As a biomedical scientist I really enjoyed this book. It is the sequel to the author's previous volume "The Billion Dollar Molecule". Both books provide a fly-on-the-wall account of Vertex Pharmaceuticals, an innovative biopharmaceutical company that brought two breakthrough medicines - one for hepatitis C and the other for cystic fibrosis - to market two years ago. Both these drugs were the first of their kind and have given thousands of patients a new lease on life. From a broader perspective however, the author's goal is to shed light both on the immensely challenging process of bringing a new drug to market and the brilliant scientists and driven personalities that make it possible.
Werth's account of Vertex focuses mainly on the hepatitis C drug, with the cystic fibrosis drug playing a smaller but still important role. The previous book was much more science-heavy than this one, emphasizing the chemistry, biology and computer science that goes into the early stages of drug discovery. In spite of the intense scientific competition and research depicted in that volume (much of it spanning the late 80s and early 90s), Vertex did not bring a successful drug to market until 2010, underscoring the challenge of drug discovery in which you have to furiously paddle simply to stay afloat. The two books thus mirror two different phases of the company: the first dealing mainly with the science and the birthing pains of a new startup, and the second dealing with the transformation of the startup into a commercial enterprise. You will thus find much more of the business, legal and commercial aspects of drug development in this volume. Boardroom deliberations and the subtleties of drug pricing litter the narrative. Both books, however, provide an excellent overview of the multiple challenging stages of drug discovery, from discovering an initial "hit", to optimizing its properties to formulating it and finally selling it in the form a once-a-day pill. The account of formulation difficulties was especially revealing to me. As the founder of Vertex put it, taking a drug all the way from initial discovery to the market is harder than putting a man on the moon, partly because the biology is so complex and incompletely understood.
Werth has always been a skilled purveyor of the personalities and egos that populate the highest echelons of the science and business and he continues this tradition in this book. Along with highly driven scientists we meet egotistic but talented lawyers, executives, government officials, Wall Street analysts and venture capitalists. The founder of Vertex is described as having a "reality distortion field" akin to Steve Jobs. The character descriptions are far more colorful in the previous book but this volume does have its share of sharp profiles: for instance one management consultant "dressed like George Will but sounded like Don Draper channeling Alan Ginsburg". One of the strengths of the previous volume was that many of the personalities portrayed in it - including academic giants like Robert Burns Woodward and industrial giants like George Merck - were fundamentally more interesting but the present account on the other hand does a better job of describing the vast and sundry set of individuals required to sustain the diverse drug enterprise. We also see how cruel the business can be, bringing failure to years of intense effort and laying off dedicated scientists who have given their heart and soul to the process.
Werth's discussion of the two Vertex drugs also raises important questions about the future of the industry. The hepatitis drug is targeted toward a vast patient population, much of which is located in poor countries. The cystic fibrosis drug is targeted toward a small patient population, much of which is located in rich countries. The stories of patients in both groups - one of which Werth documents in detail - are heartbreaking, but in both cases the challenge is to balance profits with cures. In one case the company was compelled to charge exorbitant amounts of money because of the small patient population while in the other case the lack of wealthy patients led to lower revenues. Whether you are developing a drug for millions or for thousands, the R&D costs are roughly the same - and enormous. This is the moral and financial challenge the industry faces right now; how, when it is trying to develop highly personalized therapies for smaller and smaller patient groups, can it get away with both charging reasonable prices and recovering the expenditure on R&D that it can plug into developing the next drug. Werth deftly discusses these issues along with the underlying ones of FDA approvals and Medicare and government controls.
Ironically, the successful Vertex story - which culminated last year in a move to a shining, sprawling new building near Boston Harbor - ends in a somewhat somber note. Many of the most important scientists - including the founder - who discovered the two medicines are no longer with the company and the highly-science driven approach that was described in the first book seems to have taken a backseat to commercial pursuits. The future of the company is thus not completely certain, and Werth ends with an afterword in which he discusses the fate of big pharmaceutical companies which seem to be laying off thousands, making incremental advances and cutting each others' throats to bring the next "me-too" pill to market. Unlike Vertex, many of these organizations spend much more on marketing than on R&D and are busy pleasing Wall Street and shareholders rather than patients. As Werth reminds us, if we want to advance the next groundbreaking medicines we need to remember George Merck's advice: focus on patients, the profits will follow. The story of Vertex provides both a shining example and a cautionary note.
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The Antidote: Inside the World of New Pharma (English Edition) Kindle电子书
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In this timely and much praised book, Barry Werth draws upon inside reporting that spans more than two decades. He provides a groundbreaking close-up of the upstart pharmaceutical company Vertex and the ferocious but indispensable world of Big Pharma that it inhabits.
In 1989, the charismatic Joshua Boger left Merck, then America’s most admired business, to found a drug company that would challenge industry giants and transform health care. Werth described the company’s tumultuous early days during the AIDS crisis in The Billion-Dollar Molecule, a celebrated classic of science and business journalism. Now he returns to tell a riveting story of Vertex’s bold endurance and eventual success.
The $325 billion-a-year pharmaceutical business is America’s toughest and one of its most profitable. It’s riskier and more rigorous at just about every stage than any other business, from the towering biological uncertainties inherent in its mission to treat disease; to the 30-to-1 failure rate in bringing out a successful medicine even after a molecule clears all the hurdles to get to human testing; to the multibillion-dollar cost of ramping up a successful product; to operating in the world’s most regulated industry, matched only by nuclear power.
