《医学有声英语版》纪念10000帖版庆系列活动之三 ____ 征集历届诺贝尔医学
- 发布日期：2025-01-04 18:00 点击次数：153
- 累死了2002年Sydney Brenner, born January 13, 1927, South Africa. Nationality: British Address: The Molecular Sciences Institute, 2168 Shattuck Avenue, 2nd Floor, Berkeley, CA 94704, USA screen.width-333)this.width=screen.width-333" width=152 height=201 title="Click to view full Brenner_small.gif (152 X 201)" border=0 align=absmiddle>Academic Education and Appointments 1947 MSc University of Witwatersrand, South Africa 1951 MB, BCh, University of Witwatersrand, South Africa 1954 DPhil, Oxford University, UK 1979-86 Director, Medical Research Council Laboratory of Molecular Biology, Cambridge, England 1986-91 Director, Medical Research Council Molecular Genetics Unit, Cambridge, England 1996- President and Director of Science, The Molecular Sciences Institute, La Jolla and Berkeley 2000- Distinguished Research Professor, The Salk Institute, La Jolla, USA Selected Honours and Awards 1965 Fellow of the Royal Society (FRS) 1971 Albert Lasker Medical Research Award 1974 Royal Medal, Royal Society of London 1976 Honorary DSc, University of Chicago 1978 Gairdner Foundation International Award, Canada 1980 Krebs Medal, Federation of European Biochemical Societies 1981 Ciba Medal, Biochemical Society 1985 Foreign Member of Real Academia de Ciencias, Spain 1986 Rosenstiel Award, Brandeis University, USA 1987 Prix Louis Jeantet de Medecine, Switzerland 1987 Harvey Prize, Technion - Israel Institute of Technology 1988 Waterford Bio-Medical Science Award, The Research Institute of Scripps Clinic 1988 External Scientific Member of the Max-Planck Society 1989 Honorary Fellow of the Indian Academy of Sciences 1989 Honorary Member of the Chinese Society of Genetics, Taiwan 1990 Kyoto Prize 1991 Gairdner Foundation International Award, Canada 1992 King Faisal International Prize for Science, King Faisal Foundation 1992 Associe Etranger, Académie des Sciences, Paris, France 2000 Albert Lasker Award for Special Achievement in Medical Science 2001 Novartis Drew Award In Biomedical ResearchLetter to Max Perutz>2002年H. Robert Horvitz, born May 8, 1947. Nationality: American Address: Department of Biology, Room 68-425, Massachusetts Institute of Technology,Cambridge, MA 02139, USA screen.width-333)this.width=screen.width-333" width=106 height=106 title="Click to view full horvitz.gif (106 X 106)" border=0 align=absmiddle>Academic Education and Appointments 1972 M.A. Biology, Harvard University 1974 Ph.D. Biology, Harvard University 1978 Assistant Professor of Biology, MIT Cambridge, MA 1981 Associate Professor of Biology, MIT Cambridge, MA 1986 Professor of Biology, MIT Cambridge, MA 1988 Investigator, Howard Hughes Medical Institute,Massachusetts Institute of Technology Selected Honours and Awards 1986 Spencer Award in Neurobiology 1988 U.S. Steel Foundation Award in Molecular Biology 1991 U.S. National Academy of Sciences, Member 1993 V.D. Mattia Award (Roche Institute of Molecular Biology) 1994 Hans Sigrist Award 1995 Charles A. Dana Award 1996 Ciba-Drew Award for Biomedical Science 1998 Rosenstiel Award 1998 Passano Award for the Advancement of Medical Science 1998 General Motors Cancer Research Foundation, Alfred P. Solan Jr. Prize 1999 Gairdner Foundation International Award 2000 Paul Ehrlich and Ludwig Darmstaedter Prize 2000 Segerfalk Award 2000 March of Dimes Prize in Developmental Biology 2000 Louisa Gross Horwitz Prize for Biology or Biochemistry 2000 Charles-Leopold Mayer Prize (French Academy of Sciences) 2001 Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience 2001 Genetics Society of America MedalAutobiography>2002年John E. Sulston, born March 27, 1942. Nationality: British Address: The Wellcome Trust Sanger Institute,Campus, Hinxton, Cambridge CB10 1SA, UK screen.width-333)this.width=screen.width-333" width=100 height=140 title="Click to view full sulston.jpg (100 X 140)" border=0 align=absmiddle>Academic Education and Appointments 1963 B.A. University of Cambridge, UK 1966 Ph.D. University of Cambridge, UK 1966-69 Postdoctoral fellow at the Salk Institute for Biological Studies, San Diego, CA 1969 Staff Scientist MRC Laboratory of Molecular Biology 1992-00 Director of the Sanger Centre, Cambridge, UK Selected Honours and Awards 1986 Elected to the Royal Society 1986 W. Alden Spencer Award 1991 Gairdner Foundation International Award 1996 Darwin Medal of the Royal Society 1998 Rosenstiel Award 2000 Pfizer Prize for Innovative Science 2000 George W Beadle Medal 2000 Sir Frederick Gowland Hopkins Medal 2001 Knight Bachelor in New Year's Honours list 2001 The Edinburgh Medal 2001 Prince of Asturias Award (Spain)Autobiography>1999 Günter Blobel (USA, Germany, *1936-05-21) for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell USA Rockefeller University New York, NY, USA; Howard Hughes Medical Institute AutobiographyIn 1936, when I was born in the small Silesian village of Waltersdorf in the county of Sprottau in the then eastern part of Germany, now part of Poland, the fine structure of the cell was still an enigma. After 300 years of staring through light microscopes, essentially all that biologists had learned was that the cell was delimited by a plasma membrane and contained a nucleus. Staining procedures had revealed other distinct territories in the cytoplasm and in the nucleus, but their fine structure remained unknown. A dramatic revolution occurred in 1945, when Keith Porter, Ernest Fullam and Albert Claude at the then Rockefeller Institute for Medical Research in New York City introduced the electron microscope to look at cells. The first structure they saw was a lace-like network in the cytoplasm that they termed the endoplasmic reticulum. This discovery formed the foundation for my future scientific career.1945 was also a turning point in my life. Until then my childhood was a perfect 19th century idyll. In the cold and snow-rich Silesian winters there were hour-long rides on Sundays in horse-drawn sleighs to my maternal grandparent's farm to have lunch and to spend the afternoon. The house was a magnificent 18th century manor house in the nearby Altgabel with a great hall that was decorated with hunting trophies. In the summer, of course, horse-drawn landauers were used as means of transportation. The way to school was a long one. We went there on foot and as a pack, usually consisting of one or two of my seven brothers and sisters and of children from neighboring houses.At the end of January 1945, we had to flee from the advancing Russian Red Army. My father, a veterinarian stayed behind for a few more days and left only hours before the Red Army moved in. My fourteen year-old brother, Reiner, drove my mother, my youngest brother, an older brother, the two younger sisters and me in a small automobile to relatives west of Dresden in Saxony. On the way there we drove through Dresden. We entered the city from the eastern hills. Its many spires and the magnificent cupola of the Frauenkirche (die Steinerne Glocke, the Stone Bell) were a magnificent sight even for the untrained eye of a child. Driving through Dresden, I still remember the many palaces, happily decorated with cherubs and other symbols of the baroque era. The city made an indelible impression on me. Only a few days, later, on February 13, 1945, we saw from a distance of about 30 kilometers a fire-lit, red night sky reflecting the raging firestorm that destroyed this great jewel of a city in one of the most catastrophic bombing attacks of World War II. It was a very sad and unforgettable day for me.The months before and after the end of World War II were chaotic and miserable. None of my relatives had enough space to accommodate our large family leaving us divided among several relatives in different villages. There was no communication and little food. On September 9, 1945, we learned of the death of my beautiful oldest sister Ruth who, at age 19, was killed in an air raid on a train she was travelling in on April 10, 1945. She was buried in a mass grave near the site of the attack in Schwandorf, Bavaria. Ruth was born when my mother was just 20. The two had a sisterly relationship. My mother grieved over Ruth's death until the end of her own life.Fortunately, things took a turn for the better, when my father was able to continue his veterinarian practice in the charming medieval Saxon town of Freiberg. Most members of our family were reunited there by 1947. We lived in a nice villa surrounded by a large garden on the edge of town. My way to school was along the old medieval city wall. For only 40,000 inhabitants, Freiberg had a rich cultural life with a 175 year old theater. Most impressive were the musical performances in the magnificent gothic cathedral, the Dom, with the splendid great Silbermann organ. Each week Bach cantatas were performed. The great choral works of Bach, Mozart and Haydn were regularly performed and at the highest artistic level at the major religious holidays. I even participated in singing in the cantus firmus of Bach's Matthäus Passion. So, it was almost like a 19th century idyll again, this time in a small medieval town instead of a country village.However, there was now the ever more oppressive regime of East Germany to deal with on a daily basis. When I graduated from high school in 1954 I was not allowed to continue my education at a university because I was considered a member of the "capitalist" classes. Fortunately, at that time, i.e., before the Berlin Wall, it was possible to escape and to travel freely to West Germany. So, on August 28, Goethe's birthday, I left Freiberg for Frankfurt on the Main in West Germany. The train left in the morning and in the afternoon it passed Weimar, where Goethe spent most of his life, and then Eisenach, where Bach was born and in the evening it arrived in Frankfurt, Goethe's birthplace.I studied medicine, beginning in Frankfurt and then in Kiel, München and Tübingen, graduating in 1960 from the University of Tübingen. Although I completed two years of internship in various small hospitals, I decided against continuing my medical training. I was much more fascinated by the unsolved problems of medicine than by practicing it. Fortunately, my oldest brother Hans had a similar experience in his field of study, veterinary medicine. He had obtained the prestigious Fulbright Fellowship to study in the U.S., continued his training there in microbiology and rapidly achieved the rank of full professor at the University of Wisconsin in Madison. He was extremely sympathetic to my dilemma and helped me to secure a graduate fellowship to study either with Khorana or with Van R. Potter. So, in 1962, I sailed to Montreal on a German steel freighter, and from there drove to Madison to arrive on a beautiful late day in May. Potter was a marvellous mentor, witty, energetic and stimulating. I graduated in November 1966, and decided to join George Palade's Laboratory of Cell Biology at the Rockefeller University (formerly the Rockefeller Institute). The revolution that began there in 1945, and that led to the discovery of all the major structures of the cell continued in the realm of relating cellular structures to specific cellular functions. My arrival there coincided with the end of this second phase and the exciting beginnings of a third phase, the molecular analysis of cellular functions (see below). I was fortunate enough in helping to initiate this third phase of analysis which is still in full swing.George Palade has been my most influential mentor, a good friend and a wonderful colleague. He taught me how to conceptualize a collection of disparate facts, to formulate working hypotheses and to design experiments to test these hypotheses. I am greatly indebted to him.In New York I married Laura Maioglio. Laura studied art history and, at her father's death, took over Barbetta Restaurant founded by her father in 1906. Laura has introduced me to many artistic pleasures that I had not experienced before. She greatly encouraged me in my work and never complained about the many hours I spent in the laboratory.In 1994, I founded Friends of Dresden, Inc., a charitable organization, with the goal to raise funds in the U.S. to help rebuild the Frauenkirche in Dresden. The rebuilding of many of the historic monuments of Dresden is one of the most exciting consequences of German reunification and the liberation from communism. It is a childhood dream come true.It was one of the great pleasures of my life to donate the entire sum of the Nobel Prize, in memory of my sister Ruth Blobel, to the restoration of Dresden, to the rebuilding of the Frauenkirche and the building of a new synagogue. This donation also serves to express my gratitude to my fellow Saxons. They received us with open arms when we had to flee Silesia. I spent a wonderful period of my life there and they gave me a thorough and valuable education. A few thousand dollars will also be donated for the restoration of an old baroque church in Fubine/Piemonte/ltaly, the home town of my wife's father, Sebastanio Maioglio. We have spent many happy summers there in the parental home of my wife. screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full blobel.jpg (162 X 227)" border=0 align=absmiddle>1997 Stanley B. Prusiner (USA, *1942-05-28) for his discovery of Prions - a new biological principle of infection USA University of California School of Medicine San Francisco, CA, USA AutobiographyMy history is not atypical of many Americans: born in the midwest, educated in the East, and now living in the West. My early years were shared between Des Moines, Iowa and Cincinnati, Ohio. Shortly after I was born on May 28, 1942 in Des Moines, my father, Lawrence, was drafted into the United States Navy. I was named for my father's younger brother who died of Hodgkin's disease at the age of 24. We moved to Boston briefly where my father enrolled in Naval officer training school before being sent to the south Pacific. He served as a communications officer for the remainder of World War II on an island called Eniwetok where the first hydrogen bomb was detonated a decade later.During my father's absence, my mother, Miriam, and I lived in Cincinnati where her mother, Mollie Spigel, also lived. Prior to moving to Cincinnati, Mollie had lived in Norfolk, Virginia, where she raised three children after her husband Benjamin was killed at age 50 in a traffic accident. Besides many special memories of my maternal grandmother, I have many fond reminiscences of my paternal grandfather, Ben, who emigrated to the United States in 1896 as a young boy from Moscow. He grew up in Sioux City, Iowa, as did my father with many other Russian Jews. Shortly after the end of World War II, we returned to Des Moines where I attended primary school and my brother, Paul, was born. In 1952, we moved back to Cincinnati with the hope that my father would be able to find a much better job as an architect. In Cincinnati, he practiced architecture for the next 25 years, which enabled him to provide a very comfortable home for his family.During my time at Walnut Hills High School, I studied Latin for five years, which was to help me immensely later in the writing of scientific papers. But I found high school rather uninteresting and was most fortunate to be accepted by the University of Pennsylvania where I majored in Chemistry.The intellectual environment of the University of Pennsylvania was extraordinary - there were so many internationally renowned scholars who were invariably receptive to the intrusions of undergraduate students even before the days of student evaluations of the faculty. The small size of the undergraduate student body undoubtedly contributed to the accessibility of the faculty. Besides numerous science courses, I had the opportunity to study philosophy, the history of architecture, economics, and Russian history in courses taught by extraordinarily knowledgeable professors. Although I was among the smallest of the heavyweight crew team members and thus had no chance of rowing in the varsity boat, I greatly enjoyed the many hours that I spent at this wonderful sport.During the summer of 1963 between my junior and senior years, I began a research project on hypothermia in the Department of Surgery with Sidney Wolfson. I quickly became fascinated by the project and continued working on it throughout my senior year. I decided to remain at Penn for Medical School largely because of the wonderful experience of doing research with Sidney Wolfson. During the second year of medical school, I decided to ask Britton Chance if he would allow me to study the surface fluorescence of brown adipose tissue in Syrian golden hamsters as they arose from hibernation. Chance had reported that the surface fluorescence of other organs reflected the oxidation-reduction state of those tissues. As anticipated, large changes in the fluorescence of brown fat were found during non-shivering thermogenesis.My research on brown fat allowed me to spend much of the fourth year of medical school at the Wenner-Gren Institute in Stockholm working with Olov Lindberg on the metabolism of isolated brown adipocytes. This was an exciting time and I began to consider seriously a career in biomedical research. Early in 1968, I returned to Philadelphia to complete my medical studies and to contemplate my options. The previous spring, I had been given a position at the NIH once I completed an internship in medicine. It was the height of the Vietnam war with 500,000 young Americans trying to control the spread of Communism in southeast Asia. But I was facing an internship at the University of California San Francisco (UCSF) that would require me to work every other night for an entire year, a prospect about which I was not enthusiastic. The privilege of serving in the US Public Health Service at the NIH clearly outweighed the unpleasant prospects of an internship. Although the workload was awesome, I managed to survive because San Francisco was such a nice place to live. During that year, I met my wife, Sandy Turk, who was teaching mathematics to high school students.At the NIH, I worked in Earl Stadtman's laboratory where I studied glutaminases in E. coli. My three years at the NIH were critical in my scientific education. I learned an immense amount about the research process: developing assays, purifying macromolecules, documenting a discovery by many approaches, and writing clear manuscripts describing what is known and what remains to be investigated. As the end of my time at the NIH began to near, I examined postdoctoral fellowships in neurobiology but decided a residency in Neurology was a better route to developing a rewarding career in research. The residency offered me an opportunity to learn about both the normal and abnormal nervous system.In July 1972, I began a residency at the University of California San Francisco in the Department of Neurology. Two months later, I admitted a female patient who was exhibiting progressive loss of memory and difficulty performing some routine tasks. I was surprised to learn that she was dying of a "slow virus" infection called Creutzfeldt-Jakob disease (CJD) which evoked no response from the body's defenses. Next, I learned that scientists were unsure if a virus was really the cause of CJD since the causative infectious agent had some unusual properties. The amazing properties of the presumed causative "slow virus" captivated my imagination and I began to think that defining the molecular structure of this elusive agent might be a wonderful research project. The more that I read about CJD and the seemingly related diseases - kuru of the Fore people of New Guinea and scrapie of sheep - the more captivated I became.Over the next two years I completed an abbreviated residency while reading every paper that I could find about slow virus diseases. In time, I developed a passion for working on these disorders. As I plotted out a course of action, the task became more and more daunting. The tedious, slow, and very expensive assays in mice for the scrapie agent had restricted progress and I had no clever idea about how to circumvent the problem. I did think that after working with the scrapie agent for some time that I might eventually be able to develop such an assay.Since both Sandy and I liked living in San Francisco, I accepted the offer of an assistant professor position from Robert Fishman, the Chair of Neurology, and began to set up a laboratory to study scrapie in July 1974. Although many people cautioned me about the high risk of studies on scrapie due to the assay problems, such warnings did not dull my enthusiasm. To gain a base of research support from the NIH, I initially wrote grant proposals on glutamate metabolism in the choroid plexus. Such proposals were dull but were readily funded because I had worked on glutaminases earlier. Eventually, I managed to gain modest NIH support for my scrapie studies but this was not without considerable difficulty. To rebut the disapproval of my first NIH application on scrapie, I set up a collaboration with William Hadlow and Carl Eklund who were working at the Rocky Mountain Laboratory in Hamilton, Montana. They taught me an immense amount about scrapie and helped me initiate studies on the sedimentation behavior of the scrapie agent.I had anticipated that the purified scrapie agent would turn out to be a small virus and was puzzled when the data kept telling me that our preparations contained protein but not nucleic acid. About this time, I was informed by the Howard Hughes Medical Institute (HHMI) that they would not renew their support and by UCSF that I would not be promoted to tenure. When everything seemed to be going wrong, including the conclusions of my research studies, it was the unwavering, enthusiastic support of a few of my closest colleagues that carried me through this very trying and difficult period. Fortunately, the tenure decision was reversed and I was able to continue my work. Although my work was never supported by HHMI again, I was extremely fortunate to receive much larger funding from the R. J. Reynolds Company through a program administered by Fred Seitz and Macyln McCarty and shortly thereafter from the Sherman Fairchild Foundation under the direction of Walter Burke. While the vast majority of my funding always came from the NIH, these private sources were crucial in providing funds for the infrastructure which was the thousands of mice and hamsters that were mandatory.As the data for a protein and the absence of a nucleic acid in the scrapie agent accumulated, I grew more confident that my findings were not artifacts and decided to summarize that work in an article that was eventually published in the spring of 1982. Publication of this manuscript, in which I introduced the term "prion", set off a firestorm. Virologists were generally incredulous and some investigators working on scrapie and CJD were irate. The term prion derived from protein and infectious provided a challenge to find the nucleic acid of the putative "scrapie virus." Should such a nucleic acid be found, then the word prion would disappear! Despite the strong convictions of many, no nucleic acid was found; in fact, it is probably fair to state that Detlev Riesner and I looked more vigorously for the nucleic acid than anyone else.While it is quite reasonable for scientists to be skeptical of new ideas that do not fit within the accepted realm of scientific knowledge, the best science often emerges from situations where results carefully obtained do not fit within the accepted paradigms. At times the press became involved since the media provided the naysayers with a means to vent their frustration at not being able to find the cherished nucleic acid that they were so sure must exist. Since the press was usually unable to understand the scientific arguments and they are usually keen to write about any controversy, the personal attacks of the naysayers at times became very vicious. While such scorn caused Sandy considerable distress, she and my two daughters, Helen and Leah, provided a loving and warm respite from the torrent of criticism that the prion hypothesis engendered. During the winter of 1983, I herniated a disc in my lumbar spine while skiing and this slowed the pace of my work for much of the year. After a laminectomy, I began swimming regularly, which brought relaxation and a much needed quiet time to my life.Just prior to my back problem, the protein of the prion was found in my laboratory and the following year, a portion of the amino acid sequence was determined by Leroy Hood. With that knowledge, molecular biological studies of the prions ensued and an explosion of new information followed. I collaborated with Charles Weissmann on the molecular cloning of the gene encoding the prion protein (PrP) and with George Carlson and David Kingsbury on linking the PrP gene to the control of scrapie incubation time in mice. About the same time, we succeeded in producing antibodies that provided an extremely valuable tool that allowed us to discover the normal form of PrP. In a very important series of studies, the antibodies were used by Stephen DeArmond to study the pathogenesis of prion disease in transgenic mice. Steve brought