Status: R THE SCIENTIST VOLUME 8, No:3 FEBRUARY 7, 1994 (Copyright, The Scientist, Inc.) A

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Status: R THE SCIENTIST VOLUME 8, No:3 FEBRUARY 7, 1994 (Copyright, The Scientist, Inc.) =============================================================== Articles published in THE SCIENTIST reflect the views of their authors and not the official views of the publication, its editorial staff, or its ownership. =============================================================== *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON *** *** FEBRUARY 21, 1994 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the United States: one year $58, two years $94 Canada : one year $82, two years $142 All other foreign : one year/air cargo $79, one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NEXT = next article ------------------------------------------------------------ TI : CONTENTS PG : 3 ============================================================ NEWS AIDS TASK FORCE: Proponents of the new National Task Force on AIDS Drug Development say that the panel may make a significant difference in advancing research and bringing forth new AIDS therapies. A key factor in its success, however, will be the composition of the task force, they say PG : 1 BIOTECH PROSPECTS FOR 1994: The most pressing problems facing the biotech industry this year are related, directly or indirectly, to a lack of financing. Fears associated with health-care reform and product setbacks have reduced public investment, and companies have responded by downsizing their research efforts, reducing or freezing their work forces, and merging with other companies PG : 1 BIOLOGICAL SURVEY: Environmental scientists as well as Secretary of the Interior Bruce Babbitt are hailing a National Research Council report on the new National Biological Survey. But it remains to be seen whether the report will appease critics of the agency PG : 1 ENVIRONMENTAL FOCUS AT ACS: A wide variety of issues will be discussed next month at the American Chemical Society's 207th meeting in San Diego, with environmental topics and the employment market for chemists garnering a good deal of attention PG : 3 SOCIETY, POLITICS, AND SCIENCE: The social and political contexts in which scientists work will be major themes of the 1994 annual meeting of the American Association for the Advancement of Science later this month in San Francisco. PG : 4 OPINION SCIENCE INTERNATIONAL: Jesse H. Ausubel, director of Rockefeller University's Program for the Human Environment, discusses the serious problems facing United States science as it approaches the year 2000. He considers the role the U.S. plays in the global science community, and urges creation of "international marketplaces," where researchers and policy officials can gather, exchange ideas, and, in general, conduct the increasingly complex business of science PG : 11 COMMENTARY: While the majority of Americans rank support of medical research as a top priority, the United States' governmental decision-makers are not giving it a high enough status on their agenda, a situation Research!America, an Alexandria, Va.-based research advocacy organization, is dedicated to changing in 1994, according to the group's president, Mary Woolley PG : 12 RESEARCH ECOLOGY RESEARCH LEADERS: Ecology research is attracting more attention among scientists worldwide, and while these researchers may not be as prolific as investigators in other disciplines, citation data indicate some clear leaders in the field, according to the newsletter Science Watch PG : 15 HOT PAPERS: A plant biologist discusses his paper on shade- avoidance reaction in the cucumber plant PG : 16 TOOLS & TECHNOLOGY SAFE, SENSITIVE IMPROVEMENT: Enzyme immunoassay use is escalating in the laboratory and the clinic, as more researchers are choosing these versatile detection methods as a more sensitive and safer improvement over the previously widely used radioimmunoassays and the hazardous wastes they generate PG : 17 PROFESSION GETTING PUBLISHED: Scientists may have little trouble getting their research before the proper journal publishers or agencies, but when it comes to trying to sell a popular science book to publishing houses, the services of a literary agent as a go-between are all but mandatory PG : 21 VLADIMIR A. EFIMOV, head of the Laboratory of Gene Engineering at the Shemyakin Institute of Bioorganic Chemistry in Moscow, is spending a year as a visiting scientist at Triplex Pharmaceutical Corp. in The Woodlands, Texas PG : 23 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 12 CROSSWORD PG : 13 ENZYME IMMUNOASSAY PRODUCTS DIRECTORY PG : 19 OBITUARIES PG : 23 (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Analysts Say Lack Of Cash Will Hamper Biotech Research As '94 Gets Under Way With projects on hold and downsizings, mergers, and acquisitions on rise, only firms with products in clinical trials can progress AU : SUSAN L-J DICKINSON TY : NEWS PG : 1 Among the myriad issues confronting the biotech industry in 1994, the most pressing problem companies will face is a lack of adequate financing, say industry observers. Fueled by concerns over potential drug-pricing controls related to national health care reform and two highly publicized biotech product failures, public financing has plummeted, they say, while many firms are running out of reserve capital. The New York-based accounting firm Ernst & Young reported late last year that public financing of biotechs fell by two-thirds, from $3.2 billion for the year ending June 1992 to $1.1 billion for the year ending June 1993. Meanwhile, 58 percent of public biotechs have less than two years' worth of cash reserves on hand. The lack of capital is having a major impact on science at these firms, according to company officials, industry analysts, and researchers interviewed by The Scientist. Research projects are being put on hold; many companies are downsizing, and still more face the likely prospect of merging with or being acquired by another company in the near future. "The CEOs [of biotech companies] have some painful stories," says Carl Feldbaum, president of the Washington, D.C.-based Biotechnology Industry Organization (BIO). R.D. McLauchlan, president and CEO of West Conshohocken, Pa.-based U.S. Bioscience Inc., says that the tight capital market has forced his company to restrict projects investigating their anti-cancer compounds' potential efficacy in AIDS. It's a trend, he says, that he is witnessing throughout the industry. Biotech companies "are no longer pursuing interesting sidelines, and at the first hint of a problem [with a compound] they are shelving the project," he says. "And once you make the admission that projects are being cut back, it's obvious that, somewhere along the line, a scientist is not working as a result." How much uncertainty faces biotech scientists depends, to a great extent, on the bench at which they toil, industry analysts say. Those at the 10 or so "top-tier" biotech firms enjoy the same relative security as someone employed by a large pharmaceutical concern. Companies like Amgen Inc. of Thousand Oaks, Calif., or Genentech Inc. in South San Francisco, Calif., which are relatively large and have revenue-generating products already on the market, are considered "known" entities on Wall Street. They can access cash through public financing on an as-needed basis, regardless of investor interest in biotech stocks. Burning Cash But the majority of companies are more vulnerable to fluctuations in the stock market, and these firms are burning cash faster than ever, analysts warn. In fact, according to Ernst & Young, the net burn rate--the amount of cash being expended vs. the amount of cash revenue--for public companies last year averaged $2.1 billion, up by $400 million from 1992. According to industry observers, two general factors are expected to have a strong impact on the amount of money public investors put into biotech this year. The first, a positive one, is the recent approval of two new products: Pulmonase from Genentech, which treats cystic fibrosis; and Emeryville, Calif.-based Chiron Corp.'s BetaSeron, used against multiple sclerosis. Both of these therapeutics address clinical conditions for which there has been no treatment, and industry analysts are hopeful that their successful approval and early sales will stimulate the entire sector, just as the failure of two well-publicized products--Malvern, Pa.-based Centocor Inc.'s Centoxin and Boulder, Colo.-based Synergen Inc.'s Antril--to win government approval acted to depress stock prices across the industry a year ago. An even larger factor, one that continues to dampen investor confidence in the biotech sector, according to analysts and company officials, is the drug-pricing control mechanisms proposed in President Clinton's health plan. Two proposals-- the formation of a breakthrough drug advisory committee, which would review introductory prices for cures and treatments for AIDS and other diseases, and a plan to give the Secretary of Health and Human Services the power to exempt new drugs for AIDS and other diseases from Medicare reimbursement--have investors shying away from the biotech market. In fact, a recent survey of 30 companies involved in AIDS research conducted by BIO found that 40 percent of them cited the president's proposal as the cause of the industry- wide shortage of working capital, and almost 47 percent of those companies said that AIDS and AIDS-related research was being delayed or curtailed as a result. "If such price controls become a reality, the capital markets for the industry will be frozen," predicts Nick V. Arvanitidis, chairman and CEO of Liposome Technology Inc. in Menlo Park, Calif. Feldbaum reports that BIO and its member companies are lobbying hard in Washington to have such controls removed or at least ameliorated before the final version of the health plan is hammered out. `Tougher Questions' In the meantime, whether biotechs will be able to raise the money they need over the coming year will depend to an ever- increasing extent on their ability to offer solid proof that their technology's promise can--and will soon--become reality, analysts say. "Investors are asking tougher questions about timeliness and milestones and expectations," observes Michael Hildreth, a partner in Ernst & Young's life science practice. Michael Celano, Arthur Andersen & Co.'s partner in charge of the Philadelphia office of life sciences, agrees, and predicts that in order to complete an initial public offering in 1994, a company will need to have solid, preferably later-stage clinical trial results in hand, as well as validation from a larger drug company in the form of financial support or scientific collaborations. "The less substantive, `touch-and-feel' type of facts that a company can present, the harder a time it is going to have getting financing," Hildreth concurs. The good news coming from the financial sector, analysts say, is that, based on a spate of offerings beginning last fall, the public market does appear to be interested in investing in biotech companies again. "There was some momentum gaining toward the end of the year," says Hildreth, who points out that through November and early December there were five or six initial public offerings and about 10 follow-on public offerings completed by biotechnology companies. But the financing that is taking place is bringing in less money for the companies than in years past. "The financing may be becoming available, but at what price?" asks Feldbaum. "If you look behind the deals made in late 1993; I think you will find that the companies had to give a greater percentage of their equity away." "Valuations [of companies] are down significantly in a continuing trend since 1991," concurs Hildreth. He reports that in 1991 the average valuation of newly public companies--a measurement based on the value of a share of stock times the number of outstanding shares--was approximately $105 million, a number that dropped to $85 million in 1992, and to $70-$75 million last year. "That's a reality check," he says, reflecting a view expressed by many biotech analysts: that stock prices were highly overinflated in 1991 and early 1992. Downsizings And Mergers A market correction on Wall Street translates into real financial pain for many companies and scientists in the biotech sector, observers say. Feldbaum reports that the current cash shortage is weighing heavily on the minds of industry CEOs he talks to. "They are really trying to spread their cash thinner," he observes. "They are being much less aggressive about hiring, and in some cases laying people off. Whereas in April or March [of last year] someone would tell me that they had seven or eight lines of research going, now they report their board of directors say they have to concentrate on just three of those." "I see companies downsizing," confirms Frank Martin, vice president of science at Liposome Technology Inc. of Menlo Park, Calif. He stresses that, with two products in phase III clinical trials, he foresees no immediate problems for his own company, but he knows that other companies are under financial pressure, and he is sympathetic. "We've had two downsizings in our history, and it's unpleasant," Martin says. "The most damaging thing for the scientists is how it can impact the mood in the company." He recalls a point at which Liposome Technology stock dipped to $2 per share; the scientists were depressed and unmotivated, and the mood was reflected even in the fact that the company parking lot emptied out early. Now, as Liposome gets closer to having a marketable product, he says, the scientists' morale is up: "It creates a momentum you can ride," he observes. But he also is aware that, as is true of any young company trying to develop new technology, there are undoubtedly more trials somewhere in his firm's future. "Scientists aren't stupid, and anyone can read a balance sheet. If your company is burning cash at a high rate and it doesn't have a lot of cash on hand, something is going to happen," he says. "You also need to keep in mind that these are small companies. Visitors are highly visible, so scientists know when you are trying to sell off parts of a company or technology." Martin declines to name specific companies that are feeling the pinch financially, but says it is going on all around him. "I think there is no question that there is going to be a shakeout in the industry," he says. A "shakeout," or industry-wide consolidation through mergers, acquisitions, and company failures, has been predicted by biotech analysts for the past few years. The expectation results from the fact that there are some 1,200 biotech companies and estimates on the cost of developing a single biotech drug range from $125 million to $400 million. "There isn't anywhere near enough financing to see all of these companies through to successful delivery of products to the marketplace," says Hildreth. "1994 will be the year of the merger," Celano says, a prediction he expects may bring setbacks for individual products and companies but may result in a positive move for the industry as a whole. "In two or three years," he says, "there will probably be the same number of public companies, but about two times the number of employees in the industry." And while scientists employed in the biotech industry may welcome his long-term prediction, there is certainly a feeling of uneasiness about the interim, "shakeout" phase, observers say. "A merger or acquisition is perhaps even worse than running out of money," says Martin, whose company, Liposome, spent six months putting together a merger deal that eventually fell through. He uses the words "disaster" and "nightmare" to describe the process. "If your company goes under, it's like bleeding to death; you can see the end coming," Martin says. "But a merger or acquisition is sudden and rife with unknowns." The biggest of these, he says, is the fear of losing one's job or having to relocate. New Strategies But some industry watchers note that biotech firms are developing new financing and business strategies that may ameliorate these concerns at the lab bench. One such trend, observed over the past two years, is that biotech executives are becoming increasingly creative when it comes to devising new ways to finance their operations. Another factor that has kept many of the companies from merging thus far is that they are working with a new business model, one that calls for virtual, rather then vertical, integration. Rather than try to develop a large, self-sufficient corporation that does everything from discovery through manufacturing, sales, and marketing, companies are increasingly content to aim for being highly specialized, niche players. "They are looking at what they do best and trying to leverage those strengths," Hildreth says. As an example, he points to a group of companies that are developing gene- sequencing technologies. "Only one-fourth of these companies has an expressed objective of being a fully integrated corporation," he says. "The other three are envisioning a business that licenses their knowledge to drug companies that will develop the products for commercial sale. This is a much different business model that reduces capital need and probably gives those companies a longer horizon for survival." Equally interesting for scientists at these firms, perhaps, is Hildreth's prediction that "smaller companies focused on a particular skill will be better able to replicate an academic environment, one which a lot of company founders and key scientists are familiar with and in which science moves along more quickly." But for the science to move at all, there needs to be cash, and that is the most immediate concern expressed by CEOs and bench scientists alike. "Our bench scientists are coming up with additional antibodies that are as promising, if not more so, than our lead compound, but we don't have the money to follow up on them," says Herbert Loveless, vice president for clinical development at Houston-based Tanox Biosystems. "We may have good preclinical and phase I data [on a compound], but we can't pursue these projects into the clinic. The lack of capital is creating a dam, and it's very frustrating." Susan L-J Dickinson is a freelance writer based in Philadelphia. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : National AIDS Task Force Expected To Accelerate Drug Development Bench scientists will play a major role in an ambitious effort to streamline the campaign against HIV AU : FRANKLIN HOKE TY : NEWS PG : 1 The soon-to-be-appointed National Task Force on AIDS Drug Development may have a strong, positive impact on the research and development of antiviral therapies to counter HIV infection, say industry and academic scientists, government officials organizing the task force, and members of the AIDS-affected community. Key to the task force's effectiveness, however, will be the personnel selected by Secretary of Health and Human Services, Donna Shalala, probably in early February, to serve on it, these sources say. "People's views run the gamut from cynical to optimistic," says activist Derek Hodel with the AIDS Action Council in Washington, D.C. "Those of us who are optimistic hope that the task force will be effective at its charter in identifying barriers to research and to drug development, of which there are many. If it's well-appointed and well- staffed, it's quite likely that it could have a major impact." If the task force is able to begin dismantling these development barriers, laboratory scientists pursuing AIDS therapies and vaccines--in industry and academia--may find themselves part of a more coordinated approach, overall, to conquering the disease, sources say. This new approach may include better access to screening and trial information, more standardization of data from those sources, and improved laboratory services from the government. The formation of the 15-member task force was announced at a November 30 news conference by Shalala, with HHS assistant secretary of health Philip R. Lee named as head. Underscoring the importance placed on the new group, Shalala was accompanied at the announcement by Harold Varmus, National Institutes of Health director; David Kessler, Food and Drug Administration commissioner; Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases; P. Roy Vagelos, chairman and chief executive officer of Merck & Co. Inc., Whitehorse Station, N.J.; Moises Agosto, National Minority AIDS Council; and White House AIDS policy coordinator Kristine Gebbie. A 30-day period of public nominations followed in which about 200 individuals were suggested for membership on the panel. During January, an internal planning group of about 30 representatives from various government groups responsible for combating AIDS worked to select a task force with balanced representation from the constituent groups: industry, academia, government, and AIDS patient advocates. The planning group's suggestions were to be forwarded to Shalala for her approval early this month. The task force's specific goals will be defined by the group itself at initial meetings, expected in March. But, broadly, the group's charter is clear. "They're being asked to look at the entire spectrum of AIDS drug development, everything from product screening through clinical trial issues, and even regulatory issues," says Randolph F. Wykoff, associate commissioner for AIDS and special health issues at FDA. Wykoff's office has been responsible for coordinating the nominations and staffing process. "They're going to be asked a fairly simple question," Wykoff adds. "Are there any roadblocks that currently exist that are prohibiting or delaying the rapid development of drugs for HIV and HIV-related disease? Or, are there creative new alternatives that should be tried, given that we're now 12 years into it and don't have curative agents?" Many in the AIDS-affected community are supportive of the new task force in concept, but are reserving judgment until the panel is named and begins work, according to Greg Gonsalves, a member of Treatment Action Group (TAG), an AIDS activist organization in New York. Gonsalves is a coauthor of the report, AIDS Research at the NIH: A Critical Review (Amsterdam, the Netherlands, TAG, 1992), that found the AIDS research effort at NIH to be uncoordinated and lacking in leadership. Sen. Edward Kennedy (D-Mass.) and others cited the report's analysis in moving to strengthen the Office of AIDS Research at NIH under the NIH Revitalization Act of 1993. "Everything is not expedited in AIDS research," says Gonsalves. "Maybe this committee can help speed things up and improve some weaknesses in the clinical development effort. But we're waiting to see who's going to be on it, because that's going to drive the task force." The Task At Hand At the news conference, Shalala noted that government funding for AIDS research continues to climb, with NIH, for example, receiving $1.3 billion this year for research on AIDS, a 21 percent increase over last year's figure. And only a few days after Shalala's announcement, the Pharmaceutical Manufacturers Association in Washington, D.C., released a survey of its members show- ing more than 100 AIDS-related drugs in development; other estimates suggest as many as 500 such drugs may be in testing in industry. "But the sad fact remains that not a single New Drug Application for an antiretroviral drug is currently before the FDA," Shalala said. An antiretroviral drug, in this context, would be one that successfully attacks HIV. There are only three antiviral drugs on the market today to fight HIV infection: AZT from Burroughs Wellcome Co., Research Triangle Park, N.C.; ddI from Bristol-Myers Squibb Co., New York; and ddC from Hoffmann-La Roche Inc., Nutley, N.J. Each of the three is limited in its effectiveness, partly because of HIV's ability to quickly mutate and acquire drug resistance. "Unfortunately, none of the drugs we have today are curative," Lee said at the conference. Since the news conference, on January 5, Bristol-Myers Squibb Co. announced that it had filed a New Drug Application for an antiviral, anti-AIDS compound called d4T, although it, too, is not a curative therapy. "The three drugs currently approved are all nucleoside antiretrovirals, in that they go after reverse transcriptase, which is the enzyme the virus needs to grow," says Susan Yarin, a company spokeswoman. "d4T is also among that class of drugs." The effort being expended nationally and internationally to find a cure for AIDS is enormous, scientists and government officials agree. If the task force can raise the level of information sharing among those involved in AIDS drug discovery and development, AIDS investigators say, it will serve an important purpose. "Certainly, to facilitate communication among investigators as well as among drug companies would be a big help," says Flossie Wong-Staal, Florence Riford Professor in AIDS Research at the University of California, San Diego. "At the same time, if the FDA can simplify the regulatory process, that would make it easier for a potential therapy to reach the clinic." Wong-Staal, whose laboratory is working to develop both therapies and vaccines for HIV infection, adds: "Drug discovery is a challenge, but translating a discovery to the clinic is an even greater challenge." An Industry Model At Shalala's November 30 news conference, only one person was named to the task force: the man who will head the group, Philip Lee. But most observers will be surprised if Edward Scolnick, the president of Merck & Co.'s Merck Sharp & Dohme Research Laboratories, is not also selected. Scolnick spearheaded an unprecedented cooperative effort among 15 of the largest pharmaceutical companies that is, at least partly, the model for the national task force. Scolnick currently heads the group, formed last April and called the Inter-Company Collaboration for AIDS Drug Development. Under the terms of the collaboration, company scientists have met to share information on compounds under development, at least through the early human effectiveness phases of investigation. Companies are also sharing drug supplies and discussing ways they might standardize the testing of isolates and compounds, so that data can more easily be compared. The national task force may be able to offer similar kinds of help to AIDS researchers, says FDA's Wykoff. "I don't want to sound like I know where the task force is going, because I don't," Wykoff says. "But there might be a way that a researcher in the field can find out everything that's been done with a given product through a variety of screens. There might also be some sort of standardization process, where every potential candidate [drug] would go through a pattern of four or five different screens. Perhaps folks in the field would be able to send in samples to the government for that screening. The idea is that there could be a greater reservoir of information available to the researchers and a greater amount of government service available to them." One hopeful area of cooperation for the industry collaboration centers on combination therapies, that is, using simultaneously administered batteries of drugs under development--presumably at different companies--to circumvent HIV's adap- tive capabilities. The industry task force effort, as a whole, is expected to streamline AIDS drug development and lessen redundant efforts. "If you have all the scientists in one room who are involved with the different compounds," says Gail Levinson, a spokeswoman for Hoffmann-La Roche, "it can have an impact on whether you continue to develop [a given compound], develop it in conjunction with another compound, or, perhaps, make a decision to terminate it completely." At least one Inter-Company Collaboration member has recently decided to leave AIDS drug discovery research to others in the future. Indianapolis-based Eli Lilly & Co. announced last month that, while it would continue research in some AIDS syndrome areas, such as the bacterial and fungal infections that afflict people with AIDS, it would no longer pursue new AIDS antivirals. Lilly currently has one promising antiviral compound, LY300046, that it hopes to continue developing with the help of a collaborator, according to spokesman Fritz Frommeyer. Partly for this reason, the firm intends to remain part of the industry collaboration group for the foreseeable future. Following its meetings, the industry group has met with members of the AIDS-affected community to share information with them, as well, according to Jennifer Mc-Millan, a spokeswoman for Glaxo Inc., Research Triangle Park, N.C. The national task force, while including industry representatives, is not expected to duplicate the efforts of the Inter-Company Collaboration. "Industry, by itself, has somewhat different priorities than the whole task force will have," says David Barry, senior vice president of research, development, and medical affairs at Burroughs Wellcome Co. "The industry task force is extremely focused on drugs that have gone through Phase II and the issues surrounding combination drug therapy trials. The national task force, which will have government people and activists, as well as industrial people, will be looking at a broader range of issues, including drugs to treat opportunistic infections, regulatory hurdles, preclinical requirements, and the like." Data concerning new drug development are often among the most closely guarded information at pharmaceutical companies. While there are no plans to share results at the discovery research level, the fact that the companies have agreed to share valuable screening and development data is a reflection, perhaps, of the frustration level among AIDS researchers. "We entered AIDS research in 1986," says John Doorley, a spokesman for Merck. "We're the world's largest drug company, and this is the largest discovery research project we have ever had. "Last year, we spent $1.2 billion on research, and AIDS was our biggest research project. And, like the rest of the world, we have failed repeatedly." (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : THE MINORITY VIEW AU : FRANKLIN HOKE TY : NEWS PG : 7 At least one researcher does not believe that the new National Task Force on AIDS Drug Development will be able to speed the development of cures for the disease. And he does not believe that it will be bureaucratic sloth that confounds the task force. Nor will it be because HIV, the virus thought to be responsible for AIDS, changes and mutates beyond the reach of scientists, he predicts. The task force will fail, says Peter Duesberg, a professor of molecular and cell biology at the University of California, Berkeley, because HIV is not the cause of AIDS. "Would it help to pour in ten more billions of dollars to send a man to the moon if there is no moon?" asks Duesberg. "Money and the task force and more input help if you know the enemy. But--if you ask me--we have not identified the cause of AIDS, and you can't get good public health on the basis of bad science." Very few other investigators agree with Duesberg's notion that the scientific world has come too soon to consensus on the hypothesis that HIV is the cause of AIDS. Even fewer accept his alternative explanation for AIDS, that recreational drug use is responsible. But Duesberg insists that HIV cannot be the cause of AIDS, because it is not present in a high enough proportion of the T cells of people with AIDS to account for the disease. "A virus that doesn't infect more than one in a thousand T cells can hardly be responsible for the loss of those cells," he says. "Viruses are obligatory intracellular parasites. They can't work from a distance. They can't sit on a couch and send a message to a distant cell: `Please die.' A virus is a piece of chemistry that can only kill or affect a cell by entering it. If it's not in the cell, nothing's going to happen. Now, there are not enough HIV viruses around [in the body] to explain AIDS....So, HIV is a totally inadequate explanation for one of the hallmarks of AIDS, which is immunodeficiency." Duesberg says he has paid dearly for his out-of-the- mainstream views on AIDS. It is his opinion that the lack of peer approval for his ideas cost him his National Institutes of Health funding. He also feels that his experimental science has been effectively stifled as a result, because he cannot adequately support a laboratory and students financially. "I've sacrificed my whole damned career for this thing now," he says, "and I still think I'm trying to contribute something to--not hurt--American science." The reason AIDS researchers everywhere have been frustrated over 12 years of intense efforts, Duesberg says, is that the hypothesis that HIV causes AIDS is simply wrong. "No matter how hard you hit the virus," Duesberg says, "if it is not responsible for AIDS, no matter how big and how smart the task force, you won't get anywhere." --F.H. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Observers Laud Research Council Report On Scheme To Restructure Science At U.S. Interior Department AU : KAREN YOUNG KREEGER TY : NEWS PG : 1 Environmental scientists are joining with Secretary of the Interior Bruce Babbitt in hailing a National Research Council (NRC) report that contains guidance on how to structure a new Department of the Interior (DOI) agency. The researchers say that suggestions outlined in the report provide a solid base for designing the direction the agency should take. The new agency, the National Biological Survey (NBS), composed of personnel formerly from seven existing DOI agencies, is the first federal agency devoted solely to inventorying and monitoring United States biological resources. However, it remains to be seen whether the report and operations at NBS in the next year will completely allay the concerns of critics. Before A Biological Survey for the Nation, the independent report by NRC's Committee on the Formation of the National Biological Survey, came out in late September, they questioned the wisdom of creating the survey (R. Kaufman, The Scientist, Sept. 20, 1993, page 3), saying it would not be an improvement over existing schemes. The critics were primarily concerned that the reorganization would cause inefficiency and weakening of operations at the newly created NBS and existing DOI agencies, a decoupling of basic information from resource managers, and a possible de- emphasis on state and regional issues in favor of a more national agenda. At least one observer, Arnett C. Mace, Jr., dean of the Daniel B. Warnell School of Forest Resources at the University of Georgia in Athens, says he finds the NRC report favorable overall, yet will maintain a wait-and-see attitude about how operations at NBS will sort out the sometimes different research priorities at local and national levels. "Overall, I'm satisfied with the report, is certainly premature at this time to determine what the total impact of the NBS is going to be on state, regional, and national objectives," says Mace. He says that the report has addressed his concerns, but "the question is, will those [suggestions] be implemented" by the NBS staff. On the other hand, Babbitt, in the preface to the NRC report, compared the importance of the creation of NBS to that of the U.S. Geological Survey: "Just as the U.S. Geological Survey gave us an understanding of America's geography in 1879, the National Biological Survey will unlock information about how we protect ecosystems and plan for the future." In February 1993, Babbitt turned to NRC, an arm of the National Academy of Sciences, to prepare the report, which suggests a path for NBS to follow in gathering and communicating the scientific information needed to effectively manage U.S. biological resources. Many NBS staffers feel that the NRC report, which was published after NBS became a functioning federal bureau, is fully consistent with their goals and objectives. "It's an easy one for us to deal with and implement because we're very much in agreement with the major findings," says F. Eugene Hester, deputy director of NBS and former chief of research for the U.S. Fish and Wildlife Service (FWS). The NRC report, which addressed the broader scope and direction of NBS, not its day-to-day