Cancer: Malignant Maneuvers

When President Richard Nixon signed the US National Cancer Act into law on December 23, 1971, he declared, “I hope that in the years ahead that we may look back on this day and this action as being the most significant action taken during this Administration.” Nixon killed his hope with bewildering hubris. But his call for a war on cancer remains the most astonishingly ambitious, and ultimately flawed, political commitment to a disease in the history of humankind.¹ With the joy of hindsight, one cannot help viewing Nixon’s juxtaposition of cancer next to man’s successful efforts to split the atom and walk on the moon with admiration mixed with incredulity. It is morbidly ironic that Nixon’s wife, Pat, died from lung cancer in 1993.

Today, cancer is an undefeated epidemic in all industrialized Western societies. Among American women, for example, lung, breast, and colorectal cancers remain some of the leading causes of death. Among American men, the prostate and liver replace the breast as organs of major malignant importance. There are also disturbing disparities: death rates from cancer are highest among African-Americans. Yet despite enormous investments in research, diagnosis, and treatment, one in two men and one in three women will die of cancer. Moreover, once a cancer has spread, or metastasized, the chances of stopping it by radiation or chemotherapy for more than a short period are usually very small. One American dies from malignant disease every minute. By any common-sense measure, the war on cancer has been lost.

The current leaders of that war take a very different view. They point out that in 1978 there were three million cancer survivors in the US. By 2005, that figure had swelled to ten million. They list a plethora of task forces, initiatives, programs, and studies that signify phenomenal activity. They speak of a long list of accomplishments, unprecedented opportunities, a new age of scientific discovery, and their strong sense of mission.² The National Cancer Institute (NCI) is the world’s most influential cancer research organization. Its leaders have supported the work of at least twenty Nobel laureates.

To be sure, there have been impressive signs of progress. The year 2003 saw a decline in the number of women diagnosed with breast cancer. The mass abandoning of hormone replacement therapy—an important cause of invasive breast cancer—from 61 million prescriptions in 2001 to 21 million in 2004 is one likely explanation. And new classes of treatment for some of the most intractable types of cancer, such as monoclonal antibodies for colorectal cancer, are prolonging lives.

But these isolated instances of success belie larger failures. Writing twenty-five years after Nixon launched his campaign, the respected cancer scientist Michael Sporn argued that the critical obstacle to large reductions in mortality was a misplaced emphasis on treatment over prevention. Playing catch-up with surgery, radiation, and toxic drugs once cancer has taken hold reflected an inappropriate obsession with the concept of cure. According to Sporn,

We must develop new approaches to control this plague of deaths, adopting an ethic of prevention, based on a more sophisticated understanding of the process of carcinogenesis and the potential to prevent disease before it becomes invasive and metastatic.³

Sporn’s words have not been heeded, prompting some observers to call the so-called war simply “futile.”⁴ Joining this increasingly fractious debate with devastating force, Devra Davis, director of the Center for Environmental Oncology at the University of Pittsburgh Cancer Institute, claims that the war “has been fighting many of the wrong battles with the wrong weapons and the wrong leaders.” She calculates that these “fundamental misdirections” have thrown away well over a million American lives. Her aim in The Secret History of the War on Cancer is to deliver nothing less than a “reckoning” of this terrible toll.

1.

Davis’s main charge against the cancer establishment is that it has ignored accumulating evidence pointing to environmental hazards as a—perhaps the—major preventable cause of malignant disease. Through an utterly disingenuous strategy of “doubt promotion,” cancer scientists have poured scorn on what could be the key to controlling this most resistant of modern scourges. Evidence from animal-based research indicates clear risks from environmental chemicals, argues Davis. Yet while cancer physicians accept data about potentially effective new drugs from animal experiments, they reject animal research as the basis on which to estimate risks from environmental toxins and pollutants.

This irrational double standard has fostered an “arrogance” among today’s leaders of the war on cancer. They have chosen to ignore sixty years of what Davis sees as convincing science. Why? Partly, she claims, because of “the revolving door of cancer researchers in and out of cancer-causing industries,” among them the tobacco and cosmetics industries. The result of this indolence and self-interest is that “we are treating people like experimental animals in a vast and largely uncontrolled study.” The field of oncology has become a business. One consequence is that the Food and Drug Administration (FDA), fearful of incurring the political wrath of Congress, is soft on businesses that promote possible cancer-causing chemicals in an array of drugs, lotions, and creams.

