When Yamashita was eleven or twelve, his father, on leave from Vietnam, gave him a copy of Thomas More’s Utopia. He was living on an army base in Germany with his mother and older brother during the endgame of the Vietnam War—a slight, rootless, Japanese-American sixth grader struggling ambivalently to fit in. His father, a medical technician, was a stern, remote figure whom Yamashita revered but seldom saw, and the book, about an ideal pagan city-state where everything is happily governed by reason, was a common antidote to their travails.

A third-generation itinerant whose mother still worshiped long-dead forebears at a bureau-top butsudan, a household shrine, Mason knew his father up to that point less as an intimate provider than as an icon, someone whose family history informed his and whose experience seemed an objectification of his own confusion. His father, Hisao, grew up one of seven children on a small strawberry farm in Gilroy, California, Garlic Capital of the World. Midway through World War II, when he was eleven or twelve, the farm was confiscated and the family interned.

“They were in Tule Lake,” Yamashita recalls dutifully. “Grandfather had a heart condition, and during the final days of the internment, he got pneumonia and died in the camp just before he was supposed to be sent back to Japan. During the time he was sick, he’d been asked by the American government to pledge allegiance to America or Japan, and he chose Japan. Thus the whole family got shipped off to Tokyo even after he died.

“Tokyo,” he continues, “had been destroyed. But Dad could speak English, so he got a job as a janitor in one of the mess halls. His whole family was starving. Since he was an American citizen, he went to Hawaii, got a job on a pineapple farm, and sent back all his money to Japan to keep his family alive.”

Conditions on the pineapple plantations were brutal, and the elder Yamashita, who’d lied about his age and had had little regular schooling, eventually escaped by enlisting in the army. Shipped back to Japan, he met Mason’s mother. “She’d had a horrible life,” Mason says. “Her father was an alcoholic and left when she was young. Her mother had been going to work one day on her bike and it was very snowy and she was killed by a train. Mom was adopted. The family went to Manchuria. The Russians detained them there after the war. Then she finally made it back to Japan, met Dad, and moved to the United States.”

Yamashita’s own childhood was equally bearingless and disjointed if less harsh. Raised on army bases while his father was in Korea and Vietnam, he lived mostly in Hawaii until age ten, when the family moved to Germany. “I was always in the shadow of my brother,” he recalls. “He was an incredible star: straight-A student, though also a little peculiar. He loved to perform these weird experiments on me. I remember once he went to the library and took out this Time-Life book on child psychology. He made me terrified of tornadoes by putting these images into my mind—a straw driven through a tree by the incredible force of the wind, frogs swept up from a pond by a waterspout, then raining down dead several miles away.

“He’s phenomenal. In many ways he was more my father than my dad was. The first bad thing that ever happened to me was my brother leaving to go to Caltech when we were in Germany.”

Utopia (literally meaning nowhere) launched Yamashita’s moral education. Written between 1515 and 1517 during the flowering of global exploration, it was an attack by More against the greed and injustice of a Christian Europe recently grown genocidal in its thirst for power and wealth.

“I was more like Rich [Aldrich] then—a Republican—and Dad would try to moderate me, try to make me more compassionate. I thought it was stupid.”

He pauses: “It was strange. I personally think I would have killed myself if I had to go through what he went through. I would have thought that given his history, he’d have turned bitter, sour, but he didn’t. As I get older, I’m getting to feel much more like him.”

As an adolescent, Yamashita moved to San Francisco, then back to Hawaii, where he attended public school. “It was so boring. A lot of the time I would just stare out into nothingness, do nothing, for long periods of time. I probably was strange.” His mind, however, was far from quiescent. He agonized over the right way to live and belong. He now was reading Camus’s The Plague, in which the ultimate measure of a good life is altruism: “the passionate indignation we feel,” Camus wrote, “when confronted by the anguish all men share.” Meanwhile, he fell in with a grade school friend, a Pentecostal, and the two of them spent their Saturdays as amateur soul savers at a run-down shopping mall.

Torn, Yamashita ultimately renounced the church. “In The Plague there’s a priest who admonishes his parish that the plague is a judgment placed upon them by God,” he explains. “He eventually gets sick and dies, but mysteriously, he has no symptoms. Tarrou [Camus’s main witness], on the other hand, has the most painful death. He has both bubonic and pneumonic plague. I think Camus is signifying that the religious man is shielded in his shell: He will live and die not really having lived, whereas Tarrou, having stripped away this shell, lives a very hard life, but a much more fulfilled one.

“It was a very difficult time for me, because the church was trying to drill me with rules. They were trying to build that shell around me. But I wanted to live life and suffer pain.”

He enrolled at the University of Hawaii, burning with earnestness, intensity, and, soon, dismay. Emulating Camus’s hero, he hoped to go to medical school, but got a C in sophomore biology. “I decided,” he says, “to become a chemist instead.”

Here was the tentative resolution to all Yamashita’s wandering: “It intrigued me to think that there are billions of these little things that are actually doing reactions the way you want them to. I didn’t believe it at first, because I had been trained so heavily only to believe that which I could see. But people were telling me to believe it, on the basis of spectroscopy [that branch of physics that includes both crystallography and NMR]. I have to say I had my doubts. To this day I look at crystals and say, ‘They’re nice, clear, very pretty, but are they really ordered? I mean, what am I really looking at?’ ”

In Yamashita’s moral universe, science, truth, doing right, his ambivalence toward his brother, and atoning for his parents’ suffering thus now merged. He became a scientist, it seems, out of an adolescent moral imperative. Science was stringent. It was built on order. That order resided seminally, ultimately in the smallest of objects and minutest of forces—the realm of the subatom. And yet if one was entirely careful, absolutely precise, one could see it, know it, control it. “We have such clumsy hands by comparison,” he says, “but these hands can actually direct billions of molecules to all do the same thing—to pick up a hydrogen atom or drop one. It’s amazing.” Yamashita began to see in the interconnectedness of subatomic forces and matter a perfect paradigm of human behavior, for his own transitive existence. People are attracted and pulled apart. They’re governed by simple, irremedial bonds: “the only certitudes they had in common—love, exile, and suffering,” wrote Camus near the end of The Plague. In precision lay truth, even redemption.

There was only one great proviso: You had to be absolutely right. Otherwise, everything fell apart, collapsing hellishly into entropy and abomination.

Putting his trust in spectroscopy, Yamashita took his leap of faith.

•  •  •

With the backbone of the protein provided by Moore, Yamashita attacked the final stage of solving the structure with astounding resilience. Moore, as planned, finished first, making his last assignments in mid-March and rushing to write up his results. But Yamashita dogged him incessantly, narrowing the gap. Commandeering a space in the darkened modeling room next to Boger’s office, he built his first crude “map” of FKBP-12 in less than two weeks, half of what would be considered a fast time.

It was lonely, painstaking, grueling work. Because X rays breeze through atomic nuclei, what diffracts are clouds, or “density,” of electrons, like the chalk outline at a murder scene, not the atom’s corpus but its shell, its aura. On a computer screen, this density is represented three dimensionally as contoured electronic “nets,” holes in space. Packed together, touching in spots, they crimp and blob, twist and billow, like the oily “amoebas” of a sixties light show.

