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Phone :(215)243-2205 // Fax: (215)387-1266 ================= To access THE SCIENTIST electronically: ON WORLD WIDE WEB URL:gopher:// ---- GOPHER : telnet login : gopher terminal type: vt100 (if unknown) Choose #4, 4, and 6 from successive menus. ---- TO FTP : ftp /cd pub/the)scientist login / password = anonymous / your e-mail address ================== THE SCIENTIST VOLUME 8, No:23 NOVEMBER 28, 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 *** *** DECEMBER 14, 1994 *** *** *** ******************************************************* 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 NEWS REVIEWING TRIAGE: The expanded use of triage--in which some grant applications are deemed "noncompetitive" and not discussed in National Institutes of Health study sections--has drawn praise from some NIH administrators but has engendered considerable controversy in the extramural community PG : 1 NEW LIFE FOR EMBRYO RESEARCH: If NIH accepts recent recommendations from an advisory panel, some research involving in vitro human embryos will be eligible for funding for the first time in 15 years. But critics of the panel's ethical rationale--many outside the scientific community--are already lining up in opposition PG : 1 ABOUT TIME: Colleagues of the recently announced Nobel laureates in science say such recognition is long overdue. Meanwhile, the winners are using their moment in the limelight to lobby for more governmental support of basic research PG : 1 JOINING THE FIGHT: Industry has signed on in a major way to the effort to advance science-education reform, as indicated by participation in several recent high-profile initiatives. One of these was a September conference sponsored by Merck and Co. Inc. PG : 1 A FRESH LOOK: Troubled Biosphere 2, under new management, has brought in scientists from many fields to help revitalize the most criticized aspect of its mission--the quality of its science PG : 3 OPINION CURIOUS CONVICTIONS: The Clinton-Gore administration rhetoric in support of science and technology policy is belied by its anti-technology policies, perhaps best exemplified by its punitive and often illogical regulation of biotechnology, in the view of Henry I. Miller, Robert Wesson Fellow of Scientific Philosophy and Public Policy at the Hoover Institution and a consulting professor at Stanford University's Institute for International Studies PG : 12 COMMENTARY: Basic science is in the national interest and is "strategic" for the future of the United States, facts that are not appropriately recognized by Congress or the public--to the detriment of vital investigations as well as America's students--says Michigan State University associate biochemistry professor Zachary Burton PG : 13 RESEARCH DOMINATING FROM THE DEPTHS: Biological oceanography led a recent study of the citation records of ecology and environmental sciences articles, reported in the newsletter Science Watch PG : 15 HOT PAPERS: Structural biologist Ivan Rayment discusses the muscle protein myosin; cell biologist Michael Kastan describes steps of a signal-transduction pathway in mammalian cells; epidemiologist Miriam Alter reports on a study of hepatitis C virus patients PG : 16 TOOLS & TECHNOLOGY BLOTTING: Blotting technology has recently received widespread publicity because of its use in forensic cases, but these same techniques have long been workhorses in life-sciences labs PG : 17 PROFESSION JOURNAL JOBS STIMULATING BUT SCARCE: For researchers, editorial positions in science journals have the advantages of being stimulating and often quite well-paying, but also a major drawback--being quite scarce PG : 23 ADOLFO J. deBOLD AND ERVIN G. ERDOS, research director at the University of Ottawa's Heart Institute and director of the Peptide Research Laboratory at the University of Illinois College of Medicine, respectively, have won the Ciba Award for Hypertension Research PG : 24 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 13 LEADERS OF SCIENCE PG : 14 BLOTTING APPLICATIONS AND SUPPORT MEDIA DIRECTORY PG : 19 NEW PRODUCTS PG : 21 CROSSWORD PG : 24 (The Scientist, Vol:8, #23, p.3, November 28, 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 : Colleagues Laud 1994 Nobelists As Overdue For Coveted Prize AU : EDWARD R. SILVERMAN TY : NEWS PG : 1 Colleagues of the recently announced winners of the 1994 Nobel Prizes in chemistry, physics, and medicine or physiology, in praising the decisions of the Nobel committee, say the coveted Swedish honor is long overdue for each of this year's recipients. For their part, the winners are using their newfound recognition to lobby for greater funding for basic science. Alfred G. Gilman, chairman of the pharmacology department at the University of Texas Southwestern Medical Center at Dallas, and Martin Rodbell, a scientist emeritus in the Laboratory of Cellular and Molecular Pharmacology at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., were named to share the prize in physiology or medicine for their discovery of G proteins and the role of these proteins in signal transduction. George A. Olah, director of the Loker Hydrocarbon Research Institute at the University of Southern California (USC) in Los Angeles, was selected to receive the prize in chemistry for his work on carbocations. The physics laureates are Bertram N. Brockhouse, an emeritus professor of physics at McMaster University in Hamilton, Ontario, Canada, and Clifford G. Shull, an emeritus professor of physics at the Massachusetts Institute of Technology, chosen for their contributions to the development of neutron-scattering techniques for studies of condensed matter. Each winner receives or shares a $930,000 prize, which will be presented next month. Reflecting on years spent working alongside the five winners in laboratories across North America, their associates describe the recipients as dedicated scientists who have not been afraid to take risks in pursuit of their research. Recalling his work with Rodbell at the National Institutes of Health between 1970 and 1985, for example, Constantine Londos, chief of the membrane regulation section at the National Institute of Diabetes and Digestive and Kidney Diseases, says: "Marty was an independent guy who didn't like to restrict people. He'd look at our work and wasn't concerned with how others might interpret things. He didn't like to be a conformist. He was a leader by dint of his nature." Sweden Signals Approval Rodbell, 69, and Gilman, 53, discovered G proteins, natural substances that act as signal transducers, or intermediaries to relay signals from outside cells to the inside. The G proteins, so called because they bind guanosine triphospate (GTP), control a wide range of basic life processes. An excess or deficiency in G proteins, or alterations in their genetic composition, can lead to endocrine disorders or tumors. In addition, alterations in transduction of signals through these proteins may cause symptoms of diseases such as diabetes and cholera. The two scientists' work has been the springboard for a flurry of further studies by other researchers--many of which The Scientist has identified as "hot" papers--as molecular biologists try to refine their understanding of the signal-transduction process. In 1970, Rodbell found that GTP is required in order for glucagon to stimulate production of cyclic AMP (adenosine-3_,5_-monophosphate), initiator of the process by which hormones transmit signals to cells. His two seminal papers--M. Rodbell et al.,"Glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 4. Effects of guanyl nucleotides on binding of I-125 glucagon," Journal of Biological Chemistry, 246:1872-6, 1971 and M. Rodbell et al.,"Glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 5. Obligatory role of guanyl nucleotides in glucagon action," J. Biol. Chem., 246:1877-82, 1971--have been referenced in more than 400 and 700 subsequent articles, respectively. Later in the decade, Gilman determined that G proteins are the signal transducers; they act as mo-lecular switches, shuttling between the hormone receptor and the amplifier system in the cell membrane to turn signals on and off. He made this finding while working with mutated leukemia cells, which lacked a G protein and thus did not respond to external signals. The Gilman group's landmark papers, according to the Nobelist's associates--E.M. Ross, A.G. Gilman, "Resolution of some components of adenylate cyclase necessary for catalytic activity," J. Biol. Chem., 252:6966-9, 1977 and E.M. Ross et al., "Reconstitution of hormone-sensitive adenylate cy-clase activity with resolved components of enzyme," J. Biol. Chem., 253:6401-12, 1978--have been cited more than 225 times and 460 times, respectively. In 1980, Gilman's team purified the first G protein."Rodbell initiated the study of the G proteins and then Gilman carried it on," explains Edwin G. Krebs, a professor, emeritus, in the department of pharmacology and biochemistry at the University of Washington, Seattle, and a 1992 Nobel laureate who's known both men for decades. "In fact, Gilman's work was dominant for the past 10 to 15 years." Krebs and Gilman have shared two Nobel "predictor" prizes--the 1989 Albert Lasker Basic Medical Research Award and the 1989 Louisa Gross Horwitz Prize, presented by Columbia University to honor contributions to knowledge in biology or biochemistry (The Scientist, Feb. 19, 1990, page 26). Rodbell and Gilman are likewise no strangers when it comes to sharing awards: In 1987, they were corecipients of the Richard Lounsbery Award from the National Academy of Sciences (NAS). Gilman received a Ph.D. and an M.D. from Case Western Reserve University in 1969. He has been in his present position at U. Texas since 1981. He received a Gairdner Foundation International Award --another Nobel "predictor"--in 1984. He is a member of NAS. According to Jeremy Levin, CEO of New York-based Cadus Pharmaceutical Corp., which focuses on research and development in the G protein area, Gilman is "a worthy recipient because he conceptualized a completely new field. The man conceptualized an area that had been thought about but never had the strands all pulled together." "This is a wonderful treat," Gilman notes. "All sorts of people have come out of my past. Even my old Cub Scout leader called to congratulate me." Rodbell earned his Ph.D. from the University of Washington, Seattle, in 1954. An NAS member, he received a Gairdner Award in 1984. Carbocations The work of Olah, 67, has led to the development of new fuels based on petroleum, coal, methane, and other substances, resulting in higher octane gasoline and liquified coal. His research centers on carbocations and oxonium ions--highly reactive, positively charged organic molecules that act as intermediaries in natural as well as synthetic chemical processes. In order to determine the structure of these molecules via solid-state nuclear magnetic resonance spectroscopy and X-ray crystallography, he modified them using superacids, which are billions of times more potent than "strong" acids like sulfuric acid. Olah and colleagues have demonstrated that in very strong acidic solutions, hydrocarbons--normally unreactive--can become reactive. These reactions could be used to convert simple hydrocarbons such as methane into synthetic fuels. His most significant paper, according to his colleagues--G.A. Olah, "Carbocations and electrophilic reactions," Angewandte Chemie, 12:173-212, 1973--has been referenced in nearly 200 subsequent articles. "His contribution is very fundamental in organic chemistry," says Surya Prakash, an associate professor at USC and Olah's coauthor on more than 200 papers. "He's made a major contribution to hydrocarbon research and to industry." Olah, a native of Hungary, earned his Ph.D. from the Technical University of Budapest in 1949. He worked in Canada from 1957 until 1964, when he came to the United States. He joined the USC faculty in 1977. An NAS member, he has received numerous awards from the American Chemical Society. Structure Of Matter Shull, 79, and Brockhouse, 76, share the prize for developing neutron-scattering techniques for analysis of the atomic structure of solid as well as condensed matter. Neutron beams have, for instance, facilitated investigations of the structure of semiconductors, a building block of the electronics industry. These methods also are used in studying new ceramic superconductors, catalytic exhaust cleaning, elastic properties of polymers, and virus structures. The two Nobelists conducted their prizeworthy research after World War II--Shull in the 1940s and Brockhouse in the 1950s--at some of the first nuclear reactors. Shull was cited for developing neutron diffraction, used in discerning the atomic structure of a material. His ground-breaking article--E.O. Wollan, C.G. Shull, "The diffraction of neutrons by crystalline powders," Physical Review, 73:830-1, 1948--has garnered nearly 70 citations. Brockhouse pioneered neutron spectroscopy to determine the motion of atoms. His seminal research was published in a book, Inelastic Scattering of Neutrons in Solids and Liquids (Vienna, International Atomic Energy Association, 1961, pages 113-151), which has been cited 165 times. "I've known both of them for 30 years, and they were pioneering contributors," confirms Martin Blume, deputy director of Brookhaven National Laboratory on Long Island, N.Y., whose High Flux Beam Reactor is based on the two Nobelists' work. "When you think that their work began to have a huge effect decades ago, this recognition is really long overdue," Blume asserts. Brockhouse received his Ph.D. in 1950 from the University of Toronto. He has been an emeritus professor since 1984. He holds awards from physics societies in the U.S., Canada, and the United Kingdom. Shull, who re-tired from MIT in 1986, earned his Ph.D. in 1941 from New York University. He is an NAS member and has received awards from the American Physical Society, the Royal Swedish Academy of Sciences, and the Russian Academy of Sciences. A 'Bully Pulpit' The Nobel winners, while predictably quite happy that their research was acknowledged, are modest about the accolades being heaped on them by their colleagues. "It's very gratifying, but totally unexpected," says Brockhouse. "Right now, though, I'm still going to lots of luncheons, and there's various media pursuing us. But this is the icing on the cake--not the cake, itself." Still, the sudden notoriety has presented an opportunity that Gilman is using to call attention to the state of funding for basic research, a subject that is increasingly causing concern among scientists who fear that product-oriented research is crowding out other forms of work. "I do get a little upset by people who are naysayers and complain that there isn't enough money, because that sends out the wrong message. It tells young people that you can't be a scientist anymore," he remarks. "But it is frustrating for the scientific community, and it is harder to become a scientist now than when I was young. Clearly, we could use more money for basic research in many areas." Gilman's corecipient is also using his newfound media stardom to bemoan the current dearth of research funding. In a widely publicized Associated Press report, Rodbell said he retired in June because there was no more money for his work. "I think the attitudes of Congress and the executive branch [have] always been toward the end goal," he commented. "Underlying all of that is that they are not willing to take a chance on people like myself, exploring the unknown." Physicist Shull echoes these sentiments: "The thing I resent the most is that students are becoming disillusioned with science as a field and we're losing the cream of the crop. Students see it's hard to find positions because science is not supported to the extent that it would offer opportunities to young people. There's a general malaise about scientific matters and financial support. "And it's disturbing that funding for some of these major facilities has been passed over." Olah, while noting that funding is still available for top-echelon researchers, expresses similar worries: "I must say that most of my friends find a way to get funds and, in comparison with the rest of the world, things are still good [for scientists]. But funding is getting limited." He adds, however, that he hopes the prize will bring recognition to USC, which is probably best known to Americans for its sports teams. "I'm the guy who gets all the recognition, but this prize is for everyone who worked with me," he asserts. "But there's another message here, too. And that is that my university is always improving--and we're much more than a football team!" Edward R. Silverman is a freelance writer based in Millburn, N.J. (The Scientist, Vol:8, #23, p.1, November 28, 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 Funds Possible For Embryo Research If controversial studiesare approved for NIHsupport, investigationswill likely expand beyondprivate laboratories AU : FRANKLIN HOKE TY : NEWS PG : 1 Many researchers in genetics, cancer, and developmental biology whose studies involve in vitro human embryos will be eligible for federal support for the first time in about 15 years if the National Institutes of Health follows an advisory panel's recent recommendations. At the same time, an ethical boundary on research set by the panel is being rejected, primarily_but not entirely_by critics outside the scientific community. A report produced by the 19-member group, which was convened last February, has found that research on preimplantation human embryos is scientifically significant, can be conducted ethically, and deserves government funding. Currently, most such research in the United States relies on private resources, usually in association with clinics performing in vitro fertilization procedures, and has not been subject to scientific or ethical peer review. "There is compelling evidence that research [on human preimplantation embryos], carried out under appropriately stringent guidelines, will make important contributions to a whole range of medical problems affecting people in all walks of life," said Brigid L.M. Hogan, science cochairwoman of the panel and a professor of cell biology at Vanderbilt University School of Medicine, Nashville, Tenn., at a late-September news conference at which the report was released. "In addition, federal funding will greatly facilitate collaborations between clinicians and basic scientists working at the forefront of developmental biology and mo-lecular genetics, areas in which clearly outstanding progress is currently being made throughout the world, but particularly in the United States." The types of research considered by the panel for funding involve fertilized human ova, either in vitro or flushed from the womb before implantation in the uterine wall. Examples of procedures reviewed include embryo biopsies for genetic testing, toxicological and nutritional studies, and various protocols to better understand reproductive processes. Scientists define the embryo stage as extending into the eighth week of gestation, at which point the embryo is termed a fetus, although only very early stage embryos were considered by the panel for possible use in research. If the report's guidelines for preimplantation human embryo research are approved, funding will once again be available for studies in this area after a hiatus of well over a decade. In 1975, U.S. government regulations were instituted that required approval by a Department of Health and Human Services (HHS) Ethics Advisory Board for research proposals involving human embryos. The first successful outcome of an in vitro fertilization occurred three years later, in 1978. In 1979, the ethics board issued a report endorsing federal funding for research in this area, under explicit guidelines. However, the HHS secretary allowed the board's charter to expire in 1980, resulting in a de facto moratorium on funding for human embryo research until the NIH Revitalization Act of 1993 nullified the requirement for board approval. Ethical Obstacles The moratorium on human embryo research coincided with the Republican presidencies of Ronald Reagan and George Bush. Both administrations opposed abortion, with support from some conservative political and religious groups, based on the view that human life begins when the ovum is fertilized and that the resulting embryo has legal rights to protection similar to those of an infant, child, or adult. In recent years, the Bush administration also effectively opposed fetal tissue research on related grounds, a position reversed early in Bill Clinton's presidency. Opposition to the NIH panel's recommendations is being voiced by some of the same forces. For example, in a September 19 letter to NIH director Harold Varmus, Rep. Robert Dornan (R-Calif.) and about 30 other members of Congress argued that such research should not be funded by the agency. The U.S. election results earlier this month, in which Republicans gained control of both houses of Congress, appear likely to slow NIH progress toward formulating policy in this area, although panel members and agency officials decline to speculate on this possibility. In addressing the ethics of performing research involving embryos, the panel concluded that "the preimplantation human embryo warrants serious moral consideration as a developing form of human life, but it does not have the same moral status as infants and children." The panel counseled that most investigations be discontinued about 14 days after fertilization when the so-called primitive streak appears, a groove that develops along the midline of the embryonic disk of cells. The primitive streak is the first morphological evidence of what will later develop into the nervous system and is, thus, the earliest suggestion of sentience, according to panel member Ronald M. Green, a professor of religion at Dartmouth College, Han-over, N.H. It also establishes the embryo's head-tail and left-right orientations. In