- 2013 Nobel Prize in Physiology or Medicine
Intro
2013 Nobel Prize in Physiology or Medicine
American cell biologist at the University of California, Berkeley and former editor-in-chief of Proceedings of the National Academy of Sciences.
Schekman shared the 2013 Nobel Prize in Physiology or Medicine with James Rothman and Thomas Südhof for their ground-breaking work on cell membrane vesicle trafficking.
Education and Work Experience
1971-1975, Ph.D. in Biochemistry, Stanford University School of Medicine
1975-Present, Associate Professor, Assistant Professor, Professor of Department of Molecular and Cell Biology, UC Berkeley
1991-Present, Investigator of Howard Hughes Medical Institute
Honors and Awards
1992, Member of the United States National Academy of Sciences
2002, Albert Lasker Award in Basic Medical Research
2013, Foreign Member of the Royal Society (ForMemRS)
2013, Nobel Prize in Physiology or Medicine
Major Academic Achievements
Prof. Schekman began investigating networks of intracellular membranes associated with the vesicle transport of proteins in the yeast Saccharomyces cerevisiae at Berkeley. With the aid of others in his laboratory, he screened yeast for mutations that blocked the secretion of certain enzymes from cells. The work led to the discovery of membrane fusion regulator proteins encoded by SEC genes. In subsequent work Schekman and colleagues discovered that nearly two dozen genes play a role in vesicle transport. They characterized the function of each gene’s protein and elucidated the sequence in which the proteins act to effect transport. Schekman’s work also provided insight into mechanisms of vesicle budding and protein transport from the endoplasmic reticulum.
Detailed Introduction
My parents took an apartment in St. Paul and I was born a year later in 1948. We then moved to another small apartment on the north side of Minneapolis, probably so that my mother could be closer to her parents. My sister Wendy was born in 1950 and my earliest memories are of the two of us as infants in cribs in that small apartment. My sister and I occupied the one small bedroom and my parents slept in the living room, which doubled as the dining room. My aunt Mary married Marshall Kopman, and for two years they lived together in the second bedroom of my grandparent’s home, probably no more than a mile away from our family apartment.
My oldest cousin Michael was born around that time and I am told – but do not recall – that I walked by myself to my grandparent’s home to see him, much to the horror of my parents. In the first years of my life, it was clear that I was shorter than my peers so my mother, who was quite combative as a child, decided that I needed to learn self-protection. She claimed, but again I do not recall, that she tried to teach me to hold up my fists in a threatening gesture, but it may have backfired when I resorted to the use of the top of a garbage can when I fought with a local child.
We remained in that apartment for several years. My father then designed and had built a small three-bedroom home of less than 1000 sq. ft. a couple of miles away, but still in the north side area just a block away from a home my uncle Marshall had built for his family. During the six years we lived on Upton Avenue, the Schekman family grew with two more boys, my brothers Murry and Cary, and the Kopman family grew with two girls, Jodi and Robin. We were a close knit family with daily activities revolving around playtime with my cousins and friends from the neighborhood, school at the Jewish community center and John Hay Elementary School, and afternoon Hebrew lessons at a religious school just down the block from my grandparents. The regular highlights were Friday evening Sabbath dinners at my grandparents’ home, holidays at the synagogue, a conservative congregation that my grandparents joined. My fondest memories are of
drives to the countryside for an ice cream cone, occasional sleep overs on the porch at my grandparent’s home, but most of all, our annual trips to a cottage on a lake in Northern Minnesota, where my grandfather would take us fishing in a boat in pursuit of sunfish, walleye, crappie and the special treat of early morning trolling for northern pike. We lived and associated exclusively with other Jewish families and I was unaware of anti-Semitism until one day on my way to the Jewish Community Center, an older kid slugged me in the stomach when he learned where I was headed.
I have fewer memories of my father’s family. We would occasionally see his father and new wife, Evelyn, a dear woman who was sweet to the children and whom I grew to love in later years on a high school trip to Florida where she and my grandfather moved for retirement, and then later, after my grandfather died, on a visit to her sisters and their families in the New York area. My father’s younger brother Arthur lived with us briefly in the Upton Avenue house. We had more social occasions with Arthur and my aunt Carol and their children, Scott, Ronnie and Lorrie when they moved to Southern California in the 1960s. My father’s sister Helen moved to Columbus, Georgia and raised a family of five boys, whom I am sorry to say we almost never met for family events, other than one trip with my wife and son and my parents to a meeting in Atlanta in 1987.
I have only vague memories of any particular academic interest during those years in Minnesota. My father was a mechanical engineer working at General Mills. He was drafted after the war, but never left the country after boot camp and had attended the University of Minnesota on the GI bill. My mother worked part time in a department store during and after high school, but did not attend college. It was clear that the family valued learning and college for all the children was always an expectation, but any particular professional goals beyond college never entered my mind. I remember a casual interest in astronomy and I still have some electron microscope (EM) pictures of bacterial viruses that my father took which were used in particle size calibration at work. My casual reading was almost always of boy’s adventure stories.
