{"componentChunkName":"component---src-templates-book-page-js","path":"/molecule/5/","result":{"data":{"mdx":{"id":"61fdfde5-043b-5c45-9d07-935e6541469e","body":"function _extends() { _extends = Object.assign || function (target) { for (var i = 1; i < arguments.length; i++) { var source = arguments[i]; for (var key in source) { if (Object.prototype.hasOwnProperty.call(source, key)) { target[key] = source[key]; } } } return target; }; return _extends.apply(this, arguments); }\n\nfunction _objectWithoutProperties(source, excluded) { if (source == null) return {}; var target = _objectWithoutPropertiesLoose(source, excluded); var key, i; if (Object.getOwnPropertySymbols) { var sourceSymbolKeys = Object.getOwnPropertySymbols(source); for (i = 0; i < sourceSymbolKeys.length; i++) { key = sourceSymbolKeys[i]; if (excluded.indexOf(key) >= 0) continue; if (!Object.prototype.propertyIsEnumerable.call(source, key)) continue; target[key] = source[key]; } } return target; }\n\nfunction _objectWithoutPropertiesLoose(source, excluded) { if (source == null) return {}; var target = {}; var sourceKeys = Object.keys(source); var key, i; for (i = 0; i < sourceKeys.length; i++) { key = sourceKeys[i]; if (excluded.indexOf(key) >= 0) continue; target[key] = source[key]; } return target; }\n\n/* @jsxRuntime classic */\n\n/* @jsx mdx */\nvar _frontmatter = {\n  \"author\": \"Barry Werth\",\n  \"bookTitle\": \"The Billion-Dollar Molecule\",\n  \"isBook\": false,\n  \"numSections\": 25,\n  \"tags\": [\"a\"],\n  \"templateKey\": \"book-page\",\n  \"title\": \"Chapter Five\"\n};\nvar layoutProps = {\n  _frontmatter: _frontmatter\n};\nvar MDXLayout = \"wrapper\";\nreturn function MDXContent(_ref) {\n  var components = _ref.components,\n      props = _objectWithoutProperties(_ref, [\"components\"]);\n\n  return mdx(MDXLayout, _extends({}, layoutProps, props, {\n    components: components,\n    mdxType: \"MDXLayout\"\n  }), mdx(ContentRef, {\n    id: 0,\n    mdxType: \"ContentRef\"\n  }, mdx(\"span\", {\n    className: \"stickup\"\n  }, \"I\"), \"t was \", mdx(\"i\", null, \"not\"), \" the pure protein. Thomson had isolated a substance that had the same molecular weight and abundance as Harding\\u2019s FKBP. But as he analyzed it, he discovered a second constituent\\u2014assumably another protein\\u2014almost identical in size to the first. Thomson was distraught. He believed he was jeopardizing the company and that others blamed him for it. Typically, Boger consoled him that any information, however discouraging, was \\u201Cmoney in the bank,\\u201D but Thomson refused to be cut any slack. He would now go back and find out what was in his mixture\\u2014another dark, slippery descent, as Vertex still had no specific assays to guide him.\"), mdx(ContentRef, {\n    id: 1,\n    mdxType: \"ContentRef\"\n  }, \"Science, as Nobel laureate David Baltimore has observed, proceeds \\u201Cnot from truth to truth, but from suggestion to suggestion,\\u201D and Thomson was buoyed instinctively by the suggestion that his two molecules might be linked by some other feature besides size. The chemical pathway that included FKBP remained unknown, and it was still uncertain what the protein did besides help other proteins invert themselves. If Thomson\\u2019s second constituent bound chemically to FKBP and if it was new, he conceivably had a molecule as important, as rewarding, as FKBP. This and a fear of failure to equal Starzl\\u2019s kept Thomson from relaxing his pace.\"), mdx(ContentRef, {\n    id: 2,\n    mdxType: \"ContentRef\"\n  }, \"Thomson now moved into the lab altogether. He abandoned the waist-high stack of take-out pizza boxes in his apartment and a refrigerator \", mdx(\"a\", {\n    id: \"page_80\"\n  }), \"empty but for the world\\u2019s supply of fetal eye lens protein and some beer and began those experiments that would delicately tear his two molecules from their embrace. What he needed was something that bound to FKBP but not the other component\\u2014a molecular butcher\\u2019s hook\\u2014and that Boger himself now provided. Like fly-fishermen and safecrackers, molecular researchers like to improvise their own tools. Boger, in the earliest days of the program, had designed several antibodies to FKBP, compounds with known affinities to parts of the molecule. Now, working night after night, Thomson used them to try to detect what was in his mix.\"), mdx(ContentRef, {\n    id: 3,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWhen I had a little bit of the second isolate pure enough to get sequence information and a physical photograph of it of any kind, I\\u2019d know what I had,\\u201D he recalled.\"), mdx(ContentRef, {\n    id: 4,\n    mdxType: \"ContentRef\"\n  }, \"Thomson stayed in the lab for five days, \\u201Con the hop,\\u201D as he put it, moving all the time. His feet swelled, and he was limping. Frustrated and exhausted but determined to make good on his promise, he became his own demon so that no one, not even he, could imagine doing any more. All of the scientists had known people in graduate school who never left the lab, and at one time or another, most of them had slogged through intense periods at the bench. But none of them had ever seen anything to match Thomson\\u2019s stamina or resolve. Boger, who saw the value of his scientists in competitive terms and was still crafting the Vertex mystique, said, \\u201CNot even Merck has someone like John. If they did, I wouldn\\u2019t have had to hire him when I was there.