addition, it is the first developmental point at which the embryo can be called an individual, he noted at the news conference. Prior to this time, the embryo, if divided, can give rise to twins. Critics, however, say the primitive streak may have no special ethical significance as a stopping point on the developmental continuum from conception to birth (see accompanying story). "For the life of me, I really cannot understand why this specific morphological development, which speaks to where the nervous system is going to be formed, becomes a landmark," says Robert J. White, a professor of neurosurgery and a neuroscience researcher at Case Western Reserve University Medical Center, Cleveland. White believes fertilization delineates the start of human life. "There is no neurochemical or electrical event that speaks to when something becomes human, to when something equivalent to the soul or spirit_and not so much the mind_is infused into an embryo." In forming its recommendations, the panel attempted not to construct an unassailable moral stance on a controversial subject but to create defensible public policy, according to panel chairman Steven Muller, president emeritus of Johns Hopkins University, Baltimore. That process included public testimony at panel sessions before the report's release, as well as a solicitation of public comment leading up to a meeting of the NIH director's standing advisory committee to be held early next month. At that meeting, the committee, of which the panel was a temporary subgroup, will discuss the report's recommendations and advise director Varmus, who will then make a final decision on what research in this area the agency will fund. These steps are, by and large, the usual ones in the development of new policy at NIH and elsewhere in the government, but may be crucial in advancing policy in such a controversial area as human embryo research, Muller observed at the news conference. "In a democracy, public policy is not simply imposed on citizens by a higher authority," he said. "Proper public policy develops through a public process rooted in public participation. Public participation involves a multitude of interests, many in conflict with one another. The public process which produces public policy, therefore, must strive for a balance among divergent interests, a balance sufficient to obtain and justify public support." Muller added, however, that the content of some letters received by the panel during this process prompted them to request that NIH undertake a concerted public education effort to explain the complex scientific and ethical issues involved in human embryo research. To this end, NIH held an extended special briefing for science writers a week prior to the report's release and prepared comprehensive educational materials for distribution with the report. Opening Doors Scientists note that the types of research that NIH may begin funding if Varmus accepts the panel's proposals are well supported in a number of other countries and that U.S. investigators who now must rely on private funding find themselves at a comparative disadvantage as a result. "It's very clear that this is all competitive and that countries like England and Australia are way ahead of us," says Uta Francke, a professor of genetics and pediatrics at Stanford University Medical Center in California, and chairwoman of the Institute of Medicine committee that produced the July 1994 conference report Fetal Research and Applications (Washington, D.C., National Academy Press, 1994). "Our colleagues [in other countries] have sort of looked at [us as] the poor American brothers who couldn't really do anything because there wasn't any funding for it." One promising area likely to receive an immediate boost from new government grant support, according to Francke and other researchers, is genetic diagnosis of blastomeres_embryos at the eight-cell stage, in this case_produced through in vitro fertilization techniques. Currently, prospective parents who know that one or both of them carry a disease gene are faced with few options if they wish to have a healthy child with genetic contributions from both parents. They can test for the gene by chorionic villus sampling at 10 weeks' gestation or by amniocentesis at 16 weeks. If the disease gene is present in the fetus, the couple face the difficult decision of whether to end the pregnancy. "People who are at risk and who have done that a few times often are not willing to do it again," Francke says. "It's a tremendous emotional burden." A new experimental procedure, however, allows researchers to separate a single cell from the eight-cell embryo, amplify the genetic material from the cell using polymerase chain reaction technology, and then analyze the material for the disease gene's presence. If the gene is not found, the now-seven-cell embryo can be transferred to the womb where, if it implants, it will develop normally. In practice, a number of eggs are released from the ovaries through a hormone-stimulation protocol, fertilized in vitro, and tested. Multiple embryos that have been screened for their genetic health are then introduced into the uterus in the hopes that one will implant. Worldwide, fewer than 50 pregnancies have resulted from this diagnostic technique, according to the panel's report, and more research is needed to extend and refine the procedure. Genetic disorders successfully tested for, however, already include cystic fibrosis, Lesch-Nyhan syndrome, Duchenne muscular dystrophy, and Tay-Sachs disease, as well as a number of X-chromosome-linked recessive disorders such as hemophilia A, adrenoleukodystrophy, myotubular myopathy, spastic paraplegia, and certain forms of mental retardation. Cancer And Development Certain areas of cancer research, too, may benefit from federal funding for preimplantation human embryo research. A number of genes that play critical roles in the normal development of the embryo are also suspected to play a part in some cancers. "The oncogenes that are a part of the cancer situation and the growth factors that are part of cancer scenarios are also part and parcel to those that are involved in development," says Neal L. First, a professor of reproductive biology and biotechnology at the University of Wisconsin, Madison. First is also a member of the National Advisory Board on Ethics in Reproduction (NABER), an interdisciplinary group established in 1992 by the American College of Obstetricians and Gynecologists and the American Fertility Society, but now a separate entity funded by private foundations. "Most often, oncogenes are genes that are useful in developmental processes when normally regulated, but when the oncogenes become improperly regulated, the tissues become tumorous." First adds: "We would probably enhance our understanding of cancer if we really understood the gene, growth factor, and cytokine situations for embryos as they pass through from one [developmental] stage to the next to the next." Research on human embryos will be crucial for these studies, First asserts, because animal studies have demonstrated that important developmental differences exist between species. "There's a lot of suspicion that the textbooks are not very accurate relative to human embryo development," he says. "What are the things that cause an early human cell to make its [developmental] changes, to differentiate? We can speculate from [what we know about] other species, but we wouldn't actually know until we were able to study humans." Studies involving parthenotes_unfertilized eggs that proceed to either spontaneous or induced early development as embryos_may lead to important new information about development, according to Brigid Hogan. Animal studies have shown that there are profound intrinsic barriers to normal development of parthenotes, which contain genetic material from only one parent. The reason involves a little-understood process called imprinting, in which chromosomes from both parents must be present in the embryo for normal development. Several tumor forms, relatively benign and easily treated, now appear to be linked to embryos in which only maternal or paternal genes are present. One example is a kind of trophoblast tumor called hydatidiform moles, which can progress to malignant choriocarcinoma. "We're not going to be curing anybody of these tumors by doing research," Hogan says. "On the other hand, the basic biology is extremely interesting. Studies in mice and in humans show that choriocarcinoma arises with a particularly high frequency when there are only paternal genes present. And, so, the question is why. Presumably, this is because of imprinting problems, in the sense that certain genes are going to be either active or inactive, oncogenes are going to be active, or tumor suppressors are going to be inactive in those cells." Another potentially significant area of research that may expand with federal support is in the development of techniques for culturing pluripotential human embryonic stem cells, according to Hogan. The creation of so-called immortal lines of undifferentiated cells might lead to crucial advances in cell-transplantation therapies. "A really important [advance] over the last 10 years in mouse embryo research is the development of these immortal, continuously proliferating embryonic stem cells from blastocyst-stage em-bryos," Hogan says. "You can culture them, and, as long as you continue growing them under ideal conditions and subculture them routinely, they will remain undifferentiated. But then you can stimulate them with various treatments to differentiate into various cells types. You can get muscle and nerve and bone and cartilage and so forth. So, the idea would be that maybe, down the line, you could use these for making blood cells for transplantation, and maybe some kinds of neuronal stem cells or muscle stem cells." More than 70 proposals for grants in human embryo research have already been received at NIH, in anticipation of Varmus's approval of the panel's recommendations. Most of the new proposals have been submitted to the National Institute of Child Health and Human Development at NIH. (The Scientist, Vol:8, #23, p.1, November 28, 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 : ENDURING QUESTIONS AU : FRANKLIN HOKE TY : NEWS PG : 6 The ethical reasoning of the panel advising the National Institutes of Health on human embryo research was clearly expressed by its policy cochairwoman at a news conference at which the group's report was released in September. "The basic finding of the panel is that it is acceptable public policy to fund research on the human embryo, subject to stringent guidelines," said Patricia A. King, who is also a professor of law at Georgetown University Law Center, Washington, D.C. "There were three principles that guided us in our determination. First, that the promise of benefit from doing research on the human embryo was significant and carried great potential for couples and for families and for individuals. Two, that the preimplantation embryo warrants serious moral consideration but does not have the same moral status as infants and children. And three, that federal funding and regulation will help bring about consistent ethical and scientific review of proposals to do research on the human embryo." While many--perhaps even most--scientists accept this line of reasoning, there are critics, primarily outside of research, who certainly do not. Generally members of conservative religious or political groups also opposed to abortion, these critics may find they wield increased influence on federal policies following the substantial gains made by the Republican party in elections earlier this month. For example, the first point made by the panel--that the potential benefit of human embryo studies provides a justification for such research--depends on one's view of the second point--that the embryo does not have the same moral status as infants, children, or adults--according to Richard Doerflinger, associate director for pro-life activities at the National Conference of Catholic Bishops in Washington, D.C. "A utilitarian ethic of human experimentation is going to lead to enormous abuse," Doerflinger says. "The benefits are one part of the equation, but if what you're doing is basically unjust use of a human subject, then the experiment should not be done. And that's what we feel is being contemplated here." Some scientists, including those who are basically in agreement with the panel's findings, note that the appearance of the primitive streak--the earliest morphological marker of the nervous system and, thus, sentience--may not, over time, stand as a significant developmental limit for ethical human embryo research. "It's a demarcation point," says Neal L. First, a professor of reproductive biology and biotechnology at the University of Wisconsin, Madison. First is also a member of the National Advisory Board on Ethics in Reproduction (NABER), a privately funded, nonprofit group of 13 professionals in ethics, medicine, law, religion, and public policy. "That's the most I can say. It is the point where you can begin to say, yes, this lineage would be human if it went this way, and it might be something else if it went another way. I have a suspicion that, as we learn more about human embryology, we will actually find that that delineation point comes earlier than the primitive streak." However, the question of when an embryo becomes uniquely human, and therefore no longer an appropriate research subject, presents science with a kind of Catch-22 as far as human embryo research is concerned, First notes. "You have to be able to do research to get that answer," he says. --F.H. (The Scientist, Vol:8, #23, p.6, November 28, 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 : Science Community Gives Mixed Review To 'Triage' NIH welcomes expanded use of the study-section procedure--but some extramural scientistsare less enthusiastic AU : LIANE REIF-LEHRER TY : NEWS PG : 1 The expanded use of triage--under which certain grant applications deemed to be "noncompetitive" (NC) are not discussed in study sections--by the National Institutes of Health Division of Research Grants (DRG) has met with enthusiasic response from many NIH administrators. The new system, however, has engendered controversy in the extramural community. Triage, which has been instituted on a trial basis in an increasing number of study sections since February of this year, will be used for all investigator-initiated (R01) and "FIRST Award" (R29) research grant applications beginning with those submitted for October/ November 1, 1994 deadlines. NIH expects about half of all applications to fall into the NC category. The aim of the measure is to allot more time for study-section members to discuss applications that stand a chance of getting funded, as well as to decrease the workload for reviewers and study-section heads, called scientific-review administrators, or SRAs (see story on page 8). In addition, modifications in the review system, designed to reduce paperwork and otherwise streamline the process, have been put in place (see story on page 9). For example, although all applicants will continue to receive summary statements about their proposals, these will now contain primarily the initial reviewers' reports. NC applications will lack a summary paragraph given for scored applications. Wendy Baldwin, NIH's deputy director for extramural research, hopes "triage will help focus the discussion among reviewers. "All applicants will receive comments about their proposals," she points out, "and we expect that, by sending the essentially unedited reviewers' comments, applicants will get faster feedback and a clearer view of the assessment of the application." NIH director Harold Varmus says he is pleased with the way triage is working, and that he has had positive feedback from SRAs. "Study-section meetings have improved, and that's what the objective was," he notes. "Applications in the top half [up to the 50th percentile] are getting a fuller and fairer review." Not all extramural scientists agree that triage is a positive change. Susan Leeman, a professor of pharmacology at Boston University School of Medicine, for one, considers it "inappropriate to ask scientists to spend months writing proposals and then not afford them discussion time at the study-section meeting. "If you want to triage half of all applications," she says, "perhaps one possibility would be to have scientists write brief 'intention' proposals and then invite only those who stand a chance of being funded to submit a full application." Some granting agencies already use this method of sifting proposals. Leeman is also "concerned that triage may provide an opportunity for biases to creep into the review process." Lawrence Grossman, Distinguished Service Professor of Biochemistry at Johns Hopkins School of Public Health in Baltimore and a former chairman of the biochemistry department who has served as a member and chairman of an NIH study section, was disturbed this summer when an application on which he was listed as a consultant was designated NC. "The reviewer apparently dismissed the proposal because of a flaw he perceived in a particular technique," Grossman says. The Johns Hopkins researcher contends that "the reviewer's criticism was based on ignorance of the field. Everyone working in this area of research is aware of the complication cited by the reviewer and knows how to circumvent the problem." Although Grossman currently has a MERIT Award--an eight- to 10-year grant given by NIH to established investigators with good "track records" who are working in promising research areas and get priority scores in the top 20 percent--he is disenchanted with the peer-review system "because funding decisions are based on assessment of anticipated results rather than on proven productivity." Anthony Demsey, associate director for referral and review at DRG, comments: "We hear the complaint occasionally that the reviewers made a basic, elemental error in an assessment, and such a complaint normally forms the basis for a rebuttal letter on the grounds that the reviewers lacked appropriate expertise. But this criticism has nothing to do with triage--it's just inevitable that in the peer-review system there will occasionally be human error. "If, however, the implication is that the error was due to casual review, or sloppiness, or carelessness on the part of a reviewer--looking for an easy way out of having to do a full review--well, we just haven't seen that in the triage process. If anything, the reviewers have been overly cautious." Demsey thinks "triage is a good streamlining procedure," and many SRAs and reviewers agree. SRAs And Reviewers Report SRAs are supportive of the new review process, but reviewers' responses to triage have been mixed. Teresa Levitin, SRA for Human Development and Aging-1, contends that "time saved by not having to discuss the NC applications" makes for "richer discussions of those applications that do get reviewed at the meeting." Patricia D'Amore, a member of an early "test" study section, is also positive about triage. In her opinion, "reviewers [should] spend more time judging the science rather than suggesting experiments or trying to help rewrite applications." Thomas Parsons, chairman of the Experimental Virology Review Group, concurs: "Up to now, proposals were tailored--after three or four resubmissions--to what the reviewers think should be done rather than retaining the PI's [principal investigator's] original aim." Levitin voices a similar feeling: "The study section should evaluate the quality of the PI's application, not the collective judgment of the previous study section's critiques." But a senior professor at Harvard Medical School, speaking on condition of anonymity, is adamant that "the job of reviewers is to get good research funded, and reviewers should help PIs. Some of the best scientists write the worst applications because they are too close to their own work." Some study-section members worry that triage will unduly increase an already disproportionate influence exercised by the primary reviewers. Edward Zapolski, SRA of the Metallobiochemistry Review Group, is concerned that the system "may cause reviewers to worry about getting re-proached by colleague-applicants who know which reviewers are on a study section and also know that it only takes one objection [from a study-section member] to bring an NC application back to full review." Additional controversy arises from the changes in the summary statement that have taken place along with triage. A number of scientists, including some reviewers, think the revised summary statements will deprive researchers--perhaps those most in need of advice--of important feedback about their applications. But NIH officials counter that the new summary statements actually provide grant applicants with the individual reviewers' reports, and summary statements for NC applications lack only a summary paragraph describing the study-section discussion of the application. Janet Rasey, a professor of radiation oncology and director of the Research Funding Service at the University of Washington Medical Center in Seattle, who has served two four-year terms as a study-section member, feels conflicted about the new procedures. She thinks "it's great to have more time to discuss the borderline proposals--but triaging 50 percent of applications is unrealistic; there are too many good proposals." In addition, she worries that "summary statements consisting of reviewers' reports may be confusing to PIs--especially when the reviewers disagree with each other." Moreover, Rasey says, "triage may make more work for conscientious reviewers who may feel compelled to write a more thorough critique than they would previously have done." Furthermore, she points out, "reviewers themselves may 'lose out' under the new system: Study-section discussion often helps clarify complex issues in the minds of reviewers, who can then temper their critiques