THE SCIENTIST VOLUME 8, No:2 JANUARY 24, 1994 (Copyright, The Scientist, Inc.) Articles pu

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THE SCIENTIST VOLUME 8, No:2 JANUARY 24, 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 *** *** FEBRUARY 7, 1994 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the United States: one year $58, two years $94 Canada : one year $82, two years $142 All other foreign : one year/air cargo $79, one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NEXT = next article ----------------------------------------------------------------- TI : CONTENTS PG : 3 ===================================================================== NEWS GOVERNMENT FUNDING: With the new proposed federal budget less than a month away from release, researchers, society officers, and federal agency officials reviewing the final 1994 science appropriations say they are guardedly optimistic about future support and the direction the current administration is taking in its approach to science PG : 1 ON THE DEFENSIVE: Investigators involved in NIH's Women's Health Initiative are fending off criticism of the $625 million study of women's health issues, including a recent Institute of Medicine report stating that the main hypothesis of the investigation is scientifically weak and that its planners have underestimated the costs of the project PG : 1 RUSSIAN SCIENTISTS: The International Science Foundation for the former Soviet Union, with help from several United States scientific societies as well as individual researchers, is reviewing thousands of grant proposals from Russian scientists in an effort that will culminate in the funding of some 900 proposals worth a total of more than $45 million PG : 3 PITTCON AT 45: In addition to displays of state-of-the-art tools in analytical chemistry and spectroscopy, as well as numerous symposia and workshops on the subject, attendees at the 1994 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy will be taking time to look back on the evolution of their discipline over the past 45 years that the conference has been held PG : 4 OPINION BIOSPHERIAN: In an interview with The Scientist, UCLA researcher and professor of pathology Roy Walford discusses the two years he spentin Biosphere 2; he reflects not only on the advances he made in studying human dietary needs, but also on the day-to-day life shared by him and his colleagues inside what has been described as "a planet in a bottle" PG : 11 COMMENTARY: New National Science Foundation director Neal Lane notes recent advancements that have made a difference in remedying the underrepresentation of women in science, but also stresses that much more needs to be done to solve what he calls "one of the most important and debated issues facing the science community today" PG : 12 RESEARCH RU 486 RESEARCH: Caught amid the political controversies surrounding its use as an abortion pill, research into therapeutic properties of RU 486 has nonetheless proceeded at a steady pace, despite irregular funding and a stigmatized public image PG : 14 HOT PAPERS: A molecular geneticist discusses his paper on a genetic disorder that causes myotonic dystrophy PG : 16 TOOLS & TECHNOLOGY CHROMATOGRAPHY SOFTWARE KEEPS PACE: For the various chemistry disciplines that depend on chromatographs for sample analysis, the chromatography data-handling software that supports this process has become more sophisticated over the past decade PG : 17 PROFESSION PAY DISPARITY AMONG DOCTORS: A Boston University study has found that female researchers in three areas of academic medicine--cardiology, rheumatology, and general internal medicine--receive lower salaries and fewer promotions than their male counterparts do PG : 21 WILLIAM H. PICKERING AND ARVID CARLSSON, an astrophysicist and a neuropsychopharmacologist, respectively, have each won the 1994 Japan Prize, one of the richest scientific awards in the world PG : 22 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 12 CROSSWORD PG : 13 CHROMATOGRAPHY SOFTWARE DIRECTORY PG : 19 OBITUARIES PG : 22 (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : NIH Women's Health Researchers Rebut Criticisms Of Their Study Project scientists reject Institute of Medicine claims that their ambitious initiative is scientifically and financially deficient AU : FRANKLIN HOKE TY : NEWS PG : 1 Recent criticisms that the Women's Health Initiative (WHI) at the National Institutes of Health is poor science and likely to run over budget are drawing sharp rebuttal from project investigators. An Institute of Medicine (IOM) report released late last year said that one of the study's primary hypotheses--that a low-fat diet will reduce the occurrence of breast cancer in women over 50 years of age--is scientifically weak, given the existing data. The IOM group suggested instead that the investigation of a secondary hypothesis, that a low-fat dietary pattern reduces the risk of coronary heart disease, be emphasized. The panel also found that the WHI underestimated the per-participant, per-year costs at about $1,000--far lower than the $2,000 to $3,000 required in other NIH studies--a fact that might endanger the study's successful completion. The women's health project ranked as one of former NIH director Bernadine Healy's highest priorities. As early as her 1991 confirmation hearings, she announced her intent to launch such a program as a corrective device for years of health research that excluded women as subjects. Healy pressed the project forward aggressively throughout her directorship, which ended in June 1993. The resulting WHI is the largest research study ever conducted by NIH, involving more than 160,000 women over the age of 50 at 45 clinical centers across the United States. The women are to be tracked for 14 years at a cost of more than $625 million. The study has been widely viewed as one of the foremost achievements of Healy's tenure at NIH. Partly because of the history of women's health research, however, or perhaps because of Healy's confrontational style as director, the WHI has attracted more political interest than do most NIH research efforts. Some women's health advocates suspect that, even now, the criticisms of the WHI may be, at least in part, politically based. "I believe, with all my heart, that some of this is political," says Nancy Brinker, founding director of the Susan G. Komen Breast Cancer Foundation in Dallas and chairwoman of the President's Cancer Panel Special Commission on Breast Cancer. "Politics does enter medicine and science." Brinker is among those who praise Healy's efforts to make the WHI a reality. "It was a major accomplishment," says Brinker. "Maybe the study was designed, in some people's eyes, a little too rapidly; maybe it wasn't perfectly designed. But what people forget is that Bernadine Healy had the guts to stand up and talk about [women's health] issues." WHI officials answer the IOM critique by saying that WHI hypotheses and the report's suggestions simply represent differing assessments of the existing epidemiological data. In fact, they say, this is why the WHI's clinical trial is so important--it will provide hard data against which to check these differences (see accompanying story). "The disagreement really came about as an honest scientific disagreement among people collecting data and interpreting them in various ways," says William Harlan, codirector of the WHI and associate director of NIH's Office of Disease Prevention. "It's not resolvable by further [epidemiological] studies of the same type." Estimates of study costs also were carefully done, WHI investigators say, and the study can be completed as budgeted. "We budgeted it tightly, but, we think, realistically," says Robert Wallace, principal investigator of the Vanguard Clinical Center at the University of Iowa, Iowa City. "But it's very hard to know. Obviously, budgeting for that long a period is an exercise in guesswork." So far, 16 of an eventual total of 45 WHI clinical centers have been funded; these first 16 are known as the Vanguard Clinical Centers. One coordinating center, at the Fred Hutchinson Cancer Research Center in Seattle, has also been funded. "We looked at our budget six ways from Sunday to be sure that we could do it," says Richard A. Carleton, co-principal investigator of the WHI Vanguard Clinical Center at Memorial Hospital, Pawtucket, R.I. "We can do what we have said we will do for the amount that they told us we could have," says Carleton, who is also physician-in-chief at Memorial Hospital. In addition to challenging the WHI design and budget, the IOM panel was openly angry about delays at NIH that resulted in the panel's reviewing a project that was already awarding multiyear contracts and scheduled to begin participant recruitment during the review period. The House Appropriations Committee asked for the IOM review of the WHI in July of 1992; NIH did not approach IOM about the review until February 1993, and a contract was not signed until April 1993. There were limits, as a result, to what the committee felt it could responsibly recommend. "There is a tension evident in this report," wrote committee chairwoman Marion J. Finkel, a vice president at Sandoz Pharmaceuticals Corp., East Hanover, N.J. "Had the committee been asked to design a plan for women's health research, it would not have designed this WHI." Meanwhile, advocates for improved women's health research and care say the time has come to move beyond arguments over which scientific questions should be asked by the WHI. The project--as designed--is important, they say, and should go forward. "I'm so frustrated at the length of time that this has taken, at the exclusion of women from important trials and so on, so that, at this point in 1994, we're still asking questions that should have been answered--or at least asked- -20 years ago," says Brinker. "I would hate to see this trial abandoned. I've always thought it was an ambitious, appropriate thing to do." Costing Questioned In its report, the IOM panel said that the per-participant, per-year costs might be twice or even three times the $1,000 estimated by NIH and that the total costs for the WHI clinical trial probably would be greater than the $625 million allotted. This assessment, they said, was based on comparisons to other recent, similar NIH studies of women's health. The additional costs, they said, would have to be borne by the 45 clinical centers, a fact they felt might threaten the overall WHI. "NIH and Vanguard Clinical Center representatives have indicated that the additional funds necessary for successful completion of the trial will be covered by the institutions in which the Clinical Centers are based," the report said. "This reliance on institutional support may be reasonable in the case of the [16] Vanguard Clinical Centers, but the committee felt it is unlikely that an additional 29 institutions can be identified that have both the experience to carry out the tasks of high-quality research and the ability to provide additional resources." WHI officials take strong exception to the IOM cost assessment, including disagreements on some points of fact. They say, for instance, that individual clinical centers will not be asked to take on additional expenses at any time. "Our contracts are very clear on that," says Carleton. "The IOM had an erroneous understanding, somehow, on that one." Carleton adds that the costs were carefully and conservatively analyzed, including adjustments for factors that have skewed the results of several previous studies. Such factors include, for instance, the "healthy volunteer effect." People who volunteer for clinical health studies such as the WHI tend to be in better health than the average person, it has been shown. WHI director Harlan defends the per-participant calculations that support the overall project estimate of $625 million and says IOM was not comparing "apples with apples" in its critique. "The comparisons that were made are really inappropriate," says WHI codirector Harlan. "The comparisons they made were with relatively small studies of 1,000 or fewer participants, lasting two to three years. A good part of the cost in a large clinical trial is recruitment and the early initiation of people into the treatment and measuring of the adverse effects. If you take those costs, which may be a third or 40 percent of the total cost, and amortize them over the 14-year period, the costs per participant, per year become much smaller." Harlan adds: "They didn't carry out a very careful cost analysis--in fact, they didn't provide an independent cost analysis to buttress their argument." Panel chairwoman Marion Finkel acknowledges that the panel had difficulty assessing WHI costs, but with good reason. "We didn't get sufficient detailed information from NIH to be able to make those calculations," Finkel says. "Our calculations were based upon some of the information that was supplied by the Vanguard Centers, and we just costed it up." One IOM recommendation--based on its assessment that the costs would exceed the $625 million budgeted--was that the study end sooner, in 2002 instead of 2005. This suggestion was partly a reflection of their hoped-for changes in hypotheses, also. The shortened project would allow time to test the heart disease hypothesis, for instance, but not enough time to test the effects of dietary modification on breast cancer risk. But, most important, according to Finkel, the shorter study would begin to address concerns over the budget. "It would save money," Finkel says. "The committee recommended that the NIH look at the study several years before its scheduled completion, to see if any trends were emerging that would require that the study continue, and, if there were no such trends emerging, to terminate it." In another area, the panel said that women in the study should be better informed about the potentially higher risk of breast cancer that may result from hormone replacement therapy, important in one part of the study. Here, WHI officials agree with the recommendation and plan changes in consent forms and other materials so that participants in the huge project will be more fully informed about these health risks. Dodging IOM The report noted that the House Appropriations Committee directed NIH in July 1992 to contract with IOM "to complete a review of the design and estimated costs of the WHI by February 1, 1993, in time to make adjustments, if necessary, before major study activities began." Yet NIH did not formally discuss the project with IOM until February 1993, the report says. A contract was not agreed upon until late April 1993, well after the due date requested by Congress. "Whether the delay was due to a slow-moving bureaucracy or to other causes is unknown to the IOM committee," they wrote. "As a result, however, the committee was faced with the task of critiquing a study in progress. In the interim, NIH had requested, received, and evaluated proposals, and entered into contracts with 17 research institutions to serve as the Clinical Coordinating Center and Vanguard Clinical Centers." Harlan says that the delay can be explained, at least in part, by a closer look at the necessary legislative process. While the House Appropriations Committee may have asked for the review in July 1992, he says, the appropriations bill containing the request did not become law until October. "We didn't have a bill and a mandate to carry out a study until October of 1992," Harlan says. He acknowledges, however, that NIH's delay between October 1992 and February 1993 in engaging IOM for the then congressionally mandated study cannot be entirely blamed on bureaucratic process. "Dr. Healy, who was then the director, didn't move quickly on it," Harlan says. "I don't know how else to say it. I think that probably led to some of the irate response that you sense in the report." In response to the IOM panel's complaints about being asked to review an ongoing project, Harlan says that there was never a time when the panel could have looked at a project that was still under development. "Had they started in October, which was the original presumption on the part of the House Appropriations Committee," Harlan says, "the project would still have been under way at that point, in that we had, at that juncture, funded a coordinating center and were negotiating the funding of the first 16 Vanguard Clinical Centers." Harlan does say that, with the help of new NIH director Harold Varmus, there is a "movement toward resolution" under way. WHI officials, IOM panel members, and, perhaps, others will be invited to discuss relevant scientific and other issues and to make a recommendation to the director, Harlan says. Despite the sharp nature of the IOM critique, there is general agreement on the value of the WHI and reason to believe that an accommodation can be reached. "If the committee really felt very strongly that the study had serious problems, we could have recommended that it be terminated," says Finkel. "But we didn't. We thought there were a lot of strengths in this study." (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : A HOBBLED HYPOTHESIS? AU : FRANKLIN HOKE TY : NEWS PG : 9 One of the main questions that Women's Health Initiative (WHI) investigators hope to answer, and one specifically challenged by the Institute of Medicine (IOM), is whether a low-fat diet will reduce breast cancer risk. This hypothesis arises from comparisons of epidemiological data from countries with different fat-consumption