When I was a medical student, long ago in the mid-1930s, the disease to worry about the most was tuberculosis. It was all around. Anyone could catch it, at any time, from infancy to old age, and there was really nothing much to be done about it. You might survive if you were lucky, and that was that. Your chances were somewhat better when you were lucky enough to have it spotted early and took to your bed, preferably in one of the great number of state hospitals or private sanitaria built for the exclusive care of TB. Rest was the only marginally useful treatment: rest for the whole body in bed, and technologically induced rest for the affected tissue by injecting air into the pleural space to collapse the lung temporarily, or cutting away the ribs to cause permanent collapse. There were no drugs of any value.
The great effort was to keep the disease confined to the lungs, and to hope against its spreading. This was also a matter of luck. If the bacilli spread from the lungs into the blood-stream or lymphatics, and reached the central nervous system, that was the end. Tuberculous meningitis was always fatal, and the only function for the doctor was to see to it that the end came as peacefully as possible for the patient, and to provide information and support for the patient’s family.
Everyone lived in fear of tuberculosis but it was not much talked about. Families preferred not having it known that one of the children had died of consumption; it meant something wrong with the family.
The hardest part of the disease, for both the patient and the family, was that it took so long to die. Even in its most malignant form, called galloping consumption, it went on for weeks, even months. The only relief was a curious phenomenon near the end, known as spes phthisica, when the patient suddenly became optimistic and hopeful, even mildly elated. This was the worst of signs; spes phthisica meant that death was coming soon.
There were specialists in tuberculosis, internists and surgeons who did nothing else but look after patients with this one disease. They were extremely useful and important people and were kept very busy, but their principal contribution was information; they knew, from long, concentrated experience, the natural history of the disease, and were highly skilled in making a prognosis. Also, they knew a lot about the art of making patients more comfortable.
The basic research on tuberculosis began in the 1890s with Koch, who discovered the bacillus, and the effort expanded with increasing energy over the next forty years, consuming the scientific lives of hundreds of investigators in laboratories all around the world. Gradually, they gained a fairly clear understanding of the ways in which tuberculosis became disseminated through communities, and public health techniques for early detection and isolation were developed. The underlying mechanisms enabling the tubercle bacillus to destroy living tissue were explored in depth (although this matter is still, to this day, largely a mystery). Some of the factors in the environment which affected the course of the disease were identified: crowding, malnutrition, genetic predisposition, immune responsiveness, perhaps even the stress of living.
The whole mass of results of research on tuberculosis filled numberless huge volumes in the world’s medical libraries, but throughout forty years the single, central, and absolutely crucial piece of fundamental science was the information that the tubercle bacillus was the real cause of the disease, and the sole cause. Other factors, environmental or genetic, might be contributing to susceptibility or making a difference for the final outcome, but at the center of the theoretical demonology was the bacillus. There was no argument about this. If you could get rid of the tubercle bacillus, kill it off without killing the patient, you could cure the illness.
This was the scientific achievement that led to the work of Selman Waksman, with his inspired hunch that some of the microorganisms living in the ecosystems of the soil might produce chemicals capable of restraining the growth of other, competing bacteria. Without the existence of the tubercle bacillus, in hand, there would have been no point in looking for something with the properties of streptomycin, or any technique for screening samples of soil for anti-tuberculous activity.
Streptomycin was an immense encouragement, but not good enough. It helped, but it actually cured only those patients with relatively early disease; it could not be relied on to reverse the devastations of miliary TB or TB meningitis. Also, dismayingly, it could not be used in heavy doses, or for long periods of time, because of its destructive action in the nerves for hearing and the sense of balance. Nevertheless, it was a priceless gift of hope for phthisiology: it proved that the tubercle bacillus was vulnerable in living tissues. Given this hope, investigators set about looking for other drugs to enhance the action of streptomycin, and para-aminosalicylic acid was found, and then, a few years later, isoniazid. The conquest of tuberculosis became, at last, a stunning success.
