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Licking Death

Seamus O’Mahony

The Cancer Chronicles: Unlocking Medicine’s Deepest Mystery, by George Johnson, Bodley Head, 304 pp, £18.99, ISBN: 978-1847921666

Some time in the early 1970s, cancer replaced nuclear annihilation as Americans’ greatest fear. Richard Nixon, with his keen sense of what exercised his compatriots, famously declared “War on Cancer” – no matter that declaring war on cancer makes as much sense as declaring war on death. No matter that cancer, as George Johnson reminds us in The Cancer Chronicles, is not one, but hundreds of different diseases. “Cancer” is an umbrella term for many different maladies, ranging from the completely curable to the invariably fatal. Those afflicted with cancer not only have to deal with the awfulness of the disease and its treatment, but must also bear the burden of guilt, because cancer, more than any other disease, carries the stigma of having Brought It Upon Yourself. “It is often said,” writes Johnson,, “that two-thirds of cancer cases are preventable – one-third by eliminating smoking and the other third by getting more exercise and eating healthier meals.” So: you smoked, you drank too much, you didn’t eat enough fruit and vegetables, you ate too much red meat and processed foods, you were fat, you got sunburned, you had unprotected sex with the wrong people, you didn’t take enough exercise, you didn’t take up the offer of screening programmes which might have detected your cancer at a stage when it was curable. Coupled with this guilt, many Americans believed that sinister, powerful forces – food manufacturers, the chemical industry, electricity providers, even government itself – contributed also, by poisoning food with additives and pesticides, by polluting the water supply, by exposing whole populations to carcinogenic electromagnetic fields emanating from electrical pylons. From this point of view cancer seemed to be an exception to the American dictum that “shit happens”.

Many believe that cancer is a modern phenomenon, “brought on by pollution, industrial chemicals and other devices of man”. The Cancer Chronicles however begins with an account of how bone cancer (both primary and metastatic) has been discovered in dinosaur remains. “Maybe cancer was a great rarity before man began messing with the earth,” writes Johnson, “but a core amount of cancer must have existed all along.” Studies of human and pre-human remains, too, show that cancer visited Kanam man 700,000 years ago (a tumour of the mandible, or jaw-bone, apparently). The new discipline of paleo-oncology found evidence of cancer in an Iron Age man in Switzerland and a Spanish Visigoth from the fifth century. The mummified body of Ferrante I of Aragon, who died in 1494, showed evidence of metastatic adenocarcinoma. “[T]here is something comforting,” writes Johnson, “about knowing that cancer has always been with us, that it is not all our fault, that you can take every precaution and still something in the genetic coils can become unsprung ... there is a core rate of cancer, the legacy of being multicellular creatures in an imperfect world.”

Johnson is a respected science writer, a regular contributor to The New York Times and author of the best-selling The Ten Most Beautiful Experiments. He was prompted to write about cancer following his wife, Nancy’s, experience of the disease. It strikes Johnson as manifestly unfair, that his wife, who led a commendably healthy life (“she always ate her vegetables”) should be struck down. She is diagnosed with locally invasive cancer of the uterus (womb), and undergoes surgery, chemotherapy and radiotherapy. She survives. American cancer memoirs have a peculiar flavour all of their own, which probably reflects the fact that in America, the rich, the well-connected and the well-informed receive outstanding care, and take control of the management of their disease in a manner which is not so common as yet here. David Rieff’s memoir of his mother, Susan Sontag’s, cancer treatment and death, Swimming in a Sea of Death is a good example of the genre. The patient, empowered by access to information and specialists, becomes an expert herself:

Nancy questioned everything, and I was there to help with the research. Should she be getting topotecan? She had read that the drug had been used against papillary serous carcinoma and that the response rate of doxorubicin and cisplatin were less than desired. Or did the addition of the paclitaxel tip the scales? “Cisplatin/adriamycin superior without question,” the surgeon quickly replied (he and the oncologist had given us their e-mail addresses). He attached abstracts from three papers from the Journal of Clinical Oncology and Gynecologic Oncology to compare.

Legal input seems to be a routine part of cancer treatment: “We went to a lawyer to draw up living wills and medical powers of attorney.” The second opinion at the Cancer Mecca is de rigueur: in this case, they go to MD Anderson Cancer Center in Houston. They are somewhat disappointed that the Anderson doctors conclude that the backwoods Santa Fe doctors are doing everything right: “we had hoped to be bestowed with some new laboratory finding, a promising clinical trial, some kind of Anderson magic.” Fellow science writers are recruited to make sure that no stone is left unturned: “we wondered what other possibilities might be out there, findings too new to have made it into the journals”.

