Expanding the Immunology Frontier

Expanding the Immunology Frontier

The head of the Rockefeller University's Laboratory of Cellular Physiology and Immunology has strong opinions about cancer research.

I wasn't raised in a scientific family and I didn't have a focus on science early on. In high school I took a vocational test and it concluded that I could be anything. I was interested in everything and I had absolutely no focus until I went to university at McGill. That's when I first took biology. I really became interested in physiology and medicine, though I took almost every other course in the university. I knew I loved research, but I also liked the practice of medicine a lot. As I went through medical school I became more and more focused on biology and medicine.

All along, at every educational institution, I had great teachers. They did what mentors are supposed to: they provided knowledge, support, and criticism. We always need mentors, not just when we're starting out.

My key mentors were the ones that I worked with in the lab—Orville Denstedt, professor of biochemistry at McGill, and then cell biologists Betty Hay and Jean Paul Revel at Harvard Medical School. For my postdoctoral work, I wanted to come to Rockefeller and work with Zanvil Cohn and James Hirsh. I had no second choice, in part because they were the only people taking cell-biological approaches to the immune system at the time. I learned immunology sitting right in this very room. We just read papers and that's how I learned. Working with them led me to the discovery of dendritic cells in my third year at the lab.

I feel that many people don't recognize that the immune system is involved in so many important conditions. The vast majority of people may have never heard of the word immunology. Even if they're taking an antibody that's making them well, they may have no idea this came from immunology.

The major sacrifice you make as a research scientist is that you don't get to spend enough time with your family. The other thing one gives up is time outside the lab making science understandable to the community. I do a little public speaking, but I definitely would have liked to have had more time to get out and explain what we're doing. Not only because it's fun being with people, but it really is important.

I don't like superlatives, but if I had to try to describe my most important accomplishment, it was to discover a new dendritic cell lineage of white blood cells and to show that it initiates and controls immunity. It was quite a struggle to get there, but those discoveries in 1973 and 1978 convinced us we were on the path to something new and important, and it opened up the field. Dendritic cells help you to understand how this remarkable immune system is involved in many diseases, and what you might do to prevent or treat diseases.

AIDS is our lab's main target, cancer is another, but we also want to learn to silence or tolerize the immune system in transplantation and many other settings like autoimmune diabetes. And we want to discover vaccines for many more diseases.

Some people would say the major application is to use dendritic cells in immune therapy for cancer. There is plenty of promise, but immunology in cancer is very underdeveloped. I estimate that immunology is less than five percent of the effort at the National Cancer Institute and very little of that five percent deals with cancer in patients—it's people like me doing models outside of the patient. That's one of the things I'm trying to change, but it's going very, very slowly. We need people to see this as an omission in the war on cancer that must be overcome once and for all.

When you list the properties of tumor cells, it is fair to say that one is to evade the immune system. But the immune system also knows how to reject cancer cells. We have a cancer death rate in this country of more than a half million every year and we have 22,000 cancer patients in drug trials, but hardly any are immunologic. It's a huge gap that we're not looking after. A number of immunologists who think this way have gotten together and, with help from various sources, come up with a proposal which we call a cancer immunotherapy network—a mechanism whereby scientists will work together to design the best immune-based studies in cancer patients and make them accessible to patients.

I often wonder what I'd be doing if I didn't take my biology course, but certainly if I had to do it over again I would do the same thing. I love a lot of things about my work, including being able to work on a special campus like this and in New York City. I love discovery and the way it happens. I love tackling what I believe to be a big problem. And I love the scientific profession, its internationalism and the many terrific people who are responsible for one major advance after another. I'm getting old, but because everybody in the lab is so young, I feel like one of them, you know, just tackling a problem.

View the NYAS interview with Ralph Steinman during the October 2008 Cancer Vaccines Conference.