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Phone :(215)243-2205 // Fax: (215)387-1266 ================= THE SCIENTIST VOLUME 8, No:20 OCTOBER 17, 1994 (Copyright, The Scientist, Inc.) =============================================================== Articles published in THE SCIENTIST reflect the views of their authors and not the official views of the publication, its editorial staff, or its ownership. =============================================================== *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON *** *** OCTOBER 31, 1994 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the United States: one year $58, two years $ 94 Canada : one year $82, two years $142 All other foreign : one year/air cargo $ 79 one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NXT = next article ------------------------------------------------------------ TI : CONTENTS PG : 3 ============================================================ BEHAVIORAL CHALLENGE: The search is narrowing for a director of the National Institutes of Health's new Office of Behavioral and Social Sciences Research. Social and behavioral scientists who have fought long and hard to raise the status of their disciplines at NIH say the new director will need to be strong and creative to combat the prevailing laboratory sciences culture at the agency--including, they say, the bias of NIH director Harold Varmus PG : 1 CANCER SCIENCE A VICTIM: Cancer research institutions are facing an increasingly difficult battle to maintain their high standards of scientific research in the face of diminishing federal funding. They are especially falling victim to the congressional budgetary practice of earmarking monies for specific high-profile diseases PG : 1 MORE FOR AGING: Despite a recent infusion of support for gerontological studies, ambitious investigators of aging- associated phenomena continue to lament that their field is underfunded PG : 1 LASKER WINNERS: The Lasker Foundation's medical research awards have been bestowed this year upon three investigators who exemplify "persistence and tenacity, intuition and intelligence" PG : 1 NEUROSCIENCE MEETING: The 24th annual meeting of the Society for Neuroscience, to be held in Miami Beach, is likely to be largest conference in the society's history, officials say PG : 3 BIOETHICAL PERSPECTIVES: Arthur Caplan, the nation's preeminent bioethicist, recently moved his base of operations from the University of Minnesota to the University of Pennsylvania, where he has established the Center for Bioethics. In a candid interview with The Scientist, Caplan discusses the increasing importance of his discipline and the ambitious plans he has for the center PG : 12 COMMENTARY: Science sociologist and historian Robert K. Merton, now in the 85th year of a notably productive life, was recently named winner of the National Medal of Science. In this essay, publisher Eugene Garfield reminisces about his long relationship with the eminent scholar, noting the significance of Merton's contributions and urging all scientists to become acquainted with his work PG : 13 MATURING FIELD: Like its baby boomer subjects, the branch of biomedical science that explores the effects of aging is visibly maturing PG : 14 HOT PAPERS: Developmental biologist Michael A. Rudnicki discusses his studies of the functions of myogenic regulatory factors; astrophysicist Georges Meynet reports on new grids of stellar models PG : 16 SEQUENTIAL IMPROVEMENTS: Rapidly advancing DNA-sequencing technology offers increased speed, power, and sensitivity PG : 17 INTERVIEW SKILLS: In the second installment of a three-part excerpt from his book A Ph.D. Is Not Enough!, physicist Peter J. Feibelman advises those interviewing for a job to look at the situation from the prospective employer's viewpoint and prepare accordingly PG : 23 STEPHEN J. BENKOVIC, a chemistry professor at the Pennsylvania State University, has received the American Chemical Society's Alfred Bader Award in Bioinorganic and Bioorganic Chemistry PG : 24 NOTEBOOK PG : 4 CARTOON PG : 4 LEADERS OF PG : 10 SCIENCE LETTERS PG : 13 DNA SEQUENCING DIRECTORY PG : 21 NEW PRODUCTS PG : 22 CROSSWORD PG : 24 (The Scientist, Vol:8, #20, pg.3, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Behavioral Scientists See New NIH Status Enriching Biomedical Studies AU : Franklin Hoke TY : NEWS PG : 1 A search committee will stop accepting applications for the directorship of the newly chartered Office of Behavioral and Social Sciences Research (OBSSR) at the National Institutes of Health this week. The deadline's passing sets the stage for the appointment, by year's end, of a leader whose task will be to effective- ly integrate behavioral and social sciences research into the traditional biomedical investigations for which NIH is better known. Advocates who have long struggled to raise the stature of these disciplines at NIH succeeded through pressure and persuasion in getting Congress to write the new office into the health agency's fiscal 1994 authorization. Now, they say that if a strong first director is named, OBSSR should be able to promote in-novative, interdisciplinary re- search that will significantly extend understandings of basic processes in disease and health. Some of these observers voice concerns, however, that OBSSR may not be easily incorporated into the laboratory sciences culture that prevails at NIH. The office's most important potential ally, NIH director Harold Varmus, has expressed, at best, lukewarm support for the behavioral and social sciences, they say. Although the new OBSSR director will have a high profile-- the position will carry the additional title of associate director of NIH and will reside within the NIH director's office--how the office fares will depend, in part, on the welcome it receives from Varmus. The search committee is expected to forward a short list of candidates to Varmus by late November or early December; the NIH chief will then make the final selection, pending approval of Public Health Service head Philip Lee. Once installed, the new office's chief will begin the challenging task of coordinating with various NIH institutes to promote research linking behavioral and social factors to health and disease. Scientists believe that the office's initial funding of about $2.5 million will probably not be enough to grant research awards directly. They expect, however, that the amount should be adequate to sponsor conferences, workshops, and other projects to catalyze important new scientific investigations, both within and outside NIH. "So many of the diseases facing us involve behavioral patterns participating in their pathogenesis or perpetuation," says Ira B. Black, chairman of the department of neuroscience and cell biology at the University of Medicine and Dentistry of New Jersey at the Robert Wood Johnson Medical School in Piscataway. Black, a past president of the Society for Neuroscience, Washington, D.C., was also a member of the Institute of Medicine committee that produced the report AIDS and Behavior: An Integrated Approach (Washington, National Academy Press, 1994). "There's an extraordinary need for the behavioral sciences to crosstalk more effectively with what we might call the biological sciences--even though those very distinctions that I'm drawing are artificial. If this office can contribute to that kind of interaction, it will be successful." Although generally optimistic that, with a sufficiently articulate and scientifically qualified director, OBSSR can accomplish its goals, some behavioral and social scientists worry about past statements made by Varmus that they characterize as disparaging of their disciplines. The new position is being constructed as, potentially, quite a visible post," declares Felice J. Levine, executive officer of the American Sociological Association in Washington, D.C. "We are concerned that Dr. Varmus has not seemed to appreciate the real value added of looking at the social and behavioral dynamics of health and disease. But we're hoping that this office can be part of the solution, and that he will be open to the scientific counsel of an effective director." Others note what they feel has been an excessively long wait between congressional authorization for the new office in June 1993 and action taken to create it, indicating resistance to OBSSR. Department of Health and Human Services Secretary Donna Shalala signed the necessary paperwork to establish the office on July 13 of this year. The delay has been ascribed by NIH, however, to normal bureaucratic procedure. NIH officials say that, whatever tensions may exist, OBSSR will likely join other congressionally ordered units that have been productively integrated into the office of the director--the offices for research on minority health and research on women's health, for example. "It's difficult when there are legislative mandates," observes Delores Parron, associate director for special populations in the office of the director of the National Institute of Mental Health (NIMH)--a job also created by act of Congress, in 1980--and cochairwoman of the search committee for the OBSSR director. "But with minority health and women's health, we've learned how to really make good use of these offices to do the kind of things that we need to do, to take the leadership to move us into areas where we've needed to move for a long time." Leadership Needed Because the office will not have a large budget and, hence, will have limited direct powers, the new director's leadership capabilities--both scientific and for coalition- building with other offices in NIH--will be crucial to OBSSR's effectiveness. A demonstrable understanding of the scientific methodologies used in the laboratory-focused biomedical disciplines will also be needed, researchers agree. The [OBSSR director] will have to work very closely with all the institutes at NIH, so there should be a very strong appreciation for systematic pursuit of knowledge," says Cora Marrett, an assistant director of the National Science Foundation in Washington. Marrett, the first head of NSF's directorate for the social, behavioral, and economic sciences--an office comparable to OBSSR, established at the science foundation in 1992--is a member of the search committee for the OBSSR director. "The person clearly will have to have a strong ability to communicate ideas and to bring others together, because the position will not have a lot of staff or resources initially. OBSSR, for example, "won't have the budget authority of the Office of AIDS Research [OAR]," according to Susan Persons, associate director for government affairs of the Consortium of Social Science Associations (COSSA) in Washington. OAR consolidates AIDS research budgets and planning at NIH. "That's one of the reasons that it's important that the new director be someone who's respected in the larger community as well as at NIH. Hopefully, if there's a good, strong director, that person will be able to get the institutes to collaborate more." Persons adds that a director interacting well with all parts of NIH should help ensure that duplicative research is minimized. One difficult, early objective of the new director will be establishing consensus about just what constitutes behavioral and social science. Different definitions are used throughout the health agency. "One of the first tasks for the new person coming in will be to define precisely how much [behavioral and social science] there is at NIH right now," Marrett says. According to Marrett, this will be difficult because of the breadth and diversity of what has been called behavioral or social science. For her office to coordinate well with its NIH counterpart, she says, inter- and intradisciplinary distinctions will be important. "There are some areas where most of the support would be at NSF," Marrett notes. "There is more support for anthropology at NSF than NIH, for example. But for a number of parts of psychology--physiological neuropsychology and, to some extent, cognitive psychology--there is substantially more support at NIH than at NSF currently." In many ways, links between biomedical laboratory sciences and behavioral and social sciences research are only just emerging. Perhaps for this reason, defining just what types of studies will lie within the purview of OBSSR may be difficult. Will, for example, psychosomatic medicine be included in the category? What about the search for behavior genes? "With behavior genes, you're really talking about straightforward molecular biology," says Louis Sibal, director of the office of laboratory animal research in the NIH director's office. Sibal is the official managing the process of establishing OBSSR and will be asked to help the office's new leader navigate the bureaucracy at NIH, an especially important job if the incoming person is from outside the agency. "Those kinds of [investigations] would come in the genome program, where people would be mapping the genes and finding out what their functions are." NIMH's Parron, however, suggests that work with behavior genes and psychosomatic medicine probably will both fall within OBSSR's mandate. "But coming up with an agreed-upon definition of what's encompassed is one of the main tasks the new director will be undertaking, because there has been controversy in various sectors of NIH about what the appropriate definition of behavioral science research should be," Parron points out, noting that the social sciences are more easily defined. "There are some people who say that much of the research in the neurosciences should be excluded, for example, and then others who make the argument as to why it should be included." Areas of investigation that most scientists agree will be addressed by the new office include so-called preventive research--studies on the persistence of high-risk behaviors among populations with the potential to be exposed to the HIV virus, for example, or why young people aware of the fact that smoking can lead to cancer are still attracted to cigarettes. Trouble At The Top? NIH director Varmus, a Nobel-Prize-winning molecular biologist, has been accused by behavioral and social scientists of being unsympathetic to their disciplines, and their concerns based on this impression extend to their expectations for OBSSR. The feeling that the NIH director is less than favorably disposed to behavioral and social science stems, in part, from a statement that appeared in The New York Times (N. Angier, Nov. 23, 1993, page C1). "I begin with the premise that behavior is an incredibly important element in medicine," Varmus told the newspaper. "People's habits, their willingness to take steps to avoid transmission of HIV, are all behavioral questions. But what I'm looking for are new ideas, real discoveries. When I read about genetics, I see breakthroughs every day. And while I'm trying to learn more about behavioral science, I must say that I don't feel I get tremendous intellectual stimulation from most of the things I read." Varmus's defenders insist that his comments have been misinterpreted and that he was merely expressing his personal affinity for the methodologies of molecular biology. Through spokespersons, Varmus declines to respond directly. "Dr. Varmus is a molecular biologist at heart," says Sibal. "And, obviously, he's a brilliant man who has very high standards. He's a stickler for high-quality research. That's what was intended by that remark." Behavioral and social scientists acknowledge that an ability to challenge the impression--relatively common among traditional biomedical researchers--that the behavioral and social sciences lack a rigor comparable to that of their own disciplines, will be key to the new director's success. "The scientific depth and acumen [of the new director] will be core," says Levine, "not just in interaction with Dr. Varmus but also in being able to play a leadership role across the agency." In the view of Denis J. Prager, former director of the health program at the John D. and Catherine T. MacArthur Foundation in Chicago and now head of a consulting firm for foundation planning, "there's room for some strengthening of the behavioral and social sciences." For most of the past decade, the MacArthur Foundation supported a research network for health and behavior headed by psychologist Judith Rodin, the new president of the University of Pennsylvania. Says Prager: "Certainly, there's some room for strengthening the degree to which they're integrated into the biomedical sciences. On the other hand, it doesn't take a lot of reading of the literature to become convinced that some of the most powerful determinants of health in our society are behavioral and social." Varmus is also said to be broadening his knowledge of the behavioral and social sciences as his time in office lengthens. "He's on a learning curve and open to hearing," says Anne Thomas, associate director for communications in Varmus's office. "And I've heard him express his understanding that behavioral science is important." "We've been told that he's educable, that this just isn't his area of interest, and I can understand that," counters COSSA's Susan Persons. After Congress authorized OBSSR in June 1993, she formed the Coalition for the Advancement of Health Through Behavioral and Social Science Research, consisting of 12 member societies and organizations, to monitor NIH progress toward establishing the office. Persons reports that Varmus failed to mention the behavioral and social sciences at his confirmation hearings and in other testimony before Congress. He has also refused to meet with representatives of her group, while meeting often with other biomedical researchers, raising fears that the new OBSSR will be coolly received in his office, she says. "I'm not inclined to give him the benefit of the doubt any further," Persons says. "There have been opportunities. As the NIH director, truly, he represents all of the research that is done there." She adds, however: "In spite of the slow progress in getting this done, I'm really hopeful that, once it is in place and we have a good [OBSSR] director, things will improve. I don't think we're going to be able to tackle most of the health challenges that we have without behavioral and social science. It's just impossible." Persons's views--a mix of optimism and cynicism--are shared by other scientists. "Behavioral and social scientists are enthusiastic about the fact that such an office will exist, but skeptical that it will, in fact, be well integrated into the NIH system and have much impact," Prager says. Whatever the start-up problems with OBSSR, most behavioral and social scientists agree that the questions to be addressed by the office will be critical ones for biomedical research and public health in the future. "The most interesting and most powerful science down the road is going to be that science which is capable of integrating the inputs of social, behavioral, and biological [sciences] in such a way that we get a really detailed view of how the organism operates in the real world and how it is affected by the environment within which it lives," Prager says. "If the NIH people, including Varmus, can be brought to understand that, then we're going to make much more progress, much more quickly, in promoting health and preventing disease." "I very much hope this office will be a spur for ever- increasing multidisciplinary efforts," neuroscientist Ira Black says. "We're in a position now for that to become a reality, for us to regard the biology of behavior, the behavioral output, and the behavior of interacting individuals as different facets of the same pursuit." Black adds: "Medicine of the 21st century, in large measure, may well be psychosomatic and somatopsychic medicine." (The Scientist, Vol:8, #20, pg.1, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Lasker Awards Cite Persistence Of Three Scientists AU : Barbara Spector TY : NEWS PG : 1 The Albert and Mary Lasker Foundation this year has chosen as the recipients of its prestigious Winged Victory statuettes three researchers who, according to awards program director Jordan U. Gutterman, exemplify "persistence and tenacity, intuition and intelligence." The New York-based foundation presented its Albert Lasker Clinical Medical Research Award to John A. Clements, Julius H. Comroe, Jr. Professor of Pulmonary Biology and a professor of pediatrics at the University of California, San Francisco. The Albert Lasker Basic Medical Research Award was bestowed on Stanley B. Prusiner, a professor of neurology and biochemistry at UC-San Francisco. The foundation gave its Albert Lasker Special Public Health Award--which had been presented only four times previously in the program's 49-year history--to Maclyn