Although cancer is much more often curable than its popular reputation leads one to expect, the number of its victims and the sometimes morbid dread (oncophobia) of being among them make cancer a source of human distress that is reason enough for the fear it arouses.
In Latin, French, Italian, German, and English cancer is the crab—so-called, perhaps, because of the growth pattern of the most easily visible of all tumors: the rodent ulcer. Some purists (others would say pedants) confine the use of “cancer” to malignant growths of epithelial tissues, i.e., of the tissues that bound surfaces, using “sarcoma” for malignant growths of connective and supportive tissues and of the white cells of the blood. To laymen these niceties mean nothing. For them a cancer is any threateningly malignant growth.
Dr. Thelma Dunn declares that there is an urgent need for an exact definition of cancer that will include all examples of cancer and “exclude all other abnormal growths or diseases,” and she makes much of the admission of Virchow (one of the founders of pathology) that “no man, even under torture, could say exactly what cancer is.” But in this context, as in so many others, altogether too much fuss is made of matters of definition—for the very ambition to draw a dividing line such as Dr. Dunn proposes takes for granted the pre-existence of a working distinction between growths acknowledged to be malignant and others classifiable as benign. My experience as a scientist has taught me that the comfort brought by a satisfying and well-worded definition is only short-lived, because it is certain to need modification and qualification as our experience and understanding increase; it is explanations and descriptions that are needed—and these Dr. Dunn provides in abundance.
Hers is not a textbook, though; it could be thought of as a detailed invoice for the expenditure of the very large sums of money allotted to laboratory research—in 1976 a governmental grant of $396 million was spent on basic research, a fourfold increase over the grant in 1970. In its report to the president, the President’s Cancer Panel, presided over by Benno C. Schmidt, has already argued most cogently in defense of the expenditure of these very large sums of public money. Dr. Dunn’s book, which she describes as an informal report, and not for the cancer specialist, might be read as a series of appendices to this report. She writes with the unmistakable air of an insider—a professional who spent the greater part of her working life as a biologist and pathologist at the National Cancer Institute.
Dr. Dunn pours scorn on the idea that cancer is essentially a disease of civilization and the satellite notion that cancer develops in lower animals only after contact with man, but she goes on to explain the demographic circumstances that have nourished this illusion: in most backward societies and in most non-domesticated animals, early death deprives their members of candidature for cancer, the frequency of which tends to increase as life goes on. However, her excellent chapter on cancer-producing agents shows that industrial civilization cannot be exculpated, for soots, hydrocarbon tars, smokes, a number of food additives, and above all unnaturally high doses of radiation—all unknown in Arcadia—may all cause cancers. Due weight is given to epidemiological research, beginning with Percivall Pott’s (1775) classical association of cancer of the scrotum with the occupation of chimney sweep and ending with the identification of tobacco smoke as a principal cause of cancer of the lung—a discovery which has saved thousands of lives and holds the promise of saving thousands more.
More recently still, epidemiological surveys supervised by the Harvard School of Public Health have shown that an early pregnancy confers a certain degree of protection against breast tumors which lasts throughout life. This work will one day make young women reconsider the wisdom of using the Pill to postpone until later on the birth of any child they intend to have.
Dr. Dunn allows herself a few laughs at the expense of the practitioners of ostensibly more “scientific” disciplines such as chemistry and biochemistry: one biologist she refers to was astonished to learn that his (or was it her?) biochemist collaborator supposed that the secretions from the liver and pancreas emptied directly into the stomach. She has some fun, too, at the expense of simpleminded folk who believe that rats have gall bladders. She concedes, though, that an ignorance almost equally incredible can be found among pathologists. I have myself seen the eyes of a pathologist glaze over momentarily upon my expressing a wish to discuss the at that time widely canvassed possibility that normal and malignant tissues differ in respect of the isoenzymic profiles of their respective lactic dehydrogenases. But does not everyone who uses his mind often find himself stopping miraculously short at the very brink of chasms of ignorance? Test yourself, reader, by engraving upon the head of a pin all you can call instantly to mind about the following subjects: the religious causes of the Thirty Years War, the philosophy of Spinoza, Goedel’s Theorem, the nature of deep linguistic structures, and the role of Jan Comenius in the scientific philosophy of the seventeenth century. We can all catch each other out, but fortunately cancer research is a cooperative enterprise in which we all lean upon and sustain each other.
