The Future And Cancer Research Goals
( Originally Published Early 1960's )
Victory is a reasonable expectation?
Scientists do not relish being cast in the role of soothsayers, yet prediction is one of the important functions of science. The research method yields the necessary knowledge that makes predictions more reliable, and allows man to some extent even to modify the course of future events.
So it is in cancer research, which started at the turn of this century. Its broad aims were well defined from the beginning : to find knowledge that will allow us to prevent and to cure cancer. The approaches to these goals are through the study of causative factors in the initiation of cancer, and of the nature of the cancer process, including its effects on the host.
We have gone a long way since the founding of the Imperial Cancer Research laboratories in England, in 1903, or even the creation of the National Cancer Institute in the United States in 1937. There are now portents for all to see that give us the right to renewed optimism.
In the studies on the causation of cancer, the road to its prevention, two important areas are evolving rapidly and soundly. The first is the expanded research on the occupational and other environmental factors in cancer, through the combined efforts of the epidemiologist, the engineer, the chemist and the physicist. Even the grossly concentrated industrial situations are but seldom studied with the attention they deserve. It would be useful to research to have freer access to industrial rosters for long term follow up of workers exposed to the ever increasing list of new chemical agents. Beyond these relatively limited population groups, we are confronted with an increasing load of contamination of our atmosphere, our water supplies, and our food sources and processes. More rapid methods of identifying, isolating and removing potential cancer producing hazards from our environment is a major problem of developmental and applied research.
As is so well typified by the cigarette story, individual habits may be related to increased cancer hazards also. Long-term studies are needed on human populations under defined environmental conditions and under periodic surveillance in regard to their habits and ways of life, as well as in regard to their physical and biochemical characteristics. The results of such studies may identify factors that may be related to susceptibility of developing cancer. Such "human population laboratories" should not be limited to the United States, where there has occurred a high degree of similarity in life, but should be encouraged in other portions of the world with unusual environmental or cultural situations. These investigations should not be limited to cancer, but should include other causes of mortality and morbidity, not only physical but mental and social as well.
By far the most encouraging, exciting area of research in the causation of cancer concerns viruses. The rate at which new findings of importance are being added is so rapid that even monthly summaries are outdated as soon as they appear. The artificial boundaries between tumor viruses, animal viruses, and viruses that may infect and change human cells are now chapters of the past. The initiation of sarcomas in hamsters with a latent monkey virus, SV40, and with two viruses found in the human throat, Adenovirus 12 and 18, seems to be at the very threshold of the final step of showing a direct relationship between some human cancers and viruses. The best candidate appears to be acute leukemia, in which particles resembling those of leukemia virus of chickens and of rodents are seen with the electron microscope in the blood of human patients.
We almost hesitate to follow this line of predictions, because with the identification of a virus responsible for a human cancer of any type the way is open to the cultivation of the virus in tissue culture, and the eventual trial of vaccines for the prevention of the cancer in the population. This is no longer a wild dream, but well within the realistic possibilities for which concrete research planning is on the way.
The advances being made in the elucidation of the chemicaI-physical structure of DNA and RNA, and their role in the very heart of living matter, are probably as revolutionary as man's unlocking of atomic energy. Inevitably the new knowledge will not only make its impress on cancer and other diseases, but will become a political and social problem of international proportions. These developments, too, are no longer topics for science fiction but realities we shall face within this century.
In the field of research on the diagnosis of cancer, there is acceptance of the view that no all revealing single test for all cancers is likely. The eventual availability of pure viral and tissue antigens may well provide us with immunochemical aids in the detection of certain cancers. Greater information on the hormonal levels and their eventual relationship to the development of cancer may provide leads toward the adjustment of such levels and prevention of the cancers. There is suggestive evidence from British investigators, for example, that patients with breast cancer have abnormally low levels of steroids related to the androgens. An effort is being made to define a large population of women by their hormone pattern to ascertain whether this will predict individuals who eventually develop breast cancer. If this proves to be the case, the administration of the deficient hormones may prevent the later occurrence of breast cancer. This type of study is the application of diagnosis to preventive medicine rather than a procedure on a patient with a clinically manifest disease, and is related to the search for cancer susceptibles in a population of presumably healthy persons.
Research in the chemotherapy of cancer is in a period of reconsolidation, occasioned in part by the need for analysis of the results of testing many materials on many systems. This is being done. Such analysis may very well indicate improvements in the methods that were selected before this accumulation of data.
As expression of personal opinion, it would seem that our efforts toward reaching destructive effects on tumors may be usefully supplemented by an emphasis upon less total aims of control by restoring the balance between the tumor and the host. With the exception of the hormones, which are excellent examples of balance regulating chemicals of the body, the anti-cancer agents have been notable for their severe toxicity and narrow margin of difference in effects on normal and neoplastic cells. Although it is impossible to have a patient cured of cancer unless the cancer disappears, the reverse is not necessarily true: the disappearance of cancer may be achievable only at a level that is dangerous to the life of the patient. Observations on acute leukemia of adults, and on patients with multiple myeloma indicate that there is no good correlation between the reduction in the clinical manifestations of these cancers and the length of survival. It may be that the gentler use of the known agents, and the greater emphasis upon the restoration of physiological balances in the host could provide more relief than a frontal attack on the cancer. Using the endocrine area again as an example, the search for chemical agents already present in the body such as embryonic organizers, which may be related to histone, the theoretical "wound hormones," and similar regulators of normal growth processes may be worthy of greater investment.
Although truly useful drugs for the treatment of cancer are still in the future, there is no reason but to be optimistic that they eventually will be found.
Cancer research is but a small segment of the total human endeavor in biomedical sciences. It can advance only as rapidly as progress is recorded in the various "disciplines," where the boundaries are academic conveniences. It shares in the same limitations and frustrations. It cries for more money, more trained investigators, better recognition, and at the same time is confronted with the indigestible mass of scientific re-ports, endless meetings and the complexities of communications at various levels: scientist-to-scientist, scientist-to-physician, physician and scientist-to-the-public.
As scientific research becomes a greater social investment, and as its findings increasingly become of relevance to political decisions, the investigator of cancer is also drawn closer to the problem that faced the scientists who delivered atomic energy to mankind. The problem concerns the proper role of the research scientist in society: should he remain aloof in his ivory tower, disregarding the social consequences of his discoveries, or should he become actively involved in the application and use of his findings? This is not a theoretical question even in cancer research. Should a scientist who discovers that an insecticide is a potent cancer producing chemical for rats press for action to have the chemical removed from the market? Should an epidemiologist who finds that an industrial situation increases the risk of workers to cancer be satisfied with a quiet report in a research journal?
Some of these decisions are upon us already. The extensive investigations on the causative relationship of smoking, particularly of cigarettes, to lung cancer make it abundantly clear that up to 30,000 deaths per year from this cancer alone are preventable. The universal annual performance of a vaginal smear for cytologic detection of cervical cancer could also make this entity a disease that is curable in over 90 percent of the women, for an annual eradication of 10,000 cancer deaths. The full application of known methods of diagnosing and treating cancer would further increase the salvage rate from our present 30 percent to 50 percent. Thus, in effect, we have the necessary knowledge to reduce cancer mortality in the United States by some 25 percent. This calls for research and development in better public health education, in the economic patterns of medical care, and in the social evolution toward the benefits of scientific knowledge to all of our citizens and, indeed, to all of mankind. These goals, and the study of methods to achieve them, are as important and as demanding of the scientific method as is research on the structure of the cell or the exploration of space. They are yet another frontier for the imagination and the drive for achievement with which man was endowed by his Creator.