One example Davis cites is Ritalin. As many as one in ten American children take this drug at some time in their young lives. Evidence from animal research suggests that Ritalin may cause liver tumors. Studies in children point to possible genetic damage. Davis concludes that Ritalin “may pose extraordinary risks to our genetic makeup.” Despite protests, the FDA has taken no action.

Her sharp critique goes well beyond the FDA. Early in its history, the NCI delayed and ultimately barred efforts by one of its most distinguished scientists—Wilhelm Hueper—to publish an uncompromising report on environmental carcinogenesis. His work showed how frequently used substances—asbestos, benzene, chromates, amines, together with assorted oils and dyes—were readily avoidable causes of cancer. Their elimination from industrial, civilian, and military use as “the dominant cause of human cancers” was, he said, a public health imperative. Yet in the 1950s his work was deemed anti-business and pro-Communist.

The American Cancer Society, whose leadership once included a tobacco magnate, was fifteen years late in advocating the Pap smear as a means to prevent cervical cancer. The society considered anti-cancer clinics to be “socialistic.” And it has adopted a skeptical attitude toward the value of research, betraying Mary Lasker (of Lasker Award fame), whose original and ardent support of the society was, Davis reminds us, based upon extracting a commitment from its leaders to invest generously in science. For every $4 raised, the American Cancer Society promised to spend $1 on research; it now invests only a tenth of its resources in research, an unacceptably small sum, Davis suggests.

The American Medical Association has a similar record of obfuscation. The US surgeon general’s report on smoking and health was published in 1964. Three months after its release, cigarette consumption in America had fallen by 20 percent. Yet it took a further fifteen years before the American Medical Association publicly accepted that tobacco smoke was harmful to the lungs. Even then, Davis emphasizes, this leading professional voice of American medicine had nothing to say about smoking and cancer.

One institution that should have made a muscular response to these manifest environmental dangers—the Occupational Health and Safety Administration (OHSA)—was nothing more than a “paper tiger,” according to Davis. Over a twenty-five-year period, OHSA has, on average, set environmental standards for only one human carcinogen each year, a pitifully poor record. Davis alleges that OHSA works too closely and comfortably with the industry trade association, the American Chemistry Council.

Her critical eye also takes in the International Agency for Research on Cancer (IARC) for, she claims, delaying work on the safety of mobile telephones and accepting funding from industry. She describes how the agency bullied and intimidated one of its former directors when he inquired about the status of this important research concerning a potentially common cancer-causing environmental hazard.

There are individual as well as institutional villains in Davis’s account. Robert Kehoe was the founder of American industrial hygiene. He discovered the connection between bladder cancer and benzidine in German factory workers. But from the 1930s to the 1960s Kehoe conducted secret contract research for companies, such as General Motors and Monsanto, while working at the University of Cincinnati. From that highly compromised position—posing as an independent scientist, while all the time working for the same industry he was supposed to be scrutinizing—he defended the increasingly preposterous argument that lead was a natural and unavoidable environmental contaminant.

In the 1920s, Clarence Little led a successful campaign to make the public more aware of cancer. He mobilized women into a field army to educate more women about the widespread existence of cancer. Because of his energetic efforts to persuade a largely unaware population to seek early diagnosis and treatment, Little was appointed the first director of the NCI in 1940. But he soon became part of a clandestine operation spreading doubt about the environmental causes of malignant disease. He was a founder of the Tobacco Industry Research Council, a group that aimed to deflect concerns about smoking as a cause of cancer by proposing alternative causes (air pollution), by criticizing animal research (unreliable), and by sowing public and political seeds of uncertainty (tobacco as a cancer-causing agent was merely a theory). Davis describes how Little spent the final decades of his life miserably “masterminding ways to magnify uncertainties about tobacco products.”

But these attacks are mild by comparison with her extraordinary onslaught against the aristocracy of modern cancer research. Davis’s principal target for criticism is Sir Richard Doll.

2.

For half a century, the British epidemiologist Richard Doll was one of the world’s leading cancer researchers. Beginning with his report proving once and for all that smoking was a cause of lung cancers,⁵ his work inspired generations of young scientists to study the causes of human disease. For most researchers who investigate cancer in human populations (rather than in the laboratory), Doll is a revered figure. He is spoken of with respect and admiration to this day (he died in July 2005, aged ninety-two). But for Davis, Doll is an example of a scientific egotist who sold out his discipline and his colleagues.