An agreeable feature of Dunn’s book is that, so far from regarding all work done before she put pen to paper as of merely antiquarian interest, she introduces many subjects by a brief historical account of how our understanding of them grew. I was particularly pleased to see that the name of Apolant, an assistant of Ehrlich’s, had not been forgotten, nor was that of Leslie Foulds. Because of its historical depth, roundedness, and intrinsic importance, the chapter on the mammary tumors of mice is perhaps the best in the book and certainly the one that best shows off the author’s wide knowledge and sensible judgment.
Dr. Dunn refers several times to the formation in 1802 of “a group of prominent English physicians” to investigate cancer and make authoritative pronouncements upon it. One such pronouncement was “that no instance had ever occurred or been recorded of cancer being cured by any natural process of the constitution.” Dr. Dunn herself adds, “less than 200 spontaneous cures of cancer are accepted as authentic”—and these are cancers of a special type in the regression of which special factors may intervene.
The acceptance of 200 cases of spontaneous regression in the face of a traditional presumption that no such phenomenon occurs encourages the belief that regressions are very much more common than such a low figure seems to indicate. So far as I am aware, the only agency that might bring about a “spontaneous” retrogression is an immunological reaction upon the tumor by the organism that bears it. Dr. Dunn writes a judiciously and temperately argued chapter on the intervention of immunological factors on the growth of tumors and outlines with complete accuracy the reasons why immunological theories have had their ups and downs of acceptability. I should like to add, however, that in my opinion the epidemiologically established relationship between pregnancy and the diminution of risk of breast cancer is quite clearly immunological in origin.
Dr. Dunn’s book comes right into the foreground of modern research. I saw with pleasure (since this is the field of tumor biology in which I work myself) that she cites some of the modern evidence which lends color to the old-fashioned belief that malignant tumors are to some degree anaplastic, i.e., re-acquire some of the characteristics of an embryonic cell. Here, perhaps, lies the best hope of the early diagnosis of malignant growths.
One cannot yet attempt a cost/benefit analysis of those hundreds of millions of dollars spent throughout the world on cancer research because all the credit entries are not yet complete. Cancer is not one disease and it will not have one cure, but the way things are going the treatment of a cancer patient is going to acquire more and more the characteristics of a research problem in which the patient, after scrupulously careful biochemical, pathological, and immunological assessments, will have a treatment or a system of treatments exactly tailored to suit his condition, by a physician competent to appraise and give due weight to all the evidence that will come before him of the tumor’s whereabouts, its degree of malignancy, and the patient’s natural power to combat it—which is likely to depend, at least in part, on the soundness of his immunological response system.
It may be that a new kind of physician will be called into being by these demands, much as a new kind of surgeon-scientist was called into being by the growth of therapeutic organ transplantation—a procedure which also makes special demands on the technical skills, knowledge, and physiological understanding of the surgeon—a demand which happily was met by the recruitment into surgery of some of the most able medical students that the schools of the country have produced. The sneery attitude toward surgeons that many physicians (particularly in England) were at one time wont to affect is one that nowadays seems most comically ill-judged and, just as many of the leading transplant surgeons today are as much at home in a laboratory as they are in the operating theater, so it may be that a new generation of oncological physicians will arise who feel just as much at home in the laboratory as in the cancer ward. Just one brilliant break is needed—akin to the first brilliant kidney transplant in the Peter Bent Brigham Hospital in Boston—and then recruits will come forward by the hundred, many of them, I shouldn’t wonder, clutching this book by Thelma Dunn in their hot hands.
