Three Americans To Receive Gairdner Foundation International Awards

For the third time in its 38-year history, the Gairdner Foundation of Willowdale, Ontario, Canada, has selected a scientist who is already a Nobel laureate to receive one of its prestigious International Awards. Traditionally, this award has been considered a "Nobel predictor," with 43 out of 238 honorees having gone on to win the coveted prize. Prior to this year's announcement, Frederick Sanger and H. Gobind Khorana, who won their Nobels in 1958 and 1968, respectively, were the only scientists to receive their Gairdners later--in 1971 and 1980. Joining their ranks this year is Arthur Kornberg, a professor, emeritus, of biochemistry at Stanford University School of Medicine, who won the 1959 Nobel Prize for physiology or medicine. Kornberg has been named as a Gairdner corecipient along with Bruce Alberts, the president of the National Academy of Sciences (NAS). Roger Y. Tsien, a Howard Hughes Medical Institute investigator and a professor of cellular and molecular medicine at the University of California, San Diego, also was chosen to receive a 1995 Gairdner. "Dr. Kornberg won his Nobel Prize in 1959, but he has done a lot of important work since then," Gairdner Foundation executive director Verette Pennycook says. "[The foundation] is recognizing him for these later achievements." The scientists will each receive $30,000 in Canadian funds ($22,500 U.S.), a framed inscription, and a sculpture at an official ceremony in Toronto scheduled for October. McMaster University's Bertram Brockhouse, himself a 1994 Nobelist in physics, will make the presentations. Recipients will deliver guest lectures on their research at the University of Toronto, and one other Canadian university each, at the invitation of the foundation. The Gairdner Foundation was established in 1957 by James A. Gairdner, a Canadian stockbroker and industrialist, for the purposes of rewarding and encouraging researchers who have made significant contributions in the medical sciences. Initially, the awards were made in the fields of arthritis, rheumatism, and heart disease. However, since then the prize's scope has grown to encompass several other disciplines, with more recent awards going to researchers in such fields as immunology and molecular biology. Both Kornberg and Alberts have been cited by the foundation for their contributions to the understanding of DNA synthesis. Kornberg's 1959 Nobel--which he shared with Severo Ochoa--was for his discovery of the Escherichia coli DNA polymerase I, which was the first enzyme shown to be capable of using a template to assemble a new strand of DNA from its building blocks. However, "DNA polymerase I was not the main enzyme involved in replication," Kornberg recounts. "The principal enzyme turned out to be much more complicated system--a holoenzyme--with multiple components." One of these components was DNA polymerase III, which was discovered by his son Thomas Kornberg, who also worked on this project as an undergraduate at Columbia University. In a series of papers published in 1985, Kornberg's group describes how they "worked out the components of the system and the mechanism by which it operates," Arthur Kornberg says. "The mechanism is much like [polymerase I] except that polymerase III has a higher rate of operation and shows greater accuracy or fidelity in replication. The holoenzyme has 10 distinct subunits and actually forms a dimer which has a special capacity to operate very rapidly at the replication fork of the DNA." Four of the group's papers were published in the Journal of Biological Chemistry (260:2875-83, 2884-9, 2982-6, 2987-92) and two in Proceedings of the National Academy of Sciences (82:3562-6, 3954-8). Combined, the articles have been cited in more than 300 publications through January 1995. Working along the same lines of Kornberg's group, Alberts studied the replication machinery of the T-4 bacteriophage, a virus that infects E. coli. "T-4 makes all its own replication proteins," says Alberts. "What we did was to find mutants in seven different T-4 genes that inhibited replication, and thus isolated the proteins" (B.M. Alberts et al., Journal of Molecular Biology, 71:789-93, 1972). This paper has been cited in more than 200 publications to date. "Our work showed that biology works because of some very sophisticated chemistry going on at the cellular level," comments Alberts. For the most part, the two researchers did not collaborate on their projects, although Alberts spent some time in Kornberg's laboratory in the early 1970s, which resulted in the publication of one joint paper: J.A. Huberman et al., J. Mol. Biol., 62:39-52, 1971. Alberts also collaborated with Thomas Kornberg on his studies of the T-4 bacteriophage (N. Sigal et al., Proceedings of the National Academy of Sciences, 69:3537-41, 1972). A native of Brooklyn, N.Y., Kornberg, 77, obtained his undergraduate degree in science form the