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Phone :(215)243-2205 // Fax: (215)387-1266 ================= THE SCIENTIST VOLUME 8, No:17 SEPTEMBER 5, 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 *** *** SEPTEMBER 19, 1994 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the United States: one year $58, two years $ 94 Canada : one year $82, two years $142 All other foreign : one year/air cargo $ 79 one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NXT = next article ------------------------------------------------------------ TI : CONTENTS PG : 3 ============================================================ NEWS CAREER CHOICES: Medical school administrators say the parameters young people assess in deciding to become biomedical researchers, practicing physicians, or physician- scientists will be among the changes wrought by health-care reform PG : 1 PCAST PICKS: Appointees to the recently announced President's Committee of Advisers on Science and Technology say that what's "new" about the new PCAST includes its composition--with a significantly greater representation of women--and its priorities PG : 1 A MATTER OF ETHICS: Degree programs, seminars, courses, and research centers are springing up on campuses across the United States to teach and promote scientific and medical ethics, spurred by attention to ethics from the media, government, and researchers themselves PG : 1 SHOW & TELL: Investigators from all branches of the National Institutes of Health will be gathering on the NIH campus to discuss their work and learn what their colleagues are doing at NIH Research Festival '94 PG : 3 THE LEADERS OF SCIENCE / The Readers of THE SCIENTIST: Featuring Richard E. Smalley PG : 8 GAIRDNER WINNERS: Five scientists who have found answers to important questions about the molecular bases of such biological processes as immunity and cancer development have been declared winners of the 1994 Gairdner Foundation International Awards PG : 9 OPINION ANIMALS IN THE LAB: The ongoing debate over the use of animals as laboratory research subjects shows no sign of slackening. Two essays provide evidence for this: one by Kenneth Stoller, a California pediatrician who considers animal research cruel and unnecessary; the other by Susan Paris, president of Americans for Medical Progress Educational Foundation, who contends that animal rights advocates present a threat to biomedical research and, therefore, to public health PG : 12 COMMENTARY: Triage, a recently instituted NIH practice in considering grant proposals--whereby applications can be rejected after cursory review and without reply--is intended to save time as well as reduce the pressure on and boost the morale of NIH reviewers. In reality, says pharmacology professor Jose Musacchio, a former reviewer, little time would be saved and it would be the researchers--especially young ones--who would be demoralized by the summary, unexplained rejections PG : 13 RESEARCH STRUCTURE'S REACH: The second part of a two-part series on structural biology examines the expanding number of fields being touched upon in the study of the configuration and mechanisms of macromolecules PG : 14 HOT PAPERS: Dermatologist George J. Giudice discusses the identification of a causative agent for an autoimmune skin disease; neuroscientist Terence J. Coderre reports on amino acids' role in causing pain PG : 16 TOOLS & TECHNOLOGY CYTOKINES ON DEMAND: A growing number of molecular biologists and biochemists are focusing more attention on a class of small peptide messenger molecules called cytokines, and laboratory biochemical companies are working with researchers to produce purified cytokines for study PG : 17 PROFESSION FUNDERS OF RISK: The American Health Assistance Foundation is hardly the largest or best-endowed research-granting agency. Yet scientists appreciate the modest funding the foundation provides because the organization allows them to take risks by supporting innovative ideas PG : 21 HARRY KLOOR of Purdue University has become the first U.S. student to be granted two doctoral degrees simultaneously-- in theoretical physics and chemistry PG : 22 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 13 CYTOKINES DIRECTORY PG : 18 NEW PRODUCTS PG : 19 OBITUARIES PG : 22 CROSSWORD PG : 22 (The Scientist, Vol:8, #17, pg.3, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Uncertainties Seen Complicating Future Biomedical Career Decisions AU : Barbara Spector TY : NEWS PG : 1 As the United States health-care system braces for upheaval, young Americans continue to apply to medical school in droves. But academic administrators and others say that the parameters students assess in making their career choices-- to become practicing physicians, laboratory researchers, or both--will be among the changes wrought by reform. Biomedical career decisions have never been easy. It's typical for a bright young student assessing the options to go through a period of self-examination, according to doctors and scientists interviewed for this article. Such introspection generally focuses on questions like: "Do I need to care for sick people in order to be professionally fulfilled, or would I be happier doing basic research, which ultimately could benefit millions of people?" "Will I be able to repay my medical school debts if I focus on patient- oriented research rather than a private practice?" "Do I really have the commitment to stick with an M.D./Ph.D. program? Over the next few years, with terms like "managed competition" becoming part of the national vocabulary and federal research funding still unable to keep up with the proliferation of investigators, the questions will become even more complicated. While for more than a decade researchers have been worrying about obtaining support for their projects, now phyisicians, too, are asking themselves, "Will my skills continue to be in demand?" "Our industry is facing a major overhaul," says John Noble, director of the Center for Primary Care at Boston University School of Medicine. "I don't think anyone can anticipate the extent to which things are going to be reorganized." For the moment, however, students' decisions do not appear to be radically altered by the prospect of reform. Young people "know something is going to happen," says William Jacott, assistant vice president for health sciences at the University of Minnesota, Minneapolis, and a member of the American Medical Association's board of trustees. "But their pipeline could be anywhere from eight to 12 years. It's hard for them to visualize what things are going to be like 12 years hence." Although radical changes in the practice of medicine may well be in the offing, evidently they are not deterring students from applying to medical school: According to the Washington, D.C.-based Association of American Medical Colleges (AAMC), medical school applications reached a record high in 1993-94 (see accompanying table). "The people who are very unhappy [about pending changes] are people already in practice, who are looking at a significant decrease in their income," says Kenneth Shine, president of the Institute of Medicine (IOM). "If you're a young person who's never lived that lifestyle, the [post-reform] salaries look pretty good." An aspect of the proposed reforms that many medical students are welcoming, Shine says, is the promised reduction in paperwork and bureaucracy attendant in the current insurance system. "I think it' possible that health-care reform could increase career opportunities in research," suggests Roy Silverstein, president of the American Federation for Clinical Research (AFCR) and chief of the division of hematology and medical oncology at Cornell University Medical College in New York City. If a plan were enacted that included a provision for increased research funding, Silverstein says, the effect might be "narrowing the difference in incomes between the research and clinical community--sort of leveling the playing field. But [reform] could be a disaster, too." Career Choices Practical considerations have an influence on career decisions, especially for minority students, according to Benjamin Carson, director of pediatric neurosurgery at Johns Hopkins Medical Institutions, who has been a mentor to many of these students. "Academic medicine traditionally is not something minorities have gone into, particularly for financial reasons," he says. Students from lower-income backgrounds, he explains, generally have to take out more medical school loans than their more well-to-do counterparts, and "by the time [they are] ready to practice, the major consideration is, `How am I going to pay all this stuff back?' Most of them really don't have a choice; they have to go into private practice." But opening a private practice is rarely a viable option these days. Shine notes that in 1988, more than half the medical school graduates took salaried positions in health maintenance organizations and other such arrangements. "Solo private practice opportunities are drying up," he says. Even the once-vaunted option of medical specialization is no longer considered the key to job security. A recent study in the Journal of the American Medical Association (J.P. Weiner, 272:222-30, 1994) forecasted that by the year 2000-- even if there were to be no reform at all--the U.S. will have an overall surplus of about 165,000 patient-care physicians, and that "virtually all of this surplus will consist of specialists." "Medical schools are trying to reorganize their curriculum to restore a balance between generalist and specialist [training]," says BU's Noble, whose institution has received a grant from the Princeton, N.J.-based Robert Wood Johnson Foundation to establish a generalist physician training program. This restructuring makes a research career--the struggle for funding notwithstanding--seem stable by comparison. "I'm really happy to be where I am right now [when compared with] my colleagues in private practice or tertiary care," says James Wilson, an M.D./Ph.D. researcher who is director of the Institute of Human Gene Therapy at the University of Pennsylvania. "In a day, their boss changes or the hospital ownership changes." As a case in point, he cites two Boston-based hospitals affiliated with Harvard University, long considered a "bastion of stability." In March, Massachusetts General Hospital combined with Brigham and Women's Hospital to form a new entity called Partners HealthCare System Inc. According to officials at the system, an operating plan for the united institutions is now under development, with repercussions for the staff yet to be announced. Such sweeping changes in the practice of medicine are among a number of trends identified by medical school administrators and others as likely to drive biomedical careers in the future. Clinical Research Crisis M.D.'s who do patient-oriented research are concerned about a potential shortage of physician investigators in the near future. "There is an increasing differentiation of faculty into those who do research and those who take care of patients; fewer and fewer people do both," says IOM's Shine. "The community is very worried, and I think they've got every reason to worry." A primary reason that clinical research has lost its luster is the difficulty of obtaining funds for such studies, some say. E.H. Ahrens, Jr., a professor, emeritus, of biochemistry and medicine at Rockefeller University, found that only 7.4 percent of National Institutes of Health R01 (investigator-initiated) awards in 1987 were devoted to patient-oriented research (Perspectives in Biology and Medicine, 36:194-209, 1993). He attributes this paltry figure in part to the decline in the number of M.D.'s serving on NIH study sections. "There is a concern in the research community that there is something inherently unfair about the way research on human beings is reviewed," says AFCR's Silverstein. He knows of several qualified M.D.'s who have never been asked to serve on study sections. And many physicians who are asked must decline the invitation because they are overloaded with responsibilities in the clinical ward or operating room, he adds. "The physician community has to do their share" of grant reviewing, Silverstein acknowledges. By the same token, the task could be made less of a burden if the reviewing process were altered to accommodate doctors' schedules, he proposes. NIH deputy director Ruth Kirschstein says the agency's Division of Research Grants has convened an advisory committee to examine peer review of clinical research projects. She adds that NIH is attempting to encourage more physician research through various fellowship training programs as well as its Medical Scientist Training Program (MSTP), which supports M.D./Ph.D. students (see story on page 7). "We're scratching our heads and trying to think of new possibilities," she says. But the MSTP is not necessarily the solution to this problem. In his book The Crisis in Clinical Research: Overcoming Institutional Obstacles (New York, Oxford University Press, 1992), Ahrens reports on a 1990 literature search of publications of 82 MSTP graduates in three research-intensive medical schools. He found that "of the 82 double-degree graduates, only 11 were engaged mainly in some type of clinical research," and only two were directly studying whole human beings. "There will always be new diseases--AIDS is a case in point," Ahrens notes. "If we don't have physician-scientists capable of addressing them, then we will be impoverished." Shine says that, with increased pressure on institutions to subsidize indirect costs, a smaller percentage of their patient-care income is available to finance faculty research (as well as other institutional expenses, such as education). Consequently, medical scientists are trying to take as much of their salaries as possible from NIH grants; those who cannot are finding it necessary to see more patients, devoting less time to research. In five years, Shine predicts, "only the very, very best scientists will be getting most of their salaries from grants. "From my perspective, unless the federal government and, in some cases, states are willing to take up [a greater amount of] the shortfall, there will be a significant decrease in the number of opportunities for research careers and the amount of research." Uncertainties about pricing regulations under health-care reform are causing clinical research funds from another source--the biotechnology and pharmaceutical industries--to dry up, according to Silverstein. "They seem to be scaling back somewhat," he says. "The unknown is always a threat, particularly in the business world." Young Investigators Vanish A recent National Research Council (NRC) report entitled The Funding of Young Investigators in the Biological and Biomedical Sciences found that applications for R01 grants from investigators age 36 and under dropped from 3,040 in 1985 to 1,389 in 1993, a 54 percent decrease. Shine speculates that the decline could be attributable to several phenomena: Young researchers may have to take multiple postdoctoral appointments before they are able to get their own labs and apply for grants; they may be forsaking academic research for the biotechnology industry; or they may be discouraged from applying for grants in today's tightly constrained funding environment. (NRC is planning a follow-up study to determine the causes.) "The investigator cadre is aging," says John Diggs, AAMC's vice president for biomedical research. "The more senior investigators are going to drop out of the system in five to seven years." Diggs cites a need for the biomedical community to "[do] something to assure that we have a science intellectual base that is going to carry us into the next century." Although trends cited by health-care policy-watchers and scientific administrators indicate that biomedical science is no longer a source of unlimited job opportunities, top- notch researchers should have no trouble finding work, according to Edward O'Neil, an associate professor of family and community medicine at the University of California, San Francisco, School of Medicine and executive director of the Pew Scholars Program in the Biomedical Sciences. "There's still an enormous amount of opportunity out there, but the probability of success may not be as high as in the past," he says. As an example, O'Neil describes the career outlook for a young person he knows. "There's a rising fourth-year medical student at Stanford [University] who wants to become a transplant surgeon," he says. "On one hand, I can show her numbers that say there's an oversupply of transplant surgeons. But I can also show her numbers that say she's precisely the kind of person that transplant surgery is going to need in the future [because of her] skills and accomplishment in molecular medicine. I don't think her future could be any brighter." (The Scientist, Vol:8, #17, pg.1, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : A BREED APART: THE M.D./Ph.D. AU : BARBARA SPECTOR TY : NEWS PG : 7 A young person with a high commitment to research on human disease is likely to find great rewards in undergoing the grueling amount of training involved in a combined M.D./Ph.D. program, research administrators say. M.D./Ph.D.'s are "by far the most successful group at getting grants funded," according to Salvatore Pizzo, head of the M.D./Ph.D. program at Duke University Medical Center. "They can write good grants because they know a lot about human disease; they have a unique focus because they've been through both kinds of training." An unpublished 1985 study by the National Institutes of Health found that the chance of an M.D./Ph.D.'s being funded was approximately 1 in 2, as opposed to about 1 in 3 overall, says Lee Van Lenten, administrator of NIH's Medical Scientist Training Program (MSTP), which supports M.D./Ph.D. training. However, he notes, these are old data, and current success rates are much lower than the 1985 figures. Getting the two degrees requires a minimum of six years of graduate education--and perhaps as long as eight or nine. This is followed in many cases by a residency. Students opting for this course of study "are making a decision in their early 20s for a commitment of 12 years," says Pizzo. "This is a driven bunch of students." NIH's MSTP program makes the road a bit easier for M.D./Ph.D. candidates by providing individual students with an allowance for tuition and fees plus a stipend for up to six years; funds for the remaining years come from the schools. As of July 1, NIH was funding 837 full-time training positions at a total of 33 schools. Additional students are funded by money supplied by their institution. But the so-called institutional slots are "coming under increased pressure," says Institute of Medicine president Kenneth Shine, noting that such funds are drawn from a pool that must also support research and education, faculty recruitment, equipment purchases, and, increasingly, administrative costs. What happens to M.D./Ph.D.'s once they finally finish their training? A study conducted by researchers at Washington University School of Medicine in St. Louis (C. Frieden, B.J. Fox, Academic Medicine, 66:162-4, 1991) found that 95 percent of 148 MSTP graduates had gone into residencies rather than postdoctoral fellowships. Of the 72 who had completed residencies or postdocs by 1990, 89 percent took positions in academia or at NIH. Those in academic institutions were primarily in clinical departments; most said they were devoting much of their time to basic research. A similar study by researchers at Johns Hopkins University School of Medicine (D.A. McClellan, P. Talalay, Acad. Med., 67:36-41, 1992) found that of 42 Hopkins M.D./Ph.D. graduates, 81 percent were