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Phone :(215)243-2205 // Fax: (215)387-1266 E-mail:garfield@aurora.cis.upenn.edu ================= THE SCIENTIST VOLUME 8, No:16 AUGUST 22, 1994 (Copyright, The Scientist, Inc.) =============================================================== Articles published in THE SCIENTIST reflect the views of their authors and not the official views of the publication, its editorial staff, or its ownership. =============================================================== *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON *** *** SEPTEMBER 5, 1994 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the United States: one year $58, two years $ 94 Canada : one year $82, two years $142 All other foreign : one year/air cargo $ 79 one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NXT = next article ------------------------------------------------------------ TI : CONTENTS PG : 3 ============================================================ NEWS WHITE HOUSE WHITE PAPER: United States scientists, academic administrators, and government officials are hailing a new Clinton administration report on national science priorities as both a blueprint for science policy and a commitment of government support for research and science education. But some observers say the document is long on rhetoric and short on specifics, especially in the areas of funding and the balance of basic and applied research PG : 1 WHISTLE-BLOWER PROTECTION: Advocates of whistle-blower protection are hailing a New Jersey judge's ruling of wrongful dismissal in the case of a scientist who sued Mobil Oil Corp. for retaliating against him; they say the decision is a legal affirmation of the fundamental right of employees to be protected when they voice concern about hazardous products or situations PG : 1 RU 486 PROSPECTS: The recent transfer of patent rights to the abortifacient RU 486 from its French parent company to a U.S. nonprofit research organization is drawing mixed reactions from researchers investigating the drug's potential nonabortifacient medical uses PG : 1 APPLIED CHAOS: An increasing number of researchers from diverse life sciences disciplines are finding applications of chaos theory in their work, and are joining the Society for Chaos Theory in Psychology and the Life Sciences PG : 3 SCIENCE WATCHDOG: Scientists from a variety of fields are lending support to a new watchdog group--The Advancement of Sound Science Coalition--which has pledged to scrutinize the quality of research that influences federal regulations PG : 6 OPINION SAVING PLANET EARTH: A recent essay in The Scientist by noted University of Wisconsin bioethicist Van Rensselaer Potter warned that longtime survival of our planet depends on the development of constructive bioethical dialogue between religious and scientific leaders. The essay stimulated a particularly vigorous response from readers, a sampling of which is presented here PG : 12 COMMENTARY: Accounts of the lives and achievements of scientific geniuses, while inspirational, may also serve to discourage young scientists who may see little chance of attaining such greatness; and that's unfortunate, because the scientific enterprise is equally dependent on and served by the subluminaries who participate in it and chronicle its progress, says Eugene Garfield PG : 13 RESEARCH STRUCTURAL BIOLOGY: The first part of a two-part series examines the history behind current trends in this burgeoning field PG : 14 HOT PAPERS: Geneticist Mike Mullan discusses his paper on a mutation with a possible link to Alzheimer's disease; physicist Alan D. Martin reports on his analysis of energy distributions in particles; and cell biologist Morris F. White comments on circulating insulin in diabetes PG : 16 TOOLS & TECHNOLOGY PEPTIDES TO ORDER: Peptide-synthesis services save time and money for busy biology laboratories, and provide a level of purity and quality control that some labs might be hard-pressed to match PG : 17 PROFESSION TIPS ON THE TRADES: Susan Rabiner, a longtime editor of science books for lay audiences, says scientists seeking to write for the general public should be aware of the way trade publishing works; with some research and savvy, she says, first-time trade authors should be able to find the right publisher for their projects PG : 21 PAUL C. LAUTERBUR AND ANDRE WEIL, director of the Biomedical Magnetic Resonance Laboratory at the University of Illinois College of Medicine and an emeritus professor at the Institute for Advanced Study, respectively, have won 1994 Kyoto Prizes PG : 23 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 13 PEPTIDE-SYNTHESIS DIRECTORY PG : 19 NEW PRODUCTS PG : 19 CAREER OPPORTUNITIES PG : 24 EQUIPMENT MARKETPLACE PG : 29 (The Scientist, Vol:8, #16, pg.3, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------------ TI : Whistle-Blower's Legal Victory Seen As Supporting Industry Scientists Who Criticize Their Employers Mobil Oil toxicologist who was fired after he voiced concerns about safety standards is awarded $3.5 million AU : FRANKLIN HOKE TY : NEWS PG : 1 An industry toxicologist's legal victory over his former employer may reflect an inclination on the part of the courts to extend greater protections to whistle-blowers who raise scientific issues in the workplace, according to scientists and other observers. Also, they say, the unusually large size of the whistle-blower's award in the case--$3.5 million--should serve as a warning to companies against punishing dissent among their scientists. At the same time, they caution, the direct legal ramifications of the win will probably not reach beyond the borders of the state in which the case was tried, New Jersey, although many national high-technology companies have facilities there. In late 1989, Myron A. Mehlman, who had been chief toxicologist for Mobil Oil Corp., headquartered in Fairfax, Va., found himself the subject of an internal investigation for misuse of company resources. The investigation was launched 18 hours after he told officials of a wholly owned Japanese subsidiary that they were marketing gasoline containing dangerously high levels of benzene and should stop, according to evidence presented in the case. Mehlman, who worked at Mobil's laboratories in Hopewell, N.J., was subsequently fired and filed suit in the Superior Court of New Jersey, claiming Mobil had retaliated against him for his in-house scientific assertions. Mobil charged, however, that Mehlman had used company postage and photocopying to support a private scientific publishing venture and denied any connection between the investigation and Mehlman's statements in Japan. In a July 14 ruling in Newark, presiding judge Douglas J. Hague found that Mehlman could not seek protection under the state's Conscientious Employee Protection Act (CEPA), upon which he had based his suit, because the benzene levels of gasoline in Japan had no impact on New Jersey residents. At the same time, the judge said that Mehlman, in producing five large packets of receipts for stamps, had "overwhelmingly refuted the [company's] attempt to orchestrate a smear campaign" against him and found that he had been wrongfully fired, despite the fact that he had not sued under any other employment law. Hague referred to an "almost Pavlovian response to an employee who attacks the company" and said Mobil had "lost its bearing" in its "reprehensible" actions against Mehlman. He then vacated a jury's award of $3.5 million in compensatory damages based on the whistle-blower law, but let stand their award of $3.5 million in punitive damages because of the firing. "While multimillion-dollar damage awards [such as Mehlman's] are rare, they reflect a trend in whistle-blower protection, and they're becoming increasingly part of the legal landscape for corporations who used to have the power to fire whistle-blowers with impunity," says Thomas Devine, legal director of the Government Accountability Project in Washington, D.C. The independent group provides legal and other support to government and industry whistle-blowers. "But it's difficult for any other scientist outside of New Jersey to have any confidence that Dr. Mehlman's victory will be helpful," he adds, partly because whistle-blower laws vary dramatically from state to state. "They're almost like snowflakes: No two are alike." Each side plans to appeal the aspects of the case that it lost. Mehlman's lawyer, Neil M. Mullin of the firm Smith Mullin in West Orange, N.J., will argue that CEPA does cover overseas events and that New Jersey public policy law should discourage unethical actions by its corporations outside the state. Mobil's lawyer, William J. Brennan III of the Smith, Stratton, Wise, Heher, and Brennan firm in Princeton, N.J., has said that the punitive damages should not stand if CEPA does not apply in the case. John Lord, a Mobil spokesman, declines to discuss the case in detail, except to say that benzene levels in the Japanese gasoline were within applicable legal standards at the time and that the company does plan to appeal. Lord also reiterates the company's assertion that Mehlman's statements in Japan had nothing to do with his firing. Whistle-Blower Status Despite the judge's ruling that CEPA was not applicable, the case is being viewed, by scientists and others, as a case of retaliation by an employer against an employee raising legitimate public-interest concerns. "It's a whistle-blower case," says Lee Starr, a retired vice president for technology development with Hoechst Celanese Corp., Somerville, N.J., a subsidiary of Hoechst AG, Frankfurt, Germany. "If the guy is a scientist and his figures are correct, he should be able to say what he said. I don't feel he should have been stifled." Starr also expresses surprise at Mobil's reaction to Mehlman's comments concerning the dangers of high benzene levels in the company's gasoline. "In this day and age, if one of your own people raises a question about a potential hazard, you just don't discount it," Starr says. "You go and investigate it." At least one high-profile industrial whistle-blower says Mobil's response to Mehlman--indirectly punishing him for troublesome scientific views by investigating him for misappropriation of corporate resources--fits a pattern for such cases. "Most of the time, these companies get into trouble because they're so blatant in these investigations that it's obvious what is actually taking place," says Roger Boisjoly, who heads his own "forensic engineering" consulting firm, Boisjoly Engineering Ltd. in Mesa, Ariz. "They want to kill a messenger bringing the bad news, and that's the bottom line in the whole thing." In January 1986, as an engineer with Morton Thiokol Inc. in Willard, Utah (the company has since separated into two entities), Boisjoly voiced technical concerns that he felt should delay a launch of the space shuttle Challenger, which was scheduled for the following day. The shuttle subsequently exploded with the loss of the entire crew. Although Boisjoly's analysis of the dangers was later proved accurate, his relationship with his employers degenerated, according to published reports. Mehlman, who is now a visiting scientist at the Public Health Service's Agency for Toxic Substances and Disease Registry in Atlanta, told the managers of the Japanese Mobil subsidiary that the gasoline they were selling, which he understood to have a benzene content of about 5 percent, was dangerous to public health. Excessive benzene exposure has been shown to cause leukemia in humans. He recommended that they stop selling it until that level could be reduced--a process that might entail expensive modifications to the refinery. Robert Drew, health and environmental science director for the American Petroleum Institute, a trade group in Washington, D.C., says that while it is generally accepted that benzene can cause leukemia in humans, the exposure level necessary to induce the disease has not been quantified. Scientists like Mehlman have called for erring on the side of caution because of this, but Drew suggests that this view may be excessively conservative. According to the Environmental Protection Agency's Office of Mobile Sources in Ann Arbor, Mich., most gasoline sold in the United States currently contains about 1.5 percent benzene. Under provisions of the Clean Air Act of 1990 due to go into effect in 1995, however, that level will be lowered to below 1 percent in high-ozone areas, such as cities. (The Scientist, Vol:8, #16, pg.1, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ----------------------------------------------------- TI : Science Community Praises White House Policy Report Long-awaited `white paper' receives high grades from most observers, although some say it misses target AU : BARTON REPPERT TY : NEWS PG : 1 A long-awaited White House report on United States science policy, released earlier this month, is drawing generally strong praise from key scientific and educational association leaders, as well as senior officials at several major universities. These observers view the document as a strong expression of the Clinton administration's commitment to scientific research and education as national priorities. But some scientific and academic leaders, as well as members of Congress, have voiced reservations about the report, saying it lacks specifics on issues of research funding and the balance between basic and applied research. In a joint statement, Bruce M. Alberts, president of the National Academy of Sciences; Kenneth I. Shine, president of the Institute of Medicine; and Robert M. White, president of the National Academy of Engineering, praised the report: "We applaud the administration for taking a fresh look at the nation's goals for science. It is time. The Cold War is over and no longer drives decisions in the funding of science and engineering research." The academy presidents observed that "in these changing times, the administration has laid out a wise plan to continually evaluate the nation's position in science, math, and engineering in order to assure that the United States remains a world leader in all major fields. This field-by-field assessment is an essential tool in ensuring that precious resources are properly appropriated." And Cornelius J. Pings, president of the Washington, D.C.-based Association of American Universities, which represents major U.S. research institutions, says, "I applaud President Clinton and his administration for so forcefully emphasizing the importance of fundamental research and science and engineering education." On the other hand, Lewis Branscomb, director of the Science, Technology and Public Policy Program at Harvard University, echoes the criticisms of other scientific and academic leaders who say that while the policy statement expresses admirable sentiments, it hedges when it comes to facing the real issues that are troubling U.S. science. "I would rate it an A on importance and perspective, but a B on wrestling with the really tough issues," he says. Focus On Investment The 31-page report, "Science in the National Interest," seeks to enunciate broad goals for American science in the post-Cold War era. The document--officially released on August 3--stems primarily from an administration-sponsored "Forum on Science in the National Interest," held at the National Academy of Sciences January 31 to February 1. The forum was attended by more than 200 scientists, research administrators, and science-policy experts from around the country, as well as several key members of Congress. At a news conference to formally release the report, Vice President Al Gore declared that "fundamental science--discoveries in math, physics, chemistry, biology--is the foundation on which technical progress ultimately rests. The long-term investment that we make in pioneering discovery and knowledge generation is our `venture capital' for the future." Along with the report, Gore also announced the appointments of 18 prominent experts from industry, educational and research institutions, and nongovernmental organizations to serve on the President's Committee of Advisers on Science and Technology (PCAST), an advisory arm of the Cabinet-level National Science and Technology Council (NSTC). Among those named to the committee were Nobel physicist Murray Gell-Mann and John A. Young, former president and CEO of Palo Alto, Calif.-based Hewlett-Packard Co.