Ever since Harvard survived its first headmaster, Nathaniel Eaton, who beat students with a walnut cudgel “big enough to kill a horse,” and became what historian Richard Norton Smith calls the “epicenter of American education,” Cambridge, Massachusetts, has been a place where a disproportionate number of the world’s smartest people come to prove how smart they are. Against this elite testing ground chafes another Cambridge, a minor, graying northern city in which generations of immigrants and African-Americans have lived crammed in underheated triple deckers and toiled in scores of shoe and candy factories, foundries, and machine shops. Until World War II, the city was roughly split: Harvard and MIT on the east and west and along much of the Charles River, working-class Cambridge in between and in the industrial flats across from Boston and Charlestown. Then history lurched, and Cambridge tilted. The universities, supported by the federal government’s ambitious research programs, began pushing relentlessly outward. Manufacturing died or moved away, along with those it employed. Most critical, knowledge became a big business like any other. As Harvard’s Sumner Slichter has observed, “The discovery that an enormous amount of research can be carried on for profit is surely one of the most revolutionary economic discoveries of the last century.” It was during this period that the people arriving in Cambridge to prove themselves, particularly in the sciences, added to their prerogatives the takeover of the city’s industrial real estate.

Along lower Sidney Street, an area of low-slung factories and warehouses abutting a necrotic rail yard, the overlay of the new Cambridge and the old is striking. On one short block, across from each other, are the Boston Pipe and Fittings Company and American Foundry, Inc.; within one hundred yards, in similarly drab two-and three-story brick buildings, such futuristically named companies as ImmunoGen, Bioprocess Technologies, and Holometrix. The barrackslike former St. Johnsbury Trucking Company depot, until the early 1980s a hub of grinding gears and hissing airbrakes, now produces X-ray telescopes in sleekly refurbished anonymity. Despite its new association with Harvard and the Massachusetts Institute of Technology (MIT), the presence of so many exceptional scientists, the restless incubation of so much profit motive, and the influx of so many Saabs and Acuras, the area remains dolefully nondescript, a temporary address for the new companies and a final one for the old.

Vertex started leasing 10,000 square feet in a former construction company warehouse at the corner of Sidney and Allston streets in April 1989, six months before Boger’s outing at the Vista. In keeping with his ambitions, he began to look at once for more space. The building is brick, one story, nearly square, and the occasional target of graffiti. When it was built in the 1920s, it had mullioned shop windows and ersatz Corinthian columns. Sixty years later, the columns were stuccoed over and the windows replaced with thermopanes, giving the building an air of cheap recycling, like a motor vehicle bureau that once was an armory. In fact, the windows are as superfluous as the columns. Because anything of use to a legitimate drugmaker is of substantially higher value to an illegitimate one, the company prefers not to advertise the contents of its labs. Its blinds are all but permanently drawn.

Boger was still living in New Jersey, near Merck’s giant central research campus in Rahway, when he decided to locate his then-unnamed company in Cambridge. He intended Vertex to be highly visible from the start—to the international elites of business and science, if not to pedestrians—and for that, he thought, Cambridge offered a powerful showcase.

Businesswise, it was a singularly unpromising time. During the previous decade, nearly 200 biotech businesses had sprung up, yet only one, Genentech, earned a regular profit, and even that was disappointingly small. Most of the companies had simply gone on hemorrhaging money, blindly, with no end in sight. Dozens were now failing or scrounging for buyers.

Add to that a billowing national recession and a comatose New England economy, and Boger’s decision to leave Merck and set up in borrowed offices in Cambridge in the dead of a lightless New England winter seemed fateful. Boger was anything but. The previous fall, he’d been recruited by an irresistible California venture capitalist named Kevin Kinsella, an embodiment of that flamboyant breed and originator of Vertex’s concept, and together—Kinsella on the West Coast, Boger on the East—they’d plunged ahead. Working from a ninety-page business plan that Boger had composed in less than four weeks, they knocked on doors relentlessly, talking with investors, scientists, vendors, developers, lawyers, contractors, regulators, and potential partners, leveraging commitments pyramidally. “Don’t you think this is five years too early?” Boger was often asked, to which he answered, brimming with impatience, “Yes. But five years from now it’ll be five years too late.” It was a determinedly Cambridge answer, smug, marbled with arrogance and risk. But by then, they’d enlisted perhaps the one academic collaborator who could match Boger’s pedigree, ambition, intellectual firepower, and cachet, Harvard wunderkind Stuart Schreiber. How, Boger and Kinsella wondered, could they lose?