in full-time academic posts, 14 percent worked in research institutes, and 5 percent took positions in biotechnology firms. All 42 graduates were actively involved in research, and 67 percent had clinical responsibilities. Pizzo can see changes on the horizon. "A potentially larger number of graduates will be pursuing careers with biotech companies," the Duke administrator forecasts. "Have we seen a lot of that yet? A little bit. Right now that's a shaky proposition, because companies are not doing ragingly well in the stock market, but it's a trend to watch." Another potential change, Pizzo says, is for "students [to] go into a translational research career [rather] than pure research," using their knowledge of molecular immunology and molecular biology to make diagnoses or provide treatment, such as in gene therapy. Third, while today "medicine and pathology are the classic disciplines [M.D./Ph.D. graduates] go into, I wonder if it will stay that way. As students start trying to find more niches that are going to be supportable, [they may] look at more disciplines." --B.S. (The Scientist, Vol:8, #17, pg.7, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : MEDICAL SCHOOL APPLICANTS TY : NEWS PG : 6 Class Year Applicants Accepted Applicants 1987-88 28,123 17,027 1988-89 26,721 17,108 1989-90 26,915 16,975 1990-91 29,243 17,206 1991-92 33,301 17,436 1992-93 37,410 17,464 1993-94 42,808 17,362 Source: Association of American Medical Colleges (The Scientist, Vol:8, #17, pg.6, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Burgeoning Crop Of Bioethics Programs And Courses Reflects The Deepening Of Scientist's Moral Concerns Today's researchers are being offered a host of opportunities to study philosophical implications of scientific activity AU : Karen Young Kreeger TY : NEWS PG : 1 As students at the California Institute of Technology arrive on campus for the fall semester, they're finding that a new ingredient has been stirred into the curricular mix. The Caltech catalog now lists an undergraduate major--a four-year degree program of required courses in science ethics and history--and a graduate minor called Science, Ethics, and Society. The courses--some new, some that have been taught before--cover subjects like weapons research and arms control, biotechnology, the environment, and scientific misconduct. Meanwhile, the University of Pennsylvania has established a new education and research institute called the Center for Bioethics. In addition to teaching ethics to medical students in the classroom and on hospital rounds, its faculty will conduct empirical research in such areas as informed consent and living wills. The center will also sponsor public-education forums on health-care issues. These are among the latest manifestations of a decade-long trend responding to a growing call for researchers to become more knowledgeable on philosophical matters, some extremely pertinent to and others quite far afield from the traditional focus of their lab activities. It is the study of such ethical issues that bears on the conduct, policy, and direction of scientific pursuits. Most of the courses, degree programs, seminars, and other educational and research activities cropping up in academia and other scientific and medical venues involve bioethics, which encompasses the life sciences and medical investigations and procedures. But some relate to all of science. According to figures compiled by the Hastings Center, a nonprofit bioethics research organization based in Briarcliff Manor, N.Y., and the Bioethics Online Service, a computer information source administered by the Medical College of Wisconsin in Milwaukee (see story on page 4), there are more than 100 bioethics programs and centers in the United States. Most are graduate training programs at universities; some are so-called study centers--primarily affiliated with medical institutions--which host a wide array of activities, including seminars, visits by scholars, research projects, and the development of publications. Since only a handful of such programs existed in the early 1980s, figures like those from the Hastings Center indicate that bioethics as a discipline in its own right is "here to stay now because it has received such broad institutional acceptance," says Arthur Caplan, the Penn Center's director. A number of factors have converged to stimulate this commitment to scientific and medical ethics. Spurred by increased attention to bioethical issues paid by the media, hospitals, and the research community, students and faculty- -from both science and philosophy--have been expressing a desire to have more discussion of ethics included in their classes, according to scientists and ethicists. A secondary catalyst, some say, has been increased governmental concern about ethical conduct in science, exemplified by a 1989 National Institutes of Health requirement that all recipients of NIH research training grants receive education in the responsible conduct of research (R. Eisner, The Scientist, Oct. 28, 1991, page 1). Although NIH does not specify a curriculum, format, or length of time spent in instruction, it does encourage institutions to cover the following areas: conflict of interest, responsible authorship, scientific misconduct, use of human and animal subjects, and data management. An All-Encompassing Syllabus If there is one element common to all of these programs--new or well-established--it is that they are run by interdisciplinary teams from medicine, science and engineering, law, philosophy, theology, history, policy, and business, among other fields. For instance, Penn's center-- with a core budget of $500,000 per year--will eventually have 10 faculty members, from both philosophy and science. Daniel Kevlas, the J.O. and Juliette Koepfli Professor of Humanities at Caltech and coordinator of its new ethics program, stresses that his department's program is not a prescriptive, policy-oriented one. "To explain what we intend to do," he says, "I apply the analogy of basic vs. applied research. This is really investigating long-term basic issues in the relationship of science and society, both historically and philosophically." Medical schools have also instituted ethics programs that run beyond a semester's duration. John Balint, a professor of medicine at Albany Medical College in New York, coordinates Health, Care, and Society--a four-year ethics seminar course required for all medical students at the college. He says "the mainstay" of the course is a "cadre of about 12 people," half of them physicians, the other half composed of a psychologist, a social worker, a nurse, a theologian, a sociologist, and a lawyer. In the first and second years of the program, Balint and colleagues lead classroom, laboratory, and field studies with students on such issues as sex discrimination in health care, patient confidentiality, and aging and disability. The final two years involve discussions based on cases encountered in hospital wards and clinics. Stimulus From Many Quarters The motivation for institutions and individuals to commit resources to these programs is as broad as the array of issues they are addressing. Students, faculty, alumni, and administrators all play a part. For example, Courtney S. Campbell, an associate professor in the department of philosophy and director of the Program for Ethics, Science, and the Environment at Oregon State University in Corvallis, says, "Over the past few years, philosophy faculty have, with increasing frequency, been invited to science classes to give one-shot lectures on science ethics. We in the philosophy department] felt, and our colleagues in science agreed, that education in professional ethics of science needed to be more integrated and systematic." As a result, the program began offering an undergraduate certificate in applied ethics in 1993. Students complete courses in many different departments in addition to those taught in the program; the certificate, therefore, provides "a sense of breadth" on the certificate-holder's transcript and resume, Campbell says. Caplan says that Penn's center was started because of a similar push from the bottom up: "Medical students have been asking for a program here for some time." But, he notes, there also was "leadership among the dean of the medical school, the dean of the school of nursing, and the administration" in fostering formation of the center. Endowments, donations, foundation grants, and public monies all fuel the various centers and programs. Campbell says his department received "clear direction and donations" from Oregon graduates. "The alumni felt they didn't receive enough humanities or philosophy to equip them for some of the practical [ethical] problems that they encounterd in the real world" and that an ethics program might fill that void in the school's curriculum, he says. Training Ground Broadly speaking, the centers serve one of two educational roles: teaching people who already have a background in such other disciplines as medicine, science, law, nursing, and business to apply ethical understanding to their work, and to act as a resource for others; and training and motivating faculty to include more ethics in their classes. The two-year-old master's degree program in bioethics at the Medical College of Wisconsin's Center for the Study of Bioethics in Milwaukee draws students primarily from medicine and law, says Arthur R. Derse, associate director for medical and legal affairs at the center. "We don't recommend getting the master's without combining it with some other discipline," he says. Derse reports that some graduates return to their original workplaces, such as hospitals and law offices, to set up in- house ethics programs. Still others go on to work in public service. At Penn, however, no degrees will be offered for the time being. "I think it's better to enter the field through an existing traditional discipline or profession," suggests Caplan. "My view is that it makes more sense to train doctors who can work bioethics and medical ethics into their teaching." The Center for Clinical and Research Ethics--headed by Richard Zaner, Ann Geddes Stahlman Professor of Medical Ethics at the Vanderbilt University School of Medicine in Nashville, Tenn.--has tracked the employment history of its graduates for the last decade. The center, a branch of the medical school, awards master's and doctoral degrees in medical ethics, among other activities. Since 1981, Zaner says, almost 200 students have come through the center's degree programs, with many of them now teaching in universities, medical schools, and hospitals. When hospitals started hiring staff ethicists about five years ago, he says, graduates started to work in that area, as well. Other programs, like the ones at Caltech and Oregon State, are aimed at students and faculty in branches of science other than biomedicine. Gary Comstock, coordinator of the Bioethics Program at Iowa State University, Ames, for example, heads a program in which philosophers teach science faculty--mostly in the life and agricultural sciences--how to teach ethics. "What we want to do is have an impact on existing courses. This is done so science students see that a healthy chunk of their instructors think that ethics is an important part of science--that it's right up there with meiosis and mitosis." According to Comstock, the program has had a "dramatic impact on the science curriculum at Iowa State." So far, 70 life scientists have introduced at least one hour-long discussion of ethics into more than 220 classes, reaching almost 11,000 students since the program started in 1991. The Center for Biotechnology Policy and Ethics, started four years ago at Texas A&M University in College Station, also instructs primarily science faculty. Acting director Susanna Hornig Priest says the center serves "as a facilitator for nurturing interdisciplinary activities." The center hosts informal faculty seminars that discuss various issues in diverse scientific fields, including environmental ethics. Caltech's Kevlas says his department's program has the potential to affect how future generations of scientists will approach their work: "The vast majority of students who come through here will go into technical work, at least in the early days of their careers. And it seems to me that those are the students who most need exposure to studies of this type. WeUre trying to infect those people who are going out to do bench science with a sensitivity to [ethical] issues." (The Scientist, Vol:8, #17, pg.1, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : ELECTRONIC ETHICS AU : KAREN YOUNG KREEGER TY : NEWS PG : 4 A little more than a year ago, bioethicists became electronically linked with the Bioethics Online Service, an information resource administered by the Center for the Study of Bioethics and the Office of Research, Technology, and Information at the Medical College of Wisconsin in Milwaukee. Arthur R. Derse, associate director for medical and legal affairs at the center and director of the service, says he and colleagues started the resource because people from a variety of professions--lawyers, doctors, educators, social workers, and chaplains--contacted the center for information to help them resolve questions they had on medical ethics and bioethics. The service provides an accessible and centralized forum for ethics professionals, he says. According to Derse, more than 6,000 users from nearly 40 countries have consulted the service since it started in June 1993. The service offers the following features: * Bioethics News Alert: breaking news stories that deal with medical and bioethics; * Bioethics Database: abstracts of journal articles, news accounts, legislative actions, and court decisions; * Bioethics Discussion Forum: an electronic discussion of current cases and topics open to anyone with a professional interest in bioethics; * Bioethics Resources: an archive and clearinghouse for ethics-related policies; * Bioethics Bulletin Online: articles of interest from the CenterUs publications; * Bioethics Center News and Announcements: current reports from the Medical College of Wisconsin, the Wisconsin Ethics Committee Network, and other academic and professional sources; and * links to other bioethics networks and professional organizations. How to access the Bioethics Online Service: * Via modem (any speed) and telephone line: Dial (414) 266- 5777. At the prompt (MCW >), type c min . Choose the Bioethics Online Service from the menu. * Via Internet gopher: Using a gopher client, type * Via Internet telnet: Type telnet Choose the Bioethics Online Service from the menu. For more information, contact Arthur R. Derse, Center for the Study of Bioethics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, Wis. 53226; (414) 456-8498. Fax: (414) 266-8654. E-mail: --K.Y.K. (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : PROFESSIONAL ETHICS AU : KAREN YOUNG KREEGER TY : NEWS PG : 11 There are several professional societies--some of them quite new--that facilitate communications in the field of medical and bioethics, each with its own mission and constituencies. Following is a sampling of societies dealing with bioethics. * American Association of Bioethics: formed six months ago; interested chiefly in health-care issues. Arthur Caplan, president Kim Segal, executive director FHP Center for Health Care Studies University of Utah, 2127 Annex Salt Lake City, Utah 84112 Fax: (801) 585-5489 E-mail: * American Society of Law, Medicine, and Ethics: incorporated in 1972; members are primarily lawyers and physicians. Karen Rothenberg, president Ben Moulton, executive director 765 Commonwealth Ave., 16th Floor Boston, Mass. 02215 Phone: (617) 262-4990 Fax: (617) 437-7596 * Association for Practical and Professional Ethics: formed three years ago; interested in interdisciplinary scholarship and education for ethics practitioners. Brian Schrag, executive secretary 410 N. Park Ave. Bloomington, Ind. 47405 Phone: (812) 855-6450 Fax: (812) 855-3315 E-mail: * Society for Health and Human Values: started in 1969; broad interdisciplinary interests in medical humanities. Thomas Murray, president George Degnon, executive director 6728 Old McLean Village Dr. McLean, Va. 22101 Phone: (703) 556-9222 Fax: (703) 556-8729 E-mail: * Society for Bioethics Consultation: formed in 1986; interested in clinical consultation, education, and research. George Kanoti, president Department of Bioethics P-31 The Cleveland Clinic Foundation 9500 Euclid Ave. Cleveland, Ohio 44195 Phone: (216) 444-8720 Fax: (216) 444-9275 --K.Y.K. (The Scientist, Vol:8, #17, pg.11, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Clinton's PCAST Promises To Offer New Perspectives On Science And Technology Citing broad range of challenges facing the president, observers laud diversity among advisory panel choices AU : Barton Reppert TY : NEWS PG : 1 Members of President Clinton's recently unveiled President's Committee of Advisers on Science and Technology (PCAST) as well as scientific and political observers contend that the "new" PCAST will differ considerably from its Bush- administration predecessor in several ways. Among the most notable changes, they say, are in its makeup--the new committee will have six female members, compared with one on the Bush panel--and its attention to such issues as the environment and health-care reform, which they claim, were largely ignored by the previous administration. Announced after months of delay, the 18-member panel of experts from industry, universities, and other nongovernment research organizations will provide advice to the White House on key science and technology issues. Officials of several Washington, D.C.