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The Truth In Small Doses
Why We're Losing the War on Cancer - and How to Win It
Richard Nixon launched the so-called War on Cancer on December 23, 1971, in what was supposed to be a 'moonshot' effort to cure the disease. Two years later, a Time magazine cover read, Toward Control of Cancer. Two decades after that, it announced, in bold red letters, 'Hope in the War Against Cancer,' surmising that a turning point may have been reached. In 2001, its cover asked if the blood cancer drug Gleevec is the breakthrough we've been waiting for. And this past April, the newsweekly pronounced How to Cure Cancer. Yet roughly one hundred and forty thousand Americans have died from the disease in the last three months.
Outrage over our paltry victories against cancer informs the forthcoming book, The Truth in Small Doses: Why We're Losing the War on Cancer - and How to Win It, by Clifton Leaf, who wrote a much-discussed essay on the same topic for Fortune in 2004. The title comes from a 1959 pamphlet that tells doctors to trickle out information to cancer-stricken patients, since most of them couldn't stand to know the truth: the disease would kill them and there was little that could be done about it. Today, draped in ribbons of every hue, blinded by the promises of targeted therapies and antioxidants, we have, according to Leaf, neglected a basic truth: "the cancer problem" is, in reality, as formidable a challenge as ever. (Jerome Groopman discussed the progress in cancer cures, particularly immune therapy, in the magazine last year.)
Leaf is not an oncologist, but he became acquainted with the profession at an early age; he was diagnosed with Hodgkin's disease at fifteen years old.
As an editor at Fortune, Leaf became enthralled by the promise of Gleevec, an enzyme inhibitor that, since its release in 2001, has proven highly effective at battling chronic myeloid leukemia. Many thought a new age was coming, in which the chaotic spread of cancer would be hindered by drugs that would be precision-targeted to block the replication of rogue cells. It seemed far better than indiscriminately killing both cancerous and healthy cells, as chemotherapy had been doing for the past half-century.
But Gleevec is the exception, not the rule - and C.M.L. is a relatively simple cancer compared to solid-state tumors of the lung, colon, pancreas, or breast. Once they metastasize, most cannot be cured. Those, like Leaf, who have faced cancer have good reason for their impatience: it takes an average of thirteen years to bring a new cancer drug to market. Many of these drugs are pellets fired into cancer's flank. A recent article in the New York Times titled Promising New Cancer Drugs Empower the Body's Own Defense hailed a new melanoma drug whose median survival rate was 16.8 months. An editorial this winter in The Lancet, the august British medical journal, put the matter even more bluntly: Has cancer medicine failed patients? In the words of cancer experts, the answer is yes.
Leaf argues we should be closer to an all-out cure, considering our investment in the effort. The National Cancer Institute receives roughly five billion dollars per year from the federal government. If both public and private investments are to be accounted for, then Leaf estimates the United States spends about sixteen billion dollars a year on cancer research. Nor is there a lack of political will to eradicate cancer, as there is to, say, reducing carbon emissions. Leaf calls it a 'bipartisan disease' that a Republican from Alabama would want defeated as much as a Democrat from Illinois. President Barack Obama said in 2009 that he would launch a new effort to conquer a disease that has touched the life of nearly every American, including me, by seeking a cure for cancer in our time.
In Leaf's telling, oncology is a hidebound field averse to risk, a culture that has grown progressively less hospitable to new voices and ideas over the past four decades. He yearns for the likes of Sidney Farber, the unorthodox pathologist who invented chemotherapy in the late nineteen forties at Boston Children's Hospital by injecting children stricken with acute lymphoblastic leukemia with aminopterin, which prevents cancer cells from replicating. A hero in Siddhartha Mukherjee's The Emperor of All Maladies, Farber is largely responsible for the fact that childhood A.L.L. is a manageable disease today. But his methods had a high cost: he disobeyed superiors, conducted his own trial-and-error studies, and foisted unproven drugs on sick, vulnerable children.
What made Farber an iconoclast is that he wanted to cure cancer even more than he wanted to understand it. As he would come to argue, The three hundred and twenty-five thousand patients with cancer who are going to die this year cannot wait; nor is it necessary, in order to make great progress in the cure for cancer, for us to have the full solution of all the problems of basic research ... the history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures.
Few new bold projects are being funded now, writes Leaf, noting that in 2010, the N.C.I. used the bulk of its two billion dollars in research grants on existing projects. He is as incensed that the same institutions get most of the money, writing that in 2011, the top 43 research centers got more funding ($12 billion) than did the bottom 2,574 institutions receiving any kind of NIH support. To some, this is the price of science that is both sound and safe. To others, it is a culture of scientific inefficiency, an I.B.M. mindset in a field that desperately yearns for Apple.