patterns and of data tracking the change in breast cancer occurrence among migrants moving between some of these countries. Japanese women, for example, have much lower breast cancer rates than do women in the United States, and the traditional Japanese diet contains much less fat than is the norm in the U.S. Women whose parents moved from Japan to the U.S. have breast cancer rates comparable with those of other women in the U.S. The IOM report, however, suggested that these comparisons are based on the amount of fat produced and sold, not necessarily on the amount actually consumed by women. It also noted that many epidemiologists believe the amount of fat consumed by women during adolescence, when breast tissues are developing, may be more important to overall breast cancer risk than that consumed as adults. Hence, lowering dietary fat levels in the WHI study population of women, all over 50 years of age, may have little effect on their cancer rates. Several studies also have failed to show a link between dietary fat and breast cancer rates, according to Walter C. Willett, a professor of epidemiology and nutrition at the Harvard School of Public Health, Boston. Willett is a coinvestigator in the 120,000-participant, 17-year-long Nurses Health Study at Harvard-affiliated Brigham and Women's Hospital, also in Boston. In 1989, 110,000 younger women were added, with Willett as principal investigator for that part of the study. "When investigators like ourselves started to do more detailed studies," Willett says, "where you look at fat and control for other factors, the relationship between fat intake and breast cancer hasn't shown up. As the evidence has come in, the hypothesis, which was a reasonable one-- that's why we spent a lot of time looking at it--just hasn't been supported." William Harlan, codirector of the WHI and associate director of NIH's Office of Disease Prevention, counters that these studies, many conducted within single countries, are not a fair test of the low-fat hypothesis. "The range of fat intake within the U.S. and within most industrialized countries tends to be quite high and quite narrow," Harlan says. "It does not encompass the low fat levels of some of the countries where the breast cancer rates are low--for example, in Japan." He adds: "You won't find many people [in the U.S.] down at the 20 percent level, which is a level that some people feel is the important level for total fat intake." The suggestion by IOM that the WHI switch its primary focus to the link between dietary fat and coronary heart disease is unwarranted, WHI researchers say. That link already has been demonstrated by other studies, they say, and is a less compelling goal for this landmark women's health research effort than breast cancer. "On that panel, there were assembled a group of very capable people, some of whom have experience in this particular area, some of whom do not," says Richard A. Carleton, co- principal investigator of the WHI Vanguard Clinical Center at Memorial Hospital, Pawtucket, R.I. "They looked at this and said that, in their view, the dietary modification was more likely to change coronary disease. That is not scintillating new information." Several clinical studies already provide strong evidence that dietary changes can affect heart disease outcomes, says Carleton. "You can argue a lot of those data come from men," Carleton says, "but, in this area, I don't have terribly good reasons to hypothesize that women are going to be radically different from men. If you ask yourself where is the biggest public health issue for which there are imperfect--very imperfect--data, it is breast cancer." Some critics, however, go beyond the IOM suggestion that the WHI emphasize different questions. Willett, for example, says that the WHI not only is asking the wrong questions, but also will not, in any case, be able to answer them as currently designed. "There's a fundamental problem with the design of the women's health study," Willett says, "and that's that they're changing many factors simultaneously. They're not just lowering fat intake, they're increasing fruit and vegetable and vitamin intake. So, even if you do see something, you can't say that it's due to fat. If that's an interesting question, they're doing the wrong study." Willett says the WHI may be important politically, but not scientifically. He adds that the high cost of the study amplifies the significance of the problems. "The scientific world largely believes it's a disaster," Willett says. "It's a huge investment of money--it's going to be a billion dollars or more in the end--and it can't answer the questions that it was set out to answer. No one would be disturbed about it if it were a few tens of millions of dollars, but it's definitely taking money out of lots of other laboratories." WHI investigators reject such statements and say the study questions are not only important, but that the WHI, as designed, can answer them. "The important thing about the WHI is that it will test in experimental fashion some hypotheses that have not been tested in humans any other way," says Robert Wallace, principal investigator of the Vanguard Clinical Center at the University of Iowa, Iowa City, "the fundamental one being the effect of low-fat diet on a variety of cancers. That's never been done." Echoing other WHI researchers, Wallace characterizes challenges to the dietary fat-breast cancer link hypothesis as legitimate differences of epidemiological data interpretation. "It's an honest scientific disagreement," Wallace says. "Various investigators--as we all do--lean more heavily on their own data than on others. Some studies show an effect and others don't. But low-fat diet has the potential for improving health in so many areas that it is very much worth testing." "To most of us who believe that one needs to test this, the clinical trial seems the only way to do it," Harlan says. "It's a matter of deciding whether you believe that the hypothesis merits a test." Carleton suggests that the debate over the WHI's scientific goals, in itself, shows the need for the study. "Where there are differences of opinion, the facts, usually, are not known," he says. --F.H. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: --------------------------------------------------------- TI : Reviewing Congress' Final Appropriations For 1994, Scientists Eye Future Funding With Cautious Optimism Despite dramatic cuts in several programs, observers perceive Congress as generally supportive of research AU : BARTON REPPERT TY : NEWS PG : 1 Despite severe reduction in United States government support of large-scale science proj-ects and a number of general research areas for 1994, officials at scientific associations and major research universities say they are optimistic--although "cautiously" or "guardedly" so--about the prospects for fiscal 1995. At the same time, some science budget-watchers warn that the research community will face a tough fight--in view of government-wide spending constraints--to maintain even the modest funding increases in the FY94 budget and to stave off further major-program cutbacks at the National Science Foundation and other agencies. They cite, for example, the continued downsizing of the National Aeronautics and Space Administration's space station and the total elimination of funding for the Department of Energy's superconducting supercollider (SSC) as examples of big-science projects that fell victim to these economic forces in the 1994 budget. "The simple fact is that the budget crunch is intense and it's going to continue," says Roland W. Schmitt, chairman of the American Institute of Physics, an umbrella organization of 10 physics-related scientific societies based in College Park, Md. Schmitt is also a member of the National Science Board, which oversees NSF. With the United States research community, he says, this means that "you're going to have to be in there scrambling, showing that you are relevant, you are going to be serving the national interest.... I think it's going to be a very hard sell that you've got to put forth. But I think there are ways of doing it." Schmitt, former president of Rensselaer Polytechnic Institute, says the budget for fiscal year 1995, to be proposed by President Clinton early next month, pre-sents a "mixed picture." It will be "really tough because of the total budgetary pressures," he says, while on the other hand "I don't think the science is going to be singled out-- people coming after it harder than anything else." For the 1994 fiscal year, final appropriations for which were approved late last fall, Congress provided NSF with a total appropriation of $3.028 billion--$152 million less than the Clinton administration's budget request, but an increase of 10.7 percent over the preceding year's figure. The research portion of NSF's funding went up 7.5 percent to $1.998 billion, while money for education programs increased by 16.8 percent, up to $570 million, and funds for laboratories and instrumentation jumped by 120 percent, up to $110 million. In providing for the National Institutes of Health, the legislators voted a total of $10.956 billion--$288 million more than the Clinton administration had requested, and an increase of 6.1 percent from fiscal 1993. Funding for NIH's National Center for Human Genome Research climbed by 21.3 percent to $129 million. Receiving the biggest increase for fiscal 1994 was the National Institute of Standards and Technology, for which Congress appropriated $520 million--up by 35.4 percent from the year before. This move reflected strong support from the White House and on Capitol Hill for expanding applied research to help enhance the global competitiveness of American industry. On the big-science front, Congress sent shock waves rippling through U.S. high-energy physics by voting to kill the multibillion-dollar SSC under construction in Texas. Also, it chopped back fiscal 1994 funding for the space station by 8.3 percent, to a level of $1.946 billion. After the dust had settled from the congressional actions last summer and fall, the Council of Scientific Society Presidents (CSSP) drew up a "statement on science priorities," which it has submitted to the White House Office of Science and Technology Policy and other agencies. The council is an umbrella group bringing together the heads of about 60 scientific societies, with a combined membership of some 1.3 million. The CSSP consensus statement said federal policy should emphasize the importance of "foundational" research by "continuing to devote a large part of the NSF and NIH budgets to the pursuit of foundational knowledge in the sciences and a substantial part of R&D budgets of the mission-oriented agencies to similar pursuits in areas relevant to them." Among other steps, the statement called for efforts to "increase international cooperation and multinational funding for major, costly, large science projects." Lack of more substantial international cost-sharing was one factor cited by opponents of the SSC. Schmitt, who helped to draft the CSSP statement, says that while cancellation of the supercollider was a "devastating blow" to the high-energy physics community, the project's fate "had become a political issue more than anything else, anyway. I don't know that [the SSC vote] has any great significance for the future support of pioneering or fundamental science." Robert Park, Washington, D.C.-based public affairs director for the American Physical Society, says about the research funding situation: "We seemed to do well, I think, in the NSF budget--as well as could be expected in these hard times." He observes that "we would have preferred to see the space station program canceled, instead of the supercollider. But ... the NSF came out of the year fairly healthy, though we remain concerned about the Senate report language that accompanied that appropriation." Park is referring to a Senate appropriations subcommittee's report that--in blunt language that has rankled some in the academic research community--calls on the foundation to make sure that more of its resources go to fund "strategic research" targeted at high-priority national needs (see story on page 7). Park, who is also a professor of physics at the University of Maryland, College Park, says in looking ahead to the next budget year: "I'm cautiously optimistic." Clifford Gabriel, executive director of the Washington, D.C.-based American Institute of Biological Sciences, also looks on the bright side when commenting about the past year's action on Capitol Hill: "It could have been a lot worse. I think NIH did well. With [the U.S. Department of Agriculture], their grant program received a modest increase--that's something that I think needs continued growth. NSF did reasonably well. They got a lot of support in their instrumentation and facilities programs." Overall, Gabriel says, "I'm generally pleased with how things came out last year. And if we could see something even close this year [for fiscal 1995 appropriations], that would be an accomplishment." Gar Kaganowich, public affairs director for the Federation of American Societies for Experimental Biology (FASEB), headquartered in Bethesda, Md., notes that his organization had recommended $11.75 billion for NIH in fiscal 1994--a boost of 13.6 percent. "It was helpful to see the 6.1 percent increase that we did get.... We are pleased that we did that well in the current budget environment. But obviously we were a little disappointed that we couldn't move further--closer to the number that we had recommended," he says. According to Kaganowich, FASEB's consensus recommendation for NIH in fiscal 1995 is a total of $11.934 billion, which would amount to an increase of about 8.9 percent. Cornelius J. Pings, president of the Washington, D.C.-based Association of American Universities, which represents major U.S. research universities, gives a qualified yes to the question of whether he is satisfied with the fiscal 1994 appropriations: "overall--and given the context." Pings adds: "There is the capacity to do a lot of good research in this country. And there will be some of my colleagues who say we could have used more [federal funding]. I'm sure that's true. But it's a time of choice, and I think we came out remarkably well." Regarding prospects for NSF and NIH to receive fiscal 1995 increases comparable to this year's, Pings says: "I haven't thought about increments. I think it's a time of great anxiety with that budget for '95--and the next four years, assuming that Congress and the administration stick to the discipline they've imposed upon themselves. There's a severely constrained resource ... if anything increases, something else has to decrease." The fiscal 1994 appropriations for NSF and NIH were a pleasant surprise, says Judith Argon, director of the office of research support at Duke University in Durham, N.C.: "I think we were much more encouraged than we thought we were going to be, particularly with NIH, where the increases were larger ... than we were led to expect." Also, she calls the move to more than double NSF funding for academic research facilities and instrumentation "an enormously positive step.... We'd love to see that kind of program at NIH." Looking ahead to the 1995 budget, Argon says, "I would say we're guardedly optimistic." However, the Duke official adds that "there are certainly movements--within both NIH and NSF--to see more of the funds directed toward specific initiatives.... We worry that there will be programs that will be underfunded that we've traditionally drawn support from. We'll need to watch that and try to work with those two agencies and with the Congress." The NSF budget's boost to $110 million for academic research infrastructure is "an extremely good start" toward a multiyear effort to fund badly needed facilities and instrumentation, says Norman Scott, vice president for research at Cornell University in Ithaca, N.Y. "Cornell is anxiously putting proposals together at this time to compete for those funds," he says. Alvin Kwiran, vice provost for research at the University of Washington in Seattle, says he believes that with the fiscal 1994 funding levels, "the research enterprise in the universities did remarkably well, given all the constraints on the federal budget." According to Kwiran, the University of Washington last year had a research budget totaling approximately $430 million-- with about 80 percent of the funds coming from federal sources. Kwiran says he expects to see continuing debate about the overall direction and longer-term goals of research in the United States. But he observes that "assuming no serious downturns in the economy, or no untoward events, I'm optimistic that science will continue to be funded respectably." The research administrator adds that "the big factor, of course, in recent years has been the explosive growth in the big-science projects. The decision on the SSC in some ways is extremely painful to those directly engaged in it--but probably inevitable, given the spiraling costs of that project and the budget constraints that the country faces." Fred W. Weingarten, executive director of the Washington, D.C.