McCarty, an emeritus professor of bacteriology and immunology at Rockefeller University. In addition to the inscribed statues, each winner received a $25,000 prize. The presentation took place at a luncheon in New York City on September 30. Health and Human Services Secretary Donna E. Shalala was the keynote speaker. "All three are wonderful human stories in science," proclaims Gutterman, who is also chairman of clinical immunology and biological therapy at the University of Texas M.D. Anderson Cancer Center in Houston. A Lasker award, believed by many to be the most significant United States biomedical science prize, is generally viewed as a "predictor" of the Nobel Prize. Fifty-one Lasker recipients have gone on to win the coveted Swedish honor. The Lasker Foundation was established in 1942 by Albert Lasker, the late owner of the Lord & Thomas advertising agency, and his wife, Mary, an enthusiastic advocate of biomedical research. This year's awards were the first to be given since Mary Lasker's death this past February (B. Spector, The Scientist, March 21, 1994, page 3). In her address at the luncheon, Shalala paid tribute to Mary Lasker: "One of Mary's greatest skills was her ability to hold public officials to a very high level of service and excellence. And when it came to the government's commitment to science and knowledge, she left little room for people to weasel out of those commitments. "From Franklin Roosevelt to Bill Clinton, Mary Lasker made sure that presidents and Cabinet secretaries knew the value of science to this country." Historic Achievement The award to McCarty celebrates the 50th anniversary of the landmark discovery that genes are made of DNA (O.T. Avery, C.M. MacLeod, M. McCarty, Journal of Experimental Medicine, 79:137-58, 1944). McCarty conducted this research along with Rockefeller colleagues Oswald T. Avery and Colin M. MacLeod, both now deceased. The trio, originally aiming to find a cure for pneumonia, determined that DNA was the substance that controlled the reproduction of pneumococcus--a breakthrough that launched the modern age of molecular biology and genetics. According to the Philadelphia-based Institute for Scientific Information (ISI), this paper has been explicitly referenced in more than 1,000 subsequent articles. It long ago became part of the common wisdom of the field. Joshua Lederberg, University Professor at Rockefeller, has called the group's discovery "an outstanding example of the feedback of clinically motivated inquiry into the most basic issues of fundamental biological science" (J. Lederberg, The Scientist, Feb. 21, 1994, page 11). "It was an authentic discovery of a problem as well as a solution," says Lederberg. "It wasn't a problematic issue except in the minds of one group." He notes that, at the time, it was unclear that one could go about determining what genes are made of. The profound significance of the paper took years to be appreciated, partially because it was published during World War II, and partially because the journal in which it appeared was not widely read by pure geneticists. The group's findings were also challenged by several detractors, who claimed that there was not enough evidence to support the trio's conclusion. "People didn't get it," marvels McCarty, now 83. He recalls being the second presenter at a meeting at Johns Hopkins University in 1949, at which he was to discuss the DNA research. At the beginning of the event, the room was packed. But after the first lecture--on the use of Dramamine to treat seasickness--"the sound of people leaving the hall was so loud that I had to delay the start of my paper." When he finally began speaking, "there were about 35 people left." Another factor hindering widespread acceptance of the work was Avery's reluctance to personally promote it. "His view of [self-promotion]--practiced for many years before, as well--was to get the information published with the best possible proof of the point and let the interpretations fall where they may," McCarty reminisces. Ironically, although Avery received a Lasker award in 1947, he was cited "for distinguished service through studies on the chemical constitution of bacteria" rather than his DNA work. McCarty followed the 1944 paper with two articles describing his preparation of a purified pancreatic DNase (M. McCarty, Journal of General Physiology, 29:123-39, 1946) that, in nanogram quantities, would inactivate the transforming substance (M. McCarty, O.T. Avery, J. Exp. Med., 83:89-96, 1946). This evidence backed up the conclusions of the original article. In 1946, he left Avery's group to head a Rockefeller lab investigating streptococcal infections and rheumatic fever. The Lasker Foundation's Gutterman says the award to McCarty is intended "not only to honor the work, but to honor the field and publicize what's going on." Although the discovery occurred half a century ago, Gutterman points out, only recently has an understanding developed of "how cells act, how organisms develop, what normal physiology is, and how disease develops." McCarty, a member of the National Academy of Sciences (NAS) and the Institute of Medicine (IoM), received his M.D. degree from Johns Hopkins in 1937 and came to Avery's Rockefeller lab as a research fellow in 1941. He recounts his memories of the DNA work in his book The Transforming Principle (New York, W.W. Norton & Co. Inc., 1985). Overcoming Skepticism Prusiner was cited for identifying a new class of pathogens, which he named prions. He has reported that these infectious agents are implicated in diseases marked by slow onset with progressive deterioration of the brain and nervous system, including scrapie, a disease affecting sheep; as well as Gerstmann-Strussler-Scheinker disease (GSS), Creutzfeldt- Jakob disease, and kuru in humans. Prusiner defined the prion in a 1982 paper, "Novel proteinaceous infections particles cause scrapie" (Science, 216:136-44), which has been cited in more than 425 subsequent studies. This work was greeted by skepticism in certain scientific circles. The pathogen, he maintained, was composed only of protein; he did not find DNA or RNA in the prion, contradicting the general belief that all living organisms contain genes. Further fueling doubts among some of Prusiner's colleagues was his assertion that prion diseases can be inherited as well as infectious. Moreover, he concluded that the normal prion protein has a different shape from the disease form. This, too, was heretical, because it had long been thought that each protein has only one natural conformation. According to Gutterman, Prusiner's award also recognizes his "many years of very, very painstaking work [amid] a lot of opposition." In the early 1980s, the researcher and his prion theory were the subject of uncomplimentary articles in the scientific and popular press. His detractors maintained that the agent at work in these diseases was a slow-acting virus. While some investigators continue to look for a virus, the scientific community now generally accepts the idea of prions, which are now studied by many former proponents of alternative hypotheses. Prusiner "was all by himself against the world to prove the point," comments Pierluigi Gambetti, a professor of pathology at Case Western Reserve University School of Medicine who studies prion diseases. The copious data Prusiner produced ultimately won over the skeptics, says Gambetti, noting that he himself originally "had trouble understanding the mechanism." The "breakthrough" that shifted his perspective, recalls Gambetti, was Prusiner's results with transgenic animals. "The deeper I got into this, the more controversy there was, the more people got angry, the more I wanted to figure out what this [prion] was," says Prusiner. "I couldn't figure out a better problem to work on." Prusiner, 52, received his M.D. from the University of Pennsylvania in 1968 and then moved to UC-San Francisco, where he did an internship and a residency in neurology. "Today, I believe, it is very unlikely that my initial research would have been funded by NIH, because so little money is available for basic biomedical research," he said at the awards presentation. "The truly innovative proposals by young people don't have a chance anymore, at least I believe that to be the case." The general acceptance of the prion hypothesis in the past few years has manifested itself in the form of numerous significant prizes given to Prusiner, among them a Gairdner Foundation International Award, the Richard Lounsbery Award from NAS, a Charles A. Dana Award for Pioneering Achievements in Health, and a Christopher Columbus Quincentennial Discovery Award in Biomedical Research from the National Institutes of Health. He was elected to NAS and IoM in 1992. Lifesaving Research The Lasker Foundation recognized Clements, 71, for discovering lung surfactant, a soap-like mixture of lipoproteins that coats the lungs and prevents them from collapsing, in 1957. The paper reporting on this discovery (J.A. Clements, "Surface tension of lung extracts," Proceedings of the Society for Experimental Biology and Medicine, 95:170-2) has been cited in more than 340 papers; like McCarty's seminal DNA paper, it has become textbook knowledge. In 1959, researchers Mary Ellen Avery and Jere Mead of Harvard University found that respiratory distress syndrome, a leading cause of death in premature infants, develops because the babies are born before their lungs start producing surfactant. The condition resulted in the death of Patrick Bouvier Kennedy, the two-day-old son of President John F. and Jacqueline Kennedy, in 1963. In 1961, Clements and colleagues identified the major lipid component of surfactant, which led to attempts by multiple groups to synthesize the substance. In 1985, Clements developed a synthetic surfactant. The artificial substance, called Exosurf, was licensed to Burroughs Wellcome Co. of Research Triangle Park, N.C., and received Food and Drug Administration approval in 1990. "Now it has been demonstrated that surfactant-replacement therapy has reduced infant mortality to the lowest it's been, in the U.S. and in most industrialized countries," says Harvard's Avery, a member of the 1994 Lasker awards jury. Clements acknowledges that science rarely proceeds at a pace sufficiently rapid to enable a researcher to see favorable clinical results of his basic investigations in his own lifetime: "I recognize that fact every day. I think of all the people toiling in the vineyards--a lot of them work harder than I work; most are a lot smarter. [Therefore] I have to consider that Lady Luck played a role." For example, he notes, it was serendipity that led him to study the pulmonary system in the first place. During the Korean War, he volunteered for military service and was assigned to the U.S. Army Chemical Center in Edgewood, Md. At the time, government scientists were studying the effects of nerve gases, fearing that the Soviets might use them in chemical warfare. "I was assigned the task of figuring out how nerve gases affected the lungs. I had no particular interest in how the lungs worked up to that point." Following the war, Clements remained at the Army Chemical Center as a staff member until 1959. He has been at UC-San Francisco since 1961. An NAS member, he has received a Gairdner Award and a Christopher Columbus Discovery Award, among other honors. Clements stresses that many aspects of surfactant remain to be investigated: " 'Surfactant' tends to imply that it is something simple, but--no pun intended--we've only scratched the surface. We know so little about it at this point." Among the knowledge that remains to be gained, he says, is the role the substance plays in recovery from injury to the adult lung as well as in the lung's response to disease. At the Lasker awards luncheon, Clements announced that he would donate the honorarium to the United Nations International Fund for Children's Relief. In the stories of all three award-winners, Gutterman maintains, there runs a common theme: the "spinoff back and forth between basic and clinical research." In order to ensure future breakthroughs, he declares: "We have to have environments for these discoveries to be made, and we have to have long-term investments." (The Scientist, Vol:8, #20, pg.1, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Cancer Researchers Fear Impact Of Diminishing Funding Support Redistribution of federal financial backing may have drastic implications for cancer studies, they warn AU : Steven Benowitz TY : NEWS PG : 1 With federal research funds increasingly being earmarked for such publicly visible areas of biomedical investigation as AIDS and women's health, cancer research institutions in the United States are finding themselves in a bind. Saddled with a shrinking piece of the budgetary pie, heads of the nation's basic cancer research centers are struggling to maintain their high scientific standards while making ends meet. They worry that the frustration of stagnant funding levels will drive their best researchers to seek greener pastures. And they are concerned that, in the long run, the necessity of cutting costs will serve only to hinder scientific progress. Last month, the National Cancer Advisory Board told Congress that the nation's war against cancer had stalled, and that without several changes, cancer would become the country's top killer within five years (New York Times, Sept. 3, 1994, page A25). The board suggested, among other things, additional funding to move new discoveries from the laboratory to the bedside. The National Cancer Institute (NCI), for example, currently funds only 15 percent of overall grant applications -- down from 25 percent only a few years ago, says E. Premkumar Reddy, director of Temple University's Fels Research Institute in Philadelphia, one of 14 NCI- designated basic science cancer centers. Moreover, although the National Institutes of Health has not significantly increased the dollars available for cancer research, these monies are being funneled in several different directions, especially to more applied areas. In federally funded cancer research, the emphasis has shifted to therapeutics, particularly for such high-profile conditions as breast andprostate cancers, and away from basic science, cancer scientists say. "The money is going to the same tired, unsuccessful drugs," Reddy laments. "The only real innovations will come with basic research." Reddy draws an analogy to the advent of penicillin, which ushered in a revolution in medicine in the 1950s and 1960s. "In the next four or five years," he forecasts, "basic research in molecular biology may be able to achieve the same thing in cancer treatments. But not without the money to do it." Indeed, according to Reddy, NCI has mandated that the basic research centers that are affiliated with hospitals -- such as Fels and Temple -- must make their research more "applied." "Good basic science is hurting," he cautions. A Dying Breed Some observers fear that the university researcher with the resources to command the large, easily renewed federal grant that pays for a laboratory full of postdoctoral fellows, graduate students, and technicians has become a dying breed. "There's no question that there's a general biomedical funding crunch," says Robert Young, president of the Fox Chase Cancer Center, also based in Philadelphia. Fox Chase is one of 27 NCI-designated comprehensive cancer centers, which focus on patient care as well as clinical and basic research. "We have more good research projects than are adequately funded. In the last 10 years, we've seen an increase in the percent of grants that are approved but not funded." According to NIH's Division of Research Grants, only 15.8 percent of all new R01 investigator- initiated grant submitted in fiscal year 1993 were funded. This represents a drop from 1992 and 1991, in which 20.7 percent and 21.3 percent of such grants, respectively, were funded. Young blames a "stagnant federal research budget," combined with earmarking funds for particular areas of research, both of which "have been much more prevalent in the past five years and [have] affected overall funding opportunities." As a case in point, the NIH 1993 budget for AIDS research was $1.07 billion. The estimated 1994 figure is $1.3 billion -- an increase of $226 million earmarked by Congress-- as reported by the institutes' Office of Financial Management. A significant change in the overall federal budgetary outlays is not expected anytime soon. The House of Representatives and the Senate have agreed to award NIH an overall increase of roughly 3.6 percent for 1995, enough to keep up with inflation. Most institutes, including NCI, have been granted 3 percent raises. Pushing Applications "There's been an increasing pressure from the federal government to justify basic science on the basis of some potential clinical application," Young says. Often, those links are problematic. "That's what concerns basic scientists,"he notes. "The fact that there is no easily explained application of their research in medicine doesn't mean there won't be, but rather that we don't know what they may be yet." "People have argued that many of the breakthroughs in science and medicine have come at the basic-science level," Young points out. "An important breast cancer discovery may not specifically come from a research project labeled for breast cancer." As an example, he cites the retinoblastoma gene. It's a tumor suppressor gene that's believed to play a role in causing some breast cancers. Yet it was discovered as a cause of a relatively rare childhood eye cancer. "Earmarking makes it harder for people to secure funding," Young says. "It's produced a feeling of insecurity. Twenty years ago good researchers were pretty confident they'd be able to pursue their goals. Today no one is guaranteed." Norman Drinkwater, director of the McArdle Laboratory for Cancer Research at the University of Wisconsin, Madison, worries that the tougher competition for funding will affect the next generation of scientists. "I think we'll start to lose a number of talented scientists as they become frustrated trying to establish top research programs," he predicts. He's particularly concerned about a budget shortfall for training programs and grants that include support for predoctoral and doctoral students. "As we fail to fund these training programs, we'll develop fewer first- rate scientists for the future," he warns. The funding crunch may well hinder scientific progress if something isn't done, says researcher David Schuller of Ohio State University in Columbus. "The problem is, we've reached a point today in which the rate of scientific discovery in cancer research is resource-driven -- and resource-limited." "As the level of competition for funding gets keener, you can't separate the quality of research proposals as easily," maintains Schuller, who is director of Ohio State's Comprehensive Cancer Center-Arthur G. James Hospital and Research Institute. Greater competition for the same research dollars also has made it tougher to secure support the first time around. Young investigators are competing with more seasoned researchers whose grant requests may initially have been turned down, and who are already resubmitting revised proposals. "The system tends to exclude the entry-level investigator, which affects the future of biomedical research," Schuller says. That message seems to be getting out. A report issued in July by the National Research Council (The Funding of Young Investigators in the Biological and Biomedical Sciences, Washington, D.C., National Academy Press, 1994) showed that the number of biologists under the age of 37 applying for independent NIH grants dropped by more than 50 percent in the past eight years, though applications from older colleagues increased by more than a third.Young sees little funding relief in sight, with federal budget caps and growing public entitlement budgets contributing to keeping the biomedical research funding relatively unchanged for the next several years.Yet many, like Giovanni Rovera, director of the Wistar Institute of Anatomy and Biology in Philadelphia, contend that the money is still there. But he agrees that greater competition for the same research dollars has made it tougher to secure support the first time around. The "worthy" projects will get support, Rovera forecasts. It just may take two or three grant rewrites before the money comes through. And the support may be for less time and fewer dollars than expected (see story on page 4). "The problem isn't getting the money, but rather, getting it promptly, when you want it," Rovera says. Shelley Berger, an assistant professor who came to Wistar in 1993 from a postdoctoral position at the Massachusetts