Back from Japan, Boger was rhapsodic. Touring the palatial headquarters of the Japanese drug firms, whizzing on the bullet train out and back to their spectacular but oddly underutilized labs, he’d been able to measure the gulf between their expectations and practice and it elated him. The Japanese drug industry in 1990 was a reflection of America’s in mid-1941: second tier, but with a small number of companies poised to move up. Just as Tishler and Merck had done by synthesizing vitamins in the 1930s, the companies had prepared themselves by importing technology and becoming virtuosos within the existing sphere: FK-506, a triumph of screening, was the first potential blockbuster drug developed wholly by a Japanese firm. They were supported by an activist government that in 1980 made developing pharmaceuticals for export a national priority. Having telescoped in less than forty-five years the entire evolution of industrial research from coal tar dyes to microprocessors, Japanese science, recapitulating the U.S. model, was now chasing the world’s most complex, powerful, and profitable molecules. All it needed was direction. Boger, MacArthuresque before, couldn’t but see in their courtship of him a reverence that was not entirely undeserved.

Unlike the big American drugmakers, all of which—except Merck—Boger had visited and had told him to come back when he had a promising lead, even the largest Japanese firms welcomed him and Aldrich avidly. They staged elaborate banquets for them, plying them with abalone and puffer fish, which the Americans dreaded. And yet it was the pharmaceutical wannabes, those giant noodle and steel and tobacco companies now dabbling in drug research, that enticed them most. Pulling up to the gleaming research center of Nissin, the largest Japanese noodlemaker, Boger and Aldrich were nearly toppled by three scientists in yellow pants, white shirts, and white shoes. The lobby was a tomb of black marble. “I feel like I’m going to see Dr. No,” Aldrich muttered as the scientists ushered them into an immaculate chemistry lab in which a lone technician staged experiments with yellow and pink liquids. Of all the sources of money Boger could imagine, these companies—with billions of dollars in cash and all but devoid of scientific sophistication—looked to be the easiest mark. “They wouldn’t intrude, the check would clear, and there would be zero synergy,” he said. He began thinking he might be able to sell not only immunophilins to Chugai but some other, unspecified project to another Japanese buyer as well—a prospect that had him, three days after his return to Vertex, huddling with an accountant and the company’s lawyer, his brother Ken.

“We’re looking at three to four million in ‘excess revenue,’ ” he told them proudly, “which would put us in a tax situation in our second year. If we take Nissin’s money, too”—he already took for granted Chugai’s—“we’re going to have to figure out how to avoid running a profit.”

Aldrich, contrastingly, was burnt out after the trip. A foot-long chain of Post-its hung from his computer screen, and his desk, normally as prim as a clerk’s, was suffocating under an avalanche of laminated folders. For several days after his return, he played “purposeful phone tag” with Glaxo, exploiting the time difference with London to evade Leslie Hudson even as he tried to reach him. An inveterate planner, he couldn’t plan until he heard from Chugai, and it grated on him. In by 8 A.M., he didn’t leave until 7:30 P.M., then went to a gym to work out “so I don’t feel like a total slug.” He downed a vodka every night before collapsing into bed. He daydreamed about taking off a weekend to do his taxes. “What kind of life is that?” he asked, distraught, knowing too well.

Aldrich had more experience than Boger with the Japanese and was sullen about the prospects of an easy deal. For most of the past ten years he had tried futilely to put together agreements the size of the one he and Boger were trying to engineer. Each time it had been a drawn-out, treacherous, heartbreaking failure. At Biogen he had coordinated the development of a promising anticancer drug: After spending $80 million, the company was close to licensing the molecule when the results of its first clinical trial came in; of 350 patients, none showed any improvement. He had two deals collapse at the last minute at his next firm, Integrated Genetics (IG): one when a Japanese partner backed down after a U.S. patent was issued to another company for the same drug; the other with Merck, which had been eager to license a genetically engineered antithrombolytic until such drugs proved no more effective than conventional molecules one-thirtieth the cost and, in a few well-publicized cases, caused bleeding on the brain. “We were in big-time negotiations—money, proposals changing hands, a $50-million-type deal. By the time things had taken their course, we couldn’t get people to pick up their phones.” As a practical matter, Aldrich valued Boger’s pose of inevitable triumph, finding it useful in negotiations and for morale. But he knew the odds were against one quick deal, much less two, and fretted privately about Boger’s effect on the Japanese. “They have an expression, ‘The nail that sticks out gets hammered down,’ ” he said. “I think a lot of them think Josh is cocky. They think he’ll get put in his place.”