Werth captures the full scope of Vertex’s twenty-five-year drive to deliver breakthrough medicines. At a time when America struggles to maintain its innovative edge, The Antidote is a powerful inside look at one of the most intriguing and important business stories of recent decades.
In 1989, the charismatic Joshua Boger left Merck, then America’s most admired business, to found a drug company that would challenge industry giants and transform health care. Werth described the company’s tumultuous early days during the AIDS crisis in The Billion-Dollar Molecule, a celebrated classic of science and business journalism. Now he returns to tell a riveting story of Vertex’s bold endurance and eventual success.
The $325 billion-a-year pharmaceutical business is America’s toughest and one of its most profitable. It’s riskier and more rigorous at just about every stage than any other business, from the towering biological uncertainties inherent in its mission to treat disease; to the 30-to-1 failure rate in bringing out a successful medicine even after a molecule clears all the hurdles to get to human testing; to the multibillion-dollar cost of ramping up a successful product; to operating in the world’s most regulated industry, matched only by nuclear power.
Werth captures the full scope of Vertex’s twenty-five-year drive to deliver breakthrough medicines. At a time when America struggles to maintain its innovative edge, The Antidote is a powerful inside look at one of the most intriguing and important business stories of recent decades.
商品描述
作者简介
Barry Werth is an award-winning journalist and the acclaimed author of six books. His landmark first book, The Billion-Dollar Molecule, recounts the founding and early struggles of Vertex. Werth’s articles have appeared in The New Yorker, The New York Times Magazine, and GQ, among others. He has taught journalism and nonfiction writing at Smith, Mount Holyoke, and Boston University. --此文字指其他 kindle_edition 版本。
媒体推荐
"A riveting mix of molecular science, big personalities—and big money." (Nature)
“Barry Werth’s new book does for the world of biotech drug development what The Soul of a New Machine did for the dawn of the computer age. It presents an exciting narrative about the business of bringing new products to market.” (Boston Globe)
“You can read The Antidote as a book about predicaments encountered by just about any company whose future depends on constant innovation. Yet, given Mr. Werth's welcome attention to personalities and circumstances—as well as to the recalcitrance of particular molecules and particular suffering bodies—you can also take the book at face value, as a story about what happened in one company in one fairly short period of time. ... The vividness and rich detail of "The Antidote" make it a gripping coming-of-age story for modern corporate and scientific times.” (The Wall Street Journal)
“Werth's excellent writing takes the reader deep into the heart of Vertex and into the dilemma facing the biotech pioneers, and us all.” (Fortune)
“Werth keeps a brisk pace, describing Vertex as the antidote to older pharma and Merck in particular. He infuses the book with drama, even managing to make a regulatory meeting seem exciting.” (The Economist)
“The book is an in-depth look at a company in a daunting, high-stakes, highly regulated business in which science, commerce and politics intersect.” (Pittsburgh Tribune)
“Werth very aptly captured the drama of the pharmaceutical industry … Werth was able to obtain extraordinary inside information on the workings of the pharmaceutical industry. He was able to capture the emotional and psychological state of the players, the day-to-day workings of the companies with failures and successes of research, as well as collaborations with other companies and acquisitions. … Succinct and understandable.” (New York Journal of Books)
“[Werth’s] rendering of bright, quirky individuals and their determination to make Vertex sustainable will satisfy anyone seeking an exciting biotech business story. … A revealing, readable book.” (Kirkus Reviews)
“Werth doesn’t shy away from technical details, and The Antidote has plenty of “inside baseball” for pharma industry cognosenti ... But although these nitty-gritty details are important and interesting, Werth uses them as the backdrop to ask a more broadly relevant and philosophical question: not just how to build a large drug company, but what to grow up to become? …. Sometime, somewhere, a future biopharma CEO will hopefully read The Antidote and be inspired to continue the quest.” (Pharmagellan.com) --此文字指其他 kindle_edition 版本。
“Barry Werth’s new book does for the world of biotech drug development what The Soul of a New Machine did for the dawn of the computer age. It presents an exciting narrative about the business of bringing new products to market.” (Boston Globe)
“You can read The Antidote as a book about predicaments encountered by just about any company whose future depends on constant innovation. Yet, given Mr. Werth's welcome attention to personalities and circumstances—as well as to the recalcitrance of particular molecules and particular suffering bodies—you can also take the book at face value, as a story about what happened in one company in one fairly short period of time. ... The vividness and rich detail of "The Antidote" make it a gripping coming-of-age story for modern corporate and scientific times.” (The Wall Street Journal)
“Werth's excellent writing takes the reader deep into the heart of Vertex and into the dilemma facing the biotech pioneers, and us all.” (Fortune)
“Werth keeps a brisk pace, describing Vertex as the antidote to older pharma and Merck in particular. He infuses the book with drama, even managing to make a regulatory meeting seem exciting.” (The Economist)
“The book is an in-depth look at a company in a daunting, high-stakes, highly regulated business in which science, commerce and politics intersect.” (Pittsburgh Tribune)
“Werth very aptly captured the drama of the pharmaceutical industry … Werth was able to obtain extraordinary inside information on the workings of the pharmaceutical industry. He was able to capture the emotional and psychological state of the players, the day-to-day workings of the companies with failures and successes of research, as well as collaborations with other companies and acquisitions. … Succinct and understandable.” (New York Journal of Books)