--who will serve as cochairman of the panel with presidential science adviser John H. Gibbons. Senior administration science officials on hand for unveiling of the science-policy statement were Gibbons; National Institutes of Health director Harold Varmus; National Science Foundation director Neal Lane; and M.R.C. Greenwood, associate director for science at the White House Office of Science and Technology Policy (OSTP). Greenwood said at the news conference that the report was especially significant now, because "in a world where economic competitiveness and environmental responsibility are increasingly tied to national security, we need to be concerned about our long-term R&D positioning." Goal-Oriented Report "Science in the National Interest" sets five basic goals for U.S. "stewardship of science in the national interest": * Maintain leadership across the frontiers of scientific knowledge; * Enhance connections between fundamental research and national goals; * Stimulate partnerships that promote investments in fundamental science and engineering and effective use of physical, human, and financial resources; * Produce the finest scientists and engineers for the 21st century; and * Raise scientific and technological literacy of all Americans. To help achieve these goals, the policy paper says, "NSTC will provide ongoing evaluation of America's position in fundamental science, mathematics, and engineering and recommend actions to assure world leadership in all major fields." It also asserts that "investment in fundamental science must be accompanied by careful attention to support for international collaborations. The NSTC, with advice from PCAST, will recommend policies for long-term multinational agreements for the support of large scientific projects." Total U.S. support of nondefense R&D, according to the report, is currently about 1.9 percent of gross domestic product (GDP)--below that of Germany (2.5 percent) and Japan (3.0 percent). Including defense R&D, the U.S. figure is 2.6 percent. The OSTP report contends that through continued emphasis on shifting U.S. defense R&D more toward dual-use and civilian applications, "a reasonable long-term goal for the total national R&D investment (both civilian and defense) might be about 3 percent of GDP." In the area of science education and training, it says that NSTC will produce "a human resources development policy for sustaining excellence and promoting diversity in the science and technology workforce." Critics Seek Specifics At a House of Representatives hearing the day after release of the OSTP document, Rep. George E. Brown, Jr. (D-Calif.), chairman of the Science, Space, and Technology Committee, called it "a vision statement superior to any I have seen in my experience." But he added that it would be "highly unrealistic" to expect significant growth in R&D budgets over the next few years to achieve the 3 percent of GDP level envisioned in the report. Similar concerns were voiced at the hearing by Peter Likins, president of Lehigh University in Bethlehem, Pa., who had served on PCAST during the Bush administration. "An unstated premise of this report is the kind of robust growth in national prosperity that will make it politically feasible to commit the resources required to implement the recommendations of this report," Likins testified. "There is too little acknowledgment of this challenge in the report, and in my opinion this diminishes its credibility." Harvard's Branscomb says, "There's no question that this [report] is high-level. But on close reading, it doesn't commit itself on the things that disturb scientists most ... [such as] what will be the policies that govern the balance between goal-driven and science-interest-driven research." But several academic colleagues of Likins and Branscomb were more effusive in their praise of the report. "The president's new science policy is right on target," says C. Peter Magrath, head of the National Association of State Universities and Land-Grant Colleges in Washington. "America's leadership role in the new world of the 21st century and America's science are inextricably linked." Judith Rodin, president of the University of Pennsylvania and a new appointee to PCAST, says, "I cannot imagine a stronger statement in support of basic research--the seed of discovery and of the great scientific and technological breakthroughs that have made America the world's preeminent economic and political power." She adds that "our leadership in the world's economic and technological marketplace is not unchallenged, and Americans must be knowledgeable and literate in the basic principles if we are to take advantage of, rather than be disadvantaged by, the explosion of knowledge." Charles M. Vest, president of the Massachusetts Institute of Technology--and also a member of the new PCAST--said in a statement that the document "sets forth a compelling case and framework for investment in the future through development of scientific knowledge and the education of men and women to lead in the 21st century." Substance With Symbolism Some science and government officials, in praising the report, cite its significance as a guide for science policy as well as a commitment to science from the president. A statement issued by the Council of Scientific Society Presidents--a Washington-based group bringing together the leaders of more than 60 scientific societies with a combined membership of more than 1.3 million--said, "The Clinton-Gore administration has addressed one of the nation's most pressing needs and produced an important new roadmap for the role of science in the nation's future." Albert H. Teich, director of science and policy programs at the Washington-based American Association for the Advancement of Science (AAAS), calls the OSTP report a major step toward achieving a "new compact" between science and government to guide the development of American research. "The goals it articulates are realistic, attainable, and vital for the nation," Teich says. "It is gratifying that administration officials not only consulted widely with the scientific community in the development of the statement, but that the statement itself gives evidence that they listened carefully to what members of the community had to say." Frank H.T. Rhodes, chairman of the National Science Board, the policy-setting and oversight panel of NSF, said in a statement issued by the agency that the White House report "will be welcome for its strong affirmation of science, both as a primary national resource and as a major administration policy. "It is particularly encouraging to see the recognition of the critical value of fundamental research and the determination to sustain world leadership in science, mathematics, and engineering." Federation of American Societies for Experimental Biology president Samuel C. Silverstein, chairman of the department of physiology and cellular physics at Columbia University's College of Physicians and Surgeons, praises the report as "a superb statement of forward-looking principles and thoughtful, specific recommendations. "This is much more than a report on the roles of science in maintaining national competitiveness. This report emphasizes science as a frontier for the human imagination and spirit, science as an essential element in the creation of modern culture, and scientific literacy as essential for responsible citizenship." The report is available by writing to: Office of Science and Technology Policy, Science Division, Executive Office of the President, Washington, D.C. 20500; (202) 456-6130. Fax: (202) 456-6026. It is also available on Fed World and on the Internet at whitehouse.gov, sunsite.unc.edu, and other major online sites. Barton Reppert is a freelance science writer based in Gaithersburg, Md. (The Scientist, Vol:8, #16, pg.1, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------- TI : Some Researchers Are Pleased, Others Indifferent, As RU 486 Moves Toward Ready Availability In U.S. AU : KAREN YOUNG KREEGER TY : NEWS PG : 1 Biomedical researchers working with the antiprogestin RU 486 are expressing varied opinions on the mid-May announcement that the controversial drug will eventually be more readily available in the United States and how that availability may affect their investigations. Some scientists consider the transfer by Roussel Uclaf--the Paris-based manufacturer of RU 486--of U.S. patent rights, free of charge, to the Population Council, a New York-based contraception research group, to be very good news concerning the drug's use in the U.S., both as an abortifacient and in biomedical research. "I believe that when the compound is freely available [in the U.S.], more people will study it," says Leslie Z. Benet, a professor of pharmacy and pharmacological chemistry at the University of California, San Francisco. Researchers such as Benet say that the transfer should overcome some bureaucratic hurdles in obtaining the drug and allow them to conduct research in a less politically charged atmosphere. Others, however, say the move will probably not affect their inquiries into the drug's nonabortifacient uses, as they have experienced few problems in procuring RU 486 or pursuing their studies all along. "The fact that the Population Council holds the patent probably won't affect our research at all," says Steven Grunberg, chief of the hematology and oncology unit at the University of Vermont College of Medicine in Burlington. Some investigators are maintaining a wait-and-see position about the transfer's impact on future research, based on how the Population Council may perceive its interests in supporting and facilitating nonabortifacient RU 486 research. The agreement is the latest chapter in a long international controversy involving the drug's use and availability as an "abortion pill." But biomedical researchers have also been exploring the uses of RU 486 as a potential treatment for such diseases as breast cancer, endometriosis, meningioma, and Cushing's syndrome for the past decade (M.E. Watanabe, The Scientist, Jan. 24, 1994, page 14). In 1991, the Bush administration, allegedly in response to political pressure from conservative and anti-abortion groups, imposed an import alert on the drug, banning it from being brought into the U.S. for personal use as an abortifacient. Serious movement to lift the ban started shortly after Bill Clinton took office as president. In early 1993, officials at the Food and Drug Administration (FDA) along with Secretary of Health and Human Services Donna E. Shalala began negotiations with Roussel and the Population Council, which had been conducting abortifacient research on the drug since the early 1980s. In April 1993, the White House announced that the French company would agree to transfer the rights to RU 486 to the council. The final agreement was signed and went into effect on May 15. Details of the agreement, however, are proprietary information between Roussel Uclaf and the Population Council, according to council officials, and have not been released. `Thrilling' News Benet says he is "thrilled" by the news. He was chairman of an Institute of Medicine panel that reviewed possible clinical uses of the drug. The panel produced a report in 1993--Clinical Applications of Mifepristone (RU 486) and Other Antiprogestins: Assessing the Science and Recommending a Research Agenda (M.S. Donaldson et al., eds., Washington, D.C., National Academy Press). "It's a hassle to study [RU 486] under its present conditions," says Benet, referring to the existing government approval process for obtaining the drug for research purposes. Because RU 486 has not yet been approved by FDA for any use within the U.S., scientists--with data provided by the patent owner--must submit an investigational new drug (IND) application with FDA to obtain it for research or clinical studies. Once the drug is approved for use as an abortifacient in the U.S.--a more likely prospect now, given the government-brokered transfer--the paperwork and red tape involved in procuring its use in other studies should be greatly reduced, according to many researchers. Some scientists say that lately Roussel has been less than cooperative in supporting some aspects of basic research because the company has been under pressure from its German parent firm--Hoechst AG, located in Berlin--to curtail its involvement with the drug. These scientists and other observers maintain that Hoechst's stance on the matter stems from the religious convictions of its leaders. According to Wayne Bardin, vice president and director of biomedical research at the Population Council, the nonprofit organization plans to secure a manufacturer for the U.S. market within a year. Until then, however, principal investigators proposing new research projects would still have to go to Roussel to get the drug, he says. "Roussel is still providing it for Europe and people who want it in the U.S.," says Bardin. Impact Unclear On the other hand, some investigators expect the transfer to have little or no impact on their studies. They say that Roussel has been supportive of their work and the FDA requirements have never been a major impediment to obtaining the drug or conducting their research. Vermont's Grunberg--who is conducting clinical trials of RU 486 in treating nonresectable meningioma--points out that he has had cooperative, long-term relationships with both Roussel and the council, and that his is an "ongoing, FDA-approved project." Although he says "the transition will be seamless" for his lab, Grunberg and other researchers say that it is difficult to predict what the transfer will mean to future projects without knowing which types of nonabortifacient RU 486 studies the council intends to support and involve itself in now that it controls rights to the drug. "I'm not sure how broadly they define their mandate," says Grunberg. "Say, for example, if someone were interested in breast cancer, would they [the Population Council] see that as a cancer-related issue, not in their domain, or would they also define their domain as women's-health issues?" Population Council spokeswoman Sandra Waldman says the council "definitely wants to be involved in developing nonabortifacient uses," but the council is only at the stage of reviewing the literature on the different types of nonabortifacient research. Furthermore, she says, discussions within her group for setting up an entity to deal with this type of research have only just started. She notes that the patent rights to all known medical uses--including nonabortifacient ones--in the U.S. come to the council in the agreement. "That's one of the reasons why we're not even calling it RU 486 here anymore," she says, explaining that the council has decided to refer to RU 486 by its generic name, mifepristone. Waldman says that the council expects to begin clinical trials of RU 486 as an emergency contraceptive this fall. According to FDA and council officials, this means that RU 486 could be available in the U.S. in about two years. However, FDA spokesman Lawrence Bachorik cautions, even if the agency does sanction RU 486 as an abortifacient in the U.S., approval for other uses would not be covered. "The FDA approves a drug and its labeling for a specific purpose," he says. While RU 486 approval as an abortion pill would obviate the need for other projects to submit an IND--with its extensive data requirements and other paperwork--the council or the drug's future manufacturer would still have to file a supplemental new drug application, Bachorik explains. "To us [FDA], it doesn't matter" who manufactures and distributes RU 486, he says. "We want to make sure that there'll be consistent [quality in production of the drug]. We shouldn't have to worry about variation in the product." A Politicized Patent A major effect of the transfer, scientists agree, is that future basic research using RU 486 is likely to proceed in a less politicized atmosphere than before. They expect the council to choose a company to manufacture the drug that will not be deterred by pressure from anti-abortion groups. Benet predicts that the drug will be produced "by a company that isn't continually worried about the implications of liability from the publicity aspect" of being associated with RU 486. Although many researchers say they have a good working relationship with Roussel, others say that pressure from Roussel's parent company in Germany made the French firm reticent about dealing with RU 486 in general, thus affecting some areas of nonabortifacient research. William Regelson, a professor of medicine at the Medical College of Virginia, part of