\\u201D Added Aldrich, \\u201COne of our chief goals for the next year is to keep John alive.\\u201D\"), mdx(ContentRef, {\n    id: 5,\n    mdxType: \"ContentRef\"\n  }, \"Thomson eventually isolated the contaminant. He\\u2019d been right: There was another protein in his mix. But it wasn\\u2019t new, it had no obvious connection to FKBP biologically, and there was much more of it than FKBP. Indeed, Thomson\\u2019s red herring appeared to be one of the most universal\\u2014and universally understood\\u2014of all proteins. From what Thomson could tell, he had discovered ubiquitin, which, as its name implies, is found literally in every living cell, from amoebas to carrots to people. Just as proteins are constantly being produced, they\\u2019re also being destroyed, and ubiquitin leads the kill. It\\u2019s everywhere. And now it was overrunning the FKBP in Thomson\\u2019s sample tubes.\"), mdx(ContentRef, {\n    id: 6,\n    mdxType: \"ContentRef\"\n  }, \"Thomson was undismayed by his failure to produce an important \", mdx(\"a\", {\n    id: \"page_81\"\n  }), \"new find: Dry holes are the rule in science, and he had trained himself, like most researchers, to expect nothing even as his hopes soared. But he shuddered at what the extraction suggested about FKBP. He now feared that Harding\\u2019s protein was much scarcer than he or the Merck group had originally reported\\u2014so scarce, in fact, that if its relative abundance had been known at the time, Boger might have been forced to cancel the project outright. Suddenly, Thomson\\u2019s goal became much more daunting. Even if he was able to isolate FKBP, there was so little of it, even in thymus, that he might not be able to produce enough of the substance to crystallize, which was nearly essential for determining its structure. At the very least, larger preps and much higher yields were now critical.\"), mdx(ContentRef, {\n    id: 7,\n    mdxType: \"ContentRef\"\n  }, \"He was back at square one. The Glaxo visit was less than a month away and, though no one would say so, the lack of protein meant that the other scientists, who were just as eager to prove themselves as Thomson and were falling behind their competitors elsewhere, were forced to sit idly by. It also meant that Schreiber, who was thought to have nearly a half-gram of recombinant FKBP, became a double threat. Without its own protein supply, Vertex needed more than ever to retain Schreiber and cultivate a deal with Harvard. Yet Schreiber was becoming increasingly impatient. Few goals were as critical to him as finding a crystallographer who, using his protein, would be first to solve the structure of FKBP. Stock or no stock, Schreiber was hearing the same rumors as Thomson that Merck had now produced sufficient protein and was trying to crystallize it. He could hardly be expected to forfeit his priority for the company even if he had been so inclined.\"), mdx(ContentRef, {\n    id: 8,\n    mdxType: \"ContentRef\"\n  }, \"Thomson went home and slept for twenty-four hours, showered, shaved, and changed his clothes before returning to the lab to start again. He was determined this time not only to get pure protein, but to devise an extraction process that yielded one hundred times more FKBP than either Harding or Merck had gotten. The decision meant not only doubling his standing order for thymus from five kilograms per week to ten, but experimenting with new methods at every stage of the process, going all the way back to tissue cutting. Every feature had to be optimized. \\u201CBasically I threw both papers in the trash at that point,\\u201D Thomson says. The search for \", mdx(\"a\", {\n    id: \"page_82\"\n  }), \"new protocols would no doubt slow him down sharply, but Thomson considered it essential for producing the quantities of protein that Vertex would ultimately need. Despite the rising anxiety of some of the other scientists, Boger supported Thomson implicitly, placing himself as a barrier to criticism and ensuring that Thomson would not have to deal with any haranguing but his own.\"), mdx(ContentRef, {\n    id: 9,\n    mdxType: \"ContentRef\"\n  }, \"By working slavishly, Thomson dispelled most criticism without Boger\\u2019s qualification, but he now was so unforgiving of himself that others began to worry. On January 22, 1990, for instance, less than a week after sorting out the apparent contamination with ubiquitin, Thomson entered the lab and didn\\u2019t leave\\u2014except to go home twice to shower and change\\u2014for eight days. At the end of that time, he had extracted a batch of what appeared to be pure FKBP, but it was dead\\u2014inactive. Thomson concluded that what killed it might have been his use of chloroform to segregate out the fats early in the process or perhaps the snap freezing, which he was now ready to abandon completely. \\u201CWorst comes to worst,\\u201D he said, \\u201Ctissue day around here may be a bit more nasty.\\u201D His matter-of-factness did not strike anyone who knew him as a good sign. They laughed nervously when Thomson told them that as soon as he got the protein, he planned to reward himself by buying another motorcycle.