The Truth in Small Doses: Why We're Losing the War on Cancer-and How to Win It

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9781476739991: The Truth in Small Doses: Why We're Losing the War on Cancer-and How to Win It

A "brilliant" ("Fortune"), eye-opening history of the war on cancer, "The Truth in Small Doses" asks why we are losing this essential fight and charts a path forward. Over the past half century, deaths from heart disease, stroke, and so many other killers have fallen dramatically. But cancer continues to kill with abandon. In 2013, despite a four-decade "war" against the disease that has cost hundreds of billions of dollars, more than 1.6 million Americans will be diagnosed with cancer and nearly six hundred thousand will die from it. A decade ago, Clifton Leaf, a celebrated journalist and a cancer survivor himself, began to investigate why we had made such limited progress fighting this terrifying disease. The result is a gripping narrative that reveals why the public's immense investment in research has been badly misspent, why scientists seldom collaborate and share their data, why new drugs are so expensive yet routinely fail, and why our best hope for progress--brilliant young scientists--are now abandoning the search for a cure. "Through flowing prose Leaf delivers, alongside facts and data, stories on personalities involved in research, the fascinating process of solving an unusual and highly deadly cancer in Africa, and the heartbreaking realities of cancer treatment in children today. Leaf's extensively investigated treatise will resonate with researchers and patients frustrated by the bureaucratic woes he delineates. Public policy makers, grant reviewers, and pharmaceutical researchers alike must consider Leaf's indictment and proposed solutions" ("Publishers Weekly"). "The Truth in Small Doses" is that rare tale that will both outrage readers and inspire conversation and change.

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The Truth in Small Doses Prologue

How Did We Get Here?


Two years before I came to believe that we were losing the “war on cancer,” I had concluded that we were on the brink of victory. The notion had spun out of an extraordinary conversation I’d had in February 2002 with Daniel Vasella, then the chief executive officer of the Swiss pharmaceutical firm Novartis. He was in New York for the World Economic Forum, the annual gathering of business titans, statesmen, movie stars, and savants traditionally held in Davos, a resort town tucked high in the Swiss Alps. But this particular winter, the first after 9/11, the gathering had moved to midtown Manhattan, and the forty-eight-year-old Vasella had settled into the lobby bar at the St. Regis Hotel for a string of interviews with the business press.

I was reluctant to join the line. It was late in the day, and I was sure I was in for a lengthy pitch on some revolutionary age-spot cream then in clinical trials, or a rundown of the company’s ever-expanding portfolio of medicines. I was then an editor at Fortune and oversaw the magazine’s investing coverage, among other things, so such conversations were common. But this time the phrase drug pipeline was not uttered once. Nor was revenue stream. Nor share price. Vasella hardly mentioned his company at all.

Instead, he spoke about the anguish caused by endemic malaria, the soaring cost of prescription drugs, and the preventable diseases still plaguing half the world. His industry, he said with surprising candor, had not done enough to address these crises. He spoke of the challenges of innovation in a big corporation and of dismantling the walls of ancient corporate fiefdoms. (Vasella had helped engineer, in 1996, the merger of two century-old Swiss chemical companies, Sandoz and Ciba-Geigy, and had become CEO of the newly formed Novartis.)

As the conversation continued in the dim light of the hotel bar, the subjects grew more personal and raw, and dotted lines between our histories emerged. Vasella spoke of his older sister Ursula’s battle with Hodgkin’s disease, a cancer of the lymph system, and of watching her waste away during a grueling three-year fight. Vasella was ten at the time of her death; she was eighteen.

I too had struggled with Hodgkin’s (at age fifteen), but had survived thanks to a unique chemotherapy regimen that had been pioneered at the National Cancer Institute (NCI) a decade or so prior to my diagnosis in 1978. The discovery had, unfortunately, come a few years too late to save young Ursula.

An uncannier connection was Vasella’s work in the late 1980s. In his first managerial job at a pharmaceutical company, he was responsible for an obscure injectable drug, somatostatin, that was shown to relieve some of the worst symptoms of carcinoid syndrome, a rare intestinal cancer. My mother had been one of the few people in the world to rely on the drug, which had alleviated some of the daily diarrhea and near-constant skin flushing that made her disease so debilitating. Like Vasella’s sister, she would eventually succumb to her cancer, in 1995.