Yamashita, wearing battery-powered 3-D glasses and his ever present headphones, plunged himself into this subuniverse for twelve- and fourteen-hour shifts, seven days a week. He started in late afternoon and finished, dazed, as the first arrivals came in before 8 A.M. Knowing how the protein folded made his job feasible but no less trying. The screen was a fathomless black, superimposed with a dense matrix of billowing mesh and fragments of a twisting, coiling skeleton of 1600 atoms. The idea was to lay the structure end to end within the mesh, like a ship in a bottle, without breaking it or contorting its shape. Yet the matrix wasn’t continuous. It was erratic, broken into blobs. The effect was like piecing together the skeleton of an extinct, unknown beast within the windswept fragments of its ghost.

It got worse. Yamashita’s “chain trace”—the first rough map of the protein—was only a hypothesis. It had to be proven, proof being subjective at best, given all the biases and limits of trying to simulate unseen events with incomplete knowledge, imperfect understanding, and a group of technologies that, though improving, remain far from ideal. Not all density, for instance, is protein. With FKBP-12, thousands of individual water molecules floated within the recesses of the enzyme, each with its own electron cloud. Rotating a section of protein into a pocket of density, one could easily be outside the parameters of the enzyme without knowing it. Crystallographers inevitably find themselves having to explain away much unaccounted for density and defending maps that crisscross empty space. Computers check their assertions: Do they meet the criteria for how such atoms are known to bond? Are the bond lengths and angles “legal”—plausible? Yet, as Navia says, crystallography is a “garbage in/garbage out system. You need to do a tremendous amount of refinement to purge yourself of your original sin.”

Working on the edge of this abyss, Yamashita chose to evade the moral terror of looking for truth through the bent eye of a needle, but there was a physical terror he could not avoid. Molecules, of course, exist in three dimensions; cathode ray tube images, two. The experience of depth comes, in part, from the ability to zoom in and out, up and down. Once inside a molecule, it’s frightfully easy to lose one’s orientation, slip into an unfamiliar plane, slide past the molecule’s rim, get lost, hit a void. Zooming for hours through a mass of undifferentiated density can induce a harrowing vertigo. It perhaps didn’t help that Yamashita accompanied himself with high-decibel rock and roll. One of his favorite anthems now was the Cars’ “Just What I Needed,” with its telling line: “Doesn’t matter where you been, as long as it was deep.” By the time he stood up to leave most mornings, he had a look of shell-shocked delirium. He was indeed in another place.

In fact, though outwardly detached, inwardly he was happy, at peace almost. The despair of the heavy-atom search was now behind him. After months of noisily resenting Navia, Boger, Moore, and his erstwhile rival, Merck’s McKeever, he was at the center of attention. Any new protein structure was still an event—only about 300 had been solved. An important one like FKBP-12, he knew, guaranteed major press. And it was all his. In graduate school he’d have had to hand off his structure by now to someone else for refinement, but Navia, considering map building a “one-man operation,” had let him alone. He even sensed from Navia a hint of envy, teasing in reply: “If this is what you want, you’re going to have to take a $70,000 pay cut and start working eighteen-hour days.” (Rejoined Navia, affording to be gracious, “Mason did an amazing job, but 99.99 percent of the credit is going to come to me. That’s just the way it is.”) Yamashita had become a crystallographer because crystallographers were kings. Imperiously, he now felt himself taking on his proper mantle, an assumption that wasn’t always kind. “People will read my papers and Jonathan Moore’s papers,” he said, “but they’ll give John Thomson’s papers to their technicians and say, ‘Here, get me some protein.’ It’s sad. John’s busting his gut in the wrong field.”

By the end of March, Yamashita was all but done, having only to complete his refinements. Rushing to have something on paper, he spent the weekend of March 30 and 31 writing a draft. Exhaustedly, gleefully, he brought it to the Immunophilins Project Council, Vertex’s working group on FK-506, on the morning of April 1, a painfully sunny Monday at the beginning of what Nantucketers call—for its deceptive innocence, its sudden thaw in emotions, its unexpected venom—Hate Month.

The council was irritable and cross from the week before. The progress toward solving the structure had taken its toll primarily in the punishing demand for more protein. For months a crisis had brewed. Thomson, beleaguered, finally brought his frustrations to the council. “They want 200 to 300 milligrams tomorrow,” he said, reviving an old complaint about the crystallographers. “We in biophysics have wanted that kind of quantity from the beginning and could literally use a gram tomorrow and haven’t got a sniff of it. I’m a biophysical chemist and I’ve done very little biophysical chemistry for two years.” Navia, furious, tried to remain politic and in control. Here he was asking for protein so that Vertex could crystallize FKBP-12 and FK-506 together, not for himself but to see how the two molecules fit, design a drug, catch Schreiber, beat Merck, validate Vertex’s position before the world—everything that was most important now—and Thomson was hectoring him about his own experiments. Navia deftly proposed that Vertex hire at least two more people to prepare protein, but Thomson, suspecting correctly that Navia wanted the new hires to be in Thomson’s group, thus consigning it to being even more of a protein “service” than before, suggested that Navia’s group make its own protein. Navia exploded. He refused to let the issue die. Finally, Boger had to reprimand them both. “There’s only one goal for all of the science that’s supported by this company,” he said, “and that’s to produce a drug. These,” he said, referring to Navia’s and Thomson’s concerns, “are foreign concepts to me.” Stewing, Navia left the meeting to kick chairs and pound on tables; Thomson, to seethe and grouse. They hadn’t spoken in a week.

Yamashita imagined his paper producing triumph and succor both. After the initial success with 367, the chemists were again stalled for lack of data. The company had pulled itself back into striking range of Schreiber. An X-ray structure was money in the bank. Handing out copies of his manuscript, he felt that he had single-handedly, heroically fixed several long-standing problems all at once, made things whole again. Children of concentration camp survivors often describe a deep longing to mend their parents’ broken lives, rescue them from their shattered past, heal their pain, heave themselves on it like a grenade. Yamashita seemed to be acting on such an impulse. He seemed to think he might even reconcile Thomson, his friend and confidant, and Navia, his boss and father figure, much as a child of a broken home imagines patching up his parents’ distressed marriage with a glowing report card. Generously, innocently, he listed the two of them as coauthors as well as Boger, Moore, Murcko, and several others, including the whole crystallography group, which primarily had provided moral support.

“Twenty-five guys, twenty-five cabs,” Jim Rice, ex-Boston Red Sox slugger and malcontent, once said digustedly of his famously uncollegial team. Such was the lack of unanimity, of common cause, in the council’s response.

Because no one but Thomson had read Yamashita’s draft, the discussion focused not on the paper’s content, but its existence: Now that Vertex appeared to have solved FKBP-12 both by NMR and crystallography, what publication strategy ought it pursue? Like Schreiber, Boger and Navia optimally favored back-to-back submissions, presumably to Nature, which would counter Schreiber’s acceptance into Science. In tandem, the two papers together would tell a more complete story, they argued, and rebuff Schreiber point for point. Moore, however, objected. His paper was nearly finished. To hold it up for perhaps several weeks while Yamashita continued to refine his data, he said, would be “suicidal.”

