Though it was paid for by Fujisawa, the First International Congress on FK-506 was ineluctably Tom Starzl’s show. He was conference president, host and lightning rod, the reason 1200 researchers were drawn to Pittsburgh for a week in late August, and why they came anyhow. Summer is when science meets, but Fujisawa, the drug’s manufacturer, was rumored not to want this meeting. Its much-delayed European and U.S. clinical trials were going badly. Frustrated transplanters were unable to replicate Starzl’s work. The company wanted time, a lower visibility. But Starzl had insisted. He had not slowed down in the year since his heart operation and was determined to spare no amount of effort to advance the drug. Not wanting to shut down his transplant service for the third time in two years in order to take his case to the world, he used his position to bring the world to him. Gaunt and erect in a white or red turtleneck, he had no formal speaking role but plied the cavernous conference center like a specter, dropping in on friends and competitors, occasionally approaching one of the floor mikes to ask a barbed question or lash back at one in his pursed, quietly apocalyptic low-plains drawl.

It seemed a rueful valedictory, this stalking. Starzl still believed that FK-506 was an extraordinary drug. He defended it stoutly, unequivocally. But the molecule had never been for him an end in itself. He had pursued it solely as a tool for overcoming the biological barrier to transplantation. In experimenting with it, he had become perhaps one of the world’s foremost clinical immunologists. He had taken from it what he could, and now, as always, was rushing toward the next Armageddon. “This is the last thing I’m going to work on [with FK] minus two, maybe minus one,” he said wearily on the eve of the meeting.

But Starzl couldn’t easily extricate himself. Even before the conference began, there were harsh signals that he would be called severely to account for the drug’s erratic performance, much more so than in Barcelona or San Francisco. More than a dozen medical centers in the United States and Europe now had the drug, and none of them had come close to matching his results. The discrepancy blasted away the cordial veneer that distanced him from his peers, rendering Pittsburgh once again a bunker. Not only was his data widely suspect, but many considered his promotion of the drug improper and self-serving. “It’s not the drug that we were led to believe it was,” a transplanter indignantly told a confidential marketing survey around this time. Snapped another, “I shouldn’t have to get my information about drugs from the New York Times.” Starzl had long been scorned as a heretic for his methods. Now, an ever-growing list of critics was assailing his credibility and ethics. Though he was past them now, past FK-506, perhaps even past the great span of his life’s work in transplantation, he was forced to double back to defend his flanks.

His central claim was that FK-506 was a qualitatively better drug than cyclosporine. As long as no one else had the molecule, few could argue, not that many hadn’t tried. Sandoz, maker of cyclosporine, had furiously campaigned sub rosa to discredit FK-506, dubbing it “Fujitoxin” and plying transplanters with data suggesting that the Japanese molecule, far from being unique, was what one of them called “a turbocharged cyclosporine—both good and bad.” Starzl still insisted it was more than that. Sandoz hadn’t needed to send its own researchers to the conference to rebut him. Because virtually all transplanters prescribed cyclosporine and most had taken substantial help from Sandoz, from free samples to draughts of research money, the company had no shortage of surrogates.

Leading them was Sir Roy Calne. A strutting bantam of a man, Calne, of Cambridge University in England, was Starzl’s chief and perhaps only rival. He had pioneered the clinical use of cyclosporine and had paved the way for Starzl’s rescue of FK-506 by deeming it too toxic for humans. They were publicly friendly, lavish in their mutual homages, but there seemed to be little love lost between them.

At a panel discussion the first morning, Calne confessed to being “surprised and amazed” by Starzl’s success with FK-506. But his iciest testimony concerned the drug. Noting its “almost spooky similarity” to cyclosporine, Calne predicted FK-506 would be approved but as a backup either for those who couldn’t tolerate cyclosporine or to alleviate specific side effects, such as “the very unpleasant hirsutism” among children. “It could be,” Calne sniffed, sounding at once congratulatory and dismissive, “that children will be the greatest beneficiaries.”

Neither Starzl nor Fujisawa, of course, saw FK-506 as a “crossover” drug. To them, FK-506 was a revolutionary molecule, the kind of drug, as Starzl had put it, “that comes along once in a lifetime.” Yet they were almost useless to each other as allies, so divergent were their aims, so toxic their recent relations. During the more than two years since Starzl’s initial triumph with FK-506 in liver “rescues,” Fujisawa had tried at times forcibly to wrest control of the drug’s development back from him. Fearing that his outraged refusal to compare FK-506 and cyclosporine in randomized trials would slow or even derail the drug’s approval, it had tried to cut him out of critical meetings with the FDA, above the agency’s objections. It had refused to recommend his protocols to other transplanters, urging drastically higher doses that Starzl and his people considered criminal. Strategically, Fujisawa planned to grow into a worldwide pharmaceutical company on the billions of dollars in revenues it anticipated from FK-506. The drug was to be its flagship in the United States, where it was the first Japanese company with what appeared to be a major new therapy, and its efforts to establish itself had been costly and, so far, disappointing. It was not about to yield its future to a fractious and unyielding American maverick like Tom Starzl.

