{"componentChunkName":"component---src-templates-book-page-js","path":"/molecule/17/","result":{"data":{"mdx":{"id":"8491d3ef-b3d9-5de4-8a1f-e04c4e532e18","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 Seventeen\"\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  }, \"P\"), \"ropelling both business and science, Boger had always behaved with the easy, sweatless confidence of a grand master playing chess with a dozen or so opponents in a show match. Now, with Vertex pursuing Schreiber, an IPO, a drug, a new project, and publicity for its first important publication, he seemed challenged for the first time. It was as if the games suddenly interlocked in three dimensions. A move in one varied the play in all. The time for each move was halved. Real money was on the table.\"), mdx(ContentRef, {\n    id: 1,\n    mdxType: \"ContentRef\"\n  }, \"On Tuesday, May 7, 1991, less than a week after deciding to take Vertex public, Boger arrived in Cambridge before 7 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \". with two goals utmost in mind. The previous Saturday, Schreiber had mentioned in a talk at Yale that his FKBP-12 structures would be published in \", mdx(\"i\", null, \"Science\"), \" that coming Friday. For Vertex to be able to claim a tie on the X-ray structure, that gave Yamashita and Navia a deadline of no later than noon Thursday, when advance copies of \", mdx(\"i\", null, \"Science\"), \" would be released to the media. After that, their assertion of independent discovery would be irrevocably stained. At the same time, Boger fretted being shut out in the initial burst of publicity that no doubt would follow Schreiber\\u2019s papers. Moore\\u2019s structure was scheduled to appear in \", mdx(\"i\", null, \"Nature\"), \" the following week, but \", mdx(\"i\", null, \"Nature\"), \" had a prepublication embargo that prohibited researchers from announcing their work without its consent. Violating the embargo and jeopardizing Vertex\\u2019s relationship with the journal were out of \", mdx(\"a\", {\n    id: \"page_319\"\n  }), \"the question. Also, now that Vertex was going public, it was barred from seeking any publicity that might inflate its stock price. Not yet technically in the federally mandated \\u201Csilence period,\\u201D the company nonetheless had to be careful about what it disclosed lest it delay Kidder\\u2019s tentative offering date of mid-July until August, when Wall Street goes on vacation. Boger knew that sooner or later, probably sooner, the market in new biotech offerings was going to crash. He shuddered to think about waiting until September to go out.\"), mdx(ContentRef, {\n    id: 2,\n    mdxType: \"ContentRef\"\n  }, \"He spent most of the day cloistered with Aldrich, Ken, and the Kidder people, working on the red herring, the prospectus that Vertex would submit to the SEC and eventually investors. At 10 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"P.M\"), \"., he was still at his desk. With less than forty hours left, Navia, Murcko, and Yamashita were racing furiously next door to reconstruct the protein.\"), mdx(ContentRef, {\n    id: 3,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWe\\u2019re going to have to work like crazy to get FedExes out tomorrow and get \", mdx(\"i\", null, \"Nature\"), \" to break its embargo and get the lawyers to give us an opinion that we\\u2019re not illegally hyping the company so that the SEC won\\u2019t put back our offering,\\u201D Boger groused convivially. \\u201CIt\\u2019s ugly, I hate it, but it\\u2019s part of the business.\\u201D\"), mdx(ContentRef, {\n    id: 4,\n    mdxType: \"ContentRef\"\n  }, \"Murcko, overhearing his lament, muttered, \\u201CWe\\u2019re going to have to get that guy back to being a scientist.\\u201D But of course the matter was moot and, in Boger\\u2019s mind, beyond distinction.\"), mdx(ContentRef, {\n    id: 5,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 6,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CAre you going to fire me for this?\\u201D Yamashita asked Boger at around 8 the next morning. He had been working all night.\"), mdx(ContentRef, {\n    id: 7,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI have to wait for the data,\\u201D Boger chortled.\"), mdx(ContentRef, {\n    id: 8,\n    mdxType: \"ContentRef\"\n  }, \"Typically, Boger was 70 percent joking and half serious. He in fact blamed Yamashita for very little, thought he had done an extraordinary job under crushing circumstances, and would support him even if he failed again to get the correct structure. On the other hand, having X-ray structure mattered immensely now and Boger wasn\\u2019t paying Yamashita, who had bounced back from his moral crisis with characteristic resilience, to fail indefinitely.\"), mdx(ContentRef, {\n    id: 9,\n    mdxType: \"ContentRef\"\n  }, \"Far more urgent was the exquisite irony of Vertex\\u2019s public relations conundrum. For almost two and a half years, Boger had sold the company\\u2019s story mightily, doing all that he could to make it \", mdx(\"a\", {\n    id: \"page_320\"\n  }), \"sound solidly grounded in science. He\\u2019d \\u201Cworn out three pairs of tap shoes,\\u201D he said. Yet now, at precisely the moment when it had a major discovery to announce; when \", mdx(\"i\", null, \"Business Week\"), \" and \", mdx(\"i\", null, \"Fortune\"), \", in their expanding coverage of the biotech boom, had discovered Boger and were planning articles about him and Vertex; when the publicity benefits of positive media coverage would be incalcuable as the company went public, he was forced to be guarded, silent. To the salesman and the scientist in him, the incongruity was painful\\u2014\\u201Csmothering the baby,\\u201D he called it.\"), mdx(ContentRef, {\n    id: 10,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI blew off Gene Bylinsky from \", mdx(\"i\", null, \"Fortune\"), \" this morning,\\u201D he told Aldrich, gulping exaggeratedly in disbelief.\"), mdx(ContentRef, {\n    id: 11,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CGoes against the grain, doesn\\u2019t it?\\u201D Aldrich said.\"), mdx(ContentRef, {\n    id: 12,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIt\\u2019s galling. Anybody who wants to get around the SEC, to sell junk stock, to bilk widows and orphans out of their life savings, is not going to be hurt by these rules. The only people who are hurt by this are the ones who try to play by the rules. It\\u2019s not protecting anyone. It\\u2019s enough to turn you into a raving conservative.\\u201D\"), mdx(ContentRef, {\n    id: 13,\n    mdxType: \"ContentRef\"\n  }, \"Boger\\u2019s first priority was to get \", mdx(\"i\", null, \"Nature\"), \" to lift its embargo. He might not be able to tell \", mdx(\"i\", null, \"Fortune\"), \" that Vertex was hard after Merck in developing a drug, but there was nothing in the SEC regulations to prevent the company from issuing a press release about a vital discovery with clear importance to the public health. The issue there was simply, if critically, one of timing. If Vertex announced Moore\\u2019s structure at the same time as Schreiber, Karplus, and Clardy announced theirs, the media would report a tie and Vertex could exploit it accordingly. If Vertex was forced, however, to withhold its announcement for even a week, there would be no coverage to exploit, just the crumbs of a few second-week stories in the science press. Moore began the morning by calling \", mdx(\"i\", null, \"Nature\"), \"\\u2019s Washington office. Reminded that the journal\\u2019s embargo was meant to discourage exactly the kind of commercial exploitation Vertex was proposing\\u2014exploitation that \", mdx(\"i\", null, \"Nature\"), \" believed did nothing to advance scientific inquiry\\u2014he charged back. He explained that \", mdx(\"i\", null, \"Science\"), \" was about to publish back-to-back structures of the protein. An hour later, a \", mdx(\"i\", null, \"Nature\"), \" editor in Washington called back to say the journal had changed its mind.\"), mdx(ContentRef, {\n    id: 14,\n    mdxType: \"ContentRef\"\n  }, \"Moore sped to tell Boger, who called Ken, who told him that he and Kidder\\u2019s lawyers, who were paid to be skittish about such \", mdx(\"a\", {\n    id: \"page_321\"\n  }), \"things, now agreed that the SEC had no case to delay Vertex\\u2019s offering. Hanging up, Boger strode triumphantly to the lobby, where a stack of press releases was waiting to be faxed to the \", mdx(\"i\", null, \"Wall Street Journal\"), \", the \", mdx(\"i\", null, \"New York Times\"), \", the \", mdx(\"i\", null, \"Los Angeles Times\"), \", the \", mdx(\"i\", null, \"Washington Post\"), \", the \", mdx(\"i\", null, \"Boston Globe, Business Week\"), \", and perhaps two dozen other trade, industry, and scientific journals. \\u201CThe blockade is down,\\u201D he announced. \\u201CThe ships are coming through. I want to blitzkrieg right now. When the press accounts come out, I want the footnote to say, \\u2018There are also some people at Harvard who claim to have done this.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 15,\n    mdxType: \"ContentRef\"\n  }, \"Boger hadn\\u2019t won, but he knew now he hadn\\u2019t lost. Reflecting on catching Schreiber, his overall glow was only slightly less boistrous than if he\\u2019d beaten him outright. \\u201CIt\\u2019s not quite what I want,\\u201D he explained, returning to the lunchroom. \\u201CI want to rub his nose in the dirt and step on his head. But I\\u2019ll settle.