by Lewis Thomas
ON MEDICINE AND THE BOMB
In the complicated but steadily illuminating and linked fields of immunology, genetics, and cancer research, it has become a routine technical maneuver to transplant the bone-marrow cells of one mouse to a mouse of a different line. This can be accomplished by irradiating the recipient mouse with a lethal dose of X rays, enough to destroy all the immune cells and their progenitors, and replacing them with the donor’s marrow cells. If the new cells are close enough in their genetic labels to the recipient’s own body cells, the marrow will flourish and the mouse will live out a normal life span. Of course, if the donor cells are not closely matched, they will recognize the difference between themselves and the recipient’s tissues, and the result, the so-called graft-versus-host reaction, will kill the recipient in the same way that a skin graft from a foreign mouse is destroyed by the lymphocytes of a recipient.
It is a neat biological trick, made possible by detailed knowledge of the genetics involved in graft rejection. Any new bone-marrow cells can survive and repopulate the recipient’s defense apparatus provided the markers on the cell surfaces are the same as those of the donor, and precise techniques are now available for identifying these markers in advance.
Something like this can be done in human beings, and the technique of bone-marrow transplantation is now becoming available for patients whose marrows are deficient for one reason or another. It is especially useful in the treatment of leukemia, where the elimination of leukemic cells by X ray and chemotherapy sometimes causes the simultaneous destruction of the patient’s own immune cells, which must then be replaced if the patient is to survive. It is a formidable procedure, requiring the availability of tissue-match donors (usually members of the patient’s family), and involving extremely expensive and highly specialized physical facilities—rooms equipped for absolute sterility to prevent infection while the new cells are beginning to propagate. Not many hospitals are outfitted with units for this kind of work, perhaps twenty or twenty-five in the United States, and each of them can take on only a few patients at a time. The doctors and nurses who work in such units are among the most specialized of clinical professionals, and there are not many of them. All in all, it is an enormously costly venture, feasible in only a few places but justifiable by the real prospect of new knowledge from the associated research going on in each unit, and of course by the lifesaving nature of the procedure when it works.
This, then, is the scale on which contemporary medicine possesses a technology for the treatment of lethal X-irradiation.
The therapy of bums has improved considerably in recent years. Patients with extensively burned skin who would have died ten years ago are now, from time to time, being saved from death. The hospital facilities needed for this accomplishment are comparable, in their technical complexity and cost, to the units used for bone-marrow transplantation. Isolation rooms with special atmospheric controls to eliminate all microbes from the air are needed, plus teams of trained professionals to oversee all the countless details of management. It is still a discouraging undertaking, requiring doctors and nurses of high spirit and determination, but it works often enough to warrant the installation of such units in a limited number of medical centers. Some of these places can handle as many as thirty or forty patients at a time, but no more than that number.
The surgical treatment of overwhelming trauma underwent a technological transformation during the Korean and Vietnam wars, and it is now possible to do all sorts of things to save the lives of injured people—arteries and nerves can be successfully reconnected, severed limbs sewn back in place, blood substitutes infused, shock prevented, massive damage to internal organs repaired. Here also, special units with highly trained people are essential, elaborate facilities for rapid transport to the hospital are crucial, and the number of patients that can be handled by a unit is minimal.
These are genuine advances in medical science. The medical profession can be proud of them, and the public can be confident that work of this kind will steadily improve in the future. The prospects for surviving various kinds of injury that used to be uniformly fatal are better now than at any other time in history.
If there were enough money, these things could be scaled up to meet the country’s normal everyday needs with tailor-made centers for the treatment of radiation injury, bums, and massive trauma spotted here and there in all major urban centers, linked to outlying areas by helicopter ambulances. It would cost large sums to build and maintain, but the scores, maybe hundreds, of lives saved would warrant the cost.
The Department of Defense ought to have a vested interest in enhancing this array of technologies, and I suppose it does. I take it for granted that substantial sums are being spent from the R & D funds of that agency to improve matters still further. In any conventional war, the capacity to rescue injured personnel from death on the battlefield does more than simply restore manpower to the lines: its effect on troop morale has traditionally been incalculable.
But I wonder if the hearts of the long-range planners in DOD can really be in it.
Military budgets have to be put together with the same analytic scrutiny of potential costs versus benefits that underlies the construction of civilian budgets, allowing for the necessarily different meanings assigned by the military to the terms “cost” and “benefit.” It is at least agreed that money should not be spent on things that will turn out to be of no use at all. The people in the Pentagon offices and their counterparts in the Kremlin where the questions of coping with war injuries are dealt with must be having a hard time of it these days, looking ahead as they must look to the possibility of thermonuclear war. Any sensible analyst in such an office would be tempted to scratch off all the expense items related to surgical care of the irradiated, burned, and blasted, the men, women, and children with empty bone marrows and vaporized skin. What conceivable benefit can come from sinking money in hospitals subject to instant combustion, only capable of salvaging, at their intact best, a few hundred of the victims who will be lying out there in the hundreds of thousands? There exists no medical technology that can cope with the certain outcome of just one small, neat, so-called tactical bomb exploded over a battlefield. As for the problem raised by a single large bomb, say a twenty-megaton missile (equivalent to approximately two thousand Hiroshimas) dropped on New York City or Moscow, with the dead and dying in the millions, what would medical technology be good for? As the saying goes, forget it. Think of something else. Get a computer running somewhere in a cave, to estimate the likely numbers of the lucky dead.