This was Boger’s other reason for choosing to be in Cambridge. Every young biomedical company needs in the absence of its own science the association of big-name researchers—a scientific advisory board (SAB). Most SABs are ballast for the letterhead. Boger professed to want an SAB that was more than that. Having identified as his optimal SAB five senior faculty members at Harvard and having gotten them all, most notably Schreiber, he intended to use them. Being in Cambridge meant having them within courier distance.

•  •  •

On the Saturday morning before Boger went to New York, Vertex’s SAB and its staff scientists huddled for the first time in the company’s makeshift lunchroom. Billed as an all-day strategy session, the meeting was also a critical first test of Boger’s determination to use the SAB. As with the start-up of many high-minded adventures, there was the usual air of self-selection reinforced by deprivation—a mercenary, albeit ragtag, flavor. It was the first time some of them met.

In aggregate, they were the kind of people Boger felt most comfortable with—young, male, irreverent—people like himself. Of the twenty researchers on hand, just two were women; only five were over forty. Yet despite their relative inexperience, each had sacrificed something to be here, as the setting reminded them. For weeks, jackhammers had rocked the building, leaving a pall of cement dust on books, boxes, clothes. Overhead, ceiling panels had been left out by workers, and skeins of unattached pipes stood exposed. The screen on which Boger presented a fuller version of the slide show he would take to New York was gray, steel, battered, and part of a short-term leasing agreement, as was the furniture in his office, which opened onto the lunchroom and had mounds of books and catalogs splayed chaotically along every wall. Many of the scientists were accustomed to being pampered at such meetings: Merck, where some of them had previously been associated, picked up visiting researchers by limousine and toured them around by helicopter. Lunch today at Vertex would be pizza and Greek salad served on paper plates.

In fact, the close involvement of the SAB was an unpopular idea of Boger’s that would require considerable selling within the company. Scientists in industry and scientists in academia tend to be brutally dismissive of each other. Academic researchers thrive on publication, attention and credit being oxygen to their careers. Yet to industrial scientists, whose own success most often depends on keeping their best work secret and who are less well known, most academics are recklessly, inexcusably self-serving—loose cannons. Boger had brought to this room some of the best industrial and academic researchers in their fields. Getting them to talk openly would be another matter.

The problem had first surfaced a week earlier, pungently, ominously, not a surprise, but sooner than most expected. Schreiber, a slender, enthusiastic thirty-three-year-old chemistry professor, had mildly proposed at a smaller mėeting that everyone discuss what experiments they were planning.

Coming from Schreiber the suggestion was hardly as innocuous as it seemed. He, more than anyone else at Vertex, was Boger’s equal, his other: a fast-rising star who, with the backing, position, and control he had long conceived of and only just won, was beginning to make his mark on a world stage. There were other similarities. Like Boger, Schreiber is a chemist and an avenger for the Harvard legacy, long in disfavor, of exalting chemistry above all other life sciences. He is a quick, copious thinker who can see past his own field and direct a swarming, multifrontal research effort. Schreiber worked seven days a week, had a big group of the world’s most ambitious graduate students and postdoctoral fellows, published furiously, and could smell a hot idea. “Stuart is fearless,” Boger once said admiringly. “He has a killer instinct for doing the right experiment.”

He could also be disarming. Like Boger, Schreiber exudes an easy border-state affability: He grew up at the high end of a semirural gun-and-dirtbike culture in east-central Virginia, a few hundred miles from Concord, and partied his way through high school before discovering chemistry in college. He wears imported loose-fitting tweeds and soft loafers and commutes to Cambridge from his five-story townhouse in the Back Bay in a gunmetal gray Porsche 911 with a car phone. With a smooth and eager face, respectful manner, and large swimming eyes magnified aquatically by round wire-rimmed glasses, he looks more like a successful young art dealer than one of the two or three most promising organic chemists in the world. “Eddie Haskel,” one Vertex scientist calls him.

Like Vertex, Schreiber’s group at Harvard was studying drugs that suppress the immune system, a field that was rapidly heating up in large part because of Schreiber’s own work. Angling sharply for what academic researchers want most in such new areas—priority, acknowledged leadership in the field—he was concerned about being slowed down by overlapping effort.

“I think it’s best that we consider what we’d like to do immediately and what Vertex would like to do,” Schreiber said.