City College of New York in 1937 and an M.D. from the University of Rochester in 1941. He served as a commissioned officer from 1942 to 1953 in the United States Public Health Service, during which time he headed the enzyme and metabolic section of the former National Institute of Arthritis and Metabolic Disease--which later split off into two NIH institutes--in Bethesda, Md. After a stint as a professor and head of the department of microbiology at Washington University, he came to Stanford in 1959, where he organized the biochemistry department and chaired it for 10 years. Since his retirement in 1988, he has held the position of professor, emeritus, in the department and remains active in his research. Besides the Nobel Prize, Kornberg has been showered with accolades over the years, including the National Medal of Science in 1979 and membership in NAS, the Royal Society, and the American Philosophical Society. Alberts, 56, is a native of Chicago who was educated at Harvard University, graduating with a bachelor's degree in biochemistry in 1960, and a Ph.D. in biophysics in 1965. Prior to assuming the leadership of NAS in 1992, he was a professor of biochemistry at UC-San Francisco, where he was also chairman of the department of biochemistry and biophysics from 1985 to 1990, and still maintains an active research laboratory there. Before that, from 1966 to 1976, he taught both as an assistant and associate professor at Princeton University. The recipient of numerous awards and honors over the years, Alberts was elected in 1981 to the academy he now heads. He serves on the editorial boards of several leading scientific journals and is one of the principal authors of the popular textbook The Molecular Biology of the Cell (New York, Garland Publishing Inc., 1989), now in its second edition. Roger Tsien, 43, is being cited for his work on designing methods to measure levels of chemical messengers in cells, and using the technology to track them in their native environments. "We design and build molecules that can be put into living cells to act as spies and report back to us the state of the internal biochemistry of the cells," he explains. The first substance Tsien succeeded with was calcium, for which he designed and synthesized a family of indicator molecules that change their fluorescence when they bind to calcium ions. Tsien remembers that as a graduate student at Cambridge University in England, he worked on the first of these molecules as an additional, "bootleg" project to his assigned thesis topics while shuttling between the physiology and chemistry labs. "Until then no one had considered calcium ions seriously at the physiological level," he notes. One of his early papers on this work, (R.Y. Tsien et al., Journal of Cell Biology, 94:325-34, 1982) has been cited in nearly 2,000 publications through January 1995. "This was among the first papers showing the measurements of calcium levels could be easily measured in typical mammalian cells of clinical relevance," he says. "Before this, calcium measurements were mostly restricted to giant and usually robust cells like squid axons." Tsien's laboratory went on to make molecules bright enough to be seen in single cells (G. Grynkiewicz et al., Journal of Biological Chemistry, 260:3440, 1985, which has been cited in more than 6,700 publications to date) and apply those indicators to studies of signal transduction and channel activity in cells. Although he is perhaps best known for his work on calcium, Tsien's group has also created the most commonly used intracellular indicators for hydrogen ions, sodium ions, and cyclic adenosine monophosphate (cAMP). "We have shown that cAMP can also be compartmentalized within individual neurons, which helps explain the link between short-term and longer term information storage at synapses," he says (B.J. Bacskai et al., Science, 260:222-6, 1993). Tsien received a bachelor's degree in chemistry and physics at Harvard College in 1972, before going on to the University of Cambridge for a Ph.D. in physiology in 1977. He held assistant, associate, and full professorships in the department of physiology at University of California, Berkeley, from 1981 to 1989, after which he came to San Diego. Concurrent with the announcement of his Gairdner award, Tsien was named the winner of the 1995 Artois-Baillet Latour Health Prize, from the Artois-Baillet Latour Foundation in Brussels, Belgium. First instituted in 1979, this international prize, carrying with it a cash award of roughly $200,000, is presented every other year to scientists whose studies have had "immediately useful applications." Past winners have included Cyril A. Clarke (1981), for his work in controlling Rhesus hemolytic disease in newborn babies, and Thomas Waldmann (1991), for practical applications of monoclonal antibody technology.

Three Americans To Receive Gairdner Foundation International Awards

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