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THE SCIENTIST VOLUME 8, No:7 APRIL 4, 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 *** *** APRIL 18, 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 Student rate : one year $29 (U.S.A.) THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NEXT = next article ------------------------------------------------------------ TI : CONTENTS PG : 3 ============================================================ NEWS BIOTECHNOLOGY VIS-A-VIS HEALTH-CARE REFORM: United States biotechnology industry executives and analysts are warning that some components of proposed U.S. health-care reform legislation designed to evaluate and influence drug pricing will have a chilling effect on the willingness of companies to pursue research as well as investor confidence and support of the industry. Already, they say, decreased investment and poor stock market performance have forced many firms to cut back on investigations and scientific personnel PG : 1 AAAS MEETING IN REVIEW: The February meeting of the American Association for the Advancement of Science in San Francisco was marked by presentations and discussions on traditional scientific subjects as well as a number of wide-ranging science-in-society topics, such as science fiction's role in the public's view of science, increasing drug resistance in disease-causing bacteria, and ethical questions concerning research on homosexuality. Included in a reporter's notebook are some unusual--and even curious--moments that took place both within and outside of the meeting rooms PG : 1 NEW HUGHES INVESTIGATORS: Officials of the Howard Hughes Medical Institute (HHMI) say that the latest crop of HHMI investigators will include substantially more minorities and women than in previous years. Some institute officials and other observers say the new appointments correct a longstanding imbalance in HHMI representation among these groups PG : 3 OPINION REFOCUSING AIDS RESEARCH: Robert Root-Bernstein, an associate professor of physiology at Michigan State University, contends that our ignorance concerning AIDS is profound and that significant progress in curtailing the pandemic is possible only if the sources of this ignorance are identified. He maintains that the first priority of the new national AIDS task force is, therefore, to challenge the validity of current theories about AIDS and to encourage the asking of new questions. PG : 1 COMMENTARY: Bench scientists in biotechnology companies have a great stake in the outcome of President Clinton's proposals for health-care reform, says Carl B. Feldbaum, president of the Biotechnology Industry Organization. Feldbaum warns, for example, that establishment of an advisory council to evaluate new drug pricing is sure to have a depressing effect on investment in the industry that would translate directly into lost jobs for lab researchers PG : 12 RESEARCH 1993 CITATION SURPRISE: A list of the 10 most cited papers published and referred to in 1993 includes, as expected, articles covering several fields in the life sciences, but also contains a physical science paper on a superconducting material PG : 15 HOT PAPERS: An atmospheric physicist discusses the utility of the HITRAN molecular database PG : 17 TOOLS & TECHNOLOGY PREVIEWING EXPERIMENTS: As a cost-saving method, more labs are turning to the automated design-of-experiment approach-- a way of using statistical principles to identify crucial variables in an experiment before it is conducted--and utilizing available software to enable the process PG : 18 PROFESSION MENTORS AND MONEY FOR WOMEN: The Glaxo Women in Science Scholar program provides annual stipends to female science students, and, more important, pairs them with established women researchers who act as mentors and role models as the students pursue science PG : 22 BLAS FRANGIONE AND ALLEN ROSES, a New York University Medical Center pathologist and a Duke University Medical Center neurologist, respectively, have each received the Metropolitan Life Foundation Award for Medical Research PG : 23 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 12 CROSSWORD PG : 13 EXPERIMENT DESIGN AND STATISTICAL SOFTWARE PRODUCTS DIRECTORY PG : 20 NEW PRODUCTS PG : 21 OBITUARY PG : 23 ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Agenda For U.S. AIDS Research Is Due For A Complete Overhaul AU : ROBERT S. ROOT-BERNSTEIN TY : NEWS PG : 1 A recent front-page article in The Scientist (F. Hoke, "National AIDS Task Force Expected To Accelerate Drug Development," Feb. 7, 1994, page 1) reported that a newly formed, United States government-backed, 15-member panel intends, among other things, to improve communication between pharmaceutical and biotech companies and thus speed development of AIDS-combating antiretroviral drugs and vaccines. One wonders, on one hand, what is wrong with the U.S. drug industry that such facilitation should be necessary and, on the other, whether an AIDS task force can, in fact, do anything that the industry is not already doing. The task force, it seems to me, has better things to do. In trying to imagine a more appropriate research agenda for the panel, I find myself making three idealistic and naive (and, possibly, incorrect) assumptions: (1) that it has been formed to push AIDS research--not politics--forward; (2) that among its members are the equivalents of J. Robert Oppenheimer (to protect its mission, as he did with the Manhattan Project, against external influences) and Richard Feynman (to say, as he did in the Challenger inquiries, what needs to be said in moments when stark reality confronts us); and (3) that it is willing to put the lives of people with AIDS ahead of political correctness, patronage, and economic advantage. I hope that my assumptions are correct, but I wonder. The fact that we still can neither treat AIDS effectively nor cure it strongly suggests that we do not understand it. I maintain that we have not yet asked all of the right questions about AIDS, and that our ignorance is therefore profound. Identifying the sources and types of our medical ignorance thus becomes the highest research priority. A model program for accomplishing this has been developed by Marlys and Charles Witte, two AIDS researchers in the department of surgery at the University of Arizona Medical School, and a colleague of theirs, medical philosopher Ann Kerwin. According to their model, ignorance comes in four forms, each of which must be addressed as we pursue our research on AIDS: * First, there are the things we think we know, but that we really do not. This is ignorance masquerading as knowledge. * Second, there are the things that we know we do not know. This is overt ignorance. * Third, there are the things that we do not know that we do not know. This is hidden ignorance. * Finally, there are the things we think we do not know but we really do. This is hidden knowledge masquerading as ignorance. Examples of each can readily be found in our current approach to studying AIDS, and, in my opinion, it is the job of the AIDS task force to identify and remedy as many of them as possible. False Assumptions An example of something we thought we knew, but did not, is that the human immunodeficiency virus (HIV) is the direct cause of T-cell killing in AIDS. Even such formerly stalwart proponents of this notion as Anthony Fauci and Robert Gallo now admit that this is not the case. Virtually all HIV research is now focused on finding "indirect" mechanisms by which HIV may cause immune suppression. We also thought we knew that HIV alone is sufficient to cause AIDS. But such researchers as Luc Montagnier, Shyh- Ching Lo, Joseph Sonnabend, and many others--including me-- now believe that cofactors are necessary and, therefore, that HIV by itself cannot cause AIDS. We used to think we knew that everyone is at equal risk for HIV and AIDS, and that a heterosexual epidemic was inevitable. But the epidemiology of AIDS has yet to prove consistent with that view. There is no record of tertiary (non-risk group to non-risk group) sexual transmission of AIDS in any Western country. Indeed, every study of female prostitutes in Western countries has led to the conclusion that those among them who do not use drugs intravenously have almost no risk of HIV infection and that evidence of female prostitutes acting as vectors for spreading HIV into the heterosexual population is, at best, inconclusive. We thought we knew that people in all AIDS risk groups proceed to AIDS at the same rate following HIV infection, but this also has turned out to be untrue. For young hemophiliacs, for example, the average time is more than 15 years, while for older hemophiliacs and homosexual men, the time to AIDS is 10 years. People who have acquired HIV through blood transfusions have a rate nearly double that of gay men (average onset at six years), but people who become HIV-infected during an organ transplant or cancer chemotherapy develop AIDS, on average, in only two or three years. We thought we knew that HIV always precedes immune suppression in people who develop AIDS. But many studies show that lymphocyte counts are as low in some HIV-negative gay men, intravenous drug users, and hemophiliacs as they are in nonsymptomatic HIV-positive people--and sometimes lower. We thought we knew that public health measures to combat AIDS--"safe sex," clean needles for addicts, and so forth-- work because they interrupt HIV transmission. But epidemiologic studies have shown that transmission of all suspected infections that may act as cofactors in AIDS is also interrupted. We do not know, therefore, why public health measures work. Other aspects of AIDS dogma have also been challenged-- many of them in the last year. For example, we now have evidence raising fears that current vaccines, designed to spur antibody production, may be useless or even detrimental; we have been told that significant percentages of hemo- philiacs have beaten HIV and seroreverted without resorting to antiretroviral therapies; and, most recently, the very poor efficacy of AZT has been revealed to us. If such important, and previously obvious, "facts" are now called into question, we must seriously consider how many of our remaining notions about AIDS are similarly biased by our preconceptions and are, therefore, not trustworthy. A basic role that the AIDS task force must perform, then, is to make sure that, even to the point of discomfort, we are constantly skeptical and inquiring about the things we think we know--but really do not. Hard Questions The things we know we do not know are much more obvious than the things we think we know but do not. For example, we know that we do not know how HIV causes immune suppression. We are not even sure that HIV is sufficient to cause AIDS without other immunosuppressive cofactors, since it is a documentable fact that no one who gets AIDS has HIV as his or her sole immunosuppressive risk. Although every person with AIDS has a variety of autoimmune complications, even including antibodies against his or her own T-cells, we know that we do not know what role these play in AIDS. Indeed, we do not know what triggers any human autoimmune disease, whether in AIDS or as a factor in other syndromes. We do not know, in consequence, whether treating HIV will be sufficient to cure AIDS, or whether AIDS may continue to destroy the body through autoimmune mechanisms even after the virus is eliminated. We know that alcoholism, crack cocaine use, and non-IV use of heroin greatly increase the risk of contracting HIV. But there have been no telling studies of the lifestyle or immunologic function of alcoholics, crack cocaine users, or non-IV heroin addicts at risk for AIDS, nor of the mechanisms by which these people acquire their HIV (and other) infections. Do crack users, for example, share the very high rates of sexually transmitted diseases, malnutrition, and bacterial and viral infections that characterize IV-drug users and cause immune suppression in them? Do sores in the mouth associated with crack cocaine use and oral sex with HIV- positive partners facilitate HIV transmission? Do people who use non-IV drugs participate more often in unprotected anal intercourse (the most efficient way to transmit AIDS sexually) than other people? Does intercourse during menstruation increase the probability of heterosexual transmission of HIV? Do disease conditions that are associated with immune suppression--such as diabetes, dialysis, anabolic steroid use, anorexia, and bulemia--pose additional risks for contracting HIV? We do not know the answers to any of these fundamental questions. We must address all of these matters--the things that we know we do not know--and many others if we are to succeed in defeating AIDS. The AIDS task force should therefore promote, as one of its highest priorities, the investigation of every anomalous and unexpected observation that threatens the sanctity of the current AIDS dogma. `Crazy Hypotheses' The things we do not know that we do not know are, of course, the most difficult forms of ignorance to identify. And to go about identifying them we must invent crazy hypotheses and do unthinkable experiments. I advocate this approach not because we can expect these hypotheses or experiments to work, but because the history of science shows that employing them is the most successful research strategy for addressing the unknown. The notebooks of the great biomedical scientists--Jenner, Pasteur, Fleming, Blumberg, and so forth--reveal a record of failed theories and botched experiments that ultimately led to unexpected results. In disproving an incorrect theory or in running an experiment for which there was no sound, establishment-validated rationale, these clever scientists encouraged serendipity, the wellspring of scientific insight. On accepting his 1976 Nobel Prize in physiology or medicine, Baruch Blumberg said: "I could not have planned the investigation at its beginning to find the cause of hepatitis B. This experience does not encourage the approach to research which is based exclusively on goal-oriented programs." The programmatic, rationalistic converse of the Blumberg approach is much more common, of course. But we must bear in mind the number of times that supposedly well-founded approaches to disease have turned out to be harmful. Physicians in the 19th century "knew" that germs did not cause disease; it took a physical chemist named Pasteur, working outside of the medical community, to prove otherwise. It is just these things that make sense--but are wrong--of which we must beware; and we can beware only if we control every theory by testing it against alternative theories that we do not expect to be correct. Sometimes we will be surprised, and--by being surprised--we will discover our ignorance about things we did not know we did not know. To nurture our curiosity and thus broaden our opportunities for serendipitous discovery, I suggest that we cut back funding to those animal models and test-tube studies that do not behave like human AIDS and, instead, put more effort into modeling what really happens in human beings. No one, for example, has ever mimicked in an animal the entire range of immunosuppressive agents that bombard a blood-transfusion patient: anesthetics; surgery; multiple blood transfusions contaminated not only with HIV but also with cytomegalovirus, Epstein-Barr virus, and hepatitis C virus; opiate analgesics; and high-dose antibiotics. No one has yet modeled such IV-drug-user risks as multiple, concurrent infections with sexually transmitted diseases; bacterial infections from unclean needles; constant re-exposure to alloantigens (blood, lymphocytes, tissue) on unclean needles; persistent drug addiction; chronic antibiotic use; and malnutrition. No one has repeatedly reinoculated chimpanzees or macaques rectally with semen containing HIV, herpes viruses, and mycoplasmas, while concurrently exposing them to inhalant nitrites, antibiotics, and other drugs, as has typified so many men and women who have contracted AIDS sexually. So another of the functions that the AIDS task force must take on is to make