the much needed talents of an outstanding neuropathologist to these studies. As more data accumulated, an expanding edifice in support of the prion concept was constructed. Ruth Gabizon dispersed prions into liposomes and purified scrapie infectivity on columns with PrP antibodies. Karen Hsiao discovered a mutation in the PrP gene that caused familial disease and reproduced the disease in transgenic mice while Michael Scott produced transgenic mice abrogating the prion species barrier and later artificial prions from chimeric PrP transgenes. Indeed, no experimental findings that might overturn the prion concept were reported from any laboratory. By the early 1990s, the existence of prions was coming to be accepted in many quarters of the scientific community, but the mechanism by which normal PrP was converted into the disease-causing form was still obscure. When Fred Cohen and I began to collaborate on PrP structural studies, I was again extremely fortunate. Fred brought an extraordinary set of skills in protein chemistry and computational biology to investigations of PrP structures.As prions gained wider acceptance among scientists, I received many scientific prizes. The first major recognition of my work was accorded by neurologists with many other awards coming soon thereafter. But the most rewarding aspect of my work has been the numerous wonderful friends that I have made during an extensive series of collaborative studies. It has been a special privilege to work with so many talented scientists including numerous postdoctoral fellows and technical associates who have taught me so much. Besides the many collaborators who have contributed their scientific skills to advancing the study of prions, I have had many colleagues who have contributed indirectly to my work by being supportive of the special needs that such a project has demanded. screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full prusiner.gif (140 X 198)" border=0 align=absmiddle>1983 B. McClintock (USA) "for her discovery of mobile genetic elements"USA Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA AutobiographyIn the fall of 1921 I attended the only course in genetics open to undergraduate students at Cornell University. It was conducted by C. B. Hutchison, then a professor in the Department of Plant Breeding, College of Agriculture, who soon left Cornell to become Chancellor of the University of California at Davis, California. Relatively few students took this course and most of them were interested in pursuing agriculture as a profession. Genetics as a discipline had not yet received general acceptance. Only twenty-one years had passed since the rediscovery of Mendel's principles of heredity. Genetic experiments, guided by these principles, expanded rapidly in the years between 1900 and 1921. The results of these studies provided a solid conceptual framework into which subsequent results could be fitted. Nevertheless, there was reluctance on the part of some professional biologists to accept the revolutionary concepts that were surfacing. This reluctance was soon dispelled as the logic underlying genetic investigations became increasingly evident.When the undergraduate genetics course was completed in January 1922, I received a telephone call from Dr. Hutchison. He must have sensed my intense interest in the content of his course because the purpose of his call was to invite me to participate in the only other genetics course given at Cornell. It was scheduled for graduate students. His invitation was accepted with pleasure and great anticipations. Obviously, this telephone call cast the die for my future. I remained with genetics thereafter.At the time I was taking the undergraduate genetics course, I was enrolled in a cytology course given by Lester W. Sharp of the Department of Botany. His interests focused on the structure of chromosomes and their behaviors at mitosis and meiosis. Chromosomes then became a source of fascination as they were known to be the bearers of "heritable factors". By the time of graduation, I had no doubts about the direction I wished to follow for an advanced degree. It would involve chromosomes and their genetic content and expressions, in short, cytogenetics. This field had just begun to reveal its potentials. I have pursued it ever since and with as much pleasure over the years as I had experienced in my undergraduate days.After completing requirements for the Ph.D. degree in the spring of 1927, I remained at Cornell to initiate studies aimed at associating each of the ten chromosomes comprising the maize complement with the genes each carries. With the participation of others, particularly that of Dr. Charles R. Burnham, this task was finally accomplished. In the meantime, however, a sequence of events occurred of great significance to me. It began with the appearance in the fall of 1927 of George W. Beadle (a Nobel Laureate) at the Department of Plant Breeding to start studies for his Ph.D. degree with Professor Rollins A. Emerson. Emerson was an eminent geneticist whose conduct of the affairs of graduate students was notably successful, thus attracting many of the brightest minds. In the following fall, Marcus M. Rhoades arrived at the Department of Plant Breeding to continue his graduate studies for a Ph.D. degree, also with Professor Emerson. Rhoades had taken a Masters degree at the California Institute of Technology and was well versed in the newest findings of members of the Morgan group working with Drosophila. Both Beadle and Rhoades recognized the need and the significance of exploring the relation between chromosomes and genes as well as other aspects of cytogenetics. The initial association of the three of us, followed subsequently by inclusion of any interested graduate student, formed a close-knit group eager to discuss all phases of genetics, including those being revealed or suggested by our own efforts. The group was self-sustaining in all ways. For each of us this was an extraordinary period. Credit for its success rests with Professor Emerson who quietly ignored some of our seemingly strange behaviors.Over the years, members of this group have retained the warm personal relationship that our early association generated. The communal experience profoundly affected each one of us.The events recounted above were, by far, the most influential in directing my scientific life.Born Hartford, Connecticut, U.S.A, 16 June, 1902 Secondary Education Erasmus Hall High School, Brooklyn, New York. Earned Degrees B.S. Cornell University, Ithaca, New York, 1923 M.A. Cornell University, Ithaca, New York, 1925 Ph.D. Cornell University, Ithaca, New York, 1927 Positions held Instructor in botany, Cornell University, 1927-1931 Fellow, National Research Council, 1931-1933 Fellow, Guggenheim Foundation, 1933-1934 Research Associate, Cornell University, 1934-1936 Assistant Professor, University of Missouri, Columbia, Missouri, 1936-1941 Staff Member, Carnegie Institution of Washington, Cold Spring Harbor, New York, 1942-1967 Distinguished Service Member, Carnegie Institution of Washington, Cold Spring Harbor, New York, 1967 to Present Visiting Professor, California Institute of Technology, 1954 Consultant, Agricultural Science Program, The Rockefeller Foundation, 1963-1969 Andrew D. White Professor-at-Large, Cornell University, 1965-1974 Honorary Doctor of Science University of Rochester, 1947 Western College for Women, 1949 Smith College, 1957 University of Missouri, 1968 Williams College, 1972 The Rockefeller University, 1979 Harvard University, 1979 Yale University, 1982 University of Cambridge, 1982 Bard College, 1983 State University of New York, 1983 New York University, 1983 Honorary Doctor of Humane Letters Georgetown University, 1981 Awards Achievement Award, Association of University Women, 1947 Merit Award, Botanical Society of America, 1957 Kimber Genetics Award, National Academy of Sciences, 1967 National Medal of Science, 1970 Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research, 1978 The Louis and Bert Freedman Foundation Award for Research in Biochemistry, 1978 Salute from the Genetics Society of America, August 18, 1980 Thomas Hunt Morgan Medal, Genetics Society of America, June, 1981 Honorary Member, The Society for Developmental Biology, June, 1981 Wolf Prize in Medicine, 1981 Albert Lasker Basic Medical Research Award, 1981 MacArthur Prize Fellow Laureate, 1981 Honorary Member, The Genetical Society, Great Britain, April, 1982 Louisa Gross Horwitz Prize for Biology or Biochemistry, 1982 Charles Leopold Mayer Prize, Académie des Sciences, Institut de France, 1982 screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full 1983.jpg (162 X 227)" border=0 align=absmiddle>1987 S. Tonegawa (Japan) Japan Massachusetts Institute of Technology (MIT) Cambridge, MA, USA b. 1939 AutobiographyI was born in Nagoya, Japan on September 6th, 1939, the second of three sons. I have also a younger sister. My father was an engineer working for a textile company that had several factories scattered in rural towns in the southern part of Japan. The company policy made it necessary for my father to move from one factory to another every few years. I and my brothers and sister spent most of our childhood in these small provincial towns, enjoying the space and freedom of the countryside. As my elder brother and I reached adolescence, however, my parents decided to send us to Tokyo so that we could receive a better education.I commuted to the prestigious Hibiya high school from my Uncle's home in Tokyo. During the high school years I developed an interest in chemistry, so upon graduation, I chose to take an entrance examination for the Department of Chemistry of the University of Kyoto, the old capital of Japan. After having failed once, I was admitted to this University in 1959. This happened to be one year before the first ten-year term of the defence treaty between Japan and the United States expired and the governments of both countries were preparing for a second ten-year term.The nation was deeply divided between the pragmatic pro-American conservatives and the idealistic anti-military leftists. Being the home of the most radical leftist student groups, classes at Kyoto University were often cancelled due to frequent political discussions and demonstrations on the streets. I was only a passive participant, withdrawn from the turmoil, but could not help having a feeling of defeat shared with many of my classmates when the treaty was finally extended for the next ten-year term. I believe that this experience might have been a major factor in making me give up the original goal of becoming a chemical engineer to pursue the academic life.I became fascinated by the then blossoming science of molecular biology when in my senior year I happened to read the papers by François Jacob and Jacques Monod on the operon theory. I decided to pursue graduate study in molecular biology and was accepted by Professor Itaru Watanabe's laboratory at the Institute for Virus Research at the University of Kyoto, one of a few laboratories in Japan where U.S.-trained molecular biologists were actively engaged in research. However, only two months after I started my work in his laboratory, Professor Watanabe called me into his office and suggested that I carry out my graduate study in the United States. He explained how inadequate the graduate training programs in molecular biology laboratories were in Japan, including his own, and offered to help in my application to some major universities in the United States, if I would seriously consider studying abroad.At that time, it was a common career development for a Japanese molecular biologist to go to the United States for a few years of postdoctoral study after obtaining the Ph.D. in Japan. I already had a vague wish to follow that pattern. Professor Watanabe's advice to enroll in an American graduate school therefore came to me as a bit of a surprise, but I was excited by the idea and accepted his help immediately. I cannot thank Professor Watanabe enough for this critical suggestion in the early phase of my scientific career.With the additional help of Dr. Takashi Yura, then an assistant professor in Watanabe's laboratory, I was admitted to the graduate school of the Department of Biology of the University of California at San Diego that had recently been established by Professor David Bonner in La Jolla, the beautiful southern Californian town near the Mexican border.At UCDS I studied in the laboratory of Professor Masaki Hayashi, carrying out a thesis project on the transcriptional control of phage lambda and received my Ph.D. in molecular biology in 1978. I remained in Professor Hayashi's laboratory as a postdoctoral fellow working on the morphogenesis of a phage, ØX174, until early 1979. Then I moved, also as a postdoctoral fellow, across the street to the laboratory of Dr. Renato Dulbecco at the Salk Institute.Like many others, I believed that the golden age of prokaryotic molecular biology was coming to an end and that the great excitement would be in higher organisms. However, the complexity of high organisms was baffling and the necessary tools seemed hopelessly insufficient. Small tumor viruses like polyoma and simian virus 40, the biological material primarily dealt with in Dulbecco's laboratory, seemed to offer a bridge for the gap between prokaryotes and eukaryotes. Indeed Dulbecco's laboratory was filled with first-class postdoctoral fellows from around the world, who were trained in prokaryotic molecular biology and who came there intending to expand their research into eukaryotic molecular biology.My project was to define the transcripts of SV40 during lytic infection and in transformed cells. Since this was the pre-restriction enzyme and pre-recombinant DNA age, the information I could obtain was very limited. However, being a member of the best laboratory in the field I glimpsed the excitement of the cutting edge of scientific research. Furthermore, I very much enjoyed the free and stimulating atmosphere of the laboratory. Unfortunately, as an awardee of a Fulbright travel grant, my U.S. visa was to expire by the end of 1970 and I had to leave the country for at least two years before I was eligible for another U.S. visa.I had two or three job possibilities outside of the United States, but none were particularly interesting. In the autumn of 1970, only a few months before my visa was to expire I received a letter from Renato Dulbecco who was travelling in Europe. Renato mentioned the newly established Basel Institute for Immunology in Basel, Switzerland, and suggested that the time might be ripe for a molecular biologist to tackle immunological problems. I had very little knowledge of immunology, but decided to take Dr. Dulbecco's advice and sent an application letter to the Director of the Institute, Professor Niels Kaj Jerne, who offered me a two-year contract.In the winter of 1971, I thus found myself surrounded by immunologists in this small town located in the middle of Europe. I must admit that the first year in the Institute was not easy for me. I had a continuing interest in work on SV40, but I was also keenly aware that I would not be able to take much advantage of the circumstances if I isolated myself by pursuing that subject. I therefore decided to study immunology in the hope of finding an interesting project.An immunologist, Dr. Ita Askonas, and a geneticist, Charles Steinberg, were very helpful to me on my entering the new field. By the end of 1971, I was introduced to the great debate on the genetic origins of antibody diversity. I felt from the beginning that I could contribute to resolving this question by applying the recently invented techniques of molecular biology, namely, restriction enzymes and recombinant DNA. Initially I worked only with my skillful technicians, Monica Shöld and Rita Schuller, but was soon joined by Drs. Nobumichi Hozumi, Minoru Hirama, and Christine Brack. Later, as my research group expanded, I had the good fortune to work with many capable postdoctoral fellows and devoted technical assistants. In addition, Charles Steinberg was a very important collaborator and consultant, particularly in the initial phase of the research.Looking back, the research progressed with amazing speed from 1974 to 1981, the year I left Basel. We all worked hard and had had a great deal of fun. Our work resolved the long held debate on the genetic origin of antibody diversity. It turned out that this diversity is generated by somatic recombination of the inherited gene segments and by somatic mutation. To our very good fortune, Director Niels Jerne was quick to understand the importance of our approach and became a staunch supporter of the research in its early phase.In the beginning of the 1980's I began to feel that the great mystery of antibody diversity had been solved, at least in its outlines. I thought that it might be good to change my environment to launch into a new project. I also recalled that I had initially come to Switzwerland with the intention of staying for two years and then returning to the United States. Fortunately, I received a few offers from the United States and decided in 1981 to take a professorship at the Center for Cancer Research at M.I.T. Professor Salvador E. Luria, Director of the Cancer Center, was extremely helpful, not only in bringing me to M.I.T., but also in providing me with a beautiful laboratory.The research projects on which I had decided concerned two major problems. One was to investigate the role of somatic rearrangement in the activation of the rearranged antibody gene, and the second was to extend the research in Basel to "the other half" of the immune system, namely, to the antigen receptor of T cells. Fortunately, we could contribute to the understanding of both problems by discovering a tissue-specific transcriptional enhancer in the immunoglobulin heavy chain gene and by identifying, cloning, and sequencing genes coding for the polypeptide subunits of the T cell receptor. A particularly intriguing development made during the latter study was the identification of a gene that led to the discovery of a new T cell receptor, gamma delta. While the function of the T cells bearing this receptor is currently unknown, data accumulated during the past year in our laboratory as well as many other laboratories suggest that these T cells may be involved in an entirely new aspect of immunity.When I look back on my scientific career to-date, I am amazed at my good fortune. At every major turn, I met scientists who were not only at the very top in their own fields, but who also gave me insightful advice and generous help. I am most grateful to Professors Itaru Watanabe, Renato Dulbecco, Niels Kaj Jerne, Charles Steinberg, and Salvadore Luria. I also wish to extend my unending gratitude to many colleagues and technical assistants.My parents were firm believers that education is the best asset that parents can give to their children. I am deeply grateful to them for their outstanding support of my study and professional career. I am extremely grateful to my wife, Mayumi, whom I married in September 1985 for her devotion, interest, encouragement and criticism. I also wish to express my sincere thanks to my first wife, Kyoko, for her limitless devotion during my days in La Jolla and Basel.I have been fortunate enough to receive many professional honors which include: The Cloetta Prize of Foundation Professor Dr. Max Cloetta, Switzerland (1978), Warren Triennial Prize of the Massachusetts General Hospital, U.S.A. (1980), Genetics Grand Prize of Genetics Promotion Foundation, Japan (1981), Avery Landsteiner Prize of the Gesselshat für Immunologie, West Germany (1981), Asahi Prize of Asahi-Shimbun (Asahi Press), Tokyo, Japan (1982), Louisa Gross Horwitz Prize of Columbia University, New York, U.S.A. (1982), The V.D. Mattia Award of the Roch Institute of Molecular Biology, Nutley, U.S.A. (1983), Gairdner Foundation International Awards of the Gairdner Foundation, Toronto, Canada (1983), Person of Cultural Merit "Bunkakorosha" of the Japanese Government (1983), Order of Culture "Bunkakunsho" from the Emperor of Japan (1984), Bristol-Myers Award for Distinguished Achievement in Cancer Research (1986), Robert Koch Prize of the Robert Koch Foundation, West Germany (1986). Albert and Mary Lasker Award, New York City (1987) and NOBEL PRIZE in Physiology or Medicine, Stockholm, Sweden (1987). screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full tonegawa.jpg (162 X 227)" border=0 align=absmiddle>2000年诺贝尔生理学与医学奖三位科学家分享：Arvid Carlsson，Paul Greengard，Eric R. Kandel。获奖原因：For their discoveries concerning signal transduction in the nervous system一、Arvid Carlsson（尔维德-卡尔森）简历：1923年1月25日出生于瑞典的乌普萨拉。 地址：瑞典麦迪辛纳格顿431信箱哥德堡大学药理系 教育和就职状况 1951年获得瑞典兰德大学医学博士 1951年任助理教授 1956年任副教授 1959年任瑞典加特伯格大学药理学教授 1989年退休来自哥德堡大学药理学专业的阿尔维德-卡尔森教授获奖的原因是他发现了多巴胺(一种治疗脑神经的药物)可以作为人脑中的信号传送器，而且这种药物对于人类控制其身体动作具有非常重要的作用。他的研究成果已使人们意识到，患上帕金森症的原因正是人脑某个部位中缺少了多巴胺，而且人类可以很快研制出针对这种疾病的有效药物。卡尔森教授到目前为止已做出了多个后续发现，这些发现已进一步证明了多巴胺对人脑具有重要的作用。他的研究成果还进一步显示了治疗精神分裂症药物的药效。获奖演说：> screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 1.gif (140 X 198)" border=0 align=absmiddle>Max TheilerThe Nobel Prize in Physiology or Medicine 1951 Union of South Africa Laboratories of the Division of Medicine and Public Health, Rockefeller Foundation New York, NY, USA b. 1899d. 1972 Max Theiler was born on January 30, 1899, in Pretoria, South Africa, one of the four children of Sir Arnold and Emma (née Jegge) Theiler. His father was a well-known veterinary scientist. He attended local schools except for one year in Basle, Switzerland (his father was of Swiss origin), then went on to Rhodes University College, Grahamstown and the University of Capetown Medical School (1916-1918). He then went to England to study at St. Thomas' Hospital and at the London School of Tropical Medicine, receiving his medical degree in 1922. In the same year he became a Licentiate of the Royal College of Physicians and a Member of the Royal College of Surgeons.In 1922 he joined the Department of Tropical Medicine at the Harvard Medical School, Boston, Massachusetts, first as an assistant, then being appointed instructor. In 1930 he joined the staff of the International Health Division of the Rockefeller Foundation, becoming, in 1951, Director of Laboratories of the Rockefeller Foundation's Division of Medicine and Public Health, New York.His early work, at Harvard, dealt with amoebic dysentery and rat bite fever. He also worked on the problem of yellow fever, a subject in which he had become interested whilst still in London. This was to become his major interest. By 1927 he and his colleagues had proved that the cause of yellow fever was not a bacterium but a filterable virus. He also demonstrated that the disease could be readily transmitted to mice. Previously, laboratory work on this topic had been done using monkeys as experimental animals; the use of mice enabled the cost of such research to be greatly reduced. In 1930, when he joined the Rockefeller Foundation, that body was engaged in a broad attack on the problem of yellow fever. Here, Theiler and his colleagues worked on vaccines against the disease and eventually developed a safe, standardized vaccine, 17D, one advantage of which was its ready adaptability to mass production.His other work for the Institute has been connected with the causes and immunology of certain disorders which include Weil's disease. He has also been engaged in research on dengue fever and Japanese encephalitis. The problem of poliomyelitis has been of great interest to him and he discovered an apparently identical disorder in laboratory mice which is now sometimes called Theiler's disease (encephalomyelitis).Dr. Theiler has been a contributor to two books, Viral and Rickettsial Infections of Man (1948) and Yellow Fever (1951). He has also written numerous papers in The American Journal of Tropical Medicine and Annals of Tropical Medicine and Parasitology.Honours awarded to him include the Chalmer's Medal of the Royal Society of Tropical Medicine and Hygiene (London, 1939), the Flattery Medal (Harvard, 1945), and the Lasker Award of the Lasker Foundation (1949).He married Lillian Graham in 1928. They have one daughter.From Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964 This autobiography/biography was first published in the book series Les Prix Nobel. It was later edited and republished in Nobel Lectures. To cite this document, always state the source as shown above. Max Theiler died on August 11, 1972. 