Yale immunologist Prof. Richard Flavell, just awarded an Israeli prize, appreciates harmony, both in his band Cellmates and in his multinational research lab.
By JUDY SIEGEL-ITZKOVICHrichard flavell 224.88(photo credit: Judy Siegel)
Life in the award-winning immunology lab at Yale University in Connecticut isn't all mice, microscopes, test tubes and toil. When Yale's Prof. Richard Flavell, winner of the Hebrew University-Hadassah Medical School's 2008 Shai Shacknai Memorial Prize in Immunology and Cancer Research - needs some time off, he takes his guitar out.
In 1992, Flavell and four colleagues launched a band called the Cellmates. When the British-born molecular immunologist first came to Yale, he met other music-loving scientists. "By chance we sat together and discussed forming a band," Flavell told The Jerusalem Post in an interview earlier this month at the Lautenberg Center for Immunology in Jerusalem's Ein Kerem, where he received the award.
Flavell not only plays guitar but also sings and writes songs. His Jewish second wife, Maddy (Madlyn Nathanson, the daughter of German-Jewish Holocaust survivors), plays keyboard and sings back-up; Len Kaczmarek, a professor of pharmacology, is second guitarist; Bill Philbrick, a member of Yale's department of medicine, plays drums; cell biologist Prof. Ira Mellman also plays, and a female graduate student sings.
Together, the Cellmates compose, write lyrics and play music that they call Bio-Rock, about life in the lab and current medical issues. "We produced a CD in 1997 and are currently working on a second. We also perform five or six times a year at scientific meetings, biotech companies and universities on the East Coast."
FLAVELL DID NOT receive the prestigious award - established by veteran New Jersey Senator Frank Lautenberg - for his musical ability, but for developing molecular approaches to immunological problems.
"Working in my lab, where I have some 35 young researchers, we try to understand the hundreds of autoimmune diseases. These all have a common underlying mechanism, which is the failure of immune tolerance. The body's immune system, meant to attack foreign invaders and protect the body, goes haywire."
The resulting autoimmune diseases occur in about five percent of the population; the best-known are Type I diabetes, rheumatoid arthritis, psoriasis, celiac disease, multiple sclerosis and Crohn's disease. The rest are rare. But 95% or so of the population don't have this problem because their bodies can prevent their immune system's T cells, which are produced in the thymus gland, from doing damage. "Everybody has lymphocytes directed against their own tissue, but the body has mechanisms to eliminate the worst of them," he explained.
THE VIEW that all autoimmune diseases have some principles in common is borne out by the fact that some drugs have been useful against numerous types, even though the diseases involve different organs. "We in our lab try to uncover mechanisms that protect us normally and go wrong in autoimmune patients. There will be a cure eventually. It will be incremental," Flavell suggested. "We will have better ways of arresting the course of the disease, such as by using regenerative medicine with stem cells that could bring back function. But this field is in its infancy. Other successful treatments, such as of diabetes, could be by implanting beta cells or guiding the function of the patient's own stem cells."
All autoimmune diseases have a genetic component, but environmental factors are also involved. It is perfectly logical, said Flavell, that being "too hygienic and clean" may play a role. "As a kid, I'm sure I stuck dirt into my mouth. I grew up with animals. Today, kids are treated with lots of antibiotics, so the immune system may not learn at a young age to be activated properly. I think there is something to this hygiene theory."
He works almost solely on mice. "All animal models are abstractions: You're not studying humans but a process in animals that is relevant to humans. Mice breed more quickly than rats, and are easier to work with. We have worked to give mice human immune cells, and have received a grant from the Bill and Melinda Gates Foundation to test an experimental HIV vaccine more quickly. It can be done in a few months rather than years. Our mice have human blood stem cells, so they are a reasonable model."
The Yale scientist says the Bush Administration's policy on human embryonic stem cells (it restricts federal funding to those who use them for research) is "very unfortunate. Most scientists favor prudent and constructive use of biology for the human good. Judaism's view of embryonic stem cell research is much better. The research will go on, as it will save lives of people who would otherwise die. Fertility clinics in any case discard human embryos all the time when they get old."
Flavell was born in England's Essex region in 1945; his father was principal of a primary school and a pilot during World War II, and his mother was a housewife. Of his three siblings, his older brother went into plant genomics and his younger brother into cardiovascular biology, but none of his older relatives went into science.
"We have a long tradition of teaching and being school principals."