In fact, because he was both storyteller and subject, Boger’s role in any negotiation was to be at once agreeable and insolent, personable and larger than life, and he fulfilled it in part by playing to other people’s expectations of him as a golden boy. This left Aldrich for ballast, part tactician, part monitor, glowering when Boger soared too high. (“Josh is the accelerator,” he would say; “I’m the brake.”) Up until now the two of them had worked capably together, but as more detailed legal issues evolved, Boger began to rely more and more on his brother Ken. Five years older, Ken Boger was Boger’s height, but broader, more manly looking, with a kinder, less angular face. A partner in the white-shoe Boston law firm of Warner and Stackpole, he was more introspective than Boger, his quiet stature and firewall demeanor reminiscent of Robert Duvall’s consigliere, Tom Harken, in The Godfather.

On March 12, 1990, with no word yet from Chugai, both Bogers and Aldrich met with Harvard patent officials to discuss the situation with Schreiber. By the pendulum of Harvard’s internal debate over faculty business interests, it was a perishingly bad time. That morning, the Wall Street Journal reported that all major universities were now starting to rein in their biomedical researchers and that Harvard had proposed the strictest controls. Scheduled for a vote later in the month, the plan would bar faculty members from owning stock in companies supporting their research—in the case of Vertex and Schreiber, a direct interdiction. The patent office still wanted a deal, but otherwise Harvard was riven, inhospitable.

Boger managed to elicit a tentative agreement, in part by appearing generous; he offered to let Ken do the drafting. Harvard still insisted on owning all Schreiber’s discoveries, but Vertex now won enough guarantees to block other companies from licensing them; if Vertex couldn’t control Schreiber, neither could anyone else. It was hardly what Boger, who believed Vertex had as least as much right to Schreiber’s work as Harvard did, would consider just, but it would have to do.

Thus armed, Boger now prepared to face Glaxo. Calling twice a day, the company was urging a meeting in London by the end of March. “Their tone is, ‘My God, what were we thinking, of course our strategies are compatible. In fact our noncompatible/compatible strategies are the best possible approach,’ ” Boger said. “I think they got the message: eleven days in Japan.”

There was no clear route through the shifting negotiations. But two phone calls on the morning of March 16 affirmed Boger’s exultation, even as they gave Aldrich more to fret. Finally getting through to Aldrich by phone, Leslie Hudson’s secretary invited him and Boger for two days of meetings with Glaxo’s senior scientists in London on March 27 and 28. Meanwhile, Benno Schmidt called to say that Chugai appeared to accept Vertex’s terms but that its board of directors needed to approve them at its next meeting in early April. Without misleading either, Boger and Aldrich decided to go hard at both companies. It was twenty-one business days since the initial meeting with Nagayama in Schmidt’s office and barely five months since the meat market at the Vista. Even Aldrich in his deflationary state began to revive. Boger beamed like a TV tower.

Chugai’s assurances weren’t firm enough to keep Boger and Aldrich from traveling to London, but they fortified them while they were there. Straight from the plane, they arrived at Glaxo with a preemptive gloat. Boger wanted support for twenty-five to thirty researchers. At $200,000 per scientist per year for five years—a rule of thumb that included compensation, equipment, and supplies—that was $25 to $30 million, or considerably less than the $40 million Schmidt had proposed to Chugai. If they produced a drug, Boger proposed splitting the revenues in half. Facing a group that included Hudson, Hammill, and several other ranking scientists and executives, Aldrich assumed his “practiced M.B.A. proposal scowl” in presenting Vertex’s terms.

Glaxo, unsurprisingly, had its own ideas. The company had never completely believed that Vertex would develop a drug, only that it would help Glaxo’s scientists find their own. Nonetheless, it made an unsolicited proposal: $25 million for world-wide rights to any new immunosuppressant that Vertex produced. Suddenly, what Boger had intended as a rout turned into a scraping negotiation, with Glaxo setting performance milestones and royalty schedules. Boger was incensed and dismayed. As he and Aldrich returned to their hotel, he was determined not to go back for the second day. Aldrich, however, preferred to call Glaxo’s bluff. Declining its offer, he countered by saying that it might be more consistent with Glaxo’s thinking simply to give Vertex the $25 million for biology, since Glaxo didn’t seem to value Vertex’s chemistry or biophysics or believe that it would find a drug. “We decided,” Boger said afterward, “to come in deeply provocative.”

Impatiently, the same Glaxo group listened to Aldrich’s restructured proposal the following morning, then sent him and Boger out of the room for forty-five minutes. They were supposed to meet through lunch, but “when we came back,” Boger recalls, “they said, ‘We’ve sent for your car.’