“[Werth’s] rendering of bright, quirky individuals and their determination to make Vertex sustainable will satisfy anyone seeking an exciting biotech business story. … A revealing, readable book.” (Kirkus Reviews)
“Werth doesn’t shy away from technical details, and The Antidote has plenty of “inside baseball” for pharma industry cognosenti ... But although these nitty-gritty details are important and interesting, Werth uses them as the backdrop to ask a more broadly relevant and philosophical question: not just how to build a large drug company, but what to grow up to become? …. Sometime, somewhere, a future biopharma CEO will hopefully read The Antidote and be inspired to continue the quest.” (Pharmagellan.com) --此文字指其他 kindle_edition 版本。
文摘
Antidote
Why I Went Back Inside Vertex
Twenty years ago, I wrote a book about a bold and bruising quest. It told the story of a group of entrepreneurial young scientists who left the world’s best drug company—the most admired business in America year after year—because they were confident they would be more productive on their own, starting from scratch. They aimed to design better drugs, atom by atom. Most people across the industry thought their project in a refitted construction company garage in Cambridge, Massachusetts—to build an organization that could produce dramatically improved medicines to transform the lives of people with serious diseases—was a pipe dream, a money pit, a consuming act of arrogance, an exhausting feat of hubris, a fool’s errand.
“Don’t you think this is five years too early?” founding scientist and president Joshua Boger was often asked. “Yes,” he would say, “but five years from now it’ll be five years too late.”
I found their passionate belief in science and in themselves, brimming with high purpose and combative glee, stirring and infectious as I followed them around for a couple of years while they tried to get their cash-starved company, Vertex Pharmaceuticals, off the ground. It was a rocky, exhilarating, eye-opening ride. The chase for new leads was fierce, not just against “Mother Merck” but also top academic labs, including those led by some of their own scientific advisors, who they feared were sharing Vertex’s most prized insights with its rivals. When Boger settled for a tie in a race to publication against one of them, a Harvard professor, he told me: “I’ll take it. But I want to rub his nose in the dirt and step on his head.”
Such was the knife-edge between cooperation and competition in the new biopharmaceutical order. Whatever unease I felt at witnessing up close how ferocious capitalism and scientific rivalries—rather than, say, altruism—drove the search for new lifesaving drugs receded in the wake of Vertex’s precocious early success. Boger assembled a team of talented, rampantly motivated biologists, chemists, biophysicists, and computer scientists while he and his chief lieutenant tap-danced their way around the world to raise the money they would need to compete with the pharmaceutical behemoths. Though they were spectacularly outspent and outmanned in every area, he let them organize themselves, rather than try to direct them from above. He let them fail, time and again, until they came up with better approaches. He was a visionary goal setter, an inspirer.
Against all odds, within four years Vertex proved it could compete at the forefront of drug research, against the industry leaders, in several major areas at once. It had gone public and Wall Street considered it a hot stock. What I saw impressed me as a worthy, honest, compelling, even noble effort both to beat and influence the world around it—a world where life-changing new drugs were getting harder and harder to find despite the best efforts of hundreds of companies employing tens of thousands of equally gifted and passionate researchers and spending hundreds of billions of dollars on research and development.
That was the story I told in The Billion-Dollar Molecule. I was encouraged by the company’s progress; pleased, too, that the book was acclaimed as an insightful look inside the world of commercial medicine. But I understood that the upstart-biotech-looks-promising version of events that I had reported wasn’t the full story, or even the main one. Boger had set out to build a drug company, but Vertex hadn’t yet produced a drug. Nowhere near it. For him and the other company pioneers, the larger prize wasn’t organizing a research group to find better compounds; it was to build a business that could go head-to-head with the world’s most profitable drugmakers against the hardest diseases, involving some of competitive capitalism’s most complicated science and most cutthroat marketing maneuvers.
I’d described the opening skirmish, not the war.
The modern pharmaceutical industry emerged from one of the great triumphs of twentieth-century science. Before the 1940s, there were medicines and companies that made them, but no one had invented a method for actively finding and developing new drugs. Profits in medicine were disdained as suspect—immoral—and the companies were essentially manufacturers of fine chemical compounds. Since their products could do as much harm as good, integrity was key. Then university laboratories advanced a new approach: microbial screening. Systematically harvesting large numbers of chemicals from “good bugs” and feeding them to “bad bugs,” then monitoring and improving their activity, drugmakers produced and brought to patients the first antibacterials that had been actively sought and developed.
The chase was on: for new diseases to treat, testing strategies, business opportunities, scientists, alliances with leading doctors, prestige, and money. As with all things in America, World War II was the great catalyst. Just as the companies were flexing their research and development arms to tackle other diseases, the government enlisted them in the war effort. In 1941 the Germans were rumored to have isolated the chemical secretion of the adrenal cortex, cortisone, and given it to their pilots, amping them up, emboldening them. Battlefield wounds and home-front contagions drove the need for better antibiotics, vaccines, pain relievers, and surgical products. Drugmakers were marshaled to counter the threat of a pharmacologic arms race. By midcentury, US companies had more than matched the government’s urgency, and were racing ahead, developing new biological models to screen against. Profits began to pour in. Wall Street stood up and took notice. The companies grew spectacularly.
