Weapons Against Cancer
( Originally Published Early 1960's )
Men, Material, And The Scientific Method
In the preceding 5 chapters we have discussed the broad ex-tent of the cancer problem, and what we can do now for cancer as it appears as a clinical problem. Even now, approximately one-third of all patients with cancer are being saved, and this proportion could be raised perhaps to one-half by the full application to the whole population of all that is known and all that can be done. Even under such utopian conditions, however, 50 percent of the patients would be doomed to die of cancer, unless and until new knowledge and methods become available through research.
Our victories over cancer up to now have been small but real, and hard won. Moreover, they represent only temporary campaigns toward the eventual goals of prevention and cure of cancer by methods that are simpler and easier than those available at present.
Before indicating how we can aim for these goals of the future, we should examine what has been achieved and how it has been achieved up to now. For, as Lord Byron wrote, the best prophet of the future is the past.
Our technological advances of the past and of the future depend upon the exercise of a human thought and action process we call scientific research. This approach of man to the world outside of himself was known to the ancient Greeks, and the modern era applied the methods to the world within ourselves with equal effectiveness. In the early 17th century Francis Bacon attempted to codify scientific method as observation, induction, deduction and verification.
The scientific method really is not a limited number of didactic steps, but a continuum of observations, specific questions, hypotheses, tests of validity, and conservative conclusions that are again put to further tests and that give rise to further hypotheses. Thus, the end point of scientific research is not only the answer to some specific question, but further questions that could not even be intelligently phrased before the antecedent research is completed.
Scientific research can be usefully divided according to the material it has to deal with; these categories are observational research and experimental research. In the former, man and his methods can only interpret phenomena as they reach him, without ability to manipulate the phenomena. This is the case for astronomy, for example. This is also the case for epidemiologic studies, in which relationships of various factors are sought in populations, or for pathology studies in which morphologic appearance of tumors is related to the eventual clinical course of the patient. In experimental research, the investigator is in an area where the methods and the materials available to him allow the purposeful selection and creation of situations and appropriate comparative controls.
All research starts with a question, and unless the question is clear and can be approached by existing methods, the research is at least premature until applicable methods are developed. The question, or hypothesis, is followed by the selection of the appropriate materials and methods that will test the question. Science is quantitation, and much of its advances are directly related to the mechanical tools that assist in measurement. The ruler and the thermometer are still as important instruments as the most complex electronic apparatuses.
It is also important to recognize what science is not. It is not authority, it is not opinion, it is not tradition, and it is not testimonials. Its impudent questions always have been : what is the evidence; what are the conditions under which I may anticipate the same results; what are the quantitative values? Show me !
The source of scientific advances is, and always will be, the individual scientist with a new idea. New ideas often arise in an unpredictable fashion, ignited by the confrontation of some unforseen event by a prepared mind. This event has acquired a coined word to describe it, serendipity. It is interesting to reflect that in extremely well planned experiments, the chance of unpredictable events is reduced to the minimum, whereas this chance is increased in less planned situations. In experimentation, there is a happy medium that needs to be sought, for in an entirely haphazard set of events, no event stands out as unusual and the opportunity for serendipity again disappears.
The preeminent role of the individual scientist in the progress of science in no way detracts from the fact that in the complexities of modern research the needs are the same as for any other human activity men, money, material, and time. These elements must be blended into effective forces through planning and management. Cancer research is no exception. Since 1937 the United States has been in the forefront of research directed against cancer because the public and its representatives have supported the activities, allowing expression of research as guided by councils of scientists and science administrators.
In the United States, two organizations have primary responsibility for leadership and for support of cancer research. These are the National Cancer Institute, established by an act of Congress in 1937, and the American Cancer Society, a voluntary public agency which was incorporated in 1945 but goes back to the Woman's Field Army of pre-World War I days. Funds for cancer research now exceed $200 million per year. Among the larger institutions devoted entirely to cancer research are the National Cancer Institute, a component of the National Institutes of Health in Bethesda, Md.; the Roswell Park Memorial Institute in Buffalo, N.Y.; the Memorial Sloan-Kettering Cancer Center in New York City; the M. D. Anderson Hospital and Tumor Institute in Houston, Tex. ; and the Children's Cancer Research Foundation in Boston, Mass. Many universities and medical schools have strong cancer research programs, including those at Harvard, Minnesota, Wisconsin, and California.