\"), mdx(ContentRef, {\n    id: 10,\n    mdxType: \"ContentRef\"\n  }, \"The Glaxo visit was now set for February 20, and though Vertex had other intriguing developments to show, the possession of a method for isolating protein would guarantee that Glaxo would have to take Vertex seriously not only as an ally but as a threat\\u2014a coveted position in any negotiation. Thomson and Fitzgibbon now went flat out, racing to beat not only that deadline, but an earlier one. Boger had stuffed Vertex\\u2019s labs with so much high-end equipment that the company had recently outstripped its power supply. On February 16, the labs would be shut down and the building sealed for most of the day while a utility crew installed a 50,000-watt transformer. Al Vaz, Vertex\\u2019s lab manager, had already told Thomson he would be taping shut the cold rooms, and Thomson anticipated having to stop work. With Glaxo coming four days later it would be hard enough for him to gear up again, much less salvage any experiments that might be lost when the power went \", mdx(\"a\", {\n    id: \"page_83\"\n  }), \"off. Whatever he would do, he would do by the 16th. He had two weeks.\"), mdx(ContentRef, {\n    id: 11,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 12,\n    mdxType: \"ContentRef\"\n  }, \"As Boger could have expected, Harvard grew more rectitudinous by the day. Though the licensing office favored a deal, Joyce Brinton now told Aldrich that Schreiber\\u2019s relationship with Vertex was raising red flags in other quarters. She advised him to talk with Schreiber. It was an open secret that Harvard offered tenure in chemistry only to those it believed would win a Nobel Prize. This bestowed on Schreiber a status quite incommensurate to his age or scant seniority within the university, which put a high premium on such prizes and had more of them in biomedicine than any other institution in the world. Perhaps, Brinton suggested, Schreiber could use his influence to move the deal along.\"), mdx(ContentRef, {\n    id: 13,\n    mdxType: \"ContentRef\"\n  }, \"Brinton advised that Schreiber meet with economics professor Jerry Green, chairman of the Committee on Professional Conduct, explaining what Aldrich called the \\u201Cparty line\\u201D: that collaborating with Vertex, now an established leader in immunophilin research, was vital to his work and that of his students. Not to do so, he was to imply, would deprive him, his students, and ultimately Harvard of an important opportunity to compete at a vital forefront of research. Brinton also suggested that Schreiber visit President Derek Bok. Bok had lured Schreiber to Cambridge in a tough recruitment battle with Yale and was required, because of Schreiber\\u2019s equity stake and overlapping scientific goals, to rule personally on whether his relationship with Vertex met the university\\u2019s strict conflict-of-interest guidelines\\u2014guidelines that Bok, a former dean of the law school, had promulgated amid one of the most fraught and anxious battles of the university\\u2019s history. Aldrich needed no reminder that Bok had been deeply offended by Boger\\u2019s decision to name his company Veritas and had pressed for it to be changed.\"), mdx(ContentRef, {\n    id: 14,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIt all comes back,\\u201D Boger said, hearing from Aldrich of Bok\\u2019s personal interest in the case.\"), mdx(ContentRef, {\n    id: 15,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThe circle is closed,\\u201D Aldrich said.\"), mdx(ContentRef, {\n    id: 16,\n    mdxType: \"ContentRef\"\n  }, \"Boger had hoped to present Glaxo on February 20 with a signed deal with Harvard that secured Schreiber\\u2019s services once and for \", mdx(\"a\", {\n    id: \"page_84\"\n  }), \"all. Now, without it, he needed more than ever to present an appearance of harmony. Schreiber still didn\\u2019t know of the depth of feeling against him at Vertex, and Boger, who still believed Schreiber might be naive, was determined to exploit whatever loyalty remained between them.\"), mdx(ContentRef, {\n    id: 17,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CStuart will do whatever we ask him to do,\\u201D Boger told Aldrich in his office. \\u201CWe just have to give him the right script.\\u201D\"), mdx(ContentRef, {\n    id: 18,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich was skeptical. \\u201CThe question is, Do you want to use the carrot or the stick?\\u201D As with all matters with Schreiber, Aldrich favored intolerance; he wanted Schreiber reprimanded and reminded that he was at risk of losing all his company stock.\"), mdx(ContentRef, {\n    id: 19,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI want to use the carrot for now,\\u201D Boger replied.\"), mdx(ContentRef, {\n    id: 20,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI guess it depends on where we use it,\\u201D Aldrich said.