Nobel Prizes and Laureates

The Nobel Prize in Chemistry 2012
Robert J. Lefkowitz, Brian K. Kobilka

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Robert J. Lefkowitz - Biographical

According to an article in The Times of Israel (issue of Dec. 9, 2012) by Mark Schulte, Dr. Alvin Roth (co-recipient of this year's Nobel Prize in Economic Sciences) and I share two attributes with thirty-three other Nobel Laureates. We are Jewish and we were educated in New York City public high schools. This article further highlights the fact that "the overwhelming majority" of this group descended from "Eastern European Jews who came to America between 1881 and 1924, during the great migration." In my case this was true of all four of my grandparents. My paternal grandparents, Mariam (Mary) Kremsdorf and Louis Lefkowitz, were from two nearby towns in southeast Poland, Czestochowa and Zoloshin. They were already married with one child when they immigrated to the United States in 1903, initially settling on the Lower East Side of Manhattan. They would live their entire lives in New York City, primarily in the Bronx and raise seven children, the second oldest of whom was my father, Max, (b. 1905). My grandfather was a cap maker and my grandmother, a homemaker.

My mother's parents, Bernard and Rivka Levine, were from Russia and also immigrated to New York City. My mother, Rose, was the elder of their two daughters. My maternal grandmother's family included several scholars and professionals. Her brother, Shlomo (Solomon) Polachek, was a famed rabbi and Talmudic scholar. Born in a small Russian village, he was known as a child prodigy at a young age and ultimately immigrated to the United States to become head of the Theological Seminary of Yeshiva University in New York City. One of his sons, Harry, was an ordained Rabbi and a prominent mathematician. The latter led him to become Technical Director of the Naval Applied Mathematics Lab, where he was an expert in early commercially available computers.

I was born in 1943 and raised in the Bronx, in a high rise apartment complex known as Parkchester, the only child of Max, an accountant who worked in the garment district in Manhattan and Rose, an elementary school teacher. My mother was a high-strung perfectionist. She would check my homework for the slightest imperfection and demand that it be redone if she detected any flaws, which she invariably did. My father, in contrast, was easy going and affable and delighted in helping me with any project. He had a remarkable ability with numbers and could perform complex calculations in his head more rapidly than I could with pencil and paper. He would teach me many arithmetic manipulations and tricks several years before I would encounter them in school. When my absence of athletic ability manifested itself in an initial failure to meet required school standards for rope climbing and tumbling maneuvers, he insisted on setting up makeshift props at home and coaching me to ultimate success. As an adult, I can easily discern elements of both my parents' personalities in myself.

As an only child lacking siblings and playmates, I was alone a great deal of the time. Much of this was spent reading virtually anything I could get my hands on. I began with my parents' rather modest collection of volumes but then quickly discovered the local public library, from which I would regularly cart home the maximum allowable number of books (6 as I recall). I was rather precocious in this regard. I recall joining book clubs by sending in coupons I clipped from the newspapers which entitled me to claim a free set of books on the condition that an agreed upon number of additional volumes would be purchased over the next year. In this way I acquired, for example, Winston Churchill's six-volume history, The Second World War, and Carl Sandberg's six-volume biography of Abraham Lincoln. By the time I was about thirteen I had completed both sets. My parents, initially unaware of the contracts to which I had obligated them, were left to buy the remaining volumes, further adding to the family library. Increased time for reading these books was, on occasion, gained by faking illnesses such as abdominal cramps so that I could stay home from school and read all day.

My reading at this early stage also included numerous fiction and nonfiction titles related to medicine such as Sinclair Lewis' Arrowsmithand Paul de Kruif's Microbe Hunters. My interest in these was sparked by my family physician, Dr. Joseph Feibush. By the third or fourth grade of elementary school I had decided that he was my occupational role model. I was enthralled by what he did, which included making routine house calls, performing physical exams, especially with a stethoscope, and writing illegible prescriptions. From then on I never wavered from my goal of studying medicine and becoming a physician.

