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Colleagues Laud 1994 Nobelists As Overdue For Coveted Prize Author: Edward R. Silverman Date: November 28, 1994 Colleagues of the recently announced winners of the 1994 Nobel Prizes in chemistry, physics, and medicine or physiology, in praising the decisions of the Nobel committee, say the coveted Swedish honor is long overdue for each of this year's recipients. For their part, the winners are using their newfound recognition to lobby for greater funding for basic science. Alfred G. Gilman, chairman of the pharmacology department at the University of Texas Southwestern Medical Center at Dallas, and Martin Rodbell, a scientist emeritus in the Laboratory of Cellular and Molecular Pharmacology at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., were named to share the prize in physiology or medicine for their discovery of G proteins and the role of these proteins in signal transduction. George A. Olah, director of the Loker Hydrocarbon Research Institute at the University of Southern California (USC) in Los Angeles, was selected to receive the prize in chemistry for his work on carbocations. The physics laureates are Bertram N. Brockhouse, an emeritus professor of physics at McMaster University in Hamilton, Ontario, Canada, and Clifford G. Shull, an emeritus professor of physics at the Massachusetts Institute of Technology, chosen for their contributions to the development of neutron-scattering techniques for studies of condensed matter. Each winner receives or shares a $930,000 prize, which will be presented next month. Reflecting on years spent working alongside the five winners in laboratories across North America, their associates describe the recipients as dedicated scientists who have not been afraid to take risks in pursuit of their research. Recalling his work with Rodbell at the National Institutes of Health between 1970 and 1985, for example, Constantine Londos, chief of the membrane regulation section at the National Institute of Diabetes and Digestive and Kidney Diseases, says: "Marty was an independent guy who didn't like to restrict people. He'd look at our work and wasn't concerned with how others might interpret things. He didn't like to be a conformist. He was a leader by dint of his nature." Sweden Signals Approval Rodbell, 69, and Gilman, 53, discovered G proteins, natural substances that act as signal transducers, or intermediaries to relay signals from outside cells to the inside. The G proteins, so called because they bind guanosine triphospate (GTP), control a wide range of basic life processes. An excess or deficiency in G proteins, or alterations in their genetic composition, can lead to endocrine disorders or tumors. In addition, alterations in transduction of signals through these proteins may cause symptoms of diseases such as diabetes and cholera. The two scientists' work has been the springboard for a flurry of further studies by other researchers--many of which The Scientist has identified as "hot" papers--as molecular biologists try to refine their understanding of the signal-transduction process. In 1970, Rodbell found that GTP is required in order for glucagon to stimulate production of cyclic AMP (adenosine-3¹,5¹-monophosphate), initiator of the process by which hormones transmit signals to cells. His two seminal papers--M. Rodbell et al.,"Glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 4. Effects of guanyl nucleotides on binding of I-125 glucagon," Journal of Biological Chemistry, 246:1872-6, 1971 and M. Rodbell et al.,"Glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 5. Obligatory role of guanyl nucleotides in glucagon action," J. Biol. Chem., 246:1877-82, 1971--have been referenced in more than 400 and 700 subsequent articles, respectively. Later in the decade, Gilman determined that G proteins are the signal transducers; they act as mo-lecular switches, shuttling between the hormone receptor and the amplifier system in the cell membrane to turn signals on and off. He made this finding while working with mutated leukemia cells, which lacked a G protein and thus did not respond to external signals. The Gilman group's landmark papers, according to the Nobelist's associates--E.M. Ross, A.G. Gilman, "Resolution of some components of adenylate cyclase necessary for catalytic activity," J. Biol. Chem., 252:6966-9, 1977 and E.M. Ross et al., "Reconstitution of hormone-sensitive adenylate cy-clase activity with resolved components of enzyme," J. Biol. Chem., 253:6401-12, 1978--have been cited more than 225 times and 460 times, respectively. In 1980, Gilman's team purified the first G protein."Rodbell initiated the study of the G proteins and then Gilman carried it on," explains Edwin G. Krebs, a professor, emeritus, in the department of pharmacology and biochemistry at the University of Washington, Seattle, and a 1992 Nobel laureate who's known both men for decades. "In fact, Gilman's work was dominant for the past 10 to 15 years." Krebs and Gilman have shared two Nobel "predictor" prizes--the 1989 Albert Lasker Basic Medical Research Award and the 1989 Louisa Gross Horwitz Prize, presented by Columbia University to honor contributions to knowledge in biology or biochemistry (The Scientist, Feb. 19, 1990, page 26). Rodbell and Gilman are likewise no strangers when it comes to sharing awards: In 1987, they were corecipients of the Richard Lounsbery Award from the National Academy of Sciences (NAS). Gilman received a Ph.D. and an M.D. from Case Western Reserve University in 1969. He has been in his present position at U. Texas since 1981. He received a Gairdner Foundation International Award --another Nobel "predictor"--in 1984. He is a member of NAS. According to Jeremy Levin, CEO of New York-based Cadus Pharmaceutical Corp., which focuses on research and development in the G protein area, Gilman is "a worthy recipient because he conceptualized a completely new field. The man conceptualized an area that had been thought about but never had the strands all pulled together." "This is a wonderful treat," Gilman notes. "All sorts of people have come out of my past. Even my old Cub Scout leader called to congratulate me." Rodbell earned his Ph.D. from the University of Washington, Seattle, in 1954. An NAS member, he received a Gairdner Award in 1984. Carbocations The work of Olah, 67, has led to the development of new fuels based on