The quantity of vitriol and innuendo that Davis pours on Doll’s reputation is unusual for one scientist writing about another. He “maneuvered and failed,” she writes, to get the Nobel Prize for his discovery of the link between tobacco and lung cancer.⁶ His behavior was “less than gallant.” Among Davis’s more serious charges, she claims that Doll failed to acknowledge earlier German research linking smoking to lung cancer. Although she concedes that Doll’s work had a “radical impact” and that he did, indeed, cite one piece of German research from 1939, she implies that he deliberately obscured the work of others—he refused to acknowledge “critically important precedents” for his own findings—in order to advance his own fame.

Davis argues that Doll tried to suppress the risks of asbestos, a known potent cause of cancer. In 1954, Doll, together with a colleague, John Knox, began to investigate the hazards of asbestos among workers at an industrial plant called Turner and Newall. They found that those who worked with asbestos had ten times as much lung cancer as those who did not. Turner and Newall blocked publication of these findings. Doll tried to publish his results elsewhere. But Davis alleges that he altered his conclusions, removing the suggestion that there was a risk from asbestos. Doll went on to consult privately for the company. Davis calls his actions “shocking” and “disreputable”: “he defended the company against lawsuits from some of its asbestos-exposed workforce,” she writes, thereby denying them potential compensation for their occupationally acquired illness.

A further charge is that Doll’s exoneration of radiation as a cause of cancer in 1960 delayed the regulation of medical X-rays in children for twenty-five years. Davis believes that the evidence against radiation had long been clear (and recent worries about the safety of computed tomography bear out her concerns). Our reckless use of radiation in young people could, even now, be creating more cancer, not less. Diagnostic radiation has increased to levels equivalent to hundreds of Hiroshimas. Doll played an important part, Davis suggests, in creating this “major cancer burden.”

Doll is alleged to have conspired with Robert Kehoe to hide the health hazards of gases released from coke ovens, gases that doubled the rates of lung cancer among exposed workers. Davis also points to work by Doll that grievously set back women’s health. In research published some forty years ago, Doll concluded that his results “do not provide evidence that mass cytological screening is able to reduce the mortality from cancer of the uterus.”⁷ Davis writes that he once admitted privately to being wrong about cervical screening. But he never made that admission public.

One of Doll’s most distinguished younger colleagues is Richard Peto, a brilliant scientist who has averted the deaths of thousands of people thanks to the research he has led in cancer and heart disease. But Davis ties both Doll and Peto together in her attack on the evidence they gave jointly to the US Congress in the 1970s. They were invited to analyze the risks of developing cancer in the workplace. Doll and Peto judged there was no increase in workplace-related cancer, despite concerns that as much as a fifth of malignant disease in the future may be due to occupational exposure to hazardous chemicals. Davis did her own calculations and concluded that Doll and Peto “systematically underestimated” the dangers of the workplace.⁸

But perhaps Davis tries to inflict her deepest wound against Doll’s reputation by citing his defense of the chemical vinyl chloride. This substance—which, when polymerized, is widely used in domestic items such as containers and bottles—was banned in 1978, four years after an Italian toxicologist, Cesare Maltoni, proved in laboratory animals that vinyl chloride caused a rare and untreatable liver tumor, angiosarcoma. Slowly, it became clear that angiosarcoma was not confined to animals—this cancer was also developing in workers exposed to vinyl chloride. In 1987, the IARC reexamined the risks of this chemical. Their scientists found strong evidence that vinyl chloride was also linked to cancers of the brain, lung, and bone marrow.

The chemical industry found itself under attack. Who did it turn to? Richard Doll. He wrote a long personal assessment of the case against vinyl chloride.⁹ His conclusion was that there was no increased risk of brain and liver cancers. Davis calls his analysis “limited,” and it is true that by today’s standards his report falls short of a systematic review of all the available evidence. Worse, Davis argues, “the paper did not mention that Doll had performed this work as a consultant to the Chemical Manufacturers Association.” The effects of Doll’s inadequate review, conducted under the cloud of a fatal conflict of interest, were calamitous. As a powerful and influential cancer scientist, his judgment again contributed to the failure of workers to get justifiable compensation for the cancer they developed after exposure to vinyl chloride, or so Davis suggests.

