|
 |
|
      |
|
|
|
 Research & Giving News Article  A Profile of Samuel H. Barondes, M.D. By Robin Eisner But Barondes in 1961 — the year before James Watson and Francis Crick won the Nobel Prize for DNA — had the good fortune to work in the NIH laboratory of Marshall Nirenberg. There, he participated in Nirenberg’s Nobel prize-winning research that showed how certain molecules in cells translated the four-letter alphabets used by DNA and RNA into a triplet code for amino acids, the building blocks of proteins. These and other findings laid the foundation for understanding the relationship between genes and proteins in cells, in-cluding the realization that variations in DNA can alter a protein made by a cell, and cause disease. Being a participant in such fundamental research transformed Barondes, who soon began using the novel methods of molecular biology to study the brain, as did others. Ultimately, he became a leading neuroscientist, the chair of psychiatry at the University of California in San Francisco and, today, a writer about psychiatry for popular audiences. Throughout his career, he won many awards and served on editorial and foundation boards. He joined the Scientific Council of NARSAD in 2004 and helped establish a new NARSAD schizophrenia research award. His career illustrates how a scientific revolution can occur during a lifetime and underscores how research involves luck. Indeed, one cannot predict which of today’s research projects will lead to discoveries that will solve the problems of mental illness and other diseases afflicting humanity. When Samuel Barondes was growing up in Brooklyn, New York, science, however, was not his main interest. Both his parents were Jewish immigrants from Eastern Europe, and his mother wanted him to become a rabbi and sent him to Jewish parochial schools. But the young Barondes had other ideas. By the time he entered Columbia College, at the age of 16, he had already embraced the secular intellectual world. In doing so, he happily retained aspects of his religious education that encouraged a virtuous life, but also came away from it sensitized against dogmatism and “revealed truths.” This healthy skepticism, and his attraction to ideas supported by empirical evidence, shaped Barondes as an undergraduate. He became particularly interested in the experimental psychology of B.F. Skinner, because of its emphasis on behavioral measurement, and planned to go on to graduate work in this field until an uncle persuaded him to first go to medical school — to ensure he had something to fall back on, if research did not pan out. But when Barondes attended Columbia University’s College of Physicians & Surgeons as a medical student in 1954, its psychiatry department disappointed him. Like other American psychiatry departments of that period, it was dominated by the psychoanalytic teachings of Sigmund Freud and had little interest in research. Although he had long been interested in Freud’s ideas, “the emphasis on interpretations of Freudian writings was uncomfortably reminiscent of the interpretations of established religious precepts that I had become so familiar with as a child,” Barondes says. So he turned his attentions elsewhere. His new passion became endocrinology, especially the pituitary gland. This gland, which sits right under the brain, is a controller of other glands such as the adrenal, ovaries and testes. And it was already known that it is driven by secretions from nerve cells in the hypothalamus, which are, in turn, influenced by emotions. “Endocrinology was not only grounded in science, but relevant to aspects of human behavior I found interesting,” Barondes says.* After graduating from medical school in 1958, he was a resident in medicine from 1958 to1960 at the Peter Bent Brigham Hospital in Boston. From there he went to the Clinical Endocrinology Branch of the NIH to get training in research. Life at the NIH in the early 1960s was thrilling for Barondes. He quickly underwent the transition from clinician to researcher, and began to publish findings in leading journals about the regulation of the pituitary gland by neurotransmitters. But his most important experience was meeting Gordon Tomkins, the then new head of the NIH Laboratory of Molecular Biology. Also interested in endocrinology, Tomkins had a very new view of that field. So when Barondes explained his interests, Tomkins stunned him by explaining: “You know what endocrinology really is? Endo-crinology is just molecular bio-logy.” To which Barondes naively replied: “What, exactly, is molecular biology?” Tomkins lengthy answer — which was at the cutting edge of science in early 1961 — promptly set Barondes in a new direction. The essence of what Tomkins told him is now well known: genes in the cells of our body are transcribed into molecules called messenger RNA, which are, in turn, translated into the proteins that carry out cellular functions. Most importantly, Tomkins had already realized that hormones work by changing the manufacture of certain messenger RNAs, and therefore the behavior of cells. So if endocrinology is, indeed, molecular biology, Barondes wanted to work in this new field. Tomkins got him a position in a tiny molecular biology laboratory just set up by a promising young scientist —Marshall Nirenberg. Barondes could not have made a more opportune move. Within weeks of his joining the lab, Nirenberg made a monumental discovery about the code used to translate the information in messenger RNA into the language of proteins — which was then the major problem in molecular bio-logy. Put simply, Nirenberg discovered that this code could be deciphered using synthetic RNA molecules, and went on to work out the code for each of the twenty amino acids in proteins, and to win a Nobel Prize. Barondes had the good fortune to undertake several projects that contributed to this work, making him a member of what the newspapers called “the code of life team.” In less than two years, by being at the right place at the right time, he had been transformed from not knowing what molecular biology is to being one of its card-carrying practitioners. With these accomplishments under his belt, Barondes began to think back to his old interests in behavior and psychiatry. If endocrinology is really molecular biology, perhaps psychiatry is also molecular biology. Deciding to apply the tools of molecular biology to the brain and behavior, he returned to Boston in 1963 for a psychiatry residency at McLean Hospital, which also allowed him to set up his own laboratory. At McLean he began his classic work with mice on the role of protein synthesis in memory. He found that memory that is maintained for