Institute of Technology, uses baker's yeast to examine how genes are turned on and off. Her latest grant application was funded by both the National Science Foundation and the American Cancer Society, but not by NCI. Berger acknowledges that many of her friends whose "work is just as good and worthwhile of funding" have been turned down for federal dollars. "There's plenty of science available, but just too many people who want to do it." Problem With Earmarking "Earmarking affects the way science is done in this country," asserts microbiologist Clayton Buck, deputy director of Wistar. "By forcing scientists to be more competitive, you make them focus on applied areas that they may not necessarily have chosen. Now they have to because that's where the money is -- you affect their choices of research specialties." Former NCI director Vincent DeVita, who now is director of the Yale University Cancer Center, agrees. "Earmarking is dangerous because it takes dollars from the general RO1 investigator-initiated grant pool and forces investigators to redirect their thinking to the direction of translational research," he says. "It's not that I'm against translational work; I'm just against manipulating the R01 pool." Such choices may also affect tenure and promotion decisions. "Universities [define] successful scientists as whether or not you have an R01 grant," DeVita observes. "in the old days, you could get grants and spend a few years doing research and find out whether you were any good as a scientist. You're under tighter restrictions and tougher demands today." While Young, Rovera, and DeVita decry earmarking of federal dollars as a potential threat to the future of the United States research base, Congress and the public seem to be demanding greater accountability from researchers, according to agency officials and other veteran science-watchers. For whatever problems scientists choose to address, legislators want to be sure tax dollars are resulting in clinical payoffs, or at least marketable products. Scientists have had to become more attuned to potential clinical applications of research, particularly when writing grant proposals. "We're being held more accountable by Congress and the public," says Faye Austin, associate director for extramural research in NCI's Division of Cancer Biology, Diagnoses, and Centers. "We've made a large investment in biomedical research in the last 20 years, and the public asks, "What are we getting for this?" "Things have changed since AIDS came along with the empowerment of the AIDS constituency," she notes. "They've been successful in getting resources, and have taught similar lessons to other groups." Last year, for example, the National Breast Cancer Coalition, along with other groups, lobbied Congress and persuaded it to double the money it spends on breast cancer research. "The public is putting pressure on researchers to show results," Austin adds. Steven Benowitz is a science writer for Penn State University Milton S. Hershey Medical Center in Hershey, Pa. (The Scientist, Vol:8, #20, pg.1, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : SLIMMER WISTAR IN TRANSITION AU : STEVEN BENOWITZ TY : NEWS PG : 4 The Wistar Institute of Anatomy and Biology in Philadelphia shares the woes of other basic science cancer centers: how to deal with an uncertain funding environment, given the increased push by federal funding agencies to support applied research. Compounding matters, Wistar has had the added burden of a three-year legal battle over management issues with former director Hilary Koprowski, settled in June 1993. Although just three years ago Wistar faced a $2 million budget deficit and declining morale, today the staff credits the new director, Giovanni Rovera, with streamlining the institute--closing unproductive laboratories and reducing the work force. Now, a leaner Wistar seems re-energized, with a fresh sense of purpose, according to Robert A. Fox, immediate past president of its managing board and president of RAF Industries Inc., a private investment company based in Elkins Park, Pa. Earlier this year, the institute finally celebrated its centennial--albeit three years late. In singing Rovera's praises, his supporters point to a $1 million research grant awarded in 1992 by Philadelphia- based Pew Charitable Trusts. This support, they say, has helped bring in a new wave of young scientists, while helping to strengthen scientific initiatives in structural biology, molecular genetics, and cell and developmental biology. Scientific collaborations have flourished. Scientists from Wistar and the University of Pennsylvania-- on whose campus it sits--are studying gene therapy for cystic fibrosis and a number of other diseases, for example. And Wistar and Children's Hospital of Philadelphia are using a five-year, $5.9 million grant from the National Heart, Lung, and Blood Institute to establish a pediatric cardiology center. "The institute is clearly now becoming stabilized after several turbulent years," says Rovera, a specialist in pediatric leukemias. "The focus is clearly on science, though we still must keep an eye on financial matters. Our precarious economic reality, relying mostly on federal grants, and not patient-care revenues, forces us to." As part of the centennial celebration, honors were bestowed upon Koprowski, a Polish-born virologist who headed Wistar from 1957 to 1991 and made it a world-class institution. Koprowski, who has since moved across town to Thomas Jefferson University, was named professor laureate at Wistar and given a position on the institute's controlling board of managers. Wistar is known in the research establishment for a century of accomplishments. One of 14 basic cancer centers designated by the National Cancer Institute, it carries a research budget of about $25 million, with some 75 percent of its grant funding coming from the National Institutes of Health. About 70 percent of its work is devoted to various aspects of cancer. Its many achievements include the development of the first line of continuously growing normal human cells, the design of vaccines against rubella and rabies, and the creation of specialized antibodies to seek out and destroy cancer cells. Wistar scientists have identified interleukin-12, an immune system regulator that may play a key role in AIDS, and are working on perfecting vaccines against rotavirus, which causes infantile diarrhea, and cancer. "Wistar is a unique environment," says Nancy Fogg-Johnson, vice president for administration. "It's an academic institution without teaching requirements, so the scientists can really dedicate themselves to basic science." She contends that while Wistar has done "relatively well" in securing funds for research in the past, it must "step up its efforts to get support from private sources." Wistar has also been receiving royalties for its numerous discoveries over the years, such as rubella and recombinant rabies vaccines, as well as the hybridoma method for producing monoclonal antibodies for detection and treatment of cancers. Deputy director Clayton Buck, a cell biologist and professor of pediatric cardiology who heads the new pediatric cardiology center, acknowledges that Wistar has had a poor track record in garnering private funding: "An institution of our size should have an endowment of some $150 to $200 million. We probably have a tenth of that." The grant funding base at Wistar during the past several years had been eroding because of a number of factors. One of these was the departure of several senior investigators when Koprowski went to Jefferson. "Two program projects that he had involving the genetics of cancer and multiple sclerosis were not renewed," Rovera notes. According to Rovera, Wistar scientists have been somewhat successful this year--better than expected, in fact--in securing new grants. "We've had to make adjustments; weUre increasing our emphasis in technology transfer, and being more demanding than in the past with upfront money and licensing fees. We canUt afford to wait for royalties. That's happening at other institutions, too." --S.B. (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Gerontology Investigators Press An Ambitious Agenda AU : Karen Young Kreeger TY : NEWS PG : 1 Despite a substantial increase in the flow of financial support for gerontological research during the past several years, ambitious investigators of aging-associated phenomena continue to lament that their field is underfunded. One such investigator is Denham Harman, a professor, emeritus, at the University of Nebraska College of Medicine in Omaha. The 78-year-old Harman for many years has argued that aging research deserves far more attention and financial support than it traditionally has received--especially because the United States population, according to demographic statistics, is rapidly getting older. "We need to spend more money on basic biomedical research on aging to go after its basic causes," he asserts. Harman acknowledges his gratification at seeing significant funding gestures in the past year alone by such private sources as the Charles A. Dana Foundation in New York and the Glenn Foundation for Medical Research in Santa Barbara, Calif. And he was heartened most recently to hear of a $14.3 million infusion--called the Paul Beeson Physician Faculty Scholars in Aging Program--into the gerontology research effort from a consortium of three private foundations. Harman nevertheless in-sists that backing for gerontology studies remains inadequate for the important task facing researchers in the field. "One should not be deluded," he warns. 'A Shot In The Arm' Last month's show of support through the Beeson program was announced by the initiative's three cosponsors: the John A. Hartford Foundation and the Commonwealth Fund--both New York- based private philanthropies--and the Alliance for Aging Research, a Washington, D.C., private, nonprofit advocacy group that promotes research and policy attention to issues of aging. The program's main purpose is to support young faculty members whose research relates to aging and to promote the study of aging across disciplines, especially in U.S. medical schools. The program is named as a tribute to gerontologist Paul Bruce Beeson, a professor of medicine and distinguished physician who is now retired from the University of Washington and the Veterans Administration Hospital, both located in Seattle. Robert Butler, a geriatrician at the Mount Sinai Medical Center in New York and first director of the National Institute on Aging (NIA), calls the initiative a "shot in the arm" for "young people just on the crest of their careers." Nevertheless, many observers are still calling for more funding. Over the last four years, three groups have separately proposed substantial increases for aging research. In 1990, the Pepper Commission TK, a U.S. bipartisan panel looking into comprehensive health care, recommended in its final report that the federal government move toward a funding level of $1 billion annually to finance "a research and development program aimed at preventing, delaying, and dealing with long-term illnesses and disabilities," including studies on such diseases and disorders as Alzheimer's, osteoporosis, and urinary incontinence. One year later, a committee from the Institute of Medicine echoed the Pepper Commission's recommendations. In its report, Extending Life, Enhancing Life: A National Research Agenda on Aging (Edmund T. Lonergan, ed., Washington, D.C., National Academy Press, 1991), the committee said that "a major investment in research on aging is needed urgently." This support should total "$913 million annually, a figure approaching the $1 billion recommended by the Pepper Commission," the report stated. Most recently, a group of 72 nonprofit professional and advocacy groups called the 1994 Task Force for Aging Research Funding issued a statement urging Congress and the president to "enact legislation authorizing $1 billion a year for aging research at NIH, and $2 billion a year by the end of the decade." And as Harman stated in a commentary in The Scientist (March 19, 1990, page 18), "Funding for basic biomedical research on aging is meager. Only between $25 and $50 million is available per year, largely from the National Institute on Aging. In contrast, more than $2 billion is allocated each year for two major causes of death--cancer and atherosclerosis." In fiscal 1994, close to half of NIA's total $420 million budget was devoted to Alzheimer's research, with the other half going to fund sociological, behavioral, psychological, and basic biomedical research (see story on page 14. Daniel Perry, executive director of the Alliance for Aging Research, agrees that there aren't enough funding sources to enable scientists to properly study the basic processes of aging. What the Beeson program will do, he says, "is bring a measure of high-quality science to bear on understanding the conditions that afflict older people. It will bring understanding the biology of aging into the forefront, and it will increase the sophistication of physicians in how to diagnose, treat, prevent, postpone, and rehabilitate chronic diseases in the elderly." Harman adds that the program "will increase the visibility of aging" as an area of research, so that, he says, more attention will be paid by the science community to this underrepresented discipline. Thirty In Three Years "The goal for the Beeson program," says Perry, "is to have 30 leaders [in aging research] in place at the end of three years. Only a handful of medical students have an exposure to geriatrics and gerontology, and these are not exposed to the best science on aging at that. [The Beeson initiative] is more than a step in the right direction." Each year, for three years, the program will select 10 junior faculty members and provide each with a grant of up to $150,000. The application deadline for the first round of funding is December 15, with final decisions to be announced in April. A national committee, headed by William N. Kelley, chief executive officer of the University of Pennsylvania's Medical Center and Health System and dean of Penn's School of Medicine in Philadelphia, will review applications and select the scholars. The American Federation for Aging Research (AFAR), a New York-based group that funds gerontology and geriatrics research, and the alliance will share administrative and technical support for the program. Creators of the program say its main emphasis is to attract top-flight young physician-scientists to commit their careers to research and training in aging. "The goal is to generate more well-prepared and leading junior faculty members," states Franklin Williams, scientific director at AFAR and a professor of medicine, emeritus, at the University of Rochester, New York, "and to give people who have promise the opportunity to have some really good free time for advancing their research and their careers. "I think the bulk of the applicants will probably be at the interface of biomedical and clinical research." The fields that prospective recipients could be from is "really quite open," remarks Williams, who was NIA director from 1983 to 1991. For example, he notes that the chosen scholars could just as likely have degrees in genetics, molecular biology, or physiology as in psychology or sociology. Each scholar will be paired with a senior faculty mentor from his or her home institution. The program will stage an annual meeting of scholars, mentors, and leaders in academic medicine to review and disseminate research findings of the scholars. Sign Of The Times Almost every cry for more resources for aging research --whether for work on its sociological aspects or its biomedical underpinnings-- cites the demographic shift in the U.S. population to an older majority as the impetus. "In this century, with the baby boom, we've established departments of pediatrics in every medical school in the country and only one in geriatrics [the Mount Sinai School of Medicine, New York]," says the alliance's Perry. "It is this unprecedented and profound shift to an older population that is forcing medical schools to adjust, but they haven't been forced quickly enough. "Efforts by the federal government to induce training of faculty have been modest, at best. And what we now are seeing are these three nonprofit, philanthropic entities committing over $14 million to jump-start the field in the space of three years." And, according to Perry and others in the field, there are other places--but not enough--that are starting to commit large amounts of money to support research in aging, in addition to NIA's commitment. Non-NIA funding comes from such private groups as AFAR, the New York-based Brookdale Foundation Group, and the Sandoz Foundation for Gerontological Research in East Hanover, N.J. (see story on page 11). Still others like the Charles A. Dana Foundation of New York and the Buck Center for Research in Aging in Novato, Calif., mount their own research initiatives (see story on this page). (The Scientist, Vol:8, #20, pg.1, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : WHERE GERONTOLOGISTS GET TOGETHER TY : NEWS PG : 11 Following are some of the professional societies whose memberships include biological, social science, and clinical researchers in the fields of geriatrics and gerontology. American Aging Association (AAA) American College of Clinical Gerontology (ACCG) 2129 Providence Ave. Chester, Pa. 19013 (610) 874-7550 Fax: (610) 876-7715 Arthur K. Balin, executive director of AAA and president of ACCG American Geriatrics Society 770 Lexington Ave., Suite 300 New York, N.Y. 10021 (212) 308-1414 Fax: (212) 832-8646 Harvey Jay Cohen, president Linda Hiddemen Barondess, executive vice president Gerontological Society of America 1275 K St., N.W., Suite 350 Washington, D.C. 20005-4006 (202) 842-1275 Fax: (202) 842-1150 E-mail (via Bitnet): gsa@gwuvm Linda K. George, president Carol Schutz, executive director Society for Neuroscience 11 Dupont Circle, N.W. Suite 500 Washington, D.C. 20036 (202) 462-6688 Larry Squire, president Nancy Beang, executive director (The Scientist, Vol:8, #20, pg.11, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : ACCESSING AGING ASSETS TY : NEWS PG : 11 Following are some of the funding sources for research on aging, including basic biomedical research, clinical research, and training: American Federation for Aging Research (AFAR) AFAR Research Grants: awards of up to $40,000 for one year to junior faculty for preliminary research projects. Merck/AFAR Fellowships in Geriatric Clinical Pharmacology: awards of $100,000 over two years, cosponsored by Merck & Co. Inc., Rahway, N.J., to train physicians. Glenn Foundation/AFAR Scholarships in the Biology of Aging: awards of more than $5,000 for predoctoral students--both M.D. and Ph.D.--cosponsored by the Glenn Foundation, Santa Barbara, Calif., to conduct three-month biomedical research projects. For more information on these grants and the Beeson Scholars in Aging Program, contact Odette van der Willik, grants manager, AFAR, 1414 Ave. of the Americas, 18th Floor, New York, N.Y. 10019; (212) 752-2327. Fax: (212) 832-2298. Brookdale Foundation Group (BFG) Grants of various amounts in the fields of gerontology and geriatrics. The foundation requests that prospective applicants submit a one-page letter explaining a project's concept. These are reviewed at monthly board meetings, whereupon some applicants are invited to submit a full proposal. For more information, contact Nora O'Brien, BFG, 126 E. 56th St., New York, N.Y. 10022. Sandoz Foundation for Gerontological Research Grants of up to $35,000 for one year in the areas of biology, pharmacology, immunology, geriatric medicine, psychogeriatrics, and epidemiology. The foundation is affiliated with the pharmaceutical company Sandoz Ltd. of Basel, Switzerland. For more information, contact Agnes Sisto, Sandoz Foundation, 59 Route 10, East Hanover, N.J. 07936-1080; (201) 503-8544. Fax: (201) 503-7185. --K.Y.K. (The Scientist, Vol:8, #20, pg.11, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : 24th Annual Neuroscience Meeting To Attract A Variety Of Specialists AU : Neeraja Sankaran TY : NEWS PG : 3 The 24th annual meeting of the Washington, D.C.