“My exact words were, ‘I’ve thought about that [dual submission] and I reject that alternative outright,’ ” he said. “ ‘I reject it on the grounds that if those papers are submitted together to Nature, the odds are very good that they will throw out the NMR paper or tell us to condense them. Basically, we were doing the same structure of the same protein, just by two different methods, and we were using the NMR structure to get the X-ray structure, so why not incorporate the NMR information into the X-ray paper?’ Joshua did not like that response.”

Boger, in fact, had other concerns. On Wednesday he and Aldrich would fly to New York to meet with Goldman Sachs to discuss raising tens of millions of dollars through a private stock offering. The frenzy on Wall Street for new biomedical issues had become wild, voracious, unpredictable, and Vertex needed desperately to get in on it or be left behind. The value of a well-timed, high-profile publication like Yamashita’s crystallography paper, with its tantalizing suggestion that Vertex was now but a stone’s throw from the Promised Land of structure-based drug design, could not be overestimated or oversold.

“It may be the difference between our ability to raise $10 and $20 million,” Boger said.

There was a cavernous silence. Though he hadn’t said so directly, Boger seemed to be implying he thought Vertex should withhold Moore’s paper not for any scientific reason, but because Yamashita’s would bring a better price. “That opened a lot of eyes,” Moore said. “People were wondering, ‘Are we doing science, or what are we doing here?’ ” Boger had raised the point, as he often did, only to be provocative. But to some, particularly Thomson, to whom science was an honor, an ethical imperative, the baldness of the equation—science and money—was devastating, beyond the pale.

Thomson bristled. For weeks his body language at council meetings had indicated a ripening contempt: slouching in a chair at the far end of the table, arms crossed, Ray-Bans cocked, he had sunk into stony opposition. Now, frustrated in his own work and his ongoing quarrel with Navia; bitter about the apparent auctioning of Vertex’s scientific integrity; both critical and resentful of the crystallographers, whom he saw as having wasted protein with impunity, and yet who he thought were being coddled and elevated by Boger despite the fact that Yamashita’s paper was nowhere near as evolved as Moore’s; insulted by Yamashita’s inclusion as coauthors people whose contribution to the structure he considered irrelevant and at being “used as a technician” despite his own backbreaking efforts with the protein, Thomson leapt peevishly to Moore’s defense.

“I don’t understand why NMR is being treated like the ugly sister,” he scowled. “I myself am the only one here to have read both manuscripts, and Mason’s still needs a great deal of work. Read it. You’ll agree. It’s not ready yet.”

Boger cut him off. Whatever he might have implied, it was now clear that what he intended was just what Thomson was urging. He wanted everyone to read both papers, including Jeremy Knowles and Don Wiley, a crystallographer at Harvard. As the two most respected SAB members and those most familiar with enzyme structures and with Nature’s publication policies, he sought to blunt any further animosity by enlisting their counsel. Wisely, he thought the scientists needed a cooling-off period and saw no further advantage in discussion. Reluctantly, Moore and Thomson agreed to hand-deliver both papers to Harvard that afternoon.

Yamashita, however, refused to let the matter die. Though he and Thomson were friends, he felt unfairly criticized. Waiting for the meeting to end, he approached Thomson and demanded that Thomson explain more fully his objections to the paper.

“What do you really mean, John?”

“Nothing,” Thomson said, walking away, trying to avoid a fight. “It’s just not polished.”

“Look, guys,” Navia said, inserting himself between them, an unlikely peacemaker. “Let’s settle down.”

“No,” Yamashita insisted. “I want it settled now. I want to know what John’s thinking.”

Thomson wavered. The conference room was emptying. He preferred to talk to Yamashita alone in private. He was rushing to beat the time difference to place a call home to Melbourne. But Yamashita persisted.

“You’re obviously not going to let me go until you have something,” he said impatiently. “All right. I want to know what half the authors on that paper did.”

Yamashita jolted: “Ah. That’s it! That’s what this is all about.”

Who would receive credit was not Thomson’s sole complaint or even his main one, but it was the one upon which Yamashita seized. Having pressured Thomson into confessing it, he now started attacking him on it. Thomson recoiled, shaken. Of all Vertex’s scientists, he had been perhaps the least self-serving, working ruinously at the most unglamorous tasks, chaining himself to the bench, a staunch company loyalist. Yet he now he felt himself being painted into a corner as a credit monger. Blindly, he snapped. “I don’t want to be the person around here who’s remembered for taking a Nature paper away from four people,” he told Yamashita. “Do what you want. Just leave me out of it. Take me off the paper. I refuse to be listed as an author.”

Raving, Thomson found Moore and the two of them collected Moore’s manuscript and stormed out of the building toward Harvard. Whether they failed to bring Yamashita’s paper deliberately or simply out of neglect, the point was the same. The sulfurous emotions that had once been reserved for Schreiber now flashed over inside the company. People were no longer talking, not because they hadn’t succeeded, but because they appeared to have succeeded too well. “I pride myself on fairness,” Thomson muttered in the car ride over, shaking his head. “And suddenly I’m the asshole.”

Rubbing his face in his hands, Yamashita meanwhile sat alone in the darkened modeling room next to Boger’s office. He was desolate. Everything had gone spectacularly wrong. In his manuscript, he had been careful to credit Moore for the piece of NMR structure that had enabled him to solve the X-ray structure, yet he had ended up looking as if he were trying to usurp him. He’d named a large group of coauthors in what he felt was a spirit of communalism that others would support and admire, yet had only managed to offend Thomson without whose protein there would be no structure and without whose ministrations he’d have known only grief over the past six months. He had tried to be moral, and everyone was furious at him.

The slender cord of scientific truth that was Yamashita’s moral lifeline was starting to fray heavily against the jagged edges of scientific practice. Being right was one thing, but one also had to win, and Yamashita’s moral code abhorred competition. He was in over his head and felt himself drowning. Unable to work, hating himself, he left Vertex and went home, resolving to quit the company, to quit research, as soon as his stock vested and he could afford medical school. At least there, he told himself, he would know the rules.

“I don’t think this new age of scientific collaboration is going to work,” he lamented.

•  •  •

Racing between meetings, Boger swept into Aldrich’s office late the next morning to announce Wall Street’s latest folly. “Regeneron,” he snorted derisively, “$99 million.”

Regeneron, a three-year-old biomedical start-up, which by its own admission was perhaps a decade away from making any money, had gone public—gone “out”—that morning at $22 a share. It sold 4.5 million shares, raising nearly twice as much money as it planned. Wall Street, already drunk, had chugged the offering like a college student inhaling beer through a funnel on spring break.

Aldrich glowered. He didn’t have any more faith in the stock market than in Harvard. Regeneron had hit the market at the right time with the right story: It was working on treatments for the latest vogue disease, Alzheimer’s, and had a $50+ million research partnership with Amgen. In the current climate, that was like having a deal with God to make immortality pills.