The doctors of the world know about this, of course. They have known about it since the 1945 Hiroshima and Nagasaki “episodes,” but it has dawned on them only in the last few years that the public at large may not understand. Some of the physicians in this country and abroad are forming new organizations for the declared purpose of making it plain to everyone that modern medicine has nothing whatever to offer, not even a token benefit, in the event of thermonuclear war. Unlike their response to other conceivable disasters, they do not talk of the need for more research or ask for more money to expand existing facilities. What they say is, in effect, count us out.
It is not a problem that has any real connection to politics. Doctors are not necessarily pacifists, and they come in all sorts of ideological stripes. What they have on their minds and should be trying to tell the world, in the hope that their collective professional opinion will gain public attention and perhaps catch the ears of political and military leaders everywhere, is simply this: if you go ahead with this business, the casualties you will instantly produce are beyond the reach of any health-care system. Since such systems here and abroad are based in urban centers, they will vanish in the first artificial suns, but even if they were miraculously to survive they could make no difference, not even a marginal difference.
I wish the psychiatrists and social scientists were further along in their fields than they seem to be
. We need, in a hurry, some professionals who can tell us what has gone wrong in the minds of statesmen in this generation. How is it possible for so many people with the outward appearance of steadiness and authority, intelligent and convincing enough to have reached the highest positions in the governments of the world, to have lost so completely their sense of responsibility for the human beings to whom they are accountable? Their obsession with stockpiling nuclear armaments and their urgency in laying out detailed plans for using them have, at the core, aspects of what we would be calling craziness in other people, under other circumstances. Just before they let fly everything at their disposal, and this uniquely intelligent species begins to go down, it would be a small comfort to understand how it happened to happen. Our descendants, if there are any, will surely want to know.
THE PROBLEM OF DEMENTIA
I have always tended to agree with those who criticize the government for legislating special funds for individual diseases (the “disease-of-the-month” syndrome, as it is termed) at cost to the country’s broader and, on balance, more productive programs in basic, undifferentiated science. The evidence is convincing enough: we have been learning more ways into the center of human disease mechanisms by studying normal biological processes than by mounting frontal, targeted assaults on one disease after another. When, for example, we have found our way to the epicenter of the cancer problem, as sooner or later we shall, armed with enough deep information to switch a neoplastic cell back to the normal mode of life, it will be because the crucial information will have emerged in its own time from basic research on normal cells, most of it likely to be coming from applications of the recombinant-DNA technique to fundamental cell biology.
I would, however, make one exception to the nontargeting rule, and push for special consideration and high priority for one particular human disease, not a disease-of-the-month but a disease-of-the-century, the brain disease that afflicts increasing members of our population because of the increasing population of older people in the society—senility, or, as it is now termed, senile dementia. The major form of the disorder, Alzheimer’s disease, affects more than 500,000 people over the age of fifty, most of them in their seventies and eighties. It is responsible for most of the beds in the country’s nursing homes, at a cost exceeding $10 billion now and scheduled to rise to $40 billion or more within the next few years.
It is the worst of all diseases, not just for what it does to the patient, but for its devastating effects on families and friends. It begins with the loss of learned skills—arithmetic and typing, for instance—and progresses inexorably to a total shutting down of the mind. It is not in itself lethal, unmercifully; patients go on and on living, essentially brainless but otherwise healthy, into advanced age, unless lucky enough to be saved by pneumonia.
It is not, as we used to think, simply an aspect of aging or a natural part of the human condition, nor is it due to hardening of the arteries or anything else we know about. It remains an unsolved mystery.
One acceptable guess, but pure guess, is that it could be due to a virus of the strange class known as the “slow” viruses. One such agent was isolated some years back from the brain tissue of demented patients in a landlocked tribe in New Guinea, where most members of the group lost their minds by the age of forty to a disease known locally as “kuru.” It was learned that ritual cannibalism had been a long tradition in this tribe, involving the eating of the brain of each deceased by others, including young children, and Gajdusek and his colleagues succeeded in transmitting the disease to chimpanzees by intracerebral inoculations of brain tissue. Later on, it was learned that a similar disease occurs sporadically but rarely elsewhere in the world, under the names of its discoverers, Creutzfeld and Jakob, and a similar virus has been recovered from the brain tissue of such patients.