\"), mdx(ContentRef, {\n    id: 21,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich\\u2019s distrust of Schreiber, based on his experience at Vertex, had become immense and personal. But his cynicism about Harvard was more roundly historical. As for many scions of old Boston families, the university was an essential part of Aldrich\\u2019s heritage, nearly a bloodline. His father, mother, and both of his father\\u2019s siblings had gone there, and his father and uncle had graduated from Harvard Law School. They had attended in the years around World War II, when Harvard was in the final throes of transforming itself from a Brahmin redoubt to an academic superpower and its highmindedness was unencumbered by profit motive or self-doubt. It was a time\\u2014extending ultimately into the early 1970s, when the younger Aldrich was in high school\\u2014marked by steeply ascending federal support for the sciences and an attendant virtuosity about the goals and consequences of research. For years Harvard\\u2019s patent policy was simply, \\u201CNo patents primarily concerned with therapeutics or public health may be taken out\\xA0.\\xA0.\\xA0. except for dedication to the public,\\u201D and there was little reason to suggest that it be otherwise.\"), mdx(ContentRef, {\n    id: 22,\n    mdxType: \"ContentRef\"\n  }, \"Partly because of himself (\\u201CI never found school enough of an incentive,\\u201D he says) and partly because of Harvard (underachieving young Brahmins were no longer so easily absorbed as the university rose in stature), Aldrich ended up at Boston College. From there he went to work for the headiest of the big business consulting firms of the 1970s, Boston Consulting Group\\u2014a Harvard Business \", mdx(\"a\", {\n    id: \"page_85\"\n  }), \"School spawn that introduced such buzzwords as \", mdx(\"i\", null, \"learning curve\"), \" and \", mdx(\"i\", null, \"cash cow\"), \" and led the way toward recasting American business as a shovefest over market share. Young and brash, Aldrich was a self-described \\u201Cpunk in pinstripes,\\u201D researching ways for companies to squeeze out new profits and typifying an old joke about consultants;\\u2014that they know a hundred ways to make love but don\\u2019t know any women. After getting an M.B.A. at Dartmouth, where he supported himself by marketing beer caddies at football games, Aldrich took a job developing business deals for one of the two earliest leaders in the infant biotechnology industry, Biogen.\"), mdx(ContentRef, {\n    id: 23,\n    mdxType: \"ContentRef\"\n  }, \"Biogen brought Aldrich face-to-face with the new, changing, commercially minded Harvard\\u2014a Harvard that Bok was straining to keep from going astray or, perhaps worse yet, becoming uncompetitive. Biogen was founded by Walter Gilbert, perhaps the quintessential Cambridge figure of the postwar era. A brilliant biochemist and Nobel laureate, the brindle-haired Gilbert left Harvard to run Biogen, raised $125 million, came to earn $285,000 a year and own 580,000 shares of stock, then almost lost it all before surrendering the company to experienced managers and returning to the university. He later would attempt to raise capital to compete privately with the government\\u2019s effort to map the human genome, a plan that, if successful, would have given Gilbert and his cohorts the patent to the human blueprint. In Gilbert, Aldrich saw the prototype of the new, big-name academic scientist: brilliant, yet \\u201Cmercilessly egotistical\\u201D (to use Jeremy Knowles\\u2019s phrase) and driven by a profit motive to equal anything on Wall Street. Aldrich greatly admired their ability to create value\\u2014Gilbert\\u2019s, especially\\u2014but found them as a rule \\u201Ccutthroat pirates\\u201D when it came to appropriating their share. \\u201CI have no qualms about throwing any of these guys overboard,\\u201D he said. As for Harvard, he resented that the moral certitude of his father\\u2019s era\\u2014when the school knew what it was and what it stood for\\u2014had given way to ambivalence and rank greed. A political and fiscal conservative, Aldrich, in his mid-thirties, was in this way like a man much older.\"), mdx(ContentRef, {\n    id: 24,\n    mdxType: \"ContentRef\"\n  }, \"Still, using Schreiber to motivate Harvard held a certain grisly fascination for Aldrich. He felt they deserved each other. But he was not comforted by the prospect of having to depend on \", mdx(\"a\", {\n    id: \"page_86\"\n  }), \"Schreiber for so important a mission, and he tried to calculate Harvard\\u2019s incentive for making a deal with Vertex regardless of Schreiber\\u2019s entreaties.\"), mdx(ContentRef, {\n    id: 25,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIf Harvard decides this is a positive net to Harvard,\\u201D he told Boger, \\u201Cthey\\u2019ll have a hard time not making this deal.\\u201D\"), mdx(ContentRef, {\n    id: 26,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CYeah,\\u201D Boger said, \\u201Cbut Joyce Brinton knows that come May, she may be able to walk to the table insisting on a 5 percent royalty on anything we do and say, \\u2018Take it or leave it.\\u2019 We\\u2019re stuck. We can\\u2019t wait.\"), mdx(ContentRef, {\n    id: 27,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI\\u2019ve got Stuart all ready to go. I\\u2019m going to tell him that whether we can get all or part of this resolved by the 20th will determine if the company expands or not.\\u201D\"), mdx(ContentRef, {\n    id: 28,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CExpands,\\u201D Aldrich suggested, sharpening the thought, \\u201Cwith or without Stuart involved.