I met Richard Doll only a few times. He seemed a quiet and reflective man, careful with his words and cautious with his scientific judgments. He had a lifelong passion for science. It is disappointing to learn that he had such close and undisclosed ties to industries that he must have known had good reason to buy his time and reputation. Was it naiveté? Or vanity? Or money? Or poor judgment? Or is it simply unfair to condemn a man who cannot reply to his critics and who is being judged by today’s standards of scientific probity, standards that were slacker a decade ago?

The truth is that we will never know the answers to these questions for certain. Davis’s attacks on Doll’s reputation may well become an indelible stain. He should have known better than to allow himself to have his reputation for independence undermined. But Davis paints Doll in the most unforgiving light. And, while her accumulated arguments do hurt Doll’s scientific legacy, such a partial view seems unbalanced and unjust.

3.

Davis’s view of the environment as a neglected influence on human life perhaps stems from her original training in physiological psychology and sociology. Her criticisms of mainstream science—and scientists—are no surprise. Davis began her career as a robust skeptic about science. In 1975, for example, she wrote that “science is but one sector of the economy whose role has too often been overestimated.”¹⁰

But her training in epidemiology and public health also gave her the scientific tools to interrogate orthodox beliefs about the causes of cancer. She quickly applied these techniques to back animal research as a sound basis for exploring the risks of occupational chemical exposures.¹¹ And she used her knowledge of public health to hold government agencies, such as OHSA, to account when she thought they were delaying important decisions about environmental risks.

Early on, Davis’s own research pointed to a rising number of deaths from cancer. She argued that these increases might be caused by environmental and workplace carcinogens.¹² She described how a “remarkable” worldwide epidemic of cancer seemed to be taking hold.¹³ The increase in the cancer burden was “great and rapid” and needed to be answered “aggressively.” One response should be to investigate urgently the potential dangers of workplace carcinogens and diagnostic radiation, she concluded. Her critics accused her of unwarranted alarmism and sloppy scholarship.

Still, Davis was right to draw attention to some strange and unexplained anomalies in the global cancer burden. Why is there more cancer of the colon in Egypt than America? Why is pancreatic cancer more common in younger people today? Why do we see more women with early breast cancer, especially in African-American communities? Neither age nor genes seem to explain these differences.

The reason for our perplexity about the modern epidemic of cancer may lie in our “collective amnesia.” Until the mid-twentieth century doctors knew that what one did in one’s working life influenced our health. But Davis shows how doctors and scientists are easily diverted by fashionable and mistaken ideas. She illustrates her argument with a detour into the history of eugenics. From early in the twentieth century on, perfectly sane and apparently rational doctors “underwent a shocking transformation.” They endorsed medical murder and, in extreme circumstances, put their profession in the service of evil political doctrines, such as Nazism. Davis reminds us how anatomy textbooks were published based upon the dissection of corpses taken from concentration camps. The drawings were often signed with a swastika.

What Davis seems to be saying is that current ideologies of cancer causation will one day similarly be seen to be perversions of the truth. With many scientists and their laboratories being funded by industries that have a vested interest in denying the risk of environmental hazards, perhaps we will eventually see how misled we have been by powerful economic and political forces that have subverted the “democratic tendencies” of science.

Davis gives two specific examples of our modern proclivity for delusion. The cosmetics industry is founded, she claims, on the use of toxic materials, such as ethylene oxide, which is used as a sterilizing agent. This chemical can cause cancers in human beings. When two molecules of ethylene oxide combine the result is dioxane, which European countries have banned from personal care products because it causes cancer in animals. Yet dioxane is still used in the US. The chemical is found in illegal quantities in some widely available children’s shampoos.¹⁴ Davis questions the FDA’s approach to risk—namely, that potential harm should be a matter of personal choice. The FDA places responsibility on the individual to make a judgment about the risks he or she is willing to accept. In doing so, the FDA has abdicated its responsibility to investigate and regulate human-made harms in our lives.

A second example Davis makes much of is that of mobile phones. She opens her case with a confusing array of claims. For example, she suggests that there are mysterious “untapped” data about the risks of cell phones, that scientists who raise concerns are quietly silenced, and that those people who have lost lawsuits seeking damages for mobile phone–associated cancers are the victims of a deeply flawed approach to discovering risk. Absence of evidence is not evidence of absence, Davis writes. We know that cell phone signals can penetrate the brain and damage cells in laboratory cultures. With over two billion users of mobile phones expected by 2010, surely we cannot afford to be so complacent?¹⁵ The thick climate of suspicion she creates is further fueled by her pointed allegations against the IARC.