ac- tivities, contains the following suggestions for the biological survey: * Creating the National Partnership for Biological Survey--a consortium of federal, state, and local agencies; museums; academic institu- tions; and private organizations to share and provide information for decision-makers and users. * Creating the National Biotic Resources Information System, a database of reliable biological information. * Structuring a research agenda that is broader than currently exists and that focuses on immediate and long-term needs of NBS data users. * Guiding the development of NBS by a single strategic implementation plan, under the leadership of DOI. Victoria Tschinkel, a senior consultant for environmental affairs at the environmental law firm Landers and Parsons in Tallahassee, Fla., and a report author, explains that much attention was paid to integrating the needs of resource managers at all levels when the concepts laid out in the report were developed. "To be useful, the NBS, even though it has the word `national' in its name, has to be extremely responsive to the needs of [state and local] people making decisions [about land- and water-based resources]," says Tschinkel. Although the report does not specifically address the concerns of some critics that the reorganization will cause inefficiency and disruption in routine operations within DOI, report authors and independent observers agree that there are many benefits in having a coordinated survey under one roof. The "value of the survey is that it provides information for us as a country and certainly to federal agencies to make decisions that anticipate issues and problems, rather than trying to react to problems once they occur," says Paul Risser, president of Miami University in Oxford, Ohio, and another report author. He cautions that DOI should also "retain efficient expertise in each of the departments" from which NBS staff members have been drawn. As stated in DOI's justification to Congress to approve funds for NBS in 1994, the mission of NBS is "to gather, analyze, and disseminate the information necessary for the wise stewardship of our Nation's natural resources, and to foster an understanding of our biological systems and the benefits they provide to society." The proposed partnership and the information system will be set up to accomplish this. Hester describes the tasks ahead for NBS as addressing five interrelated questions that the report also mentions: who has which data, what format are the data in, how accessible are the data, how can the data be aggregated (such as in a geographical information system), and what are the research gaps. Hester responds to criticism that the reorganization will cause inefficiency by noting the partnership concept suggested in the NRC report: "One of the advantages of having inherited resources from the [DOI] bureaus is that these bureaus have different strategies" for collecting information about biological resources and that NBS can "look across that and pick [strategies] from several bureaus that work well." According to other NBS staffers, they have already incorporated some of the concepts in the NRC report into their strategic plan, such as the partnership. Overall, they view the NRC report as a blueprint for how to make NBS a clearinghouse of information for decision-makers. Suzanne Mayer, acting assistant director for research at NBS, a wildlife management expert, and past deputy regional director at FWS, says that NBS will facilitate the bringing together of information from disparate sources: "In some cases, there are areas of the country where research has been going on by all different sorts of entities . . . and it's all scattered and dispersed." NBS And Environmental Science Even though NBS is working with an almost 15 percent increase in its budget for 1994--$163 million, compared with $141 million reappropriated from existing DOI agencies in 1993--a comparable increase in hiring is not expected to follow in the near future. However, no jobs have been lost in DOI as a result of the reorganization. Mayer adds that "had the research programs remained in the separate bureaus there probably would not have been [separate] comparable increases." She also does not foresee NBS as ever being a big contract-awarding agency like the National Science Foundation. However, in the future, when research gaps have been identified, NBS staffers agree that there will probably be collaborative contracts. Michael Ruggiero, acting chief of the inventory and monitoring divisions of NBS, thinks that the creation of the agency will encourage a greater recognition of contributions by the inventory and monitoring area of biological sciences. For example, he says, groups with large datasets--museums with taxonomic databases, for example--that do not now have a clear outlet to disseminate their work to potential users could contribute to their field and others by lending their data to the database NBS will create. He also hopes NBS will develop into an agency that produces credible standards for inventorying and monitoring biological resources, much as the Environmental Protection Agency has done with water- and air-quality standards. Jane Lubchenco, a marine ecologist with the department of zoology at Oregon State University in Corvallis, feels that the move to create a nationwide biological database is long overdue. Ecologists and others would "benefit tremendously by having an accurate database that would not only inventory what's there, but allow people to see trends and to evaluate the status of different groups--be they species or higher levels of taxonomic groupings or whole ecosystems," says Lubchen-co. However, she also points to the challenging task of making sure that the science that bolsters management decisions stays in close contact with decision-makers. Mayer explains that "some synergism [in information sharing] will occur because of the consolidation: There is research that takes place on national parks, Bureau of Land Management lands, and FWS refuge lands that are applicable to all three [agencies], but may be only going on one." This information can be shared, she says, and NBS is seen as the facilitating agency to make this happen. Although this does occur now, the technical capabilities NBS will develop will make information sharing easier and more accessible, and, as Mayer puts it, "we will get a bigger bang for the buck." NBS has a full plate for 1994. In addition to dealing with the administrative details a massive bureaucratic reorganization entails and incorporating the NRC report's recommendations into a strategic plan, the NBS staff is currently involved in identifying likely customers and gauging workable boundaries for their diverse information needs. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Environment And Biotechnology To Be Big Draws At ACS AU : NEERAJA SANKARAN TY : NEWS PG : 3 Fuel, silk, sunscreens, clean air, law, and the job market are just a smattering of the wide variety of topics on the agenda at the 207th meeting of the American Chemical Society (ACS). The national spring meeting, scheduled to run from March 13 to 17 in San Diego, will offer its 11,000-plus attendees more than 5,700 papers over 625 technical sessions sponsored by various divisions of the society. "Some of the `hot button' items have to do with environmental issues," says ACS president Ned Heindel, a professor of pharmaceutical chemistry at Lehigh University, Bethlehem, Pa. "One symposium titled `Benign by Design' has to do with retooling industrial processes chemically, so as to make the byproducts less polluting and more `green.' "There will also be a session on oxygenates--gasoline additives [added to reduce lead] that have come under a lot of fire lately because of their believed health hazards." Scheduled at the conference is a presentation dealing with the health implications of oxygenates and a discussion of some recent data from the Environmental Protection Agency that report insufficient evidence to support claims of any health risk. Given the uncertain climate surrounding the job market for chemists (B. Spector, The Scientist, Nov. 15, 1993, page 1), professional development and employment will receive a lot of attention this year. "There is a bevy of activities for chemists searching for jobs," says Heindel. "The job market is quite obviously sour now, but I see very little difficulty in placing people with environmental and analytical backgrounds and people in process research. "There is an increased amount of temporary and contract employment, particularly by the larger companies like Merck and Kodak," says Heindel, referring to Rahway, N.J.-based Merck & Co. Inc., and Eastman Kodak Co. of Rochester N.Y., which were major employers of chemists in the past. "One bright spot in the employment scene are the start-up companies," he adds. "We at ACS are trying to identify the high-tech firms with less than 30 employees and make them aware of the employment services we have to offer." The employment services include a clearinghouse of names of professional chemists and a job database for ACS members. Another subject to receive extensive coverage at the 1994 conference is biotechnology, the focus of about 175 papers in 28 different symposia sponsored by the biotechnology secretariat. An ACS secretariat is a group of symposia encompassing talks from several different divisions that pertain to some common thematic material. Polymer chemistry, the law, biosensors, and the environment are just a sample of the topics that will be covered in the symposia of the biotechnology secretariat. "The theme is the industrial applications of biotechnology," says Charles G. Gebelein, one of the chairmen of the biotechnology secretariat this year and an adjunct professor at Florida Atlantic University in Boca Raton. "Based on past performances, I expect that the session on legal aspects will be a big one," predicts Gebelein, who also holds an emeritus professorship at Youngstown State University in Ohio. Patrick Turley, cochairman and moderator for the symposium titled "Legal and Regulatory Issues in Biotechnology," explains that the popularity of this session is due to the growth of the biotechnology industry. "With so many cutbacks, people are increasingly looking to their intellectual property as a primary source of funding. They are thus interested in issues such as patents, for example," says Turley, a patent attorney with the Houston- based law firm of Baker and Botts. "Also, biotechnology has moved from the realm of basic research into that of actual products, which raises interest in FDA licensing," another topic to be covered in the day-long session (see story on page 8). "Personally, I would like to see more people at the sessions on biotechnological polymers," says Gebelein, whose area of expertise is polymer chemistry. "There is a tremendous amount of good information about the uses of proteins from rather unusual sources--spider silks, for example. Another intriguing one is melanin, whose polymers are being used in sunscreening agents to protect against the sun's radiation." One of the presentations at this session will be by Joseph Cappello, director of polymer research at Protein Polymer Technologies Inc., a biotechnology company in San Diego. Cappello will be talking about the potential uses of a synthetic polymer being developed by his company that contains blocks of commercial silk in its structure. "Silk is a very robust protein, and the addition of these blocks gives our protein high strength and the ability to withstand very high temperatures of 180 to 200 degrees [Celsius]," he explains. He anticipates that the synthetic polymers will have applications in surgical repair, particularly in cases of abdominal and gynecological surgery. Ideally, surgical material would prevent tissues from sticking to one another during the healing process, but disappear eventually. Currently used materials do not disappear and can thus cause other complications in the body. "We are trying to produce a resorbable material that will last for a predetermined time in the body," says Cappello. The symposium on industrially important biotechnological polymers is scheduled to run over two days, Tuesday, March 15 and Wednesday, March 16. Complete details on all the technical sessions, expositions, and workshops are published in the February 7 issue of Chemical and Engineering News. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Policy Aspects Of Science Dominate 1994 AAAS Meeting AU : FRANKLIN HOKE TY : NEWS PG : 4 "Science and a Changing World" is the theme of the 1994 annual meeting of the American Association for the Advancement of Science (AAAS), to be held February 18-23 in San Francisco. The choice of theme extends a trend established in recent years of focusing prominent symposia on the social and political contexts in which scientists work. Career development meetings are also scheduled, and ongoing efforts to reform science education will be reviewed. Sessions discussing advances in traditional science areas will be offered, including seminars on mapping and modeling the brain, evolution and extinction, and the extracellular regulation of cell behavior. About 5,000 scientists are expected to attend 130 sessions with nearly 800 speakers at the San Francisco Hilton and Towers at this year's AAAS meeting, the 160th such gathering. "We came to the theme--science in a changing world--because of the readjustments that we as a nation are going through now," says Eloise E. Clark, program chairwoman for the meeting and vice president for academic affairs at Bowling Green State University in Ohio. Among these readjustments, she says, are national policy changes in science support and financial problems confronting the universities, which represent much of the foundational support for science. As a reflection of the meeting's emphasis on science policy, Clark says, the keynote address will be given by John Gibbons, presidential science adviser and director of the Office of Science and Technology Policy. Gibbons's address is entitled "Science, Technology, and the Clinton Administration." Also, Rep. George E. Brown, Jr. (D-Calif.), chairman of the House Committee on Science, Space, and Technology, may speak at the meeting, according to Clark. Chang-Lin Tien, cochairman of the program committee and chancellor of the University of California, Berkeley, concurs that changes in society, domestically and internationally, will affect the way science operates. "With the new administration and post-Cold War adjustments," Tien says, "I hope this meeting will have a good exchange of information, providing a basis for decisions in the coming decade." Post-Cold War changes in the world will be addressed specifically in a symposium called "Regional and International Security and Defense Conversion." Several speakers will discuss the conversion of nuclear arms laboratories to other purposes, in the former Soviet Union as well as in the U.S. Symposia topics that will address social questions include "Health Care Reform and Advances in Medicine," "Industry, Policy, and the Changing Infrastructure of Science," and "Science, Ethics, and the Law." Health care is, perhaps, one of the strongest examples of an area in which social policy and science are likely to interact dynamically, both Clark and Tien agree. Clinton administration officials are focusing on cost-cutting and restructuring in health care, including a stronger emphasis on preventive measures. Several sessions at the AAAS meeting will discuss these and related issues. One session of the "Health Care Reform and Advances in Medicine" symposium, for example, is entitled "Increasing the Healthy Life Span: Advances in Health and Aging," and will include a talk on health-status assessment and preventive interventions. One seminar, "Eating and Health," will include a session on nutrition and disease prevention. Nobel Prize-winning geneticist Harold Varmus, now director of the National Institutes of Health, will participate in the meeting. His presentation will be part of the seminar "Half the Secret of Life Is Outside the Cell," a full-day session cosponsored by the American Society for Cell Biology and aimed at undergraduate life sciences majors and graduate students. The seminar will focus on understanding how extracellular cues regulate cell behavior, with emphasis on development, the nervous system, and cancer. An employment exchange, through which those seeking or offering research work can register, will also be offered. Individuals who are AAAS members may register for free, while nonmembers will be asked to pay a $10 fee. On-site interviews will be conducted. In addition, a career development seminar called "Changing Scientific Careers" organized by Catherine Didion, executive director of the Association for Women in Science, will include a session exploring alternative careers that may be open to those with science degrees and research training. Potential new career tracks will be the focus of several talks, including "Scientists as Consultants," "Environmental Law," and "Science, Women, and Technical Trades." Science journalism as a job option also will be discussed. One symposium, "Communicating Science," includes a likely- to-be-jammed session called "The Science of Star Trek: Bringing Science to a Different Public." The aim is to look into how science is treated in science fiction, using the popular television show as a example. The session will also suggest ways that the show might be used as an informal science learning tool. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : AT A GLANCE 1994 AAAS MEETING: SCIENCE AND A CHANGING WORLD About 5,000 scientists are expected to attend the 1994 annual meeting of the American Association for the Advancement of Science, to be held in San Francisco February 18-23. Keynote Speaker: * John Gibbons, Assistant to the President of the United States for Science and Technology, and Director of the Office of Science and Technology Policy: "Science, Technology, and the Clinton Administration." Symposia Highlights: * "Health Care Reform and Advances in Medicine": Sessions will focus on the discovery of AIDS therapies in an era of health care reform, ethical issues in the testing of preventive HIV vaccines, and information technology supporting research, health care, and the AIDS-affected community. * "Industry, Policy, and the Changing Infrastructure of Science" One session, "Building a U.S. Technology Policy," will target the efforts of the Clinton administration to develop a set of policies linking technology development, technology utilization, and U.S. economic competitiveness. * "Science, Ethics, and the Law": Sessions will include "Scientists and Human Rights: Activists, Victims, and Advocates," with presentations by former dissident scientists Yuri Orlov of the former Soviet Union and Fang Lizhi of China. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: NOTEBOOK ------------------------------------------------------------ TI : Bound For Glory TY : NEWS (NOTEBOOK) PG : 4 Rachel Fuller Brown and Elizabeth Lee Hazen, New York State Department of Health researchers who collaborated in the 1940s and 1950s on the world's first antibiotic against fungal infection--nystatin, named after the department--were posthumously inducted into the National Inventors Hall of Fame. The pair, only the second and third women to be so honored, will be inducted in a ceremony in Akron, Ohio, site of the hall, on April 23. Brown and Hazen were among the numerous scientists caught up in the post-World War II rush to develop antibiotics after the discovery of penicillin. They made their discovery from a bacterium found in a clump of dirt--picked up by Hazen on a farm where she was vacationing in Virginia--and produced a practical antibiotic in 1954. It cured many disfiguring and disabling fungal infections of the skin, mouth, throat, and intestinal tract, and eventually was used in over-the-counter drugs and veterinary preparations. Brown and Hazen donated royalties from their invention--more than $13 million by the time the patents ran out--to academic science. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Scientific Responsibility TY : NEWS (NOTEBOOK) PG : 4 The Poynter Center for the Study of Ethics and American Institutions at Indiana University will sponsor a conference on the relationship between scientific misconduct and broader issues of social responsibility on Indiana's Bloomington campus on May 24. The goal of the conference, entitled "Scientific (Mis)Conduct and Social (Ir)Responsibility," is to foster discussion between scientists and ethicists and generate interest in teaching scientific responsibility in graduate classes, according to Kenneth Pimple, a research associate at the Poynter Center. The keynote address will be delivered by Rosemary Chalk, a senior program officer at the National Academy of Sciences and the Institute of Medicine, who has directed academy studies on integrity in science, conflict of interest, and health and rights issues. The conference will also include a panel discussion on teaching research ethics; other sessions are being planned. The conference is free, but preregistration is required by April 15. For more information, contact Pimple at the Poynter Center, 410 N. Park Ave., Bloomington, Ind. 47405; (812) 855-0261. E-mail: (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Bully For Herman TY : NEWS (NOTEBOOK) PG : 4 Herman, the world's first transgenic bull, is the proud father of eight transgenic offspring, all of whom carry, as he does, a gene for human lactoferrin, an antibacterial protein produced in human milk, officials for GenPharm International Inc. announced last month. The calves were the first births from among 55 pregnancies produced through in vitro fertilization with Herman's semen at GenPharm's European facilities in Leiden, the Netherlands. GenPharm officials hope the transgenic breeding program will enable large-scale production of lactoferrin--which provides protection against bacterial infections of the gastrointestinal tract--to be produced in cow's milk. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Expanded Wellcome Funding TY : NEWS (NOTEBOOK) PG : 4 Bolstered by $400 million endowment from their London-based sister foundation, the Wellcome Trusts, the Burroughs Wellcome Fund of Morrisville, N.C., has announced expanded program initiatives in biomedical research. The Career Awards in the Biomedical Sciences provide medical faculty in their initial years $500,000 grants to help them make the transition to independent investigators. Deadline for applications is October 1. The Hitchings-Elion Fellowship Program, named after Nobel laureates George H. Hitchings and Gertrude B. Elion, provides $135,000 for three years of postdoctoral support in biomedical and behavioral sciences for researchers seeking experiences in laboratories in the United Kingdom. Applications are due March 10 and September 10. The Burroughs Wellcome Fund is also increasing support to $150,000, from $60,000, for its three-year New Investigator Awards in Molecular Parasitology. These awards are for researchers at the instructor or early assistant professor level engaged in parasitology research. Applications are due in January of each year. For information on all of these awards, contact the Burroughs Wellcome Fund, Morrisville, N.C., 27560-9771; (919) 991- 5100. Fax: (919) 941-5884. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : `You Are Getting Healthy...' TY : NEWS (NOTEBOOK) PG : 4 A University of Florida study suggests that hypnosis can help boost the immune system. Psychoneuroimmunologist Beree R. Darby's investigation analyzed different levels of lymphocytes, the cells that make up the immune system. Blood samples were taken from 22 female and six male graduate students, both before and after self-hypnosis training. In the training sessions, the subjects were instructed in the biochemical details of the immune response and research findings in immunology, as well as direct and indirect suggestions for increased self-confidence and improved immune response. The study found a significant difference in the level of lymphocytes in the group taught self-hypnosis vs. a control group. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : When More Is Less TY : NEWS (NOTEBOOK) PG : 4 U.S. universities and colleges spent more on research and development in 1992 than the year before, but the increase was smaller than the average growth rate of the past decade, according to figures from the National Science Foundation. Total R&D expenditures reached $19 billion in 1992, up 7 percent from the year before, but only 4 percent when adjusted for inflation. Yearly increases from 1982 to 1991 averaged 6 percent when adjusted for inflation. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Following Women's Footsteps TY : NEWS (NOTEBOOK) PG : 4 The Center for Research on Women has released Pathways for Women in the Sciences: The Wellesley Report Part I, the first phase of a study of why women choose to enter science and what promotes or impedes their success. The study, which focused on Wellesley College students, follows women's science career trajectories from undergraduate through graduate and early career years, and examines the personal and professional factors that encourage women to persist in science or choose other career paths. Among the report's central findings are: Interest in pursuing science or math is developed before college; neither undergraduates nor alumnae favored employment for mothers of young children, but anticipated being employed when they themselves had children; factors such as race/ethnicity, class, and historical cohort make a difference in women's experiences in the sciences; and the majority of alumnae experienced discrimination, harassment, or both in graduate school and the workplace. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: OPINION ------------------------------------------------------------ TI : Global Science Needs Better `International Marketplaces' AU : JESSE H. AUSUBEL TY : OPINION PG : 11 *** Editor's Note: Jesse H. Ausubel, director of the Program for the Human Environment at New York's Rockefeller University, is concerned about the challenges facing the international science community as it moves toward the 21st century and beyond. He expressed these concerns last month in a Washington, D.C., address before the Committee on Science, Engineering, and Public Policy (COSEPUP), a panel created by the national academies of sciences and engineering and the Institute of Medicine. Central to Ausubel's apprehensions regarding the global scientific community are some very serious problems facing United States science; in his talk he cited, for example, the soaring costs of research, the confused mission of the country's national laboratories, uncontrolled growth of its academic research enterprise, and the dubious track record of its industrial research sector. Ausubel believes that recent debates surrounding the superconducting supercollider and space station Freedom have boldly underscored the fact that frustrating challenges and conflicting interests do indeed exist--and that the pursuit of remedies through productive dialogue is a matter of consequence and urgency. To a great extent, he noted in his talk, the problems are byproducts of U.S. science's increasing involvement in a much larger arena: the global research community, which he elects to term "Science International." If America now suffers these problems, Ausubel believes, so, in one way or another, do all other nations. And progress toward resolution, he contends, can be achieved only through the establishment of dynamic, effective international organizations--both governmental and nongovernmental--that are chartered to address them within a global context. The following essay is drawn from his talk before the committee. *** Science has lived until now with ad hoc arrangements for international dealings in each of its fields. The time has come to create better meeting places for all concerned-- marketplaces, in a sense--in which potential participants in international scientific cooperation can gather, trade information, and, should they so choose, do business. We do not need to create bureaucracies to create science internationally, but as the volume of global transactions in science increases, we need frameworks that allow us to conduct our affairs reliably and efficiently. In referring to the global science community, I choose to use the term "Science International." This phrase, which happens also to be the name of the newsletter of the International Council of Scientific Unions (ICSU), sounds stronger than the more common reference, "international science." And--perhaps because it echoes the term "Socialist International"--it even sounds somewhat conspiratorial. It should: Science, worldwide, is a single cognitive formation, and always has been. Of course, over time, the locations of its clubhouses have changed. At one time, the largest were in Athens and Alexandria; at another in London and Leiden. Now they are in such places as La Jolla and Geneva. That Science International has historically functioned as a cognitive unity is graphically displayed in the systematic discovery of the elements of the periodic table, a process that began in the 18th century: Chemists searching from Uppsala to Edinburgh, from Transylvania to Castile, and in the New World functioned as one coherent, multinational entity. So, scientists are dual citizens--of their own countries and also of what sociologist Michael Polanyi more than 30 years ago termed "the Republic of Science." My concern here is with the role that United States scientific institutions should be playing in this planetary republic. The health of Science International is always worth examining; and it is natural to explore those factors that are impairing the health of its wealthiest, largest, and most capable subsidiary. Danger Signals I believe three factors dominate: * Cost. In some fields (particle physics and astronomy are clear examples), research results are costing much more to obtain than ever before. Derek de Solla Price--the late, great, and usually prescient historian of science-- conjectured in 1963 that scientific results grow as the cube root of the expense of research and that costs of science would increase as the square of the number of scientists. If true, this is discouraging. However, science is a service industry, and let us hope that information technology will reduce the cost of our business, as it promises to do in other service industry sectors. If not, we have deep reasons for concern. * Conjunctural crisis. We are living through one of the periods of simultaneous economic, political, and technological fluctuation that profoundly restructure the world every 50 years or so. If the society shivers, science feels it. World War II and the Cold War drew or refigured a set of institutions that have been important for science. In the U.S., they included the Atomic Energy Commission, the Defense Advanced Research Projects Agency, the National Aeronautics and Space Administration, and the National Science Foundation. Internationally, they included the North Atlantic Treaty Organization, the Organization for Economic Cooperation and Development, and the International Atomic Energy Agency. These organizations generated tens of billions of dollars for science and successfully justified the expenditures in the political system. As the missions of all these organizations come into question, science looks for new patrons, partners, and goals. * Overcapacity of the U.S. scientific infrastructure. Although it is unpopular to say it--especially in the halls of the National Academy of Sciences--I believe we now suffer from overcapacity in the nation's R&D establishment. I refer to the three major performers of research--government, industry, and academia. In government, the most easily recognizable excess is associated with the $20 billion set of national laboratories. It is hard for anyone to argue that those labs are now responding to felt needs or opportunities. Meanwhile, although industry is frequently criticized for underinvestment in R&D, one cannot overlook, for example, the mismatch now apparent in the pharmaceutical industry. The 10 or so of this sector's largest firms support enormous in-house R&D efforts; those giant firms are producing few new products or insights of significance while, fortunately, some 1,400 U.S. biotech firms are bubbling with ideas. As for America's universities, their population and research activities have expanded to the point at which they now are financially dependent for survival on the export of services and the import of talent. If other nations truly begin to compete in advanced research and graduate education, U.S. universities may experience in the next 50 years some of the pains stemming from the imprudent growth and uneven product quality that our steel and auto industries have suffered in the past 50. Addressing Needs Given the pressures of rising costs, conjunctural change, and overcapacity, it is appropriate that Americans examine the framework that supports Science International. We must explore the implications of these factors for individual disciplines, programs, and projects; strategies for individual institutions; and the restructuring of national scientific enterprises. In this context, I suggest that there are two paramount, long-term needs that NAS can play a major role in addressing. On one hand, there is the need for nongovernmental organizations that are able to convene scientists from around the globe as individual experts and also in professional groupings, generally established according to scientific discipline. On the other hand, there is the need for a mechanism to bring together the individuals within national governments who control the bulk of the resources for science. Nongovernmental Infrastructure An appropriate point of departure for considering the international nongovernmental structure in science is the Paris-based International Council of Scientific Unions. ICSU, established in 1931, is an organization of organizations. It includes 23 international scientific unions, which are largely disciplinary, and 92 national bodies, which are academies of sciences and like organizations. ICSU also operates some 20 interdisciplinary bodies in fields such as water and ocean research. ICSU shows promise of progressing as an effective mechanism for convening and networking the international scientific community. In principle, ICSU connects hundreds of thousands of scientists worldwide; in practice, few scientists know of ICSU itself, although many know particular adhering organizations. At the same time, familiarity with ICSU is growing among its principal partners, national governments, and international organizations. The main reason is ICSU's contributions to the development of global research programs in the field of environment. ICSU must continue to demonstrate its utility. The best way is to expand its role in both assisting the formation of policies and plans for scientific research and education within the scientific community itself and in providing scientific information and advice to governments and industry for policy-making. A useful proposal is for ICSU to carry out a comprehensive, globally consistent study on human resource flows in science and engineering. Such a study requires participation by the science and engineering communities in all countries; it must address the professional interests of the participants; and it must serve governments, industry, and intergovernmental organizations. If ICSU is to grow into the international counterpart of the National Research Council, it will be through testing itself on such substantial questions of science and technology policy as international flows of talent. Even as ICSU grows--particularly as ICSU grows--a serious evaluation of that organization is needed. ICSU has not matched its accomplishments in environment in other fields-- for example, genetics and high-energy physics. It also has weak links in engineering, medicine, and the social sciences. A 12-member executive board with elected officers now governs ICSU. The nature of the roles and commitment