-based Computing Research Association, notes that Congress trimmed back fiscal 1994 funding for high- performance computing and communications programs--by $12 million at NSF and by about $40 million at the Pentagon's Advanced Research Projects Agency. These cuts came even though the Clinton administration has strongly endorsed efforts to develop the "national information infrastructure." Looking to the next budget go-round, Weingarten says: "We've got a tough fight. We're going to have to make our case. We've got some heavyweights on our side, and we think we've got good arguments. But we've got to be realistic, too.... There's only a limited number of times in which politicians will stick their necks out and defend you." Peter Boyce, executive officer of the American Astronomical Society, also based in Washington, has some reservations about the fiscal 1994 appropriations. "The money for NSF was very heartening," he says, but in the final budget for NASA- -in which, aside from the space station cutback, R&D funds increased by 4.9 percent, up to $9.284 billion--"there are a couple of things which really give us pause." One particular area of concern, he says, was the scrapping by Congress of NASA's High-Resolution Microwave Survey, the radio astronomy program that had previously been known as the Search for Extraterrestrial Intelligence (SETI). "They canceled it and they saved $12 million," Boyce says. "And it was done with a lot of demagoguery--no consideration of where the program was, how well it had met its goals ... and the fact that after planning and work for 10 years, the search was just starting." Boyce adds that he doubts any funding can be restored for the program in fiscal 1995. "It's just too much of a fight," he says. "It's too tempting a target for people to use to grab headlines." Barton Reppert is a freelance science writer based in Gaithersburg, Md. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : SENATE APPROPRIATIONS COME WITH STRONG ADVICE AU : BARTON REPPERT TY : NEWS PG : 7 For the second year in a row, policy-making officials at the National Science Foundation are faced with toughly worded guidance from a Senate subcommittee that wants to see concrete progress soon in shifting NSF toward greater emphasis on supporting "strategic research." Some in the academic research community view the Senate panel's language as a highly unwelcome attempt to "micromanage" NSF and dictate specific areas of scientific inquiry. Other observers, however, say that--semantic differences aside--they share many of the subcommittee's espoused aims for research and can learn to live with the policy guidelines. The language at issue was crafted by a Senate appropriations subcommittee chaired by Sen. Barbara A. Mikulski (D-Md.) and published in a report accompanying the appropriations bill that included fiscal 1994 funding for the NSF. Overall, the report said, NSF "is at a crossroads in its future.... In short, the foundation can be at the heart of helping to shape the administration's science and technology policy in pursuit of specific national goals, or it can diminish into becoming nothing more than a national endowment for science." The subcommittee contends that NSF and the National Science Board have given "mixed signals" as to whether they intend to actually work toward implementing the "bold vision" that was sketched out in the November 1992 report of the Commission on the Future of the NSF. "It is time for the foundation to move beyond rhetorical statements about the value of strategic research or the importance of using science for the transfer of knowledge and technology," the Senate report stated. "That, in the committee's view, is a fact of life and political reality.... The agency must spell out how much of its mission should clearly be strategic and applied in nature, and then implement these parameters through its budget process." The Mikulski subcommittee warns that if NSF fails to do that, "future federal R&D budgets should instead be allocated more generously to agencies such as the National Institute of Standards and Technology, NASA, the national energy labs, or the National Institutes of Health, all of whom seem poised to pursue critical technologies with entrepreneurial vigor and enthusiasm." In its report issued last September, the Senate panel calls on NSF officials to revise the foundation's strategic plan for the 1995 fiscal year to incorporate various specific changes. They need to take steps, the subcommittee says, to ensure that "not less than 60 percent of the agency's annual program research activities should be strategic in nature." Robert Park, public affairs director for the American Physical Society, asserts that "the Senate report language attempts to micromanage the foundation." He calls the latest Mikulski subcommittee report, compared with one issued the year before, "much more aggressively worded." Kathleen Ream, head of the department of government relations and science policy at the American Chemical Society, comments that "there is a concern about the ultimate direction in which the Senate appropriations [subcommittee report] seemed to be pushing the foundation." She says the issue over strategic research poses the question of whether that involves just "categorizing basic research," or instead "dictating what can be done." Cornelius J. Pings, president of the Association of American Universities (AAU), says he also is somewhat concerned about the Mikulski subcommittee report, but doesn't want to see the academic research community get overly worried about it. "I'm concerned about the language," he says. "And many of us were left trying to understand what really the rationale and the intent is, and what the follow-on implications would be. One fear might be that it portends micromanagement"-- although Pings adds that he himself doesn't see in the subcommittee report such micromanaging of NSF. "I hope that we all don't get too stirred up here on something that may, after the fact, appear only to have been a semantic difference," says the AAU president. Pings notes that "much of our work in basic research in this country is directed in the sense that it is concentrated in certain areas. That's been a political decision" by Congress and federal funding agencies, and that "furthermore, we know that that work supports outcomes in technology and applications. What we want to make sure of is that we let it be an outcome--not that we overdirect it going in." NSF officials point out that a substantial portion of the agency's research funding already goes to areas that are considered strategic--such as high-performance computing and communications, advanced materials, and biotechnology. One NSF official, speaking on condition of anonymity, calls Mikulski an "activist" subcommittee chairwoman who, with her staff, "wrote that language to get [the academic research community's] attention, and she sure as heck did." Within the agency, this official says, NSF policymakers view the latest Mikulski report as "telling us to continue to do the difficult job of setting priorities.... It doesn't mean abandon anthropology. It does mean, though, that high- performance computing ought to have high priority." --B.R. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------- TI : FEDERAL RESEARCH FUNDING (In millions of dollars) TY : NEWS PG : 6 FY 1994 FY 1994 FY 1993 Request Approp. National Science Foundation 2,734 3,180 3,028 National Institutes of Health 10,326 10,668 10,956 Department of Energy -- Superconducting supercollider 517 640 --- -- Other civilian research 2,626 2,730 2,765 National Aeronautics and Space Administration -- Space station 2,122 1,946 1,946 -- Other R&D 8,847 9,529 9,284 National Institute of 384 533 520 Standards and Technology Environmental Protection 323 354 339 Agency (R&D) National Oceanic 202 214 226 and Atmospheric Administration Department of Agriculture -- National Research Initiative 97 130 112 Source: Various federal agencies listed (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Societies Aid In Large-Scale Effort To Support Russian Science AU : TRACEY D. WEBB TY : NEWS PG : 3 The International Science Foundation for the Former Soviet Union (ISF), with the help of discipline-specific panels composed of representatives of United States scientific organizations and more than 200 American and European scientists, is conducting what participants are calling an unprecedented peer-review process. The effort is scheduled to culminate this month with the funding of about 900 research proposals from scientists in Russia and other Baltic states. The grants will total $45 million to $50 million and will fund 10 percent to 20 percent of the proposals under consideration, according to Chris Williams, an executive assistant at ISF who is involved in the grant-review process. Williams says that, in all, 11,000 proposals were submitted to ISF; of these, he notes, 9,000 passed a formal screening of minimum requirements. "The criteria [were] rather strict, but even though the scientists in the former Soviet Union are confined by a crumbling technical and equipment structure, the human capital is quite incredible," Williams says. Criteria for scientists and their proposals included: * a degree equivalent to a Ph.D.; * at least five articles published in science publications from inside or outside Russia since 1988; * employment in scientific and/or educational institutions in the former Soviet Union; * proposed research to be conducted in the natural sciences; and * citizenship or at least six months' residence in the former Soviet Union. The Process Each proposal author was asked to provide the names of six reviewers familiar with his or her work from the relevant research community in the former Soviet Union, according to Irving Lerch, director of international scientific affairs at the American Physical Society (APS). While the comments of the reviewers were treated as referees' comments, "the panelists have the responsibility for making the final judgment," Lerch says. Each panel had a secretary from the former Soviet Union who was responsible for collecting the proposals, ensuring that they were submitted in the proper format, and submitting them to the appropriate panel in Washington, D.C., for peer review. The panelists are 220 scientists representing the U.S., Western Europe, Russia, the Ukraine, and other Baltic states. The meetings, held over the past two months, have been coordinated by staff members from the National Academy of Sciences, APS, the American Geophysical Union (AGU), the American Astronomical Society, the American Mathematical Society, and the American Chemical Society (ACS). Panelists were selected by the scientific societies, ISF's executive council, and an advisory committee in Moscow. "The professional organizations have been tremendously helpful in providing administrative assistance," says Williams. "While ISF is responsible for funding the selected proposals, the scientific societies have overseen the organization of panel meetings, maintained day-to-day contact with panel members, and helped administer the review process of proposals in specific disciplines." Eugene Bierly, director for education and research at AGU, says that the peer-review process did have some snags. "The process didn't work that well in terms of timeliness, and I suspect the reason was that our colleagues in Moscow did not have experience in getting so many proposals out in a timely manner," Bierly says. "Peer review is a new way of doing things to scientists in the former Soviet Union. I suspect at the next opportunity, things will go much smoother and faster." John Malin, administrator of ACS international activities, notes that the joint peer-review process is the largest ever undertaken by ACS or any scientific organization. "This [review process] means the ACS's Office of International Activities is handling a proposal load equal to that administered each year by the entire chemistry division of the National Science Foundation--a very tough job," Malin says. "Never before in grants administration has such an intense effort been organized and completed in so short a time." Lerch says his organization was eager to participate in the process because it will help preserve important scientific work in the former Soviet Union. "We believe there is a need to try and preserve at least the most important research grants there," he says. "Our view is that whatever we can salvage will be extremely important to science internationally." Scientists in Russia and neighboring Baltic states have long been hindered by a bloated science bureaucracy and a struggling economy. One year ago, Hungarian-born tycoon and philanthropist George Soros established ISF with the objective of providing scientists in the former Soviet Union with the opportunity to conduct research based on individual merit (B. Goodman, The Scientist, Jan. 11, 1993, page 3). Under the current structure, senior scientists were given money to distribute among junior colleagues. Malin, who recently returned to the U.S. from a visit to Russia, says that country's struggle to change to a market- oriented economy poses a major challenge to scientists. "Their scientific establishment was probably overbuilt," he says. "Now that they are learning about peer review, they are probably going to have to look at science in a more competitive way." Funds received by scientists will help defray costs for equipment, travel related to research, and salaries, Williams says. "Scientists in Russia and neighboring states report that the highest annual salaries are at about 45,000 rubles a month, the equivalent of about $500 a year," he notes. Malin adds that the work of researchers in the former Soviet Union has also been limited by an information blackout. "A serious problem we found in many of the proposals was a grave lack of contact with the latest scientific information," he says. "Because of the monetary problem with the devaluation of the ruble, they just don't have the buying power to purchase the latest science publications." To help solve that problem, U.S. science organizations are donating journals to libraries and other institutions around the former Soviet Union. ACS, for example, is donating up to 500 recent and current ACS journals, with a market value of about $500,000, to several Russian libraries across the former Soviet Union. Malin says the Fisher Chemical Co. of Pittsburgh has pledged to donate about $600,000 worth of chemicals to ACS, which in turn will give them to the N.D. Zelinski Institute of Organic Chemistry in Moscow. "We're excited about this process," Malin says. "There are some fine chemists in Russia and the other former Soviet countries, and ACS and ISF want to do all we can to help them." Williams says the combined efforts of ISF, the scientific societies, and individual scientists should help researchers in Russia and other newly independent states reach their full potential. "We think these grants and other programs will break the mold because they are opening up opportunities to more scientists based on merit rather than bureaucracy," Williams says. Tracey D. Webb is a freelance writer based in Philadelphia. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : PITTCON '94 `Greatest Show Ever' For Analytical Chemists AU : NEERAJA SANKARAN TY : NEWS PG : 4 "From a Handful of Scientists to the Greatest Science Show Ever!" is the slogan for the 1994 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy (PITTCON '94), to be held February 27 to March 4 in Chicago. Indeed, the annual meeting where companies and scientists meet to exchange information on the latest in analytical instrumentation and technique has expanded dramatically in 45 years. The first meeting, held in Pittsburgh in 1950, had 20 technical papers, three exhibits, and perhaps 100 conferees. This year's attendance is expected to top 30,000. Almost 1,000 companies will be displaying their newest products in about 3,100 booths at the exposition. Among these are companies like Danvers, Mass.