I briefly belonged to a troop of cub scouts, but that sort of regimented activity had little appeal. Correspondingly, my most unpleasant memory of that time was of a military outfit that my parents bought for one of my birthdays.
In 1959, my father answered an ad for an engineering position in Southern California. On returning home from Los Angeles he announced that we would move at the end of the year to the great frontier of the Golden State. Neither of my parents had known anything other than Minnesota and yet my father somehow knew his future lay in the burgeoning computer industry of Southern California. My mother was traumatized by the move. She was emotionally dependent on her parents and could not bear the thought of such a geographic separation. For years after the move, she was inconsolable – when visits to Minnesota and/or of her parents to us in Southern California came to an end.
For me however, the move was a great adventure. We packed up the car and drove off in the deep cold of December 1959, traveling through snow flurries in the Midwest over the 2,000 miles to Los Angeles. The weather delayed our excursion and when we finally arrived on December 31, the reservation my father had made at a motel was cancelled and we had to scrounge for a single unheated room where the children bundled into one bed for warmth on New Year’s Eve. Still, Southern California was a dream with the network television studios just down the block from the motel we occupied for several weeks before moving to a rental home in Pacoima. I still recall with awe my first glimpse of the vast Pacific Ocean and the maze of freeways, not yet impassable with the choked traffic of today.
My father expected his children to be industrious and to work for extra money. I baby sat for the children of my parents’ friends, mowed lawns and held a paper route delivering news for the now defunct Los Angeles Examiner. My memories of school are not particularly strong. I remember the expectation of academic performance instilled by my parents, but until around 7th grade, I recall no particular interests or ability at the end of elementary and beginning of junior high school.
That began to change when I received a toy microscope and collected a jar of pond scum from a local creek. I recall with amazement the rich microbial life seen in a drop of that pond scum, even just from squinting into the plastic lens of that toy.
In the spring of 7th grade, I attended the school science fair and was captivated by the dozens of projects that the older students had assembled. The vivid memory of that simple event resonated somehow in a way that nothing else in my experience in school ever had. Here were simple but clearly individual efforts on display for recognition by fellow students, teachers and parents. In retrospect, this may have been the single event in my youth that fixed my path in science. In the following year, I spent countless hours looking into or projecting an image onto a sintered glass screen of paramecia and rotifers gliding or crawling across my field of view. I built a science project display based on my simple observations for my first entry in 8th grade, and although I recall no particular recognition for that work, I was nonetheless hooked, and the annual science fair became my one abiding academic passion through junior and high school.
Another revealing moment came that year when I recounted my excitement about these protozoa in a family conversation at the dinner table. My father, perhaps recalling his own experience with EM images of bacterial viruses, was dubious that anything of value could be seen in my toy microscope. At that point, I resolved to save and buy a student professional microscope using the money from my odd jobs.
Time went on, but I never seemed to reach my goal of $100 because my mother would borrow the money for family expenses. One Saturday I became so upset that after mowing a neighbor’s lawn, I bicycled to the police station and announced to the desk officer that I wanted to run away from home because my mother took my money and I couldn’t use it to buy a microscope. My father was called in and words were exchanged behind a closed door, the net effect of which was that we purchased my microscope at a pawnshop in Long Beach that afternoon! That microscope became my treasured possession for the rest of my years at school, but it was inevitably put aside as I went ahead to college and graduate school. Fortunately, my parents saved it and sent it up to my current home in the San Francisco Bay Area, where it languished in the dust for decades until the call from Stockholm at which point I realized it might be more interesting to visitors at the Nobel Museum. My old microscope is now on display, together with the tale of how it was acquired in a fit of childhood pique.
In the fall of 1966, I drove my motorcycle the 30 miles to UCLA where I took up residence in the student co-op dormitory along with my high school buddy Peter Wissner. The timing was perfect because just one week earlier my mother had given birth to my youngest brother, Tracey, and as hectic as college was, it would have been even more disruptive with a new baby back home. I threw myself into my studies and spent every waking hour in class or in study in a library. My courses were generally wonderful, particularly freshman chemistry then taught by a brilliant lecturer, Kenneth Trueblood, who received a standing ovation at the end of the term. I did well enough in that course to be admitted to an honors section for the third term, a course taught by Willard Libby, a Nobel Laureate who had won the prize for C14-radiodating of ancient materials.
Although I had started UCLA with an aspiration to attend medical school and become a pathologist, the experience of my first year changed my outlook completely. I was disappointed that most of my pre-medical classmates were more interested in getting high marks than in the science itself. In contrast, the one term experience in Konrad’s lab combined with Watson’s book convinced me that my future lay in experimental science, preferably as an academic in a research university. The summer after my first year in college I worked with my father at his computer data firm. He had hoped to enthuse me about writing computer code, but I found it boring and my mind turned to how to pursue a basic molecular biology research project when I returned to UCLA for my second year. I cooked up an idea to look at the effect of a mild organic solvent, DMSO, on the uptake of viral DNA by bacterial protoplasts. After a couple of disappointing approaches to various faculty members, I found another new assistant professor, Dan Ray, of the then Zoology Department who was willing to gamble on me.