Vasella had been surrounded by illness and tragedy as a child. At the age of five, his asthma grew so severe during the summer months that his parents sent him to live on a farm in the mountains, away from the family. When he was eight, a bout with tuberculosis, followed by meningitis, forced him to spend a full year in a hospital and sanatorium. Five years later his father, a history professor, died of complications from surgery. Then a second sister died as well, from a car accident.

Vasella related only a tiny portion of this story as we sat with our Scotches in the hotel bar.

He had gone to medical school, received his degree, and practiced medicine in Bern, Switzerland, before giving it up for a junior marketing position at Sandoz. Six years later he was in the corner office. Among the chief executives of major drug companies, Vasella was the only physician, the only one who had ever taken care of patients.

A few journalists would later venture that it was this clinically trained eye that helped him see the vast potential of the leukemia drug called Gleevec, which many oncologists were then hailing as a genuine breakthrough and as a model for cancer therapy in the generation to come. Others involved in the drug’s development would give Vasella far less credit. I knew none of this at the time.

What I did know, what I could hear in our first conversation, was how Vasella spoke of the drug, which had been approved by the Food and Drug Administration just nine months earlier. He spoke the way a first-time parent speaks about his child’s first recital.

Gleevec worked, he explained, in a radically new way: by homing in on a “mutant” protein found in the white blood cells of patients with an uncommon form of leukemia. This aberrant protein, created as the result of a genetic glitch, relayed instructions that sent those white blood cells into a continual replicative loop. They divided and divided until eventually they crowded out every other type of cell in the blood, and the patient died. Novartis’s remarkable molecule blocked that protein from passing along its deadly message. And it was so precisely aimed that, even as it shut down the mutants, it spared the healthy cells around them. (Traditional chemotherapy, by contrast, is a sledgehammer: it decimates many normal cells as it strikes the malignant.)

Gleevec, said Vasella, had established the principle of targeted cancer therapy. Now it was only a matter of time until scientists designed molecules to disable the wayward signaling mechanisms central to every cancer.

As dramatic and exciting as the story line was, I failed to grasp its significance. Over the next few months, Vasella and I spoke again and again, but little about cancer. Our sprawling conversations focused on the challenges of running an enormous global company, the unyielding pressure from Wall Street, and the unexpected crises of confidence that leaders face—subjects closer to Fortune’s editorial focus. (He and I turned the interviews into an essay for the magazine, entitled “Temptation Is All Around Us,” in which Vasella thoughtfully, and forthrightly, bared some of his driving fears and desires.)

As for the revolution then going on in cancer therapy, I did not think about it again until another drug company CEO, Sam Waksal, was in the news. Waksal had founded, with his brother Harlan, a small biotech company called ImClone, which also had a targeted cancer medicine in development.

Sam Waksal was the anti-Vasella—a showman and socialite famous for hosting lavish, celebrity-brimming parties at his “art-filled SoHo loft,” as New York’s gossip pages put it. In 2001, he made tens of millions of dollars cashing in ImClone stock, which had soared on rumors of the imminent approval of the company’s cancer agent. Like Gleevec, this new molecule was designed to interrupt the growth signaling of a specific protein.

ImClone’s experimental agent, soon to be known as Erbitux, operated by way of a different mechanism: a biological one. Unlike traditional chemistry-based drugs, Erbitux was an antibody, one cultivated in the living factories of cultured cells. Conceived by a well-respected cancer researcher at Houston’s MD Anderson Cancer Center, the molecule had been in the making for some twenty years. And by late 2001, at long last, it looked as if the agent would be approved by the Food and Drug Administration.