Nonetheless, there were some early signs of interest in chemistry and biology as well. Among my favorite "toys" was my 1950s era chemistry set. Together with a friend we would follow the instructions in the manual, producing solutions of various colors or precipitates. We would copy out the experimental protocols from the guidebook into a notebook and make our own comments about what we saw. We told ourselves that we were creating a "chemistry textbook." A "lab notebook" would have been a better description. A toy microscope of relatively low magnification was another favorite. Through it I viewed human hairs, insect parts of all sorts and a variety of prepared slides that came with the microscope set.

Lest I present myself as a totally bookish nerd at this stage (partial would be a better description), I hasten to point out that I enjoyed a wide range of activities typical of kids growing up in New York City during the 40s and 50s. These included stick ball, punch ball, trading baseball picture cards and riding bicycles. I was also an ardent fan of the New York Yankees major league baseball team ("the Bronx Bombers") and can still repeat the batting order and uniform numbers of the teams from the early 1950s. I was active in the Boy Scouts and for many years took piano lessons, demonstrating relatively little talent. I played the drums, to the dismay of those living in neighboring apartments who would beat on the heating pipes to alert me that I was too loud. I was a member of the first generation of children to watch television, the earliest tiny sets arriving in some of my friends' apartments when I was about five and in our home several years later. However, I can still remember listening to my favorite radio shows sitting on the floor in front of a large console radio.

One other influence which shaped me as a youngster was my participation in a family society called the Associated Kremsdorf Descendants (AKD's). This family circle, consisting of the extended family of my paternal grandmother, would meet once a month for a meal, fellowship, entertainment and a formal business meeting. Complete with elected officers, committee reports and following strict rules of parliamentary procedure, these gatherings attracted dozens of family members from multiple generations. Such organizations were quite common among Eastern European immigrant Jewish families living in the northeast in the mid-20th century (as depicted in the movie "Avalon"). From these gatherings, which I greatly enjoyed, I gained a sense of the importance of family and a respect for, and appreciation of, the older members of the extended family who had all come from Europe.

The Bronx High School of Science
After attending public elementary and junior high schools I entered The Bronx High School of Science (10th grade) in the autumn of 1956, graduating at age 16 in 1959. "Bronx Science" is one of several public high schools in New York City which admits students on the basis of a competitive examination. The student body, representing approximately the top 5% based on the exam, are gifted and interested in science and math. The accomplishments of graduates of this high school are quite remarkable. For example, I am the 8th Nobel Laureate to have graduated from this school, the 7 previous ones having received their prizes in Physics. For me, attending this school was a formative experience. Whereas in elementary and junior high school I was not greatly challenged, here I was among a group of remarkably bright, interesting and stimulating classmates. The curriculum featured many advanced classes at the college level. I was particularly drawn to chemistry and, as a result of taking these college level classes, I was able to receive full credit for two years of chemistry when I entered Columbia College in 1959. Thus I began as a college freshman with organic chemistry, a course generally taken by juniors.

The level of scholarship maintained by the student body was such that even with an average of about 94% my final class rank was about 100th out of 800. A classmate and friend at the time and at present, the famous geneticist David Botstein, had an almost identical average, a fact we tease each other about to this day.

Along with dozens of classmates, I moved on to Columbia University where I enrolled as a pre-medical student majoring in chemistry. The two year core curriculum in "Contemporary Civilization" was required of all students. With an emphasis on reading classic texts in history, philosophy, sociology and the political sciences and discussing these in small seminars, it was for me an opening to a whole new world. In addition, I took courses with and was exposed to, such intellectual giants as the literary critic Lionel Trilling, the cultural historian Jacques Barzun and the sociologist Daniel Bell, among others. I have very fond memories from this period of spending many hours in the public reading room at the 42nd Street New York Public Library, researching papers for those classes.