Unlike Dr. Dunn, Larry Agran is an amateur, but he is so intelligent and sensible that it hardly matters. Sometimes, though, in disclaiming personal clinical authority he stands too far back from his subject: “Cancer, it seems, is not really a single disease susceptible to a single cure.” Why “it seems”?—surely no one can have tempted him to think that a contrary opinion is widely held.
Agran says that billions of dollars have been poured into cancer research in the US and throughout the world, but my guess is that the order of magnitude is 108, not 109. However that may be, he cites actuarial statistics to show that although some rare tumors (Hodgkins’ disease is one) are being mastered, recovery from the commonest and most destructive tumors—mammary and colonic—has not improved as much as this large expenditure authorizes one to hope.
What, then, is to be done? asks Agran. An early mention of Percivall Pott (see above), the culture hero of cancer epidemiology, reveals the direction his thoughts are taking, and he goes on to mention the now fully attested cancer-producing actions of radioactive substances and certain food additives and fibers. He goes on to say that the National Cancer Institute estimates that the vast majority of all human cancers—perhaps up to 90 percent*—are attributable to environmental carcinogens. “Cancer today, therefore, is actually a disease of man-made origin. What this means, of course, is that cancer is largely a preventable disease.”
I think this case is overstated. The idea that cancer is a disease of industrial civilization accords very well, of course, with modern Arcadian thinking, but in a context in which many figures are quoted Agran should surely have attached an exact weighting to his figures of cancer incidence to make clear just how much of the increase is to be attributed to the fact that we live an average of forty or fifty years longer than our ancestors. There can be no caviling, though, at the proposition that preventable cancers should be prevented.
Where a physician would document his argument with case histories and graphs, Agran does so by skillfully written semifictional though factually based narratives relating to victims of environmentally induced cancers. Writing of the activities of OSHA (the Occupational Safety and Health Administration), Agran cites it as one of their axioms that “there is no known ‘safe’ level of exposure to a cancer-causing agent.” The operative word here is “safe” and although it is by no means impossible that detoxication and repair processes are such that threshhold levels of exposure to some carcinogens do exist, the cost in time and human lives prohibits any attempt to find out what they are.
I think Agran is a little unworldly in reproaching OSHA for aiming at “compromise” levels of exposure for political reasons. Surely such compromises are inevitable: we are all sickened by the carnage for which the automobile is responsible, and though it is most doubtful if there is any safe threshhold level of speed below which no such carnage would occur, yet we can neither abolish automobiles nor (as in the early days in the United Kingdom) do we require each moving automobile to be preceded by a pedestrian carrying a red flag.
It is however not at all unworldly to suggest that manufacturers who expose their workpeople and residents nearby to special hazards should be registered, licensed, required to take preventive measures, and perhaps exposed to unannounced lightning visits by an inspectorate recruited for the purpose. Such considerations apply with special force to the manufacture of asbestos fibers and the more notoriously carcinogenic chemicals such as BCME (bischloromethyl ether—a chemical used in the manufacture of water purification resins).
In the latter part of his book Agran’s narrative built around personal case histories is particularly good: some of his stories are moving and disturbing. They may be taken to illustrate how very often it is true to say that the social malefactions blamed upon science and technology or upon “progress” generally are in reality the outcome of the persistence into the twentieth century of some of the worst elements of nineteenth-century laissez-faire capitalism.
The worst sin Agran could be charged with is the use of somewhat heightened colors in the picture he paints; but in his defense it should be pointed out that he is writing of very important matters to do with human welfare, and matters that call urgently for attention. For such purposes as this, monochrome won’t do.
Dr. Priscilla Laws’s book is in the same genre as Agran’s and every bit as good. It is about X-radiation. X-rays are good and useful through their power to make the human body, in effect, transparent and thus make possible the recognition or localization of internal abnormalities. In addition, they cause a disruption of the cell nucleus that is put to good effect in the treatment of cancers, and although X-radiation can sometimes make people very ill, it can have the advantage over drugs taken by injection or by mouth that its action can often be more strictly localized and its dosage more exactly quantified. Above all X-rays can be switched off when they are thought to have done their task.