Although results from the initial trials with the antibody were nowhere near as dramatic as those for Gleevec, Erbitux’s quarry was more plentiful—a protein receptor found in excess on cells in roughly a third of all cancers. Its “market,” therefore, was potentially huge. That was why giant Bristol-Myers Squibb had invested a head-shaking $2 billion in ImClone earlier in the year, and why several Wall Street analysts were predicting that Erbitux would become a billion–dollar-a-year medicine. ImClone’s antibody, proclaimed the brokerage firm UBS Warburg as early as January 2001, “represents a significant market opportunity, with an overall target population of well over 400,000 patients and blockbuster sales potential.” Morgan Stanley Dean Witter chimed in, “In our view, ImClone is poised to become one of the next commercial success stories in biotechnology.” Erbitux was to be Gleevec writ large.

But there was a snag. As 2001 drew to a close, reviewers at the FDA refused even to evaluate ImClone’s antibody for licensing, citing critical problems with the way the company had set up its clinical trials and analyzed its data, among other complaints. Sam Waksal tried to dump shares of ImClone stock before the bad news came to light, passed along the confidential information to family members (who also sold stock), misrepresented the FDA’s objections to public shareholders, and got caught. The style doyenne Martha Stewart also sold shares after getting advance warning. She and Waksal would both go to jail.

Every nugget from the story was savored in the press. My own magazine published nearly a dozen articles on the subject over a two-year stretch. The name ImClone became an eponym of corporate scandal like Enron, WorldCom, and so many others. Yet this story was different from the others. Waksal’s white-collar crimes had a cost, it seemed, that went well beyond shareholder loss. They had left a good drug, a lifesaving drug, in the lurch.

Had ImClone’s top management not botched the Erbitux clinical trials, then papered over the problems, then outright lied, the medicine might have been in cancer patients in months. It would now take years.

That was the sad coda to so many ImClone stories in the media. And that, oddly enough, was what made me think we were winning the war on cancer.

There was a narrative that connected the sober, truth-telling Dan Vasella with the double-talking New York social climber Sam Waksal. ImClone, the company that couldn’t shoot straight, and Novartis, the one that couldn’t miss, were aiming at the same surprising scientific bull’s-eye.

So were dozens of other companies. And at least according to the FDA, a few were hitting it. In May 2003, the US drug agency approved two highly touted cancer medicines: Iressa, from the European pharmaceutical company AstraZeneca, and Velcade, from a small biotech firm based in Cambridge, Massachusetts. Both were of the new genus of sophisticated drugs that zoomed in on specific antigens, enzymes, or receptors to interrupt an improper growth command or gum up a cellular mechanism that had gone dangerously awry. Iressa was going after the same high-stakes target as Erbitux.

A few weeks later, more than twenty thousand cancer doctors gathered in Chicago for the annual meeting of the American Society of Clinical Oncology (ASCO), the world’s leading guild for cancer physicians. There, too, the major headlines focused on the new breed of inhibitors—notably, an antibody called Avastin, which was designed to squeeze the life out of tumors by robbing them of their blood supply. Indeed, when researchers announced the results of a new clinical trial testing Avastin in patients with advanced colon and rectal cancers, the packed hall at the McCormick Place Convention Center erupted in applause.

I had followed these developments not as a cancer patient whose life depended on knowing what new treatments offered hope, nor as a doctor who understood the context of these gains and the desperate need of those whom they cared for, nor as a science writer who studied the vagaries of the drug-discovery process and the nuances of these agents’ biological mechanisms. I had followed these apparent milestones—I am embarrassed to admit—with the detached eye of a business editor. The pharmaceutical industry had long boasted of the progress it was making in the war on cancer. Here was proof, it seemed.

Even the medicine that Sam Waksal had hawked—and nearly destroyed through his carelessness—had come back from the brink of irrelevance. The evidence dangled from ImClone’s suddenly lofty stock price. Between June 12, 2002, when Waksal was arrested for insider trading, and June 10, 2003, when he was sentenced to more than seven years in prison, ImClone’s share price had soared 364 percent. (The Standard & Poor’s 500 stock index had dropped by 3 percent over the same period.) Erbitux, the firm’s only major drug, was still months away from approval. But reports from various clinical trials had been promising. It now seemed as if both the oncology experts and investors might be right after all: The antibody worked. Many were betting on that, at any rate.