Oncologists in the field with whom I spoke agreed with this overall assessment of the War on Cancer. Andrea Hayes-Jordan, a pediatric surgical oncologist at the M. D. Anderson Cancer Center in Houston, told me that 'Our strategic attacks are improving, and we are winning some battles, but not the war yet.' Silvia Formenti, who chairs the radiation oncology department at New York University's Langone Medical Center, was even more negative in her assessment of the War on Cancer. She wrote to me in an e-mail, "We have managed to make cancer a huge business, and a national 'terror,' but the progress in reducing mortality is quite questionable."
The book suggests some remedies, foremost among them preventing cancer before it strikes. At Stage 0, a cancerous growth can be detected and removed before it has diversified and spread. By the time a tumor is the size of a grape, it has as many as a billion cells. Those cells become increasingly heterogeneous, and once they break through the basement membrane that acts as a final barrier between organs and tissues, they are free to metastasize throughout the body via the bloodstream or the lymphatic system.
The book finds great promise in the chemoprevention pioneered by Dartmouth researcher Michael Sporn, who wants to treat pre-invasive lesions as seriously as full-blown cancers. This seems to fly in the face of the cautious watch-and-wait philosophy popular with many oncologists, who have become convinced (not without reason) that the cure - toxic chemotherapy, high doses of radiation - could be worse than the disease.
However, other than the breast cancer drug tamoxifen and the H.P.V. vaccine - both of which can reduce the risk of getting cancer, not cure the disease - the promise of chemoprevention remains largely unrealized. A recent paper by two preventative oncologists concluded, "There have been numerous chemoprevention trials in the past 10 years, but the number of approved chemoprevention drugs is still quite small." Another recent study on older men with prostate cancer suggested that 'watchful waiting' was often the best route, noting that many patients opted for expensive treatments they didn't need, thus leading to impotence and incontinence. And a federal task force ruled four years ago that women should delay getting mammograms until age fifty (ten years later than the previous recommendation) because of the procedure's own potential dangers.
Leaf acknowledges these dangers, and also points out an even more serious problem with chemoprevention: biomarkers that would signal carcinogenesis in its earliest stages have not been found. So while he is correct to highlight the potential promise of a prophylactic approach, Leaf's own description of the failed biomarker hunt is, indirectly, a defense of why oncologists today are left with no choice but to wait until the disease develops.
The desire for an accelerated approach to cancer has antecedents in the AIDS activism of the nineteen-eighties. As Mukherjee describes in his book, organizations like ACT UP made the FDA out to be a woolly bureaucratic grandfather - exacting but maddeningly slow. That had repercussions in cancer medicine, where patients also demanded quicker access to potentially life-saving therapies. Especially en vogue by the early nineties was megadose chemotherapy for breast cancer, complemented by a bone marrow transplant. (The original marrow would have been destroyed by the high toxicity of the purported cure.) Yet as Mukherjee notes, by early 2000, the procedure was discovered to have been supported by fictional studies. One of its main proponents, a South African oncologist named Werner Bezwoda, had charmed his fellow practitioners with astounding results that masked the true, fatal dangers of this excessive approach. Mukherjee calls Bezwoda's influential drug trials 'a fraud, an invention, a sham,' yet he was hardly the lone cheerleader for megadose chemotherapy. Any urge to hasten the War on Cancer - however justified that urge may be - must grapple with the risk of promising anecdotes curdling into hideous truths.
Of course, some approaches are neither terribly controversial nor difficult, at least from a medical standpoint: Debu Tripathy of the University of Southern California's Norris Cancer Center told me that he believes that ninety per cent of all lung cancers could be eliminated through the cessation of cigarette smoking. Studies have shown a link between red meat consumption and an elevated risk of cancer. Here, then, may be cancer prevention in its simplest form.
On the whole, Leaf is much less optimistic than Mukherjee. Surveying the state of cancer medicine as it was in 2005, Mukherjee concludes, "The empire of cancer was still indubitably vast ... but it was losing power, fraying at its borders." Surveying some three thousand years of humanity's battle with cancer, Mukherjee's is the more meditative work. Leaf's book is more urgent, more insistent - the voice of a frightened patient who yearns for a cure, rather than of the sober oncologist concerned with getting the science right. 'Emperor' is a story; 'Truth' is an argument.
Earlier in June, researchers discovered a tumor of the rib bone of a Neanderthal believed to be a hundred and twenty thousand years old. What plagued him then still plagues us today, much as it plagued Atossa, the ancient Persian queen who is believed to have suffered from breast cancer, as well as the London chimney sweeps stricken with scrotal malignancies. This war has been a long one.
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