I also studied advanced Organic Chemistry with Cheves Walling and Physical Chemistry in a department which was strongly influenced by the then recently retired prominent physical organic chemist, Louis Hammett. However, the chemistry professor who had the most profound influence on me was actually a young Assistant Professor of Chemistry, Ronald Breslow. As a college senior I took an advanced seminar in biochemistry which he taught single handedly. This introduction to the chemistry of processes in living organisms really excited me in part, I suspect, because of his very lively teaching style. None of this, however, in any way diverted me from my goal of studying to become a practicing physician. In fact, by midway through my second year at Columbia it had become clear to me that, as a consequence of the credits I had received for college level courses taken in high school, I would be eligible for graduation after only three years. I needed only a couple of courses in summer school, graduating in 1962 at the age of 19, and moving uptown to the Columbia University College of Physicians and Surgeons.

Medical school
I greatly enjoyed my four years in medical school. I had dreamed about becoming a physician since grade school and now I was finally doing it. As a freshman immersed in the basic medical sciences I was able to deepen my interest in, and fascination with, biochemistry. Our biochemistry professors included a remarkable array of scholars (not that any of us appreciated that at the time). We heard lectures on metabolism from David Rittenberg, Chair of the Department; from David Shemin on porphyrins; from Irwin Chargaff on nucleic acids; and from David Nachmansohn on cholinergic neurotransmission. As stimulating as these subjects were to me, it was the clinical work that I was really pointing toward. Much as I enjoyed learning about biochemistry, at this stage the idea of actually doing research never entered my mind. In fact, although short blocks of time were available for research electives, I always chose clinical ones instead.

One young professor left a lasting impression on me. Paul Marks was then a young academic hematologist who taught the Introduction to Clinical Medicine course in which we studied clinical problems for the first time, examined case histories, and looked at blood specimens. Not only was he a good clinician but he assigned readings from the basic science literature that were relevant in a very meaningful way to the cases we studied. This showed me how scientific information could be brought to bear on clinical problems. Among my classmates and friends in medical school was Harold Varmus, who was the co-recipient of the 1989 Nobel Prize for the discovery of oncogenes.

At the end of my first year of medical school, I married Arna Gornstein and our first two children, David and Larry, were born in 1964 and 1965.

House staff
Upon graduation in 1966, I remained at Columbia for two years of house staff training in internal medicine at the Columbia Presbyterian Medical Center. This experience was intense, exhausting as well as exhilarating. I was doing what I had longed to do and I loved it, but I was not sleeping very much. As interns we followed a two week on call cycle in which one week was five nights on duty and two off, and the second was two nights on call and five off. "On call" meant that one slept in the hospital, though it was rare indeed to get more than a very few uninterrupted hours. It was not rare, however, to go two successive nights and intervening days with absolutely no sleep. This consistent sleep deprivation taught us what the limits of our endurance were and fostered a remarkable work ethic. However, it simultaneously degraded our performance at work and our ability to enjoy family time when at home, since the need to sleep overwhelmed all else. Needless to say, this schedule left precious little time for keeping up with the scientific or medical literature. Regulations now prevent working anything like these hours for house staff physicians.

At this time the Vietnam War was raging and there was general conscription with a separate "doctor draft" for physicians. Regardless of which branch of the service you joined, the only certainty was that you would spend a year in Vietnam. One way around directly participating in this very unpopular war, which was of particular interest to budding academic physicians, was to join the commissioned corps of officers in the United States Public Health Service and to be assigned for two years to clinical and laboratory duties at the National Institutes of Health in Bethesda, Maryland. Obtaining one of these commissions was extremely competitive at the time but, because of my strong academic record and recommendations, I was successful.

On July 1, 1968 I moved my family (now including the recently born Cheryl) to Rockville, Maryland to begin my research career at the NIH in nearby Bethesda, Maryland. I had been assigned, through a matching program, to work with Drs. Jesse Roth and Ira Pastan in the Clinical Endocrinology Branch of the National Institute of Arthritis and Metabolic Diseases (NIAMD), now known as NIDDK, the National Institute of Diabetes and Digestive and Kidney Diseases. I was a Clinical Associate, meaning that in addition to doing full time research ten months out of the year, for two months I also supervised a clinical endocrinology in-patient service. Because of this, I gained a remarkable exposure to unusual endocrine diseases which were under study at the time. An example of this was acromegaly.