科学贡献： > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 2.gif (140 X 198)" border=0 align=absmiddle>The Nobel Prize in Physiology or Medicine 1930 :the discovery of human blood grouping.Biography Karl Landsteiner was born in Vienna on June 14, 1868. His father, Leopold Landsteiner, a doctor of law, was a well-known journalist and newspaper publisher, who died when Karl was six years old. Karl was brought up by his mother, Fanny Hess, to whom he was so devoted that a death mask of her hung on his wall until he died. After leaving school, Landsteiner studied medicine at the Univerisity of Vienna, graduating in 1891. Even while he was a student he had begun to do biochemical research and in 1891 he published a paper on the influence of diet on the composition of blood ash. To gain further knowledge of chemistry he spent the next five years in the laboratories of Hantzsch at Zurich, Emil Fischer at Wurzburg, and E. Bamberger at Munich.Returning to Vienna, Landsteiner resumed his medical studies at the Vienna General Hospital. In 1896 he became an assistant under Max von Gruber in the Hygiene Institute at Vienna. Even at this time he was interested in the mechanisms of immunity and in the nature of antibodies. From 1898 till 1908 he held the post of assistant in the University Department of Pathological Anatomy in Vienna, the Head of which was Professor A. Weichselbaum, who had discovered the bacterial cause of meningitis, and with Fraenckel had discovered the pneumococcus. Here Landsteiner worked on morbid physiology rather than on morbid anatomy. In this he was encouraged by Weichselbaum, in spite of the criticism of others in this Institute. In 1908 Weichselbaum secured his appointment as Prosector in the Wilhelminaspital in Vienna, where he remained until 1919. In 1911 he became Professor of Pathological Anatomy in the University of Vienna, but without the corresponding salary.Up to the year 1919, after twenty years of work on pathological anatomy, Landsteiner with a number of collaborators had published many papers on his findings in morbid anatomy and on immunology. He discovered new facts about the immunology of syphilis, added to the knowledge of the Wassermann reaction, and discovered the immunological factors which he named haptens (it then became clear that the active substances in the extracts of normal organs used in this reaction were, in fact, haptens). He made fundamental contributions to our knowledge of paroxysmal haemoglobinuria.He also showed that the cause of poliomyelitis could be transmitted to monkeys by injecting into them material prepared by grinding up the spinal cords of children who had died from this disease, and, lacking in Vienna monkeys for further experiments, he went to the Pasteur Institute in Paris, where monkeys were available. His work there, together with that independently done by Flexner and Lewis, laid the foundations of our knowledge of the cause and immunology of poliomyelitis.Landsteiner made numerous contributions to both pathological anatomy, histology and immunology, all of which showed, not only his meticulous care in observation and description, but also his biological understanding. But his name will no doubt always be honoured for his discovery in 1901 of, and outstanding work on, the blood groups, for which he was given the Nobel Prize for Physiology or Medicine in 1930.In 1875 Landois had reported that, when man is given transfusions of the blood of other animals, these foreign blood corpuscles are clumped and broken up in the blood vessels of man with the liberation of haemoglobin. In 1901-1903 Landsteiner pointed out that a similar reaction may occur when the blood of one human individual is transfused, not with the blood of another animal, but with that of another human being, and that this might be the cause of shock, jaundice, and haemoglobinuria that had followed some earlier attempts at blood transfusions.His suggestions, however, received little attention until, in 1909, he classified the bloods of human beings into the now well-known A, B, AB, and O groups and showed that transfusions between individuals of groups A or B do not result in the destruction of new blood cells and that this catastrophe occurs only when a person is transfused with the blood of a person belonging to a different group. Earlier, in 1901-1903, Landsteiner had suggested that, because the characteristics which determine the blood groups are inherited, the blood groups may be used to decide instances of doubtful paternity. Much of the subsequent work that Landsteiner and his pupils did on blood groups and the immunological uses they made of them was done, not in Vienna, but in New York. For in 1919 conditions in Vienna were such that laboratory work was very difficult and, seeing no future for Austria, Landsteiner obtained the appointment of Prosector to a small Roman Catholic Hospital at The Hague. Here he published, from 1919-1922, twelve papers on new haptens that he had discovered, on conjugates with proteins which were capable of inducing anaphylaxis and on related problems, and also on the serological specificity of the haemoglobins of different species of animals. His work in Holland came to an end when he was offered a post in the Rockefeller Institute for Medical Research in New York and he moved there together with his family. It was here that he did, in collaboration with Levine and Wiener, the further work on the blood groups which greatly extended the number of these groups, and here in collaboration with Wiener studied bleeding in the new-born, leading to the discovery of the Rh-factor in blood, which relates the human blood to the blood of the rhesus monkey.To the end of his life, Landsteiner continued to investigate blood groups and the chemistry of antigens, antibodies and other immunological factors that occur in the blood. It was one of his great merits that he introduced chemistry into the service of serology.Rigorously exacting in the demands he made upon himself, Landsteiner possessed untiring energy. Throughout his life he was always making observations in many fields other than those in which his main work was done (he was, for instance, responsible for having introduced dark-field illumination in the study of spirochaetes). By nature somewhat pessimistic, he preferred to live away from people.Landsteiner married Helen Wlasto in 1916. Dr. E. Landsteiner is a son by this marriage.In 1939 he became Emeritus Professor at the Rockefeller Institute, but continued to work as energetically as before, keeping eagerly in touch with the progress of science. It is characteristic of him that he died pipette in hand. On June 24, 1943, he had a heart attack in his laboratory and died two days later in the hospital of the Institute in which he had done such distinguished work.From Nobel Lectures, Physiology or Medicine 1922-1941, Elsevier Publishing Company, Amsterdam, 1965 This autobiography/biography was first published in the book series Les Prix Nobel. It was later edited and republished in Nobel Lectures. To cite this document, always state the source as shown above. Karl Landsteiner died on June 26, 1943. screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full landsteiner.jpg (162 X 227)" border=0 align=absmiddle>Earl W. Sutherland, Jr.The Nobel Prize in Physiology or Medicine 1971 Curriculum VitaeBorn: Burlingame, Kansas, November 19, 1915 Married: 1963 Children: 2 sons, 2 daughters Education B.S. Washburn College, 1937 M.D. Washington University, School of Medicine 1942, St. Louis Professional Experience Interneship, Barnes Hospital, 1942 Assistant in Pharmacology, School of Medicine, Washington University 1940-42 Instructor in Pharmacology, School of Medicine, Washington University 1945-46 Instructor in Biochemistry, School of Medicine, Washington University 1946-50 Assistant Professor of Biochemistry, School of Medicine, Washington University 1950-52 Associate Professor of Biochemistry, School of Medicine, Washington University 1952-53 Professor Pharmacology and Director of the Department, School of Medicine, Western Reserve University, Cleveland, Ohio, 1953-63 Professor of Physiology, Vanderbilt University, School of Medicine, Nashville, Tenn., 1963- present Career Investigator - American Heart Association 1967 Memberships American Society of Biological Chemists American Chemical Society American Society for Pharmacology and Experimental Therapeutics AAAS Sigma Xi Alpha Omega Alpha National Academy of Sciences Editorial Board Biochemical Preparations, 1951-56 Journal of Pharmacology and Experimental Therapeutics, 1957-58 Panel of Metabolism, Section on Biochemistry of the Committee on Growth (Nat. Res. Council) 1953-54 Study Section (Pharmacology and Experimental Therapeutics) Public Health Service, 1954-58 Member, National Institutes of Health Pharmacology Training Committee 1958-62, 1963-65 Member, National Institutes of Health Arthritis and Metabolic Disease Program Committee 1966- From Nobel Lectures, Physiology or Medicine 1971-1980, Editor Jan Lindsten, World Scientific Publishing Co., Singapore, 1992 This CV was first published in the book series Les Prix Nobel. It was later edited and republished in Nobel Lectures. To cite this document, always state the source as shown above. Earl W. Sutherland, Jr. died on March 9, 1974. screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full sutherland.jpg (162 X 227)" border=0 align=absmiddle>Ronald RossThe Nobel Prize in Physiology or Medicine 1902United Kingdom University College Liverpool, United Kingdom b. 1857(in Almora, India)d. 1932 Ronald Ross was born on May 13, 1857, as the son of Sir C.C.G. Ross, a General in the English army. He commenced the study of medicine at St. Bartholomew's Hospital in London in 1875; entered the Indian Medical Service in 1881. He commenced the study of malaria in 1892. In 1894 he determined to make an experimental investigation in India of the hypothesis of Laveran and Manson that mosquitoes are connected with the propagation of the disease. After two and a half years' failure, Ross succeeded in demonstrating the life-cycle of the parasites of malaria in mosquitoes, thus establishing the hypothesis of Laveran and Manson. In 1899 he joined the Liverpool School of Tropical Medicine under the direction of Sir Alfred Jones. He was immediately sent to West Africa to continue his investigations, and there he found the species of mosquitoes which convey the deadly African fever. Since then the School has been unremitting in its efforts to improve health, and especially to reduce the malaria in West Africa. Ross' researches have been confirmed and assisted by many distinguished authorities, especially by Koch, Daniels, Bignami, Celli, Christophers, Stephens, Annett, Austen, Ruge, Ziemann, and many others.In 1901 Ross was elected a Fellow of the Royal College of Surgeons of England and also a Fellow of the Royal Society, of which he became Vice-President from 1911 to 1913. In 1902 he was appointed a Companion of the Most Honourable Order of Bath by His Majesty the King of Great Britain. In 1911 he was elevated to the rank of Knight Commander of the same Order. In Belgium, he was made an Officer in the Order of Leopold II.In 1902 a movement was set on foot to commemorate the valuable services rendered to the School of Tropical Medicine by its originator and Chairman, Sir Alfred Jones, by founding a Chair of Tropical Medicine in University College to be connected with the School. The movement was met with enthusiastic support, and an amount of money was quickly collected sufficient to found «Sir Alfred Jones' Chair of Tropical Medicine». Ross was appointed to the Professorship in 1902 and retained the Chair until 1912, when he left Liverpool, and was appointed Physician for Tropical Diseases at Kings College Hospital, London, a post which he held together with the Chair of Tropical Sanitation in Liverpool. He remained in these posts until 1917, when he was appointed Consultant in Malariology to the War Office, his service in this capacity, and in special connection with epidemic malaria then occurring on combatant troops, being recognized by his elevation to the rank of Knight Commander, St. Michael and St. George, in 1918. He was later appointed Consultant in Malaria to the Ministry of Pensions. In 1926 he assumed the post of Director in Chief of the Ross Institute and Hospital of Tropical Diseases and Hygiene, which had been created by admirers of his work, and he remained in this position until his death. He was also a President of the Society of Tropical Medicine. His Memoirs (London, 1923) were «inscribed to the people of Sweden and the memory of Alfred Nobel».During this active career, Ross' interest lay mainly in the initiation of measures for the prevention of malaria in different countries of the world. He carried out surveys and initiated schemes in many places, including West Africa, the Suez Canal zone, Greece, Mauritius, Cyprus, and in the areas affected by the 1914-1918 war. He also initiated organizations, which have proved to be well established, for the prevention of malaria within the planting industries of India and Ceylon. He made many contributions to the epidemiology of malaria and to methods of its survey and assessment, but perhaps his greatest was the development of mathematical models for the study of its epidemiology, initiated in his report on Mauritius in 1908, elaborated in his Prevention of Malaria in 1911 and further elaborated in a more generalized form in scientific papers published by the Royal Society in 1915 and 1916. These papers represented a profound mathematical interest which was not confined to epidemiology, but led him to make material contributions to both pure and applied mathematics. Those related to «pathometry» are best known and, 40 years later, constitute the basis of much of the epidemiological understanding of insect-borne diseases.Through these works Ross continued his great contribution in the form of the discovery of the transmission of malaria by the mosquito, but he also found time and mental energy for many other pursuits, being poet, playwright, writer and painter. Particularly, his poetic works gained him wide acclamation which was independent of his medical and mathematical standing.He received many honours in addition to the Nobel Prize, and was given Honorary Membership of learned societies of most countries of Europe, and of many other continents. He got an honorary M.D. degree in Stockholm in 1910 at the centenary celebration of the Caroline Institute. Whilst his vivacity and single-minded search for truth caused friction with some people, he enjoyed a vast circle of friends in Europe, Asia and America who respected him for his personality as well as for his genius.Ross married Rosa Bessie Bloxam in 1889. They had two sons, Ronald and Charles, and two daughters, Dorothy and Sylvia. His wife died in 1931, Ross survived her until a year later, when he died after a long illness, at the Ross Institute, London, on September 16, 1932.From Nobel Lectures, Physiology or Medicine 1901-1921, Elsevier Publishing Company, Amsterdam, 1967 This autobiography/biography was first published in the book series Les Prix Nobel. It was later edited and republished in Nobel Lectures. To cite this document, always state the source as shown above.For more updated biographical information, see: Ross, Ronald, Memoirs. John Murray, London, 1923. 获奖演讲： > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 3.gif (140 X 198)" border=0 align=absmiddle>补全98年的Robert F. FurchgottThe Nobel Prize in Physiology or Medicine 1998 1/3 of the prizeUSASUNY Health Science Center Brooklyn, NY, USAb. 1916生平介绍： Early educationI was born in the lovely coastal city of Charleston, S.C. in 1916 and lived there until I was thirteen. In Charleston I first became enamored of "natural history" when I attended nature study classes and field trips to nearby beaches, marshes and woods, sponsored by the Charleston Museum. I became an avid shell collector and bird watcher (that was before the term "birder" was coined), and I still enjoy these hobbies. In 1929, my family moved from Charleston to Orangeburg, S.C., an inland, rural town of about 8,000 inhabitants, where my mother had grown up and still had some family. The reason for the move was that the Furchgott department store in Charleston, which had been started by my grandfather and was being run by my father and his two brothers, was unable to survive in the midst of the Depression, and my father decided to open a women's clothing store in Orangeburg. So I spent my high school years in Orangeburg, enjoying small town life and competing with my first cousin Edwin Moseley for the highest grades in our class. He won.Within the first couple of years of high school, I knew that I would like to be a scientist. My parents were encouraging: they gave me chemistry sets and a small microscope as presents. I liked to read popular books about scientists, although there were not many available at that time. My father subscribed to the Sunday New York Times, in which there was often a column on science that I found very exciting.During the four years that I was in high school, my older brother Arthur was at the University of North Carolina at Chapel Hill. I wanted to attend college there also, but that was not possible when I finished high school in 1933 because tuition for me, as an out-of-state resident, was more than my father could afford at that time. So I spent my freshman year at the University of South Carolina, where my tuition was much less. However, by the summer of 1934, my father moved his business from Orangeburg to Goldsboro, N.C., where he felt that the local economy was better. So now, as a resident of North Carolina, I was able to register at the University at Chapel Hill as a sophomore majoring in chemistry.At Chapel Hill, I had a number of excellent teachers in chemistry. During my junior and senior years, I had a small amount of financial support from an NYA job (NYA being the initials of the National Youth Administration set up by the federal government to help students during the Depression). In that job, I was a lab assistant in research to a junior faculty member working on the physical chemistry of solutions of cellulose. I had decided early in my college years that I would go on to graduate work in some branch of chemistry. My preference by the time I was a senior was physical organic chemistry. I sent letters to dozens of chemistry departments applying for a graduate fellowship or teaching assistantship. I had an excellent academic record, but by graduation time I still had no definite offer of a position for graduate training. I was almost resigned to taking a job in chemical industry, when around the middle of June while I was in Florence, S.C., where my parents now lived, an unexpected offer of a teaching assistantship came to me from the Physiological Chemistry Department of Northwestern University Medical School in Chicago. I was to be a graduate student of Dr Henry Bull, who had recently come to Northwestern, and whose research interests were physical chemical aspects of biochemistry.Northwestern and Cold Spring Harbor (1937-1940)Before I went to Chicago, I worked for two summer months in 1937 for Eastern Airlines at the Philadelphia airport - a job which my older brother Arthur, who was employed by that airline, helped me obtain. The job allowed me to save some money and also allowed me free air travel to Chicago. That helped a lot since my stipend as a teaching assistant at Northwestern was only $50 a month for a nine-month academic year. When I arrived in Chicago, it had already been arranged for me to share a room with two more advanced graduate students. Living in Chicago was quite a change from living in the Carolinas. When I would walk to work in the winter from our rooming house, which was about a mile from the medical school, the chill wind whipping in from Lake Michigan along Chicago Avenue was quite an experience for a Southern boy.My course work at Northwestern was partly at the medical school, and partly at the Evanston campus to which I would travel via the El. At the Evanston campus, my courses were mainly in physical chemistry under Dr Malcolm Dole, who was also on my PhD advisory committee. At the Chicago campus, I had to take physiology and bacteriology (along with medical students), Henry Bull's course on physical chemistry in biochemistry, and some assorted graduate courses in physiology and biochemistry. The physiology course was under the direction of Dr Andrew Ivy, who had built up a sizeable physiology department faculty for those times. In contrast, the biochemistry faculty consisted only of the chairman, Dr Chester Farmer, Dr Bull and two part-time lecturers.My laboratory work with Bull started out with the preparation of purified egg albumin. He was studying physical chemical changes in this protein after different methods of denaturation. He had begun to involve me in some of his studies when the summer of 1938 came along, and that turned out to be a special summer for me. Bull had been invited to present a paper on his work at the sixth Cold Spring Harbor Symposium on Quantitative Biology which was to take place at the Cold Spring Harbor Biological Laboratory of the Long Island Biological Association. The theme of the symposium, which was to run for five weeks in a leisurely fashion was the structure and function of proteins. Bull had obtained permission from the director of the Cold Spring Harbor Laboratory, Dr Eric Ponder, for me to attend the symposium, while earning my room and board by running the lantern slide projector at the lectures. The symposium was very exciting. I met many distinguished scientists. Ponder and a physician-scientist, Harold Abramson, arranged to have me assist in a research project at the laboratory for the rest of the summer after the symposium was over. The project was on the electrophoretic mobility of rabbit erythrocytes and ghosts, measured with the use of a microelectrophoresis cell and light- and dark-field microscopy.By the end of the summer, I had become very interested in the physical chemistry of the red blood cell membrane. When I returned to Northwestern in the fall of 1938, Bull approved continuation of my research on red blood cells as a PhD thesis project. In particular, I was fascinated by the unexplained phenomenon of the transformation of mammalian red blood cells, suspended in unbuffered isotonic saline from discs to perfect spheres when a small drop of the suspension was placed between slide and coverglass. I discovered that the disc-sphere transformation depended on two factors. The first was a rise in pH to over 9.0 in the unbuffered suspension, as a result of the alkaline nature of the glass surfaces (pH being measured with a semi-micro glass electrode that I constructed). The second factor was the removal from the suspension of the red blood cells by adsorption onto the glass surfaces of the slide and coverglass of a substance in the suspension that prevented sphering on elevation of pH of the suspension. I demonstrated that this substance, which I termed the anti-sphering factor, was serum albumin which could not be effectively removed from the red cells simply by multiple washing and centrifuging. In addition to the work on shape changes in erythrocytes, my PhD thesis work involved additional studies on the electrophoresis of the cells under various conditions and on other aspects of the physical chemistry of erythrocyte membranes.In the summer of 1939 at the invitation of Ponder, with whom I had extensive correspondence during the year and who had become in effect the major advisor for my PhD thesis research, I returned to Cold Spring Harbor to continue research on red blood cells. To earn my room and board, I waited on tables in the communal dining room. I also was able to attend the symposium talks of that year, which were on the subject of biological oxidations. There I first became aware of the new developments in oxidative energy metabolism and the importance of high energy phosphate compounds. Among the many outstanding biochemists attending were L. Michaelis, Fritz Lipmann and Carl Cori. Ponder and his young wife Ruth were very hospitable to me. I was much impressed with his skill in applying mathematics in his research, his facility in scientific writing, and his large collection of records of classical music.I was able to complete and defend my thesis in time to receive the Ph.D. degree in June of 1940. Earlier that spring I had attended the annual meeting of the Federation of American Societies for Experimental Biology (FASE in New Orleans. I had fortunately been asked by Henry Tauber, an Austrian biochemist working for a pharmaceutical firm in Chicago, to share the driving in his car on the round trip to New Orleans as well as his room in a rundown hotel in New Orleans. Thus, I was able to attend this meeting at very little expense. At the FASEB meeting in New Orleans, where gatherings of participants were still called "smokers" and even a fancy meal was not more than two dollars, I had some interviews with persons about possible post-doctoral jobs. One of the interviews was with Dr. Ephraim Shorr, an Associate Professor of Medicine at Cornell University Medical School in New York City, whom I had met at Cold Spring Harbor the summer before. A few weeks later Shorr offered me a postdoctoral position in his laboratory. Although I was hoping to get a position which would allow me to continue work on physical chemistry of proteins or cell membranes, none came through, and I accepted the position with Shorr, with the understanding that I would begin in September.The reason for waiting until September to begin work at Cornell was because I wanted to spend one more summer at the Biological Laboratory at Cold Spring