\\u201D\"), mdx(ContentRef, {\n    id: 16,\n    mdxType: \"ContentRef\"\n  }, \"To the scientists, \", mdx(\"i\", null, \"Nature\"), \"\\u2019s second reversal in a month was illuminating, improbable, and not without its jealousies. \\u201CThis is the value of working in hot areas,\\u201D Moore told Harding. \\u201C\", mdx(\"i\", null, \"Science\"), \" and \", mdx(\"i\", null, \"Nature\"), \" have no idea whether any of these structures are right, but they\\u2019d obviously rather publish shitty structures of important proteins than exquisite structures of boring proteins.\\u201D Swept up in the tide of anti-Schreiberism, he added, \\u201CWe\\u2019re going to spoil his party. We\\u2019re going to be a very sharp dart in his ass.\\u201D\"), mdx(ContentRef, {\n    id: 17,\n    mdxType: \"ContentRef\"\n  }, \"Harding was sullen, dismal. While the spotlight had shifted to Moore and Yamashita, he had been working since January to identify other FKBPs. Characterizing one at last, he\\u2019d just learned that morning that SAB member Steve Burakoff had a paper in press identifying the same protein. \\u201CThey want to do their work, that\\u2019s fine,\\u201D Harding grumbled, referring to Burakoff and Barbara Bierer, Burakoff\\u2019s chief collaborator and a Vertex consultant, \\u201Cbut there\\u2019s never any sharing of any information.\\u201D He was now working furiously to file a patent application to establish a priority date before Burakoff\\u2019s paper appeared in print. It was another instance of Vertex being beaten by one of its own advisors, and Aldrich, furious, now wanted to fire the entire SAB.\"), mdx(ContentRef, {\n    id: 18,\n    mdxType: \"ContentRef\"\n  }, \"Harding, long-suffering and perplexed, shuffled back to his desk, a pale shadow of Moore\\u2019s and Boger\\u2019s fire-breathing personae. It was to be for him another long, lightless day.\"), mdx(ContentRef, {\n    id: 19,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 20,\n    mdxType: \"ContentRef\"\n  }, mdx(\"a\", {\n    id: \"page_322\"\n  }), \"Throughout the morning and into the afternoon, Mark Murcko, Vertex\\u2019s chief molecular modeler, performed \\u201Cdynamics runs\\u201D on the protein. Now that he had a refined crystal structure of FKBP-12, the key questions were, What does it do and how does it do it? A simple snapshot wouldn\\u2019t do. Murcko had to simulate the molecule\\u2019s natural activity, bring it alive, posit its existence in not only space, but time. He had to \\u201Cfeel\\u201D it. \\u201CKarplus\\u2019s group did this a month ago,\\u201D he said. \\u201CThey had twenty postdocs and access to an order of magnitude [ten times] more computing power. It\\u2019s that against basically a couple of us, but who am I to be different?\\u201D\"), mdx(ContentRef, {\n    id: 21,\n    mdxType: \"ContentRef\"\n  }, \"Sitting at a workstation diagonal from where Yamashita was completing his refinements, Murcko programmed it to simulate the protein\\u2019s natural wriggling. Atoms gyrate in nanoseconds\\u2014billionths of a second. To slow them down, Murcko used the computer like an ultrafast strobe, freeze-framing every 0.3 picosecond (0.3 trillionth of a second). He then ran the images back in slow motion. They resembled the \\u201Cwashboarding\\u201D of bees, a herring-boning, a shimmy. The entire dance lasted just a few seconds, though in it Murcko thought he saw hints of how the molecule might work.\"), mdx(ContentRef, {\n    id: 22,\n    mdxType: \"ContentRef\"\n  }, \"He was especially interested in the active site. Most of the molecule shuddered only slightly; it was highly constrained. But at the opening of the hollowed-out core that Navia and Yamashita speculated was its \\u201Cbusiness end,\\u201D the place where its atoms interacted with other molecules, including FK-506, Murcko noticed a remarkable flexibility. On one side was a group of atoms that he compared to a flap. At one point during the run, about midway, the flap swung open perhaps thirty degrees, like a miniature gate, then snapped shut. The implications for drug design were profound. If true\\u2014and Murcko was quick to volunteer his usual reservations and disclaimers\\u2014this movement in the flap area suggested several possibilities about the enzyme: that in binding it could accommodate larger groups of atoms than the size of its opening would normally allow; that the flap might act like a trap, holding the bound molecule in place once it had infiltrated the active site; most tantalizing, that the shape of both the protein and the small molecular binder, such as FK-506, changed significantly as the flap curled \", mdx(\"a\", {\n    id: \"page_323\"\n  }), \"around the inhibitor. Murcko began to speculate that unlike in Schreiber\\u2019s hypothesis, which was that part of the drug bound to the enzyme while the rest reached out and interacted with another protein, there was a subtler geometry at work. He thought the combined entity of drug and protein might form a new shape and that the new conformation accounted for its action.\"), mdx(ContentRef, {\n    id: 23,\n    mdxType: \"ContentRef\"\n  }, \"In the race with Schreiber, Murcko\\u2019s simulations provided a potent new thrust. Vertex had hoped only to catch Schreiber, but now, as Navia put it, \\u201CWe\\u2019ve got our own story.\\u201D Navia, particularly, was elated. \\u201CThis paper is going to be a killer,\\u201D he told Murcko. \\u201CIt\\u2019s going to be a lot more interesting than I had dared believe.\\u201D Privately, he began to look forward to a full-scale debate with Schreiber, a high-profile slugfest that would avenge the split between them and climax, most probably, in a head-to-head confrontation at the FK-506 conference in Pittsburgh. There, with the scientific world watching, Vertex for the first time might challenge Schreiber\\u2019s priority in the field by offering a new theory on the central issue of how the protein worked. At the very least, it now had something to offer as scientific interest shifted to structural biology.\"), mdx(ContentRef, {\n    id: 24,\n    mdxType: \"ContentRef\"\n  }, \"The deadline for submitting the paper\\u2014it was now Wednesday afternoon\\u2014was less than twenty-four hours away. Yamashita was scrambling to finish the structure, though in fact his contribution\\u2014and the pressure he had felt\\u2014had already begun to recede. All he had left were a few refinements around the active site and to account for the water molecules in his density. Otherwise the onus was on Navia, who had worked until 3 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \". the past two nights drafting the paper for \", mdx(\"i\", null, \"Nature\"), \" and would shepherd it through to completion. It was strange. Yamashita had wanted to solve the structure of the protein more than anything in the world. He had pushed himself dangerously for more than a year to do it, been beaten, recoiled bitterly, recovered, blundered badly, collapsed, recovered again, and was now within a day of being lead author on what was likely to be a career-making paper\\u2014a paper that Navia, his \\u201Cnemesis,\\u201D was writing for him and that seemed all but certain, based on prior agreement, to be accepted into one of the world\\u2019s premier scientific journals. He had gotten, it appeared, almost everything he wanted, yet the pain of getting it had been so great that he felt no pleasure, only a comforting distance, as though he \", mdx(\"a\", {\n    id: \"page_324\"\n  }), \"were alone in a life raft drifting from the scene of an excruciating disaster\\u2014the wreck of his own life. His prayers nearly answered, he was wary, numb, cynical, and oddly composed.\"), mdx(ContentRef, {\n    id: 25,\n    mdxType: \"ContentRef\"\n  }, \"Besides cleaning up his final structure, he had one major matter left\\u2014authorship. As lead author, it remained Yamashita\\u2019s responsibility to name those who would share credit with him, a choice that had previously opened rifts that he now hoped to close. He and Thomson had shakily repaired their friendship after their fight a month earlier, but Yamashita had not brought up the issue, and Thomson had continued to insist that he didn\\u2019t want his name on the paper. Meanwhile, Thomson and Navia had reached an icy standoff, with Thomson complaining about what he considered Navia\\u2019s ineptitude with the protein and Navia insisting that Thomson was blackmailing crystallography by holding protein hostage. Working again around the clock, Thomson had developed a severe case of conjunctivitis and wouldn\\u2019t be in until after four\\u2014an hour away.\"), mdx(ContentRef, {\n    id: 26,\n    mdxType: \"ContentRef\"\n  }, \"Yamashita sought Boger\\u2019s counsel. He wanted Moore and especially Thomson back on the paper, though he understood Boger\\u2019s determination to get the scientists to think less about individual credit and more about drugmaking. Boger was snappish; he\\u2019d heard Navia\\u2019s complaints, and though he didn\\u2019t believe them, he wanted to make sure Yamashita wasn\\u2019t including Thomson simply to pacify him. \\u201CI own you and I own John Thomson, and there\\u2019ll be no quid quo pros here,\\u201D he said. Yamashita responded that he also didn\\u2019t think Thomson was witholding protein, but that he wanted to share authorship with him so that Thomson would continue to talk and work with him. \\u201CIf you do that,\\u201D Boger said, \\u201CJohn\\u2019s name won\\u2019t be on the paper and John will be fired. Tell me how that\\u2019s different from going into your dry cleaners and saying, \\u2018This is a dangerous neighborhood, and it\\u2019s going to be even more dangerous if you don\\u2019t give me $500.