of its elected officers, potentially key spokespersons for the international scientific community, must be reconsidered. The positions of president and secretary- general of ICSU should probably become full-time, compensated positions, and the other officers should probably become part-time compensated positions. Consideration must also be given to enlarging the organization's small, permanent secretariat (now only seven persons) and, perhaps, to changing and decentralizing it. ICSU must also reinforce relationships with nongovernmental scientific organizations that are, or can be, strong in geographic regions or other meaningful subsets of the world community. These include the Third World Academy of Sciences, the African Academy of Sciences, and the International Institute for Applied Systems Analysis, as well as Academia Europaea and other nongovernmental scientific organizations emerging on the European level. Science International also must be able to reach out to organizations that are effective in concentrating global talent in engineering and technology. (The rapidly growing Council of Academies of Engineering and Technological Sciences [CAETS], which assembles national academies of engineering and like organizations, shows great promise in this regard.) More broadly, the bridges between international science and international industry need to be enhanced. Industrial organizations share concerns with the scientific community ranging from mathematics, science, and engineering education at all levels, through environmental quality, to such matters as the disposition of pharmaceutical products that are critically needed in developing countries but for which market demand may not support a supplier's cost of development and distribution. Former NAS foreign secretary Walter Rosenblith raised many of these issues in a pair of ICSU conferences on "International Science and Its Partners" held at Ringberg, Germany, in 1985, and in Visegrad, Hungary, in 1990. Momentum for further analysis and action needs to be regained. Now is the time to consider, comprehensively, the hierarchy, or perhaps network, of effective organ- izations, including national associations for the advancement of science, national academies of sciences, regional institutions, and global organizations that are ultimately required for effectiveness at the global level. I am unaware of any well- drawn visions of the nongovernmental side of Science International. The Carnegie Commission on Science, Technology, and Government made a few rough sketches, as has NAS from time to time. The American scientific community, singly and in cooperation with its counterparts, should try depicting some visions more fully and identify the steps needed over the next 10 to 20 years to achieve them. The exercise will involve abstract debate about models of consent, rationality, and decision-making; it also will involve haggling over specific issues, including membership, financing arrangements, and bylaws. Intergovernmental Bodies The question of ICSU's counterpart on the intergovernmental side is more difficult. The leading figures for science in each national government can include a minister for science and technology, the president of a national science foundation or research council, a science and technology adviser to the president or prime minister, and others. There is at present no congenial and constructive context in which these individuals, representing at least the 20 or so leading scientific powers, regularly convene. I see at least four possibilities to create such an organization: * Make the "S" in UNESCO work better. Over the last couple of decades, the leading governmental figures in science have rarely used UNESCO as the venue for their high-level consultations. * Take the "S" out of UNESCO and form a new science organization within the United Nations context. The success of the World Meteorological Organization demonstrates that it is possible to sustain a high-quality, technically oriented institution within the U.N. system. * Start a new intergovernmental organization for science. Such an organization could nucleate around the quasi- periodic meetings of heads of major national science foundations or science and technology advisers to heads of state. One of the promising consequences of the Carnegie Commission has been the formation of the "Carnegie Group" of science advisers, including the science advisers of the G-7 nations, Russia, and the top science and technology figures in the European Union. This group, however, does not include Sweden, Switzerland, the Netherlands, Israel, China, India, or Brazil, to name a few, all of which are significant members of Science International. Another entity around which to build productive intergovernmental exchange is the Paris-based Organization for Economic Cooperation and Development (OECD)--the "economic club" of the 30 or so leading industrialized nations--which has established a "Forum on Megascience." Unfortunately, China, India, and Brazil do not belong to OECD, either. * Form a "bicameral ICSU," as proposed by Robert M. White, president of the U.S. Academy of Engineering, more than a decade ago. In this model, ICSU would have a "governmental council" of its own. The World Conservation Union in Geneva- -the leading international organization for biodiversity preservation--is an example of an international group that has a governmental council as well as a nongovernmental structure. This organization, while predominantly nongovernmental, nevertheless has some 60 "state" members that pay dues; its dual character has enhanced its ability to stimulate intergovernmental action and conventions in areas such as protection of endangered species. Each of these options and others should be explored thoroughly. In any case, the broad question of science in the U.N. system is badly overdue for examination. Science and technology have again come to the fore in the U.N. because of interest in sustainable development. The U.N. is not, however, carrying out its ongoing reorganization with attention to science and technology per se. But consideration of the U.N. will probably not be fruitful except in a larger context embracing NATO, OECD, the European Union, and other intergovernmental organizations important to science--and all currently in turmoil. A Matter Of Urgency Now is the right time to begin to set in place the infrastructure for Science International for the next 50 years--for the science of the 8 billion who will inhabit the planet by 2020, and for the billions more who will follow. There is no alternative for solving many of our the globe's problems than to do more and better science, and, if nothing else, everyone needs to be prepared for the costs. Some fields, such as international agricultural research, have established mechanisms to debate priorities, evaluate performance, and improve dialogue among researchers, funders, and potential practitioners. Many others have not. To define the set of needed changes and build support for them, Science International should explore, with government and industry, the creation of a major international commission to assess and make recommendations about the global infrastructure of science, both nongovernmental and governmental, across all fields. Such a commission needs to be independent of ICSU and the U.N. system, in part because it must examine and address these bodies. The U.S. scientific community can do much to set the process in motion. Moreover, a comprehensive, ambitious, long-range review of the international infrastructure for Science International can succeed only if the U.S. science and technology community and the U.S. government provide strong support. We, as citizens of both Science International and America, have much to gain. Jesse H. Ausubel is director of Rockefeller University's Program for the Human Environment. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: COMMENTARY ------------------------------------------------------------ TI : Research!America: Big Plans For 1994 AU : MARY WOOLLEY TY : OPINION (COMMENTARY) PG : 12 "Medical research is a slow and painstaking process, but the fulfillment that comes when one is able to save lives and alleviate suffering makes it all worthwhile." This statement by Nobelist Gertrude Elion, gracing the cover of Research!America's 1993 annual report, sums up our organization's fundamental mission. Research!America is determined to increase public awareness of medical research's value--of its role in improving the quality of life for everyone. In late November, we released the results of a nationwide Harris poll--commissioned by our organization--showing that the American public overwhelmingly considers medical research to be the single most valuable type of scientific research, with two-thirds of respondents ranking it as their top priority. The poll indicated that nine of 10 Americans feel the nation should spend more than it already spends to diagnose, prevent, and treat disease. And three-fourths of those surveyed said they are willing to support additional research by paying a dollar a week more in taxes, a dollar a week more in health insurance, and a dollar more per prescription drug. The survey data provide us--and should provide all citizens- -with strong indications that the nation's governmental decision-makers are not making medical research a high enough priority. I testified to that effect before the United States Senate Committee on Labor and Human Resources on December 8. Members of this committee were clearly alerted to the priorities of their constituents: Americans want a greater national commitment to medical research. Research!America is dedicated to making biomedical research a higher national priority. The commissioning of the poll and my congressional testimony marked a new level of visibility for Research!America's work and set the stage for our efforts this year. On March 9, our organization will hold its annual meeting in Washington, with Harold Varmus--the new director of the National Institutes of Health--serving as our keynote speaker. In conjunction with the meeting, Research!America will convene a forum to forge a consensus agenda and action plan for 1994 to those who are concerned that research and health care reform may be on a collision course. The value of a unified message can hardly be overemphasized as we mount a campaign to ensure that health care is being driven by research, rather than driving research away. The annual meeting is to serve as a rallying point for action toward achieving our organization's 1994 advocacy goals. Members will be called on and will be given the tools to translate rhetoric into reality. In partnership with such groups as the American Medical Association, the Federation of American Societies for Experimental Biology, the Association of American Medical Colleges, the National Health Council, and the National Pharmaceutical Council, Research!America will convene a summit meeting this spring to develop a shared vision of research and health, endeavoring to get beyond the annual, incremental, crisis- driven approach to support that has characterized the last decade. Consistent with our goal of significantly broadening the public constituency for research, half of those invited to this summit will be drawn from outside the research community. By involving a wider spectrum of stakeholders to participate alongside the members of the research "family," we expect to develop strategies, tactics, and programs that can be used nationwide to immediately activate strongly felt but rarely expressed public support for research. Research!America will quickly transmit the outcomes of both our forum on research and health care and the summit on research and health to citizens and elected officials across the nation. We will also use the lessons of those sessions in hands-on fashion as we scale up our grass-roots efforts with a campaign designed for metropolitan New York City. Given the popularity and sustained effectiveness of outreach programs in previous years (Maryland in 1992 and North Carolina in 1993), our organization is now ready to focus on one of the world's largest metropolitan areas. With the support of the medical, biotechnology, academic, voluntary, and philanthropic communities, "Research!New York City" will establish a powerful coalition to deliver the message to citizens, opinion shapers, and decision-makers that it's time to increase and sustain government and private-sector funding for research into cures, treatments, and preventions for physical and mental disorders. Like the promise of medical science, advocacy for medical research has unlimited potential. Research!America is dedicated to tapping that potential. Mary Woolley is president of Research!America, a research advocacy organization. For information on membership and other matters, write 1522 King St., Second Floor, Alexandria, Va. 22314; or call (703)-739-2577. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------- TI : History Of Science AU : PHILIP SIEKEVITZ TY : OPINION (LETTERS) PG : 12 The article on the history of science (F. Hoke, The Scientist, Nov. 15, 1993, page 1), a good one indeed, omitted what I think is an important aspect of science history. If one examines many biology or biochemistry textbooks, one finds a woeful omission of the historical aspects of any particular subject. The student comes away feeling that, all of a sudden, insight sprung from Zeus's head, knowledge without a precedent. There is nothing to indicate that many past discoveries, some going back 100 years, have formed the foundations for any particular subfield. The history of experimental research is conspicuously missing, and is becoming lost to today's students. If I may say so, a singular exception to this is the third edition of a biology, biochemistry, and molecular biology textbook, Cell Structure and Function, by A. Loewy, P. Siekevitz, J. Menninger, and J. Gallant (Philadelphia, Saunders College Publishing, 1992), in which, at the beginning of each chapter, a few pages are devoted to the past important discoveries, and how they had led up to the present-day view of the science in that subfield. PHILIP SIEKEVITZ Rockefeller University 1230 York Ave. New York, N.Y. 10021-6399 (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Animal Research Protection AU : BRANDON L. MILLETT TY : OPINION (LETTERS) PG : 12 Thank you for your Oct. 18, 1993, article regarding the Department of Justice (DoJ) report on animal rights terrorism [R. Kaufman, page 1]. I'm pleased The Scientist gave the report coverage and called attention to animal rights extremists' attempts to target researchers with vandalism, death threats, and other acts of intimidation. Readers may be interested to know that in response to the DoJ report and recent animal rights attacks in Montgomery County, Md., Congressman George Gekas (R-Pa.) has introduced legislation that would further protect researchers. Called the Animal Enterprise Personnel Protection Amendment, the bill would extend existing federal protection from the animal enterprises to the individuals who work for them. Gekas's bill would give federal authorities another tool to investigate and prosecute animal rights terrorists and strengthen criminal investigators by creating a federal central intelligence network for these crimes. The bill would also send a strong public message that Americans value the contributions to society by biomedical investigators, and will not tolerate attacks on these dedicated men and women. BRANDON L. MILLETT Americans for Medical Progress Inc. 1735 Jefferson Davis Highway Arlington, Va. 22202-3401 (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Animal Models AU : JEROD M. LOEB TY : OPINION (LETTERS) PG : 12 Neal D. Barnard's letter to the editor (The Scientist, Nov. 15, 1993, page 12) concerning the recent commentary by Frederick K. Goodwin and Adrian R. Morrison (The Scientist, Sept. 6, 1993, page 12) is telling. Once again, Barnard cleverly zooms in on grains of truth and uses highly selective data, ignoring completely the vast body of information that does not support his ideological bias. While Barnard comments on anecdotal evidence relating to several cases in which data derived from animal experiments were not applicable to human clinical situations, he completely misses critical points. For example, according to the Pharmaceutical Manufacturers Association, each year approximately 5,000 new chemical entities are synthesized. Of these 5,000 new chemical entities, 500 are tested in isolated systems, 250 are tested in animals, five are tested in human clinical studies, and only one is ultimately approved by the Food and Drug Administration. Obviously, the important lesson in these data is the protection afforded to society by these rigorous testing processes. At issue is not what we have failed to learn, but rather what we have learned. We must all beware of pronouncements made by an individual whose scientific acumen is driven by personal philosophy that ignores valid research data. JEROD M. LOEB American Medical Association 515 N. State St. Chicago, Ill. 60610 (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: RESEARCH ------------------------------------------------------------ TI : Citation Records Indicate Leaders In Ecology Research Editor's Note: The newsletter Science Watch, published by the Philadelphia-based Institute for Scientific Information (ISI), last year decided to devote more attention to a research arena that, clearly, was attracting more attention among scientists worldwide: ecology and environmental science. After analyzing ISI's Science Indicators Database, the newsletter published last November (Science Watch, 4[9]:7-8, 1993) its first-ever list of leading papers in this burgeoning field--a compilation focusing on research productivity in the late 1980s. Following is Science Watch's report, written for the newsletter by Peter D. Moore, who is reader in ecology and chairman of human and environmental sciences in the Division of Life Sciences, King's College, London. The report is presented here with the permission of Science Watch and ISI. Science