Yet to him and Boger, the company’s “internals”—its proprietary technology, competitive base, and, most particularly, progress toward developing a drug and making a profit—were unimpressive. It had unclear patent positions on two nerve growth factors: natural proteins that might help reverse the deteriorating brain cells in people with Alzheimer’s and Parkinson’s diseases. But Alzheimer’s especially was going to be a nightmare for any company trying to develop a treatment. No one had a clue how the disease worked. Did Regeneron have any evidence that it could make an effective, safe, deliverable drug to stop the rotting inside people’s brains? Proteins worked well in test tubes but were notoriously hard to deliver within the body, requiring shots directly into the diseased area. Was Regeneron going to shoot its drugs into patients’ frontal lobes? How many people would buy such a drug? How would it be tested? The only way to calculate whether a drug against Alzheimer’s, where the clinical picture is clouded by spontaneous remission, actually works was to examine brain cells for the hard plaque associated with the disease. That meant waiting for hundreds of test subjects to die before one knew whether one had anything. It could be decades before one had enough data for the FDA. Meanwhile, the whole area of neuroactive drugs was awash with litigation: depressives and insomniacs suing for tens of millions of dollars because, they claimed, top-selling sleeping pills and antidepressants had made them psychotic; families of homicide victims coattailing, piling on; personal injury lawyers, seeing in the drug industry a huge, elephantine target, advertising for cases; sympathetic juries.

If one studied the fine print in Regeneron’s prospectus, all this was implied, but few, it seemed, bothered. At that moment, the company’s value was a bloated, absurd $341 million, which worried Aldrich far more than its shabby internals. To justify such a valuation, Regeneron would have to be a Fortune 500 company years before it ever turned a profit. As that was extremely unlikely, Regeneron’s stock was all but inevitably headed down, perhaps right away. Now that the money on Wall Street had been lured back into risky biomedical plays, Aldrich dreaded it being scared off again by a sudden free-fall.

“If Regeneron tanks,” he said, looking up desultorily from his computer, “it may burn the market.”

Boger nodded. By his own admonition, the key to raising money on Wall Street was getting in and out at the right moment. Now, the duration of that moment, which he, like everyone else in the industry, had failed to anticipate, looked as if it might be tauntingly brief.

“It’s going to turn very fast,” he predicted. “A couple of billion is going to get soaked up and that’s going to be the end of it.”

Speed was everything now, speed and size, for Regeneron had also dramatically raised the ante. Tens of millions of dollars were suddenly insufficient when some small companies had several times that amount. The new, richer, more muscular start-ups could buy better scientists, add more projects, retain the value on their discoveries, all while withstanding the preproduct financial drought that yawned before the whole sector like the jaws of death.

“You can say what you want about Regeneron,” Boger said, “but they’re not going to die anytime soon. They can make mistakes for ten years. They may have nothing now, but they’ve got a lot of time to improve on that position.”

Vertex had no choice but try to scrabble up to this new financial tier. But how? Boger thought it still best to try to raise the money privately. Compared with Regeneron, he thought, Vertex’s internals were sterling, blue chip: It might be no closer to having a drug (though Boger doubted it), but it was going after proven targets with the kind of small molecules of which all previous best-selling drugs were made. The company was pursuing clearly established markets without the sort of capricious patent situation hanging over it that had decimated GI and could clothesline a protein company like Regeneron.

And yet Boger didn’t delude himself about where the company stood or where it was headed. It was years away from profitability. Neither of its two programs could yield a drug. Its burn rate, though not irresponsible, was exorbitant and was destined to become astronomic. When it came to money, Boger had grown up in a tight, conservative world. His father’s mother, from thick pioneering German stock, had an iron-fisted rule—“Don’t spend capital”—so penurious that she had refused to bail out the family even when his father’s squandering had caused it periodically to become strapped. With the Regeneron offering, Boger recognized instantly the sudden rise in stakes but was not about to exchange his veil, as he might compare it, for pasties and a G-string. He would make the case for a $40 to $50 million private offering to Goldman Sachs, enough to get through the next few years, and put off going public until Vertex’s own internals were stronger. He would move quickly but not be stampeded. He would let events take over.

Boger favored keeping Vertex private for another reason: control. Publicly held companies were subject to intense scrutiny: from shareholders, analysts, regulators, the media, and ultimately the unwashed public itself. A parade of outsiders suddenly looking over one’s shoulder. How’s the company doing? What’s it discovered? When will it have a drug, make a profit? Boger considered such questions anathema to science. More, like many scientists, he disdained the right of nonscientists to ask them. He was an affirmed elitist, saying, “The only problem with autocracy is that there aren’t enough autocrats.” Boger intended Vertex to become a major pharmaceutical company, a giant. He had left the best public company in America because he thought Wall Street’s myopic insistence that it grow 20 percent a year had forced it to become cautious, constricted, myopic itself. As he had at Merck, he knew what he had to do to change the world, but it had to be done right or it wasn’t worth doing, and public inspection, public expectation, could only interfere. Good as he was at selling, Boger couldn’t glad-hand, and going public, whatever riches it might induce, would force him to placate forces he disrespected, exhort people he scorned. “I couldn’t do anything where I had to deal with the idiot public all day long and smile about it,” he said.

To Boger, the larger prize was not wealth or fame but success, winning. His every decision was calculated to optimize for that fact. But Vertex was still far from optimal even for the inevitable, transitive step of becoming a public company. It was barely two years old. It had fifty scientists working on two early-stage projects in temporary labs. Its managerial infrastructure was unfinished. “I wish this was all happening a year to eighteen months from now,” Boger said after the Regeneron offering. “I would feel more comfortable with a time-certain outcome. Going public now would accelerate our growing up. It might force me to hire more senior management, maybe a CEO—something I would deny vigorously up until the day we go public but that is true. At the same time, it’s infinitely harder to attract people to a public company. You lose your legal ability to issue penny stock. The company’s morale rises and falls with the stock price, the circus atmosphere increases . . .” He paused. “Then again, you shouldn’t underestimate the value of having $50 million in the bank. You lose some people but attract others. No question Manuel would have been here faster if we had that much at the beginning.”

Aldrich saw in the Regeneron offering the seeds of “another long nuclear winter in biotech” and fretted Vertex’s lateness in getting to the market. “There’s all kinds of product out there, cranking, soaking up money,” he said. But Boger was strangely uplifted. If Wall Street thought Regeneron was worth $350 million, what must Vertex be worth? As it had at the Vista eighteen months earlier, Wall Street’s breathtaking gall, its utter shamelessness, amused and intrigued him like some exotic peep show. “It’s really wild,” he said. “There’s no rudder in the whole process.”

Boger left Aldrich’s office as he’d arrived, laughing. Laughter was his all-purpose antidote, his innoculation against an ambiguous moral universe and the ironic human failure to apprehend it: He who laughs outsmarts the world. A lot of people thought Boger’s laugh arrogant, self-congratulatory, and didn’t like it. And yet it was also a measure of his fearlessness: He who laughs expunges doubt, pain. In a male-dominated world, especially, he who laughs leads.