“It was great. It was the perfect negotiation for us. It showed we were better able to structure and think through a deal than they were.

“I began to think we really should be doing something together. We have similar arrogance levels. Arrogance doesn’t bother or impress us. We understand arrogance.”

If Glaxo’s unceremonious dismissal gave cause for worry, neither Boger nor Aldrich seemed troubled. “Glaxo can’t afford to be beaten in this area,” Boger said in early April. “It’s too front page. They’ll be back.” Harvard, however, was another matter. Its arrogance, real or imputed, was world famous, a whipping boy for U.S. presidents. The university didn’t need Vertex, as Boger believed Glaxo did, and Vertex had no fallback, such as Chugai. The delayed faculty vote on the new conflict of interest guidelines aside, Schreiber’s status remained as fraught as ever. Seduced by Chugai, mired in brinksmanship with Glaxo, muddling scientifically as his staff pressed him increasingly to do something about Schreiber, Boger now resolved to bring the situation to a head.

For six hours on April 4—“six hours of trading insults,” as he would recall it—Boger, Ken, and Aldrich met in Vertex’s conference room with Harvard’s licensing team. They knew they couldn’t prevent Schreiber from working with FK-506 but were relying on Harvard’s desire to avoid what Ken Boger called “a very messy situation” with respect to one of its distinguished professors.

Joyce Brinton, director of Harvard’s licensing office, also seemed eager to eliminate the problems arising from Schreiber’s overlapping research deal with Roche. However, she was now joined by a representative of Harvard’s sponsored research office, who’d been invited to address how and when any discoveries resulting from a Vertex-Schreiber collaboration would be publicized and who allowed with some satisfaction that Harvard was now considering investigating the entire matter.

Ken Boger, who seldom uses a litigious tone, leaned forward in the manner of a courtly but calculating southern lawyer. “We would certainly be very interested in learning what conceivable basis Harvard has for an investigation,” he said. Joshua, impassive, said nothing although he dreaded such a probe, not for what it might reveal, but how it would look. “It would be your basic congressional investigation,” he said later, “covered by the Crimson, which is the only student newspaper in America read in the executive suite of every major drug company. We can’t afford that. We can’t afford to be scapegoated.”

Nettled by the escalating ironies of making concessions to Harvard, which he considered irrelevant, to protect his relationship with Schreiber, whom he distrusted, in order to have access to science he had little use for other than to impress companies whose research he disdained, Boger now grew impertinent. “I bet your college education still isn’t paid for,” he snapped at the sponsored research man. “My research grants not only paid for my education, but also supported the English Department. You should be thanking me.” When the man said, “Harvard doesn’t accept the notion of confidentiality. Harvard exists for the dissemination of information,” Boger spat, “Is that why you charge $30,000 a pop for FKBP?”

Boger was ready to kill. In four weeks, as outside Vertex’s ramparts Cambridge slouched morosely toward spring, he had fallen from conquering Japan to berating academic functionaries.

And he still had no deal.

•  •  •

If negotiating with Glaxo and Harvard resembled a stag match in rutting season, with weeks of posturing punctuated by the crack of heads, contact with Chugai was more subtle, a caress with a mysterious figure slipping in and out of a mist. After its board met in early April, the company faxed Boger a three-paragraph letter stating its intention “to move forward with the project.” To Boger, self-schooled in Japanese culture, the letter represented a carefully worded statement of principle—a bond—which it would be a grave dishonor to break. Aldrich, who’d been misled before, considered it annoyingly vague and felt manipulated.

“Americans think that what people say publicly is not the real truth; the real truth is what people tell each other in private,” noted David Livingston, who knew nothing about the communication at the time—none of the scientists did—but who had negotiated with Japanese companies alongside Aldrich at Integrated Genetics. “In negotiating with Japanese firms the opposite is true. What businessmen say to one another privately is thought to mean very little. They’ll say anything. What matters—what lasts—are more public forms of communication, like letters.”

Intrinsically, Boger agreed. He began assessing Vertex’s chances of doing a deal with Chugai at 95 percent. Again he told Aldrich to stall Glaxo, which, as Boger predicted, recovered from its pique and was now pressing for a more detailed proposal.