There was a palsied silence, the Vertex scientists all looking tentatively at one another or at their shoes. Finally, Boger brushed aside the question by saying how many people he planned to hire and in what disciplines—a coded message that indicated the general direction of Vertex’s research but no specifics. Though Schreiber was being paid $25,000 a year to attend perhaps a dozen such meetings, owned 150,000 shares of Vertex stock, and had been recruited largely for the benefit of sharing information and materials with his lab, it was clear he was not going to be fully trusted as a collaborator, not even by Boger. Sensing he would get no further, Schreiber said, “OK then, on the table, anybody who gets to an experiment first should do it.” With everyone agreeing, the conversation moved uncomfortably on.

With the labs still unopened, it was too early for the threat of such competition to arise among Vertex’s own scientists, but here, too, were tremors. Boger had recruited an exceptional group of researchers; of the company’s ten most senior people, all but one had worked at Merck, Harvard, MIT, or Yale. Moreover, Vertex planned to integrate the most advanced disciplines of molecular biology, which deals with function, and of chemistry, which addresses structure and mechanics—whose practitioners, like behaviorists and Freudians, have little good to say about each other. Already the company had more submicroscopic disciplines—medicinal chemistry, X-ray crystallography, nuclear magnetic resonance spectroscopy, molecular modeling, computational chemistry, protein engineering, protein chemistry, enzymology—than a small university, and competition over hiring and lab space had grown fierce. As in war, victory in science is measured in bodies, territory, and materiel, and Vertex, it seemed, would be no different. Coupled with the personal ambitions of those who saw Vertex as a major drug company in the making and themselves growing in power and influence along with it, a secondary ambience of intramural squabbling had already begun to poke through the initial looseness and camaraderie.

Now, in the lunchroom, Boger moved to unite all sides. Far from being disturbed by the general testiness, he considered it affirmation that his ideas about corporate culture—a culture of enlightened self-interest—were taking root. Boger wanted people who were unbowed by competition; people who, like himself, insisted upon being best. He wanted an orgy of bristling, militantly selfish creativity of the kind he grew up with. “Arrogance doesn’t disturb or impress us,” he once said in another context. “We understand arrogance.” As with much of what Boger said during this period, the remark seemed at least partly calculated, like a short man’s swagger, to compensate for certain disadvantages: Vertex, despite its talent, would be competing against labs that were vastly richer and more experienced; outsized, even outrageous, boasts were good for morale.

And yet Boger also believed, or seemed to believe, every word he said. Devoutly irreligious in his personal life, he had a faith in himself and in science that was Himalayan, towering over most other people’s. Boger’s convictions were huge, and he expressed them with such confidence that it was hard not to agree with him.

Boger chose not to make the case for cooperation himself. Instead, he turned the meeting over to Rich Aldrich, Vertex’s vice president for business development. Aldrich, a tall, curly-haired thirty-five-year-old with an M.B.A. from Dartmouth, was the group’s sole layman. His ancestors arrived in Plymouth in 1630, ten years after the Mayflower, and have been ensconced in the state, in law and banking, ever since. Within those staid Yankee confines, Aldrich’s decision to put his career in risky biomedical start-ups marked him as something of a family rebel. But that didn’t grant him instant acceptance among the scientists in the room. On the contrary, many of them, even if they didn’t know his background, viewed him as a political and cultural nemesis, a “suit.” Aldrich, who was dressed today in khakis and a blue oxford shirt, enjoyed turning the disparity between business and science back on them directly. “Design any drugs lately?” he’d ask.

Despite their differences, everyone at Vertex had one thing in common. Under the terms that enable impoverished, unknown companies to recruit top scientists and expect them to work Saturdays, they’d all begun to amass large amounts of stock—from 10,000 shares for a junior scientist to, in Boger’s case, 780,000 shares. These holdings were at present worthless but would likely make them all rich if and when the company went public, and extravagantly rich if Boger was right and Vertex became a major drug company. In Boger’s view, this shared fortune was so obviously compelling that no one need be reminded of it; it should automatically restrain even the most rapacious ego. And indeed, as Aldrich now began to discuss the company’s plans for raising the tens of millions of dollars it would need over the next couple of years, the scientists’ collective attention focused as sharply as a team of accountants’.