sure that no assumption goes unchallenged, and to provide sufficient freedom for nonconformist research that might well yield serendipitous surprises. Let's start with messy reality instead of assuming that HIV is the entire answer. Hidden Knowledge Finally, there are the things that we do know, but we think we do not. Most important, we think that we do not know of any cure for AIDS at present, but, really, we do. That there is a cure is clearly evident all around us--the hundreds of documented cases of people who have been infected with HIV, who have developed T-cell deficiencies, and who have subsequently returned to a normal immunologic status, lost all signs of HIV, and remain healthy. There are people who have had antibody to HIV for more than 10 years who display no signs of immunologic damage. And there are those rare cases of people who have had full-blown AIDS for more than a decade and are still alive. These people are living proof that there are things about AIDS that we do not know we know; they are walking data banks, waiting to be tapped, waiting to reveal to us the knowledge that we possess but are unaware of. We need to uncover the hidden knowledge that is within our reach by studying these people to find out whether the strains of HIV that have infected them are nonpathogenic and therefore protective against pathogenic strains; whether they are genetically different from other human beings; or whether they have treated themselves differently and so hold the clues to treatment of other HIV-infected people. Limited formal studies and much anecdotal evidence suggest that no seroreverters and very few long-term survivors of HIV have been treated with retroviral drugs; most have drastically altered their lifestyles to eliminate ongoing immunosuppressive risks, including re-exposure to HIV and other sexually transmitted diseases; they have ceased drug use; and most have adopted high-nutrition diet supplements to boost immune function. These people may be telling us that we know how to treat AIDS successfully through risk elimination and immunologic boosters rather than antiretrovirals or HIV vaccines. One reason we do not know that we know this is because these people have succeeded by ignoring mainstream medical advice, and their knowledge is therefore outside the structure of biomedical science. I suggest that whatever these survivors know must be combined with what the world of official biomedical investigation knows and become a focal point of AIDS research as soon as possible. We must refocus AIDS research on seroreverters, long-term survivors of HIV infection, and long-term survivors of AIDS. Of course, we must also place whatever knowledge we get in such unorthodox ways back into a standard scientific form: What we do not know that we know tends to be expressed in terms of anomalies--things that do not fit our expectations- -and are therefore generally overlooked or ignored. The AIDS task force should pursue studies involving these survivors and see how much of AIDS can be prevented by focusing on cofactors. An Open Field Recognizing the extent of our scientific ignorance of AIDS leads me to conclude that we have narrowed our focus too precisely. AIDS is more complex than just HIV. It includes everything that predisposes people to HIV infection, everything that can synergistically work with HIV once present, and everything that can cause immune suppression in people at risk for AIDS independently of HIV. Recognizing this increased complexity does not displace HIV from its place at the center of AIDS research, but it does provide a wide range of new targets for prevention and treatment. The useful function that an AIDS task force can play is to make sure that the utmost reaches of our ignorance are quickly and efficiently identified. We will not do that by staying in the rut that has been gouged out during the past decade, but rather by deviating from it. A diversity of opinion and of research has never hurt science. Dogmatism and politically motivated programs often have. The AIDS task force can foster one or the other, but not both. Robert S. Root-Bernstein, an associate professor of physiology at Michigan State University, East Lansing, is the author of Rethinking AIDS: The Tragic Cost of Premature Consensus (New York, Free Press, 1993) and Diversity (Cambridge, Mass., Harvard University Press, 1989). He is a former MacArthur Fellow (1981-1986). ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: -------------------------------------------------------- TI : Fear Of `De Facto' Price Controls Forcing Cuts In Biotech Innovation, Officials Say With health-care reform proposals threatening financial prospects, firms are shelving projects, laying off researchers AU : SUSAN L-J DICKINSON TY : NEWS PG : 1 The biotech industry is marshaling its forces for what many of its executives view as the political fight of its life. Financial analysts and other observers agree with the executives, saying that the industry faces financial threats posed by various mechanisms in President Clinton's health plan designed to influence drug pricing. These observers warn that such mechanisms, if legislated, would result not only in the loss of promising drugs, but also in significant declines in the biotech work force--thus dealing a major blow to the industry overall. Particularly ominous, they contend, is a Clinton-plan proposal for an advisory council that would evaluate the pricing of certain new drugs. Already, the concerned sources point out, the proposed legislation has prompted reluctance among venture capitalists to risk biotech investments, which, in turn, has forced some biotech firms to lay off employees, freeze expansion plans, and put entire lines of research on hold. "The fear of the advisory board is heads and shoulders over any other concern" currently facing biotech companies, says Lisa Conte, chief executive officer of South San Francisco, Calif.-based Shaman Pharmaceuticals Inc. "It's terrifying, and it could destroy this industry." At the center of the controversy are two mechanisms included in the Clinton health plan by which government could influence the pricing of drugs. One is the establishment of a Department of Health and Human Services (HHS) advisory council on breakthrough drugs--drugs that either treat previously untreatable conditions or are the first effective therapeutics against a disease--that would review introductory prices for these therapeutics, and publicize its disapproval of any price. Another would give the HHS secretary the power both to blacklist certain drugs from Medicare reimbursement if government-required rebates on drug prices proposed by a company are deemed unacceptable by the secretary, based in part on the findings of the new council. In addition, the proposed health-care legislation would require drug manufacturers to pay special rebates to Medicare on new drugs for cancer, AIDS, and other diseases, also based in part on the advisory board's review. The Clinton administration has insisted, both in meetings with the biotech industry and in press reports, that these components of the proposed health-care legislation do not constitute price controls, as the council's reviews of the drugs are nonbinding, and their findings could be used only to regulate prices in the case of Medicare reimbursements. The administration has also professed that it wants to work with the industry in support of its important technology. Repeated calls by The Scientist to White House and health- plan task force officials were not returned. Biotech industry officials are claiming--and their assertions are supported by many industry analysts--that the proposed legislation constitutes de facto price controls because insurance companies and the public will balk at paying prices the council may criticize. They also say that fear of the legislation's impact is already having a detrimental effect on investment in biotech. "It's just price controls by a different name, and it is recognized as such by our investors," says Conte. In fact, several market statistics indicate that since January 1993, when the president first intimated that some form of government evaluation of drug prices would be included in his health-care reform plan, investors have been moving away from biotech stocks, analysts say. Vector Securities International Inc. of Deerfield, Ill., reports that the total assets in health-care mutual funds--which might be inclined to invest in drug or biotech companies-- dropped throughout 1993, from $4.3 billion at the beginning of the year to $3.6 billion at the end, in part because of the proposals. And Michael Celano, accounting firm Arthur Andersen & Co.'s partner in charge of its Philadelphia office of life sciences, says that the number of biotech initial public offerings (IPOs) fell from 43 in 1992 to 25 in 1993. Those that were financed were offered at a harmfully discounted rate, in part because of fear of the health-care proposals, he says. Other biotech officials report similar situations. Shaman's Conte, for example, saw her company's stock price plummet by almost 50 percent, from $15 for its IPO in January 1993 to $8.50 for its secondary offering, held in early December. And Mitchel Sayare, CEO and chairman of Cambridge, Mass.- based ImmunoGen Inc., says his company closed on an offering in mid-February 1994 at $7 per share--this after an IPO price in 1989 of $10 and an intermediate high price of $19. "I have been out there on the street, trying to get a deal done," Sayare reports. "And it is extremely difficult. Paying for the innovation we are working on here already represents a serious challenge." Mitigating Factors Biotech officials concede that other factors have contributed to stock devaluation throughout the industry over the past year. Two highly publicized clinical trial failures--of Malvern, Pa.- based Centocor Inc.'s Centoxin and Boulder, Colo.- based Synergen Inc.'s Antril--acted to depress biotech stock prices in early 1993, as did decreased earnings at industry leader Amgen Inc. of Thousand Oaks, Calif. But investors and analysts also say that the specter of price controls is making them wary. "It's a negative factor, and a reasonably big one," says Skip Klein, a health-care analyst with T. Rowe Price Associates Inc. in Baltimore. Sayare explains that when his investors originally decided to put their money into biotech, there were essentially three risks: technology (whether or not the products would work); regulatory hurdles (getting the products approved by the Food and Drug Administration); and the market (having the products accepted in a competitive marketplace). "What the investors see now is that there is a fourth risk," he says. "And that is that ImmunoGen will not be able to set prices for its drugs that it needs to recover its costs and to provide our investors with a fair return." Drug manufacturing has always been a high-risk business. A study conducted at Tufts University over two decades and released in 1991 found that the odds that a drug entering clinical testing will actually reach the market are about one in five; and a recently completed Duke University report revealed that only 30 percent of marketed drugs actually recoup their R&D cost. "If you are going to ask investors to take that kind of risk," says Steve Push, a spokesman for Genzyme Corp. of Cambridge, Mass., whose stock price plummeted 39 percent last year, "you have to offer rewards commensurate with that risk." "Innovation requires investments in terms of both human and financial capital," observes Gregory Brown, vice president of Vector Securities. "And that capital will flee if there is no possibility of return." Research Woes Against the backdrop of this political and economic debate, research projects and the scientists who perform them within this industry are being negatively affected. Two recent surveys conducted by the Biotechnology Industry Organization (BIO) found that 44 percent of companies specializing in cancer research and 47 percent of firms working primarily on AIDS have already had their work delayed or curtailed because of capital constraints. Forty- one percent and 40 percent of cancer and AIDS companies, respectively, cite what they term the administration's proposed "de facto" price controls as the dominant reason for their lack of capital; and 62 percent and 63 percent, respectively, predict further restrictions on research if the legislation is passed. Michael Fung, senior scientist at Tanox Biosystems in Houston, says that, owing to lack of financing, in part because of investor uneasiness over the proposed legislation, his company hasn't been able to take its lead product, antibody AIDS-439, into clinical testing as planned. "The compound is literally sitting in the refrigerator, waiting," he says. "The longer we wait, the greater the possibility that the antibodies will deteriorate, and all of the effort will go down the drain." Thomas J. McKearn, CEO and cofounder of Princeton, N.J.- based Cytogen Corp., saw his company's stock drop $23 per share in 1993, for a total of $370 million in lost value. McKearn says the firm had to cut back both on staff and projects: In September, 58 people were laid off, 83 positions were eliminated, and R&D personnel was reduced by 40 percent. Three phase I studies for cancer imaging agents were canceled. William H. Rastetter, president and CEO of IDEC Pharmaceuticals Corp. in San Diego, says he has been forced to make a similar decision: IDEC's lead compound, IDEC-C2B8, is in pilot phase II studies for B cell lymphoma, and the company believes that it could also be therapeutically beneficial in leukemia and myeloma. But it's on hold indefinitely. "If our stock were at [$]15 or [$]20, we would be in phase I trials for these conditions [leukemia and myeloma] now, and our product might get to market sooner for these patients," Rastetter says. "But given the current financial environment, we can't do the trials." IDEC went public in September 1991, garnering a value of $15 per share. Today each share is worth around $6. At Waltham, Mass.