I put her allegations of industry bias and data censorship to Peter Boyle, the IARC’s director. He denies that IARC is “in any way” responsive to industry pressure. The work Davis claims IARC is suppressing is the “Interphone study,” a series of multinational investigations to discover whether cell phones increase the risk of cancer. The study is not yet complete, but according to Boyle, it is “reaching completion,” contrary to Davis’s implied accusation of delay. Interphone will be the largest study of its kind. Some of the results from the scientists participating in Interphone are already available. The results are mixed. Most country studies show no increased risk of brain cancer with mobile phone use. Some already published studies, however, suggest increased risks of particular types of brain cancer after ten or more years of cell phone use on the side of the head where the phone is held.¹⁶ Nothing is being hidden from public view.

What is one to make of Davis’s case against the international cancer establishment? Some of her arguments make good scientific sense. Exposures to chemicals that might seem safe at first may exact damage to the body at a later date. There is much that we do not, but should, know about a large number of widely used chemicals in household products. There seem to be few incentives to study these chemicals and their risks to human life. A “medical surveillance” program to monitor these potential hazards is a good idea. There are too many vested financial interests in medical research, deflecting scientists from studying important questions of public health. And we do need to discover new ways to defeat cancer.

But taken together, Davis’s arguments are little more than a collection of vague exhortations to do something based on an often distorted reading of the cancer literature. Her loose speculations weaken her entirely reasonable claim that the war on cancer has been little more than an erratic skirmish.

4.

If treatment comes too late (as it often does), and if Davis’s prescription for prevention turns out to be largely a house of cards (as I suspect it will), what can be done to control the world’s escalating cancer burden?

The two biggest environmental drivers of cancer are tobacco and obesity. Astonishingly, aside from historical anecdotes about smoking and health, Davis has little to say about either. The risks of smoking are well known. Tobacco remains the largest and most preventable global cause of cancer today. In the US, owing to tobacco’s additional harmful effects on the heart and lungs, smoking is the leading overall cause of death in adults, killing 260,000 men and 178,000 women each year. About one in every five deaths is caused by tobacco.

Yet despite these widely known facts, 21 percent of Americans continue to smoke. Lung cancer is the commonest type of smoking-related death. With heavily increased tobacco use among women since 1950, female lung cancer deaths have increased sixfold. Davis could have delivered a far more telling critique of the war on cancer if she had concentrated her efforts on tobacco.

An increasingly worrying trigger for cancer is our expanding waistline, which seems to know no limits. Substantially increasing one’s weight is directly linked to cancers of the uterus, esophagus, kidney, pancreas, ovary, breast (in post-menopausal women), colon, and rectum, together with leukemias, lymphomas, and multiple myeloma.¹⁷

To rein in our inclination to eat our way toward cancer, the World Cancer Research Fund has advised that we should all try to be lean.¹⁸ Their scientists, led by the British cancer epidemiologist Michael Marmot, concluded that

Maintenance of a healthy weight throughout life may be one of the most important ways to protect against cancer.

Marmot’s report also recommends physical exercise, avoiding fatty foods and sugary drinks, eating fruits and vegetables, and limiting one’s consumption of meat, alcohol, and salt. Adhering to this advice could, Marmot and his team of experts write, prevent a third of all cancers. That figure amounts to three to four million cases of cancer averted each year.

The importance of tobacco and obesity does not rule out other aspects of the environment as carcinogenic hazards. For example, IARC recently (and rather bravely, in my view) identified the effects on people working day and night shifts as a probable cause of cancer.¹⁹ But Davis’s investigation into why the war on cancer has failed itself largely fails to deliver on its promise of a “reckoning.” Partly, this is because she has chosen the wrong targets. Partly, it is because she builds her arguments into towering yet brittle threats, out of all proportion to the real and more robust dangers that face us every day.

Davis’s analysis is all the more disappointing given the promise of her early work. A decade ago, she correctly anticipated what is today one of our most urgent public health crises. Davis was an early and powerful advocate for measures to control climate change in the interests of human health.²⁰ But this prescient work is now diminished by what, at times, feels like a crude and sometimes indecent settling of old scores.