\\u201D\"), mdx(ContentRef, {\n    id: 29,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 30,\n    mdxType: \"ContentRef\"\n  }, \"The morning of February 16 broke over Boston with deep-winter, arctic clarity, freezing the undulate white fumes from the smokestacks in midcurl and impaling them against an ice blue sky. A bone-slicing wind slashed in from the harbor, bowing commuters. The unplowed whalebacks of ice on Allston Street were as hard and gray as plank steel.\"), mdx(ContentRef, {\n    id: 31,\n    mdxType: \"ContentRef\"\n  }, \"Such frigid weather played havoc with Vertex\\u2019s chemistry lab, at the center of the building, and with the rest of the facility. Chemists do most of their work inside glass-enclosed safety hoods that rapidly remove gases from the environment. The hoods also remove the environment. Several high-powered roof units continuously heat the air in the lab, then suck it out. A new atmosphere comes and goes every three minutes, which in the early predebugging period of the company regularly produced wild thirty-degree temperature swings on cold days. A young crystallographer who had begun working almost as much as Thomson, Mason Yamashita, took to napping on the floor next to the X-ray generator because, he had found, it was the warmest place in the building. The glass front door, several corridors away, slammed violently from the backdraft whenever someone opened it. For all but a few employees, Vertex\\u2019s extreme technical demands now accounted for a welcome Thursday \", mdx(\"a\", {\n    id: \"page_87\"\n  }), \"morning in bed while the electric company came to triple the company\\u2019s power supply.\"), mdx(ContentRef, {\n    id: 32,\n    mdxType: \"ContentRef\"\n  }, \"Alone in the labs, John Thomson drained a cup of coffee and rushed back to the protein sequencing room, an alcove adjacent to his cold room, which contained a small hood and six feet of benchtop. A single computerized instrument covered the bench. Approximately every eighteen minutes the machine spat out a three-letter code\\xA0.\\xA0.\\xA0. Gly\\xA0.\\xA0.\\xA0. Val\\xA0.\\xA0.\\xA0. Gln\\xA0.\\xA0.\\xA0. Val\\xA0.\\xA0.\\xA0. Glu\\xA0.\\xA0.\\xA0. Thr. Each code was an abbreviation for one of the twenty amino acids from which all proteins are assembled\\u2014Gly for glycine, Val for valine, Glu for glutamic acid\\u2014and which are themselves bundles of atoms: a carbon atom in the center of a small, tightly configured constellation of oxygen, nitrogen, carbon, and hydrogen atoms. Like fingerprints, no two protein sequences are the same. Thomson was looking for the sequence that Harding and the Merck group had both identified as belonging to FKBP.\"), mdx(ContentRef, {\n    id: 33,\n    mdxType: \"ContentRef\"\n  }, \"Thomson had been in the lab for six days. He was beyond exhaustion or relief, feeling simultaneously awake and asleep, dead and alive, crippled and immortal. He stared at the machine, unshaven, his hands and feet raw and red and pumping nervously. The codes came; they were indifferent to him. Yet with each syllable he knew that what the computer was analyzing could only be pure, isolated, biologically active FKBP. It was a trace amount, nowhere near enough to supply crystallography. But it was there, as he had pledged, four days before the meeting with Glaxo.\"), mdx(ContentRef, {\n    id: 34,\n    mdxType: \"ContentRef\"\n  }, \"Thomson stood at the machine, recording the sequence, and was still standing numbly when the power went down and there was nothing left for him to do. With no one to share his triumph, he celebrated by returning to the lunchroom and, in the sullen half-light and unfamiliar silence, sitting down to close his eyes.\"), mdx(ContentRef, {\n    id: 35,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 36,\n    mdxType: \"ContentRef\"\n  }, \"Benno Schmidt\\u2019s twenty-third-floor office in. Rockefeller Center looks directly down upon the twin gothic spires of St. Patrick\\u2019s Cathedral, rising somberly across Fifth Avenue. \\u201CGod\\u2019s view,\\u201D Boger calls it, less because Schmidt is Vertex\\u2019s board chairman and one of its largest stockholders than because, as a founding partner \", mdx(\"a\", {\n    id: \"page_88\"\n  }), \"in J. H. Whitney and Company, the world\\u2019s prototype venture capital firm, and ex-chairman of the federal government\\u2019s War on Cancer, the eighty-one-year-old Schmidt is the senior gatekeeper of biomedical innovation in the United States. Ensconced in the office since he became Whitney\\u2019s managing partner in 1959, Schmidt, a lawyer, arguably has influenced the course of medical research during the past twenty years more than any other nonscientist. He looks the way God would look if he were an unreconstructed Texas Republican who came to New York in the muscular years after World War II and, working with one of the great private fortunes of the time, became hugely rich and powerful by merging old-boy eloquence and an instinct for making deals with charm, charisma, a flair for agenda building and an exceptionally well-placed network of friends and associates. Along the walls, amid faded floral drapes and surrounding a titanic desk, are pictures of Schmidt\\u2014his looming frame, robust jowls, sleeked salt-and-pepper hair, and extravagant white eyebrows\\u2014with every U.S. president since Richard Nixon.