-based ImmuLogic Pharmaceutical Corp. president and CEO Richard Bagley says that, although his company's market valuation has held up thus far, his R&D decisions are nonetheless being driven by the negative environment. He has moved both staff and financial resources from longer-term efforts in the area of autoimmune disease to work with allergy drugs that are closer to clinical testing. Before the health plan was proposed, ImmuLogic established a discovery research group that today is staffed at only one-third the original target level, Bagley says. "Money is needed for clinical trials," he says. "We'd better be prudent." Rastetter says he is frustrated over, essentially, being forced to manage in a short-sighted manner, focusing money and energy on development, to the detriment of research: "If companies in the sector had better access to capital today, the pipeline of innovative health-care products would undoubtedly be richer seven to eight years from now." Executives also say they are aware of the negative impact these decisions are having within the companies' labs. Fung talks about the frustration he and his fellow scientists feel at having their promising project put on hold, and says that Tanox is already finding it more difficult to attract excellent, experienced scientists. "They want more security about their future," he says. "People are hesitant to commit their careers to a company that has had to cut its budget." McKearn says the aftermath of laying off one-third of Cytogen's work force has been like dealing with a death. "It is just as agonizing for the people who are left," he says. "There is an intense period of grieving, and morale is on a roller coaster for quite a while afterward." At ImmunoGen, head of research Walter Blattler describes the difficulty even in putting a project on hold for a while and redirecting the efforts of his scientific staff away from their primary interests. "How do you explain to a scientist that his or her project is no longer important?" he asks. "I have worked hard to give our people intellectual ownership of their projects; now I have to take that away. It's not easy." Killing The Cure Biotech industry officials say their ultimate concern is that if research is cut, cures will not be found. "The irony is that in the name of health-care reform this legislation will render the patients the ultimate losers," Rastetter says. "If you cut innovation, you are doomed to using older technologies." The Clinton administration's focus on pricing of "breakthrough" drugs is at the heart of their worries. "Having an advisory panel on breakthrough drugs really urges companies to go into generics," or products that offer only incremental increases in therapeutic value, says BIO president Carl Feldbaum. "It's counterproductive, and anti- innovation." A number of industry analysts point out that the proposal is the opposite of one that is spurring research investment in Japan. There, they say, a government- dictated pricing structure rewards innovation by setting prices for innovative drugs often at two to three times prices paid in the U.S.; the longer a drug is on the market, the lower the price it is awarded. Feldbaum says he has been told by one person involved in the design of the legislation that the health-care task force's concern was the power any company that came up with a cure for AIDS or other currently incurable disease would have to charge any price for its product. "Our response to such a concern," says Feldbaum, "is that the problem is not that there is a cure for AIDS, the problem is that there is not a cure for AIDS. If you squelch R&D on just breakthrough drugs, you are going to postpone or prevent the day that there will be one." BIO and a number of industry executives are proposing an alternative to the advisory board, one which relies on the Department of Public Health's existing-outcomes research group to evaluate drug prices. "This office is already collecting information on outcomes research--how a given treatment or drug compares with options for a specific disease," Feldbaum says. "We are urging that the health-care alliances have the ability to access that information, and determine for themselves what price they are willing to pay. We are confident that, on such a basis, biotech drugs will be able to compete." Biotech executives and analysts say that the market is already demanding pharmacoeconomic studies and cost- effectiveness data on promising compounds. "Cost- effectiveness is one of the critical issues of the future," says Sarah Gordon, biotech analyst for Amerindo Investment Advisors Inc. in New York. "Today I'm much more careful to get detailed analysis about how a company is going to evaluate cost-effectiveness [of its product], and I look to have those measures built into the phase III trials." Industry officials and analysts are insisting that free- market pressures, not political ones, are the way to keep drug prices in control. "The market is already correcting a lot of the failings that the Clinton plan is trying to address," says Vector Securities' Brown. "The market is correcting it by demanding that new technologies prove themselves cost-effective. We don't need a regulator to tell us to do that." Susan L-J Dickinson is a freelance writer based in Philadelphia. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Reporter's Notebook: AAAS Meeting In San Francisco Offered Mix Of Hard Science, Social Ramifications AU : FRANKLIN HOKE TY : NEWS PG : 1 According to the American Association for the Advancement of Science (AAAS), precisely 4,148 scientists, students, and others concerned about "Science and a Changing World"--this year's theme--attended the group's 1994 meeting, held Friday, February 18 through Wednesday, February 23, in San Francisco. The meeting also drew well from Washington, D.C., science-policy circles, with Harold Varmus, head of the National Institutes of Health; Neal Lane, director of the National Science Foundation; and Rep. George Brown, Jr. (D- Calif.), chairman of the House Science, Space, and Technology Committee, among those participating. John H. Gibbons, chief of the Office of Science and Technology Policy, gave the keynote address. As is customary at the annual AAAS meeting, a wide variety of current science-and-society topics were addressed in the sessions. Among these were: the dangers posed by the rapid spread of drug resistance in disease-causing bacteria, the role of science fiction in presenting science to the public, and the ethical questions raised by recent research showing that some men may be genetically predisposed to homosexuality. Following is an account of several of the meeting's more interesting--sometimes curious--moments, taken from this reporter's notes: When speaking in public, scientists--like politicians and others--often use metaphors, parables, and quotations to add that down-to-earth feeling or touch of erudition, as needed. Keynote speaker John Gibbons was exemplary in this regard, incorporating the thoughts of philosopher Machiavelli, poet Edna St. Vincent Millay, political thinker Antonio Gramsci, and others into his talk Friday evening, along with several vivid images and informal tales. In one combined flurry, Gibbons began by describing the federal deficit as a "wild card" in science-policy deliberations. A physicist by training, Gibbons paused to recall learning the laws of thermodynamics in graduate school using another card-game metaphor: You can never win, you always lose, and you can't even get out of the game. On the deficit--and society's unwillingness to face it squarely--he quoted Bertrand Russell's observation that mankind would rather commit suicide than learn arithmetic. Gibbons then pursued the topic of deficit spending with his two-part "theory of holes": "If you're in one, stop digging," and "If the hole is deep enough, you have to find a way to climb out." Finally, to bring the deficit point home, Gibbons quoted economist Herb Stein: "That which cannot go on forever must come to an end." While waiting for a Saturday morning session called "The Changing Work-face: Women, Men, and the Dynamics of Inclusion," two married women scientists discussed their lives in the laboratory. "When I was in graduate school 12 years ago, discrimination was out in the open, where you could see it," said one to the other. "People now, I think, don't understand it so clearly." Conversation continued on the difficulty of being a female scientist and of balancing a research career with domestic obligations. "Well, just by being in science, you break one rule," the first woman said. "But by having a relationship, you break another." The difficulties faced by these two are, it would seem, emblematic of certain societal shifts. In the session, Cornell University sociologist Henry A. Walker spoke of the dramatic rise this century in the representation of women in the workplace. He made the further point, however, that while single women formerly dominated this group, the biggest statistical change since World War II has been in the number of married women and women with children going to work. Almost three-fifths of working women are married now, and women with at least one child between the ages of six and 17 are more than two and one-half times as likely to be at work now as in 1950. A somewhat alarmed lunchtime crowd listened on Saturday as Rockefeller University microbiologist Alexander Tomasz detailed the possible collapse of biomedicine's antibiotic arsenal. Multi-drug resistance in disease-causing bacteria is on the rise worldwide, Tomasz said. The genes for resistance, he explained, do not necessarily arise first in dangerous bacteria, but often appear in harmless bacteria and are then transferred among species. Among the innocuous bacteria acting as such "arms dealers" in resistant genes, Tomasz said, might be mouth or gut bacteria "with which we have no quarrel, but who have witnessed the entire host of antibiotics" and have thus developed defenses against those drugs. Of the roughly two dozen antibiotic agents available to combat pneumonia, only two are still effective against resistant strains, Tomasz noted--and the resistance genes for those drugs are already present in other microbes. "A post-antibiotic era in which control of microbial disease would be lost again is no longer science fiction but a very real possibility," Tomasz wrote in an abstract of his work. Perhaps in search of a time slot that would not place him in competition with any other meeting event, George Brown held a wide-ranging 7:30 A.M. news conference on Sunday. Continuing his crusade to ferret out and eliminate pork- barrel science projects, Brown said he is considering legislation that would prohibit institutions that receive research funding congressionally earmarked for a specific project from also receiving any NSF funding. It was not immediately clear how such a link could be legally established or enforced, and reporters' questions on the subject failed to elicit substantial details. In discussing the superconducting supercollider, now destined for dismantling following Congress' refusal to fund the project last year, Brown noted, "There will be a lot of unemployed high-energy physicists for a while, because there just aren't enough jobs for them.... They may have to go into low-energy physics or something." Midway through the six-day session, the scientific deliberations were enlivened by a chilling article in the Sunday edition of the San Francisco Examiner: "Death and hideous destruction engulfed the Bay Area in its full horror at first light this morning," the article began. "The long- feared but widely disregarded `Big One,' an earthquake registering 7.5 on the Richter scale, roared to life along the Hayward Fault at 2:32 A.M. Sunday, causing more damage than any temblor in California history ...." The frightening story ran under a three-inch-high banner headline reading "Deadly Denial." Beneath the headline, in small type, was a disclaimer line: "A major earthquake could strike the Bay Area next week or 15 years from now. When it does, this is the kind of story that will be published." According to an Examiner reporter, the story was written to draw public attention to the dangers posed by the Hayward Fault, smaller than some other regional faults but running through densely populated Northern California areas. On the other hand, San Franciscans can rest assured that their city will be around for many years to come, according to Natalie Foster, an associate professor of chemistry at Lehigh University in Bethlehem, Pa. Her proof? Twenty- fourth-century cadets, as portrayed on the television show "Star Trek: The Next Generation," train at Star Fleet Academy--located in a still-standing San Francisco. Foster spoke at a Sunday morning session titled "The Science in Star Trek: Bringing Science to a Different Public." She used two "Star Trek" episodes, one from the 1960s progenitor of "The Next Generation" and one from the current series, to point up what she sees as an attitudinal sea change among biomedical scientists in the intervening decades--years marked by researchers' frustration with cancer and AIDS. The episodes ("The Deadly Years" [1967] and "Unnatural Selection" [1989]) both concern premature aging. As the medical team struggles to understand and cure the disease in the first episode, a young doctor named Janice Wallace tells Capt. James T. Kirk, "We know the problem; we know the progress of the affliction. Therefore, once we find the proper line of research, it is only logical that we find a solution." And, indeed, a cure is found by episode's end. In the second episode, the doctors are dealing with a different challenge, the accidental result of a research experiment gone wrong. Here, also, a cure is found. But during the search, the entire crew of a starship, the U.S.S. Lantree, dies, as do several other people. The doctor of the U.S.S. Enterprise, Katherine Pulaski, in her record of the case, writes: "Scientists believe no experiment is a failure, that even a mistake advances the evolution of understanding. But all achievement has its price. For one brief glimpse of the mysterious blueprint of human evolution, the men and women of the U.S.S. Lantree paid with their lives. Their sacrifice is thus noted in this scientist's log." With life-sized cardboard cutouts of current "Star Trek" officers Cmdr. William T. Riker and Lt. Cmdr. Geordi LaForge beside her, Foster said, "I'd like you to contrast that statement of Dr. Pulaski's--`all achievement has its price'- -to Janice Wallace's very confident statement in the 1960s.... Those two quotes, in themselves, underscore the tremendous confidence we had in the 1960s, both as a nation and as scientists, that once we knew the problem, we could solve it. Kate Pulaski is much more circumspect--`all achievement has its price.' That's risk-benefit analysis. And you'll have to agree that's one of the big differences between the 1960s and the 1990s in science." Social, ethical, and scientific perspectives on biological research into sexual orientation were discussed at a Monday morning news conference organized by the National Organization for Gay and Lesbian Scientists and Technical Professionals (NOGLSTP). Speakers at the conference included sociologist Pepper Schwartz from the University of Washington, Seattle, and Dean Hamer, senior researcher at the National Cancer Institute. Schwartz, a researcher on human sexuality, is also the immediate past president of the Society for the Scientific Study of Sex, Mount Vernon, Iowa. Hamer and his research team published findings last summer showing a link between specific DNA markers on the X chromosome and homosexual orientation in some men, suggesting a genetic predisposition in their sexuality (Science, 261:321-7, 1993). Both Schwartz and Hamer expressed hope that such research into the possible genetic bases for aspects of sexuality will not be misinterpreted or misused. According to Schwartz, psychologists speak of an "intolerance of ambiguity" in sexuality, which can lead to misunderstandings of findings such as Hamer's. Even granting a predisposition to homosexuality, Schwartz says, there remain many sociological and psychological influences on sexuality, as well as more diversity in sexuality than is generally accepted. "People don't want a range of sexuality," Schwartz said. "They want to be something or the other, particularly in societies that demand it.... We seem to be overwhelmed with the power of homosexuality, so that we reify in that direction in the same way we do in racist societies, where we say that if somebody has any of the stigmatized color in their biological background, that's the color they are, as opposed to the ratio of colors they might be. ... In our society, one homosexual likely to reify you in that direction rather than in any other.... There may be different kinds of homosexuality, some of which may be more hard-wired than others." "As we come closer to actually finding genes that are involved, the ethical quandaries are made much more real," Hamer said. For instance, he said, there are concerns that the military, insurance companies, or others might develop blood tests for sexual orientation that they might use without people's permission. Amniocentesis tests might be developed that could lead to a situation where expectant mothers might abort fetuses that they fear may be homosexual. "My own position is very straightforward," Hamer said. "That would be wrong, unethical, and a terrible abuse of the research." After a seven-year effort by NOGLSTP members, the AAAS council voted on Tuesday to recognize the group as an affiliate. NOGLSTP, founded in 1980, has about 200 members currently. Rochelle Diamond, a laboratory manager for two biology labs at the California Institute of Technology, heads the group. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Hughes Institute Moves To Bolster Female And Minority Participation AU : KAREN YOUNG KREEGER TY : NEWS PG : 3 Among the 44 scientists--triple the usual number of new nominees--expected to be named Howard Hughes Medical Institute (HHMI) investigators, 20 are women and six are members of minority groups, say institute officials. According to an HHMI spokesman, African Americans, Native Americans, and Hispanics are among the represented ethnic minorities, but the number of women included in this minority group was unavailable at press time. Institute officials say the number of new female appointees for this year will nearly double the current roster of 25 women who are HHMI investigators. At the same time, the total number of minority scientists will increase from three to nine. The new investigators will join an existing body of 225 United States researchers, which includes five Nobel laureates and 21 members of the National Academy of Sciences. At press time, Purnell Choppin, president of the Chevy Case, Md.-based philanthropy, had declined to release names of the new appointees, since, a spokesman explained, details of "the employment process" had yet to be finalized for all of them. According to the spokesman, publication of the list-- which would reveal the identities of the new women and minority researchers--was expected by April 1. Choppin and other HHMI officials say that their organization made a conscious effort to recruit underrepresented groups of scientists in this latest expansion. Says Choppin: "We indicated [in the nomination solicitation] that we were interested in having outstanding women and minorities nominated .... I am gratified that this took place." He notes, however, that quality of research--rather than consideration of race or gender--was the main attribute for selection. HHMI solicited nominations from biomedical institutions from around the country. The 44 appointees were then selected from this group by a review panel of eminent researchers. Corrective Measure To some HHMI officials and other observers, the unprecedented focus on women and minorities serves to correct a past imbalance. Applauding the move, for example, is Shirley Tilghman, a professor of molecular biology at Princeton University and a Hughes investigator for the past five years. Tilghman, who is a forceful advocate for women in science, says there was room for improvement by HHMI in this area. (According to an HHMI spokesman, only nine women were among the 83 scientists hired by HHMI from 1990 through early 1994.) Commenting on the new group of appointees, Tilghman adds, "I think some really excellent scientists will be recognized." Also praising the institute's selections is N. Maxwell Cowan, a neuroscientist and vice president-chief scientific officer at HHMI. Cowan says he has been concerned about the underrepresentation of women and minorities since he started at HHMI six years ago. The institute "has made great strides towards rectifying this," says Cowan, describing the current effort as "affirmative action in the very best sense of the word." And Irving S. Shapiro, chairman of the HHMI board of trustees, says that selecting women and minorities brings a "broader diversification of people" to HHMI research, as well as a better representation "of the population of our country than we have had in the past." A Bumper Crop The group of appointees to be named is notable for its size in addition to its makeup, since the 44 appointees is triple the number of scientists that HHMI is in the habit of bringing on each year. From 1988 to 1992, for example, the institute hired about 16 new investigators annually. The current crop of 44 investigators was harvested from a field of 287 nominees, says Cowan. "The competition was extremely steep," he says. "Being among those nominated is in itself a mark of distinction." "We're delighted," says Choppin, "at a time when opportunities [for discovery] are great and when funding is tight overall that we're able to increase our activities." He explains that an outstanding return on HHMI's endowment investment allowed for "the current jump forward" in funding. HHMI, the largest private philanthropy in the U.S. (with 1993 assets greater than $8 billion), spent $268 million on biomedical research in 1993. This is more than 21 percent of the total support for biomedical research in the U.S. from nonprofit groups, according to HHMI. For Princeton's Tilghman, the take-home message of the expansion is that there has been a major injection of funding for biomedical research. She lauds HHMI's policy of supporting individual researchers rather than, like the National Institutes of Health and other organizations, specific research projects. This investment in people, Tilghman says, "is a critical part of [HHMI's] success." She says that this approach to funding biomedical research lends value and importance to the independent, free-thinking aspects of scientific inquiry. Young Blood Choppin says that this year's anticipated appointments reflect the institute's interest in encouraging and supporting younger talent. Scientists, he explains, can become HHMI investigators at one of three levels--assistant, associate, and full--a structure that roughly corresponds to the professorial structure of universities. Each level has a progressively longer period of review for renewal--three years for assistant, five years for associate, and seven for full investigators. In the current round of appointments, Choppin says, there are more assistant investigators nominated than at any other rank. "We have been encouraging more nominations at the assistant level, but not to the exclusion of senior-level ranks," he adds. Nevertheless, Shapiro points out, the latest group of investigators poses more opportunities for young researchers who, in his words, "have the potential to be great scientists." According to institute officials, as a result of the latest round of appointments, the number of institutions that have HHMI laboratories will increase from 53 to 63 and, consequently, the national research staff supported by HHMI (now nearly 2,000 people) will increase substantially. The names of these laboratories will not be made public, however, until all of the individual appointments have been announced. QUID PRO QUO When scientists accept a nomination to become Howard Hughes Medical Institute (HHMI) investigators, they become employees of HHMI, receiving full financial support for salary, staff, and equipment in renewable appointments of three, five, or seven years. However, HHMI investigators--who conduct their work at universities and medical centers across the United States-- still maintain their institutional appointments. Under a collaborative agreement between these institutions and HHMI, investigators must spend 75 percent of their time doing research, while the other 25 percent can be devoted to activities such as teaching, mentoring graduate students, and serving on committees. In return, the investigators receive support for themselves, research technicians, and post- doctoral fellows. HHMI also pays for administrative services and laboratory overhead and supplies. --K.Y.K. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: NOTEBOOK ------------------------------------------------------------ TI : Healthy Dialogue TY : NEWS (NOTEBOOK) PG : 4 The National Institutes of Health is presenting a free, nine-week series of "easy-to-understand, entertaining, and informative" lectures about the basics of biomedical research for the general public. Sessions--which began March 31 and take place on consecutive Thursday evenings until May 26 at NIH headquarters in Bethesda, Md.--are to cover a range of topics including alternative medicine, the biology of aging, and toxicology. A lineup of well-known speakers is planned. For example, Harold Varmus, NIH director, will teach a class on cancer, and Francis Collins, director of the National Center for Human Genome Research, will discuss genetics. Contact NIH at (301) 402-2828 for more information. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Human Rights--Via E-mail TY : NEWS (NOTEBOOK) PG : 4 The American Association for the Advancement of Science (AAAS) invited Liu Gang, the 32-year-old physicist imprisoned for his role in the nonviolent Chinese democracy movement of 1989, to attend its annual meeting in San Francisco in February. When no response came, C.K. Gunsalus, chairman of the AAAS Committee on Scientific Freedom and Responsibility and associate vice chancellor for research at the University of Illinois, Urbana-Champaign, wrote Chinese Premier Li Peng on February 16, just before the start of the meeting, to express the concern of her group over Liu Gang's fate. Still no response. So, at the meeting in San Francisco, the AAAS committee--in cooperation with the Committee of Concerned Scientists, an independent group of scientists monitoring human rights--circulated a petition addressed to Li Peng and other Chinese officials protesting "inhumane conditions of internment" for Liu Gang and other scientists being held for nonviolent political offenses. Meanwhile, the AAAS group has also inaugurated an E-mail Human Rights Action Network (HRAN) for scientists interested in helping persecuted colleagues around the world. To join the network, send the message "SUBSCRIBE AAASHRAN firstname lastname" to the Internet E-mail address "". ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Top Banana TY : NEWS (NOTEBOOK) PG : 4 According to Keith Bezanson, president of the Ottawa, Canada-based International Development Research Centre, a new fungus-resistant breed of banana bearing the name "Goldfinger" could "save the world's banana export industry from collapse as diseases take an unsurmountable toll." The new hybrid, says Bezanson, owes its creation to years of research in selective breeding aimed at developing a replacement for currently popular banana varieties--such as the Cavendish--that are plagued by pesticide-resistant fungal diseases. Goldfinger was developed by a team from the Honduran Foundation for Agricultural Research in La Lima, Honduras. Its hardiness, say developers, means that it can be grown without pesticides, a plus for the environment and farmers in the developing countries where it will be planted. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : SSC Yard Sale TY : NEWS (NOTEBOOK) PG : 4 Now that funding for the superconducting supercollider (SSC) has been scrapped by Congress, the Department of Energy and the Texas National Research Laboratory Commission are soliciting suggestions for what to do with the assets remaining at the Waxahachie, Texas, site. The existing facilities and equipment are: extensive cryogenic facilities and superconducting tooling and test equipment; the 550,000- square-foot central facility, which includes office and lab space, a machine shop, and a liquid helium refrigerator; buildings for the linear accelerator and its negative hydrogen ion source; and an integrated network of distributed computer workstations. Expressions of interest in the facilities are due April 15. Only those who submit this material will be eligible for grants. For information, contact the DOE SSC Project Office at (214) 708-2414. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Learning About Learning TY : NEWS (NOTEBOOK) PG : 4 The New York-based Charles A. Dana Foundation recently announced the formation of a new consortium to identify the role of brain dysfunction in language-based learning disabilities (L/LD). Backed by a three-year, $2.3 million grant, the researchers at five universities will work on developing methods for early diagnosis of L/LD, using imaging techniques to pinpoint the sources of neural dysfunction and to develop treatment strategies for the disorders. L/LD, which is said to affect at least 7 percent of children in the United States, is characterized by a difficulty in learning to speak (developmental dysphasia), followed by reading problems (developmental dyslexia). Members of the consortium include Rutgers University, Newark, N.J.; Harvard Medical School; New York University Medical Center; University of California, San Francisco; and Washington University School of Medicine in St. Louis. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : New Gynecology Journal TY : NEWS (NOTEBOOK) PG : 4 The Society for Gynecologic Investigation, headquartered in Washington, D.C., has issued the first volume of an international quarterly, the Journal of the Society for Gynecologic Investigation, published by New York-based Elsevier Science Inc. Rogerio A. Lobo of the University of Southern California Women's Hospital in Los Angeles is editor-in-chief. For information, contact: Cheryl Kahan, Marketing Manager, Elsevier Science Inc., P.O. Box 882, New York, N.Y. 10159; (212) 633-3922. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : A Global Warming Mystery TY : NEWS (NOTEBOOK) PG : 4 Popular theories of global warming center on the notion that burning fossil fuels adds carbon dioxide (CO2) and other gases to the Earth's atmosphere in quantities greater than plants and forests can absorb--with the accumulating layer of gases drastically altering climate patterns. But geologists have uncovered evidence that, millions of years ago, CO2 levels were more than 16 times higher than they are now, while the Earth's temperature was cooler. Their findings are based on studies of goethite, a hydrogen- bearing iron oxide that is 440 million years old. A specimen found in a tropical area by a team led by Crayton Yapp, a University of New Mexico professor of earth and planetary sciences, indicated high levels of CO2, as well as a coolish 73-degree average temperature for the region. The evidence coincides with indications of continental ice sheets forming at the time as well as a massive extinction described by paleontologists for the period. According to the New Mexico scientists, the discovery seems to show that global warming effects may be more complex than simply high levels of CO2, and that by reconstructing past changes, scientists may more accurately predict such future phenomena as global warming. Yapp warns, however, that "we try to solve mysteries, but many of the clues have been destroyed by nature itself." ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: COMMENTARY ------------------------------------------------------------ TI : Bench Scientists Had Better Pay Attention To The Threats Posed By Health-Care Reform AU : Carl B. Feldbaum TY : OPINION (COMMENTARY) PG : 12 I fear that bench scientists in biotech companies may be taking the current debate over health-care reform much too casually. They may be thinking that, aside from how the outcome will affect the cost of their own individual insurance coverage, the matter is something that only people in Washington, D.C., need to care about. Well, if they feel that way, they're wrong. Already, health- care reform is having a damaging impact on the scientific work force--and the implications for the future are even more threatening. The CEOs of two small biotech firms and I recently met with the editorial board of the Baltimore Sun. During the meeting, one of the executives explained that, like 99 percent of United States biotechnology companies, his enterprise had no products yet on the market. Without earning revenues from sales, and certainly without profits, his company relies on private venture capital and potential stock offerings to finance its research. Uncertainty about price-control provisions in various health-care reform proposals--including President Clinton's--have driven investors away in droves. Their reasoning? "The science is tough enough," they say, "and then you have to get through years of clinical trials and FDA approval. Now you're telling us there's going to be some faceless government bureaucrat at the end of the whole, long process to tell you what price to set? We look at the bottom line, the return on our investment. We'd do better investing in the computer industry or in fast food or any other industry with a more promising return on investment!" The result? The biotech CEO I mentioned was recently forced to lay off 15 employees--all bench scientists. This sort of cutback is becoming common these days and represents a bitter irony. Shouldn't health-care reform promote and support, rather than suppress, the innovative research necessary to create therapies and cures for various cancers, cystic fibrosis, multiple sclerosis, Alzheimer's, AIDS, and countless other diseases and conditions? And isn't it individual researchers, after all, who constitute the backbone of any biotech firm's product-development efforts? Unfortunately, the various health-care reform proposals currently before Congress could very well establish impenetrable barriers between biotech companies and the capital they need to continue their work and maintain their staffs at full level. As things stand now, President Clinton's health-care reform program would create an advisory council empowered to evaluate the "reasonableness" of new drug pricing. While the council wouldn't be able actually to set prices, it could publicly voice its disapproval of a particular drug's price, and the Secretary of Health and Human Services would be able to "blacklist" it from Medicare coverage. The depressing financial impact that such a practice would have on a biotech enterprise's return on investment is obvious. And the consequent impact on the bench-scientist work force should be obvious as well: Since most of the 1,300 biotech companies in the U.S. have fewer than 75 employees, and less than 1 percent of these companies have products on the market, they have very few ways to reduce costs besides laying off employees. The growing threat presented by health-care reform is exacerbating the economic situation for small biotech companies. Dried-up capital markets are now forcing biotech firms to curtail research and clinical trials. A survey taken by the Biotechnology Industry Organization late last year showed that almost half of its member companies conducting AIDS research had to slow down their efforts because of a lack of available capital. Another survey in February of this year, focusing on cancer research, showed a similar pattern. Given such work force reductions, it is likely that patients suffering from AIDS, cancer, and other diseases may have to wait even longer than the current seven to 18 years generally needed to bring new drugs or therapies to market. I presume it is clear that less research means fewer researchers. Still another survey--released last month by the Gordon Public Policy Center of Brandeis University-- showed that nearly 70 percent of biotech companies polled would be further forced to cut research and development if the Clinton plan or something similar were enacted. To me, it is unjust and wholly inappropriate that the biotech sector should be put to the sword. While current health-care reform proposals paint the drug industry as the bad guy, drugs make up only 7 percent of all health-care costs--and biotech drugs represent only 3 percent of that 7 percent. Furthermore, prices of most biotech drugs--which are less expensive in the U.S. than they are abroad--have never been raised since their launch dates. As the health-care debate evolves through Congress, all Americans should ask themselves why excellence and medical advancement should not be compatible with universal coverage. We should also consider whether it is wise or just that innovative scientists--of all people--are turning out to be casualties of the reform movement. Please keep your eyes open--and your guard up--as this situation unfolds. Carl B. Feldbaum is president of the Biotechnology Industry Organization (BIO), a Washington, D.C.-based national trade association for the biotech industry. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: LETTERS ------------------------------------------------------------ TI : Basic Research Support AU : Wells E. Farnsworth TY : OPINION (LETTERS) PG : 12 Recently, in The Scientist ("Scientists Should Make Sure They Give NIH Proper Credit For Funding Their Research," Nov. 15, 1993, page 12), Samuel C. Silverstein, Frank W. Fitch, and John D. Loike made the critically important observation that not only the general public but also members of Congress grossly undervalue government-supported basic biomedical research for two reasons. First, they reported, investigators fail to credit National Institutes of Health sponsorship of their work. Second, they noted, researchers do not clearly communicate the significance and utility of their basic findings to the advancement of medicine, the environment, or the economy. Sen. Barbara Mikulski (D-Md.), for example, views basic science efforts as "curiosity-driven activities," which she equates with pork. Members of Congress fail to see that usable concepts arise, as do oaks from acorns, through development and nurture of new, at first unappreciated, ideas. Little wonder that the current administration, in its plans for funding health research initiatives, is shifting priorities away from basic biomedical research, which has been America's source of justified pride, to pragmatic "preventive research" and "health service research." Both these efforts feed on what we have done but stifle continuation of theoretical progress. The following three ideas may help stop this erosion of the image of the research establishment: 1. Investigators must aggressively communicate their findings in an intelligible and wholly honest manner to the general public and to Congress. As Mary Woolley, president of Research!America, stresses in her address entitled "The Public's View of Federal Support for Medical Research" (The Physiologist, 36:53, 1993), we must be advocates. 2. People must be aware that almost all the advances that have sustained our preeminence in biomedicine have been made possible by the tax dollars provided by NIH and the high- quality work that this institution ensures. 3. Besides reaching out to the public as advocates of research, we must be sure that we in the profession are aware of the worth and innovation of those outside our ivory tower. While we are indebted to The Scientist for providing this currency, especially through its "Hot Papers" section, I suggest that the publication include acknowledgment of the source of support of all these projects. So informed, each can be a credible advocate of the work of others and a champion of their support. WELLS E. FARNSWORTH Adjunct Professor Northwestern University Medical School Tarry Building 11-715 303 E. Chicago Ave. Chicago, Ill. 60611-3009 ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: RESEARCH ------------------------------------------------------------ TI : 1993's Top 10 Papers: Superconductor Report Surfaces In Sea Of Genetics AU : KAREN YOUNG KREEGER TY : RESEARCH PG : 15 Following a well-established pattern, papers in the field of gene research dominated the list of hottest articles in science for 1993--as determined by citation analysis. It is noteworthy, however, that a physical science report describing a new superconductor placed in a list of the 10 most cited papers published and referred to last year. Based on data compiled by the Philadelphia-based Institute for Scientific Information (ISI), a listing of the most frequently cited papers covered topics in molecular biology, genetics, and other life science specialties. Life science papers, say ISI analysts, generally tend to gain far more citations, on average, than papers in physics, chemistry, or other fields. This is partially attributable to the comparatively greater number of published papers and researchers in life sciences, as well as the higher average number of articles they cite. As a result, more than half of the "hottest" papers of 1993 related directly or indirectly to molecular genetics, as reported earlier this year in ISI's newsletter Science Watch (G. Taubes, 5[1]:1, January 1994), which used ISI's "Hot Papers" database to come up with its tallies. The newsletter focused on papers describing original research, not review articles. The list that the newsletter published contained 37 papers, each of which had gathered at least 24 citations by the end of the year. Of the 10 most cited papers (see accompanying table), six fall, broadly speaking, into the category of gene research. Three of these articles (Nos. 3, 7, and 8) describe the role of various proteins in the signal-transduction pathway of cells and how this ultimately relates to oncogenesis. Two other papers identify a genetic cause for amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease (No. 1), and X-linked agammaglobulinemia (No. 6). Among the top 10, the remaining gene research paper (No. 9) covers the role of the p53 tumor suppressor gene in genetically programmed cell death. The other papers in the top 10 discuss the activity of HIV during the AIDS latency period (Nos. 2 and 4) and adult respiratory distress syndrome (No. 10). Other life science papers in Science Watch's report encompassed such diverse subjects as the identification of carbon monoxide as a putative neural messenger; a genetic linkage analysis in familial breast and ovarian cancer; genetic mapping of human colorectal cancer; and the isolation of a candidate gene for Menkes disease. Also placing quite high in the rankings was a physical science paper describing the discovery and properties of a new mercury-bearing superconductor (No. 5 on the accompanying table). Leading The Pack The most frequently cited 1993 paper was an article from the March 4 issue of Nature. The 33 collaborators in this research, working at 13 institutions, report that mutations in copper/zinc-binding superoxide dismutase (SOD1)--an enzyme that normally prevents cellular damage from highly reactive chemicals such as superoxide--are associated with familial ALS. Until now, the cause of ALS--a fatal neurodegenerative disorder of motor nerve cells of the spinal cord, brain stem, and cortex--has been unknown, although about 10 percent of the cases are inherited through a dominant gene on a non-sex chromosome, say ALS researchers. "It's an amazing breakthrough in that this is the first signal that we're getting in terms of what could be causing the disease," says Daniel Rosen, a molecular biologist at the Day Neuromuscular Research Laboratory at Massachusetts General Hospital in Charlestown, and first author on the ALS paper. "We think the value of this research is that it points to a pathophysiological mechanism [for ALS] ... We believe that it is possible that free radical damage could be the cause for the damage" seen in ALS patients, says Rosen. Free radicals--highly reactive atoms or groups of atoms, mostly oxygen--attack cellular constituents such as membrane lipids, proteins, and nucleic acids. This research "represents the first definition of a biochemical defect that can cause this disease" in the more than 120-year history of ALS research, notes Rosen. He explains that the research described in the 1993 Nature paper builds on past work at Massachusetts General, which was directed by Robert Brown, Jr., head of the Day lab. One of the reasons that this paper is so heavily cited might be that researchers are using this information to look into possible therapies and drugs to fight ALS, surmises Rosen. He says that, because of the research in this report, a new avenue of investigation in terms of clinical investigations and therapy has opened up. According to Rosen, this breakthrough comes none too soon for the ALS research community. "There's a great deal of helplessness associated with it [ALS]," he says. "The patient slowly withers away and the physician feels impotent in terms of being able to treat them.... There's a general desire to find some straw that people can grab onto which would provide an answer for this disease," Rosen continues. This discovery may also have implications for solving the mysteries surrounding other neurological conditions, such as Parkinson's disease, says Rosen. "There may be a common mechanism in neurological diseases that involve free radicals," he adds, although no experimental evidence yet exists to link diseases like Parkinson's to free radical scavenging. Best Of The Rest The second- and fourth-most-cited papers address the recently discovered activity of HIV in the lymph node during the latency period of AIDS. Both studies found that lymphoid organs function as major reservoirs for the virus, even during the asymptomatic phase of AIDS. Because the extent of viral activity in infected people has been underestimated up to now, say AIDS researchers, these papers point to the importance of studying infection early in the course of the disease. The "general picture is that these changes [in how HIV affects cells of the lymph node] not only allow us to understand the viral pathogenesis, but they are allowing us to understand the major progression [of AIDS]," says Giuseppe Pantaleo, a researcher at the National Institutes of Health's National Institute of Allergy and Infectious Diseases in Bethesda, Md., and an author on the second-most- cited paper. Ashley Haase, a microbiologist from the University of Minnesota, Minneapolis, and an author of the fourth-most- cited paper, concludes that "the two big messages [from paper No. 4] are that there is massive covert infection that establishes a reservoir to perpetuate infection" and that there are a "large number of cells that are capable of producing virus at any given time and [are capable of making a] substantial dent in the immune system." Haase explains that a covertly infected cell contains the viral genome, but has no external evidence of infection such as detectable viral proteins or messenger RNA. As far as the immune system is concerned the cell is not infected, but carries the potential to infect, he adds. Both Pantaleo and Haase say that a major implication of these discoveries is that quite early in the course of AIDS much damage to the immune system has already occurred, which has important ramifications for AIDS therapy. "The idea is that you'd want to come in very early in the disease with very effective anti-retrovirus therapies" to limit the size of the reservoir, says Haase. However, he says, finding effective therapies is still a problem and the body could build up a resistance to drugs like AZT if used early on, making the fight against later opportunistic infections more difficult. "I'm actually somewhat optimistic about vaccines," says Haase, explaining that the initial infection might involve relatively small numbers of infected cells so we "might be able to make a huge dent with a vaccine that is only partly efficacious." The third-most-frequently cited paper describes the identification of the SH3 binding domain, a 10-amino-acid long region found on many types of proteins, including kinases, Ras activators, and transcription factors. Ruibao Ren, a postdoctoral fellow in the laboratory of David Baltimore at Rockefeller University, and first author of the paper, explains that "SH3 appears in many important proteins, including many types of oncogenes.... Their binding sites involve other proteins which are mostly all involved in signal transduction," a series of steps whereby information from outside a cell is passed, or transduced, via protein-protein interactions, to the cell nucleus where genes are activated. Because information like this controls basic cellular functions such as growth, immune response, and differentiation, Ren describes the importance of this paper as "real-ly finding the key to how proteins interact ... now people can understand the mechanism of how normal signals are transduced and how, during oncogenesis, normal signals get derailed." Ren attributes the high frequency of citations of this paper to two factors. He explains that because SH3 domains are ubiquitous, the identification of the SH3 domain will guide other researchers in their tests to determine whether the proteins they have isolated contain an SH3 binding domain. In addition, he says that SH3 binding domains will "eventually serve as a target for pharmaceutical treatments to block aberrant pathways," in cancerous cells, for example. Superconductor Surprise An unexpected entry on the top 10 list is the fifth-most- cited paper, a physical science report by a Russian-French team that describes the discovery of a mercury-containing copper oxide superconductor. Massimo Marezio, an author on the paper and a physicist with a dual appointment as director of research at the Laboratoire de Cristallo-graphie in Grenoble, France, and a member of the technical staff at AT&T Bell Laboratories in Murray Hill, N.J., explains the impact of this paper: "At the beginning [the new superconductor] looked like just another compound"; however, "a posteriori, its chemistry looked very interesting because of the specific crystal chemistry of the mercury cations." "Because it is much simpler [than other superconductors], from the structural point of view" he says, we "can study it more easily than more complicated [superconductor] systems, thus providing a simpler model for theorists" who study the properties of superconductors. For now, Marezio describes the potential for practical applications of the superconductor as "promising ... but we are still in the preliminary stages." He attributes the report's high number of citations to the new compound's "physical properties, not its applications." The authors of these highly cited papers all say that they are continuing the lines of research described in the 1993 reports--the Day lab team is conducting genetic analyses to identify other ALS genes; Pantaleo's group is studying infection mechanisms of HIV during the earliest and latest stages of AIDS; Hasse's group is investigating aspects of host immunity; Ren and colleagues are characterizing other SH3-containing proteins; and Marezio and associates are studying pressure effects on the mercury-containing superconductor. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : TEN MOST CITED PAPERS FOR 1993 TY : RESEARCH PG : 15 Rank Paper Citations 1 D.R. Rosen, et al., "Mutations in Cu/Zn 54 superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis," Nature, 362(6415):59-62, 1993. 2 G. Pantaleo, et al., "HIV infection is 53 active and progressive in lymphoid tissue during the clinically latent stage of disease," Nature, 362(6418):355-8, 1993. 3 R.B. Ren, et al., "Identification of a 47 ten-amino acid proline-rich SH3 binding site," Science, 259(5098):1157-61, 1993. 4 J. Embretson, et al., "Massive covert 43 infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS," Nature, 362(6418):359-62, 1993. 5 S.N. Putilin, et al., "Superconductivity at 41 94 K in HgBa2CuO4+d," Nature, 362(6417): 226-8, 1993. 6 D. Vetrie, et al., "The gene involved in 40 X-linked agammaglobulinemia is a member of the src family of protein-tyrosine kinases," Nature, 361(6409):226-33, 1993. 7 T. Sollner, et al., "SNAP receptors implicated 39 in vesicle targeting and fusion," Nature, 362(6418):318-24, 1993. 8 C.A. Lange-Carter et. al., "A divergence in 33 the MAP kinase regulatory network defined by MEK kinase and raf," Science, 260(5106):315-9, 1993. 9 A.R. Clarke, et al., "Thymocyte apoptosis 33 induced by p53-dependent and independent pathways," Nature, 362(6423):849-52, 1993. 10 R. Rossaint, et al., "Inhaled nitric oxide 32 for the adult respiratory distress syndrome," New England Journal of Medicine, 328(6): 399-405, 1993. Source: ISI's Hot Papers Database, 1993 ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: HOT PAPERS ------------------------------------------------------------ TI : ATMOSPHERIC PHYSICS TY : RESEARCH (HOT PAPERS) PG : 17 L.S. Rothman, R.R. Gamache, R.H. Tipping, C.P. Rinsland, M.A.H. Smith, D.C. Benner, V.M. Devi, J.-M. Flaud, C. Camy- Peyret, A. Perrin, A. Goldman, S.T. Massie, L.R. Brown, R.A. Toth, "The HITRAN molecular database: Editions of 1991 and 1992," Journal of Quantitative Spectroscopy and Radiative Transfer, 48:469-507, 1992. Laurence S. Rothman (Air Force Geophysics Directorate, Phillips Laboratory, Hanscom Air Force Base, Mass.): "Most molecules have strong absorption features in the infrared and microwave region of the spectrum. The HITRAN database is a compilation of fundamental parameters of molecular transitions that permit users to identify and make quantitative determinations of transmission and radiance through atmospheric, laboratory, or other gaseous environments. Advances in sensor technology, high-resolution spectrometers, and computer power have enabled excellent discrimination of background sources, such as smokestack effluents through long-path observations. "More than 30 gases, including their principal isotopic variants, have been archived as a result of high-resolution experimental and theoretical efforts. The database now contains almost three-quarters of a million transitions (each transition consisting of 100 bytes of information concerning basic properties such as resonant frequency, intensity, and quantum identification) from the millimeter region to the visible portion of the electromagnetic spectrum. In addition, cross-sections of anthropogenic gases, such as the chlorofluorocarbons, have been archived. The HITRAN program has above all been a major effort in directing, coordinating, and validating massive amounts of data. "The HITRAN database is recognized as the international standard in spectroscopy. It has been used for extensive military and civilian applications, including remote sensing, laser beam propagation, atmospheric modeling, and fundamental laboratory research. Remote sensing, global climate modeling, and pollution monitoring are currently among the most prevalent applications. Remote sensing applications from ground-based instrumentation and from satellite platforms have matured into a major endeavor that drives the development of the HITRAN database. "HITRAN has also recently become available on a convenient medium for the user: compact optical disk. Thus, there are now a vast number of users who have migrated their spectral analyses from mainframes to desktop computers." ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : CELL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 17 P. Dent, W. Haser, T.A.J. Haystead, L.A. Vincent, T.M. Roberts, T.W. Sturgill, "Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro," Science, 257:1404-7, 1992. Paul Dent (Department of Medicine, University of Virginia Health Sciences Center, Charlottesville): "Investigators in signal transduction want to understand in detail the molecular steps by which growth factors, hormones, and oncogenes regulate cell function. Much of this control is via protein phosphorylation. MAP kinase is activated by dual phosphorylation at tyrosine and threonine residues, occurring in a TEY motif, catalyzed by a protein- tyrosine/threonine kinase termed MAP kinase kinase, or MEK (MAP kinase/ERK kinase). MAP kinase kinase (MKK) is remarkably specific for MAP kinase as the protein substrate and is itself regulated by serine/threonine phosphorylation. "At the time we initiated these studies, the activating kinase for MKK had not been identified. Several clues suggested that it was worthwhile to test the ability of v- Raf to phosphorylate and activate MKK. Similar stimuli activate Raf and MAP kinase, and both appeared to function downstream from p21 Ras, inferred from studies by K.W. Wood and colleagues (Cell, 68:1041-50, 1992; Hot Papers, The Scientist, July 12, 1993, page 15) of the ability of a dominant-negative mutant of p21 Ras to inhibit their activation in PC12 cells in response to nerve growth factor. "Because the mechanism of activation of c-Raf was unknown, but the truncated oncogenic protein is arguably active (or else cells would not be transformed), we studied activation of MKK in NIH 3T3 cells transformed with v-Raf. We found that MKK was activated constitutively in these cells and that either v-Raf partially purified from the cells or a GST-v-Raf fusion protein from E. coli phosphorylated and activated MKK in vitro. These results strongly implied that MKK is a physiological substrate for Raf. John Kyriakis, Ulf Rapp, and Joe Avruch (from Harvard University and the National Cancer Institute) independently demonstrated that c-Raf immunoprecipitated from stimulated cells activated MAP kinase kinase (Nature, 358:417-21, 1992). Other MKK activators have also been identified. "The discovery that MKK is a Raf substrate has been rapidly followed by exciting discoveries from several labs. Ras binds tightly to the regulatory domain of Raf, implying that Ras may directly participate in Raf activation. MAP kinase is translocated to the nucleus and regulates transcription of c-fos. Through the efforts of many, we now understand most of the steps in a signal transduction cascade from the cell membrane to the nucleus." ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: TOOLS & TECHNOLOGY ------------------------------------------------------------ TI : Experiment Design Software: Better Data, Less Work AU : CAREN D. POTTER TY : TOOLS & TECHNOLOGY PG : 18 With the cost of research continuing to climb, life scientists increasingly are looking beyond their own laboratories for ways to balance their budgets. From their colleagues in industrial research, many are hearing now about the cost-saving potential of an approach to their investigations called design of experiments--DOE for short-- and about the software tools available to automate DOE. DOE is a way of using statistical principles to identify what will be the crucial variables in an experiment before the hands-on work begins. By knowing these variables in advance, a scientist can create an experiment that will need fewer runs to complete and will later require less complex statistical analyses. Even though the experiment and analysis are simpler, if the DOE approach has worked correctly, the results yield more useful information than traditional, ad hoc approaches to experimentation. "All experiments are designed experiments," says Kinley Larntz, chairman of the applied statistics department at the University of Minnesota, St. Paul. "Some of them are just designed very badly." The principles of DOE can be applied without computer assistance, but for large and complex experiments, applying DOE without a computer can be too time-consuming to be practical, scientists say. In such cases, it is wise to turn to software that automates the DOE process (see accompanying story). Statistical Help The ideas behind DOE, at first glance, appear to be nothing more than good science. And, to a degree, this is true. "DOE is really just the application of statistical principles for data collection," Larntz says. Another, more formal definition of DOE is provided by Doug Montgomery, a professor of engineering at Arizona State University in Tempe and author of the textbook Design and Analysis of Experiments (New York, John Wiley & Sons, 1991): "A designed experiment introduces systematic changes into the variables of a system with the objective of discovering which variables are responsible for the observed changes in the output." But when people talk about applying DOE techniques to their research, it's usually with the goal of obtaining the most informative data from the minimum number of trials. "The method is aimed at small experiments where resources are expensive," explains Larntz. "The goal of small, expensive experiments with multiple factors is that every data point you collect is useful. DOE lets you set up the experiment so that you get a good amount of information from every point." Development of the principles behind DOE dates back to the 1920s. Software that automates the designed-experiment method goes back to the early days of mainframes. "DOE software systematically looks at all the experimental factors and levels and picks, out of all the possible combinations, a small subset," says Larntz. "By working with this subset, you get predictive abilities from your analysis to help you predict optimal conditions. Those optimal conditions may not be conditions that you ever actually test, and that's the real beauty of the approach. DOE holds a tremendous potential for scientists." In the last 10 years or so, as with other software, DOE programs have migrated from mainframes to personal computers, becoming available now to most scientists. "Frankly, anyone who does DOE manually today needs to have his head examined," says Montgomery. "If you do it manually, you have to understand more about the theory of statistical design and more of the operational aspects of the statistical methods. If you use a computer program, you only have to understand the basic concepts of experimental design. The software leads you through the rest." DOE software uses one of two approaches to lead the researcher through experiment design. One approach is a question-and-answer dialogue in which the program asks certain questions and the user supplies the answers. The other approach involves a menu structure. The user selects an item from a main menu, which leads to another, more specific menu, which leads to another, and so on until the researcher has provided all the required input. Montgomery prefers the menu approach. "I personally don't like the question-and-answer approach very well," he says. "When you ask someone how many experiments he wants to run, the answer is `zero.' A question-and-answer approach often closes off some of the attractive alternatives. I prefer choosing items from a well-structured, narrow menu, then having other menus pop up and guide you as to what to do. You don't want to allow a sort of a global decision, like how many runs you want, to be made too early in the game." DOE software is available from the larger, well-known statistics software companies such as SAS Institute Inc. of Cary, N.C., and BBN Software Products of Cambridge, Mass., as well as smaller companies that have a DOE package as their sole product. DOE software from the larger vendors is usually supplied as a module that works in conjunction with the company's other statistics products. For example, SAS's DOE offering is called SAS/QC, and it can be integrated with the company's broader SAS System for statistics. Similarly, BBN's RS/Discover works with the company's RS/Series of statistical software. Stand-alone DOE software is available from companies such as Stat-Ease Inc. of Minneapolis, which makes the Design-Ease and Design-Expert packages. The advantage of stand-alone, personal-computer-based DOE programs is an affordable price (Design-Ease costs $395; Design-Expert sells for $795) and the fact that it's possible to buy just the DOE capabilities needed without getting a much larger, more comprehensive statistics system. The advantage of going with a vendor such as SAS or BBN is getting a powerful system geared for a large enterprise. These vendors' products run on a variety of hardware platforms and also support networking, client/server computing, and other state-of-the-art computing functions. Biological Applications Minnesota's Larntz believes that there should be more factorial studies, and consequently more DOE, in the biological sciences. However, as he says, this idea "hasn't taken off very well" yet. One of the ideas behind DOE is that it helps the researcher control variability, which, according to Larntz, could make DOE particularly useful in life sciences. "There is lots of variation in the biological sciences, often more variation relative to response than in physical sciences," Larntz says. "Because of that variation, biological research requires larger studies, but the balanced factorial approach of DOE would work well in this arena." Larntz is currently applying DOE principles to a large- scale, community-based clinical trial of various treatments for opportunistic diseases related to HIV infection. It is what he calls a pragmatic design involving real-world patients and primary-care physicians. Typically, a study such as this would investigate one treatment per patient. Larntz's approach will permit multiple treatments on the patients and investigate the effect of different treatments in combination with each other. "That's the idea of a factorial design," he says. "We're trying to set up an experiment where we are looking at many things simultaneously, possibly the interactions between the drugs. These are DOE ideas." However, while DOE software is available to Larntz, he is not using it for this study. "It's such a very large experiment that designed-experiment principles will prevail without need for any specialized software," he says. "The typical