to broker the introductions.

•  •  •

In Japan, Boger and Aldrich called on nearly a dozen companies, scrabbling by cab and train between their headquarters in Tokyo and Osaka. Their reception was thoughtful but ambiguous. A courtesy call early in the week to Chugai, which hosted a lavish banquet for them, convinced him that the company was still pleased with its investment. Meeting with Nissin the next day, Boger assessed the prospects for an AIDS deal at fifty-fifty. Altogether encouraged, he and Aldrich returned to Boston with the self-satified glow of travelers who had courted hostility by bartering for antiquities in a strange country, only to return with a bounty of new leads.

But by then something far more reaching had happened to reshape their world, something that would have implications beyond a productive sales mission. On March 7, 1991, as Boger and Aldrich were midway through their trip, a Washington appeals court ruled sweepingly in favor of Amgen in its five-year patent battle with GI over EPO, the long-disputed antianemia drug. Overturning a lower-court ruling, the decision gave Amgen a complete patent monopoly in the United States over the sale and production of EPO. Amgen’s stock, already widely thought to be overvalued, soared on the news, rising $12 to $113. GI’s shares sank $21.75, to $40.25.

Wall Street might not know a clone from a clown, but a rout it understood. With the victory, Amgen’s stock was now on its way to rising a stupendous 900 percent in two years. Where else could one make that kind of money? Where else could a few smart people (aided by sharp patent lawyers) make something that could produce $1 billion a year, as EPO was expected to, and be protected by the government—the government—from competition?

For a decade Wall Street had stood by like an abused suitor waiting for the market in small biomedical companies to make up its mind. Would they pay out or wouldn’t they? Now, at least for the victors, the answer was thunderous.

Boger could feel the temblors all the way in Japan. He had left a week earlier with Wall Street groggily shaking off years of indifference, and now he could feel its heat rising. By the time he returned to Cambridge two days after the ruling, the landscape was reverberating wildly. Several companies not much older than Vertex and, Boger believed, nowhere nearer to making money, announced big private placements. Others filed to go public. Public. For years the acid test for such companies had been having a drug in clinic, a moneymaker near at hand. These companies weren’t even close. Two months earlier the institutional investors who buy up most initial stock sales wouldn’t have thought it worth the cab fare to meet with them. Now, Boger heard, they were tripping over each other to get in on the action.

The billions of dollars in investment capital that Boger had watched roiling on the sidelines was now beginning to burst the dikes of caution and pour into biotechnology, all of it looking for the next Amgen. Like everyone else in his position, he shifted his sights instantly toward the tsunami. He discreetly forgot about HIV and Japan and began assessing the larger sweep of events. “I have no problem saying the company is worth $35 to $40 million right now,” he said, reviewing the suddenly goiterous evaluations being placed on the other companies in Vertex’s class. “Is it worth $120 million? If somebody else thinks it is, I’d be a fool not to agree.”

The EPO ruling had immediate and volatile consequences. In addition to GI, the other big loser was Chugai, which had licensed EPO in the United States and was expecting to become a global player on the strength of the drug’s American sales. The setback would undoubtedly slow Chugai’s growth and make it at once more dependent upon—and more anxious about—Vertex. “I’m glad we had dinner with them early in the week,” Boger joked. “If we’d seen them Friday, we’d have been lucky to have gone out for noodles.” When some of the scientists openly wondered whether Chugai might be forced to pull out of immunophilins, Boger assured them that things weren’t that bad. A few were not encouraged.

But Boger was way past them now. He could see the changing business geometry as clearly as he could visualize the whirling of molecules in space. Dozens of small companies like Vertex would soon be circulating through Wall Street, looking for capital. They would have their hands out like guests at a party or, in another sphere, like small molecules in the cytoplasm of a cell. Each would shake a lot of hands, just as molecules do in a sense, their atoms, their fingers, touching, probing, interpenetrating. A few would clasp harder, more enduringly. These would be the winners. The markets would welcome them in, and through their connection, they would succeed, success meaning above all else survival. Their binding, as with molecules, would be strictly competitive—that is, those with the highest affinity, that fit the best, won. As for the others, they would be stripped, discarded, as Boger believed GI would now be. “They’re about 300 people too big,” he said. “They’re going to crash and burn and the smart money will pick up the pieces.”