Watch has decided to add ecology and environmental sciences papers to its regular roundup of the Top 10 in research. The first grouping of the Top 10, listed in the accompanying table, features papers published in 1987, 1988, and 1989 that were most cited by the end of 1992. For this field of research one might well ask, "Just how hot is hot?" If one compares ecology with, say, molecular biology, the answer is, "Not very, on the whole." But such a comparison is hardly fair, since each field exhibits its own characteristic publication pattern and citation profile. In this group, the peak citation count for any single paper in any single year rarely exceeds 40, but that is often achieved within a two-month period in disciplines such as immunology and biochemistry. So citations as measured here are lower by a factor of five or six when compared with those in other biomedical disciplines. The number of investigators active in a field, the average number of references listed in a paper, the degree to which interest of researchers is either focused on a few universal physiological mechanisms or diffused broadly across a wide variety of phenomena--all of these and more help shape a field's bibliometric nature. It is also very clear, from a glance at the annual citation counts for ecology and environmental-sciences papers, that they take a longer time to accumulate citations than other papers do. Of the top 15 papers, 12 have only just peaked or are still rising three to four years after their publication. Of the journals that are most cited in this field, Nature is far and away in the lead, having four of the top 10 papers. No other journal has more than one in the Top 10, and only Ecology placed two in the top 15. Despite recognizing differences such as these, one is still able to distinguish--among this less flamboyant population of papers--which ones have attracted the most attention. Of the topics covered by these 10 papers, three are particularly prominent: population ecology and genetics of birds, aquatic productivity and carbon cycling, and trace metal distribution and biological response. Spying On Sparrows The application of genetic fingerprinting techniques in bird populations has evidently generated considerable interest. The two most cited papers for the period were published side by side in Nature in 1987. Both groups of United Kingdom researchers, the first from Queens Medical Center in Nottingham (paper No. 1) and the second from the Zoology Department of Leicester University (No. 2), use DNA fingerprinting in a study of house sparrow populations and find the technique adequate for the tracing of family relationships within the birds and therefore of value for studying extra-bond copulation (infidelity), sexual selection, egg dumping, breeding behavior, and other aspects of the social life of these vulgar, communal little birds. The subsequent success of the techniques, incidentally, is demonstrated by the fact that a further paper in 1989 by T. Burke and his Leicester group reaches No. 15 in the ranking (despite its late publication in the period under review here) and concerns the sexual behavior of another small, brown British bird, the dunnock, which has the added behavioral complication of being polyandrous (T. Burke, et al., Nature, 338[6212]:249-51, 1989; total citations: 91). Do the males feed the young of those other males who share their partner? DNA fingerprinting shows that they do. But, on the other hand, those that have most access to the female also do most of the feeding; presumably they reckon that they are most likely to be the father anyway. Beneath The Waves Aquatic productivity and carbon cycling certainly has a grip on the chart, with three in the Top 10 concerned with this subject. Paper No. 10, by S.R. Carpenter and his colleagues, has wide general implications in both theoretical and applied ecology. This group wanted to document the controlling factors in determining plankton productivity and balance in fresh-water lakes. In particular, they were interested in the impact of higher trophic levels on the plankton, so they increased the level of fish removal from a test lake, and the outcome was an increase in the zooplankton and a decrease in algal biomass. When piscivory was decreased, on the other hand, zooplankton decreased and algal biomass increased. In the unaltered, control lake, fluctuations in plankton levels resulted from abiotic variables, such as climate. Such findings are not of themselves surprising, but the experimental demonstration of population controls by predation levels higher in the food chain is reassuring to some theoretical ecologists. The role of oceanic bacterioplankton in productivity and carbon cycling has a high interest rating. S. Lee and J.A. Fuhrman's paper in the No. 3 spot describes a technique for estimating the biomass of bacterioplankton, which is necessary for the assessment of the importance of this group in carbon cycling. A further paper by S.W. Chisholm and colleagues, describing a new group of prochlorophyte organisms that occupy and photosynthesize at the base of the euphotic zone, just fails to make it to the Top 10, coming in at No. 11 (S.W. Chisholm, et al., Nature, 334[6180]:340- 3, 1988; total citations: 103). Heavy-Metal Menace Trace metals supply a predictable source of interest for environmental research, and two papers in the Top 10 deal with them. In paper No. 7, J.A. Nriagu and J.M. Pacyna's work provides an extensive and detailed survey of a range of metals in the atmosphere, hydrosphere, and biosphere. They conclude from their studies that human activities currently dominate the global biochemical cycling of these elements. The problems that the heavy metals pre-sent to plants has then been investigated by Grill and coworkers in paper No. 8, and they report the pre-sence of compounds in plants (phytochelatins) that chelate with heavy metal ions and render them nontoxic. These compounds are found in a wide range of plants, from algae to orchids, and are more abundant in forms that demonstrate an ecological tolerance of heavy metals in nature. Physiologically, they are equivalent to the metallothioneins in animals, but the chemical solution to the heavy metal problem has evidently taken plants and animals along different evolutionary tracks. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : WHAT'S HOT IN ECOLOGY/ENVIRONMENTAL SCIENCES RANK PAPER CITATIONS THROUGH 1992 ===== ====== ============ 1 J.H. Wetton, R.E. Carter, D.T. Parkin, D. 170 Walters, "Demographic study of a wild house sparrow population by DNA fingerprinting," Nature, 327(6118):147-9, 1987. (Queens Medical Center, Nottingham, U.K.) 2 T. Burke, M.W. Bruford, "DNA fingerprinting in 148 birds," Nature, 327(6118):148-52, 1987. (University of Leicester, U.K.) 3 S. Lee, J.A. Fuhrman, "Relationships between 133 biovolume and biomass of naturally derived marine bacterioplankton," Applied Environmental Microbiology, 53(6):1298-1303, 1987. (State University of New York, Stony Brook) 4 J.H. Martin, G.A. Knauer, D.M. Karl, W.W. 123 Broenkow, "VERTEX: Carbon cycling in the northeast Pacific," Deep-Sea Research Part A, 1484(2):267-85, 1987. (Moss Landing Marine Labs, Calif.; University of Hawaii, Honolulu) 5 J. Gomez, D. Sanchez-Martinez, V. Stiefel, J. 119 Rigau, P. Puigdomenech, M. Pages, "A gene induced by the plant hormone abscisic acid in response to water stress encodes a glycine-rich protein," Nature, 334(6179): 262-4, 1988. (CSIC, CIF, Barcelona, Spain) 6 K.A. Nagy, "Field metabolic rate and food 116 requirement scaling in mammals and birds," Ecological Monographs, 57(2):111-28, 1987. (University of California, Los Angeles) 7 J.O. Nriagu, J.M. Pacyna, "Quantitative 113 assessment of worldwide contamination of air, water, and soils by trace metals," Nature, 333(6169):134-9, 1988. (National Water Research Institute, Ontario, Canada; Norwegian Institute of Air Pollution Research, Lillestrom, Norway) 8 E. Grilli, E.L. Winnacker, M.H. Zenk, 113 "Phytochelatins: a class of heavy-metal- binding peptides from plants, are functionally analogous to metallothioneins," Proceedings of the National Academy of Sciences USA, 84(2):439-43, 1987. (University of Munich, Germany) 9 J.J. Cole, S. Findlay, M.L. Pace, "Bacterial 110 production in fresh and saltwater ecosystems: a cross-system overview," Marine Ecology-Progress Series, 43(1-2):1-10, 1988. (New York Botanical Garden, Millbrook, N.Y.) 10 S.R. Carpenter, J.F. Kitchell, J.R. Hodgson, 105 P.A. Cochran, J.J. Elser, M.M. Elser, D.M. Lodge, D. Kretchmer, X. He, C.N. Vonende, "Reputation of lake primary productivity by food web structure," Ecology, 68(6):1863-76, 1987. (University of Notre Dame, South Bend, Ind.; University of Wisconsin, Madison; Northern Illinois University, De Kalb; St. Norbert College, De Pere, Wis.) Source: Science Watch/ISI's Science Indicators Database, 1987-1992 (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: RESEARCH HOT PAPERS ------------------------------------------------------------ TI : MEDICINE TY : RESEARCH (HOT PAPERS) PG : 16 W.O. Spitzer, S. Suissa, P. Ernst, R.I. Horwitz, B. Habbick, D. Cockcroft, J.-F. Boivin, M. McNutt, A.S. Buist, A.S. Rebuck, "The use of bETA-agonists and the risk of death and near death from asthma," New England Journal of Medicine, 326:501-6, 1992. Samy Suissa (Department of Epidemiology and Biostatistics, McGill University, Montreal): "Asthma is a common disease that affects 5 percent to 10 percent of people. Numerous effective medications have been developed to treat this disease, by way of either bronchodilation or inflammation reduction. "In the 1980s, the mainstay of asthma therapy was based on bronchodilators, which included theophyllines and b- agonists. Extremely effective, these latter drugs were used rather liberally, to the point at which they were available without prescription in some countries. Unexpected increases in asthma mortality in several parts of the world have induced investigations of the possible role of drug therapies in these mortality patterns. "In 1989, a case-control study from New Zealand suggested that one of these b-agonist bronchodil-ators, namely fenoterol, was associated with a higher risk of death from asthma, while the other popular one, salbutamol, was not. We and other scientists were puzzled by this premise that two drugs from the same class could show different risk profiles. Conscious of the limitations of this type of epidemiologic study design, we decided to conduct our own investigation. "Using a more rigorous population-based design, we found that the excessive use of any or all inhaled b-agonists, including fenoterol and salbutamol, was associated with fatal and near-fatal asthma. A significant number of the 12,300 asthmatics studied were using inordinate amounts of inhaled b-agonists, much more than the maximum recommended quantity, and these formed the basis for the elevated risks we found. It was clear that these drugs had become victims of their remarkable effectiveness. "Our study generated great attention primarily because it put in question the current practice of asthma therapy. Instantly, the uncontrolled use of inhaled bETA-agonists became no longer admissible. Physicians and patients were now to monitor the use of these drugs and, if this use increased, indicating worsening disease, to supplement therapy with anti-inflammatory inhaled corticosteroids. The latter indication has since been confirmed by our subsequent analyses of the data (P. Ernst, et al., Journal of the American Medical Association, 268[24]:3462-4, 1992), which suggest that the use of inhaled corticosteroids reduces the risk of fatal or near fatal asthma 10-fold. Our study has, in essence, substantiated the recent international guidelines on the management of asthma." (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : VIROLOGY TY : RESEARCH (HOT PAPERS) PG : 18 L.A. Donehower, M. Harvey, B.L. Slagle, M.J. McArthur, C.A. Montgomery, Jr., J.S. Butel, A. Bradley, "Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours," Nature, 356:215-21, 1992. Larry Donehower (Division of Molecular Virology, Baylor College of Medicine, Houston): "The p53 tumor suppressor gene has recently received a great deal of attention because its loss or mutation occurs in more than half of all human tumors. Despite all this attention, the normal role of p53 in regulating cellular processes is only beginning to be understood. "The work described in this paper was an attempt to provide insights into the role of p53 in mammalian development and tumorigenesis by a `knockout' of the gene in the mouse germ line using some of the novel gene-targeting techniques that our collaborator Allan Bradley had developed. "Our hypothesis was that knockout mice missing both normal p53 alleles would die early in their development, since it had been known that p53 had important effects on the cell cycle. In fact, the surprising result was that these null p53 mice appeared normal in every measurable way. "However, it soon became clear that all was not normal when the null animals began developing tumors as early as eight weeks of age and three-quarters had succumbed to cancer by the age of six months. "I think the major impact of this paper was that it helped people to reassess the function of p53 in the normal cell. Thriving p53-deficient mice indicated that p53 played no essential role in normal cell proliferation and differentiation. "Where p53 might be important is in the response of the cell to DNA damage events. Mike Kastan's group showed that ionizing radiation stimulated p53 activity in irradiated cells, and this resulted in cell division arrest (S.J. Kuerbitz, et al., Proceedings of the National Academy of Sciences, 89:7491-5, 1992). "A model was outlined that postulated that the role of p53 might be to arrest cells following DNA damage, allowing time for the damage to be repaired so that the affected DNA would not be propagated as mutations or chromosome abnormalities in progeny cells (D.D. Lane, Nature, 358:15-6, 1992). "Therefore, without the p53-facilitated correction mechanism, our p53-deficient mice would be more likely to incur genetic lesions in cancer-associated oncogenes and tumor suppressor genes and develop tumors. "Two groups have provided elegant support for this hypothesis by showing that cells missing p53 are much more prone to certain types of genetic rearrangements than normal cells are (L.R. Livingstone, et al., Cell, 70:923-35, 1992; Y. Yin, et al., Cell, 70:937-48, 1992). "Consequently, a secondary impact of the paper is that it introduces a potentially powerful tool for carcinogenesis studies. Animals deficient in p53 (and cells derived from them), which are more sensitive to the effects of mutagens and carcinogens, might be useful to cancer researchers and toxicologists." (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : PLANT BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 E. Lopez-Juez, A. Nagatani, K.-I. Tomizawa, M. Deak, R. Kern, R.E. Kendrick, M. Furuya, "The cucumber long hypocotyl mutant lacks a light-stable PHYB-like phytochrome," Plant Cell, 4:241-51, 1992. Enrique Lopez-Juez (Laboratory of Plant Biological Regulation, Frontier Research Program, Riken Institute, Wako, Japan): "Through light signals, plants can decide when to germinate, to stop elongating underground and start expressing genes for leaf components (de-etiolate), or in which season to flower. The modification of growth pattern to avoid shading by competing neighbors (shade-avoidance reaction) is one such response. Characterized for more than 20 years, it is a function of phytochrome, a key plant photoreceptor. Enrichment in far red light in shade, through selective filtering/reflectance, lowers the proportion of active phytochrome, triggering the response. "During the 1980s it became clear that, besides the `bulk' phytochrome very abundant before de-etiolation, now known as PhyA, some other phytochromes existed. In previous physiological work on the cucumber lh (long hypocotyl), a mutant having normal `bulk' phytochrome and able to de- etiolate, we showed that this plant displays a constitutive, saturated shade-avoidance reaction. This suggested that such a response depends on a new phytochrome type, inactive or missing in the mutant. What we show here is that, in fact, different antibodies raised against a phyB gene, which detect a minor phytochrome-like polypeptide in the wild type, distinct from PhyA, all failed to recognize any protein in the mutant. The message is that PhyB is the main actor in the shade-avoidance reaction, and can dramatically affect plant development. "This result was the fruit of a collaborative effort of those who sequenced a phyB cDNA, set up the protein expression and antibody production techniques, and produced the antibodies and used them to characterize the mutant. Since the paper was published, intensive work in several labs has continued. It has been found that a lh-like mutant in Arabidopsis is indeed mutated in the phyB gene itself. But a new major question has been opened: Now that we have a role for PhyB, the phenotype of new PhyA-specific mutants tells us that PhyA does very little of what we thought it might do, and that we must find what controls the de- etiolation responses." (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: TOOLS & TECHNOLOGY ------------------------------------------------------------ TI : Uses Of Enzyme Immunoassays Growing In Laboratories And Clinics AU : HOLLY AHERN TY : TOOLS & TECHNOLOGY PG : 17 Many biological researchers who need to identify an interesting protein or determine its concentration in a sample say that enzyme immunoassays are their tool of choice. Using these versatile detection tests, they can, for example, pinpoint a specific gene from an organism's genome or analyze the kinetics of an enzyme. Clinical investigators can use enzyme immunoassays to detect circulating antibodies to disease-related antigens, distinguish among different Salmonella cell wall proteins, or identify substances in body fluids that signify the occurrence of a heart attack. Also, new automated enzyme immunoassay systems can now speed the diagnosis process dramatically. Researchers