-based science and industry associations say they are enthusiastic about or at least satisfied with the composition of the new advisory committee. They observe that the administration apparently made efforts to select a group that is diverse and broadly representative of the research community (see profiles on page 10). They note, for example, the presence of the panel's cochairman, industry official John A. Young, former president and chief executive officer of Hewlett-Packard Co. Young, along with presidential science adviser John H. Gibbons, will be presiding over the deliberations of such science figures as 1969 Nobel physicist Murray Gell-Mann and biologist Phillip A. Sharp, who won the Nobel in medicine or physiology last year. "I think they worked very hard to have a balanced group that represents different constituencies," says Daniel F. Burton, Jr., president of the Council on Competitiveness, which seeks to enhance the status of United States industry in global markets. Several observers take note of the significant rise in the number of women on the committee, which includes University of Pennsylvania president Judith Rodin and former astronaut and physicist Sally K. Ride. Catherine Didion, executive director of the Association for Women in Science, says, "I'm glad to see some women on there. I think it's really important. With the focus of the administration on science and technology, [PCAST] could conceivably have a very critical role." Their comments echo those of Vice President Al Gore, who, in a news conference announcing PCAST's membership last month, said, RIt is a remarkable group of people. They will bring diverse perspectives and expertis--and a track record of achievement--to their work with us. It's great to have this new committee to advise the president on the federal investments in science and technology best able to help us achieve our national goals." Gore called the group "a crucial information link with the private sector." At the same time, some veteran Washington science-policy watchers caution that it remains to be seen how much the new PCAST--whose membership was not announced until August 3, more than 18 months after the administration took office-- will actually be able to accomplish. Bruce L.R. Smith, a science-policy expert at the Brookings Institution in Washington, D.C., says, " think it's an able group. I'm impressed with the very high quality [of the panel members]--good people. But the proof is in the pudding here. We'll have to see whether [they'll do] anything." Forming The Panel The White House Office of Science and Technology Policy (OSTP) suggested the diverse committee members, who were then approved by the administration. The naming of the PCAST members came a day after the White House made another long- anticipated policy-committee personnel statement. The administration announced its nomination of six new members to the National Science Board, an advisory and oversight group for the National Science Foundation (see story on page 23). Their appointment to the board is subject to Senate confirmation. Cochairman Young leads a group of six panelists from industry, along with nine from universities and two associated with other organizations involved with research. Although he declines to comment in detail on what PCAST's priorities and activities should be, Young says the significance of the committee's mission has made him look forward to cochairing the new panel: "I wouldn't be doing it if I didn't think it was important." Young notes that "science and technology policy has been a subject that I've been interested in for the last 10 years, because I think it's so integral to the competitiveness of the country. So we will be focusing on ways in which we can get productivity growth rates--and therefore the real earnings of Americans--to increase." Members View Their Role Several members of the new panel, however, were more forthcoming about what they say are priority areas that deserve attention from PCAST. These include the impact of restructuring the U.S. health-care system on funding for biomedical research; applying advanced technologies to environmental cleanup; international scientific cooperation; the future of high-energy physics; and stepped-up efforts to shift the focus of the Department of Energy's national laboratories from military to civilian work. Many of them point to the diversity of the committee as key to enabling PCAST to objectively address such a range of issues. Nobelist Gell-Mann, who served on an earlier PCAST manifestation, the President's Science Advisory Committee (PSAC), during the Nixon administration, says that "what the White House needs most is scientific and technical advice that comes from a broad perspective," transcending the viewpoints of particular departments and agencies. Gell-Mann, a founder of the Santa Fe Institute in New Mexico as well as an emeritus professor of physics at the California Institute of Technology in Pasadena, was one of the earliest members of a committee of scientists and engineers formed to support the Clinton-Gore ticket during the 1992 election campaign. He says the administration has made a good-faith effort to live up to its campaign promises in the science and technology area, but that some things are beyond its control. "Certainly the administration has tried to do a great many things that were promised," he says. "It has succeeded in accomplishing some of them. But in every case it's happened in a very close vote of Congress, and with a great deal of bargaining and compromise. That seems to be a general feature of the political landscape. It's a terrible struggle to get things done." Gell-Mann, who received the Nobel in 1968 for research in elementary particle theory, says he was "very disappointed" that Congress voted to kill the superconducting supercollider (SSC), calling that move "a conspicuous setback for human civilization." He says that if adequate support is received from European countries, together with the U.S., Japan, and Russia, it may prove possible for some of the work previously planned for the SSC to be carried out instead utilizing the Large Hadron Collider (LHC) at CERN in Geneva. Another issue PCAST members express a desire to tackle is the environment. Appointee Diana Mac-Arthur, chairwoman and chief executive officer of Dynamic Corp., an environmental services company in Rockville, Md., says she hopes that PCAST can help to promote a "new mindset" in the environmental industry so that it will be more eager to adopt high-tech methods in analyzing and coping with problems. A collaborative effort she'd also like to see the committee look into is promoting conversion of the national laboratories from military to civilian research. As a particularly promising example, she points to the increasing involvement of Los Alamos National Laboratory in New Mexico with "computational biology" utilizing supercomputers. MacArthur says this could lead to major advances for the pharmaceutical industry, which in the future is going to be largely based upon the "analysis and manipulation of biological information" contributing to the design of new drugs. PCAST member Francisco J. Ayala, president of the American Association for the Advancement of Science, also named the environment as a priority of the panel. Ayala, a professor of biological sciences and of philosophy at the University of California, Irvine, says he was disturbed over the "very sorry event" of the Bush administration's refusal to sign the biodiversity treaty at the 1992 world environmental summit in Rio de Janeiro. He says he would rate as "very good" the Clinton-Gore administrationUs performance on biological and environment- related matters. "I think we have undone the mischief of the previous two administrations," he says. "At least we have endorsed the Rio convention and we have created within the Department of Commerce an agency to evaluate biodiversity in the United States." In addition to the environment, areas Ayala says are of particular concern to him are sustained funding of investigator-initiated research and expanded involvement of the U.S. with collaborative international science projects. Some members see the role of the new panel on a more fundamental level. Nobel laureate Sharp, head of the biology department at the Massachusetts Institute of Technology, says he believes that Rthe most important priority is to inject into the deliberations of the administration the view from out in the hinterlands that this is a really difficult time for science and science education." Observing that the past year has seen a slackening rate of increase for biomedical research funding, Sharp says one of the biggest issues facing the administration and the research community is whether, along with national health- care reform, "there will be structures put in place that will pay for the education and research that was there and supported under the more dispersed form of health-care costs." Two years ago, Sharp, corecipient of the 1993 Nobel for his research on gene structure, participated in the strategic- planning process at the National Institutes of Health, and he has also served on the governing council of the National Academy of Sciences. But he notes that "I have not been as deeply involved as this in an administration-related advisory activity, so I'll get somewhat of an education. Clearly that's something I'm interested in." Mixed Reviews Some outside observers say they are largely satisfied with the new PCAST, along with OSTP's overall performance so far under Gibbons. Mary Woolley, president of Research!America, an Alexandria, Va.-based organization promoting greater support and public awareness of biomedical and other research, comments about PCAST that "I'm very enthusiastic about it. I was delighted to see the diversity in the makeup of the group. I think that's refreshing and timely." She adds: "I think the vice president, in particular, [and] certainly John Gibbons and [OSTP associate director for science M.R.C.] Greenwood, are really serious about a new social contract between the scientific community and the nation as a whole. And they are hopefully going to draw on PCAST to help accomplish that." Other science-policy observers are taking a wait-and-see approach in their assessments of the new panel and its potential effectiveness. Brookings' Smith indicates that he has mixed views about the extent to which the new PCAST may make a significant contribution to dealing with major problems confronting U.S. researchers. Instead of a building task, he says, "the challenge that they face is to downsize the scientific community" in the wake of the Cold War and amid severe budgetary pressures. "We'll see whether they're able to really make some tough decisions, or whether this is just a kind of puffy effort to ingratiate with the scientific community," the science- policy analyst says of the panel and of the administration's science efforts. D. Allan Bromley, who served as President Bush's science adviser--and chairman of the previous PCAST (bearing the same acronym, but with "council" rather than "committee" in the formal name)--has some kind words for the Clinton administration panel, observing that "they have some very distinguished people on their list." Bromley, now dean of the School of Engineering at Yale University, points out, however, that with 18 members rather than 12, as previously, "it's a substantially larger group than we had in the Bush administration. I suspect that has both advantages and disadvantages. I felt that it was wiser to keep the number smaller, so we could keep it more manageable." The Wait The administrationUs intention to create a new PCAST was announced in November 1993, along with plans to establish a Cabinet-level National Science and Technology Council (NSTC), chaired by Clinton. Then in late January, Gibbons told reporters that a list of potential PCAST nominees had been sent by OSTP to the White House for further consideration and clearance procedures. The specific reasons why the PCAST appointments were not publicly announced until August 3 remain unclear. According to Brookings' Smith, after the Clinton administration took office, Gibbons at first was disinclined to reconstitute a White House science and technology group-- preferring instead to rely on various other lower-level advisory committees. "At least initially, Gibbons didn't feel a strong need to have one," Smith says. Burton, of the Council on Competitiveness, notes that administration officials had been busy with setting up NSTC, which held its first full meeting on June 29, and "reinventing how PCAST would fit into that. So there was a reconceptualization that took place up front. But then I just think that to get the people lined up and get the clearances through ended up taking much, much longer than anyone had anticipated." Barton Reppert is a freelance science writer based in Gaithersburg, Md. (The Scientist, Vol:8, #17, pg.1, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : THE NEW PCAST TY : NEWS PG : 10 NORMAN R. AUGUSTINE Chairman and CEO of Martin Marietta Corp., Bethesda, Md. Currently serving on the Defense Policy Advisory Committee on Trade and as chairman of the National Security Telecommunications Advisory Committee. Served as undersecretary of the Army in 1975-77. FRANCISCO J. AYALA Donald Bren Professor of Biological Sciences and professor of philosophy at the University of California, Irvine. President of the American Association for the Advancement of Science (AAAS). MURRAY GELL-MANN Professor at the Santa Fe Institute, Sante Fe, N.M., and cochairman of its science board. R.A. Millikan Professor Emeritus of Theoretical Physics at the California Institute of Technology. Awarded the 1969 Nobel Prize in physics for his research in elementary particle theory. Served on President's Science Advisory Committee during Nixon administration. DAVID A. HAMBURG President of the Carnegie Corporation of New York. Former president of AAAS. Former president of the Institute of Medicine (IOM). Former professor and chairman of the psychiatry department and Reed-Hodgson Professor of Human Biology at Stanford University. JOHN P. HOLDREN Class of 1935 Professor of Energy at the University of California, Berkeley, and visiting scholar at the Woods Hole (Mass.) Research Center. Former chairman of the Federation of American Scientists. Trained in aeronautics and astronautics and in theoretical plasma physics. DIANA MacARTHUR Chairwoman, CEO, and cofounder of Dynamic Corp., Rockville, Md., a company providing integrated environmental services including life sciences consulting, natural resources management, and hazardous waste engineering. SHIRLEY M. MALCOM Head of the Directorate for Education and Human Resources at AAAS. Former high school teacher and university professor. Serves on several advisory committees relating to the evaluation of educational reform. MARIO J. MOLINA Lee and Geraldine Martin Professor of Environmental Sciences at Massachusetts Institute of Technology. Formerly senior research scientist at the Jet Propulsion Lab. Has served on advisory committees for the National Aeronautics and Space Administration, NSF, and NIH. PETER H. RAVEN Director of the Missouri Botanical Garden and Engelmann Professor of Botany at Washington University in St. Louis. Currently home secretary of the National Academy of Sciences. Has served as a member of the National Science Board. SALLY K. RIDE Former astronaut and currently director of the California Space Institute at the University of California, San Diego. Also a professor of physics at UC-San Diego. Served on the Presidential Commission on the Space Shuttle Challenger Accident. JUDITH RODIN Psychologist and president of the University of Pennsylvania. Former provost and dean of the graduate school at Yale University. CHARLES A. SANDERS Chairman and CEO of Glaxo Inc., Research Triangle Park, N.C. Former head of the science and technology division of Squibb Corp. Also worked as general director of Massachusetts General Hospital and a professor of medicine at Harvard Medical School. PHILLIP A. SHARP Professor of biology, head of the department of biology, and former director of the Center for Cancer Research at MIT. Corecipient of the 1993 Nobel Prize in physiology or medicine for research on gene structure. Cofounder and member of the board of directors of Biogen Inc. DAVID E. SHAW CEO of D.E. Shaw & Co., New York, a group of technology- oriented financial firms. Member of the board of governors of the New York Academy of Sciences. Served on the faculty of the computer science department at Columbia. CHARLES M. VEST President of MIT and a professor of mechanical engineering. Former provost, vice president for academic affairs, and dean of the College of Engineering at the University of Michigan. VIRGINIA V. WELDON Senior vice president for public policy for Monsanto Co., St. Louis. Former professor of pediatrics, deputy vice chancellor for medical affairs, and vice president of the Medical Center at Washington University School of Medicine, St. Louis. LILIAN SHIAO-YEN WU Member of the research staff at IBM Corp.'s Thomas J. Watson Research Center, Yorktown Heights, N.Y. Serves as a director of the International Institute of Forecasters, and on the National Research Council's Committee on Women in Science and Technology. JOHN A. YOUNG (cochairman, along with presidential science adviser John H. Gibbons) Former president and CEO of Hewlett-Packard Co., Palo Alto, Calif. Served as chairman of the President's Commission on Industrial Competitiveness. Founder and former chairman of the Council on Competitiveness. (The Scientist, Vol:8, #17, pg.10, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : CLINTON NOMINEES TO NSB TY : NEWS PG : 23 On August 2, the White House announced that President Clinton was nominating six new members to the National Science Board, the National Science Foundation's advisory and oversight group. The nominees are: * John A. White, dean of the College of Engineering at Georgia Institute of Technology in Atlanta; * Claudia Mitchell-Kernan, an anthropologist and director of the Center for Afro-American Studies at the University of California, Los Angeles; * Diana B. Natalico, president of the University of Texas, El Paso, and a professor of languages and linguistics; * Robert M. Solow, an economist and Institute Professor at the Massachusetts Institute of Technology in Cambridge; * Warren M. Washington, director of the climate and global dynamics division at the National Center for Atmospheric Research in Boulder, Colo.; and * Eve L. Menger, director of technology administration and services for Corning Inc., Corning, N.Y. (The Scientist, Vol:8, #17, pg.23, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Annual NIH `Show And Tell' Celebrates Intramural Research Advances AU : Neeraja Sankaran TY : NEWS PG : 3 For five days beginning September 19, researchers from the 25 institutes, centers, and divisions of the National Institutes of Health will be getting together to talk about their work and learn what their colleagues are doing. They will be convening at an event called "NIH Research Festival '94." The gathering, held annually for the past seven years at the agency's Bethesda, Md., campus, will feature three days of symposia, poster sessions, and workshops by intramural scientists, followed by a two-day exposition of scientific equipment and services. Organizers say that the program--with an expected attendance of 8,000--is intended primarily as an occasion for NIH scientists to interact with each other and compare notes. But the festival does attract other people, as well, particularly from the surrounding biomedical community. "This is an all-purpose show-and-tell event for NIH--a celebration of what we are," says Gordon Guroff, deputy scientific director of the National Institute of Child Health and Human Development (NICHD). "Postdocs get an opportunity to meet some of the senior people. We also encourage reporters and congressional people to come to the meeting." Kicking off the festival will be the Distinguished Alumni Symposium--an annual seminar run by a different institute each year and dedicated to a distinguished alumnus of that institute. This year, NICHD is holding the seminar--focusing on developmental biology--in honor of Philip Leder, now a professor of genetics at Harvard University Medical School in Boston and a Howard Hughes Medical Institute investigator there. Among Leder's accomplishments at NICHD was establishing and developing its Laboratory of Molecular Genetics. Following talks on their current research by five other noteworthy NICHD alumni, Leder will deliver a lecture on his recent work entitled "Limb Deformity: A Morphogenic Paradigm in the Mouse." He will also receive an award from NICHD director Arthur Levine. Three of the five other featured speakers--Tasuku Honjo of Kyoto University Faculty of Medicine in Japan; Stuart Orkin of Children's Hospital, Boston; and Shirley Tilghman of Princeton University in New Jersey--are "products of Leder's lab," says Guroff. William W. Chin, a researcher at Brigham and Women's Hospital in Boston, and Gerald D. Fischbach of Harvard's medical school also will be speaking. The broad scope of research conducted at the various NIH agencies will be apparent in the variety of posters and workshops to be presented in the three days. Some 300 posters, grouped by subject into 14 different categories, will be displayed in special tents set up in parking lots adjacent to the NIH clinical center (Building 10). Besides such general subjects as immunology, neurobiology, and epidemiology, posters under such specialized categories as apoptosis, signal transduction, and transgenic animal models will offer insights into today's particularly active fields of biomedical research. Fifty-two workshop sessions are to include such widely disparate topics as "Intracellular Trafficking," "Genetics and Substance Abuse," and "Molecular Epidemiology of Cancer Risk." In addition, NIH's Division of Computer Research and Technology (DCRT) has put together a special, day-long workshop on the applications of computers in molecular biology. "There is a vast amount of computation being expended to support different research projects at NIH," says Adrian Parsegian, who is the chief of the laboratory of structural biology at DCRT. "The [Human] Genome Project requires computer support for collecting DNA sequence information, as well as comparisons and analysis. The study of three- dimensional protein structures is also computer-intensive-- we have software to convert long lists of numbers into meaningful structures. "The workshop is a way to keep researchers abreast of what can be done with computers and how to do it," he adds. The two-day trade show following the symposia and workshops is being sponsored by the Technical Sales Association (TSA), a nonprofit trade organization based in Falls Church, Va., that puts together such exhibitions for the biomedical research community. About 400 TSA members, including large companies such as Fullerton, Calif.