\"), mdx(ContentRef, {\n    id: 37,\n    mdxType: \"ContentRef\"\n  }, \"Schmidt was not born to such company. He grew up in Abilene, in the western Texas hill country. His mother, widowed when he was twelve, worked as a secretary at the county welfare association. Attending public schools, he graduated at the top of his class at the University of Texas Law School, then went on to teach at Harvard. He enlisted in the army two days after Pearl Harbor, eventually rising to the rank of colonel and joining the State Department after the war. In 1946, he was approached by John Hay Whitney, heir to what once had been the largest individual estate ever assessed in the United States, to start a company to invest in new technologies. Schmidt didn\\u2019t know Whitney, but it was hard not to know of him. \\u201CJock\\u201D Whitney was one of those men of vast personal resources and style who defined the nation\\u2019s attitude in the decade surrounding the war, a man for whom, a friend once observed, money had three purposes: \\u201Cto be invested wisely, to do good, and to live well off.\\u201D Whitney, dashing and competitive, was famous for all three: he bankrolled the filming of \", mdx(\"i\", null, \"Gone with the Wind\"), \" and was ambassador to Britain; he spent $40 million trying to rescue the \", mdx(\"i\", null, \"New York Herald Tribune\"), \" and gave millions more to victims of discrimination; he played high-goal polo, bred racehorses, and amassed \", mdx(\"a\", {\n    id: \"page_89\"\n  }), \"one of the world\\u2019s finest private art collections, including a number of Matisses that traveled with him as he moved among his eight residences, among them a town house on East 63rd Street, a 500-acre estate on Long Island, and a 19,000-acre refuge in Georgia. As America was preparing to exploit its success in war and men like Whitney resumed their places of prominence, Whitney invited Schmidt to sit beside him.\"), mdx(ContentRef, {\n    id: 38,\n    mdxType: \"ContentRef\"\n  }, \"Schmidt quickly adopted Whitney\\u2019s penchant for doing good by doing well. Coining the phrase \", mdx(\"i\", null, \"venture capital,\"), \" he and his partners began underwriting small companies that Wall Street and other lenders considered too risky. They were gamblers, speculating on new talent and new ideas and reflecting the rising expectations and romance of the time. \\u201CWe don\\u2019t live so much on our batting average as our slugging average,\\u201D Schmidt once said. \\u201CWe live off our extra-base hits.\\u201D Within a year, the company had invested in two small firms\\u2014Minute Maid, which invented frozen orange juice, and Spencer Chemical Company, a midwestern fertilizer concern\\u2014that paid off so spectacularly that Schmidt had his fortune. Like his benefactor Whitney, he began a life of conspicuous public service: chairman of the Bedford-Stuyvesant Development and Services Corporation, the Fund for the City of New York, the Welfare Island Planning and Development Committee, and, most presciently, president of the Memorial Sloan-Kettering Cancer Center, one of the world\\u2019s premier cancer research facilities.\"), mdx(ContentRef, {\n    id: 39,\n    mdxType: \"ContentRef\"\n  }, \"Laurence Rockefeller, who worked with Schmidt on the Sloan-Kettering board and was an old friend of Whitney\\u2019s, recommended that Schmidt be appointed in 1971 to a commission studying the federal government\\u2019s role in fighting cancer. Not since World War II had there been so much pressure to put research in the service of a distinct medical goal, and Schmidt, known for getting things done, was put in charge. He remained as chairman of the President\\u2019s War on Cancer through the administrations of Nixon, Ford, and Carter, and though no cure for cancer was found, the surge in directed research and outpouring of federal money gave rise to a new, entrepreneurial era in biomedicine\\u2014an era in which Schmidt, as a businessman and investor with incomparable connections among research directors and in Washington, was consummately positioned to become a major broker. Coming full circle, J. H. \", mdx(\"a\", {\n    id: \"page_90\"\n  }), \"Whitney and Company, under Schmidt\\u2019s management, began investing heavily in those new companies spawned to capitalize on gains in basic research that grew out of the War on Cancer. \\u201CMaking plays,\\u201D he called it.\"), mdx(ContentRef, {\n    id: 40,\n    mdxType: \"ContentRef\"\n  }, \"One of Schmidt\\u2019s most successful plays was in a company called Genetics Institute (GI). Founded by two Harvard molecular biologists, GI was launched in 1980 at Harvard, and for a time, before Wally Gilbert and others registered such an outcry that the university was forced to withdraw, Harvard intended to buy most of it. Harvard\\u2019s retreat, coming just as the initial fever over biotechnology was spiking, worked in Schmidt\\u2019s favor. He and William Paley, chairman of CBS and Jock Whitney\\u2019s brother-in-law, presented the scientists with an intoxicating alternative: take their labs private. Why work for Harvard when they could work for themselves? GI went on to become one of the glamour companies of the new biomedical age, with Schmidt, who became chairman, compiling for himself and Whitney a combined stake of more than 250,000 shares.