Fujisawa kept a determinedly low profile at the congress. Several of its scientists delivered talks, but mainly its contingent remained ensconced in a food- and smoke-filled lounge one flight up from the main hall. All but invisible to the mass of scientists, they met in scattered groups among themselves and with a few invited business guests. “Scientifically, we are very confident that the drug works,” said a senior research executive, “but whether this can be a good drug or not from a marketing point of view we are still uncertain. We have to accumulate data to show superiority to cyclosporine.”

Starzl’s people, conversely, were ubiquitous, embattled, contentious, and indignant. Having dominated the meeting’s organization and with the most experience with the drug, they gave the most talks, sat on the most panels. They swarmed in and out, occasionally substituting for one another so that they could race across town to the larger drama of the transplant wards. Throughout the week, they led intense, nonstop parallel lives—one minute immersed, steel-eyed, in a maelstrom of medical center, the next engaging in scientific brinkmanship in the conference hall. As with Starzl, the exigencies of the first gave rise to a profound disrespect for the second.

Their tribulations were extreme. For instance, within an hour of staving off criticism during a discussion on blood monitoring, Andreas “Andy” Tzakis, a soft-spoken Greek-born surgeon with bulging, forlorn eyes and a Harpo Marx-like insouciance, one of Starzl’s closest lieutenants, was back at the liver clinic at Pittsburgh’s Children’s Hospital ministering to Mary Arthur, a pretty seventeen-year-old from Louisville, and to Arthur’s family.

Nineteen months earlier, in January 1990, she had had “everything out”—her entire lower viscera—as the first recipient of an experimental “cluster” transplant, wherein the insulin-producing cells in the pancreas are infused into a newly grafted liver. Her surgery, insulin production, and immunosuppression had been uniformly successful—a breakthrough on several fronts—and she had returned home to an active life. Then, in January 1991, a metastatic cancer reappeared. Despite intensive chemotherapy, a tumor materialized in her jaw and had grown virulently, tripling in size in the past two weeks. Sitting with her anxious parents in a noisy waiting room, fingering a small gold cross on a chain around her neck, her cheek delicately puffed, she told Tsakis she wanted to do “whatever will get rid of the cancer.” For the next two hours, he and several other doctors—oncologists, radiologists—wearily discussed what to do. Their desperation about recommending radical surgery that might destroy her appearance while only buying her a few months’ time was plain, particularly Tsakis’s, whose exhaustion and anguish seemed to weigh on him like irons.

It was a posture of interminably beset moral urgency that many of Starzl’s people shared and that was represented most vehemently at the conference by Dave Van Thiel, Starzl’s acerbic, 300-plus-pound field manager and intellectual second-in-command. “They’re overdosing their patients,” groaned Van Thiel, Pittsburgh’s chief of gastroenterology, during a panel on European and Asian clinical testing. “It’s remarkable,” he said after Calne’s left-handed remarks, destroying a Styrofoam coffee cup by inches. “Despite the fact that they’re poisoning people, they still think it’s a good drug.”

That FK-506’s value as a drug was anything but foregone was a medical issue: It would be resolved in the clinic. But Starzl, determined as ever to cull whatever he could, also recognized the pivotal role of basic research in answering practical questions about the drug. Like Boger and Schreiber, he had long since stepped beyond the narrow limits of his field. Only by probing the cellular and molecular biology, he knew, would the drug’s maximal value be revealed.

Of course, those questions invited their own rivalries, and Starzl was forced to become involved in them as well. Schreiber, by virtue of his continuing priority in the field, had been given along with his friend and collaborator, Gerry Crabtree of Stanford, the longest presentation—each had a thirty-five-minute plenary talk, early on the second morning. It was more than repayment for good work or because he had promised big news. Both as a member of the committee that reviewed abstracts and as cochair of the session on cellular biology, Schreiber had known for months what everyone else would be presenting. In at least one case, he apparently influenced the scheduling, requesting that a Merck scientist named John Siekierka, one of the codiscoverers of FKBP-12 and a presumptive competitor of his in the search for new partner proteins, be moved to a less featured slot.

“Siekierka is pissed purple because we put him in a different position,” acknowleged Starzl, who smoothed things over by inviting Siekierka back onto the second day’s program, though only after, and with less time than, Crabtree and Schreiber. With Vertex SAB member Steve Burakoff, Schreiber’s other main collaborator in immunology, introducing the morning session, Schreiber was guaranteed that he wouldn’t be upstaged. Indeed, it hardly mattered. By now Starzl had come to see in Schreiber a key ally and had taken—unsolicited—to praising his work lavishly. Even without Starzl’s interceding, Schreiber was a made man.