It was the heyday of interest in second messenger signaling after the discovery of cAMP by Earl Sutherland. He would receive the Nobel Prize in Medicine and Physiology for this in 1971. One hormone after another was being shown to stimulate the enzyme adenylate cyclase thus increasing intracellular levels of cAMP. The idea that these different hormones might work through distinct receptors was talked about but was controversial. Moreover, at the time there were no direct methods for studying the receptors. I was assigned the challenging task of developing a radioligand binding method to study the putative receptors for adrenocorticotropic hormone (ACTH) in plasma membranes derived from an ACTH responsive adrenocortical carcinoma passaged in nude mice. Lacking any prior meaningful laboratory experience, I spent my first year failing at virtually everything I tried and not handling this very well.

Toward the end of 1968 I traveled with my family to New York City to spend the Thanksgiving holiday with family. I discussed my great frustration, unhappiness and lack of progress with my father. He counseled me to just "hang in there" while making plans to continue my clinical training in medicine and cardiology after the completion of my two year stint at the NIH. We agreed that I obviously was not cut out to be a scientist and besides I had always dreamed of being a physician anyway. This plan made good sense to me. Our conversation, however, turned out to be the last time I spoke with my father, who died several weeks later after suffering his fourth myocardial infarction at age 63. His death affected me deeply and I felt, in some odd way, a responsibility to fulfill the plan of my future career that he and I had devised together during our last conversation. His death, combined with my repeated failures in the laboratory during 1968–69, made this one of the most difficult years of my life.

Accordingly, over the next few months I made plans to move to the Massachusetts General Hospital (MGH), one of the Harvard teaching hospitals, in July 1970 for an additional year of medical residency followed by two years of cardiology fellowship. Then, during the summer of 1969, my experiments began to bear some fruit. I was successful in developing the binding assay for ACTH and over the next year wrote my first scientific papers and presented my findings at meetings for the first time. It was exhilarating and fun. For the first time I began to consider the possibility of a career that included a research component. These musings were moot, however, since by now I was committed to moving on to full-time clinical training in Boston.

Recently, two Nobel Laureates, Mike Brown and Joe Goldstein, published a brief essay discussing the remarkable number of Nobel Laureates (9 so far) who have in common the fact that they came to the NIH as physicians during the brief space between 1964–1972 for postdoctoral research training. (1)

They dissect the unique convergence of circumstances which may have been responsible for this extraordinary result, including the quality of basic science mentors on the full time NIH staff, the competitiveness of "the best and the brightest" to obtain these positions during the Vietnam War years, and the now bygone emphasis on teaching of basic sciences in medical schools in the 1960s.

I was particularly fortunate to have access to two physician scientists as mentors, individuals with very different styles and personalities. Jesse Roth was highly imaginative, creative and burned with an infectious enthusiasm for almost any experimental result. Ira Pastan, no less creative, was much more staid, methodical and critical of every result. He could always spot a crucial control I had left out of my experiment, thereby rendering the result essentially uninterpretable. In addition to guiding me through these early days of my scientific career, they provided ongoing support during the period of repeated failure. I owe to these two men my introduction to research in general and to receptor biology in particular. As with my parents, I can readily perceive aspects of both of their approaches in my own scientific investigation and mentoring.

Lineages among Nobel Laureates are often commented upon. In my case, Jesse Roth had trained with Solomon Berson and Rosalyn Yalow whose development of radioimmunoassay led to the Nobel Prize in Medicine and Physiology to Yalow (1977) after Berson's untimely death in 1972. Moreover, training in Ira Pastan's laboratory contemporaneously with me was my medical school and house staff classmate and future Nobel Laureate, Harold Varmus. Ira had himself trained in the lab of another NIH career scientist, Earl Stadtman, who also trained a future Nobel Laureate, Mike Brown.