-based Society for Neuroscience, to be held November 13 to 18 in Miami Beach, Fla., is likely to be the largest conference in the association's history, according to society officials. Almost 15,000 of the society's 23,000 members are expected to attend. The event will offer a mixed bag of topics in about 17 symposia and 15 lectures, in addition to various workshops, courses, panel discussions, and more than 10,000 posters and slides. "Our meeting is unique in that it draws a large proportion of society members," remarks Larry Squire, the current president as well as a professor of psychiatry and neuroscience at the University of California, San Diego, and a staff research scientist at the San Diego Veterans Affairs Medical Center (VAMC). "It would be hard to pick any special themes of interest--we have everything from molecular and cellular research to cognitive studies." (See accompanying list for a sampling of topics.) Squire's own area of expertise--the biology of memory--is the subject of a special presidential symposium, and by itself demonstrates the scope of the neurosciences. The two- hour session will include discussions on genetic, regulatory, and chemical aspects of memory. This year the symposium commemorates Walle J. Nauta, a noted neuroscientist from Harvard University who died earlier this year, shortly after being named the winner of the National Academy of Sciences Award in the Neurosciences (N. Sankaran, The Scientist, April 18, 1994, page 1). In addition to the symposium, there will be three special presidential lectures, including one on the evolution of the brain by Harvard University evolutionary biologist Stephen Jay Gould. Scheduled for 11:15 a.m. on Wednesday, November 16, this lecture will be simultaneously videocast to a second room to accommodate attendees unable to fit in the lecture theater. Death In Development A particularly "hot" area of neuroscience research nowadays, say many scientists, is developmental neurobiology--the study of how nerve cells differentiate in the embryo and achieve their final form. Several sessions at the meeting, including one of the presidential lectures, will discuss advances in this subdiscipline. The featured speaker, H. Robert Horvitz, a professor of biology and a Howard Hughes Medical Institute investigator at the Massachusetts Institute of Technology, will discuss the role of programmed cell death--also called apoptosis--in development. "A great number of cells die in the course of normal development; the question is why and how," says Horvitz. His studies on the phenomenon in the nematode Caenorhabditis elegans revealed that the genes and proteins involved in the programmed death of nerve cells in this organism were similar to certain genes and proteins found in humans (J. Yuan et al., Cell, 75:641-52, 1993). "It is [my] hypothesis that the pathway of programmed cell death is highly conserved between nematodes and humans," he adds. Horvitz will also talk about the applications of his work in understanding such neurodegenerative diseases as Parkinson's and Alzheimer's. Attention On Animals A regular feature at the society's annual conferences has been a forum or panel discussion organized by its Committee on Animals in Research. The subject is particularly important to the society because of the significant amount of neuroscience research that uses animals as experimental models, according to committee chairman Stuart Zola-Morgan, a professor of psychiatry at UC-San Diego and a research scientist at the San Diego VAMC. This year the discussions will focus on two issues. One is public opinion on the use of animals in research, including polling data showing how men's and women's views vary on this subject. The other issue is a recent strategy implemented by animal rights groups to promote their cause, whereby they align themselves with women's groups, targeting perceived parallels between the use and treatment of animals in research and the exploitation of women. Panelists include Mary Woolley, president of Research!America, a research- advocacy group based in Alexandria, Va.; Sandra Bressler, director of scientific and educational activities at the California Medical Association; and Andrea Zardetto-Smith, a professor of psychology at the University of Iowa, Iowa City. Zola-Morgan will act as the moderator for the session. Animal research will also be touched on during a workshop for high school students to be held at the conference. "We feel an obligation to explain the importance of animal [models] in research, particularly with the resurgence of animal rights concerns in schools," says Squire. Capitol Neuroscience A special workshop entitled "Educating your legislators or suffering the consequences" is scheduled this year, to introduce the society's members to the process of law-making and the dispensation of research funds by Congress. "The workshop will talk about how Congress deals with various scientific and funding issues, and how scientists can affect those decisions," says workshop presenter Frankie Trull, vice president for government affairs at Capitol Associates Inc., a government-relations consulting firm in Washington, D.C. "What kind of funding goes to a particular type of research depends on the importance given to it by Congress," she notes, "and the best option for a scientist is to speak directly to Congress and arm them with relevant knowledge so that they can make informed decisions. "This workshop will deal with some of the dos and don'ts-- don't argue, do express yourself clearly, and do follow up," advises Trull. For more information on the society's meeting, contact Joseph Carey or Julie Ziegler at the Society for Neuroscience, 11 Dupont Circle, N.W., Suite 500, Washington, D.C. 20036; (202) 462-6688. A computerized Program Search System listing the title, author and affiliation for each abstract along with the date and time of presentation can be obtained ahead of time, for a fee, along with registration. (The Scientist, Vol:8, #20, pg.3, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : AT A GLANCE (SOCIETY FOR NEUROSCIENCE - PROGRAM FOR THE 24TH ANNUAL MEETING) TY : NEWS PG : 3 The 24th annual meeting of the Society for Neuroscience will run from Sunday, November 13 to Friday, November 18, at the Miami Beach Convention Center in Miami Beach, Fla. Following is a list of the planned symposia and lectures scheduled du- ing the conference: Sunday, November 13 Decade of the Brain Lecture, 8:00 p.m.-9:00 p.m.: "Consolidating the gains in brain" Monday, November 14 Presidential Special Lecture, 10:00 a.m.-11:00 a.m.: "Cell death in development and disease" History of Neuroscience Lecture, 1:00 p.m.-2:00 p.m.: "Evolving concepts of function of the neocortex" Special Lectures 11:15 a.m.-12:15 p.m.: "Molecular studies of physiological functions of glutamate receptor" 4:15 p.m.-5:15 p.m.: "The molecular biology and biophysics of prions causing CNS degeneration" Symposia 8:00 a.m.: "Molecular mechanisms of axon guidance"; "Genes with triplet repeats in neuropsychic illness" 1:00 p.m.: "Neuroscience implications of inborn errors of metabolism"; "Mo-lecular mechanisms of controlling K+ channel diversity and distribution in the nervous system" Presidential Symposium 8:00 p.m.-10:00 p.m.: "The biology of memory: From synapses to systems" Tuesday, November 15 Presidential Special Lecture, 4:15 p.m.-5:15 p.m.: "Transient and enduring effects of experience: Functional studies of the visual and motor cortex" Grass Foundation Lecture, 8:00 p.m.-9:00 p.m.: "In your ear: Transduction, tuning, and transmission by hair cells" Special Lectures 11:15 a.m.-12:15 p.m.: "Membrane receptors and ion channels: Electron crystallographic studies of their design and action" 1:00 p.m.-2:00 p.m.: "Evolutionary origins of neocortex: Reshuffling neurometers to make a new deck?" Symposia 8:00 a.m.: "New approaches to understanding dendrites"; "The amygdala: From circuits and synapses to emotional memory" 1:00 p.m.: "Cytokines and neural development"; "Autonomic integration in the control of food intake" Wednesday, November 16 Presidential Special Lecture, 11:15 a.m.-12:15 p.m.: "Adaptation and exaptation in the evolution of the human brain" Special Lectures 1:00 p.m.-2:00 p.m.: "The role of local signals in the control of CNS neuronal development" 4:15 p.m.-5:15 p.m.: "Potassium channels" Symposia 8:00 a.m.: "Early development and molecular plasticity in the mouse brain"; "Molecular plasticity in epilepsy and ischemia" 1:00 p.m.: 8:00 a.m.: "Early development and molecular plasticity in 8:00 a.m.: "Early development and molecular plasticity in 8:00 a.m.: "Early development and molecular plasticity in Toward a neurobiology of visual consciousness"; "Developmental control of electrical excitability" Thursday, November 17 Warner-Lambert Lecture, 11:15 a.m.-12:15 p.m.: "Ins and outs of programmed cell death" Special Lectures 1:00 p.m.-2:00 p.m.: "Brain map for movement" 4:15 p.m.-5:15 p.m.: "Muscimol, memory, and motivation in the basal ganglia" Symposia 8:00 a.m.: "Structure, function, and regulation of glutamate receptors"; "General anesthetic effects on somatomotor processing" 1:00 p.m.: "The cell biology of secretion vesicles"; "Neuropeptide regulation of brain development: From cells to animals" Friday, November 18 Symposium 8:00 a.m.: "Neural coding of visual space: Visual mechanisms of multimodal integration" (The Scientist, Vol:8, #20, pg.3, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: NOTEBOOK ------------------------------------------------------------ TI : Calling All Taxonomists TY : NEWS (NOTEBOOK) PG : 4 The National Science Foundation's division of environmental biology recently announced a special grant competition-- called Partnerships for Enhancing Expertise in Taxonomy--to stimulate taxonomic research and training. The initiative is spurred by concern over dwindling numbers of younger scientists taking up taxonomy--the study of the general principles of scientific classification--and systematics and the limited knowledge that exists about thousands of species. Specifically, NSF is seeking applicants to submit ideas on how to train future generations of taxonomists and how to translate current expertise into electronic databases to broaden accessibility of taxonomic data, as well as research proj-ects on taxonomy and evolution, especially of little-known species. The deadline for applications is March 1. For more information, contact the division of environmental biology at (703) 306-1480. E-mail: (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) NXT: ------------------------------------------------------------ TI : For Young Experimenters TY : NEWS (NOTEBOOK) PG : 4 Science students and teachers seeking ideas for classroom science projects or contests can now turn to the Science Experiments and Proj-ects Index. Written and edited by the staff of the Columbus (Ohio) Metropolitan Library, the source describes 8,400 hands-on, interactive experiments and project ideas. The book is published by Fort Atkinson, Wis.- based Highsmith Press, (800) 558-2110 or (414) 563-9571. (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) NXT: ------------------------------------------------------------ TI : Clearing The Air TY : NEWS (NOTEBOOK) PG : 4 Beginning this month, the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, N.C., is establishing a clearinghouse to provide information or referrals for questions about health and the environment. Users can call EnviroHealth toll-free at (800) NIEHS94 (643-4794) to receive information about NIEHS research and training programs as well as referrals to other NIH offices; clearinghouses; toll-free numbers; federal, state, and local agencies; and information sources. (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : In The Name Of Cheeses TY : NEWS (NOTEBOOK) PG : 4 In keeping with the age-old link between fermentation and religious orders--some of the best wines hail from monasteries--Sister Noella Marcellino, a member of the Benedictine Abbey of Regina Laudis in Bethlehem, Conn., and a graduate student in microbiology at the University of Connecticut in Storrs, is conducting research on the microbes that flourish in naturally ripened cheeses and how those organisms impart their distinctive flavors and aromas. Her work gained her a Fulbright grant to travel to France for nine months to study the microbes in such specialty cheeses as Camembert and St. Nectaire, which are produced in the Auvergne region. Sister Noella's microbial studies will be conducted in a laboratory in Burgundy, where many traditional cheeses are produced. In addition, she will investigate traditional methods of ripening cheeses in caves. (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Natural History Online TY : NEWS (NOTEBOOK) PG : 4 Now available free of charge over the Internet is the full catalog of Yale University's Peabody Museum of Natural History. With more than a million entries, the catalog offers information on the New Haven, Conn., collection's nearly 11 million specimens, including some of the most scientifically significant dinosaur fossils in the world. To access the Peabody database, use the gopher command to connect to "" at port number 70. For more information, contact Peabody's Lawrence Gall at (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : A Helping Handbook TY : NEWS (NOTEBOOK) PG : 4 The Grant Application Writer's Handbook, by Liane Reif- Lehrer--a former Harvard Medical School researcher and National Institutes of Health study section member--was issued earlier this month by Boston-based Jones and Bartlett Publishers. The book covers both the psychology and the mechanics of proposal writing, taking readers through the steps of planning, outlining, drafting, revising, and finishing an application. For more information, contact Jones and Bartlett Publishers, One Exeter Plaza, Boston, Mass. 02116; (800) 832-0034. Fax: (617) 859-7675. (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Cool Comfort TY : NEWS (NOTEBOOK) PG : 4 The Multiple Sclerosis Association of America (MSAA) and the National Aeronautics and Space Administration (NASA) have signed a "Memorandum of Understanding" that expands their collaborative efforts to further develop a spin-off NASA technology--known as microclimate cooling--used to produce lightweight vests, dubbed "cool suits," worn by MS patients who suffer from heat stress. Those donning the suit have experienced improvements in their speech as well as relief from fatigue and other symptoms associated with the disease, according to MSAA. For more information about microclimate cooling and other MSAA services, call (800) 833-4MSA. (The Scientist, Vol:8, #20, pg.4, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: OPINION ------------------------------------------------------------ TI : ARTHUR CAPLAN DISCUSSES ISSUES FACING THE GROWING FIELD OF BIOETHICS AU : FRANKLIN HOKE KAREN YOUNG KREEGER TY : OPINION PG : 12 Editor's Note: In May 1994, preeminent bioethicist Arthur Caplan moved his base of operations from the University of Minnesota, Minneapolis, where he had established the Center for Biomedical Ethics, to the University of Pennsylvania in Philadelphia. There, he launched the Center for Bioethics, hoping to expand the purview of his activities through association with the extensive biomedical research community at Penn and in the greater Philadelphia area-- initially, for example, sharing temporary offices with the university's Institute for Human Gene Therapy. The 44-year-old Caplan, who is the author of dozens of scholarly papers, also strives to make critical bioethical debates comprehensible to the public, most recently in his book Moral Matters: Ethical Issues in Medicine and the Life Sciences (New York, John Wiley & Sons Inc., 1995). As the fall semester got under way at Penn last month, Caplan met with Senior Editor Franklin Hoke and Associate Editor Karen Young Kreeger of The Scientist for a wide-ranging discussion of his views and plans. Following is an edited presentation of the interview. Q Why did you decide to move to Penn? A Well, Minnesota--the medical school in particular--had oriented itself very strongly toward some high-tech forms of transplantation, like bone marrow, while Penn has this emerging gene therapy, testing, and screening interest and was pulling together a group of people to do molecular medicine. So, intellectually, that was a big draw for me. Also, Minnesota didn't have much of a group doing health economics and policy. But Wharton [Penn's business school] does, and that was another attraction. Q Is Philadelphia a good place to practice your discipline? A Surprisingly, Philadelphia has not been a major presence on the bioethics front, although it has all these medical schools and hospitals--Fox Chase [Cancer Center], the [American] College of Physicians, and so forth--and it has a lot of pharmaceutical companies. So it looked like a place where one could go and make something happen. Q What are some of the new things you hope to do here? A We'll definitely be moving into the genetics area, and we'll try to work with Penn's very good history and sociology of science units in the areas of eugenics, heredity, and human nature theories. So, we'll go into everything from the most practical questions--such as insurance implications--to lofty theoretical matters [like] what's a disease and whether medicine has, as its mission, to improve or enhance as well as repair things. Q What bioethical areas are you most concerned about? A I'm especially interested in the rationing of health care, both at the bedside and in terms of who gets access to high-tech treatment--things like that. I'm also interested in how to divvy up the health-care budget for the readers of The Scientist. Should we spend more money on research or put some kind of embolism in the research pipeline to slow down cost? And what is the proper incentive system for technology transfer? And then there are end-of-life care decisions--termination- of-treatment- and assistance-in-dying- type matters. And questions of research on children--do we have a system that protects their interests? If I tell you that your daughter is sick and we can lop off half her pancreas to try to save her, and you ask, "What are my options?" and I say, "None," and you say, "Okay, you have my consent"--is that good enough? Does informed consent mean anything in the context of very sick kids? My hunch is that it doesn't--and then how do we replace or supplement informed consent? Q Do you have a particular technique for exploring this sort of issue? A When I was in Minnesota, our center had a reputation for trying to integrate descriptive empirical work with prescriptive things, and I think we will do that at Penn, too. Before I tell people what to do, I'd like to know sort of what they're doing first. It may turn out that what they're doing is what they're supposed to do, and it may waste a lot of time to fish around for what they ought to do if you don't know what they're doing already. I have the feeling that most people don't read the informed consent form, so shaping it into a finely honed document is probably not useful for a lot of people. On the other hand, there may be issues coming up from the subjects that are not captured on the informed consent form. But if you don't debrief them you'll never know that they were mad about this or that nobody ever told them, for example, that they were going to be nauseated after a certain test. That's the place where I think we can do some interesting empirical examination. Q What are the origins of bioethics? A Well, bioethics more or less started in response to scandals over such things as the Tuskegee Study, where people were deceived about getting treated for their syphilis and not told that they had syphilis; or the Brooklyn Jewish Chronic Disease Study, where demented, terminally ill elderly patients were given live cancer cells with no one's consent; or the Texas Contraceptive Trial, where women were given placebos to test the effectiveness of birth control pills. In response to these early T60s scandals, bioethics shows up in the late T60s and says, "We're going to fix this." Q You say that "descriptive empirical work" is important to you. Is that approach new to bioethics? A Yes, it's definitely new. The scope could be anything from what happens to someone who's signing up as a subject for a research project all the way out to how a doctor decides who gets access to a CAT scan. You just come in and interview a dozen or so people at length, almost like a journalist would, and sort of follow them over time and paint the picture. Now, I'm not sure that anybody can say, statistically, what number of case studies is enough to generalize out to. But we are not interested in generalizing--we're not interested in saying we understand the whole population. Our empirical approach lets us pick up what the problems are. I don't care if only one person encounters a problem or 10 do; even if it's a problem of one person, it's still a problem. Q Does the use of an empirical approach help make bioethics a science? A The goals of ethics research aren't the same as those of scientific study. The scientist may want to know how common a problem is or, if