Leading now, Boger entered his next meeting with his laugh solemnly squelched. He usually laughed hardest with the scientists, Robin Hood merrying his men, but he had not thought funny yesterday’s eruption of competitiveness. Scrimmaging was one thing, but this was game time, and Boger was furious. He thought the scientists were being infantile, selfish, and he meant to correct the situation fast before it spread. “Strategic thinking about a project is everybody’s business,” he’d said earlier in the day. “There’s no honor or distinction in having the last Nature paper before Vertex goes under because it can’t raise any money.”

Boger had singled out Navia, Yamashita, Murcko, Moore, and Thomson—the five scientists most involved with solving the structure and, with the exception of Murcko, the most aggrieved and divided. Thomson, nursing his rage, had yet to come to work, though it was now after lunch. The others had spent the morning fuming and threatening to quit. Now, they were like schoolboys caught fighting in the yard, hangdog but unrepentant. Boger, waiving his customary bonhomie and the rational, we’re-all-adults-here presumption of his social experiment, rapped their knuckles hard.

“No one here but me is not expendable,” he snarled at them. “Rewrite, cooperate, and smile, or you’re fired.” He then told them that having read both papers, he didn’t think either one was publishable in its present form. “We were all devastated,” Moore recalled. “He said some things in that meeting to whip us into shape that were not true. He said Jeremy [Knowles] had read both drafts and said neither was in any shape to be submitted to any journal. When I asked him later what Jeremy had said, he said ‘Oh nothing, your paper was fine.’

“Oh,” Moore said, switching voices, “Thanks for kicking me in the groin and then saying, ‘Ooops, sorry.’ ”

Boger was more severe than any of the scientists had ever seen him. They had all at one time or another, usually when they weren’t getting their way or losing to Schreiber, asked for a Mussolini, someone to direct them, tell them what to do. He had steadfastly refused, putting matters back on them. Now, however, he was steely, cold. Navia asked to say something, and he cut him off abruptly.

“I don’t want to hear a word from any of you until tomorrow,” he snapped, turning on his heel and bounding out.

By then, however, the next move was clear. Moore’s paper would go on to Nature alone, and all efforts would be made to ensure its timely and orderly departure.

•  •  •

“After leaving UCLA, I had an incredible pride in crystallography,” Yamashita said. “I had extreme trust in it. I also realized that if you optimized for speed, like I unfortunately do, you could make mistakes and you could cover your tracks.”

Perhaps because a certain amount of unknowability was forgiven and because Yamashita trusted his mentors, he had been able to abide this contradiction. He had been faithful. But now, as he raced to refine his structure, his faith began to erode, displaced, not surprisingly, by an angry despair. He was working constantly, eighteen hours a day or more, and pushing himself and his methods to where he could convince himself of the absolute factuality of nearly any assertion.

Observed Murcko, “In all the things we do with proteins, what we’re really doing is calculating all the forces between atoms: the stretches and the bends, the nonbonded interactions and the tugs between charged particles. But not all the equations we use to describe those interactions are accurate. Some of them are fudge factors. Some of them are thought to be correct even though the experimental data they’re based on are wrong, only nobody knows that because nobody’s gone back and double-checked the experiments. Some are pure guesses. There are assumptions, biases. There’s user error. There’s imprecision in the hardware and software. Sometimes they’re actually determined from lots of valid experimental data, but that’s unfortunately rare.”

Yamashita became deeply, inextricably depressed. Despite the precarious methodology, bona fide protein structures had indeed been solved by crystallographers but often only after years of painstaking refinement and with elaborate teamwork. Yet he was alone, rushing now to finish within weeks. Achingly, he pressed ahead, lashed by a fury if not to succeed, at least not to fail. On a bulletin board above his computer he placed a drawing from a children’s book of dogs feverishly digging bones in a yard. “Dogs at work,” it read, “Work, dogs, work.” Another picture was of a little boy dressed in ancient warriors’ clothes. “All Japanese raise their children to be as militant as possible,” he explained. The modeling room—dark as a cave and lined with the halos of Coke cans, styro-foam food boxes, compact discs, software manuals, and twin cyclopean computer screens—smelled as earthy as a gym.

He quit smoking because after every cigarette he felt tired for ten minutes—it was slowing him down—but he continued to drink, smuggling a bottle of vodka into the lab and sipping from it late at night when no one was around. The accumulation of map building and vodka made him surly. On a night not long after the manuscript fiasco, he hurled a glass at the half wall separating Boger’s office from the lunchroom, leaving a golf-ball-sized hole. On another night he lit a small fire in the lunchroom sink, quickly extinguishing it and laughing about it afterward. “It’s been very painful,” he said on April 11, 1991, with only 30 percent of the structure still refined. “I think I’d be willing to sacrifice a finger not to have to go through this.”

It had been a hectic, disparate day, typical of the period and of science. In the morning, Harding delivered to Jeff Saunders, one of the project’s senior chemists, the latest animal results on compound 367 and two others that were structurally similar, 398 and 426. “It’s available,” he said wanly of 367. Saunders beamed. Despite Harding’s effort at downplaying, both of them knew the news was critical. The molecule had already proven as active as cyclosporine in cell assays. Now, fed orally to mice, it survived the gut, gently penetrated T cells, and was still detectable in their blood eight hours later. The animals hadn’t died and were showing no ill effects, scratchily scampering in their cages two weeks afterward. On the evolutionary ladder of drug development, oral availability was a hugely important rung, the difference between a promising molecule and a salable pill or, perhaps more to the point, between major profit and interminable loss.

Boger was ecstatic. He told the chemists to scale up production of the three compounds for Chugai, which would test them in larger animals. “I told them that if I saw a requisition for four plastic canoe paddles from Herman’s, I wouldn’t bat an eyelash,” he joked about the sudden need to go from mixing micrograms to mixing grams, a millionfold increase. By the end of the year, perhaps, the molecule, or more likely a more potent descendant, would be tested in beagles, even primates. It might not be a drug, but it was a candidate, and Boger wouldn’t be lying to potential investors if he told them the company had a promising new immunosuppressant now substantially along in development. It was a lot more, he mused, than Regeneron could say. Yamashita, meanwhile, spent the morning soaking 367 into crystals of FKBP-12. He had already done the same thing with FK-506, and those crystals were now on the X-ray beam, relinquishing data. Once he finished the structure of the native enzyme, and if the soaking experiments worked, Yamashita would attempt these so-called complexed structures in order to show how the molecules interacted, just as Schreiber and Clardy apparently had done. Snapshots, they would give Murcko and the chemists their first hard look at the relevant topography for making a better drug.

Around midday, Boger got a fax from Nature in reponse to Moore’s paper. It was a rejection. The editors had decided not even to send it out for review. Boger was appalled, incredulous. Nature, like most important journals, relies on outside experts to determine a manuscript’s scientific merit, yet the British in-house editors—generalists, by and large—had ruled Moore’s solution of the structure of FKBP-12 unworthy of such peer review.