Boger had always said the time to go to Wall Street was when Wall Street was ready. Now was that time. Whether the company itself was equally prepared was something neither he nor anyone else had the luxury to consider.

•  •  •

John Moore gazed dully at his computer screen. Five theoretical structures of FKBP were overlaid before him like traceries. Where they overlapped, the lines erupted in a luminous purple, pieces of spine. Where they didn’t, the filaments of individual atoms burst into an angry matrix, like threads springing from a rotting twill. Overall, the protein’s shape was now clear, though similes for it revealed as much about the beholder as about the molecule. Al Vaz, Vertex’s facilities manager, thought it looked like “a crushed beer can”; Boger, “a hermit crab shell.”

In their sameness the individual structures told a compelling story, but it was their differences that now most troubled Moore. Unlike crystallography, NMR measures molecules in their native state, in water, where they flop about like jellyfish. To get a high-resolution picture, Moore needed another ten high-quality structures at least—perhaps another week or two of painstaking work. Only then could he average them mathematically, cleaning up the discrepancies on the screen. Knowing the approximate location of all of the atoms was not enough. A publishable structure required exactness, certainty. The field, still dominated by crystallographers, didn’t tolerate unresolved noise. One didn’t design a drug to fill the core of a beer can.

Moore was now consumed with finishing the structure and submitting it to a good journal. “It would be very simple for somebody with twenty people in his lab to make the kill at this point,” he said on March 11, two days after Boger returned from Japan. He had worked all weekend and was pushing ahead as he had for the past six months, alone. Increasingly exhausted, he’d now begun to doubt that strategy. “The way people conceive the field, it’s that Schreiber’s done everything. We’d like to change that,” he said. “But I’ve put myself in a vulnerable position. I may end up very disappointed.”

Although he never thought he would win in the first place, Moore’s expectations remained firmly grounded, but that wasn’t true of Yamashita. His behavior became increasingly erratic. In the two months since Moore had first identified the protein’s backbone, Yamashita alternately was aloof and obsessive, dispirited and rash. One Monday in January, after working until 4 A.M., he said, “It’s good that we lost. This is my work, not my life.” A minute later he changed his mind: “I guess if I’m willing to work on this bullshit all night, I’m taking it seriously.” He worked slavishly, leaving Vertex only on Sunday nights to volunteer in the emergency room at Brigham and Women’s Hospital, a grim change of scene but one that Yamashita enjoyed. He began talking about becoming a doctor, fascinatedly reporting about the first person he saw die—a Salvadoran pizza deliverer who was shot in the head during a holdup. Yamashita had counted the money in the man’s pocket—$78—and filled out his death certificate. He thought perhaps in medicine he could do something both important and satisfying.

His hands took on a different cast. His left hand turned yellowish; his right, raw and pink. He insisted it had nothing to do with his work, but it recalled a time in graduate school when he had to turn off a robotic X-ray beam arm that had gone askew and was scattering radiation throughout the lab. Then, his white cell count spiked for several days and he had to be hospitalized although the doctors assured him that he’d only absorbed a localized dose. “No scars,” he would later say, “at least not any that anyone can see.” Temperamentally, he was now subject to long periods of strained composure broken up by jagged fits of rage. “It really helps,” he said, “to be intensely violent for about five minutes.” To settle himself down, he’d begun going out drinking regularly with Thomson and Laura Engle, who listened sympathetically but didn’t know what else to do for him.