accordingly." Rasey maintains, however, that triage and other remedies obscure "the real problem," which is "that there's not enough money to fund all the really good grants; tinkering with peer review is largely cosmetic." Many of her peers concur. Conflicting Views A few people contend that much of the negative response to triage stems from a misunderstanding of the new system. Some SRAs and reviewers say that triage is nothing more than a formalization of the way in which study sections already operate, because applications not likely to be funded are generally given only brief discussions, anyway. However, Levitin and other SRAs, as well as some study-section chairpersons, say applicants will get adequate feedback from the reviewers' reports despite lack of discussion by the whole study section, especially because critiques for NC applications--initially restricted to one page in the February 1994 triage trials--no longer have a page limit, and a number of reviewers will write longer tutorial reports because they want to help PIs. Jane Koretz, a professor of biology and biophysics at Rensselaer Polytechnic Institute who served as a member of an NIH study section from 1989 to 1993, believes the new form of the summary statement is "good for PIs because they get to see conflicts between reviewers that were sometimes 'papered over' in the integrated summary statements written by SRAs." She also thinks the verbatim presentation of the reviewers' remarks on the summary statements may encourage "a higher and more objective standard of review than some reviewers, unfortunately, currently practice." But Koretz does not like the use of triage. She says that "the NC classification institutionalizes a trend toward awarding 'fundable' and 'non-fundable' priority scores that began when NIH funding got tight." She contends that "study sections should be in the business of assessing scientific merit, rather than trying to figure out whether a proposal is competitive or not." Gerhard Ehrenspeck, SRA of the Cellular Biology and Physiology-2 study section, is in favor of triage and thinks "it is working well." He observes: "I have had no negative feedback from reviewers in my study section nor from any of the PIs whose applications were designated NC by my study section in February or July." Others think that, in any case, study sections should stop spending time on applications that stand little chance of succeeding at current funding levels. Garrett Keefer, SRA of the Experimental Virology Review Group, which has used triage since February, predicts that NC designations are likely to be on target. In his February study-section meeting, 27 of 90 proposals were designated NC. Of the 27, one was recalled for full review but in the end got an NC score, anyway. Parsons further suggests that "an application designated NC two or three times in a row should not be permitted to be submitted again in the same form." Meanwhile, scientists will have to deal with triage. In the long run, observers believe, it may save time for applicants because summary statements for NC applications will be returned quickly, allowing more time to revise or make other plans if an application is turned down. Also, they point out, writing revisions to an application that doesn't stand a chance of getting funded is a waste of precious research time. In any event, NIH officials say they hope PIs will give triage a fair chance and provide DRG with objective feedback about the various aspects of the modified system of peer review. Liane Reif-Lehrer is president of Erimon Associates, a consulting firm based in the Boston area, and the author of Grant Application Writer's Handbook (Boston, Jones and Bartlett Publishers, 1995). She gives workshops on grant-proposal writing and related subjects. (The Scientist, Vol:8, #23, p.1, November 28, 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 : WHAT IS TRIAGE? AU : LIANE REIF-LEHRER TY : NEWS PG : 8 The National Institutes of Health announced in the September 23 NIH Guide for Grants and Contracts that it will extend its use of a triage system to all investigator-initiated research grant (R01) and "FIRST Award" (First Independent Research Support and Transition Award, R29) applications submitted for October/November 1, 1994 receipt dates and reviewed by the NIH Division of Research Grants (DRG) at the February 1995 study-section meetings. Under triage, R01 and R29 applications deemed by reviewers to be "noncompetitive" (NC) at current funding levels are not discussed at study-section meetings and are not routinely forwarded to the relevant advisory council, the second level of NIH peer review. To be categorized as NC, an application must be judged so by at least two assigned reviewers--but an application can be recalled for full review by even a single study-section member at any time before or during the meeting. Members are advised to opt for full review in borderline cases. It should be noted that NC is very different from the voting category "not recommended for further consideration" (NRFC), which came into use in 1991 and was used for the last time in autumn 1994 in about half of the study section meetings. Whereas NRFC indicated that an application did not have substantial scientific merit, NC implies nothing about the quality of an application but rather indicates that the application is not likely to be funded in the current budgetary climate. Although the announcement about expanded use of triage in the September 23 NIH Guide states that about half of all applications will be designated NC, the figures to date at the test study sections have been lower: The average in the four study sections in the February test group was 36.5 percent (range: 30 percent to 51 percent); the average in 12 study sections in a July test group was 35.4 percent (range: 27 percent to 43 percent). NIH hopes the new procedure will allow more time at study section meetings to discuss applications that stand a chance of getting funded. The agency also hopes to decrease the workload for reviewers and scientific review administrators (SRAs) of study sections. SRAs say that although the reviewers' workload has not changed appreciably--and in some cases may have even increased--study-section meetings have been shorter, and their burden has been eased. --L.R.-L. (The Scientist, Vol:8, #23, p.8, November 28, 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 : A NEW LOOK FOR SUMMARY STATEMENTS AU : LIANE REIF-LEHRER TY : NEWS PG : 9 Summary statements for National Institutes of Health grant applications (often referred to as "pink sheets," although they have not been printed on pink paper since 1991) will be formatted differently from now on: * Summary statements will consist primarily of the individual reviewers' critiques. * Scientific review administrators (SRAs) will write summaries of the study-section discussion (including budget recommendations, if appropriate) only for applications that undergo full review by the study section. Because "noncompetitive" (NC) applications are not discussed at the study-section meetings, their summary statements will not contain a paragraph summarizing the discussion by the study-section members about the application. * Summary statements for scored applications will continue to have a "Description of Project," but NC applications will no longer contain this paragraph. * Summary statements for NC applications will contain an explanation of this designation. * Summary statements will no longer contain a separate paragraph about investigators. * Reviewers will be expected to modify their written critiques during the review of an application--for example, removing a criticism that was deemed to be invalid following group discussion. NIH officials contend that SRAs will save appreciable time as a result of these changes, as they will no longer have to integrate the reviewers' reports into a cohesive summary statement. Garrett Keefer, SRA of the Experimental Virology Review Group, reports that he was able to generate summary statements much faster after the February meeting than he could under the old system. Principal investigators will profit by getting the summary statements for their applications more promptly. --L.R.-L. (The Scientist, Vol:8, #23, p.9, November 28, 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 : Industry And Educators Team Up AU : KAREN YOUNG KREEGER TY : NEWS PG : 1 Citing a need to replenish and train their own work force, United States companies are joining academia, government, and communities in the effort to reform science education, as indicated by several recent initiatives. Industry officials and others maintain that their participation can infuse a business perspective, as well as a "sense of urgency" and focus that is lacking in the national dialogue on this issue. Bassam Shakhashiri, a professor of chemistry at the University of Wisconsin, Madison, who was assistant director for science and engineering education at the National Science Foundation from 1984 to 1990, contends that industry involvement in this effort is more than a welcome contribution; it is a necessity. "The business community must be involved intimately in the science education reform arena because they have expertise that academic communities can benefit from," he asserts. Shakhashiri says that this expertise ranges from "technical know-how" in science areas to management tools, such as strategic planning, that can be applied to the U.S. educational system. He warns, however, that for any undertaking to be effective, U.S. educators have to be receptive to change and that change must be coordinated among all stakeholders, "not just the participation of the private sector." One such effort in this movement took place last September in a conference entitled "Corporate America's Impact on Elementary Science Education." Hosted by Merck & Co. Inc. at its Whitehouse Station, N.J., facility, the meeting was sponsored by the National Science Resources Center (NSRC), the National Academy of Sciences (NAS), and the Smithsonian Institution in collaboration with Bristol-Myers Squibb Co. of New York; Dow Chemical Co., headquartered in Midland, Mich.; Hewlett-Packard Co., Palo Alto, Calif.; and Pittsburgh-based Miles Inc. Participants in the conference included about 80 delegates--educators, development officers, top-level executives, and researchers--from industry, government, and academia. Biotech, pharmaceutical, chemical, publishing, manufacturing, and computer and electronics firms were all represented. Attendees discussed ways in which corporations are contributing to science education reform and how their current and future efforts could be more effective. In a luncheon address at the meeting, NAS president Bruce Alberts summed up the role he feels corporate representatives should take. "We need advocates in every local region for science. The basic message I have for you is that we need all of you to be involved and to spread the word and to take the scientists and engineers throughout this country who really want to contribute [to science-education reform] and enable them to be effective volunteers." In other high-profile collaborations, the National Aeronautics and Space Administration, the Department of Education, and the 28 largest U.S. aerospace contractors signed the NASA-Industry Education Initiative this month. The agreement created a partnership to work on improving such areas as students' academic performance in science and mathematics and strengthening the teacher work force. And in mid-December, the National Research Council (NRC) is cosponsoring a two-day symposium to explore ways that corporations can contribute to reform efforts. Whereas the focus of the Merck meeting was on elementary science education, the upcoming NRC-sponsored conference will concentrate on K-12 science as well as mathematics education, although some overlap is expected, say NSRC officials. Conferences like these are, in part, outgrowths of the GOALS 2000 Educate America Act signed last March by President Bill Clinton, which authorized $400 million in grant funds to state and local educational agencies to develop and implement reforms. Experts say that the National Science Education Standards--a project started in 1991 to formulate a set of curriculum, teaching, and assessment guidelines (R. Kaufman, The Scientist, July 6, 1992, page 3)--also account for the heightened corporate participation in science education. For example, these specifically articulated goals mirror the mission statements and goals of the education programs of the five collaborating corporations at the Merck conference. Industry Role Many U.S. firms have been involved in science education in an "ad hoc way," according to one corporate official, for several years, but lately their involvement has been stepped up and formalized. For example, many companies are devoting millions of dollars to create educational institutes and positions within corporations; sponsor programs within schools at the local and regional level; and spearhead national education initiatives through NSRC and other groups. No statistics are available that itemize corporate contributions to K-12 science education. However, according to the Conference Board, a New York-based nonprofit business research organization, out of 371 companies surveyed in 1992, the proportion of corporate contributions to precollege education out of total corporate charitable giving was 4.3 percent. "Money is no longer the only thing. It's really the expertise that we can add to the partnership," says Carlo Parravano, director of the Merck Institute for Science Education, based in Rahway, N.J., "We want to go beyond giving away a check." The corporate representatives interviewed for this story concur, noting that their firms' nonmonetary contributions fall into three main categories: facilitating volunteerism for employees, donating equipment to schools, and promoting advocacy activities. "Advocacy, in my opinion, is the most important" of Dow's contributions, asserts Robert Henson, manager of education affairs at Dow. For example, voicing opinions on education reform at school board meetings and writing editorials are ways in which Dow employees take on an advocacy role, he says. Systemic Reform According to Sally Goetz Shuler, deputy director for external relations, development, and outreach at NSRC, the new initiatives address systemic reform--the suite of changes in educational methods that reformers espouse--involving all "stakeholders," including children, teachers, administrators, educators at universities, parents, community leaders, and scientists and engineers. Shuler, who spent 15 years as a classroom science teacher and a science specialist for the Fairfax County Public Schools in Virginia, says that overhauling curriculum, establishing professional development programs, creating educational materials and equipment, conducting performance evaluations, and devising ways to involve community leaders all fall under suggested reform measures. NSRC's official involvement with corporations began about four years ago with Dow and Hewlett-Packard, she says. The Merck meeting was spawned by a less formal gathering sponsored by Hewlett-Packard in 1992. "Both of these meetings had similar goals: These corporations wanted to share what they were learning about reform with other corporations in order to get more communities involved and to engage more corporations in the whole process," she reports. Participants in the Merck meeting say, for the most part, that it did accomplish its goal of increasing awareness, but that the meeting should be viewed only as a beginning. Dow's Henson adds that organizers "needed to close the deal. Part of the meeting could have been [dedicated] to gaining some commitment in the form of coalitions and alliances." In the two months since the conference, however, Shuler notes that about 10 corporations have contacted her for more information on ways to participate. "I'd like to see us have at least 10 or 15 corporations involved at the same level [as the five sponsoring corporations at the conference] in the next five years," she says. "Right now these five corporations are working with 97 communities, representing about 700,000 children in 18 states and two Canadian provinces." Corporate Payoff Corporate representatives cite "big-picture" reasons to explain why they are devoting more and more resources to educational reform. They say that developing an informed and diverse work force for the future is a wise business investment in people and communities. "It's a work-force issue," maintains Sande Deitch, executive director of the Pittsburgh-based Miles Inc. Foundation. "Getting involved will help develop [a company's] own qualified pool of talented people." Merck's Parravano agrees, adding: "Another payoff is having a work force that is well trained" in the skills that firms anticipate will be needed in the future. Corporate executives list some general examples of these desired abilities: problem-solving, assessing data, working in teams, having subject-matter expertise, and possessing knowledge of and a high comfort level with technology. Parravano and others also view their involvement as "an investment" in the communities in which they are located. "Having a strong school system spills over into the entire community," he contends. Corporate officials emphasize that another long-term payoff for society is improved science literacy. "I think in today's global economy, whether you're tossing hamburgers on a grill or whether you're running a process-control system within a plant, more and more jobs are going to require some deeper level of knowledge of technology," contends Henson. Industry representatives assert that businesses can contribute to education reform in a way that is different from the involvement of others. "One of the things that really impresses me about working in a corporation such as Merck is [industry's] ability to focus on a problem," says Parravano, who, before coming to Merck in 1993, was a professor of chemistry and chairman of the division of natural sciences at the State University of New York, Purchase. "I spent 20 years in academia and I rarely if ever saw that [ability to focus]. Business is good at sitting back and asking: 'What did we learn from this? How does this improve our next step?' I think that that's a perspective that corporations can bring to the educational environment." Dow's Henson also notes that corporations can contribute "a sense of urgency" to promoting changes in science education. "If you talk to educators, they don't [seem to] have a sense of urgency. They take your ideas, and say: 'Well, we do need to do that, but it's going to take further research.'" And Miles' Deitch says that, as far as students are concerned, corporate America can bring a "business point of view" to discussions on reform. "[We can show] these kids what they are going to have to know when they get out of school. I think it's very important because kids have to have some idea about why they're learning something." What Can A Scientist Do? Corporate and NSRC brochures and representatives circulating at the meeting offered numerous examples of how researchers can contribute to science education in their communities. Some scientists conduct tours of the plants where they work, participate in student science and math clubs, and serve on school district curriculum-review committees. Others mentor students, give classroom presentations, and build demonstration equipment for teachers. Still others serve on school boards and judge science fairs. "The most important thing is to mentor teachers," Parravano stresses. "If a teacher has a question on a specific topic or is having trouble with some material, they have somebody [with subject-matter expertise] that they can call." He adds that this arrangement is especially important for teachers who have less experience with hands-on science. And at Hewlett-Packard, Bess Stephens, manager of K-12 education relations, says that at the local level, company technical staff and researchers are assigned to school districts in communities where the firm has plants. "That scientist is the primary conduit" between Hewlett-Packard and the students, she explains. But how do scientists make time in their busy research schedules to help out in schools? Most firms have an informal arrangement with employees who volunteer, while some others have a more formalized mechanism to facilitate volunteering. According to Stephens, Hewlett-Packard has a policy that allows scientists to use company time to volunteer in schools. "It's not at all uncommon for some of these individuals to [also] contribute some of their personal time," she adds. One of the first things Stephens did when she assumed the newly established post at Hewlett-Packard was to "create an environment that encouraged people to volunteer." The standard is roughly four hours per month, distributed in many possible combinations. She maintains that it is important for any company that wants to engage in educational reform to set up formal policies because it sends a strong message to employees that management is serious about their efforts to become involved. (The Scientist, Vol:8, #23, p.1, November 28, 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 : Under New Management, Biosphere 2 Explores Research Opportunities AU : NEERAJA SANKARAN TY : NEWS PG : 3 Long plagued by logistical problems and dogged by controversy, the troubled Biosphere 2, under new management, is attempting to revitalize one of the most criticized aspects of the program--the quality of its science. Since the summer, more than a dozen geologists, biogeochemists, ecologists, and climate modelers have visited the 3.15-acre Oracle, Ariz., facility--the world's largest enclosed artificial ecosystem--to evaluate its potential experimental uses and have made recommendations, in a series of "white papers," for various investigations that might take advantage of its unique features. The evaluation is part of an effort by the new management team to generate a long-term scientific plan and restructure the enterprise as a full-scale research center. The scientists' proposals span three broad areas of possible study within the facility: biogeochemical cycles; ecology and plant biology; and modeling systems. A member of the new team of scientific consultants who is quite familiar with the enclosure and the program's troubled past is Walter Adey, director of the Washington, D.C.