It was a great story—and, frankly, an upbeat one in an era beset by scandal. So in the fall of 2003, I set out to report on the scientific revolution that was transforming cancer medicine. The thesis was not original. (Fortune’s longtime rival BusinessWeek had done a fine cover story on the subject a few months earlier, focusing on Erbitux.) I had promised myself to look more broadly, if possible, to see how the long war on cancer was being won on multiple levels, not just with a new fleet of drugs.

Right from the start, however, I was confused. The numbers did not add up. For years, even before drugs such as Gleevec and Erbitux came on the market, US health officials were saying that the death rate from cancer had steadily been dropping. But in the simplest terms—in raw numbers—more people in the United States were dying of cancer each year. Officials used a death rate that adjusted for both the rising population and its changing age demographics. But even with such filters in place, the rate had barely budged since 1971, when President Nixon signed the National Cancer Act, launching what became known as the war on cancer. Nor had the rate dipped much from its 1950 level.

Nor did it look as if the vaunted new cancer medicines, the targeted agents, would be able to make much of a dent. The more data I read from completed clinical trials, difficult as they were to read and comprehend, the more I wondered if the new therapies did any good at all. I was missing something, obviously. Cancer officials had been talking of declining death rates for years. Every few weeks, it seemed, came reports of a new clinical advance.

I kept looking. The nation was spending far more to study cancer, and exponentially more to treat it, than we had a decade or two earlier. Official patient survival rates had crept up a little, but even these figures were suspect, as I would discover later.

In an unexpected way, the cancer story was unfolding like so many of the sordid business sagas that had appeared in Fortune and BusinessWeek and the Wall Street Journal over the previous few years. There was a profound disconnect between the rhetoric of top management and the numbers. NCI officials and leading oncologists were talking about “steady progress” and “turned corners” and “breakthroughs,” but the statistics told a far more depressing tale.

I began to get that old Wall Street feeling: Could we be losing the war on cance...

Revue de presse :

“As a cancer patient and advocate, I applaud Clifton Leaf for so boldly pulling back the curtain on the ‘cancer culture’ to reveal why we've made limited progress toward cures. The Truth in Small Doses, a book told with the rigor of a brilliant journalist but with the heart of a cancer survivor, is certain to disrupt the conversation on the state of cancer research and inspire new approaches to win this war.” (Kathy Giusti, founder and CEO, Multiple Myeloma Research Foundation and Multiple Myeloma Research Consortium)

“In this brave and important book, Clifton Leaf explains the state of cancer research today, traces the battles we have won and lost in the war on cancer, and most importantly shows the ways in which doctors, researchers, and even patients might improve what we are doing to combat this disease. Leaf’s own path—from cancer patient to journalist to author—is an inspiring story itself, and his book will benefit both patient and doctor alike. The Truth in Small Doses will be the most important ‘discovery’ in cancer this year.” (David B. Agus, M.D., author of The End of Illness)

"In this lucid, convincing, and gripping book, Clifton Leaf lays out, in heartbreaking detail, why our well-intentioned war on cancer has produced such dispiriting results. Leaf's command of the science is masterful, his passion is palpable, and his critique of a broken research system is utterly convincing. But, like the best advocacy journalism, The Truth in Small Doses is ultimately inspiring, pointing the way toward a more hopeful future. It is a landmark achievement." (Jason Tanz, executive editor of WIRED)

"Beautifully written, with the twists, turns and suspense of a great novel, The Truth in Small Doses tells the tale of the great individual successes and collective failure of both government and the pharmaceutical industry to impact the increasing number of cancer diagnoses and deaths in the U.S. But Clifton Leaf offers more than a history of our national cancer effort: He provides a vision and a roadmap for a creative and bold national cancer strategy." (Frank M. Torti, MD, MPH, Dean, University of Connecticut School of Medicine, former director Wake Forest Comprehensive Cancer Center and former acting commissioner of the FDA)

"An important evaluative study meriting serious public discussion." ( Kirkus)

"It matters because: We’ve been at war with cancer since 1971, and despite endless promises, are not much closer to truly winning that battle. In this refreshingly impassioned volume, Leaf explains why while offering a path forward…Perfect for: Anyone curious about the history of medicine, as well as the fraught intersection of pharmacology, public policy and the corporate world." ( TheAtlanticWire.com)