\"), mdx(ContentRef, {\n    id: 41,\n    mdxType: \"ContentRef\"\n  }, \"GI had already paid off handsomely for Schmidt, but the largest prize, in the winter of 1990, remained to be taken. It was a molecule called EPO, for erythropoietin, a protein that stimulated red blood cell production, which GI and Amgen, a California company, were competing for the right to market first in the United States. Here were the all-or-nothing stakes of the new biomedical order writ large. Developed initially to treat kidney dialysis patients, who become severly anemic and can\\u2019t, because of their condition, be transfused, EPO was long recognized as a likely blockbuster, perhaps the first billion-dollar drug of the biotech age. It was one of perhaps two or three molecules guaranteed to catapult a new company from making bonfires of its cash to Fortune 500 profitability\\u2014while granting its early backers, like Schmidt, a more than hundredfold increase in their initial investments\\u2014and GI and Amgen both possessed the key for making it.\"), mdx(ContentRef, {\n    id: 42,\n    mdxType: \"ContentRef\"\n  }, \"That was the problem. Patent laws grant drugmakers exclusive markets for their new products for seventeen years, and Amgen and GI sued to block each other\\u2019s patent claims. The lawsuits, carried on simultaneously on both coasts, dragged on for more than four years, even after Amgen won FDA approval to begin selling the drug, and still had not been resolved in November when a federal \", mdx(\"a\", {\n    id: \"page_91\"\n  }), \"court in Boston ruled that both companies\\u2019 patents and infringement claims were valid. With each side now spending millions of dollars annually on legal fees and issuing press releases nearly every time they filed a brief, the ruling was appealed by both sides.\"), mdx(ContentRef, {\n    id: 43,\n    mdxType: \"ContentRef\"\n  }, \"Even with the uncertainty about the U.S. market, the world\\u2019s largest for pharmaceuticals, the news for Schmidt was hardly all bad. Like nearly all small, research-based companies, GI couldn\\u2019t afford to develop EPO itself and in 1985 had licensed it to a partner, Chugai Pharmaceutical Company of Japan, one of a rising class of Japanese drug companies with global ambitions. Chugai had bought the rights to market GI\\u2019s EPO both in Asia and as a joint venture in the United States, and though its U.S. prospects were now stalled, in January 1990 the company had received approval to begin selling EPO in Japan, which consumes more legal drugs per capita than any country in the world. The Japanese market for EPO, in which Chugai had no competition, was estimated at $200-400 million. GI would get a 5 percent royalty\\u2014not a spectacular annuity, but tens of millions of dollars nonetheless. Meanwhile, Chugai, feeling flush, had begun looking to make another play in the United States and was seeking Schmidt\\u2019s counsel.\"), mdx(ContentRef, {\n    id: 44,\n    mdxType: \"ContentRef\"\n  }, \"Schmidt had not meddled before in Vertex\\u2019s business development; he was busy and he wanted to let Boger run his own show. But in early February he called and invited Boger to meet his \\u201Cold friends\\u201D from Chugai sometime in New York, and Boger, not wanting to kill a day freezing idly in Cambridge, suggested that he and Aldrich take the shuttle down early on the morning of the 16th. That Glaxo would be coming the following Monday favored Boger\\u2019s calculations neatly. Introductory business meetings with the Japanese were largely ceremonial, and deals with them most often moved glacially and took years to complete. And yet even if nothing happened, Boger would be able to state to Glaxo with unimpeachable accuracy that Vertex was now considering other options, implying that Glaxo needed to move fast or lose an opportunity. Boger had an affirmative distaste for negotiations where the power balance heavily favored the other side, and he didn\\u2019t want to be held up while Glaxo shopped around. At 6 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \"., as Thomson slumped over the protein sequencer, Boger, Aldrich, and Manuel Navia climbed aboard the Trump Shuttle for LaGuardia.\"), mdx(ContentRef, {\n    id: 45,\n    mdxType: \"ContentRef\"\n  }, mdx(\"a\", {\n    id: \"page_92\"\n  }), \"Schmidt set the tone of the meeting, sweeping around the room, pumping hands like a host at a barbecue, his blue eyes boring into each charmed gaze from under the great cirrus of his eyebrows. The head of the Chugai group was a surprisingly young man in a conventional dark suit and aviator glasses, Osamu Nagayama, the company\\u2019s deputy president and son-in-law of its aging chairman. Most Japanese businesspeople who are in a position to spend their company\\u2019s money came of age during World War II and affect an unapproachable resolve, particularly with Americans. But Nagayama, who was forty-three, spoke English well enough to enjoy its jokes and seemed to relish Schmidt\\u2019s informality. Boger, Aldrich, and Navia, mindful of the emphasis that the Japanese place on gestures of respect and on social hierarchy, dutifully presented their English-Japanese business cards and addressed Nagayama and the others by their honorifics\\u2014Nagayamasan, Ohtasan. Schmidt called Nagayama \\u201CSam\\u201D and said that he\\u2019d had some business cards printed up in 1946 but hadn\\u2019t seen them in some time.