-based Fisons Instruments Inc. and Perkin-Elmer Corp. of Norwalk, Conn., which exhibited their products at the very first Pittsburgh Conference, as well. Some of the original equipment shown by these and other companies will be on display at the "Antiquities Museum," a special exhibition of instrumentation that has played a significant role in the advancement of analytical chemistry. "The museum will give today's scientists the chance to review the advances in their fields and get back to their roots," says W. Richard Howe, president of PITTCON '94. "There has been a conversion from the earlier `wet' chemistry to modern analytical techniques. Imaging techniques are becoming more important now, as are computers and network systems," says Howe, who trained as a chemist and is currently an associate dean at the University of Pittsburgh. Old And New One of the items on display at the museum will be an original gas chromatograph, the GC Fractovap, Model GI, manufactured by Fisons Instruments and shipped over from the company's manufacturing site in Italy. "It [the Fractovap] is the size of a huge refrigerator," says Cathy Schaub, marketing communications manager of the company. "A modern GC sits on a bench top." Fisons will also have parts from its early mass spectrometers (manufactured in the United Kingdom) on display in the Antiquities Museum. A visit to Fisons' 4,400-square-foot booth--one of the largest exhibit booths at the exposition--will give conferees an idea of how technologies have evolved over the past 45 years. On display will be new instruments such as the VG Platform-II mass spectrometer for benchtop analysis, and the Quattro-II line of mass spectrometers, which has applications in areas of pharmaceutical and biopolymer analysis. In addition to the exposition, PITTCON '94 will feature more than 35 symposia with 1,800 papers and posters from specialists in various fields of analytical chemistry and spectroscopy. Organizers of this year's PITTCON created three miniconferences on the special subdisciplines of bioanalytical chemistry, quality management, and process analytical chemistry, "to personalize it for those who feel it [PITTCON] is becoming too big," says Vincent Conrad, the 1994 programs chairman, a research chemist at Pittsburgh- based CONSOL Inc. Research and Development, a member of the CONSOL Coal Group. Each of these miniconferences will contain all the elements of a full-fledged conference, including symposia, invited talks, posters, workshops, and panel discussions. Though it has long outgrown its original home of Pittsburgh, PITTCON retains its name because of its sponsors: the Society for Analytical Chemists of Pittsburgh and the Spectroscopy Society of Pittsburgh. All the members of the organizing committee are volunteers who hold regular full- time positions elsewhere. AT A GLANCE PITTCON '94, the 45th annual Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, is being held at the McCormick Place-on-the-Lake in Chicago from February 27 to March 4. The program will consist of 40 different symposia, with more than 200 invited speakers. In addition to these presentations, the technical program features more than 1,700 contributed papers and in excess of 40 short courses. Almost 1,000 companies dealing with analytical and spectroscopic instrumentation will be exhibiting their products in about 3,100 booths at the exposition, which will run from February 28 to March 3. New this year are three miniconferences on special issues, each including the components of a regular conference. MINICONFERENCE HIGHLIGHTS Bioanalytical Chemistry Symposia Monday, Feb. 28 * 8:30 A.M.: Techniques for Food Safety and Environmental Monitoring * 1:30 P.M.: Chemical Sensors: A Tribute to Wilhelm Simon (Simon is best known for his pioneering work toward developing ion-selective electrodes. He was a professor at the Swiss Federal Institute of Technology in Zurich until his death in November 1992.) Tuesday, March 1 * 8:30 A.M.: On-line Process Analysis on the Micron Scale * 1:30 P.M.: Pharmaceutical Analysts Poster Session Monday, Feb. 28 to Tuesday, March 1 Managing Quality Symposia Tuesday, March 1 * 1:30 P.M.: The ISO 9000 Series and Global Harmonization of Standards (The ISO 9000 is a series of standards established by the National Institute of Standards and Technology for addressing quality standards within organizations worldwide.) Wednesday, March 2 * 1:30 P.M.: Laboratory Accreditation, Atomic Absorption, and Atomic Fluorescence Panel Discussion Wednesday, March 2 * 8:30 A.M.: Quality Systems Poster Session Wednesday, March 2 Process Analytical Chemistry Symposia Wednesday, March 2 * 8:30 A.M.: The Role of the Analytical Laboratory in Process Analysis Thursday, March 3 * 8:30 A.M.: Transferring Analytical Technology from the Laboratory to the Plant Poster Session Wednesday, March 2 User-Manufacturer Information Exchange Sunday, Feb. 27 (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : PITTCON '94 TACKLES THE ENVIRONMENT TY : NEWS PG : 5 PITTCON '94 features several sessions focusing on the practical applications of spectroscopy and analytical techniques in environmental remediation and monitoring. Listed are some of the major symposia, workshops, and short courses offered at the conference. Monday, Feb. 28 8:30 A.M. Symposia * Techniques for Food Safety and Environmental Monitoring (bioanalytical miniconference) * Surface Mass Spectroscopy: Probing Real-World Samples Tuesday, March 1 8:30 A.M. Short Course * 234: Supercritical Space Extraction: Practical Considerations and Applications in Environmental Analysis Wednesday, March 2 1:30 P.M. Short Course * 209: Introduction to Environmental Mass Spectroscopy Thursday, March 3 8:30 A.M. Symposia * Advances in Purge and Trapping Gas Chromatography * Analysis of Environmental Biohazards * Environmental Mass Spectroscopy 1:30 P.M. Symposium * Indoor Air Measurements Workshop * Lead Laboratory Accreditation Friday, March 4 8:30 A.M. Symposium * Advances in Environmental Remediation Workshops * Detection and Quantitation Definitions and Issues * Field Water Sampling Using In Situ Solid Phase Extraction (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: NOTEBOOK ---------------------------------------------------------- TI : Whole Lotta Shakin' Goin' On TY : NEWS (NOTEBOOK) PG : 4 Seismologists for the New York State Geological Survey, a research arm of the State Museum in Albany, are searching for personal accounts, photos of damage, and other information related to four earthquakes that struck the state earlier in this century. The events occurred in the counties of Attica on Aug. 12, 1929; Warrensburg on April 30, 1931; Massena on Sept. 5, 1944; and Essex and Hamilton on Oct. 7, 1983. The data and documentation the scientists obtain will be compiled in an education package to be used by teachers around the state in their earth sciences classes. The museum already has an extensive collection of data on earthquakes in the region, dating back more than two centuries. In addition to educating students and teachers about these seismic events, the museum is trying to educate the public about earthquake risks in a region of the United States where that might not be a foremost topic. Anybody with information on the four quakes is requested to contact Gary Nottis of the survey at (518) 474-5816. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Bioscience Hotspots TY : NEWS (NOTEBOOK) PG : 4 The University of California, Davis, is fertile ground for the biosciences, according to a report by the National Research Council. Using 1991-92 academic year figures, the Summary Report 1992: Doctorate Recipients from United States Universities (Washington, D.C., National Academy Press, 1993) declared UC-Davis the national leader in awarding doctoral degrees in the biological sciences, with 126. Rounding out the top five in this category were the University of Wisconsin, Madison (120); the University of California, Berkeley (94); Yale University (82); and the University of Minnesota (79). (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Chaos In The Works TY : NEWS (NOTEBOOK) PG : 4 The Society for Chaos Theory in Psychology and the Life Sciences is calling for abstracts of papers, posters, and session proposals for its next annual conference, to be held June 24-27 at Johns Hopkins University in Baltimore. The society brings together researchers and practitioners interested in applying dynamical systems theory, self- organization theory, neural nets, fractals, and other forms of chaos and complexity theory to the study of nonlinear independent systems. Conference topics--around which the meeting will be organized, rather than disciplines--include chaos theory, methods, research, and application to all types of clinical practice; organization psychology; anthropology; neuropsychology; sociology; economics; education; and the humanities. Abstracts of 800 words or fewer should be submitted by March 15 to: Jeffrey Goldstein, 29 Hayes Rd., Amityville, N.Y. 11701. E-mail: goldstein@adlibv.adelphi.edu. For information about the society, contact Katherine E. Robertson, Society for Chaos Theory, P.O. Box 7226, Alhambra, Calif. 91802-7226. E-mail: 0005699249@mcimail.com. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : A Closer Look At Inner Space TY : NEWS (NOTEBOOK) PG : 4 Researchers at AT&T Bell Laboratories have developed a technique for detecting and identifying single molecules with more than 100 times the sensitivity of previous methods, the company announced. Their discovery has potential applications in numerous areas, including molecular engineering, analytical chemistry, cell biology, and genetics. Eric Betzig and Rob Chichester of the Murray Hill, N.J., firm's Physical Research Laboratory used a "near-field" scanning optical microscope to funnel a lightbeam, used to detect molecules, through a tapered optical fiber with an opening 100 billionths-of-a-meter wide, reducing the volume of a sample to the point at which single molecules can be detected repeatedly with improved sensitivity. The technique eliminates a long-standing problem of "background haze" from the rest of the sample by its ability to focus the probe beam to a dimension smaller than the order of the wavelength of the probe light, which is a billion times larger than the volume of the molecule itself. Betzig and Chichester's technique allows researchers to generate a precise map of the location of individual molecules at the surface of specimens. "As a bonus," Betzig notes, they can use the technique to determine the orientation of each molecule. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Funding For Minority Doctors TY : NEWS (NOTEBOOK) PG : 4 The Robert Wood Johnson Foundation's Minority Medical Faculty Development Program is a four-year, postdoctoral research fellowship for outstanding minority physicians who are committed to careers in academic medicine. The fellows chosen will receive a $50,000 yearly stipend and a $25,000 annual research grant to conduct research in areas of interest to them. The postdocs are open to minority physicians who are U.S. citizens and who have completed their clinical training. Applicants' materials will be reviewed and semifinalists will be chosen for interviews. The deadline for requests of application materials is March 22; the deadline for the receipt of the completed applications is April 15. For information, contact James R. Gavin III, Program Director, Minority Medical Faculty Development Program, 4733 Bethesda Ave., Suite 350, Bethesda, Md. 20814; (301) 913-0210. Fax: (202) 913-9022. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Networking For Human Rights TY : NEWS (NOTEBOOK) PG : 4 The AAAS Program on Science and Human Rights is calling on individuals concerned about persecution of scientists, engineers, health professionals, and science students to join the AAAS Human Rights Action Network, an electronic network accessible through Internet. The purpose of the network is to facilitate letter-writing and information campaigns directed at U.S. and international officials to help persecuted scientists around the world. There is no charge to join the network. Send the message "SUBSCRIBE AAASHRAN[first name, last name]" to the E-mail address listerv@gwuvm.gwu.edu. For information, contact AAAS, 1333 H St., N.W., Washington, D.C. 20005. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Brainstorm Awards TY : NEWS (NOTEBOOK) PG : 4 A Washington, D.C.-based organization, Intellectual Property Owners, is calling for nominations for its 1994 National Inventor of the Year award. The winners of the award, whose purpose is to increase awareness of current inventors and their benefit to society, will receive a $5,000 cash grant and a plaque. Winners will be honored, along with Distinguished Inventor runnersup, during a ceremony on Capitol Hill. An inventor is eligible for an award if the invention is covered by a U.S. patent, either was patented or first became available commercially in 1993, and was made in the U.S. Last year's award went to Gary H. Rasmusson and Glenn F. Reynolds of Rahway, N.J.-based Merck & Co. Inc. for Proscar, the first drug for treatment of prostate enlargement. The deadline for nominations is March 4. For information, contact National Inventor of the Year, Intellectual Property Owners, 1255 22rd St., N.W., Suite 850, Washington, D.C. 20037; (202) 466-2396. Fax: (202) 833- 3636. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: OPINION ------------------------------------------------------------ TI : A Scientist Reflects On His `21st-Century Odyssey' Within Biosphere 2 TY : OPINION PG : 11 Editor's Note: On Sept. 26, 1993, four men and four women emerged from two years inside a giant Arizona greenhouse described by the New York Times as "the world's largest and strangest test-tube experiment, a planet-in-a-bottle called Biosphere 2." Among those emerging was 69-year-old University of California, Los Angeles, researcher and professor of pathology Roy L. Walford, who for more than 20 years has studied the effects of low-calorie, nutrient-dense diets in animals. Walford continued this research in Biosphere 2, a glass-sealed, 3.15-acre space, replete with an ocean, grassy savanna, and 3,800 species of plants and animals. The difference was that this time, Walford's subjects were humans, rather than mice and rats. According to Walford and the other so-called biospherians, their two-year mission within the "closed ecological support system and research facility" was a resounding success. They count among their most significant accomplishments growing approximately 80 percent of their own food, recycling 100 percent of all human and domestic wastes as well as all water in their environment, and setting a new rec-ord for living in a closed system by surpassing the previous record (six months) set by Russian researchers in 1984. The mainstream scientific community, however, has been less congratulatory. A number of scientists have criticized the venture for setting aside rigorous scientific methods in its attempt to meet its goals of finding new ways to sustain human life in outer space and to combat pollution. Some scientists also have criticized the circus-like atmosphere surrounding the project. A number of attractions including a bookstore and espresso bar, a "Biosphere Cafe" and a "Biosphere 2 Postal Center--are near the experimental facility, which is located in the foothills of the Catalina Mountains north of Tucson in Oracle, Ariz. In a recent interview with Ridley Park, Pa.-based freelance writer Julia King, Walford described what it was like--as a scientist and as a human being--to leave Biosphere 1, the Earth, for two years and to live and work in the closed atmosphere of Biosphere 2. Following is an edited version of the interview. Q What were your scientific research goals in the biosphere? A First of all, I didn't plan a great deal of research when I went in. I figured I was just going to be a country doctor inside. However, a lot of strange things happened, and because of my background in research, I was able to seize upon these and make them into what you might call an experiment of nature. For example, we had projected that we would have 2,500 calories per day per person. But there we had only about 1,800 for the first six months [because of] low light, insects, pests, and so forth. The diet turned out to be a low-calorie, low-fat, and nutrient-dense diet. This is like the diet I've been studying for years in my research in animals, which extends life span, retards the rate of aging, and induces a number of physiologic changes. This is a big area in gerontology, and yet it happened just by a freak of chance that I would be positioned inside, taking care of these people, when the same kind of diet was forced upon them. So this, then, was an experiment of nature. Q Have you published any results of your studies? A My report on the first six months of work in the biosphere was published in the Proceedings of the National Academy of Sciences [89:11533, December 1992]. That became quite a famous paper because it was the first rigorous human study of this kind of nutrition. Q What did the diet consist of? A It was largely vegetarian--beans, grains, some fruits, mainly bananas. There was meat once a week, an egg about every two weeks, starches, potatoes, sweet potatoes, white potatoes, vegetables. There was a moderate amount of variety, but not a great variety, so the biospherians had to learn how to make a cuisine out of a limited amount of food, and that turned out quite well. Q I've read several articles in which other biospherians report being obsessed with food, having constant cravings, and so forth. I also understand that everyone inside lost quite a bit of weight. Did you experience any particular cravings? What kind of weight loss did you experience? A I maintain a fairly vegetarian diet generally, so I didn't go around craving food. Nothing in the area of oral consumption was a big problem for me. The average weight loss was 18 percent of body weight for men and about 10 or 12 percent for women. My personal weight was about 145 going in. The lowest point I reached was 119. When I came out I was 124. [Walford's height is 5 feet, 7 inches.] Q There have been rumors that you and the other biospherians were forced to secretly import food into the biosphere as a result of the poor growing conditions and low food supply. Was food imported? A None was imported. There was some stored food already inside--about two or three months' worth. Also, there were a lot of beans and so forth that were stock for planting, which, instead of planting, we ate. Q So, you could say that the planting beans were, in a sense, intended for consumption anyway? A Only if we could not make the grade agriculturally. I think we grew about 80 to 85 percent of the food we consumed. Q What was the focus of your dietary research? A What I measured in the biospherians were different physiologic changes, such as blood pressure and cholesterol. There was an enormous drop in cholesterol, low blood sugar, a low white blood cell count--all hallmarks of the same changes that occur in animals on such a diet. Q If these hallmarks are the same for humans as they are for animals, do you think other effects of