by Lewis Thomas
Under the electron microscope, sliced into thin sections by a diamond knife and magnified 50,000 times, the mycoplasma changes from a featureless blue speck to something as big as a house, and as busy-looking. There is no cell wall, like the rigid, thick boundary that envelops ordinary bacteria, only a delicate two-layer membrane. Inside are the ribosomes, from which the proteins needed for living are manufactured, and here and there, in a delicate meshwork visible between the ribosomes, are the strands of DNA carrying the instructions. Some mycoplasmas are very small and round with little knobs at one pole, others are long snaky filaments; some become enormously swollen, the size of a human leukocyte. Some have their own viruses inside, similar to the bacteriophage particles of ordinary bacteria. No one knows what the viruses are doing there; they are obviously lodgers of some sort, perhaps a messenger service for carrying genetic information from one set of mycoplasmas to another. Conceivably, the toxins of mycoplasmas may be coded by DNA brought in by a bacteriophage, as seems to be the case with diphtheria and streptococci, but this remains to be determined.
The mycoplasmas are unique among microbes. Taxonomically, they cannot be classed among either the bacteria or the viruses. Some investigators believe they are the descendants of ancient bacteria that long ago lost their cell walls. This is an attractive notion, since it is known that you can take the walls off bacteria without killing the organisms, and when this is done the wall-less bacteria grow in tiny colonies indistinguishable from mycoplasmas. However, there are enough differences between mycoplasma DNA and that of all bacteria thus far studied to make the relationship arguable, and the argument goes on.
For all their small size and fragile appearance, mycoplasmas are tough and extraordinarily adaptable. Tissue culture laboratories are plagued by them: suddenly a pure line of someone’s carefully cultured, highly treasured mammalian cells will begin to disintegrate because of contamination by mycoplasmas, brought in from the laboratory air or from the breath of the investigator. Once in, they are nearly impossible to exterminate from the cultures; they take up residence within the surface coating of the tissue culture cells, or even deep inside, and manage thus to protect themselves against the antibiotics that would ordinarily kill them off. Mycoplasmas have been found living in the tissues of insects, and some plants are evidently infected in this way. They can adapt themselves to unusual environments: one species has been found living free in a smoldering coal-mine hillock, another flourishing at 80 degrees Centigrade in a hot spring.
You have to respect forms of life like these.
They are even proposed, from time to time, on wholly speculative grounds, as candidates for the ancestral precursors of nucleated cells. They are highly plastic, because of having no boundary beyond the unit membrane, and capable of enlarging to the size of a proper nucleated cell. Moreover, they have cholesterol incorporated into their membranes, like nucleated cells and unlike bacteria. It is imaginable that they may have served at one time as hosts for other prokaryotic organisms. Primitive microorganisms of one kind or another may have crossed the thin boundary and lodged inside more than a billion years ago, and these boarders may have evolved, how I cannot guess, into the nuclei, mitochondria, and chloroplasts of today’s plants and animals. It is only a guess, anyone’s guess, probably (but not necessarily) beyond experimental proof. But it is one more reason, in my view, for feeling affection for these dear and enchanting little beings.
18
MSKCC: THE MEMORIAL SLOAN-KETTERING CANCER CENTER
The Memorial Sloan-Kettering Cancer Center, where I have worked for the last ten years, stands on most of two city blocks between York and First avenues, linked at the corner of Sixty-eighth and York to the Rockefeller University and New York Hospital–Cornell Medical Center across the street. Memorial Hospital is itself the largest and most comprehensive cancer facility in the world, and the most extraordinary hospital I have ever observed from the inside. It is at once the most specialized and most general of hospitals, dealing not only with the specific problem of this one disease but with the numberless other ailments that can afflict patients who have cancer, from newborn infants to people in their nineties.
I don’t know how many times I’ve been asked across dinner tables by sympathetic strangers who know where I work: “How do you stand the place, all those deaths?”
A few years ago Hubert Humphrey was a patient, in for treatment of the recurrent bladder cancer which eventually killed him, fully aware of the gravity of his situation, worried and somber on the evening of his admission, quiet and thoughtful, alone in his room at the time of my visit. We talked for a while; he was well-informed about his plight, knew that his chances for survival were slim, almost nil. But the “almost” was the focus of his attention. Over the next few days he transformed himself, I think quite deliberately, into the ebullient, enthusiastic, endlessly talkative Humphrey—not so much for his own sake as for what he saw around him. There were about forty patients on his floor, all with cancer of one type or another, some just arrived and undergoing diagnostic procedures in preparation for treatment; some due for surgery or chemotherapy next morning; others getting ready to go home with high hopes, cured once and for all; some at the end of the line, beginning to die.