Five years after her cancer treatment, Nancy bought a horse, and then another horse, and then a small ranch: “She was determined not to waste a day of a future she had almost lost.” I felt a little deflated, then, to turn the page and read: “The next spring at the ranch, I’m told, the salsola was as bad as ever. I wasn’t there to see it. During that year our marriage ended, seventeen years after it had begun. For a long time our lives had been diverging. The cancer had brought us closer but now it was gone. Brushing so near death makes a person think about how she wants to spend what is left of life. Nancy had her reasons for deciding it was not with me.” One possible reason is Johnson’s own admission that he hadn’t wanted children. He suggests that Nancy did, and admits that her childlessness may have contributed to her developing uterine cancer. (It has been long been known that nuns are at higher risk of this form of cancer.)

Shortly after Nancy leaves him, Johnson’s brother Joe is diagnosed with oral cancer. He is not as lucky as Nancy. Like her, he undergoes surgery, chemotherapy and radiotherapy, but the cancer recurs rapidly. Joe, unlike his brother, is a devout Christian, and firmly believes he will make a full recovery: “He believed deeply in God and his doctors, and his wife and daughters kept him looking ahead. ‘I have a virtual army of people praying for my health and recovery – from all cultures, all denominations,’ he wrote on a webpage his family maintained to keep people apprised of the news. “I have no doubt I will get rid of this cancer and will be back to normal – whatever it takes to do it. I am so blessed that I know in the depths of my soul that I will defeat this.’”

Johnson envies Joe’s faith: “It would be good to believe in God.” His downhill trajectory is relentless and cruel. He retains his cheerfulness to the end, dying at home, having told his family that he loves them. “At his memorial service, the minister talked about the mystery of death, the love that cancer can never take away, the power of God to unbind and set free. He told how Joe had sent him an e-mail the morning before surgery. He said he felt like Commander Adama on the science-fiction series Battlestar Galactica. He was going in to remove the invader.”

The Cancer Chronicles is an awkward mix of personal memoir, history, cancer biology and epidemiology, which doesn’t entirely work. Johnson is good at explaining complex genetics, but I can’t personally understand the attraction of this sort of stuff for a general audience. Clearly, there is a general audience, as shown by the success of books such as Sherwin Nuland’s How We Die, which explained in some detail the biology and pathology of common fatal diseases. It is said that many lay Americans (including Mel Brooks) are subscribers to The New England Journal of Medicine, so evidently there is an avid existing American readership for I am John’s Mutated DNA. His style is spare and direct – apparently Cormac McCarthy looked over the manuscript. The narrative jumps rather jarringly from palaeontology to Nancy’s story, to cancer genetics, then to anthropology, cancer epidemiology, and back to Nancy.

Cancer is caused by DNA mutations triggered by chemicals, radiation and the effects of ageing. Inevitably, therefore, genetics was thought to hold the key to developing better treatments for cancer. The Cancer Chronicles has a lot to say – rather too much, in my view ‑ about genetics, epigenetics and even embryology. A visit to the annual meeting of the Society for Developmental Biology in Albuquerque leaves him “feeling frazzled” by the complexity of the science. Although the entire human genome has been mapped, genetics has not delivered the Great Breakthrough it had promised. Johnson doesn’t say this directly – geneticists are notoriously touchy – but he raises the possibility that the current cancer research orthodoxy may be barking up the wrong tree. He looks at less conventional approaches, inspired by theoretical physics, computer science, robotics, even game theory – “an attempt to break the stalemate in the War on Cancer”.

Johnson is a shrewd assessor of the available evidence, and understands the uncertainties and limitations of that evidence. He concludes, for example, that “the evidence associating any particular diet with cancer is discouragingly thin”. The five-a-day rage began after a 1997 report produced by the World Cancer Research Fund and the American Institute for Cancer Research, which concluded that “Diets containing substantial amounts of a variety of vegetables and fruits may on their own reduce the overall incidence of cancer by over 20 percent.” Unfortunately, it wasn’t quite so simple. Most of the evidence backing this assertion was derived from retrospective studies of dietary habits, a method which is notoriously flawed. A follow-up report in 2007 concluded that “in no case now is the evidence of protection judged to be convincing.” Eating a lot of blueberries and bok choy may make you feel virtuous, but the chances of such a diet reducing your risk of cancer are at best slight: “synthetic carcinogens were not the smoking gun, and now it appeared that fruits and vegetables were not a magic bullet”. Diet, however, is not entirely irrelevant, as obesity is now reckoned to account for 20 per cent of cancers, with tobacco accounting for 30 per cent.