Virginia Commonwealth University in Richmond, alleges that these pressures stymied Roussel's pursuit of promising breast-cancer research in the late 1980s. "The reason why I look upon this as good news is that we will now have a rational company that is not lying to us [the biomedical research community]," says Regelson. "I think the basic reason why [Roussel] never pursued [the breast cancer research], even though I was given all sorts of excuses, was that they were told by the Hoechst people to lay off." A Fair Shake Researchers say the politics surrounding RU 486 as an abortifacient should not be relevant to investigating its other promising uses. John Link, director of the Breast Center and Cancer Institute at Long Beach Memorial Medical Center in California--where clinical trials of RU 486 to treat a form of breast cancer have just started--says he "would be very disappointed if the drug wasn't given a fair trial in breast cancer because the only people who would suffer are the women with the disease. "This aspect of the potential use of the drug really is beyond politics and socioeconomic issues," he adds. And, according to Michael Friedman, associate director of the National Cancer Institute Cancer Therapy Evaluation Program, the institute--which has been modestly funding RU 486 research, including Grunberg's, for several years--is keeping an open mind about new proposals for potential investigations into nonabortifacient uses of the drug. "We are very interested in seeing what drug companies and independent investigators will generate," says Friedman. (The Scientist, Vol:8, #16, pg.1, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: -------------------------------------------------------------- TI : Chaos Theory Finding New Applications In Life Sciences AU : NEERAJA SANKARAN TY : NEWS PG : 3 Researchers from a broadening array of life science disciplines say they are finding applications of chaos theory in their work. These scientists point out that it was recognition of the mathematical theory's relevance to their field that prompted psychologists four years ago to form the Society for Chaos Theory in Psychology, and a similar realization among life scientists that induced the organization to rename itself the Society for Chaos Theory in Psychology and the Life Sciences last year. And, society president Jeffrey Goldstein says, the list of diverse researchers utilizing the versatile concept is growing. Simply stated, chaos theory says that in a changing system, a small difference will be magnified exponentially over time. While exact outcomes are unpredictable, discern- able patterns emerge that help in understanding how varying conditions affect a system. Life scientists are finding the concept particularly useful in analyzing dynamical systems that characterize their work. The society was first established four years ago in San Francisco by a group of 40 scientists--primarily psychologists, along with some computer scientists and mathematicians. These individuals were interested in applying the principles of the theory in complex psychological and social systems. "Initially, mathematical psychologists were interested in chaos as a supplement to the statistical tools they used in their analyses," says Goldstein, a professor of organizational psychology at Adelphi University in Garden City, N.Y., who is applying the principles of chaos in studying theories of organization changes. But as the theory itself was developed further, he says, many psychologists began to realize its power as an analytical tool in its own right, because of its applicability to understanding systems that are not subject to statistical rules. Meanwhile, according to Mark Shelhamer, a biomedical engineer at Johns Hopkins University School of Medicine in Baltimore, this realization of chaos theory's utility has begun to carry over to researchers in other fields where complex systems abound. "Ever since [James] Gleick wrote his book [Chaos, New York, Penguin Books, 1987], describing the rise of this `new' field, everyone has been trying to find chaotic theory in his or her favorite system," Shelhamer says. "We were no exception." Shelhamer's work involves looking for chaotic patterns in reflexive eye movements. "The society began to attract these people, since there was no place for such a mix of people to meet and discuss these new methods," says Goldstein. This influx--the group now boasts more than 300 members from 10 countries--caused the Amity Harbor, N.Y.-based society to officially change its name last year to include the life sciences, Goldstein says. The society has attracted representatives from disciplines as diverse as neuroscience, physiology, economics, and philosophy--more even than the current name suggests. This expansion and diversification, says past president Sally Goerner, director of the Triangle Center for the Study of Complex Systems, a consulting firm in Chapel Hill, N.C., represents a "vindication of the life sciences and a reconciliation with physics." As Goerner, who has graduate degrees in both computer science and psychology, explains, "The deterministic principles of classical physics, which set the image of what science is 400 years ago, worked fine as long as they were applied to simple phenomena. "The life sciences were regarded almost as a second-class science [by the physical scientists] because they could not be made to fit within [deterministic] rules." Chaos theory, she says, is changing all that by providing life scientists with the "mathematical tools to meet the conceptual complexity" of their work. "The rest of the scientific community has been viewing this work with a `wait-and-see' sort of attitude," says Goldstein. "Only now are we starting to get the means to prove the validity of these new tools." Based on the papers and talks presented at the group's most recent annual meeting (held this year in June at Johns Hopkins) the society has put together a book, titled Chaos Psychology: A Reader, to be published by Lawrence Erlbaum Associates Inc. of Hillsdale, N.J., and scheduled for release in spring 1995. "This is the beginning of what we hope will be a series on the subject," says Goldstein, adding that the society has already begun collecting articles for a second volume. The group is also developing an electronic journal, which it hopes to launch sometime this winter. "It is only now that we have some of the computational and analytical tools to effectively explore chaotic behaviors in actual data from experiments," says Shelhamer. "The theory is giving us the power to ask questions about systems in a way we have not been able to so far. "For example, in my work, if the eye movements do appear deterministic rather than random, we can ask if the nervous system deliberately introduces the variability [chaos] and why," he says. "Is a chaotic system more flexible and adaptable than one with less variability?" Gary Burlingame, a group psychotherapist and researcher at Brigham Young University in Salt Lake City, Utah, explains the utility of chaos in his work: "Using the data from psychotherapy sessions, we can try and see if a chaos-like pattern emerges. While I will never be able to predict what Johnny is going to do at 5 P.M. tomorrow, we can use the theory to determine a fundamental global pattern of what happens in the sessions, and relate events to positive or negative effects on the group as a whole." The society's annual conference reflected the diversity of applications of chaos theory. Paul Rapp, a physiologist from the University of Pennsylvania in Philadelphia, discussed the evidence for chaos in the central nervous system of humans, while two materials scientists from the Maxwell Air Force Base in Alabama attempted to identify chaotic behavior in warfare systems. Still others discussed the theory's applicability in creativity, economics, psychotherapy, and psychopathology. For more information about the society, contact: The Society of Chaos Theory in Psychology and the Life Sciences, 29 Hayes Rd., Amity Harbor, N.Y. 11701; (516) 789-4145. E-mail: goldstein@auvax1.adelphi.edu. (The Scientist, Vol:8, #16, pg.3, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------- TI : DEFINING CHAOS AU : NEERAJA SANKARAN TY : NEWS PG : 9 Chaos theory garnered immense publicity last summer, when the bespectacled "chaotician" in Steven Spielberg's film Jurassic Park (based on Michael Crichton's novel by the same name) apparently predicted that a theme park's dinosaurs, cloned from fossil DNA, would escape from human control. Another well-known image of the theory at work is the Lorenz butterfly--the principle that a butterfly flapping its wings in North America could affect monsoons in China--which was used by meteorologist Edward Lorenz (now a professor, emeritus, at the Massachusetts Institute of Technology) to demonstrate the complexity of weather systems. But these popular perceptions of chaos theory may actually have served to give people a misconception of what the theory is really about and what it can be used for, according to Sally Goerner, a psychologist and computer scientist who is director of the Triangle Center for the Study of Complex Systems, a consulting firm in Chapel Hill, N.C. "These examples may give people the idea that there's no use in attempting to use the theory, since there will always be too many factors affecting a system," she says. "But absolute prediction is not what this is about." The real power of chaos theory, she says, lies in its potential as a tool to understanding patterns in various complex biological, psychological, and social phenomena. "Technically," says Jeffrey Goldstein, a professor of organizational psychology at Adelphi University in Garden City, N.Y., "chaos theory describes the behavior of a dynamical [changing] system, which is extremely sensitive to its initial conditions." Thus, he explains, a small change in the initial conditions leads to exponentially larger changes in the outcome, resulting in chaos, or the impression of randomness in a system. "People often confuse chaos with randomness, which is wrong," says Goldstein. "Anything can happen in a random system--it is entirely unpredictable--while a chaotic system is deterministic." "[A chaotic] system is deterministic in that behavior is completely specified at all times and there are no statistical [variables affecting] it," says Mark Shelhamer, a biomedical engineer at Johns Hopkins University School of Medicine in Baltimore. "Yet its behavior is unpredictable for all practical purposes." But over time, says Goldstein, chaotic systems settle down to following some sort of pattern. These patterns can be discerned by using attractors--pictorial representations of how systems behave over time, obtained by plotting each state against its previous one. "Simple systems have very simple attractors," explains Goldstein. "Take a pendulum, for example. An unpushed pendulum would eventually approach a single point--hence referred to as having a point attractor--and a regularly oscillating one would settle down to an elliptical pattern. "A chaotic system has a far more complicated attractor, but on closer observation you can see that it starts to follow some sort of pattern over time," Goldstein says. "At no instant will the system ever go to a previous state, but it can get infinitesimally close." "Science is about looking for regularities or patterns in nature," says Gary Burlingame, a group psychotherapist and researcher at Brigham Young University in Salt Lake City, Utah. "A chaotic system follows a nonrepeating, yet self-similar, recognizable pattern." Goerner agrees. "Chaos theory is actually the study of organization, structures, and patterns," she says, "and these are what the life sciences are all about. Psychology, for instance, has always been a study of patterns. Finally we are getting the mathematical tools to meet the conceptual complexity of our systems." (The Scientist, Vol:8, #16, pg.9, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: NOTEBOOK ----------------------------------------------------------------- TI : Regal Rewards TY : NEWS (NOTEBOOK) PG : 4 The Royal Society, the United Kingdom's national academy for promoting both the natural and applied sciences, recently announced the winners of two of its prestigious awards: The Royal Society Mullard Award, consisting of a silver gilt medal and Pounds Sterling 2,000 (approximately $3,500 U.S.), will be shared by microscopist John White of the Integrated Microscopy Resource at the University of Wisconsin, Madison; and cell biologist Brad Amos, computer scientist Richard Durbin, and engineer Michael Fordham, all of the Medical Research Council laboratory of molecular biology in Cambridge, England. The researchers are being recognized for developing a laser confocal imaging system that improves the clarity and definition of microscopes, allowing the examination of structural details within a cell. This annual award goes to an advancement in science, engineering, or technology that leads directly to national prosperity in the U.K. Meanwhile, engineers Trevor Whittaker, Raghu Raghunathan, and Adrian Long of Queen's University in Belfast, Ireland, and Alan Wells, the former director general of the Welding Institute in Cambridge, England, were named winners of the Royal Society Esso Award for 1994 for designing and developing a shoreline wave power station--a device that converts the energy from ocean waves to electricity. Whittaker, a professor of coastal engineering, headed the team of scientists who built and are currently testing a prototype version of the station off the western coast of Scotland. The Esso award--consisting of a gold medal and Pounds Sterline 2,000-- is given annually to an outstanding contribution toward the efficient mobilization, use, or conservation of energy resources. (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ----------------------------------------------------------------- TI : Stamp Of Approval TY : NEWS (NOTEBOOK) PG : 4 The American Association for the Advancement of Science is seeking support for its campaign to create a commemorative postage stamp to honor the organization's 150th anniversary in 1998. The AAAS Commemorative Stamp Committee will submit its proposal for a first-class stamp to the Citizen's Stamp Advisory Committee--an 11-member group appointed by the Postmaster General--next March after the AAAS annual meeting in February. Letters of support and suggestions for a theme and design can be sent to the AAAS Commemorative Stamp Committee, Office of Communications, Room 801, 1333 H St., N.W., Washington, D.C. 20005; (202) 326-6440. (AAAS encourages sending letters via the United States mail rather than by electronic mail to indicate a potential market for the stamp.) (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ----------------------------------------------------------------- TI : Mathletes TY : NEWS (NOTEBOOK) PG : 4 Among several international competitions taking place this summer--the World Cup, the Goodwill Games, and the Tour de France, to name a few--perhaps the U.S.'s best showing was the performance of a team of American high school students last month in Hong Kong. Competing against teams from 69 other countries, the six students took first place in the 35th International Mathematical Olympiad with an unprecedented six perfect scores. Jeremy Bem of Ithaca High School in New York; Aleksander L. Khazanov of Stuyvesant High School in New York City; Jacob A. Lurie of Montgomery Blair High School in Silver Spring, Md.; Noam M. Shazeer of Swampscott High School in Massachusetts; Stephen S. Wang of Illinois Mathematics and Science Academy in Aurora; and Jonathan Weinstein of Lexington High School in Massachusetts each received gold medals. The top five finishers, in order, at the Olympiad were: the U.S., China, Russia, Bulgaria, and Hungary. (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ----------------------------------------------------------------- TI : Illuminating Bioluminescence TY : NEWS (NOTEBOOK) PG : 4 Aided by the polymerase chain reaction (PCR), marine biologists from the Scripps Institution of Oceanography, La Jolla, Calif., have been able to shed some light on the physiology and genetics of bioluminescent bacteria. A research team led by Margo G. Haygood, an assistant professor at Scripps, studies the glowing bacteria that live inside tropical flashlight fish and deep-sea anglerfish to better understand these little-studied microorganisms. Until recently, the bacteria of these fish could not be cultured in the laboratory. But, using PCR, Haygood made copies of the fish bacteria's genes and compared them with those of other bioluminescent bacteria. These studies indicated that the bacteria were members of two previously unknown taxonomic groups. Research on the basic biology of bioluminescent bacteria has practical applications in detecting contaminants in water and for medical diagnoses, the researchers say. (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ----------------------------------------------------------------- TI : Importing Botanical Knowledge TY : NEWS (NOTEBOOK) PG : 4 With the addition of a recent shipment of 62,500 pressed and mounted specimens of Chinese plants, the Missouri Botanical Garden's collection of such flora has become the largest outside of China, the botanical garden announced. The acquisition is part of the Flora of China project, a six-year-old Sino-American effort to revise, condense, and translate into English China's huge catalog of plants. China currently has around 30,000 species of vascular plants; 7,000 are of horticultural importance and nearly 5,000 are used for medicinal purposes. For example, Trichosanthes kirilowii, a member of the gourd family found only in China, is being studied for its activity in combating the HIV virus. (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ----------------------------------------------------------------- TI : The Pocket Merck TY : NEWS (NOTEBOOK) PG : 4 The Merck Manual, one of the most widely used medical reference books in the world, is now being produced in a pocket-sized electronic version as part of the Franklin Digital Book System of Franklin Electronic Publishers Inc., Mount Holly, N.J. The manual, now in its 16th edition, is put out by the publishing arm of Merck & Co. Inc., Whitehorse Station, N.J. The electronic "book" measures 5" x 3" x 1/2" and weighs 4 ounces. Data cards containing up to 200 megabytes of text each snap into the back of the unit, which features a five-line display. (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ----------------------------------------------------------------- TI : Changing Monikers TY : NEWS (NOTEBOOK) PG : 4 The American Council of Independent Laboratories, a national trade association representing independent commercial engineering and scientific laboratory, testing, consulting, and R&D firms, has adopted a new name, sort of. As of June, the Washington, D.C.