Aldrich told them that Vertex was considering a range of options, but the most promising were its discussions with other drug companies. Vertex had approached eight other companies about the possibility of their underwriting part of its research in return for certain “downstream” development rights. In other words, he and Boger were aggressively talking with potential competitors about the company’s science even before it had unpacked its first test tubes. Standard practice, the discussions nevertheless startled some of the group’s academicians.

“Isn’t one in danger,” drolly interrupted Jeremy Knowles, a brilliant and much admired enzymologist who’d come to Harvard from Oxford and had been Boger’s thesis advisor, “of giving away all we’ve got before we’ve got anything? I mean, yes, there are some splendid ideas here, and some superb people, and we will do it. But what’s to stop boring old Glaxo [a British firm that had jumped from twenty-fifth to second among the world’s drug companies on the strength of the world’s best-selling drug, the antiulcer agent Zantac] from saying, ‘Oh, oh, we see. Maybe we can do what you’re telling us ourselves.’ ”

“But they can’t do it, Jeremy,” Boger interjected.

“But Merck can.”

“No,” Boger paused resolutely. “Merck can’t either.”

It had already become an article of faith at Vertex—as at most start-up companies—that large corporations were dinosaurs: too unadaptable and slow moving to compete at the forefront of research. But Knowles was not alone in suggesting that daring these companies to try might be an act of fatal arrogance, especially from a firm without a single hard scientific lead.

If there was a danger in Boger’s intellect, Knowles knew this was it. Boger was too smart and too competitive to ignore what he could learn from others. But because he was so certain of himself, he often underestimated them, turning against them with a haughty disdain. He especially liked to tweak the mighty. This had been the case when he and Kinsella spent months searching for a name for their new company and decided on Veritas. It was one thing for a fledgling business to draw on its contact with Harvard faculty members, another to appropriate the school’s 350-year-old motto. More than most schools, Harvard anguished publicly about being involved with outside businesses. Knowles began receiving rueful, cautionary phone calls from senior administrators, including the university’s legal counsel. Though Boger clearly relished Harvard’s angst, Knowles quickly persuaded him of the “sensitivity, the horror, the absolute unacceptability” of Veritas, and the name was changed to Vertex.

•  •  •

Peculiarly, Vertex was at or near the apex of the science now being discussed in the lunchroom despite having done no experiments. In February, when Boger had considered what project to undertake first, his decision to improve on the experimental drug FK-506 had seemed prescient. Now, several developments had put Vertex at the center of one of the most promising areas in drug research.

Drugs are molecules. They attach themselves along critical points in the pathway of a disease. Since not all molecules are drugs, the difficulty, from a drugmaker’s standpoint, is discovering those that are. There are other challenges. A drug molecule must be sufficiently unique to patent and must be capable of getting to its relevant target, another molecule within the toweringly complex molecular universe of the body. Raquel Welch, in the 1960s movie The Fantastic Voyage, discovered the extreme hazards of this. She and a miniaturized team of doctors undertook a harrowing repair mission inside the human body. Solubilized in an infinitesimal submarine, they tumbled through billowing plasma, dodged the clinging death grip of chainlike antibodies, and breached greasy cell walls to fix a remote area of the brain. The journey, lasting an hour, approximates the life cycle of at least one class of drugs—those delivered by injection into the bloodstream.

Those that come in pill form run an even riskier gauntlet. It’s the job of the gut to dismember chemical compounds, atom by atom, so that their constituents can be used by the body. Like machine tools in a vast automated recycling plant, enzymes in the digestive tract and liver facilitate—at speeds of up to 10 billion operations per second—the stripping and reassignment of incoming atoms. Some are saved, some reconstituted, some burned up, some discarded as slag. Because molecules are groups of atoms chained together like pop beads, a drug entering the body orally must be small, durable, and extremely resistant to being crushed or picked apart. An hour in the gut, and the nuclear sub in The Fantastic Voyage would look like a car left overnight on the shoulder of the Cross-Bronx Expressway.

Prior to World War II, only a handful of drugs worked, and most of those derived from some combination of luck and empiricism. Since then, however, the search for new drug molecules has narrowed to where they are most likely to be found: in soil and sludge. By far the most prolific producers of the sort of small carbon-based molecules that make the best drugs are those microorganisms that seethe invisibly underfoot. Thus the front end of any drug discovery effort at most of the world’s great pharmaceutical companies consists of lab-coated scientists cooking obscure dirt samples in fermentation broths and screening them for activity. If some constituent of this foul black chemical soup is active against a disease target in the laboratory, then the search begins for the active molecule.