you change variables, will it go away. I am more interested in finding out simply what problems exist out there. I sometimes think of this as "moral systematics." It's like doing taxonomy. I talk this way in part because I grew up as an evolutionary biologist, but it seems to me that I'm closer to moral ethology in a sense of how an animal behaviorist might study what's going on out in nature and look for problem identification and classification. The other type of empirical work involves what I could call historical-sociological studies. We might, for example, be looking at genetics as part of a historical review of what happened in eugenics. Does anybody really know what the Nazis did? Has anyone really looked at their arguments about why they did it? And do we really understand enough about the German or American experience with eugenics? I am interested in looking at old laws, old policies, old ethics arguments. What did the scientist in Germany say about working in the camps? Q And what are the present-day applications? A I would call that an analogical examination. Does the analogy hold up? Is it tight enough? Do you see the same arguments today that you saw in the camps? Are the empirical circumstances different from what they are today? We want to see if the analogies, metaphors, and similes hold up in relation to current issues. If someone compares abortion to the Holocaust, for example, is that because fetuses are a target of government policies intended to eliminate inferior genetic human beings? If they mean that what the Germans did in their genocidal activities is like what we have as a policy about terminating pregnancies, we know, through our analogical examination, that this comparison is not correct. So, that argument against abortion falls away--even though you still might think there must be moral standing for the fetus. I am interested in knowing if the ethnic arguments from the past are convergent, divergent, homologous, or analogous so as to understand whether I'm looking at a real phenomenon or an accidental similarity. It's important to do this; if you just start from your armchair to come up with ethical theories, you may arrive at something very interesting, but something close to what a mathematician does, or a math modeler. Q Like people who would model an ecosystem without ever stepping into nature? A Right, they don't step in the lake, and they don't care to. But that's not my bent--my bent is to step into the lake, to be sort of a moral naturalist and look for phenomena. That's why I like being around the hospital; that's why I like tying in to the people who do the work with social science tools. Q What influences led you to bioethics? A Actually, those go all the way back to my early days, at Columbia University, where as a graduate student I spent a year at its medical school. So, I got interested in health- care ethics by hanging around the hospital and the clinic. That's how the idea of using the hospital as the laboratory began, and out of that came my strong belief that if you're going to be credible to doctors and scientists, you must understand their world, their limits, their time constraints, the financing that they're up against, and how they talk. Q You mean that before laying down ethical laws to people, you have to understand what really influences what they can and can't do? A You shouldn't set your morality beyond what's possible. Sometimes, a limit on morality is human nature, fallibility, mistakes, a certain amount of egoism and greed. In order to take that into account, you don't want to pretend that it's a world of saints with infinite resources and unlimited time and that we should all act in this way. Q Returning to the subject of gene therapy, will there be an organizational relationship between your group and Penn's institute? A The tie is really through me. I have an appointment in the department of cellular and molecular engineering, as a professor. I'm written into many of their grants, to sort of watch that the gene therapy protocols meet the requirements of the human subjects' study. So, it's not a center-to- center marriage; it's more of a faculty-to-faculty marriage. Q But doesn't the National Institutes of Health's Recombinant DNA Activities Committee [RAC] already have a very developed pattern of thinking about the ramifications of gene therapy before the protocols are in place? A To tell you the truth, while I'm not against having a national RAC, the NIH committee may have outlived its usefulness at this point in time in terms of the level of review necessary for protocols relative to the risks. Most of the people who are on RAC do gene therapy; they want to do it right--but they also want to do it. I'd like to think we can come at gene therapy at Penn with a little bit more of an objective eye in terms of saying, "We don't care whether it proceeds or not, we're just interested in looking at the ethical issues." Q What type of issues? A Remember the incident in California involving gene therapy for brain cancer? Basically, RAC had all these rules about what you had to do to get gene therapy, and then they threw them out the window when a woman who knew a senator made an appeal. That's the kind of thing we'd like to look at and say, "Don't let politics override the system." It's not a good idea. It's not compassionate, necessarily, to grant a terminally ill person access to a gene therapy intervention that's not on a protocol. But it was hard for them to say it, because they were getting influenced by national politics. It's easier for us, at Penn, to say it; we're not accountable to NIH or Congress or anything like that. Q Where does the Human Genome Project [HGP] office for ethical, legal, and social implications [ELSI] fit into the spectrum? A ELSI is interesting, because it is the only area of NIH that has been set up with a specific allocation of money to look at ethical issues. And that's good. On the other hand, I think that they have spent a lot of their time committing themselves on issues identified by people who weren't in close contact with what was going on in genetics. I will tell you, flat out: Bioethics, in my view, is weak in genetics. There are not a lot of philosophers, theologians, and lawyers who know anything about it--I mean anything! I'm talking about, do they know a chromosome from a gene from an aardvark? It's an area where bioethics has not intersected well with the scientific community. Most of the people who come into bioethics have much more of a clinical focus than a basic science focus. It's hurt the ELSI program in a lot of ways. And I lobbied [HGP official] Francis Collins pretty hard about this, saying I think it's time we sort of get past the declarations of morality into the nitty-gritty of it. Q Don't you think a lot of researchers fear that bioethical influences will impose too many constraints on their work? A There's a common equation between ethics and saying no. But my argument is that sometimes the job of ethics is to say yes. I'll give you an example. I'm working on an article that you'll probably hear about because people will be streaming down the street to lynch me. It's called "What's wrong with eugenics?" or "What's wrong with germ-line engineering?" I happen to think the answer to both those questions is, nothing, intrinsically. The question of whether I should be able to pick blue eyes or brown or tall people or short--I don't think there's anything wrong with that, fundamentally. Q It's a matter, then, of when to say yes or no? A There may be reasons we ought not practice eugenics that have to do with politics and the fear that some people may go down the slippery slope, as the Germans did. If you're worried about coercion--and the Chinese force that kind of stuff--you oppose it. But if it's a pure question of, if I turned on gene X and made my child grow another two inches, and there was no risk to the kid, and nobody made me do it, I don't see the problem. You know, you make children play the piano an hour a day, seven days a week, for 10 years, and you understand that you've imposed a lot of views on them of what they should become. You start to think about it, it's like, cripes, making him two inches taller may be the least of his worries. It's more whether you make him study in the yeshiva seven hours a day after school. That's imposing a much more cognitive type of thing on a kid. So, I don't buy the idea that the mission of ethics is to say no or go slow or don't do it. That's an oversimplified view. My idea is, sometimes it means yes and go faster and you ought to do it, so why aren't you doing it? It seems to me if you could do germ-line therapy to eliminate killer diseases, not only should you do it, you must do it. If you could eliminate sickle cell or Tay-Sachs by a safe form of altering sperm or egg or embryo, I think it's morally incumbent upon you to do it. Q In connection with AIDS research, what are some significant bioethical considerations--for instance, those connected with arriving at an adequate experimental protocol that could be used by AIDS researchers in developing a live attenuated-virus vaccine? A If it looked like some lines of vaccine research were promising but were limited by the absence of an animal model, then I'd be surprised if we wouldn't take the proper steps. Specifically, we might try vaccines on people who are brain dead and who are about to have their life support disconnected. We might decide that we could add a provision to their living will or their transplant donor card that said, "You could use me for a limited period of time to test a vaccine." You might get some information that would make you feel more secure before you went to a living human. It seems, as a reasonable place to turn, you may find individuals who are terminally ill who want to volunteer as human models. The other population that's likely to be morally appropriate for this are those groups in high-risk categories whose behavior can't be changed. Of course, there's always an obli-gation to try to get somebody to stop doing what puts them at risk. But there's some truth in the idea that if you go to a group of, let's say, sex workers in Thailand and say, "You've got to get out of this business," and you come back in two months and say, "You've got to get out of this business and you've got to use condoms," and they're still working there, that probably is the population you want to go to for your vaccine trials. You've done everything you can, and you continue to do it throughout your entire study, to get them out of the business, even if it hurts the study. But if you know they're going to do it, and you're not going to get them out, that's where you go for vaccine development. Q You're aware how radical these ideas are. A The intuitive thing is to say, "Well, you can't do this and, I don't know, we just have no vaccines." I think the right answer is, "Well, let's think more carefully about how could we do this and feel comfortable that we haven't hurt anybody or made them worse off." We've got an epidemic, and we've got to do something. Q Another area of considerable debate is technology transfer between universities and industry. What are the ethical considerations that must be addressed in the push to commercialize research results from academic labs? A There are really serious issues there. At one level, it's been a fight about conflict of interest and disclosure, and NIH is still struggling to come out with guidelines. They basically rely on disclosure, the assumption being if you tell people that you have this technology-transfer arrangement, it'll be okay because they'll know how to read your data or interpret what you say about whatever gizmo or drug it is that you're working on. The other argument is, you have to restrict how much scientists and doctors can work outside the university. A day a week is a common rule about how much outside work you can do. I think those provisions are nice, but they're not getting down to the real nitty-gritty questions. What's the impact of privatization on basic vs. applied research? If a university is supposed to be a place that pursues basic research more than a company would do, and yet companies underwrite more and more research or commercialization, will we find ourselves richer in the short run but poorer in the long run because we spent so much time developing this generation of technology that we don't have anybody working on the basic science for the next one? Also, what happens to the graduate students who work in the labs of people who are involved in corporate ventures? They can't do their thesis because they've got to do work for a guy who's making money, and they're a kind of cheap labor for that person. But if a company has a gizmo that you can't get at the school lab and if the company provides in-kind services worth hundreds of thousands of dollars that you could never get from your school, is that enough to pull your lab in an unacceptable direction? Remember, this is basically a subtle kind of a bribe to get you to do things. There are many, many interesting questions about how commercialization and for-profit motives are shaping biological and medical science. What you may need to do is teach that senior professor that you don't push the graduate students around, and you can't exploit them to do your work on the side, and you're not going to get promoted for how many inventions you make. You're still going to get promoted on the basis of how many students put out good papers from this lab. Q Why does bioethics seem to be such a hot area now? A I think bioethics is especially of interest these days for a couple of reasons. One, the cost of health care, the cost of medical research, the cost of certain medical innovation is up. So people always take an interest in what they're getting for all this money. There is still a kind of cornucopia of new technologies. Investments in the T50s and T60s are now paying off with different kinds of devices, so there are a lot of technology-driven questions: turning it on, turning it off, when to use it, who gets it, that sort of stuff. I think bioethics is of interest because we don't have any other place to turn. To some extent, our religious and political leaders fail us in terms of understanding enough about science to allow us to talk about what's going on. And to some extent, science has taken on the guise of secular religion. You may say that people go to the doctor with the same hopes that they once brought to the minister: Save me, prepare me, redeem me. In the Middle Ages, you used to see cathedrals; now, what you see are towering medical centers dominating the landscape. Q In your new book, Moral Matters, you make a strong case for the enduring value of ethical thinking.A I think a lot of scientists have the view that ethics is subjective--that it's all a lot of talking and yakking and blather that amounts to nothing--and that science is concrete. A computer scientist said he once asked the faculty at [the Massachusetts Institute of Technology], "How many people think that 1,000 years from now people will believe that the speed of light is 186,000 miles per second?" Half the faculty raised their hands. Then he asked, "How many people will believe 1,000 years from now that the road to hell is paved with good intentions?" Everybody raised their hands. The point is that ethics is more concrete in the long run than the physical stuff, which is contingent. And I believe that. (The Scientist, Vol:8, #20, pg.12, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: COMMENTARY ------------------------------------------------------------ TI : A Tribute To Robert K. Merton On Receiving The National Medal Of Science AU : EUGENE GARFIELD TY : OPINION (COMMENTARY) PG : 13 Last April 28, I had the pleasure of hearing my good friend Robert Merton, the eminent sociologist and historian of science, deliver the American Council of Learned Societies' 1994 Haskins Lecture. The talk, presented at the American Philosophical Society in Philadelphia, centered on Bob's "life of learning"-- the subject addressed each year by a notable "humanist" invited by ACLS to deliver the prestigious lecture. As Bob spoke about his boyhood in Philadelphia, his coming of age as a young Harvard intellectual, and the factors that fueled his preoccupation with the history of science and the behavior of scientists, I was touched by a variety of emotions. As often during the 30 years or so that I've known him, I was fascinated by his capacious intellect and his knack for originating concepts and expressing them in clear, evocative terms. (Whether writing or speaking, he knows how to hold his audience.) I was also proud, since he has worked closely with me as mentor, colleague, and coauthor. I must confess as well to a certain amount of civic pride, since The Scientist--like Bob Merton--has its roots in the City of Brotherly Love. ACLS couldn't have made a more appropriate selection for the 1994 Haskins lectureship. That was also my reaction to the recent news that Bob was among the eight individuals selected by President Clinton to receive the 1994 National Medal of Science. As we reported in our coverage of the event (N. Sankaran, "Eight To Receive National Medals Of Science," The Scientist, Oct. 3, 1994, page 1), he is the first sociologist to be so honored. Evidently, I am not alone in holding my good friend in high regard. Indeed, as I listened to his lecture, the thought ran through my mind that, if there were a Nobel Prize category for the sociology of science, Bob Merton would have to be a recipient. I am pleased by the honors this Nobel-class thinker is receiving, as the international community of historians and sociologists of science must also be--not that there has been a dearth of recognition of this great mentor, now in the 85th year of an incredibly productive life. His record is indeed impressive. His masterpiece of theoretical sociology, Social Theory and Social Structure (New York, The Free Press, 1949; enlarged editions, 1957, 1968) has gone through 30 printings and ranks among the most cited books in the social sciences. Two other seminal works, The Sociology of Science: Theoretical and Empirical Investigations (University of Chicago Press, 1973) and On the Shoulders of Giants: A Shandean Postscript (University of Chicago Press, 3d ed., 1993), should be, in my opinion, required reading for all scientists. While treating matters of serious consequence, Bob Merton maintains a sense of irony, self-deprecating humor, and a fondness for wordplay that has seasoned and humanized his writings. In a recent note to me, he commented on a close- to-hand example of a phenomenon he first described in an article titled "The Matthew effect in science; the reward and communication systems of science" (Science, 159:56-63, 1968). His neologism, "the Matthew effect"--named after a passage in the Gospel of St. Matthew--holds that patterns of biased peer recognition of authors of collaborative papers are often "skewed in favor of the more established scientist." And so it is, he wryly observed, that papers written jointly by him and his colleague, companion, and wife, sociologist Harriet Zuckerman--now vice president of the Mellon Foundation--were often mis-cited as having been written by "Merton and Zuckerman"--even though, as he noted, "Harriet is explicitly designated as the first author." He went on: "It is ironic, of course, inasmuch as I am here the dubious 'beneficiary' of the Matthew effect"--a phenomenon that he had identified, named, and harshly criticized. The conceptual impact of the Merton oeuvre has been vast; however, while he has profoundly influenced many aspects of 20th-century science, or at least our ways of thinking about it, the influence has not been confined to the scientific realm. Such Merton concepts as "the self-fulfilling prophecy" and such Merton innovations as "the focused interview" have found their way into our everyday lives. And many of his visionary notions concerning the clockworks of human behavior, while often pertaining originally to the world of research, have been extended in application to matters of family, business, and religion. I congratulate my old friend Bob Merton on receiving the National Medal of Science. And I encourage young scientists who have not yet studied with this master to get to the library or bookstore as soon as possible. A valuable treat is in store for you. (The Scientist, Vol:8, #20, pg.13, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: LETTERS ------------------------------------------------------------ TI : NIH Triage AU : HUGH STAMPER TY : OPINION (LETTERS) PG : 13 Jose Musacchio's commentary, entitled "Triage at NIH: A Smoke Screen Concealing The Real Problems Facing