Vertex, as Boger had promised, sent a large group: Thomson, Harding, Livingston, Moore, Peattie, Nelson, Stuart, and several others. However, none of them—Boger suspected an illicit boycott by Schreiber—had been invited to give a major talk. They would, in the pyramidal hierarchy of many such meetings, deliver so-called open papers—ten minutes from the podium—or posters, standing next to blowups of their work in the lobby during designated hours, like vendors at a trade fair. In fact, a few of the calls were questionable: Moore, whose Nature paper was both well known and highly regarded, was only given a poster. But on the whole, the assignments seemed to reflect what the scientists already knew: that their research so far had been important but hardly earth-shattering and of less than general interest to a medical audience.

Boger had talked for months about coming himself but, conceding that Schreiber “owned the meeting,” finally decided against it. “This could have been an important meeting for Vertex,” he’d said, “but it won’t be because of Stuart. When Vertex can flash a slide and say, ‘This is a small molecule inhibitor of FKBP that can be made by a masters-level chemist in his or her kitchen in an afternoon,’ that’s when we bring down the house at an FK-506 meeting.

“The second annual FK-506 meeting,” he vowed.

Navia also changed his plans. Invited only to give a poster, he decided first to fly in for just twenty-four hours, then canceled abruptly at the last minute. It had been a grim time for him professionally. In July, after months of deliberating, Nature finally rejected his and Yamashita’s structure paper. The structure itself was still wrong, and he and Yamashita humiliatingly had to correct it using Schreiber’s and Clardy’s coordinates. Meanwhile, his “baby,” using cross-linked enzyme crystals as supercatalysts, was rejected by Science, and he still hadn’t produced structures showing Vertex compounds inhibiting HIV protease. Navia had come to Vertex boasting that his group would be a powerhouse, but it had faltered repeatedly while he had been increasingly absent and, it seemed, consumed by his own ambitions. Consummately concerned about his place among crystallographers, he hadn’t published any work in more than two years, since he left Merck.

What with the Yamashita psychodrama and Boger’s decision—widely resented within Vertex—to make him an officer, Navia had become alienated, morose, unsure of himself since the road show, and prone increasingly to sudden rages alternating with acts of contrition. The thought of standing by a poster of a protein structure that he had needed Schreiber’s help to solve while Schreiber himself dominated the congress from the stage would have been unbearable. He still believed Schreiber’s effector hypothesis was too simplistic, but without data or an adequate place to stand, he was not about to challenge him on it in Pittsburgh. Latching on plaintively to Hurricane Bob, then blowing off the Atlantic coast and playing havoc with flight schedules, he asked Harding and Moore to put up a sign at his poster station saying Hurricane Victim. “Yeah,” sneered Thomson sardonically, “Hurricane Stuart.”

If Navia was a casualty, he was a casualty of the need of all scientists to be first and of his putting his neck out too far. He had misjudged—himself, the competition, the questions he was trying to answer. But even those who had succeeded and were now struggling for priority were at risk of being subsumed. FK-506, if anything, had proven more mysterious and powerful than any of them had imagined. They had all striven to know the molecule: its shape, how it interacted, what it did, what it was capable of doing, how to manage and control its extraordinary potential as a drug, what to do with it. They had dared one another and themselves to know more, do more, explore more deeply. And yet even the most Promethean of them—Starzl—had met with inevitable dissatisfaction.

FK-506 had pushed Starzl relentlessly beyond himself, beyond even his own murderous strictures for reaching past what was possible and for cheating death. Once islet cell transplants like Mary Arthur’s proved successful, for instance, he immediately pushed his group to the next logical step: the intestines. Without the ability to absorb food, islet cell recipients continued to suffer greatly. They were either tied to feeding tubes or, like Arthur, nibbled down protein shakes and bagels, unable to gain even a few ounces. And yet the intestines were, as Starzl observed, “the forbidden organ”—filled with deadly bacteria that if they broke into the bloodstream caused massive, often fatal infection. Still, of the first five patients to receive new bowels, all survived, eating and—after a grueling recovery—digesting food.

With each new round, the attacks on Starzl grew. “I read . . . the report . . . with mounting horror,” a British doctor wrote after reading Tzakis’s published account of Mary Arthur’s operation. “I thought that this sort of mutilating surgery had ceased long ago. How many more cruel and inhumane operations will be done in the name of advancement of science?”

Starzl had always been obsesssed, but his urgency and resistance to criticism had been case-hardened by age and ill health. At sixty-six he finally seemed to be acknowledging his mortality. Ever youthful and irreverent, he had long ago given up any religious hopes for himself. But transplanters cannot but be changed by their patients, many of whom are sustained only by a profound and abiding faith. A hand-written note on the wall next to a young woman who’d just had a liver transplant quoted Romans 8:18: “For I reckon that the sufferings of this present time are not worthy to be compared with the glory which shall be revealed to us.”