Besides Vertex’s dire need of money and benediction, Boger’s and Aldrich’s own ambitions also now came into play. Barely a year old, with only twenty-five employees and still very little science to speak of, the company was more of an experiment than a corporation. How big it grew and who would lead it through the wrenching expansion that seemed to lay ahead depended largely upon its ability to raise enough money to incinerate in the labs and satisfy its investors. The company’s board of directors—Kinsella, Schmidt, and several other venture capitalists—was delighted with Boger’s performance so far. But in every emerging business there lurked the specter of the fallen, overreaching founder. Steven Jobs, whose example Kinsella had used to extract Boger from Merck, eventually lost control of Apple Computer when its board sought a more seasoned executive to manage its sprawling operations. The sooner Boger and Aldrich could claim a major deal, the quicker the board would put aside discussion about the company needing what Aldrich called “white hair”—bona fide executives who would take over and run Vertex as it became a drug company. Conversely, if they lost Chugai and/or Glaxo after coming this far, the board might be dismayed and want to replace them soon.

The Chugai negotiations were particularly sensitive in this regard. Boger and Aldrich had done all the legwork with Glaxo themselves, but acting on their own, in the fall, they’d twice been unable to arrange even an introductory meeting with Chugai’s licensing office. They would hardly be impatiently exchanging provocative faxes, much less contemplating the transfer of tens of millions of dollars, without Schmidt’s bearhugging of “Sam” Nagayama, the company’s young deputy president. Chugai was Benno Schmidt’s deal. As desperately as Boger and Aldrich wanted it, a Vertex/Chugai alliance would do more to enhance Schmidt’s legend than Boger’s story and would require them to prove themselves in yet another negotiation.

On April 26, 1990, four days before Boger and Aldrich were to meet with Nagayama in Schmidt’s office—and a week and a half after Glaxo’s deadline for a revised proposal had passed—Chugai wrote that it was no longer interested in the type of deal the two companies had been discussing. The pullback seemed to derive from Chugai’s growth strategy, which is to buy heavily into those U.S. companies whose products it licensed. As a second-level Japanese firm with global ambitions, Chugai was determined not only to barter its way into the U.S. market, but gain access to its newest technologies. The previous fall, it had paid $100 million for Gen-Probe, a California diagnostics firm, eliciting shrieks of protectionist horror from those who feared a raid on U.S. biomedical “seed” much like Japan’s infiltrations of other leading industries. Just as American dominance in biomedicine, one of the country’s last unchallenged technological strongholds, was coming full circle fifty years after its triumph over the Germans, Chugai was pushing hard to be a leader among the new class of upstart Japanese contenders. It knew precisely what it wanted from Vertex, which included enough stock to warrant a seat on the company’s board. It was displeased with Boger’s reluctance to include more than token equity in any agreement.

Characteristically, Boger and Aldrich interpreted Chugai’s sudden reversal differently. “They played us perfectly,” Aldrich fumed. “They kidnapped us. They kept us from talking to anyone else for six to eight weeks. It may have really fucked us up.” Boger, alternatively, was cavalier. “It’s dropped back to a 45 percent deal ironically because they’ve become more interested in us,” he said. “Are they really going to walk away from this because we disagree on the price of the entry fee?

“If they want to buy 30 percent of the company for $100 million, I’ll think about it. I won’t say I’ll do it, but I’ll think about it.”

Whatever their disagreements on the meaning of Chugai’s hesitancy and their varying stakes personally, Boger, Aldrich, and Schmidt all now favored a firm response. They agreed that Chugai wanted a deal badly but was exercising the Japanese custom, as Boger put it, of “beating you up at the end on price.” With Aldrich straining to revive the discussions with Glaxo, they resolved to force Chugai into a decision—a task that fell to Schmidt during the meeting on April 30.

“We’ve had a lot of other inquiries about this program,” Schmidt told Nagayama and four other senior company officials in his office. “Joshua,” he turned, “it’s time to start returning some of those phone calls.” He then set a two-week deadline for Chugai to respond. “That shouldn’t be a problem for Chugai since I don’t think we can close another deal by then,” Schmidt said, again eyeing Boger. Immediately after the meeting, Nagayama and Schmidt flew together in Schmidt’s private jet to Washington, where they lobbied FDA officials on EPO, the promising antianemia drug that Chugai had licensed from GI and that was still held up by patent problems. Whatever Nagayama’s views of Vertex, it was unlikely they were unaffected by being squired around Washington by Schmidt, whose connections there were still strong.

Said Boger, “That trip may be the difference between Chugai being a $l-billion-a-year company and a $2-billion-a-year company. The key now is how much rope the board gave Nagayama.”

•  •  •

“This is high-stakes bluff poker,” Boger said. “It’s an objectively tough sale. I mean we turned down $21 million. Turned it down. We’re having to reeducate everybody. People don’t do that. We may make a deal in the twenties rather than the thirties, but if we do that, we’re going to take back chunks of the world.”