Merck, where Boger started his career in 1979 after getting a PhD in chemistry at Harvard and doing a postdoctoral stint with future Nobel laureate Jean-Marie Lehn, was their paragon. It best represented the qualities that the industry exalted, a patient-centered, high-science focus combined with unrivaled organizational commitment to R&D. It wasn’t always the most profitable drug company—Pfizer and others were better at making money—but its research campuses in New Jersey and outside Philadelphia attracted the most promising scientists. It was where you wanted to be, the top of the pyramid.
In the 1970s and 1980s, with the swift expansion of government-sponsored research spurred on by the “war on cancer,” and as the universities and Wall Street simultaneously discovered a bonanza in the life sciences, there was an explosion in medical understanding, and the low-hanging fruit were quickly plucked. Merck’s labs launched the first or second significant drugs for cholesterol, hypertension, osteoporosis, and asthma, as well as a class of pain medications known as COX-2 inhibitors. At Merck as elsewhere, scientists burned to do pathbreaking work on new medical frontiers, but increasingly, in management suites and boardrooms across the industry, the consequences of success yielded a conservative strategic consensus: move cautiously rather than struggle to produce breakthroughs; settle for modest “quick-to-market” improvements where treatments already exist, and where the resulting products can be aggressively marketed to doctors and people with chronic diseases.
Gradualism held zero appeal for Boger. “Now, I don’t think there’s anything wrong with bringing an incremental advance to the marketplace; you’re not a bad person,” he says. “It’s just I don’t want to do that; life’s too short.” Biotechnology companies by now had joined the competition. A few top university professors or government scientists with a tantalizing idea could raise tens of millions of dollars, go out and test it, then go public—public—when all they had to sell to investors was a theory and the only certainty in their business model was years and years of progressively more unprofitable darkness. Wall Street blew hot and cold, periodically falling hard for their stories of genetic breakthroughs and miracle cures before returning to its senses. Merck, recognizing Boger’s talents (if not buying into his ideas about building better drugs by applying advances from the biotech, software, and computer graphics industries), encouraged him to do his experiment, letting him piece together a team in immunology. But he quickly felt thwarted, impatient. Pent-up.
His frustrations crystallized in the late 1980s, as many things did across the medical world, with the AIDS crisis. Drugmakers at first ignored the epidemic, seeing a small market. Off-the-shelf compounds were ineffective and toxic. When Merck entered the arena, many doctors, public health officials, and even some activists felt that the cavalry had arrived. Boger’s closest scientific friend in the company, a brilliant and brash young biologist named Irving Sigal, led Merck’s project, and Boger cleared the decks in his group to help. CEO Roy Vagelos announced he was “damn optimistic” about Merck’s chances. In late 1988, returning from a meeting in Europe, Sigel was killed when Pan Am Flight 103, carrying 259 people and a terrorist organization’s bomb in a cargo container, exploded in a fireball over Lockerbie, Scotland. He was thirty-five. Merck scrambled to recover from its loss.
Within a month, Boger was gone.
So I was there when Vertex set out in its garage to overtake the “bigs.” And what I saw were staggering contrasts. The major pharmaceutical companies were lumbering along; mightily equipped, cash-rich, charging higher and higher prices while bringing out fewer and fewer important new drugs, their reputation for putting profit before patients replayed and reinforced in the AIDS epidemic. It was fifteen years into the war on cancer, and cancer was winning in a rout. The biotechs had yet to pay out, and Wall Street was skittish about their high failure rate and the chronic risk and volatility of an industry where horizons were measured in decades. It was into this environment that Boger led his young company.
Now leap ahead to early 2011: the grinding recovery from the worst financial crisis in eighty years, the raging political storm over Obamacare, a drumbeat of lurid press reports about the drug business, revealing an industry in crisis and under siege. Vertex, after twenty-two years and $3.6 billion in losses, was about to launch its first drug under its own name, a major breakthrough against the leading cause of advanced liver disease. It had a second drug nearing regulatory approval that promised to revolutionize the treatment of the most common inherited fatal disease in the United States and Europe. Just as the world around it was shuddering, Vertex was poised to soar. What better vantage point for witnessing the mounting collision of medicine, money, and society?
I went back inside Vertex to learn what it takes—to succeed in science and business, yes, but also in fleshing out and struggling to achieve a radical vision of a better future. Could a group of very bright, very determined people make a difference in a market dominated by profits and Wall Street? Could true believers in the idea that the purpose of pharmaceutical research is to put patients first and transform the lives of sick people compete in an industry where it was far preferable to develop, say, a marginally better fifth statin compound for high cholesterol and market the hell out of it, as Pfizer had done with the bestselling drug of all time, Lipitor? Or bury a $500 million sweetheart reimbursement in the Fiscal Cliff deal, as Amgen did with its army of seventy-seven lobbyists? Or pay a generic company $42 million not to market a cheaper version of your drug, so you can keep selling it at ten times the cost to consumers, as in a recent restraint-of-trade case before the Supreme Court? Could Vertex still be Vertex in our genomic age, when understanding which drugs to prescribe will depend on an ever-deepening biological profiling of individual patients?