So it now seemed with Starzl. For thirty years, he had not stopped working. He had performed thousands of grueling and macabre operations despite being tormented each time he picked up a scalpel by the horror of what he was about to do. In the process, he had imperiled himself—overcoming hepatitis twice, an ulcer, temporary blindness after an operating room accident with a laser, and his recent bypass surgery—and destroyed his first marriage. Meanwhile, he had become the most prolific scientific author in the United States, publishing 503 scholarly articles between 1981 and 1990, many in prestige journals and all, if not dictated personally, written with his unstinting—many of his staff would say bullying and heavy-handed—editorial assistance.

And yet the ultimate prize had eluded him, not only a key biological discovery that moved medicine irremediably ahead, but the honor that science reserves for those who account for such breakthroughs. Schreiber, whose own ambitions were clear, recalled talking to Starzl by phone on the day the previous fall when two other transplanters shared the Nobel Prize for medicine, all but foreclosing another Nobel for transplantation anytime soon. Schreiber marveled at Starzl’s steely equanimity. He had not gone into seclusion, as one of Schreiber’s Harvard colleagues was known annually to do, but kept up a full eighteen-hour work schedule throughout the day and in the days ahead.

Starzl knew his dominance was coming to an end. He had already decided to devote the rest of his career to research, having stopped operating earlier in the year, and was now facing the turbulent conclusions drawn from all his restless endeavors: that the future of transplantation, as it always had, lay ultimately in the ability to control rejection and that even that would never be enough. Mary Arthur’s resurgent cancer, like so many relapses before it, reminded Starzl and his people dramatically of the ultimate futility shadowing even their greatest successes. Transplantation went only so far.

This was the great imperative of Starzl’s life: to go further. And it explained his zeal in trying to ensure his legacy. Bursting headlong into several new areas at once, brimming with his customary resolve, Starzl also had recently begun campaigning more actively for recognition, an effort that included flying off more and more frequently to receive awards and prizes he once would have spurned, aggressively cultivating the media, and publicizing his achievements. The Pittsburgh conference itself, however important medically, was equally an effort by Starzl to orchestrate the attention of several worlds on his molecule, even as its cachet began to fade.

“There is a strange thing about the dimming vision of aging eyes,” he would soon write in his memoirs—another of those self-promotional acts to which Starzl now committed himself utterly—which he wrote in the breathtaking time of just three months. “What cannot be seen clearly, the mind fills in more vividly than reality.” Thus it had become with immunosuppression. Peering into the heart of immunology, Starzl had begun to perfect his own understanding of it. What he lacked in data, he more than made up from an unparalleled breadth of experience, of vision. No one else, certainly no surgeon, had descended the ontological ladder so completely, from organism to organ, from organ to cell, from cell to molecule, bearing such powerful witness at each stage.

Ironically, he began thinking more and more about multidrug therapies that not only abridged the need for the kind of radical surgery he’d spent his life advancing, but might eliminate it. “Transplantation,” he began to say, “may just be a footnote to this entire story.”

This was the message Starzl intended to press at the conference. However, there were problems. His best data had been developed by an Italian liver expert, Antonio Francavilla. Starzl’s team had always been a polyglot group, with Japanese doctors struggling to communicate with Greeks, Swedes with Italians, and all of them attempting to overcome—with greater and lesser success—deficient English. Yet even in that mix, Francavilla’s accent was persistently torturous. (“His English was worse than imperfect,” Starzl would recall twenty years after their first meeting. “I could not understand a word he said.”)

The problem had surfaced acutely two days earlier on the eve of the conference. As Starzl and nearly one hundred members of his regular Monday night FK-506 group gathered to rehearse their presentations, he began to doubt whether Francavilla, who pronounced the drug’s name as “effa-kaya-fiva-oah-seex,” wouldn’t simply garble his.

“This piece is a companion piece to Schreiber’s,” Starzl had begun encouragingly as Francavilla stepped up to practice his talk. “We have to very critical about this. If it’s not precise, our message will be lost.”

Van Thiel, sensing that the one real piece of “earthshaking” science that the Pittsburgh group would be presenting was being strangled, was less patient. “I think we should scrap the first two conclusions. They’re somebody else’s,” he cut in after Francavilla showed his first several slides. After another incomprehensible explanation, Van Thiel wrung his huge hands. “I think it would be great if Tony spoke perfect English,” he muttered. “I don’t think you want Tony to defend that slide. I wouldn’t want to defend it in Italian.”

“Can we practice again?” Starzl looked up, exasperated. Franca villa, apologetic and perplexed, said he would try.