in both the clinic and the lab are calling enzyme immunoassays a major improvement over radioimmunoassays, widely used in past years for many of the same purposes. Users who are changing their systems cite the elimination of radioisotopes with their inherent health risks and disposal problems as a key advantage. "Enzyme immunoassays are at least as sensitive as radioimmunoassays," says Keld Sorensen, a senior research scientist for Pierce Chemical Co. in Rockford, Ill. "And any time you can change a procedure to get radioactivity out of the lab without affecting sensitivity, it's an improvement." The essential components of an enzyme immunoassay are an antibody specific to a target substance and an enzyme that makes detection of the bound antibody possible. Immunoassays performed in a solution, for example, respond to the initial reaction of the antibody and its target antigen, which then modulates the catalytic activity of the enzyme, allowing detection. Enzyme immunoassays combine the specific recognition of antibodies for their targets with the catalytic power of enzymes into a single sensitive and relatively simple test. The sensitivity of an enzyme immunoassay depends on the ability of antibodies to home in on a particular antigenic target, such as a protein, a bacterial or viral antigen, or other antibodies. Coupling this specificity to the catalytic ability of some enzymes to convert colorless chemicals to brightly colored products results in a detection system that can be adapted to a wide range of applications. ELISA Leads The Pack With the growing emphasis on nonradioactive detection in molecular biology applications, enzyme immunodetection kits are becoming increasingly popular for use with Western blot (protein detection), Southern blot (DNA detection), and other procedures. In these tests, researchers first separate their samples by gel electrophoresis and then blot them to a support matrix made of nitrocellulose or nylon. After applying a primary antibody specific for the target, an enzyme-conjugated second antibody binds to the primary antibody, catalyzing a chromogenic reaction that leaves behind a dark precipitate on the support membrane. The sensitivity of these nonisotopic detection systems--such as the Genius kit for DNA detection from Indianapolis-based Boehringer Mannheim Biochemicals and the Immun-Blot assay kits from Bio-Rad Laboratories of Hercules, Calif., used in Western blotting procedures--is comparable to that of the more conventional radioisotopic detection schemes. By far the best known of the enzyme immunoassay techniques is ELISA (enzyme-linked immunosorbent assay). Because most ELISAs involve several washing steps to remove excess reactants before the next reagent is added, the tests are performed in the solid phase, which means that some component of the system is hooked to a solid support material. An investigator's choice of solid phase varies with the application, but the choices include microtiter plate wells, plastic or glass beads, emulsions of latex particles, and paper or nylon membranes. Scientists can design ELISAs in various ways to accommodate their specific application. The initial step is to adsorb one of the reactants--either the primary antibody, in order to capture the target antigen, or the antigen itself--to the solid phase. After the excess is washed away, the second component is added and reacts specifically with the first. "Linking the test system to a solid phase allows for the sequential amplification of the initial antibody's recognition of the target substance," says Paulette McCormick, a cell biologist at the State University of New York, Albany. The final step is the chromogenic reaction of the enzyme with its substrate that identifies the complex bound to the solid phase. The amount of colored end product is proportional to the amount of target substance in the test. In what is called an ELISA sandwich assay, a suitable antibody is adsorbed first to the solid phase, often the wells of a microtitration plate, and the excess washed away. Then a sample, which might be a patient's serum or a mixed solution of proteins, is applied to the wells. If the target substance is present in the sample, it will be specifically bound by the antibody on the well's surface. Unbound substances are washed away. Next, a second enzyme-labeled antibody is added, which binds to another epitope on the antigen, leaving an enzymatic tag. When the chromogenic substrate is added, the enzyme converts it to a brightly colored product that signifies the antigen's presence. Variations on the sandwich theme abound. Antigen can be bound to the solid phase in an antibody capture assay, where it competes with a sample antigen for recognition of the enzyme-labeled antibody. Capture assays can also be used in reverse, with the primary antibody attached to the solid phase competing for sites on the antigen with a labeled second antibody. To detect antibodies rather than antigens in an ELISA system, a sample antibody reacts with an antigen attached to the solid phase. In this method, termed an indirect antibody capture assay, a second antibody carrying the enzymatic tag is added, which binds to the captured target antibody. This form of ELISA is typically used by scientists screening clones for important antibody-secreting hybridomas. Laboratories that screen for specific antibodies in serum from immunized animals also use this technique. The choice of ELISA enzyme label is highly dependent on an investigator's application. The two most common enzyme choices are horseradish peroxidase (HRP) and alkaline phosphatase (AP). "Approximately 80 percent of all commercial ELISAs incorporate HRP in the system, and most of the rest use AP," says Pierce's Sorensen. A few other enzymes, such as acetylcholine esterase or a- galactosidase, are sometimes used. The popularity of HRP and AP, however, stems from their stability and the wide range of chromogenic substrates available for each enzyme. According to Sorensen, HRP is preferred over AP because, as a plant product, it is more easily produced and less expensive. Most ELISA kits developed are for use in human diagnostics. Using ELISA, investigators can detect hepatitis C virus in samples of body fluids, for example; discover contaminants such as Salmonella in foods before they are consumed; determine if a woman is pregnant; and identify people at risk for certain cancers. Physicians can perform diagnostic tests in their offices or clinics. Other types of enzyme immunoassays offer tests for therapeutic drugs or drugs of abuse or to assess a patient's thyroid function. Recently, enzyme immunoassays have been incorporated into automated testing systems, leading to additional applications. "Enzymatic immunoassays lend themselves to automation," says immunologist Gary Kitos, laboratory director at Allergy Testing Laboratory in Fort Lauderdale, Fla. "Most of the assay steps can be completed with robotics." A number of companies, including Ciba-Corning Diagnostics in Norwood, Mass., and Tosoh Medics Inc. in Foster City, Calif., have developed random-access immunoassay analyzers that automate the various enzyme immunoassay steps. Automated immunoassays for drugs, antigens, and hormones are already on the market, with more expected to follow shortly. Customizing Assays Investigators also are finding that ELISA can be made to order. The only qualifier is the requirement for a suitable antigen or an antibody, which can be conjugated to an enzyme label in the lab. Companies like Pierce and Bio-Rad market various ELISA components, including primary and enzyme- conjugated antibodies, blocking reagents, and conjugating reagents and enzymes, which enable individual researchers and commercial manufacturers to design their own specific immunoassay systems. For many applications, a large array of kits containing all of the necessary components is available. A number of kits that are small and self-contained have allowed investigators to take ELISA into the field. One area in which the simplicity and lower cost of enzyme immunoassays have resulted in the availability of many new tests is environmental analysis. Using enzyme immunoassays, environmental scientists can detect contaminants such as pesticide residues, industrial chemicals, and microbial toxins in samples of water, soil, or air. Many of these types of tests are portable enough to take directly to a suspected hazardous waste site. For environmental testing to detect the presence of pesticide residues, including triazines such as atrazine, propazine, and simazine, in water samples, Millipore Corp. in Bedford, Mass., markets the EnviroGard test kit, used either in the laboratory or in the field. The kit, developed by Millipore subsidiary ImmunoSystems Inc. of Scarborough, Maine, is "complementary to the conventional methods of gas chromatography and HPLC," according to Jim Fecteau, group manager at ImmunoSystems. The test, which is based on an antigen-capture method, is performed in antibody-coated test tubes. Using the kit, field investigators can detect the presence of contaminants at a site and determine their approximate concentration simply by adding a sample and kit reagents to the supplied test tubes. "In some cases we can detect chemical contaminants in the parts-per-trillion range," adds Fecteau. Animal scientists can benefit from compact ELISAs in their field work, as well. Idexx Corp. in Westbrook, Maine, produces membrane-based ELISA kits that allow such specialists to perform diagnostic ELISAs in the field--a barn, for example--as well as in their clinics. Enzyme immunoassays are also being used in quality and safety testing of foods. Immunoassays that detect numerous food components and contaminants--including amino acids and sugars, pesticide residues, and antibiotics--are becoming increasingly available. Current methods of testing for microbial contaminants in foods based on conventional microbiological techniques can take up to five days to complete. To speed the detection of bacterial agents in food, Organon Teknika/Biotechnology Research Institute in Rockville, Md., has developed an ELISA in which whole bacterial cells are captured by antibodies attached to a solid phase. Tests for Listeria species and E. coli are also in developmental stages at Organon Teknika. Use of ELISA tests by the food industry could decrease the time necessary to identify a bacterial contaminant to 24 to 48 hours. Although testing of this kind is not yet widely accepted by food-safety critics, enzyme-based immunoassays are clearly a positive step. In-solution assays, an alternative to the solid phase testing, are limited mostly to analyses of small molecules to maximize the effect of the reaction between the antibody and the enzyme. The best known of these is EMIT (enzyme- multiplied immunoassay technique) from Syva Co. in San Jose, Calif., often used by clinicians to detect drugs of abuse and for therapeutic drug monitoring. Holly Ahern is a freelance science writer based in Albany, N.Y. She teaches cell and molecular biology at the State University of New York, Albany. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : SUPPLIERS OF ENZYME IMMUNOASSAY KITS AND PRODUCTS TY : TOOLS & TECHNOLOGY PG : 19 The following vendors develop and/or market enzyme immunoassay kits and products for a variety of research and clinical laboratory uses. For more information about products, services, and prices, please contact these companies directly. 5 Prime - 3 Prime Inc. 5603 Arapahoe Rd. Boulder, Colo. 80303 (303) 440-3705 Fax: (303) 440-0835 AAI-Abtech P.O. Box 376 Yardley, Pa. 19067 (800) 233-2197 Fax: (215) 321-7099 AMAC Inc. 160 B Larrabee Rd. Westbrook, Maine 04092 (207) 854-0426 Fax: (207) 854-0116 American Qualex 14620 E. Firestone Blvd. La Mirada, Calif. 90638 (714) 521-3753 Fax: (714) 994-1203 Amersham Corp. 2636 South Clearbrook Dr. Arlington Heights, Ill. 60005 (708) 593-6300 Fax: (708) 437-1640 Bio-Rad Laboratories Life Sciences Group 2000 Alfred Nobel Dr. Hercules, Calif. 94547 (510) 741-1000 Fax: (510) 741-1055 BioSource International Inc. 887 Mitlen Rd. Burlingame, Calif. 94011 (415) 698-4015 Biotecx Laboratories Inc. 6023 South Loop East Houston, Texas 77033 (713) 643-0606 Fax: (713) 643-3143 BioWhittaker Inc. 8830 Biggs Ford Rd. Walkersville, Md. 21793 (301) 898-7025 Fax: (301) 845-4491 Boehringer Mannheim Biochemicals 9115 Hague Rd. Indianapolis, Ind. 46250 (800) 428-5433 Fax: (317) 845-2000 Calypte Biomedical 1440 Fourth St. Berkeley, Calif. 94710 (510) 526-2541 Fax: (510) 526-5381 Cayman Chemical Co. 690 KMS Place Ann Arbor, Mich. 48108 (313) 662-6756 Fax: (313) 662-6896 Ciba-Corning Diagnostics 115 Norwood Park South Norwood, Mass. 02062 (508) 359-7711 Fax: (508) 359-3599 Cistron Biotechnology 10 Bloomfield Ave. Pine Brook, N.J. 07058 (201) 575-1700 Fax: (201) 575-4854 Endogen Inc. 68 Fargo St. Boston, Mass. 02210 (617) 439-3250 Fax: (617) 439-0355 Exocell Inc. 3508 Market St. Suite 420 Philadelphia, Pa. 19104 (800) 234-3962 Fax: (215) 222-5325 Genzyme Diagnostics Division of Genzyme Corp. One Kendall Square Cambridge, Mass. 02139 (617) 252-7744 Fax: (617) 252-7600 Granbio Inc. P.O. Box 392140 Temecula, Calif. 92589 (909) 676-0049 Human Biologicals Inc. P.O. Box 50862 Phoenix, Ariz. 85076 (602) 893-8817 Fax: (602) 893-8817 Hycor 18800 Von Karman Irvine, Calif. 92715 (714) 440-2000 Fax: (714) 440-2222 ICN Pharmaceuticals ICN Plaza 3300 Hyland Ave. Costa Mesa, Calif. 92626 (714) 545-0113 Fax: (714) 641-7275 Idexx Laboratories One Idexx Dr. Westbrook, Maine 04092 (207) 856-0300 Fax: (207) 856-0346 Immuno-Dynamics Inc. P.O. Box 766 La Jolla, Calif. 92038 (619) 452-1270 Fax: (619) 458-3515 ImmunoSystems Inc. 4 Washington Ave. Scarborough, Maine 04074 (207) 883-9900 Fax: (207) 883-8088 ImmunoVision 1506 Ford Ave. Springdale, Ariz. 72764 (800) 541-0960 Fax: (501) 751-7002 Integrated Biosolutions Inc. 4270 U.S. Route 1 Monmouth Junction, N.J. 08852 (908) 274-1778 Fax: (908) 274-1733 Kronus 1000 Calle Amanecer San Clemente, Calif. 92673 (714) 366-9100 Fax: (714) 366-9300 Lampire Biological P.O. Box 170 Pipersville, Pa. 18947 (215) 795-2838 Fax: (215) 795-0237 Life Technologies P.O. Box 6009 8451 Helgerman Court Gaithersburg, Md. 20884 (301) 840-4150 Fax: (800) 331-2286 MGM Instruments Inc. 925 Sherman Ave. Hamden, Conn. 06514 (203) 248-4008 Fax: (203) 288-2621 Nordic Immunological Labs Drawer 2517 Capo Beach, Calif. 92624 (714) 498-4467 Fax: (714) 361-0138 Organon Teknika/ Biotechnology Research Institute 1330 Piccard Dr. Rockville, Md. 20850-4396 (800) 354-0809 Fax: (301) 840-2161 Oxford Biomedical Research Inc. P.O. Box 522 1858 Starr Batt Dr. Rochester Hills, Mich. 48309 (810) 852-8815 Fax: (810) 852-4466 Paracelsian 222 Langmuir Laboratories Cornell Technical Park Ithaca, N.Y. 14805 (607) 257-4224 Fax: (607) 257-2734 Perceptive Diagnostics 735 Concord Ave. Cambridge, Mass. 02138 (617) 499-1433 Fax: (617) 497-6927 Pharmacia Hepar Inc. 160 Industrial Dr. Franklin, Ohio 45005 (800) 447-3846 Fax: (513) 746-8055 Pierce Chemical Co. P.O. Box 117 Rockford, Ill. 61105 (800) 874-3723 Fax: (815) 968-7316 R & D Systems 614 McKinley Place, N.E. Minneapolis, Minn. 55413 (612) 379-2956 Fax: (612) 379-6580 Repligen Corp. 1 Kendall Square Building 700 Cambridge, Mass. 02139 (617) 225-6000 Fax: (617) 494-1786 Scimedex Corp. 400 Ford Rd. Denville, N.J. 07834 (201) 625-8822 Fax: (201) 625-8796 Serex Inc. 203 West Passaic St. Maywood, N.J. 07607 (201) 368-5700 Fax: (201) 368-7850 Syva P.O. Box 4901 San Jose, Calif 95161-9013 (800) 227-8376 Fax: (408) 239-2206 TAGO Inc. 887 Mitten Rd. Burlingame, Calif. 94010 (415) 692-4015 Fax: (415) 692-9004 Takara Biochemical Inc. 719 Allston Way Berkeley, Calif. 94710 (510) 649-9895 The Binding Site Inc. 5889 Oberline Dr. Suite 101 San Diego, Calif. 92121 (619) 453-9177 Fax: (619) 453-9189 Tosoh Medics Inc. 373 Vintage Park Dr. Foster City, Calif. 94404 (415) 578-2600 Fax: (415) 578-2626 USA Scientific Plastics P.O. Box 3565 Ocala, Fla. 34478 (904) 237-6288 Fax: (904) 351-2057 Vector Laboratories 30 Ingold Rd. Burlingame, Calif. 