\\u2019 It\\u2019s extortion.\\u201D Yamashita left more confused than ever.\"), mdx(ContentRef, {\n    id: 27,\n    mdxType: \"ContentRef\"\n  }, \"In the modeling room Navia was asleep in his chair, sitting upright, his tie still straight, looking comfortably ursine with his broad chin sunk to his chest. He was snoring lightly. Nancy Stuart came in. Stuart, Aldrich\\u2019s chief assistant, had become Vertex\\u2019s all-purpose factotum. Monitoring the project councils, developing \", mdx(\"a\", {\n    id: \"page_325\"\n  }), \"marketing strategies, she strove to keep the scientists on task. At thirty-two, she was the person on the business side the scientists most trusted, having worked for a time at the bench herself and having a natural empathy for people. Gently, she tried to shake Navia awake. He didn\\u2019t budge. She tried again, Rolfing him this time.\"), mdx(ContentRef, {\n    id: 28,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI need to talk to you about our \", mdx(\"i\", null, \"Wall Street Journal\"), \" strategy,\\u201D she said. \\u201CEverything has to go through [enterprise reporter David] Stipp. But you\\u2019ve got to call Waldholz.\\u201D Veteran medical writer Michael Waldholz had covered the HIV protease story for the \", mdx(\"i\", null, \"Journal\"), \" and was one of the few reporters any of the scientists, including Boger, knew personally, much less respected. Sluggishly, Navia removed himself from his seat, from science, and placed the call.\"), mdx(ContentRef, {\n    id: 29,\n    mdxType: \"ContentRef\"\n  }, \"Yamashita stared at a new field of density. He could identify the active site in his sleep, but he was looking for something else, evidence of Vertex\\u2019s lead molecule, 367. By itself, the structure of FKBP-12, much as it had nearly destroyed him, was insufficient for drug design or figuring out how the molecule worked. The ultimate test was to solve the structure of the enzyme bound by other molecules, so-called complexes\\u2014in other words, to show the lock together with a variety of keys so that researchers could see and compare exactly which points made contact. Schreiber and Clardy had apparently already solved the complex of FKBP-12 and FK-506. Having complexes with Vertex\\u2019s own compounds would show what changes the chemists might make to improve the activity of their molecules.\"), mdx(ContentRef, {\n    id: 30,\n    mdxType: \"ContentRef\"\n  }, \"There were two ways to grow complexes, equally devilish and uncertain: soak the drug into existing crystals or, more tryingly, coax them into crystallizing as a unit. Yamashita had tried first to soak in the drug, but now, as he looked at the results on the screen, there was no additional pocket of density in the active site, no unaccounted-for netting. The soaking experiment had failed. Discouraged, Yamashita reported the result to Murcko, then left immediately for the cold room to begin trying to crystallize FK-506 and FKBP-12 together. \\u201CWe know that it must work because Stuart\\u2019s done it,\\u201D he shrugged. \\u201CAnyway, its the logical next step.\\u201D\"), mdx(ContentRef, {\n    id: 31,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIt\\u2019s a serious blow,\\u201D Murcko said, looking up painfully from his \", mdx(\"a\", {\n    id: \"page_326\"\n  }), \"simulation. \\u201CInstead of going home tonight at midnight and having the first glimmerings of where 367 sits in the active site, we don\\u2019t know. I have no idea when I\\u2019ll know. Is it a week? A month? Three months? Six months?\\u201D He stopped himself, frustrated. After more than a year at Vertex, he still didn\\u2019t have the information he needed to design with any real conviction new molecules, and the gap between Vertex\\u2019s promise and its reality had begun to cause him to complain more than he liked. Science was tenuous enough without one\\u2019s having to doubt whether one was a fraud. \\u201CI\\u2019ll continue to do things to be useful,\\u201D he murmured, \\u201Cbut in the absence of real data, anything I\\u2019m going to say is going to be speculative.\\u201D\"), mdx(ContentRef, {\n    id: 32,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 33,\n    mdxType: \"ContentRef\"\n  }, \"Boger was in command mode, managing a half dozen issues at once, another half dozen roiling at bay. He was jocular, intense, flippant, stern, unfiltered. He was moving from chessboard to chessboard with rifling speed. At his desk, the fingers of his right hand rolled over his turbomouse like a magician\\u2019s over an eight ball as he stared imperturbably at the big screen of his Macintosh, his looking glass, his muse. He juggled phone calls\\u2014with Ken, with Holman, with Schmidt, with Kinsella\\u2014with round-robin visits from the scientists, Aldrich, and Nancy Stuart.\"), mdx(ContentRef, {\n    id: 34,\n    mdxType: \"ContentRef\"\n  }, \"His ego, never restrained, was incendiary. To Ken he suggested calling the Harvard patent office \\u201Cto put the fear of God in them.\\u201D Vertex no longer had any claim on Schreiber, but now that it had pulled nearly even with him, Boger wanted to spray his path with tacks by suggesting that the timing of his agreement with Clardy might have violated his Vertex contract. Flipping through another company\\u2019s red herring, he dug into an imaginary trench coat. \\u201C\\xA0\\u2018Pssst. Hot area. Inflammation,\\u2019\\xA0\\u201D he sneered, then spat, \\u201CIt\\u2019s a technological Ponzi scheme written by investment sharks\\xA0.\\xA0.\\xA0. It\\u2019s Florida land that\\u2019s land only six hours a day.\\u201D Talking to Aldrich, he resolved to tell Burakoff: \\u201CWe consider what he\\u2019s doing a serious breach of contract and he\\u2019s worthless to us as an SAB member as long as he\\u2019s working in the same area.\\u201D Taking pleasure in warning Kinsella that he might have to cancel a flattering \", mdx(\"i\", null, \"Wall Street Journal\"), \" article about him\\u2014a profile that Kinsella had eagerly coveted to promote his new company with Schreiber\\u2014he cackled when \", mdx(\"a\", {\n    id: \"page_327\"\n  }), \"Schmidt, on another line, couldn\\u2019t remember Kinsella\\u2019s name, referring to him as \\u201Cthat guy on the board who put in the least money.\\u201D\"), mdx(ContentRef, {\n    id: 35,\n    mdxType: \"ContentRef\"\n  }, \"Knowles, who had seen Boger this way ever since he was in graduate school, demurred in his call to Boger, \\u201CPerhaps I\\u2019d better be out of town for a few weeks.\\u201D\"), mdx(ContentRef, {\n    id: 36,\n    mdxType: \"ContentRef\"\n  }, \"Boger popped into the lunchroom. Ever since he\\u2019d started Vertex, he\\u2019d intended the area to be like his kitchen when he was growing up, a hub. It was here that the scientists, each reeling in his own orbit, took their pit stops. Scarfing some Ritz crackers and a juice, standing as always, Boger sidled toward Yamashita, who sat picking through the \", mdx(\"i\", null, \"Times\"), \". Towering benignly, he told him the price of the chair he\\u2019d smashed was $280 and that it would be deducted from his paycheck.\"), mdx(ContentRef, {\n    id: 37,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWhen I was a kid, each of my brothers and I had a spitting tree,\\u201D Boger said. \\u201CWhen we were really mad, we could spit. I used to slime that tree all the time.\\u201D\"), mdx(ContentRef, {\n    id: 38,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI like to physically destroy metal,\\u201D Yamashita said.\"), mdx(ContentRef, {\n    id: 39,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CYou\\u2019re too high-tech.\\u201D\"), mdx(ContentRef, {\n    id: 40,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CMaybe. My lab chief in graduate school gave me an old terminal and a sledge hammer to smash it with,\\u201D Yamashita said. \\u201CIt was wonderful.\\u201D\"), mdx(ContentRef, {\n    id: 41,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CYou look relaxed now.\\u201D\"), mdx(ContentRef, {\n    id: 42,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CAnd I didn\\u2019t even have to destroy anything.\\u201D\"), mdx(ContentRef, {\n    id: 43,\n    mdxType: \"ContentRef\"\n  }, \"It was a loose, giddy moment, the first between them in weeks, and Yamashita seemed relieved to be able to joke about the violence that had only recently threatened to consume him. Indeed, nothing now was taboo. When Navia came over to congratulate him on his refinement, saying \\u201CThese geometries are fabulous,\\u201D Yamshita replied, \\u201COr a fabrication.