-based organization has become ACIL: The Association of Independent Scientific Engineering and Testing Firms. According to ACIL officials, the new name reflects changes in the industry and the expansion into new technology on the part of ACIL's 400- plus members. This is the second name change for the 57-year-old association; it was founded in 1937 as the Association of Commercial Laboratories, and was renamed in the American Council of Independent Laboratories in 1952. For information, contact the organization at 1629 K St., N.W., Suite 400, Washington, D.C. 20006; (202) 887-5872. Fax: (202) 887-0021. (The Scientist, Vol:8, #16, pg.4, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------------ TI : Watchdog Group On Lookout For Misuse Of Science In Policymaking AU : KAREN YOUNG KREEGER TY : NEWS PG : 6 Scientists from a variety of disciplines in industry, academia, government, and other areas are reportedly lending their support to The Advancement of Sound Science Coalition (TASSC), an organization that has pledged to scrutinize the quality of scientific research that influences federal regulations. According to former New Mexico governor Garrey Carruthers, the founder and chairman of the ad-hoc coalition of scientists, academicians, industry representatives, and former public officials, TASSC aims to encourage policymakers to avoid or reconsider decisions based on "poorly executed research to justify preconceived policies." Carruthers says the Washington, D.C.-based group's main purpose is to advocate the basing of scientific studies affecting federal regulations--including those concerning food, agriculture, and the environment--on standard scientific principles rather than on political expediency or pressure. By this, he says, he means relying on research that is peer-reviewed, replicated, and unbiased. "So much of the crusade kind of science is [stated in] absolute truths," says Carruthers. "It's almost divine in nature. The crusaders never qualify their stuff. They never have it peer-reviewed and they never replicate their experiments." Among the efforts recently undertaken by Carruthers's group is a scientific challenge to advocacy groups opposed to the use of the growth hormone bovine somato-tropin in dairy cows, which has been approved by the Food and Drug Administration (FDA). TASSC is also supporting FDA's sanctioning of the genetically engineered Flavr Savr tomato--which also has been facing strong opposition from some quarters. Carruthers says the coalition has made its views known through a variety of means--newspaper opinion articles, press releases and news conferences, speeches, and letter-writing campaigns directed at govern- ment officials. Carruthers says that TASSC has acquired about 550 statements of support, a third of which have come from scientists, since its launch last November. Backers of the coalition as well as outside observers say the group has the potential to provide scientists and policymakers at federal agencies with information that might not otherwise be brought to their attention when they formulate governmental regulations. However, this same group of supporters and observers has some reservations about a science-advocacy organization's involvement in politics. Jeff Davidson, executive director of the Pennsylvania Biotech- nology Association, a trade organization based in State College, Pa., says the coalition can make a useful contribution to policymakers and the general public because it emphasizes science, as opposed to economic or political interests, as criteria for decision-making. But, he adds, he would be concerned if the group were to begin addressing controversial issues on other than a scientific basis and, thereby, drift from its "original mission." Building A Coalition Carruthers, governor of New Mexico from 1987 to 1990, says he started TASSC last year with the help of APCO Associates Inc., a Washington, D.C.-based public affairs firm, which is handling communications for the organization, among other administrative functions. APCO also provides some office space for the coalition's activities. Carruthers was a professor of agricultural economics at New Mexico State University in Las Cruces before entering politics in the early 1980s. He was also an assistant secretary at the Department of the Interior from 1981 to 1984. He says he founded the coalition because "it began to occur to me that science wasn't being used very often in public policy development. Most of this development was based more on emotion and vested interests than it was on scientific results." Since last November, he has sent out a letter of introduction to researchers and others explaining the goals and purpose of the coalition. In the letter, the recipients were invited to fill out a statement of support, which allowed TASSC to use the scientists' names on its list of backers. Carruthers says that the coalition currently has a list of about 180 scientists and academicians from a wide variety of disciplines to address specific scientific issues. About 130 of these 180 researchers--a group that has grown from about 30 scientists since the coalition's inception nine months ago, Carruthers says--work at universities and research centers, with the remainder coming from industry, consulting firms, government agencies, and advocacy groups. The list includes many scientists with high standing in their disciplines and a degree of public visibility, such as Bruce N. Ames, a professor of biochemistry at the University of California, Berkeley, and director of one of NIH's 18 National Institute of Environmental Health Sciences-supported research centers. Also on the list are scientists from a wide range of industrial firms, including such biotechnology companies as Biosys in Palo Alto, Calif., and Mycogen Corp. in San Diego, and such giant companies as 3M Chemicals and General Motors. Thus far, according to coalition officials, funding for TASSC has come from individual donations from almost 125 researchers, businesses, and other supporters, ranging from tens of dollars to a few thousand dollars. Carruthers adds that at this point the coalition has no foundation support, but plans to seek this type of funding by the end of this year. For now, Carruthers is the coalition's only officer; however, he says, TASSC plans to form an executive committee and several working groups in the future, as the coalition grows and takes on more causes. So far, he says, the coalition has been operating generally on an "ad hoc" basis, taking on issues that are brought to its attention by various supporters. Indeed, most of the positions the organization has addressed have been on issues affecting many of TASSC's industrial backers, including chemical, biotech, agricultural, and petroleum companies. Coalition statements cite the Natural Resources Defense Council's study on Alar as an example of poor research leading to bad public policy. This 1989 study, along with a story on the television news program "60 Minutes," suggested that Alar, a plant-growth regulator used in the apple-growing industry, caused cancer in children. The resulting debate about whether Alar was a carcinogen or not--which Carruthers and others say was never demonstrated scientifically-- led to the banning of the substance. This decision, TASSC and other critics charge, caused unnecessary financial hardships to apple growers. In a recent TASSC newsletter, the organization announced the development of a "Bad Science News Alert" system that will "immediately" fax supporters news of "policy decisions based on unsound science." The key to identifying "unsound" science, says Carruthers, is to "look for scientists that talk in a particular way. A lot of bad scientists say: `I can prove to you that this product is dangerous to your health.' [Good] scientists qualify their claims. They say things like: `There's abundant evidence. The majority of the evidence supports. . . ' " Qualified Support Donald Stedman, Brainerd Phillipson Professor of Chemistry at the University of Denver, says that he decided to become involved with TASSC because "policymakers ought to be aware that they need good science. I think part of the problem is that they are not getting good science from their own bureaucrats who are themselves politicized." Stedman has written statements critical of government regulations on air quality and auto emissions for the coalition. For example, in a recent statement he said that "many scientific reasons exist for opposing EPA's [Environmental Protection Agency] mandate for the use of ethanol in the reformulated gasoline market," including a lack of scientific evidence that ethanol is cleaner than some other fuel products. Warren Cheston, director of external affairs for the Wistar Institute of Anatomy and Biology in Philadelphia, is also among the scientists who have given their support to the coalition. He says the group's intended goals could be beneficial to such federal agencies as FDA, EPA, and the Department of Agriculture because these agencies regularly rely on scientific and technical data in formulating their policies. Some of the coalition's supporters caution, however, that to remain credible TASSC must maintain a clear balance among its many constituencies. Other researchers have chosen not to sign, citing doubts about the organization's ability to objectively look at the issues. Gary Comstock, an associate professor in the philosophy department and coordinator of the Bioethics Program at Iowa State University in Ames, says he was sent a letter inviting him to join TASSC, probably because he was a speaker at the Biotechnology Industry Organization's (BIO) Eighth International Biotechnology Meeting held in Toronto last May. He says he debated whether to join, but, after reading the letter and enclosed fact sheets, decided against it because "I was concerned that this group would turn out to be a front for pro-industry political activity and not a group in which both sides of the issues were represented." Although Wistar's Cheston says he is a proponent of the coalition's mission, he also says he would have to rethink his position if its leadership turned out to have a pre-set agenda. "If there's a political agenda, I suspect quite a few of us who joined will decide not to stay on because, as a scientist, one tries to avoid the political aspects of [policy-making]. It's not what we ought to be involved in. We ought to be involved in just providing information to the people who make those political and social decisions." But Stedman contends that one of the coalition's strengths is that "it has no specific backing from any particular well-heeled industry." He adds that TASSC cannot be self-supporting unless it gets money from parties on each side of an issue, "in order to be perceived to be holding a rather careful middle ground." And Carruthers maintains that the diversity of the people behind the coalition will prevent it from becoming single-minded. "It's a very diverse group, and that was intentional," he says. "We didn't want to be singled out as `the petroleum industry group' or `the farm group.'<|>" He points out that letters of invitation to support the coalition were sent to researchers in a wide variety of disciplines, from physiology to philosophy. Open Debate Government officials like Rob Brenner, director of the office of policy analysis and review in the office of air and radiation at EPA, say they welcome the open debate on policy issues that groups like the coalition foment, as long as both sides of an issue are aired. Brenner says EPA "is always having to make decisions [on environmental regulations] in the face of [scientific] uncertainty. Therefore, what science can do is narrow the uncertainty." He says that groups like the coalition can be helpful by suggesting ways to reduce the scientific uncertainty surrounding policy issues such as setting air- and water-quality standards and suggesting whether it makes sense for policymakers to act in the face of this incertitude. He adds, however, that it is not helpful when "science groups claim that if you just get the science right it will tell you what to do." For more information on the coalition, contact Carruthers at The Advancement of Sound Science Coalition, P.O. Box 18432, Washington, D.C. 20036; (800) 369-6608. Fax: (800) 251-5253. (The Scientist, Vol:8, #16, pg.6, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: OPINION ------------------------------------------------------------ TI : On The Dialogue Between Science And Religion: Our Readers Respond TY : OPINION PG : 12 Editor's Note: A recent essay in The Scientist ("Science, Religion Must Share Quest For Global Survival," May 16, 1994, page 12) sounded a call on behalf of Planet Earth by Van Rensselaer Potter, Hilldale Professor of Oncology, emeritus, at the University of Wisconsin, Madison. In his essay, Potter praised what he considers to be unprecedented efforts by German theologian Hans Kng to forge, for the sake of humankind's survival, a creative and specifically targeted alliance between science and religion. Potter's recommendation that religious and scientific leaders move immediately to foster constructive bioethical dialogue that would yield such an alliance elicited an unusually vocal response from The Scientist's readers. Following are excerpts from several of these responses. I was glad to see someone making an effort to get the scientific community to recognize its important role in contributing to the ethical issues confronting society. I sense, however, the presence of a factor that may undermine the discourse between science and religion that Potter's essay encourages--a factor I have observed during the course of my efforts to get scientists to address the ethics of using the tissue of aborted fetuses. That is, how can we gain consensus on the importance of controlling population growth and then construct an ethical framework for implementing controls if we cannot even generate a dialogue on the simple question of what is a human being? Although there is a plethora of scientific