Evolutionary Episodes in the Concept of Viral Oncogenesis

EVOLUTIONARY EPISODES IN THE CONCEPT OF VIRAL ONCOGENESIS RICHARD E. SHOPE* During the course of the past ten or twelve years our thinking with regard to the etiology ofcancer has undergone great modification. What would have been considered revolutionary, unorthodox, and even dangerous views as short a time as twenty years ago are now attaining great respectability and, at the present time, have reached the point where they modify and influence the spending policies ofboth the federal government and the major fund-granting agencies so far as cancer research is concerned. I am referring, of course, to the currently great enthusiasm with which both the scientific and lay communities have leaped to accept the possibility that filterable viruses may be of basic etiological importance in cancer. A question which comes to the minds of those seriously interested in the solution ofthe cancer problem concerns the basis for the current concept ofviral oncogenesis and its validity. With our present great interest in the possibility that cancer may be a viral disease, are we perhaps being led up a blind alley and are our scientists being diverted in their investigations from more promising approaches? I believe that it is self-evident that our current concept of viral tumorigenesis was not arrived at in any single step and that the results of much experimental work have contributed to our present thinking. There is, of course, no way of telling at this point what further modifications may be made in our thinking concerning viral oncogenesis, but we do know pretty well how we have reached our present concept. It has been arrived at through a series of studies, each ofwhich has constituted an episode in viral tumor research and each of which has changed to a greater or lesser extent our earlier thinking. * The Rockefeller University, New York, New York 10021. This Philip B. Price Lecture was presented June 3, 1965, at the University ofUtah College ofMedicine. 258 Richard E. Shope · Concept of Viral Oncogenesis Perspectives in Biology and Medicine · Winter 1966 As a generality, it may be said that cancer is a biological phenomenon occurring in many and perhaps all species ofanimals, and it may be assumed that mammalian—and probably also avian—tumors are broadly comparable to those in man. Despite this similarity of cancer in animals and man, the matter ofdirectly associating viruses as causative agents has been limited to those tumors occurring in birds and animals aside from man. The reason for this is that usually, and except as I shall discuss later, each tumor is specific for the host in which it naturally occurs and can be transmitted or transplanted only to members of the same species. In the cases oftumors ofrabbits, mice, or chickens, for instance, this restriction does not limit the studies of the cancer investigator, and direct tests for the presence of a causative agent can be made by the inoculation of tumor material into normal individuals of the same species. From these studies there is no longeranyquestionabouttheabilityofvirusesto induce malignant growths in many species of animals. The intriguing question that remains is whether they can and do also cause malignant disease in man. In human cancer, the direct approach to determine a causative agent cannot, for obvious reasons, he applied as it is in animals. Determination ofthe causal factors ofcancer in man must therefore be made by indirect approaches or by applying the findings with animal cancer to man where they seem to have a possible bearing. Thus far no human tumor, except the common wart, has been proven to have a viral cause. Neither has any experimental animal yet been shown to acquire neoplastic disease by inoculation with an agent derived from a human tumor. Conversely, there is no direct evidence that any animal or bird tumor virus can cause neoplastic disease in man. Historically, evidence for the view that viruses may serve as the cause of certain types of malignant disease goes back to the end of the last century. In 1896, Sanarelli in Uruguay observed an outbreak of illness among the rabbits in his laboratory. The disease, which became known as infectious myxomatosis, was characterized by the development of multiple tumors in the...