Johnson goes on to look at the evidence linking “environmental” factors, such as food additives, industrial waste, pollution and pesticides with cancer. Americans in the 1970s commonly believed that “if we or someone we knew ever got cancer we were quick to wonder whether corporate America was to blame”. In the 1970s, the US Office of Technology Assessment commissioned Richard Doll and Richard Peto, the two epidemiologists who definitively established the link between lung cancer and cigarette smoking, to review the evidence linking these environmental factors with cancer. (Richard Doll was undisputedly the pre-eminent epidemiologist of the twentieth century, and shamefully passed over by the Nobel committee.) Their report, The Causes of Cancer, published in 1981, concluded that fewer than 1 per cent of cancers could be attributed to industrial products such as paints, solvents and food additives. When smoking-related cancers were excluded, cancer deaths in America (at least in the under-sixty-fives) had been steadily falling since 1953. It wasn’t what the environmentalists wanted to hear, but they found it difficult to dismiss an epidemiologist as distinguished (and understated) as Doll.

Johnson turns his forensic gaze to so-called “cancer clusters”, areas with a higher than average incidence of a particular cancer. Back in the 1990s, one such putative cluster – that of breast cancer in Long Island, New York – led to the inevitable hysteria, with the usual suspects (power lines, pesticides, industrial waste) being fingered. The politicians were put under intense pressure, and Congress duly commissioned a study by the National Cancer Institute. Ten years and $30 million dollars later, the report appeared. The incidence of breast cancer was slightly higher in Long Island than the US average, but no link was found between pollutants and breast cancer. The causes were more prosaic: Long Islanders tended to be older, richer, fatter, more sedentary, more likely to be Jewish, all risks for breast cancer. Long Islanders were also more likely than say, poor women in Appalachia, to have screening mammograms, which can detect tiny, slow-growing (and possibly harmless) “in-situ” cancers.

A similar cancer cluster was thought to exist in the district bordering the Love Canal in Niagara Falls, New York. Toxic waste dumped into the canal was blamed for causing birth defects and cancers in people living in the area. Yet again, epidemiology provided the answer. The New York State Department of Health followed up the population for thirty years, and concluded in 2008 that “the overall cancer rate was actually a little lower than for the general population”. Johnson admits to experiencing a degree of cognitive dissonance:

For many of us who grew up during the exuberant beginnings of the environmental movement of the 1970s and 1980s, that outcome was almost beyond belief. We were influenced by Silent Spring, Rachel Carson’s elegant warning about pesticides and the environment, and scathing polemics like Samuel Epstein’s The Politics of Cancer. We worried about saccharine and Red Dye No. 2, and later about Alar on apples. We were told of a modern epidemic of cancer – “the plague of the twentieth century” – that was being imposed on the public by irresponsible corporations and their effluents. Food additives, pesticides and herbicides, household cleaners – all of these were said to be corrupting our DNA.

Another statistical illusion which is quickly dismissed is the supposed link between brain tumours and mobile phones: in fact, the risk may be slightly lower in regular users. One environmental factor which does increase cancer risk is radioactive radon in the soil. Radon is associated with lung cancer; it seems to increase the risk mainly in smokers. Soil radon levels vary geographically. Johnson, naturally, had his house tested many years ago, and a modest amount of radon was detected, but as a non-smoker, he decided not to worry. That changed when he started this book: “as I began to learn more about cancer, I felt a need to conduct another radon test – this time in a room where I had recently been sitting for weeks writing this book.” Commercial providers of radon-testing will be delighted with this book, which will doubtless prompt many readers to engage their services.

Cancer is a serious business, but Johnson does find some light relief when he attends the annual meeting of the American Association for Cancer Research in Orlando. He captures some of the flavour of the American mega-conference, with all its hubris, absurdity and pomposity. I have some experience of such events, and his account made me wince with recognition. He mingles with sixteen thousand fellow delegates, “carrying a copy of the proceedings as thick as a telephone book”. He is surprised that leading cancer researchers are hand in glove with Big Pharma: “I was taken aback by how many top university researchers had a hand in the commercial world.” Every presentation at this conference began with an obligatory slide proclaiming any conflict of interest: “there was clearly some resentment over the requirement”. Contemporary medicine could do with a David Lodge, as these meetings are full of comic possibilities. Although Johnson is deadly serious, I think Lodge would approve of this passage:

As I pondered what counts as a blockbuster drug, the auditorium was aroused by a fanfare of strings. This was a first for me – a scientific meeting with its own musical theme. Harold Varmus, the director of the National Cancer Institute, was taking the stage. To accommodate an audience of thousands of people, each speaker’s image was projected on six sets of double screens – one half for the video of the lectern and the other for the PowerPoint slides. The images loomed so large that the speaker himself, off in the distance, appeared comically small, the man behind the curtain in The Wizard of Oz.

MD Anderson Cancer Center host a reception at the Orlando meeting, and he notices that since he and Nancy had gone there for their second opinion, the logo had been changed, with a slash added through the word “Cancer”. “I wondered what marketing fool had come up with that.” We are sharply reminded that in the US, cancer is big business.