Humphrey took on the whole floor as his new duty. Between his own trips to X ray or various other diagnostic units, he made ward rounds. He walked the wards in his bathrobe and slippers, stopping at every bedside for brief but exhilarating conversations, then ending up in the nurses’ station, bringing all the nurses and interns to their feet smiling. During the several weeks he was in and out of the hospital, Humphrey’s rounds became famous. One evening I saw him taking Gerald Ford along, introducing him delightedly as a brand-new friend for each of the patients. Together, Humphrey in his bathrobe and Ford in a dark-blue suit, nodding and smiling together, having a good time, Ford leaning down to be close to a sick patient’s faint voice, they were the best of professionals, very high class.
It was an unusual event because of the eminence and conversational skill of Humphrey and his visitors, including especially Muriel Humphrey—one of the world’s nicest women. But this sort of thing goes on all the time in Memorial. Patients who can be up and around are constantly circling the floor, finding new friends, stopping by the bedsides of others, making small talk. One hears, down the corridor, someone’s voice saying, “Oh, I had that and it was nothing, really nothing. You just wait, you’ll be feeling better.”
The direct, day-to-day involvement of laymen in the creation and sustenance of institutions like Memorial Sloan-Kettering is a uniquely American phenomenon. The government had nothing to do with the original decision to build such a place, nor much to do with sponsoring it until the post–World War II years. The Rockefeller family was responsible at the outset. John D. Rockefeller, Jr., perceived, late in the nineteenth century, the need for combining a hospital specializing in cancer treatment with a research facility committed to this one disease, and assembled the land on which the present buildings were begun in the 1930s. His son Laurance has committed much of his time and energy to the whole center, serving as a chairman of the board for a quarter century, and enlisting help from other members of his family and a wide circle of friends to keep the endowment growing.
And then there are the volunteers, several hundred men and women of all ages, some of them healed patients or relatives of patients, some who simply came on the scene asking to help, and during summertime scores of teenagers swarming in and out of all parts of the center. These people do hard work, and a good many do it every day, part-time or all day long, whatever can be spared from their regular occupations. They push carts filled with books and magazines from room to room, bring flowers, run errands, help at the desks in the busiest parts of the outpatient clinics, and make conversation with the patients and their families whenever called upon for friendship, which is almost all the time. The fifteenth floor contains a commodious pavilion and a w
ell-stocked patients’ library, run by a skilled librarian and her volunteer associates. There is a piano, played any time by patients and ceremonially played several times weekly by professional performers together with other instrumentalists and singers who come in for the pure pleasure of entertaining patients with cancer.
The reason all this works is that in Memorial there are no minor problems, no small stakes. Some patients who come in with the diagnosis of cancer are discovered to have a lesser disease and go home elated. Others who have been operated on or given chemotherapy previously are admitted because of a suspected recurrence, and are vastly relieved to find that it isn’t so. But all of the patients who enter Memorial do so in the full expectation that they do indeed have cancer, with no choice but to face up to it and have done whatever can be done. They, and their families and friends, are frightened by this disease as by no other, and they come to their rooms fearing pain and death, in need of all the reassurance they can find.
Sometimes the reassurance comes promptly and with solid scientific evidence. Women with early breast cancer and without lymph node spread can be surgically guaranteed a 95 percent prospect of lifetime survival without recurrence; for those with nodes the outlook is chancier, but the survival figure with combined surgery and chemotherapy stands now at around 70 percent. Lung cancer, perceived as incurable just a few years ago, seems now to be curable in as high as 40 percent of patients if their disease is spotted in its earliest stage, thanks in large part to the work of master surgeons like Edward Beattie and his colleagues. The malignancies of childhood, including leukemia, used to be the most rapidly lethal of all forms of cancer, but now, with combinations of various new drugs, they are becoming the most easily cured (“cure” is a word that has to be used provisionally, but many of these children have by now become young adults, healthy and free of any sign of disease). Testicular cancer, a malignancy of young men, was uniformly and rapidly fatal a short while ago; now, with new forms of chemotherapy, it appears to be curable in most patients.
The statistics show that in recent years approximately half of all Memorial patients are free of disease and in restored general health when discharged from treatment.
So, coming into the hospital is a sort of gamble, with 50–50 odds in favor of both the house and the patient. This is no comfort to the patients with advanced lung cancer, or those with widespread metastases from breast or colon or prostate cancers. These people know there is no real hope, and they need hope more than anything. What they can be given is a very small piece of hope: there are very few forms of cancer, even the most widespread and rapidly growing, that cannot be slowed down by chemotherapy. Months, as much as several years, can be added to productive life. For the elderly this brief extension of living comes as a boon, giving time for finishing any number of necessary tasks, setting affairs in order, preparing as we all must sooner or later for dying, but with time to concentrate on the preparation. For the younger patients the gain of a few months or even a few years seems much less of a reward, but they have something else to hope for: that in the meantime something new may emerge with the capacity to turn their cancer cells around. This, by the way, is an entirely rational prospect to have in mind. The pace of current biomedical research, particularly in the basic sciences relevant to cancer, has become so rapid, and the new insights so illuminating for the biology of normal and neoplastic cells, that it is reasonable now to hope for totally new therapeutic approaches, sooner rather than later.