94010 (415) 697-3600 Fax: (415) 697-0339 (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) =================== NEXT : ------------------------------------------------------------ PROFESSION ------------------------------------------------------------ TI : Literary Agents Offer Assistance To Scientists Writing For The Public AU : RICKI LEWIS TY : PROFESSION PG : 21 The writing that is a major part of a scientist's professional life does not usually languish unread. Rarely, for example, is a go-between needed to direct a paper or grant proposal to the appropriate journal or agency. And attention and encouragement are intense for those who respond with in- terest to a textbook publisher's quest for authors. But for a researcher trying to sell a popular science book to a potential publisher, it's another matter entirely. In such instances, it is essential for the writer to have a literary agent who will smooth the way, scientist- authors say. Agents Open Doors "Most major trade publishers will not consider unsolicited material. You can be an MIT professor and Simon & Schuster will send you a form letter telling you to get an agent," says Michael Snell, a literary agent in Truro, Mass. Snell spent a dozen years in academic publishing as an executive editor at Wadsworth Publishing Co. of Belmont, Calif., before becoming an agent in 1979. He represents scientist and physician writers, many of whom come to him after unsuccessfully trying to attract publisher interest on their own. "The trade book situation is so different from academic publishing. You have to use an agent to get them to look at anything," says William Calvin, an associate professor of psychiatry and neurobiology at the University of Washington in Seattle. He has published seven popular science books, including How the Shaman Stole the Moon (New York, Bantam Books, 1992), a neurobiology book. Calvin says his agent, New York-based John Brockman, has been invaluable. "A writer's first priority is to find an agent, for they are the essential gatekeepers," Calvin says. Writer's Market (Cincinnati, Writer's Digest Books, published annually), a bible of sorts for writers, defines a literary agent as part sales representative, part business manager. An agent screens proposals for those that are publishable, and attempts to place them with publishers. The agent typically receives 15 percent to 20 percent of the author's income from advances or royalties. Robert Pollack, a professor of biology at Columbia University, raves about his agent. "She was professional, efficient, clear-minded, and I knew that she was implacably on my side," he says. "I went from a poor shlep trying to be taken seriously by publishers to a person who would be revealed to the appropriate person at the appropriate time and to the appropriate publishing house." Pollack's book, Signs of Life: The Language and Meanings of DNA, is scheduled for publication this winter by Houghton-Mifflin Co. of Boston. What An Agent Does A literary agent first helps a scientist-author find a niche for the type of book he or she has in mind. "Is it cutting- edge science, or a review of a traditional field? If the topic is genetics, will the writer zero in on a particular aspect, or present an overview?" says Regula Noetzli, an agent specializing in science trade books at the Charlotte Sheedy Agency in New York. Writing to a particular audience on a level it can understand is crucial, too. A book to introduce an area of science to other scientists in different fields, for example, would use a style quite unlike that of a health-oriented book for consumers with little scientific savvy. Agents also help writers polish their proposals before they are sent to publishers. In trade publishing, the proposal is de rigueur: An author submits a proposal and perhaps a sample chapter or two. A proposal must be concise, clear, and riveting; moreover, the idea that is described must have an identifiable market. The art of proposal writing involves more than just putting words on a page, says Snell: "It is developing and organizing the proposal, studying the competition, and identifying the audience and market." Here is where a scientist should accept an agent's suggestions--a concept to which some academic researchers find it hard to adjust, since "professors are so used to telling their students what's right," Snell says. "I tell scientists, `I can't tell you about vertebrate physiology, but you can't tell me much about publishing,'" he says. Once a proposal is fine-tuned, it begins the rounds of publishers. "An agent knows which publisher is likely to be interested, and has entre to an editor," says Calvin. If a publisher is interested in the scientist's proposal, the agent helps negotiate a contract. "There are a lot of things a publisher can slip past an author who lacks contract experience," says Snell. Many novice authors, for example, are not aware that the cost of artwork will be deducted from royalties or the advance--unless they haggle at contract time for the publisher to pick up this expense. "Half of the items on a contract are routinely crossed off, but some things publishers won't budge on. Agents know that, and because they deal with the same editors over and over, they do not have to win the same argument over and over," says Calvin, who retained electronic publishing and translation rights to his books. In addition to knowing what a publisher is likely to compromise on and what is written in stone, an agent brings a distancing that an author cannot, agents say. "Most writers are unprepared to negotiate on their own behalf," Snell says. "It is your work, so you are emotionally involved. It's hard to be objective, as you need to be in this business." A successful proposal earns a lump-sum advance against royalties. Since royalties usually do not amount to much-- and in fact often come to less than the advance--the advance is often the only income the author sees. But advances can be quite impressive. "You'd think a publisher wouldn't buy a book until it was written, but that's absolutely not true. They pay a $100,000 advance on the basis of a four- to five- page prospectus," says Calvin. Prospective authors should realize, however, that only the most successful scientist- turned-authors command such fees. A first-timer is more likely to get between $25,000 and $50,000, he says. Setting Up Collaborations A major obstacle in moving from grant writer or article author to trade publishing is the fact that many scientists are not skillful writers. "If they try to write a popular science book, they do not know what they can expect in the basic knowledge of the audience," says Noetzli. Agents and editors pinpoint a major problem in many scientists' attempt at popular writing--the stilted, remote passive voice that pervades scholarly journals. "Scientists seem to be hesitant to write a simple, direct, declarative sentence," says Bob Kalish, coauthor of Global Alert, a book on ozone (New York, Plenum Publishing Corp., 1992). Snell offers an example of a scientist's prose passed on to him by an editor at Wadsworth: "The small quadruped effected its descent from the arboreal habitat to engage in the ingestion of sustenance." The editor crossed it out and penciled in: "The squirrel came down from the tree to eat." To combat the problems caused by the scientist who has a great idea and an impeccable background--but who also tends to discuss quadrupeds in arboreal habitats--some editors offer yet another service: They hook up the aspiring scientist author with an established writer who can effectively communicate the researcher's ideas to the public. Such help can come from several sources. A coauthor contributes original chapters or polishes the scientist's writing, or both. "The main thing I contribute is a sense of style," Kalish says of his part in this literary symbiosis. "I make it interesting." A coauthor splits the advance or royalties, the percentage reflecting the amount of work involved. A ghostwriter is generally paid a fee by the author, but relinquishes the credit that a coauthor would retain. Another option is for the author to hire a developmental editor. This is someone who coaches the author in how to rewrite a garbled or overly technical manuscript--a service that was once provided by the publisher after an author submitted a manuscript (see story on page 21). Writing teams are formed in various ways. Noetzli, for example, keeps a list of writers on staff at a well-known mass-market science magazine who are available for collaborations. Jack Fishman, an atmospheric scientist at the National Aeronautics and Space Administration in Langley, Va., found his own coauthor--Bob Kalish, who is his cousin. Together, they produced Global Alert. "Fishman had done research on surface ozone, and written articles for professional journals that he felt the general public should be aware of, but he knew that what he wrote was too technical," says Snell, their agent. "But he had a cousin who was a professional writer, who had a couple of successful novels, and who had ghostwritten a few books with doctors. When put together, they could create a book that neither could have done alone." How To Find An Agent Many authors find their agents by word of mouth. This was the case for Pollack. He originally sent his book about DNA sequences to university presses where he had contacts, although he sought a broader readership. These publishers sent his manuscript to other biology professors for review, hardly a valid test of how the book would fare among the shopping-mall bookstore set. "So I contacted Horace Judson, who wrote The Eighth Day of Creation [New York, Simon & Schuster Inc., 1979], also about DNA," Pollack recalls. "Coincidentally, he had already read my manuscript for one of the university presses, and said, `It's not a university press book. You need an agent.'" So Pollack approached Judson's agent, who took him on. For those without personal tips, the best place to look for an agent is a book available in libraries, Literary Market Place, or LMP (New York, R.R. Bowker Co., published annually). "For an agent to obtain a listing in LMP, he or she must establish credentials of having sold three books for advances in the past 12 months--and they check it out. If you're not listed, you have no track record," says Snell. Another good source for finding an agent is Writer's Market. Agents offer the following tips for aspiring authors: Once you find an agent who specializes in science trade books, send a one-page query letter describing your planned book, why it will sell, and why you are qualified to write it. Submit a publication list, including both professional and popular articles. Pollack, for example, mentioned an op-ed piece he had written that was published in the New York Times. Swamping an agent with reprints from the Journal of Experimental Zoology may not help you plead your case. If an agent is interested in representing you, he or she will then ask to see a proposal and perhaps a sample chapter or two. Calvin managed to sell his first book, Inside the Brain (New York, New American Library, 1980), without an agent--and with a lot of luck, he says. But his editor quickly put him in touch with an agent, and his writing career has been much easier ever. "As far as I can see, you need an agent all the time," he says. Ricki Lewis is a freelance science writer based in Scotia, N.Y. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : THINGS THAT CAN GO WRONG AFTER THE CONTRACT IS SIGNED AU : RICKI LEWIS TY : PROFESSION PG : 21 Once a scientist signs a contract to write a trade book, the agent usually fades into the background, handling payments and other business matters while the writer writes. But having a contract isn't a guarantee that you'll have a book. Your book may never see the light of day if it isn't adequately developed. "At many publishing houses, editors are overloaded from all the mergers and downsizing, so they no longer have the time to nurture a book," says Michael Snell, a literary agent specializing in science books in Truro, Mass. "Ten years ago an editor may have had four or five books per season. Now it's 20 to 25 books per season. Therefore, a lot of what gets turned in is ultimately abandoned," Snell says. And if a publisher decides to drop its science line, the firm can back out of contracts, says William Calvin, an associate professor of psychiatry and neurobiology at the University of Washington in Seattle and author of seven trade books. Another author's nightmare is seeing his or her prized book on the discount table at K-Mart. This is what happens when a book is "remaindered," says Calvin. "In the mid-1970s, federal tax law provided a large incentive if books don't sell well to get rid of them. This is how they end up on clearance tables in bookstores," he says. Calvin is most disturbed about the short lives of his books, only one of which has gone beyond an initial printing. "Books from academic presses and textbook publishers tend to remain available for half-a-dozen years. But in trade publishing, if it isn't big, in two years, it is unavailable," he says. Calvin is now in the frustrating position of having his books that are out of print in the United States being published in Dutch and German. A professor who wanted to assign one of Calvin's books to his students couldn't, because the book was no longer for sale. A financial hedge against a book's being abandoned is to secure a hefty advance. And agents say that means having one of them on the author's side. "The trade publishers expect an agent to filter material," says Snell. --R.L. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ PEOPLE ------------------------------------------------------------ TI : Russian Scientist Takes Sabbatical With U.S. Biotech AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 23 Vladimir A. Efimov, head of the Laboratory of Gene Engineering at the Shemyakin Institute of Bioorganic Chemistry, Moscow, is spending a year's sabbatical as a visiting scientist at Triplex Pharmaceutical Corp. in The Woodlands, Texas. The four-year-old biotechnology company is working on producing novel drugs to inhibit the onset of certain viral disease and cancers. Its approach is based on using oligonucleotides--short sequences of DNA building blocks-- that form triple helical complexes with specific regions of DNA, thereby preventing the genes from expressing themselves. Efimov was invited to help in designing the specific oligonucleotides. "This approach is very promising for the future of pharmaceuticals," says Efimov, whose expertise is in nucleic acid chemistry and recombinant DNA technology. "We are trying to produce oligonucleotides that can bind tightly and specifically to the regulatory regions of genes causing viral diseases or oncogenes." "Dr. Efimov will lend his expertise to the chemical modification program, to improve the DNA-binding capabilities of the oligos, and to ensure their uptake by cells," says Krishna Jayaraman, head of the oligonucleotide chemistry group at Triplex. "We have to be able to reduce the quantity [of oligonucleotide] needed 100 times in order for it to be used as a drug," says Efimov. "My approach involves modifying the structure of the backbone so as to improve binding and uptake." Efimov received his Ph.D. in bioorganic chemistry from the Shemyakin Institute of Bioorganic Chemistry, Moscow, in 1974, and, in 1989, a doctor of sciences (Sc.D.) degree from the same institute. He has been associated with the Shemyakin Institute since 1971, first as a student and later as a researcher and teacher. He has received numerous awards in his home country, including the Order of Honour for Scientific Achievements, and the USSR Medal for Outstanding Achievements in Labor; in addition, he holds three patents. Although he has visited the U.S. before, this is his first extended stay; previously, he came for symposia and meetings. "I hope to organize a bridge between the U.S. lab and my lab in Moscow," he says. --Neeraja Sankaran (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Two Researchers From France, Australia Receive U.S. Nobel `Predictor' Award AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 23 Nicole Le Duarin, a developmental biologist and a professor at the College de France, Nogent-sur-Marne, and Donald Metcalf, a research professor of cancer biology at the University of Melbourne in Australia, were the recipients of Columbia University's 1993 Louisa Gross Horwitz Prize, presented in December. The two scientists shared the $22,000 prize, which has been awarded annually since 1967 for outstanding research in biology or biochemistry. Both Le Douarin and Metcalf were cited for their discoveries of how different types of cells in the body develop from a single type of precursor cell. Their work established that, in addition to the genes that code for various functions, environmental influences play an important role in determining cellular fate. The primary focus of Le Douarin's research has been the development of nerve cells in the embryo. She tracked the migratory routes of the precursor cells in the embryo to discover the precise point at which they begin to change. She discovered two growth hormones that determine whether these precursor cells become neural cells or cartilage or pigment cells. Le Douarin, 63, obtained her doctoral degree from the University de Paris. She taught high school from 1954 to 1960 and worked at the Centre National de la Recherche Scientifique (CNRS) from 1960 to 1965, as well as at the University de Clermont-Ferrand and the University de Nantes from 1965 to 1975. In 1975 she became the director of the Institut d'Embryologie at CNRS, a position she still holds. Metcalf's major contributions have been in studying the development of blood cells, and applying this knowledge to cancer therapy. He identified, purified, and found the genes for various factors that control the development of blood cells. Most recently, he isolated a new factor, called the leukemia inhibitory factor, that has powerful effects in precursor cells and adult liver and bone-forming tissues. Metcalf, 64, received a Ph.D. from the University of Sydney in Australia in 1953. Since 1954 he has been associated with the Walter and Eliza Hall Institute of Medical Research at Melbourne, where he is currently a research professor of cancer biology and head of the institute's cancer research unit. Last year, he received the Albert Lasker Clinical Medical Research Award (B. Spector, The Scientist, Oct. 18, 1993, page 1). More than half of the Horwitz prize winners--28 out of 51-- have gone on to receive the Nobel Prize. --Neeraja Sankaran (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================ NEXT: OBITUARY ------------------------------------------------------------ TI : Bernard D. Davis TY : PROFESSION (OBITUARY) PG : 23 Bernard D. Davis, a professor at Harvard Medical School since 1957 and a pioneer in microbial genetics research, died of prostate cancer at his home in Belmont, Mass., on January 14. He was 78 years old. Davis, who had been Adele Lehmann Professor of Bacterial Physiology at Harvard and director of the Bacterial Physiology Unit there, did ground-breaking work on the regulation of genes in bacteria, membrane transport systems, and the action of antibiotics. He established a technique to isolate mutant bacteria using penicillin. Davis also was widely known for his writings on social issues in science, such as the uses of recombinant DNA, the dangers of genetic engineering, and the Human Genome Project (The Scientist, Oct. 29, 1990, page 13). In 1976 he was at the center of a heated controversy over the publication of his opinions on affirmative action and medical school admissions. At the time of his death he was working on a book about another public controversy: that surrounding Nobel laureate David Baltimore. Baltimore had coauthored and then later defended a paper published in the journal Cell (45:247, April 1986) against claims of fraud and faked data. Davis had come out strongly in defense of Baltimore. Davis received an M.D. from Harvard Medical School in 1940. (The Scientist, Vol:8, #3, February 7, 1994) (Copyright, The Scientist, Inc.) ================================


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