-based Beckman Instruments Inc. and smaller, local firms such as Biotech Research Laboratories, Rockville, Md., will be on hand to display and promote their products and services. According to TSA members, exhibiting at targeted, on-site programs such as the NIH Research Festival holds some distinct advantages over appearing at larger trade shows. "The cost to attend [for an exhibitor] is very reasonable--a few hundred dollars instead of a few thousand at the larger meetings--and the attendance [of researchers] is very, very good," says Victor Erickson, a representative of Biotech Research Laboratories, a company providing laboratory and technical support services in molecular and cell biology to laboratories in the Washington and Maryland areas. "The percentage of quality research leads that are converted to sales at this show have been [very] high," says Jerry Kravetzker, a Columbia, Md.-based manager for Beckman Instruments. Kravetzker also points to the timing of this meeting, held for the past few years during the third week of September, as being particularly opportune for exhibitors, noting that "the scientists who come get ideas for new equipment for the next fiscal year." Among the devices that Beckman will display this year are: BIOMEK-2000, a robotic workstation that automates pipetting at the microliter scale; and P/ACE- 5500, a capillary electrophoresis machine that can separate extremely minute quantities (on a picogram scale) of material. For more information about the Research Festival, contact Gregory Roa at the NIH Visitors' Center, (301) 496-1776. Questions about the TSA trade show can be addressed to Suzanne Snyder, TSA exhibit manager, Global Trade Production Inc., 5203 Leesburg Pike, Suite 1313, Falls Church, Va. 22041; (703) 671-1400. (The Scientist, Vol:8, #17, pg.3, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : AT A GLANCE Symposia: * Monday, September 19, 8:45 a.m.-noon: NICHD Distinguished Alumni Symposium: Contributions of Basic Science to Human Biomedical Research (Bldg. 10, Masur Auditorium) * Tuesday, September 20, 8:30 a.m.-noon: HIV Pathogenesis and Therapy (Bldg. 10, Masur Auditorium) * Tuesday, 8:30 a.m.-noon: Apoptosis and the Cell Cycle (Bldg. 10, Lipsett Amphitheater) * Wednesday, September 21, 8:30 a.m.-noon: Genetic Predisposition to Diseases (Bldg. 10, Masur Auditorium) * Wednesday, 8:30 a.m.-noon: Imaging (Bldg. 10, Lipsett Amphitheater) * Wednesday, 8:30 a.m.-noon: DNA Repair (Bldg. 38A, Lister Hill Auditorium) Poster Session: Monday, 1:00 a.m.-4:00 p.m.. (Research Festival tents in Parking Lot 10-D) Workshops: * Wednesday, 8:30 a.m.-5:00 p.m.: Computing for Molecular Biology (Bldg. 12A, Rooms B-45, B-51, 2047) * Tuesday, 2:30 p.m.-5:00 p.m., and Wednesday, 8:30 a.m.- 11:00 a.m. and 2:30 p.m.-5:00 a.m.: 52 sessions to be held Technical Sales Association Scientific Equipment Show: Thursday, September 22 and Friday, September 23, 9:30 a.m.- 4:00 p.m., (Research Festival tents in Parking Lot 10-D) (The Scientist, Vol:8, #17, pg.3, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: NOTEBOOK ------------------------------------------------------------ TI : Israel's Other Milestone TY : NEWS (NOTEBOOK) PG : 4 Given the international attention accorded the recent Israeli-Palestinian peace agreement, another historic cross- cultural event taking place in Israel has received somewhat less publicity. Khaled El-Shami, a surgical intern from Alexandria University Hospital, has become IsraelUs first doctoral student from Egypt. The 29-year-old El-Shami, who holds a masterUs degree in molecular biology from the University of Sussex in England in addition to an M.D. from the University of Alexandria, will be spending the next four years at the Weizmann Institute in Rehovot studying the use of genetic engineering in cancer therapy. According to El- Shami, the adjustment to his new surroundings and colleagues was made easier by his strong friendship with several Israeli students while at Sussex. His decision to choose Weizmann, however, was mainly professional. "There are only a few leading centers in the world where advanced studies are being carried out on gene therapy for cancer," he explains. (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Government Robot Center TY : NEWS (NOTEBOOK) PG : 4 With a telerobotic vehicle turning the first shovelful of earth at groundbreaking ceremonies, Sandia National Laboratories has begun construction of a $33 million Robotic Manufacturing Science and Engineering Laboratory (RMSEL) on the lab's Albuquerque, N.Mex., grounds. Sandia officials say the 70,000-square-foot RMSEL will be one of the United States' premier facilities for research on and development of intelligent robotic systems. Housing about 150 staff, the facility is expected to handle all of the future R&D requirements in robotics and automation for Sandia and the Department of Energy. RMSEL will also serve to transfer new technologies to private industry. (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Healthy Technology Grants TY : NEWS (NOTEBOOK) PG : 4 The National Science Foundation and the Washington, D.C.- based Whitaker Foundation are teaming up to provide funding for research into technical innovations that promise to reduce health-care costs. Grants of up to $250,000 are being offered as part of the Cost-Reducing Health Care Technologies program. Information on the program is available on NSF's Science and Technology Information System (STIS) and BMEnet, a biomedical-enginineering system sponsored by Whitaker. On STIS, refer to publication NSF 94- 99. For information about STIS, contact NSF's publications section at (703) 306-1130 and request "STIS Flier," NSF Publication 94-4, or send E-mail to (Internet) or stisinfo@NSF (Bitnet). Access BMEnet at gopher:// or send E-mail to (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Red-Hot Therapeutic TY : NEWS (NOTEBOOK) PG : 4 Any Mexican food enthusiast with a healthy respect for the power of chili peppers should not be surprised at the potential efficacy of an ointment being prepared for clinical trials by a Johns Hopkins University neurologist. Marco Pappagallo is researching a salve to relieve the severe pain of peripheral neuropathy, a problem experienced by 10 percent of people with AIDS whose pain nerves in their legs and feet are infected with HIV. The balm, which contains a high concentration of ground peppers, has been shown to knock out the pain receptors of rats and mice, Pappagallo says, and he is hoping it will do the same in humans. Pappagallo notes, however, that the searing sensation produced when it's applied is so intense that clinicians at Hopkins' Blaustein Pain Treatment Center in Baltimore have to numb first-time patients with a spinal anesthetic beforehand. (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Guide To Undergraduate Research TY : NEWS (NOTEBOOK) PG : 4 The Directories of Undergraduate Research, published biannually by the Council on Undergraduate Research (CUR), are available. The directories describe 2,000 science departments at various schools stressing undergraduate research. For information, contact CUR, University of North Carolina at Asheville, 1 University Heights, Asheville, N.C. 28804; (704) 251-6006. Fax: (704) 251-6002. E-mail: (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Standards Software TY : NEWS (NOTEBOOK) PG : 4 The National Institute of Standards and Technology (NIST) in Gaithersburg, Md., has announced the availability of its Standard Reference Data Catalog 1994. Two of its 92 computerized databases and compilations, an NIST statement notes, are databases that could be useful to life and physical scientists. One new database, CHETAH, version 7.0, is designed for chemists to predict the performance of substances that they use routinely. Another, the Solution Kinetics Database, version 2.0, used by environmental scientists, chemists, and pharmacologists for modeling chemical reactions in solution, has been expanded. It now holds data on the rates of 10,800 free radicals derived from more than 14,000 experiments. For more information, contact SRDP, A320 Physics Building, NIST, Gaithersburg, Md. 20899- 0001; (301) 975-2208. Fax: (301) 926-0416. E-mail: (The Scientist, Vol:8, #17, pg.4, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Fore-tuitous Research TY : NEWS (NOTEBOOK) PG : 4 A North Carolina State entomologist is fighting bugs with bugs in an attempt to battle a pest threatening one of the state's cherished institutions: its golf courses. Rick L. Brandenburg, a professor and entomology specialist, is using pollen-eating flies and parasitic nematodes to take on the mole cricket, a tunneling insect with an appetite for grass. Golf courses are especially hard hit. But, says Brandenburg, "the red-eyed fly and entomogenous nematodes are the natural predators of the mole cricket" and are "genetically programmed to seek out and destroy it." Red-eyed flies attack and kill the crickets by laying eggs in them; the nematodes are parasitic worms that carry a bacteria lethal to the crickets. Brandenburg has worked with groundskeepers to conduct controlled releases of the flies and nematodes at North Carolina courses with successful results. (The Scientist, Vol:8, #17, pg.4 , September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : THE LEADERS OF SCIENCE The Readers of THE SCIENTIST PG : 8 RICHARD E. SMALLEY Gene and Norman Hackerman professer of chemistry and professor of physics, Rice University, Houston. Richard Smalley believes that "science is a crucial enterprise, not just to keep us economically competitive with other nations but, more important, to develop practical solutions to the dilemmas facing society." In his Rice University laboratory, Smalley developed a new technology-- supersonic cluster beams -- that enables a more detailed understanding of polyatomic structures. This technology provided an unprecedented look at the structure and character of chemical bonds in larger molecules. This research also led to the discovery of C60, the third elemental form of carbon in addition to diamond and graphite, in 1985. A soccer-ball-shaped molecule, C60 is known as buckminsterfullerene, or "buckyball," because its structure resembles the geodesic domes made famous by R. Buckminster Fuller. Smalley is currently concentrating on producing continuous carbon fibers, which essentially are giant single fullerene molecules. Just a few nanometers wide but many centimeters long, the fullerene fibers are expected to be the strongest fibers ever manufactured, perhaps 100 times stronger than steel. When eventually produced in large quantities, fullerene fibers promise to have widespread practical applications in the chemical, automotive, aerospace, and other major industries. Throughout his distinguished research career, Smalley has maintained a strong commitment to teaching. This year, he is teaching freshman chemistry to help inspire the next generation of scientists and educators. He has also succeeded in making Rice an important center for basic research, having founded the interdisciplinary Rice Quantum Institute in 1979. Despite his demanding schedule, Smalley takes the time to read THE SCIENTIST. He says "THE SCIENTIST is fun to read, topical, and up to date. It tells you about the interesting people who do science, as well as their interesting results." (The Scientist, Vol:8, #17, pg.8 , September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: OPINION ------------------------------------------------------------ TI : The Use Of Animals In Laboratory Research: Debate Presses Forward Experimentation On Animals Retards Progress Of Science AU : Kenneth P. Stoller TY : OPINION PG : 12 I have found that some scientists and some of my fellow physicians have thoughtful insights about the scientific and ethical issues raised by animal experimentation. Most, however, denounce critics of animal experimentation in a way that demonstrates little understanding or consideration of positions conflicting with their own. This is very disturbing. Unfortunately, the use of nonhuman animals in laboratories has always been entrusted to people in the habit of ardently shutting out criticism. Research bureaucrats, for example-- those who determine funding priorities--regularly sidestep criticism of animal experimentation, even if it comes from within the ranks of science and medicine. But certain challenges to their position are irrefutable. Since animal models are mere analogues to their human counterparts, experiments on animals can neither confirm nor disprove any scientific theory about humans. Thus, I suggest, changes in research priorities relating to animal experimentation are in order--changes that would likely accelerate the pace of medical progress. Reallocation of funds from research depending on animal models to clinical studies using human subjects would see funds being effectively applied to investigations that stand a better chance of reliably generating and testing hypotheses about humans. In their arguments, proponents of animal experimentation tend to cite laboratory animals' lack of specific human characteristics--intelligence, language capacity, close social ties, the capacity for suffering, and so forth--as justification for excluding them from ethical or moral consideration. But the reasoning and, consequently, the ethical positions of these animal-use advocates are faulty, since none of the aforementioned attributes is unique to our species. If, for example, the human capacity to suffer gains moral consideration for humans, then this reasoning should apply moral consideration to all nonhuman animals--even those lacking other human attributes--that share with humans that same capacity. And the fact that members of all other vertebrate species, as well as innumerable invertebrates, possess the capacity to suffer is documentably beyond dispute. Some defenders of animal experimentation claim that only 6 percent of laboratory animals suffer pain. This oft-cited statistic--a product of research conducted by the United States Department of Agriculture--is based on experimenters' reports of perceived animal pain. However, judging from documentation connected with the research, experimenters often classify painful procedures, such as lethal-dose toxicology tests or nonterminal surgery, as painless. Nor does the statistic take into consideration that animals used in experimentation experience other forms of suffering beyond the purely physical, such as environmental deprivation. The utilitarian argument that the benefits of animal experimentation outweigh its costs is equally bereft for several reasons. For example, it absurdly involves weighing the benefits to one's own group (humans) against the costs to another group (nonhumans). Furthermore, animal experimentation's benefit to humans has been grossly exaggerated by those who ultimately benefit in some way from being able to continue the practice. Most important, perhaps, the rationale of utility has been offered throughout history to justify all sorts of inhumane practices, including child labor and human slavery. Utilitarian arguments do not have a good track record. While it is true that more animals are abused, suffer, and die in connection with other human enterprises--agriculture, for example--than are maltreated in laboratories, this fact serves only to indict these other enterprises. It in no way exonerates animal research. Similarly, the fact that free-living animals suffer nature's hardships in no way entitles humans to add to the suffering. In recent years, those who are directly involved in animal experimentation have enthusiastically adopted the role of injustice sufferers, ever eager to play the righteous and defensive victims of animal-rights "extremists." For most of these so-called extremists, however, the propensity for violence is greatly exaggerated; and for those few among them who do commit acts of destruction, the useless folly of their behavior is obvious. The proponents of animal experimentation have become no less sanctimonious as a result of the extremists' violent acts--and laboratory animals have become no more protected. Surrounded by like-minded colleagues, many scientists confidently dismiss, as either uninformed or misanthropic, others' concerns about animal experimentation's scientific value and moral legitimacy. Given society's large financial stake in animal experimentation and the millions of animals harmed annually, we all have an obligation to address these issues. Kenneth P. Stoller is a pediatrician in private practice in Burbank, Calif. (The Scientist, Vol:8, #17, pg.12, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : The Use Of Animals In Laboratory Research: Debate Presses Forward Animal Rights Advocates' Actions Pose Big Threat To Public Health AU : Susan E. Paris TY : OPINION PG : 12 Owing to the ongoing debate over health-care reform, we've all become conversant on such once-esoteric subjects as "managed care" and "universal coverage." We're all interested in the matter, and the fact that politicians are meeting the issue head-on illustrates the power of public pressure. But there is one threat to human health that has slipped through a loophole in the public consciousness. It is a threat that has the potential to slow medical progress to a tedious crawl, delaying and sometimes stopping the search for cures and treatments. This threat takes the form of an anti-medical research movement, better known as animal rights. And because the public has failed to expose the movement's agenda and to condemn its tactics, it is growing stronger, more destructive, and more difficult to stop. This is no longer a movement composed of a small band of extremists. Membership in animal rights groups has grown fivefold since 1984, making it one of the fastest-growing social movements in the United States today. Further, letters concerning animals now constitute the third largest volume of mail to the U.S. Congress, exceeded only by those concerned with Social Security and the federal deficit. The animal rightists have also got the support of Hollywood's wealthy elite. Noted celebrities Kim Basinger, Alec Baldwin, and Paul and Linda McCartney, for example, all wave the animal rights banner for People for the Ethical Treatment of Animals (PETA), the largest animal rights group in the U.S. This widespread support has been achieved through a tremendous public manipulation