Chugai’s fax, dated Friday, May 11, was as explicit as its previous ones were vague. The $40-million deal Schmidt and Boger were proposing was too rich. Chugai countered by halving the offer. Boger, predictably, was confident an agreement could still be struck. He saw Chugai’s refusal as a ploy. Aldrich, equally, was somber, morose. Because Nagayama had left New York favoring a deal, Aldrich believed that only a bloody battle on the board of directors could have subverted it. If that was true, there were now ominously bad feelings in Japan that would prevent Chugai from agreeing at a lower price. “I guess we played hardball too hard,” he said sullenly. “They couldn’t handle the money.”

Schmidt’s original proposal called for splitting the U.S. market with the rest of the world going to Chugai, which already had Asian and European sales forces “on the ground.” Now, working through the weekend, Aldrich drafted a counterproposal to reduce Vertex’s asking price. Facing the central dilemma of all small biomedical firms—how to avoid giving up, as the price for developing a new drug, all but a shred of its value—Aldrich suggested taking back Europe. Vertex could decide to sell a drug there itself, or it could license it to another partner, perhaps netting another $50 million in a few years. In effect, Vertex would now capture—for the reduced price of something less than $30 million—half the world market for a molecule it was nowhere near yet designing. Not as breathtaking as Schmidt’s original gambit, the idea was audacious nonetheless and Aldrich wasn’t counting on it. Reviving his counterproposal to Glaxo, he prepared to send it the minute that Chugai turned Vertex down.

Schmidt called Nagayama with the new proposal. It was still his negotiation, although his faith in it, conveniently for Boger and Aldrich, now appeared to waver slightly. Soon they would begin to say that Schmidt had interpreted Chugai’s last fax as irrevocable and had given up hope of making a deal. Schmidt disagreed. “Maybe they were more disheartened by the letter than I was, but I never thought the deal was dead,” he said several months later. “I do think it was fortuitous, though. I could ask for things I would not have asked for before, in a context of responding to [Chugai’s] wishes.

“If Chugai got a big drug out of it, what we were asking them for was chicken feed. Survival for us, but chicken feed for them.”

Predicted Boger, ultimately caring less than Aldrich whose deal it was as long as it succeeded: “I think we’ll be eating sushi real soon.”

•  •  •

Boger’s equable demeanor, his humor, his arrogance, his confidence in negotiations, all derive from the central theme of his own competence. Believing he’s right and that others—even nature itself—will eventually come around gives him a consistently placid air. Seldom does he show strain or even annoyance without also joking about it. Once, while lightly describing a tortuous and costly three-month campaign to recruit a key scientist away from Merck, he calmly tore a Pepsi can in half, but otherwise few difficulties raise in him more than a hollow chortle or a quick verbal jab.

Schreiber is the major, outsized exception. Two days after Schmidt conveyed Vertex’s final terms to Chugai, as Boger waited anxiously but unemotionally for a reply, Schreiber sent him a preprint of an article he had submitted on the binding activity of FKBP. Boger was livid: “This is Dingell Committee stuff!” he exploded unironically. He was referring to Michigan Congressman John Dingell, whose staff had recently launched several highly publicized investigations of scientific fraud. The article itself made no large point. It seemed intended, as with much of Schreiber’s lesser work, to “plant the flag”: keep his name associated with the protein while obtaining publication credits for his students and identifying new areas of inquiry that he could claim to have suggested first in print if they became important later on. In it, however, he cited—with far from thorough attribution—data that Boger knew had first been developed at Vertex and Merck. Calling the paper “a gross abuse of ethics,” Boger concluded more determinedly than ever that Schreiber cared more about his own reputation than doing legitimate science and that he couldn’t be trusted—a view, he would say, that Schreiber helped confirm by announcing around that time at Stanford that “Manuel Navia at Vertex” had crystals of FKBP.

“At this point, I’m ready to go to Glaxo and lay every single dirty piece of laundry on the table,” Boger fumed. “I’ll tell them, ‘You don’t want this guy.’ I’ll stipulate that we would consider it an unacceptable breach of security to have Stuart anywhere near this project.”

“He’s a loose cannon,” Aldrich agreed, staking out the alternative position that Boger, in his rage, had suddenly abandoned, “but if he’s on our deck, we can chain him down. If he’s on someone else’s deck and he’s pointed in our direction, we can’t deter him.”

“And if he’s an exploding cannon, who’s deck do you want him on?” Boger asked.