But it took only one chemistry teacher when Flavell was 15 to get him inspired by science. "I was a very bad pupil and lacked motivation. I found everything boring - until this teacher taught me chemistry. I would do chemistry experiments in a little shed in the back of the house. I was also interested in natural history, collecting and watching little amphibians and reptiles. My parents were very supportive, and from that chemistry class, I began to take an interest in everything, especially science. I became very academically oriented and wanted to learn. I was not driven by the desire to cure people; I wanted to discover things," he recalled.
Today, two of his three adult children from his first (Dutch) wife are scientists. Both are graduate students, with the oldest son studying for his PhD and MD simultaneously at Manhattan's Rockefeller University and another at Harvard, doing his doctoral work in neuroscience.
"My sons always saw me having fun in my work. And you have to have a personality for science." But his daughter, a freshman at Skidmore College in New York, has "vowed not to study science."
Flavell left England for the first time in 1970, when he did postdoctoral work at the University of Amsterdam with Prof. Piet Borst; then he went to the University of Zurich to do another post-doc with Prof. Charles Weissmann, director of the institute of molecular biology. Flavell returned to the University of Amsterdam to work for five years as a junior faculty member, and then went back to England to head a lab investigating gene structure and expression at the National Institute of Medical Research. In 1982, he went to the US to work as vice president for research and development at Biotech, and then became chief scientific officer at Biogen in Cambridge, Massachusetts.
"I was so happy and have had such a good time. Sometimes I thought of going back to England, but I never did. I am a US citizen and feel at home in America, but I've always been very comfortable wherever I have lived. I don't feel torn. I speak English and Dutch fluently and a bit of German, French, Italian and Spanish."
His multilingual skills must come in handy in his lab, as researchers who work for him come from 12 countries, including Israel, Morocco, Algeria, China, Japan, Korea and Europe. It is almost like a mini-UN... except the staffers get along. "The Israeli and Moroccan post-docs particularly get along very well," Flavell noted. "You learn in a lab that people are people, not stereotypes."
He gets about 100 applicants a year. "We check their curriculum vitae, look over their letters of recommendation, and then invite about 10 to come to the lab to try out. Candidates then give seminars, and all lab staffers have an open vote to choose about five who will remain for about four years. It's a big commitment, and though it's getting harder to find a satisfying job after post-doctoral work, a majority of them go on to become professors."
Post-doc researchers earn $35,000 a year or more and work crazy hours, but voluntarily. Flavell has never thrown anybody out, but on rare occasions, he will tell some that they are not suited to research and will help them find another job.
He has noticed that fewer applicants are native-born white Americans, including Jews. "They generally want to go into lucrative professions like business, computers and banking. Immigrants have more to gain. The best way for them to become scientists is to learn in the US. About half of them remain and the rest go back to their native countries," Flavell said. "But I'm not very worried that a massive amount of US know-how will be exported because many stay, marry, have children and become Americans."
About a third of his lab researchers are women. "I like to recruit them because they are very good and provide role models for others. One Korean woman in my lab told me it's almost impossible for a woman scientist to get a position in Korea. Women generally have to put up with more to get where they are. Many of them have children. They are very persistent."
Flavell is very honored to win the Shacknai Prize, which was named by Lautenberg in memory of his Jerusalem-born Reform rabbi, Shai Shacknai, who led his synagogue in Wayne, New Jersey and tragically died of skin cancer at the age of 38. The senator was heavily influenced by the young rabbi.
Some of the recipients go on to get additional awards, including the Nobel Prize. Flavell himself has published more than 700 papers, reviews and chapters in books, and has been recognized by numerous awards and honors, including membership in the US National Academy of Science and being a fellow in the Royal Society.
"Israeli cancer and biology research are extremely good," Flavell stated. He is distressed by efforts in the UK and elsewhere to launch an academic boycott against Israel. "It is perfectly ridiculous to target academics in a country for political and other reasons. A boycott completely violates academic principles. I have occasionally been asked to sign petitions against Israel. I have nothing against the expression of political opinion, but am totally opposed to such actions."
Flavell has known many leading Israeli immunologists and cancer researchers like Prof. Howard Cedar and Prof. Yehudit Bergman of the Hebrew University -Hadassah Medical School for many years. "I have been to Israel seven or eight times, the first time for a joint Weizmann-Pasteur Institute conference in 1979. It was then I saw Jerusalem for the first time: It was like magic."
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