American Science" (The Scientist, Sept. 5, 1994, page 13), contains several misperceptions. While it is true that the use of triage in peer review would relieve some pressure on review staff at the National Institutes of Health, it has never been suggested, as Musacchio implies, that it would "solve the problems undermining American science." As now applied at NIH, triage focuses on reducing time spent at review meetings by eliminating discussion on applications whose scores would fall below the committee's midpoint (50th percentile) and are unlikely to be changed by further discussion. These noncompetitive applications, however, are carefully reviewed in advance of the meeting. In fact, reviewers report spending the same amount of time evaluating applications that are ultimately deemed noncompetitive under triage as they did when triage was not used. Reviewers prepare written comments in advance of the meeting, as they have always done. Contrary to Musacchio's perception, under triage, all applicants receive summary statements. Furthermore, the use of triage has facilitated the move from summary statements composed of carefully integrated comments to those in which reviewers' prepared comments are released intact and virtually unedited. Thus, contrary to the suggestion that reviewers are no longer accountable to applicants receiving a noncompetitive rating, reviewers are more accountable, since their actual comments are received by applicants. Finally, Musacchio confuses the issue of triage by intertwining it with funding aspects. Triage is not a culprit that prevents worthy research from being supported. The primary objective of peer review--and triage is consistent with this--is the identification of the best research so that reasonable funding decisions can be made. Availability of funds and the making of funding decisions must continue to be assiduously separated from peer review. Certainly, triage will not cure all the ills related to obtaining research support. It does, however, permit reviewers and NIH staff to spend time more efficiently, while allowing the outcome of review to be communicated more forthrightly to both successful and unsuccessful applicants. Staff at NIH will continue to seek improvements that will ensure fair, equitable, and efficient peer review. Hugh Stamper Director, Division of Extramural Activities National Institute of Mental Health Parklawn Building, Room 9-105 5600 Fishers Lane Rockville, Md. 20857 E-mail: (The Scientist, Vol:8, #20, pg.13, October 17, 1994) (Copyright, The Scientist, Inc.) -------- NXT: ------------------------------------------------------------ TI : Conduct Meeting AU : Charles W. McCutchen TY : OPINION (LETTERS) PG : 13 The article entitled "Meeting On Science Conduct Seen As A Noble Attempt That Fell Short" by Franklin Hoke (The Scientist, July 25, 1994, page 1) says that "many of the attendees [at the 'Convocation on Scientific Conduct'] note with some dismay that active research scientists were largely absent from among the approximately 250 people [in the audience]." Did they really think that many would come? Displaying an interest in misconduct is not a path to advancement in science. Remember what happened to Walter Stewart and Ned Feder. Only scientists who have already sacrificed their careers would dare to come, and why should they swell the audience for this latest show put on by the biomedical science establishment to give an appearance of action? If the establishment ever decides to do anything real to halt scientific misconduct, it will use the same subterranean methods it now employs in the service of cover-ups. There will be no fanfare. Charles W. McCutchen 5213 Acacia Ave. Bethesda, Md. 20814 (The Scientist, Vol:8, #20, pg.13, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: WHERE TO WRITE: Letters to the Editor The Scientist 3501 Market Street Philadelphia, PA 19104 Fax:(215)387-7542 E-mail: Bitnet: ===================================== NXT: RESEARCH --------------------------------------------------------------- TI : Biomedical Researchers Step Up Efforts To Probe Mysteries Of Aging AU : Karen Young Kreeger TY : RESEARCH PG : 14 The population of the United States is aging. According to the U.S. Census Bureau, the proportion of Americans aged 65 and older is expected to increase from about 12 percent today to about 20 percent in 2030. By then, the average baby boomer--those born in the years immediately following World War II--will be upwards of 80 years old. And, like its subjects, the field of biomedical science that explores the physical, psychological, and sociological effects of the aging phenomenon is visibly maturing. As the baby boomer generation gets older, increased attention is being focused upon geriatrics (the study of illness in older people) and gerontology (the basic science of aging processes). For scientists in these fields, the demographic sea change has conceptually affirmed the need for a more aggressive approach to aging research and, consequently, has fueled growth in funding for it in recent years (see story on page 1). NIA's Broad Mission Immunologist Richard Hodes is addressing the challenges of this broad field of scientific study in two venues: the director's office of the National Institute on Aging (NIA), where he's responsible for administering the efforts of about 6,000 intramural and extramural investigators and a budget of more than $420 million; and at the bench of his NIA lab, working with a team of investigators on the relationship of the immune system to the biology of aging. NIA, which was formed in 1974, is the primary source of financial support for aging research in the U.S. According to Hodes, the institute "evolved to provide a perspective that was different from each of the organ- or disease- specific institutes. It developed into an institute with a very broad mission, which is based on the biomedical, behavioral, and social aspects of the quality of life of older citizens." Hodes explains that the research sponsored by the institute looks at a blend of the molecular and cellular mechanisms that influence aging and longevity; behavioral factors, such as diet and exercise, which play a role in mediating the aging process; and the sociological implications of providing care for an aging U.S. population. NIA researchers agree that the dramatic shift in the makeup of the population toward an older majority is the impetus for the growth in their field. "The demography is really the driving force," says Zaven Khachaturian, associate director of the of aging program in neuroscience and neuropsychology. "It's been happening since the turn of the century. People are living longer, and the older age group--85 and over--is growing at a much faster rate than other age groups." These demographic changes have had a direct impact on NIA funding almost from the time the institute was formed. "When I came here 15 years ago, the whole institute had a $28 million budget. And now our budget for fiscal year T94 is over $400 million," notes Richard Sprott, associate director for the biology of aging extramural program. "That would not have happened without the demographic imperative. "Aging and AIDS have been the largest growth areas in health sciences for the last decade." According to George Martin, science director of the intramural program, a significant avenue of NIA research is identifying risk factors such as diet and exercise habits for certain age-related diseases. Sprott adds that NIA's research mission "is not to produce 100-year-old people, but to improve the quality of the terminal third of the lifespan that we've got." And it seems that goal is starting to be realized. A recent National Research Council report funded by NIA and entitled Demography of Aging (L.G. Martin, S.H. Preston, eds., Washington, D.C., National Academy Press, 1994) states that the prevalence of disability among the older population in the U.S. decreased during the 1980s. Focus On Alzheimer's One major area that NIA funds--both intramurally and extramurally--is the study of Alzheimer's disease. "Research relevant to Alzheimer's is the single largest investment currently at the institute," Hodes says. Khachaturian heads the largest extramural program at the institute--neuroscience and neuropsychology--which primarily funds basic and applied Alzheimer's disease research. Just over $190 million--half of the total NIA extramural budget-- is devoted to this program, with about 80 percent going to fund Alzheimer's-related work. Khachaturian says that research supported by the neuroscience program, which he set up in 1978, ranges from molecular-level basic research to epidemiological studies involving many human subjects. "The notion is," he explains, "that the study of the aging nervous system should not only be done at the basic science level, but that it should be done at the systems level, starting at very molecular, basic areas like genetics and protein chemistry, moving up to neurons and neural systems, and on to behavior and effects on society. "This approach has proved to be very fruitful, as demonstrated by the success of the Alzheimer's program," Khachaturian adds. "There was very little known about the disease in 1978. But in a short time, we have moved Alzheimer's out of the dark ages to the cutting edge of neuroscience because we integrate basic scientists with the clinicians. "In fact, I went out of my way to recruit people from other disciplines--like protein chemistry, medicinal chemistry, molecular biology, and genetics. If you look at the history of many of the people who are in the field now, five to 10 years ago they weren't studying aging nervous systems or Alzheimer's. They're all converts." According to Hodes, it is with good reason that mounting attention has been paid to Alzheimer's disease: "The genes that appear to be responsible for some of the rare, familial, early-onset forms have been identified, although the mechanisms by which they influence disease remain to be elucidated. And most recently, a lot of excitement has been generated in the last year about the identification of the ApoE gene, which has been identified as an epidemiological risk factor for disease. "This is an important first step. It will ultimately allow an avenue by which we can understand the biology [of Alzheimer's] and, hopefully, eventually the cause of the disease, thus leading to diagnostic and, most importantly, therapeutic intervention." The Biology Of Aging Another extramural program focuses on trying to unravel the nature of longevity and aging from a biological perspective. "The main thrust of almost everything we fund is aimed at trying to understand the basic processes that go on at the cellular and molecular levels that underlie the aging phenomenon," says Sprott, referring to the biology of aging program he heads. The "aging phenomenon" has two parts, explains Sprott: "those things that might be the aging processes themselves as well as those which have an influence on age-related phenomena, such as hip fractures and Alzheimer's." Elucidation of the underlying mechanisms of aging processes has become possible because of recent advances in molecular biological techniques, he says: "In the last eight to 10 years, modern molecular biology grew up and provided us with techniques that began to allow us to get answers." As an example, Sprott cites a recent NIA-funded study concerning the possible relationship between the telomere--a part of the human chromosome--and the lifespan of certain populations of cells. "There's been this recent discovery that every time the cell divides the telomere gets shorter. It's as if you're knocking off a little piece and the telomere length is in fact a counter and it can count how many times a cell line has doubled, and when it runs out the line dies." He says this finding is significant because of the possibility that there is a physical "counting mechanism" that would explain human mortality. Another aspect of research in Sprott's program is understanding the relationship among cell maintenance, aging, and genetics. "Inside the cell the job of certain genes is to maintain a very, very delicate balance between senescence, which must happen, vs. immortality. If the senescence genes become too active, they kill off cells, and if they aren't active enough, [the cells] become immortal, or cancerous, and the whole organism dies anyway," Sprott explains. NIA-funded investigators have found single genes that are responsible for maintaining this control over senescence. They call them longevity-assurance genes, or LAGs, according to Sprott. He also mentions that colleagues at the National Cancer Institute have found tumor-suppressor genes that are very similar in composition to LAGs. "What it looks like is that they may be the same genes arrived at from two different directions," says Sprott. "I think that what this says is that, as we understand the basic processes of aging, we're going to understand the basic processes of a lot of other things." The Baltimore Study Although much of NIA-funded work is devoted to basic biomedicine, another important facet of the NIA mission is to conduct holistic studies of human aging. One intramural program centered at NIA's Gerontology Research Center in Baltimore--the Baltimore Longitudinal Study--is the longest continually running scientific study on human aging. The study started in 1958 with 58 male subjects and was directed by the former National Heart Institute. It now includes more than 1,100 men and women ranging in age from 20 to 96. Its overall purpose is to follow individuals throughout their lifetimes in order to understand the process of aging in the human mind and body. Hodes describes the study as an "insightful venture that recognizes the importance of evaluating aging by studying individuals as they age over time rather than by comparing a given group of people who are young at a specific time with a group of people who are old at the same time." He says that the study has dramatically altered what researchers consider "normal aging." The study has dispelled stereotypes of what it means to grow old, such as the commonly held scientific notion that the amount of blood pumped per minute, or cardiac output, always decreases with advancing age. Now, according to information from the Baltimore study, gerontologists have revised their description of the aging heart. They have found that disease-free hearts in older individuals have a comparable cardiac output to that of younger people. So far the study has generally concluded that there is no single, simple standard to describe human aging. For more information on research grants offered by NIA, contact Miriam Kelty, associate director of NIA and director of the office of extramural affairs, NIH-NIA, Gateway 218, Bethesda, Md. 20892; (301) 496-9322. Fax: (301) 402-2945. The electronic mail address is: (The Scientist, Vol:8, #20, pg.14, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : NIA: COMING OF AGE AU : KAREN YOUNG KREEGER TY : RESEARCH PG : 14 The National Institute on Aging (NIA) is celebrating its 20th anniversary this year. It was established in 1974 when Congress passed the Research on Aging Act, charging the institute to conduct and support biomedical, social, and behavioral research as well as training and education on the process of aging and the diseases and special needs of older individuals. "Our research is very far-ranging, from basic research into cell regulation and cell death, to aging and cancer, to the social and behavioral aspects of aging," says Miriam Kelty, associate director of NIA and director of the office of extramural affairs. Some current NIA statistics: NIA's appropriated budget for fiscal year 1994 is $420 million, of which $38 million went to fund intramural research. For fiscal year 1995 the total appropriated budget is $434 million, with almost 9 percent of that assigned to the intramural program. The extramural program supports more than 900 research project grants in four main areas--the biology of aging; geriatrics; neuroscience and neuropsychology; and behavioral and social science--totaling nearly $250 million. The majority of intramural researchers work at the Gerontology Research Center in Baltimore, while the rest work on the NIH campus in Bethesda, Md. The intramural program covers 11 areas of research, including cardiovascular science, molecular genetics, and cognitive studies. --K.Y.K. (The Scientist, Vol:8, #20, pg.14, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: HOT PAPERS ------------------------------------------------------------ TI : DEVELOPMENTAL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 T. Braun, M.A. Rudnicki, H.H. Arnold, R. Jaenisch, "Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death," Cell, 71:369-82, 1992. M.A. Rudnicki, T. Braun, S. Hinuma, R. Jaenisch, "Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development," Cell, 71:383-90, 1992. M.A. Rudnicki, P.N.J. Schnegelaberg, R.H. Stead, T. Braun, H.H. Arnold, R. Jaenisch, "MyoD or Myf-5 is required for the formation of skeletal muscle," Cell, 75:1351-9, 1993. Michael A. Rudnicki (Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada): "Gene targeting has allowed the genetic dissection of the roles played by the myogenic regulatory factors (MRFs) in the development of skeletal muscle. The introduction of null [loss-of-function] mutations in Myf-5, MyoD, and myogenin into the germline of mice has revealed insights into the hierarchical relationships existing among the MRFs and established that functional redundancy is a feature of the MRF regulatory network. "Mice lacking a functional MyoD gene were found to have no overt abnormalities in skeletal muscle and are altogether viable and fertile (M.A. Rudnicki et al., Cell, 71:383-90, 1992). RNA and histological analysis could not detect any difference between wild type and mutant MyoD mice. The amount of Myf-5 mRNA is increased in mutant MyoD mice, which suggests that Myf-5 may substitute for the absence of MyoD in the development of skeletal muscle. RAs with MyoD mutant mice, histological and northern-blot analyses of newborn Myf-5-deficient animals did not reveal any abnormalities in skeletal muscle. Muscle development is delayed until the MyoD is expressed. As an indirect consequence of this delayed development, Myf-5 mutant mice have rib abnormalities that prevent normal respiration (T. Braun et al., Cell, 71:369-82, 1992) and therefore die soon after birth. The onset of MyoD expression, however, occurs normally, followed by the expression of myogenin and other differentiation-specific markers (T. Braun et al., Development, in press). These results suggest that the activation of MyoD occurs independently of Myf-5 and that MyoD can substitute for the absence of Myf-5 in the development of skeletal muscle. "The potential ability of Myf-5 and MyoD to substitute for one another led to the hypothesis that Myf-5 and MyoD have, at least to some degree, functionally redundant roles in the development of skeletal muscle (M.A. Rudnicki et al., Cell, 71:383-90, 1992). To test this hypothesis, Myf-5 and MyoD mutant mice were interbred. Newborn mice deficient for the two MRFs are totally devoid of skeletal myoblasts as well as muscle (M.A. Rudnicki et al., Cell, 75:1351-9, 1993). Mutant pups are born alive but are immobile and die within minutes. The spaces normally occupied by muscle are filled with amorphous connective and adipose tissues, and desmin- containing myoblast cells are absent. "Other investigators have targeted the remaining MRF genes. Mice lacking a functional myogenin gene are immobile and die perinatally owing to deficits in skeletal muscle differentiation (P. Hasty et al., Nature, 364:501-6, 1993; Y. Nabeshima et al., Nature, 364:532-5, 1993). The skeletal muscle in mice lacking myogenin display a marked reduction in myofibers. However, myoblasts are present, and these are organized in groups similar to wild-type skeletal muscle, suggesting myogenin is not involved in patterning. Myogenin- deficient mice also display a relatively mild rib deformity. These results indicate an essential in vivo role for myogenin in terminal differentiation of myoblasts into myotubes. "The absence of myoblasts in mice lacking both Myf-5 and MyoD places these two factors upstream of myogenin in the regulatory pathway. Moreover, this result suggests that Myf- 5 and MyoD are involved in the determination of myoblasts, as these cells are absent when these factors are missing. However, it is important to note that these results do not preclude a role for Myf-5 and MyoD as differentiation factors. For example, while myoblasts lacking myogenin fail to differentiate efficiently in vivo, they form normal multinucleated myotubes in vitro (Y. Nabeshima et al., Nature, 364:532-35, 1993). This suggests that in arrested myoblasts in vitro MyoD can substitute for the role myogenin plays in differentiation. The fourth myogenic factor MRF4 may function late in the myogenic pathway, as has been implied by its expression pattern in cultured cells. Alternatively, MRF4 may have a vital role early in the development of the dorsal subdomain of the dermamyotome, as suggested by its expression in vivo (T.H. Smith et al., Journal of Cell Biology, in press). "The ability to target specific genes for inactivation in the mouse has proved to be an extremely powerful tool to genetically dissect complex biological phenomena. In the near future, targeted inactivation of other important players involved in skeletal myogenesis will certainly provide much information as well as a few surprises." (The Scientist, Vol:8, #20, pg.16, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : ASTROPHYSICS TY : RESEARCH (HOT PAPERS) PG : 16 G. Schaller, D. Schaerer, G. Meynet, A. Maeder, "New grids of stellar models from 0.8 to 120M; at Z=0.020 and Z=0.001," Astronomy & Astrophysics Supplement Series, 96:269-331, 1992. Georges Meynet (Geneva Observatory, University of Geneva): "The evolution of galaxies is intimately related to the evolution of one of their main components--the stars. Stellar evolution is responsible for the different colors of galaxies. When the galaxy presents no sign of recent star formation, most of its luminosity is due to red giant stars. Inversely, a young stellar population manifests itself through the presence of numerous blue stars as O-type and/or Wolf-Rayet stars. In starburst galaxies, one can even observe stellar populations that are completely dominated by very young stars born a few million years ago. "The chemical composition of the galaxies is also mainly due to the enrichment of the interstellar gas by new material synthesized in stars. Again, the metallicity of a galaxy (the fraction of the mass of a galaxy in the form of elements heavier than hydrogen and helium) is an indication of its past stellar formation history. "Stars may also deeply affect the dynamic and physical properties of the interstellar medium. These few examples show that in many active areas of astrophysics research-- such as the evolution of the galaxies, origin of the elements, stellar-formation processes one needs information on the way the stars evolve. "At the Geneva Observatory, we have recently computed extended grids of stellar models covering a wide range of parameters such as initial mass and initial metallicity. We have also investigated the effects of a change of the mass loss rates on the outputs of massive stars models. This article is the first of a series of five papers presenting the whole set of stellar models (D. Schaerer et al., Astron. & Astrophys. Suppl., 98:523-7, 1993; C. Charbonnel et al., Astron. & Astrophys. Suppl., 101:415-9, 1993; D. Schaerer et al., Astron. & Astrophys. Suppl., 102:339-42, 1993; G. Meynet et al., Astron. & Astrophys. Suppl., 103:97-105, 1994). The homogeneity of these data, computed with the same physical ingredients and the same code for a great range of important physical parameters, make them attractive for people interested in stellar populations and the chemical evolution of galaxies. Moreover, for many years we have continuously improved the physical ingredients incorporated in our stellar evolutionary code, taking into account recent advances in stellar opacities calculations, measurements and computations of nuclear cross-sections, and neutrino- emission processes. "Some of the physical ingredients of the stellar models cannot be obtained with sufficient accuracy from experiments alone or from purely theoretical considerations. In these cases, we tried to constrain these quantities with detailed comparisons between some theoretical predictions of the stellar models and some well-established observed properties of stars. In this way, we concluded that the mass loss rates of massive stars during the periods when the stellar winds are essentially driven by radiation pressure must be higher than those given by the commonly used semi-empirical laws. "At present our stellar models can account quite well for many observed properties of the stars, and we hope that they will represent a good starting point to go ahead in the fields of stellar and galactic evolution." (The Scientist, Vol:8, #20, pg.16, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: TOOLS & TECHNOLOGY ------------------------------------------------------------ TI : DNA Sequencing: Today's Technology And Beyond AU : Scott Veggeberg TY : TOOLS & TECHNOLOGY PG : 17 Since the basic chemistry for DNA sequencing was developed in the 1970s by Frederick Sanger of the Medical Research Council, Cambridge, England, this technology has become a ubiquitous tool in genetics, molecular-biology, and microbiology labs. But the fastest-growing application of DNA sequencing today is in clinical diagnostics. Also, rapid advances in DNA sequencing have pushed the technology beyond its conventional base in polyacrylamide slab gel electrophoresis. These new approaches involve capillary gel electrophoresis and even glass-plate DNA "chips" made with photolithography processes. The current market in automated DNA sequencers is a well- ordered one, dominated by a handful of manufacturers. The leading companies making these products all currently use Sanger's basic chemistry for producing nested sets of progressively longer DNA fragments. These sets of DNA fragments are tagged with fluorescent dyes and then separated by gel electrophoresis and automatically scanned for identification of base-pair sequences. "A DNA sequencer is nothing but an automated DNA electrophoresis detection and analysis system," explains Jack Ball, vice president of molecular biology systems at Pharmacia Biotech Inc. in Piscataway, N.J., which markets the ALF (automated laser fluorescence) DNA sequencer. From Ball's description, this may sound like a simple enough instrument, but sequencers are not cheap. Prices range from $55,000 for an aggressively priced system introduced this summer by Molecular Dynamics Corp. of Sunnyvale, Calif., to $110,000 for the market leader, made by Applied Biosystems Inc., a division of Perkin-Elmer Corp. in Foster City, Calif. The Major Players Researchers interested in purchasing a DNA-sequencing system have a basic choice. They may select a device from Applied Biosystems, whose sequencer offers the highest throughput-- that is, the most number of bases that can be read in a day. Alternatively, they may choose one of several other manufacturers' systems, which cannot offer the same throughput but are lower priced and offer higher sensitivity as well as, in at least one case, longer read length-- referring to the base-pair length of DNA fragments. In fact, one system, available from Lincoln, Neb.-based LI-COR Inc., can routinely read DNA fragments up to 800 and even 1,000 bases in length, compared with the 500 bases typically read by its competitors. But in the final analysis, all of the commercially available automated sequencers, and the supporting reaction chemistry, are quite similar. The current market in sequencers, dominated by a few major manufacturers, may begin to fragment, however, as new technologies--and the companies developing them--start breaking onto the sequencing scene. The Human Genome Project, with its ambitious goal of mapping the entire human genome in a matter of years, has increased demand for far faster, less cumbersome sequencing methods than are available at present. This has catalyzed the development of a number of new and unconventional approaches that could allow a single scientist to sequence up to 10 million bases per year. At this rate, the entire human genome, with its 3 billion bases, could be sequenced in a single year by just 300 workers. "Everything that spins off the Human Genome Project will [also] require confirmatory sequencing," says Ball. That is, sequences derived rapidly will have to be confirmed, and thus "the market for DNA sequencers will be absolutely huge," he predicts. New applications for DNA-sequencing technology, most notably in the clinical diagnostic arena, will also expand the market for sequencers, bringing new technologies and lower- priced instruments to commercialization, say many industry observers. Alternative approaches--such as capillary gel electrophoresis, hybridization, and time-of-flight mass spectrometry--may bear fruit before the end of the decade. But until then, the current technique of using slabs of polyacrylamide gel to separate DNA fragments will remain the method of choice. And, at least for now, the Applied Biosystems technology is predominant. Applied Biosystems claims to have about 85 percent of the market in automated DNA sequencers in the United States, leading Steve Lombardi, product manager for the AB 373 DNA sequencer, to boast, "We own the market." One of the main reasons for the company's market dominance is that it was the first to come out with a sequencer, introducing the AB 373 in June 1986. Another reason is throughput. With its unique four-dye technology, Applied Biosystems sequencers read all four nucleotides in a single lane. Other systems require four parallel sequencing reactions for a single DNA strand. This multiplexing approach quadruples Applied Biosystems' output over competing manufacturers, according to the company. Applied Biosystems, as well as Molecular Dynamics, also sells automated robotic systems that perform the pre- separation reaction chemistry developed by Sanger, which is still the basis for DNA-sequencing technology. "Our goal is to automate the molecular biology lab and all the different applications in that lab," says Lombardi. "We don't just sell sequencers anymore. We sell genetic analyzers." In addition to DNA sequencing, these systems can be used to perform DNA fingerprinting, mutation screening, linkage mapping, and microsatellite analysis. Sequencing The Sanger Way The chemistry used to prepare samples for the currently available automated sequencers is based on the tried-and- true method developed in the 1970s (F. Sanger, Proceedings of the National Academy of Sciences, 74:5463-7, 1977). In this reaction, DNA is fragmented with restriction enzymes into single-stranded lengths that readily pass through gels, with the preferred length about 500 bases. The single- stranded fragment is then mixed with DNA polymerase, and with free nucleotides. The DNA polymerase runs along the strand, "repairing" it by building a complementary strand. If left alone, the reaction would end when the entire double strand was completed. However, this would provide no information on the sequences within the strand. The trick used in the Sanger method is to force DNA polymerase to occasionally terminate the reaction at base number 1, then base number 2, number 3, and so on, resulting in sequential DNA strands up to 500 base pairs in length. To do this, a small amount of aberrant nucleotides, called dideoxynucleotides, is mixed in with the normal deoxynucleotides. These aberrant nucleotides lack the usual free 3*-OH, which is needed to continue the polymerization reaction. Whenever the DNA polymerase picks up an aberrant nucleotide and incorporates it into the complementary strand, the reaction halts. In the end, the test tube is filled with a series of fragments ranging from one to 500 bases in length. This is the point at which the manufacturers' technologies diverge. AB utilizes four dyes, each of which is specific to a particular dideoxynucleotide. One dye would react only with dideoxyguanosine, another would react only with dideoxyadenosine, and so on, so that each base fluoresces at a characteristic wavelength, allowing all four bases to be read in the same lane of the gel. In the next step, the fragments are loaded manually onto a DNA sequencer gel, which separates the fragments into discrete bands that differ in length by one base. These fragments will then migrate down the gel at a rate proportionate to their length, with the shortest passing through the most quickly. The length is thus determined by its time of migration, and the base is determined by which of the four wavelengths it fluoresces at. The other manufacturers use a single-dye approach. At the chain-termination step, the DNA fragment is put into four separate reaction tubes, each one having only one of the four possible aberrant nucleotides. The four separate reactions are then loaded into four separate lanes on the gel, with each lane corresponding to a different nucleotide. The lower throughput obtained on these systems is simply a consequence of needing four separate lanes, instead of just one, to run one DNA strand. The single-dye approach has advantages, however, explains James Nelson, product manager for the Vistra line of sequencers from Molecular Dynamics: "Because it's a single- dye system, it's selected for much less expensive optics and laser systems." The Applied Biosystems technology uses a fairly complex argon laser, which is designed to produce excitation wavelengths matched to the four different dyes. As such, its output is not optimized for each individual dye's absorption maxima, says Nelson. The single-dye system used by Molecular Dynamics allows use of an inexpensive helium-neon laser optimized for the company's dye. The LI-COR system uses a simple infrared (IR) laser, the same type of laser used in compact disc players. According to Abraham Oommen, an applications scientist at LI-COR, the IR laser system is far more sensitive than other detectors, allowing less sample to be loaded. Plus, he notes, "most biological molecules don't fluoresce in the infrared, so background [interference] is negligible." Less interference translates to longer read lengths, with LI-COR claiming that researchers can routinely read out to 800 bases with "base calling," or the identification of the bases, accomplished automatically by the computer software. Longer read lengths mean that fewer subclones have to be generated, which can be a great cost and time advantage for university investigators. But LI-COR does not claim to be competitive with AB when it comes to throughput. "Massive sequencing facilities would not benefit from our machine," Oommen says. "We get out to 1,000 bases, but not with thousands of samples. So, if you want to process 100 samples a day, go with an Applied Biosystems machine." Falling Prices As is true of any lab equipment, price is always a powerful consideration for researchers considering the purchase of a sequencer. The $110,000 price tag for an Applied Biosystems machine is something only the most dedicated user or core facility can afford. For those on a tighter budget, Pharmacia offers a sequencer that lists at $90,000 but can usually be discounted into the $75,000 to $80,000 range, says Ball. "And that's a significant [reduction] in prices." Besides being a laser-excited, single-fluorescent dye system with computer-based, automated base calling, the ALF sequencer has a thermally jacketed gel plate, allowing precise temperature control of the separation process. Also, sequencing and data analysis are controlled by a 486 computer running under an OS/2 operating system. The OS/2 system was selected because it is truly multi-tasking, meaning that data from one run can be manipulated, stored, or printed with a completely different application while the computer is running the separation and data analysis for the current run. The LI-COR system, which also takes advantage of the multitasking capability of OS/2, is significantly less expensive than Applied Biosystems' sequencer, however. Priced at about $79,000, it has the advantage of longer read lengths and higher sensitivity over other systems. The Applied Biosystems and Molecular Dynamics sequencers run on a Macintosh-based system. And, as Molecular Dynamics' Nelson points out, "If you look out into the marketplace, all the software [for genomic analysis] has been written for the Mac. That's not because it's superior. It's just history." Apple aggressively marketed its Macintosh systems to colleges and universities, and much of the DNA software written by professors and students is Mac-based, he says. In light of this, Molecular Dynamics' sequencer allows the user to easily interface with the extensive repertoire of existing Mac-based programs by running on an Apple Quadra 610. But the real advantage of Molecular Dynamics' Vistra system is its comparatively low price, listing at just $54,900, half the cost of an AB 373. A robotic system, also available from Molecular Dynamics, that can be used for automating sequencing and PCR reactions may be added for $59,000. Thus, for the price of an AB 373, a lab can get both an automated sequencer and reaction system. Will this competitive price put Applied Biosystems at a market disadvantage? Lombardi contends that Applied Biosystems has no intention of dropping its prices to compete with the newcomer. "As the market leader, you don't really like to respond," he explains. "We just say that for $110,000, you're going to get a well-respected instrument that's going to do the work that needs to be done." Instead of competing head-to-head with Applied Biosystems, Molecular Dynamics is focusing on a different market. "The AB system has been targeted at core labs and genome sequencers with high throughput requirements," says Nelson. "We're focusing on a different market niche, where throughput is not as much an issue." Throughput is relatively immaterial to Lonnie Ingram, a professor in the microbiology and cell science department at University of Florida, Gainesville, who has a LI-COR sequencer in his lab. He confirms that the LI-COR will give a longer read length than an Applied Biosystems sequencer, and for his lab that's an advantage, since there are fewer subclones and less wasteful overlapping of sequences. His lab was doing all its sequencing manually before getting an automated system. One big advantage of going from a manual to an automated system was getting the radioactive isotopes used in manual processes out of the lab--and the radiation safety department off his back. Capillary-Based Sequencing A number of new sequencing approaches are under active development, with some of them possibly coming onto the market within the next few years. Chief among these technologies is multiple-capillary gel electrophoresis. Molecular Dynamics and Beckman Instruments Inc. of Fullerton, Calif., are both reportedly working on such systems, though neither company's representatives would comment on exactly what stage of development it has reached nor when the units might become available. Capillary gel electrophoresis differs from the conventional method in that the polyacrylamide, instead of being poured out as a slab, is pumped into a 100-micron (internal diameter) capillary. This narrow-bore capillary permits the use of a much higher field strength, allowing separations to be completed in about an hour, instead of the usual six hours or more. With currently available systems, only one capillary can be run at a time, so throughput is not very high. Under development, though, is a capillary array in which 24, 48, or even 96 capillaries can be bundled and run in parallel, allowing more sample lanes than a slab gel and a six-fold increase in throughput over the current Applied Biosystems technology. One of the drawbacks with such a system is that the price of the capillaries does not lend them to disposability. And once the polyacrylamide gel is cross-linked it cannot be scraped out as is done to recycle conventional gel plates. But Barry Karger, a chemist at the Barnett Institute of Northeastern University in Boston, says he is close to a solution: "What we're pushing pretty hard is replaceable matrices for capillaries." In this approach, the linear polyacrylamide is not cross-linked and can thus be blown in and then blown out of capillaries at the end of each run. In a commercial system, the capillary preparation steps could even be automated, he says. Better yet, unlike gel slabs, which require tedious manual loading of samples, the sample loading in a multiple-capillary system can be automated by simply dipping the capillaries into sample wells and letting the electric field draw in the DNA. When will a multiple-capillary system be available? Karger says that Molecular Dynamics has already debuted a 48- capillary system at a recent trade show. While the company didn't actually demonstrate the separation of DNA samples with this system, it showed that it has solved some of the design issues, such as how to scan the array of capillaries with the laser. Karger thinks it could be as soon as "a year or so" before such a system hits the