Harbor. This time, however, I went there as an invited speaker at the symposium which that summer was on the topic of permeability of cell membranes. My talk was entitled "Observations on the structure of red cell ghosts." At that symposium, there were again a number of established distinguished scientists like K.S. Cole, Robert Chambers and F.O. Schmitt; and in addition, a number of bright young scientists like Hans Neurath, who had also been at the 1938 symposium, Hugh Davson, who with Danielli had developed the lipid bilayer membrane model, and Benjamin Zweifach, with whom I was to collaborate later in research.Cornell University Medical College (1940-1949)I stayed at Cornell University Medical College working in the laboratory of' Ephraim Shorr for nine years. When I arrived, Sam Barker, a young research associate, was there to instruct me in methods and procedures they were using to study tissue metabolism (largely using Warburg manometers) and the turnover of rather ill-defined tissue organic phosphate fractions from canine cardiac muscle during incubations in vitro. For such studies the lab was one of the first to use radioactive phosphate, which we obtained from the cyclotron laboratory at Berkeley. Barker left toward the end of my first year at Cornell; and I was then responsible for running the laboratory for Shorr. Shorr himself, would sometimes take part in preparing tissue for the Warburg experiments. He was quite capable in the laboratory in addition to being a busy and excellent clinician.During my first two years at Cornell, my major project was on phosphate exchange and turnover, using radioactive phosphate and slices of dog left ventricular muscle. A full paper on the work was published in the journal of Biological Chemistry in 1943. The methods and equipment we used in that work have long been superseded, but we did manage with chemical and some early enzymatic methods to show the extremely fast turnover of creatinine phosphate and the terminal phosphate of ATP in resting cardiac muscle.The 1943 paper was my first full publication after three years of work at Cornell. One likely reason for sparse output was that the United States had entered World War II in December of 1941, and Shorr, like many others, began to undertake research that had more relevance to the war effort. With government and other support, he shifted the major research in the lab to circulatory shock - first on changes in tissue energy metabolism resulting from hypoxia associated with hemorrhagic shock, and then mainly on factors that might account for "irreversible" shock, the condition in which restoration of blood volume is no longer able to raise pressure and sustain life in the animal subjected to maintained low blood pressure as a result of controlled hemorrhage. To help in this new line of research, Shorr recruited Benjamin Zweifach, then a bright young physiologist who had trained with Robert Chambers and had developed a beautiful method for microscopic observation of blood flow in part of the mesentery (the "mesoappendix" area) of the anesthetized rat. In brief, the "rat mesoappendix test", conducted by Zweifach and technicians whom he trained, produced evidence by 1944 for two vasoactive factors in circulatory shock. The first factor appeared in the plasma of dogs in the early reversible (by transfusion) stage of hemorrhage. Intravenous injections of this plasma increased the sensitivity of the small arterioles and pre-capillary sphincters to topically applied epinephrine in the mesoappendix test. This factor was termed VEM (for vasoexcitatory materials). As the irreversible stage of circulatory shock developed, VEM activity disappeared from the plasma and a new factor appeared which markedly decreased the sensitivity to epinephrine in the mesoappendix test. This factor was termed VDM (for vasodepressor material). We developed evidence, in part from in vitro experiments with tissue slices, that hypoxic kidney was the probable source of VEM and that hypoxic liver was the probable source of VDM. By late 1945, these developments led to a lead article in the journal Science by Shorr, Zweifach and myself.During the war years, I was not solely involved in research on tissue metabolism and circulatory shock. In 1943, Eugene DuBois, chairman of the Department of Physiology at Cornell, arranged that I join his department as an instructor in order to replace a staff member lost to military service. Although I was teaching in physiology, I still spent most of my time in research in Shorr's lab, which was partially funded by the federal Office of Scientific Research and Development. The work on VEM and VDM continued after the war ended. I had attempted to isolate the VEM-like material that accumulated in incubation fluid when kidney slices were incubated anaerobically. I was able to concentrate it somewhat and it appeared to be a labile dialyzable peptide, but I failed to isolate it. On the other hand, Abraham Mazur, a professor of biochemistry at the City College of New York who worked part time with us, purified a VDM-like material from liver which appeared to be ferritin. (Ferritin or not, we might now wonder whether VDM could somehow be related to nitric oxide!)Unfortunately, the only bioassay procedure for detecting VEM and VDM activity was that involving changes in sensitivity to epinephrine in the rat mesoappendix test. Intravenous injections of solutions containing high levels of impure VEM or purified ferritin did not effect blood pressure in experimental animals. Attempts to develop an in vitro bioassay system also failed. These failures tempered my enthusiasm, and I think that of Zweifach, for the significance of VEM and VDM in the regulation of circulation. However, the failed attempts to develop an in vitro bioassay for VEM and VDM were very important for me for they introduced me to the pharmacology of smooth muscle, a subject that has been a major interest of mine ever since.Two of the isolated smooth muscle preparations that I unsuccessfully tested for bioassay of VEM and VDM were a helically-cut strip of rabbit aorta, which responded with contraction to epinephrine, and a longitudinal segment of rabbit duodenum, which exhibited spontaneous rhythmic contractions that were inhibited by epinephrine and stimulated by acetylcholine. At that time, contractions of such smooth muscle preparations mounted in organ baths were recorded with isotonic levers on kymographs. One day in the course of making tests on segments of rabbit duodenum mounted in oxygenated Krebs solution, I was surprised to see that during the first hours of the experiment, contraction amplitude did not stabilize as usual but declined gradually and markedly even though the rhythmic frequency remained unchanged. I suspected that my technician had forgotten to add glucose to the Krebs solution. Adding glucose now quickly increased contraction amplitude to the normal level. This finding led to a simple procedure for finding out what sugars and fatty acids could be utilized for energy for contraction in the intestinal smooth muscle under aerobic and anaerobic conditions and to analyze the sites of action of metabolic inhibitors.In the spring of 1949, 1 had two interesting offers at the assistant professorship level - one in physiology at Duke and one in pharmacology at Washington University School of Medicine. I decided on Washington University, partly because the new chairman there, Oliver Lowry, was someone I had known in the Enzyme Club in New York City and partly because I had begun to be very interested in pharmacology as a discipline. This was partly because of the studies I had begun on the effects of drugs and other agents on smooth muscle preparations in vitro, but also in large part because of my close friendship with Walter Riker, who was then a junior member in the Pharmacology Department at Cornell at the beginning of a distinguished career. His enthusiasm for research in pharmacology was contagious.In the summer of 1949, my family and I drove from New York to St. Louis. My wife, Lenore, a native New Yorker, said she felt like she was going West in a covered wagon. By that time we had two daughters, ages four and one. Later we had a third daughter born in St. Louis. It might be noted here that none of my daughters became scientists. Instead, they all went into art (like my younger brother, Max). It might also be noted here that my wife Lenore died in 1983; and that now I have a new wife, Margaret (Maggie). I have been very fortunate in having wives who encouraged my work, even though it often reduced the time I could give to family matters.Washington University (1949-1956)My seven years in the Pharmacology Department at Washington University were enjoyable ones. Oliver (Ollie) Lowry had been appointed chairman of that department a year or so before I came. He was already well recognized for his ingenuous methods involving enzymology , spectrometry and fluorometry in the quantitative analysis of important enzymes, substrates and products in extremely small amounts of tissue. He was very helpful in introducing me to enzymatic-spectroscopic methods (as developed by kalckar) for analysis of ATP, ADP and AMP. As a new chairman, Lowry inherited two faculty members, Helen Graham and Edward Hunter, and recruited two new ones, namely myself and Morris (Morrie) Friedkin. I had never had a course in pharmacology as a student, much less taught in one, and so I had to spend a lot of time during my first year in St. Louis keeping ahead of the medical students. Later, when I set up my own department in Brooklyn, I adopted for the pharmacology course there much of the lecture, laboratory and conference program that I had participated in at St. Louis.Lowry's department was a stimulating place for research. Over the years I was there, the departmental staff grew steadily. Lowry attracted outstanding postdoctoral fellows, such as Eli Robbins and Jack Strominger. We often joined the members of Carl Cori's Biochemistry Department for seminars and journal club meetings.My first research project at Washington University was a continuation of the work I had begun at Cornell on energy-metabolism and function of rabbit intestinal smooth muscle. I was able to obtain a small grant to support my research on smooth muscle, and to hire a technician, Marilyn (Wales) McCaman, who later became my first graduate student. By the middle of 1951, my favorite in vitro smooth muscle preparation had shifted from the rabbit duodenum to the rabbit thoracic aorta. I had found that the helical (spiral) strip of that vessel, properly cut and mounted in organ chambers for isotonic recording, gave very reproducible contractions to epinephrine and norepinephrine after equilibration in oxygenated Krebs bicarbonate solution. I had at first planned to study the effects of disturbances in energy-metabolism on these contractions, but I became much more interested in using the aortic strip for studies on drug-receptor interactions.By 1953, I had published a paper entitled "Reactions of strips of rabbit aorta to epinephrine, isoproterenol, sodium nitrite and other drugs". Among the other drugs was acetylcholine. I found that it only produced contractions, whether it was added to resting strips or strips precontracted with some other agent. That was a paradoxical response since acetylcholine was known to be a very potent vasodilator in vivo. Little did I suspect then what I was able to show many years later - namely, that relaxation of arteries by acetylcholine is strictly endothelium-dependent, and that my method of preparing the strips inadvertently resulted in the mechanical removal of all the endothelial cells.In 1954, I published a paper on the use of dibenamine in differentiating receptors in the aortic strip, and in 1955 a review in Pharmacological Reviews on the pharmacology of vascular smooth muscle. In that review, I tried to develop receptor theory as a logical base for interpreting the responses of vascular smooth muscle to many neuro transmitters, hormones and drugs. In order to derive equations to account for the very slow onset and offset kinetics of competitive antagonists as compared to the fast kinetics of agonists, I developed a biophase model in which the agents moved between an aqueous extracellular phase and a lipid membrane phase containing the receptors. Although I paid homage in my review to A. J. Clark for his pioneering work in developing receptor theory, I took issue with his hypothesis that response of a tissue to an agonist is proportional to the fraction of receptors occupied by the agonist. Our results with dibenamine, which behaved as an irreversible competitive blocking agent of adrenergic -receptors, had indicated that with a strong agonist like epinephrine, one could still achieve well over half of the maximum contraction when only a small fraction of receptors were still active. This was the beginning of my interest in the concept of "receptor reserve" or "spare receptors." (A year later, R.P. Stephenson published his classic paper on the subject in which he introduced the concepts of efficacy, full agonist and partial agonist.)In the review of 1955, I also briefly reported on a newly discovered phenomenon - namely, that strips of rabbit aorta undergo reversible relaxation when exposed to light of proper wavelength and intensity. This photorelaxation was an accidental discovery that came from the observation that in one experiment active contractile tone of two strips in one pair of organ chambers fluctuated with time, whereas that of two strips in another pair of chambers remained steady. The two strips showing fluctuations did so synchronously. Those two strips, but not the other two, were in organ chambers near a window through which they were exposed to skylight. Suspecting that the fluctuations in tone were due to fluctuations in light intensity on the strips near the window (it was a cloudy-bright day), I closed the shade on the window and both strips increased in tone. I opened the shade and both decreased in tone. From that point on, we never allowed our strips to be exposed to direct skylight. (The usual overhead fluorescent lights do not produce photorelaxation.) Some studies on the characteristics of photorelaxation were begun in St. Louis, and then extended when I moved to Brooklyn.In addition to working on in vitro smooth muscle preparations at Washington University, I also began what became many years of research on the pharmacology of an in vitro cardiac muscle preparation - namely the isolated electrically-driven right atrium of the guinea pig. In starting that work, I had the assistance of a very able technician, Taisija De Gubareff. Using chemical and enzymatic methods for analysis of creatinine phosphate, ATP, ADP, and AMP, we showed that neither development of "experimental failure" in vitro (a steady loss of contractile force over hours) nor recovery from failure on addition of a cardiac glycoside was due to changes in concentration of these high-energy phosphates. We also reported on the effects of anaerobiosis and of a number of positive and negative inotropic agents. We collaborated with my good friend William Sleator of the Physiology Department in the study of changes in cellular action potentials (measured with intracellular microelectrodes) associated with the changes in contractility of the guinea pig atrium in response to epinephrine and acetylcholine, and a number of other inotropic agents.Suny Medical Center in Brooklyn (1956-)In 1956, I accepted the position of chairman of the new Department of Pharmacology at the State University of New York (SUNY) College of Medicine at New York City (actually in Brooklyn, and later changed in name to SUNY Downstate Medical Center and more recently to SUNY Health Science Center at Brooklyn). The department had previously been part of a joint physiology and pharmacology department headed by Chandler Brooks but with the opening of a new, relatively huge (for the time) basic science building for the medical school and with good financial support from the State University, there was ample room and resources for a separate department. From the former joint department, I inherited Julius Belford as an associate professor and Bernard Mirkin as an assistant professor. For additional faculty, I recruited Kwang Soo Lee, Leonard Procita, Lowell Greenbaum, Walter Wosilait and Arthur Zimmerman, all in time for them to teach our first course for medical students. The following year C. Y. Kao joined the staff. Also during the first year, we accepted our first graduate students, namely Maurice Feinstein, who worked with me, and Arnold Schwartz, who worked with Lee. During that year I didn't do much bench work in the research lab since most of my time was spent organizing the department and learning how to be a chairman. (I never became a well-organized administrator and was always poor at delegating authority.)In Brooklyn, I continued research on photorelaxation of blood vessels, factors influencing contractility of cardiac muscle, peripheral adrenergic mechanisms, and receptor theory and mechanisms. Then, about twenty-three years after moving to Brooklyn, the research in my laboratory largely shifted to endothelium-dependent relaxation of blood vessels. For convenience, I shall divide the discussion of research in Brooklyn into subsections corresponding to the areas that I have listed.Photorelaxation of Blood VesselsHelping with this research were Eugene Greenblatt, my first postdoctoral fellow, and Stuart Ehrreich, my third graduate student. Among other things, we were able to obtain an accurate action spectrum (with a peak at 310 nm) for the photorelaxation. Later we observed that addition of sodium nitrite to the bathing medium greatly sensitized the rabbit aortic strip to photorelaxation and shifted the peak of the action spectrum to about 355 nm. Ehrreich and I found that many other smooth muscle preparations (from stomach, intestine and uterus) which did not ordinarily relax in response to radiation did so in the presence of inorganic nitrite. Percy Lindgren, a visiting faculty member from the Karolinska Institute, also worked with us for a while on photosensitization by nitrite.Many years later in the early 1980's, after the discovery of endothelium-derived relaxing factor (EDRF), I again began research on photorelaxation. Although photorelaxation did not depend on the presence of endothelium on the strip or ring of rabbit aorta, we found many similarities between it and endothelium-dependent relaxation (as produced by acetylcholine or A23187). Not only was photorelaxation, like endothelium-dependent relaxation, causally dependent on the elevation of cyclic GMP as a result of stimulation of guanylate cyclase, but both were inhibited by hemoglobin and by methylene blue. This work was carried out with Desingarao Jothianandan, who has been a most helpful research associate in my lab over the past seventeen years. Then, after EDRF was identified in 1986 as nitric oxide, Kazuki Matsunaga (a postdoctoral fellow) and I reinvestigated the potentiation of photorelaxation by sodium nitrite. Using a cleverly designed perfusion-bioassay type apparatus, Matsunaga clearly demonstrated that the potentiation was due to the photoactivated release of NO from nitrite. It is tempting to hypothesize that light (in the absence of added nitrite) produces relaxation of vascular smooth muscle by photoactivating the release of NO from some endogenous compound in the muscle cell.Factors Influencing Contractility of Cardiac MuscleMy first graduate student in Brooklyn, Maurice Feinstein, did his Ph.D. thesis research on the effects of experimental congestive heart failure, asphyxia and ouabain on high energy phosphates and creatine content of the guinea pig heart. My second graduate student, Albert Grossman, who began work in 1957, did his thesis research on the effects of frequency of stimulation, extracellular calcium concentration and various drugs on calcium exchange and contractility of the guinea-pig left atrium. Grossman and I published three papers based on his thesis research, which was one of the first attempts to determine the rates of exchange of calcium (using 45Ca) between extracellular fluid and various intracellular "pools" of calcium in cardiac muscle under various conditions affecting contractility. We showed that the positive inotropic effects of norepinephrine and strophanthin-K were correlated with an increase in rate of exchange of calcium in an intracellular pool associated with the contractile process and that the negative inotropic effects of acetylcholine and adenosine were correlated with a decrease in rate of exchange in that pool.We also continued work with ryanodine, which produced a negative inotropic effect on the guinea-pig atrium and actually changed the force-frequency effect from a positive to negative staircase (mimicking the normal staircase in frog heart). Sleator, De Gubareff and I had shown that the decrease in force with ryanodine (unlike that with acetylcholine or adenosine) was not associated with a decrease in duration of the action potential. The thesis research of Grossman and a few years later that of another graduate student, Peter Wolf, also using 45Ca to measure effects of ryanodine on calcium exchange, led to a hypothetical model that fits fairly well with more recent work of others on the reactions of ryanodine with "receptors" involved with calcium transport in the sarcoplasmic reticulum.Peripheral Adrenergic MechanismsIn writing the 1955 review on the "Pharmacology of vascular smooth muscle," I had become very interested in the mechanisms by which sympathetic postganglionic denervation and certain drugs like cocaine markedly potentiate the response of effector organs to epinephrine and norepinephrine, yet markedly reduce the response to the sympathomimetic tyramine. My second postdoctoral fellow, Sadashiv (Sada) Kirpekar, was assigned to work in this area. He proved to be a gifted investigator, and we published a number of papers together on work carried out between 1959 and 1962. In one paper, with the running page heading of "the cocaine paradox," we presented evidence that in aortic strips of rabbit and isolated electrically-driven atria from guinea pig and cat, cocaine potentiated responses to norepinephrine and inhibited those to tyramine by blocking one and the same site on adrenergic nerve terminals. Blockade of this site inhibited the neuronal uptake of no repinephrine from the region of the adrenergic receptors, thus potentiating its action; however, blockade of the site also inhibited uptake of tyramine, whose sympathomimetic action depends on release of norepinephrine from neuronal storage sites, thus inhibiting its action. The site, which we called the "transfer site" later became known as the uptake-1 (UI) site. In the same paper we showed that reserpine, which depleted neuronal storage granules of norepinephrine, did not interfere with activity of the uptake site. In addition to Kirpekar, Peter Cervoni came in as a postdoctoral fellow to work on peripheral adrenergic mechanisms. Both he and Kirpekar later became faculty members in the department with Kirpekar staying on and becoming a stellar figure in the field of adrenergic mechanisms before his untimely death in 1983.In 1960, I was invited to present a paper on some of my studies on receptors for sympathomimetic amines at a CIBA Foundation conference on Adrenergic Mechanisms held at CIBA House in London. It was the occasion for my first trip abroad and was very exciting. Among the many distinguished pharmacologists at the conference were Sir Henry Dale, Sir John Gaddum and J.H. Burn. Burn at that time was pushing his "cholinergic-link" hypothesis for norepinephrine release at adrenergic nerve terminals. I felt strongly that he had misinterpreted the experimental results which had led to the hypothesis and in the discussion sessions I presented our own results with isolated atria which indicated that there were nicotinic cholinergic receptors on adrenergic nerve terminals which when stimulated by nicotine or acetylcholine triggered a transient release of norepinephrine, but which played no role in release of norepinephrine on electrical stimulation of the nerve.In 1962-63, 1 spent a sabbatical year in the Department of Physiology of the University of Geneva, where Jean Posternak was chairman. Although I did some research and teaching there, I spent most of my time writing papers on research that my colleagues and I had completed during the preceding few years and on a review on receptor mechanisms (see below). I also visited a number of laboratories in Europe where outstanding research on adrenergic mechanisms was in progress. Among these were the laboratories of S. von Euler in Stockholm, E. Muscholl in Mainz and John Gillespie in Glasgow.Between 1965 and 1970 I was fortunate in having a number of very competent coworkers in research on peripheral adrenergic mechanisms. In addition to Kirpekar, there were Pedro Sanchez-Garcia, (a visiting research associate who later became a leading pharmacologist in his native Spain), Jerome Levin (a postdoctoral fellow) and Arun Wakade (a graduate student who