Besides the staggering cost and dependence on luck (you may have the right compound but the wrong target), the biggest problem with screening natural products is the molecules themselves. Though they work, in many cases astonishingly well, their activity is most often happenstance. There would seem, for instance, to be no logical reason for a molecule made by a fungus—a molecule that has evolved structurally over 4 billion years to perform some function that is eons removed evolutionarily from human cells—to reduce cholesterol, and yet most of the leading cholesterol-lowering agents, including Merck’s Mevacor, a $1.6 billion seller, have been discovered this way. The best explanation is that the molecules mimic something else. And yet because they are approximations and not perfect, they may also fit with other targets or include toxic elements superfluous to their function, inciting other, unwanted activities—side effects.

It was the imperative of screening that Boger and Vertex now sought to dethrone. Quantum gains in the molecular understanding of disease and in computer technology have recently suggested another approach for finding drugs. Called rational or structure based, it presumes to design them—atom by atom—based on a precise understanding of how molecules interact. Drugs work by selectively sticking to discrete molecular receptors, or targets, which usually are within cells. Like pieces of a jigsaw puzzle, they interconnect—scientists use the word bind—based on complementary conformations, or fit. Thus the rationale for structure-based design: to optimize the shapes of drug molecules. “Connecting the dots,” Aldrich liked to call it in a heroic oversimplification that made some of the scientists at the tables wince. In effect, the goal is the very opposite of screening: building the molecules one wants rather than fishing for approximations in nature.

The advantages of such drugs presumably would be enormous. Because they would be more specific, they’d be safer; there would be fewer side effects. And because they would be safer, they could be used far more widely, at higher doses; this meant untold new uses (and not incidentally market opportunities and profits). Structure-based drugs, as Boger and others have pointed out, are the industry’s Holy Grail, although “like many holy objects,” Boger says, “they have been more often referred to than taken seriously.”

As a first project for demonstrating structure-based design at Vertex, the makeover of FK-506 suited Boger’s hubris perfectly. The molecule belonged to another company, Fujisawa Pharmaceuticals Company of Japan, which had only recently begun testing it in humans; a powerful immunosuppressant, it appeared to stop transplant recipients from rejecting their organs better than any other agent. Immunosuppression occurs when some but not all of the body’s defenses are disarmed. As a therapy, it is especially crucial for transplant patients, who risk having their grafts destroyed by hyperactive immune cells (the “immunological conscious,” Sir Peter Medawar called it). Yet that was perhaps the least of FK-506’s powers. Cyclosporine, which acts similarly to FK-506 and is the only selective immunosuppressant to be licensed, also helps dramatically against those diseases where the immune system mistakenly starts killing the body’s own cells, but is much too toxic for general use. Multiple sclerosis (MS), juvenile diabetes, rheumatoid arthritis, Crohn’s disease, psoriasis, lupus: perhaps dozens of autoimmune diseases could be cured with a similar, though more specific and thus safer, molecule—a molecule that Boger was convinced could now be designed at Vertex. It wasn’t lost on him that the potential market for a drug of such sweeping effectiveness might be as much as $5 billion per year.

FK-506 and cyclosporine are conventional drugs: both were discovered in dirt samples (cyclosporine near the Arctic Circle in Norway, FK-506 on a mountainside in Japan) and were found serendipitously to fight disease. They’re also poisonous. Many of those taking cyclosporine suffer kidney damage so severe that they require further transplants. FK-506, though it looked promising in humans, had been fatal in some dogs—a discrepancy that the Food and Drug Administration (FDA) would want resolved before approving it for general use. Thus, these two tantalizingly powerful molecules were, ultimately, limited.

Here was Vertex’s presumed edge. Structure-based drug design is most often compared with making a key to fit a lock. Using a model of the cylinder, you design a device to touch only the tumbler pins. What is essential—what would give a company its advantage—is knowing the conformation of the cylinder, how it works.

