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 cancer?
Over the next few months of reporting I came to believe the answer was yes.
I wrote a cover story for Fortune in March 2004 that made that sad argument. The analysis was based on more than just the numbers. Interviews with scores of scientists and doctors, regulators, and other warriors in the cancer arena had painted a disturbing picture. Their often candid testimony described what I called a dysfunctional “cancer culture”—
a groupthink that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs; that fosters isolated (and redundant) problem solving instead of cooperation; and rewards academic achievement and publication over all else.
At each step along the way from basic science to patient bedside, investigators rely on models that are consistently lousy at predicting success—to the point where hundreds of cancer drugs are thrust into the pipeline, and many are approved by the FDA, even though their proven “activity” has little to do with curing cancer.
Each participant in the system did the proverbial best he or she could. Everyone involved wanted to contribute. But the way the system worked day in and day out seemed almost designed to keep progress at bay—to discourage substantive collaborations, to prevent the timely sharing of data, to slow the rate at which new laboratory discoveries could be developed into viable therapies. As Andy Grove, longtime CEO of microchip maker Intel, cancer survivor, and philanthropist, described it to me in early 2004, “It’s like a Greek tragedy.”
The letters poured in, as they always did after a provocative Fortune cover. I had anticipated a spirited defense from cancer doctors, but instead I got dozens of invitations.
Researchers, medical oncologists, cancer center directors, and patient
advocates wrote with requests to continue the conversation. Some said, with surprising amiability, that I had gotten some things dead wrong; most wanted to tell me more—to share with me their own frustrations with a broken system. Patients and, harder to bear, the parents of children with cancer wrote me of their panic and despair—and, often, “in spite of what some Fortune reporter had written,” of their resolute, unshakable hope. One man told of the high school sweetheart he had married and lost to the disease, though he still refused to believe she was gone; a father e-mailed to see if there was anything, anything at all, that could fend off his daughter’s far-gone lymphoma.
My wife and I read the letters, one by one, and cried. She was seven months pregnant with our first child when the story came out. I was then an executive editor at the magazine—a business magazine, I reminded myself. One that published stories about Walmart and IBM; that opined about corporate strategy and investment opportunities. It was not the time to continue my inquiry into the war on cancer. I had never written a “science” article other than this one. I nearly failed high school biology, and for good reason. I wasn’t qualified to write about any of this.
And yet I couldn’t stop myself. There was still a story I wanted to tell. It was the one prompted by a question that went unanswered in interview after interview. If the efforts to win the fight against cancer were paralyzed by a dysfunctional cancer culture, how did we get here?
Those five words—How did we get here?—became the focus of my life for the next nine years. They are, indeed, the core of this book.
Cancer scientists speak eloquently about the need to study the biological mechanisms of cancer, to understand its genetic roots. Only with such comprehension, say many, can we figure out ways to stop the disease. The same can be said for the culture of cancer science: we need to know how it became the way it is before we can fix it.
The forces in this culture—some dramatic, others subtle, a few nearly imperceptible—have evolved over decades, if not centuries. Trying to single them out is like trying to point to the rainstorm that carved a canyon. But that is the thing about cultures: they form in such slow motion that the process is often ignored until the ground has been thoroughly redrawn.
I have tried nonetheless. Over the past nine years, I have spoken with well over a thousand people involved in the cancer fight around the world—oncologists, geneticists, pharmacologists and drug designers, university professors, officials at the NCI and the FDA, surgeons and radiologists, statisticians, politicians, big-company executives and start-up entrepreneurs, foundation leaders, cancer nurses, veteran advocates, caretakers, and, most of all, patients. Some of the conversations have been formal interviews; many more have been chats over coffee in the hallway of a conference center, or long-running e-mail exchanges.
In the process of reporting and writing this book, I have changed as well, beginning the journey as a business editor and ending, in some ways, as a proponent of reform.
I served for three years on the national board of directors for Susan G. Komen for the Cure not as a journalist, but as an advocate for Komen’s tens of thousands of volunteers and for millions of people with breast cancer. I served as a grants reviewer, and on various advisory boards and committees, not as a reporter, but rather as a participant, panelist, or member. My experiences in these roles have shaped my perspective.
In all this time I have emerged certain of only one conclusion: this is a story without any villains. Unlike in so many aspects of American business, personal greed has played little part in the failure of the national cancer enterprise. Some readers may find that assertion difficult to believe—or may find it naïve of me to make it—but after nine years of wandering in this realm I am confident of this claim.
That said, plenty of heroes appear in the pages that follow, and through their stories—tales of lessons learned and lost, and of Herculean struggles waged for decades—this book’s argument is made. In Part One, I have tried to give a complete assessment of the growing cancer burden, one now carried by millions of people, but which is barely reflected in the statistics health officials use in reporting progress in the cancer war. Part Two shows why the scientific strategy we have chosen cannot succeed in lessening the terrifying human cost of cancer, and offers the only viable path to achieving that goal, which in my view is to interrupt the disease process in its earliest stages of development. (As chapter 7 makes
clear, the barriers to this approach are hardly insignificant. We have little choice, though, but to attack these challenges head-on.)