Massachusetts General Hospital
A defining experience occurred during my first six months back in clinical service as a Senior Resident at MGH. I gradually became aware of the fact that I missed being in the lab. Deprived of my daily "fix" of data, I felt somehow unsatisfied. This, despite the fact that I was again enjoying the hectic pace of the clinical work. Upon completion of the first six months of my residency year I was entitled to choose clinical electives for the next six months. Instead, and in clear violation of hospital rules for resident physicians, I elected to start back in the laboratory. Dr. Edgar Haber, the Chief of Cardiology and a prominent immunochemist, allowed me to begin working in his lab. I was fascinated by receptors and what I saw as their potential to form the basis for a whole new field of research just waiting to be explored. I spent a great deal of time analyzing which receptor I should attempt to study. As an aspiring academic cardiologist I wanted to work on something related to the cardiovascular system. I also wanted a receptor known to be coupled to adenylate cyclase. I initially focused on two models, the cardiac glucagon and β-adrenergic receptors. However, my attention quickly became focused on the latter, for very practical reasons. Unlike the case for peptide hormones such as glucagon or ACTH, literally dozens, if not hundreds of analogs of adrenaline and noradrenaline, as well as their antagonists were available which could be chemically modified to develop the types of new tools which would need to be developed to study the receptors. These would include radioligands, photoaffinity probes, affinity chromatography matrices and the like. Moreover, the first β-adrenergic receptor blocker ("β-blocker") had recently been approved for clinical use in the United States, adding further to the attractiveness of this target to me.

So in the early months of 1971 I began the quest to prove the existence of β-adrenergic receptors, to study their properties, to learn about their chemical nature, how they were regulated and how they functioned. This work has consumed me for the past forty years. Over the next several years in Boston, working mostly with membrane fractions derived from canine myocardium, I sought to develop radioligand binding approaches to tag the β-adrenergic receptors. I focused initially on the use of [3H]labeled catecholamines such as norepinephrine, which are agonists for the receptor. Specific saturable binding could be demonstrated, and I thought initially that we had developed a valid approach to label the receptors. However, it became increasingly clear over the next few years that the sites being labeled lacked many of the properties that would be expected for true physiological receptor binding sites. Coming to this realization was difficult.

During this time I also published some of the very first studies demonstrating GTP regulation of β-adrenergic receptor stimulated adenylate cyclase following after the work of Martin Rodbell on GTP regulation of glucagon sensitive adenylate cyclase. I was now a cardiology fellow. As at the NIH, nights on call were often spent in the lab doing experiments while hoping that my on call beeper would remain quiet. During these years, I had many stimulating and profitable discussions with Geoffrey Sharpe, a faculty member in the Nephrology Division with an interest in cell signaling and adenylate cyclase.

The period in Boston from 1970–1973 was one of the busiest in my life. In addition to my "day job" as a Medical Resident and Cardiology Fellow, I also worked several "moonlighting jobs" to help support my growing family (my fourth child, Mara, arrived in 1971). I worked in various emergency rooms, did physical exams for insurance companies, and even served as team physician for a high school football team for two seasons (they never won a game during this time).

In the summer of 1972, I was recruited by Duke University Medical Center to join their faculty to develop a program in "molecular cardiology."This was to begin upon the completion of my fellowship at MGH in 1973. The overtures came from the Department of Medicine (Chair, Dr. James B. Wyngaarden), the Cardiology Division (Chief, Dr. Andrew Wallace) and the Department of Biochemistry (Chair, Dr. Robert Hill). I initially declined their offer but, when they subsequently raised the ante including an Associate Professor rank in Medicine, it seemed like an offer "I couldn't refuse." Now, my course was set to move to Duke in Durham, North Carolina, to begin my faculty career on July 1, 1973.