As against these advantages, X-rays, like gamma rays and other powerful ionizing radiations, can themselves cause cancer and—as Herman Muller was the first to point out—can also cause genetic mutation. Dr. Laws is not against X-rays in any comprehensive sense but only against the misuse and overuse of diagnostic radiology. Her book is sociologically sophisticated and she sees quite clearly the pressures that have led to the overuse of diagnostic radiology. These include that revolution of rising expectations of health which puts a constant pressure upon the medical profession. It includes the enthusiasm of the radiologist for a skill in which he becomes increasingly proficient as he practices his art, and which makes an important contribution to his standard of living.
A less obvious but also important consideration is that now that litigation at the expense of the medical profession is becoming something of an indoor pastime in the United States physicians feel they have to safeguard themselves against much unreasonable litigation. A slight danger of Dr. Laws’s book is that if laymen and particularly lay women read it uncritically they may be inclined to blame X-radiation for almost any medical misadventure that befalls them, including miscarriages. Dr. Laws is full of anecdotes of which the following is a representative specimen:
“About 15 years ago when I was pregnant, I had a lot of back pain. During my seventh month the pain became more severe, so the doctor took several X rays of my lower back. At the time I was young and very bewildered.
“Well, anyway, the very next day I delivered a 4-pound 11-ounce boy…. Some years later when my son started school, his teachers told me he was mildly retarded. I don’t know if the X rays might have had anything to do with it or not.”
The medical profession is rightly ridiculed by scientists for using anecdotes to bear witness to the therapeutic efficacy of some treatment they are interested in. For fairness’ sake it must be said that such evidence is equally inadmissible when it comes to discrediting a medical procedure. Nevertheless the general tendency of Dr. Laws’s book is good: X-radiation will go on being used and if it is used with more discretion as a result of what Dr. Laws has written then she has every reason to feel rather pleased with herself.
Lawrence LeShan’s book is about the complicity of emotional and personality factors in susceptibility to and recovery from cancer. “After two decades of work with cancer patients,” LeShan, a psychotherapist, believes that “the cancer victim usually has a psychological orientation that increases the chances of getting cancer and makes it more difficult for many individuals to fight for their lives when they do develop a malignancy.’
LeShan’s ambitions are very explicitly stated:
First, I intend to set forth the extensive existing evidence that there is a general type of personality configuration among the majority of cancer patients, and to suggest some reasons why the emotional responses of these individuals make them more susceptible to cancer.
Secondly, and most importantly, I wish to outline a number of ways in which people whose personality or life history conforms to this pattern of susceptibility can take steps to protect themselves against the possibility of cancer.
With these notions very properly in mind (for it is now universally admitted to be an illusion that any research can start with the mind a clean slate) LeShan set himself the task of collecting information about the personality make-up of cancer patients. For this purpose he first applied to them the Rorschach (ink blot) test. He thinks this gave him an insight into the patients’ unconscious and made it possible for him to assess the strength and consistency of the ego. But he goes on to explain in psychologese that it didn’t actually reveal what they were like, so he dropped the test after only thirty trials and tried next the Thematic Apperception Test (TAT): “In this test, the patient is shown a series of pictures, of the typical magazine illustration type, and asked to make up a story as to what is happening in the picture.”
TAT was thought to give a broader picture of the patient’s personality but “reactions to it were once again negative.” So eventually the “Worthington Personal History” test was chosen—something a bit more personal than a conventional curriculum vitae that is used in applying for jobs. This test, it was felt, “gave an understanding of the major unconscious stresses, the ego defenses and the techniques of functioning and relating used in everyday life. It also gave a picture of where the patient had been in his life, what he had done and how he felt about different periods of his personal history.”
These various tests, supplemented by carefully thought out personal interviews, occupied the first two years of LeShan’s research. But later, when he felt he had gained sufficient basic insight into the particular problems of cancer patients, he “undertook the more complex and sensitive task of seeing many patients for intensive individual psychotherapy. Over 70 people eventually entered into such treatment.”