To Boger, such a perfunctory rejection was not only stupid, but unacceptable. He resolved to change it. He wrote back to Nature. His letter was strident, barbed. “I took all the ‘you twits’ out before I printed it,” he said. He wrote that Moore’s structure was the first by NMR of the hottest, if not most important, biologically relevant molecule in the world and should be peer-reviewed on that basis alone. He also made two points that the Nature editors, for their own reasons, could only find irresistible. He said that Vertex understood that Science, the magazine’s premier rival, had received two papers purporting to have solved the same structure by NMR and crystallography and that Vertex was within weeks of also having the crystal structure by molecular replacement. The implication, none too subtle, was that Nature was about to be beaten to press in a crucial, high-visibility area and that Vertex could save it with the X-ray paper provided it first changed its position and sent Moore’s paper out to be juried.

Editors of all journals, not just scientific ones, generally and regally adhere to a policy toward unsolicited manuscripts that is a variant of divine right: Once they’ve ruled, especially in the current cutthroat climate where publication is everything, that’s it. Nature, ineffably British, is known especially to frown on overtly pushy displays of scientific gamesmanship. Boger’s ploy, however, worked. While Moore was still smarting from the unexpected reversal of fortune, Boger called to tell him that Nature had reconsidered. It would send his paper out for review after all. Conducted by fax, favored by a global information network that, like a shark, never sleeps, the entire refusal, negotiation, and reconsideration had taken just less than twenty-four hours.

Boger was steaming on, crosscutting now whatever stood in his way. He and Aldrich met that afternoon with Merrill Lynch, which had taken Regeneron public and was Wall Street’s largest underwriter of initial public offerings (IPOs). Unimpressed by Goldman’s figures for a private placement, they’d decided to conduct a “beauty pageant”—bring in a parade of investment bankers, let themselves be swayed. Regeneron had already “tanked,” as Aldrich predicted. “Merrill pigged out,” Boger said. “They bumped the price, sold all their subscriptions at the IPO, and left no aftermarket.” Regeneron was now trading at about $15, down a window-jumping 30 percent in just ten days. Boger unsurprisingly thought Merrill’s suggestion that Vertex also consider going public a bit arch and self-serving.

“I’m looking for the answer to a very simple question,” Boger said scientifically after the Merrill visit. “I want to raise $30 million: What’s the best way to do it? The best way to answer that question is to get people favoring one approach over another—to the exclusion of the other—so excited about it that we can get some real information.”

The following Thursday, with Goldman on hold and Merrill “ready to go,” Boger and Aldrich met with an investment banker from Kidder Peabody. Historically one of three or four Wall Street firms to specialize in biomedical stocks, Kidder is much smaller than either Goldman or Merrill. It also was recoiling from a well-publicized series of disasters. In 1986, at the height of the big brokerage frenzy, it had been bought by General Electric for three times what anyone else thought it was worth. Some months later, its star merger strategist, Martin Siegel, was implicated in an insider trading scandal. Another broker was hauled from Kidder’s headquarters in handcuffs; the company paid the SEC $25 million, presumably to get the government off its back; losing money, it cut bonuses, inciting an exodus of top managers that Business Week likened to a “meltdown.” Kidder had a good track record for taking small companies public, had scaled back, taken account of itself. But it was still listing badly. It was conspicuously overshadowed by Merrill and the other large companies in the recent surge of biotech offerings.

Kidder’s investment banker was a mild Harvard Business School graduate with a brisk, officious air named Al Holman. In his mid-thirties, Holman broadcasts earnestness. A slender, well-dressed, boyish-looking blond who has the smooth manners of ambition yet who likes to roll up his sleeves, he came to Kidder right out of graduate school in 1980 at that moment when both biotech and the stock market began bristling with fabulous expectations, and had survived the depredations of the past few years well enough to become one of its few remaining stars. A vice president and partner, he ran its Japanese investment banking group, raised money for a variety of firms large and small, and maintained his own list of clients. He had taken eight companies public in the past ten years and had evaluated hundreds more, visiting most of them in person. Flying up to Boston from New York with Kidder’s biotech analyst, Bob Kupor, he was instantly taken by Boger.

“If I had seen in the last year fifty companies,” Holman would say, he knew within fifteen minutes, “Vertex was at the top of the heap.”

Holman was “stunned” especially by Boger’s management ethos. “A lot of small companies are started, they get forty or fifty employees, and all of a sudden the president has a corner office, and he has an assistant, and everyone reports to the assistant. I remember walking through the labs and Manuel saying, ‘Here’s my office,’ and pointing to a drawer in a filing cabinet. I knew that would play well with my constituencies.”

Returning to New York, Holman and Kupor swept everything else aside in an all out effort to win Vertex’s business. “It was the most intriguing story I’d heard in five years, so the issue became one of figuring out whether or not it was real and if Josh was real or not,” Holman says. “We came back to the office that night, put together four or five people, and worked through the night and all the next day. We spent the next twenty hours on it nonstop.”

To Holman, the key was weaning Boger from the idea that the company was still better off staying private. He had seen the entire cycle of the biotech industry and knew that the market, even with Regeneron and a couple of other companies “falling out of bed on their IPOs,” would not soon again so heavily favor going out. Regeneron “shook everybody up,” he says. “People said, ‘My God! Rather than raise money privately at $40 million valuation, I can go out and raise money at $100, $150, $200 million valuation.’ That disparity had not occurred since the mid-1980s. Regeneron broke through the barrier. Here’s a company that’s doing a $200 million valuation even after it’s cratering. It presented an umbrella for all sorts of companies to come out.”

In Wall Street’s perverse calculus, Regeneron had become not an embarrassment, but an asset, a selling point. Nor was Vertex’s lateness any longer an issue. “It was a totally virginal story,” Holman says. “They hadn’t been contemplating an IPO for seven months and talked to eighty people. That gave us the opportunity to say, ‘This is how, if we were you, we would position it.’ We were all sort of stunned by the market opening up, and none of us believed it was going to stay open a long time. So our recommendation was, If you’re really interested in raising money, do it now, and do it as quickly as you can.”

Friday was Boger’s fortieth birthday. The following Tuesday morning, five days after their initial visit, Holman, Kupor, and the rest of the Kidder team flew to Cambridge with several copies of a fifty-page bound booklet outlining the case for an IPO. There were comparisons with other companies, market analyses, a week-to-week time and responsibility schedule showing all the regulatory and sales deadlines for a fast-track public offering. There was a grueling road show schedule set for early July, taking Boger and Aldrich around the world in two and a half weeks to talk to investors, that had them sprinting at the end between two U.S. cities a day. “The ultimate death march,” Aldrich whistled respectfully.

Far from boilerplate, each of the charts and schedules was what Boger called “real stuff,” the precise information Boger had presumed to get through the “beauty pageant.” One graph in particular impressed him. It showed three ascending lines: the stock market, which had gone up spectacularly since the first of the year; the pharmaceutical industry, which was even hotter than the market as a whole; and arcing high above the other two, a clarion, new biotech issues. It was a rare alignment: the most money ever to flood into the industry, at a time when capital could make a hefty return in far more reliable areas but was deliriously pursuing companies like Vertex instead.

“This configuration will never again be the same,” Boger said wistfully. “I don’t want to be trying to go out when notebook computers are leading the market.”

