Physician-scientists like Jay Bradner, MD, (right) are building on the cancer-care advances made decades ago by Tom Frei III, MD, and others..
Dr. Bradner: What strikes me most about all the work you did is not only how pioneering it was, but how enduring it is. The strategies you established for childhood leukemia are only modestly different than what are used today. The same is true for lymphoma.
Dr. Frei: It's interesting that we are doing work now based on the same fundamental concepts that we used originally. The tools are different and better, but the concepts are the same. The real opportunity, of course, has come in basic science that speeds forward into the clinic.
At the time, we didn't really know which way things were going to go. The big challenge back in those days was not only the science itself, but the attitude that many people had with respect to cancer. On a good day, we felt we were going to see cures for various forms of the disease in three to five years. But there was a good deal of cynicism directed at therapeutic research and the value of chemotherapy, so we vacillated between being confident and concerned.
Many of the basic scientists, including some at Dana-Farber, thought that an investment in basic science for cancer was not worth it. Science had not advanced far enough so that its application to the clinic could likely be proven.
Bradner: Discoveries, I imagine, went a long way to changing peoples' minds. Was there a particular period when you were able to sway them into believing there was a chance for this to work?
Frei: There was a nucleus of people, including Dr. Sidney Farber [founder of Dana-Farber Cancer Institute], Dr. Freireich, Dr. Holland, and myself who felt strongly that progress could be made. That was based, to some extent, on faith. The focus of our studies was children with acute lymphocytic leukemia. There is nothing quite as compelling as a child with cancer for getting the public, as well as basic and clinical scientists, to respond.
The moment in time when we were translating advances to cures was in late 1959 and early 1960, when we first used vincristine and prednisone in combination. With this multi-agent, leukemic cells disappeared in two or three days. It was so dramatic that you couldn't help but believe something fundamental was happening. That proved to be true. Complete response was achieved in more than 90 percent of patients, and this provided an opportunity to come in with other curative therapies. Then in Hodgkin's disease, non-Hodgkin's, and lymphoma, we continued seeing progress.
Bradner: It's my understanding from those years that the role of the physician- scientist in the development of these treatments was more casual than it is today. The collaboration between clinical investigators at the National Cancer Institute and the pharmaceutical companies they would partner with to develop these agents was a close, fluid relationship. Now there seem to be more barriers. Do you agree?
"Today with almost every cancer patient, you think 'cure' first. You can almost always do something for somebody."
—Emil Frei III, MD
Frei: Yes, it was much less formal back then. There were fewer regulations and people involved. There weren't more than a handful of people doing clinical cancer research in 1955 when I started out. There was a small group at Memorial Sloan- Kettering, St. Jude's Hospital, and the National Cancer Institute.
The prognosis was poor during this period. I remember seeing a sign back then: "Cancer = Death." It was a real problem going around to see patients with advanced cancers that were spreading when you knew there wasn't much you could do for them. Your help was often given in a supportive, emotional, friendly way, not a substantive one. Today with almost every cancer patient, you think "cure" first. You can almost always do something for somebody.