later became a faculty member).In early 1971, I began my second sabbatical leave, this time at the relatively new medical school of the University of California at San Diego (located in La Jolla). I became a visiting professor in Steve Mayer's Pharmacology Division of the Department of Medicine. One reason for this choice of a sabbatical site was that I wanted to learn the method for analysis of cyclic AMP that Mayer had developed (this was before the development of radioimmunoassays for cyclic nucleotides). However, I did not do a lot of research at La Jolla, partly because a fair amount of my time that year was devoted to duties as president of the American Society for Pharmacology and Experimental Therapeutics.On returning from La Jolla to Brooklyn in 1972, I continued research on the role of receptors located on prejunctional terminals (varicosities) of adrenergic nerves. I collaborated with Kirpekar in an attempt to characterize the inhibitory prejunctional -adrenergic receptors on the nerve terminals in cat spleen. At the same time, one of my graduate students, Odd Steinsland, was conducting a very exciting thesis project on cholinergic receptors on prejunctional adrenergic nerve terminals in the isolated, perfused central ear artery of the rabbit. He first pharmacologically characterized with the use of various muscarinic agonists and antagonists the prejunctional receptor through which acetylcholine produces a marked inhibition of norepinephrine release (monitored by both the degree of vasoconstriction and [3H]norepinephrine release). He then went on to study the release of norepinephrine from the adrenergic neurons in the ear artery by cholinergic agonists acting on prejunctional nicotinic receptors. At the same time I was continuing studies, with the assistance of Taruna Wakade, on the pharmacology of cholinergic nicotinic receptors on adrenergic prejunctional terminals in the guinea-pig left atrium.Receptor Theory and MechanismsWhen I first gave a course on receptor theory and mechanisms to graduate students in 1957-1958, the literature on the subject was relatively sparse: papers by Clark, Gaddum, Schild, Ariëns, Stephenson, Nickerson and myself. I became interested in developing suitable theory (occupation theory) and in vitro procedures for differentiating and characterizing receptors. In particular, I concentrated on receptors for adrenergic and cholinergic agents using as test tissues the rabbit aortic strip, duodenal segment, and stomach fundus muscle, and the guinea-pig electrically driven left atrium and tracheal ring.In 1963, toward the end of my sabbatical year at the University of Geneva, I completed a review on "Receptor Mechanisms" for Volume 4 of the Annual Review of Pharmacology. In it, I took the opportunity to stress the importance of Stephenson's ideas on efficacy and spare receptors. In 1965 at a symposium on receptor mechanisms at Chelsea College in London, I presented a paper on the use of -haloalkylamines, as irreversible receptor antagonists, in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes. Using a slightly modified form of Stephenson's equations and introducing a term, , for intrinsic efficacy, I derived a simple equation that predicted that the slope and ordinate intercept of a double reciprocal plot of equiactive concentrations of an agonist before and after irreversible inactivation of a fraction of its receptors, could permit the determination of both the fraction of receptors still active as well as the dissociation constant (KA) of the agonist-receptor complex. For different agonists acting on the same receptor, one could calculate from the KA values the fractional occupation by each to obtain the same standard response before receptor inactivation, and thus obtain relative efficacies. Using this approach, Paula (Bursztyn) Goldberg (a graduate student) and I compared the dissociation constants and relative efficacies of agonists acting on muscarinic cholinergic receptors of isolated strips of rabbit stomach fundus muscle; and later John Besse (a postdoctoral fellow) and I compared the dissociation constants and relative efficacies of agonists acting on 1-adrenergic receptors of rabbit aorta. In light of what is now known about receptor signalling pathways through G-proteins, it is probably better to admit that the pharmacological procedure which we developed for obtaining agonist-receptor dissociation constants can only give approximate relative values. Nevertheless, the procedure has proven useful in a number of studies.In 1972, I published a review entitled "The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory". In it I attempted to formulate the methods and necessary conditions for the classification and differentiation of receptors by pharmacological procedures designed to give accurate dissociation constants of competitive antagonists, acting on a given receptor, and accurate relative potencies and, if possible, dissociation constants of agonists acting on the same receptor. In particular, I attempted to point out pitfalls in such procedures and how to avoid them. For example, I derived theoretical equations to illustrate how removal of the agonist from the region of the receptor by active uptake or enzymatic destruction could markedly alter the slope of a Schild plot for competitive antagonism from the theoretical slope of 1. Later, Aaron Jurkiewicz, a visiting research associate from Sao Paulo, Niede Jurkiewicz and I successfully used these theoretical equations in the analysis of propranolol antagonism to isoproterenol in guinea-pig tracheal strips before and after blockade of removal of the agonist by active uptake.In 1977, I organized for the annual FASEB meeting a symposium on receptors. By then binding of radioligands (usually 3H-labelled competitive antagonists) had been used for several years for quantifying specific receptors in membranes from homogenized cells and for determining the dissociation constants of competitive antagonists and agonists for those receptors. Most of the papers at the symposium were reports of studies with radioligands (e.g., R. J. Lefkowitz on both -and -adrenergic receptors; P. Seeman on dopamine receptors; S. Snyder and colleagues on serotonin receptors and opiate receptors). My paper at the symposium was partly a discussion of how pharmacological procedures for differentiating and characterizing receptors based on occupation theory were still very useful in conjunction with the exciting new developments in receptor research being made with specific radioligands.Also, I reviewed work that had been carried out in my laboratory on -adrenergic receptors mediating relaxation of guinea-pig tracheal smooth muscle, and presented results of pharmacological experiments that showed that this smooth muscle did not have exclusively the 2-type of the -adrenergic receptor, as dogma of that time would have it, but had an admixture of the 1-type as well - usually as a small fraction of the total of -receptors, but, depending on the guinea-pig used, sometimes much more.Endo Thelium-dependent RelaxationHaving obtained pharmacological evidence that guinea-pig tracheal smooth muscle sometimes has a sizeable fraction of the 1-type adrenergic receptor along with the 2-type (see above), I decided that it would be well to reexamine the smooth muscle of rabbit thoracic aorta to see if it also might have varying amounts of the 1-type receptor mixed with the 2-type. However, in the very first experiment designed for this new study in May 1978, an accidental finding as a result of a technician's error completely changed the course of research in my laboratory. The accidental finding was that on the preparation of rabbit aorta being used in the experiment, the muscarinic agents acetylcholine and carbachol induced relaxation rather than the expected contraction. Why this accidental finding was so exciting, how it led to our discovery of the endothelium-derived relaxing factor (EDRF), and how that factor was eventually identified as nitric oxide will not be discussed here since those matters will be considered in detail in my Nobel Lecture.In 1982, I resigned from the chairmanship of the Department of Pharmacology at the SUNY Downstate Medical Center, but continued as a professor. In 1989, I retired from my professorship (receiving emeritus status), so that I now was free of teaching duties and committee work related to the medical curriculum but could still continue research in the department. My retirement also now allowed me to spend about three and a half months each winter as an adjunct Professor in the Department of Molecular and Cellular Pharmacology of the University of Miami School of Medicine. Most of my time there I have spent trying to catch up on the writing of manuscripts and on the reading of the burgeoning literature in the field of nitric oxide research - an impossible task these days! During the winter sojourns in Miami, I keep in touch with what is going on in my research laboratory in Brooklyn by means of an occasional visit, but mainly by frequent fax and telephone communications with my one or two coworkers there. I consider myself very fortunate in having this Brooklyn-Miami arrangement. Of course, an additional advantage for my wife Maggie and me is that the arrangement allows us to enjoy the very pleasant winter weather in Miami and some of the outdoor activities that it fosters (golf, for instance, in my case).From 1982 until the present writing, I have been the recipient of a number of honors and awards for my research. Naturally, I have been very pleased to be the recipient. Yet, in thinking back about what aspects of my research have given me the greatest pleasure, I would not place the honors and awards first. I think that my greatest pleasure has come from each first demonstration in my laboratory that experiments designed to test a new hypothesis developed to explain some earlier, often puzzling or paradoxical finding, have given results consistent with the hypothesis. It is not just the immediate pleasure of obtaining such results but also the anticipated pleasure of discussing the results with others doing research in the same area - obviously an ego supportive aspect.I still enjoy doing bench work in the laboratory with my co-workers. The research still is rather "old fashion" pharmacological research. I was very lucky to stumble on unexpected results in 1978 that led to the finding of endothelium-dependent relaxation and EDRF, and eventually to NO; for if I had not, I would probably have still concentrated on research on receptor theory and mechanisms, and been left far behind by others in that field who have so brilliantly and successfully developed and used molecular biological and other advanced methodologies in their research.From Les Prix Nobel. The Nobel Prizes 1998, Editor Tore Frängsmyr, [Nobel Foundation], Stockholm, 1999 This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate. To cite this document, always state the source as shown above. > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 4.gif (140 X 198)" border=0 align=absmiddle>Louis J. IgnarroThe Nobel Prize in Physiology or Medicine 1998 1/3 of the prizeUSAUniversity of California School of Medicine Los Angeles, CA, USA b. 1941 生平介绍The first two decades of my life were spent in the New York City area, where the families of both my parents had settled in the 1920s after immigrating from Italy. My father had been a ship builder in Naples but my mother was still a young child when she came from Sicily. They met for the first time in Brooklyn, New York in the 1930s, were married, and then moved to the nearby coastal city of Long Beach. I was born on May 31, 1941 in Brooklyn and my brother, Angelo, followed on January 10, 1944. My father worked as a carpenter, whereas my mother elected to bring up her two sons at home.Long Beach was a beautiful town, about 25 miles east of New York City located on the south shore of Long Island. We had a lovely home within walking distance of the beach along the Atlantic ocean. I can still recall walking to the beach and going for a swim nearly every day in the summer. My greatest joy each morning was building gigantic sand castles using dripping sand wetted by the incoming tide. All my friends believed and predicted that I would grow up to become an architect or engineer. This view was reinforced by my eagerness even as a young child to disassemble anything I could find and put it back together again. The joy of discovering that I could actually get the object to function again was quite rewarding and satisfying. But my greatest joy came when I was 8 years old. To my surprise and delight, mother and father finally responded favorably to my relentless request to have a chemistry set, and bought me one. I can recall vividly following every step of every experiment and becoming overjoyed at the success of each one. This was much more fun than building sand castles on the beach. My inquisitiveness drove me to the library to study more applied aspects of chemistry. Soon after completing dozens of additional experiments and going through several larger chemistry sets, I realized that what I really wanted to accomplish was to build a bomb and to send up a rocket. After about one year of experiments, I finally achieved those goals, albeit at the expense of numerous horrified reactions from the neighbors.My interest in chemistry remained strong at Central Grade School and Long Beach High School, which led me to apply to Columbia University in New York City to study chemistry and pharmacy. I was especially pleased when I learned that I had been accepted to the freshman class at Columbia. I wanted to attend a university that was within commuting distance of home because I did not want to leave my family and friends in Long Beach. During my high school years I had developed a great interest in playing ball and racing cars, and I did not want that to come to an end, at least not just yet. My favorite sport was one-on-one stickball, the New York City sport of sports, where a "bouncy" rubber ball is thrown by the opponent pitcher against a brick or cement wall on which is drawn a "strike zone". The batter uses a stick conveniently detached from a suitable broom or mop to hit the fast pitched ball. When I was not playing stickball I was building and racing cars at the West Hampton Drag Raceway. I guess I could never get away from taking things apart and putting them back together again. Indeed, I spent many long hours thinking about whether I should study chemistry or open up my own drag racing shop out on Long Island. Well, chemistry it was. I took dozens of chemistry courses, but a course in pharmacology, although poorly taught, really caught my attention. I studied the subject well beyond the course requirements and tried to hang around the pharmacology laboratories as often as I could. The result of this was my application to graduate school in pharmacology upon graduation from Columbia University in 1962.I was delighted to be admitted to the pharmacology program at the University of Minnesota in Minneapolis, which was considered to be one of the best departments of pharmacology in the nation at that time. Actually, I had applied to the University of Wisconsin in Madison, where the department was located when I first applied. But for one reason or another, the entire department was relocated from Madison to Minneapolis just after I had been accepted in Madison. A bit confused, I reported to Minneapolis in September of 1962 to study pharmacology. At first, things were difficult for me because I had left my family, friends, stickball, racing cars and the beach behind. And then things got even worse when I experienced my first winter season of -40°F with winds of 30 mph. But I survived my first winter and went on to enjoy the upper midwest and the "Big Ten" college football games.My studies in graduate school involved developing a better understanding of why and how neurons of the sympathetic nervous system innervate the heart and produce and release norepinephrine. I spent three of the most intense years of my life in the laboratory, where I was determined to unravel every bit of information possible within the time frame allotted to me to satisfy the research requirements for the PhD degree in pharmacology. My research was different from most in that it required, in addition to pharmacology, a great deal of knowledge in several other distinct disciplines such as physiology, biochemistry and anatomy. My major, of course, was pharmacology and I selected cardiovascular physiology as my minor. But that was insufficient, so I took several additional courses in biochemistry and anatomy. The most demanding course I took was enzymology, taught by Paul Boyer, who was awarded the Nobel Prize in Chemistry last year (1997). I have not stopped using enzymology in my research since taking that course. My research turned out to be acceptable to my committee, chaired by the late Frederick E. Shideman, MD, PhD, who was also Chairman of the Department of Pharmacology at the University of Minnesota. He decided that I should write four separate manuscripts on my thesis research and that we should submit them to the Journal of Pharmacology and Experimental Therapeutics. The editors of the journal accepted all four papers and published them back-to-back in one issue of the journal, a feat never again repeated either by the journal or by me.After Minneapolis, I accepted a postdoctoral position at the National Institutes of Health in the Laboratory of Chemical Pharmacology in the National Heart, Lung and Blood Institute. My mentor was Elwood Titus, a brilliant scientist who was able to mix chemistry and pharmacology with the greatest of ease. I tried to learn as much as I could from him in two years. Perhaps I tried a bit too hard. For example, he asked me to study the chemistry of beta adrenergic receptors and I decided that I was going to isolate, characterize and elucidate the chemical structure not only of beta but also of alpha adrenergic receptors, all in two years. Having published four consecutive papers in a distinguished journal on my first try, I thought that my research career was going to be a breeze. The N.I.H. proved to me that this was not going to be the case, and it was not. My work resulted in only one publication, but the agony of frustration caused me to mature quickly. The atmosphere of the N.I.H. was highly conducive to learning science and I had the opportunity to discuss my work and research in general with Bernard Brodie, Jim Gillette, Julius Axelrod and other distinguished scientists.My first real job after my research training was with the drug industry. Geigy Pharmaceuticals recruited me in 1968 with an attractive package including the responsibility of heading the biochemical and antiinflammatory program. Although this was an entirely new research topic for me, I accepted the position because of the enormous responsibility that would suddenly be mine. The work was quite satisfying in that I became a part of a larger group whose efforts led to the development and marketing of a new nonsteroidal antiinflammatory drug (diclofenac). About half way through my career at Geigy, my daughter, Heather, was born. I recall that day vividly (January 10, 1970) because I had to rush my wife to the nearby hospital in the midst of a snow storm. But all turned out well and I found myself devoting a great deal of time to something other than my own research. With the birth of Heather came a move from a small apartment in Hartsdale to a much larger unit in Irvington on the Hudson. This was a lovely neighborhood in which to raise a child.In addition to my work on drug development, Geigy allowed me the freedom to pursue basic research in biochemical pharmacology, which led to my interest in studying the relatively new cyclic nucleotide, cyclic GMP. Although I enjoyed my work at Geigy Pharmaceuticals, when the company merged with Ciba Pharmaceuticals I decided to try my hand at academic research and teaching. In January of 1973, I accepted the position of Assistant Professor of pharmacology at Tulane University School of Medicine in New Orleans. I chose to go to Tulane because I wanted to continue my research on cyclic GMP, and there was a young pharmacologist at Tulane with the same interest. We moved to New Orleans, where we bought our first home in Terrytown, an attractive nearby suburb.My interest and motivation in studying the possible physiological significance of cyclic GMP grew and grew during my first two years at Tulane. Thanks to my own laboratory and those of other interested collaborators, we made many significant contributions to the field of cyclic GMP and cyclic nucleotide research in general. My early work with cyclic GMP involved leukocytes and the heart, but this eventually led to an interest in blood vessels. I recall reading an interesting paper by Ferid Murad's group in 1977, in which nitric oxide and various nitro compounds were shown to activate the cytosolic form of guanylate cyclase and to elevate cyclic GMP levels in various tissues. Nitroglycerin was one of those nitro compounds that Ferid had studied and speculated might release nitric oxide which then activated guanylate cyclase. It occurred to me that nitric oxide might account for the vascular smooth muscle relaxing action of nitroglycerin and that cyclic GMP might be the second messenger responsible for mediating the vasorelaxant effect of nitric oxide. In 1979 we published the first account of the capacity of nitric oxide to relax vascular smooth muscle. We purchased a small cylinder of nitric oxide gas, made a dilution in nitrogen (nitric oxide is very unstable in the presence of oxygen), and injected a fine stream of gas bubbles into an organ bath in which was mounted a strip of bovine coronary artery precontracted by addition of phenylephrine. The result was a rapid and profound relaxation of the coronary artery strip. This vasorelaxant effect of nitric oxide was blocked by addition of hemoglobin, which promotes oxidation of nitric oxide, and methylene blue, which had been known to inhibit guanylate cyclase. And so we knew right away that nitric oxide was probably responsible for the vasorelaxant effect of nitroglycerin and that cyclic GMP was the likely ultimate mediator of relaxation, just as Ferid Murad had predicted.We wondered whether the platelet antiaggregatory action of certain nitrovasodilators could also be attributed to nitric oxide and cyclic GMP. A relatively straightforward experiment was conducted with human platelet-rich plasma, in which we examined the influence of added nitric oxide on ADP-induced platelet aggregation. The results were dramatic. Nitric oxide potently inhibited platelet aggregation and actually reversed aggregation once it had occurred. This effect was mediated by cyclic GMP. Thus, at least two biological actions of nitric oxide were clear from these early studies. Nitric oxide is a vasorelaxant and inhibitor of platelet aggregation, and both effects are mediated by cyclic GMP.The next step was to elucidate the mechanism by which nitroglycerin is converted to nitric oxide by vascular smooth muscle. After reading nearly every paper in the field of organic nitrate esters and their vasodilator effects, I was motivated by the work of Phil Needleman, who showed that the vasodilator action of nitroglycerin and other organic nitrate esters was dependent somehow on the presence of thiols. A long and tedious series of experiments in my laboratory led to the discovery that thiols were required for the activation of guanylate cyclase by nitroglycerin and related nitrovasodilators. Interaction between thiols and nitro compounds led to the formation of intermediate S-nitrosothiols, which were chemically unstable and decomposed to liberate nitric oxide gas. Depletion of tissue thiols resulted in diminished vasorelaxation by nitroglycerin because nitric oxide could no longer be generated. Moreover, tolerance to the vasodilator action of nitroglycerin appeared to be due to thiol depletion, which could be reversed by adding back thiols in order to generate more nitric oxide. This work was published in 1981 in the Journal of Pharmacology and Experimental Therapeutics.Having elucidated the mechanism of action of nitroglycerin as a vasodilator, the next step was to understand how nitric oxide activates guanylate cyclase. An elegant series of experiments was published in the late 1970s by Patricia Craven and Fred DeRubertis, showing that activation of guanylate cyclase by nitric oxide might require the presence of heme. This made sense to me because heme iron had long been known to have a high binding affinity for nitric oxide. Suppose guanylate cyclase had a heme prosthetic group that bound nitric oxide and somehow became activated to generate more cyclic GMP from GTP? In 1981 we set out to purify and characterize guanylate cyclase from bovine lung. A young biochemically trained postdoctoral fellow from Yale University, Mike Wolin, joined my laboratory to tackle this project. After an incredibly long and tedious series of experiments, each often lasting for 96 consecutive hours, we found the heme in purified