Even if Boger was ready to break with Schreiber, his question raised the potential of an even more damaging scenario, that Schreiber would “drag the rest of the SAB with me,” as he had recently threatened to Matt Harding.

“It would be incredibly embarrassing to have an SAB blow up at this point,” Aldrich said. “Apocalyptic.”

Boger grinned for the first time in the conversation. “There are certain advantages in life you wish only on your enemies.”

•  •  •

John Thomson limped into the lunchroom, put up a pot of coffee, and announced he wasn’t leaving the building until he’d concentrated a slug of FKBP sufficient to grow crystals that were large enough to solve its structure. The night before, he’d gone drinking with Mason Yamashita, Vertex’s young second crystallographer, to celebrate his one-year anniversary at the company. The two had recently become close friends. Working the same hours, driven by similar compulsions, it was their work—Thomson’s with supplying protein and Yamashita’s with divining its atomic structure—that Boger was relying on chiefly to advance Vertex into the arena of designing drugs. Thomson was drained—“Every little thing that happens now breaks me,” he said—and Yamashita, under Navia’s direction, was next in line to inherit the protein and its attendant burdens. Thomson was determined to bequeath him both.

“The moment I see spots on that screen,” Thomson had said, referring to the radarlike color monitor atop Yamashita’s X-ray machine that indicated if a crystal was diffracting and thus ordered enough to reveal a protein’s structure, “I’m on my bike and out of here.”

“Where?”

“West.”

“How far west?”

“West.”

Thomson’s frustrations had only mounted since he first isolated FKBP in mid-February. To grow protein crystals—ideal, unnatural forms in which huge numbers of floppy and unstable molecules spontaneously arrange themselves in a lattice, then repeat the process billions of times outwardly in all directions—one must first create an infinitesimal Nirvana. The individual molecules must be bathed in a state of calm or they begin chewing each other up or themselves up or become agitated and bolt from solution rather than submit to a rigidification they abhor. In other words, they must be doped. To keep proteins happy and serene once they’ve been wrenched from their native environment, biochemists suspend them in mother liquors, chemical buffers that have the effect of amniotic fluid laced with heroin. The problem is, as chemical entities, all proteins are different, and thus identifying the right mother liquor is hit or miss. Worse, one must sacrifice scarce protein to do so and may still find that no perfect elixir exists. Only a fraction of the tens of thousands of known proteins has ever been crystallized, largely because the right conditions for growing them are so exasperatingly hard to find.

Torn from the thymus juice and placed in its own solution, FKBP was jumpy, excitable, a resistant hostage. For several weeks in February and March, Thomson and Matt Fitzgibbon had pushed batch after batch of the material to final purification, only to watch it “crash”—precipitate out of solution. They eventually delivered Navia and Yamashita a total of five milligrams—500 times as much as Harding and Merck had isolated initially in discovering the protein—but it was unstable. Worse for Thomson, the crystallographers’ goals and priorities were the opposite of his. Though he had struggled mightily to keep the protein in solution, they now, with considerably less care, tried to coax it out. Navia, though competent at growing crystals, was traveling a lot and seemed distracted by other projects. He had little of Thomson’s devotion to benchwork, leaving most of it to Yamashita, who had never worked on such a scarce or important protein before. Though it had been all he had labored for and though he liked Yamashita, Thomson now found it excruciating to pass the protein to other researchers whose qualifications for handling it he couldn’t help but distrust.

Navia quickly dispelled Thomson’s grief by growing fulsome crystals of what he believed was pure, native protein, but they were too small to identify; he needed more material. To Thomson, still optimizing his procedures, the smallness was also an invitation to push the protein to sharply higher concentrations, which if it worked would help the molecules pack together more, or if it didn’t, could make them crash out before the crystallographers ever saw them. “We’ll all have FKBP earrings before long,” he boasted to Navia and Yamashita on April 5.

That was six weeks ago. Now Thomson began another siege that would last, with few interruptions, until the end of May. And unlike his previous attempts to isolate the protein, what he feared most wasn’t what he didn’t know, but what he did.

For his final concentration, Thomson used a pump-loaded microfiltration system that pushed the protein through a narrow, eight-inch column packed with ultrafine silica, a sandlike substance. First he saturated the column with a salt concentrate, then extruded the protein through with a thin stream of distilled water. Seeking refuge from the caustic salt, the protein molecules jumped to the outside of the column, then “caught the wave” as the water flushed them, drop by drop, into a rack of test tubes. Only by watching a computer readout could Thomson tell whether this molecular surfing was successful or, as had happened with his previous batch, the protein stuck to the silica and was “gone forever.”