What was I seeking? Hope, really. The $325 billion prescription drug business is America’s most challenging and one of its most profitable. It’s tougher and riskier at nearly every stage than any other business. Yawning biological uncertainties haunt every experiment; the failure rate even after a candidate clears all the myriad hurdles to reach human testing is 30 to 1; the cost of ramping up a successful product typically exceeds $1 billion. Drugmakers operate in the world’s most regulated commercial environment, matched only by nuclear power. Small companies face an extra test. Dependent on Wall Street for financing, they must navigate a myopic trading culture that disdains and crowds out long-term thinking and investment. All progress in the pharmaceutical business is backbreaking, freighted with unknowns, takes twice as long as you think it will, and is liable to “blow at any seam,” as Tom Wolfe wrote about the endless ineffable peril of staking it all on a lofty high-risk mission.
Mostly I wanted to see what it had taken to prevail against such harrowing obstacles: What had Boger’s vision become, and did it represent a true way ahead in our boundlessly promising and still barely comprehended new biological epoch? After he’d resigned from Merck—alone, without first taking anyone with him, and without any assurance that anyone would follow—Boger went home and sketched his goals on a whiteboard: “Make better drugs, faster. Create the 21st century biopharmaceutical company. Become Merck, only better.” It was almost a haiku. He thought it would take him twenty years and $1 billion. Now, just two years late, at nearly four times the cost, Vertex verged on proving all that he had set out to do.
“One of the most common questions I’ve gotten lately is, ‘Gee, did you ever imagine this would occur?’ ” he told Vertex’s sales troops that spring. It was a few days after Osama bin Laden was killed in Pakistan after a decade-long manhunt, and the company was counting down to launch, primed to go one-on-one against Merck for the richest commercial opportunity in pharma. “My completely unsatisfying answer is, ‘Yes, absolutely.’ Now, that comes across to some people as fairly arrogant, and to that I say arrogance is only a problem if it doesn’t turn out to be true. If it turns out to be true, it’s just persistence.”
I’d discovered at Vertex that biomedical research emits a high emotional heat. It may be tempting to think that the competitive commitment in other disruptive tech industries is similar but the comparison is slender. In Silicon Valley, you’re trying to make a better product, not cure cystic fibrosis or Parkinson’s disease. Here the difference between success and failure can be the difference between life and death. Vertex was about to debut not only the first drugs discovered and developed by its own people and commercialized under its own label. It was about to debut itself, an organization of nearly two thousand people sculpted as much by the changing health care economy and the gyrations of its industry over the past two decades as by Boger and the others who joined him. They had had notable early success in the crucible of that new biomedical order—AIDS—but that victory had been pyrrhic because, while it had produced a drug, Vertex hadn’t fully emerged along with it. Now the company would correct that disparity.
Boger was right about arrogance. We may not like it in our faces, but it’s a problem only when it doesn’t turn out to be true. --此文字指其他 kindle_edition 版本。
INTRODUCTION
Why I Went Back Inside Vertex
Twenty years ago, I wrote a book about a bold and bruising quest. It told the story of a group of entrepreneurial young scientists who left the world’s best drug company—the most admired business in America year after year—because they were confident they would be more productive on their own, starting from scratch. They aimed to design better drugs, atom by atom. Most people across the industry thought their project in a refitted construction company garage in Cambridge, Massachusetts—to build an organization that could produce dramatically improved medicines to transform the lives of people with serious diseases—was a pipe dream, a money pit, a consuming act of arrogance, an exhausting feat of hubris, a fool’s errand.
“Don’t you think this is five years too early?” founding scientist and president Joshua Boger was often asked. “Yes,” he would say, “but five years from now it’ll be five years too late.”
I found their passionate belief in science and in themselves, brimming with high purpose and combative glee, stirring and infectious as I followed them around for a couple of years while they tried to get their cash-starved company, Vertex Pharmaceuticals, off the ground. It was a rocky, exhilarating, eye-opening ride. The chase for new leads was fierce, not just against “Mother Merck” but also top academic labs, including those led by some of their own scientific advisors, who they feared were sharing Vertex’s most prized insights with its rivals. When Boger settled for a tie in a race to publication against one of them, a Harvard professor, he told me: “I’ll take it. But I want to rub his nose in the dirt and step on his head.”
Such was the knife-edge between cooperation and competition in the new biopharmaceutical order. Whatever unease I felt at witnessing up close how ferocious capitalism and scientific rivalries—rather than, say, altruism—drove the search for new lifesaving drugs receded in the wake of Vertex’s precocious early success. Boger assembled a team of talented, rampantly motivated biologists, chemists, biophysicists, and computer scientists while he and his chief lieutenant tap-danced their way around the world to raise the money they would need to compete with the pharmaceutical behemoths. Though they were spectacularly outspent and outmanned in every area, he let them organize themselves, rather than try to direct them from above. He let them fail, time and again, until they came up with better approaches. He was a visionary goal setter, an inspirer.