\"), mdx(ContentRef, {\n    id: 46,\n    mdxType: \"ContentRef\"\n  }, \"After the introductions, they moved into the partners\\u2019 dining room, Schmidt\\u2019s sanctum. It was formidably paneled in butternut stripped from the Fifth Avenue mansion of Jock Whitney\\u2019s parents and decorated with some of Whitney\\u2019s early American holdovers and a Mir\\xF3 that Boger thought resembled a molecule. Boger ran through his standard slide show, which remained long on generalities and short on details. Even had he known about Thomson\\u2019s breakthrough that morning, he would hardly have disclosed it, proprietary information being best saved until there is the prospect of real money on the table. He scarcely mentioned Schreiber. Then Nagayama gave a brief summary of Chugai\\u2019s strategic goals. With the development of EPO now complete, he said, the company was entering the second phase of a fifteen-year growth plan in which it intended to triple its sales to $3 billion, do 30 percent of its business overseas, and become one of the top thirty drug companies in the world. The company, he added, had another, longer-range plan that ran through the year 2100.\"), mdx(ContentRef, {\n    id: 47,\n    mdxType: \"ContentRef\"\n  }, \"To Aldrich, who had negotiated with Japanese companies ever since his days at Biogen, it was an unusually promising exchange\\u2014not for what was said but for who said it. Most negotiations with \", mdx(\"a\", {\n    id: \"page_93\"\n  }), \"the Japanese begin with low-level licensing people who have no authority to move things along within the ritualized consensus-building process by which virtually all Japanese firms are run. But Nagayama was one step away from the board. He had the confidence of chairman Kimio Uyeno, son of the founder, who had parlayed the best-selling hangover remedy in Japan into a nascent global empire. Aldrich figured that by this one meeting alone they had gained a year, perhaps eighteen months, toward the prospect of Chugai\\u2019s underwriting Vertex\\u2019s immunophilins program.\"), mdx(ContentRef, {\n    id: 48,\n    mdxType: \"ContentRef\"\n  }, \"Even more than Boger, Aldrich hated sharing Vertex\\u2019s \\u201Cvalue\\u201D with those he thought contributed nothing to it. That was why he favored research partnerships over other types of financing. He knew that if he and Boger didn\\u2019t find a development partner soon, they would end up going back to venture capitalists (VCs) like Schmidt for more money, which, although potentially a boon for Schmidt and the other board members, was the most expensive route for the company. Aldrich\\u2019s frequent use of the generic \\u201Cbloodsucking VCs\\u201D reflected this point. Because of the high risk they take, venture capitalists expected the highest return for their money of any investors. More, as board members, they priced stock that they then sold to themselves. Aldrich wanted nothing more than to free Vertex from its indentured condition through a deal of his and Boger\\u2019s own making, and he was delighted to think that the ground had suddenly been laid for one. That Chugai seemed not to care about Schreiber was a stroke so fortunate he hadn\\u2019t even dared consider it up to that moment.\"), mdx(ContentRef, {\n    id: 49,\n    mdxType: \"ContentRef\"\n  }, \"Schmidt, eyeing the exchange avuncularly, also thought he smelled a deal. He had two tests for doing business: Is this a field you want to be in and are these people you want to be in it with? Viewing the situation from both sides, he thought the auguries promising. Casually, he suggested a roughly even split. If Vertex produced a new immunosuppressant, the two companies would market it as a joint venture in North America and Europe, with Chugai getting the Far East and paying Vertex a sizable royalty there. From a pharmaceutical marketing standpoint, the rest of the world is a write-off; Schmidt didn\\u2019t mention it.\"), mdx(ContentRef, {\n    id: 50,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI outlined my ideas of a deal and asked Sam if that sounded to \", mdx(\"a\", {\n    id: \"page_94\"\n  }), \"him like the makings of a deal, and he said it did,\\u201D he later recalled. \\u201CSo I wrote down a price on a little piece of paper and I handed it to him.\\u201D\"), mdx(ContentRef, {\n    id: 51,\n    mdxType: \"ContentRef\"\n  }, \"Schmidt\\u2019s figure\\u2014for a project that was scarcely any closer to producing a drug than it was three months earlier when the company had no labs, a project whose chief selling point, Schreiber, was now persona non grata and perhaps even a double agent and competitor\\u2014was $40 million. Nagayama folded the scrap of paper and, committing nothing but a reply, returned with it to the company\\u2019s headquarters in Tokyo.\"));\n}\n;\nMDXContent.isMDXComponent = true;","fields":{"slug":"/molecule/5/"},"frontmatter":{"isBook":false,"title":"Chapter Five","bookTitle":"The Billion-Dollar Molecule","numSections":25,"tags":["a"],"author":"Barry Werth"}}},"pageContext":{"id":"61fdfde5-043b-5c45-9d07-935e6541469e"}},"staticQueryHashes":["4080856488"]}