\\u201D\"), mdx(ContentRef, {\n    id: 44,\n    mdxType: \"ContentRef\"\n  }, \"With Boger providing the emotional cues, there followed an outbreak of verbal riffing that culminated, inevitably, with a mass skewering of Schreiber. The structure of FKBP-12, though it had been solved by Schreiber\\u2019s and Karplus\\u2019s graduate students and by Clardy\\u2019s group at Cornell, was clearly going to be Schreiber\\u2019s moment. By the rights and rules of science\\u2014credit accrues upward to the senior investigator; initiating an idea counts more than proving it\\u2014even the X-ray structure, which Schreiber had contributed to \", mdx(\"a\", {\n    id: \"page_328\"\n  }), \"mostly by providing protein and synthesizing heavy-atom derivatives, was likely to be known as \\u201CSchreiber\\u2019s structure.\\u201D His string of path-breaking discoveries with FK-506 remained unbroken, and his crossover into biology was progressing even better than he\\u2019d hoped. And yet on the day of perhaps his most notable achievement, he was about to find himself sharing honors with an upstart company that had ingloriously fired him eight months earlier, a place where he was reviled. The scientists loved it, though clearly not as much as Boger and Aldrich, who gloated radiantly.\"), mdx(ContentRef, {\n    id: 45,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CImagine Stu-Bob [Boger\\u2019s and Aldrich\\u2019s name for Schreiber] driving down Storrow Drive in his Porsche on his way to Harvard, hearing it on National Public Radio,\\u201D Aldrich said. \\u201CHe\\u2019ll wrap it around a tree.\\u201D\"), mdx(ContentRef, {\n    id: 46,\n    mdxType: \"ContentRef\"\n  }, \"Navia picked up the theme. Humming the familiar introduction to \\u201CAll Things Considered,\\u201D he pretended to be driving self-satisfiedly. Suddenly his face contorted: \\u201CScreeech! Craaash!\\u201D\"), mdx(ContentRef, {\n    id: 47,\n    mdxType: \"ContentRef\"\n  }, \"Only Thomson refused to join in. Sitting away from the group, glowering at Navia\\u2019s clowning, Thomson nursed his conjunctivitis and a painful upper body rash that afflicted him during long sieges of cutting tissue and washing glassware. \\u201CNobody appreciates what we have to go through,\\u201D he said. \\u201CA lot of unpleasant, up-to-our-armpits-in-slop work that\\u2019s caused a lot of ailments [he pronounced it \\u201CI\\u2019ll-ments\\u201D] that if we were in an industrial setting would qualify us for workman\\u2019s comp. For every one hundred milligrams of protein we produce, we have to process a fifty-five-gallon drum\\u2019s worth of phosphylated thymus juice with a lot of nasties in it in one-pint chloroform jars. But we do it.\"), mdx(ContentRef, {\n    id: 48,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI\\u2019d like to know,\\u201D he muttered, \\u201Cwhat some of the others do.\\u201D\"), mdx(ContentRef, {\n    id: 49,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 50,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CJosh and I don\\u2019t want to be quoted,\\u201D Aldrich told the disembodied voice of Vertex\\u2019s PR man on the speaker phone in his office. \\u201CNothing about billion-dollar drugs. When calls come in, if they ask for me, the front desk is going to say I\\u2019m unavailable. If they ask for a scientist,\\u201D he nodded to Moore, who had been corralled for the briefing, \\u201Cit\\u2019ll kick over to you.\\u201D\"), mdx(ContentRef, {\n    id: 51,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich wasn\\u2019t opposed to exaggerating claims on principle, but he knew that Vertex had to be exceedingly careful about how it \", mdx(\"a\", {\n    id: \"page_329\"\n  }), \"handled press inquiries about Moore\\u2019s paper. Moore sensed his caution. Though he thought the rehearsal unnecessary and disdained being coached by a PR person whom he couldn\\u2019t see, he was eager to cooperate. Like a rookie pitcher in his first outing, he thought he\\u2019d play it safe. \\u201CI\\u2019ll just say it\\u2019s an important step,\\u201D he volunteered.\"), mdx(ContentRef, {\n    id: 52,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CFacts, not suppositions,\\u201D Aldrich advised. \\u201CYou can say something like, \\u2018This is an important step, but it\\u2019ll be several years before there are drugs to show from it.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 53,\n    mdxType: \"ContentRef\"\n  }, \"The PR man counseled, \\u201CYou don\\u2019t want to be in the position, Jon, of saying \\u2018No, no, no. I can\\u2019t answer that.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 54,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI could just tell them research itself is never patentable.\\u201D\"), mdx(ContentRef, {\n    id: 55,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CYou don\\u2019t want to say that,\\u201D Aldrich interrupted, joking. \\u201CYou never know what we may want to patent around here.\\u201D\"), mdx(ContentRef, {\n    id: 56,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich and Nancy Stuart had prepared a backgrounder, explaining the importance of Moore\\u2019s discovery and answering hypothetical questions. The PR man complimented them and, as was his job, intimated great things.\"), mdx(ContentRef, {\n    id: 57,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWe\\u2019re going to put it on the wire so everyone and his grandmother will know about this,\\u201D he said.\"), mdx(ContentRef, {\n    id: 58,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThat\\u2019s OK with us,\\u201D Nancy Stuart said, smiling. Aldrich rubbed his chin thoughtfully. Moore tried not to roll his eyes.\"), mdx(ContentRef, {\n    id: 59,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 60,\n    mdxType: \"ContentRef\"\n  }, \"Sitting next to Navia in the X-ray lab at around 7:30 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"P.M\"), \"., Yamashita hastily concluded that the solution to the authorship problem was to remove his own name from the paper. Quickly, he reconsidered. \\u201CCamus says it\\u2019s stupid to try to make a point to the world by committing suicide,\\u201D he said. \\u201CIn a likewise fashion, if they give me first authorship and even if I might feel very strongly I shouldn\\u2019t take it because other people are being screwed, does it help for me to say no?\"), mdx(ContentRef, {\n    id: 61,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI may be unexpectedly ill tomorrow.\\u201D\"), mdx(ContentRef, {\n    id: 62,\n    mdxType: \"ContentRef\"\n  }, \"Navia leaned over from his microscope. \\u201COne of these moments,\\u201D he said, \\u201Cwhen you get a chance, I\\u2019d like you to see what a spectacular job you did.\\u201D\"), mdx(ContentRef, {\n    id: 63,\n    mdxType: \"ContentRef\"\n  }, \"He was scanning Yamashita\\u2019s cocrystallization attempts with 367, not those from that afternoon, but others from earlier in the week. \", mdx(\"a\", {\n    id: \"page_330\"\n  }), \"In several of the wells, he saw incipient needlelike crystals growing in clear formation. Unlike a year ago, when Yamashita\\u2019s first putative crystals of FKBP turned out to be salts, Navia had no doubt these were protein.\"), mdx(ContentRef, {\n    id: 64,\n    mdxType: \"ContentRef\"\n  }, \"\\u201COh, man. That\\u2019s crystalline.\\u201D\"), mdx(ContentRef, {\n    id: 65,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CDo you think so?\\u201D Yamashita said, tempering himself. \\u201CWe\\u2019ll see tomorrow.\\u201D\"), mdx(ContentRef, {\n    id: 66,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CNo, Mason, I think you\\u2019ve got it.\\u201D\"), mdx(ContentRef, {\n    id: 67,\n    mdxType: \"ContentRef\"\n  }, \"Slapping Yamashita on the back, Navia left to rejoin the paper-writing effort. Obliterating all further thoughts of martyrdom, Yamashita shrugged.\"), mdx(ContentRef, {\n    id: 68,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThat\\u2019s the way life goes,\\u201D he sighed. \\u201CI\\u2019ve learned from being here, you just find the next experiment to do. That\\u2019s what keeps us from destroying ourselves.\\u201D\"), mdx(ContentRef, {\n    id: 69,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 70,\n    mdxType: \"ContentRef\"\n  }, \"Boger charged from his office a half hour later with a first draft of the \", mdx(\"i\", null, \"Nature\"), \" abstract. A summation of no more than one hundred words, it was the most critical part of the paper, the \\u201Ctake-home message\\u201D most readers would scan as they foraged through the journal. Boger, who\\u2019d taken several stabs at it while Navia updated the text, handed it to Navia without a word.\"), mdx(ContentRef, {\n    id: 71,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CHow far do we want to put out our necks?\\u201D Navia asked.\"), mdx(ContentRef, {\n    id: 72,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWhat \\u2018we,\\u2019 Kemo Sabe?\\u201D Boger said. It was yet to be decided whether Boger\\u2019s name would appear on the paper, though as a general rule, he, like Tishler, opposed being named except in those cases where he\\u2019d made a direct contribution. He was less interested in his r\\xE9sum\\xE9 than in the larger prize of producing a drug. Credit, he thought, was the prerogative of those who did the hard intellectual work of eliciting data, not those who simply set it in motion or interpreted it comfortably afterward. A chemist, he applied the chemist\\u2019s restrictive code for deciding whose name to put on a patent; either you drew the cartoon or you made the molecule. Everything else was superfluous.