We are, today, probably somewhere along in this sequence of scientific events for cancer. The ambiguous word “somewhere” is needed here, because we do not yet possess pieces of information about the central causation of cancer with anything like the power of Koch’s identification of the tubercle bacillus. We know a fair amount about environmental influences, including the irrefutably convincing evidence about cigarettes in lung cancer, but we do not yet know what happens, at the center of things, to switch normal cells into the unrestrained life of neoplastic cells. However, we seem to be getting there; at least I think so. It is unlikely, although still a possibility, that a virus or any other kind of infectious agent is involved, but it is a high probability that a centrally placed mechanism, whose nature remains to be elucidated, has gone wrong, and that it is the same mechanism for all forms of cancer.
Twenty-five years ago, cancer was like tuberculosis in the old days, before there was much of anything in the way of selective therapy. Surgery and radiation were useful for the extirpation of primary lesions, and some cases of cancer of the breast, colon, stomach, prostate, and a few other organs could be cured in this way. But the dissemination of neoplastic cells to other tissue sites could be neither prevented nor treated. The earliest days of chemotherapy, involving nitrogen mustard at the outset, were encouraging to a handful of investigators but regarded by most as simply too dangerous and appalling in their side effects. But a few cases of leukemia were observed to undergo dramatic remissions, and it was realized, for the first time, that cancer cells might be specially vulnerable to certain drugs. The long, frustrating, tedious, and risky effort to develop the new discipline of cancer chemotherapy had begun.
Ten years ago, the field had moved far enough along for the oncologists to be persuaded, once and for all, that they were on the right track. Acute leukemia in children could be brought to a standstill in over 50 percent of cases, and many of these patients were able to take up normal lives without further treatment, and without disability. Dramatic regressions of extensive solid growths were observed to occur in other forms of cancer, and even though these were usually only transient improvements, lasting at best a few months, it was obvious that the chemicals becoming available at that time were capable of extraordinary and apparently selective effects, despite being still frighteningly toxic.
But the solidest evidence of scientific progress has come just in the past five years. The drugs now in use are nothing like as debilitating as those available ten years ago, and much has been learned about the value of intermittent therapy with combinations of several drugs, as well as the value of combining chemotherapy with radiation treatment. Meanwhile, there have been major advances in the complicated technology of radiation itself, to the extent that Hodgkin’s disease, an untreatable condition a generation ago, is now generally accepted to be a curable disease. The malignancies of childhood, including bone sarcomas, are beginning to respond so well to chemotherapy that it is becoming permissible to talk, tentatively at least, about cures. Disseminated breast cancer can be brought under control for periods of seven years or longer; these are not yet in any sense cures, but they represent something of much greater benefit than what used to be implied by the term “palliation,” and they carry much more hope for the future.
In short, real advances have been made, and are being made today, in the treatment of cancer, and we should all be feeling optimistic for the future. The National Cancer Program, launched early in this decade amid strident disagreements and loud predictions of failure, is really going very well indeed. Research at the basic science level is turning up new bits of information in the fields of molecular genetics, immunology, cellular biology, membrane structure, and the like, and although nobody would claim that we have yet an understanding of the underlying process of neoplasia, it is now generally agreed that the problem is an approachable one; it is a puzzle that will eventually be solved. There are still disagreements about the National Cancer Program, but not, I think, around this point. Cancer is no longer the absolutely blank, unapproachable, imponderable mystery that it seemed to be when I was a medical student. There are many scientists who believe that we should be concentrating more effort, and much more money, in basic research, but there are no responsible voices raised against basic research itself.
The major argument today, and the bitterest one, is around the issue of applied research, and particularly the magnitude of today’s programs for the improvement and amplification of chemotherapy. Despite the evidences of partial therapeutic success, even total success in some cases, there are some who believe this to be the wrong time for highly organized, centrally controlled applied research. We have too much still to learn about the deepest mysteries of cellular life, it is said; we should wait for more meaningful illuminations before trying for new therapies. After all, it is said, today’s chemotherapeutic agents are not specific for cancer cells; they are directed at the process of cell replication, and any dividing cell, anywhere in the body, is as vulnerable as a cancer cell. The plain fact that under chemotherapy cancer tissues tend to shrink in size, and sometimes vanish altogether, while the rest of the body remains intact, fails to impress these critics. They have a higher, more exacting ambition, and high hopes for therapeutic agents in the future which can be aimed exclusively at cancer cells, touching nothing else. They are dissatisfied with forms of treatment which cure only a minority of patients with some kinds of cancer, and produce only a prolongation of life for a few months, even a few years.