Arriving at Duke on July 1, 1973, with my wife and 4 children (ages 2–9), I proceeded to set up my lab in a brand new building, the Sands Bldg., on Research Drive. I would occupy this space for fifteen years before moving to the new CARL building. It was clear that we still needed to develop a radioligand binding assay for the β-adenergic receptors in order to be able to study them. This would ultimately take us close to another year. However, in work with postdoc Marc Caron in the spring of 1974, we succeeded in developing [3H]dihydroalprenolol. Contemporaneously, Gerald Aurbach at the NIH, and Alex Levitzki at the Hebrew University in Jerusalem also developed similar approaches using different radioligands. This was a watershed event because it finally opened the door to direct study of the receptors. Together with M.D./Ph.D. student Rusty Williams we developed comparable assays for the α-adrenergic receptors shortly thereafter. Over the next several years we developed a variety of tools such as photoaffinity probes and affinity chromatography matrices for the various adrenergic receptor subtypes as well as computer based analytical approaches for analyzing ligand binding data. These approaches greatly facilitated the discovery of new receptor subtypes and led to new ways of conceptualizing receptor G protein interactions (for example the ternary complex model).

During my first five years at Duke I juggled clinical and laboratory responsibilities, attending Cardiology clinic each week as well as making teaching rounds on the Medical Service. As the years passed I gradually reduced these clinical activities, but I continued to make teaching rounds until 2003. For the past 10 years I have not engaged in clinical work.

For the first 20 of my 40 year career at Duke, I focused on three essential questions about G protein coupled receptors: what is their chemical nature; how do they signal; how is their function regulated? This period included the isolation of all four of the then known adrenergic receptor subtypes; cloning of their cDNAs revealing the homology with rhodopsin and the existence of the much wider gene family of seven transmembrane G protein coupled receptors; the discovery of the arrestin and G protein coupled receptor kinase gene families, the products of which desensitize the receptors; and the discovery of constitutively active mutant receptors, now known to be the cause of a growing number of inherited and acquired diseases. Our early work with the adrenergic receptors provided a template upon which many labs were able to build, using the first sequences of these receptors and homology cloning techniques to rapidly build out the family of GPCRs to its current huge size of ~1,000 genes in humans. The sheer size of this family, including hundreds of olfactory receptors, was not anticipated.

The next 20 years, until the present, have been focused more on the β-arrestin proteins. Originally discovered in the context of their role in desensitizing receptors, we have found that they are also key molecules involved in receptor signaling and endocytosis. I have been particularly interested in the phenomenon of "biased agonism"at GPCRs. This term refers to the unexpected ability of some receptor ligands to stimulate some receptor-promoted responses while blocking others. Working initially with the angiotensin AngII1A receptor we found peptide ligands that could stimulate β-arrestin mediated signaling while serving as antagonists for G protein mediated responses ("β-arrestin-biased"). The existence of such biased ligands has important implications for both basic and clinical research. For example, it strongly implies that there must be multiple active conformations of the receptor which have now become the object of biophysical and structural studies. Moreover, this discovery suggests that such biased GPCR ligands might represent an entirely new class of drugs which might display more specific actions with fewer side effects. To try to develop such agents, about five years ago, I co-founded a company called Trevena with my Duke colleague Howard Rockman. Details of many of the discoveries mentioned above are provided in my Nobel Lecture.

Throughout my scientific career there have been a number of sources of special satisfaction. One has been the trainees whom I have mentored, more than 200 at this point. Many of these have gone on to distinguished careers in academia, biotechnology and the pharmaceutical industry. My co-recipient of the 2012 Nobel Prize in Chemistry, Brian Kobilka, joined my lab as a cardiology fellow in 1984 and left for Stanford in 1989. He played a major role in our cloning of the adrenergic receptors. Even during those early years in training he demonstrated an appetite for risk and the talent for developing bold, original technical approaches to difficult scientific problems which have characterized his independent career ever since. In a gratifying turn of events over the past several years, Brian and I have been collaborating again on several projects of mutual interest.