\"), mdx(ContentRef, {\n    id: 73,\n    mdxType: \"ContentRef\"\n  }, \"It was after 9:30 when he, Murcko, and Navia stopped to eat. Tearing into containers of pan-fried dumplings, pan-fried vegetables, and egg rolls, they ripped with equal ferocity into the draft. It was the first Boger had eaten all day.\"), mdx(ContentRef, {\n    id: 74,\n    mdxType: \"ContentRef\"\n  }, mdx(\"a\", {\n    id: \"page_331\"\n  }), \"\\u201CHere\\u2019s what I\\u2019m after,\\u201D he said, legs swirled, pinching a dumpling with his chopsticks, stabbing the air for emphasis. \\u201CStuart already owns the binding domain, effector region hypothesis, but I don\\u2019t hear any enthusiasm around here for that hypothesis. I think the answer is going to be that something about it is right, but that it\\u2019s not enough. I want us to stake out the alternative hypothesis. I want us to put forward the last great hope of biological explanations, a hypothesis through which you may be able to drive a truck-train later on but that stakes out new ground now.\\u201D\"), mdx(ContentRef, {\n    id: 75,\n    mdxType: \"ContentRef\"\n  }, \"Navia told him about Murcko\\u2019s latest simulations in which he\\u2019d modeled one of Vertex\\u2019s best inhibitors into the enzyme\\u2019s active site. \\u201CIt may be too small,\\u201D he said. \\u201CThe flap may be coming in and crushing it. We need a doorstop for the flap.\\u201D\"), mdx(ContentRef, {\n    id: 76,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CA molecular doorstop,\\u201D Boger said tantalizingly, as if finding the light switch in a dark room. \\u201CIt\\u2019s a larger hypothesis than Stuart\\u2019s, but entirely consistent with it. Not only do you need an extended effector region, but you\\u2019ve got to hold the flap open just so.\\u201D In other words, Boger speculated, it was not just the atoms that stuck from the bound conformation like a gaff that accounted for FK-506\\u2019s biological activity, but the way that those atoms changed the outer shape of the protein, like a tongue pressing hard inside a cheek. It could be a critical observation for drug design as well as a direct challenge to Schreiber, and Boger, pleased, was comfortable with asserting it, even though Vertex hadn\\u2019t proven it.\"), mdx(ContentRef, {\n    id: 77,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThe sin in science is not making mistakes,\\u201D he said, hungrily spooning out more vegetables for himself. \\u201CIt\\u2019s overinterpreting your data. If you\\u2019re disproved by a massive amount of new data, that\\u2019s fine. What you don\\u2019t want to be is disproven by a little more data. That means you went almost but not far enough.\\u201D\"), mdx(ContentRef, {\n    id: 78,\n    mdxType: \"ContentRef\"\n  }, \"Abandoning the mess in the lunchroom, Boger, Navia, and Murcko returned to their computers to justify their latest observation. With fourteen hours to go, they would do the next set of experiments.\"), mdx(ContentRef, {\n    id: 79,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThis is really enjoyable,\\u201D Murcko said, knowing he would now be working through the night and right up to the next day\\u2019s deadline, scrambling to produce simulated data to support a speculative theory that had been hatched spontaneously just moments before, \\u201Cin a perverse sort of way.\\u201D\"), mdx(ContentRef, {\n    id: 80,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 81,\n    mdxType: \"ContentRef\"\n  }, mdx(\"a\", {\n    id: \"page_332\"\n  }), \"In the chemistry lab, Roger Tung and Dave Deininger labored against less theoretical constraints. For weeks they had been working most nights until midnight, trying to make new molecules to inhibit HIV protease. Unable to sell the AIDS project in Japan, Boger had also been unable to expand it, and Tung and Deininger had chiefly borne the consequences. The company had now poured $2 million out of capital into HIV research, and the project was foundering in a kind of catch-22: They couldn\\u2019t move ahead without more resources, and they couldn\\u2019t recruit more resources without more progress. Tung, exhausted, was especially anxious and irate.\"), mdx(ContentRef, {\n    id: 82,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWe don\\u2019t have a singular strategy. We don\\u2019t have enzyme. We don\\u2019t have crystals. We don\\u2019t even have structure activity at this point,\\u201D he said. \\u201CI\\u2019ve been sitting here saying \\u2018Lord take me now. Let me open my veins.\\u2019\"), mdx(ContentRef, {\n    id: 83,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWe\\u2019re banking that by incorporating some of the changes that other companies have used we\\u2019ll be able to improve the overall biological activity of our molecules, but it\\u2019s idiosyncratic. It changes from compound to compound. Mixing horses and donkeys doesn\\u2019t necessarily get you mules.\\u201D\"), mdx(ContentRef, {\n    id: 84,\n    mdxType: \"ContentRef\"\n  }, \"If anything, Tung knew, the decision to go public would now increase the pressure. Immersed so thoroughly in his own work that he had not seen or talked with most of the other scientists in weeks, he was only dimly aware of how the requirements of doing business had come to dominate science elsewhere in the company. But he knew precisely the effect it was going to have on him and Deininger. They were going to have to produce with a late start and a fraction of the number of chemists engaged at Merck and elsewhere what no other company had been able to make: a convincing case that it was close to having a pill to help cure AIDS. To Tung, the very notion was an affront to science.\"), mdx(ContentRef, {\n    id: 85,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWe\\u2019re in a situation where we can\\u2019t afford to make mistakes,\\u201D he moaned. \\u201CIt\\u2019s terribly foolish.\\u201D\"), mdx(ContentRef, {\n    id: 86,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 87,\n    mdxType: \"ContentRef\"\n  }, \"At 2 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \". Navia, exhausted, again fell asleep in his chair. Boger woke him and told him to go home, then edited the manuscript \", mdx(\"a\", {\n    id: \"page_333\"\n  }), \"himself until 5 before driving to Concord, showering, and grabbing a quick breakfast with Amy and the boys. He was back at his desk at 7:30. It was now Thursday morning, the day of the \", mdx(\"i\", null, \"Nature\"), \" deadline. Murcko, who\\u2019d gotten home at 4, was at his computer screen by 8. For a year, he\\u2019d tried to be careful about what he ate, but now he was chugging Diet Pepsi and scarfing the gnarled crumbs from a Dunkin\\u2019 Donuts box. The room was littered with empty potato chip bags and pizza boxes. Murcko\\u2019s briefcase, his floating office, overflowed at his elbow with paperwork\\u2014purchase orders, articles he\\u2019d been reviewing, candidate\\u2019s r\\xE9sum\\xE9s.\"), mdx(ContentRef, {\n    id: 88,\n    mdxType: \"ContentRef\"\n  }, \"To test his hypothesis about the flap and to begin designing new drugs, Murcko modeled several inhibitors into Yamashita\\u2019s finished structure. Boger wandered in, joined by some of the chemists. Collectively, they donned 3-D glasses and speculated on the molecular doorstop theory, whether what they were seeing was real, and what it might suggest.\"), mdx(ContentRef, {\n    id: 89,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIt\\u2019s reaching in the dark,\\u201D John Duffy, a bluff, red-headed chemist, said, looking at a tiny affector region sticking out from the wheel of the protein like a twig from a burl.\"), mdx(ContentRef, {\n    id: 90,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThere\\u2019s not enough stuff out there to do what Stuart says,\\u201D Boger agreed. \\u201CSomething else has to occur. But our bigger problem is we need a factor of one hundred in activity. We need a break, a bunt single, something as dramatic as the first semaphor.\\u201D The semaphor, a two-pronged subunit grafted onto the core of FK-506 like a miniature dousing stick, had been Vertex\\u2019s first major success in chemistry, making its molecules as potent as cyclosporine.\"), mdx(ContentRef, {\n    id: 91,\n    mdxType: \"ContentRef\"\n  }, \"The scientists began suggesting several ways to mimic FK-506, but Boger bluntly waved them off. \\u201CNature didn\\u2019t design FK too exquisitely,\\u201D he said. \\u201CThis is a molecule that lucked into a use. We shouldn\\u2019t be too anal about mimicking it.\\u201D\"), mdx(ContentRef, {\n    id: 92,\n    mdxType: \"ContentRef\"\n  }, \"Murcko, taking the cue, disentangled an inhibitor from the protein and spun it around, breaking several crucial atomic bonds. \\u201CThis is kind of extreme,\\u201D he said, looking up from his keyboard. \\u201CDon\\u2019t try this at home.\\u201D\"), mdx(ContentRef, {\n    id: 93,\n    mdxType: \"ContentRef\"\n  }, \"The others laughed. The process of discovery at Vertex, as collaborative as it was meant to be, had a way of shifting the pressure from one scientist to another, like a relay. It was now Murcko\\u2019s \", mdx(\"a\", {\n    id: \"page_334\"\n  }), \"turn, and he was mindful of how the experience had scalded Thomson, Moore, and Yamashita before him. Boger left, then Duffy, then the others, until just he and Yamashita were left staring into the reflective darkness of their screens.