Against all odds, within four years Vertex proved it could compete at the forefront of drug research, against the industry leaders, in several major areas at once. It had gone public and Wall Street considered it a hot stock. What I saw impressed me as a worthy, honest, compelling, even noble effort both to beat and influence the world around it—a world where life-changing new drugs were getting harder and harder to find despite the best efforts of hundreds of companies employing tens of thousands of equally gifted and passionate researchers and spending hundreds of billions of dollars on research and development.
That was the story I told in The Billion-Dollar Molecule. I was encouraged by the company’s progress; pleased, too, that the book was acclaimed as an insightful look inside the world of commercial medicine. But I understood that the upstart-biotech-looks-promising version of events that I had reported wasn’t the full story, or even the main one. Boger had set out to build a drug company, but Vertex hadn’t yet produced a drug. Nowhere near it. For him and the other company pioneers, the larger prize wasn’t organizing a research group to find better compounds; it was to build a business that could go head-to-head with the world’s most profitable drugmakers against the hardest diseases, involving some of competitive capitalism’s most complicated science and most cutthroat marketing maneuvers.
I’d described the opening skirmish, not the war.
The modern pharmaceutical industry emerged from one of the great triumphs of twentieth-century science. Before the 1940s, there were medicines and companies that made them, but no one had invented a method for actively finding and developing new drugs. Profits in medicine were disdained as suspect—immoral—and the companies were essentially manufacturers of fine chemical compounds. Since their products could do as much harm as good, integrity was key. Then university laboratories advanced a new approach: microbial screening. Systematically harvesting large numbers of chemicals from “good bugs” and feeding them to “bad bugs,” then monitoring and improving their activity, drugmakers produced and brought to patients the first antibacterials that had been actively sought and developed.
The chase was on: for new diseases to treat, testing strategies, business opportunities, scientists, alliances with leading doctors, prestige, and money. As with all things in America, World War II was the great catalyst. Just as the companies were flexing their research and development arms to tackle other diseases, the government enlisted them in the war effort. In 1941 the Germans were rumored to have isolated the chemical secretion of the adrenal cortex, cortisone, and given it to their pilots, amping them up, emboldening them. Battlefield wounds and home-front contagions drove the need for better antibiotics, vaccines, pain relievers, and surgical products. Drugmakers were marshaled to counter the threat of a pharmacologic arms race. By midcentury, US companies had more than matched the government’s urgency, and were racing ahead, developing new biological models to screen against. Profits began to pour in. Wall Street stood up and took notice. The companies grew spectacularly.
Merck, where Boger started his career in 1979 after getting a PhD in chemistry at Harvard and doing a postdoctoral stint with future Nobel laureate Jean-Marie Lehn, was their paragon. It best represented the qualities that the industry exalted, a patient-centered, high-science focus combined with unrivaled organizational commitment to R&D. It wasn’t always the most profitable drug company—Pfizer and others were better at making money—but its research campuses in New Jersey and outside Philadelphia attracted the most promising scientists. It was where you wanted to be, the top of the pyramid.
In the 1970s and 1980s, with the swift expansion of government-sponsored research spurred on by the “war on cancer,” and as the universities and Wall Street simultaneously discovered a bonanza in the life sciences, there was an explosion in medical understanding, and the low-hanging fruit were quickly plucked. Merck’s labs launched the first or second significant drugs for cholesterol, hypertension, osteoporosis, and asthma, as well as a class of pain medications known as COX-2 inhibitors. At Merck as elsewhere, scientists burned to do pathbreaking work on new medical frontiers, but increasingly, in management suites and boardrooms across the industry, the consequences of success yielded a conservative strategic consensus: move cautiously rather than struggle to produce breakthroughs; settle for modest “quick-to-market” improvements where treatments already exist, and where the resulting products can be aggressively marketed to doctors and people with chronic diseases.
Gradualism held zero appeal for Boger. “Now, I don’t think there’s anything wrong with bringing an incremental advance to the marketplace; you’re not a bad person,” he says. “It’s just I don’t want to do that; life’s too short.” Biotechnology companies by now had joined the competition. A few top university professors or government scientists with a tantalizing idea could raise tens of millions of dollars, go out and test it, then go public—public—when all they had to sell to investors was a theory and the only certainty in their business model was years and years of progressively more unprofitable darkness. Wall Street blew hot and cold, periodically falling hard for their stories of genetic breakthroughs and miracle cures before returning to its senses. Merck, recognizing Boger’s talents (if not buying into his ideas about building better drugs by applying advances from the biotech, software, and computer graphics industries), encouraged him to do his experiment, letting him piece together a team in immunology. But he quickly felt thwarted, impatient. Pent-up.
His frustrations crystallized in the late 1980s, as many things did across the medical world, with the AIDS crisis. Drugmakers at first ignored the epidemic, seeing a small market. Off-the-shelf compounds were ineffective and toxic. When Merck entered the arena, many doctors, public health officials, and even some activists felt that the cavalry had arrived. Boger’s closest scientific friend in the company, a brilliant and brash young biologist named Irving Sigal, led Merck’s project, and Boger cleared the decks in his group to help. CEO Roy Vagelos announced he was “damn optimistic” about Merck’s chances. In late 1988, returning from a meeting in Europe, Sigel was killed when Pan Am Flight 103, carrying 259 people and a terrorist organization’s bomb in a cargo container, exploded in a fireball over Lockerbie, Scotland. He was thirty-five. Merck scrambled to recover from its loss.