“[An] eye-opening look at why the U.S. is losing the war on cancer… The Emperor of All Maladies got Americans talking about the stalled battle against cancer. Leaf’s book keeps the conversation on track.” ( Booklist)

"Through flowing prose Leaf delivers, alongside facts and data, stories on personalities involved in research, the fascinating process of solving an unusual and highly deadly cancer in Africa, and the heartbreaking realities of cancer treatment in children today. Leaf's extensively investigated treatise will resonate with researchers and patients frustrated by the bureaucratic woes he delineates. Public policy makers, grant reviewers, and pharmaceutical researchers alike must consider Leaf's indictment and proposed solutions." ( Publisher's Weekly)

""Why have we made so little progress in the war on cancer?" Clifton Leaf asked Fortune in 2004. His groundbreaking story went on to describe the failures of researchers and drugmakers alike, and a system so focused on incremental improvements in the treatment of the disease that it could not arrange itself to tackle the roots of a persistent (and still growing) problem. For a decade Leaf has followed the story, and though we are no closer to ‘curing’ cancer, we can now imagine—thanks to his lucid and fascinating work—what that solution might look like. In Leaf’s brilliant new book, he reframes the challenge as one of engineering, not science. As Leaf writes, "Science determines the limits of the possible. Engineering lets us reach them."" ( Fortune)

"According to Leaf, a journalist and cancer survivor, the [1971 National Cancer Act] failed because of the flawed research culture it spawned. In this history of the fight against cancer, he describes how scientists often cannot secure funding for risky research in a culture that rewards competition over collaboration." ( Recommended by Scientific American)

“Leaf’s book serves as a powerful call-to-action that our current system is too structurally flawed to provide the transformation in cancer care we all seek…the longer format has given Leaf room to explore the wide range of issues in more detail, and several chapters merit reading as stand-alone pieces…Leaf’s analysis is clear and accessible to scientists and non-scientists alike, and should probably be read and debated by senior executives at all oncology-focused drug companies.” ( Pharmagellan.com)

“A fascinating resource for anyone interested in understanding more about the biological mechanisms of cancer and curious about the history, politics, and ethics of the current cancer culture.” ( HuffingtonPost.com)

“Exhaustively researched.” ( Nature)

“Provocative…his prescription is dead on.” ( New York Post)

“A ferocious call to action, backed up by both data and experience.” ( Newsweek)

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Description du livre SIMON SCHUSTER, United States, 2014. Paperback. État : New. Reprint. 220 x 146 mm. Language: English . Brand New Book. A brilliant (Fortune), eye-opening history of the war on cancer, The Truth in Small Doses asks why we are losing this essential fight and charts a path forward. Over the past half century, deaths from heart disease, stroke, and so many other killers have fallen dramatically. But cancer continues to kill with abandon. In 2013, despite a four-decade war against the disease that has cost hundreds of billions of dollars, more than 1.6 million Americans will be diagnosed with cancer and nearly six hundred thousand will die from it. A decade ago, Clifton Leaf, a celebrated journalist and a cancer survivor himself, began to investigate why we had made such limited progress fighting this terrifying disease. The result is a gripping narrative that reveals why the public s immense investment in research has been badly misspent, why scientists seldom collaborate and share their data, why new drugs are so expensive yet routinely fail, and why our best hope for progress--brilliant young scientists--are now abandoning the search for a cure. Through flowing prose Leaf delivers, alongside facts and data, stories on personalities involved in research, the fascinating process of solving an unusual and highly deadly cancer in Africa, and the heartbreaking realities of cancer treatment in children today. Leaf s extensively investigated treatise will resonate with researchers and patients frustrated by the bureaucratic woes he delineates. Public policy makers, grant reviewers, and pharmaceutical researchers alike must consider Leaf s indictment and proposed solutions (Publishers Weekly). The Truth in Small Doses is that rare tale that will both outrage readers and inspire conversation and change. N° de réf. du libraire AAS9781476739991

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