Throughout, the strains escalated. Invoking Schreiber time and again, Starzl exhorted his researchers one after another to push their conclusions, particularly with autoimmunity. It was here, on the clinical side, that Pittsburgh still maintained an edge, and Starzl was determined to wring every advantage he could. He had wanted the FDA, for instance, to approve a clinical study with FK-506 for patients with MS. But the agency had resisted authorizing treatment for a disease of the nervous system with a drug of known neurological toxicity. Now, when a neurologist named Benjamin Eidelman reported that three patients with MS—two transplant recipients and one other—had been receiving FK-506 and had shown dramatic improvement, Starzl was ebullient. He noted: “I saw the third patient today and she looks ravishing. She’s flakier than hell, but she’s ravishing.”

Eidelman, a senior researcher in his own right and not prone to excessive claims, was cautious. He dourly reminded Starzl that MS is notorious for spontaneous remissions, but Starzl pressed on. “You’re sitting on your hip pockets,” he said. “You’re telling a great what-a-big-boy-I-am story, but you’re being too conservative. Jesus Christ. With three MS patients, this is really big news.”

“Neurotoxic means neuroactive,” Van Thiel reminded them. “It’s a matter of dose.”

Eidelman again resisted, but by now Starzl was on him. “I would deemphasize the what-a-big-boy-am-I character,” he said tautly. “Who gives a shit? The important thing is that the drug’s been used now for three patients with MS. It’s almost the biggest news of the whole damn thing. The public needs to know this. This is the big glitch with the FDA. This is where they need to feel some pressure to come along.”

Eidelman stood his ground. He would not make any claims for the drug, only report his findings. Starzl, smiling through gritted teeth, accepted his decision.

“One of the things about discovery,” he lectured, “is that you’ve got to know you’ve discovered something. You don’t want to be afraid all the time.”

It was an oddly fateful reprise of the scene at Vertex months earlier when Boger and the others were preparing Yamashita’s crystallography paper, driving till the last minute to make the most of their data, risking overstatement to build a more magnificent bridge.

But by now it seemed too late. By relegating himself to the role of arbiter and coach, Starzl could only, as he put it, “engineer . . . make sure of quality.” The larger lessons of the drug’s action no longer favored those who made their observations in the operating room and the clinic, but in the lab. Despite his high-handed treatment of Eidelman, Starzl seemed resigned to the fact. Indeed, in a sense, he’d already ceded it. The next morning, after working through dozens more papers and staying up much of the night, he advised reporters at an opening press conference what he thought their story would be: “It’s unfair to focus on anyone, but I think that Schreiber’s group in Boston has big news. . . . I think you ought to talk to Schreiber.”

•  •  •

Schreiber wandered through the conference at an airy distance from the proceedings. Not only did he know very few of the participants—he and Starzl had only just met face-to-face—he was practically incognito. Most of the surgeons and other doctors had probably not talked to a synthetic chemist since they were undergraduates, and the molecular and cell biologists, even if they knew Schreiber’s name from his articles, were unlikely to put it together with the loping, mildly self-conscious figure casually perambulating through their midst. Schreiber was like a sightseer, famous in his own country, but now abroad, waiting for someone to notice him. Like Starzl, he had crossed several intellectual time zones to get to this place, yet was still something of a stranger. Even the oversized video monitor at the entrance to the hall showing a computer model of the complex structure of FKBP-12 and FK-506 (Clardy’s structure “courtesy of the Harvard Chemistry Department and S. L. Schreiber”) elicited near total indifference. Most of the conferees didn’t know what they were looking at.

Those who did know him, of course, were his former colleagues from Vertex, and Schreiber and several of them sought each other out. Always irrepressible, Schreiber was dying to talk about his new work. After restlessly sampling the crowded poster session after lunch on the first day, he finally tracked down Moore and Harding, who, hearing the rumors of his impending announcement, had begun looking for him. Not just curiosity, but time drove their search. The sooner they knew what Schreiber had, the sooner they could respond. Merck, if it hadn’t been already, would soon be all over him. Boger had once said of the chase for data: “The average third-year revenue on a new drug is $300 million, so three months now could be worth $75 million later on.” Every day, every hour, had a price. Eagerly, the three of them huddled by the coffee and picked-over danish near Moore’s poster.

“We’ve got it,” Schreiber blurted. “We’ve got the immediate receptor for both complexes. It’s going to blow everybody away.”

Harding was stunned. It was literally, as Livingston would say, “a transcendent discovery”; as Calne would put it, “a revelation.” Since the discovery first of cyclosporine, then of FK-506, there had been a rising tide of questions about the drugs’ actions: How do they work? Why are they immunosuppressive? Are their side effects intrinsic or superfluous? Are there partner proteins? What are the relevant portions of the molecules for drug design? Why are they so strikingly similar? Together the questions had formed one of the most tantalizing mysteries of modern biochemistry. Now, incredibly, exasperatingly, Schreiber appeared to have solved them all, affirming in the process almost everything he had predicted.