There is no way that I can acknowledge here the many other individuals whose work, in aggregate, was recognized by my Nobel Prize. However, during the 70s and 80s, Marc Caron was a long term partner and deserves special mention.

A second major source of satisfaction has been the rapid translation of many of our findings and techniques into practical consequences in drug development. GPCRs are one of the commonest targets of therapeutic drugs. Thus, the development of radioligand binding methods and associated computer based analytic techniques fundamentally altered the way in which drug candidates were screened and developed, as well as how receptor subtypes were discovered. The cloning of the receptors led to discovery (by others) of many new "orphan" receptor drug targets. More recently our discovery of so called "biased" ligands which can preferentially activate G protein or β-arrestin signaling has suggested an approach to development of more specific drugs with potentially fewer side effects. A special aspect of my career has been my relationship with the Howard Hughes Medical Institute. I became an HHMI Investigator 37 years ago in 1976, at a time when there were only about 50 Investigators. Today there are well over 300 and I am one of the two longest serving Investigators (the other being Richard Palmiter). The Institute's "Investigator" based support, rather than the "project" based support of conventional grant funding agencies has given me great freedom over the years to pursue my research goals in an unfettered and very privileged way. My research has also been supported throughout my career with grants from the NIH.

Along the way to receipt of the Nobel Prize I have been fortunate to receive a number of other awards for my research. Among others, these include: The Gairdner Foundation International Award (1988); Bristol-Myers Squibb Award for Distinguished Achievement in Cardiovascular Research (1992); Fred Conrad Koch Award - The Endocrine Society (2001); Jessie Stevenson Kovalenko Medal of the USA National Academy of Sciences (2001); Institut de France - Fondation Lefoulon-Delalande Grand Prix for Science (2003); The National Medal of Science (2007); The Shaw Prize in Life Science and Medicine (2007); The Albany Medical Center Prize in Medicine and Biomedical Research (2007); Research Achievement Award, American Heart Association (2009); BBVA Foundation Frontiers of Knowledge Award (2010).

I have been elected to membership in the National Academy of Sciences, the Institute of Medicine of the National Academy of Sciences, the American Academy of Arts and Sciences, The American Society of Clinical Investigation and The Association of American Physicians.

I have a strong family history of coronary artery disease, my father having died at age 63 of a myocardial infarction and my mother having suffered a myocardial infarction at age 57. Perhaps not surprisingly, I developed angina at age 50 and had quadruple bypass surgery in 1994. I have tried to minimize my risk factors as aggressively as I can with daily physical exercise, a vegetarian diet and appropriate medications.

I have five children with my first wife, Arna: David (b. 1964); Larry (now Noah Jordan)(b. 1965); Cheryl (b. 1968); Mara (b. 1971) and Joshua (b. 1977). At the time of this writing I have five grandchildren: (Maya, Jonah, Madeleine, Samantha and Ethan). I have been married to the former Lynn Tilley of Durham, North Carolina, since 1991.

Robert J. Lefkowitz with family and relatives after the Nobel Prize Award Ceremony at the Stockholm Concert Hall, 10 December 2012

My family has always been a great source of pride, love and support for me throughout my career. While there can be little doubt that my obsessive focus on my science somewhat limited the time I could spend with each of my children as they were growing up, I like to believe that my work ethic, passion and enthusiasm for my life's work provided a valuable role model for them. I started my family when I was quite young. My eldest child, David, was born when I was only 21 and my youngest, Joshua, was born when I was 34. In consequence, I have had the pleasure and privilege of relating to them for many years as adults. Having all of them, their spouses and significant others, two of my grandchildren and my wife Lynn with me during the festivities of Nobel Week was a joyous experience which we will always remember (Fig. 1).

1. Goldstein, J.L. and Brown, M.S., "A Golden Era of Nobel Laureates," Science 338:1033– 34, 2012.

From The Nobel Prizes 2012. Published on behalf of The Nobel Foundation by Science History Publications/USA, division Watson Publishing International LLC, Sagamore Beach, 2013

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.

Copyright © The Nobel Foundation 2012


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