evidence relating to this question as it arises in the context of prenatal life, I have been impressed by the unwillingness of most scientists to discuss the matter. I fear that the current burden of "political correctness" stifles much of the discussion that should occur in this and other areas where science can bring relevant information to bear. Even more problematic will be getting religiously diverse groups to agree on the fundamental questions, owing to the different premises held by each. KEITH A. CRUTCHER Department of Neurosurgery University of Cincinnati Medical Center 231 Bethesda Ave. Cincinnati, Ohio 45267 E-mail: crutcher@beh.san.uc.edu ------------------ I enjoyed Potter's article very much. However, I dare say he is more optimistic than I. It may well be that Judaism, Islam, and Christianity are fundamentally incompatible with rational approaches to humankind's continued existence on this planet. (Eastern religions are quite a different matter.) Regardless of what some theologians espouse, leaders and followers of these religions seem quite content to use/abuse the planet's resources willy-nilly, since their "real" existence will be in the "afterlife" and since, in their view, man has been "ordained" by their god to be the lord of creation, not merely its steward. When push comes to shove, probably very few of the espousers of these religions would agree that global survival has primary value compared to attainment of their heaven or nirvana or paradise or whatever. To them, Hans Kng is the aberration; Jerry Falwell or Pat Robertson or John Paul II is not. By the same token, I wonder if it is realistic to look to scientists to guide us out of the morass. There are, to be sure, eminent and non-eminent scientists who think deeply about their larger existence and responsibilities. But a myopic worldview, apathy, and greater concern for acquisition of position, power, and reward afflict the scientific establishment to at least the same extent as the general population. In the final analysis, it might be more effective to broaden the vision and strengthen the training of elementary schoolteachers so that questions about and a concern for global issues can be inculcated early on. THOMAS SNEIDER Department of Biochemistry and Molecular Biology Colorado State University Fort Collins, Colo. 80523 E-mail: tsneider@vines.colostate.edu ------------------- I greatly appreciate the depth and rationality of Potter's very timely article regarding global survival and the need to effect beneficial "dialogue between secular science and organized religion." Of course, global survival is highly important; more important, however, is the quality of human existence. Thus, high-quality survival ultimately should be the worldwide goal toward which wise and determined scientists and organized religionists must work. After being joined by many others, they should be able to attain the goal. I am pretty sure that, in a conceptualization of the desired "dialogue," one would want it to take a variety of forms, to be dispassionate, and to be broad in its concerns. (Surely, for example, such dialogue could be effective in moving toward greater global education, and even greatly increased industrial movement, aimed at the prevention, treatment, and disposal of waste.) I agree that a most urgent need is for this dialogue between science and religion to focus on, as Potter says, "such important population-problem specifics as abortion, contraception, and reproductive freedom for women." That and related aspects of population control are central to global survival. We should not conclude that the situation is hopeless. Concerned scientists, religionists, and all others must move toward far greater constructive interaction and reasoned action. HARRY G. DAY Department of Chemistry Indiana University Bloomington, Ind. 47405 -------------------- Regarding the shared quest for global survival between science and religion, I am impressed with Potter's willingness to address a controversial subject. But this is not an unabashed fan letter. Three years ago I attended a consultation on the environment organized by the Union of Concerned Scientists and the Jewish Theological Seminary. During the course of the gathering, it became apparent to me that when scientists talk about a cooperative effort between science and religion, they are really talking about religion's redefining its priorities and philosophies under the guidance of science. Scientists do not hold open the idea that religion has something to say about the way scientists conduct themselves, think about life, or interact with the natural world. Indeed, far from religion's being intolerant and dismissive of scientific knowledge, it is scientists who confuse knowledge with wisdom by dismissing the contributions that religion makes on its own terms to global survival. As for population control, I agree that overpopulation threatens us all. But to call for stasis or decline in current population levels is to call for status quo in terms of all societies' world presence. And that is not just: I will encourage Jews to stop having lots of babies when you find me 6 million volunteers to restore us to the critical mass we need to ensure the presence not just of human animals, but of a balance of human variety in this world. Without a philosophy of a higher power--I call it "God"-- there is no reason to ensure survival. After all, short of ego, without a "religious" mandate, what is the purpose of maintaining life? There's a question science doesn't presume to answer. JACK MOLINE Rabbi Agudas Achim Congregation 2908 Valley Dr. Alexandria, Va. 22302 E-mail: p00779@psilink.com --------------------- I welcome Potter's clarion call for religious and scientific leaders to combine their efforts in a common ethic for human survival and the well-being of our home--Planet Earth. I would be remiss, however, if I did not point out that Hans Kng was not the first to bridge the gap of religion and science, nor the first to invoke human survival, particularly with respect to the problem of overpopulation, as being the focus of our "stewardship." I think the seminal contribution in this regard rests with Earthkeeping: Christian Stewardship of Natural Resources (L. Wilkinson et al., Grand Rapids, Mich., Eerdmans, 1980). In that book, the authors state: "If we are to exercise care for each other, as well as for the planet entrusted to us, we must temper our abilities with wisdom and love in order to achieve consciously what has been the case through most of human history--a relatively stable population. The alternative is to let the blind destructiveness of starvation, war, and disease do what we should do as a matter of careful stewardship. In order to maintain the planet as home to a million different kinds of creatures, it is necessary to have a limited human population. To work toward such a population is clearly one of the tasks of Christian stewardship." This decidedly Christian position may not fit within the confines delimited by Kng's ecumenical yardstick. If anything, it testifies to the rift among Christians, since the non-Catholic position is unequivocally out of step with that of the Vatican. ROBERT WONDERGEM Department of Physiology East Tennessee State University Box 70576 Johnson City, Tenn. 37614 ---------------------------- Baha'u'llah (1817-1892), the founder of the Baha'i faith, stated more than a century ago that science and religion are the two most potent forces in human life. He advocated the harmony of science and religion as a necessary step toward the establishment of a global civilization. Since then, humanity has made quantum leaps in science and technology, yet spiritually it has declined, in part because of clinging to irrelevant and old religious beliefs and in part because of neglecting its own spiritual needs. We travel at the speed of sound and communicate at the speed of light yet are unable to resolve personal conflicts, to say nothing of those of global dimension. Potter's suggestion that science and religion should join together in the struggle against environmental degradation and population explosion is vital for the survival of humanity; however, it should be broadened to include the improvement of the quality of man's intellectual, social, moral, and spiritual life. Baha'u'llah taught the unity of humanity, a concept that is spiritual yet supported by sciences such as physiology, psychology, and anthropology. The acceptance of this concept will elevate humanity to a new paradigm compatible with a global system. Within this paradigm, science and religion can effectively cooperate and work to solve the planet's critical problems. Science offers effective means to pragmatically resolve these problems, while religion inspires, motivates, and transforms people to do the tasks. Neither can do this alone. KEYVAN NAZERIAN United States Department of Agriculture 3606 E. Mount Hope Rd. East Lansing, Mich. 48823 ----------------------- (The Scientist, Vol:8, #16, pg.12, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: COMMENTARY ------------------------------------------------------------ TI : Pure Genius: It's Great If You Have It--But It's Not A Prerequisite To Success In Science AU : Eugene Garfield TY : OPINION (COMMENTARY) PG : 13 Two recent articles--one in the New York Times Magazine, the other in Nature--set me to thinking about the role pure genius plays in stimulating and sustaining the scientific enterprise. On one hand, individual displays of awesome intellect can certainly be inspiring; but I suspect they can also be discouraging for budding researchers who realize that their grasp on things will never equal that of an Einstein, Fermi, or Feynman. And that's truly unfortunate. In the Times Magazine piece ("Murray Gell-Mann: The Man Who Knows Everything," May 8, 1994, page 24), writer David Berreby reports on the man who won the 1969 Nobel Prize in physics for his classification of elementary particles. Berreby makes no secret of his reverence for Gell-Mann and his vast erudition--a scope of interest and knowledge that extends far beyond physics. The superscientist who discovered the quark, Berreby points out, is also, among other things, an accomplished linguist, ornithologist, and entomologist--knowledgeable on subjects as diverse as tropical diseases, kissing bugs, and the writings of James Joyce. Fifteen years ago, by the way, I noted in an essay the etymology of "quark," which Gell-Mann had come across in Joyce's Finnegans Wake (Current Contents, Issue #4, Jan. 23, 1978; reprinted in Essays of an Information Scientist, Vol. 3, Philadelphia, ISI Press, 1980, pages 393-9). In the Nature article ("Intellectual Mastery Over Nature," 368:109, 1994), writer Peter Harman--a historian at England's University of Lancaster--discusses a recently published collection of essays on the life and work of German scientist Hermann von Helmholtz (1821-1894), whom Harman calls "a scientific polymath of extraordinary accomplishment." The book, titled Hermann von Helmholtz and the Foundations of Nineteenth-Century Science (David Cahan, ed., Berkeley, University of California Press, 1994) explores the contributions of this verifiable genius, whose intellectual excursions extended over many fields: mathematics, physics, physiology, hydrodynamics, and the philosophy of science. He even developed a theory of music, Harman points out. Of course, accounts of Gell-Mann, von Helmholtz, and other such remarkable scientists make fascinating reading. And studying the lives of the "giants" should not in any way deter others from aspiring to careers that, while offering little in the way of legendary achievement, are just as important to scientific progress. I've devoted much of my life as an information scientist to monitoring, analyzing, and reporting on the contributions of scientists--from Nobelists like Gell-Mann to bench researchers whose publishing rec-ords are qualitatively and quantitatively minuscule by comparison. I have concluded that all who strive to unlock the mysteries of nature participate as equals in keeping the great machine of science in motion--no matter how great or small their success. Moreover, I believe that the scientific enterprise would be neither complete nor fruitful if the work of all researchers were not monitored, described, defined, and otherwise put into intelligible form. Every bit as important to science is the work of the librarians, encyclopedists, historians, journalists, and information scientists like me. We are inclined by nature and intellect to spend our days not toiling at a lab bench, but reflecting on the past, assessing the present, and, one hopes, helping to shape the future of research. One must not be humbled, then, in learning about a Gell-Mann or a von Helmholtz. All of us, whether working at the core or on the periphery of scientific discovery, share in fostering progress. Doing science--seeking and measuring relationships among phenomena--is, for the most part, an a priori process. Mapping the world of science is a distinctly different, a posteriori process. Both are necessary. Today, many aspiring scientists are attempting to build careers in a world where, owing to a precarious national economy, research positions are becoming less available. Young men and women who may once have dreamed of winning a Nobel Prize will find themselves having to apply their scientific training instead to jobs in such fields as law, publishing, and information science. For these people, mental agility, readiness to adapt, intellectual honesty, and an open mind will be of great value. And since most of the "giants" of science have embodied these qualities, studying their lives and achievements should serve to instruct and inspire. (The Scientist, Vol:8, #16, pg.13, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: LETTERS ------------------------------------------------------------ TI : Corporate Boards AU : Charles G. Smith TY : OPINION (LETTERS) PG : 13 A follow-on comment to the recent correspondence regarding scientists on corporate boards (R. Finn, The Scientist, Jan. 10, 1994, page 21; I.S. Johnson, The Scientist, May 2, 1994, page 13) is in order. Further to the excellent comments of Johnson, it should be pointed out that serving on boards of directors for young companies is not without potential personal financial exposure as a result of the frequent legal action directed against board members in the United States. It has been reported that approximately one-third of all public biotech-type companies have been sued by shareholders. I support Johnson's comment about the great value of outside scientists with drug-development experience serving on boards to help guide the decision-making process. Many of us who serve with small company boards have yet to realize any significant monetary gains from stock appreciation (the major reward to board members) because the companies are still in early stages of commercial development. On the other hand, many scientific directors have struggled through adversarial legal proceedings that could not have been imagined in light of the sincerity, diligence, and caution with which their boards operate. As a result, some of us have made the decision to not serve on boards of directors. In my opinion, lack of participation by experienced scientists at the board level will, in the long run, be detrimental to the interests of shareholders. CHARLES G. SMITH Pharmaceutical Consultant P.O. Box 9814 Rancho Santa Fe, Calif. 