Big Pharma gets off lightly in this book, though Johnson does land a few glancing blows. He visits the Amgen booth at the Orlando meeting: “For more than a decade Amgen had been working on an angiogenesis inhibitor. Combined with paclixatel in a clinical trial, it extended the lives of women with recurrent ovarian cancer from 20.9 months to 22.5 months, or about forty-eight days.” Johnson is such an earnest writer that I can’t be sure if this is meant to be ironic. He describes the work of a Harvard scientist, Judah Folkman, who reported remarkable results in mice tumours with a group of drugs known as angiogenesis inhibitors. James Watson, co-discoverer of the double helix, announced: “Judah is going to cure cancer in two years.” Unfortunately, what worked in mice was not quite so effective in humans. Avastin, an angiogenesis inhibitor used for treating advanced breast cancer, “can add a few months to a patient’s life at a cost of tens of thousands of dollars ... several months after the Orlando meeting, the Food and Drug Administration, weighing the risks and benefits, revoked approval for Avastin as a treatment for metastatic breast cancer.”

Johnson is good too on the sentimentality surrounding cancer: “Now there is a cancer culture, and whether you had a harmless in situ carcinoma removed with a simple lumpectomy or are fighting the terminal stages of metastatic melanoma, you are called a survivor. In the first case there was nothing to survive. In the second case there will be no survival.” He describes a “Stand Up to Cancer” telethon: “with singing, laughing, and sometimes somber celebrities vowing to ‘eradicate’ cancer of all kinds”. An unnamed teenage actress promises that “someday no child will die from cancer”. Stevie Wonder says “We must beat it back and beat it out of existence.” Johnson continues: “A ticker tape message scrolled across the bottom of the TV screen: ‘Cancer Doesn’t Discriminate.’ But it does. Against the elderly, the obese, the poor. Demographically the young, beautiful people on the show were exceptions.” Our own Irish Cancer Society has launched an “ambitious new strategy statement” for 2013 to 2017 entitled “Towards a future without cancer.” It modestly concedes that “this may not be achieved in the lifetime of this strategy statement”.

Johnson bravely questions the breast cancer culture. He draws support from the writings of Barbara Ehrenreich, who has had the disease herself, and has called it a cult which trivialises the condition. Less fashionable cancers, such as the generally fatal pancreatic, lose out when it comes to public awareness and research funding. Johnson points out too that screening for breast cancer with mammography is a dubious enterprise, with no convincing evidence that it is beneficial. Male-only cancers (principally prostate) don’t benefit from “the pink ribbon enthusiasm”, and screening for prostate cancer (by checking levels of blood PSA) is also of uncertain benefit.

Johnson is curiously silent on the economics of cancer. He fails to mention, for example, the Lancet Oncology Cancer Commission report from 2011, Delivering affordable cancer care in high-income countries, the most incendiary document on cancer I have ever read. The commission consisted of leading academic cancer specialists from around the world. That it was commissioned and published by The Lancet, a conservative and long-established journal, makes it all the more remarkable. The commission concluded that cancer care in developed countries is rapidly becoming unsustainable and unaffordable, driven by overuse and futility:

First, the medical profession and the health-care industry have created unrealistic expectations of arrest of disease and death. This set of expectations allows inappropriate application of relatively ineffective therapies, including surgery, in the name of care. In developed countries, cancer treatment is becoming a culture of excess. We overdiagnose, over treat, and overpromise. This extends from use of complex technology, surgery, and drugs to events related to the acceptance of treatment side-effects. Second, we are a society that focuses almost exclusively on benefit, and such benefit is often small. For example, a 20% improvement in survival for a patient with a non-resectable metastatic solid tumour translates into a benefit of 4-6 weeks at best. Perspective is almost exclusively absent as we focus solely on what is perceived as benefit.

A perfect storm is gathering, driven by (in no particular order) an ageing population, expensive new technologies, unrealistic patient expectations, rising litigation against doctors, sensationalist and ill-informed journalism, powerful single-issue lobby groups, inadequate regulation, poorly informed politicians and policy-makers, lack of independent (that is, non-Pharma) research. If these trends continue unchecked, only the rich will be able to access high-level cancer treatment. The Lancet commission noted the “political toleration of unfairness”. These are the issues around cancer that a lay readership needs to know about, not the cell biology and genetics.

Although Johnson steers clear of politics and economics, he gently advises his readers to curb their enthusiasm for the War on Cancer, reminding us that “as the population ages, cancer is outrunning us”. Put simply, if we lived long enough, we would all get cancer. “And the biggest risks will always lie beyond our grip: old age and entropy. Cancer is not a disease. It is a phenomenon.”
23/9/13

Seamus O’Mahony is a consultant physician and a regular contributor to the Dublin Review of Books.

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