a few hours or more depends on brain protein synthesis, whereas short-term ephemeral memories do not. He also showed that proteins move along the length of a nerve and are deposited at synapses, within fifteen minutes of being synthesized. Both findings were published in Science and have been seminal for understanding how the brain changes in response to stimuli. Upon completion of his training in 1966, Barondes took a job at then new Albert Einstein College of Medicine with a joint appointment in psychiatry and molecular biology. One of his important discoveries while there was that certain proteins in the brain, called tubulins, turn over every few days, a finding which helped change the prevailing view that the brain is structurally very stable. Then a personal tragedy upended him: his 29-year-old wife, Ellen Slater, was diagnosed with breast cancer. Nevertheless, when she had an excellent response to treatment, the couple accepted an offer to move west, to La Jolla, where Barondes became a founding member of the new University of California Medical School in San Diego. While there he played a major role in the creation of its premier psychiatry department and in the development of its neuroscience program, which is now a world leader. But two years after they moved to UCSD, Ellen succumbed to the cancer, and Barondes was left to raise his two young daughters, then 5 and 7. As he recovered from this tragedy, he began to develop a new research interest. Since his time at Einstein, he had become interested in the possibility that the complex sugars that coat all cells may play a role in determining how cells selectively stick to each other. What he had in mind was a code of cellular recognition, which could, he thought, be based on the interaction of specific complex sugars with proteins that selectively bind to them. This code might be responsible for the selective binding of nerve cells in the brain to establish the circuits that control behavior. But in 1971 a problem of this kind was too difficult to approach directly by studying the brain. So he turned to a simple organism — a cellular slime mold — that also shows specific cellular associations, but is much easier to study. To his great delight he found that as slime mold cells begin to associate in a Petri dish they make huge amounts of a simple protein, which he and his group were able to isolate. And this protein, which he named discoidin, is a lectin — a sugar-binding protein of just the type he had been looking for. Although the function of discoidin in slime molds turned out to be complex, the finding set the stage for the later discovery of a class of human proteins called “discoidin domain proteins” because of their resemblance to discoidin. Among these human proteins are several now known to play a role in the formation of synapses in the brain. By the 1980s, as new techniques developed, Barondes decided to begin looking for lectins in the complex tissues of mice and people, and found quite a few, including some in the brain. This large family of proteins, which he named galectins, is turning out to have a variety of functions. During this period Barondes also recognized the time was right to start applying the new genetic technologies to psychiatry, and he helped organize early attempts to identify gene variants that influence the risk of developing bipolar disorder. In 1986, with both his daughters enrolled at UCLA, Barondes left his beloved colleagues at UCSD to become the chairman of the department of psychiatry at the University of California, San Francisco, and director of the Langley Porter Psychiatric Re-search Institute, a position he held until the end of 1993. During this period he recruited a number of young psychiatrist-scientists to UCSF, and founded the Center for Neurobiology and Psychiatry, which he still directs. In 2002 his prolonged widowhood ended when he married Dr. Louann Brizendine, a clinical professor of psychiatry at UCSF. As his work in the laboratory began winding down, Barondes became interested in writing books about psychiatry for a general audience. This new career began when he was commissioned by the Scientific American Library to write Molecules and Mental Illness, which was published in 1993. He went on to write Mood Genes, about the hunt for variations in genes that in-crease the risk of developing bi-polar disorder, published in 1998; and Better than Prozac, about the history of psychiatric drugs and the creation of new ones, published in 2003. He currently is working on a book about personality disorders. Throughout his career, Barondes has served on the boards of biotechnology companies and re-search institutes. His longest continuous association has been with the McKnight Endowment Fund for Neuroscience, which began with the fund’s inception in 1976, and for which he served as president for a decade. He also has served his scientific alma mater, NIH, almost without interruption since his departure in 1966, most recently as chair of the Board of Scientific Counselors of National Institute of Mental Health. For the past 11 years, Dr. Barondes also has worked with the Staglin Family Music Festival for Mental Health in Rutherford, California. Shari and Garen Staglin, who own a vineyard in the Napa Valley, have raised more than $25 million for mental health research since the program — which includes scientific talks and a concert — began a decade ago. Last year, Barondes worked with the Staglins and NARSAD to create the Staglin Family Music Festival NARSAD Schizophrenia Research Award. The grant, which will be awarded each year, provides $250,000 to assist the development of a schizophrenia research program by an investigator under the age of 45. The first recipient is Linda M. Brzustowicz, M.D., a professor of genetics at Rutgers University, and an associate professor of psychiatry at the University of Medicine and Dentistry of New Jersey. When Dr. Barondes looks back on his life as a psychiatrist and scientist he is gratified by the growth of research on the brain and on mental disorders. “I am continuously amazed by how much we have learned and keep learning,” he says. “But I am also disappointed that such great science has not yet made as much of a difference to the mentally ill as I had hoped.” Nevertheless, he remains optimistic. As he has seen during his long, distinguished career, huge strides can be made even in one scientist’s lifetime. *A major source for this article is a memoir by Dr. Samuel H. Barondes in “A History of Neuroscience in Autobiography” Vol. 5, The Society of Neuroscience, in press. |
Media Contact
Upcoming NARSAD Events
Latest News from NARSAD
Spotlight
|
|
For the Media