In a single, brilliant set of experiments, he, his graduate students, and collaborators at Stanford had shown how both drugs worked. Once in cells, FK-506 bound to FKBP, and cyclosporine to cyclophilin—that much was never in doubt. But the drugs themselves didn’t do anything. Only upon half-burrowing into their hosts and presenting their remaining atoms to, in each case, a third molecule did they initiate a biological response. Schreiber and his collaborators identified that common molecular partner as calcineurin, an abundant enzyme found in all cells.

“Of course you always hope for the simplest possible scenario, which is that the immediate target is the same,” Schreiber said. “And it is. It is!”

Schreiber was smiling wildly, a Roman candle: “My God. It’s unbelievable. They bind competitively—two different drugs, two different structures, two different immunophilins, and they bind to the same site. How did that ever happen?

“I mean,” he continued, “nature evolves these two microbial products, and they’re glue. They’re molecular glue.

“These drugs,” he grinned fabulously, telegraphing his punchline, “aren’t drugs at all.”

Harding maintained a dispassionate front. He asked the obvious questions: How big a protein was calcineurin? What did it do? What were its partners? Was there anything else, either a natural product in the body or another drug, that inhibited it? Yet behind his resolve lay an angry snarl of emotions.

Harding was prey to a seething envy: He had wanted badly to discover the relevant biological target for the drug himself, to explain how it worked, to maintain his priority, and had been routed by his brilliantly successful ex-collaborator and friend. As he often did, he also now felt resentful, betrayed, as if by some combination of his own accommodating character and the overpowering forcefulness of those around him, he had been oppressed, pushed aside, rebuked. He felt defeated, a victim. He had come to Vertex two years earlier at the peak of his promise, codiscoverer of cyclophilin and FKBP-12, to collaborate with Schreiber: two young conquerors overtaking the world. But Schreiber had now gone on beyond him alone. Worse, Schreiber’s new work had instantly and thoroughly eclipsed their earlier accomplishments together. A protein’s cachet—and its discoverers’—rose and fell strictly according to its biological significance, what it did. Science, like fashion, could be exceptionally cruel as it moved ahead. And here was Harding, codiscoverer of two proteins that in the end didn’t do anything but present atoms, like servile eunuchs, to the real molecular kingpin, the real “protein of interest.” Because inhibiting FKBP-12 was apparently no longer what mattered for immunosuppression or drug design, so did the protein become instantly marginalized, passé, a footnote. Harding could feel himself going with it. (It was more than spontaneous diminution or paranoia: The next day, Schreiber put up a slide during his speech that credited “Schreiber et al.” with the discovery of FKBP-12. Harding, first author of the Nature paper, was never mentioned.)

The conversation broke up, with Harding and Schreiber chatting perfunctorily and making plans to get together. Moore, barely concealing his astonishment and admiration, returned to his poster; Schreiber, to the meeting. Harding, immediately, instinctively, headed through the skywalk and up to his room on the eleventh floor of the adjoining hotel, a Vista. He was going to call Boger.

In the elevator, all his resentments from the past two years hewed to the surface like a sudden, violent rash. To Harding, Schreiber’s triumph and the corollary of his own defeat were a referendum not on which of them was the better scientist, but on which was the better system for doing science, Schreiber’s or Boger’s. In his mind there had been no contest: Schreiber had won every round. And he and the other scientists had had to pay for it with their careers, their invisibility.

Angrily, his face reddening, his eyes more mournful than usual, he began to blame Boger. Boger’s supreme maxim was, Do the experiment. But doing the experiment at Vertex had become harder and harder, at times next to impossible, he thought. There were the incessant pressures to produce, run assays, test compounds. There was the chronic understaffing, the shortage of reagents, Boger’s absences, the vagaries of the project councils, the clashes of egos, the distrust of outside collaborators, the niggling distractions of having to help sell the company’s story to bankers and lawyers and assorted financiers. There was no time or place to think. Schreiber had won, Harding concluded, because he was utterly devoted to winning. He, on the other hand, had lost because of a handicap. He was a victim of priorities that were as unfocused and at odds as Schreiber’s were singular and acute. “I’m a technician with a Ph.D.,” he muttered. “I was hired to be a scientist, but all Josh expects me to do is come in day after day and flog away at the bench. That’s not science.

“It’s heartbreaking for me, because if I was back, bitching and moaning, working at Yale transplants, I’d be one of the world’s most highly recognized scientists now.”

It was understandable that Harding’s bitterness would be shared by others in the Vertex camp as news spread of Schreiber’s bonanza: They had been killing themselves over the wrong protein. But the outpouring was swift, violent, total. Boger had no defenders in Pittsburgh. Whatever their individual response to Schreiber’s victory, it occasioned for each an opportunity to air long-festering grievances that they felt Boger had made it impossible to discuss. For some of them, the mood would flash over loudly into desperation.

