ROLE OF CHANCE OBSERVATIONS IN CHEMOTHERAPY: VINCA ROSEA *

This paper may seem somewhat unorthodox in a monograph on screening procedures. However, we are eager to present the role of chance in obtaining new leads for chemotherapy and to illustrate this with a specific example. The results of our research, which are presented here in detail for the first time,” should not be considered in terms of a new chemotherapeutic agent, but rather in terms of a chance observation that has led to the isolation of a substance with potential chemotherapeutic possibilities. The cancer worker in the smaller institution or the academic department must view with awe the vast chemotherapeutic screening projects in progress in the United States; a t the same time, however, he must consider what contribution he is in a position to make. Perhaps the role of chance observation is neglected in his consideration of ways of searching for new agents. Although somewhat irregular in comparison with the systematic prediction, synthesis, and screening of an entirely new series of compounds, chance observations may well be worthy of greater consideration than they have received. The chain of events that led to our present problem originated in our laboratory in 1949 because we had been working with, and were somewhat intrigued by, various plant extracts to which historical hearsay had ascribed empirical uses by primitive peoples. The disease of cancer was certainly far from our thoughts when we learned of a tea made from the leaves of a West Indian shrub that was supposedly useful in the control of diabetes mellitus. C. D. Johnston of Black River, Jamaica, Federated West Indies, had been curious about the reputed benefits of a tea made from the leaves of the white-flowered periwinkle, Vi’inca rosea; he forwarded a supply of the material to us. The effects of extracts of the plant given orally to experimental animals proved disappointing, and essentially no alterations in the blood sugar of normal or diabetic rats or rabbits could be induced. Similarly, no effect on the response to glucagon was found. Whether there is any basis for the use of this material in diabetes could not be ascertained, despite a brief visit by J. C. Rathbun and H. A. McAlpine of our department to Johnston. As we became aware later, a number of earlier workers had investigated the properties of periwinkle extracts on carbohydrate metabolism, with essentially negative r e ~ u l t s , ~ ~ although a pr&ietary preparation, Vinculin, had been marketed in England for some time as a “treatment” for diabetes. More recently Hugh-Jonese has com* The research for this paper was supported in part by a grant from the National Research Council, Ottawa, Ontario, and in part by a grant from the National Cancer Institute, Toronto, Ontario, Canada. t British Empire Cancer Exchange Fellow and Medical Research Associate, National Research Council, Ottawa, Canada. $ Research Fellow, National Cancer Institute, Toronto, Canada.