And sitting now at opposite ends of Vertex’s lunchroom were Schreiber and a bearded, moon-faced, mild young immunologist named Matt Harding. Schreiber had been the youngest full professor of chemistry in Yale’s history at age twenty-six before he was wooed to Cambridge by former Harvard President Derek Bok; Harding, whom Boger had recently hired away from Yale Medical School, was Schreiber’s main collaborator in the area of immunosuppression. The locks for drug molecules are nearly always proteins, the working molecules in cells, and between them Schreiber and Harding knew more about the protein receptors for cyclosporine and FK-506 than perhaps any other scientists. Harding had shared in discovering both targets, which because of their affinity for immunosuppressive compounds were called immunophilins, and together he and Schreiber had just produced the first available quantities of the receptor for FK-506 (FK-506 binding protein, or FKBP). To possess this receptor, a virtual carbon copy of the protein through which FK-506 presumably works within the body, was no small matter, because even a few thousandths of a gram of a reagent can give a company a significant advantage in its experiments. Along with Merck, which had discovered FKBP independently and had its own minuscule quantity, Schreiber now controlled the world supply of the protein.

Once a drug target is identified, the next task is to solve its structure—to reveal the lock’s inner workings with its tumblers exposed. Steeped in fifty years of advanced science, this remains something of a black art. To calculate to within one ten-billionth of a meter the precise location of every atom within a protein (most proteins are floppy and have thousands of atoms) requires a minimum of $1 million in equipment and, generally, a highly specialized and, by tradition, temperamental researcher known as an X-ray crystallographer. Crystallographers are the most prized of all protein scientists. Association with one of the rare few who have actually solved the structure of a protein can make a company’s name. Hiring one is tantamount to a franchise. And sitting in the room with Schreiber and Harding was Harvard’s Don Wiley. Wiley’s recent discovery of the structure of a key immune system protein was considered so critical to understanding autoimmune diseases that it had raised, for the first time, the hope of eventually curing such diseases with drugs. Wiley would not be trying to solve the structure of FKBP for Vertex himself, but that wasn’t a concern. Within weeks Boger would announce that he had hired perhaps the most famous crystallographer in the pharmaceutical business, Manuel Navia. In 1988, in the record time of three months, Navia had led a team that found the structure of a major protein that causes the acquired immune deficiency syndrome (AIDS) virus to replicate, a feat of such stunning general interest and public relations value to his employer that it landed him improbably on the Today show. Navia, Boger liked to gloat, was coming from Merck.

Boger had decided alone what project to undertake first and had recruited the scientists accordingly. Yet the most critical development making immunophilins a ripe area for Vertex had occurred elsewhere, beyond Boger’s control. That immunosuppressants like cyclosporine and FK-506 made remarkable drugs had long been known, though how they worked remained a mystery. Yet two recent papers in the scientific journal Nature suggested an appealing answer. They identified cyclophilin, the apparent target of cyclosporine, as an enzyme, the most complex and active of all molecules. According to the authors, cyclophilin seemed to accelerate the folding of other proteins into active shapes by catalyzing a key reaction.

It was a hugely promising observation. Proteins are nothing without folding, just chains of atoms. Yet loop them and coil them into precise, genetically ordained conformations and they snap to life. With various enzymes grabbing and splicing and assembling atomic subunits, high-speed protein folding is at its height during the manufacture of new cells, protein being half of all living matter. Thus the implication of the Nature papers: that cyclosporine worked like a well-thrown monkey wrench, invading a key part of the assembly and bringing the operation to a halt. No new protein folding meant no new attack cells, which meant no graft rejection or autoimmunity. Boger, like many others, was tantalized by the simplicity.

The Nature papers appeared in February, midway through Boger’s three-month slog after seed money. Choosing a first project was undoubtedly the most critical decision he faced, since the company would have to support it on its own, without—as Vertex’s competitors would all have—other programs to pick up the slack. The economics of drug discovery were dicey enough—only one in ten projects yields a drug—not to have a hedge, and Boger had already stretched the odds dangerously. Unhesitantly, he threw all of the young company’s resources into immunophilins.

His reasoning was persuasive. The protein-folding hypothesis suggested a straightforward goal: to build a better monkey wrench. If structure-based design was to work, Boger believed, it would have to start with simple, well-understood biochemistry, which the immunophilins now appeared to have. Also, the theory provided what had been missing from the search for new immunosuppressive drugs—an assay, a simple laboratory experiment for testing new compounds. As Vertex began making its own molecules, it could screen them initially on their ability to bind to and block the protein-folding action of FKBP, the enzyme discovered by Harding and controlled by Schreiber. The company was unlikely again to be so strongly positioned in so wide open an area.

“FK-506 is the only exciting molecule in the pharmaceutical industry now,” Boger told the scientists. “Within a year we have the opportunity to be a leader in this field.”