Thomson, not surprisingly, was the most upbeat. A connoisseur of proteins, good science, and the Nietzschean overtones of Boger’s and Schreiber’s rivalry, he couldn’t help but admire Schreiber’s hat trick, even though it meant his own achievement with FKBP-12 was now as diminished as Harding’s; even though he would soon be up to his armpits in calf brains, extracting and purifying calcineurin. The next morning, before his talk, he would say, “I feel like getting up and saying, ‘I don’t want to waste your time. I give my ten minutes to Stuart so he can talk some more.’ ” From the podium, simulcast in his bomber jacket at ten times his size on the projection screen behind him, he repeated the panegyric by congratulating Schreiber publicly—an unusual gesture. He was dismayed again over the loss of Schrieber as a potential collaborator, moaning, after a researcher from Smith-Kline acknowledged Schreiber’s generosity in providing materials, “Is there anyone here who doesn’t have reagents from Dr. Schreiber other than the company he was scientific advisor to?” But he failed to blame Boger for either the rift or the outcome. He reveled in Schreiber’s achievement and was politic enough to pay tribute, though not before calling Vertex and telling Matt Fitzgibbon to order from Sigma, a major protein supplier, its entire stock of calcineurin so that no one else would be able to get it.

The biologists were not as forgiving. Dave Livingston argued that Vertex should shut down chemistry completely for six months while biology confirmed whether or not Schreiber was right and came up with a reliable assay for testing new compounds. What good was it, he asked, to keep making molecules to inhibit FKBP-12? It was ridiculous. He, Debra Peattie, Harding, even Patsi Nelson, perhaps Vertex’s truest believer and one of its most uncomplaining scientists, all bemoaned Boger’s decision to pick a project where the biology was so poorly understood. Unanimously, they agreed that his lack of formal biology led him repeatedly to underestimate it and them. They were horrified, irate, that Vertex was claiming to do structure-based drug design while it still wasn’t clear what they were designing molecules to do. “So do you guys have a drug yet, or do you just have a target?” a nephrologist from Tampa would ask Harding on Wednesday at a communal lunch table. “Until a half hour ago we had one of each,” he grumbled, “but now we have three more targets.”

As in the ritual slaying of a king, Boger was blamed for everything. One group, led by Thomson and Moore, complained that he hadn’t been directive enough, hadn’t simply told them what to do and made sure they’d done it; another, spearheaded by Livingston, Peattie, and Harding, countered that he had been too directive, making major decisions unilaterally. Livingston theorized that he was, in fact, both, each at the worst time. For example, he said, Boger had promised Chugai, without consulting his senior scientists, that Vertex would deliver on two major priorities—small molecule inhibitors of FKBP-12 and the structure of the protein—before it had determined whether those goals were relevant. He then let the scientists decide largely how to meet them. It was perverse, Livingston said. It should be the other way around. Boger, he argued, should consult his senior people before setting goals and priorties, then use his authority to execute decisions on his own. To Livingston, the inversion reflected Boger’s arrogance, the failure of which now seemed egregiously apparent to those who worked for him.

There was little joy or vindication in the analysis: Livingston, like the others, was disappointed, bitterly frustrated, dismayed. He dreaded confronting Boger, knowing how Boger turned things around. Even if what he said was true—that by his pose of being smartest in the class, Boger had created a cult of personality that was bad for the company’s science—he also knew better than the others that Boger’s approach had been the right one. Boger had no choice but to be arrogant. He had no choice but to make bold promises based on incomplete data. Vertex would be dead otherwise. There was no way Boger could have raised $70 million in two and a half years, packed the labs with world-class scientists and equipment, put them in the middle of the hottest areas and made them competitive, given them stock that was now worth hundreds of thousands of dollars and jobs that were secure for at least several years, no way that he could have done any of this without flaring the great calipers of his ego.

Had Boger been there to defend himself, he’d have said what Livingston and the others knew to be true: that Vertex was a drug company; that it was not in business to make important biological discoveries but to use them; that the competition with Schreiber was a sideshow in which Schreiber had all the advantages. He’d have pointed out that Schreiber, supported by Harvard and the federal government, hadn’t had to tap-dance his way around the world several times a year to scrape together capital. He’d have noted provocatively that Schreiber had at his disposal dozens of the world’s smartest, most aggressive graduate students and postdocs with no more complicated goals than to please him, not a contentious, ego-driven group of journeymen researchers with their own oversized ambitions (who, he’d have added, he thought were acting like children). Schreiber didn’t have to run a fast-growing company, which either grew or collapsed; he did. Schreiber didn’t have to make anyone rich; he did. Schreiber didn’t have to satisfy Wall Street, only himself. Indeed, it was best to let academics like Schreiber sort out the biology while Vertex chased the supreme prize: designing molecules.