guanylate cyclase. Subsequent experiments revealed that the presence of enzyme-bound heme was an absolute requirement for guanylate cyclase activation by nitric oxide. We went on to propose that nitric oxide reacts with heme iron to alter the configuration of the catalytic binding site for GTP and promote the conversion of GTP to cyclic GMP and pyrophosphate. In conducting these experiments, we discovered that the non-nitric oxide containing substance, protoporphyrin IX, activated heme-deficient guanylate cyclase by kinetic mechanisms that were indistinguishable from the mechanism by which nitric oxide activates heme-containing guanylate cyclase.Although the above observations were exciting, they were also puzzling because it was unclear why mammalian cells were so sensitive to nitric oxide. Why do we have receptors for nitric oxide, an air pollutant and a metabolite of nitroglycerin? Was it possible that our own cells actually produced nitric oxide or nitroglycerin but we were unaware of it? In 1983, my laboratory set out to determine whether or not mammalian cells can produce either nitric oxide or a nitro compound that could be metabolized to nitric oxide. A separate project in the laboratory was to study endothelium-dependent vasorelaxation and to attempt to identify the mysterious "EDRF" (endothelium derived relaxing factor) discovered three years earlier by Robert Furchgott. Both research projects came together in 1984 when we suddenly realized that EDRF and nitric oxide possessed similar pharmacological and biochemical properties. EDRF and nitric oxide were both chemically unstable and both activated guanylate cyclase and elevated tissue levels of cyclic GMP. The cyclic GMP elevating and vasorelaxant effects of both EDRF and nitric oxide were inhibited by addition of methylene blue to organ chambers. These findings, reported in 1984, prompted me to ascertain whether EDRF, like nitric oxide, required bound heme on guanylate cyclase in order to activate the enzyme and stimulate cyclic GMP formation. I can recall vividly the positive results of the first experiment, and I knew we had it. EDRF must be nitric oxide. I first reported these findings in the summer of 1986 at a vascular conference held at the Mayo Clinic in Rochester, Minnesota. Unexpectedly, at least to me, my colleague Robert Furchgott presented his own evidence that EDRF might be nitric oxide. I presented additional evidence a few months later at the fall American Heart Association meeting in Dallas and at the spring FASEB meeting in Washington, DC in 1987. So now it was clear why nitric oxide is such a potent vasorelaxant. This small lipophilic chemical is produced by vascular endothelial cells and functions to decrease vascular smooth muscle tone and to inhibit platelet aggregation.The frenzy and excitement of these times in the mid-1980s was stalled at times by my divorce and my decision to leave Tulane University and begin a new personal life and academic career at UCLA School of Medicine. I moved to Los Angeles in May of 1985 and bought a small home in Encino, just 12 miles from the UCLA campus. My daughter, Heather, joined me in 1988 and attended California State University at Northridge. As a result of witnessing her dad's commitment to many long hours of research and teaching, Heather chose to major in radio, film and television. At first, her decision to shy away from a career in science concerned me, but then I realized how talented she was and how successful she would become.The discovery that EDRF was nitric oxide led to an avalanche of studies that created an exciting new field in biological research. New physiological and pathophysiological roles for nitric oxide were being discovered on a weekly basis. In record time, several prominent laboratories elucidated the biochemical mechanisms involved in the synthesis of nitric oxide by various cell types. While studying the relaxant effects of nitric oxide on vascular and nonvascular smooth muscle from corpus cavernosum erectile tissue, we realized that the naturally occurring physiological neurotransmitter involved in the erectile response in mammals was unknown. John Garthwaite had just reported that nitric oxide was a neuro transmitter in the brain, and we wondered whether or not nitric oxide could be the neurotransmitter in the so called nonadrenergic noncholinergic neurons that were known to innervate the corpus cavernosum smooth muscle. After all, nitric oxide released from such nerves would be expected to diffuse into the nearby vascular and nonvascular smooth muscle and cause relaxation. Such an effect could account for the marked relaxation of both vascular and nonvascular smooth muscle that accompanies the erectile response and allows for the engorgement of blood in the sinusoidal or trabecular network of blood vessels in the corpus cavernosum. The first carefully designed experiment was successful. Electrical stimulation of strips of rabbit corpus cavernosum caused a transient but marked smooth muscle relaxation that was prevented by addition of a nitric oxide synthase inhibitor and enhanced by addition of a cyclic GMP phosphodiesterase inhibitor. Addition of authentic nitric oxide to organ chambers mimicked the effects of electrical stimulation. A subsequent experiment revealed that electrical stimulation results in the production of nitric oxide in the corpus cavernosum. Further studies using human tissue showed that patients with impotence suffer from an impaired nitric oxide cyclic GMP pathway in the erectile tissue, and this work laid the foundation for the development by others of a drug that proved to be effective for the treatment of impotency in humans. Sildenafil (ViagraR) promotes the erectile response by inhibiting a specific isoform of cyclic GMP phosphodiesterase and allowing cyclic GMP to accumulate when guanylate cyclase is activated by nitric oxide released from the nerves innervating the erectile tissue.In the fall of 1994, I met Sharon Elizabeth Williams, a lovely and charming medical student here at UCLA. Sharon had been a nurse anesthetist for several years and then decided to obtain an M.D. degree in order to practice anesthesiology at a more professional level. After graduating from UCLA, Sharon moved to the east coast to begin her internship and residency at Johns Hopkins University. Shortly after her move, we started dating by long distance and were married in July of 1997. A year later, in the spring of 1998, Sharon transferred back to UCLA to continue her residency in anesthesiology. Finally, we were together. During the week we reside in an apartment adjacent to the UCLA campus in Westwood and we spend our weekends in my home in Malibu.As a result of my work during the past decade, many investigators jumped in to extend our findings. This led to the development of close collaborations with numerous laboratories and the formation of close and genuine friendships in many different parts of the world. I treasure these friendships even more than the awards I have received for my research accomplishments. I also realize that these accomplishments would not have been possible without the interest, hard work, and commitment on the part of my technical assistants, graduate students, postdoctoral fellows, medical fellows, visiting scientists, research collaborators at home, and collaborators at other institutions.Another rewarding development has been my discovery that I also have a real knack for and love of teaching what I know to medical and graduate students. I have consequently made teaching a regular part of my schedule since I came to UCLA and I cherish the Golden Apple teaching awards I have won from my classes. I trust that I have helped guide at least some of these young people toward careers that will be a blessing to them and to humanity. In my own case, the combination of biomedical research and teaching continues to provide me with an exciting and useful life, and I am exceedingly grateful.From Les Prix Nobel. The Nobel Prizes 1998, Editor Tore Frängsmyr, [Nobel Foundation], Stockholm, 1999 This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate. To cite this document, always state the source as shown above. > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 5.gif (140 X 198)" border=0 align=absmiddle>Ferid MuradThe Nobel Prize in Physiology or Medicine 1998 1/3 of the prizeUSAUniversity of Texas Medical School at Houston Houston, TX, USAb. 1936生平介绍： My father, Jabir Murat Ejupi, was born in Albania in 1892 and was the oldest of four children. His mother died when he was 13 years old. He and his family were shepherds and he subsequently ran away from home to sell candy in the Balkan countries as a teenager for several years. Although he had less than a year of education, he learned to speak seven languages before he died at the age of 84 in 1976. He met a group of other teenagers in Austria and they immigrated to the United States. The immigration officer at Ellis Island, August, 1913, asked his name, after which the officer declared him to be John Murad and stamped his papers. It was not uncommon to have names changed and abbreviated upon immigration. After working briefly in the steel mills and factories in Cleveland and Detroit, he settled in Chicago where he had several friends. His career was quite diverse and although he never admitted it, I learned subsequently from some of his colleagues that he was quite a playboy with fancy automobiles, perhaps the reason for my love of nice cars.My mother, Henrietta Josephine Bowman, was born in 1918 in Alton, Illinois and was the third of six surviving children of Elizabeth Lillian and Andrew Orvie Bowman. My grandmother was a kind and wonderful woman. Only six of her eleven children survived due to stillbirths and some died of diseases and other conditions of poverty. My mother went to grade school for several years before she too quit to help her mother and younger siblings while her mother and two older sisters went to work. My grandfather was a carpenter who generally worked part-time and frequently spent his modest paycheck at the local bars before going home. The childhood poverty of both my parents and their minimal education did much to influence me and my two younger brothers in our education and career choices. One brother became a dentist and the other a professor of anthropology with a PhD degree.My mother also ran away from home at 17 in 1935 to marry my father who was 39. I was born September 14, 1936 at home in their hot and small apartment over a bakery in Whiting, Indiana. My brothers John Abderhaman and Turhon Allen were born in 1938 and 1944. We were raised in a four room aparttment behind my parents' restaurant in Whiting, Indiana. This small apartment undoubtedly influenced my desire for large expensive homes.The restaurant business had a profound effect on my future and that of my two brothers. When we were able to stand on a stool to reach the sink we washed dishes and later when we could see over the counter, we waited tables and managed the cash register. I did this throughout grade school and high school each evening and on weekends. I created a game from those chores and learned to memorize all of the customer's orders in our restaurant with a capacity of 28 customers and before they left I would tally their bills mentally and meet them at the cash register. I met a diverse and wonderful group of customers that ranged from laborers in the local refineries and steel mills to local bankers, businessmen, families and school teachers. My parents worked long hours as is typical of a family business, particularly a restaurant. My father worked 16 to 18 hours daily while my mother put in similar hours between the restaurant and raising three children. They owned the building that also included two other small apartments, another small business and 21 sleeping rooms upstairs. Many of the tenants were old and retired and my mother would often care for them and prepare their meals when they were sick. I learned from my mother and grandmother Bowman about compassion and generosity for people and this in turn influenced my career choice in medicine. My father taught me some business skills and how to repair numerous items that were continually breaking down in this old building. He was quite good at remembering how he took anything apart in order to repair it and reassemble the pieces as I stood at his side as a youngster passing him tools.With this background I knew that I wanted considerable education so I wouldn't have to work as hard as my parents. Also, I knew at the age of 12 that I was going to become a doctor. My parents always encouraged us to get an education and establish a profession. However, my brothers and I grew up with considerable freedom whether it was saving or spending our tips from the restaurant or our career choices. This was also applied to our religious choices as my father was Muslim, my mother Baptist and we were raised in a Catholic community. Subsequently, my brothers became Catholic when they married Catholic wives and I was baptized Episcopalian in college. My wife of more than forty years is Presbyterian, two of our daughters married Jewish men and one married a Catholic man.In eighth grade the class was asked to write an essay of our top three career choices. My choices were 1) physician, 2) teacher and 3) pharmacist (in 1948 clinical pharmacology was not yet a discipline in medicine). Today I do just that, as I am a board certified physician and internist doing both basic and clinical research with considerable teaching in medicine, pharmacology and clinical pharmacology and with a PhD in pharmacology. While I am probably working much harder and longer hours than my parents, I certainly love my profession and have considerably more enjoyment and disposable income than they did. Until my graduation from high school only three of my cousins had finished high school and no relatives had ever gone to college. Grade school, middle school and high school were relatively easy for me and with little studying I was an honor student every semester graduating 5th in my high school class. Fortunately several high school teachers, some of whom frequented our restaurant, Jack Taylor in Spanish and history, LaDonna Thue Elson in art, Bernard Quebeck in music, Jesse Allen in math, and coach Peter Kovachic convinced me I had some potential and were wonderful counselors and advisers. I lettered in track and cross country as a distance runner in the one and two mile events and music. I also played football and basketball but spent most of my time keeping the bench warm. I played offense and defense left guard at 5'11 " and 140 pounds. After three monsters ran over the top of me I spent more of my energy with distance running in cross country. While I started to play golf in grade school, I stopped playing for many years during college and medical training and I continue to struggle with my game after I began playing again about 20 years ago.There was one notable friend since kindergarten, Ronald Delismon, who influenced me considerably. We competed constantly with everything: grades, chess, fencing, sports, etc. Today he is an aeronautical engineer recently retired from Boeing. His projects were always top secret such as the stealth bomber and some of the star war defense projects. He would never discuss his work with me for security reasons and often joked with me by saying, "if I told you, I would then have to kill you". After 57 years we remain the best of friends and still compete, generally at golf, skiing and more pleasant encounters. His recent comment was, "one Nobel to zero".The University of Chicago had a new program in the 1950s that accepted students after three years of high school and friends in the restaurant who were alumni from the University of Chicago encouraged me to apply. However, after considerable thought I decided not to enter college prematurely but rather completed my senior year in high school. In retrospect, this was the correct decision for me as my senior year in high school was wonderful. I coasted through the year with excellent grades and lots of fun participating in the school's chorus and took the lead in several operettas. This was probably the only year in school where I wasn't compulsive about grades and didn't study constantly.Since my parents couldn't afford to help me with my college costs, I looked for a school that offered the best scholarship. I considered the military programs at the Naval Academy and Westpoint, but I knew I wouldn't have received the biology training for medical school since these were primarily engineering programs with a requisite four years of military duty afterwards. I competed successfully for a Rector Scholarship at DePauw University in Greencastle, Indiana, a small and excellent liberal arts university and went there from 1954 to 1958 on a tuition scholarship. The first year my grades were okay but not great with several A's, one C and the rest B's due to the hazing and distractions of being a pledge in the fraternity. In subsequent years my grades progressively improved as I was developing more self confidence and better study habits. I lived in "annexes", or small apartments with other fraternity brothers since the fraternity couldn't accommodate all of us and I generally chose other premeds as roommates. We often studied together and competed for grades. I was the scholarship chairman of the fraternity and remained a premed major with a second major in chemistry as I enjoyed both biology and chemistry. Throughout college I waited tables, taught the anatomy and embryology labs and worked one and sometimes two jobs during the summers to cover my expenses. If I had only one summer job I would take additional classes at one of the local extensions of Indiana University for additional math or literature classes in order to take more courses in biology, chemistry, physics or Greek and Latin at DePauw. The Greek and Latin courses in high school and college were of great value subsequently in learning the root derivatives of many scientific words.In the spring of my junior year in 1957 on spring break in Fort Lauderdale, Florida, I met Carol Ann Leopold, my wife to be. She and her family were from St. Louis. We were at DePauw together where she was an English and Spanish major planning to become a teacher. Although she dated many of my fraternity brothers, I had not met her previously. After spring break we began to date and I gave her my fraternity pin a month later. Our dates were primarily "study dates" at the library (the only thing I could afford) and after mostly A's in my senior year I was elected to Phi Beta Kappa. At Christmas we were engaged and married within several weeks of graduation from DePauw on June 21, 1958.During my senior year of college I began to apply to medical schools and planned to go to Washington University Medical School in St. Louis. However, my faculty advisor Forst Fuller, a professor in the biology department and also my mentor during an elective research project to understand how fish managed calcium metabolism without parathyroid glands, suggested that I consider a new MD-PhD program at Western Reserve University. A fraternity brother, Bill Sutherland, also advised that I consider this new combined degree program that his father Earl Sutherland, Jr initiated in Cleveland in 1957. The program paid full tuition for both degrees and provided a modest stipend of $2000 per year. I quickly applied and was interviewed on a Saturday morning in February of 1958 by the entire Pharmacology Department. Needless to say, I was awed by the attention they gave me and decided immediately to accept their offer. Carol, my fiancée, was somewhat concerned that I was now planning seven more years of education but she has always been understanding and supportive of my training, career path and numerous moves around the country. The game plan was to have Carol teach high school English as I went through the combined degree program. These plans abruptly changed within three months when Carol became pregnant. After teaching for only one semester, she was asked to resign when the pregnancy "began to show". Subsequently, she was a substitute teacher, part time secretary and hospital clinic coordinator as we progressed with our family; four girls, including a set of identical twins before I finished medical school and graduate school in 1965. Number five, the first boy, was born as I finished my residency in 1967. Fortunately, we didn't stop as planned after number four was born.As I entered the new combined degree program my mentors were Earl Sutherland, Jr. the chairman of the Pharmacology Department and Theodore Rall a new young assistant professor and collaborator of Sutherland's. The year before I arrived they had discovered cyclic AMP as a "second messenger" of epinephrine - and glucagon-mediated effects on glycogenolysis in liver preparations. My assignment was to show that the catecholamine effects on cyclic AMP formation were due to effects through the beta adrenergic receptor. Alquist had previously reported that adrenergic effects could be classified as alpha or beta depending on the relative potency of several catecholamines. The new and only beta adrenergic receptor antagonist, dichloroisoproterenol, had also been just described and was to become a useful antagonist in our work. We found that catecholamine effects on adenylyl cyclase activation in both heart and liver preparations were, indeed, due to beta adrenergic effects as shown by the relative potencies of l-isoproterenol, l-epinephrine and l-norepinephrine with inhibition by dichloroisoproterenol and failure of alpha blockers and agonists to have effects. I also found that acetylcholine and other cholinergic agents inhibited adenylyl cyclase preparations, the first description of hormones, inhibiting cyclic AMP formation. I then became interested in agents that could block the effects of cyclic AMP on phosphorylase kinase and phosphorylase activation. This required some novel assays and an acquaintance with numerous cyclic AMP analogues and other nucleotides including cyclic GMP, cyclic IMP, cyclic CMP, etc. Many of these nucleotides and their analogues were synthesized by Theo Pasternak, a professor from Geneva who was on sabbatical collaborating with Sutherland and Rall. This work subsequently influenced my desire to work with cyclic GMP as described in my Nobel lecture. Later I again played organic chemist to make some nucleotides.I was first in my class every year in medical school and graduate school. This was a wonderful and exciting time in my life working with these mentors, watching a new area of biology develop and actively participating in the work. I loved research as Earl Sutherland was quite a visionary who was able to bring together multiple disciplines and areas to apply to his work. Ted Rall taught how to do those fool proof "Sunday experiments" as we came to call them. It was on Sundays that I could design and conduct those large and complex experiments with all of Ted's required controls such that the data were "publishable". We and others in the department were able to determine that multiple hormones including catecholamines, cholinergics, ACTH, vasopressin, etc. could increase or decrease adenylyl cyclase activity and cyclic AMP formation. Prior to this the view of Sutherland was that receptors and adenylyl cyclase were a single macromolecule or a tightly associated complex in cell membranes. My work as a student and the work of others questioned this hypothesis and suggested that different receptors for this growing list of hormones must be coupled to adenylyl cyclase in yet to be determined complex ways (see Gilman's and Rodbell's Nobel lecture of 1994 for a greater description of their subsequent work).I also enjoyed medical school and found myself learning everything presented before me. I knew that I couldn't determine what was to be true and important and many of our faculty acknowledged this as well. Since anything could be important, I began to learn everything taught. The new experimental integrated organ-system approach to medical education at Western Reserve permitted me to assimilate and integrate information more readily. I also thoroughly enjoyed my clinical rotations in medicine, surgery, OB-GYN, pediatrics, orthopedics, neurology, etc. There were few clinical rotations that I didn't think about as a possible discipline for my future academic career. I subsequently learned that I was at the top of the medical school and graduate school class each year and received prizes at graduation for both clinical medicine and research. I was in my element and loved it. There was no doubt in my mind about an academic career in medicine, research and teaching.In order to supplement my stipend with so many children, I moonlighted at the Cleveland Clinic working one or two nights per week on the OB-GYN service to follow mothers with pelvic exams as they progressed through labor, assisted in deliveries and Caesarian sections and then scrubbed tables and floors after each delivery. All of this for $20.00 per night for 12 hours of work from 7:00 p.m. to 7:00 a.m. one or two nights