-based Smithsonian Institution's marine systems laboratory and the primary consultant in designing the original miniature ocean for Biosphere 2. Adey resigned from the project over scientific differences, but has returned to take part in the reexamination. Adey sees unique value to the Biosphere project in the realm of ecosystem modeling. Biosphere 2 "is not really a new endeavor," he remarks. "It's just that it is on a much larger scale than any other model system before." Built in the late 1980s by a group of environmentalists, Bio-sphere 2--which includes miniature versions of a savanna, rain forest, marsh, farm, and ocean enclosed within glass-and-steel domes--was touted as an attempt to better understand the workings of the Earth's own biosphere and to see if an artificial ecosystem could sustain humans entirely on its own. The $150 million effort was financed by Edward P. Bass, a Texas multimillionaire with an interest in ecology and conservation. The original endeavor at self-sufficient existence within the interconnected domes commenced in September 1991, when an eight-member team was sealed inside for two years. Among a number of problems they experienced were poor crop yields, leading to inadequate food supplies, and dangerously high carbon dioxide levels. The so-called Biosphereans often went hungry, and oxygen had to be pumped in to supplement air supplies. More controversy swirled around the administration of the project. There was considerable criticism from the scientific community because several of the Bio-sphereans were not well-credentialed scientists and because of an aura of secrecy--which was compounded by a lack of published data--maintained by the nonscientist management. Because of sharp internal disputes, many of the initial scientific advisers quit the project last year. This April, Bass took legal action to dismiss the top management. A nonprofit consortium--called the Biosphere 2 Research Group--was formed in July by project executives and Columbia University's Lamont-Doherty Earth Observatory in Palisades, N.Y., to set a new scientific course of action. One of its first activities was to commission white papers from independent scientists in various disciplines relevant to the areas of research that the facility is equipped to support. "A critical aspect of these papers is that they make suggestions for work that could be done only in Biosphere 2," explains Bruno Marino, a biogeochemist from Harvard University's department of earth and planetary sciences who joined as the new scientific director in August. "How could their [the white paper authors'] current research be expanded by the unique perspective that these facilities offer?" He adds that each white paper "might spawn many further proposals--the investigators could identify other people to carry on research here. We are not yet 100 percent sure what we are going to do." Marino, who wrote a paper on the topic of isotope biogeochemistry, hopes to find some common ground among the various white papers to help set an agenda for the future of Biosphere 2. While there are no set plans for the future, researchers involved do not anticipate another cycle of isolated residents at the facility. "I can see no reason to have 'Bio-sphereans' in there," says Wallace Broecker, a professor of geochemistry at Lamont-Doherty and a member of the executive committee of the newly formed consortium. "They've already proved the point [that they can survive]." Laying The Groundwork Marino says the first step--even before any new research projects are initiated--will be to "unpack the data collected over the past 2H years" and fully understand how the ecosystems enclosed within the giant greenhouse have developed. In some cases, the advisers say, errors incorporated into the design and construction of the facility need to be rectified. For instance, Adey, who originally designed the miniature ocean, sees a "particularly strong need to redesign the model aquatic system." In a rush to complete construction, many important features of the original design were either modified or left out altogether, he says, resulting in technical difficulties-- such as destruction of pumps by plankton--as well as a "skewed outcome" in mimicking the natural ecosystem of an ocean. As a result of the changes, Adey, a marine ecologist, resigned from the original project but returned to take part in the reevaluation. He estimates that between six months and a year will elapse before new projects are set up. Adey concurs with Marino's view that the present system must be understood before proceeding with further experiments: "If we want to understand the effects of perturbing an environmental parameter within a system, we first have to understand the [existing] system." In order to correlate results from Biosphere 2 to Earth's own bio-sphere, Adey stresses, scientists need to gauge the modeling effects resulting from the difference in size extremely carefully. "Because of the dimensional differences, the other parameters--temperature, humidity, air composition--must be as close to the wild ecosystem as possible," he cautions. Marino and Broecker also point out the need for extremely rigorous controls in modeling experiments. "We have to create controls--to see what happens under 'normal' conditions," Broecker explains. Biosphere 2 scientists are not yet decided on whether the controls will be set up in new units or be incorporated into the existing facility. Spheres Of Investigation The scientists commissioned to prepare the white papers are calling Biosphere 2 a tremendous intellectual lure. Broecker's white paper is entitled "Elemental and nutrient models." In the document, he suggests a number of different experiments to describe past, present, and perhaps future processes in the Earth's atmosphere, oceans, and crust. He offers as one possible course of experimentation a study of the long-term effects of enhanced levels of carbon dioxide on various life forms. Another project he envisions is an attempt to analyze what he calls "the fattening of the bio- sphere," or "anthropogenic greening." "If we add up the total amount of carbon in [burned] fossil fuels and forests, it exceeds the amounts accounted for by the increases in atmospheric and oceanic carbon dioxide," he says. "Therefore there must be a carbon sink--which we believe is the terrestrial biosphere, including soil organisms and [standing] forests." The closed system of the biosphere, containing a miniature forest, is an ideal place to test the hypothesis, he contends. The artificial ocean has generated many ideas among the visiting scientists. Francois Morrell, a professor of environmental engineering at the Massachusetts Institute of Technology, is proposing studies into the organic and inorganic chemistry of aquatic systems, while Marino hopes to expand this into investigations of oceanic flora and fauna. "The research potential is great," Marino comments. "Right now [the ocean] is more like a harbor environment with severe environmental perturbations," observes Adey. "It could be a useful model of a coral reef." A possible project, he says, could be a study of the degradation of reefs in response to increasing carbon dioxide. One of the major priorities for Bio-sphere 2's patron Bass is the subject of ecology and the roles of different living organisms in maintaining an equilibrium, Broecker says. To this end, the new scientific directors commissioned several white papers in the areas of ecology and biology. For example, Graham D. Fahrquar, an environmental biologist at the Australian National University in Canberra has written a paper entitled "Plant biology and physiology"; Mary Firestone, a microbial ecologist from the University of California, Berkeley, is contributing her ideas in "Soil biochemistry and microbial ecology"; and Stanford University's Peter Vitousek, an expert in the area of biological diversity, has written a paper on "Ecological approaches to interaction between plants, soils and the atmosphere." In addition to basic research, Biosphere 2's new directors hope to utilize the facility as an educational tool, and efforts are already under way to establish such a program. Broecker envisions it as an "outdoor science museum, for young people to come and learn about the Earth's environment and ecosystems. "It is not a perfect analog for the planet," Broecker concedes, "but [it] comes pretty damn close, all things considered." (The Scientist, Vol:8, #23, p.3, November 28, 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 : BLUEPRINTS FOR A GREENHOUSE (BIOSPHERE) AU : NEERAJA SANKARAN TY : NEWS PG : The reshaping of Biosphere 2 into a fully operational scientific facility is occurring under the management of the Biosphere 2 Research Group, a nonprofit consortium of scientists formed as a result of a collaboration between the Oracle, Ariz.-based facility and Columbia University's Lamont-Doherty Earth Observatory at Palisades, N.Y. Members of the new executive council overseeing the research group are: * Bruno D.V. Marino: the new director of science and research for Biosphere 2. Marino, a biogeochemist, formerly worked in Harvard University's department of earth and planetary sciences. * Wallace S. Broecker: Newberry Professor of Geology at La- mont-Doherty. He first became involved with the project during the tenure of the first group of Biosphereans, to investigate the causes of the dramatic drop in oxygen levels in Biosphere 2. * Michael M. Crow: vice provost of Columbia University, a professor of science policy in Columbia's School of International and Public Affairs, and the driving force behind the school's Global Systems Initiative. * Stephen K. Bannon: an investment banker and administrative head of Space Biosphere Ventures, the parent company of the Biosphere 2 project. In addition, the group consists of a science committee, responsible for evaluating the current situation at Biosphere 2 and setting up a long-range scientific plan. The committee is chaired by Michael B. McElroy, chairman of Harvard University's department of earth and planetary sciences. Recently Harold A. Mooney, Paul S. Achilles Professor in Environmental Biology at Stanford University, was appointed vice chairman. One of the main tasks of the committee was to commission white papers on potential experiments at Biosphere 2. Following are the white papers that were prepared. * "Elemental and nutrient models," by Broecker. * "Experimental agronomy," by Joe Tom Cothern, a professor of agronomy in Texas A&M University's department of soil and crop sciences. * "Environmental science and engineering," by Jay C. Davis, associate director, division of environmental programs, Lawrence Livermore National Laboratory. * "Plant biology and physiology," by Graham D. Fahrquar, a professor and head of the environmental biology group at the Research School of Biological Sciences, Institute of Advanced Studies, Australian National University, Canberra. * "Soil biochemistry and microbial ecology," by Mary K. Firestone, chairwoman of the University of California, Berkeley's department of environmental sciences, management, and policy. * "Soil physics and biology," by Eugene F. Kelly, an assistant professor of pedology at Colorado State University's department of soil and crop science. * "Ecological modeling of complex systems," by Christopher G. Langton, visiting professor, Santa Fe Institute, and John B. Corliss, a member of the Biosphere 2 Science and Research Department. * "Isotope biogeochemistry," by Marino. * "Organic and inorganic chemistry of aquatic systems," by Francois Morrell, a professor of civil and environmental engineering at the Massachusetts Institute of Technology. * "Trace gas interactions with vegetation," by Karl Turekian, Stillman Professor of Geology and Geophysics and founder of the Center for the Study of Global Change at Yale University's Institute for Biospheric Studies. * "Ecological approaches to interactions between plants, soils, and the atmosphere," by Peter Vitousek, Clifford G. Morrison Professor of Population and Resource Studies at Stanford University. Also serving as advisers to the scientific committee are Walter Adey, director of the marine systems laboratory of the Smithsonian Institution, Washington, D.C., and John C. Mutter, acting director and senior research scientist at Lamont-Doherty. --N.S. (The Scientist, Vol:8, #23, p.3, November 28, 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 : Musical Chairs TY : NEWS (NOTEBOOK) PG : 4 The Republican electoral earthquake that rumbled through Capitol Hill this month will result in the unseating from committee chairs of veteran Demo-crats, including Rep. George E. Brown, Jr., widely recognized as Congress' "Mr. Science." Brown has headed the House Science, Space, and Technology Committee since 1991. He was re-elected from his Southern California district but will lose the chairmanship when the GOP takes charge of Congress in January. Rep. Robert S. Walker of Pennsylvania, who has served as ranking minority member of the committee, is in line to take over as chairman. However, Walker first intends to try for a House leadership position--majority whip. If he succeeds in that bid, the committee leadership is likely to go to Rep. Sherwood L. Boehlert (R-N.Y.) or Rep. F. James Sensenbrenner (R-Wis.). In the Senate, Sen. Larry Pressler (R-S.D.) is expected to head the Commerce, Science, and Transportation Committee, replacing Sen. Ernest F. Hollings (D-S.C.). At press time it was still unclear who would succeed Sen. Jay Rockefeller (D-W.Va.) as chairman of the committee's science, technology, and space subcommittee. Among other Democrats who will be relinquishing committee posts are Sen. Barbara A. Mikulski, chairwoman of the Senate appropriations subcommittee that oversees funding of the National Science Foundation, the Environmental Protection Agency, and the National Aeronautics and Space Administration; Rep. John Dingell of Michigan, chairman of the House Energy and Commerce Committee; Rep. Henry Waxman of California, chairman of the energy committee's health subcommittee; and Sen. Tom Harkin of Iowa, chairman of the Senate Appropriations committee subcommittee for NIH. According to reports, Dingell or Waxman may be replaced by Rep. Thomas Bliley, Jr. (R.-Va.). The powerful congressional appropriations committees are expected to be taken over by Sen. Mark Hatfield of Oregon and either Rep. Joseph McDade of Pennsylvania, who is under indictment for corruption, or Rep. John Myers of Indiana. The House appropriations subcommittee for NIH is expected to be chaired by longtime NIH supporter Rep. John Porter of Illinois. (The Scientist, Vol:8, #23, p.4, November 28, 1994) (Copyright, The Scientist, Inc.) ================================ NXT: ------------------------------------------------------------ TI : Another Electoral Battle TY : NEWS (NOTEBOOK) PG : 4 As defeated members of Congress begin to pack up their offices, another election battle is heating up in Washington, D.C. Cornelius Pings, president of the Washington-based Association of American Universities and the official nominee for president of the National Academy of Engineering (NAE), will likely be challenged by Harold Liebowitz, dean emeritus of engineering at George Washington University, who garnered an astounding 42 percent of the vote when he bucked the NAE establishment and ran as an independent in 1991. To run in this March's election, he needs signatures of 5 percent of the membership, from 10 separate institutions. Liebowitz asserts : "I think the academy needs change, and I represent that to a great extent." Pings, by contrast, comments that the academy is "in very good health" and that he "would not go in with any reform agenda." (The Scientist, Vol:8, #23, p.4, November 28, 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 : Job Security TY : NEWS (NOTEBOOK) PG : 4 In his weekly "What's New" E-mail broadsheet for November 4, Robert L. Park, American Physical Society executive director for public relations, reports that the Department of Energy (DOE) chief is being considered for other jobs in the White House. "The administration has been trying to figure out what to do with Hazel O'Leary," he writes, recounting speculation that she might be made ambassador to South Africa or head of the Central Intelligence Agency. As to why something needs to "be done" with the popular secretary, a source close to DOE, requesting anonymity, says: "She's generally regarded as not a good team player within the administration. A little bit of that showed up in this openness initiative of hers, when she released the results of [past DOE] radiation testing [experiments on humans]. Nobody objected to her releasing [that material], but she didn't warn anybody [in the administration]." As for rumors that O'Leary may be in line for other work, DOE spokesman Jeff Sherwood says, "She's been denying that for some time now." He adds that O'Leary is committed to the job, at least through Clinton's first term, although "she's not promising a second term." (The Scientist, Vol:8, #23, p.4, November 28, 1994) (Copyright, The Scientist, Inc.) ================================ NXT: ------------------------------------------------------------ TI : PCAST Session TY : NEWS (NOTEBOOK) PG : 4 In the midst of this year's election turmoil, the White House's senior outside advisory group on science issues and policy is reconnoitering the "wide horizon" of its mission after an inaugural meeting that included a chat with Vice President Al Gore. The 75-minute, closed-door session with Gore came at the start of a 1Z\x-day meeting to launch activities of the President's Committee of Advisers on Science and Technology (PCAST), consisting of 18 science and technology experts plus presidential science adviser John H. Gibbons. During the October 25-26 meeting, PCAST members discussed a possible long-term agenda involving such issues as education, environment, health, R&D investment, and international affairs. John A. Young, PCAST co-chairman (with Gibbons) and former president and CEO of Hewlett-Packard Co., describes the session with Gore as "very inspiring." Young adds: "He is really quite well grounded in and obviously loves science and technology issues. I thought he made an excellent set of challenging points, to stretch our thinking." Expanding on the direction of the discussion, PCAST member Mario J. Molina, a professor of environmental sciences at the Massachusetts Institute of Technology, says, "We wanted to get some sense of what constraints we had, or what limits. On the one hand, we have constraints in terms of the economy and what society can afford, for research and so forth. But we don't have constraints in terms of possible directions we can take as a group. From that point of view, we have a wide horizon." (The Scientist, Vol:8, #23, p.4, November 28, 1994) (Copyright, The Scientist, Inc.) ================================ NXT: ------------------------------------------------------------ TI : Online Headaches TY : NEWS (NOTEBOOK) PG : 4 Researchers traveling the information superhighway are contemplating the issues brought out by two recent incidents involving electronic-mail networks. Last month David Farber, a professor of computer and information sciences at the University of Pennsylvania, posted an online notice regarding a news brief in Information Week (Oct. 31, 1994, page 10) about British physicist Laurence Godfrey, who reportedly is suing colleague Philip Halam-Baker for placing derogatory messages about him on the Usenet. And the Chronicle of Higher Education (41[9]:A24, Oct. 26, 1994) published an item about Grady Blount, an associate professor of environmental science at Texas A&M University, who reportedly was the victim of a break-in to his Internet account. The intruder used Blount's account to post racist messages to approximately 25,000 people, many of whom retaliated with angry notes to the Texas A&M faculty member. "We're in a period of chaos because the norms of what's appropriate use [of the Internet] are in the process of changing," says Robert Kraut, a professor of social psychology and human computer interaction at Carnegie Mellon University--a school that recently had its own online troubles when it tried to shut down sexually explicit Internet discussions. (The Scientist, Vol:8, #23, p.4, November 28, 1994) (Copyright, The Scientist, Inc.) ================================ NXT: ------------------------------------------------------------ TI : New Year's Persecutions TY : NEWS (NOTEBOOK) PG : 4 The Science and Human Rights Program of the American Association for the Advancement of Science (AAAS) has just released the 1994 edition of its Directory of Persecuted Scientists, Health Professionals and Engineers. The booklet lists 468 individuals from 42 countries whose human rights have been violated--119 cases more than appeared in last year's edition. AAAS project coordinator Elisa Munoz says the rise can be attributed to two factors: an improvement in the program's data-collection methods--it is developing its own sources rather than relying primarily on Amnesty International--and the fact that "most human-rights organizations have said there is definitely more repression this year." (The Scientist, Vol:8, #23, p.4, November 28, 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 : Administration's Technology Rhetoric Is Belied By Its Policy Actions AU : HENRY I. MILLER TY : OPINION PG : 12 Nowhere is the disparity between politicians' rhetoric and actions more pronounced than in United States science and technology