Late in the afternoon on May 28, Thomson loaded the column with what he calculated to be almost 200 milligrams of pure FKBP, the result of more than a month’s preparation. It was a significant portion of the world’s supply, half as much as Schreiber’s group had produced recombinantly in six months. Thomson had been in the lab for five days, his chin a mass of stubble, his eyes red and raw. Tapping his foot incessantly, he stared unblinking at his equipment.

“Damn,” he said suddenly, “it’s going off scale. It’s too concentrated.” Tiny white particles now bubbled at the surface of his sample. The protein was metastable—at the very margin of stability, like a volatile liquid about to explode—and Thomson quickly added a buffer to stanch the precipitation. “I’m scared that getting it ready to put back on that column may have pushed it over the limit. Shit.

“You’ve missed the fun and games, Matt,” he told Fitzgibbon, his assistant, who had drifted over with several others. “We may have lost the lot.”

“I hate this protein,” Navia said. He put his hand on Thomson’s shoulder: “Take it easy, big guy.”

“The big guy is having a coronary here,” said Saunders.

Sucking in air, exhaling deeply, Thomson riveted his eyes on a liquid crystal display readout. “Get up!” he said. “Get up!” It was several minutes before the test tubes containing the FKBP solution were full and he could remove them from their carriage. Holding them to the light, he flicked each one three or four times with his thumb. The liquid was clear. There was no change in density from his earlier samples. Thomson heaved a voluminous sigh.

Next morning in the lunchroom, he quietly handed Navia two small nose-cone-shaped locking plastic tubes, each smaller than a thimble, containing 130 milligrams of high-concentration FKBP.

He had wanted to conduct the exchange in private, but Saunders, whom Thomson had still not forgiven over the loss of his girlfriend, noted what was happening and quickly gathered witnesses from the library. The room erupted in applause. In the highest scientific tradition, Mark Murcko, a computer design expert recently arrived from Merck, proposed a new coinage: the Thomson Unit—one hundred milligrams of ultrapure enzyme.

With 1.3 Thomson Units of FKBP, Navia and Yamashita quickly began sketching a barrage of new experiments to increase the size of their crystals. It still wasn’t clear whether the protein was the target Vertex was looking for or even whether the earlier crystals were of FKBP, but science proceeds mostly from an abundance of materials, not understanding. Having at last experimental quantities of protein gave Vertex one of the two vital reagents—the other being money—it most desperately needed. “Either we’ve already been beaten,” Navia said, “or we’re going to win.”

Two days later, Thomson, his vitality inching back, went to his doctor for a three-hour physical—a requirement for working with human tissue. As he had stated back at the first SAB meeting, he was now planning to begin cutting up spleens.

“I have a rare ailment called thymophilia,” he reported to Laura Engle, one of Boger’s assistants. “The only known cure is six weeks in the Bahamas, followed by a liquid diet administered in the south of Spain. Four or five months and they said I should feel like new.”

•  •  •

“What’s up?”

It was midafternoon, late the following Thursday. Navia had just returned from an NIH site visit and observed Yamashita typing quickly but desultorily in the X-ray lab. A plate-glass window between the lab and the hall forbade any privacy.

“Not much.”

“Anything doing.”

“No.”

Yamashita’s face was a mask, dark and rigid. He looked like a young kick boxer or medical student, slight, with square shoulders, a broad face and glistening black hair parted unceremoniously in the middle. He wore an oversized Big Dog T-shirt, black polyester pants, running shoes, and, around his neck, lightweight headphones attached to an ever present Sony Discman. At twenty-seven, he had gotten his Ph.D. a year earlier at UCLA, then moved east to work for Vertex, buying a duplex that he seldom saw around the corner from the labs. Though Boger had hired him as a full scientist, his absence of any personal life, endless days in the lab, and all-around slavishness shouted postdoc.

Yamashita was lying: A lot was doing, all bad. Immediately upon getting the protein from Thomson, he and Navia had begun trying to grow FKBP crystals under a variety of conditions. By the time Navia had left two nights earlier, they each had incipient crystals, and Yamashita had been ecstatic. Growing crystals is the trickiest, most critical task in finding a protein’s structure, and the part Yamashita was least skilled at. At the same time, FKBP was now fast becoming one of the biggest prizes in biophysics. A recent conference of the American Crystallographic Association had ranked it among the most important protein structures to be solved, ratcheting the competition. Wafted by the opportunity to lunge ahead on a career-making problem and perhaps impress Navia in his absence, Yamashita had tried the night before to see if the crystals diffracted.

