Yale School of Medicine immunologists and Howard Hughes Medical Institute investigators Richard Flavell and Ruslan Medzhitov were named winners of the Vilcek Prize for Biomedical Sciences, receiving $100,000 for their work on the role of the immune system in a range of diseases, including Type 2 diabetes. Flavell sat down with the News and spoke about his research.
Q: So, tell me about some of your recent discoveries.
A: Our work since the mid-’90s focused on sensing molecules found inside the cell. This sensing system plays a very important role in maintaining homeostasis with the microbes present in our bodies. We have to live in harmony with those microorganisms, and usually we do. But what we found in the last few years is that when that sensing system breaks down, then homeostasis is lost with the microbes on our surfaces, and that leads to disease.
Q: What kind of disease?
A: This encompasses many diseases that are plaguing developed societies, ranging from obesity to heart disease, and including allergies and autoimmune disease. We’ve shown directly that animals that have lost homeostasis get fatter. They also develop susceptibility to inflammatory bowel diseases like Crohn’s disease, and they can develop Type 2 diabetes. And these microbes are infectious to mice that are normal, so we actually have infectious obesity and infectious Type 2 diabetes. There could well be an infectious component in humans as well, and we’re very interested in doing human work now.
Q: What does this mean for how we treat diseases like diabetes?
A: In the future there could be much more sophisticated ways of treating these diseases with microbes. If there are selective kinds of microbes that were bad, one could try to develop antibiotics that are specific to them. Of course, this is still pure speculation.
Q: What research will you use the prize money on?
A: We want to translate what we’ve done in mice to people. We’re very much interested in understanding what’s going on in people with those diseases and see whether we find the same basic principles, and we’ll use that to model therapeutic approaches. And in parallel, we’re still trying to fully understand the mouse situation. We still need to understand what microbes cause trouble and how they do it. We don’t know enough about why they’re a problem. We want to delve deeper.
Q: Why did you choose to do research at Yale?
A: I moved to the U.S. in 1982, and became the chief scientific officer of Biogen, which strengthened my interest in immune system. After that stint in biotech, I decided I would like to return to academia to focus my energies on really figuring out the immune system. And then Yale decided it wanted to create a new freestanding Department of Immunobiology. At the time, there was no such thing in the country. So I was approached by Yale to see if I would like to lead that, and that was a wonderful opportunity both to build a program that had never been built before and to develop my own research. This has been a wonderful decision for me.
Q: What’s the most rewarding part about your work?
A: The two main things are discovery and the growth of the people who do the discovering in the university setting. [In terms of discovery], there’s the idea that comes first — oh my gosh, the world should work like this — and the vindication of that idea — oh my gosh, it really does work like that! And those two steps are very exciting. The other side is working with tremendously talented people. It’s just great to see them develop, to see them make those discoveries. And they go on to become scientists, and they teach other people.
Q: What frustrates you about it?
A: You have to be able to deal with a lot of failure. There’s more failure than success, and you’re constantly being beaten down by experimental forces. At the moment, probably the most frustrating thing is that we can do so many great things now — the methodologies are available, and the ideas are all around — but the amount of money available is dreadful now. It’s really become so bad that the most talented people in this country can barely work in some cases. We’re a pretty well-known group, and even we have tremendous trouble covering the costs of what we do. We have to make extreme efforts to cut costs, eliminate functions and keep constraints on everything we do in ways we never had to do before in my career.
Q: So the funding is worse than before?
A: It’s much, much worse than before. This is the worst I’ve ever seen in this country. It’s very discouraging for young people.
Q: What are your hobbies?
A: I have numerous hobbies. One is that I have a bio rock band called the Cellmates. Other Yale colleagues are members of the band, and it’s a tremendously enjoyable way of letting off steam.