petroleum, coal, methane, and other substances, resulting in higher octane gasoline and liquified coal. His research centers on carbocations and oxonium ions--highly reactive, positively charged organic molecules that act as intermediaries in natural as well as synthetic chemical processes. In order to determine the structure of these molecules via solid-state nuclear magnetic resonance spectroscopy and X-ray crystallography, he modified them using superacids, which are billions of times more potent than "strong" acids like sulfuric acid. Olah and colleagues have demonstrated that in very strong acidic solutions, hydrocarbons--normally unreactive--can become reactive. These reactions could be used to convert simple hydrocarbons such as methane into synthetic fuels. His most significant paper, according to his colleagues--G.A. Olah, "Carbocations and electrophilic reactions," Angewandte Chemie, 12:173-212, 1973--has been referenced in nearly 200 subsequent articles. "His contribution is very fundamental in organic chemistry," says Surya Prakash, an associate professor at USC and Olah's coauthor on more than 200 papers. "He's made a major contribution to hydrocarbon research and to industry." Olah, a native of Hungary, earned his Ph.D. from the Technical University of Budapest in 1949. He worked in Canada from 1957 until 1964, when he came to the United States. He joined the USC faculty in 1977. An NAS member, he has received numerous awards from the American Chemical Society. Structure Of Matter Shull, 79, and Brockhouse, 76, share the prize for developing neutron-scattering techniques for analysis of the atomic structure of solid as well as condensed matter. Neutron beams have, for instance, facilitated investigations of the structure of semiconductors, a building block of the electronics industry. These methods also are used in studying new ceramic superconductors, catalytic exhaust cleaning, elastic properties of polymers, and virus structures. The two Nobelists conducted their prizeworthy research after World War II--Shull in the 1940s and Brockhouse in the 1950s--at some of the first nuclear reactors. Shull was cited for developing neutron diffraction, used in discerning the atomic structure of a material. His ground-breaking article--E.O. Wollan, C.G. Shull, "The diffraction of neutrons by crystalline powders," Physical Review, 73:830-1, 1948--has garnered nearly 70 citations. Brockhouse pioneered neutron spectroscopy to determine the motion of atoms. His seminal research was published in a book, Inelastic Scattering of Neutrons in Solids and Liquids (Vienna, International Atomic Energy Association, 1961, pages 113-151), which has been cited 165 times. "I've known both of them for 30 years, and they were pioneering contributors," confirms Martin Blume, deputy director of Brookhaven National Laboratory on Long Island, N.Y., whose High Flux Beam Reactor is based on the two Nobelists' work. "When you think that their work began to have a huge effect decades ago, this recognition is really long overdue," Blume asserts. Brockhouse received his Ph.D. in 1950 from the University of Toronto. He has been an emeritus professor since 1984. He holds awards from physics societies in the U.S., Canada, and the United Kingdom. Shull, who re-tired from MIT in 1986, earned his Ph.D. in 1941 from New York University. He is an NAS member and has received awards from the American Physical Society, the Royal Swedish Academy of Sciences, and the Russian Academy of Sciences. A 'Bully Pulpit' The Nobel winners, while predictably quite happy that their research was acknowledged, are modest about the accolades being heaped on them by their colleagues. "It's very gratifying, but totally unexpected," says Brockhouse. "Right now, though, I'm still going to lots of luncheons, and there's various media pursuing us. But this is the icing on the cake--not the cake, itself." Still, the sudden notoriety has presented an opportunity that Gilman is using to call attention to the state of funding for basic research, a subject that is increasingly causing concern among scientists who fear that product-oriented research is crowding out other forms of work. "I do get a little upset by people who are naysayers and complain that there isn't enough money, because that sends out the wrong message. It tells young people that you can't be a scientist anymore," he remarks. "But it is frustrating for the scientific community, and it is harder to become a scientist now than when I was young. Clearly, we could use more money for basic research in many areas." Gilman's corecipient is also using his newfound media stardom to bemoan the current dearth of research funding. In a widely publicized Associated Press report, Rodbell said he retired in June because there was no more money for his work. "I think the attitudes of Congress and the executive branch [have] always been toward the end goal," he commented. "Underlying all of that is that they are not willing to take a chance on people like myself, exploring the unknown." Physicist Shull echoes these sentiments: "The thing I resent the most is that students are becoming disillusioned with science as a field and we're losing the cream of the crop. Students see it's hard to find positions because science is not supported to the extent that it would offer opportunities to young people. There's a general malaise about scientific matters and financial support. "And it's disturbing that funding for some of these major facilities has been passed over." Olah, while noting that funding is still available for top-echelon researchers, expresses similar worries: "I must say that most of my friends find a way to get funds and, in comparison with the rest of the world, things are still good [for scientists]. But funding is getting limited." He adds, however, that he hopes the prize will bring recognition to USC, which is probably best known to Americans for its sports teams. "I'm the guy who gets all the recognition, but this prize is for everyone who worked with me," he asserts. "But there's another message here, too. And that is that my university is always improving--and we're much more than a football team!" Edward R. Silverman is a freelance writer based in Millburn, N.J.

Colleagues Laud 1994 Nobelists As Overdue For Coveted Prize

Nov 27, 1994

Colleagues Laud 1994 Nobelists As Overdue For Coveted Prize

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