Gibbs Award
Vallée honored for metalloenzyme research "Bert Vallée is a man with an exceptionally independent mind and philosophy who has had to fight all his life to be innovative in the face of people who have told him, 'that won't work.' " That's the way F. Albert Cotton, inorganic chemistry professor at Texas A&M University, describes his long-time friend. Cotton and others gathered in Chicago last week to honor Vallée, this year's recipient of the Willard Gibbs Medal presented by the Chicago Section of the American Chemical Society. The annual award recognizes outstanding achievement in pure and applied chemistry. Vallée is Paul C. Cabot Professor in Biochemical Sciences and head of the center for biochemical and biophysical sciences and medicine at Harvard medical school and Brigham and Women's Hospital, Boston. He is Research Council included studies of being honored for his pioneering dis- the survival of red blood cells using coveries in the field of metalloenzyme what was then a new technique— chemistry. His accomplishments isotopic labeling of the iron in hemorange from developing analytical globin. After the bombing of Hirotechniques to study metalloenzymes, shima it was noticed that white blood through discovering and character- cells disappeared in victims of the izing many of these compounds which bombing. are now known to play key roles in "I was very enthusiastic and very metabolism, to working out an un- ignorant," Vallée says of himself at derstanding of how some of these key that time, "and I wondered whether metalloenzymes function, and finally we couldn't study white blood cells in applying these discoveries directly to the same way we had been studying problems of human health. red cells." The problem was that As the statement supporting his there were no colored metal ions in nomination for the Gibbs Medal puts leukocytes, and biochemists of the it, "Bert Vallee's discoveries in the time thought it silly to expect to find field of metalloenzyme chemistry are any metals there. Careful study of the literature soon so pioneering, so original, and so important that he is generally regarded convinced Vallée that the whole field as the father of bioinorganic chem- of metals in enzymes had simply not been explored. The field was 30 or 40 istry." "Metal ions play an enormous role years behind what was then mainin biochemistry, and it is chiefly stream biochemistry in which rethrough Vallee's contributions that searchers were working out metabolic we understand this now," says Cot- pathways and chemical structures, ton, who was awarded last year's particularly for carbohydrates. For Gibbs Medal. "When he started, metalloenzymes, the analytical techniques to even detect them (unpeople said, 'He's crazy!' " Vallée himself remembers how far less they happened to be colored) had from the mainstream his work yet to be developed and many of the seemed when he first began. All of his nutritional studies that would show early work on metals in enzymes had their importance were still to be to be done "after hours"—between 5 done. Much of Vallee's metalloenzyme PM and midnight after a full day of work has focused on zinc, which early conventional research. Vallee's interest in metals in en- on he found was not only present in zymes began at the end of World War leukocytes but at remarkably deII when his research for the National creased levels in leukemia cells. When 46
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he began, there was only one enzyme known to contain zinc. Now about 160 zinc metalloenzymes have been identified, many by Vallée or his students. They include enzymes from every major class. Zinc is now known to be critical to enzymic catalysis, to hormonal and other regulatory functions and their control, and to the synthesis and stabilization of proteins and nucleic acids. Vallee's work pulls together many different branches of chemistry and biology. These include analytical techniques from inorganic chemistry, isolation procedures from physical biochemistry, mechanism studies from organic chemistry, and techniques from molecular biology. "I always have people from all disciplines and all ages in my laboratory," Vallée says. "And they have shaped my attitudes, of course." These researchers have worked first to establish that metals are present in enzymes, Vallée explains, then to demonstrate that their presence is important to the chemical reactions of the enzymes, and, finally, to show what their mechanism of action is. His current explanation of what metals are doing in enzymes focuses on their capacity to be catalysts. In a theory called the entatic state concept, Vallée and R. J. P. Williams of Oxford University propose that the protein component of a metalloenzyme functions, in part, to place the metal ion in an unusual geometric configuration which puts the energy levels of the ion closer to those of its transition state than to those of a conventional stable molecule. Thus, the metal is poised to react with a substrate when it appears. The theory helps explain the speed of enzymic reactions compared to other, metalcatalyzed reactions as well as the unusual spectra that metal ions in enzymes have. Vallee's laboratory continues to pursue its long-time studies of zinc metalloenzymes. One current project examines the role of zinc in the transfer of genetic information, particularly the muddling of this transfer associated with cancer. Another project is studying the detailed mechanism of action of carboxypeptidase, the first zinc metalloenzyme
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CIRCLE 26 ON READER SERVICE CARD C&EN May 18, 1981
that Vallee identified. "I want to find out what zinc does in one particular system," he explains, "and this is the one I have chosen." Another active area of zinc metal loenzyme research is the study of alcohol dehydrogenase, an enzyme system that is involved both in the formation of alcohol in yeast and its detoxification in man and other animals. Vallee has found that in humans alcohol dehydrogenase is not a single enzyme but a collection of closely related ones, called isozymes. Genetics seems to play a role in determining the exact mix of these isozymes present in an individual, and Vallee hopes to explore the chemical, biological, and genetic factors that regulate alcohol metabolism and, perhaps, alcoholism. This work is supported by a $5.8 million endowment from Seagrams Co. Another major corporate grant, from Monsanto, supports a very different Vallee project—an investigation of the early differentiation and growth of the circulatory system in a developing organism. Vallee's interest is in how this system is chemically controlled. "I've wanted to study the chemical basis of organ formation since I was 17," Vallee says, "and I thought I knew enough at this point that I would try." Vallee is something of a chemical pioneer in another area, too, that of pursuing major academic research projects that are supported by funds from industrial corporations. Both the Monsanto and Seagrams projects were firsts of their kind when they began. Although each project is set up differently, Vallee says that neither of them infringes at all on the conventional freedoms of academic researchers to publish their findings and discuss them with their scientific peers. In fact, he is enthusiastic about corporate sponsors, saying that they are as encouraging and enthusiastic about his work as any group he has ever been associated with. Such a partnership, Vallee believes, is built on trust and mutual respect for the different, but equally impressive, talents of corporate executives and research scientists. "They trust me to do things that will not be run-of-the-mill," Vallee says. It's a trust that seems to be well founded. As Cotton says, innovative research has become a Vallee trademark. "Biology uses chemistry that we haven't thought of yet," Vallee says with obvious glee. Clearly, he is a man who wants to unravel more of it. Rebecca Rawls, Washington
Chemical Hazards in the Workplace Measurement and Control
ACS S y m p o s i u m Series N o . 149 G a n g a d h a r C h o u d h a r y , Editor National Institute for Occupational Safety and Health Based on a symposium sponsored by the Division of Chemical Health and Safety of the American Chemical Society. A collection of recent information on measurement and control methods in the workplace. This volume presents a current perspective on both the state of the art and future di reckons of monitoring and measurement procedures for the occupational environment — making valuable reading for industrial hygienists, chemists, toxicologists, occupational health professionals, and health insurance companies. As the field constantly changes, professionals need to keep abreast of the new technologies and procedures contained in this book. CONTENTS Thirty-eight chapters are grouped into five subject areas: methodology, monitoring and control, special toxicants, quality assurance, and new technologies. Specific topics include new analytical techniques and methods development, occupational environmental monitoring and control technology (including medical monitoring and analysis), and quality assurance and requirements of compliance statistics. 628 pages (1981) Clothbound $43.00 LC 81 -130 ISBN 0-8412-0608-2 Order from: SIS Dept. 51 American Chemical Society 1155 Sixteenth St., N.W. Washington, D.C. 20036 or CALL TOLL FREE 800-424-6747 and use your credit card.