Hope is itself a kind of medicine. I believe this, although I cannot prove it. I have not had a long personal experience in observing cancer patients, but some of my savviest colleagues who have been oncologists all their professional lives are convinced that patients who are able to maintain some sense of optimism do better, live longer, and recover more often than those who are discouraged from the outset and give up hope. There are a few studies published in the medical literature to back up this impression, but not enough data to make it solid. One paper by an Australian oncologist compares the mode of dying in patients who are convinced that they are doomed to the “bone-pointing” syndrome observed in aboriginal societies: when a witch doctor points a bone at a person, death follows within a few weeks. The great Harvard physiologist Walter Cannon once made a study of the hexing phenomenon and concluded that certain human beings do indeed slip into a state of apathy and die simply because of being told that this will happen. Neither Cannon nor anyone else has ever been able to guess how such a thing can happen, but happen it does, raising the possibility that the opposite sort of assurance given to genuinely sick people in the process of dying might have the effect of increasing resistance to the process. It may be because of this that so many charlatans have achieved temporary success in treating cancer. Their biologically inert pills or injections may seem to work wonders for a while, because of belief alone.
Cancer is generally thought to be a painful disease. Sometimes it is, especially in those cases where the bones and nerves become involved in the process, but the majority of patients with fatal cancer do not have pain. Indeed, dying from cancer is for most people a much less painful and a considerably more peaceful experience than death from other causes. When pain does occur, it can almost always be fully controlled. My colleagues who run the pain clinic at Memorial tell me that it can always be controlled by morphine or the newer derivatives of morphine, provided the physicians and nurses are skilled in drug administration and not resistant to using whatever doses are needed. The last thing to worry about in caring for a patient with terminal cancer is addiction, but some doctors and nurses do still worry about this, and their patients are subjected to unnecessary pain.
Up to now, most of the improvements in our technological capacity to deal with neoplastic diseases have arrived piecemeal, one by one, individualized for each of the different forms of cancer. The drugs that work so beautifully for childhood leukemia are not much help for adult patients with metastatic growths. Breast cancer can be dealt with by hormonal therapies that do not affect other tumors. Radiation treatment alone will eliminate certain cancers, while others are totally resistant. Because of such different responses it is believed in some quarters that cancer is really not a single disease but perhaps a hundred different ones, each requiring its own separate research program and, ultimately, its own special kind of treatment. Sometimes this rather bleak point of view is put forward defensively by the groups most concerned with public support for cancer research, within government and in the philanthropic foundations, in apprehension that public expectations of something easy and quick—a universal “answer to cancer”—are essentially unrealistic and may result in a backlash retreat from the necessary long-term commitment.
My own belief, based more on hunch than data, is that the notion is fundamentally wrong. In the end, when all the basic facts are in, I think it will turn out that all forms of cancer, in whatever organs and of whatever cell types, are a single disease, caused by a single, central controlling mechanism gone wrong. It is still too early to lay bets, but I would bet anyway that there is a gene or a set of genes in all cells, normally held under repression in healthy cells, which somehow escapes control and leads to cancer. The genes may be related to those switched on during early embryonic development, when rapid and almost unrestrained multiplication of cells is necessary, and then switched off when differentiated tissues have been perfected. There is already some evidence for such a mechanism, emerging from current research in molecular genetics. It has been proposed that the viruses known to cause cancer in experimental animals do so by carrying along within their own DNA some of the mammalian genes which release other genes responsible for unrestrained and undifferentiated growth. It will eventually turn out, I believe, that the chemical carcinogens act at the same locus within cells, switching on the same pathological mechanism that is involved in virus-induced tumors.
The idea that cancers in different organs represent separate, different diseases seems
to me beyond belief even at today’s level of knowledge. There are chemical carcinogens that will cause solitary cancers of the liver or kidney or lung or brain depending on the age of the animal, the dosage of the chemical, or relatively minor molecular modifications of the molecule. Viruses that produce cancer of one organ, the liver, say, in one animal species will cause cancer in the kidney or lung of others. A German investigator, Druckrey, showed long ago that a nitrosamine derivative that produces liver or lung tumors in adult rats will produce brain tumors when administered to fetal rats, but the brain cancer does not begin to grow until the fetus has reached late adult life.
All of which suggests, to my mind anyway, that cancer is still a problem for basic science. But progress in the related fields of cell biology, molecular genetics, and immunology has moved along so rapidly in just the last three or four years that it will not come as a great surprise to learn that there is, in fact, a single determining mechanism underlying all types of human cancer—although the nature of that mechanism is, of course, bound to be an astonishment. When it comes, this level of deep information will begin to generate pharmacologic ideas aimed at switching the mechanism off, or turning it around, and when this point is reached, we can begin talking about “a” cancer cure.