The labs crackled simultaneously that morning with their own news. Nature, in a near record turnaround, had accepted Moore’s paper, sending terse congratulations in a one-page fax. It was twelve days since its initial rejection. As Moore would discover, a majority of the reviewers deemed the structure of FKBP-12 of such widespread scientific interest that they had urged immediate publication, regardless of whether or not the crystallography paper was forthcoming. Moore was dumbstruck, floating. “I’m just going to wander around and let people congratulate me,” he said.

Of all the myriad implications of Moore’s acceptance, the most compelling was Vertex’s sudden and immediate validation. Most small companies and many large ones go for years without publishing in Science or in Nature, which, in particular, has been both arbiter and house organ to the great scientific revolutions of the past one hundred years. When Watson and Crick discovered the double helix of DNA, they announced it in a 700-word letter to Nature. It was thus exceptional that Vertex, in its first publication, should stake its flag at such a tier, especially after getting the normally impervious Nature editors to bend one of their cardinal rules. It was fully the kind of aggressive, gate-crashing role that Boger had forecast for Vertex from the start, and now, having been achieved, it was like a rush of hormone to the system. Boger, deep in discussions with Kidder, gloated appropriately when he heard.

Each of the paper’s four authors—Moore; Debra Peattie, who had worked on the molecular biology; Matt Fitzgibbon, Thomson’s assistant; and Thomson—enjoyed a fresh surge in status. Thomson especially gleamed at the news, though it distracted from neither his work nor his moral struggles. A year after first isolating the protein, all but recovered physically yet looking older and more haggard, he was again working around the clock, processing twenty-five pounds of thymus, trying to isolate a half gram now of protein. Shy of laurels, he received the congratulations of the other scientists with a practiced shrug and a smile. He was still angry at the crystallographers, and, one sensed, nursing other grudges that even the powerful vindication of the most prestigious paper of his career couldn’t quite unseat.

Throughout the morning, the structure papers—Moore’s and Yamashita’s—were the hot topic in the labs while Boger and Aldrich entertained Kidder’s pitch for going public behind the closed door of the conference room. Starting out separately, the discussions quickly, inevitably, merged. Now that Vertex was going to have one, and most likely two, such papers in print and was within sight of the information it said it needed to design a new drug, its internals suddenly looked much more sound, sound enough to support, if not a Regeneron-sized deal, something close. Boger had always said the money was the chief reagent that Vertex ran on; now, it appeared, the company could raise $50 million or more if it was willing to capitalize quickly on its scientific achievements, however preliminary and incomplete.

Kidder, meanwhile, wanted to know just how meaningful the structure of FKBP-12 was—not just its short-term public-relations value, which was considerable—to the claim of actually being able to design drugs. The line between business and science, always tenuous, now vanished. Boger summoned Murcko, Navia, and Harding away from a meeting where Murcko was busily showing some new potential inhibitor designs based on Moore’s structure. For the next two hours, they uncomfortably answered Kidder’s questions about what they did and the likelihood that they would succeed. Boger had long ago made his peace with selling speculation, with putting a triumphant face on uncertainty, with prophesying in order to leverage reality, but Murcko and Harding in particular now swallowed hard. As scientists they were trained to trust data and data alone, and Vertex’s structural work, though promising, was still much too inconclusive for either of them to feel confident enough to support Boger’s boldest claims. They said so. A prophet who turns out right is a seer; one who’s wrong is a charlatan. Neither of them had Boger’s desire or incentive to cast himself in that role.

Yamashita, 70 percent done with his refinement and pressing ahead, was too junior and too busy to be called in on the discussion, but the repercussions reached him just the same. It was ironic: At the very moment he was doubting severely whether one could determine with absolute certainty the atom-by-atom structure of a protein, especially within the pressure cooker of industrial research, Boger was needing more than ever to make the case for the unimpeachable veracity of the structures he and Moore had generated. In fact, the irony was darker than that. Now that his was nearly complete, Yamashita could see that his and Moore’s structures were significantly at odds. “The scientific community will see no particular problem that we’re this different,” he said gamely, attributing the distinctions to different methodologies. But he was also haunted by the disparities. Navia was beginning to check over his structure, but he was being dragged away more and more by business meetings. Meanwhile, Yamashita was factoring in the water molecules, one of the principle techniques crystallographers use to explain unaccounted for density—and cover up any mistakes they may have made. “Manuel’s reviewing my map,” he said, “but I’m rushing ahead with the waters now so I don’t have any incentive to listen to him.”

Beaten by Moore, still at odds with Thomson, doubting both his discipline and his structure and despairing alternately about contradicting and disappointing Boger, Yamashita continued all afternoon staring desperately at his computer. He was exhausted, beyond consolation. He’d been staring bleary-eyed at density for twenty hours, since the night before, and had continued throughout the Kidder visit. Finally, shortly after the Kidder team left, he crumpled on one of the pink settees in the lunchroom, curled up, and began muttering to himself. “Life,” he said, “is a series of intractable problems.” Laura Engle, sitting nearby, tried to humor him: “You’ll look back on this problem a year from now and say, ‘Hah, I thought that one was bad, look at this one.’ ” Yamashita wasn’t assuaged.

“I’m having a nervous breakdown,” he said, much louder this time, pleading. “I just want this to work. I just want to go home. I’ve been having bizarre dreams about killing everybody in this fucking place. I want to leave this fucking place. It’s all I see every day of my life. I’m tired. I’m very tired.”

He moaned plaintively and then stopped.

“God,” he groaned, “hates crystallographers.”

Navia, witnessing this, came across the lunchroom. “Move over,” he said in a fatherly manner to which Yamashita responded by quieting himself. As long his seniors needed him, it seemed, he would serve them.

“We must get the structure right,” he said later that night, protectively. “Manuel will be destroyed if it isn’t.”

•  •  •

Yamashita’s moral plank, his idealism, was breaking beneath him, foundering on imperfectability, which he took to be a violation of truth. He felt there was no longer any possibility of victory for him, for even if he finished the structure and tied Schreiber, he could only do so by cutting corners and compromising principles, by lying. It was one thing to fail oneself, another to be failed by one’s ideals, one’s God, in a sense. Yamashita’s disillusion was absolute, and he saw all those who did not agree with him as hopelessly and evilly compromised.

Only his protectiveness toward Navia kept him going. Whatever his personal feelings, his disgrace, he felt a deep responsibility to shield Navia from both the pain of losing and from embarrassment. Ever the dutiful Japanese son whose father has suffered and whose lifelong job it is to atone, he now gave up on saving himself but not on saving Navia, who indeed had once gotten a structure wrong and had been stung by it severely.

That was with HIV protease. In his urgency to finish, to get the structure first and get it out to the world, Navia had misinterpreted a small portion of the density, about 15 percent. The region was away from the active site of the enzyme and had no apparent bearing on its biological activity; for purposes of drug design, it was both correct and sufficient. But biophysics is an exacting field. “Unless a physicist invented and built the machine that the experiment was done on,” Boger once quipped, “he refuses to believe the result.” Purists attacked Navia for making “serious errors” that along with other recent flaws had undermined the biological community’s faith in X-ray structures as “gospels of truth.” In some academic circles, Navia was considered an apostate, a fallen man. “It’s a cautionary tale that we have to be careful in interpreting these things,” Alexander Wlodawer, who ultimately solved the structure correctly using Navia’s and McKeever’s crystallization conditions, told Science. “We’re not infallible, unfortunately.”