On collating his records LeShan found evidence “in record after record” that the patient had lost the sense of raison d’être but some time before the first symptoms of cancer were observed. The patients who had lost their sense of purpose had at one time participated much more fully in life. “At that time they had had a relationship with a person or group that was of great and deep meaning to them.” On the surface, these people seemed psychologically normal, but underneath there was an absence of direction or goal: “They felt a lack of any stable reference points for themselves in the universe.”
A second trait LeShan discovered was “an inability on the part of the individual to express anger or resentment“—they seemed to suppress and swallow their hostile feelings, though they did have quite strong aggressive feelings. Third, there were indications that the cancer patient showed some evidences of emotional tension concerning the death of a parent. Not much came of this correlation, though. “Nevertheless, a start had been made.”
Before turning to an evaluation of LeShan’s attempts at psychotherapy I must comment on the hypotheses as they have unfolded so far. In evaluating an epidemiological theory such as LeShan’s, the first stage is to demand clear answers to a range of fairly standard questions: What exactly were the controls, i.e., in respect of just what characteristics were the controls matched with the propositi? Just how many patients with the full gamut of emotional characteristics LeShan refers to did not get cancer? and how many contracted ailments other than cancer?—a fair question having regard to the fact that various personality defects are likely to affect the behavior in ways that diminish the power to combat diseases of other kinds. Again, may not a malignant tumor on the one hand and an emotional disturbance on the other be collateral manifestations of an underlying physical—e.g., hormonal—disturbance?
I am sorry to have to say that LeShan’s answers to these questions are not such as make it possible to evaluate his theories critically—indeed, his argument has a distressing tendency to sag perceptibly just at points where it ought to tighten up.
I do not put these questions in a hostile spirit, for in spite of several triumphs, it cannot be said that cancer epidemiology is at present so far advanced as to justify a contemptuous or dismissive attitude toward speculations such as LeShan’s. Indeed, as an earnest of my antipathy toward dismissive criticisms of the possibility of a psychosomatic element in the natural history of cancer I shall cite evidence that may be unfamiliar to LeShan and that lends unexpected color to this very possibility. If there is any natural opposition to the growth of tumors, it is almost certain to be immunological in character and to be the outcome of an immunological reaction of much the same kind as that which leads to the rejection of foreign transplants.
Immunity of this kind—“cell-mediated immunity”—plays an important part in resistance to tuberculosis, an affliction in which a psychosomatic element is admitted even by those who contemptuously dismiss it in the context of any other ailment. The skin test that is used to reveal a current or previous exposure to tubercle bacilli is known as the Mantoux test or tuberculin reaction; a group of workers of the British Medical Research Council led by one of the world’s foremost immunologists, Dr. J.H. Humphrey, showed conclusively that the outward—in effect vascular—manifestations of the tuberculin reaction could be profoundly influenced by hypnotic suggestion—as neat a demonstration as one could wish of the influence of mind over matter.
In the course of his book LeShan describes his experience of the intensive psychotherapy of seventy patients with “terminal malignancies.” As his treatments went on he began to get a fuller picture of the character make-up which he thinks causally significant in the genesis of cancer: the patient had a sense of loneliness and unrelatedness and suffered the acquiescent passionless grief of which Elizabeth Barrett Browning has written so movingly. LeShan is quite confident of his ability to distinguish cart from horse and specially emphasizes that the world view which, he says, goes with cancer, “predates the development of cancer.” This is a risky statement because there may be a long, long gap—perhaps as long as fifty years—between the inception of a tumor and its bursting forth into a malignant growth.
LeShan’s clinical experiences are recounted in the form of a number of anecdotes that are interesting and sometimes rather moving. There seems little doubt that he made many of his patients happier as a result of his psychotherapy, but the entire structure of this research is not of a kind that could possibly demonstrate the therapeutic efficacy of psychotherapy in the sense in which, for some tumors, treatment with a drug such as methotrexate is judged to be therapeutically efficacious.