engineering study has 16 runs. This study has 5,000 patients. There wouldn't be a big gain from optimization with DOE software." There are several reasons that some industrial research areas picked up on DOE before others and before academia. For one, the nature of some industrial research lends itself perfectly to DOE. "In the chemical industry, for example, it is relatively easy to manipulate factors such as time, temperature, and concentration," says Mark Anderson, vice president and general manager at Stat-Ease. "DOE is ideal for finding optimum formulations, and its payoffs in the chemical industry are tremendous." Second, the highly competitive nature of some industries forced them to turn to an approach--such as DOE--that might give them an edge. This is particularly true of the semiconductor industry. "They got forced into using these tools and techniques probably earlier than anybody here in the United States because it was a matter of survival," says Montgomery. "They had to really figure out how to understand their products and their processes and how to make them better, faster, and cheaper." A third reason is the nature of some academic research, especially that involving the life sciences. "The difference between a life science application and an engineering-based industrial application," explains Minnesota's Larntz, "is that in a typical large clinical trial, for example, you do not have many different treatments. It's commonly a comparison of drug A vs. drug B. In a typical engineering application, you have time, pressure, temperature, catalysts, and concentrations--lots of factors. You can take advantage of DOE to manage those large factorial designs." Another characteristic of much life sciences research is that the studies are quite large. "It's fairly clear how to design these according to statistical principles without a computer," Larntz says. A fourth reason for the relatively minor use of DOE techniques and DOE software in academic research compared with industry is simply that many academic researchers have not received training in this area. In industry, DOE often falls under the realm of quality control, and with the huge push for better quality control in the U.S., many industrial researchers are being exposed to DOE. It is possible to go through a typical Ph.D. program in many basic science disciplines and not be exposed to these principles. Robert Launsby of Launsby Consulting, Colorado Springs, Colo., tells the story of one client who had gotten a Ph.D. in organic chemistry and then gone on to start his own biotechnology company. When he realized the potential DOE held for his company, he called in Launsby's firm--which specializes in suggesting ways for industrial clients to use DOE principles in their experiments--to implement the approach. After seeing its success, he thought back on his dissertation process and said wistfully, "You know, I wish I'd known about these techniques before I started my dissertation. I would have done it in half the time and would have gotten as good or better results." Caren D. Potter is a freelance science writer based in McKinleyville, Calif. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : STREAMLINING THE EXPERIMENTAL PROCESS AU : CAREN D. POTTER TY : TOOLS & TECHNOLOGY PG : 18 For scientists faced with a large, complex research investigation, computer programs that bring design-of- experiment (DOE) ideas to bear on the task can save considerable time, materials, and aggravation. Consider the situation faced by Robert Launsby of Launsby Consulting, Colorado Springs, Colo., on a job he did for a biomedical-industry client. Launsby's firm specializes in suggesting ways for industrial clients to use DOE principles to streamline their experiments. In this case, the task was to find the best buffering solution for a particular, expensive enzyme. The challenge was to create, from a list of hundreds of possible buffers, the most effective solution for that enzyme. Relying on experience, the company's scientists were able to initially narrow the list of buffers. But since a buffer is placed into solution--of sodium chloride; magnesium; ethylenediaminetetraacetic acid (EDTA); ethylene glycol-bis- N, N '-tetraacetic acid (EGTA); or the like--the experiment would have to investigate enzyme activity not only in the presence of the different buffers, but also with each buffer in a different solution. The experimenters would have to consider buffer A in sodium chloride, magnesium, EDTA, or EGTA, then buffer B in sodium chloride, magnesium, EDTA, or EGTA, and so on. And since solutions can be formulated in different concentrations, the experiment threatened to become even more complex--buffer A in sodium chloride at a low concentration would have to be tested, for example, and then buffer A in sodium chloride again, but at a higher concentration. Potentially, the client's scientific team was confronted with a very unwieldy experiment. "They were making a reagent for a glucose monitoring device and studying enzyme activity," Launsby explains. "They ended up with something like 96 possible buffer-solution combinations to investigate." The company hired Launsby to apply the principles of DOE to this problem. In the past four years, Launsby Consulting has helped set up close to 500 experiments using the DOE approach. In this case, Launsby used a program called RS/Discover from BBN Software Products, Cambridge, Mass., to implement DOE. The software identified, from the 96 possible combinations of buffer, solution, and concentration supplied by the scientists, 12 that would provide sufficient data to determine the best buffering solution for that particular enzyme. "We could have applied DOE principles by hand and gotten to the same 12 combinations, but it's very labor-intensive," Launsby says. "With DOE software, you supply some information--your variables, your levels, your responses-- and the program leads you through the selection of the best design to meet your needs. The result is an experiment with the minimum number of runs, as opposed to having to run all the combinations." --C.D.P. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : SUPPLIERS OF EXPERIMENT DESIGN AND STATISTICAL SOFTWARE TY : TOOLS & TECHNOLOGY PG : 20 The following companies offer software tools that aid in the design of experiments or in statistical analysis of experiments and data. Please contact the companies directly for more information concerning specific products. Abacus Concepts 1918 Bonita Ave. Berkeley, Calif. 94704 (510) 540-1949 Fax: (510) 540-0260 Advanced Systems Management 1200 S. Acadian Suite 110 Baton Rouge, La. 70806 (504) 343-7151 Fax: (504) 383-3048 BBN Software Products Corp. 150 Cambridge Park Dr. Cambridge, Mass. 02140 (617) 873-5000 Fax: (617) 873-4020 BMDP Statistical Software Inc. 1440 Sepulveda Blvd. Suite 316 Los Angeles, Calif. 90025 (310) 479-7799 Fax: (310) 312-0161 Dionex Corp. P.O. Box 3603 1228 Titan Way Sunnyvale, Calif. 94088-3603 (408) 737-0700 Fax: (408) 739-4398 DSP Development Corp. One Kendall Square Building 100 Cambridge, Mass. 02139 (617) 577-1133 Fax: (617) 577-8211 Exeter Software 100 N. Country Rd. Setauket, N.Y. 11733 (516) 689-7838 Fax: (516) 689-0103 Europa Scientific Software Corp. 14 Clinton Dr. Hollis, N.H. 03049-6595 (603) 595-7415 Fax: (603) 889-2168 Galactic Industries Corp. 395 Main St. Salem, N.H. 03079 (800) 862-6004 Fax: (603) 898-6228 Graphpad Software 10855 Sorrento Valley Rd. Suite 203 San Diego, Calif. 92121 (619) 457-3909 Fax: (619) 457-8141 GW Instruments Inc. 35 Medford St. Somerville, Mass. 02143 (617) 625-4096 Fax: (617) 625-1322 HEM Data Corp. 17336 Twelve Mile Rd. Suite 200 Southfield, Mich. 48076 (313) 559-5607 Fax: (313) 559-8008 Idea Works 607 Jackson St. Columbia, Mo. 65203 (314) 875-5827 Fax: (314) 875-5812 Infometrix 2200 Sixth Ave. Denny Bldg., Suite 833 Seattle, Wash. 98121 (206) 441-4696 Fax: (206) 441-0841 Jandel Scientific 2591 Kerner Blvd. San Rafael, Calif. 94901 (415) 453-6700 Fax: (415) 453-7782 Keithly Metrabyte 440 Myles Standish Blvd. Taunton, Mass. 02780 (508) 880-3000 Fax: (508) 880-0179 Labtronics Inc. 95 Crimea St. Unit 2-C Guelph, Ontario N1H 2Y5 Canada (519) 767-1061 Fax: (519) 836-4431 Manugistics 2115 E. Jefferson St. Rockville, Md. 20852 (301) 984-5000 Fax: (301) 984-5094 MathSoft Inc. 210 Broadway Cambridge, Mass. 02139-1901 (617) 577-1017 Fax: (617) 577-8829 MicroCal Software Inc. 1 Roundhouse Plaza Northampton, Mass. 01060 (413) 586-2013 Fax: (413) 585-0126 Millipore Corp. 80 Ashby Rd. Bedford, Mass. 01730 (617) 275-9200 Fax: (617) 275-5550 Minitab 3081 Enterprise Dr. State College, Pa. 16801 (814) 238-3280 Fax: (814) 238-4383 Nicolet Instrument 5225 Verona Rd. Madison, Wis. 53711-9075 (608) 271-3333 Fax: (608) 276-6222 Omega Engineering Inc. 1 Omega Dr. Box 4047 Stamford, Conn. 06907 (203) 359-1660 Fax: (203) 359-7640 Research Systems Inc. 2995 Wilderness Place Suite 203 Boulder, Colo. 80301 (303) 786-9900 Fax: (303) 786-9909 SAS Institute Inc. SAS Campus Dr. Cary, N.C. 27513 (919) 677-8000 Fax: (919) 677-8123 Signal Technology 104 W. Anapamuma Dr. Santa Barbara, Calif. 93116-1950 (800) 235-5787 Fax: (805) 968-2620 Stat-Ease Inc. 2021 East Hennepin Ave. Minneapolis, Minn. (612) 378-9449 Fax: (612) 378-2152 Statistical Graphics Corp. Five Independence Way Princeton, N.J. 08540 (609) 924-9374 Fax: (609) 452-7792 Statistical Sciences 1700 West Lake Ave. North Suite 500 Seattle, Wash. 98109 (206) 283-8802 Fax: (206) 283-8691 StatSoft 2325 E. 13th St. Tulsa, Okla. 74104 (918) 583-4149 Fax: (918) 583-4376 Systat 1800 Sherman Ave. Evanston, Ill. 60201 (708) 864-5670 Fax: (708) 492-3567 The Math Works Inc. 24 Prime Parkway Natick, Mass. 01760 (508) 653-1415 Fax: (508) 653-2997 Trinity Software P.O. Box 960 Main Street Campton, N.H. 03223 (603) 726-4641 Fax: (603) 726-3781 Visual Numerics Inc. 9990 Richmond Ave. Suite 400 Houston, Texas 77042 (713) 954-6496 Fax: (713) 781-9260 Waterloo Maple Software 450 Phillips St. Waterloo, Ontario N2L 5J2 Canada (519) 747-2372 Fax: (519) 747-5284 Wolfram Research Inc. 100 Trade Center Dr. Champaign, Ill. 61820-7237 (217) 398-0700 Fax: (217) 398-0747 ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEW PRODUCTS ------------------------------------------------------------ TI : Unisyn Releases Medium For Growing Hybridomas TY : NEW PRODUCTS PG : 21 Unisyn Technologies, based in San Diego, has introduced Hybrid Grow specialized basal medium for growing hybridomas in the company's Cell-Pharm hollow-fiber bioreactors. The medium elevates glucose and glutamine levels to deliver nutrients to the tissue-dense hollow-fiber hybridoma cultures. According to Unisyn, Hybrid Grow simplifies downstream processing and reduces regulatory concerns because it is free of bovine products. Addition of defined medium supplements to the product increases production rates in serum-free environments, the company says. Hybrid Grow does not contain pherol red, which can interfere with charged-based separation media, such as ion-exchange gels. Unisyn notes that Hybrid Grow is produced in a Class 100 clean room in compliance with Food and Drug Administration Good Manufacturing Practices using water tested against USPXXII Water-for-Injection standards. It is also dispensed through filling equipment that sterilizes filling ports between each use. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Ashton Pumpmatic Offers Pipetting System Designed To Reduce Contamination TY : NEW PRODUCTS PG : 21 Ashton Pumpmatic Inc. of Dayton, Ohio, offers the Pumpmatic closed pipetting system, designed to sample and dispense fluids of an unknown or potentially hazardous nature. According to the manufacturer, each single-use Pumpmatic is accurate (0.75 percent), reduces technician exposure to questionable liquids, and virtually eliminates the risk of cross-contamination. Available in 1-, 5-, and 10-ml capacities, Pumpmatics are said to allow rapid, single- handed sampling and transfers without drips or spills. Samples can be dispensed rapidly or in single drops. Made of polystyrene and available in sterile or non-sterile form, Pumpmatics conform to Occupational Safety and Health Administration guidelines for pipetting devices. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Gelman Sciences Introduces Minispike Acrodisc Filter TY : NEW PRODUCTS PG : 21 Minispike Acrodisc syringe filters, from Gelman Sciences Inc. of Ann Arbor, Mich., allow samples up to 10 ml to be filtered directly into an instrument vial without sample runoff that is due to the small size of vial openings. The syringe filters, when used for high-performance liquid chromatography and analytical sample preparation, eliminate the extra step of transferring samples from test tubes to vials with disposable pipettes. Minispike Acro-discs are suitable for use with chromatography and spectroscopy autosampler vials, as well as nuclear magnetic reson- ance tubes and capillary electrophoresis vials. The filters are available in four membrane types: PVDF, nylon, PTFE, and GH Polypro, with membranes incorporated into a 13-mm polypropylene housing with a female luer inlet and a Minispike outlet available in 0.2 mm and 0.45 mm. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Database Package From Advanced Imaging Concepts TY : NEW PRODUCTS PG : 21 Advanced Imaging Concepts, located in Princeton, N.J., has introduced Image Central, a user-definable image database software package designed for image management and archiving. The Windows-based package can accommodate both color and monochrome images acquired from scanners, video cameras, and still digital cameras. Image Central works with live images or those stored in formats such as TIFF, TGA, PCX, GIF, and BMP. The package is available in single-user or network versions for existing PCs or as a full-featured, turnkey workstation system. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Hamamatsu Corp.'s Avalanche Photodiode TY : NEW PRODUCTS PG : 21 The S4402 silicon avalanche photodiode from Hamamatsu Corp. in Bridgewater, N.J., is suitable for applications such as low-light detection and laser-beam alignment. It has a 1 mm active area divided into four equal sections. With a spectral response of 400 to 1,000 nm and peak sensitivity wavelength of 800 nm, the photodiode's quantum efficiency is 75 percent at peak, and dark current is typically 0.8 nA, according to the manufacturer. The device will operate from -20 degrees to +60 degrees C. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Perkin-Elmer Unveils New Workstation For Chromatography TY : NEW PRODUCTS PG : 21 Perkin-Elmer Nelson Corp., based in Norwalk, Conn., has made available the v4 Turbochrom, a software package designed for integrated data handling and instrument control for gas chromatography and high-performance liquid chromatography applications. The latest version of the company's Windows- based chromatography workstation, v4 Turbochrom, offers flexible data-acquisition architecture that allows users to work simultaneously with up to eight instruments from different vendors. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Nanoprobes' Gold-Probe Protein Labeling Kit TY : NEW PRODUCTS PG : 21 Stony Brook, N.Y.-based Nanoprobes Inc. offers the Nanogold- Fab ', a gold-probe kit to covalently label Fab ', IgG, and other proteins containing cysteine, peptides, and other molecules with sulfhydryls. According to the company, Nanogold is the smallest gold probe commercially available that allows penetration into cells, tissue blocks, and nuclei over colloidal gold probes. Instead of just sticking to proteins, like colloidal gold, the compound covalently reacts at specific sites under mild, normal buffer conditions--resulting in a product that can be purified chromatographically. Additionally, the covalent attachment of the gold probe adds stability over time and over the range of pH and ionic strength, according to the company. Nanogold makes possible direct, one-step labeling, according to the manufacturer. Offered in monomaleimido-Nanogold form, the probe reacts with free sulhydryls and is mixed with Fab ' or protein to be labeled. Following a total elapsed time of two hours, the product is ready for use after purification on a gel filtration column, according to Nanoprobes. Nanogold develops with silver developer, which grows the gold into silver grains of various sizes-- depending on total development time--making the probes useful for electron, light, and confocal microscopy. With further development, Nanogold can be used in immunoblots or Westerns for detection of 0.1 pg of antigen. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Ultraviolet And Visible Transillumination Products From Hoefer TY : NEW PRODUCTS PG : 21 Hoefer Scientific Instruments of San Francisco has announced the MightyBright line of transilluminators: 305 nm UV transilluminators with dual intensity in two sizes, 15 x 20 cm (UVTM-19) and 21 x 25 cm (UVTM-25); the MightyBright Double Vision Transilluminators, which provide both 305 nm UV and visible light, 20 x 20 cm each (UVVIS-20); and a large-format Visible Light Box, 40 x 45 cm (PH90). According to the company, the units have smaller footprints and lighter weights than older-style transilluminators--which allows for easier handling and storage. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Nikon's Zoom Stereo Materials Microscopes TY : NEW PRODUCTS PG : 21 Nikon Inc., located in Melville, N.Y., offers two stereo microscope packages, the SMZ-U and the SMZ-10, designed to offer enhanced image quality in materials research. The SMZ- U features a 10:1 zoom ratio and magnifications from 3.75x to 450x. In addition, the microscope uses Nikon's ED glass, which, according to the company, provides aberration-free performance throughout the zoom range. Optical components of the SMZ-U can be customized according to the needs of the user, allowing set-up of magnification, working distance, depth of focus, and field diameter for several applications. Users can also select either low or ultra-low eye-level binocular tubes for fatigue-free observation. A variety of both reflected and transmitted light stands with built-in transformers are available; most elements of the system can be custom-configured from standard modular components. The SMZ-10 is mounted on a die-cast pillar with reversible and opal-and-black plate to provide optimum background contrast of surface-illuminated specimens. All viewing heads mount directly above the zoom ring and rotate with the optical body through 360 degrees. The teaching head allows two users to easily view a specimen at the same time. Both translucent and transparent specimens can be precisely lit by the diascopic base with built-in illuminator. Additionally, the drawing tube is designed for use as an aid for recording extensive details of a specimen. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: PROFESSION ------------------------------------------------------------ TI : New Glaxo Grants Support Undergraduate Women's Science Studies AU : RENEE TWOMBLY TY : PROFESSION PG : 22 Lisa Sease wonders now if she would have drifted from major to major--physical therapy to pre-med--if she had met Tona Gilmer four years earlier. "I wasted time looking into these fields, and at the same time, I didn't get a good insight into areas I would have liked, such as research," says Sease, 21, who expects to graduate from Lenoir-Rhyne College in Hickory, N.C., this spring. As it is, she plans to go on to graduate school for advanced study in pharmacology, a subject she hit upon as she cast about in the sea of different biology concentrations. But now she knows that she can call Gilmer, a cell biologist at Glaxo Inc. in Research Triangle Park, N.C., at any time for advice about her career, thanks to Sease's nomination as a Glaxo Women in Science Scholar by the major pharmaceutical firm. Sease may even work in Gilmer's Glaxo lab this summer, soaking up the fundamentals of research to make up for lost time. Gilmer, 39, is a mentor to Sease, who is one of 22 students at 11 North Carolina colleges and universities who were named Glaxo Women in Science Scholars late last year, the first awards to be given in the new initiative by the giant drug company. To get the program under way, Glaxo gave each institution $25,000 to establish an endowed scholarship. The scholarships will provide two undergraduate students from each school a stipend of $1,000 per year until they graduate. In addition, the company pairs each student with a female scientist at Glaxo to form a mentoring relationship. All of the mentors in the program volunteered to help out. "I can share my experiences with Lisa, and show her the camaraderie that exists between women in my lab and at Glaxo," says Gilmer, project leader for a group that is looking for novel chemotherapeutics. "Women in science need other women as role models, or even in a companionship role, helping with such issues as how to balance your professional life as a scientist with your family life. I think this is very progressive on Glaxo's part." The first award winners ranged in age from 18 to 37, and were primarily biology or chemistry majors, although the disciplines of physics, mathematics, geology, and agricultural economics were also represented. Undergraduates who are not seniors will continue receiving the scholarship and will stay with a mentor until they graduate. A Perpetual Program The program is meant to be permanent, says John S. Thomas, executive director of the Glaxo Foundation, the philanthropic arm of Glaxo Inc., one of the United States' largest research-based pharmaceutical firms and a subsidiary of British drug company Glaxo Holdings PLC. "On a permanent basis, I think this is the kind of thing that can keep women encouraged and on the right track to a career in science," says Thomas. Although Glaxo's scholarship program may eventually produce a new Glaxo scientist or two, Thomas maintains the company isn't out to recruit new employees. Instead, he says, "It's part of our good citizenship and a way to recognize the gifts and talents of our employees." Thomas says he thought about such a program when he came to Glaxo a year ago from Duke University, where he had been a vice chancellor, and saw "the number of women in science working at Glaxo and the impact they were making." Almost half the scientific staff at Glaxo are women, says Thomas, a fact he doesn't think is often matched elsewhere. "Looking at industry and business in general, I know we are the exception, not the rule," he says. At the same time, Thomas says he was impressed by the spate of press articles that talked about the "leaking pipeline" and the "50 percent drop-out rate" of women pursuing or studying for science careers. Part of the solution, he believed, was to establish a system of mentors who would encourage younger women, help them define their goals, and serve as examples of scientific achievement. There was no model to follow in setting up the program, Thomas says. "I know of no other scholarship that includes both a stipend and mentoring," he says. "It's unique to the state, and I don't think there's another like it in the country." With just a few guidelines--the scholars were required to demonstrate a strong interest in science and maintain a grade-point average between 3.0 and 4.0--selection of students was left up to the schools, says Thomas. In most cases, the colleges then established a three-person committee--made up of the school's dean, the chairperson of the math and science division, and the director of financial aid--to make their choices. The relationship between the mentors and their students is set by each pair; it can be informal, consisting of occasional telephone calls, or highly structured, with regular visits, says Thomas. `A Pat On The Back' "Glaxo needs a pat on the back. It's a unique scholarship in many ways," says Don Sink, dean of arts and sciences at Appalachian State University in Boone, an 11,000-student branch of the University of North Carolina system. "It's the only scholarship in the sciences at the school that's directed to women exclusively," says Sink. "It's also unique because of the company's initiative in coming to the schools. Usually we go begging," he says. "Glaxo has made some unusually heavy commitments in this program." While the stipend amount is less than many other scholarships at the university, "to students, $1,000 is a gold mine," says Sink. But what's more, the mentorship is a "thing that doesn't exist in most cases," he says. The only mentoring program the school has is an informal program between new and seasoned faculty, says Sink. The school felt its way through the first selection. Because a pharmaceutical firm was sponsoring the program, Sink asked for nominees from biology and chemistry department heads, and two students from the upper classes were chosen. Next year, however, the school will try to pick the best and brightest from the incoming freshman class so that they can follow the program for four years, says Sink. Such an incentive may also help the university recruit good students, he points out. Kimberly Curseen, 19, has a good idea of what she wants to be in life--an emergency room physician--but she also says she sometimes feels "strange" at her small school, North Carolina Wesleyan College, because "you just don't see women scientists there." That sense of isolation disappeared, however, after she spent several days at Glaxo, talking with her mentor, Nicole Valvano, a researcher in medicinal chemistry, and other women scientists. "Glaxo seems so alive and full of energy," Curseen says. "Although my mentor and I are in two different areas, she gave me a lot of confidence that I can go for a career in science. She opened my eyes to research." For her part, Valvano, 24, says that it's "good to get out and change the stereotype of scientists as men. I want to motivate women to keep on, and I'll be here for moral support and advice." Curseen is grateful. "Even if I never spoke to [Valvano] again," she says, "I saw someone that I could possibly be one day, and that's meant a lot." For more information about the program, contact John Thomas, Executive Director, Glaxo Foundation, 5 Moore Dr., Research Triangle Park, N.C. 27709; (919) 248-2488. Renee Twombly is a freelance writer based in Durham, N.C. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: PEOPLE ------------------------------------------------------------ TI : Two Alzheimer's Disease Researchers Are Awarded Met Life Foundation Prize AU : KAREN YOUNG KREEGER TY : PROFESSION (PEOPLE) PG : 23 Blas Frangione, a pathologist from New York University Medical Center and Allen Roses, a neurologist from Duke University Medical Center, Durham, N.C., were presented the Metropolitan Life Foundation Award for Medical Research on February 16 in Washington, D.C. Each received $200,000 toward his research and a $50,000 personal prize. Roses, chief of neurology and head of a research team at the Joseph and Kathleen Bryan Alzheimer's Disease Research Center at Duke, describes the award as critical to allowing his team's research to move forward. "The Met Life award basically gives us funds so that we can initiate a number of experiments that we would ordinarily have to wait months for grant applications to filter through the system [in order to have funding to conduct]," he says. Frangione, a professor of pathology and head of NYU's division of Alzheimer's disease research, hopes to increase the efficiency of his laboratory with his award. "With part of the money, I would like to update my equipment, which is almost 20 years old and requires a lot of material to run each month," he says. Frangione developed a method for extracting cerebral amyloid (Journal of Experimental Medicine, 158:623-8, 1983), a protein found in the brain that is thought to contribute to the degradation of brain cells in people with Alzheimer's disease, the fourth-leading cause of death among adults. More recently, Frangione identified a mutation of an apolipoprotein (APOE4) that is elevated in Alzheimer's patients, as a possible "pathological chaperone" (Neuroscience Letters, 135:235-8, 1992). In normal situations, these chaperones are "proteins that bind to other proteins and change the shape of the molecule in order for the molecule to perform its function," explains Frangione. However, he hypothesizes that APOE4 causes deleterious changes to amyloid protein molecules, thus possibly explaining some of Alzheimer's pathology. Roses studies late-onset Alz-heimer's disease using genetic techniques similar to those used in researching cystic fibrosis. As he explains, "sporadic-form patients [older patients without a family history of Alzheimer's] were not previously considered to have a genetic basis" to their disease. However, in 1992, using information from families with a history of Alzheimer's disease, Roses and his team found evidence that the gene associated with Alzheimer's disease coded for APOE4, in both familial and sporadic forms (Neurology, 43:1467-1472, 1993; Science, 261:921-3, 1993). Frangione explains that the research in his and Roses's laboratory is very important to the study of Alzheimer's disease because they combine "new ways of thinking to develop new approaches" for combating the disease. Their work may potentially lead to a therapeutic approach and, possibly, a predictive test for relative risk for Alzheimer's. Frangione received his M.D. from the University of Buenos Aires in 1953 and his Ph.D. from Cambridge University, United Kingdom, in 1969. Roses received his M.D. from the University of Pennsylvania in 1967. --Karen Young Kreeger ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: OBITUARY ------------------------------------------------------------ TI : HOWARD TEMIN TY : PROFESSION (OBITUARY) PG : 23 Howard Temin, a Nobel laureate and a professor of oncology at the University of Wisconsin, Madison, died on February 9 in Madison, Wis. Temin, who was well known for his lifelong campaign against cigarette smoking, died of adenocarcinoma, a type of lung cancer not usually related to smoking. He was 59 years old. Temin received the 1975 Nobel Prize in medicine or physiology, along with Renato Dulbecco, his Ph.D. adviser, and David Baltimore, for their work in understanding the role that viruses play in the onset of cancer. In the 1960s, he proposed, from his work with cancer-causing viruses that carry their genetic information in RNA instead of DNA, that these viruses could copy their RNA into an infected cell's DNA. This idea challenged the current theory that genetic information always passes from DNA to RNA. In 1971, Temin discovered reverse transcriptase, a viral enzyme that copies RNA into DNA. Reverse transcriptase was independently discovered by Baltimore. These and other contributions by Temin over the past 35 years have advanced the field of molecular biology, particularly in the technology that resulted from the discovery of reverse transcriptase. For example, this allowed researchers to find and identify the AIDS virus. Temin started work at the Mc-Ardle Laboratory for Cancer Research at UW-Madison in 1960 and continued there until his illness, which first manifested itself 17 months ago. He held the American Cancer Society Professorship of Viral Oncology and Cell Biology, the Harold P. Rusch Professorship of Cancer Research, and the Steenbock Professorship of Biological Sciences. In addition to the Nobel Prize, Temin had been awarded many honors for his lifetime work in unraveling the mechanisms of cancer. These included election to the National Academy of Sciences in 1974, foreign membership in the Royal Society of London in 1988, and the President's National Medal of Science in 1992. He was an author of more than 300 publications and served on numerous editorial boards and national and international advisory committees on cancer and AIDS research. Temin received his bachelor's degree from Swarthmore College in 1955 and his Ph.D. from the California Institute of Technology in 1959. ---------- 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. (The Scientist, Vol:8, #7, April 4, 1994) (Copyright, The Scientist, Inc.) ================================


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