I was born on December 29th, 1957 in Chicago, IL, USA. My earliest memory is of newly fallen snow blanketing the earth around our home, probably in December of 1959. “Who did that?” I asked, suspecting that my older brothers, sometimes mischievous, had somehow been responsible. It was the last snowfall I would see for several years, because my family moved to the small city of Arcadia, near Los Angeles, CA, where I grew up.
Mine was a family with strong academic standards. Three of the four children would become physicians, and the remaining child a successful software designer and businessman. My father and his parents, refugees from Nazi Germany, were physicians themselves. My mother, born in America to immigrants from Ukraine, was a homemaker, and for some years a technical writer. As a child I felt duty-bound to excel in school, and usually did well. I had a clear goal in mind. From the age of 7 or so, I wanted to be a biologist, and nothing else. Even now, it is difficult for me to imagine pursuing a different career.
My interest in biology grew from a deep fascination with nature, animals in particular. The ability of atoms and molecules to assemble themselves into living creatures, endowed with consciousness, volition, and mobility, and seeming much more than the sum of their parts, inspired awe. “Molecular biology” seemed the right appellation for what I wished to understand, and Watson’s “Molecular Biology of the Gene,” which I read while in high school, impelled me to study genetics and biochemistry in depth. Luckily, there were special ways for me to do so. When I was 14, my father, himself an esteemed scientist, first allowed me to work in his laboratory at the City of Hope Medical Center, where I learned to purify proteins, and to characterize erythrocyte enzymes. I also worked in the laboratory of Susumu Ohno, a mammalian geneticist famous for recognizing the essential role of gene duplication in evolution.
With a sense of mission, I hurried to finish high school and college, skipping several grades and graduating from the University of California at San Diego at the age of 18. At my father’s suggestion, I went to medical school at the University of Chicago, to learn about physiology, pathology, and pharmacology, and to see firsthand the major challenges confronting medicine. I believe this was excellent advice, since biomedical inquiry sometimes yields profound insight into how living systems operate.
After graduating from medical school I completed an internship in medicine and a year of residency in neurology at the University of Texas, Southwestern Medical Center at Dallas. But my foremost wish was to devote myself to scientific work. I did so, beginning in 1983, with a fellowship and later a faculty appointment at the Rockefeller University. I returned to UT Southwestern as an HHMI investigator in 1986; then moved to the Scripps Research Institute in La Jolla, CA, in 2000. I will rejoin the faculty of UT Southwestern later this year.
My most important scientific accomplishments have included: 1) the isolation of mouse tumor necrosis factor (TNF), and discovery of its inflammatory properties; 2) the invention of recombinant inhibitors for TNF, now widely used for the treatment of inflammatory diseases; and 3) the discovery of the receptor for lipopolysaccharide (LPS), which revealed how mammals sense infection, and how certain inflammatory diseases begin.
These advances were made sequentially between 1984 and 1998, and were intimately tied to one another. Each was rooted in the exploration of innate immunity: the ability of multicellular organisms to sense infection and resist it. In the early 1990s, while at UT Southwestern, I first embraced a classical genetic approach to the study of innate immune responses. The genetic philosophy is one in which hypothesis is renounced in favor of a search for exceptions to the norm, induced by mutation. Using genetics to answer questions about mammalian immunity was an epiphany for me, and genetics will likely sustain my work for the rest of my life.
I married while still in medical school, at the age of 22, and between 1983 and 1987 had three sons: Daniel, Elliot, and Jonathan, with whom I remain very close today, although my marriage ended in 1988. They witnessed much of my career in science, and saw firsthand the commitment, rewards, and traumas that science entails: relentless work punctuated sometimes by joyful enlightenment, and sometimes by frustration. None of my sons became scientists, but they do have an avocational interest in science, often leading to animated discussion. Two of them share with me a deep admiration for J.S. Bach (which in my own case, materialized rather suddenly, at a performance of the Matthäus-Passion, attended when I was 15 years old). Indeed, many members of my family, living and deceased, have enjoyed music of the baroque era. Perhaps this is a heritable trait!
28 September 2011, Hong Kong