policy. Government officials extol the importance of research activities to the national economy, jobs, and quality of life, while their policies tell a quite different story. One need only contrast the too-often-negative consequences of the Clinton administration's biotechnology policies with the lofty goals that are outlined in a slick administration booklet entitled "Science and the National Interest" (B. Reppert, The Scientist, Aug. 22, 1994, page 1; C. Macilwain, Nature, 370:317, 1994). Consider several examples among the document's science-policy goals. One is to "enhance connections between fundamental research and national goals," including "stable policies on research funding." In fact, public-sector funding of research is down. Budgets for 10 biomedical institutes of the National Institutes of Health were on the administration's cost-cutting block for fiscal year 1995. While the NIH budget as a whole rose 3.6 percent, that increase goes primarily to the Human Genome Project and the office of the NIH director. Funding of investigator-initiated basic research at the National Science Foundation is also in deep trouble. Although funding for NSF overall increased 14 percent, the increase for research was only 5.4 percent, only a percentage point or so above inflation. Moreover, much of the NSF research budget is being shifted toward non-basic research (C. Macilwain, Nature, 370:401, 1994). Overall, as a percentage of the nation's gross domestic product, the White House's proposed science budget was the lowest since 1958. Another goal is to "stimulate partnerships that promote investments in fundamental science and engineering and effective use of physical, human, and financial resources." The reality is that biotech is caught both directly and indirectly by White House assaults on drug prices and physicians' prescribing, and its insistence on rebates for government-subsidized drugs. While many of these proposed changes remain in limbo along with health-care reform, the expectation that first lady Hillary Clinton; Ira Magaziner, senior adviser for policy development to the president; and some members of Congress will exact their pound of flesh from what they characterize as drug companies' profiteering continues to make investors wary. In addition, a climate of increased stringency of regulations, irrational aversion to any kind of risk, and mistrust of technology generally--and biotechnology in particular--have conspired to discourage investment. Not surprisingly, small biotech firms were harder hit by potential investors than pharmaceutical giants. These firms have seen investment capital from public offerings drop more than 80 percent between 1991 and 1993, and stock market valuations have fallen precipitously. Consider this lead from a front-page story in the September 23 issue of BioWorld Today (L. Piercey, 5:1, 1994): "The New York biotechnology investment firm D. Blech & Co. suffered a liquidity crisis on Thursday [September 22] as its capital reserves dipped below federally regulated levels and it ceased trading activities on NASDAQ. The news caused the stock prices of many Blech-financed companies to plummet--a portfolio of 11 of the firm's biotechnology concerns lost more than $168 million in the course of the day, more than 30 percent of their combined market valuation." While this collapse cannot be ascribed wholly to administration policies, to be sure, they have created an investment climate in which small biotech companies are less viable--and their stocks less valuable. Regulatory Rhetoric An additional goal is "a stable, science-based regulatory system." The Clinton-Gore report asserts that the administration has "taken significant steps . . . towards accelerating the development of technologies critical for long-term economic growth and for increasing productivity while reducing environmental impact . . . [via] fundamental science." The reality is that at the same time that funding is down, biotechnology regulation, the bte noir of the administration's policies, has become increasingly anti-innovative, unscientific, and focused on negligible-risk activities. The United States Department of Agriculture (USDA) has required unnecessary permits for more than 1,400 field trials of genetically modified plants, all of them of negligible risk to public health or the environment. The Food and Drug Ad-ministration (FDA), which has a generally positive 15-year track record on regulating biotech, has been revising its regulatory approach according to instructions from the administration. The agency recently announced that it will soon require food manufacturers to notify FDA before marketing foods made with high-precision recombinant DNA techniques--while exempting those crafted with other techniques, regardless of possible risk. By exposing these biotech techniques alone to public scrutiny--for no scientifically sound reason--FDA is casting suspicion on these products, making them vulnerable to the boycotts, threats, and accusations of anti-technology groups. The biotech regulatory policies of the Environmental Protection Agency (EPA) are the most egregious and arbitrary of all. In early September, EPA published regulations for biotech biocontrol agents. Inexplicably, EPA targets only products made with the most precise and predictable new genetic methodologies, as opposed to products made with older, cruder techniques of genetic manipulation (which, in fact, are more likely to exhibit unexpected traits). The agency also plans to expand its regulatory dominion to a whole new category of products--plants that are made resistant to pests by using the new genetic techniques. These garden and farm plants will be regulated even more stringently than chemicals similar to DDT or parathion. Yet plant breeders have been creating and farmers using genetically improved plant varieties--many with genes moved across species or genus lines--safely for more than a century without government regulation. These rules make neither scientific nor economic sense. USDA, FDA, and EPA regulatory approaches fly in the face of a broad scientific consensus that the new biotechnology is an extension, or refinement, of earlier techniques of genetic manipulation that often have been subject to no regulation at all. Their regulatory policies constitute, in effect, a tax on innovation that uses the new biotechnology. Ineluctably, these anti-innovative policies will discourage research using the newer, more precise techniques, denying consumers more varied and nutritious produce grown with fewer chemicals. Gore's Antagonism One might well wonder about the etiology of such actions by those who extol the importance of technology. The vice president's long-held antagonistic attitudes provide a clue. In a 1991 article in the Harvard Journal of Law and Technology (5:19-30, Fall 1991), Al Gore displayed remarkable lack of appreciation of the historically positive linkage between science and economic development when he disdainfully described investors' eager reception of South San Francisco, Calif.-based Genentech Inc.'s 1980 stock offering as the first sellout of the "tree of knowledge to Wall Street." He went on to deride biotechnology research, claiming that "the decisions to develop ice-minus [bacteria], herbicide-resistant plants, and bovine growth hormone . . . lent credibility to those who argued that biotechnology would make things worse before it made things better" [emphasis added]. Moreover, in Gore's Earth in the Balance (New York, Houghton Mifflin, 1992), he uses repeatedly the metaphor that those who believe in technological progress are as sinister as the perpetrators of World War II's Holocaust. These views from the government's technology czar are difficult to reconcile with the recent, upbeat verbiage in the administration's report. Whole emerging industrial sectors--bioremediation, agbiotech, food production, even biopharmaceuticals--have been damaged by regulatory or other disincentives. The bitter irony in the administration's policies is that, under the guise of concern for safety, they have undermined research on precisely the kinds of low-value-added but societally important products--safer and more nutritious foods, improved bioremediation agents, alternatives to chemical pesticides and fertilizers, and other environmentally friendly innovations--that should have universal appeal. The administration's record on biotechnology, including the technology's most environmentally friendly manifestations, has made a shambles of a success story. The new, rosy rhetoric cannot remedy that. Henry I. Miller is the Robert Wesson Fellow of Scientific Philosophy and Public Policy at the Hoover Institution and a consulting professor at Stanford University's Institute for International Studies in California. (The Scientist, Vol:8, #23, p.12, November 28, 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 :BASIC SCIENCE IS 'STRATEGIC' FOR THE FUTURE OF THE U.S. AU : Zachary Burton TY : OPINION (COMMENTARY) PG : 13 Basic science is in the national interest and is "strategic" for the future of the United States. In addition to being very inexpensive for the services we provide, scientists contribute a tremendous amount to our culture and communities--a fact that is not appropriately recognized by Congress or the public. As a member of an apparently dispensable generation of scientists, I would like to express my views about congressional micromanagement of national science policy. My field is basic biomedical research. In this area, the U.S. is committing less than half the funds and is funding fewer than half the grant proposals that are minimally required for healthy functioning of the enterprise. The problem for scientists who cannot obtain reasonable or consistent funding for excellent research is acute. It extends to our students, who realize that they must be more talented and creative than the people who are training them to survive in this field in the future. The most competitive study sections at the National Institutes of Health and the National Science Foundation have been funding about 10 percent of worthwhile proposals for the last several years. With the lid screwed down so tightly on funding, we are wasting much of the productivity of this generation of scientists. We are also harming the next generation, since they must know that they will have to be among the top 5 percent to 10 percent of their colleagues to be funded in the future. I do not believe I would have taken an academic position if I had known the federal government would let science slip into this deep recession. A primary casualty of federal neglect of science has been education. Research and teaching are natural complements because involvement in research allows us to teach newer and more sophisticated material. This makes education more relevant and applicable when students graduate into the work force. Ironically, however, I must now spend about half my time writing grant proposals, and thus have less time to devote to teaching. My students' vision of what they can become is marred by the travails of their teacher. I do basic research on the functions of proteins that bind to RNA polymerase II in the human and yeast systems. From my point of view, understanding mRNA synthesis is fundamental to understanding cancer and viral infection. I expect that within five to 50 years, information accumulated about the mechanism and regulation of transcription will contribute to curing a significant number of now-fatal human diseases. In this endeavor, applied science is not as practical as basic research at this time. Yet currently, my re-search enterprise is not so much driven by the thrill of discovery as it is by the hope of survival in a desperately competitive field. The idea of scientists correcting this problem by redirecting basic research to make it more "strategic" is laughable, as we are already doing what we can to advance important goals of society. Industry is also dependent on basic scientists. I train people who take jobs in the biotechnology industry. I also have interactions with several biotechnology companies as a consultant and manufacturer of a product. Industry cannot afford to do basic research as we can do it in aca-demia. Personnel cost too much in the private sector, and the free flow of ideas in academic institutions rarely can be duplicated in industry. In supporting academic science, society gains big dividends in biotechnology and medical science for a relatively small federal investment. Congressional leaders contend that they are unable to provide additional money for basic research, although it is unclear to me why this should be so. Basic research is a very important and practical investment that must be made by the federal government, since no one else can do it adequately. Without additional funds, scientists must spill each other's blood to make more money available for basic research. In the absence of increased investment, I suggest the following Draconian measures: (1) Cap overhead on federal grants at 35 percent; (2) cap federal grant awards at $150,000 per year in direct costs; (3) make the NIH intramural program subject to competitive, external peer review; (4) end program project grants, except for research facilities that require shared use of expensive, specialized instruments; (5) end federal targeting of research dollars; (6) end "pork barrel" funding of research; and (7) end federal funding for short-term applied research. These measures have serious consequences, but they could be applied to stop the hemorrhaging of the basic research enterprise. Zachary Burton is an associate professor of biochemistry at Michigan State University, East Lansing. E-mail: (The Scientist, Vol:8, #23, p.13, November 28, 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 : HHMI At Yale AU : GERARD N. BURROW TY : OPINION (LETTERS) PG : 13 We write concerning what we believe are misrepresentations of Howard Hughes Medical Institute (HHMI) policies that operate at the Yale School of Medicine, as expressed in the article by Karen Young Kreeger (The Scientist, Oct. 3, 1994, page 3). Statements in the article incorrectly imply that HHMI investigators and their facilities are separate from the rest of the school and that their equipment is inaccessible to others. HHMI investigators occupy space in different buildings throughout the school, including two floors of a newly constructed, four-floor research building, called the Boyer Center for Molecular Medicine, which was opened in 1990. Their laboratories are indistinguishable from those of other Yale faculty in the building, and their equipment, purchased with HHMI funds, is as accessible to other Yale faculty and students as any in the school. Because HHMI investigators rely heavily on a set of core laboratories supplying peptides and oligonucleotides and amino acid sequencing services, HHMI contributes to the support of technicians who operate these facilities, which are, of course, open to all investigators. This is just one example of many ways in which HHMI's support benefits the entire Yale community. Gerard N. Burrow Dean Yale School of Medicine Vincent T. Marchesi Director, Boyer Center for Molecular Medicine Yale University New Haven, Conn. 06520 (The Scientist, Vol:8, #23, p.13, November 28, 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 : Alternative Perspectives AU : RODNEY GRANT SEMCHUK TY : OPINION (LETTERS) PG : 13 The views expressed by Graeme Fricke (Letters, The Scientist, June 27, 1994, page 13) regarding the integration of alternative medical approaches with conventional biomedical treatments appear reasonable, relative to evaluating treatment efficacy and safety. Where I find these views wanting is in perspective. Open-minded intellectual curiosity is required to realize that the broadest possible perspective will yield the best data for analysis, and lead to greater understanding of a particular subject. This approach to scientific investigation describes an unbiased, open perspective, and indicates respect for the intellectual integrity of those with different viewpoints. A predetermined or biased approach inhibits the development of broader knowledge. Bias is unintentional in most instances, and most often arises from too narrow a perspective, rather than from some self-serving motivation. Therefore, I would ask what Graeme Fricke's perspective is when using terms such as "mainstream," "so-called medical professionals," "real medicine," and "purveyors." What are the implied attitudes and apparent judgments regarding alternative medicine? I ask this so as not to misconstrue his interest in the development of a more informed knowledge base. If profit is being implied or denigrated, who would not acknowledge that the profit motive is hardly absent among many "purveyors" of conventional biomedical approaches to health care; but no call is made for the world to do without the benefits of conventional medicine based on this fact. As a research immunologist, I, along with many other scientists and clinicians, value the common ground found among all medical approaches, including conventional medicine. All input is welcome in developing a greater synthesis of knowledge for the benefit of all. We presume that everyone involved is striving to improve therapy. The fulfillment of potential in all areas and on all levels demands integration of knowledge; this can be achieved only through interdependence. Let us contribute to a greater realization of all potential, through open minds and mutual support. Rodney Grant Semchuk The Argus Group 245 W. 25th St. New York, N.Y. 10001 E-mail: (The Scientist, Vol:8, #23, p.1, November 28, 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 : THE LEADERS OF SCIENCE THE READERS OF THE SCIENTIST PG : 14 DONALD P. FRANCIS Clinical Researcher Genentech Inc. South San Francisco, CA. "THE SCIENTIST covers important research breakthroughs and summarizes key information in a way that all of use with demanding schedules can absorb quickly." While serving with the World Health Organization, Geneva, Donald Francis was involved in eradicating smallpox from Sudan, India, and Bangladesh in the early 1970s. He comments: "I can walk in India now and not see the scarred faces and blind eyes. Completely eliminating smallpox was an historic public health accomplishment made possible by the efforts of people working together, despite very difficult conditions and poor communications." One of the first scientists to suggest that AIDS is caused by an infectious agent, Francis directed the Centers for Disease Control and Prevention's (CDC) AIDS laboratory in Atlanta. His team worked closely with the Institut Pasteur, Paris, to demonstrate HIV's involvement in AIDS. Recognizing early on the devastating impact that HIV would have on the U.S., he has been a tireless advocate for a federal government response to AIDS that equals the urgency of the epidemic. During his 20 years with CDC, Francis's continuing goal was to cure and prevent infectious disease and promote public health. "When that effort succeeds, as with smallpox, it is incredibly rewarding. But when progress is slow, as it is today with AIDS, it can be incredibly frustrating," he observes. Drawing on his long research experience with AIDS and vaccines, Francis is currently developing an HIV vaccine. Looking forward to success in this effort, he is also founding an organization to establish a global HIV vaccination program. Working at the frontiers of biomedical research, Francis feels a need for information from many different fields. THE SCIENTIST helps to meet that need. He states: "THE SCIENTIST covers important research breakthroughs and summarizes key information in a way that all of us with demanding schedules can quickly absorb." (The Scientist, Vol:8, #23, p.14, November 28, 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: RESEARCH ------------------------------------------------------------ TI : Oceanic Plants Are At The Root Of Ecology's Most-Cited Studies TY : RESEARCH PG : 15 Editor's Note: A little more than a year ago, the newsletter Science Watch, published by the Philadelphia-based Institute for Scientific Information (ISI), began conducting analyses of the citation record of ecology and environmental sciences on a regular basis (The Scientist, Feb. 7, 1994, page 15). Since then, the newsletter has found that citation leaders in this burgeoning area come from a wide array of disciplines, including plant science, oceanography, bioremediation and pollution ecology, conservation biology, statistics, and animal behavior. It is interesting to note that, in a recent analysis--using ISI's Science Indicators Database--half of the 10 most-cited papers from 1991-92 were from the field of biological oceanography. Following is the June 1994 Science Watch report, written by Peter D. Moore, a reader in ecology and chairman of human and environmental sciences in the Division of Life Sciences, King's College, London. The report--with an update on the number of citations each of the 10 papers has garnered through September 1994--is presented here with the permission of Science Watch and ISI. The swing of this survey of ecological and environmental citations is distinctly toward the ocean. Papers published during 1991-92 and cited through 1992 show a very strong marine influence, with five of the top 10 having a phytoplankton focus. (Note, however, that Nos. 3 and 10, although bearing 1990 publication dates, did not enter ISI's database until 1991.) The main questions being asked center on the productivity and nutrient cycling of plankton and the ways in which these processes might affect global atmospheric carbon budgets. Two of the papers on phytoplankton productivity (Nos. 1 and 7) report results derived from the Research on the Antarctic Coastal Ecosystem Rates (RACER) program and show that the high productivity one often associates with Antarctic waters is mainly confined to the Antarctic Peninsula coastal zone, other areas being of generally low productivity. The Bransfield Strait, studied by O. Holm-Hansen and B.G. Mitchell (Paper No. 1), lies off the northern tip of the Antarctic Peninsula, and here the greatest phytoplankton biomass was found, especially during the bloom months of December and January. An understanding of what limits the productivity of these waters and controls the blooms is obviously of interest not only to oceanographers, but also to the fishing industry and even to climatologists who still look wistfully to the phytoplankton as a possibly influential carbon sink. But the RACER program, perhaps not surprisingly, fails to come up with a simple answer. Nutrient limitations are not favored as an explanation either of the bloom decline or the low productivity of many Antarctic areas. Temperature may be involved, but the case is unproven. Light may be important, but the bloom declines faster than the light intensities as the Antarctic summer fades. So the answer may lie in the grazing intensity of the zooplankton, which can account for more than 50 percent of the productivity in a season. The significance of grazing is also apparent in the nitrogen cycle of the oceanic surface layers, as shown by the work of P.A. Wheeler and S.A. Kokkinakis in the subarctic Pacific. Here they showed that nitrate (NO3-) ions were between 15 and 40 times more abundant than ammonium (NH4+) ions. This does not appear to be due to efficient microbial nitrification (the oxidation of NH4+ to NO3-), but rather to the preferential uptake of NH4+ by phytoplankton, followed by grazing and then excretion (or decomposition to) ammon-ium ions. These ions are quickly sequestered once more by the next generation of phytoplankton. The cycle virtually bypasses the nitrate ion. Iron Fertilization Fantasy This movement of opinion away from nutrient, or even trace-element, limitation of phytoplankton productivity takes the dream of iron fertilization of the oceans to create an unlimited carbon sink even further into the realms of science fantasy. Two other papers (Nos. 2 and 6) in the top 10 also assist in this process. W.G. Sunda and associates (Paper No. 6) use an experimental approach to examine the iron requirements of different diatom species, one of which--Thallassiosira oceanica--is an open-ocean species and the other--T. pseudonana--an estuarine type. The oceanic species achieved maximum growth at two moles of iron per mole of carbon, while the estuarine species required four times this amount of iron for maximum growth. The early proposals by J.H. Martin and his colleagues (Science Watch, 5[2]:7-8, February 1994) concerning iron limitations were based on the assumption that higher concentrations were optimal for phytoplankton growth. But this may not prove appropriate for open-ocean conditions. Yet one more ferric nail is driven into the coffin of the fertilization/carbon-sink theory by T.