Sometimes a little sweet talk goes a long way. A silver tongue catapulted Ruslan Medzhitov from Tashkent to Yale, where he's helped revolutionize our understanding of the immune system.
The early 1990s were a bleak time for science in the Soviet Union. As the empire crumbled, scientific resources drained away, until just a single battered copy of the weekly journals made the rounds at Moscow University. As a graduate student there, Medzhitov yearned to keep up with the latest advances, and his weekly hour with Science and Nature wasn't enough. So he headed to the Academy of Natural Sciences, which was then engaged in its own detente with the university. For various bureaucratic reasons, university students weren't allowed access to the library. "So I had to go and flirt with the librarians—there were several of them—and eventually they all knew me and let me in secretly and told me not to tell anyone," says Medzhitov.
There, in the stacks, the young biology student stumbled on a copy of Cold Spring Harbor Symposia. In it was the paper that launched his career. Written by the late Yale immunologist Charles Janeway (an HHMI investigator), the article sketched a new theory for how the immune system recognizes and responds to pathogens. Little was known then about the so-called innate immune system and how it identifies and reacts to invaders. Janeway's ideas ignited Medzhitov, sending him to his university's sole e-mail terminal. "I was able to send messages once a week," says Medzhitov. "And my first message was to Charlie." Medzhitov asked the professor for more details about his ideas. To Medzhitov's delight, Janeway responded, and the pair exchanged several more messages.
"Charlie's paper was the only paper that made sense of a lot of things," says Medzhitov. "That was the point I first thought about being a researcher in immunology. As an undergraduate student, I never had a course on immunology."
With a career path now in mind, Medzhitov landed a fellowship at the University of California, San Diego. There, working with protein evolution pioneer Russell Doolittle, Medzhitov contacted local immunologist Richard Dutton, who knew Janeway and recommended Medzhitov for a postdoctoral position in Janeway's lab. Janeway said yes. "I felt very lucky," says Medzhitov.
When he arrived at Yale—after a detour to Moscow to defend his thesis and sweat out a government coup and six months of uncertainty—Medzhitov felt overwhelmed. "Janeway's lab was very famous, and I imagine competition to get in was very high. And I was coming from just a few e-mail exchanges and a recommendation. My challenge was, not only did I not speak English well, I also had never done any experiments. In Russia, there was no money to do anything. All I could do was sit in the library. So I arrived without any experience, basically zero. I had to learn as quickly as I could."
It turns out that lack of experience helped Medzhitov in another way. Janeway's theory of how innate immunity acted, by recognizing bits of invading organisms, was "extremely speculative." And that meant it was risky to work on. But, being "oblivious to concerns about career," Medzhitov jumped in on the project. "I was just happy to be in a place where I could do science," he says.
In 1996, after just a few years working together, Janeway and Medzhitov made a breakthrough. They discovered receptors that alerted the second arm of the immune system, the more familiar T cells and B cells that attack pathogens. Studying these proteins, dubbed Toll-like receptors, quickly became one of the hottest areas in biology. "That was an extremely exciting time," says Medzhitov. "We didn't realize how much would come out of it eventually, that it would become such a huge area of research."
In the decade-plus since then, Medzhitov has piled one discovery after another upon the first, dramatically expanding our understanding of the key roles Toll-like receptors play in infection control, chronic inflammation, and even the growth of tumors. At the same time, he's branched off in a dozen directions: One example of many, Medzhitov is learning how commensal bacteria—which live in our guts and help us digest food—also help protect our intestines from injury.
Medzhitov now thinks that Toll-like receptors and related proteins may trigger the chronic inflammation that leads to coronary artery disease, Alzheimer's, and diabetes—some of our biggest killers. "I like a lot of areas of biology and it's hard for me to focus on only one," he says. Now, with plenty of journals to read and experiments to conduct, he doesn't have to.