\"), mdx(ContentRef, {\n    id: 94,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CVertex is entirely driven by hubris,\\u201D Murcko muttered, half admiringly, half filled with free-floating dread. \\u201CWe have no reason to expect that we can win, but we refuse to think anything else.\\u201D\"), mdx(ContentRef, {\n    id: 95,\n    mdxType: \"ContentRef\"\n  }, \"He was still uneasy about how speculative his work was, more so now that the company was depending heavily on him for its next critical breakthrough, now that its competition was no longer Schreiber but Merck. And yet he needed data. To do serious calculations he needed the coordinates for pinpointing exactly where and how FK-506 bound to FKBP-12\\u2014coordinates for which, at the moment, there was only one source: Schreiber and his collaborators. The previous Saturday Murcko had driven to Yale to hear Schreiber. Afterward, Schreiber told him he planned to release the coordinates as soon as his paper was published. Unhesitantly, Murcko called him now. The orgy of posturing, of Schreiber-bashing, was one thing, but this was science. Cordial as ever, Schreiber promised him the information.\"), mdx(ContentRef, {\n    id: 96,\n    mdxType: \"ContentRef\"\n  }, \"Murcko marveled: \\u201CStuart\\u2019s really, really good at extracting what he wants from people and dumping them, which is what a lot of people say about Joshua.\\u201D\"), mdx(ContentRef, {\n    id: 97,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 98,\n    mdxType: \"ContentRef\"\n  }, \"At 11 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \"., after a final strategy session with Boger, Navia, Murcko, and Yamashita, and with the deadline less than an hour away, the X-ray paper was finally done. Moore had taken a couple of calls from the press, but the center of activity had shifted\\u2014and held\\u2014with the crystallographers. They had made their deadline. Working together, Yamashita and Navia had accomplished what they\\u2019d been unable to do apart. The emotional storm of two weeks ago had dissipated, replaced by an uneasy calm.\"), mdx(ContentRef, {\n    id: 99,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CSupervising someone else is like sailing a good boat,\\u201D Navia reflected. \\u201CEverything\\u2019s perfectly aligned. The sails are well trimmed, and all you occasionally have to do is gently touch the rudder to steer. With Mason, I\\u2019ve had to have my hand on the rudder full-time.\\u201D\"), mdx(ContentRef, {\n    id: 100,\n    mdxType: \"ContentRef\"\n  }, mdx(\"a\", {\n    id: \"page_335\"\n  }), \"In another room Yamashita murmered bitterly, \\u201CManuel is a compromised man.\\u201D\"), mdx(ContentRef, {\n    id: 101,\n    mdxType: \"ContentRef\"\n  }, \"Yamashita spent the morning agonizing over whom to name as authors. At 11:30, he, Navia, and Murcko wedged themselves uneasily into one of two small private writing rooms off the lunchroom to discuss the matter for the last time. The rooms, barely large enough for a desk, a computer, and a chair, were a concession by Boger to the scientists, a quiet place to think outside the relentlessly public channels of his social experiment. The scientists called them the \\u201Cdomes of science.\\u201D\"), mdx(ContentRef, {\n    id: 102,\n    mdxType: \"ContentRef\"\n  }, \"Determined to salvage a shred of idealism from the ruins of his experience with the manuscript, Yamashita had decided to make the decision employing \\u201Cpure logic, even if we were obliterated by it.\\u201D Rationally, that meant naming fewer authors rather than more as he\\u2019d previously tried. He now agreed with Boger that the struggle for credit that had erupted so venomously with his original draft of the paper was tearing the company apart and that it was in Vertex\\u2019s best interest\\u2014in the best interest of science\\u2014to downplay such disputes by keeping the number of authors to a bare minimum, perhaps just those two or three who had done the actual work described in the manuscript. In the credit-driven world of academic science, there was an increasing tendency to include all those who, like one\\u2019s collaborators, had done other work that had paved the way for a discovery or, like one\\u2019s graduate students and postdocs, needed it for their r\\xE9sum\\xE9s. Boger despised the practice as inflationary and dishonest, and Yamashita now agreed. Coming 180 degrees, he suggested in the dome of silence naming just himself, Navia, and Murcko.\"), mdx(ContentRef, {\n    id: 103,\n    mdxType: \"ContentRef\"\n  }, \"It was a martyr\\u2019s position, the most treacherous for Yamashita personally. Thomson and Moore would be\\u2014deservedly, Yamashita thought\\u2014furious. Moreover, he would look like a credit monger, though that wasn\\u2019t his intent. Distraught once again at doing what he had deduced logically to be the right thing, he had already gone to Boger that morning to tell him of the decision, and Boger, anxious to have the scientists put aside their lust for credit, had promised to support him against the inevitable firestorm. Navia, too, now agreed with him. Only Murcko, hoping to lift some of the tension, balked. Telling Yamashita that he hadn\\u2019t done enough to \", mdx(\"a\", {\n    id: \"page_336\"\n  }), \"warrant credit, he asked him to take his name off of the paper, too.\"), mdx(ContentRef, {\n    id: 104,\n    mdxType: \"ContentRef\"\n  }, \"Thus it was decided. Vertex would set an austere precedent on authorship, striking a blow against fatuous self-interest in research. The X-ray paper would bear just the names of the crystallographers, Yamashita and Navia.\"), mdx(ContentRef, {\n    id: 105,\n    mdxType: \"ContentRef\"\n  }, \"However, what\\u2019s logical isn\\u2019t always practical, and Boger had designed Vertex above all else to work. Abhorring an anticlimax, he suddenly peeked in, uninvited, yet as if on cue. \\u201CI\\u2019ve changed my mind,\\u201D he said. He told them he now favored crediting all those whose contributions, though not described centrally in the paper, were nonetheless vital. He urged Yamashita to reinstate Thomson, Fitzgibbon, and Moore. Smiling, he ducked out as swiftly and provocatively as he\\u2019d entered.\"), mdx(ContentRef, {\n    id: 106,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWe were flabbergasted,\\u201D Yamashita would recall. \\u201CShocked beyond belief. He said that under the rules of pure logic, it may have been wise for us to confront the problem of authorship now, once and for all. It was probably wiser to sacrifice me rather than to compromise. But he said he understood my pain and Manuel\\u2019s pain and Mark\\u2019s pain and that the issue wasn\\u2019t worth hurting us any more than it already had. He said he\\u2019d made a mistake by not letting John publish right away. If he had, he said, the whole question of whether John should be credited on the structure paper would have been a non-issue.\\u201D\"), mdx(ContentRef, {\n    id: 107,\n    mdxType: \"ContentRef\"\n  }, \"Boger\\u2019s reversal settled the matter, saving Yamashita from all further attempts at self-immolation. At 11:55, Boger faxed the X-ray paper to \", mdx(\"i\", null, \"Nature\"), \", feeding the pages into the machine himself. Titled \\u201CX-Ray Structure of the Major Binding Protein for the Immunosuppressant FK-506, Solved by Molecular Replacement Using a Structural Fragment Derived from an NMR Study,\\u201D it listed as authors Yamashita, Murcko, Boger, Moore, Thomson, Fitzgibbon, and Navia, in that order. Thomson and Moore agreed to be named as coauthors, though in the rush to get the paper out, neither of them saw it before it went. Miffed and annoyed, they refused to share in the overall rejoicing.\"), mdx(ContentRef, {\n    id: 108,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 109,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CWhat\\u2019s a Judas goat?\\u201D Yamashita asked.\"), mdx(ContentRef, {\n    id: 110,\n    mdxType: \"ContentRef\"\n  }, \"He, Navia, and Murcko were still scrambling late that afternoon \", mdx(\"a\", {\n    id: \"page_337\"\n  }), \"to assemble photographs and diagrams in order to FedEx them to \", mdx(\"i\", null, \"Nature\"), \" by 5. The air was aflurry with self-congratulation, forgiveness, the telling back and forth of small lies meant, like an antiseptic, both to sting and heal.\"), mdx(ContentRef, {\n    id: 111,\n    mdxType: \"ContentRef\"\n  }, \"Navia, wolfing a sub and scrambling to make a 6 o\\u2019clock flight to St. Louis, where he was due\\u2014another of his sidelines\\u2014to direct an NIH site visit, explained that it was a goat kept by stockyards to lure other goats to slaughter. A professional traitor, he said. The worst kind.\"), mdx(ContentRef, {\n    id: 112,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CLet\\u2019s stop playing head games with Mason,\\u201D Murcko laughed, pausing. \\u201CAs long as Mason stops playing head games with us.\\u201D\"), mdx(ContentRef, {\n    id: 113,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI don\\u2019t want to,\\u201D Yamashita said. \\u201CHow about Judas chickens? Judas cows? Judas\\xA0.\\xA0.\\xA0.\\u201D\"), mdx(ContentRef, {\n    id: 114,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CMason is totally awesome,\\u201D Murcko said.