The interest in cancer is world wide, and several other countries are strongly represented in cancer research. In England, the many contributions of the Imperial Cancer Research Fund, and of the Chester Beatty Research Institute in London have been outstanding since the turn of the century. In the Soviet Union, the Academy of Medical Sciences emphasizes cancer research, and has two large institutes devoted to cancer: the Institute of Experimental and Clinical Oncology in Moscow, and the Oncology Institute in Leningrad. The Gustav Roussy Institute near Paris, the new Japanese National Cancer Institute in Tokyo, and the Tata Memorial Institute in Bombay indicate the international interest and concern with the cancer problem.
Animal cancers, particularly in well controlled laboratory species, have been research materials of inestimable value to cancer research. In fact, cancer research became possible with the discovery, late in the i 9th century, that cancers could be inoculated and grow in related animals.
Geneticists, by means of selective inbreeding, developed many strains or families of mice, rats, and guinea pigs that are as identical as twins, and have predictable occurrences of certain types of cancer. For example, the strain A albino mouse develops primary lung tumors and, among breeding females, breast cancers. The strain C3H is noted for its early development of breast cancer in females, and of liver tumors in the males. Other strains, such as the C57 black, are useful because they have been selected for low occurrence of tumors. Yet other strains have been developed for characteristics that mark certain genes, enabling studies on the relationship of such features to the development of cancer. Inbred animals, carefully maintained in special laboratory centers, are as valuable to biologists as are pure chemicals to the chemist.
All animals, including the pure inbred strains, harbor a large variety of microorganisms. Many of these are saprophytic, or even useful to the host. The role of the bacteria world is being better understood by the development of germ-free animals, which are removed from the uterus under sterile conditions and live out their lives in tanks from which all bacteria are excluded. Although the experiments have not been extensive, germ-free animals do develop cancer when injected with cancer-info-producing chemicals, and no important role of bacteria is evident in the reactions leading to cancer.
Cancers in laboratory animals are of three types: the spontaneous tumors, induced tumors, and transplanted tumors. The term "spontaneous" is a misnomer, since all it means is that these tumors arise in the animals without known cause, such as an injection of a cancer-info-producing chemical. As Wilhelm Hueper of the National Cancer Institute has stated, cancer, like all other diseases, is not a mysterious phenomenon of spontaneous creation but the result of the action of definite chemical and physical, animate or inanimate, endogenous and exogenous pathogenic agents.
Induced tumors differ from the spontaneous tumors only in that some known agent or procedure was introduced, to which the cancer is then attributed. They are, therefore, tumors of known etiology.
Transplanted tumors should be distinguished from the spontaneous and induced tumors because they represent a different biological system. A healthy animal that has not been exposed to the initiating stimulus of the tumor is a recipient of a small bit of fully developed tumor tissue from another animal. There must be genetic and immunologic compatibility between the tumor tissue and the new host. Even in closly related, inbred animals, this compatibility may not be fully maintained when the tumor is transplanted through many generations of animals. Thus, the host-tumor relationship in the transplanted tumor system may be, and often is, quite different from the relationship between the host and the spontaneous or induced tumor that develops from the tissue of that individual animal. Many observations on immunologic responses to tumors, and of regression of tumor growth, when performed with transplanted tumors, cannot be made when spontaneous or induced tumors are used. Cancer research records many instances in which failure to recognize this has led to prematurely optimistic conclusions.
It is the general scientific consensus, clearly indicated not in words but in the efforts that are being expended, that cancer is a solvable problem. The general directions of the profitable lines of attack also have been agreed upon. These include the studies on the causation of cancer, especially of chemical and physical agents that can evoke the cancer transformation, and of the role of viruses in these processes. The second line of research is on the nature of cancer, including the study of the structure and of the intracellular mechanisms that characterize cancer, which may provide us with the necessary leads toward the treatment of cancer by interfering with these mechanisms.