Not many UCLA undergraduates worked in a research lab during that time, but I was happy to work alone well into the evening. Although my coursework was also going well, I increasingly began to feel that I was perhaps misplaced at UCLA, and that I might benefit by transfer to a school such as the University of Chicago that had a reputation for serious scholarship at the undergraduate level. James Watson himself had been an undergraduate at Chicago. Indeed, in the fall of 1967 I read Watson’s The Double Helix, which as much as his textbook had steeled my determination to live the life of a scholar in pursuit of a basic understanding of life. But as a simpler and much less expensive alternative, I learned of the University of California education abroad program and I applied and was accepted for a year at the University of Edinburgh.
The most enduring influence of my year in Edinburgh was my acquaintance with Leonard (“Len”) Kelly, a graduate student in the lab next door in the Molecular Biology Department. Len shared correspondence with his brother Regis (“Reg”) who was then a postdoctoral fellow in the laboratory of Arthur Kornberg, whom I knew to be the leading DNA enzymologist of this era. Reg had discovered that the DNA polymerase was capable of removing thymine dimers from UV-irradiated DNA in a repair-like replication reaction. The work was elegant and precise in a way that I had not experienced; I resolved to learn biochemistry from a master such as Kornberg.
My last year at UCLA brought emotional highs and lows. On the upside, I had the opportunity to meet Arthur Kornberg and to discuss my interest in the biochemistry of DNA replication and then in the spring of the next year, I was admitted to Kornberg’s department at Stanford for graduate school. But before that, just as I returned home from my summer at Harvard, I was greeted by my mother at the Los Angeles airport with the news that my sister Wendy had been diagnosed with acute leukemia and was given just months to live. Wendy’s rapid decline and our family’s anguish at her loss left a scar that is never far removed from my thoughts, even 45 years after her death. My mother was tortured by the loss of her one daughter and never fully recovered from the emotional blow.
My personal life at Stanford was also a mix of highs and lows. Although I was thrilled to be in such an exciting environment, my immaturity led to personal isolation. Most of my fellow PhD students came from elite private universities and I felt insecure as one of the few students from a public university. Kornberg once asked me why I hadn’t enrolled in a “better” school, to which I responded that it was the best my family could afford. But looking back at what I was able to accomplish then, and now after nearly 40 years at UC Berkeley, I can state with confidence that I had the best preparation and that our great public institutions, the University of California in particular, offer educational and real life experiences that are second to none.
After a period of personal decompression (I was placed in small lab room by myself as penance for my obnoxious behavior), I slowly developed great friendships that have lasted a lifetime. Costa Georgopoulis, a postdoctoral fellow in Dale Kaiser’s lab, took pity on me and invited me to join a group for a camping trip in a nearby state park. Costa deflated my ego by calling me a turkey, a term of endearment that seemed to fit and which stuck for some years. But my greatest friendship came when Bill Wickner joined the Kornberg lab in 1971. Although we were in a somewhat competitive situation in the first months of his time at Stanford, I will never forget the favor he did me when, after I made an aggressive remark, he lifted me from the floor by the front of my shirt and told me to settle down!
But Bill did more than that for me. After a few more months of intense and close cooperation, he could see that my personal life was going nowhere so he and his wife Hali conspired to find a suitable mate for me. After one failed effort at matchmaking, Bill had a call from a former girlfriend, Nancy Walls, whom he had dated in Boston. Nancy had completed her training as a nurse at Massachusetts General Hospital and decided to make a clean break to the West Coast. Feeling lonely herself, she called Bill at Stanford but learned that he had in the meantime married Hali, but he had a lab partner who needed distraction. I still remember our first date at a Greek restaurant in San Francisco and our first kiss goodnight. Nancy and I grew close quickly as these things happen when you are young. We moved into a small duplex home in Palo Alto and Nancy took a job as a nurse at Stanford Hospital. We would meet for a goodnight kiss while she was on a night shift and I worked into the wee hours of the morning in the lab. Nancy and I married in a ’70s style outdoor wedding in Huddart Park in Woodside, near the Stanford campus. Our years at Stanford were fulfilling in every way.
I grew emotionally secure in a loving relationship and even with the intense and sometime acrimonious battles I had with Kornberg, I left graduate school equipped with the intellectual and technical skills that made my subsequent career possible.
In my Nobel essay, I described in detail the contributions of my students and postdoctoral fellows that led to our dissection of the secretory pathway in yeast and the many molecular insights that developed from our discovery of the SEC genes and their protein products. I had the good fortune to attract some of the finest young scholars from around the world to join in that effort. But I owe at least as much to the many colleagues at Berkeley who taught me how to be a constructive citizen of science. Among them, I wish to offer a special tribute to Dan Koshland, Howard Schachman, Bruce and Giovanna Ames, Bob Tjian, Jeremy Thorner and Mike Botchan. They offered counsel and friendship that has enriched my life as a scholar and teacher.