Yamashita was also working alone. Propelled as much as Moore to prove himself, he had rejected any help from Navia, who, recognizing his need for independence, had vowed to let him make his own mistakes. It was far from easy. With each successive failure with heavy atoms, Navia had to restrain from simply imposing himself. Boger supported Navia’s forbearance, it being in keeping with his social experiment. But there was no question it was delaying vital information. “We don’t go after structures because of some implied need,” Boger said. “We go after them because they help us know things we can’t know any other way.” Without that data, Vertex’s chemistry effort was stalled. Not only were the heavy atoms not working, but Vertex’s crystals were behaving badly. For two weeks at the end of February—two weeks during which Yamashita’s behavior became steadily more obtuse—he barely could grow them at all despite using the same conditions as before. He was distraught. He told Murcko that he thought the situation was now hopeless, that he would never get the structure, and that he was quitting crystallography. “It’s too mind-wrenching,” he said. “I need something more predictable with a higher success rate.”

Desperate, he finally took Navia’s suggestion to change his mother liquor, a move that at once stabilized the protein and gave Yamashita sudden confidence that he not only would solve the structure, but soon, perhaps in the next two months. “We now have a basic crystallographic problem like other crystallographers have,” he declared in early March, relieved finally to have something go right, “not one unique unto ourselves.”

It thus was in a rare moment of dual optimism—Moore’s and Yamashita’s—that Boger first heard the rumor that Schreiber and his collaborators had defeated them both. According to Boger’s information, Schreiber and Martin Karplus, the other former SAB member let go by Vertex, had submitted an NMR structure to Science at the end of January, then, a week later, he and Clardy had delivered an X-ray structure. Back-to-back, the two papers purported to show not only what FKBP looked like, but how FK-506 affixed to the protein, how the two molecules bound.

It was an astonishing coup, so strategically bold and technically brilliant that even Boger had to concede that Schreiber now “owned the field.” As Moore had guessed after his phone call to Schreiber at the end of January, his group had finished the NMR structure months earlier. However, they had waited for Clardy to catch up and confirm their findings.

“The final refinement went with lightning speed,” Schreiber would recount. “We were working around the clock. Clardy and [graduate student] Greg Van Duyne came up here with all their data on February 6, 7, and 8 or so, right around my birthday. I put them up at the Charles Inn. We’d come in in the morning, work on the paper, analyze our data, go out to Bartley’s Burger, work, have dinner working on the paper, come back, work until the wee hours of the morning.”

It was the existence of the two papers, still under review, that Boger first heard rumored on March 12, 1991, more than a month later. Two days after that, on March 14—“Black Thursday,” the scientists would call it—he confirmed the story and broke the news to Yamashita and Moore.

“How are you, Mason?” he asked, poking his head into the modeling room where Yamashita was working. The visit was so unusual that Yamashita suspected at once that Boger hadn’t come to swap salutations.

“I’m fine, Joshua. How are you?”

“I’m fine.”

“Oh,” Yamashita said, “did Merck beat us?”

“No.”

“Who beat us?”

That it was Schreiber and not Merck so disjoined Yamashita that he was oddly subdued, dispassionate. “I was worried because Mason had taken it all quite well,” Boger would recall. Moore characteristically cursed a few times and went back to work.

Boger’s mood was stout. He has a relentless talent, as Saunders puts it, for “finding the pony”—an admiring reference to the eternal pragmatist, who, led into a roomful of manure, reaches for a shovel and begins to dig. Inheriting from his mother a rigid intolerance, as his brother Ken observes, for “anomie,” he never broods or pities himself. Now, he saw at once the great opportunity in Schreiber’s triumph. Schreiber and his collaborators had found the structure first but that didn’t mean they had won, not officially. Publication, not discovery, was the ultimate test of winning, and Schreiber’s structures were not yet in press. Thus, as Boger saw it, there was still time for a tie. Schreiber might have won, but that didn’t mean that Vertex had lost. The company had until Schreiber’s publications were accepted and in print to submit its own, something Boger was convinced that no one else, not even Merck, was now as close to doing. Within minutes, he managed to convert Schreiber’s rout into a scenario where a photo finish between them was still well within reach and quite possibly Vertex’s alone to lose.