the low-fat, low- calorie, nutrient-dense diet that you have observed in animals may also manifest themselves in humans? A One can infer that humans are acting in the same way. And if you wish to make that inference for the other things found in such a diet, you would also obtain in humans retardation of aging, health enhancement, and resistance to tumor development. That research has been continuing. I got a great deal more data on it during the next year and one- half [following the PNAS paper], and still more now that I've come out. In collaboration with the metabolic people at the National Institutes of Health, I'll be doing further work with frozen plasma serum that I drew inside. Q What were some of your other research pursuits inside the biosphere? A I've also done a fair amount of work on oxygen depletion because there was a period when the oxygen level in the biosphere declined to about 14 percent, as opposed to the outside atmosphere of 21 percent. Fourteen percent is the equivalent of being at about 13,500 feet up a mountain. In this way of thinking, our ascent up the mountain was about 700 feet per month, and this induced a long-term gradual hypoxia in the biospherians. I've done quite a few studies on that, which are not yet written up. They were interesting because the biospherians did not acclimatize in the usual way to that kind of oxygen depletion. Their hemoglobin levels didn't rise very much, and they did not experience the kinds of changes in blood chemistry that one might expect. I might say that I'm in the process of founding a new medical specialty, which you can call biospheric medicine. Q What is biospheric medicine? A Biospheric medicine is not just a kind of extension of space medicine, but will be a subspecialty in its own right and will deal with the practice of medicine or other sciences when you're in a situation where things go off in unpredictable directions. I predicted upon going into the biosphere that the main problems would be infection, trauma, and toxicity. In fact, none of these happened to any great degree. What happened was calorie depletion and oxygen depletion, and these were unpredicted. I think in the future, as we develop more biospheres, that other things will be happening that are not very well predicted. The biospheric physician has to have the kind of mind or kind of training that allows him to handle or adapt to the unpredictable. Q How do you respond to critics of biosphere research, which is regarded by much of the mainstream scientific community as less than rigorous? A That's not the case for my work. I don't think people have criticized my work. The [PNAS] paper is very respectable, of course, and people expect me to come out with more on that category. I think the criticism is directed toward the major focus of the biosphere, which is as an ecological laboratory doing scientific investigations into ecology. I think the criticism is premature. I think it's very clear-cut what needs to be done is to justify the project scientifically. It is a long-term project, so I think the other biospherians deserve an other year or two or three. But, then, if they don't come out with substantial papers in major journals, the criticism is correct. Q Did you know the other seven researchers prior to living with them for two years in Biosphere 2? A Sure. Everybody who went in had periods of training. Space Biospheres Ventures [the company that built and sponsored Biosphere 2] has a cattle ranch in western Australia where everybody goes to spend a season. That's a strenuous deal. I was stringing barbed wire across the landscape, pounding fence posts, and riding horses herding cattle all day for six weeks. I suppose you could call it a stamina test. Q What were your relationships like inside the biosphere? A Well, I think we had a community with four people and the other four were like some separate group. There was a fair amount of factionalism inside. I feel fairly close to three other people that I was in with and not so close with four. [The factionalism] caused a lot of problems, but I think everybody was so devoted to making the biosphere work that everything held together despite personal conflicts. There weren't any fights or heated arguments, but there were people who got on each others' nerves. But we overlooked that because we had a job to do. Q What was a typical day like in the biosphere? A Usually you get up at 6:00 or 6:30 A.M.; breakfast is at 8:00. You may have various things to do between when you get up and breakfast--milking goats or watering something or, in my case, drawing blood. I wanted pre-breakfast blood on the biospherians. After breakfast there was about two hours of heavy-duty agricultural work--weeding, trenching, carrying buckets, gathering animal fodder, and so forth. Then there might be another hour of crew work of some kind. One of the things I did quite a bit was repair and take care of the sensors. It was electrical work. There are more than 100 sensors for temperature, humidity, and so forth. In the afternoon I usually worked on medical or computer work. Other people would have agricultural work. One person would work in the rain forest, another in the terrestrial wilderness--doing research or propping up plants or planting. That would be it. Then dinner would be at 6:30 P.M., and the evenings were pretty much free time. Q What would you do for entertainment? A Well I should tell you everybody had to cook. Every eighth day you had to cook breakfast, lunch, and dinner for all eight people, and that was about a 10-hour job. Entertainment? Well, I'd read, watch television, talk to other people, something like that. I did a lot of video inside and I'm getting together an art exhibit with an outside performance artist that I interacted with while I was in the biosphere. We're doing an art piece that we're working up for a gallery exhibit called "The 21st Century Odyssey." Q And how would you communicate with the outside world? A E-mail, telephone, telecommunications, picturetel, videophone, fax . . . telepathy. All of the methods of communication. Q What was it like when you came out? A Re-entry was easy, but kind of confusing. When you settled into two years of pretty much of a routine, you knew where everything was, in a sense. So when we came out, everybody got kind of confused and forgot where they put this or that. For a few days or a week, everybody was losing their papers, their books. They couldn't remember where they put their keys and so forth. It was also funny to deal with money again. I felt like going to a restaurant, pulling out $20, and saying, "Bring me that much food." This is what a savage would do. We felt kind of like that, like you had come in from the jungle and all of a sudden you were in civilization. I think everybody had the experience that when they drove first in the car, the landscape went by so fast that it was kind of psychedelic. You had to shut your eyes. You weren't accustomed to taking in visual information and change that rapidly. Q Did anything change substantially in the world outside from the time you entered the biosphere? A I don't think anything really took me by surprise because we had television and communications. Of course while we were in, the Russian Empire fell, the economic scene deteriorated--stuff like that--but I expected it. Q What's your next adventure? Would you go back into the biosphere? A Not a second time. But it was worthwhile to do it once. For my next adventure, well, I have a number of books to write. I have a lot of work to do in getting up an art exhibit. I used to publish quite a bit of journalism, a moderate number of short stories and poetry. Now I have some more serious books I want to write. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Women In Science: Much Has Been Accomplished, But Much Remains To Be Done AU : NEAL LANE TY : OPINION (COMMENTARY) PG : 12 One of the most important and most debated issues facing the scientific community today is that of underrepresentation by women of all ethnic groups. I address the topic here in the hope that increased discourse will lead to increased understanding. The Nov. 15, 1993, issue of The Scientist contained a page- one article (R. Twombly, "Congresswomen Take NIH And NSB To Task Over Gender Bias") that correctly noted that women are underrepresented at the top levels of national science policy. Since that article appeared, President Bill Clinton, in keeping with his commitment to increase the number of women and minorities in positions of federal responsibility, has nominated Shirley Malcom to fill the only vacancy on the National Science Board (NSB). Malcom currently is head of the directorate for education and human resources programs of the American Association for the Advancement of Science (AAAS). Upon her confirmation by the Senate, she will be an outstanding addition to NSB. Yet, as important as it is to have highly visible role models as participants at the top levels of science and technology policy, the task we face is much broader. We must redouble our efforts and continually push to increase the number of qualified women at all levels of involvement in science, mathematics, and engineering. As a society, we must undertake these efforts because it is the right thing to do. For those who need a more pragmatic argument, demographic trends indicate that, between now and the turn of the century, nearly two-thirds of new entrants into the work force will be women. The jobs potentially available to these new working women will require higher skill levels in science, engineering, and mathematics than ever before. These statistics are quite well known; what is more difficult to identify and change are the root causes of the cultural attitudes that continue to limit the full potential of women in science and engineering. While we consider the challenges and work ahead, let us not be blind to the progress that has already been made. According to 1993 National Science Foundation statistics, during the most recent 10-year period for which data are available, the proportion of women receiving Ph.D.'s in science, mathematics, and engineering increased from 22 percent to 27 percent. In engineering, the proportion of women earning doctorates nearly doubled, from 4 percent in 1981 to 7.7 percent in 1991. In a few scientific disciplines today--such as psychology and agricultural and biological sciences--a higher percentage of undergraduate degrees are being awarded to women than to men. This movement needs to be encouraged and expanded. Although society is moving beyond the simplistic stereotypes regarding women (and members of other underrepresented groups), many of the values and assumptions that underpin those stereotypes remain. In spite of some notable progress, there are still problems at the top. Most of our scientific and technical institutions, including NSF, are managed primarily by men. And many men, I believe--no matter how concerned and sensitive they may be--have great difficulty understanding the obstacles that women have had to overcome to pursue careers in science, mathematics, and engineering. And these obstacles are compounded for women of color. We simply cannot know the discouragement that girls often experience in their homes and schools throughout their childhood, only to be followed by similar negative experiences in colleges or universities--and even in the workplace, provided they can stay with it. If we did understand better, perhaps unpleasant and even hostile learning and working environments would be rare. Perhaps the structures of our institutions would long ago have been changed. Perhaps the glass ceilings would have disappeared. Why is it so difficult to understand? Why can't we do more to change the climate and structure of our working environments? It's time we found out. Otherwise, women are not likely to be attracted in greater numbers to careers in these fields that are so important to the future of the nation. And that would be a tragedy for all of us. I call on all members of the science, mathematics, and engineering community to accelerate progress to provide women the same career opportunities as men. Let us work together to share approaches that have been shown to be effective and to explore new ideas. I invite readers to share with me their ideas on this matter--to let me know what more NSF can do. Neal Lane is director of the National Science Foundation, 4201 Wilson Blvd., Arlington, Va. 22230. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: LETTERS ------------------------------------------------------------ TI : A Scientific Tradition AU : WILLIAM RAINE TY : OPINION (LETTERS) PG : 12 The endeavors undertaken by Peyrets Goldmacher and the Association of Engineers and Scientists for New Americans (P. Goldmacher, "Let's Give Russian Scientists The Chance To Succeed--And Contribute--In The U.S.," The Scientist, Oct. 4, 1993, page 12) deserve further consideration. Despite Goldmacher's plea, the task of job hunting should be easy for them. This can be understood by looking at the refugees' U.S. counterparts, such as myself. I am a product of an American academic institution imbued with only two centuries of scientific tradition, for even though Georgetown University is the oldest Catholic institution of higher learning in the United States, ours is a young country. While English is my second language, I learned it at a young age and thus speak it without too much difficulty. This skill was put to good use by teaching physics at my alma mater, first as a graduate student and subsequently as a postdoctoral fellow. Unlike the Russian scientists with "doctorat nauk" degrees Goldmacher mentions, I will not be able to do considerable research beyond my Ph.D. because the number of applications for each assistant professor or postdoctoral position at even the least prestigious U.S. academic institutions is in the several hundreds. While most of my U.S. colleagues (many of whom are first- generation Americans themselves) possess far nicer c.v.'s than mine, some of them have found that they too will be forced to sit on the sidelines. The truth, which U.S. universities are only beginning to recognize, is that scientists from Europe and the former Soviet Union survived a grueling process of elimination, which often begins in grammar school. Those pedagogical methods are simple and efficient, ensuring finalists of the highest quality for a preselected number of slots designed to prevent a glut in their market. The U.S. market, on the other hand, has been glutted for 30 years because, rather than hold tough examinations such as the Tripos, the Concours des Grandes Ecoles, or the types of examinations made famous by Lev Landau's school of physics, we merely required comprehensive qualifying examinations at the master's and Ph.D. levels. Two generations of younger Americans had been aggressively encouraged to become scientists. In May, as a result, I shall be obliged to leave physics, that which I love most and to which I have devoted all the youthful years of my life. In May, I will be happy to answer Goldmacher's call for volunteers to aid emigre scientists in the affirmative. WILLIAM RAINE Department of Physics Georgetown University Washington, D.C. 20057 (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : Animal Research Data AU : DONALD J. BARNES TY : OPINION (LETTERS) PG : 12 Ron Kaufman's report ("Scientific Merit, Rather Than Morals, Guides Use Of Animals In Lab Research," The Scientist, July 12, 1993, page 1) and Martin L. Stephens's letter (The Scientist, Nov. 1, 1993, page 12) state that biomedical researchers choose their experimental subjects on a scientific rather than a moral standard. This is simply not true. There is no doubt that humans are the most scientifically valid surrogates for other humans. The dilemma is in the scope of one's ethical purview--that is, nonhuman animals are simply not included in the ethical systems of many biomedical researchers. Herein lies the crux of the debate; when one expands one's circle of compassion to include all animals, alternatives must be found for entertainment, clothing, dietary needs, and even biomedical research. Through the National Anti-Vivisection Society's support, the International Foundation for Ethical Research is actively seeking means of advancing the goals of biomedicine without causing stress, pain, suffering, and death to other creatures. Is it not axiomatic that moral considerations should necessarily take precedence over scientific hypotheses? DONALD J. BARNES Director of Education National Anti-Vivisection Society 53 W. Jackson Blvd. Chicago, Ill. 60604-3795 (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: RESEARCH ---------------------------------------------------------- TI : RU 486 Research Forges On, Despite Political Hurdles AU : MYRNA E. WATANABE TY : RESEARCH PG : 14 It has been a year since President Bill Clinton, in one of his first major acts, called for an import alert on the drug RU 486, commonly called "the abortion pill," to be reconsidered. The alert, imposed by the Bush administration in 1991, allegedly in response to political pressure from conservative and right-to-life groups, prohibits the importation of the drug into the United States for personal use. Since then, agreements have been reached between the drug's French manufacturer, Paris-based Roussel-Uclaf, and the New York-based Population Council to begin clinical trials of RU 486 as an abortifacient in the U.S. Furthermore, the head of