campaign. Like many extremist groups, the animal rights movement cloaks its radical intentions under the guise of compassion, hoodwinking the public into believing animal extremists wish to strike a balance between human and animal interests. Yet, unlike the concept of animal welfare, which we all support, the animal-rights agenda calls for a fundamental change in the relationship between humans and animals--from one of responsible stewardship to one of absolute equality. Chief among the animal rights movement's goals is to abolish all medical research work with animals, no matter how necessary or humane. Ingrid Newkirk, cofounder and president of PETA, has stated publicly: "Animal research is immoral, even if it is essential." Of course, you won't find this statement in PETA's direct- mail fund-raising letters, or in its public presentations. But every single dollar of the $10 million donated annually to PETA fuels the spread of this philosophy. The same is true for the other $190 million donated to other animal rights groups nationwide. The animal rights movement uses a classic extremist strategy. The political wing presses forward on the propaganda front while the covert wing plants the bombs. Animal-rights lobbyists have had great success stopping medical research with legislative red tape and regulation. They have helped shift billions of dollars in medical- research funds into compliance with excessive regulations that do not contribute to the welfare of animals, but simply waste scarce resources. For example, laboratories, zoos, animal dealers, and auction operators spent an estimated $2 billion in 1990 complying with tougher federal rules covering the housing, feeding, watering, sanitation, and ventilation of animals. Those extremists for whom the legislative process moves too slowly resort to more dangeroud tactics. The Department of Justice issued a report to Congress in September 1993 that documented 313 instances of animal-rights terrorism in the U.S. since 1977, causing an extimated $1.37 million in direct damages. According to the report, security costs for animal enterprises have risen anywhere from 10 percent to 20 percent as a result of extremist animal-rights activity. Bulletproof glass had to be installed in the windows of the laboratory animal-care facility at the University of California, Berkeley. The cost of this security measure was $55,000. It is impossible to account for the costs in terms of human suffering and loss as a result of delayed or aborted research. But is is easy to see how the hopes of those in need of cures and treatments are left in a pile of debris with the torched remains of our nation's research enterprises. American recognize a need to deal with the health-care crisis. We have seen the problematic signs--rising costs of care and Americans without coverage--and we have acted. But all of the work being put into improving our health-care system will be for naught if we allow a powerful band of self-righteous activists to deny us the privilege of studying nonhuman animals--medical science's most valuable tool in the fight against disease. Susan E. Paris is president of Americans for Medical Progress Educational Foundation, an Arlington, Va.-based nonprofit organization dedicated to informing the public, the media, and policymakers about biomedical research. E- mail address: (The Scientist, Vol:8, #17, pg.12, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: COMMENTARY ------------------------------------------------------------ TI : Triage At NIH: A Smoke Screen Concealing The Real Problems Facing American Science AU : JOSE M. MUSACCHIO TY : OPINION (COMMENTARY) PG : 13 The National Institutes of HealthUs effort to streamline its peer-review process by virtually dismissing, after cursory examination, as many as half the research proposals it receives is not a good idea. This experiment at whatUs come to be known as "triage" will not solve any of the problems facing United States science; indeed, it will create new ones. Theoretically, early-stage identification and rejection of "noncompetitive" applications would relieve the pressure that burdens NIH scientific review administrators, project officers, and auxiliary staff who are overworked, demoralized, and under considerable stress. Reviewers, it is hoped, would have more time and presence of mind to consider in depth those comparatively few applications deemed at first glance to be especially virtuous. However, reviewers' demoralization cannot be attributed to the large number of applications they must deal with; they are used to putting in grueling, 12-hour days. That is one of the qualifications for the job, and their track record for hard work and productivity is one of the reasons they were chosen as reviewers. If the flow of NIH grant applications is heavier than the review administrators can handle, the problem is not that the number of proposals is too high, but that the number of administrators is too low--and the federal government's hiring freeze must bear the blame for that. What demoralizes reviewers is the awareness that a large number of excellent applications are not being funded and that the determination of which proposals are accepted and which rejected is largely arbitrary, since priorities above and below the funding line are not substantially different. It is frustrating for reviewers to work in a system in which insignificant differences in priority scores are the basis for making very significant decisions. Moreover, the triage concept will not save much of the reviewers' time, anyway, since all applications, as usual, will have to be initially evaluated to decide whether they merit full review. The only time reviewers will save is that expended in writing their reports on the proposals--which provide valuable feedback to applicants. And even the relatively trivial amount of time saved here will be significantly offset by that needed to communicate back and forth with scientific administrators until the two or three reviewers involved in the initial perusal of a specific proposal agree on how to proceed. Isn't it naive to think that such measures will solve the problems undermining American science? With triage, the demoralization of all extramural scientists will be aggravated. This will be especially critical with young scientists, who, without appropriate feedback, will never know what went wrong with their summarily rejected applications. In a sense, they will be suffering punishment for an unknown crime--perhaps one that they never committed- -and they will have no avenue of appeal. For more experienced investigators--those who have successfully pursued NIH funding in the past--the situation is likely to be infuriating as well as frustrating: "Do you mean," one might ask, "that after so many years in the business, I don't deserve the courtesy of a study-section review?" What we will have is a Kafkaesque situation that will demoralize everybody even further. In any case, the notion of triage--praised by some as a refreshing new concept--is by no means a true innovation. Informally, a version of it has always been used. Poor applications were rarely discussed in depth, and their budgets were never subjected to detailed, time-consuming scrutiny. However, applicants of even the obviously poor applications always got the benefit of a summary statement-- a public document for which the reviewers are accountable-- that the applicant could use in revising his or her application. With the current experiment in triage, thousands of applications will be rejected without discussion for reasons that will remain secret, because the valuable summary statements will be dispensed with. The critical problems facing American science do not stem from the review process, but from an economic condition allowing only a relatively few projects to be funded. Overselling the beneficial effects of triage is little other than a smoke screen concealing the deep problems of the status quo and the incapacity of NIH to really solve them. Jose M. Musacchio, a professor of pharmacology at New York University, served until recently on the National Institute of Mental Health's review committee for molecular, cellular, and developmental neuroscience. He is the author of "American science in crisis: the need to revise the NIH funding policy" (FASEB Journal, 8:679-83, July 19, 1994). (The Scientist, Vol:8, #17, pg.13, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: LETTERS ------------------------------------------------------------ TI : Reviewing The Reviewers AU : ARTHUR M. SHAPIRO TY : OPINION (LETTERS) PG : 13 Regarding the article "Critics Sharpen Assault On Peer Review" in the May 30, 1994, issue of The Scientist [P. McCarthy, page 1]: Most of us have probably suspected that our manuscripts were being reviewed by ill-informed and unqualified reviewers, but rarely do we get a clear indication that such is the case. Twice within the past few years I have done the same inadvertent experiment by accidentally omitting a pivotal citation from a manuscript. Anyone qualified to review either paper should have spotted so glaring an omission at once--and flagged it in the review. In both cases I spotted the error myself after the manuscript had gone out for review, then sat back and waited to see if the reviewers would spot it, too. The two manuscripts had a total of six reviewers, who among them picked a variety of nits. But not one of the reviewers caught the missing citation. Arthur M. Shapiro Section of Evolution and Ecology Division of Biological Sciences University of California Davis, Calif. 95616 (The Scientist, Vol:8, #17, pg.13, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Discriminatory Mentoring AU : MARGARET JENSVOLD TY : OPINION (LETTERS) PG : 13 In the article "Sex Discrimination Case Hinges On Concept Of Mentoring" (F. Hoke, The Scientist, May 16, 1994, page 3), the suggestion was made that the significance of the most precedent-setting aspect of Jensvold v. Shalala (that mentoring is covered under the discrimination law) for other women professionals is unclear. That is not correct. The most precedent-setting aspect of Jensvold v. Shalala to date came in the August 1993 summary judgment ruling on the case, not in the 1994 trial. The August 1993 ruling found that mentoring is protected under Title VII of the 1964 Civil Rights Act. That ruling is unaffected by subsequent events. On April 1, a unanimous jury of eight Maryland citizens ruled that David Rubinow's treatment of Margaret Jensvold at the National Institute of Mental Health constituted discriminatory mentoring, as well as sex discrimination and retaliation. This was precedent-setting in that it was the first time, to our knowledge, that a person has been found to have committed discriminatory mentoring. When the Supreme Court ruled on April 26 that the Civil Rights Act of 1991 is not retroactive, the jury's decision in Jensvold v. Shalala reverted to an advisory ruling. The judge will now rule on the merits of the case, taking the juryUs decision into advisement. So far Jensvold has won both rounds of summary judgment rulings and has won with the jury. The aspect of the case with broadest significance to women and minority professionals, including any graduate students, postdocs, residents, or fellows dealing with discrimination- -the August 1993 ruling extending the Title VII law to cover mentoring--is alive and well, unchanged. Margaret Jensvold Institute for Research on Women's Health 1616 18th St., N.W., Suite 109 Washington, D.C. 20009 (The Scientist, Vol:8, #17, pg.13, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- WHERE TO WRITE: Letters to the Editor The Scientist 3501 Market Street Philadelphia, PA 19104 Fax:(215)387-7542 E-mail: Bitnet: ===================================== NXT: RESEARCH ------------------------------------------------------------ TI : Molecular Structures Provide Insights Into Larger Questions In Biology AU : NEERAJA SANKARAN TY : RESEARCH PG : 14 **** Editor's Note: This is the second part of a two-part series on the field of structural biology. Part 1, presented in the Aug. 22, 1994, issue of The Scientist (page 14), discussed the evolution of this booming discipline. This article focuses on structural biology's key areas of basic and applied research and looks ahead to its future. **** Structural biologists have always considered their work--the study of the three-dimensional configurations of biological macromolecules such as proteins and nucleic acids-- profoundly important because it leads to understanding the relationships between form and function of subcellular components. But with rapid advances being made in the field, these scientists are coming to realize that structural studies hold the key to answering many larger questions in both basic and applied biological research. In the realm of basic investigations, structural biologists probe into problems that apply to both the plant and animal kingdoms. Guy Riddihough, editor of the fledgling journal Nature Structural Biology (Macmillan Magazines Ltd., London, England), points to such fundamental processes as photosynthesis and energy transformation in muscles as examples of biological reactions whose mechanisms are not fully understood because of inadequate information about the structures of the proteins involved. Other areas of basic research in which investigators are attempting to describe protein activity via their molecular structures include: antigen-antibody recognition, signal transduction (the transfer of messages across cell membranes), and the activation of cellular events such as RNA transcription and DNA replication. The wide reach of structural biology is also seen in industry, scientists say, because it is the basis for designing drugs and engineering various proteins such as vaccines, antibodies, and enzymes. As Riddihough puts it, when designing a drug against a particular virus, knowing the structure of the virus is important so that "we know what to inhibit." Molecular Machines One of the most intriguing puzzles in fundamental biological research is elucidating the structural basis of energy transformation, say many scientists. Examples of such reactions are the conversion of light to chemical energy in the case of photosynthesis, and of chemical energy to motive power in muscles. Photosynthesis involves the capture of photons--discrete packages of light energy--by plant cells. This energy is used to split water molecules, ultimately producing food for the plant in the form of sugar and oxygen. "Photosynthesis is the single most important reaction on planet Earth--all life is dependent on it," says Kenneth Miller a researcher at Brown University, in Providence, R.I. "Even a 1 percent increase in efficiency of the process would have tremendous implications for the productivity of the land," adds Riddihough. While the first three-dimensional structure of a protein was described in the early 1950s on the basis of X-ray crystallography, the structure of the photosynthetic complex--the part of a plant's cell that captures photons-- proved more elusive. The main reason for this, say scientists, is that the photosynthetic apparatus is a complicated mixture of membrane-bound proteins intricately linked with light-sensitive pigment molecules called chlorophylls. "The standard `rap' was that membrane proteins could not be crystallized because of their hydrophobic nature," says Miller. But, notes Johann Deisenhofer, an investigator at the Howard Hughes Medical Institute Research Laboratories at the University of Texas Southwestern Medical Center in Dallas, his former colleague, crystallographer Hartmut Michel, "believed that a membrane protein [could] also be crystallized." Using a combination of detergents to solubilize the membrane proteins without distorting its conformation, Deisenhofer, Michel, and Robert Huber--working at the Max Planck Institute for Biochemistry in Martinsreid, Germany-- crystallized and solved the structure of the photosynthetic apparatus of the cyanobacterium Rhodopseudomonas viridis (H. Michel, Journal of Molecular Biology, 158:567-72, 1982). For this achievement, they received the 1988 Nobel Prize in chemistry. "Suddenly, in one glance, the field was advanced by a decade," says Miller. "We could see the bacteriochlorophyll pigment sitting in the heart of the reaction center." The reaction center is the location in the photosynthetic complex where photons are absorbed, and the resulting energy is used to split water molecules. But the photosynthesis story is still incomplete, researchers point out, with the light-harvesting complex in higher plants--called photosystem II--still defying all attempts at complete characterization. This leaves researchers with many questions--answers to which they hope to find as more structural details about the system become evident. For instance, Miller says that there is "a real prize" waiting for researchers in discovering the details of the water-splitting site of the photosynthetic membrane. A second trophy will come with an understanding of the conversion of a molecule called adenosine diphosphate (ADP) to its high-energy triphosphate form (ATP), which happens in response to the proton gradient generated when a water molecule is split during photosynthesis. Understanding the mechanisms of energy transfer involving ATP is also a target for those delving into the structural biology of the muscle proteins actin and myosin, according to Ivan Rayment, a scientist at the Institute for Enzyme Research in Madison, Wis. Myosin "is a funny-shaped molecule with two heads attached to a very long tail," says Rayment, who has been investigating its three-dimensional configuration. The structural details of myosin, he notes, made it finally possible to postulate how the molecule works as a motor to generate motion from ATP's chemical energy (I. Rayment, H.M. Holden, Trends in Biochemical Sciences, 19:129-34, 1994). Industrial Designs The structural approach to understanding how molecules work has been of great practical importance to the pharmaceutical industry, say scientists, pointing to the many firms with large research groups of protein crystallographers. A dozen leading drug companies--including Abbott Laboratories, Abbott Park, Ill.; New York City-based Bristol-Myers Squibb Co.; Glaxo Inc. of Research Triangle Park, N.C.; Philadelphia-based SmithKline Beecham; and Procter & Gamble Co. in Cincinnati--have formed a consortium called the Industrial Macromolecular Crystallographic Association (IMCA) to share costs on building a common structural biology facility. IMCA will construct a $12 million experimental station, with a beam line off the Advanced Photon Source (APS), a U.S. Department of Energy-funded synchrotron-type X-ray source at Argonne National Laboratory in Illinois. APS will supply highly intense and focused X-rays that IMCA scientists will use in their various research projects. "We will share the costs of the facility, but each company will conduct its own research," says Cele Abad-Zapatero, a protein crystallographer at Abbott Laboratories and a member of IMCA's committee to supervise the building of the beam line. For his company, Abad-Zapatero adds, "it will be like having a synchrotron in our backyard" because of the proximity of APS and Abbott's headquarters. Since the X-rays from APS are several times more brilliant than those produced in-house by any of the companies, researchers at the new facility will be able to conduct their experiments far more efficiently than before, says Steven Jordan, a scientist representing Glaxo Inc. in IMCA. Jordan will use the X-rays to facilitate his research on anti-cancer drugs, which he is designing to inhibit a class of enzymes called tyrosine kinases. "An