X rays, like light, deflect off some objects and pass through others. Because their wavelengths are about 1000 times shorter than visible light, they slice through organic molecules, which is why they permeate flesh and tissue like wind through a fence and stop only at dense, mineralized bone. Train an X-ray beam on a large, well-ordered crystal, however, and it scatters against the electrons: thus the rationale for X-ray crystallography. It’s like firing a laser at a crystal chandelier, then trying to determine from the millions of spots on the ceiling, walls, and floor the precise placement of each lozenge of glass.

Crystallographers nearly always solve a protein’s structure once they have a large enough crystal. But they need to know if they’ve crystallized protein and not some other constituent in the mother liquor. This is what Yamashita had attempted the previous night. Inserting a crystal into a sealed capillary tube, he had mounted the tube, like a slender drill bit, in a rotating chuck atop Vertex’s X-ray generator. The machine, filling a third of the lab, is the size and shape of an industrial freezer and is jacketed with computers. It buzzes constantly. Yamashita, perched on a library stool and hunched over the superstructure that sends the beam through the crystal and catches the diffracted X rays, set the crystal precisely, punched in several commands at a keyboard, then waited for a pattern to emerge on a monitor. He was listening to Sinead O’Connor’s “Nothing Compares 2 U” loud, on his headphones.

At the sight of the first spot, Yamashita began jumping up and down. But after several minutes, a few more appeared. Proteins, with hundreds of atoms and thousands of electrons, produce galaxies of spots, but this was something else. Two or three atoms at the most. A salt molecule maybe. Yamashita was bereft: “It was throat-cutting time,” Thomson recalled. Miserably, they left the lab and went to a bar.

Like Thomson, Yamashita abhors failure. He, too, wanted desperately to prove that Vertex could design drugs and saw his own work as vital to the company. And yet now in his first real job, he was also ambivalent.

He had come to Vertex not, as Boger had, along a fast stretch of straight track, but circuituously and alone. Raised on army bases, he had alternated in adolescence between being an amateur Pentecostal and a rabid existentialist. Ever since, he had drifted in isolation, seeking a moral way to live. He had few friends and was reeling from the break-up of a lopsided romance. The main constant in his life was science—in particular, computational chemistry, through which he believed one could know the truth about the world’s most basic events.

That crystallography, in which he had “extreme trust,” confronted him now with an undesired outcome pained Yamashita deeply. Normally polite to a fault, he spent the morning cursing. He still didn’t know what he had crystallized. Meanwhile, Navia began examining his own experiments. He, too, was dismayed. Opening the well on a particularly promising crystal, he instantly noticed the faint odor of compost. “Bacteria shit,” he scowled. Microbes had fouled his sample.

Hearing from Yamashita about his failure the night before, Navia suggested poking the suspect crystals with tweezers. Protein crystals are delicate, crumbly, like Halva: The individual molecules are attached by few atoms relative to their mass and are easily separated. Salt crystals, on the other hand, are brittle. They snap. Yamashita was horrified by the thought of deliberately destroying a crystal, but he eventually gave in. When a few moments later Navia cracked one of his crystals sharply like a sliver of mica, Yamashita burst out of the room.

“I don’t want to be here,” he hissed, though clearly he also didn’t want to be around Navia, with whom he compared himself. It was an inapt comparison: Navia was seventeen years older, highly successful, a well-regarded investigator. He knew it sometimes took years to grow decent crystals and that once grown, they might never grow again. Navia, more equable about his own disappointments, thought he understood Yamashita’s: “His point is, my career is established. I can take a few hits. But he can’t. He’s got to do everything right the first time.”

Yamashita found Thomson at his bench and offered to drive him to Stoughton, in the suburbs, to pick up Thomson’s new motorcycle. It was a used Honda V 1000 R, a 440-pound racer with more horsepower than an Accord. A hellish machine, it wasn’t as fast as the one Thomson had totaled in the fall, but still what transplant surgeons call a “donorcycle.” Thomson had planned to take it away for a week but now, hearing of the setback in crystallography, decided to stay. Sympathetic, he was also put out: “How do you think I feel, their growing bugs and precipitating salts in the world’s most sought after protein?”

That night, Yamashita slouched in the blackened conference room, his feet up on a chair, listening morosely to the girl group, the Bangles, on his Discman. Navia sat studiously in the library, his tie still straight, reading and taking notes until well after 9. No one else was in the building, but they didn’t seek each other out. “A fraternity of grief,” Mark Murcko once called science. A fraternity particularly unforgiving of failure.

“I’ve got to talk to him,” Navia said, although plainly he wished he didn’t.