per week for four years. On slow evenings I was able to study, analyze lab data and write research protocols. Some nights required that I work all night and then attend a full day of classes the next day. I continued this during my clinical clerkships requiring my absence from my family as often as 4 to 5 nights per week. However, I tried to have dinner with my family as often as my schedule permitted. My wife and children were very understanding. They grew up as wonderful children and adults in spite of my absence, obviously due to a devoted wife and mother. My current fetish is my 5 grandchildren who I try to spend as much time with as possible, undoubtedly due to my guilt as an absent father. I did manage to spend several weeks each summer with my family as we took them camping all over the U.S. to various scientific meetings. There are only a few states where we have not camped together as a family and they all became proficient swimmers at a young age.I decided to go to Massachusetts General Hospital for my internship and residency in medicine (1965-67). What a wonderful experience this was with some of the worlds' leading scientists, teachers and clinicians. Our group of 14 housestaff included exciting bright minds such as Tom Smith, Tony Gotto, Jim Willerson, Ed Scolnik and others that had considerable influence on me. My attendings and chief residents included Alex Leaf, Dan Federman, Roman DeSanctis, Frank Austen, Sam Thier, Ken Shine and others. As a resident Joe Goldstein and Mike Brown were two of our interns. I couldn't have asked for a greater introduction to medicine in spite of being on call every other night and weekend. I did, however, miss the laboratory and each spring I found myself in the library reading many of the abstracts of the Federation meeting (currently FASEB meeting) to see what I was missing in "second messengers and hormone signaling". I generated a notebook that contained numerous "obvious experiments" to be done. When I subsequently went to NIH as a clinical associate in the Heart Institute I was able to do many of the planned experiments in Martha Vaughan's laboratory. She too was an excellent mentor with a style different from either Sutherland or Rall. She gave me considerable freedom to pursue a number of areas related to cyclic AMP and hormonal regulation. Her husband, the late Jack Orloff, while superficially a gruff and tough man, was a sensitive person and talented scientist. I was indeed fortunate that they and many others at NIH influenced my thinking and career planning. I soon learned that I had numerous role models and attempted to extract the best features of each as I planned my career path and future.I remained at NIH for more than three years (1967-70) when the University of Virginia called to recruit me to develop a new Clinical Pharmacology Division in the Department of Medicine with an appointment as an Associate Professor in medicine and pharmacology. I couldn't resist the offer from Ed Hook, the new chairman of medicine and Joe Larner, the new chairman of pharmacology. Other faculty such as Tom Hunter, the Vice President of Medical Affairs, Ken Crispell the Dean, Bob Berne, Bob Haynes and others influenced my decision to leave NIH. I had known Larner, Berne and Haynes since they were faculty at Western Reserve when I was a student. Charlottesville was also an appealing place to raise my five children. Some colleagues around the country, particularly David Kipnis, another one of my role models, questioned me about going to Charlottesville. Just the previous year I called him to apply for a fellowship in endocrinology at Washington University. I was then 33 years old with 5 children and his advice was appropriate. He said, "Fred, time for you to get a job and support your family", and I took his advice to heart.I joined the faculty at the University of Virginia, September 1, 1970 and nervously thought about how I could launch my own independent research career. I decided to work with cyclic GMP as it was beginning to emerge as a possible new "second messenger" to mediate hormone effects. This is detailed in my Nobel lecture. I remained at the University of Virginia from 1970 to 1981 where I was promoted as one of the youngest professors in 1975; I was also asked to become the Director of their Clinical Research Center in 1971 and the Director of Clinical Pharmacology in 1973. I built a research program with both clinical and basic studies and started to recruit many exciting students and fellows to work with me. Of the 82 fellows and students I have trained and collaborated with to date twenty are professors, chairmen, research directors and division chiefs around the world. I view them as offspring and keep in contact with most of them in my travels. There is no question that one of my greatest accomplishments is to have participated in the training of such successful scientists in my own laboratory and also influenced the careers of many talented medical students, graduate students and housestaff.After looking at many university positions around the country as a chair of medicine or pharmacology and industrial positions, I decided to go to Stanford in July 1981 as Chief of Medicine of the Palo Alto Veterans Hospital, a Stanford affiliated hospital. I was a professor of medicine and pharmacology and the associate chairman of medicine. While it was difficult to leave many friends and colleagues at the University of Virginia where we conducted the first experiments with the biological effects of nitric oxide, I couldn't turn down this exciting opportunity at Stanford. Ken Melmon was chairman of medicine and during our first three years together we recruited about 30 new young faculty. Inspite of the large administrative and clinical teaching demands, I continued to supervise a large and productive laboratory with about 15 students, fellows and staff. Trainees continued to come to our laboratory from all over the world. Some of my students and fellows subsequently went to medical school and after completing residencies have become very productive physician scientists at a number of institutions.After a stint as Acting Chairman of Medicine at Stanford (1986-88), I left to become a Vice President at Abbott Laboratories as I was becoming concerned about managed health care on the horizon and its possible effects on patient care, research and education. After considering several industrial positions, I chose Abbott primarily because of its president Jack Schuler, a sales and marketing person with an MBA from Stanford who also had considerable vision. We worked well together as he taught me many business principles and I taught him about drug discovery and development. I enjoyed the access to all of Abbott's resources, scientific staff, instrumentation and what initially seemed like an unlimited research budget. I eventually learned that one can never have enough resources when one looks for novel therapies of major diseases; it's an expensive undertaking. Nevertheless, in four years of directing their pharmaceutical discovery and development programs we were able to discover many novel drug targets and we brought forward about 24 new compounds for clinical trials for various diseases. I continued to have a very productive lab with two NIH grants, some outside funding for fellows and about 20 scientists working with me on nitric oxide and cyclic GMP. The administrative demands and travel were considerable since I was a corporate officer, vice president and also overseeing many industrial collaborations around the world. When I left Abbott I was supervising about 1500 scientists and staff and probably earned the equivalent of an MBA from the experience on the job plus periodic management courses required by the company. Before my arrival at Abbott the company had no postdoctoral fellows or extramural funding. When I left we had about $3.5 mill. per year of extramural grant support and about 35 fellows in pharmaceutical research. Unfortunately, Abbott reorganized its senior management and my business roll models were asked to leave. As Abbott's senior scientist I found myself wedged between upper management, the marketing staff and the scientists and constantly was defending my decisions about the research programs. There were always considerable marketing pressures on me that in my opinion were often the wrong decisions to develop novel therapeutics for diseases without adequate therapy.I left Abbott in 1993 to be a founder, President and CEO of a new biotech company, Molecular Geriatrics Corporation. The plan was to create another intensive research-based biotech company. Unfortunately, my investment banker never raised the amounts of money promised and he eventually lost a major personal fortune with his leveraging tactics. I found myself skipping around the world to find investors and partners to keep the company afloat and pay the bills. After a partnership with a major pharmaceutical company and some more financing as a private company, I left to rejoin academics, hopefully much wiser.After considering a number of Vice President, Dean positions and Chairmanships, I realized that such positions would probably totally remove me from the laboratory, fellows and students, things I could not give up. In April 1997, I became the University of Texas-Houston's first chairman of a newly combined basic science department, Integrative Biology, Pharmacology and Physiology. I am also creating a new Division of Clinical Pharmacology jointly between our department and medicine. I plan to continue an active basic and clinical research program and will participate in clinical medicine and teaching again. Thus, I have come full circle. I am back in my academic element again and I love it. I also expect to continue some business adventures and exercise my entrepreneurial skills, areas that I also enjoy and view as lucrative hobbies. The freedom and intellectual environment of academic medicine and bright young students and fellows are exciting and a daily joy for me. After all, I hope to tell Ron Delismon some day "Two Nobels to zero".From Les Prix Nobel. The Nobel Prizes 1998, Editor Tore Frängsmyr, [Nobel Foundation], Stockholm, 1999 This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate. To cite this document, always state the source as shown above. Addendum, September 2005It has been seven years since receiving the Nobel Prize for Physiology or Medicine for my work with nitric oxide and cyclic GMP. Life has been extremely busy. I have continued as chairman of the Department of Integrative Biology and Pharmacology at the University of Texas - Houston. I have expanded the department with the recruitment of six new, young, faculty, but some retirements and one death in the department kept us about the same size until some of the Dental School faculty joined us to consolidate some of the Dental School.My laboratory has been very active with about 15 to 18 scientists which is our usual size for the past 25 years. We have found ourselves redirecting some of our research interest with nitric oxide and cyclic GMP into some new directions to maintain our lead in the field and address new challenging questions with soluble guanylyl cyclase regulation, and the role of nitric oxide and cyclic GMP in mouse and human embryonic stem cell proliferation and differentiation.While research grant applications and support are always a nervous and time consuming process, several foundations and donors have generously supported our work and provided me with a handsomely endowed chair. These flexible and discretionary research funds have been most appreciated to pursue some of our research ideas, or accept another outstanding young scientist and trainee.The academic world like the business world is busily involved with layers of review and compliance. With about one-half of the number of scientists in our department that I had as Chairman of Medicine at Stanford University the paper work has probably tripled. The developers of e-mail should be admonished for destroying so much paper and trees and wasting hours and hours of my time. It seems that everyone in the University feels obliged to send me all of their email copies, often after four pages of addresses, followed by a brief useless message. Perhaps all employees should be allocated some annual allotment of emails which, if exceeded, results in salary reductions.Shortly after the Nobel Prize, I was asked to become the Director of our Institute of Molecular Medicine which I also accepted. For the past eight years I have held two senior positions in the University, as Chairman of the Department and Director of the Institute, each normally a full-time position. While at the University of Virginia, Stanford University, and Abbott Laboratories I also held two positions simultaneously. This is perhaps due to my workaholic tendencies.Being the Director of the Institute has also provided me with a significant building and recruiting opportunity. I was able to convince the University President to engage in a major fund raising campaign of $200 million. About half was used to build a new research building, of about 230,000 sq ft for the Institute, and the other half to recruit new faculty and scientists. The state of Texas, the Houston community, and local foundations have been most generous and we will be moving into our new research building in mid-2006. We expect to recruit 30 to 40 new faculty over the next three to five years, plus their research staff and trainees. We expect to triple our current number of scientists.A very time consuming activity in the past seven years has been my travel and lecturing. I have visited about 35 to 40 countries during the past seven years and traveled about 100,000 to 150,000 miles per year. I am invited to all sorts of meetings and functions around the world to dedicate buildings, hospitals, participate in conferences, scientific meetings, university seminars, consult for companies and governments, etc ... Presumably, it is assumed that by having received the Nobel Prize you are automatically an expert on all topics, fields and disciplines. I have even been invited on panels of Nobel Laureates to discuss methods to promote peace and education around the world. While participating in these many travels and meetings, I have also declined many invitations because time does not permit the travel or because of conflicts in scheduling. After all, I do have a day job and must be home occasionally to pick up my paycheck. I have had many memorable experiences and meetings and fortunately my wife, Carol, accompanies me on much of my travel. I have had meetings with Palestine's Chairman Yasser Arafat, Israel's Prime Minister Netanyahu, Presidents Lee and Chen of Taiwan, Chief Executive Tung of Hong Kong, President Medani of Albania, President Trajkovski of Macedonia, Premier Wen Jiabao of China, President Clinton, President Bush, many congressman and senators, governors and mayors.I have also met dozens of Nobel Laureates and attended conferences and meetings with them. Carol and I have become friends of many Laureates and their spouses and many travel and lecture as much as I do. For those who are retired, it hasn't been quite so demanding or difficult.My office and home are filled with artifacts, photographs, plaques, medals, statues, gifts and memorabilia. You receive numerous honorary degrees and certificates to wall paper your office at both work and home. We have run out of wall and surface space in my office and home and have begun to create piles to organize in the future. Since I have no plans for retirement, my children and grandchildren will probably have to organize the materials some day. One of the more humorous and memorable events was being grand marshall of the fourth of July Parade, with my wife and some of our grandchildren on the float, in my home town Whiting, Indiana. I have also given lectures to children in schools, churches and mosques. After a number of such requests, I prepared a children's educational video that can be viewed on the Nobel website that discusses the Nobel Prize and nitric oxide.On one of my several trips to Macedonia, my father's homeland, Carol and I arranged for one of our daughters to adopt a three-month-old Albanian baby girl. The trip, at our expense, required that I give several lectures and meet with many dignitaries. I consider this one of my best honorariums.The Nobel Prize has also influenced my grandchildren who have been asked to discuss nitric oxide and the Nobel Prize in their classes after a classmate's new premature sibling required inhaled nitric oxide for pulmonary hypertension. Press conferences with the media and radio, and television interviews are frequent. The media often wants to talk about Viagra, while I attempt to lead them into more medically significant areas: such as, pulmonary hypertension in premature babies, wound healing, endothelial dysfunction with atherosclerosis, hypertension, or diabetes, where nitric oxide can be much more important medically.While the Nobel Prize ceremonies in 1998 in Stockholm were quite a treat, the 100th anniversary Nobel Reunion in 2001 allowed me the opportunity to participate in the ceremonies and festivities, again, with less anxiety and an opportunity to absorb and savor the activities and functions. Life after the Nobel Prize is quite exciting, interesting and also demanding. I thought the attention and notoriety would subside within several months after receiving the Prize. However, there is no indication that this is the case seven years later. Wherever you go you can't escape the media and the attention. The numerous invitations to travel, lecture, attend conferences, consult for governments, universities, and companies have not subsided. It is exciting, rewarding, educational, lucrative and exhausting. You can rarely let your guard down and hide or relax. You don't dare pick your nose or scratch in some places for fear that someone will catch you on camera or video. When you travel, you often feel like you are on "Candid Camera".Although I receive multiple faxes, phone calls and FedEx's when I travel, when I return there are stacks of correspondences and long lab meetings with my staff to review our research progress before preparing for the next trip. > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 6.gif (140 X 198)" border=0 align=absmiddle>Georg von BékésyThe Nobel Prize in Physiology or Medicine 1961USA Harvard University Cambridge, MA, USA b. 1899(in Budapest, Hungary)d. 1972 生平介绍： Georg von Békésy was born in Budapest, Hungary, on June 3,1899, the son of Alexander von Békésy, a diplomat, and his wife, Paula. He received his early education in Munich, Constantinople, Budapest, and in a private school in Zurich. Having passed the Swiss «Maturitätsprüfung» he studied chemistry at the University of Berne. After a short military service he received his Ph.D. in Physics in 1923 from the University of Budapest. Later on he entered the services of the Hungarian Post Office in Budapest where he stayed until 1946. He worked one year at the Central Laboratory of Siemens and Halske A.G. in Berlin, at that time one of the centers in the development of telecommunication. During vacations he spent his free time in different workshops learning how to use a file for many hours without hurting the hands.His work in the research laboratory of the Hungarian Post Offce was concerned mainly with problems of long-distance telephone transmission. The friendly and efficient atmosphere of this laboratory made it possible for him to spend considerable time in the study of the ear as a main component of the transmission system. Soon he became a nuisance to the autopsy rooms of the hospitals and the mechanical workshops of the Post Office. There they did not like to find their drill press full of human-bone dust in the morning. But the wonderful laboratory spirit helped to overcome all difficulties, except those produced by the destructions of World War II.During the years 1939-1946 he was also Professor of Experimental Physics at the University of Budapest. He left Hungary in 1946 for Sweden, where he was a guest of the Karolinska Institute and did research at the Technical Institute in Stockholm. It was during this period that he developed a new type of audiometer which is operated by the patient and has applications outside the field of hearing. For instance, it has permitted the determination of the change in sensitivity of the eye of pigeons during dark adaptation.In 1947 he went to the United States and has worked since then at Harvard University in the Psycho-Acoustic Laboratory. Lately he has been interested in developing a mechanical model of the inner ear with nerve supply, the nerve supply being represented by the skin of the arm. This model shows such close similarity to phenomena in hearing that it has become a useful tool in the investigation of some specific problems that have been pursued for many years.His honours include the Denker Prize in Otology (1931), the Guyot Prize for Speech and Otology of Groningen University (1939) and the Shambaugh Prize in Otology (1950). He was the recipient of the Leibnitz Medal of the Berlin Academy of Sciences (1937), the Academy Award of the Budapest Academy of Science (1946), the Howard Crosby Warren Medal of the Society of Experimental Psychologists (1955), and the Gold Medals of the American Otological Society (1957) and the Acoustical Society of America (1961). Honorary doctorates (M.D.) were conferred on him by the Universities of Munster (1955) and Berne (1959).From Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964 This autobiography/biography was first published in the book series Les Prix Nobel. It was later edited and republished in Nobel Lectures. To cite this document, always state the source as shown above. Georg von Békésy died on June 13, 1972. 获奖原因： > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 7.gif (140 X 198)" border=0 align=absmiddle>Emil Adolf von BehringThe Nobel Prize in Physiology or Medicine 1901Germany Marburg University Marburg, Germany b. 1854d. 1917 生平介绍： Emil Adolf Behring was born on March 15, 1854 at Hansdorf, Deutsch-Eylau as the eldest son of the second marriage of a schoolmaster with a total of 13 children. Since the family could not afford to keep Emil at a University, he entered, in 1874, the well-known Army Medical College at Berlin. This made his studies financially practicable but also carried the obligation to stay in military service for several years after he had taken his medical degree (1878) and passed his State Examination (1880). He was then sent to Wohlau and Posen in Poland. Besides much practical work he found in Posen time to study (at the Chemical Department of the Experimental Station) problems connected with septic diseases. In the years 1881-1883 he carried out important investigations on the action of iodoform, stating that it does not kill microbes but may neutralize the poisons given off by them, thus being antitoxic. His first publications on these questions appeared in 1882. The governing body concerned with military health, which was especially interested in the prevention and combating of epidemics, being aware of the ability of Behring, sent him to the pharmacologist C. Binz at Bonn for further training in experimental methods. In 1888 they ordered him back to Berlin, where he worked-undoubtedly in full agreement with his own wishes - as an assistant at the Institute of Hygiene under Robert Koch. He remained there for several years after 1889, and followed Koch when the latter moved to the Institute for Infectious Diseases. This appointment brought him into close association, not only with Koch, but also with P. Ehrlich, who joined, in 1890, the brilliant team of workers Koch had gathered round him. In 1894 Behring became Professor of Hygiene at Halle, and the following year he moved to the corresponding chair at Marburg.Behring's most important researches were intimately bound up with the epoch-making work of Pasteur, Koch, Ehrlich, Löffler, Roux, Yersin and others, which led the foundation of our modern knowledge of the immunology of bacterial diseases; but he is, himself, chiefly remembered for his work on diphtheria and on tuberculosis. During the years 1888-1890 E. Roux and A. Yersin, working at the Pasteur Institute in Paris, had shown that filtrates of diphtheria cultures which contained no bacilli, contained a substance which they called a toxin, that produced, when injected into animals, all the symptoms of diphtheria. In 1890, L. Brieger and C. Fraenkel prepared, from cultures of diphtheria bacilli, a toxic substance, which they called toxalbumin, which when injected in suitable doses into guinea-pigs, immunized these animals to diphtheria.Starting from his observations on the action of iodoform, Behring tried to find whether a disinfection of the living organism might be obtained if animals were injected with material that had been treated with various disinfectants. Above all the experiments were performed with diphtheria and with tetanus bacilli. They led to the well-known development of a new kind of therapy for these two diseases. In 1890 Behring and S. Kitasato published their discovery that graduated doses of sterilised brothcultures of diphtheria or of tetanus bacilli caused the animals to produce, in their blood, substances which could neutralize the toxins which these bacilli produced (antitoxins). They also showed that the antitoxins thus produced by one animal could immunize another animal and that it could cure an animal actually showing symptoms of diphtheria. This great discovery was soon confirmed and successfully used by other workers.Earlier in 1898, Behring and F. Wernicke had found that immunity to diphtheria could be produced by the injection into animals of diphtheria toxin neutralized by diphtheria antitoxin, and in 1907 Theobald Smith had suggested that such toxin-antitoxin mixtures might be used to immunize man against this disease. It was Behring, however, who announced, in 1913, his production of a mixture of this kind, and subsequent work which modified and refined the mixture originally produced by Behring resulted in the modern methods of immunization which have largely banished diphtheria from the scourges of mankind. Behring himself saw in his production of this toxin-antitoxin mixture the possibility of the final eradication of diphtheria; and he regarded this part of his efforts as the crowning success of his life's work.From 1901 onwards Behring's health prevented him from giving regular lectures and he devoted himself chiefly to the study of tuberculosis. To facilitate his work a commercial firm in which he had a financial interest, built for him well-equipped laboratories at Marburg and in 1914 he himself founded, also in Marburg, the Behringwerke for the manufacture of sera and vaccines and for experimental work on these. His association with the production of sera and vaccines made him financially prosperous and he owned a large estate at Marburg, which was well stocked with cattle which he used for experimental purposes.The great majority of Behring's numerous publications have been made easily available in the editions of his Gesammelte Abhandlungen (Collected Papers) in 1893 and 1915.Numerous distinctions were conferred upon Behring. Already in 1893 the title of Professor was conferred upon him, and two years later he became «Geheimer Medizinalrat» and officer of the French Legion of Honour. In the ensuing years followed honorary membership of Societies in Italy, Turkey and France; in 1901, the year of his Nobel Prize, he was raised to the nobility, and in 1903 he was elected to the Privy Council with the title of Excellency. Later followed further honorary memberships in Hungary and Russia, as well as orders and medals from Germany, Turkey and Roumania. He also became an honorary freeman (Ehrenbürger) of Marburg.In 1896 Behring married the 18 years old Else Spinola, daughter of the Director of the Charité at Berlin. They had seven children. Behring died at Marburg on March 31, 1917.