aberrant form of this enzyme is seen, associated with several cancers," he says. In addition to designing drugs that inhibit the protein components of infectious agents, industrial researchers are looking into modifying the structures of proteins themselves. For instance, Abad-Zapatero has worked on improving the characteristics of the enzyme alkaline phosphatase, which is used by Abbott Labs in various diagnostic kits and assays. "Originally we used [alkaline phosphatase] from calf intestines, but this was a very labile enzyme," he says. A cheaper, stabler form of the enzyme was discovered in the bacterium Escherichia coli. But Zapatero explains that the activity of the enzyme was too low to be substituted for the calf enzyme in the assay kits. Through a combination of mutagenic and X-ray crystallographic techniques, the researchers were able to pinpoint the location of the enzymatic activity to engineer improved forms of the bacterial enzyme for use in their kits. The structure of the mutant enzyme is described by Abad- Zapatero and his colleagues in a paper in the journal Protein Engineering (L. Chen et al., 5:605-10, 1992). Things To Come As the scientific community is flooded with a torrent of structural data, researchers are looking ahead to future challenges and discoveries that the study of proteins will bring. "One of the biggest challenges is to use the structural information more efficiently," says Jordan. "We need to understand the dynamics of structure properly." For instance, he says, scientists still can't predict exactly how a drug is going to behave when it comes in contact with a protein. "Not all structures generate a great `aha' of instant insight into biological activity," wrote Wayne Hendrickson and Carl Ivan-Branden, the editors of a new journal, Structure, (Current Biology Ltd., London) in the first editionUs opening essay (Introductory issue, pages i-ii, 1993). But recognition of the biological significance of a new structure is often inspirational, they add. "The implications [of structural biology] are profound in the extreme," says Guy Riddihough. He speculates that biological structures could yield meaningful insights into some of the most fundamental puzzles that scientists are attempting to solve: "Questions about the origin of life could be answered." (The Scientist, Vol:8, #17, pg.14, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : STRUCTURAL SUPPORT TY : RESEARCH PG : 14 Following are some of the professional organizations whose memberships include structural biologists: American Chemical Society 1155 16th St., N.W. Washington, D.C. 20036 (202) 872-4600 Fax: (202) 872-4615 * Ned Heindel, president * John K. Crum, executive director American Crystallographic Association P.O. Box 96, Ellicott Station Buffalo, N.Y. 14205-0096 (716) 856-9600 Fax: (716) 852-4846 E-mail: * Elinor Adman, president * William L. Duax, executive officer American Society for Biochemistry and Molecular Biology 9650 Rockville Pike Bethesda, Md. 20814-3996 (301) 530-7145 Fax: (301) 571-1824 * Gordon G. Hammes, president * Charles Hancock, executive officer Biophysical Society 9650 Rockville Pike Room 0512 Bethesda, Md. 20814 (301) 530-7114 Fax: (301) 530-7133 E-mail: * Ralph G. Yaunt, president * Emily M. Gray, executive director Protein Society 9650 Rockville PikeRoom B109 Bethesda, Md. 20814 (301) 530-7026 (800) 99-AMINO, Ext. 7026 Fax: (301) 530-7049 E-mail: * Joseph Villafranka, president The following new journals publish structural biology research: Structure * Editors: Wayne A. Hendrickson and Carl-Ivar Branden Main office: 34-42 Cleveland St. London, U.K. W1P 5FB Phone: (44) (71) 580 8377 Fax: (44) (71) 580 8428 E-mail: U.S. editorial office: 251 Hugo St. San Francisco, Calif. 94122 (415) 566-4880 Fax: (415) 566-4594 U.S. managing editor: Rebecca Ward Nature Structural Biology * Editor: Guy Riddihough Editorial office: 1234 National Press Building Washington, D.C. 20045 (202) 626-2518 Fax: (202) 626-2528 E-mail: (The Scientist, Vol:8, #17, pg.14, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: HOT PAPERS ------------------------------------------------------------ TI : AUTOIMMUNOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 G.J. Giudice, D.J. Emery, L.A. Diaz, "Cloning and primary structural analysis of the bullous pemphigoid autoantigen, BP180," Journal of Investigative Dermatology, 99:243-50, 1992. George J. Giudice (Departments of Dermatology and Biochemistry, Medical College of Wisconsin, Milwaukee): "Our investigation of an autoimmune skin disease has uncovered a novel protein that may function in cell-matrix adhesion. The disease, bullous pemphigoid, is characterized by a blistering of the skin due to a detachment of the epithelium from the connective tissue layer, and by the production of autoantibodies directed against the cutaneous basement membrane zone. In an attempt to identify and characterize self antigens associated with this disease, we screened a cDNA expression library with serum from a bullous pemphigoid patient. In this way we cloned a novel epidermal protein, BP180, which localizes to the hemidesmosome, a cellular structure involved in anchoring basal epithelial cells to the basement membrane. "Our analysis revealed that BP180 has a very unusual domain organization--a single, membrane-spanning, signal-anchor sequence and a long carboxy-terminal collagenous tail (the ectodomain) that projects from the epidermal cell into the basal lamina. We speculated that the ectodomain of BP180 forms a collagen-like triple helix and may interact with one or more components of the extracellular matrix. Further, it was postulated that autoantibody-mediated disruption of BP180 function might play a key role in the pathogenesis of bullous pemphigoid. "The subsequent search for pathogenically relevant autoantibody-reactive sites on the BP180 protein focused on non-collagenous segments of the BP180 ectodomain--sites that were predicted to be accessible to circulating autoantibodies prior to tissue injury. Using deletion mutation analysis, we succeeded in mapping an immunodominant extracellular epitope on BP180 that is recognized by most bullous pemphigoid sera (G.J. Giudice et al., Journal of Immunology, 151:5742-60, 1993). Remarkably, antibodies that react with the corresponding site on the murine BP180 homolog are highly active in inducing a skin disease that closely mimics bullous pemphigoid at the clinical, histological, and immunological levels (Z. Liu et al., Journal of Clinical Investigation, 92:2480-8, 1993) when passively transferred into neonatal mice. "Future studies will be directed at more precisely defining the role of BP180 in the structure and function of the skin under both normal and pathological conditions. We hope that this information will eventually lead to the development of more effective therapeutic strategies for treating this autoimmune disease." (The Scientist, Vol:8, #17, pg.16, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : NEUROSCIENCE TY : RESEARCH (HOT PAPERS) PG : 16 T. J. Coderre, R. Melzack, "The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury," Journal of Neuroscience, 12:3665-70, 1992. Terence J. Coderre (Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Canada): "It has become increasingly evident over the past few years that, in addition to a sensitization of peripheral nociceptors, peripheral tissue injury leads to a sensitization of neurons in the central nervous system (CNS). This sensitization is a form of neuronal plasticity that may contribute to the development of persistent pain and hyperalgesia. It has also become evident that excitatory amino acids play a critical role in the development of various forms of neuronal plasticity, including long-term potentiation, neuronal growth, and neurotoxicity. Our studies were aimed at examining the potential involvement of an excitatory amino acid-dependent neuronal plasticity to the development of persistent pain following peripheral tissue injury. "When injected subcutaneously into a ratUs paw, the chemical irritant formalin produces an acute barrage of C-fiber afferent activity, followed by a prolonged phase of persistent activity in dorsal horn neurons. Behaviorally, the injury produces a brief acute phase of nociceptive behaviors (such as paw elevation, flinching, and licking), followed by a delayed, long-lasting second phase. The second-phase dorsal-horn neuronal responses (A.H. Dickenson, A.F. Sullivan, Pain, 30:349-60, 1987) and the behavioral nociceptive responses (T.J. Coderre et al., Brain Research, 535:155-8, 1990) to formalin are attenuated by pretreatment with intrathecal opioids or local anesthetics, which are active during the first phase. These data suggest that neuronal activity during the first phase is required to initiate the enhanced excitability and persistent nociceptive behaviors expressed in the second phase. "Studies published prior to this paper demonstrated that excitatory amino acids contribute both to a cumulatively increasing post-synaptic depolarization or wind-up of dorsal horn neurons in response to repetitive afferent nerve stimulation (S.N. Davies, D. Lodge, Brain Research, 424:401- 6, 1987; A.H. Dickenson, A.F. Sullivan, Neuro-pharmacology, 26:1235-8, 1987) and to increases in the excitability of flexor motor neurons following intense stimulation of afferent nerves (C.J. Woolf, S.W.N. Thompson, Pain, 44:293- 9, 1991). The featured paper extended these findings by providing evidence that the persistent nociceptive responses to formalin-induced tissue injury were critically influenced by excitatory amino acid transmission. Persistent nociceptive responses were maximally enhanced by pretreatment with the endogenous excitatory amino acids L- glutamate and L-aspartate, as well as by combined pretreatment with the selective excitatory amino acid receptor agonists NMDA and AMPA, or NMDA and trans-ACPD. "Nociceptive responses after formalin injury were also dose- dependently attenuated by selective NMDA receptor antagonists. Importantly, the pretreatment with excitatory amino-acid agonists and NMDA receptor antagonists had much more pronounced effects on the persistent second phase of nociceptive responses than on the acute first phase. This suggests that excitatory amino acids are more critically involved in the development of persistent nociception associated with central sensitization or hyperexcitability than in the initial brief response to noxious stimuli. Furthermore, it was shown that administration of NMDA antagonists before--but not after--formalin injury attenuated persistent nociceptive responses, suggesting that activity at NMDA receptors is required to initiate central sensitization leading to persistent nociception, but not to maintain it. "These findings demonstrated a clear role for excitatory amino acids in a behavioral pain model that is dependent on central sensitization. Subsequent studies have shown that excitatory amino acid receptors play a critical role in the development of spontaneous nociceptive behaviors and hyperalgesia in both inflammatory (K. Ren et al., Pain, 50:331-44, 1992) and neuropathic (J. Mao et al., Brain Research, 598:271-8, 1992) pain models. Our companion paper (T.J. Coderre, R. Melzack, J. Neuroscience, 12:3671-5, 1992) implicated a contribution of the influx of extracellular calcium through NMDA receptor-operated calcium channels to persistent nociception after formalin injury. In addition, more recent data from several other laboratories have shown that various intracellular messengers that are linked to excitatory amino acid receptors (such as nitric oxide, arachidonic acid, and protein kinase C) play a critical role in the development of persistent nociception following formalin-induced tissue injury (A.B. Malmberg, T.L. Yaksh, Journal of Pharmacology and Experimental Therapeutics, 263: 136-46, 1992; T. Yamamoto et al., Anesthesia and Analgesia, 77:886-90, 1993; T.J. Coderre, K. Yashpal, European Journal of Neuroscience, 6:1328-34, 1994)." (The Scientist, Vol:8, #17, pg.16, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: TOOLS & TECHNOLOGY ------------------------------------------------------------ TI : Cytokines Play Growing Role As Research Reagents In Biological Labs AU : Holly Ahern TY : TOOLS & TECHNOLOGY PG : 17 Molecular biologists and biochemists these days are focusing an increasing share of their investigations on the activities of a class of small peptide messenger molecules called cytokines. These incompletely understood substances, secreted by immune-system cells and transported in the blood, function chiefly as facilitators for a multitude of immune-system responses, such as inducing inflammation in targeted tissues or inhibiting the replication of viral invaders in the body. Receptors for these biochemical messengers are present on the surfaces of many types of cells throughout the body, and cytokines are important players in a wide array of cellular activities, both normal and pathologic. For example, genetically modified mice--so-called knockout mice--that lack genes for cytokines or cytokine receptors generally die either before or shortly after birth, implying, among other things, that cytokines play critical roles during the development process. Other areas currently under study include the biology of endothelial cells, vasculogenesis, angiogenesis, and atherosclerosis. In the last decade, an avalanche of such research findings about cytokines has led to a booming demand for these molecules as reagents to facilitate study of their unique properties. The list of commercially available purified cytokines is growing exponentially, with suppliers of laboratory biochemicals working closely with researchers in producing cytokines that may have uses in investigations of cancer, arthritis, HIV, and other diseases. In cell and developmental biology, an especially active area of investigation concerns the stimulatory effects of cytokine growth factors on cells in culture. "Ninety to 95 percent of the calls we receive are from researchers who are trying to stimulate the growth of a particular type of cell, such as a nerve cell or a particular hybridoma clone, with a growth factor," says Willis Eubanks, a technical specialist in cell biology for Life Technologies Inc. in Gaithersburg, Md. Cytokines help increase the production of antibodies from hybridoma cells, for example. Typically, the hybridoma cells are kept in a hollow-fiber growth chamber, separate from their secretions, to increase yield. "By stimulating the growth of the hybridoma clone there is a higher yield of antibody," Eubanks says. Life Technologies markets cytokine growth factors in association with tissue-culture media and reagents through its parent company, Gibco BRL in Grand Island, N.Y. Gibco also sells an array of cell-culture media, serum, and growth factors. Cytokines, with their wide range of biological activity, are among the most intriguing and actively studied members of the multicomponent system responsible for the body's strategic defense against disease. Other members of this complex network of cells and cellular biochemicals include white blood cells--some, such as macrophages, scavenge rogue particles and clear them from the body, while others secrete antibodies to neutralize toxic substances. Cytokines secreted by immune-system cells scurry between these cells bearing messages to step up the attack or slow it down. Although the list of identified cytokines is long, researchers have only begun to appreciate how complex this interactive network of regulatory substances really is. "Cytokines perform a myriad of different functions in the body," says Jordan Fishman, director of scientific operations and cofounder of Quality Controlled Biochemicals Inc. (QCB) in Hopkinton, Mass., a biochemical reagents supply company. "Generally, cytokines act as intercellular messengers, particularly in response to an infection. They affect cells in many of the major organ systems as well as the immune system, where they cause the proliferation and differentiation of immune cells like T cells and the various T-cell subsets, B cells, and macrophages." QCB is another of the growing number of companies that sell cytokine products such as human cytokines, mouse cytokines, and cytokine assay reagents. But QCB, along with companies such as R&D Systems of Minneapolis and Endogen Inc. in Cambridge, Mass., also offer more specialized items. Endogen, for example, markets three principal product lines, consisting of reagents and immunoassay test kits to human and mouse cytokines, and for cell-adhesion studies. Many Aliases Cytokines were initially recognized in the mid-1960s as potent mediators of cell division and differentiation. Lymphocytes in culture could be stimulated to produce these biologically active substances when they were treated with specific antigens or with nonspecific mitogens such as poke weed, which induces many kinds of cells to proliferate. Early investigators characterized these mysterious substances by the functional response they gave. The scientific literature was peppered with reported discoveries of a large number of cell factors with stimulatory or inhibitory activities, bearing names like lymphocyte-activating factor (LAF), T-cell growth factor (TCGF),B-cell-activating factor (BAF), and mitogenic factor (MF). Once the individual factors were purified and cloned, researchers found that many of the reported activities could actually be traced to a much smaller number of substances, which were all small-molecular-weight proteins apparently secreted by various immune-system cells. As a group, these secreted biochemicalswere eventually dubbed "cytokines," to denote their interactive role in cellularcommunication. "In a general sense, growth factors, interferons, and interleukins could all be categorized as cytokines," says Eubanks of Life Technologies. "The confusion in the nomenclature stems from the field growing so rapidly. If you look at the history of an individual cytokine, you might see it referred to as a specific growth factor or stimulating factor before it became known as an interleukin." Cytokines act by binding to a receptor molecule on the surface of a cell, causing an intracellular message to be transduced across the cell membrane. Although the precise mechanisms involved are not completely understood, the transduced signal appears to be able to activate the genes responsible for cell division, differentiation, or other cell processes. In many cases, the cytokine message stimulates target cells to produce more and different kinds of cytokines. Sometimes, a cytokine can stimulate certain cells to divide or differentiate, while at the same time deactivate other cells involved in the same immune response. "Cytokines complement each other," says Eubanks. "One cytokine might stimulate one type of cell where another might suppress it." For example, says Albert Millis, a cell biologist at the State University of NewYork, Albany, "TGF-B has been shown to induce the expression of connective tissue-like molecules, while at the same time suppressing or inhibiting the expression of certain metalloproteinases that degrade this type of tissue." Millis uses cytokines like TGF-B in his studies on fibroblasts and smooth muscle cells and notes that, at least in vitro, these effects seem to be concentration-dependent."At one concentration TGF-B appears to be an inhibitor, while at other concentrations this same cytokine stimulates growth." Packing A Punch The concentration dependency of cytokines may have something to do with the extraordinary potency of these small proteins. "Cytokines act in the picomolar to femtomolar range," says Fishman. "Even at very low concentrations, their effect is profound." Because cytokine receptors