Roussel has met with David Kessler, the chief of the U.S. Food and Drug Administration, to discuss the drug. Nonetheless, the ban still remains in effect, until such trials result in FDA approval of the drug. At the time the embargo first went into effect, biomedical researchers in different fields had been studying the drug's promising mechanisms and therapeutic effects in nonabortifacient uses for several years--as a potential treatment for cancer and immune system and neurological disorders, and as a contraceptive. The ban, many of these scientists feared, would have a chilling effect on their studies, limiting availability of the drug and support for their work. But that did not happen, according to many RU 486 researchers, with supplies of the drug and government funding for research remaining essentially unchanged from before the embargo. Given the Clinton administration's supportive attitude, it would have been reasonable to expect that an upsurge in studies and trials might have occurred over the past year. Yet very little new research is being done on the drug in the U.S. and there has not been a significant increase in the modest numbers of projects receiving federal support. Scientists studying the drug, as well as science agency administrators, have several theories on why this is so. A few researchers are concerned that the stigma surrounding the drug because of its abortifacient uses may have carried over to non-abortion-related uses of the compound. Some even worry that this reticence to carry out research may extend to Roussel itself, which is the only source of the drug and a major supplier of research funds for it. And yet still others believe RU 486 is being neglected because it is perceived as a "women's drug," suffering the same lack of federal funding as studies of other women's diseases. On the other hand, some scientists and some agency officials believe that the main reason for the nonproliferation of studies is that similar drugs are showing equal, if not greater, promise. Whatever the case, several investigations with the drug are under way in a variety of biomedical areas. The State Of RU 486 Research Clinton's call for reevaluating RU 486 opened the way for scientific comment on possible clinical uses of the drug. The Institute of Medicine (IOM) of the National Academy of Sciences was commissioned by the Henry J. Kaiser Family Foundation to write a report on the scientific status of research with RU 486 and similar antiprogestin compounds. The distinguished scientific panel made recommendations for further studies in the report, which is based, in part, on a two-day seminar held in Washington, D.C., last spring and attended by some of the top researchers using RU 486 (M.S. Donaldson, et al., eds., Clinical Applications of Mifepristone (RU 486) and Other Antiprogestins: Assessing the Science and Recommending a Research Agenda, Washington, D.C., National Academy Press, 1983). The panel concluded that antiprogestins have many potential applications aside from abortion--as contraceptives, in uterine diseases, in breast and ovarian cancers, in Cushing's disease, and against nonmalignant menin-giomas, among others--but needed much additional study. Some of these studies are ongoing and others are just beginning, but they give an indication of extensive medical research potential for a drug that would have been consigned to public obscurity until approval were it not for the abortion controversy. RU 486 (or mifepristone, as it is called generically) and similar antiprogestins interact with progesterone receptors. The effects of these compounds are broad, and indications are that they may be used in treatment of numerous diseases, many unrelated to reproductive function. RU 486 also has a strong antiglucocorticoid effect that makes it useful in treating diseases in which glucocorticoid receptors can be blocked (see accompanying story). Kathryn Horwitz, a molecular endocrinologist at the University of Colorado School of Medicine in Denver and one of the foremost researchers on the role of hormone receptors in breast cancer, explains that breast cancers grow in response to estradiol and progesterone. Antiestrogens, like tamoxifen, are used clinically to inhibit growth of the cancer tissue. Now, Horwitz says, it is important to study the role of antiprogestins, such as RU 486, to complement the suppression of the estrogenic component. She expects that in the future, antiestrogens and antiprogestins could be combined in a treatment regimen. "Right now, we have very little clinical information on the antiprogestins alone," she says. Horwitz is one of a few researchers receiving funding from the National Cancer Institute (NCI) for her studies on breast cancer cells and RU 486. Some clinical evidence of the drug's potential use with breast cancer patients may be forthcoming. A very small test of the drug in women with advanced breast cancer will be conducted at Long Beach Memorial Medical Center in California. The one Phase III clinical trial supported by NCI is a study of the effects of the drug on nonresectable meningioma. Meningiomas are nonmalignant, recurring growths on the meninges, or the covering of the brain, that lead to death. According to Steven Grunberg, who is coordinating the trial and is chief of the hematology and oncology unit at the University of Vermont College of Medicine in Burlington, 70 percent of meningiomas, whether in male or female patients, have high levels of progesterone receptors. RU 486, as an antiprogestational agent, would be able to block the receptors on the tumors, discouraging tumor growth. A pilot study, begun in 1987 while Grunberg was at the University of Southern California, showed positive results. The trial is coordinated through the Southwest Oncology Group (SWOG) in San Antonio, Texas, and institutions throughout the U.S. are participating. In a number of small clinical tests, Samuel S.C. Yen of the University of California, San Diego, has been studying the effects of RU 486 on two very common, nonmalignant, painful conditions related to uterine tissue: endometriosis and leio-myoma. Current pharmaceutical regimens have potentially serious side effects and are therefore limited to the short term; minimally invasive surgery also results in only temporary relief. The only cure is hysterectomy. Thus, a drug that can be administered on a long-term basis with minimal side effects would become the preferred method of treatment. Women treated in trials with RU 486 showed greater improvement than is usually seen with other drugs, Yen says. One of the research projects is based on the drug's effectiveness in promoting uterine contractions. Marilynn Frederiksen, an obstetrician-gynecologist with Northwestern University Medical School in Chicago, has had some success in clinical studies stimulating labor using RU 486 in women carrying dead fetuses. She currently is negotiating with Roussel for a clinical study on the kinetics and efficacy of the drug in inducing labor in cases of stillbirth. RU 486 has several mechanisms of action. One of these is as an antiglucocorticoid. George Chrousos and Lynnette Kaye Nieman of NIH's National Institute of Child Health and Human Development (NICHD) are using RU 486 to treat some patients with a certain subtype of Cushing's syndrome, a disease characterized by excess production of adrenocorticosteroid hormones, such as cortisol. Because glucocorticoids are important in suppression of inflammatory response, Chrousos has used the drug in other basic research on the action of glucocorticoids in humans. The antiglucocorticoid function of the drug has resulted in another clinical study to determine if RU 486 will foster memory improvement in Alzheimer's disease patients. This trial, to total 40 patients, is being carried out by Nunzio Pomara, director of the Geriatric Psychiatry Center of the Nathan Kline Institute for Psychiatric Research in Orangeburg, N.Y., at the New York University School of Medicine, where he is a research associate professor of psychiatry. Pomara explains that in animal studies, high endogenous and exogenous corticosteroid levels have been found to damage the hippocampus. He says that some Alzheimer's patients have increased cortisol levels that cannot be pharmacologically decreased, and many Cushing's syndrome patients--who have high cortisol levels--show signs of cognitive and memory deficits, some even having dementia. Thus, Pomara reasons, blocking glucocorticoid receptors with RU 486 in Alzheimer's patients may decrease damage to the hippocampus. Why So Little New Research? With such fascinating and diverse projects using the drug, the question arises as to why so few projects are being funded by the government. Almost all the researchers contacted for this story believe that the political fallout because the drug's major use is in inducing abortion is, at most, a mild undercurrent in terms of reduced federal support for RU 486 projects. Because the drug is treated as an unproven new drug by FDA, investigators must file an investigational new drug application (IND) in order to obtain supplies of it. But these scientists say that FDA has, by and large, not inhibited their ability to get the drug and has approved their INDs. NCI has been funding basic research on RU 486 for several years. The institute's total support, however, is small. For example, in 1992 the agency disbursed $281,000 in grants; in 1993, $276,000 in grants and $157,000 for the clinical meningioma trial. When asked why NCI is not funding more research with the drug, Michael Friedman, associate director for the Cancer Therapy Evaluation Program at NCI, explains, "There was an important need to evaluate this agent in patients with meningioma and so we were happy to help investigators perform a Phase III study. For breast cancer and other indications, the company, that is, Roussel-Uclaf, showed us all the data they had. Although some patients seem to have benefited from the agent, it looked to be no different than other hormonally active agents." Friedman adds, "We are reevaluating this position regularly so that if new information becomes available, our enthusiasm might change." Ana Murphy, director of the division of reproductive endocrinology at Emory University School of Medicine in Atlanta, who has been studying the drug for endometriosis and fibroids along with UCSD's Yen, has another theory. She believes that RU 486 is being treated as a drug for women, and "there's no money in the budget for a lot of women's diseases." Although some researchers have had very productive experiences working with and receiving funding from Roussel, others fault the drug company. They say that political and economic pressures within the company and from its parent firm, Hoechst AG in Berlin, may be adversely affecting its ability to fund these projects. They also say that other companies, such as Berlin-Teknika in Belgium, have other drugs that may be better than RU 486. Thus, most projects have been funded, at least in part, by researchers' own sources. Yen, optimistically, submitted a grant application to NIH, but he doesn't expect funding because of budgetary problems. Meanwhile, the import ban on personal use that sparked the controversy involving RU 486 will continue until it receives FDA approval. "The FDA's position," according to spokesman Lawrence Bachorik, "is that somebody should submit an NDA [New Drug Application] so we can evaluate the data." Myrna E. Watanabe is a biotechnology consultant based in Yonkers, N.Y. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : RU 486 AS A RECEPTOR BLOCKER AU : Myrna E. Watanabe TY : RESEARCH PG : 14 RU 486, discovered more than 10 years ago, is an antiprogestin. Antiprogestins attach to progesterone receptors on the cell membrane in competition with the steroid hormone progesterone. When progesterone binds with a receptor, a cascade of biochemical events leads to DNA transcription. An antiprogestin, once bound to the progesterone receptor, suppresses transcription. In the uterus, this leads to hormonal and biochemical changes that can prevent implantation of a fertilized ovum or, if implantation has occurred, interrupt the pregnancy. Because the uterus is not the only site in the body that has progesterone receptors on its cells, other medical uses of antiprogestins are evident. The most prominent possible uses are in breast or ovarian cancers that may respond by growing in the presence of estrogens and progesterones. RU 486's other potential clinical uses result from its ability to block glucocorticoid receptors in cells throughout the body. They are particularly important in illnesses like Cushing's syndrome, in which the adrenal cortical hormone, cortisol, which affects carbohydrate and protein metabolism, is produced in excessive amounts. --M.E.W. SUGGESTED READING G.P. Chrousos, P.W. Gold, Journal of the American Medical Association, 267:1244-1252, 1992. G.P. Chrousos, et al., The Adrenal and Hypertension: From Cloning to Clinic, pages 273-284, eds. F. Mantero, et al., Serono Symposia Series, New York, Raven Press, 1989. M.T. Gomez, G.P. Chrousos, Cushing's Syndrome, Current Therapy in Endocrinology and Metabolism, pages 134-137, ed. W. Bardin, Philadelphia, B.C. Decker, Inc. K.E. Greene, et al., Fertility and Sterility, 58:338-343, 1992. L.M. Kettle, et al., Fertility and Sterility, 56:402-407, 1991. A.A. Murphy, et al., Journal of Clinical Endocrinology and Metabolism, 76:513-517, 1993. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: HOT PAPERS ---------------------------------------------------------- TI : CELL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 H.Y. Lin, X.-F. Wang, E. Ng-Eaton, R.A. Weinberg, H.F. Lodish, "Expression cloning of the TGF-b type II receptor, a functional transmembrane serine/threonine kinase," Cell, 68:775-85, 1992. Herbert Y. Lin (Netherlands Institute for Developmental Biology, Utrecht): "Transforming growth factor-b1 (TGF-b1) was initially identified about a decade ago as a prototypic negative growth factor, arresting cell growth at the G1 to S transition of the cell cycle. More than 20 other related members of this TGF-b superfamily of ligands have now been described. They appear to play important roles in many areas of biology, including development, embryogenesis, and morphogenesis, as well as in cell growth. Understanding how TGF-bs achieve their potent effects would greatly enhance our understanding of these processes and may provide insights into diseases such as cancer. "In our work we describe the expression cloning of the type II TGF-b receptor and demonstrate that the receptor has serine/threonine kinase activity. The cloning of the type II receptor, which proved to be similar to the activin type II receptor (L. Mathews and W. Vale, Cell, 65:973-82, 1991), provided the heretofore unknown first clues to the first steps of TGF-b signal transduction. Our results directly implicated serine/threonine phosphorylation as the initial event in TGF-b signal transduction and raised the following question: What are the immediate downstream targets for the type II receptors? "Recently, a type I TGF-b receptor has been cloned (R. Ebner, et al., Science, 260:1344, 1993), and it is also a receptor serine/threonine kinase. Surprisingly, the type I receptor appears to require the type II receptor in order to bind TGF-b, and type I and type II receptors appear to interact in a hetero-oligomeric complex (J. Wrana, et al., Cell, 71:1003, 1992; M. Inagaki, et al., Proceedings of the National Academy of Sciences, 90:5359, 1993). Even more surprisingly, the TGF-b type III receptor appears to enhance the ability of the type II receptor to bind TGF-b (F. Lopez- Casillas, et al., Cell, 73:1435, 1993). The details of how these receptors interact with each other remain problems for future work. "What makes this field particularly exciting at the moment is that the signal transduction system used by receptor serine/threonine kinases appears to be so different from other known signal-transduction systems that each new finding has turned out to be unexpected and unpredicted: true surprises. Future discoveries will no doubt be as surprising and exciting." (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : MOLECULAR GENETICS TY : RESEARCH (HOT PAPERS) PG : 16 J. Buxton, P. Shelbourne, J. Davies, C. Jones, T. Van Tongeren, C. Aslanidis, P. de Jong, G. Jansen, M. Anvret, B. Riley, R. Williamson, K. Johnson, "Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy," Nature, 355:547-8, 1992. Keith Johnson (Department of Anatomy, Charing Cross and Westminster Medical School, University of London): "Myotonic dystrophy (DM) is the most common form of adult-onset muscular dystrophy and is inherited as an autosomal dominant disorder with the mutation mapping to chromosome 19. Several features of the phenotype associated with DM were extremely puzzling to geneticists prior to the discovery of the mutation that causes it, given that a single gene defect was suspected of underlying it from its Mendelian mode of inheritance. DM has a highly variable age of onset within families, usually with earlier onset in subsequent generations (a phenomenon known as anticipation). In a single family a range of symptoms can be seen in differently affected individuals with widespread variation in the symptoms' severity. Of note is the almost exclusively maternal transmission of the most severe form of the disease, congenital DM. Coupled with these observations was the fact that there are no sporadic