But Boger wasn’t there, which, to the scientists, was just the point. By running the company’s business, by isolating himself out of necessity but also self-righteousness, he had also isolated them, stranding them in a world that thrives at the forefront on access and collaboration. Merck, Starzl’s group—they were big enough to go it alone; Vertex wasn’t, and the flaws of hubristically thinking that it was now etched themselves in its defeat.

To Schreiber, this also was the crux of his breakup with Boger. “A characteristic quality of Vertex that is highly unusual—and many people recognize it—is that they are absolutely determined to do everything completely themselves,” he said. “I really don’t think they want any input from the outside.

“That’s the real issue between myself and Vertex. The other stuff,” Boger’s concern about what he perceived as Schreiber’s utter lack of ethics, credit mongering, and apparent contempt for the company’s need for secrecy, “is a smoke screen.

“I have a certain visibility in this field, and from that point of view, they take a certain risk, in interacting with me, that the perception may exist that I have had a lot of influence over what they’re doing and therefore should get some credit for what they’ve achieved. They have to evaluate that concern. It’s not to say that they can’t solve every one of their problems by themselves, except that the more activity they’re made aware of, the quicker they will learn.”

Symbolically, Pittsburgh had captured the fundamental difference between them. In their sense of their own superiority, in their drive to be great, Boger and Schreiber had drawn sharply different conclusions about the need for other people. Schreiber inhaled other people, their ideas, sublimating them effortlessly, without pangs, into his own ambitions. They were his instruments. He expected the same of them. Boger, just as solipsistic, treated others as he treated himself. He believed they were as omnipotent as he was and thus unneeding of anything more than opportunity. He thought they should do the right thing, intuitively, on their own because it was less fun and efficient not to. Those under him he let make their own mistakes.

Throughout the conference, the scientists would become more and more frustrated with Boger’s view, even if grudgingly they agreed with it. It might be right for Vertex, for business, for the drug industry, for making better molecules, even for leading an ethical life, as Boger insistently maintained. But it was wrong for the world of winner-take-all science for which the conference was a stand-in. Here Schreiber was everyone’s darling, a figure of immense respectability and esteem, having a status distinctly at odds with their own anonymity. They had done well, but he had won. At a gala reception in the Vista ballroom on the night after his talk, Schreiber glided in an almost ethereal light. He was surrounded by people. If Boger’s laughing confidently with Holman and Aldrich outside a waiting limousine had become the defining, if ambivalent, image of his newfound success, this was Schreiber’s: to be at the center of a group of well-dressed senior researchers, all leaders in their fields and with some of the most powerful labs and connections in the world at their disposal, heading off brightly, their drinks clinking in the powering din, to have dinner together, to talk about, as Starzl put it, “our strategy . . . what we’re going to do next.” Starzl was in the group. So were Burakoff and Barbara Bierer, still a Vertex consultant. And sitting off to the side of this shining tableau was Vertex—desultory, remote, cursing Boger loutishly for their fortunes. Harding, drinking heavily, would spend the night in a fever of abject jealousy.

•  •  •

Harding got off the elevator, slid the card key into the lock, and entered his hotel room. The room, bright, had an air of pleasant abandonment, like a classroom during vacation. It had just been cleaned. It was that hour approaching midafternoon when the halls of convention hotels are empty as tombs, with the guests gone and the maids having finished up. He dialed Vertex.

“Stuart’s identified the critical partner protein,” Harding told Boger. He was purposely breezy, as if he was reporting a dramatic car wreck in which no one had been hurt. “It’s calcineurin.”

“I don’t know what that is,” Boger said. His voice was cool, restrained: Harding could see him scrolling through the contents of his computer screen. Then, softly: “How does he keep doing this?”

They spoke for several minutes, Harding doing almost all the talking. Boger, assumably taking notes, asked basic questions that, on the one hand, he needed answered to begin his own data collection and, on the other, showed how completely and stunningly original Schreiber had been.

“How do you spell calcineurin?” he asked.

Harding told him.

“How big is it?”

Boger wanted a rough measure of how hard it would be to solve the structure of the protein. Harding told him. “Good,” he said, finding out that it had a molecular weight of about 55,000. “We don’t have to worry about Stuart beating us with NMR. It’s too big.”

Boger asked several more perfunctory questions. Then, business done, he permitted himself a terse groan.

“How does he keep doing this?”

“You mean why is he so lucky? It’s because he sits all day, every day, thinking about what he wants to do and how he’s going to get it done, and he’s got an army of people who are willing to work hard.”

“Supposedly we do, too.” Boger sounded more exasperated than acid, though clearly he was annoyed.

“He’s blessed,” Harding volunteered.

Silence.

“Why,” Boger asked, answering his own question, “does it always have to be Stuart?”