are expressed on the surfaces of such a large number of diverse cells, the response elicited by these chemical messengers is often swift and far reaching. And they seldom act alone. In an immune response to a foreign particle, for example, a single lymphocyte might secrete several different cytokines into the extracellular mileu. How target cells respond to the secreted mix of cytokines varies. Some cells proliferate, others might produce antibodies, while still other cells secrete additional cytokines that call phagocytic scavengers into the fray. Ultimately, a complex network of interacting immune cells is generated that effectively disarms the offending particle. Once the battle is over, additional cytokines signal the immune system to turn down the response and get back to daily business. Lymphocytes and macrophages aren't the only cells under the influence of the cytokine network. Researchers L. Maximilian Buja and Roger J. Bick at the University of Texas Health Science Center in Houston have added cytokines to cultures of cardiac cells, or myocytes, and observed how the cells and substances interact during periods when the myocytes are stressed, such as in the case of reduced blood flow to the heart, or ischemia. In their studies, cytokines IL-1a and IL-1o, along with TNF, were found to modulate the activity of the myocytes, perhaps playing a key role in maintaining cardiac function during periods of acute stress. Many researchers believe that there is logic in this natural strategy. "Even things like liver regeneration have been shown to be influenced by cytokines," says QCB's Fishman. RTo a point, the proliferation or differentiation of a cell is going to be similar regardless of the cell type. If you can modify the activity of a blood cell [with cytokines], you should be able to do the same thing with a parenchymal cell or a hepatocyte, and studies are proving that it works." Several cytokines are known to be involved in regulating the body's inflammatory response. In acute inflammation, cytokines IL-1, IL-6, and TNF-a are released from tissue macrophages and, acting together, cause the body to respond with a plethora of biological activities, including the release of more cytokines and other biochemicals with greater systemic influence. The net effect might be fever, increased vascular permeability to the inflamed area, production of new platelets, and the synthesis of antibodies, along with other responses, all aimed at killing off an invader or healing the inflamed tissue. In the case of a chronic infection, as is sometimes seen with some infectious agents and in several autoimmune disorders, this form of massive response can go too far, causing cytokine- mediated damage to the surrounding tissue. The destruction of joint tissues in diseases like arthritis begins this way, for example. Therapeutic Tools? Because cytokines play such an important role in the overall functioning of the immune system, many researchers are looking at ways of using cytokines or cytokine inhibitors as human therapeutic agents. In the body, cytokines have been praised as potent viral and cancer-fighting agents, and conversely accused of promoting arthritis and severe allergic attacks. Thus cytokine research is multipronged--in some studies the goal is to boost cytokine production, while in others it is to turn it down or off. Research opinion is mixed over using cytokines as human therapeutics. For a time in the 1980s, many investigators were hopeful that certain cytokines could be used to treat some cancers. When tumors were found to draw the attention of the immune system, particularly natural killer cells, researchers turned to the potent properties of cytokines to enhance the body's inherent anticancer response. Clinical trials of diverse interleukins, interferons, and TNF have shown varying degrees of success. In in some people, tumors regress; but in other patients, regression is partial or undetectable. Moreover, the cytokine approach to tumor treatment has been fraught with technical problems, including the short lifespan of the soluble substances along with the variety of adverse side effects brought on by cytokine treatments. Because of the variations in the results of these types of studies, the focus of cytokine research along these lines has switched to the test tube. Using cytokines to activate cells taken from a cancer patient and grown in culture has shown promise, especially for inoperable tumors. When the cytokine-treated cells are infused back into the cancer patient, the activated cells target the tumor for destruction by the immune system. Another approach is gene therapy. Cells removed directly from a tumor can be supercharged with extra cytokine genes with the hope that the engineered tumor cells will produce cytokines to step up the defense effort by attracting the patientUs own immune cells. "The immune system is very powerful," says Fishman, "and cytokines are very potent modulators of the immune response." A cytokine-focused immune attack could selectively kill off the cancerous cells, leaving the healthy tissue intact. Viral infections are known to induce specific patterns of cytokine production, particularly from T-cells. Some cytokines produced in response to HIV infection have been implicated at many levels in the pathology of AIDS. On the other hand, for viruses like HIV, which hide inside of cells, a T-cell-mediated response may be the only way for the immune system to bring an infection under control. It may be possible to use cytokines to selectively stimulate the subsets of lymphocytes that fight viral diseases like AIDS. "The immune system doesn't always do the right job," concludes QCB's Fishman. "But perhaps with the right combination of cytokines we could achieve `super-human' results." Holly Ahern is a science writer and an assistant professor of biology at Adirondack Community College in Queensbury, N.Y. (The Scientist, Vol:8, #17, pg.17, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : SUPPLIERS OF RESEARCH REAGENT CYTOKINES TY : TOOLS & TECHNOLOGY PG : 18 The following companies provide a broad array of cytokines and related products for use in biological research laboratories. For more information, please use the Reader Service Card inserted in this issue. Accurate Chemical & Scientific Corp. Westbury, N.Y. Circle No. 049 on Reader Service Card AMAC/Immunotech Inc. Westbrook, Maine Circle No. 050 on Reader Service Card Amersham Corp. Arlington Heights, Ill. Circle No. 051 on Reader Service Card BACHEM Bioscience Inc. King of Prussia, Pa. Circle No. 052 on Reader Service Card Becton Dickinson/ Falcon Labware Franklin Lakes, N.J. Circle No. 053 on Reader Service Card BoehringerMannheim Biochemicals Inc. Indianapolis Circle No. 054 on Reader Service Card Calbiochem Novabiochem Corp. San Diego Circle No. 055 on Reader Service Card Chemicon International Inc. Temecula, Calif. Circle No. 056 on Reader Service Card Endogen Inc. Cambridge, Mass. Circle No. 057 on Reader Service Card Fitzgerald Industries International Concord, Mass. Circle No. 058 on Reader Service Card Genzyme Diagnostics Cambridge, Mass. Circle No. 059 on Reader Service Card Harlan Bioproducts for Science Indianapolis Circle No. 060 on Reader Service Card Immunocorp Montreal Circle No. 061 on Reader Service Card INAMCO Chemicals & Lab Equipment Flushing, N.Y. Circle No. 062 on Reader Service Card INCSTAR Corp. Stillwater, Minn. Circle No. 063 on Reader Service Card Intergen Co. Purchase, N.Y. Circle No. 064 on Reader Service Card Life Technologies Inc. Gaithersburg, Md. Circle No. 065 on Reader Service Card Mallinckrodt Chemical Inc. Chesterfield, Mo. Circle No. 066 on Reader Service Card Oncogene Science Cambridge, Mass. Circle No. 067 on Reader Service Card PerSeptive Diagnostics Cambridge, Mass. Circle No. 068 on Reader Service Card PharMingen San Diego Circle No. 069 on Reader Service Card Pierce Chemical Co. Rockford, Ill. Circle No. 070 on Reader Service Card Promega Madison, Wis. Circle No. 071 on Reader Service Card Quality Controlled Biochemicals Inc. Hopkinton, Mass. Circle No. 072 on Reader Service Card R&D Systems Inc. Minneapolis Circle No. 073 on Reader Service Card Research Diagnostics Inc. Flanders, N.J. Circle No. 074 on Reader Service Card Sigma Immunochemicals St. Louis Circle No. 075 on Reader Service Card StemCell Technologies Inc. Vancouver, B.C., Canada Circle No. 076 on Reader Service Card Unisyn Technologies San Diego Circle No. 077 on Reader Service Card VMRD INC. Pullman, Wash. Circle No. 078 on Reader Service Card (The Scientist, Vol:8, #17, pg.18, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : NEW PRODUCTS TY : TOOLS & TECHNOLOGY PG : 19 Hewlett-Packard's Benchtop ICP-MS System Debuts Hewlett-Packard Co. recently introduced what it claims to be the first benchtop inductively coupled plasma mass spectrometer (ICP-MS) system. The HP 4500 ICP-MS features the Omega lens ion-optics system, which bends the ion beam, allowing a hyperbolic quadrupole and detector to be mounted off-axis and reducing the random background to less than 2 cps across the mass range. The combination of very low background and high transmission quadrupole results in detection limits in the parts-per-trillion (ppt) or sub-ppt range for most elements, according to the company. In addition, the ShieldTorch interface is said to virtually eliminate many polyatomic interferences, enabling the determination of potassium, calcium, and iron at ppt levels. Other features include a compact, solid-state quadrupole radio-frequency generator operating at 3.0 Mhz, which provides abundance sensitivity, and a discrete dynode detector with a dual-mode acquisition system that gives eight orders of linear dynamic range. The system is controlled entirely through an HP Vectra PC, and all system parameters--including vacuum, sample-uptake rate, gas flows, ICP RF power, ion lenses, and quadrupole and detector voltage--are software-controlled. In addition, stepper motors adjust the plasma position in all three planes, and intelligent autotuning optimizes the system automatically. Circle No.78 on Reader Service Card Hewlett-Packard Co., Analytical Products Group, San Fernando, Calif. ------ Dynal's Dynabeads For Protein Purification Dynabeads M-280 Immunomagnetic Separation Technology is intended as an alternative to conventional methods of protein purification. The technology is said to offer reproducible results and reduced nonspecific binding, which results in fewer interference bands and lower background. Dynabeads M-280 products are uniform superparamagnetic polystyrene beads that provide a magnetic solid phase, which facilitates protein purification. They bind to the ligand/target molecule to form a complex that can readily be separated from the heterogeneous sample by exposure to a magnet. Elution of the pure captured protein is performed by standard elution procedures. Dynabeads M-280 Sheep anti- Mouse IgG and Dynabeads M-280 Sheep anti-Rabbit IgG are designed for use with primary antibody ligands, and Dynabeads M-280 Streptavidin is available for use with biotinylated ligands. Dynabeads M-280 Tosylactivated products are also available for use with unique proteins. Circle No. 79 on Reader Service Card Dynal Inc., Lake Success, N.Y. ------ New RNA PCR Kit From Perkin-Elmer The GeneAmp EZ rTth RNA PCR Kit is designed for rapid, sensitive and easy sample screening with RNA polymerase chain reaction. It uses both the verse transcriptase and DNA polymerase activities of a singel thermostable DNA polymerase, rTth DNA polymerase. RNA PCR facilitates the detection and analysis of gene expression at the RNA level as well as detection of RNA species at very low copy numbers, such as cullular RNAs and viruses. The new kit contains all the necessary components for reverse transcription of RNA to cDNA and subsequent amplifications, using the GeneAmp PCR process with a single enzyme, rTth DNA polymerase, in a single reaction vessel and single buffer system. The transition form reverse transcriptase actiivity to DNA polymerase activity occurs without buffer changes or subsequent reagent addition steps. The use of rTth DNA polymerase, a thermoactive and thermostable enzyme, allows for increased specificity in primer binding as well as alleviation of problematic secondary structures in the RNA template, according to the company. The kit uses a bicine buffer rather than the standard Tris-HCI buffer. This enables the buffering of both the metal and hydrogen concentration, which reportedly allows for efficient DNA polymerase activity at high temperature. Perkin-Elmer Corp., Applied Biosystems Division, Foster City, Calif. ------ Molecular Dynamics' New Laser-Based Densitometer Molecular Dynamics says its Personal Densitometer SI system is the first laser-scanning densitometer that works with both Macintosh and DOS personal computers. The system uses the small computer standard interface (SCSI) protocol to send and receive data to and from the computer. This enables users to connect the Personal Densitometer SI in-line with magneto-optical drives, additional Molecular Dynamics scanning instrumentation, and other devices. The new densitometer is optically accurate from 0 to 4 O.D. and uses a light-collecting cylinder for photon capture and quantitation. This makes the instrument a good tool for membrane-based assays requiring fine O.D. discrimination against high background levels of absorbance. Molecular Dynamics, Sunnyvale, Calif. Circle No. 81 on Reader Service Card ------ CHEMiCALC Software Is Upgraded CHEMiCALC software for Windows, Macintosh, and DOS systems combines seven specialty-software tools in a single package: a periodic table database; a molecular-weight calculator; a chemical-reaction stoichiometry calculator; a solutions calculator; a unit-conversion program, including compound units; an empirical-formula calculator; and a salt- solubility database. The software also includes the RPN scientific calculator. All of these calculation tools are interactively tied together with a periodic table interface. Chemical Concepts Corp., Ann Arbor, Mich. Circle No. 82 on Reader Service Card ------ Intermountain Offers In-Situ Hybridization, Amplification System The OmniSlide system for in-situ hybridization and amplification features a thermal cycler with an advanced microprocessor that allows control over sample temperature. The system's software provides for a variety of features, such as power failure restart, display of projected time of finish of the experiment, and card programmability. Up to 20 slides can be loaded into the system's slide rack and placed onto twin cycling blocks. A humidity chamber surrounds the blocks to maintain sample integrity while cycling. A temperature-controlled wash module allows samples to be incubated with a minimum amount of solution while maintaining a precise temperature environment. The module has two independently controlled chambers, each with a capacity for 20 slides. Scientific Corp., Kaysville, Utah Circle No. 83 on Reader Service Card ------ MDL Releases ISIS/Desktop 1.2 The ISIS/Desktop 1.2 software package features the new ISIS Structure-Activity Relationship Table (ISIS SAR Table). A single command allows scientists to place selected data in a Microsoft Excel spreadsheet. The data include not only text and numbers but also a series of chemical structures displayed in their entirety or as a common core plus substituents. Once these data are stored, the user can format, sort, graph, and report relationships between chemical structures and their biological activity as well as other properties. ISIS/Desktop consists of two products--ISIS/Draw, a chemical drawing package, and ISIS/Base, a chemical database program for managing structures and data stored in the user's desktop computer. ISIS/Desktop runs under Microsoft Windows, on the Macintosh, and on the Silicon Graphics Indigo line of workstations. The ISIS SAR Table is currently available only for Windows and Macintosh. Circle No. 84 on Reader Service Card MDL Information Systems Inc., San Leandro, Calif. ______ ATCC Issues Software For Automating Cloning Applications Vector NT is a software package capable of automatically designing new genetic molecules based on user specifications of desired molecules. The knowledge-based tool contains more than 3,000 rules for genetic engineering design. It also includes a database of 80 commonly used vectors and allows transferring changes to molecules in child-parent trees. New molecules may be added to the database by importing files in GenBank, EMBL, or ASCII formats. All molecules can be analyzed to identify sequences for PCR primers, restriction sites, open reading frames, and sequence motifs. The user has complete flexibility in adding new enzymes or motif descriptions. A free demonstration disk and tutorial documentation are available. American Type Culture Collection, Rockville, Md. Circle No. 85 on Reader Service Card ------ FluoroLink MAb Labeling Kit From BDS The Fluorolink MAb Labeling Kit provides a two-step method for directly tagging small quantities of monoclonal antibody or other proteins with Cy3 (orange), Cy5 (far-red), and FluorX (green) fluorescent dyes. The dyes are supplied as water-soluble NHS-esters, which are packaged in premeasured amounts for consistent labeling. Conjugations with the dyes are said to run smoothly under mild, aqueous conditions at room temperature, which reportedly minimizes the loss of biological activity in the target molecule. Purification of the reaction mixture by gel filtration chromatography enables nearly 100 percent recovery of antibody, according to BDS. The kit supplies materials for two conjugations and purifications of 0.1 mg protein each. Immunoconjugates produced with the kits are said to be intensely fluorescent, exhibit low non-specific binding, and provide good photostability for improved sample analysis. Biological Detection Systems Inc., Pittsburgh Circle No. 86 on Reader Service Card ------ Mini-Hybridization Oven Is Introduced By Hoefer The Hoefer HB 400 mini-hybridization oven, for western, northern, or Southern blot hybridizations, is designed for easy blot development. The blot remains in a tube throughout blocking, binding, and washing; there is no need for periodic membrane manipulation. The oven accommodates one large tube, one small tube, or four mini-tubes ranging in size from 32 nm to 80 mm in diameter. The oven measures 36 cm wide 3 22 cm deep 3 27 cm high and is said to be especially useful for labs requiring one oven set to hybridization temperatures and another set to washing temperatures. A syringe is used to add solutions, minimizing the danger of radioisotope spills and contamination. Hoefer Scientific Instruments, San Francisco ------ Whatman Unveils New Series Of Adjustable Micropipettors The POPPETTE series of adjustable, positive-displacement micropipettors is designed for polymerase chain reaction, DNA hybridization, and radioactive applications. The devices feature a disposable plunger and tip unit. Whatman LabSales Inc., Hillsboro, Ore. Circle No. 88 on Reader Service Card ------ Unisyn Technologies Develops Monoclonal Antibody Purification Kit MAb Pharm is a new kit for producing and purifying research- scale quantities of monoclonal antibody (MAb). The kit includes the Micro Mouse hollow-fiber bioreactor cell culture system; the Hybrid Grow basal medium, specialized for growing hybridomas; and AvidChrom for MAbs, formulated specifically for purifying monoclonal antibodies. Unisyn Technologies, San Diego Circle No. 89 on Reader Service Card ------ New Quantitative Immunoassays From Oncogene Science Cathepsin D ELISA measures both the pro- and mature forms of cathepsin in human cytosols and extracts, as well as material derived from cell