Boger instantly began engineering Vertex’s comeback. Schreiber’s strategy may have been impeccable, but holding the NMR paper had left him exposed. “Schreiber knew we were working on the NMR structure. I told him,” Moore said. “But he wanted to have the X-ray paper, too, because it told a more complete story. That’s what left the door open for us. That saved our asses.” Boger’s strategy was to have Moore rush to finish his structure and submit it to a competing journal within four weeks. Meanwhile, Moore was immediately to give as much of the structure as he was sure of to Yamashita, who would try to use it to sidestep the need for heavy atoms through so-called molecular replacement, the experimental shortcut first proposed by Navia in December and avoided by all parties since. With Moore’s paper planting the flag, Yamashita and Navia would try to complete the X-ray structure by the time Schreiber and Clardy’s paper appeared in print, thus legitimizing Vertex’s claim to a tie.

“It’s first and goal,” said Boger, who didn’t care about football but had picked up on the national rage for its metaphors during the Gulf War. Happily in Schwarzkopf mode, he assured the scientists they’d have every edge, every resource they needed, “every computer in the place”—he tapped the turbomouse on his desk—“including this one.”

•  •  •

It was a giddy, bullish moment in American history. A week before, the members of Congress had jumped to their feet to lionize George Bush, chanting his name and war-whooping on the floor of the Capitol. The Democrats had worn American flag lapel pins, but they were bested by the Republicans, who paraded out small American flags that showed up better on TV. The Democrats had had to beg for a share of the flags so that they, too, as the Times reported, “could wave to the folks back home.” A corresponding delirium on Wall Street prompted similar depths of patriotism. During the seven weeks of the Gulf War, the Dow had surged more than 500 points. Frenzied investors, suddenly making money again, spread their largesse among all sectors of the economy, big and small, profitable and nonprofitable. That the nation remained deep in recession and that the war had failed in its central objective of extirpating Saddam Hussein barely touched the good-time fever radiating from the nation’s power centers. America was a winner again. The country was drunk on unexpected success. Improbable delusions were not only licensed, but nurtured, as if it didn’t matter that you could see the artifice behind them, so powerful were the pleasurable images they conveyed.

For the emerging biomedical industry, it was showtime. The suddenness of Wall Street’s and the nation’s insobriety was matched by a near instantaneous parade of strapping young companies that had rehearsed for just such a moment, such a splurge. Each had a sizzling story about miracle cures, new technologies, riches beyond words, and each, like the Republicans and Democrats, was determined to capitalize on the rapture of the moment by trumping its competitors and upping the stakes. Encouraged by Wall Street, which had begun to enjoy the return of rich commissions and fast-growing portfolios, the companies rushed to announce bigger and bigger deals, earlier and earlier in their development, with less and less science to back them up. Companies no older than Vertex—and no closer to profitability—were now raising upward of $40 million in public offerings. They were being valued higher than manufacturing companies ten times their size with millions a year in profits.

On Black Thursday, the day Boger confirmed the news of Schreiber’s victory, an article in the Wall Street Journal announced the latest “mega-start-up,” as Boger called it: a company rushed into existence to exploit the new climate on Wall Street and that had been able to raise in its first round of financing several times the $10 million that Vertex had been launched with just two years earlier. Details were scant; there was little to tell. According to the Journal, the company was yet unnamed, would be located on the East Coast, planned to develop “pharmaceuticals that piggyback on the cell’s own mechanism to fight disease,” and had raised earlier that week $30 million. The source of the information was—startlingly, if not surprisingly—Kevin Kinsella, whose Avalon Ventures was said to be launching the company with New York investor David Blech, a thirty-four-year-old former stockbroker and part-time musician who had already started and held large stakes in nearly twenty biotech companies. Blech’s system of practically giving away stock to brokers and prominent business leaders who then have a stake in promoting his deals had earned him more than $300 million while placing him at the center of a network of influential investors, including Gerald Ford, Bill Gates, and former Citicorp Chairman Walter Wriston, all of whom sat on the boards of Blech’s firms. According to Kinsella, the new company, which had no employees or labs and was still months away from opening, already had a market value of $45 million.