This is all very well, psychotherapists may think, but in real life we can’t conduct experiments with the neat cut and dried precision of oncologists working in a backroom with inbred strains of mice. This is a rebuke which all experienced cancer research workers are familiar with and always accept. For all that, the shortcomings of analysis such as LeShan’s should not be glossed over: it matters not at all that the patients were in a certain degree self-selected in being well disposed toward the notion of psychotherapeutic treatment and willing to think that it might do them good. What does matter is the degree of randomization in respect to the nature of the cancers treated; for some cancers are notorious for alternating periods of remission with periods of acerbation. Diseases with a natural history such as this—multiple sclerosis is among them—lay cruel traps for would-be therapists: the patients they treat sometimes get better, and sometimes don’t—so much so that the people treating them can come to regard themselves as the victims of a conspiracy of nature.
For reasons I hope I have made clear, LeShan’s exposition would have benefited greatly if his text had been checked by an all-round tumor biologist before publication. Jane Brody, a medical science writer for The New York Times, was wise to write in collaboration with a senior officer of the American Cancer Society. She herself is a biochemistry major and a very experienced science writer. The portents are good, then: this ought to be a good book, and I am happy to say that it is. I turned first, out of curiosity, to the pages (271-276) that deal with psychological factors in the causation of cancer and thought the authors’ treatment sensible and temperate. After reviewing various experiments on the relation between stress and cancer, she writes,
But all experiments have not yielded consistent results. A psychologist at Kent State University in Ohio found that when rats were subjected to the stresses of overcrowding or electric shock, the development of induced breast cancer in the animals was slowed down and in some cases stopped.
What, if any, significance can be attached to such a collection of findings in animals and man will depend largely on the extent to which scientists are able to decipher the precise biochemical effects of stress and personality patterns. If it can be shown that persons who respond to stress in certain ways suffer metabolic, hormonal or immunological upsets that diminish their resistance to cancer, the belief that stress and personality are somehow related to this disease will gain much wider acceptance in the medical community.
As a matter of editorial policy, one very widely read magazine adopts such a rosy-tinted view of all human ailments that one wonders how it comes about that anyone dies at all. Brody and Holleb manage to be simultaneously sanguine and realistic; they hold out hopes where it is reasonable to do so, but are shocking where there is every reason to be so. In addition to the stern lecture on smoking which we expect—and would resent the omission of—there is also some stern writing about the folly of exposing oneself unduly to the rays of the sun; nor do they gloss over the potential evils of diagnostic X-radiation.
In writing of what can almost be described as an epidemic of diagnostic X-radiography the authors observe that “while many of these X-rays are important to the patient’s welfare and may even be life-saving, according to the United States Bureau of Radiological Health, at least 30 percent of them do not contribute any useful information.” The authors take a conventional but not wholly accurate view of the relevance of immunology to cancer, for research on the subject has already got beyond the level it had achieved when this book went to press. The value of this book to American readers is greatly increased by a series of appendices indicating where a cancer victim can turn for help.
Not long ago I rode on what could have been my last earthly journey, between Rockefeller Hospital and NYU Medical School: the taxi driver, under the impression that I was a practitioner, nearly assaulted me on the grounds that I and my kind had ruined him and his kind because his wife had had a cancer which had ruined him financially, adding (what I did not challenge) that one cannot work more than twenty-four hours in each day. For me the most shocking piece of information in the book by Brody and Holleb was that “initial treatment of cancer costs an average of $2,000, but it may cost $20,000 or more to care for a patient with advanced cancer.” It is shocking that such statements can be true of any civilized society. With increasing evidence of the contribution of environmental causes to cancer, and the lack of strong fiscal or commercial incentives to correcting them, a society can no longer regard the treatment of cancer as a personal transaction between the patient and his physician, particularly if a patient’s whole family can be ruined by a disease which he may have contracted through no fault of his own. Federal donations to Cancer Research are in reality not much more than conscience money: nothing will do except legislation on a national scale that will save a patient’s livelihood no less effectively than his life.
June 9, 1977