Within a month, Boger was gone.
So I was there when Vertex set out in its garage to overtake the “bigs.” And what I saw were staggering contrasts. The major pharmaceutical companies were lumbering along; mightily equipped, cash-rich, charging higher and higher prices while bringing out fewer and fewer important new drugs, their reputation for putting profit before patients replayed and reinforced in the AIDS epidemic. It was fifteen years into the war on cancer, and cancer was winning in a rout. The biotechs had yet to pay out, and Wall Street was skittish about their high failure rate and the chronic risk and volatility of an industry where horizons were measured in decades. It was into this environment that Boger led his young company.
Now leap ahead to early 2011: the grinding recovery from the worst financial crisis in eighty years, the raging political storm over Obamacare, a drumbeat of lurid press reports about the drug business, revealing an industry in crisis and under siege. Vertex, after twenty-two years and $3.6 billion in losses, was about to launch its first drug under its own name, a major breakthrough against the leading cause of advanced liver disease. It had a second drug nearing regulatory approval that promised to revolutionize the treatment of the most common inherited fatal disease in the United States and Europe. Just as the world around it was shuddering, Vertex was poised to soar. What better vantage point for witnessing the mounting collision of medicine, money, and society?
I went back inside Vertex to learn what it takes—to succeed in science and business, yes, but also in fleshing out and struggling to achieve a radical vision of a better future. Could a group of very bright, very determined people make a difference in a market dominated by profits and Wall Street? Could true believers in the idea that the purpose of pharmaceutical research is to put patients first and transform the lives of sick people compete in an industry where it was far preferable to develop, say, a marginally better fifth statin compound for high cholesterol and market the hell out of it, as Pfizer had done with the bestselling drug of all time, Lipitor? Or bury a $500 million sweetheart reimbursement in the Fiscal Cliff deal, as Amgen did with its army of seventy-seven lobbyists? Or pay a generic company $42 million not to market a cheaper version of your drug, so you can keep selling it at ten times the cost to consumers, as in a recent restraint-of-trade case before the Supreme Court? Could Vertex still be Vertex in our genomic age, when understanding which drugs to prescribe will depend on an ever-deepening biological profiling of individual patients?
What was I seeking? Hope, really. The $325 billion prescription drug business is America’s most challenging and one of its most profitable. It’s tougher and riskier at nearly every stage than any other business. Yawning biological uncertainties haunt every experiment; the failure rate even after a candidate clears all the myriad hurdles to reach human testing is 30 to 1; the cost of ramping up a successful product typically exceeds $1 billion. Drugmakers operate in the world’s most regulated commercial environment, matched only by nuclear power. Small companies face an extra test. Dependent on Wall Street for financing, they must navigate a myopic trading culture that disdains and crowds out long-term thinking and investment. All progress in the pharmaceutical business is backbreaking, freighted with unknowns, takes twice as long as you think it will, and is liable to “blow at any seam,” as Tom Wolfe wrote about the endless ineffable peril of staking it all on a lofty high-risk mission.
Mostly I wanted to see what it had taken to prevail against such harrowing obstacles: What had Boger’s vision become, and did it represent a true way ahead in our boundlessly promising and still barely comprehended new biological epoch? After he’d resigned from Merck—alone, without first taking anyone with him, and without any assurance that anyone would follow—Boger went home and sketched his goals on a whiteboard: “Make better drugs, faster. Create the 21st century biopharmaceutical company. Become Merck, only better.” It was almost a haiku. He thought it would take him twenty years and $1 billion. Now, just two years late, at nearly four times the cost, Vertex verged on proving all that he had set out to do.
“One of the most common questions I’ve gotten lately is, ‘Gee, did you ever imagine this would occur?’ ” he told Vertex’s sales troops that spring. It was a few days after Osama bin Laden was killed in Pakistan after a decade-long manhunt, and the company was counting down to launch, primed to go one-on-one against Merck for the richest commercial opportunity in pharma. “My completely unsatisfying answer is, ‘Yes, absolutely.’ Now, that comes across to some people as fairly arrogant, and to that I say arrogance is only a problem if it doesn’t turn out to be true. If it turns out to be true, it’s just persistence.”
I’d discovered at Vertex that biomedical research emits a high emotional heat. It may be tempting to think that the competitive commitment in other disruptive tech industries is similar but the comparison is slender. In Silicon Valley, you’re trying to make a better product, not cure cystic fibrosis or Parkinson’s disease. Here the difference between success and failure can be the difference between life and death. Vertex was about to debut not only the first drugs discovered and developed by its own people and commercialized under its own label. It was about to debut itself, an organization of nearly two thousand people sculpted as much by the changing health care economy and the gyrations of its industry over the past two decades as by Boger and the others who joined him. They had had notable early success in the crucible of that new biomedical order—AIDS—but that victory had been pyrrhic because, while it had produced a drug, Vertex hadn’t fully emerged along with it. Now the company would correct that disparity.