\"), mdx(ContentRef, {\n    id: 115,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI\\u2019ve been saying that since the day he got here,\\u201D Navia said.\"), mdx(ContentRef, {\n    id: 116,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CHis total awesomeness,\\u201D Murcko exulted, \\u201Cis exceeded only by his modesty.\\u201D\"), mdx(ContentRef, {\n    id: 117,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 118,\n    mdxType: \"ContentRef\"\n  }, \"If Boger\\u2019s ability to set improbable goals and then meet them, seemingly against all odds, had not impressed the scientists before, it did now. He had steered the company all week through the sloppy conflation of business and science without so much as getting wet. Now, Friday, was to be his\\u2014and their\\u2014reward.\"), mdx(ContentRef, {\n    id: 119,\n    mdxType: \"ContentRef\"\n  }, \"The media blitz had worked to perfection. The \", mdx(\"i\", null, \"Wall Street Journal\"), \"\\u2014the only paper that really mattered now, given Vertex\\u2019s intention to go public\\u2014reported the discovery of the structure in that morning\\u2019s paper as an unambiguous three-way tie between Schreiber (in collaboration with Karplus), Clardy (also with Schreiber), and Vertex. \\u201CThree teams of scientists reported they had uncovered a key molecular secret of a powerful drug that suppresses the immune system,\\u201D the \", mdx(\"i\", null, \"Journal\"), \" reported prominently on the front page of the second section. Though Schreiber and Karplus were mentioned first, Vertex, being the only business, was identified in boldface, according to the \", mdx(\"i\", null, \"Journal\"), \"\\u2019s standard, busy-executives-don\\u2019t-have-time-to-read concession to its readers. Investors looking for an item for their tickler files might not understand the importance of the discovery, but they now had a new name to associate \", mdx(\"a\", {\n    id: \"page_338\"\n  }), \"with the \\u201Cmultibillion-dollar market\\u201D for new drugs prophesied by Clardy. Of the other papers reporting the story, only the partisan \", mdx(\"i\", null, \"Harvard Gazette\"), \" failed to mention Vertex prominently.\"), mdx(ContentRef, {\n    id: 120,\n    mdxType: \"ContentRef\"\n  }, \"Schreiber, as Boger had hoped and predicted, was stunned. Recalling his conversation with Moore in late January, which left him, he said, \\u201Cwith the strong sense that they were miles away from having the structure,\\u201D he\\u2019d also forgotten Moore\\u2019s name, the younger, more junior Moore having joined the company after Schreiber became persona non grata and was no longer around. Schreiber had known for weeks that \", mdx(\"i\", null, \"Nature\"), \" would be reporting a tie, had even heard reference to \\u201CMoore et al.,\\u201D but had failed to make the connection. \\u201CNo, I was real surprised,\\u201D he would later say, shaking his head.\"), mdx(ContentRef, {\n    id: 121,\n    mdxType: \"ContentRef\"\n  }, \"What the confluence of papers most provided and what was practically forgotten in the stampede to get Vertex\\u2019s out the door was affirmation. The ultimate test of whether a molecular structure is right, because it can\\u2019t be seen even with the most powerful electron microscope, is whether other researchers, working independently, can duplicate it. That Moore\\u2019s and Schreiber\\u2019s NMR structures were practically identical and varied only slightly from Clardy\\u2019s X-ray structure certified that they were probably both correct. Moore, especially, was relieved: Seeing a preprint of Schrieber\\u2019s paper on Thursday, he had exaggeratedly crossed himself. He knew that the differences with Clardy were probably due to the presence of FK-506 in Clardy\\u2019s structure. Much more troublesome was the fact that Yamashita\\u2019s structure still varied from the other three in several key respects, particularly in the flexibility of the flap. None of the others had the flap swinging so freely. In the general euphoria, the differences between Moore\\u2019s and Yamashita\\u2019s structures were overlooked, but in private neither of them could release himself entirely from a deep sense of foreboding, of irreconcilability. The idea of a molecular doorstop depended wholly and utterly on the leniency in Yamashita\\u2019s structure. Something had to give.\"), mdx(ContentRef, {\n    id: 122,\n    mdxType: \"ContentRef\"\n  }, \"In the scientific community, eyebrows were raised about the latest example of what had become a suspect phenomenon: joint announcements of apparent ties. Under the subhead, \\u201CRace to Publish Results,\\u201D the \", mdx(\"i\", null, \"Journal\"), \" noted \", mdx(\"i\", null, \"Nature\"), \"\\u2019s decision to break its \", mdx(\"a\", {\n    id: \"page_339\"\n  }), \"news embargo. And in \", mdx(\"i\", null, \"Nature\"), \"\\u2019s News and Views, Dagmar Ringe, a crystallographer at Brandeis University, wrote scathingly that interest in immunophilins had invited a \\u201Cplague\\u201D of publications about them. \\u201CMore collaboration and less competition in this field would be a damn good thing,\\u201D she wrote. For those who worried that biomedicine was being corrupted by blind competition; that in the race to publish, papers were being indiscriminately reviewed or, in certain instances, not reviewed at all; that publicizing discoveries in the media before they had been evaluated by other researchers led to errors, distortion, and fraud; that the need for businesses and academics alike to capitalize on their discoveries created an environment where meaningless redundancy was valued over rigor and innovation, there was now a new case to cite. Not surprisingly, Vertex, as the private entity in the affair, was hoised widely as the black hat.\"), mdx(ContentRef, {\n    id: 123,\n    mdxType: \"ContentRef\"\n  }, \"Boger, of course, had no such qualms. His purposes were clear, and now that he achieved them, he was on to the next siege: going public. He, Aldrich, and Nancy Stuart left Vertex early Friday morning for Warner and Stackpole, the downtown Boston law firm where Ken was a senior partner and which had become a redoubt for Kidder and its lawyers, up from New York. The firm was in one of several overbuilt, underleased, marble-heavy holdovers from the construction boom of the mid- to late 1980s, though the firm itself was prospering. With its ovoid suite of offices encircling a postmodern rotunda, it was the antithesis of Vertex: polished, subdued, conspicuously stylish\\u2014old money with a new sheen.\"), mdx(ContentRef, {\n    id: 124,\n    mdxType: \"ContentRef\"\n  }, \"The central question of offering stock in a company is how to value it. With an established business\\u2014one that makes money\\u2014the process is relatively direct: The underwriter simply mulitiplies earnings by some number reflecting the company\\u2019s performance, then divides by the number of shares. With small, unprofitable companies years from having their first product, however, valuation is more mysterious. It depends on an amalgam of assumptions and guesses: When will the company start turning a profit? How much will it make? For how long? What rate of return will investors require, given what they can expect to earn elsewhere? With emerging biomedical companies like Vertex, the questions are particularly elusive. The FDA, not the company, determines \", mdx(\"a\", {\n    id: \"page_340\"\n  }), \"when it can market a new product; a company may find out it has nothing to sell only after years of costly development. There are patent infringements, unanticipated shifts in technology, endless questions of product safety. The odds overwhelmingly favor complete, unutterable failure. Still, underwriters try, and the companies do all they can to help them, to put a value on these companies, using formulas and ratios and other more or less empirical measures of things that, like the objects of much scientific study, can\\u2019t be seen and may be unknowable.\"), mdx(ContentRef, {\n    id: 125,\n    mdxType: \"ContentRef\"\n  }, \"Boger had long since made his pact with these vagaries, but Kidder now wanted separate confirmation. It wanted to see, as Holman had put it, \\u201Cif Josh was for real.\\u201D Thus the task fell to others: chiefly Nancy Stuart as well as the scientists, who, dressed for the occasion, drove over from Vertex in shifts and cycled in and out of Warner and Stackpole\\u2019s conference room like witnesses before a grand jury.\"), mdx(ContentRef, {\n    id: 126,\n    mdxType: \"ContentRef\"\n  }, \"The lone woman in a roomful of men, Stuart led deftly through Vertex\\u2019s timelines for making money. The company, she said, expected to identify a new immunosuppressant by the end of the year, launch clinical tests by early 1993, and begin marketing a drug in 1997\\u2014some six years away. With HIV, she offered an even more aggressive timeline: identification of a lead molecule by late summer, a drug in clinic the end of 1992, income in 1995. It was a spectacular claim: an AIDS drug ready and available for testing in people in just over eighteen months, profits in less than four years. Stuart tried ably to defend it. Vertex now had novel compounds that were active against HIV in cells, she told the lawyers. It had contracted with a California company to test them by midsummer in a new breed of genetically engineered laboratory mice that had most of the components of a human immune system and were infected with HIV. If the compounds worked, Vertex would be able to short-circuit the normal preclinical schedule and go directly into primates. Like Merck, it would then launch European clinical trials while compiling data for the FDA, which was desperate for new AIDS drugs and was pushing ahead furiously anything that looked the least bit promising.