It is this issue that troubles the eminent French oncologist Dr. Lucien Israël the most, and is the reason for his book. He writes with surprising clarity for a doctor involved in a densely technical field, and lays out an abundance of solid, reliable, and, I should think, highly useful information for a lay public increasingly interested in cancer. He writes as a reasonable man and an able, compassionate, and skilled clinical scientist. But he is visibly upset by the drift of opinion within the medical profession about his field, and the book is really a long, urgent argument, sometimes a restrained polemic.
Dr. Israël believes that the benefits of cancer chemotherapy have already been amply demonstrated by thorough, unimpeachable scientific studies, most of them carried out in the United States, and he cannot understand why so many of his colleagues, especially those surgeons and radiotherapists concerned with cancer, do not share his enthusiasm for the present achievements and future prospects of his field. He is more understanding, but no less disappointed, with the skeptical attitude expressed by physicians in other disciplines; he believes that these professionals have simply not had the opportunity to see what he has seen, or to read the journals he reads.
He maintains, throughout the book, and with ample citations of the literature as well as anecdotal case reviews to support his position, that most of the critics are basing their views on what chemotherapy was ten years ago, without recognizing the advances within the past two or three years. He is also guardedly optimistic about the possibilities for immunologic approaches to therapy in the near future.
He is right about this, in my opinion, but the skeptics and critics are partly right as well. There is another argument going on, difficult to state plainly and even more difficult to engage in. It has to do, finally, with the value of limited benefits in diseases like cancer. How much is it worth, or is it worth anything, to be able to live six months longer with a disease that will surely be fatal at the end of that time? What about one year? Three years? Five years? Ten?
This is the sort of question being asked these days of many cancer patients and their families. It is, thanks to refinements of technology, no longer complicated by other, harsher terms: very few patients are in any way incapacitated by chemotherapy, contrary to the popular impression of chemotherapy. They are not “poisoned”; beyond a few hours of nausea and transient weakness they are not made to feel sick; some of them lose scalp hair but only temporarily, and wigs serve adequately while the new hair grows back in as it always does. Almost all of them are far more comfortable and free of pain than they would be without treatment. So it is really the question about time. Is it possible to live well under the nonetheless certain and predictable prospect of dying?
One answer is, of course, that this is what life is like for all of us. We are all sure of dying, but most of us are not obliged to accept this, and are allowed to believe that we’ll go on forever.
Another answer comes from many of the patients undergoing this kind of treatment, and there is no question about their feeling. They want very much to be treated. They feel better for it, they can usually return to the activity of their former lives, and, most important of all, they receive hope. The hope comes in two forms: there is the hope of being one of the number, still a small number to be sure, of permanent cures. And there is the hope that in a field of clinical science moving as rapidly and surprisingly as this one, something new and decisively effective may turn up next year.
Two years ago, the outlook for a young man with testicular cancer was a matter of a few months, no longer. Then the astonishing effect of a new class of platinum salts was discovered, and the patients with this disease are alive and free of signs of cancer in their second year. The field is moving forward.
I have no doubt that Lucien Israël will be criticized for this book, from several sides. It will be said by a good many internists and surgeons that he is an overenthusiast, pushing his own field with too much zeal and too few misgivings. The large and influential community of basic scientists will be disturbed—and I must confess I also was somewhat distressed by this in the book—that Israël places less emphasis than he should on the potential power of basic research in getting at a final solution for the treatment of cancer. The environmentalists in medicine will be sore because he pays so little attention to the role of carcinogens, and indeed, apart from an eloquent and urgent harangue about the overwhelming influence of cigarettes, so little attention to prevention at all. Those who oppose the National Cancer Program because of its high cost will not like a book that recommends spending even more money on the development of a costly and complex technology.
But I hope all of these people will read the book carefully, all the way through. Whether one agrees with his position or not, this is an honest piece of work, by a man who knows what he is writing about.
Death of TB January 25, 1979