科学贡献： > screen.width-333)this.width=screen.width-333" width=140 height=198 title="Click to view full 8.gif (140 X 198)" border=0 align=absmiddle>The Nobel Prize in Physiology or Medicine 1907Charles Louis Alphonse Laveran（1845－1922）,in recognition of his work on the role played by protozoa in causing diseasesFrance Institut Pasteur Paris, France 简介： Charles Louis Alphonse Laveran（1845－1922）,因发现了疟疾的病原体－疟原虫及其在原虫病方面的研究而获得了1907诺贝尔生理与医学奖。Laveran，法国籍医生、病理学家、寄生虫学家，出生于法国巴黎，工作于法国巴斯德研究所。毕业于斯特拉斯堡大学医学系，作为军医参加了普法战争(Franco-German War,1870-71)，并长期从事军事医学研究及教育工作。随后进入巴黎巴斯德研究所工作。并于1907年在巴斯德研究所建立了热带病（Tropical Diseases ）实验室。Laveran对热带病学（tropical medicine）的研究有重大影响，在锥虫病（trypanosomiasis）、利什曼病（leishmaniasis）和其他原虫病的研究方面建树颇多，而其对于疟疾的研究更具有划时代的意义。1880年，Laveran作为外科军医在阿尔及利亚服役期间，通过对死于疟疾的病人的尸检发现了疟疾的病因，找到了疟疾的病原体－疟原虫，并将其命名为Oscillaria malariae。英文简介1：in full Charles-Louis-Alphonse Laveran French physician, pathologist, and parasitologist who discovered the parasite that causes human malaria. For this and later work on protozoal diseases he received the Nobel Prize for Physiology or Medicine in 1907. Educated at the Strasbourg faculty of medicine, he served as an army surgeon in the Franco-German War (1870–71) and practiced and taught military medicine until 1897, when he joined the Pasteur Institute, Paris. While serving as a military surgeon in Algeria in 1880, Laveran discovered the cause of malaria in the course of the autopsies he conducted on malaria victims. He found the causative organism to be a protozoan which he named Oscillaria malariae, though it was later renamed Plasmodium. Laveran was a powerful influence in developing research in tropical medicine, carrying on fruitful work in trypanosomiasis, leishmaniasis, and other protozoal diseases, as well as his epochal work in malaria. He established the Laboratory of Tropical Diseases at the Pasteur Institute (1907) and founded the Société de Pathologie Exotique (1908). Laveran's extensive writings include Trypanosomes et trypanosomiasis (with Félix Masnil; 1904); Traité des fièvres palustres avec la description des microbes du paludisme (1884); and Traité des maladies et épidémies des armées (1875).英文简介2：Alphonse (Charles Louis) Laveran had a long career as a physician, pathologist and parasitologist. He began as an army surgeon in the Franco-German War (1870-71). By 1874, he was appointed as professor of military medicine and epidemic diseases at the military college of Val de Grâce (1874-78, 1884-94). In Algeria, 1879-83, Laveran began his research at the military hospital of Bône. At the outset, he only set himself the task of explaining the role of the particles of black pigment found in the blood of people suffering from malaria. After 1850, when these particles, called melanins, were discovered, methods had been discussed of determining whether they were only to be found in patients suffering from malaria, or were present in other diseases as well. By careful observation viewing blood slides under a microscope, Laveran discovered that it was a parasite in red blood cells that causes human malaria (1880). Laveran later showed that the parasites, during their development in the red blood corpuscles, destroy them; and the red pigment in the corpuscles is changed into the melanin particles. The new parasite discovered by Laveran was not a bacterium. Although it was impossible to classify accurately, certain resemblances to other micro-organisms put it in the same group as the protozoa. From extensive negative results searching for the parasite in samples of water, soil, and air, Laveran hypothesized that the marsh-fever parasite must undergo one phase of its development in mosquitoes, and be inoculated into humans by their bites. He made an analogy with Manson's mosquito-borne mode of transmission of the Filaria worm. When Laveran was recalled from Algeria to Paris, and so forced to interrupt his work on malaria, he had already clearly formulated the problems that had first to be solved in this field. He then tried to solve them by an indirect approach, by studying animal parasites. Parasites of birds had only recently been discovered and showed resemblances to the malarial parasites. He became the founder of the medical field of protozoology doing important work on other protozoal diseases, including sleeping-sickness and kala-azar. Laveran's careful studies, more than anyone else, extended the understanding of the finer points of the morphology, biology, and pathological activity of the parasites. He published his discoveries, sometimes in collaboration with other workers, in many articles and annotations, and later, in 1904, he gathered them together in one great work, thus far unique of its kind: Les trypanosomes et trypanosomiasis. For the remainder of his life, from 1896, he was a researcher the Pasteur Institute at Paris. In 1907, Laveran founded the Laboratory of Tropical Diseases at the Pasteur Institute and founded the Société de Pathologie Exotique (1908). In recognition of his work on the role played by protozoa in causing diseases, he received the 1907 Nobel Prize in physiology or medicine. He died in 1922. Laveran's published work includes Traité des fièvres palustres avec la description des microbes du paludisme (1884); and Traité des maladies et épidémies des armées (1875). 详情请参阅诺贝尔奖网站相关链接：Biography： > screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full laveran.jpg (162 X 227)" border=0 align=absmiddle>The Nobel Prize in Physiology or Medicine 1909Emil Theodor Kocher(1841-1917)， for his work on the physiology, pathology and surgery of the thyroid glandSwitzerland Berne University Berne, Switzerland 简介：Emil Theodor Kocher，因其在生理学、病理学和甲状腺外科方面的成就而获得1909年诺贝尔生理与医学奖。Kocher 1841生于瑞士伯恩。1865年毕业于瑞士伯恩大学并获博士学位，此后从事外科工作。1872年，年仅31岁的Kocher被伯恩大学聘为外科教授和外科主任。他是最早采用无菌原则的外科医生之一，对感染和感染预防颇有研究。一生发表的大量著作，除了甲状腺外，还涉及止血法、防腐处理、外科感染、枪弹伤、急性骨髓炎、绞窄性疝和腹部外科等。他关于甲状腺外科的新理念最初颇有争议，但随着成功治疗了甲状腺肿并显著降低死亡率，他的观点很快得到承认。1892年Kocher首次报告甲状腺功能缺失呆小病伴发迟缓性肌松弛的肌肉肥大综合征，此病后来以他和另外两外研究者的的名字命名为Kocher-Debre-Semelaigne (KDS)综合征。许多外科器械和外科技术也都以他的名字命名。他用诺贝尔奖金建立了伯恩Kocher研究所。（相关知识：Kocher-Debre-Semelaigne (KDS)综合征又称甲状腺功能减退(甲减)伴肌病综合征，1892年Kocher首次报告甲状腺功能缺失呆小病伴发迟缓性肌松弛的肌肉肥大综合征，病因尚不清楚，可能为常染色体隐性遗传性疾病。本病的临床特征为甲状腺功能减退伴全身肌肉假性肥大，发病年龄为5个月～10岁，肌肉较紧硬，运动时可有疼痛感，动作迟缓，肌酶升高，肌肉活检可见肌纤维肥大及粘蛋白沉积。治疗为终生服用甲状腺激素替代治疗，并辅以多种维生素及矿物质，特别应重视对患儿的智能训练）英文简介1：Emil Theodor Kocher was born in Berne, Switzerland in 1841. He finished his medical studies in 1865 and went into surgery, where he had teachers like Demme, Lycke, Billroth and Langenbeck. In 1872, only 31 years old he was appointed professor of Surgery and Head of the University Clinic in Berne. He held this position until retirement. He was one of the first surgeons to apply the aseptic principles of Lister. Kocher was very early scientifically active and published a large number of experimental and clinical work in various surgical fields. He had a particular interest in infections, especially how to prevent surgical infections. He made early and important contributions to the condition of osteomyelitis and its relation to chronic staphylococcus infection. 英文简介2：Born in Bern. He studied in Zurich, Berlin, London and Vienna, obtaining his doctorate in Bern in 1865. From 1872 he succeeded Georg Albert Lucke as Ordinary Professor of Surgery and Director of the University Surgical Clinic at Berne. He published works on a number of subjects other than the thyroid gland including haemostasis, antiseptic treatments, surgical infectious diseases, on gunshot wounds, acute osteomyelitis, the theory of strangulated hernia, and abdominal surgery. His new ideas on the thyroid gland were initially controversial but his successful treatment of goitre with a steadily decreasing mortality rate soon won him recognition. The prize money for the Nobel helped establish the Kocher Institut in Berne.A number of instruments and surgical techniques are named after him as well as the Kocher-Debre-Semelaigne syndrome.更多详情请参阅诺贝尔奖网站相关链接：Biography: > screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full kocher.jpg (162 X 227)" border=0 align=absmiddle>The Nobel Prize in Physiology or Medicine 1910Albrecht Kossel （1853－1927 ），in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substancesGermany University of Heidelberg Heidelberg, Germany 简介：Albrecht Kossel（1853－1927），因其在细胞化学，特别是蛋白质及核物质方面的研究工作而获得1910年诺贝尔生理与医学奖。Kossel 1853年生于德国海得堡，1878毕业于罗斯托克大学医学系，1901年后担任海得堡大学生理学教授并担任海德堡大学蛋白质研究所主任。1879年Kossel开始从事关于核蛋白的研究，并发现核蛋白是由蛋白成分和非蛋白成分即核酸组成。1885年至1901年期间，他发现核酸包括腺嘌呤、胞嘧啶、鸟嘌呤、胸腺嘧啶和尿嘧啶。另外，他还发现了组氨酸、胸腺核苷酸、精胺。对细胞生物学研究做出了重要贡献。英文简介1：Albrecht Kossel[Al´brekht kOs´ul] Pronunciation Key, 1853–1927, German physiologist. He was professor at Heidelberg from 1901. He specialized in the physiological chemistry of the cell and its nucleus and of proteins, including nucleins. He discovered the purine adenine and the pyrimidine thymine. For this work he received the 1910 Nobel Prize in Physiology or Medicine. He wrote Protamines and Histones (tr. 1928).英文简介2：Ludwig Karl Martin Leonhard Albrecht Kossel (September 16, 1853 – July 5, 1927) was a German medical doctor.BiographyKossel was born in Rostock as the son of Prussian consul Albrecht Kossel and his wife Clara. In 1872, Kossel went to the University of Strasbourg to study medicine, where he visited lectures of Anton de Bary, Waldeyer, Kundt, Baeyer and Felix Hoppe-Seyler. He graduated in 1878 at the University of Rostock.Kossel was awarded the 1910 Nobel Prize in Physiology or Medicine for research in cell biology, especially proteins and nucleic acids. He also discovered the amino acid histidine (1896), thymic acid and agmatine (1910).英文简介3：German biochemist who was awarded the Nobel Prize for Physiology or Medicine in 1910 for his contributions to understanding the chemistry of nucleic acids and proteins. He discovered the nucleic acids that are the bases in the DNA molecule, the genetic substance of the cell. After graduating in medicine (1878) from the German University (now the University of Strasbourg), Kossel did research there and at the Physiological Institute in Berlin. In 1895 he became professor of physiology and director of the Physiological Institute at Marburg, going in 1901 to a similar post at Heidelberg, where he eventually became director of the Heidelberg Institute for Protein Investigation. In 1879 Kossel began studying the recently isolated substances known as “nucleins” (nucleoproteins), which he showed to consist of a protein portion and a nonprotein portion (nucleic acid). From 1885 to 1901 he and his students used hydrolysis and other techniques to chemically analyze the nucleic acids, thus discovering their component compounds: adenine, cytosine, guanine, thymine, and uracil. Kossel also discovered the amino acid histidine (1896), thymic acid, and agmatine.更多详情请参阅诺贝尔奖网站相关链接：Biography： > screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full kossel.jpg (162 X 227)" border=0 align=absmiddle>The Nobel Prize in Physiology or Medicine 1911Allvar Gullstrand（1862－1930）， for his work on the dioptrics of the eyeSweden Uppsala University Uppsala, Sweden 简介： Allvar Gullstrand（1862－1930），瑞典眼科医生，因其在眼球屈光系统方面的研究而获得1911年诺贝尔生理与医学奖。Allvar Gullstrand 1862生于瑞典乌普萨拉，1890年于斯德哥尔摩完成其学业，并获医学博士学位。1894－1927年间担任乌普萨拉大学生理和物理光学教授，从事眼科疾病治疗和眼球光学系统的研究。他将物理数学方法应用到眼球屈光和成像系统的研究中，并因此获得1911年诺贝尔生理与医学奖。他的其他成就还包括对散光的研究，以及改进了眼底镜和白内障术后矫正镜，发明了Gullstrand裂隙灯。英文简介1：Allvar Gullstrand[Al´vAr gul´strAnd] Pronunciation Key, 1862–1930, Swedish ophthalmologist. He was professor (1894–1927) successively of eye therapy and of optics at the Univ. of Uppsala. He applied the methods of physical mathematics to the study of optical images and of the refraction of light in the eye. For this work he received the 1911 Nobel Prize in Physiology or Medicine. He is noted also for his research on astigmatism and for improving the ophthalmoscope and corrective lenses for use after removal of a cataract from the eye. 英文简介2：Allvar Gullstrand (born June 5, 1862 in Landskrona - died July 28, 1930 in Stockholm) was a Swedish ophthalmologist.He was professor (1894–1927) successively of eye therapy and of optics at the University of Uppsala. He applied the methods of physical mathematics to the study of optical images and of the refraction of light in the eye. For this work he received the Nobel Prize in Physiology or Medicine in 1911.Gullstrand is noted also for his research on astigmatism and for improving the ophthalmoscope and corrective lenses for use after removal of a cataract from the eye.He is interred in the Norra begravningsplatsen in Stockholm.英文简介3：Gullstrand studied in Uppsala, Vienna, and Stockholm, earning a doctorate in 1890. He became professor of diseases of the eye at Uppsala in 1894 and in 1913 was appointed professor of physiological and physical optics there. Gullstrand contributed to knowledge of the structure and function of the cornea and to research on astigmatism. He improved corrective lenses for use after surgery for cataracts and devised the Gullstrand slit lamp, a valuable diagnostic tool that facilitates detailed study of the eye. Gullstrand's investigations led to a new concept of the theory of optical images. He expanded the classic theory of the German physicist Hermann von Helmholtz to include the redisposition of internal parts of the lens structure in accommodation, a mechanism by which the eye can focus for near or far vision within certain limits. Gullstrand showed that although accommodation depends about two-thirds on the increase in convexity of the lens surface, the remaining one-third does not.更多详情请参阅诺贝尔奖网站相关链接：Biography： > screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full gullstrand.jpg (162 X 227)" border=0 align=absmiddle>The Nobel Prize in Physiology or Medicine 1914Robert Bárány（1876－1936），for his work on the physiology and pathology of the vestibular apparatus Austria Vienna University Vienna, Austria 简介：Robert Bárány，奥地利耳科医生，因其在内耳前庭生理与病理方面的研究而获得1914年诺贝尔生理与医学奖。他发明了检测前庭疾病和小脑功能以及二者与平衡失调的研究方法，他的研究使得外科手段治疗前庭疾病成为可能。Bárány 1876年出生于维也纳。1900年毕业于维也纳大学并获医学博士学位。作为外科医生参加了第一次世界大战，并被俄军俘虏，1914年获得诺贝尔奖时尚被关押在俄国监狱，后通过瑞典王子和国际红十字的外交努力而获释，1916年得以参加诺贝尔奖颁奖典礼。1917年后任职于瑞典乌普萨拉大学。（鉴于上述两位诺贝尔奖得主均来自瑞典乌普萨拉大学，在此简要介绍一下该学校。Uppsala University 瑞典乌普萨拉大学是一所公立大学，位于瑞典东部乌普萨拉省省会乌普萨拉市。乌普萨拉大学建于1477年，是瑞典及整个斯堪的纳维亚半岛最早的大学。八位诺贝尔奖得主更进一步提高了在全世界的知名度。）英文简介1：Robert Bárány (April 22, 1876 – April 8, 1936) was an Austrian physician of Hungarian-Jewish descent. For his work on the physiology and pathology of the vestibular apparatus of the ear he received the 1914 Nobel Prize in Physiology or Medicine.Bárány was born in Vienna. He attended medical school at Vienna University, graduating in 1900. As a doctor in Vienna, Bárány was syringing fluid into the inner ear of a patient to relieve the patient's dizzy spells. The patient experienced vertigo and nystagmus (involuntary eye movement) when Bárány injected fluid that was too cold. In response, Bárány warmed the fluid for the patient and the patient experienced nystagmus in the opposite direction. Bárány theorized that the endolymph was sinking when it was cool and rising when it was warm, and thus the direction of flow of the endolymph was providing the proprioceptive signal to the vestibular organ. He followed up on this observation with a series of experiments on what he called the caloric reaction. The research resulting from his observations made surgical treatment of vestibular organ diseases possible. Bárány also investigated other aspects of equilibrium control, including the function of the cerebellum.He served with the Austrian army during World War I as a civilian surgeon and was captured by the Russian Army. When his Nobel Prize was awarded in 1914, Bárány was in a Russian prisoner of war camp. He was released in 1916 following diplomatic negations with Russia conducted by Prince Carl of Sweden and the Red Cross. He was then able to attend the Nobel Prize awards ceremony in 1916, where he was awarded his prize. From 1917 until his death he was professor at Uppsala University英文简介2：Austrian otologist who won the Nobel Prize for Physiology or Medicine in 1914 for his work on the physiology and pathology of the vestibular (balancing) apparatus of the inner ear. Bárány graduated in medicine from the University of Vienna in 1900. After study at German clinics he became assistant at the ear clinic of the University of Vienna and, in 1909, a lecturer on otological medicine. He devised new tests for detecting vestibular disease and for examining activities of the cerebellum and their relation to disturbances of equilibrium. Bárány served in the Austrian army in World War I and was taken prisoner by the Russians in 1915. He was a prisoner of war when the Nobel Prize was awarded to him that year. From 1917 until his death he taught at Uppsala University, where he was head of the ear, nose, and throat clinic.英文简介3：Robert Barany[rO´bert bA´rAnE] Pronunciation Key, 1876–1936, Austrian physician. For his work on the physiology and pathology of the vestibular apparatus of the ear he received the 1914 Nobel Prize in Physiology or Medicine. From 1917 until his death he was professor at the Univ. of Uppsala. 更多详情请参阅诺贝尔奖网站相关链接：Biography： > screen.width-333)this.width=screen.width-333" width=162 height=227 title="Click to view full barany.jpg (162 X 227)" border=0 align=absmiddle>新来的战友还有以下可选Nobel Prizes in Medicine and Physiology(List, not checked) 1906 C. Golgi (Italy) S. Ramón y Cajal (Spain) 1908 P. Ehrlich (Germany) I. Metschnikow (France, Russia) 1915 - 1916 - 1917 - 1918 - 1919 J. Bordet (Belgium) 1920 A. Krogh (Denmark) 1921 - 1922 A. V. Hill (United Kingdom) O. Meyerhof (Germany) 1923 F. G. Banting (Canada) J. J. R. Macleod (Canada) 1924 W. Einthoven (Netherlands) 1925 - 1926 J. Fibiger (Denmark) 1927 J. Wagner-Jauregg (Austria) 1928 Ch. Nicolle (France) 1929 Chr. Eijkman (Netherlands) Sir F.G. Hopkins (United Kingdom) 1931 O. H. Warburg (Germany) 1932 Ch. S. Sherrington (United Kingdom) E.D. Adrian (United Kingdom) 1933 Th. H. Morgan (USA) 1934 G. R. Minot (USA) W. P. Murphy (USA) G.H. Whipple (USA) 1935 H. Spemann (Germany) 1936 Sir H.H. Dale (United Kingdom) Otto Loewi (Austria, 1873-06-03 - 1961-12-25) 1937 A. Szent-Györgyi von Nagyrapolt (Hungary) 1938 C. Heymans (Belgium) 1939 G. Domagk (Germany) 1941 - 1942 - 1943 H. Dam (Denmark) E. A. Doisy (USA) 1944 J. Erlanger (USA) H.S. Gasser (USA) 1945 E. B. Chain (United Kingdom, Germany) Sir A. Fleming (United Kingdom) Sir H. W. Florey (United Kingdom) 1946 H. J. Muller(USA) 1947 Carl F. u. Gerty T. Cori (USA, Czechoslovakia) B. Houssay (Argentina) 1948 P. Müller (Switzerland) 1949 W. R. Hess (Switzerland) A. Egas Moniz (Portugal) 1950 Ph. S. Hench (USA) E. C. Kendall (USA) T. Reichstein (Switzerland) 1952 S. A. Waksman (USA, Russia) 1953 H. A. Krebs (United Kingdom, Germany) F.A. Lipmann (USA, Germany) 1954 J. F. Enders (USA) F. C. Robbins (USA) Th.H. Weller (USA) 1955 H.A.T. Theorell (Sweden) 1956 A.F. Cournand (USA, France) W. Forssmann (Germany) D.W. Richards (USA) 1958 G.W. Beadle (USA) J. Lederberg (USA) E.L. Tatum (USA) 1959 A. Kornberg (USA) S. Ochoa (USA, Spain) 1960 Sir P.M. Burnet (Australien) P.B. Medawar (United Kingdom) 1962 Francis H. C. Crick (United Kingdom, 1916-06-08 - 2004-07-28) James D. Watson (USA, *1928-04-26) Maurice Wilkins (United Kingdom, 1916-12-15 - 2004-10-05) for their discovery of the structure of DNA (deoxyribonucleic acid) 1963 Sir J. C. Eccles (Australien) A. L. Hodgkin (United Kingdom) A. F. Huxley (United Kingdom) 1964 K. Bloch (USA, Germany) Feodor Lynen (Germany) 1965 F. Jacob (France) A. Lwoff (France) J. Monod (France) 1966 C. B. Huggins (Canada) F. P. Rous (USA) 1967 R. Granit (Sweden) H. K. Hartline (USA) G. Wald (USA) 1968 R. W. Holley (USA) H. G. Khorana (USA) M. W. Nirenberg (USA) 1969 M. Delbrück (USA, Germany) A. Hershey (USA) S. Luria (USA) 1970 B. Katz (United Kingdom) U. S. v. Euler-Chelpin (Sweden) J. Axelrod (USA) 1972 G.M. Edelman (USA) R. Porter (United Kingdom) 1973 K. v. Frisch (Austria) K. Lorenz (Austria) N. Tinbergen (Netherlands) 1974 A. Claude (Belgium) Ch. de Duve (Belgium) G.E. Palade (USA) 1975 D. Baltimore (USA) R. Dulbecco (USA) H. Temin (USA) 1976 B. Blumberg (USA) D.C. Gajdusek (USA) 1977 R. Guillemin (USA) A. Schally (USA) R. Yalow (USA) 1978 W. Arber (Switzerland) D. Nathans (USA) H. Smith (USA) 1979 A. M. Cormack (USA) G. N. Hounsfield (United Kingdom) 1980 B. Benacerraf (USA) George Davis Snell (USA, 1903-12-19 - 1996-06-06) J. Dausset (France) 1981 R. W. Sperry (USA) D. H. Hubel (USA) T. N. Wiesel (Sweden) 1982 S. K. Bergström (Sweden) B. I. Samuelsson (Sweden) J. R. Vane (United Kingdom) 1984 N. K. Jerne (Denmark) G. F. K. Köhler (Germany) C. Milstein (Argentina) 1985 M. F. Brown (USA) J. L. Goldstein (USA) 1986 St. Cohen (USA) R. Levi-Montalcini (Italy, USA) 1988 Sir J. W. Black (United Kingdom) Gertrude B. Elion (USA, +1999-02-21) G.H. Hitchings (USA) 1989 Michael J. Bishop (USA) Harold E. Varmus (USA) 1990 Joseph E. Murray (USA) E. Donnall Thomas (USA) 1991 E. Neher (Germany) B. Sakmann (Germany) 1992 Edmond H. Fischer (USA, *1920) Edwin G. Krebs (USA, *1918) Discovery of mechanisms for the regulation of proteins in the human body 1993 Richard J. Roberts (USA, *1943) Phillip A. Sharp (USA, *1944) (Mosaic genes) 1994 Alfred G. Gillman (USA, *1941-07-01) Martin Rodbell (USA, *1925-12-01) Signal transfer within cells, discovery of G proteins 1995 Christiane Nüsslein-Volhard (Germany, *1942-10-20) Eric F. Wieschaus (USA, *1947-06-07) Edward B. Lewis (USA, *1918-05-20) for their discoveries concerning the genetic control of early embryonic development (studies of Drosophila melanogaster, cf. Nature 287, 795 (1980)) 1996 Peter C. Doherty (Australia, *1940-10-15) Rolf M. Zinkernagel (Switzerland, *1944-01-06) for their discoveries concerning the specificity of the cell mediated immune defence (T lymphocytes) 2001 Leland H. Hartwell (USA, *1939) R. Timothy (Tim) Hunt (United Kingdom, *1943) Sir Paul M. Nurse (United Kingdom, *1949) for their discoveries of key regulators of the cell cyclesimon81 wrote:这个网站我早就知道，我相信还有其他的相关网站。但是办这个活动的目的一是把很多资料综合在一个帖子里方便浏览节省时间，二是我相信大家在参与的过程中自己会学到很多。诚然，网络上的资料很多，如何深度挖掘利用是个问题。为了方便大家的浏览，做了个索引点击后是按Threaded浏览的，个人认为比上面汇总的好一些版主可以把它复制了放顶上, 方便以后的整理、浏览截至当前发帖时间。此外搜索一下，其实好多地方都已经做好了索引的>imagelab wrote:为了方便大家的浏览，做了个索引点击后是按Threaded浏览的，个人认为比上面汇总的好一些版主可以把它复制了放顶上, 方便以后的整理、浏览截至当前发帖时间。此外搜索一下，其实好多地方都已经做好了索引的感谢imagelab！确实很多地方都做好了索引的，但是这些网站链接地址变化的话可能以后就看不到了。另外，以后发帖的话还想让大家相应地翻译成中文，不再简单地贴英文了。
