By now most people are familiar with philosopher Daniel Dennett’s characterization of natural selection as Darwin’s dangerous idea-- dangerous because it acted as a corrosive acid capable of dissolving the established structures of human society. That acid can be just as corrosive of scientific structures, which one might have thought more impervious to the damage. Thus a Darwinian idea has eaten away at some of the foundations of my own field of research for the past half-century, tumor biology, and forced cancer researchers to reexamine some cherished notions about the origins of cancer that were current during the first half of the century. Today, with the discovery of new genes that contribute to the development of cancerous cells, we are keenly aware that cancer is, above all, a disease of DNA. But more important, we know that this disease does not occur in a preprogrammed manner. Only through the gradual emancipation of a cell from the controls that govern its normal process of division does a cell turn cancerous. And that emancipation, it turns out, proceeds by the mechanics of Darwinian evolution.
In hindsight, perhaps, that is not surprising. Since Darwin’s day we have known of the power of natural selection to shape the organisms of the world. And over the past 50 years biologists have come to understand how mutations in DNA provide the array of genetic variation through which natural selection operates. Yet the importance of evolution has only slowly crept into the field of cancer research. To be sure, the process by which cells of the body turn malignant is a very limited one compared with the evolution of a species. But just as we have come to understand that microorganisms evolve resistance to drugs, we now know that cancerous cells evolve to become unresponsive to the growth-controlling forces of the body. How those genetic changes occur is based on Darwinian principles of variation and selection.
That insight changes our understanding of cancer. It lays to rest the hopes of finding a single key change or infectious agent that can explain all forms of the disease. When I started working in cancer research, in the late 1940s, the search for that key change was still in full swing, and it wasn’t long before one prominent theorist--the famed biochemist Otto Warburg, of the Max Planck Institute in Berlin--thought he had found it. Warburg proposed that what made cancer cells different from others was their unusual use of the cell’s energy sources--sugar and oxygen. As it happened, Warburg devised his theory, in part, based on cells I had worked with. When I gave my first talk at an international congress in 1950, I was one of the most junior participants. I spoke about ascites tumors in mice, which are generated by the growth of freely floating cancer cells in animals’ abdominal fluid. Unbeknownst to me, an assistant of Warburg’s was in the audience. A week later the great man sent me a letter requesting the cells, which I promptly sent.
In the following year or two, Warburg published several papers stating that ascites tumor cells preferred to burn sugar as if oxygen was not available, even if it was. He concluded that cancer cells, unlike normal cells, could thrive under conditions of great oxygen shortage. Some years later Warburg wrote that I had made a very important contribution to cancer research by sending him the cells with which he had solved the cancer problem.