The episode, coming shortly after Irving Sigal’s death and the unraveling of the HIV protease project at Merck, affected Navia bitterly, though not as Yamashita believed. It didn’t cause Navia to doubt himself, as Yamashita did. On the contrary, it reinforced—case-hardened—Navia’s precepts for doing commercial science and for working in the drug industry. It made him more determined than ever to put a premium on speed and practicality, his ultimate reason, he says, for coming to Vertex.

“The world has changed,” he explains. “The reason why people do structures now is not for the purpose of doing structures. People who say, ‘Well, structures are sloppier now,’ have to remember that the structures that people first worked on were practically minerals, and they worked on them for thirty years and spent a tremendous amount of time worrying whether or not the experimental data for each reflection had the correct shape.

“Now the process is driven by biology. One of the things that was assumed on the first day I arrived at Merck [in 1980] was that ‘you’re not going to work on a structure because the crystal is available, but you’re going to work on this problem, for which we don’t even have protein.’ Well, when you do that, what you end up with are structures that don’t diffract very well—and HIV protease is not a good diffractor. But what are you gonna do? In the old days somebody would have looked at that crystal and said, ‘We don’t want to work on it. This crystal’s a piece of shit, it doesn’t diffract well, I’m not going to be able to deal with it. I’m not going to get good data.’ ”

“Well,” he snorts, “we’re talking about AIDS, a planetary disease. The human race is going to go extinct. So what am I going to do, solve the perfect structure? Of course not.”

Far from feeling that he had abrogated morality, Navia believed he was practicing a higher ethic. “My personal mission is to use this methodology to make drugs,” he says. “I’m not an academic. When you work in a place like this, and you’re cranking out a structure in four months or nine months, you’re cutting a lot of corners. You’re supposed to cut corners. My job here is not to provide perfect structural information. It’s to provide adequate structural information—adequate for the purpose of having the Mark Murckos of the world do something with it and give something to the guys in chemistry. It’s not to provide them with perfect crystal structures two and a half years from now; it’s to provide them with adequate crystal structures now.

“This,” he says, “is the essence of what I was trying to communicate to Mason—that for us to have taken a year and a half or two years to solve the structure of HIV protease would have been immoral. You can’t. There are people out there dropping like flies . . .

“So you cut the corner, you get the structure, you buy somebody a month.”

On Thursday, the day after Yamashita’s eruption in the lunchroom, Navia and Murcko began analyzing his structure, now all but refined. As Yamashita caught up on his sleep and then began rewriting his paper, they examined the position of each atom, both as it tracked through the electron density and as compared with the known geometry of protein formation. Mason’s interpretation of the density seemed fine given the generally low resolution. But they soon discovered “holes” in the structure—ten- to twenty-angstrom gaps between sections of the molecule that, if real, would make it impossible for it to exist. The twists and turns of the protein chain were similar to Moore’s, but the distances indicated that such a molecule couldn’t hold together, much less function biologically. “At first we thought it was a programming glitch,” recalled Murcko. They went back and reviewed Yamashita’s calculations. By the end of the day, however, it was clear: The structure was wrong, not just in a single region, but in its essential formation. Whatever the image on the screen that had been generated, it was not FKBP-12.

Navia and Murcko waited until the next morning to confront Yamashita. Navia, despite his equanimity the night before, was incensed and wanted time to cool down. His claim to caring only about the therapeutic application of X-ray structures had been subsumed by more temporal, more fiery concerns. He had let Yamashita work alone on the most biologically intriguing structure in crystallography not only because he had faith in him, but because it was convenient. It had allowed him to do what he wanted, especially to advance and promote his idea for using enzyme crystals as supercatalysts. But now that plan had backfired. Nature, in which he had published his own career-making structures, including HIV protease, was expecting Vertex’s manuscript. The company was endeavoring to make the crystal structure of FKBP-12 its main stand-in for a drug as it tried to raise tens of millions of dollars to survive. Though he would deny its importance to him personally, the scientific world was waiting hypercritically to see whether he would redeem himself with a flawless piece of work. And all he had, after nine months, was an unpresentable failure. Kicking filing cabinets, cursing, he had exploded. He blamed Yamashita for resisting him, for being persistently egocentric and immature. He knew he had to be calmer when he confronted him lest he add to his already precarious condition.

When they told Yamashita, he first became defensive, then hostile, then—Murcko observed—“suicidal.” He ranted for nearly an hour. Navia, who had ended up yelling at him almost from the outset, also blew up repeatedly. The two of them stood screaming at each other in the modeling room, toe-to-toe, their snarling intonations echoing through the labs like dogs barking under a bridge. Boger came in. He tried to get them to focus on the science, but it was no use. Months of hostility and frustration, going back to the initial attempts to crystallize the enzyme, poured out of them. Finally, Yamashita, hysterical, lifted up an upholstered steel chair and smashed it so hard against the floor that it buckled.

“You will all be stricken down!” he screamed.

It took Boger to stem the panic. Objectively, what had been lost were just the two weeks during which Yamashita had been refining the structure. Now that the problem had been recognized, it could be solved. Boger instructed the two of them to begin revising the structure together, anticipating that they would have to stall Nature for a couple of weeks but confident that their bargain with the journal would still hold. Meanwhile, he did a quick analysis of the situation and determined to prevent it from ever recurring. “I hate rules,” he said, “but this one I’m casting in stone. No structure at Vertex will ever again be solved by one person. It’s too hard. All this could have been avoided if Manuel had looked at Mason’s work two weeks ago.” Added Murcko, whose own work had now been set back indefinitely, only half joking: “This is because of the insufferably large egos that all crystallographers have. It’s a universal truth.”

Like a catamaran righting itself after a spill in rough seas, Vertex quickly resumed its course and fleetness. Within days, Navia and Yamashita began closing in on a structure that, if not perfect, was, in Boger’s careful phrase, “good enough”; good enough to satisfy Nature and the crystallographic community; good enough to draw attention away from Schreiber and tantalize Wall Street; most important, good enough to begin to design drugs. Boger never seemed to make any moral distinction between truth and utility: What was true was useful, what was useful, true. Life was for him not a series of intractable problems, but of tractable ones, and he was solving them now as fast as they arose. Those he couldn’t vanquish, he simply let ripen until he had more data.

He was certain now that Vertex would go public, indeed that it would be perilous not to do so. The market was holding: other companies had gone out after Regeneron and were selling out their shares at prices above their preferred range. A company’s ability to raise money by selling shares derived from a single feature—its valuation—and, as Holman had noted, the gap between what Wall Street thought companies like Vertex were worth and what private investors thought was simply too great to disregard. Secretly, on May 1, Boger flew to New York to meet with Benno Schmidt to secure his blessing as the company’s financial rabbi and chairman before he told the scientists. Meeting in Schmidt’s conference room, the two were as usual in instant, universal accord.

“If you’re thinking of raising fifty million dollars, raise seventy,” Schmidt twanged. “If fifty looks good, seventy is going to look even better.” But Boger, smiling, auguring, was already with him.