cultures. The uPA ELISA detects uPA bound to its receptor or to PAI-1 in tumor and serum cell culture-derived samples. Oncogene Science Inc., Cambridge, Mass. Circle No. 90 on Reader Service Card ------ Micro-Tech ScientificUs Dynamic Mixer Debuts The Dyna-Mix Plus is a high-pressure, microgradient dynamic mixer designed for microbore and packed capillary chromatography HPLC. It can mix flow rates from less than 5 'l/min to 500 'l/min in a low-volume, two-stage mixer. Mixing rotors may be changed to optimize for solvent, viscosity, and gradient slope for microgradient liquid chromatography. Micro-Tech Scientific, Saratoga, Calif. Circle No. 91 on Reader Service Card ------ Eppendorf Releases New Microinjectors The Transjector Models 5246 and 5246 Plus are designed for injecting or transferring micro volumes of liquids into living cells. The Transjector 5246 features an on-board pressure supply, a remote keypad controller, and dual pressure outlets. The 4246 Plus model additionally features the ability to transfer micro volumes from one cell to another. Eppendorf North America Inc., Madison, Wis. Circle No.92 on Reader Service Card ------ Mettler Toledo Unveils New Series Of Improved Analytical Balances The new AG balances, which replace the AE series, feature higher, hexagonal draft shields and motorized calibration. Four models are available, offering the LocalCan universal interface, selectable units, a formula weighing program, dynamic weighing, and piece counting. Mettler Toledo Inc., Hightstown, N.J. Circle No. 93 on Reader Service Card ------ PCR Tubes From Robbins Strip-Ease-12 consists of strips of 12 thin-walled 0.2 ml PCR tubes and matching caps for various sample processing requirements. Made from virgin polypropylene, they are available in sterile or non-sterile forms and are certified RNase- and DNase-free. Robbins Scientific Corp., Sunnyvale, Calif. Circle No. 94 on Reader Service Card ------ Millipore Releases Centrifugal Filters Ultrafree-20 centrifugal filters are designed to process biological samples from as little as 0.5 ml to 20 ml. In addition to concentration, purification, and desalting, applications include recovery of enzymes, virus, bacteria, yeast, and peptides from biological samples. The filters may also be used for the recovery of low-molecular-weight components from cell lysates, culture media, or fermentation broths. Millipore Corp., Bedford, Mass. Circle No. 95 on Reader Service Card ------ Microcal Introduces Version 3.5 Of Origin Software Origin is a Windows-based software package designed to acquire, manipulate, and present data for scientific and engineering applications. The 3.5 version features enhancements to previous applications as well as three new add-on modules for real-time data visualization and manipulation, peak fitting, and file utilities. Microcal Software Inc., Northampton, Mass. Circle No. 96 on Reader Service Card ------ PhosphorImager System From Molecular Dynamics The PhosphorImager 445 SI allows researchers to replace traditional X-ray film and developing chemicals with reusable tritium-sensitive storage phosphor screens that reportedly are 10 to 100 times more sensitive than film. The system works with Mac, PC, PowerPC, or Pentium benchtop computers, and comes with ImageQuaNT analysis software that uses the 32-bit operating system of Windows NT. Molecular Dynamics, Sunnyvale, Calif. Circle No. 97 on Reader Service Card ------ Kamiya Introduces Reagent For Fatty Acid Analysis ADAM (9-anthryldiazomethane) reacts with carboxylic acids at room temperature to yield fluorescent esters that can be quantitated with high-performance liquid chromatography. No heating or catalyst is required, and most organic solvents may be used as a reaction medium. In addition to detecting picomole quantities of fatty acids, ADAM may be used to measure microgram amounts of oxalic acids in biological samples. Kamiya Biomedical Co., Thousand Oaks, Calif. Circle No. 98 on Reader Service Card ------ Hewlett-Packard Introduces API-Electrospray LC/MS System The HP atmospheric pressure ionization (AIP) electrospray liquid chromatograph/mass spectrometer (LC/MS) system detects and measures proteins and peptides from low-picomole to high-femtomole levels. It measures the molecular weights of peptides, intact proteins, and oligosaccharides up to 150,000 daltons with an accuracy better than 0.02 percent. The system can be coupled with conventional HPLC methods for online characterization of enzymatic digests of proteins. It automatically matches masses to amino acid sequences. Hewlett-Packard Co., Palo Alto, Calif. Circle No. 99 on Reader Service Card (The Scientist, Vol:8, #17, pg.19, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: PROFESSION ------------------------------------------------------------ TI :Small Foundation Enables Grantees To Take `Side Trips' In Research AU : Edward R. Silverman TY : PROFESSION PG : 21 In the big-money world of funding for biomedical research into high-profile conditions like Alzheimer's disease, heart disease, and glaucoma, the Rockville, Md.-based American Health Assistance Foundation (AHAF) might seem like small potatoes: Since its inception 21 years ago, AHAF has disbursed only about $35 million in grants for investigations into these three disorders. But for scientists like Kristine Ann Erickson, an associate professor of ophthalmology at Harvard Medical School and a research associate at the Massachusetts Eye & Ear Infirmary in Boston, AHAF's grant program provides a much-needed opportunity to expand their research. "I'm trying to define the pharmacology of the outflow system, the system that goes wrong" when glaucoma develops, says Erickson, who is in the midst of a two-year project to study the disease, aided by $25,000 in funding from the foundation. "People don't know how the drugs work. With AHAF, though, there's a possibility of going on some side trips [from the main area of investigation], and I have a chance to do innovative things." Although the nonprofit foundation has only about 30 employees (just one of whom, research director Sherry Marts, is a scientist) and offers only modest-sized grants, researchers say they value its funding programs because they allow them to take chances that larger funders discourage. "You might have innovative ideas that are chancy," says Erickson. "I'm exploring areas one couldn't put together reasonably in a tight little hypothesis to the National Institutes of Health. It's an opportunity to explore." This is the sort of reputation that AHAF has worked hard to foster. And its officials acknowledge that funding may go to research that offers no guaranteed outcome. "We don't target specific areas of research. We leave it up to the investigator to do their work," says Marts. "We're here to provide significant support to get a project going. It's risky." A Low Profile The foundation was begun in 1973 by Eugene Michaels, a systems analyst now retired from C&P Telephone in Maryland, whose father suffered from heart disease. Michaels is currently the president of AHAF. The foundation has no endowment; its funds have largely been derived from individual contributions. AHAF's National Heart Foundation grant program began in 1975, with the National Glaucoma Research program added in 1978 and the Alzheimer's Disease Research program instituted in 1985. Total support in the fiscal year ended March 31, 1994, amounted to $13.4 million, including about $1.1 million in donations made to a family relief program for relatives of Alzheimer's patients. According to Marts, the average first-time donation to AHAF is just $15. Donations are generally dedicated to a specific program. The average amount per donor making subsequent contributions is $40 for research into Alzheimer's, $69 for glaucoma, and $45 for heart research. Overall, 82 percent of AHAF's revenue came from direct-mail contributions. Alzheimer's researchers can receive up to $100,000 over a two-year period, although many grants are smaller. Grants for heart disease top out at $15,000; for glaucoma, the maximum is $25,000. In the 12 months ended last March, $2.7 million in grants was awarded to 28 investigators, with $2.2 million going to Alzheimer's and $410,000 to glaucoma. About $90,000 was dedicated to heart disease. "What determines the amount of money given away is how much is given to us," Marts explains. AHAF has succeeded in soliciting donations even as it keeps a low profile, particularly when compared with such better- known organizations as the American Heart Association. "We don't see ourselves as functioning as public mouthpieces for the diseases," says Marts. "We want to keep overhead as low as possible. And we see this as complementary [to the work of the larger foundations], not competitive. ThereUs so much to be done in these areas." "This organization has been able to raise a significant amount of money for [Alzheimer's] each year," says Daniel Perl, the director of neuropathology at Mount Sinai Medical Center in New York and a member of AHAF's Alzheimer's review committee. "I think it's particularly important these days, with federal research money declining. ItUs getting rough out there." `Top-Flight Ideas' As research money becomes harder to obtain, the quality of applications to the foundation has been rising, Perl adds. "Every year, the grants get better and better; over the last couple of years, they've been first-rate. A $25,000 grant these days isn't enough to get major research done, but the number of top-flight ideas proposed has increased." Reviewers look for proposals for worthwhile research that, while far-ranging, doesn't stray from the need at hand. They also evaluate the project's potential for disseminating new results, the applicantUs investigative track record, and the merits of the idea itself. Awards are made to nonprofit institutions in the United States or other countries on behalf of a principal investigator, who is expected to hold either an M.D. or a Ph.D.; grants are often given to younger researchers. The foundation allows its grant recipients to apply for competitive renewals. The foundation recruits and maintains a scientific review committee for each research program, drawn from scientists in academia, government, industry, and research institutes throughout the U.S. and Canada, to judge the applications. There are 24 scientists on the AlzheimerUs Disease Research committee, 10 on the National Glaucoma Research committee, and five on the National Heart Foundation committee. Committee members receive a small stipend for their efforts. "It's already made a difference for me," says Harvard's Erickson. "I also have a postdoc fellow working with me. She has a chance to broaden her interest as a scientist. So it becomes a pathway for her to have her own lab and facilitates my job as a developer of more junior people. And there are innovative prospects [for the research]. It's an ideal situation." For more information about AHAF, contact the organization at 15825 Shady Grove Rd., Suite 140, Rockville, Md. 20850; (301) 948-3244. The deadline for applications to the Alzheimer's and heart disease programs is October 31. The deadline for the glaucoma program is November 30. Edward R. Silverman is a freelance writer based in Millburn, N.J. (The Scientist, Vol:8, #17, pg.21, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: PEOPLE ------------------------------------------------------------ TI : Bioengineer Is Named As First CEO, President Of Houston-Based Biotechnology Start-Up Firm AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 22 Mitchell D. Eggers, a bioengineer who headed the bioelectronics division of The Woodlands, Texas-based Houston Advanced Research Center (HARC), is the first president and CEO of a new biotechnology company in the Houston area called Genometrix Inc. The new firm opened its doors on August 1. Temporarily housed at HARC, a nonprofit research organization that conducts biomedical studies, Genometrix will be targeting its efforts toward developing and manufacturing novel instrumentation for health care and biotechnology that combines microelectronics and molecular biology. Such devices would result in quicker, cheaper diagnostic methods, according to Eggers. "We want to miniaturize the laboratory--from test tubes to microchips, and from days to minutes," he says. Currently, Genometrix's researchers are working on developing two instruments: a bioscanner, a high-speed, sensitive instrument to provide images of samples tagged with fluorescent, radioactive, or chemiluminescent labels; and a "genosensor," a square-centimeter-sized chip to perform mutation analyses on DNA samples. Eggers anticipates the bioscanner, which he describes as a molecular "copy machine," to be available within two or three years. The genosensor will take a little longer--three to five years, he says--because as a diagnostic tool it has to undergo more rigorous testing and will be subject to government regulations. Eggers, 36, received his Ph.D. in electrical engineering at Texas A&M University, College Station, in 1984. In addition to his position at Genometrix, he holds adjunct associate professorships in bioengineering and electrical engineering at Baylor University College of Medicine and Rice University, both in Houston. --Neeraja Sankaran (The Scientist, Vol:8, #17, pg.22, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : Purdue Student Receives Two Ph.D.'s At Once AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 22 Harry Kloor has become the first individual in the United States to receive two doctoral degrees simultaneously, according to the Washington, D.C.-based National Research Council and the United States Department of Education's National Center for Education Studies. On August 7, Kloor, 31, graduated from Purdue University, West Lafayette, Ind., with doctorates in theoretical physics and in chemistry. Kloor, who defended his theses for both subjects within a few hours of each other on July 29, says that the two research projects were entirely distinct--"about as far apart as things can get in science." His physics research involved a search for new forces beyond the four known varieties: gravity, electromagnetism, and the two types of nuclear forcesQstrong forces that hold particles such as protons together, and weak forces responsible for phenomena such as radioactive decay. "It is sort of like a Sherlock Holmes hunt," says Kloor. "We look for possible interactions or forces at every level, from subatomic to astronomical scales, and then try to constrain the possibilities of these new interactions." For his chemistry dissertation, Kloor worked on developing a model to explain a phase transition that occurs in the mineral magnetite, also called lodestone, at 120o Kelvin. "It is a marvelous puzzle," he says, "to figure out how the material changes all of its electron-transporting and thermodynamic properties just by reorganizing the electrons around the iron groups." He explains: "I used a paradigm shift to develop my model-- taking a quantum-mechanical point of view rather than using classical concepts." Prior to beginning his graduate work at Purdue in 1988, Kloor had obtained two bachelor's degrees, in physics and chemistry, from Southern Oregon State College in Ashland. "As a child, it always seemed to me that the great scientists--both real and fictional--knew everything," he offers as a reason for pursuing two subjects at once. "Also, nowadays the great events in science are happening in interdisciplinary areas." Kloor maintains an active interest in communicating science to the public, having served as a corporate liaison for the department of physics and as codirector of a physics outreach program at Purdue. He is not yet clear about his postgraduation plans but hopes to eventually "settle down and do research in promoting science education." --Neeraja Sankaran (The Scientist, Vol:8, #17, pg.22, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: OBITUARY ------------------------------------------------------------ TI : Julian S. Schwinger TY : PROFESSION (OBITUARY) PG : 22 Julian S. Schwinger, a theoretical physicist whose fundamental work in quantum electrodynamics earned him the Nobel Prize in physics in 1965, died July 16 in Los Angeles of pancreatic cancer at age 76. Schwinger shared the 1965 Nobel with physicists Richard P. Feynman and Shin'ichiro Tomonaga of Japan for their independent work in quantum electrodynamics. Schwinger and FeynmanUs research in the 1940s and 1950s in quantum field theory is credited with laying the groundwork for the progress in physics made since then, particularly in ultra-high-energy physics and the search for the ultimate structure of matter. Schwinger's mathematical formulas led to a better understanding of the interaction between charged particles and an electromagnetic field. Schwinger published his first paper at 17. His published work comprises nearly 200 papers and numerous books. He had been a member of the faculty of the University of California, Los Angeles, for 22 years, beginning in 1972 as a professor of physics and then as a University Professor. Schwinger received a Ph.D. from Columbia University in 1939, at the age of 21, although he had completed the research for his doctorate at 19. He subsequently went to the University of California, Berkeley, to work with renowned physicist J. Robert Oppenheimer. >From 1943 to 1946, he was a member of the wartime staff of the Radiation Laboratory at the Massachusetts Institute of Technology, contributing to the development of radar. After the war, Schwinger went to Harvard University as an associate professor, becoming a full professor in 1947 at the age of 29. Between 1948 and 1950, he published the papers on quantum electrodynamics for which he won the Nobel. Schwinger was lauded by his colleagues and students as a superb educator. He directed more than 70 doctoral theses, and three of his students went on to win Nobel Prizes--Ben R. Mottelson (1975, physics), Sheldon L. Glashow (1979, physics), and Walter Gilbert (1980, chemistry). (The Scientist, Vol:8, #17, pg.22, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : WILLIAM WILSON MORGAN TY : PROFESSION (OBITUARY) PG : 22 William Wilson Morgan, a professor of astronomy at the University of Chicago and the discoverer of the spiral structure of the Milky Way, died June 21 in Williams Bay, Wis., at the age of 88. The cause of death was a heart attack, according to officials at the university. Morgan was Bernard E. and Ellen C. Sunny Distinguished Service Professor, emeritus, at Chicago, from which he received his Ph.D. in 1931. He conducted research at the university's Yerkes Observatory--where he was director from 1960 to 1963--for more than 60 years. Morgan's studies centered on astronomical morphology, the structures of stellar populations. He was best known for four major contributions to the field: the development, with astronomer Philip Keenan, of a two-dimensional classification system--known as the MK, for Morgan Keenan, system--for stellar spectra and luminosity; the discovery of the Milky Way's spiral structure; the development of a precisely defined system to determine the brightness of stars; and the development of the Yerkes system of classification of the optical forms of galaxies. Morgan used the MK system to determine the distances of bright stars within the Milky Way, and thus discovered the galaxyUs spiral structure (Sky and Telescope, 11:138, 1952). When he announced his finding at a meeting of the American Astronomical Society in 1951, he was given a rare standing ovation. (The Scientist, Vol:8, #17, pg.22, September 5, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. --------


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