cases of DM, indicating that all affected individuals inherit their disorder. "At the end of 1991, thanks to an international collaborative effort, the region in which the gene was located had been narrowed down sufficiently for a detailed search to be undertaken. This search threw up a DNA probe from the candidate region that detected alterations in the size of DNA fragment from DM patients compared with the control group. This finding was similar to the reported mutations underlying Kennedy's disease and fragile X mental retardation, which were both due to expansions in copy number of trinucleotide repeats. Soon after the publication of three papers describing the instability of the region in DM patients (this paper as well as C. Aslanidis, et al., Nature, 355:548-51, 1992; and H. Harley, et al., Nature, 355:545-7, 1992) came the confirmation that this was indeed the third example of trinucleotide repeat instability. The repeat altered in a way that correlated very well with the phenomenon of anticipation, the repeat getting longer in earlier-onset cases. There are now several cases of DM reported that show the repeat can also contract on transmission and that this almost invariably happens when inherited through the paternal germline. Since the DM mutation discovery two more inherited disorders, Huntington's disease and, most recently, a form of spinocerebellar ataxia (SCA1) have been found to have a similar underlying mechanism. There is evidence that a number of other diseases may have a similar etiology and this form of mutation probably represents a large and important class of inherited disorders. The term `dynamic mutations' has been coined to describe this form of mutation. "The discovery of the DM mutation immediately led to more informative prenatal and presymptomatic diagnoses for those at risk, although the long-term goal of being able to intervene in the disease pathway and call a halt to its progression seems to be still a long way off. The reason for this is that dynamic mutations represent a totally new and unexpected form of mutation. Although they are inherited from one generation to the next in a Mendelian fashion, the way in which they rapidly expand over one or two generations is clearly non-Mendelian. We still have a long way to go in understanding how expansion of repeats, in the case of the DM mutation in the 3-untranslated region of a putative protein kinase-encoding gene, leads to the disease phenotype. Indeed, there are contradictory reports about the effect of the repeat on expression of the protein kinase gene in the case of DM (C. Ezzell, Journal of NIH Research, 5:54-8, 1993)." (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : MEDICINE TY : RESEARCH (HOT PAPERS) PG : 16 W.O. Spitzer, S. Suissa, P. Ernst, R.I. Horwitz, B. Habbick, D. Cockcroft, J.-F. Boivin, M. McNutt, A.S. Buist, A.S. Rebuck, "The use of a-agonists and the risk of death and near death from asthma," New England Journal of Medicine, 326:501,6, 1992. Samy Suissa (Department of Epidemiology and Biostatistics, McGill University, Montreal): "Asthma is a common disease that affects 5 percent to 10 percent of people. Numerous effective medications have been developed to treat this disease, by way of either bronchodilation or inflammation reduction. In the 1980s, the mainstay of asthma therapy was based on bronchodilators, which included theophyllines and a-agonists. Extremely effective, these latter drugs were used rather liberally, to the point at which they were available without prescription in some countries. Unexpected increases in asthma mortality in several parts of the world have induced investigations of the possible role of drug therapies in these mortality patterns. "In 1989, a case-control study from New Zealand suggested that one of these a-agonist bronchodilators, namely fenoterol, was associated with a higher risk of death from asthma, while the other popular one, salbutamol, was not. We and other scientists were puzzled by this premise that two drugs from the same class could show different risk profiles. Conscious of the limitations of this type of epidemiologic study design, we decided to conduct our own investigation. "Using a more rigorous population-based design, we found that the excessive use of any or all inhaled a-agonists, including fenoterol and salbutamol, was associated with fatal and near-fatal asthma. A significant number of the 12,300 asthmatics studied were using inordinate amounts of inhaled a-agonists, much more than the maximum recommended quantity, and these formed the basis for the elevated risks we found. It was clear that these drugs had become victims of their remarkable effectiveness. "Our study generated great attention primarily because it put in question the current practice of asthma therapy. Instantly, the uncontrolled use of inhaled a-agonists became no longer admissible. Physicians and patients were now to monitor the use of these drugs and, if this use increased, indicating worsening disease, to supplement therapy with anti-inflammatory inhaled corticosteroids. The latter indication has since been confirmed by our subsequent analyses of the data (P. Ernst, et al., Journal of the American Medical Association, 268[24]:3462-4, 1992), which suggest that the use of inhaled corticosteroids reduces the risk of fatal or near fatal asthma 10-fold. Our study has in essence substantiated the recent international guidelines on the management of asthma." (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: TOOLS & TECHNOLOGY ---------------------------------------------------------- TI : New Chromatography Software Keeps Pace With Hardware AU : CAREN D. POTTER TY : TOOLS & TECHNOLOGY PG : 17 As the power of personal computers has grown, so has the capability of chromatography data-handling software. Basic computer-mediated functions, such as instrument control, data acquisition and analysis, file management, and report preparation all have become increasingly available over the last 10 years or so to the wide array of chemistry disciplines that depend on the chromatograph for sample analysis. Now, the current crop of chromatography software also offers such up-to-the-minute enhancements as user-friendly graphical interfaces, the ability to run a number of different experimental programs simultaneously (called multitasking), and the option of transferring chromatography data to other application programs. Chromatography is an analytical process in which gases, liquids, or solids in a mixture or solution are separated by one of several related techniques--by selective adsorption on a medium in a column, for instance--in order to detect and quantify the component substances. Support for several relatively new analysis tools--such as photodiode array detectors, also called diode array detectors--is available. Another significant enhancement is the software's ability to run on a network in what is called a "client/server" configuration. The significance of these recent advances varies according to the particular needs of the laboratory using the system, but choices are expanding. "The biggest benefit of using personal computers in chromatography is the ability to store the actual data points that describe the [charted] peaks," says Greg Murphy, group manager for network products at the Waters Chromatography Division of Millipore Corp. in Milford, Mass. With the data points on file, rather than only the printed or displayed chart results, researchers can later integrate the data in different ways, even trying alternative analyses, Murphy says. For example, one of the most difficult analytical tasks in chromatography is interpreting so-called noisy peaks, or peaks that are not clearly defined, according to scientists and instrument vendors. Today, most chromatography data systems provide mathematical peak-fitting functions that assist in better integrating data so peaks are more clearly visible. Chromatography originally required laboratory workers to measure with a ruler the peaks of a chromatograph as printed by strip chart recorders and to then calculate the area under the peaks for analysis. Sometimes technicians carefully cut these paper peaks out for weighing on an analytical balance. In the early 1970s, devices called computing integrators arrived and were welcomed as replacements for strip chart recorders. Computing integrators drew chromatographs on-screen and were able to calculate the areas under curves for the researcher. Then, in the 1980s, personal computers (PCs) began to take over these chores from computing integrators and have since steadily added capabilities. These computers are now a routine sight in labs that perform chromatography. PC-based chromatography data systems improved on computing integrators by performing more functions. Today, while many labs use sophisticated chromatography data systems provided by the same vendor that supplies their chromatographs, there is also the option of buying a stand-alone software system able to support instruments from many vendors. More Accessible Software Perhaps the most obvious change in chromatography data software in recent years is the way it looks on screen. This change is due to the nearly wholesale adoption, by both users and developers of software, of the Windows operating system with its graphical user interface. Instead of the sometimes forbidding text-based screens of the MS-DOS operating system and programs written for it, there are now colorful screens featuring pull-down menus of program options, images called icons to denote files and applications, and multitasking. These enhancements are more than cosmetic, scientists say. "It's definitely easier to work through icons and menu boxes," says Nicholas Milner, a senior scientist at Hoffmann-La Roche Inc. of Nutley, N.J. However, as Milner points out, it's easier only after users have become familiar with Windows. Many--but not all--lab workers have used Windows previously in some other application. If not, they are required to learn two things at once. "Initially, it's difficult to deal with both the complexity of the chromatography software and the newness of Windows," Milner says. Milner uses the Millennium 2020C/S chromatography data system from Waters. In his lab, Millennium is used with eight high-performance liquid chromatographs (HPLCs), also from Waters. In one pharmaceutical study involving food- producing animals, a PC running Millennium controls either one or two instruments, as needed. Milner says that the biggest benefit of the Windows interface for his group is the multitasking ability to control two instruments simultaneously by opening two windows on the screen. Within Millennium, multitasking allows multiple-instrument control, but this feature is not confined to one software application. In a laboratory, for instance, multitasking also would permit a technician to open a word processing program and prepare a report while the same PC simultaneously runs the chro- matography data system to control instruments and acquire data. Another benefit of Windows is the ability to take data from one application and move them into another. This feature is useful for transferring chromatography data to a spreadsheet, for example. There is, however, a more powerful way to move and manipulate chromatography data, through a client/server network architecture. In a client/server network configuration, PCs serve as the "clients" and handle local tasks such as running chromatographs. A larger central computer system is the server and functions as a data repository. Data from the clients travel by network to the server. When a comprehensive data-handling system such as a laboratory information management system (LIMS) is in use, for example- -not uncommon in a networked laboratory--the LIMS will reside on the server, taking in data from the client PCs. Some advantages of the client/server set-up are security and a better use of computing resources. Having a central data repository is more secure than keeping data on individual PCs, and PCs are less likely to be overloaded beyond their storage or computing capacities. Also, having data from many different instruments stored in one location makes report preparation much easier because access to data is greatly simplified. "The biggest benefit [of the client/server approach] for us," says Tom Weber, a biochemist at Synergen Inc., a biotechnology company in Boulder, Colo., "is the ability to transfer data over a network from the PCs to a server and into our LIMS system. When you're running hundreds of samples a week, this is a big time-saver. But it also means that an analyst doesn't have to type all the numbers [into the LIMS] and possibly make mistakes." Chromatography is used at Synergen for analysis of protein purity and for degradation studies of protein-based pharmaceuticals. Sixty HPLCs from Beckman Instruments Inc. of Fullerton, Calif., are used along with five to 10 HPLCs from Hewlett-Packard Co., Palo Alto, Calif. System Gold, a chromatography data system from Beckman, is used to operate the Beckman instruments, and Hewlett-Packard's ChemStation is used with the Hewlett-Packard devices. The client/server architecture is well suited to larger operations such as Synergen's, Weber says. Even midsize labs processing many samples per day can take advantage of similar configurations. In a lab with only a few instruments or one instrument processing only a few samples in the course of an experiment, however, the client/server architecture may represent excess capacity. The client/server architecture improves on this older approach by replacing single-function "boxes" with multipurpose PCs. The client/server architecture may also be beneficial to Milner's work at Hoffmann-La Roche. Milner, who is looking for a way to resolve his laboratory's data-management problems, thinks the client/server approach has pos- sibilities. "File management would be easier with a centralized system," he says. "One person could be responsible for backing up data on a regular basis. And, when you update a program, you would load one version of the new software instead of eight or nine." The current practice in Milner's group is to store chromatograph data on the PC hard disks, and then back up the data on floppy disks. "That's a laborious process because the software incorporates a [spreadsheet] database, and you need to record an entire project rather than an individual chromatogram," he explains. "It takes a long while to back up that many disks, so we are now in the process of going to a tape backup system." Many of the vendors of chromatography data systems offer a version of their software that supports the client/server architecture. These include Beckman Instruments (System Gold); the Waters division of Millipore (Millennium 2020C/S); Hewlett-Packard (Chem-Station/Chem-Server); and PE Nelson, Cupertino, Calif. (Turbochrome). Stand-Alone Software It is not necessary to buy chromatography software from the same vendor that supplies the instrument. Not only are there third-party suppliers of chromatography data systems, but also most of the larger vendors claim that their software will work with instruments made by their competitors. This may not be as easy as they make it sound, however. "You might be able to finagle something where you could almost, maybe, possibly make one vendor's software work with a different instrument," says Synergen's Weber. "But, realistically, their systems are designed to control their own instruments." "What the customer perceives is a very close match between one vendor's instrument and its software," says Alan Koontz, vice president of marketing and sales for Axxiom Chromatography Inc. of Moorpark, Calif. "That's because they've been designed as tightly integrated systems. But it is possible to use HP's ChemStation, for example, with Beckman instruments. It just might not be convenient. What we're trying to do is give users that same tight integration with one software system and instruments from a variety of vendors." Axxiom's data-handling software package, the Pyramid Chromatography Manager, is able to accommodate HPLC, gas, ion, and capillary electrophoresis instruments from any vendor, according to Koontz. The software not only accepts data from all these different devices, but also can be easily customized so that the user interface on each workstation matches the instrument as closely as the software offered by its vendor, he says. The benefit of being able to control many instruments with a single software system might be obvious to researchers who work in the typical lab containing instruments from a variety of vendors. When each different brand of instrument has its own chromatography data system, the result is a collection of data systems with different features, interfaces, and data structures. By contrast, one software system capable of handling data from all of a lab's instruments can simplify data management and training by providing a consistent data format and user interface. One situation in which compatibility between different vendor's products is not yet possible, however, is with photodiode array detectors, Koontz says. "Diode array detectors don't produce an analog signal such as that produced by a UV or fluorescent detector," Koontz explains. "They produce an extremely complex file that the data system has to sort out very quickly. Each vendor uses a different file format and the system must be tailored to that format." For Axxiom, which supports a number of photodiode array detectors in its Pyramid system, it takes "a major programming effort," Koontz says, to add support for a new detector. For labs that are not in the market for comprehensive chromatography data systems, there is also stand-alone software tailored to one central aspect of the chromatography process--data analysis. Typical of this approach is PeakFit from Jandel Scientific of San Rafael, Calif. Peak-fitting software enhances the accuracy of analysis by using non-linear curve-fitting techniques to reduce noise, adjust for backgrounds, and detect peaks that might otherwise be missed. "Our HPLC analysis gives very noisy data," says Vijay Dhawan, a biophysicist in the department of neurology at North Shore University Hospital in Manhasset, N.Y., an affiliate of Cornell University. Dhawan's research on the dopaminergic system in patients with Parkinson's disease uses chromatography to trace the uptake of dopamine by the brain over the course of two hours. "There will be four peaks of different magnitudes throughout the course of the study," Dhawan explains. "They represent the dopamine and three metabolites. "You can see the individual peaks, but they are very noisy, and to separate them arbitrarily becomes very difficult, if not impossible. With PeakFit, you can smooth out the curves and distinguish the four peaks clearly." PeakFit, which runs on a PC, takes chromatography data from the instrument in the form of an ASCII file. Initially, it took Dhawan a lot of time to find the best mathematical functions to fit the curves, he says, but once that was established, the process became "almost push-button." Caren D. Potter is a freelance science writer based in McKinleyville, Calif. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : VENDORS OF CHROMATOGRAPHY SOFTWARE AND DATA SYSTEMS TY : TOOLS & TECHNOLOGY PG : 19 The following vendors market software products for use with chromatography instrumentation. For more information about specific products, their capabilities, and prices, please contact these companies directly. Alltech Associates 2051 Waukegan Ave. Deerfield, Ill. 60015 (708) 948-8600 Fax: (708) 948-1078 AMBIS Inc. 3939 Ruffin Rd. San Diego, Calif. 92123 (619) 571-0113 Fax: (619) 571-5940 Analog & Digital Peripherals P.O. Box 499 Troy, Ohio 45373 (513) 339-2241 Fax: (513) 339-0070 Anspec Associates Inc. 50 Enterprise Dr. Ann Arbor, Mich. 48103 (800) 521-1720 Fax: (313) 665-6402 Antek Instruments Inc. 300 Bammel Westfield Rd. Houston, Texas 77090-3508 (713) 580-0339 Fax: (713) 580-0719 Applied Biosystems Division of Perkin-Elmer Corp. 850 Lincoln Center Dr. Foster City, Calif. 94404 (800) 345-5224 Fax: (415) 572-2743 Autochrom Inc. 113 Cedar St., Suite S-6 Milford, Mass. 01757 (508) 478-2670 Fax: (508) 478-0217 Axxiom Chromatography Inc. 11988 Challenger Court Moorpark, Calif. 93021-7122 (800) 441-8888 Fax: (805) 523-2313 Beckman Instruments Inc. 2500 Harbor Blvd. Fullerton, Calif. 92634 (714) 871-4848 Fax: (714) 773-7600 Bio-Rad Laboratories Life Sciences Group 2000 Alfred Nobel Dr. Hercules, Calif. 94547 (510) 741-1000 Fax: (510) 741-1055 Bio-Rad Sadtler Division 3316 Spring Garden St. Philadelphia, Pa. 19104 (215) 382-7800 Fax: (215) 662-0585 Bioanalytical Systems Inc. 2701 Kent Ave. West Lafayette, Ind. 47906 (317) 463-4527 Fax: (317) 497-1102 Dionex Corp. P.O. Box 3603 1228 Titan Way Sunnyvale, Calif. 94088-3603 (408) 737-0700 Fax: (408) 739-4398 ESA 45 Wiggins Ave. Bedford, Mass. 01730 (617) 275-0100 Fax: (617) 275-5529 Fisons Instruments Inc. 55 Cherry Hill Dr. Beverly, Mass. 01915 (508) 524-1000 Fax: (508) 524-1019 Galactic Industries Corp. 395 Main St. Salem, N.H. 03079 (800) 862-6004 Fax: (603) 898-6228 Gilson Inc. 3000 W. Beltline Hwy. P.O. Box 620027 Middleton, Wis. 53562 (800) 445-7661 Fax: (608) 831-4451 Hewlett-Packard Co. 2850 Centerville Rd. Wilmington, Del. 19808 (302) 633-8188 Fax: (302) 633-8916 IN/US Systems Inc. 5809 N. 50th St. Tampa, Fla. 33610-4809 (800) 875-4687 Fax: (813) 623-3708 ISCO Inc. 4700 Superior St. Lincoln, Neb. 68504-1398 (800) 228-4250 Fax: (402) 464-01318 Jandel Scientific 2591 Kerner Blvd. San Rafael, Calif. 94901 (415) 453-6700 Fax: (415) 453-7769 Jasco Inc. 8649 Commerce Dr. Easton, Md. 21601 (800) 333-5272 Fax: (410) 822-7526 JM Science Inc. 5820 Main St., Suite 300 Buffalo, N.Y. 14221-5734 (800) 387-7187 Fax: (716) 634-1970 Justice Innovations Inc. 1240 L'Avenida Ave. Mountain View, Calif. 94043-1426 (415) 969-6122 Fax: (415) 969-6140 Linc Quantum Analytics 363 Vintage Park Dr. Foster City, Calif. 94404 (800) 437-9701 Fax: (415) 312-0303 Micro-Tech Scientific Inc. 140 S. Wolfe Rd. Sunnyvale, Calif. 94086 (408) 255-8701 Fax: (408) 730-3566 Millipore Corp. Waters Chromatography Div. 34 Maple St. Milford, Mass. 01757 (508) 478-2000, Ext. 3571 Fax: (508) 478-5591 Omega Engineering Inc. One Omega Dr., Box 4047 Stamford, Conn. 06907 (203) 359-1660 Fax: (203) 359-7640 Oxford Biomedical Research Inc. P.O. Box 522 1858 Starr Batt Dr. Oxford, Mich. 48371 (810) 852-8815 Fax: (810) 852-4466 Oxford Clycosystems 133-33 Brookville Blvd. Rosedale, N.Y. 11422 (718) 712-2693 Fax: (718) 712-3364 PE Nelson Division of Perkin-Elmer Corp. 761 Main Ave. Norwalk, Conn. 06859 (800) 762-4000 Pharmacia Biotech Inc. 800 Centennial Ave. Piscataway, N.J. 08855-1327 (800) 526-3593 Fax: (908) 457-0557 Rainin Instrument Co. Inc. 5400 Hollis St. Emeryville, Calif. 94608 (510) 654-9142 Fax: (510) 652-8876 Thermo Separation Products P.O. Box 10235 Riviera Beach, Fla. 33419 (800) 532-4752 Fax: (407) 845-8819 Varian Associates Inc. 3045 Hanover St. Palo Alto, Calif. 94304 (415) 424-5756 Fax: (415) 858-0480 (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: PROFESSION ---------------------------------------------------------- TI : Study Finds Gender Disparities In Pay For Medical Researchers AU : EDWARD R. SILVERMAN TY : PROFESSION PG : 21 A recent study conducted by researchers at Boston University has found that women in three areas of academic medicine-- cardiology, rheumatology, and general internal medicine-- receive less money and fewer promotions than their male counterparts. The study, published in Annals of Internal Medicine (P.L. Carr, R.H. Friedman, et al., 119:908-13, 1993), found that these differences existed even though the women physicians surveyed performed similar duties and were just as productive. The survey of 1,693 full-time United States physicians found that 47 percent of the men had achieved the rank of full or associate professor, compared with 33 percent of the women. In addition, it found that the women researchers received an average of $72,000 in annual compensation, while the average figure for men was $79,600. The $7,600 average difference "represents about a 10 percent differential even after adjustment for factors relating to seniority and region of the country," the article reported. Debunking A Myth The results should dispel any myths that women earn less because they work less, said the study's authors, who defined academic productivity by counting an individual's research grants awarded, papers published in refereed journals, and abstracts accepted. They controlled for such variables to account for factors that may contribute to disparities in pay. "Not only are the hours worked per week similar but the allocation of those hours to the various professional activities of academic medicine are also similar," the article stated. The researchers, who surveyed faculty at 107 major U.S. teaching hospitals, also took into consideration the younger average age of women in medicine, a significant issue in measuring productivity because women have entered medicine only recently."This [survey] is a tool that women physicians can take to their department heads [to] show the differences in the way rewards are handed out," says Phyllis Carr, a coauthor of the study. "And this study does that by not putting any person on the spot," says Carr, a clinical instructor at Harvard Medical School and visiting physician at Massachusetts General Hospital, who led the study at Boston University, where all data were collected and analyzed. "No one is pointed at as the problem, because everyone is the problem." "Because the results of our study and others support the conclusion that sex bias exists," the article stated, "it behooves academic departments to scrutinize their policies and attitudes toward women faculty, including the opportunities they provide for promotion and advancement and the compensation they offer." An `Open-And-Shut Case' Although the study is culled from data first collected in 1986 as part of another project, the authors say the problems are still relevant and need redressing. "Have things changed substantially in the last seven years? That's a judgment call," says Robert Friedman, an associate professor of medicine and public health at Boston University's School of Medicine and a coauthor of the report. "I think most observers would say that things haven't changed," he says. "And in terms of job profiles, we've shown that women have reached parity. So I think that's a pretty open-and-shut case. Gender bias is implicated by ruling out other things." A possible explanation for the finding of inequitable rewards doled out to men and women is that some aspects of performance may not have been measured in the study, such as the quality of teaching or administrative work. Friedman also adds that some women may not be as good as their male counterparts in negotiating for higher salaries, raises, or promotions. Barbara Turner, an associate professor of general internal medicine at Jefferson Medical College, part of Thomas Jefferson University in Philadelphia, agrees with this assessment. "I think it's a self-esteem thing," she says. "It's possible some women are so bloody grateful just to get a job. "It's a woman's problem. We don't learn how to negotiate hard. I came out [of medical school] with a fellowship and didn't think of my salary as part of the picture. It doesn't mean you're a mercenary, but it's part of the job." Beyond recognizing the problem, however, lies a quandary: what to do about it. While the study's authors urge academic departments to scrutinize their policies and attitudes toward women faculty, Turner points out, many medical researchers would still remain in the dark about their true status because most salary information is kept confidential, preventing staff from learning whether inequalities exist. "The problem is that ... there's no access to comparative information," Turner says, recalling her anger a few years ago after learning that a man doing the same work and holding the same rank--but with fewer qualifications--made more money at another institution. "The only way I can find out is by hook or by crook." Edward R. Silverman is a freelance writer based in Millburn, N.J. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ---------------------------------------------------------- TI : ACADEMIC RANK, POSITION, AND COMPENSATION OF INTERNAL MEDICINE FACULTY (ADJUSTED VALUE*) Men Women Full or associate professor 47% 33% Tenured 42% 45% Division chief 32% 25% Compensation (all faculty) $79,100 $72,600 Compensation (with tenure only) $79,300 $70,300 Compensation (without tenure) $75,700 $71,000 * Adjusted for 10 variables: rank, year of graduation, fellowship training, membership in honor society, hours worked per week, faculty rank, division chief and division type, number of grants funded as principal investigator, number of refereed journal publications as first author Source: P.L. Carr, R.H. Friedman, Annals of Internal Medicine, 119:908-13, 1993. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: PEOPLE ---------------------------------------------------------- TI : Prestigious Japan Prize To Be Awarded To Two Researchers From U.S., Sweden AU : PHIL BECK TY : PROFESSION (PEOPLE) PG : 22 American astrophysicist William H. Pickering, whose contributions to space technologies have been central to space exploration, and Arvid Carlsson, a Swedish neuropsychopharmacologist who discovered dopamine as a neurotransmitter and its role in mental and motor functions and disorders, have been named recipients of the 1994 Japan Prize. At about $467,000 for each recipient, the prize, to be presented in a ceremony in Tokyo in April, is one of the world's richest scientific awards. Deep-Space Research Pickering, an 83-year-old emeritus professor of the California Institute of Technology, is being honored in the category of aerospace technologies for "leadership in unmanned lunar and planetary exploration and for pioneering achievement in the development of spacecraft and deep-space communications," according to the Tokyo-based Science and Technology Foundation of Japan, which awards the prize. After obtaining a Ph.D. in physics from the California Institute of Technology in 1936 and while an assistant professor of engineering there, Pickering joined the Jet Propulsion Laboratory as a research scientist in 1944. He remained there for the next 32 years, becoming director of JPL in 1954. He retired in 1976. In November 1957, shortly after the launch of the Soviet space satellite Sputnik, Pickering and his JPL colleagues were part of a team assigned to send up the United States' first artificial satellite. Pickering's lab developed the upper three stages of the launching rocket, the telemetry equipment for data transmission from the satellite's cosmic radiation measuring instrument, and the system integration of the payload. Less than three months later, Explorer 1 was launched. In 1959, Pickering led the design of Pioneer 4, which became the first U.S. man-made object to escape from Earth's gravitational field. Pickering's research also contributed to the lunar topography survey by the Ranger and Surveyor spacecraft, the Mariner series' exploration of Venus and Mars, and the soft landing by Viking on Mars. Pickering's communications, data acquisition, and tracking research and instrumentation have led to the deep-space tracking network, a system of three stations equipped with 70-meter parabolic antennae. He also developed coding and decoding systems, and numerous other space-related systems. Under Pickering, JPL labs developed some of the first technology for digital communications and digital image processing, making possible later advances such as high- definition television. Monoamines Elucidated Carlsson is to be given the prize in the category of psychology and psychiatry. His research contributed to the clarification of the functions of monoamines, especially dopamine, in the brain. The 71-year-old emeritus professor at Gothenburg University in Sweden discovered in the late 1950s the reversal of reserpine-induced akinesia and sedation by DOPA, a direct precursor of dopamine. He also found that dopamine serves a critical agonist function in the regulation of psychomotor activity. This was the first evidence that dopamine acts as a neurotransmitter in the brain and led to a new understanding of the role of dopamine in motor functions, especially in Parkinson's disease, enabling doctors to treat the ailment efficiently. It also revealed dopamine's role in mental functions and in the actions of psychotherapeutic drugs. In the early 1960s Carlsson published the first evidence that neuroleptics, or antipsychotic drugs, act by blocking dopamine receptors, facilitating the development of several new drugs to treat psychoses. Other dopamine-related discoveries since then by Carlsson have led to understanding of the pathogenesis of Parkinson's and disorders associated with cognitive, emotional, and endocrine functions. Carlsson received his M.D. from the University of Lund in 1951, and taught there until 1959, when he became a professor and chairman of the department of pharmacology at the University of Gothenburg. He remained chairman of the department until 1976 and became an emeritus professor at the university in 1989. --Phil Beck (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: OBITUARY ---------------------------------------------------------- TI : Dixy Lee Ray TY : PROFESSION (OBITUARY) PG : 22 Dixy Lee Ray , former governor of Washington state and an accomplished zoologist, died January 2 in Seattle. Ray had suffered from a severe bronchial condition for several months before her death, according to reports. She was 79 years old. Ray began her career as an associate professor of zoology at the University of Washington in 1945, a position she held for the next 27 years. In addition, she was director of the Pacific Science Center in Seattle from 1963 to 1972 and a special consultant in biological oceanography for the National Science Foundation from 1960 to 1963. Her public-service career started with a position as chairwoman of the Atomic Energy Commission from 1972 to 1975. She was appointed an assistant secretary of state, overseeing the Bureau of Oceans, International Environmental and Scientific Affairs in 1975, and served as governor from 1977 to 1981. Ray was a strong supporter of the nuclear industry and a harsh critic of environmental groups she deemed excessive in their protests against it. An essay she wrote for Imprimis, a journal of Hillsdale College in Michigan, appeared in The Scientist ("Who's To Blame When The Public Misunderstands Science?" April 16, 1990, page 17). Ray earned her master's degree from Mills College in 1938 and her Ph.D. from Stanford University in 1945. (The Scientist, Vol:8, #2, January 24, 1994) (Copyright, The Scientist, Inc.) ================================

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