-H. Peng and W.S. Broecker (Paper No. 2), who have modeled the atmosphere/ocean carbon flux on the assumption that the iron-limitation hypothesis is correct. They found that the drawdown of carbon from the atmosphere becomes limited by the slow process of vertical mixing within the water. They calculate that in 100 years the atmospheric load of carbon dioxide could be reduced by 10 percent q 5 percent, as a result of enhancing phytoplankton productivity. So, even if the iron limitation proposal is correct (which we have reason to believe is not the case), the impact of mass oceanic fertilization with soluble iron would have little impact on the greenhouse effect. For The Landlubber Moving to somewhat drier realms, but sticking with the effects of elevated atmospheric carbon dioxide, R.B. Thomas and B.R. Strain (Paper No. 4) have examined the idea that plant life will grow better in a high-carbon-dioxide world. In general, plants are often limited in their productivity by the availability of carbon dioxide, but these two researchers find that if root growth is restricted, the plant does not respond to increased carbon dioxide. They term this observation "sink-limited feedback inhibition," which basically means that if the plant cannot grow adequately it shuts down its carbon dioxide acquisition, even though gas may be present in higher-than-normal concentrations. It is conceivable that this effect could result in a greenhouse world, especially if root competition were severe. Biotechnology is effectively becoming synonymous with microbial domestication. Two of the highly cited papers on the list (Nos. 5 and 9) indicate the potential value of our bacterial neighbors in cleaning up some of the mess we regularly make of the planet. Both relate to the ability of certain free-living denitrifying bacteria to degrade such toxic molecules as benzene, toluene, and xylene that can con-taminate soils and aquifers as a result of gasoline spills. Denitrifying bacteria operate in anoxic conditions, in which they use nitrate ions rather than oxygen in the respiratory breakdown of organic molecules. These conditions provide bacteria with energy and result in the release of nitrogen gas along with carbon dioxide. P.J. Evans, D.T. Mang, and L.Y. Young (Paper No. 9) have found that a very wide range of soils, sediments, effluents, and sludges contain de-nitrifying bacteria that are able to use toluene, some types of xylene, and benzene as substrates; these bacteria also can completely degrade toluene in culture within three months. S.R. Hutchins and colleagues (Paper No. 5) have conducted similar experiments using cultures from aquifers, and they also conclude that denitrifying bacteria can degrade such aromatic hydrocarbons as toluene. They, however, express caution about the value of such bacteria as cleaning agents because mixtures of aromatic molecules--as found in jet fuels, for example--may lower biodegradation rates overall, owing to the inhibitory influence of some of the mixture's components on denitrification. (The Scientist, Vol:8, #23, p.15, November 28, 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 : WHAT'S HOT IN ECOLOGY AND ENVIRONMENTAL SCIENCES TY : RESEARCH PG : 15 Rank (Through 1992) Paper Citations Through 1/93- 1992 9/94 1 O. Holm-Hansen, B.G. Mitchell, "Spatial 26 16 temporal distribution of phytoplankton and primary production in the western Bransfield Strait region," Deep-Sea Research, 38:961-80, 1991. 2 T.-H. Peng, W.S. Broecker, "Dynamic 21 9 limitations on the Antarctic iron fertilization strategy," Nature, 349:227-9, 1991. 3 P.A. Wheeler, S.A. Kokkinakis, "Ammonium 21 19 recycling limits nitrate use in the oceanic subarctic Pacific," Limnology and Oceanography,35:1267-78, 1990. 4 R.B. Thomas, B.R. Strain, "Root 20 45 restriction as a factor in photosynthetic acclimation of cotton seedlings grown in elevated carbon dioxide," Plant Physiology, 96:627-34, 1991. 5 S.R. Hutchins, G.W. Sewell, D.A. Kovacs, 20 19 G.A. Smith, "Biodegradation of aromatic hydrocarbons by aquifer microorganisms under denitrifying conditions," Environmental Science & Technology, 25:68-76, 1991. 6 W.G. Sunda, D.G. Swift, S.A. Huntsman, 19 13 "Low iron requirement for growth in oceanic phytoplankton," Nature, 351:55-7, 1991. 7 M. Huntley, D.M. Karl, P. Niiler, 17 1 O. Holm-Hansen "Research on Antarctic Coastal Ecosystem Rates (RACER): An interdisciplinary field experiment," Deep-Sea Research, 38:911-41, 1991. 8 M. Raymond, A. Callaghan, P. Fort, N. 17 29 Pasteur "Worldwide migration of amplified insecticide resistance genes in mosquitoes," Nature, 350:151-3, 1991. 9 P.J. Evans, D.T. Mang, L.Y. Young, 17 10 "Degradation of toluene and m-xylene and transformation of o-xylene by denitrifying enrichment cultures," Applied and Environmental Microbiology, 57:450-4, 1991. 10 L.M. Smith, T.R. Schwartz, K. Feltz, 17 42 T.J. Kubiak,"Determination and occurrence of AHH-active polychlorinated biphenyls, 2,3,7,8- tetrachloro-p-dioxin and 2,3,7,8- tetrachlorodibenzofuran in Lake Michigan sediment and biota: the question of their relative toxicological significance," Chemosphere, 21:1063-85, 1990. Source: ISI's Science Indicators Database, 1991-94 (The Scientist, Vol:8, #23, p.15, November 28, 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 : STRUCTURAL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 I. Rayment, W.R. Rypniew-ski, K. Schmidt-Base, R. Smith, D.R. Tomchick, M.M. Benning, D.A. Winkelmann, G. Wesenberg, H.M. Holden, "Three-dimensional structure of myosin subfragment-1: A molecular motor," Science, 261:50-8, 1993. (Total citations through October 1994: 107) I. Rayment, H.M. Holden, M. Whittaker, C.B. Yohn, M. Lorenz. K.C. Holmes, R.A. Milligan, "Structure of the actin-myosin complex and its implications for muscle contraction," Science, 261:58-65, 1993. (Total citations through October 1994: 76) In the first of this pair of papers, Ivan Rayment, Hazel Holden, and their colleagues at the University of Wisconsin's Institute for Enzyme Research in Madison describe the structure of the muscle protein myosin. The reason this paper is so important to many other researchers, says Rayment, is that the "three-dimensional structure [of myosin] gives a molecular framework that is essential for understanding how [the molecule] works. "There is an enormous interest in the way that muscles contract and a vast amount of literature on this subject. In this paper we have actually described the three-dimensional configuration of the motor domain of the protein." Perhaps one of the most intriguing problems in fundamental biology is the structural basis of energy transformation in living systems (N. Sankaran, The Scientist, Sept. 5, 1994, page 14), a point that is addressed in the second paper, with specific reference to muscles, where chemical energy in molecules like adenosine triphosphate (ATP) is converted to movement. "In this paper we have proposed a hypothesis of how the muscle proteins accomplish the task of converting chemical energy into motive energy," explains Rayment. This paper and its hypothesis are the result of an international collaboration involving the laboratories of K. Holmes at the Max-Planck Institute in Heidelberg, Germany, and R. Milligan at the Scripps Research Institute, in La Jolla, Calif., in addition to the Wisconsin group. "The [myosin] protein hydrolyzes ATP to ADP [adenosine diphosphate] and an inorganic phosphate, and releases chemical energy, so as to be able to do work," says Rayment. "But in order to do work you need something to work against, and that something is actin. The ATP is hydrolyzed before any work is done; the released energy is first stored in myosin and subsequently used to move myosin past actin. "One of the questions we had was how the actin-binding site and ATP-binding site, which are quite far apart on the myosin molecule, communicate with each other." Based on the structures of the muscle proteins detailed in both papers, as well as new electron microscopic and X-ray diffraction data from Holmes and Milligan, Rayment believes this molecular communication occurs through the rearrangement of a series of domains in myosin. The next step the group will take, he reports, is to "test the hypothesis by proving the occurrence of the suggested structural changes by X-ray crystallographic studies on myosin in the presence of ATP." One reason Rayment offers to explain the high number of citations to his articles is that both the data and hypothesis presented in the papers "influence the way people think about the molecular basis of motility. All of the [current] work on muscle proteins and motility will benefit from our information. The structure of the motor domain is already finding its way into standard biochemistry textbooks. "These papers tie together everything we already knew about myosin biochemistry--it is a capstone on the field and a tribute to the rest of biochemistry." (The Scientist, Vol:8, #23, p.16, November 28, 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 : CELL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 M.B. Kastan, Q. Zhan, W.S. El-Diery, F. Carrier, T. Jacks, W.V. Walsh, B.S. Plunkett, B. Vogelstein, A.J. Fornace, Jr., "A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia," Cell, 71:587-97, 1992. (Total citations through October 1994: 246) This paper is one of a number of publications from the laboratory of Michael Kastan at the Johns Hopkins Oncology Center in Baltimore that describe various steps of a signal-transduction pathway in mammalian cells. It follows up an earlier paper by Kastan's group (M.B. Kastan et al., Cancer Research, 51:6304-11, 1991) that was also identified by The Scientist as a "hot paper" (Sept. 20, 1993, page 16). "We had previously demonstrated that the p53 gene product--the most commonly mutated gene in human cancer--controls cell-cycle arrest in response to damage," says Kastan. In this paper the authors have identified two new participants in the damage-response pathway, using cells from patients with ataxia-telangiectasia [AT], a disease characterized by hypersensitivity to radiation and high susceptibility to cancer. "In normal cells, when DNA is damaged by ionizing radiation, the p53 protein levels rise rapidly and arrest the cell cycle," explains Kastan. When the cell cycle is not arrested, cells continue to replicate, which, in the face of damaged DNA, could ultimately contribute to the development of tumors. The investigators found that in AT cells the levels of p53 following radiation were abnormally low, thus indicating an additional factor--the AT gene--in the pathway. "While previously it was not known when the cell used p53 to halt the cell cycle, our data showed that p53 acted in response to the damaged DNA," reports Kastan. The reason the results are exciting, he suggests, is that they demonstrated one mechanism by which cells could be set up for the onset of cancer, such as in a condition like AT, in which patients are also known to be highly prone to cancer. The article also reports another participant in the damage-response signal-transduction pathway called the GADD45 gene, whose induction is dependent upon p53. Though the exact function of GADD45 is not yet known, Kastan notes that accumulating data point to its role in DNA repair, replication, and possibly even apoptosis (M. Smith et al., Science, in press). Since the publication of this paper, observes Kastan, other investigators have shown that p53 is involved "not only in cell-cycle arrest, but in apoptosis or programmed cell death as well. [S. Lowe et al., Nature, 362:847-49, 1993; A.R. Clarke et al., Nature, 362:849-52, 1993]. This means that the p53 pathway is important in determining the fate of the cell following DNA damage." This finding, he adds, has implications for understanding tumorigenesis as well as for improving the outcome of cancer therapy. "The major focus for the future," he adds, "would be to find out all the participants in the pathway. We can then determine what causes a cell to arrest its growth or alternatively commit suicide and investigate ways to induce one response over the other." (The Scientist, Vol:8, #23, p.16, November 28, 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 : EPIDEMIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 M.J. Alter, H.S. Margolis,K. Krawczynski, F.N. Judson, A. Mares, W.J. Alexander, P.Y. Hu, J.K. Miller, M.A. Gerber, R.E. Sampliner, E.L. Meeks, M.J. Beach, "The natural history of community acquired hepatitis-C in the United States," New England Journal of Medicine, 327:1899-1905, 1992. (Total citations through October 1994: 76) This paper reports the results of a study tracking the onset and course of hepatitis C virus (HCV) infection in patients over a four- to six-year period. "We looked at the natural history of the disease--namely what happens over time with respect to infection and clinical symptoms," says Miriam Alter, chief of the epidemiology section of the hepatitis branch at the Centers for Disease Control and Prevention (CDC) in Atlanta. "We found that 62 percent of the patients developed chronic hepatitis and that all of them remained persistently infected even in the absence of liver disease or inflammation." >From an epidemiological perspective, this study proved significant, Alter explains, since "it showed that the majority of cases did not contract the disease from transfusions, which are believed to be the most common mode of spread. Most people get it [HCV] as a result of community-based exposure--sharing contaminated needles, for instance, or from having multiple sexual partners." Another reason Alter offers for the high number of references to this study is that "it has been the only follow-up study of community-acquired HCV, and it showed the extremely high rate of persistent infections." The studies indicate that HCV may be one of the major causes of chronic liver disease in the United States. CDC is continuing to follow up on the original patients to further track the course of the infection. Determining the natural history of HCV infection will be important in developing therapeutic and prevention strategies, according to Alter. (The Scientist, Vol:8, #23, p.16, November 28, 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 : Blotting Technology's Permanence Is Assured As Its Applications In The Laboratory Flourish AU : HOLLY AHERN TY : TOOLS & TECHNOLOGY PG : 17 Nearly everyone within earshot of a television or radio has become familiar with the molecular biology term "Southern blotting," thanks to the publicity attached to some highly publicized forensic cases such as the O.J. Simpson murder trial. Southern blotting is the technique that may ultimately determine Simpson's fate, by matching--or not matching--his genetic profile obtained through DNA fingerprinting with the DNA pattern derived from blood found at the scene of the murder of his wife, Nicole, and at his Brentwood, Calif., home. In Southern blotting, DNA fragments separated by gel electrophoresis are transferred to a support membrane made of nitrocellulose, nylon, or some other type of support material. The process is named after the technique's inventor, biochemist Edward M. Southern, Oxford University, England. The paper describing this technique (E. M. Southern, Journal of Molecular Biology, 98:503, 1975) has been explicitly cited more than 25,000 times, according to the Institute for Scientific Information in Philadelphia. Northern blots (the transfer of RNA molecules from a gel to a membrane) and Western blots (the transfer of proteins) were later developments. Once blotted to a membrane, the bound macromolecules can be analyzed in numerous ways--probed with labeled oligonucleotides to detect specific genes for example, or treated with antibodies to identify a single protein in a cellular extract from among several hundred. All three of these techniques quickly became workhorses in the molecular-biology laboratory and for several other life-sciences disciplines, such as developmental biology and evolution. "These types of techniques have basically reached commodity status," explains Keld Sorensen, senior research scientist at Pierce Chemical Corp. in Rockford, Ill. "Blots are generally no longer the focus of a scientist's research, but they are often the essential tools that allow researchers to get on with their studies." Molecular biologists rely on Southern blots in conjunction with Westerns and Northerns to aid in cloning genes and characterizing the gene products. Cell biologists and organismal scientists use blotting assays to study signal transduction or gene expression, for example, or to analyze the events that occur during development. Evolutionary biologists perform Southern blots to study the evolution of conserved genes. "Assays involving blotting are protected by history," comments George Dearden, a technical specialist with Schleicher and Schuell Inc., a company specializing in blotting membranes and equipment in Keene, N.H. "To get results published, you have to show the standard Southern and Northern blot results and prove that the assays are sensitive and repeatable." The scientific concepts governing all of the various forms of blotting are essentially the same, with only the starting material--DNA, RNA, or proteins--as the major difference. The macromolecules separated in a gel or colonies growing on culture media in a petri dish are placed in contact with a suitable support material along with vast quantities of buffer. Capillary action causes the buffer to flow through the gel toward the solid support. The macromolecules in the gel are transported along with the buffer to the support membrane where they bind, producing an exact replica of the gel or petri plate on the membrane. Using a labeled probe, researchers can detect their target and localize it to specific colonies on the plate medium, for instance, or to a specific molecular weight on the original gel. Southern, Western, and Northern blots are all performed in the same general way. In its original and still widely used form, blotting is achieved via capillary transfer. Gels are overlaid with the support membrane and then topped by huge stacks of paper towels or some other absorbent material. The stacks are crowned with a weighted object, usually the lab's largest and heaviest molecular biology handbook, and left overnight. Buffer from below wicks upward through the gel and the membrane, toward the absorbent paper towels above. Variations on this standard theme began to evolve shortly after blotting techniques were developed. Although capillary transfers, which require very little in the way of equipment, remain popular, additions and improvements to the standard blot are gaining ground with researchers who want to decrease the time required to complete an experiment by speeding the movement of macromolecules out of the gel and onto the membrane. Systems for vacuum blotting--in which vacuum pressure literally sucks the macromolecules out of the gel--and electroblotting equipment that operate on a principle similar to electrophoresis are available from a number of companies that specialize in electrophoresis, such as Bio-Rad Laboratories, based in Hercules, Calif., along with companies that supply life-sciences