Part Three is the story of the dysfunctional cancer culture itself. It begins with a wrong turn at a critical juncture in history: the start of the modern cancer effort in 1971. Chapter 8 tells the surprising tale of what happened in the legislative wrangling over the National Cancer Act—and how that act of Congress, instead of hastening a “cure,” set in place (or reinforced) many of the barriers to success we face today.
No doubt many will assume that the biggest of these barriers involves money. Nearly every cancer scientist and advocate, after all, contends that our failure to make significant headway against the disease is due to a lack of sufficient funding, and politicians and stewards of the national cancer program have long agreed. Chapter 9 punctures that myth. Money is at the core of many of the failings in the modern cancer effort. The greatest of these problems stem, however, not from a lack of money, but rather from the way it is spent. This chapter, along with the next three, make that clear.
Chapter 10 reveals the career and financial incentives (and academic traditions) that push investigators to think narrowly and impede collaboration. Chapter 11 bares the mind-set that limits risk-taking in cancer drug development and all but ensures that treatment will improve in the slowest, most incremental fashion; while chapter 12 shows how thin the line between risk-taking and recklessness can be, and why we sometimes have to be willing to approach that line to save lives. Chapter 13 explains why so much of the raw data generated in the modern high-tech research effort never translates into clinical knowledge, and why even a tiny investment in low-tech infrastructure might change that.
What may be surprising to many readers is how well-known these systemic failures are to the cancer community—not only to rank-and-file researchers and oncologists, but also to those in positions of leadership in science, medicine, industry, and, yes, government. One official report after the next has cataloged the problems and promised reform. Still, little of substance is ever done to change them.
Part of the reason, indeed, may be due to the cancer culture itself. In
this realm, there is little incentive for investigators to look to the past—to search for wisdom in the pages of ancient, musty journals, to follow up on the fledgling insights, or experimental teases, of scientists who came earlier. The result is that much of what is learned in one generation is forgotten in the next.
Among these myriad bits of lost wisdom, one stands out: It is the story, told in chapter 14, of a one-eyed, Irish surgeon named Denis Burkitt, who taught the world how powerful true scientific collaboration can be. Far-flung investigators, working together, unraveled a cancer mystery that no single scientist would ever have solved on his own. The tale in this chapter took place half a century and half a world away, but its lesson remains as essential today as ever.
Part Four, notably, is the shortest section of the book. It contains but one chapter (“Matterhorn”), where I have tried to lay out a way forward in our century-old cancer crusade. It may seem to some that a three-hundred-page history of how and why we have failed in the war on cancer ought to be balanced by more than a single, brief chapter for the proposed solution. There may seem to be something cowardly in spending so much time dissecting a broken system without also offering a litany of concrete “fixes.” Over the past several years, I have felt that way many times myself.
But then, as will have been made clear by then, I hope, the route to victory in the cancer war is not as complex as it might seem. It does not require another act of Congress—a thousand-page bill forming new committees, oversight boards, and complicated mandates. Nor does it necessarily take a huge influx of taxpayer money to create a system that encourages researchers to think in novel ways, to share ideas more freely, and to take more entrepreneurial leaps in their scientific exploration. What is needed to reach this goal is a different sort of political will: a fierce public commitment to undo the incentives, rules, and daily practices that don’t work. Many of them are so entrenched that it will take an army of citizen–scientists and warrior patients to remove them. It will take even more public will to pursue an authentic “war” on cancer, one that honestly lays out the mission and follows a coordinated plan to achieve it.
Mustering a nation’s will is no easy aim. Summoning it depends first on telling the truth about the cancer burden today, and what the future holds as the American population continues to expand and age. Admittedly, some people will have a difficult time accepting such a blunt message. Grateful survivors may reflect upon their own victories and conclude that the effort is not failing at all.
Each rescued life, certainly, is a victory over cancer that ought to be celebrated. But the fact that there are millions of cancer survivors does not validate our approach in the anticancer campaign—any more than a growing number of soldiers returning from the front suggests a war is being won. All it really means is that more people have been sent into battle.
Others may contend that reporting on the lack of progress made against cancer steals precious hope from those who need it most. With each life saved, with each report of success, they say, comes renewed hope for those newly diagnosed, and for their loved ones.
I do not dispute the raw power of hope. I have felt it myself, believed in its magic to help me through my own bout with cancer long ago. I have seen my mother rely on it, wield it, call it forth in the darkest hours of her own fight. None of us, perhaps, could live without it.
But for hope to be more than mere wishing, it needs vision; it needs a commitment of will; it needs a clear perspective on where we are and where we need to go.
And for that, it helps to know how we got here.