The virus is itself the most peculiar of all forms of life. It is in the first place almost impossible to kill, resisting such traditional sterilizing procedures as boiling and exposure to alcohol, formaldehyde, and other disinfectants; indeed, the agent was recovered intact from several specimens of brain tissue that had been placed in formalin and stored in pathological museums for a decade or longer. When injected into susceptible laboratory animals (chimpanzees, guinea pigs, mice, hamsters) it produces no evidence of disease for periods of eighteen months or longer, after which the brain undergoes rapid destruction. Unlike other viruses it cannot be shown—or hasn’t yet been shown—to consist of particles visible by electron microscopy, nor has anyone found nucleic acid to account for its ability to multiply many times over in the affected brain, even when the brain is known to contain a trillion infectious “units.” If it is not made up of nucleic acid, and can nonetheless replicate itself, it will surely be the strangest of all creatures on this planet, but this is not yet known for sure; perhaps it possesses its own DNA or RNA, hidden away where it cannot be found, or it may be similar to a class of naked, very small viruses seen in plants. At present, it is a mystery.
Creutzfeld-Jakob disease is rare, accounting for only a small minority of cases of dementia in this country, but it could well be that it is not so unique as it seems. The idea that it may be related in its causative mechanism to the larger group of brain diseases labeled Alzheimer’s is not outlandish. But it would still be a considerable gamble to launch a new laboratory on the hypothesis that Alzheimer’s is caused by a similar slow virus, and very few such projects are planned or under way.
But quite apart from a general reluctance to take on such a long shot, there is another reason for reluctance. Even if it should turn out to be a valid notion, the work would require more time, and more money, than most biomedical scientists believe they have at their disposal these days. If you were planning to inject samples of suspected virus into an array of experimental animals, the thought of an interval of a year and a half or two years before you could reasonably expect even a preliminary, tentative answer would stay your hand, especially if you were a scientist just beginning a career. By the time you finished your first experiment you would be near the end of your first grant, most likely with nothing to show for it: no annual report, no publications, nothing to put before a faculty committee charged with considering your eligibility for promotion.
The climate is wrong for research problems like this one. Most NIH grants are awarded for periods of two to three years, most young investigators have their personal salaries paid from such grants, and there is a general, feverish sense that the research projects have to be absolutely sure things, bound to result in published papers and grant renewals by the end of the first year.
Even if an investigator decided to take a safer (and perhaps more productive) route into the problem by studying, say, the detailed characteristics of some of the already known slow viruses—“scrapie,” a disease of sheep transmissible to mice, or a similar disease affecting mink brains—in hopes of learning something new about the structure or function of such viruses (if that is what they are) that might then be applied to the human disease, there is still the barrier of time and money. Each experiment requires many months of waiting, and the cost of maintaining mice or guinea pigs in good health over such long periods of time is formidable. Scientists, even those consumed by curiosity over intriguing and engrossing puzzles, tend to stay away from problems like these.
What is needed is a new kind of research support mechanism, designed specifically and selectively for the problem of senile dementia. Such a mechanism must provide money, of course, and a good deal of money, but it must also take care of the problem of time, which is peculiar to this particular biological puzzle, and it must do so in a way not available—or anyway not yet available—within the research support mechanisms of the NIH. Something of the order of ten years of guaranteed support for each laboratory is necessary, with assured increments annually indexed for inflation. At least six new laboratories should be organized and launched within the country’s major research universities.
&nbs
p; Ten years may seem an extraordinarily long period of commitment for a scientific program, and indeed it is. But it may not be long enough, and I would not argue against fifteen, or even twenty.
Now, who should foot that bill, and assume all that responsibility? Not the federal government, obviously. Governmental agencies cannot obligate themselves for such a stretch of time; they are good at thinking two years ahead, sometimes four, but no further. Who then?
I believe this is a task for the several large private foundations that have staked their mission in what is called the Health-Care Delivery System. Senile dementia is, or should be, high on their agenda of concerns, nagging away at their staffs because of the present high cost, the predictable escalation of cost in the coming decades (enough to swamp all other parts of any health-care system), and, above all, the plain fact that nothing at all can be done to alleviate this disease problem by reorganizing existing medical-care facilities or by building new ones. No training programs, no enlistment of new professionals or nonprofessionals, no rearrangements of payment mechanisms, nothing based on today’s level of information about the disease can possibly be useful. The only hope lies in research, and the research will not be done—not on the scale appropriate to the problem—unless the foundations step in.
The trustees of some of the largest foundations have resolved to stay away from any involvement in basic biomedical science, in the belief that the federal government should shoulder that responsibility, and up to now they have held to that resolve, spending many millions each year on wholly commendable efforts to improve the delivery of health care. Now they have done that, and good for them. I would be glad to contribute to a banquet in their honor, to celebrate their achievements, and all my friends would come, provided that on the occasion the trustees would announce that henceforth, for the next fifteen years, one-half of their endowment income would be committed to research on dementia.