research tools, like Life Technologies of Gaithersburg, Md., and Stratagene Inc. of La Jolla, Calif. New designs based on the standard capillary-transfer technique also increase the efficiency of the method. The Turbo Blotter from Schleicher and Schuell, for example, is a capillary blot system in which blots proceed downward with gravity rather than upward. "The downward blot is a more natural progression of events and the nucleic acids move out of the gel quickly," says Judith Peter, marketing manager at Schleicher and Schuell. "Transferring DNA or protein to a support membrane is absolutely essential, because most applications such as nucleic acid hybridization cannot be carried out in gels," says Richard P. Cunningham, a professor of biology at the State University of New York, Albany. "Hybridization reactions in solution have been performed, but the results lack context. With a blot, the hard-copy results can be analyzed spatially in terms of molecular weight or relative position." "There will be a place for blotting membranes in research laboratories for the foreseeable future," agrees Michael Mansfield, a consulting scientist with Millipore Corp. in Bedford, Mass., which specializes in filtration and separation technologies. "Blotting allows researchers to conduct studies that simply can't be done any other way." DNA Fingerprinting One area of blotting that is attracting the attention of numerous scientists in clinical and forensic laboratories as well as in molecular biology labs is RFLP (restriction fragment length polymorphism) analysis. Known also by its more common designations of genetic or DNA fingerprinting, this application has advanced Southern blotting beyond the research lab and into new areas of forensic science and diagnostic testing. "There were inklings that Southerns were on their way out because of the development of new procedures along the lines of PCR that would enhance researchers' abilities to perform DNA analysis without first blotting to a membrane," says Mansfield. "However, the standard RFLP procedures currently in use are the most deeply entrenched right now from a legal standpoint. As other techniques develop they will have to go through the same sort of scrutiny before gaining widespread acceptance within the legal community." To produce a DNA fingerprint, DNA from a sample of blood or a forensic specimen is extracted and treated with a restriction enzyme, which cuts the genomic DNA derived from the cells in the specimen into millions of small fragments. The fragments are separated by gel electrophoresis, and then Southern-blotted to a support membrane. After the bound DNA is denatured by alkaline treatment, a labeled probe is added to the blot. The probe may be specific for regions in the DNA that occur frequently (multi-locus probes) or for sequences found singularly within specific genes (single-locus probes). The bands that appear following the detection steps are compared. Matches in the band patterns indicate that samples came from the same source. A DNA fingerprint made from a tissue sample left at the scene of a crime can identify the perpetrator with virtual certainty. Forensic scientists are not the only group benefiting from the use of Southern blots in genetic fingerprinting. Scientists can study the evolution of genes across species and ecologists can study the parentage of animals in selected niches using RFLP applications. Human geneticists use RFLPs to track diseases through families, with the potential for identifying sequences that can be used as genetic-disease markers. Add these to the large numbers of researchers currently involved in the Human Genome Project and you find lots of individuals interested in the Southern blot. Gene mappers who are sorting through the millions of nucleotide bases that make up the 23 pairs of human chromosomes are developing technologies aimed at speeding up and miniaturizing the DNA-sequencing process. DNA sequence data are already available for a sizable portion of the human genome. "Ultimately, however, all of the data obtained from sequencing will have to be related back to what's really going on in the tissues," Mansfield says. "And that will probably be accomplished using standard Southern blot technology." Developers and users of Western blot technology maintain that it, too, is here to stay. One area in particular that is keeping this market moving forward comes as an outgrowth of work done with HIV. "With HIV, suddenly there was a disease that was approachable only by Western blot," for mass screening purposes, according to Mansfield. "With that model out there, it seems likely that other diagnostic applications will be taking off in the near future." Mansfield notes the appearance of a Western blot screening test within weeks of the recent hantavirus outbreak in the Southwest (K.Y. Kreeger, The Scientist, July 11, 1994, page 14; July 25, 1994, page 15). "The real hurdle now appears to be improving the technology to make it applicable to viral outbreaks in Third World countries, where the worst diseases continue to prevail," he adds. In these and most types of Western blot assays, looking for a single protein in an extract of cells can be likened to a search for a needle in a haystack. Just as employing a magnet in the needle search would quickly localize the needle, using a specific antibody expedites the search for a target protein on a Western blot. Companies such as Pierce Chemical, Upstate Biotechnology Inc. in Saranac Lake, N.Y., and St. Louis-based Sigma Chemical Co. provide antibodies as well as the reagents required to detect antibody binding to scientists in search of a protein. Enzyme-antibody conjugates bearing an isotopic or enzymatic tag, buffers and blocking reagents, and detection systems for visualizing the antibody-bound target are available alone or together in kit form, depending on a user's individual preferences. "Researchers are asking more of manufacturers in terms of higher-quality biochemicals, such as cleaner enzyme-antibody conjugates and better-defined reagents," says Pierce Chemical's Sorensen. "They are also relying more on provided protocols. Rather than working up their own Western blot systems, the trend is toward purchasing kits that supply the reagents along with a protocol in a system that is guaranteed to work." One of the most commonly used applications of Western blotting is immunodetection of a target protein using a labeled antibody. Although there are other methods, such as ELISA (enzyme-linked immunosorbent assay) and immunoprecipitation, that can provide essential information about the presence of a protein in a mixed sample, these procedures lack a feature that many researchers find important. "A Western blot of electrophoretically separated proteins provides spatial resolution that no other method provides," says Sorensen of Pierce Chemicals. "A major reason for performing a Western blot analysis of a cell extract is to first confirm the presence of a protein and then characterize it by molecular weight," SUNY-Albany's Cunningham adds. Sequencing proteins by mass spectroscopy is a recent addition to the Western blot's repertoire of applications. Performing protein analysis by mass spectroscopy is a procedure that requires equipment that is not found in most laboratories because of the expense. Although scientists interested in protein chemistry may not have access to a mass spectrometer, they are likely to have standard blotting equipment available in their labs. "Once the proteins are blotted, the membrane can be transported to someone with a mass spectrometer who can perform the mass analysis," says Mansfield. "This looks like the wave of the future for protein sequencing." Hot Or Not? As in many other areas of science, blotting technology is moving away from radioactivity. "The trend away from radioactivity is nearly universal," says Sorensen. "Blotting is an area where it has been shown that you can get the same sensitivity without the use of radioactivity." For Southern and Western blot techniques, nonisotopic labeling and detection systems based on chromogenic or chemiluminescent substrates are widely available from suppliers like Boehringer Mannheim Biochemicals of Indianapolis, Madison, Wis.-based Promega Corp., Bio-Rad, Pierce, and many others. Labeling systems for RNA, such as Life Technologies' Nonradioactive RNA Labeling system used in conjunction with their BluGene or PhotoGene detection system, are emerging. Nonisotopic detection systems for Southern and Western blots are in many cases easier to use than isotope-based systems, and they virtually eliminate the complications associated with the disposal of radioactive waste. Sensitivity with nonisotopic detection systems is reportedly as good as the sensitivity achieved with radioisotopes. The backbone of the blot is the support membrane that holds the transferred molecules. Membranes made of nitrocellulose, nylon, polyvinylodine fluoride (PVDF), and even copier paper have occupied different niches within the blotting world. Membrane suppliers such as Scheicher and Schuell and Millipore generally have a selection of membranes available to meet the preferences of individual users whose choice of membrane hinges on the application. For proteins, nitrocellulose appears to be the membrane of choice for blotting because proteins are inherently attracted to the polymer and remain permanently attached. For nucleic acids, which carry a negative charge, PVDF and nylon membranes are more widely used. "There are a lot of different types of membranes available," says Sorensen. "Researchers may try one and find that it works in their application. If they like it, they stick with it." Developing new polymers or chemically treating old ones in new ways are areas under consideration within the blotting membrane industry. "As more polymer chemistries are searched out where the interactions between the biomolecule and the membrane are more than simply an affinity, it should be possible to do things that we could not have been done in membranes in the past," Mansfield observes. An example is studies of small molecules and peptides. These small substances do not stick well to the supports currently available. Changing the qualities of membranes to allow these molecules to attach more securely will open the door to a host of new research applications. According to the manufacturers and users of blotting equipment, there is no reason to view blotting membranes as simply an inert support to which proteins or DNA can be applied. In newer procedures the membrane is involved in the application. For many of the PVDF-based applications, the membrane is used first as a vehicle for purification. Once the macromolecules are anchored on the membrane, biochemical analysis can be performed right on it. This circumvents the need to elute the protein off of a membrane or out of a gel before the chemical analysis can take place. Using membranes, it is possible for researchers to look at reactions between different proteins or between a protein and some ligand such as GTP. To study DNA-binding proteins, for instance, proteins on a blotting membrane can be probed with a fragment of DNA containing a possible recognition sequence (a Southwestern blot). Other small biologically active substances such as signal molecules can also be studied this way. "Activity blots such as the Southwestern blot can be used to look at physiologically relevant reactions," Mansfield explains. "These types of assays are of interest to many researchers, especially in the area of development." Southwestern blots and the potential to perform specialized chemistries right on blotting membranes are indications of blotting's permanence in the lab. "It is unlikely that blotting technology will be completely superceded by another technology," says Mansfield. "Procedures will be changed and different technologies will be allied with it, but blotting will continue to have an important place in research and diagnostic laboratories." Predicts Sorensen: "The future of blotting is evolution, not revolution." Holly Ahern is a science writer and an assistant professor of biology at Adirondack Community College in Queensbury, N.Y. (The Scientist, Vol:8, #23, p.17, November 28, 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 : Blotting Applications And Support Media Suppliers Directory TY : TOOLS & TECHNOLOGY PG : 19 Advanced Biotechnologies Inc. Columbia, MD Circle No. 100 on Reader Service Card Advanced Genetic Technologies Corp. San Diego, CA Circle No. 101 on Reader Service Card Ahlstrom Filtration Inc. Mount Holly Springs, PA Circle No. 102 on Reader Service Card American Bioanalytical Inc. Natick, MA Circle No. 103 on Reader Service Card Boehringer Mannheim Corp. Indianapolis, IN Circle No. 104 on Reader Service Card P.J. Cobert Associates St. Louis, MO Circle No. 105 on Reader Service Card Crescent Chemical Inc. Hauppauge, NY Circle No. 106 on Reader Service Card DuPont NEN Boston, MA Circle No. 143 on Reader Service Card Fluka Chemical Corp. Ronkonkoma, NY Circle No. 107 on Reader Service Card Gallard-Schlesinger Industries Inc. Carle Place, NY Circle No. 108 on Reader Service Card Hoefer Scientific San Francisco, CA Circle No. 109 on Reader Service Card ICN Biomedicals Costa Mesa, CA Circle No. 110 on Reader Service Card Innotech Biosystems International Lansing, MI Circle No. 111 on Reader Service Card Intermountain Scientific Corp. Kaysville, UTCircle No. 112 on Reader Service Card Life Technologies Inc. Gaithersburg, MD Circle No. 113 on Reader Service Card Micron Separations Inc. Westboro, MA Circle No. 114 on Reader Service Card Midwest Scientific St. Louis, MO Circle No. 115 on Reader Service Card Millipore Bedford, MA Circle No. 116 on Reader Service Card Novex San Diego, CA Circle No. 117 on Reader Service Card Oncor Inc. Gaithersburg, MD Circle No. 118 on Reader Service Card Pierce Chemical Co. Rockford, IL Circle No. 119 on Reader Service Card Sartorius Corp. Bohemia, NY Circle No. 120 on Reader Service Card Schleicher & Schuell Inc. Keene, NH Circle No. 121 on Reader Service Card Thomas Scientific Swedesboro, NJ Circle No. 122 on Reader Service Card VWR Scientific West Chester, PA Circle No. 123 on Reader Service Card Whatman Lab Sales Inc. Hillsboro, OR Circle No. 124 on Reader Service Card (The Scientist, Vol:8, #23, p.19, November 28, 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: NEW PRODUCTS ------------------------------------------------------------ TI : NEW PRODUCTS TY : NEW PRODUCTS PG : 21 Stratagene Releases New DNA Markers Three new DNA markers have been developed to allow sizing and quantitation of linear and supercoiled, double-stranded DNA. The Kb DNA Ladder contains 15 linear fragments from 250 bp to 12 kb. Bands are produced in 1,000-bp increments from 1 kb to 10 kb. The ends of each fragment have 5_ overhangs and may be radiolabeled with a-labeled dATP, dTTP, or dUTP. Alternatively, the ladder may be radiolabeled by exchanging the 5_ phosphate using T4 polynucleotide kinase and g-labeled rATP. The Illuminator Kb DNA is a version of the Kb DNA Ladder that has been prelabeled with fluor-12-dUTP for use with the Illuminator nonradioactive detection system. The Supercoiled DNA Ladder produces bands from 2 kb to 10 kb at 1-kb increments. Stratagene, La Jolla, CA Circle No. 126 on Reader Service Card ------ Balance Draft Shield From Airfiltronix The DS-1 Balance Draft Shield is designed to protect samples from air currents during weighing with sensitive balances. The shield encloses the balance and is equipped with a hinged front door for direct access to the weighing pan and controls. A 3-inch hole on the top lid allows for sample dispensing when the lid shield is in place. A collar on the back of the shield is available for exhaust ventilation. Airfiltronix Corp., Clifton, NJ Circle No. 127 on Reader Service Card ------ Electrophoresis Gel Visualization, Documentation System The FP 1000 Visualization System incorporates a high-resolution charge-coupled device (CCD) camera with a 600 nm filter, a 256 gray-scale thermal printer, a monochrome 9-inch monitor, and a low-profile darkroom with a viewing port for electronic, instant photography of stains, wet gels, and audioradiograms. The companion PHD 2000 Documentation System allows digital storage and archiving of photographed images on a 3.5-inch floppy diskette. It also provides for serializing and dating stored images as well as image enhancement. Ultra-Lum Inc., Carson, CA Circle No. 128 on Reader Service Card ------ Sun BioScience's Compact Microcentrifuge Debuts The Personal Microcentrifuge, measuring 6H** x 6H**, reportedly achieves a full operating speed of 14,000 x g within three seconds. Designed for quick spins at any workstation, including the coldroom, the centrifuge can be used for nucleic acid preparation, protein separation, polymerase chain reaction product sedimentation, binding studies, and a variety of microchemical determinations. It is available in three capacities (6 x 1.5 ml, 12 x 1.5 ml, and 24 x 0.5 ml) and a selection of fixed-angle rotors. Sun BioScience Inc., Branford, CT Circle No. 129 on Reader Service Card ------ VWR Scientific Unveils Sterile Syringe Filter The VWRbrand sterile syringe filter uses a surfactant-free cellulose acetate membrane in a modified acrylic housing. Its applications include sterilization of aqueous solutions, biological and immunological samples, and cell-culture media components as well as filtration of sera, antibodies, buffers, and tissue-culture media. The filter is available in 0.2 mm and 0.45 mm pore sizes and is certified sterile, noncytotoxic, and nonpyrogenic. VWR Scientific, Philadelphia, PA Circle No. 130 on Reader Service Card ------ ATI Unveils Its New Line Of PerpHecT pH Meters The PerpHecT line of pH meters and electrodes gives users fully temperature-compensated pH measurements without a separate temperature probe, according to the manufacturer. The meters feature LED displays and tactile keypads as well as auto-buffer recognition. Three models are available. Model 310 provides basic pH and temperature measurements. Model 330 adds an mV mode for ORP measurement and RS232C output capability. Model 370 gives direct ISE (ion) concentration measurement plus mV and relative mV capabilities. With the PerpHecT ROSS electrodes, the meters can compensate pH measurements for both Eo and Nernstian temperature effects. Analytical Technology Inc., Boston, MA Circle No. 131 on Reader Service Card ------ Hitachi OffersHPLC System The ConcertChrom Series HPLC System includes an isocratic and quaternary pump system, a diode array, UV-Vis and fluorescence detectors, autosamplers, an integrator, and a PC-based data station. The system's four modules are designed to be stacked in a 10-inch-wide tower configuration. Its software runs on the Windows NT operating system, providing a security logbook and networking capabilities. Hitachi Instruments Inc., San Jose, CA Circle No. 132 on Reader Service Card ------ Forma Scientific's Non-CFC Freezers The Model 8500 Series ultra-low-temperature freezers use nonchlorofluorocarbon (CFC), nonhydrochlorofluorocarbon (HCFC), non-flammable refrigerants to maintain _867C tem-peratures. Both the chest and upright models incorporate a variety of new enhancements, including the internal PEAK Control System to protect compressors; 50 percent larger condensers for heat removal; front-to-back airflow through the compressor housing; and a reusable polyester foam filter. Forma Scientific Inc., Marietta, OH Circle No. 133 on Reader Service Card ------ Hewlett-Packard's Multitechnique Instrument Software The HP ChemStation software package is a Windows-based program that provides control, automation, and data handling for up to four instruments, including the company's gas chromatograph (GC), liquid chromatograph (LC), and capillary electrophoresis (CE) systems. An analog-to-digital (A/D) interface option is available for acquiring data from non-HP instruments. The software enables users to both acquire and analyze data from HP GC, LC, CE, and A/D systems. The software is a standard reporting package; researchers with custom requirements can use the ChemStation custom report generator or Dynamic Data Exchange to export data to other Microsoft Corp. packages for reporting. The ChemStore software package for sample organization and results storage is optional. Hewlett-Packard Co., Palo Alto, CA Circle No. 134 on Reader Service Card ------ Promega Launches mRNA Isolation Systems PolyATtract Series 9600 mRNA Isolation Systems provide a means to isolate amplification-quality mRNA for developmental and tissue-specific screening purposes from milligram quantities of plant and animal tissues or less than 105 cells per sample. The systems facilitate the simultaneous isolation of polyadenylated mRNA from up to 96 tissue extracts or cell lysates. A 96-pin magnetic separation array is used in the purification process. Two systems are available: One contains M-MLV Reverse Transcriptase and other reagents for conversion of the mRNA to cDNA directly in the wells of the plate; the other lacks these reagents to accommodate researchers who prefer to synthesize cDNA by other means. Promega Corp., Madison, WI Circle No. 135 on Reader Service Card ------ Eppendorf Microcentrifuge Available From Brinkmann The Eppendorf Micro Centrifuge Model 5417, now available through Brinkmann Instruments, offers a choice of three interchangeable, autoclavable rotors with lid: a standard, 24-place, fixed-angle rotor; a 24-place aerosol-tight rotor; and a 12-place swing-bucket rotor. The 24-place models hold tubes from 0.25 ml to 2 ml or 12 aerosol-tight capsules. For use in the lab or coldroom, the centrifuge has a programmable selection of speeds up to 14,000 rpm and g-force settings up 20,800 x g.Brinkmann Instruments Inc., Westbury, NY Circle No. 136 on Reader Service Card ------ Molecular Probes' One-Step Bacterial Viability Kit The LIVE/DEAD BacLight Viability Kit uses fluorescent dyes that distinguish bacteria with intact plasma membranes from dead bacteria