market. Sequencing On A Chip Also just over the horizon is the hybridization approach, such as the one being developed at Affymetrix Inc. in Santa Clara, Calif. According to Robert Lipshutz, a mathematician and director of bioinformatics at Affymetrix, the company is developing a "DNA chip," which takes advantage of the propensity of single-stranded DNA to complex with complementary strands of DNA. A set of probes, consisting of oligomers from eight to 20 nucleotides in length, can be generated that will adhere to the target DNA. In the Affymetrix approach, these oligomers are attached to glass plates using the process of photolithography, widely used in making computer chips and nano-machines. In this application, a 1.28 x 1.28 cm region of a glass surface is chemically prepared so that linker molecules, terminated with a photolabile compound, are attached. Next, using a photolithographic mask, a stripe of light is beamed across a quarter of the plate's width, thus removing the photolabile compounds in that area. Then, adenosine, for instance, can be covalently bound to the glass through the linker molecule. The free end of the nucleotide is capped with a photolabile group to prevent any further reaction until it is next exposed to light. The process is repeated until there are four stripes: one with adenosine (A), one with guanosine (G), one with cytosine (C), and one with thymine (T). Afterward, the mask is turned 90 degrees to form a cross hatch of stripes with A, G, C, and T attached to the first set of nucleotides so that all 16 possible nucleotide dimers are formed. Using successively finer stripes of light, the oligomers can be built up to a chain with a length up to 20 nucleotides, which are attached to the glass plate at known positions, says Lipshutz. "We can make a high-density chip with over 65,000 probes in 30 to 60 steps, taking about 10 minutes per step." And the company can make 16 identical DNA chips at the same time. Fluorescently labeled DNA strands can then be washed over the DNA chip, whereupon the DNA will hybridize with the complementary sequences in the probes. The fluorescence is determined by reading the chip with a confocal microscope linked to an automated image scanner. For sequencing, this approach could be extremely rapid, but there is still the "ambiguity problem" to overcome, explains Lipshutz. That is, DNA occasionally will form mismatches when complexing with the oligomers. Affymetrix is currently working out how to detect and deal with these mismatches. "It's still a ways off until people can do de novo sequencing," he says. But high-speed genome sequencing is not the company's first goal. Affymetrix would like to see the DNA chips applied to the rapid determination of mutations in HIV, for example. When the virus is challenged with a drug like AZT, which targets the reverse transcriptase (RT) enzyme, the virus develops resistance via mutations in the RT gene. What the DNA chip could provide is information on when that mutation has taken place so that an alternative drug regimen can begin. Lipshutz says the company hopes to commercialize the DNA chip technology by 1996. Clinical Diagnostics The fastest-growing application for traditional DNA sequencing today is in clinical diagnostics. Take, for example, the well-known oncogene p53--mutations of this gene play a role in a growing list of cancers. The p53 gene consists of 11 exons, and it encodes for a 53,000-dalton phosphoprotein that regulates cell proliferation. What's been found, says Pharmacia's Ball, is that there are dozens of different mutations that the p53 gene can undergo. For researchers to discriminate among these mutations, the p53 gene from a patient's tumor is sequenced to see whether it is an aggressive type or one that is more treatable. Another application is in diagnosing retinoblastoma (RB), a rare inherited eye tumor that can cause blindness but, if detected early, can be eradicated with laser surgery. To date, more than 300 mutations of the RB gene have been documented. The Eye Research Institute of Canada, affiliated with the Hospital for Sick Children in Toronto, is using a Pharmacia system to rapidly identify members of families that carry a mutation of the RB gene. This allows the researchers to exclude the unaffecte Despite the promise of newly emerging capillary- and chip- based technologies, users shouldn't expect that conventional sequencing will vanish any time soon, says Pharmacia staff scientist Anthony Murray. "I don't think the slab is dead," he asserts. Detectors capable of reading narrower lanes will allow higher lane densities to be read on conventional gel systems, which will extend the life span of the existing technology. "I think in the near term, the gel approach is going to be pretty hard to displace," he says. Scott Veggeberg is a freelance science writer based in Swarthmore, Pa. (The Scientist, Vol:8, #20, pg.17, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : SUPPLIERS OF DNA SEQUENCERS, SYSTEMS, AND SOFTWARE TY : TOOLS & TECHNOLOGY PG : 21 American Bioanalytical Inc. Natick, MA Circle No. 101 on Reader Service Card Amersham Corp. Arlington Heights, IL Circle No. 102 on Reader Service Card Applied Biosystems Division of Perkin-Elmer Foster City, CA Circle No. 103 on Reader Service Card Beckman Instruments Inc. Fullerton, CA Circle No. 104 on Reader Service Card Biomed Instruments Inc. Fullerton, CA Circle No. 105 on Reader Service Card Biomedical Research & Development Labs Inc. Gaithersburg, MD Circle No. 106 on Reader Service Card Bio-Rad Laboratories Life Science Group Hercules, CA Circle No. 107 on Reader Service Card Boehringer Mannheim Corp. Indianapolis, IN Circle No. 108 on Reader Service Card C.B.S. Scientific Co. Del Mar, CA Circle No. 109 on Reader Service Card DNA ProScan Inc. Nashville, TN Circle No. 110 on Reader Service Card DNASTAR Inc. Madison, WI Circle No. 111 on Reader Service Card EG&G Berthold Nashua, NH Circle No. 112 on Reader Service Card Fisher Scientific Pittsburgh, PA Circle No. 113 on Reader Service Card Hoefer Scientific Instruments San Francisco, CA Circle No. 114 on Reader Service Card Inotech Biosystems Lansing, MI Circle No. 115 on Reader Service Card Integra BioSciences Inc. Woburn, MA Circle No. 116 on Reader Service Card IntellliGenetics Inc. Mountain View, CA Circle No. 117 on Reader Service Card Intermountain Scientific Corp. Kaysville, UT Circle No. 118 on Reader Service Card Jordan Scientific Co. Inc. Bloomington, IN Circle No. 119 on Reader Service Card Laboratory & Research Products New Haven, CT Circle No. 120 on Reader Service Card Li-Cor Inc. Lincoln, NE Circle No. 121 on Reader Service Card Life Technologies Inc. Gaithersburg, MD Circle No. 122 on Reader Service Card Marsh Biomedical Products Inc. Rochester, NY Circle No. 123 on Reader Service Card Midwest Scientific St. Louis, MO Circle No. 124 on Reader Service Card Molecular Biology Resources Inc. Milwaukee, WI Circle No. 125 on Reader Service Card Molecular Dynamics Sunnyvale, CA Circle No. 126 on Reader Service Card National Biosciences Inc. Plymouth, MN Circle No. 127 on Reader Service Card Owl Scientific Woburn, MA Circle No. 128 on Reader Service Card Perkin-Elmer Norwalk, CT Circle No. 129 on Reader Service Card Pharmacia Biotech Inc. Piscataway, NJ Circle No. 130 on Reader Service Card Promega Corp. Madison, WI Circle No. 131 on Reader Service Card Scanalytics Billerica, MA Circle No. 132 on Reader Service Card Stratagene La Jolla, CA Circle No. 133 on Reader Service Card Textco Inc. West Lebanon, NH Circle No. 134 on Reader Service Card Time Logic Inc. Moorpark, CA Circle No. 135 on Reader Service Card UVP Inc. Upland, CA Circle No. 136 on Reader Service Card Zymark Corp. Hopkinton, MA Circle No. 137 on Reader Service Card (The Scientist, Vol:8, #20, pg.21, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : NEW PRODUCTS TY : TOOLS & TECHNOLOGY PG : 22 Hamamatsu Introduces Low-Light CCD Camera The C4880 dual-mode, cooled charge coupled device (CCD) camera is designed for use in measurements requiring low light and high dynamic range as well as in photometry and precision still-image acquisition. It has a sensitivity of 10 lx to 10-7 lx and a resolution of 1 million pixels (1,000 x 1,018 pixels). The C4880 offers both fast- and precision- scan modes. It has an analog-to-digital conversion rate of up to 10 MHz per pixel. Its digital output of up to 16 bits is compatible with most frame-grabber and display hardware on the market. The camera may also be controlled by computer through its RS-232C serial interface. Hamamatsu Corp., Bridgewater, NJ Circle No. 138 on Reader Service Card ----- ScanalyticsU RFLPscan Package For Protein, DNA Analysis Version 2.0 of RFLPscan is a Windows-based software package for performing genetic analyses derived from DNA restriction fragment patterns, DNA fingerprints, protein typing patterns, and other identity-profiling gel images. It is able to analyze images obtained from film densitometers, flatbed scanners, CCD video cameras, storage phosphor devices, and radiometric detectors. The software offers comprehensive databasing capabilities that permit the comparison of lane profile data from gels as well as pairwise and simultaneous matching of individuals. Scanalytics, Billerica, MA Circle No. 139 on Reader Service Card ----- ImageSpace Software Available As Stand-Alone Product ImageSpace 3.1 software was previously available only as a part of Molecular DynamicsU CLSM systems. The confocal package offers an integrated environment for rendering, processing, analysis, and display of confocal images, using an intuitive graphical user interface. Running on a Silicon Graphics workstation, ImageSpace software allows investigators to perform quantitative image analysis on three-dimensional data. Advanced analytical capabilities include automated object counting, seeding, and segmention; the program features tools for quantitative co-localization studies. The different 3-D analysis and 3-D visualization tools can be combined. Molecular Dynamics, Sunnyvale, CA Circle No. 140 on Reader Service Card ----- Gilson Announces Robotic Liquid Handler The 215 Liquid Handler is an XYZ coordinate system robot that automates various manual liquid-handling procedures and sample- preparation protocols. It has the capability to pierce thick tube septa to reduce the risk of exposure to potentially hazardous or infectious samples. Non-piercing probes for open-tube sampling are also available. The system is fully programmable and performs with a positional accuracy of 1 0.5 mm in the X and Y axes. It features a built-in dilutor for autodilution tasks, a large selection of syringe sizes, 15 standard and thermostatic racks, and several tube options. Gilson Inc., Middleton, WI Circle No. 141 on Reader Service Card ----- New Electroporation System From BTX The Electro Cell Manipulator (ECM) 600 for electroporation of prokaryotic and eukaryotic cells features two voltage ranges (2.5 kV/500 V), an additive capacitor bank, and resistance timing, and makes possible instantaneous monitoring within a single unit. It is equipped with internal monitoring that measures true peak voltage and pulse length. The system includes a safety stand, cuvette rack, and a package of 50 sterile, disposable cuvettes in 1 mm, 2 mm, or 4 mm gap sizes. BTX Inc., San Diego, CA Circle No. 142 on Reader Service Card ----- Storage And Reaction Tubes Offered For PCR Applications HotStart 100 storage and reaction tubes are 0.5 ml thin-wall polymerase chain reaction (PCR) tubes with a wax bead preadhered on the interior surface. The wax forms a uniform convective vapor barrier, which is said to reduce mispriming and primer oligomerization. The convective barrier also allows for separation of reaction components until the annealing temperature of the PCR reaction has been reached. The wax barrier seals the PCR product or prealiquotted master mixes for long-term storage in a lab freezer or standard refrigerator. Molecular Bio-Products Inc., San Diego, CA Circle No. 143 on Reader Service Card ----- Bio-Rad Unveils Vertical Electrophoresis Cell PROTEAN II xi cells perform a variety of separations, including SDS-PAGE, native, preparative, gradient, and high- resolution nucleic acid agarose electrophoresis. In addition, with the two-dimensional electrophoresis technique, they are able to separate in both the first and second dimension. The cells enable users to run one, two, or four slab gels, or up to 16 IEF tube gels simultaneously. They are available in 1 cm or 2 cm gel lengths with a selection of combs and spacers. Bio-Rad Laboratories, Hercules, CA Circle No. 144 on Reader Service Card ----- Double-Stranded, Site-Directed Mutagenesis Kit The Chameleon kit is designed for single- and multiple-base substitution, insertion, and deletion mutations in virtually any double-stranded plasmid. Its site-elimination mutagenesis procedure introduces a new mutnS host strain, XLmutS, which is EndAQ. The endA mutation removes an endonuclease that degrades miniprep DNA. The kit can be used with almost any plasmid template containing a unique, nonessential restriction site and does not require CsCl-purified DNA. Stratagene, La Jolla, CA Circle No. 145 on Reader Service Card ----- WhatmanUs SMART Colorimeter The SMART Colorimeter and SMART Reagents offer menu-driven operation for analysts measuring a variety of water-quality parameters. The SMART Colorimeter uses a tungsten lamp to deliver colorimetric analysis of absorbance readings from 1 to 2A and %T readings from 0 to 100 percent. In the laboratory or field, the alphabetical test selection plus 39 prepackaged reagents are designed to reduce analysis time and save on reagent time and preparation. Whatman LabSales Inc., Hillsboro, OR Circle No. 146 on Reader Service Card ----- Mettler-Toledo's Volumetric Evaluation Printer Debuts The LC-PVolume is a compact printer designed for evaluating the performance of volumetric equipment by means of gravimetric analysis. The single-balance system, based on guidelines from the National Committee for Clinical Laboratory Standards, automatically performs complex calculations and prints them in a user-defined report. Features of the system include storage of 60 programs, password protection, alphanumeric input, and a verification report for International Standards Organization and Good Laboratory Practices requirements. Mettler-Toledo Inc., Hightstown, NJ Circle #147 ----- MathWorks Releases MATLAB Update For Windows A new feature of MATLAB version 4.2c for Windows is the MATLAB Notebook, which integrates the softwareUs Technical Computing Environment with Microsoft Word 6.0. The Notebook Suite also provides an intuitive front-end for MATLAB through a dynamic link with Microsoft Word 6.0. This enables users to incorporate MATLAB graphics and commands directly into reports via a word-processing application interface; make changes in one portion of the document or any underlying data; and recalculate graphic and data results throughout the entire document. MathWorks Inc., Natick, MA Circle No. 148 on Reader Service Card ----- (The Scientist, Vol:8, #20, pg.22, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: PEOPLE ------------------------------------------------------------ TI : Penn State Researcher Chosen To Receive American Chemical Society's Bader Award AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 24 Stephen J. Benkovic, a professor of chemistry at the Pennsylvania State University at University Park, has been named as the winner of the American Chemical Society's 1995 Alfred Bader Award in Bioinorganic and Bioorganic Chemistry. He will receive the award at ACS's national meeting next spring in Anaheim, Calif. Benkovic's research over the years has focused on understanding how enzymes catalyze chemical reactions. "My early work involved looking at the mechanisms of organic reactions of small molecules that mimic biological processes, and extrapolate that information to how an enzyme might work," he explains. During his years as a graduate student at Cornell University, Ithaca, N.Y.--where he received a doctorate in 1963--and a postdoctoral fellow at the University of California, Santa Barbara, he coauthored a two-volume set of books defining the subject of bioorganic chemistry along with his research supervisor, Thomas Bruice (Bioorganic Mechanisms, Vols. I and II, New York, Benjamin, 1966). "Over the years my work evolved to the study of the enzymes themselves," adds Benkovic, who now does research on a variety of enzymes and catalytic antibodies, and recently reported an antibody that catalyzes peptide synthesis. (R. Hirschmann et al., Science, 265:234-7, 1994). Benkovic, 56, conducted his undergraduate studies in both literature and chemistry at Lehigh University, Bethlehem, Pa., before going on to Cornell. The chemist, who has been at Penn State since 1967, serves as Evan Pugh Professor and holds the Eberly Family Chair in the chemistry department there. He was elected to the National Academy of Sciences in 1985. --Neeraja Sankaran (The Scientist, Vol:8, #20, pg.24, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Illinois Congressman Honored For Devotion To Biomedical Research AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 24 The American Association of Immunologists presented Rep. John Porter (R-Ill.) with a Public Service Award during a special ceremony held at the United States Capitol on September 20. Porter is the first recipient of an award that the 6,000-member, Bethesda, Md.-based scientific society established to recognize individuals from the lay community who have demonstrated the im-portance of basic biomedical research to the public. The congressman was honored for promoting the importance of the National Institutes of Health and its research on Capitol Hill. As a member of the House Appropriations Committee, and the ranking Republican on the committee's Labor, Health and Human Services subcommittee--which funds NIH research--Porter has made basic biomedical research a priority. Last year, he played a leading role in ensuring that the 1994 budget supported NIH research with a 6 percent increase, rather than the 1 percent recommended in President Clinton's first budget. "That level of funding would have proved devastating to biomedical research," Porter maintains, adding that the budgetary increase to NIH was appropriated without spending additional money. Porter, 59, received his J.D. degree from the University of Michigan Law School in 1961, and practiced law in Evanston, Ill., until his election to Congress in 1980. He says that, in supporting basic research, "it is very, very important that politicians don't put themselves in the position of managing science. Our role is to give it the tools for advancement." --Neeraja Sankaran (The Scientist, Vol:8, #20, pg.24, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Torrey Botanical Club Elects New President AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 24 The Torrey Botanical Club, one of the oldest professional societies in the United States, has elected a new president, Steven N. Handel, an associate professor of plant ecology in the department of biological sciences at Rutgers University in Piscataway, N.J. Handel, who will serve a one-year term during the 1995-96 academic year, was installed as president-elect last month. Handel succeeds Margaret Basile, a botanist who is currently a research associate at the City University of New York's Lehman College in the Bronx. Named after 19th-century botanist John Torrey, the club was initially founded in 1866. Current worldwide membership stands at about 650. Although it has no official headquarters, it holds monthly meetings at the Bronx (N.Y.) Botanical Gardens and hosts a symposium at the annual meeting of the American Institute of Biological Sciences, a Washington, D.C., organization of professional societies. "One of the things I hope to do as president is to arrange a symposium on restoration ecology that gets academics, city officials, and public-policy regulators together in one place to talk about what can be done in big cities like New York," says Handel, 49, who specializes in reproductive ecology in plants and the evolution of pollination systems. He currently is involved in a project--jointly funded by the National Science Foundation and New York City's sanitation department--to see how plant ecology can help in restoring native vegetation in landfill sites in the New Jersey and New York area. He is a visiting professor at Macquarie University in Sidney, Australia, where he studies pollination in orchids. --Neeraja Sankaran (The Scientist, Vol:8, #20, pg.24, October 17, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. --------


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