\"), mdx(ContentRef, {\n    id: 127,\n    mdxType: \"ContentRef\"\n  }, \"Stuart worried that the Kidder men would consider the story too \", mdx(\"a\", {\n    id: \"page_341\"\n  }), \"speculative, too filled with holes, too pat. \\u201CPeople have heard this a hundred times before: new technology, bright people. \\u2018Yeah, yeah,\\u2019\\xA0\\u201D she interrupted herself, speaking afterward, \\u201C\\xA0\\u2018so tell us about your clinical candidate.\\u2019\\xA0\\u201D But Kidder was impressed. The biggest worry about small biomedical companies was that they would go on hemorrhaging money forever, but Vertex was obviously determined to make money soon. Indeed, it was the main reason it had ultimately gone into AIDS. True, dozens of other companies were fast-tracking potential AIDS drugs for entirely the same reason, but once again Holman found Vertex\\u2019s story exceptional.\"), mdx(ContentRef, {\n    id: 128,\n    mdxType: \"ContentRef\"\n  }, \"The scientists, on the other hand, were haunted. To make public their aggressive timelines simply added to their stress. \\u201CThe HIV project is stretched outrageously thin,\\u201D Tung complained. \\u201CWhat concerns me is that even in the most optimistic scenario, we may not be able to do what we\\u2019ve said we\\u2019re going to do. It would be hard enough if we were fully staffed, but I don\\u2019t see that happening now. We\\u2019re running a lot more on luck than skill and that worries me. It worries me a lot.\\u201D\"), mdx(ContentRef, {\n    id: 129,\n    mdxType: \"ContentRef\"\n  }, \"Murcko, who also was interviewed, was even more outraged. He was disgusted by the intrusion. Yanking off his tie as he returned to the modeling room, he snapped: \\u201CA $500 lunch for fifteen people, and they billed us for every Coke we ordered.\\u201D\"), mdx(ContentRef, {\n    id: 130,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 131,\n    mdxType: \"ContentRef\"\n  }, \"Back and forth between the real world of scientific speculation and the illusory one of Wall Street Boger and the scientists swung. At noon, while Boger, Murcko, and Navia were lunching at Warner and Stackpole, a fax arrived from \", mdx(\"i\", null, \"Nature\"), \". It said that in light of the similar X-ray structure of FKBP-12 appearing in that day\\u2019s issue of \", mdx(\"i\", null, \"Science\"), \", the journal had decided not to send Vertex\\u2019s manuscript out for review. Yamashita, reading it, went cold. Twenty-four hours earlier, he, Navia, Murcko, and Boger had exulted not only about catching Schreiber, but about staking out an important new hypothesis about the biology of the world\\u2019s hottest protein. They had driven themselves recklessly to meet a deadline that served \", mdx(\"i\", null, \"Nature\"), \" as much as it did them. Yet now their work wouldn\\u2019t even be seen by those in a position to judge its scientific merit. Again, as it first \", mdx(\"a\", {\n    id: \"page_342\"\n  }), \"had with Moore, \", mdx(\"i\", null, \"Nature\"), \" seemed to be rejecting a potentially vital piece of science for no reason but its own competition with a rival journal.\"), mdx(ContentRef, {\n    id: 132,\n    mdxType: \"ContentRef\"\n  }, \"Boger took the letter immediately on his return and began composing his reply, an artful, exaggeratedly civil single-spaced three-page rant. Yet another occasion for Boger to rise to after a week of nearly continuous crises, it showed him at his most brilliant and most caustic.\"), mdx(ContentRef, {\n    id: 133,\n    mdxType: \"ContentRef\"\n  }, \"Scientifically, he wrote, \", mdx(\"i\", null, \"Nature\"), \" had \\u201Ccompelling\\u201D reasons to reevaluate its decision. First, there was the significance of the structure itself: It was unique. Unlike Clardy\\u2019s structure, it was unbound (it was the first X-ray structure of the enzyme by itself), yet it was distinct enough from both Moore\\u2019s and Schreiber\\u2019s NMR structures to raise the question of what the protein really looked like. At the same time, it posed a direct challenge to Clardy and Schreiber, who had observed that when the protein bound to FK-506 its overall conformation \\u201Cchanges little\\u201D from its native state. \\u201CAs you will note from our data,\\u201D Boger wrote, \\u201Cthis would appear to be obviously and significantly incorrect.\\xA0.\\xA0.\\xA0. Rather significant changes in protein structure \", mdx(\"i\", null, \"must occur\"), \" [emphasis added] on binding FK-506, especially in the \\u2018flap\\u2019 region that guards the binding site.\\u201D He also stressed the collaboration between Yamashita and Moore\\u2014\\u201Conly the second case of NMR data being used to solve an X-ray structure\\u201D and \\u201Cthe first time\\u201D a fraction of an NMR structure had solved the problem of molecular replacement.\"), mdx(ContentRef, {\n    id: 134,\n    mdxType: \"ContentRef\"\n  }, \"Any of these points might have been enough to warrant \", mdx(\"i\", null, \"Nature\"), \"\\u2019s reconsideration: Taken together, they made a convincing case. But Boger couldn\\u2019t resist going further. He bluntly reminded \", mdx(\"i\", null, \"Nature\"), \"\\u2019s editors of the deal they had made in deciding to reconsider Moore\\u2019s NMR structure. \\u201CWe would not be frank if we did not express our disappointment at your abrupt reaction to our manuscript,\\u201D he wrote near the end. \\u201CThe favorable editorial decision in mid-April to send the NMR manuscript for review was made only after, \", mdx(\"i\", null, \"at your request\"), \", we laid out in detail our X-ray observations and plans and committed ourselves to sending the as-detailed manuscript to you. We fully and completely met our side of what we cannot help but view as something akin to a bargain.\\u201D\"), mdx(ContentRef, {\n    id: 135,\n    mdxType: \"ContentRef\"\n  }, \"Boger had not come this far to be denied. He concluded the letter \", mdx(\"a\", {\n    id: \"page_343\"\n  }), \"by giving \", mdx(\"i\", null, \"Nature\"), \" until the end of business Monday to reverse itself\\u2014one day. Otherwise, he said, Vertex would take its side of the FK-506/FKBP-12 story\\u2014\\u201Cperhaps the \\u2018hottest\\u2019 subject in medically relevant biology,\\u201D he reminded scoldingly\\u2014to a competing journal.\"), mdx(ContentRef, {\n    id: 136,\n    mdxType: \"ContentRef\"\n  }, \"To the scientists, including Navia and Yamashita, whose names Boger affixed to the letter above his own, the letter was brash, impolitic, shocking, and potentially ruinous. They feared \", mdx(\"i\", null, \"Nature\"), \" would never again publish a manuscript with the company\\u2019s name on it. Yet by now they had no choice but to go along. \\u201CWe\\u2019ve already torched rule 1\\u2014\\u2018Never publish a paper we\\u2019ve already rejected,\\u2019\\xA0\\u201D Navia said gamely. \\u201CThere should be no problem torching rule 62\\u2014\\u2018We don\\u2019t publish second X-ray structures.\\u2019\\xA0\\u201D Still, underneath lay a jagged ribbon of fear. All they could do was wait and hope that Boger\\u2019s hubris wouldn\\u2019t lead them into an all-out Icarus-like plunge.\"), mdx(ContentRef, {\n    id: 137,\n    mdxType: \"ContentRef\"\n  }, \"There was a five-hour time difference between London and Cambridge. \", mdx(\"i\", null, \"Nature\"), \" had until noon Monday, local time, to respond.\"), mdx(ContentRef, {\n    id: 138,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 139,\n    mdxType: \"ContentRef\"\n  }, mdx(\"i\", null, \"Nature\"), \"\\u2019s second reversal in a month came exactly twenty-seven minutes late, at 12:27. Boger accepted it munificently. It still meant that others\\u2014others more rigorous, closer to the situation\\u2014would have to approve the X-ray paper, but to Navia, the last great obstacle was now cleared. The stage was set for a full-scale confrontation with Schreiber\\u2014a confrontation he was every bit as confident as Boger that Vertex could win.\"), mdx(ContentRef, {\n    id: 140,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CStuart has stuck his neck out,\\u201D Navia said. \\u201CHis work is a hypothesis driving a conclusion. He thinks FKBP is an inconvenient intervener in the process, that it\\u2019s a socket for FK-506. But he doesn\\u2019t understand biology. The \", mdx(\"i\", null, \"Nature\"), \" paper is going to rough him up a bit.\"), mdx(ContentRef, {\n    id: 141,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIf we get the complex,\\u201D he said, almost as an afterthought, \\u201Cwe\\u2019re going to chop his balls off.\\u201D\"));\n}\n;\nMDXContent.isMDXComponent = true;","fields":{"slug":"/molecule/17/"},"frontmatter":{"isBook":false,"title":"Chapter Seventeen","bookTitle":"The Billion-Dollar Molecule","numSections":25,"tags":["a"],"author":"Barry Werth"}}},"pageContext":{"id":"8491d3ef-b3d9-5de4-8a1f-e04c4e532e18"}},"staticQueryHashes":["4080856488"]}