92067 (The Scientist, Vol:8, #16, pg.13, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Science Contests AU : Michael Holloway TY : OPINION (LETTERS) PG : 13 Regarding Lee Katterman's article about the Westinghouse Science Talent Search [The Scientist, May 2, 1994, page 1], a portion of the eligibility requirements should be of interest to many life science researchers. The following is taken from the Westinghouse Science Talent Search entry form. "VERTEBRATE ANIMALS: No projects involving live vertebrate animal experimentation will be eligible. However, if a student is working in a laboratory where animal experimentation is taking place, the student's research is eligible for entry in the Science Talent Search (1) if the student has no physical contact with the animals; (2) if the material on which the student is working (tissue, blood, etc.) is supplied to the student by the supervising scientist; and (3) if the animals involved are sacrificed, it is for some purpose other than the research being done by the student. In these cases, a statement from the supervising scientist attesting to the above must be included with the student's Science Talent Search research report." I feel that the only reason for this clause is to capitulate to a perceived threat of animal-rights protests. It sends the wrong message about the use of animals in research and excludes many worthwhile projects in biology. MICHAEL HOLLOWAY Department of Pediatrics State University of New York Stony Brook, N.Y. 11794 E-mail: mhollowa@epo.som.sunysb.edu (The Scientist, Vol:8, #16, pg.13, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- NXT: ------------------------------------------------------------ TI : Literature Reviews AU : Thomas H. Maren TY : OPINION (LETTERS) PG : 13 The article by Paul McCarthy in the May 30, 1994, issue of The Scientist [page 1] on peer review struck a responsive note. I, too, have come to distrust journal reviewers and National Institutes of Health pink sheets despite good fortune with publications and grants over many years. Responsibility and devotion are far less than they were one and two generations ago, perhaps a mirror of our end-of- century society. But I have a solution, at least for journal reviews. I do favor signed reviews, but this will probably never fly. But why shouldn't reviewers be required to document their comments, citing appropriate literature? Can't these godlike, nameless shadows be brought into scientific focus? THOMAS H. MAREN University of Florida College of Medicine P.O. Box 100267 Gainesville, Fla. 32620-0267 (The Scientist, Vol:8, #16, pg.13, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- WHERE TO WRITE: Letters to the Editor The Scientist 3501 Market Street Philadelphia, PA 19104 Fax:(215)387-7542 E-mail: Bitnet: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com ===================================== NXT: RESEARCH ------------------------------------------------------------ TI : Building On Firm Foundations: Structural Biology Is Coming Of Age AU : NEERAJA SANKARAN TY : RESEARCH PG : 14 Structural biology--the study of the three-dimensional shapes of biological macromolecules--has always been a facet of biological research, from the detection of cells in the earliest days of microscopy in the late 17th century to the first X-ray crystallographic images of proteins in the 1950s and the development of DNA technologies that made proteins more accessible for study through the 1970s and 1980s. But over the past 10 years, scientists agree, this field has been experiencing a boom. Its growth is evidenced by the impressive proliferation of protein crystallographic data and research being produced by various segments of the biological community, spurred by technological breakthroughs from a wide array of disciplines. The forums and facilities sprouting up to accommodate this flood of information and interest are further indications of the discipline's rapid emergence. "Structural biology is now at the stage DNA research was at about 50 years ago," says Guy Riddihough, editor of Nature Structural Biology, one of two peer-reviewed journals devoted entirely to the subject that were created in the past year to keep up with the volume of new information. Structure, published by the London-based Current Biology Ltd., was launched in September 1993, and Nature Structural Biology--an offshoot of the journal Nature and published by Macmillan Magazines Ltd. in London--came out this past January. In just the past three years, Brookhaven National Laboratory's Protein Data Bank (PDB) in Upton, N.Y., has doubled the amount of data on protein structures it has received from researchers throughout the United States, PDB officials say. PDB was established in the early 1970s by the National Science Foundation to collect and store such data. It is now funded jointly by the U.S. Department of Energy (DOE), the National Institutes of Health, and NSF. "The number of protein structures [PDB is] receiving is rising exponentially," says Edwin West- brook, director of the new Advanced Photon Source (APS) Structural Biology Center at Argonne National Laboratory (ANL) in Illinois. "They are having trouble keeping up." DOE is spending nearly a half-billion dollars to build APS, a circular--more than a half-mile in cir- cumference-- synchrotron X-ray facility that will produce high-intensity X-rays. DOE has invested a further $15 million to establish the APS Structural Biology Center at the lab, which will use the synchrotron's X-rays for various structural studies. APS resources will also be used by two other structural biology research centers currently being constructed nearby: one by the University of Chicago and the other by a newly created consortium of pharmaceutical firms called the Industrial Macromolecular Crystallography Association. The Search For Structure Modern structural biology focuses on the three-dimensional configurations of macromolecules--in particular the proteins and nucleic acids--that make up the cells and perform various important biological functions such as DNA replication, photosynthesis, and the formation of antibodies (see accompanying story). David Davies, an X-ray crystallographer and a researcher at NIH, says that the discipline really took hold in the 1930s and 1940s with the application of X-ray diffraction to obtain the shapes of molecules from crystals. In 1953, James Watson and Francis Crick, using crystallographic data and molecular modeling, proposed the structure of DNA, which revolutionized the field of genetics. According to Wayne Hendrikson, an editor at Structure, this first determination of a macromolecule's configuration ushered in the field of modern structural biology. Also during that time, British crystallographers Max Perutz and John Kendrew began to produce the first structures of proteins such as hemoglobin and myoglobin. But structural studies on proteins proceeded at a modest pace, until, fueled by technical advances in X-ray crystallography, nuclear magnetic resonance (NMR), recombinant DNA technology, and computing, it has come into full flower over the last decade. Driving Forces In addition to the technological achievements that have facilitated continuing breakthroughs in structural biology, the field has been driven by advances in other disciplines, such as physics, chemistry, biochemistry, and biophysics, researchers say. For instance, the guiding principles of methods like X-ray crystallography and NMR, required for determining structures at the atomic level, are rooted in physics and chemistry. X- ray crystallography uses the diffraction patterns of high- intensity X-rays bounced off protein crystals to determine the locations of the atoms within the crystals. NMR spectroscopy--a more recent technique--is used to determine the structures of proteins that are still in solution. "NMR was developed as a method to [determine] protein structures in the late 1970s," says Gerhard Wagner, a professor of biological chemistry and pharmacology at Harvard Medical School in Boston. "Essentially, each hydrogen nucleus [in the molecule] has a characteristic resonance at a particular frequency, depending on the atoms around it." The measurement of these various resonances gives the distances between different nuclei, enabling the three-dimensional structure of the molecule to be calculated, he says. Adding to the value of these techniques in structural biology has been the field of molecular biology, which has seen considerable progress of its own in the past few decades. "Recombinant DNA technology, expression vectors, and the ability to produce almost any protein in large amounts opened the doors to a lot of proteins," says Johann Deisenhofer, a 1988 Nobel laureate in chemistry who is an investigator at the Howard Hughes Medical Institute Research Laboratories at the University of Texas Southwestern Medical Center in Dallas. With the capability of producing large quantities of proteins, scientists have been able to try more approaches to growing crystals. "What drove structural studies earlier was the availability of large amounts of proteins and the ability to crystallize them," says Riddihough. "Crystallization of proteins is a lot like cookery--there are very few rules." Molecular-biological tools, such as some enzymes, have also helped to overcome some of the limitations of NMR in determining protein structure, says Wagner. The maximum size of a protein that can be examined with NMR is 30 kilodaltons; many proteins are considerably larger than this. "We now have strategies to cleave larger proteins into structurally and functionally intact subdomains that can be readily studied by NMR," he says. Coming Of Age Wagner notes that "crystallography and NMR are now mature techniques that students and postdocs learn as a matter of course, rather than approach as goals in methods research. Where previously people with physics backgrounds focusing on methods development were dominant [in crystallography and NMR laboratories], there is now a new class of scientists [who are proficient in these techniques] with a focus on biological problems." "When I began as a graduate student in Oxford, in 1949, it typically took us about one year to determine the structure of a 12-atom molecule," recalls Davies. These molecular-imaging technologies have undergone substantial refinement since then, he says, not just in terms of speed, but also with respect to the quality of information. "With higher-intensity X-rays now being produced in various synchrotrons around the world, we can obtain crystallographic information with much more resolution and rapidity," Riddihough says. "Technical advances have had a quiet but tremendous effect on the progress of the field," says Deisenhofer. "Data collection [measuring the various diffraction lengths] is fully automated now, and the same computer that cost $3 million when I was an undergraduate is now about $1,500." Advances in computer science have been tremendously important in bolstering structural research--both as devices to collect and speedily analyze imaging data, and as tools for modeling molecules, say researchers. Scientists say that the current explosion of research is only the beginning and in the years to come structural biology will gain even more importance. Riddihough predicts: "In a few years people will be taking the products of this research for granted, just as we do [DNA] sequence information now." (The Scientist, Vol:8, #16, pg.14, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : BUILDING BLOCKS AU : NEERAJA SANKARAN TY : RESEARCH PG : 14 "Every biological process occurs within, or is associated with, some structure," says Kenneth Miller, a professor of biology at Brown University, Providence, R.I. And in order to truly understand these processes, he says, there is no substitute for knowing the molecular details of that structure. Miller and other researchers agree that proteins--more than any other macromolecule--are the functional units of biological activity. Some of the more important proteins that are studied by structural biologists are: enzymes that catalyze such vital processes as DNA replication, respiration, energy-transfer reactions, and photosynthesis; receptor molecules on cell membranes; and antibodies that ward off infections. The field of structural biology primarily focuses on elucidating the three-dimensional structures of proteins. While such other macromolecules as DNA and RNA are also fundamental to living systems and processes, structural biologists point out that the linear sequence of these nucleotides, rather than their three-dimensional configuration, is the most important aspect of their structure. "I like to think of DNA as the one-dimensional repertoire of information for producing the three-dimensional information for proteins," says Edwin Westbrook, director of the new APS Structural Biology Center at Argonne National Laboratory. "To use a theological analogy, it's like the Word made flesh." Retrieving DNA sequence information is now a standard technique, with large national efforts such as the Human Genome Project routinely using the procedure. Researchers also point out that obtaining the amino acid sequence of a protein is only the first step in determining a protein's structure. The basis of function, they say, lies in the three-dimensional conformation of the molecule; for example, an enzyme molecule can be rendered active or inactive just by changing its shape. Thus, a structural biologist's task is to dissect the details of protein conformation--how it is folded, the relative positions of atoms in the molecule, and the nature of hydrogen bonds between amino acid residues not adjacent to each other. Using such sophisticated techniques as crystallography and nuclear magnetic resonance, scientists are now conducting detailed analyses on the atomic-level structures of various proteins. (The Scientist, Vol:8, #16, pg.14, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: HOT PAPERS ------------------------------------------------------------ TI : GENETICS TY : RESEARCH (HOT PAPERS) PG : 16 M. Mullan, F. Crawford, K. Axelman, H. Houlden, L. Lilius, B. Winblad, L. Lannfelt, "A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of b- amyloid," Nature Genetics, 1:345-7, 1992. Mike Mullan (Molecular Genetics Laboratory, Department of Psychiatry, University of South Florida, Tampa): "The discovery of a handful of mutations in the b-amyloid precursor protein (bAPP) gene leading to familial early- onset Alzheimer's disease (AD) was a significant advance in the study of AD. Collectively these proteins suggested that the parent bAPP molecule, or one of its products, is directly implicated in the Alzheimer process, and that a further look at these variants might provide a model for the disease. "The bAPP 670/671 mutation was discovered by genetic linkage analysis of two related Swedish pedigrees with disease onset in the mid-1950s. We examined the co-segregation of the bAPP gene with AD in these families. The analysis was slightly complicated by the fact that one family appeared to show minimal evidence of linkage to bAPP. This turned out to be due to a technical nuance of linkage analyses--one of a number that confound the analysis of neuropsychiatric disorders. However, there was sufficient evidence of linkage for us to proceed to sequence the bAPP gene, beginning with the two exons that encode the Ab peptide, which is deposited as plaque in the brains of all AD cases. The variant (with the lysine in position 670 replaced by asparagine, and methionine at 671 by leucine) cosegregated with the disease in both families. These changes, particularly the loss of the 671 methionine, which is immediately adjacent to the N- terminal of the Ab cleavage site, suggested that an alteration in Ab processing caused the disease in these families. "The 670/671 mutation was the first to be discovered at the N-terminal of Ab, its flanking location suggesting that it is the Ab fragment of bAPP that is important in AD pathogenesis. In contrast to the C-terminal mutations, the 670/671 was soon shown to have an obvious effect in transfected cells--overexpressing the Ab fragment five to eight times (M. Citron et al., Nature, 360:672-4, 1992; X.D. Cai et al., Science, 259:514-6, 1993). "Therefore, from the outset, the bAPP 670/671 mutation promised to reveal a simple pathway from mutation to disease. Such a pathway, albeit grossly epidemiologically unrepresentative of the common form of the disease, would nevertheless provide a pathogenic skeleton to which more common pathways could be added (a notion supported by the phenotypic similarity of the bAPP mutant cases and the more common late-onset form of AD). "Moreover, as result of this dramatic in vitro effect, this mutant promised an equal effect in transgenic animals, making it particularly useful for modeling the disease. Given the inauspicious beginning of AD transgenics, this was an encouraging prospect. We await the detailed analysis and follow-up of such animals." ------------------------- ------------------------------------------------------------ TI : CELL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 J.M. Backer, M.G. Myers, Jr., S.E. Shoelson, D.J. Chin, X.J. Sun, M. Miralpeix, P. Hu, B. Margolis, E.Y. Skolnik, J. Schlessinger, M.F. White, "Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation," EMBO20Journal, 11:3469-79, 1992. Morris F. White (Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston): "Nailing down the pathways involved in insulin signaling