“If that’s the standard for $45 million,” Boger snorted, “then we’re up around Amgen.”

The Journal failed to account for how Kinsella calculated the extra $15 million, though Boger knew. Kinsella, who was still on Vertex’s board and a major stockholder, had told him. The “piggybacking” was actually a reference to signal transduction, the new hot area in immunology. And the company had assembled an extraordinary SAB—“SAB of the Gods,” Boger called it—that included several Nobel laureates and, more to the point, Schreiber, whose high-visibility work gave the field much of its cachet. Indeed, the company had been a direct result of Schreiber’s firing. Angered by the loss to Vertex, Kinsella had hurriedly flown east in October to hear Schreiber’s side of the story. Still miffed, and after inviting Schreiber to discuss his bitterness with the full board (Schreiber declined), he asked Schreiber what else was new. Schreiber burst into his stock speech about signal transduction. Sensing a huge new opportunity that instantly overshadowed his regret at losing Schreiber at Vertex, he and his partners began at once assembling the new start-up that he now was flogging in the press and on Wall Street.

Boger had been stunned by Schreiber’s involvement. He didn’t view the company as a threat—“They’re not going to be a factor for a long time,” he declared—but he despised “the cuckolding aspect” and was astonished that Kinsella would set up another company so close in form to Vertex that they would likely end up cannibalizing each other.

“It’s a grotesque situation,” he rankled. “Kevin thought it was a terrible mistake to boot Stuart off the SAB. He wanted to keep him out of the hands of the competition. So now they’re the competition together.”

Echoed Aldrich, “I don’t know how the guy sleeps at night.”

It had been enough for Vertex’s scientists to be beaten again by Schreiber scientifically, but that he now might also be competing with them in drug design all but unnerved many of them.

“Regardless of what you think of the guy, he isolated FKBP, he cloned FKBP, he expressed FKBP,” Armistead said. “He’s got an NMR structure and a crystal structure, and he’s a chemist. Now he can do what he’s best at. Hell, I think he can compete with us. I think he can compete with anybody.”

“We’ve always said that the ones that are going to win in this area are the ones with the most information,” said Livingston. “Stuart now has a lot of very good information that, in the right hands, could be very dangerous to us. I hope he sells it to Wyeth Ayerst, but there’s nothing in principle to stop him from selling it to Merck.”

Or, it went hauntingly unsaid, to Kinsella’s unnamed company. It hadn’t been lost on Boger that Schreiber might press Harvard to license his FKBP-12 structures exclusively to his and Kinsella’s new firm as he’d once been willing to do with the protein to Vertex. The race for the structure was therefore now even more of a showdown between him and Schreiber. Not only were they combatants over enshrining chemistry and the primacy of immunophilins in that cause, but they were conceivably now rivals in the arena of drug design—the one area Schreiber had always sworn never interested him, the one area where Boger’s ambitions were greatest. Before, he and Schreiber were failed collaborators. Now they were at war. As with all scientific conflicts, Boger recognized that the ultimate outcome might be settled not in the laboratory, but in court. He asked Ken to begin reviewing all possible legal claims against Schreiber and Kinsella.

Suddenly, Vertex was a much more dangerous place emotionally—dark, coiled, apocalyptic.

“Joshua thinks he’s Christ and Stuart is the anti-Christ,” explained Thomson, who himself took a more mordant view. He came to work the next day wearing a T-shirt that said Shit Happens. “To cheer everybody up,” he said.