Whether Boger was simply drumbeating or this was true, the idea that a company that still existed largely on paper might compete at the fore of what was potentially one of the most profitable and scientifically most rewarding areas in all of drug research was intoxicating for the scientists. It placed them precisely where they wanted to be.

And yet the project was far from ideal. There were the scientific questions. Could the toxicity of cyclosporine and FK-506 be separated from the drugs’ activity, or were the two linked inextricably? More critically, was FKBP the correct target or was there another, yet undiscovered molecular interaction that caused the drug to work? A wrong answer to either question could kill the project—and, conceivably, the company—in a day.

There also was the competition. FK-506 was a new enough molecule that no company hoping to beat Vertex had an insurmountable lead. But many companies, most notably Merck, had already recognized the opportunities that Boger had seen and were moving rapidly ahead. Indeed, Boger had launched Merck’s program, creating possible legal problems now. Though the project appeared well suited to a small, highly focused effort like Vertex’s, as Knowles pointed out, it could be foolish for Vertex to challenge Merck and the other big firms.

Boger raised these issues only to brush them aside. More than anything, he was a rationalist. He believed ineradicably that no decision was ever wrong. A decision based on incomplete information might be, in his word, “suboptimal,” but it couldn’t be incorrect, not logically. The key was to have the best information possible. Given the data now available—about the protein-folding activity of cyclophilin, about the similarities between cyclosporine and FK-506, about the state of the art of drug design and the people he had assembled to do it, about who else was in the field—Boger was convinced that Vertex had as good a chance as anyone, including Merck, of designing the next great immunosuppressive drug, one that would not only capture the $800-million-a-year transplant market, which cyclosporine now dominated, but open up the autoimmune market as well. Now that he had assembled everything he needed in order to, as he would put it at the Vista, “redesign [FK-506] and eliminate its undesired properties,” he had no choice but to believe that he would do it. As the afternoon went on, those in the lunchroom came to believe more and more, as Boger had planned for them to, that they might do it as well.

One of the day’s final speakers was a thirty-one-year-old Australian protein chemist named John Thomson. Chiefly responsible for supplying Vertex with FKBP for its other experiments and attempts to solve its structure, Thomson was, in effect, the company’s lead-off batter, a pivotal, high-visibility position he wouldn’t have had any other way.

Thomson’s work was as unglamorous as it was vital. One of the few researchers of his generation to prefer extracting protein from animal tissue to the more modern recombinant methods, he revels in an earthy image. As a graduate student and postdoctoral at MIT, he spent several years isolating a protein from the lenses of fetal eyeballs. Now, in the lunchroom, he presented a price list from a research supply house for human organs—“Igor,” Boger code-named it.

As FKBP was concentrated primarily in the adult spleen, Thomson explained, he would be buying those first. The base charge for an organ from a brain-dead cadaver was $360. Those discarded during transplantation of other organs were discounted at $200, although, as Thomson pointed out, there might be other charges: $25 for sterile or undiseased specimens, $25 for snap freezing.

“If we want same-day delivery,” Thomson said in his thick Melbourne accent, “that’ll be about $85.”

Surprised by the efficiencies of the marketplace, many of the researchers groaned. But Boger picked up the theme. If Vertex was to solve the structure of FKBP—indeed, if it was going to design a drug—then nothing was scientifically more important now than developing an abundant supply of the protein. Even having Schreiber would be of little help if a collaboration with Harvard for his recombinant FKBP couldn’t be worked out soon. Thomson, Boger explained, would first attempt to isolate protein from the thymus glands of unborn calves as a model system for the scarcer and more expensive human spleen. Boger didn’t like to set priorities in stone, but this one he did.

“If we get to a situation where we have to bring a cattle truck up to the back door and start unloading calves,” Boger said, “we’ll do that.”

The daylong session lasted until five, and though it was a luminous fall Saturday at the height of the New England leaf season, no one rushed out. The fifteen staff scientists, nine of them Ph.D.’s, had been sitting around telling themselves for months that they would be doing the best science of their lives here. Now, hearing each other and the SAB and, most important, seeing Boger’s expansiveness played out on a larger scale in front of senior people who might, but didn’t, dent his enthusiasm, they felt their own optimism vindicated. Boger’s promise that Vertex could do what no one else could suddenly looked more real to them. And so they left, as Boger had intended, with a renewed degree of confidence, although nothing compared with the feeling of rare preparedness, of triumph before the fact, that now seemed to consume Boger and still transported him several days later at the cattle call in New York.