with compromised membranes. Live bacteria fluoresce green, while dead cells fluoresce red. Bacteria can be viewed directly after the dye mixture is applied without washing or destaining steps. The stained bacteria retain staining specificity and intensity after treatment with glutaraldehyde or formaldehyde fixatives. The kit may be used to determine viability of bacteria in mixed-cell populations and in samples that contain other cell types, including eukaryotic cells. The proportion of live and dead bacteria in a suspension may also be quantitated with a fluorometer, fluorescence microplate reader, or flow cytometer. Molecular Probes Inc., Eugene, OR Circle No. 137 on Reader Service Card ------ HEMCO Offers Modular Enclosure Systems The UniLab Cleanroom, capable of achieving Class 100 air quality, is available in hard wall or soft vinyl curtain models in a selection of standard sizes or custom configurations. The UniMax Hazardous Containment Enclosure is designed to isolate toxic and hazardous substances from the work area or lab. It features ventilation and filtration systems in conjunction with grated flooring and secondary containment basins. HEMCO Corp., Independence, MO Circle No. 138 on Reader Service Card ------ Power Supply For Electrophoretic Applications The Bio-Rad PowerPac 3000 has an output of 3,000 V, 400 mA, and 400 W. It offers three modes of operation in constant voltage, current, or power: manual mode for timed, volt-hour, or continuous runs; program mode for more demanding methods with up to nine separate steps; and temperature mode for electrophoresis at a set constant temperature. Each mode is programmable via menu-driven user interface and graphics LCD. Bio-Rad Laboratories, Hercules, CA Circle No. 139 on Reader Service Card ------ Drummond Introduces Microinjection Pipette The Nanoject Auto/Oocyte Injector is microprocessor-controlled and equipped with a nonrotating plunger. It is available in a standard 46-nanoliter fixed-volume model or a 16-step, 4.6- to 73.6-nanoliter variable-volume design. Attachable to most micromanipulators, the Nanoject is supplied with enough glass capillaries to pull 300 tips. Drummond Scientific Co., Broomall, PA Circle No. 140 on Reader Service Card ------ New England Biolabs Releases Phagemid Cloning Vectors The LITMUS Cloning Vectors are phagemid vectors for cloning, mutagenesis, and in vitro transcription. They feature universal sequencing primer sites; a pUC-derived plasmid backbone; M13 origin for single-stranded mutagenesis template production; blue/white selection; ampicillin resistance; and polylinkers containing 32 unique restriction sites that represent all commercially available 4-base extensions. They also contain a system for generating RNA probes in either direction using only T7 RNA polymerase. New England Biolabs, Beverly, MA Circle No. 141 on Reader Service Card ------ Cohesive Biotechnologies' Prepacked Columns For Bioseparations Bio-S and Bio-RP are two new prepacked columns and chemistries from the Bio-Protocol line. The columns are available in 10 mm, 20 mm, and 50 mm particle sizes. Bio-S is a strong cation exchange media that provides high dynamic capacity, resolution, and throughput for protein purification. Bio-RP is a mildly hydrophobic reverse-phase media for use in initial capture steps and in final polishing processes. The mild hydrophobicity reportedly minimizes use of organic solvents while retaining a high degree of selectivity and resolution. Cohesive Biotechnologies, Acton, MA Circle No. 142 on Reader Service Card (The Scientist, Vol:8, #23, p.21, November 28, 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: PROFESSION ------------------------------------------------------------ TI : Competition Is Intense For Jobs In Science Journal Publishing AU : PAUL MCCARTHY TY : PROFESSION PG : 23 These days, with funding for research far from assured, scientists are seeking alternative careers that provide opportunities for them to continue using their scientific training and remain in touch with their fields. One such alternative is journal publishing, a natural venue for those researchers who have a way with words. Generalizations about editorial jobs are risky. While some journals rely on part-timers or even volunteers to handle editing tasks, others--particularly those in medicine--remunerate their editors handsomely: Several of them offer salaries in the hundreds of thousands of dollars. Still, it's only the weekly and biweekly medical journals that have a need for full-time scientific editors, as opposed to the monthlies and quarterlies, which use part-timers. The Journal of the American Medical Association (JAMA), for instance, has five full-time positions and the New England Journal of Medicine (NEJM) has seven. But these are the United States' largest medical journals and are the exception, not the rule. Edward Huth, who served as edit or-in-chief of the Annals of Internal Medicine for 19 years, says that, in all of the world's English-language medical journals, there are only 25 or 30 physicians editing full-time. Understandably, the competition for full-time slots is stiff. Recently, when NEJM advertised for a deputy editor, 60 physicians, all prominent in their fields, applied. How They Got There Researchers come to publishing through a variety of routes. Huth, who started at the Annals in 1965 as an associate part-time editor and moved up to editor-in-chief in 1971, calls his career switch "one of those accidents of life." While Huth was conducting kidney-function investigations at the University of Pennsylvania, a colleague was tapped to be editor-in-chief at the Annals and asked him to sign on, too. Huth had written for a college magazine and decided to give it a try. He retired from the Annals in 1990 but recently came out of retirement to "hold things together" when his successors, Robert and Suzanne Fletcher, took positions at Harvard Medical School. NEJM editor-in-chief Jerome Kassirer had a long track record in publishing before taking his present job. He had coedited the monthly "Nephrology Forum" for 14 years at the journal Kidney International, edited a column called "Clinical Problem Solving" for the Journal of Hospital Practice, and served as editor-in-chief of a textbook, Current Therapy in Internal Medicine (St. Louis, Decker, 1991). In 1974 Peter Newmark, a chemist in the United Kingdom who felt stuck in a tedious area, left a lecturer's position to become the biology editor at Nature. Now he is managing director of Current Biology Ltd. in London. The company publishes nine journals; Newmark personally edits and publishes Current Biology. In addition, the company produces books and databases and will soon be putting out CD-ROMs. Editors Of All Stripes Editors of life-sciences journals can network and get assistance from the Chicago-based Council of Biology Editors (see accompanying story). Some journals use deputy and associate full-time editors to supervise the scientific side of editing research papers. They make certain that the syntax is clear, the research designs are adequate, and the conclusions are justifiable. In addition, they sometimes write editorials. And most journals have a copy editor--NEJM has seven. These individuals have extensive editing backgrounds, some with a little science thrown in, but most with undergraduate credentials. They dot the is and cross the ts and get paid on a baccalaureate scale. Because there are so few jobs available, "earning a living at journal editing is a long shot," says George Lundberg, who is in his 13th year as JAMA's editor-in-chief. But it is a good living for some, notes NEJM's Kassirer. Salary depends on experience and the candidate's previous income, he points out. "If I brought in a cardiologist who was making $130,000, I'd pay him that, where I would pay an endocrinologist a little less." Adds Lundberg: "It's all a matter of negotiation based on supply and demand." Huth guesses that the pay ranges from $100,000 to $250,000 per year and parallels what physicians in diverse specialties with wide-ranging experience could earn teaching. Various arrangements exist for the part-timers who occupy the vast majority of editorial positions. Most have university jobs and edit, too. Some part-timers are paid on top of their university salaries, while the journal picks up a share of the university salary for others. Still others edit gratis, to learn and obtain experience. Even though there are a lot of part-time positions, getting one is not easy. One reason, according to Lundberg, is that there may be only a handful of journals in a re-searcher's specialty. On top of that, editors may stay for five to 10 years. Society Journals Journals that are published by scientific societies are able to keep staffing costs low, according to William J. Whelan, editor-in-chief of the FASEB Journal, a publication of the Federation of American Societies for Experimental Biology. Whelan, a full-time professor of biochemistry and molecular biology at the University of Miami School of Medicine, works part-time out of his academic office for the journal and has 20 percent of his university salary paid by FASEB. Such an arrangement is economical "because generally the institution is not demanding any overhead for space [and other costs], and many of these journals are subsidized in that way," notes Whelan, who also was involved in starting FEBS Letters, the European Journal of Biochemistry, and several other publications. "I must say that, in comparison with private journals like Nature, we have much smaller and leaner staffs." He adds that a way to reduce costs and thus keep subscription costs low is to "limit the number of people you need in the central office and then spread your work out to the other [outside] editors. We pay the editors a small fee for each manuscript they handle--we are paying for the mail or faxes [and so forth], but nobody makes a dime out of it." The World Beyond Biomedicine The take from outside biomedicine is a little different. J.P. Keener, who edits the SIAM Journal of Applied Mathematics, is a volunteer. Keener, a professor of mathematics at the University of Utah, notes that the math community is small and has little money. In mathematics "I don't see the opportunity for anyone to make a living editing," he says. More promising is Physical Review Letters (PRL). Although the chief editor is part-time, there are six full-time senior editing positions for people with Ph.D.'s in physics, according to Stanley Brown, a senior editor at the journal. Starting salaries are competitive with postdoctoral stipends in the field. Still another way of allocating editing chores is found at the Journal of the American Chemical Society (JACS), which publishes 25 journals. Twelve part-time editors, all of whom have full-time teaching positions, keep the wheels turning. According to Charles Bertsch, who heads up ACS's journals department, ACS's part-time editors are paid anywhere from $1,000 to $30,000 per year, depending on the journal's circulation, size, and number of associate editors. Allan Bard, the part-time editor-in-chief, has presided over JACS for 13 years, although the term is usually five years. JACS looks for people with a demonstrated record of scholarship. These individuals do not apply for jobs at the journal but are tapped by a search committee. Having What It Takes Of course, not everyone is suited to editing. Huth says the most important qualities to have are a firm grasp of the nature of scientific evidence, a broad knowledge of the field, and a journalistic instinct to know when to publish something "that may not stand up, but is substantial and provocative enough to merit an airing." Kassirer, on the other hand, emphasizes administrative ability and past editing experience. There are drawbacks, too. Lundberg cautions that editors attract controversy: While they are considered the friend of those whose papers they accept, they are often viewed as the enemy of those they reject. And then there's the isolation, says Huth. Although editors-in-chief are sometimes quite visible, they spend most of their time cooped up in an office. People accustomed to the activity of a large academic center often are not prepared to deal with the solitude, he warns. "You have got to recognize that it is a tyranny--that it goes on almost 365 days a year," cautions FASEB Journal's Whelan. "If you are away for a few days you are constantly in touch by fax because you can't hold manuscripts up--you always have to meet deadlines. "You have to accept that it is very demanding and you can't put it down even for a short time, otherwise things are going to go wrong. You are a vital link between the authors and the production office, and the production office is always screaming politely to meet their deadlines." Still, for an editor-in-chief, the job can be pretty heady. Huth points out that it's a chance to be visible. It also provides a forum to say what one thinks almost without contradiction and an opportunity to develop national positions on issues in ways that the average academic can't. Not insignificantly, the job carries considerable clout. "If you are with an important journal, you decide what information is provided to large numbers of readers and to a substantial extent set the agenda for medicine and health care in the country," comments Lundberg. One drawback to editing, according to PRL's Brown, is rejecting papers from scientists one knows personally. When he signed on during the job crunch of the 1970s, he recalls, he was immediately faced with rejecting a former office-mate, but had someone else write the letter. "Since then I've become more calloused," he says. Editing isn't all rejection, however. Brown reports that he gets a good overview of physics, is involved in publishing important research, and gets to rub shoulders with smart and interesting people. "And it's a way to keep in touch with physics and still get paid for it," he notes, something he wasn't sure he would be able to do because of the tight job situation when he finished his dissertation in the 1970s. The biggest negative for JACS's Bard is the time editing takes from his other work. When he's busy, he acknowledges, "I am less than happy to spend time on other people's papers." He has also found that, while most scientists accept how the system works, now and then a simple rejection ends up straining personal relationships. Even so, Bard likes the work. Through editing he sees the big picture in chemistry: "I get to learn a lot about modern frontier science and the people doing it." Advice For Aspirants Current Biology's Newmark says his chemistry training has helped him enormously because it has given him a feeling for science and has enabled him to "talk the talk" with the scientists whose work he publishes. But he says that the power of persuasion, or the ability to develop it, is the most important quality for a would-be editor to have. Whether it's editing journals, writing books, or reviewing papers, he says, "a lot of publishing is persuading busy academics to do things that they really don't have time to do." For the researcher who wants to make the switch, Newmark thinks the most important thing is to send a grammatically correct application letter. He also wants to see some evidence that the applicant has previously shown an interest in publishing. JAMA's Lundberg recommends first getting on an editorial board to learn about the journal and "so they can learn about you." Competition for jobs with physics journals is arduous because there is currently a job crunch in the discipline, according to PRL's Brown. He reports that he has seen several hundred applications in recent months. He advises job-seekers not to get their hopes up about a job at his journal. On occasions when he does have a job open, Brown says, he looks for someone with at least some postdoctoral experience and some writing inclination, even as little as having worked on a student newspaper. "It shows they have an interest in communication and words," he comments. Academics sometimes come up short in two areas, according to Newmark. First, they often don't have a bottom-line mentality, thinking that a journal will sell automatically because it is good or important. "You can produce a wonderful [publication] and not sell it," says Newmark, "because you neglect the marketing." The other mistake, he cautions, is to assume that a publishing job carries with it employment security. "You don't come here and get a job for life," he says. "You succeed or you don't." Paul McCarthy is a freelance science writer based in Honolulu. (The Scientist, Vol:8, #23, p.23, November 28, 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 BIOLOGY EDITORS GET TOGETER TY : PROFESSION PG : 23 The 1,200-member, Chicago-based Council of Biology Editors, established in 1957 by a joint action of the National Science Foundation and the American Institute of Biological Sciences, provides resources for journal editors in the life sciences, offers a means for them to collaborate, and fosters "effective communication practices," according to its mission statement. The group sponsors an annual meeting (next year's gathering, scheduled to take place in Kansas City, Mo., in May, will focus on the challenges of the electronic aspects of publishing) and publishes a style manual for life-sciences journals, as well as a newsletter. Council of Biology Editors 11 S. La Salle St., Suite 1400 Chicago, Ill. 60603 Phone: (312) 201-0101 Fax: (312) 201-0214 * President: Bradley Hundley * Managing Director: Cindy Clark (The Scientist, Vol:8, #23, p.23, November 28, 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 : Pair Of Eminent Peptide Biochemists Receive 1994 Ciba Award For Hypertension Research AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 24 Adolfo J. deBold, a professor of pathology and physiology at the University of Ottawa and director of research at the University of Ottawa Heart Institute in Ontario, Canada, and Ervin G. Erdos, a professor of pharmacology and anesthesiology and director of the Peptide Research Laboratory at the University of Illinois College of Medicine, Chicago, have received the Ciba Award for Hypertension Research. Cosponsored by the Houston-based American Heart Association's Council for High Blood Pressure Research and the Ciba-Giegy Corp. Pharmaceuticals Division, Summit, N.J., this annual award--including a cash prize of $20,000 to be shared by the winners--recognizes contributions toward the improved understanding of hypertension. The award was presented during the American Heart Association's annual meeting, held in Chicago in September. DeBold was the first to demonstrate that the heart has an endocrine function in addition to its role as a pump in the circulatory system. He discovered and isolated a hormone called atrial natriuretic factor (ANF), named thus because it is produced in the heart's atria and has very powerful diuretic and hypotensive properties. In general, deBold explains, ANF counteracts the renin-angiotensin-aldosterone system in the body, which increases blood pressure and blood volume. "The characterization of this hormone led to numerous insights at the physiological level about water and electrolyte balance," he says. Currently, the peptide, which acts by "improving perfusion of blood into the kidneys and their filtering capacity," is being tested in clinical trials for the treatment of acute kidney failure. DeBold's original paper describing the hormone--A.J. deBold et al., Life Sciences, 28:89-94, 1981--was designated a Current Contents "Citation Classic" in 1991 and has been explicitly referenced in more than 1,800 subsequent articles. DeBold received his undergraduate degree in clinical biochemistry from the National University of Cordoba in his native Argentina in 1968. He attended graduate school at Queens University, Kingston, Ontario, in Canada, where he received M.Sc. (1972) and Ph.D. (1973) degrees in pathology. He held various appointments at Kingston from 1972 through 1985, when he moved to the University of Ottawa. Since 1989 he has also been a Distinguished Research Professor at the Heart and Stroke Foundation of Ontario. Erdos was recognized for his role in defining the critical enzymes involved in the metabolism of peptides that regulate blood pressure, particularly for finding that the enzymes angiotensin I converting enzyme (ACE) and kininase II are identical. "We discovered that this enzyme exerted a dual effect on blood pressure--by controlling two oppositely acting peptides," recalls Erdos. "It activates the vasoconstrictor angiotensin, which raises blood pressure, while also inactivating bradykinin, which is a vasodilator." His seminal paper discussing this work--"Angiotensin I converting enzyme," Circulation Research, 36:247-55, 1955--was featured as a "Citation Classic" in Current Contents in 1986 and has received more than 200 citations. This work was an important stepping stone in the development of the class of drugs called ACE-inhibitors. "Besides blocking ACE, these inhibitors also act by prolonging the half-life of bradykinin, and that has beneficial effects on the heart and blood pressure," Erdos explains. Examples of such drugs include captopril and enalapril, which are used for the treatment of such conditions as hypertension and congestive heart failure, in addition to preventing complications that can lead to stroke. A native of Hungary, Erdos graduated in 1950 from the University of Budapest Medical School, and obtained an additional M.D. from the University of Munich Medical School in Germany in the same year. He first came to the United States in 1954, and taught at several universities before moving to Chicago in 1985. His work on peptides and enzymes has garnered him other prestigious awards,including a gold medal in 1988 from the Frey-Werle Foundation of the University of Munich. --Neeraja Sankaran (The Scientist, Vol:8, #23, p.24, November 28, 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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