and identifying the ones that fail in 12 million Americans with non-insulin- dependent diabetes have been difficult problems. Since the discovery of insulin more than 70 years ago, generations of scientists have added pieces to the puzzle, but the molecular links between circulating insulin and the intracellular biological responses remain undefined even today. "Insulin is the principal hormone controlling blood glucose; it stimulates glucose influx and metabolism in muscle and fat, inhibits gluconeogenesis in the liver, and, along with the insulin-like growth factor-1, controls cell growth. Non- insulin-dependent diabetes mellitus (NIDDM) occurs when tissues no longer respond to ordinary or elevated levels of circulating insulin, disturbing carbohydrate metabolism, which can cause life-threatening complications. "In the 1980s, the receptor for insulin was shown, like other growth factor receptors, to autophosphory-late on tyrosine and to contain an intrinsic tyrosine-kinase activity, but the mechanisms for `downstream' signaling remained elusive for years. Then, the discovery of signaling molecules with phosphotyrosine binding sites, called Src homology-2 (SH2) domains, began to clarify the picture. In rapid succession, activated receptor tyrosine kinases were shown to interact with ras-GAP, GRB-2, PLCg, and the phosphatidylinositol 3-kinase (PI3K), all of which contain SH2 domains. In these early days, we could never pursue this exciting direction because the insulin receptor binds weakly, if at all, to the known SH2-domain proteins. Besides, other than forming large molecular aggregates, the consequence of occupying an SH2 domain with phosphotyrosine was difficult to show. "The discovery of IRS-1, the first insulin receptor substrate defined at the molecular level, provided a new piece in the puzzle. IRS-1 contains 21 potential tyrosine phosphorylation sites, including six actual sites in YMXM motifs that show a high affinity for the SH2 domains in the 85-kilodalton regulatory subunit of the PI3K (X. Sun et al., Nature, 352:73-7, 1991). In this paper we showed that PI3K is activated during association with phosphorylated IRS-1. This elucidation of an allosteric regulatory function for the SH2 domain generated much general interest. Although others tried similar experiments, the tandem phosphorylated YMXM motifs in IRS-1 apparently occupy both SH2 domains of p85, providing a maximal and readily detectable activation. Recent work demonstrates that IRS-1 and other peptides also activate the SH2-containing tyrosine phosphatase Syp (SH- PTP2, PTP-1D) in a similar manner. "Since PI3K is implicated in the control of mitogenesis, cellular growth and differentiation, and vesicle translocation, our finding provided something for everyone. In our field of insulin action, this paper provided one answer to the quest for a molecular link between circulating insulin and cellular enzymes. The next steps in this pathway are under intensive investigation by many groups. We hope these efforts will lead to new, rationally based therapies for NIDDM." ------------------------------------ ------------------------------------------------------------ TI : PHYSICS TY : RESEARCH (HOT PAPERS) PG : 16 A.D. Martin, W.J. Stirling, R.G. Roberts, "New information on parton distributions," Physical Review D, 47:867-82, 1993. Alan D. Martin (Centre for Particle Theory, University of Durham, England): "The use of energetic electrons (and other leptons) to probe the structure of the proton has had a long and successful history. These so-called deep-inelastic experiments have shown that the proton is composed of quark and gluon constituents--the more energetic the bombarding electron, the better its resolution and the more partons (quarks and gluons) that are `seen.' Parton distributions describe how the proton's energy is shared among its quark and gluon constituents. By measuring these distributions we can learn about how quarks and gluons interact, and test the theory of the strong interaction. "In any high-energy collision involving the proton, the interaction takes place at the partonic level. That is, in a collision the proton delivers only part of its energy, since the rest is carried by the constituents that do not interact (the spectator partons). This, for example, explains why the discovery of the heavy Z-gauge boson at the CERN proton- antiproton collider required a total collision energy some six times greater than the mass-energy of the boson, whereas in electron-positron colliders a collision energy equal to the mass-energy of the boson is sufficient. "Clearly, a detailed knowledge of parton distributions is essential for predicting and interpreting energetic interactions involving protons. Over the last few years, much high-precision data on deep-inelastic scattering have been obtained in experiments at particle accelerator laboratories around the world. By performing a global analysis of all these data, we have been able to considerably improve the knowledge of the parton distributions. A quantitative determination of these distributions is vital for precision tests of the standard model of particle physics, which, it is hoped, will reveal a more fundamental underlying theory. "This subject is topical because of the new measurements coming from the large experiments at the recently commissioned electron-proton collider, HERA, at Deutsches Elek-tronen-Synchrotron in Hamburg, Germany. Our results were used as the standard with which the new measurements are compared. The experiments revealed a dramatic growth of the distributions in the new kinematic regime opened up by the accelerator, which were more consistent with a particular set of our distributions that was motivated by calculations based on the emission of large numbers of gluons (the mediators of the strong interaction) in the deep-inelastic process." Editor's Note: This article, the first part of a two-part series on the burgeoning discipline of structural biology, discusses the evolution of the field. The second part, to appear in the September 5 issue, will look at the scientific challenges structural biologists currently are addressing and where the field is headed. (The Scientist, Vol:8, #16, pg.16, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: TOOLS & TECHNOLOGY ---------------------------------------------------------------- TI : Peptide-Synthesis Services Lift A Load From Biological Research Labs AU : FRANKLIN HOKE TY : TOOLS & TECHNOLOGY PG : 17 Among today's rapidly growing fields of biological study are those focusing on neurotransmitters, hormones, and various immunological and pharmacological agents. Central in many of these investigations is the analysis of biologically active peptides--chains of amino acids ranging from as few as two to more than 50 acids. Since these peptides can't be derived naturally in sufficient quantities--indeed, some cannot be naturally derived at all-- scientists increasingly are depending on synthetic development of peptides to meet their experimental needs. While many researchers have access to automated peptide-synthesis technology in their own laboratories or in core support facilities at their institutions, many are finding substantial advantages in contracting out the precise and time-consuming task of building a peptide to order. Thus, the growing need for peptides has spawned a robust young industry composed of commercial firms specializing in the synthesis of these amino acid chains. There are several virtues to using these outside suppliers. In- house resources may be overworked or technically limited, for instance. In some cases, it may simply be more cost-effective to turn to private support. In addition, recent advances in the catalytic chemistries used in peptide synthesis and improved instrumentation continue to extend the capabilities of these firms. "Many well-funded labs have gotten into doing peptide synthesis," says Martha Knight, president of Peptide Technologies Corp. in Gaithersburg, Md. "If they have money, they buy the synthesizer. But then they need to have a highly skilled technician or postdoc to do the work--and it's a lot of work. After a while they realize they're spending too much time in the synthesis and then characterization and purification of peptides. They'd rather be doing their more unique work. Researchers in biomedical labs everywhere now--medical schools, government labs, pharmaceutical companies--are coming to small companies like ours who make peptides." "With so many people asking for their services, the core facility of the university can get really loaded up," says Bosco Fong, an executive vice president of Peninsula Laboratories Inc. in Belmont, Calif. "When that happens, they go out and ask commercial companies like ours to do the peptide synthesis for them. We also get work from pharmaceutical companies for the same reasons. Most of the time, companies have their own facilities, but they are also getting too busy. They can't support all their R&D groups." Fong also points to another benefit of using commercial peptide- synthesis services: "When Scientist A asks Scientist B to do collaborative work [such as peptide synthesis], and there's a result, they have to coauthor on any papers. They don't have to do that with us. We provide them with the peptide, and they get all the credit." Automated peptide-synthesis tech- nology has helped meet the needs of researchers for specific peptides since its invention in the 1960s by biochemist Robert Bruce Merrifield, now a professor, emeritus, at Rockefeller University in New York. In 1984, Merrifield was awarded the Nobel Prize in chemistry "for his development of methodology for chemical synthesis on a solid matrix." Improvements in the chemical reagent systems and the equipment used in the process of synthesizing peptides have led to better product yields. Still, the basic technique underlying the synthesis today remains the same as when Merrifield devised it. "It's possible to get purer long peptides with the methods used now than, say, 10 years ago, because there's been some improvement in the chemistry," says Knight, who trained in the labs of Merrifield and Rockefeller colleague John M. Stewart. "But the basic design of the chemistry still originates from Merrifield's work." Merrifield's Invention "Our idea was to put the first amino acid of the peptide chain on a solid support, a polystyrene resin bead," says Merrifield. "You put it on by a rather stable bond. Then you carry out the addition of the second amino acid, so that you now have a dipeptide. You filter these polystyrene beads and wash them thoroughly to effect a partial purification. Then you're all ready to add the next amino acid, and you go through the same procedure." In this way, the peptide is built one amino acid at a time to the desired length. At the end of the synthesis, the peptide is removed from the solid support to be purified and characterized. "It's like stringing pearls," says Knight, "but you want to put them on in a certain sequence." In order for the synthesis to proceed in a controlled way, the several reactive parts of each amino acid must be activated and deactivated at appropriate times. Molecular "protecting groups" are added or removed to deactivate or activate the different parts, as needed. Commonly, the amino acid sequence to be synthesized is provided by the contracting researchers, perhaps implied by a cDNA sequence from a biological system they are currently studying. "There are three parts of an amino acid," says Freeman Stanfield, senior peptide scientist at Genosys Biotechnologies. "There's the carboxyl terminus, the side chain, and the amino terminus. "In the Merrifield method, 20 years ago and today, the carboxyl terminus is linked to the resin, the insoluble support, and there may or may not be a side chain protecting group, depending on the particular amino acid. And then there's an amine protecting group [at the amino terminus]. "At every cycle, the amine protecting group is removed, generating a free amino group. The amino terminus and, if necessary, the side chain of the incoming amino acid are also protected. The carboxyl terminus, then, of that second amino acid is coupled to the free amino [terminus] of the first amino acid. That process is repeated n number of times to make whatever size peptide that you want." New Chemistries Unfortunately, the chemistry used in this step-by-step synthesis process produces more side products as the peptide chain grows longer, resulting in smaller proportions of the desired peptide in the final product and a more difficult purification stage. It is in this area that new chemistries have been able to extend the technique's capabilities. The original Merrifield process uses a chemical called tBoc (tertiary butyloxycarbonyl) to protect the amino terminus and various benzyl groups to protect the side chains. An acid called TFA (trifluoroacetic acid) is the reagent used to remove the tBoc, in order to activate the terminus to receive the next amino acid. In the last step, a stronger acid, anhydrous hydrogen fluoride (HF), is used to cleave the peptide from the insoluble support. "The problem with that is that your peptide is exposed to [TFA] at every cycle," says Stanfield. "Over the [process of synthesizing], say, a 30- or 40-residue peptide, that's very deleterious. It's known that the benzylic side chain protecting groups in tBoc chemistry are not totally stable [during] the TFA treatment. So, you begin getting side products from that in longer synthesis." In a newer chemistry becoming more widely used, tBoc is replaced with a chemical called Fmoc (fluorenylmethyloxycarbonyl) to protect the amino terminus and tertiary butyl groups are used to protect the side chains. TFA is used only in the last cleavage step. As a result, the synthesis of longer peptide chains with fewer side reactions is now possible. The scientists at custom peptide-synthesis companies often engineer instruments according to their own specifications. At Genosys, for example, peptides are synthesized using a patented technique called segmented wafer synthesis, which is based on an adaptation of the company's proprietary DNA-synthesis machine. Over the years, however, a number of instrument manufacturers have identified peptide synthesis as a growing area and have developed automated machines for the task. Among these companies are Beckman Instruments Inc., Fullerton, Calif.; Biosearch Inc., Bedford, Mass.; Advanced Chemtech, Louisville, Ky.; Applied Biosystems, Foster City, Calif.; and Shimadzu Scientific Instruments, Columbia, Md. Often, these instrument makers will not seek to compete directly with the custom peptide-synthesis firms, but instead will target development of new chemistries and instrumentation that they then supply to the generally smaller service companies. At Biosearch, for example, chemical research and development is the company's focus, and it offers a number of proprietary reagents for peptide synthesis, according to Susan Hantman, a technical-applications specialist. For peptide synthesis, Biosearch markets the 9050 Plus PepSynthe- sizer for $59,500. The instrument is capable of synthesizing three peptides simultaneously and of using multiple activation chemistries within a single synthesis. Achieving Purity With biologically active peptides, the purity of the final product is crucial. The omission or inadvertent inclusion of even one amino acid can dramatically alter the biological activity of a peptide. For this reason, a great deal of time and effort is expended after the synthesis in purifying and characterizing the peptide. Among the analytical methods commonly used are high- performance liquid chromatography (HPLC), mass spectrometry, electrophoresis, and amino acid analysis. "For analyzing a crude synthetic product to see how successful the synthesis was and for purifying that crude product to homogeneity, to whatever the desired purity level is, overwhelmingly HPLC is the method of choice," says Stanfield. "The other very useful analytical tools, in approximate order of importance, are mass spectrometry and amino acid analysis." Peptide-synthesis services range in cost from hundreds to thousands of dollars, depending on the length of the amino acid chain and other factors. While there are ways to reduce expenses in the synthesis process, Fong cautions that there are things customers may want to consider when trying to save money on peptide services. The analysis stage of peptide synthesis is an area in which some