Boger was right about arrogance. We may not like it in our faces, but it’s a problem only when it doesn’t turn out to be true. --此文字指其他 kindle_edition 版本。
基本信息
- ASIN : B00DPM7ZW6
- 出版社 : Simon & Schuster (2014年2月4日)
- 出版日期 : 2014年2月4日
- 语言 : 英语
- 文件大小 : 2157 KB
- 标准语音朗读 : 已启用
- X-Ray : 已启用
- 生词提示功能 : 已启用
- 纸书页数 : 449页
- 亚马逊热销商品排名: 商品里排第131,284名Kindle商店 (查看Kindle商店商品销售排行榜)
- 商品里排第199名Medicine(医学)
- 商品里排第333名Social Sciences（社会科学）
- 商品里排第388名Science & Nature（科学与自然）
- 用户评分:
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此商品在美国亚马逊上最有用的商品评论
美国亚马逊：
3.8 颗星，最多 5 颗星
18 条评论
Ashutosh S. Jogalekar
4.0 颗星，最多 5 颗星
The tribulations and triumph of drug development
2014年2月6日 -
已在美国亚马逊上发表已确认购买
47 个人发现此评论有用
William A. Thayer
5.0 颗星，最多 5 颗星
Good insight into the extreme difficulty of bringing a drug to market
2014年6月1日 -
已在美国亚马逊上发表已确认购买
My son participates in Phase 1 and Phase 3 drug trials at the Univ of Texas. That is complex stuff. The scientific development of the drugs being tested is much more difficult. This book gives you some idea of what is involved. I wish that there were more books like this on other drug companies. This book was particularly good on giving you some idea of the gyrations of the stock price of these companies and what is behind the gyrations. Vertex brought a drug to the market to cure hepatitis C. Possibly one might come up with some discounted cash-flow analysis which would give a value for the company......but after Vertex got its drug to market someone came along with another better drug. How do you model that?
I admire Vertex's quest for innovation. But 20 years of research before it can bring a drug to market is almost unbelievable. How they managed to finance this is amazing.
The key to all economic growth is innovation. One of the vital issues is how to finance this innovation which requires so much research. There aren't any easy answer. The US seems to be doing better than most other countries.
I admire Vertex's quest for innovation. But 20 years of research before it can bring a drug to market is almost unbelievable. How they managed to finance this is amazing.
The key to all economic growth is innovation. One of the vital issues is how to finance this innovation which requires so much research. There aren't any easy answer. The US seems to be doing better than most other countries.
2 个人发现此评论有用
Marvin Burns
3.0 颗星，最多 5 颗星
Interesting but repetitive after a while
2014年3月17日 -
已在美国亚马逊上发表已确认购买
This book was well done, but it lost its message somewhat along the way. It is worth reading but the characters are not as real as they probably are in real life.
2 个人发现此评论有用
Thomas J. Dougherty
5.0 颗星，最多 5 颗星
The Vertex Story continues
2016年1月1日 -
已在美国亚马逊上发表已确认购买
Extremely interesting followup to his previous book (The Billion-Dollar Molecule: The Quest for the Perfect Drug) on the biotech company Vertex. Many of the characters from the prior book have either moved on to other ventures or moved up the corporate ladder. Werth traces the evolution of Vertex from a feisty startup focused on perfecting an immunological anti rejection compound for transplants to the more mature company with a different focus and portfolio that it has become over three decades. It also serves as a cautionary tale for the drive to keep a company afloat with investors and in placing too much emphasis (HepC) on a single disease and compound for a company's success. Vertex dominated the HepC market, but only for a brief instant in time. Eric Olson (who has left Vertex) spearheaded the cystic fibrosis program which is now the leading product and dominant revenue stream for the company. Read both books to see how the company started out to design drugs de novo from protein structural information, and by a very convoluted path ended up where it is today.
3 个人发现此评论有用
Clergyboy
5.0 颗星，最多 5 颗星
Epic Journey of Scientists trying to save the world
2014年4月20日 -
已在美国亚马逊上发表已确认购买
This book is amazing because I never thought a corporation can have so many souls dancing inside, let alone a Pharma company. I want to say that I exaggerated only a little to compare this book's story to the 10 year Trojan War.
What really touched me are the stories of individuals. The Bogers who "bore the torch" in the early days of doing great science and exploring the frontiers, the successors who financed and commercialized the founders' vision, the Wall Street analysts wanting to milk the new Pharmas like they did with the old, the patient advocates who wanted Vertex to remain true to its mission even when it is burning through hundreds of thousands of dollars a day... Those are real people competing viciously with selfish aims and playing out in a ruthless business world where billions of dollars would be won or lost on any single day. The deciding factors at the end of the day are two things: luck and balls.
Who doesn't become exited when warm humanitarian ideas and cold hard cash were tossed together and shaken violently by a group of crazy scientists? I will have that straight up any day.
What really touched me are the stories of individuals. The Bogers who "bore the torch" in the early days of doing great science and exploring the frontiers, the successors who financed and commercialized the founders' vision, the Wall Street analysts wanting to milk the new Pharmas like they did with the old, the patient advocates who wanted Vertex to remain true to its mission even when it is burning through hundreds of thousands of dollars a day... Those are real people competing viciously with selfish aims and playing out in a ruthless business world where billions of dollars would be won or lost on any single day. The deciding factors at the end of the day are two things: luck and balls.
Who doesn't become exited when warm humanitarian ideas and cold hard cash were tossed together and shaken violently by a group of crazy scientists? I will have that straight up any day.
6 个人发现此评论有用
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