companies try to trim costs, he says. "One word of caution for people looking for cheap custom synthesis is to make sure that, if they're quoted a very cheap price, the peptides have gone through stringent quality-control tests," Fong advises. Inadequately purified and characterized peptide products put the reliability of whatever experiments a researcher might later conduct with that peptide at risk. "The cost of the peptide then becomes insignificant," says Fong, "when compared with the time wasted." (The Scientist, Vol:8, #16, pg.17, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ------------------------------------------------------------ TI : SUPPLIERS OF PEPTIDE-SYNTHESIS SERVICES AND EQUIPMENT TY : TOOLS & TECHNOLOGY PG : 19 Advanced Chemtech Louisville, Ky. Circle No. 202 on Reader Service Card Applied Biosystems Foster City, Calif. Circle No. 203 on Reader Service Card Bachem California Torrance, Calif. Circle No. 204 on Reader Service Card Biosearch Inc. Bedford, Mass. Circle No. 205 on Reader Service Card Clontech Laboratories Inc. Palo Alto, Calif. Circle No. 206 on Reader Service Card Coast Scientific San Diego Circle No. 207 on Reader Service Card Crescent Chemical Hauppauge, N.Y. Circle No. 208 on Reader Service Card Eppendorf North America Inc. Madison, Wis. Circle No. 209 on Reader Service Card Genosys Biotechnologies Inc. The Woodlands, Texas Circle No. 210 on Reader Service Card ICN Biomedicals Inc. Costa Mesa, Calif. Circle No. 211 on Reader Service Card INAMCO Chemicals & Lab Equipment Flushing, N.Y. Circle No. 212 on Reader Service Card Multiple Peptide Systems San Diego Circle No. 213 on Reader Service Card Peninsula Laboratories Inc. Belmont, Calif. Circle No. 214 on Reader Service Card Peptide Technologies Corp. Gaithersburg, Md. Circle No. 215 on Reader Service Card Peptides International Inc. Louisville, Ky. Circle No. 216 on Reader Service Card Perkin-Elmer Corp. Norwalk, Conn. Circle No. 217 on Reader Service Card Rent-A-Lab Inc. Vernon Hills, Ill. Circle No. 218 on Reader Service Card Research Genetics Huntsville, Ala. Circle No. 219 on Reader Service Card Research Organics Inc. Cleveland, Ohio Circle No. 220 on Reader Service Card Shimadzu Scientific Instruments Inc. Columbia, Md. Circle No. 221 on Reader Service Card Sigma Peptides & Amino Acids St. Louis Circle No. 222 on Reader Service Card Star Biochemicals Inc. Torrance, Calif. Circle No. 008 on Reader Service Card (The Scientist, Vol:8, #16, pg.19, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: NEW PRODUCTS ------------------------------------------------------------ TI : Bio-Rad Announces New Universal Beam Accessory TY : NEW PRODUCTS PG : 19 Bio-Rad's new universal beam accessory creates multiple external beams for any current model of the company's FT-IR spectrometers. According to the manufacturer, the low-cost accessory enhances the versatility of its spectrometers and can be added at any time. Bio-Rad's external sample compartment (ESC), micro/IR, GC/IR, or TGA/IR accessories can be attached to the exit beam ports. Bio-Rad, Digilab Division, Cambridge, Mass. --------- ------------------------------------------------------------ TI : Ultrapure Bovine Serum Albumin Available From PanVera Corp. TY : NEW PRODUCTS PG : 18 Bovine serum albumin (BSA) is often used as a carrier protein or stabilizing agent in research and diagnostic applications. The demand for high-quality reagents has grown as the sensitivity of these applications has increased. PanVera's new Ultrapure BSA reportedly has the lowest levels of contaminating RNase and DNase of the commercially available BSAs. This purity level has been achieved by exhaustive purification of native BSA rather than by chemical modification methods, such as acetylation. In addition to nuclease activity, PanVera Ultrapure BSA is tested for protease activity, alkaline phosphatase and peroxidase, and ultralow fluorescence background, according to the company. It is said to be well-suited for applications in which the absence of degradative enzymes is critical. Applications include probe-based diagnostics, immunoblotting, receptor-binding studies, antibody dilution, radioactive quenching, enzyme stabilization, ELISAs, radioimmunoassays, immunofluorescence, and enzyme assays. PanVera Ultrapure BSA is filter-sterilized and available as a 10 percent solution in water. PanVera Corp., Madison, Wis. --------- ------------------------------------------------------------ TI : Molecular Devices Introduces SPECTRAmax 250 TY : NEW PRODUCTS PG : 20 The SPECTRAmax 250 microplate spectrophotometer has a xenon flash lamp and grating monochromator that facilitate direct UV measurement of DNA, RNA, and protein in microplates. Up to 96 assays can be run at one time using disposable or quartz microplates. The purity of DNA can be measured with A260/A280 ratios. Also, users can perform spectral scans from 250 nm to 750 nm to simplify qualitative analyses of numerous samples. The product reportedly reduces sample volumes in experiments because the assays are performed in a microplate instead of cuvettes. SOFTmax PRO microplate data- analysis software, for use with the SPECTRAmax 250, provides built-in spreadsheet capabilities for easy data analysis and reporting. Molecular Devices Corp., Menlo Park, Calif. Markson Science Unveils New Conductivity Meter Line The Next Generation line consists of three models of conductivity meters that are designed for accurate and reliable measurements in the lab or field. The portable conductivity meters have easy-to-read simultaneous displays, and two models offer total dissolved solids (TDS) capabilities. The TDS models can switch from conductivity and temperature measurements to TDS and temperature measurements. Features include: manual or user-select auto-ranging in five conductivity ranges; auto or manual temperature compensation; adjustable temperature coefficient; and sufficient memory to store 16 sets of measurements, including five-point conductivity and TDS calibrations. Markson Science Inc., Hillsboro, Ore. --------- ------------------------------------------------------------ TI : ICN Releases IsoBlue Radiolabeled Nucleotides TY : NEW PRODUCTS PG : 19 IsoBlue radiolabeled nucleotides have been designed to be used as a direct substitute for traditionally formulated products that require storage at -20oC, avoiding any extensive alteration in the labeling protocols. The IsoBlue nucleotides include a stabilizing agent that allows storage at 4oC without affecting their performance in labeling reactions. In addition, the inclusion of an inert dye enables visualization of the small aliquots of material that are typically drawn up for labeling. Testing at ICN and independent research labs reportedly has demonstrated no effect of the stabilizing agent or dye on performance in a number of applications. These tests included labeling of DNA and RNA probes using random primer labeling, nick- translation, and reverse sequencing under both chemical modification and chain-termination methods. ICN Biomedicals Inc., Costa Mesa, Calif. --------- ------------------------------------------------------------ TI : BioCad/SPRINT's Perfusion Chromatography System TY : NEW PRODUCTS PG : 20 The BioCad/SPRINT Perfusion Chromatography System is said to be capable of performing bioseparations in 30 seconds to three minutes. The system uses POROS perfusion chromatography media, which reportedly deliver far higher speed, resolution, and capacity through a combination of advances in particle and surface design. The SPRINT system handles diverse applications, including analytical, preparative, and low-pressure chromatography as well as high-performance liquid chromatography. The fluid path is fully biocompatible, and the instrument can operate at flow rates up to 20 ml/min at 3,000 psi. An optional autosampler is available. The system can also document all critical chromatographic parameters, including pH, conductivity, and pressure. A data package for peak integration is available. PerSeptive Biosystems Inc., Cambridge, Mass. --------- ------------------------------------------------------------ TI : Ohaus's Electronic Toploading Balances TY : NEW PRODUCTS PG : 19 The Precision Advanced Series of electronic toploading balances offers a new selectable GLP protocol that provides time and date, calibration data, and a balance ID number for users required to comply with external standards or regulations. The balances also offer memory capacity for 255 values used with the statistics function as well as 12 additional new features. The balances come with a five-year warranty. Ohaus Corp., Florham Park, N.J. --------- ------------------------------------------------------------ TI : Labconco's Digital Rotary Evaporator With LED Display TY : NEW PRODUCTS PG : 20 The Digital Rotary Evaporator for distillation processes continuously displays bath temperature, vapor temperature, or flask rotation speed on a front-mounted digital display. It is equipped with a built-in electronic lift assembly, whose capacitor motor provides a lifting speed of 1.4 cm/sec, up to a height of 140 mm. The lift may also be operated manually. A stainless-steel bath includes a level control and can be moved sideways to accommodate different flask sizes. A safety temperature limiter automatically turns off the bath when maximum temperature is reached. Two baths are available with temperature ranges of 20 to 100<198>C for water bath and 40 to 240<198>C for oil bath. Four condenser styles are available: diagonal, vertical, reflux, and dewar. Labconco Corp., Kansas City, Mo. (The Scientist, Vol:8, #16, pg.19, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: PROFESSION ------------------------------------------------------------ TI : Learning The Trade: Advice For Scientists Seeking Book Publishers AU : SUSAN RABINER TY : PROFESSION PG : 21 The well-publicized commercial successes of science books for the lay, or trade, market--going all the way back to The Double Helix by James Watson (New York, Atheneum Publishers, 1968), and through the more recent A Brief History of Time by Stephen Hawking (New York, Bantam Books, 1988)--provide indisputable evidence that science titles can have broad appeal and even occasionally become mega-bestsellers. Less well-publicized have been those many science titles that never achieved such broad recognition, yet still returned handsome profits for their publishers. But how does a researcher who has never before written for any audience other than his or her own professional colleagues find a trade publisher--and how can the scientist be sure that the publisher will treat the work with the care it deserves? There are two aspects of publishing that a scientist looking for the right trade publisher should be aware of. The first involves certain important differences between university- press and trade publishing; the second concerns where today's science editors see the market for science books. Generally speaking (and I speak as someone who was a university press editor for more than a decade), a proposal found worthy of publication at one university press will be similarly seen at all of them. Why? Because all university presses publish for the same market--other scientists in the same or related disciplines. And they all use the same methods to determine publishability--outside review by well- known figures, again, in the same or related disciplines. Trade publishing, on the other hand, is not so single- minded. Some of us publish for the well-informed serious reader; others for a much broader market; still others for specific segments of the general reading public. Thus, the same proposal submitted to five different trade houses may be rejected outright by three and accepted at two others. Further, the two that accept the proposal may offer very different advances and plan very different first print runs. Let me explain. At the most commercial trade publishing houses, editors are under enormous pressure to fish out of the river of proposals flowing past their desk only those projects with prospects for best-sellerdom. At these houses, your science project will have to compete not only with other science books but also with cookbooks, self-help books, fiction, and so forth. A proposal for a fully publishable trade science book, but not a potential blockbuster, may well be at the wrong house here. But this should not be taken to mean that authors of serious science projects must either simplify their work to appeal to a less-educated reader or reconcile themselves to publication only by university presses, with their smaller advances and more limited distribution. There are still many trade houses that are looking for quality science titles, whether or not they have the potential to make best-seller lists. Moreover, because they consider their back lists (those titles published in seasons prior to the current one) to be valuable assets, they are not under the same pressure to be in the black within weeks of a book's publication. That the names of such publishers may not be household words is related at least in part to this commitment to serious nonfiction at the expense of more commercial books. It is thus not surprising that Harvard University zoologist Stephen Jay Gould and the late Nobel physicist Richard Feynman--scientist authors who could have written their own tickets at any of the most commercial houses--chose instead a house like W.W. Norton & Co. of New York, known as a publisher of serious nonfiction, or that noted scientists like Robert Gallo and Gerald Edelman publish with my own small imprint, Basic Books, also in New York. Such houses (and there are many others, as well) not only publish a much broader range of science titles than the typical high-profile publisher, but also do so, I would argue, more wisely--resulting in far fewer books that fail to fulfill the reasonable expectations of the house, the editor, and the author. For those who are looking for trade publication of their work and are finding it difficult to get a foot in the door, the following should be helpful. The Role Of The Agent As suggested in a recent article in The Scientist (R. Lewis, Feb. 7, 1994, page 21), agents play a vital role in science publishing. By virtue of their continuing relationships with publishers, agents are in a special position to bring to the attention of particular editors projects of a kind those editors have shown an interest in publishing. Many agents also play a role in helping authors put together proposals that are more likely to provide all the information an editor wants to have in hand when making that "publish or pass" decision. Obtaining representation, however, is not a guarantee of publication. Once brought to the attention of an editor, agented and unagented proposals and manuscripts are read alike. More important for the young scientist who has not yet made a reputation, agent involvement cannot guarantee that a project will be marketed appropriately. This consideration should be of special interest to all those whose primary profession is science rather than writing and who consider the respect of their peers to be of even greater importance than book sales. Appealing To An Editor We are in a period in which demand among the general book- buying public for both scientific literacy and currency seems at an all-time high. While the general public may not know the sales history of books such as Douglas Hofstadter's Godel, Escher, Bach (Basic Books, 1979) or Timothy Ferris's Coming of Age in the Milky Way (New York, William Morrow & Co. Inc., 1988), editors who regularly publish science books know that such titles were very profitable for their houses. It is my feeling that scientists are now in a better position to have their work published, and even to get wide review attention for it, than serious nonfiction writers in other fields (see accompanying tips). Of course, all science projects are not equally attractive to all editors. Broadly speaking, here are the categories of science books for which editors regularly receive proposals. First, and most desirable (because they have the greatest prestige and greatest sales potential) are books written by leading scientists (without the help of cowriters) that are based on the scientist's own work and the work of colleagues and attempt to add a new conceptualization to their field. Such books are often hard reads. In this regard they violate a precept that has become almost gospel in most other types of publishing--namely, the most accessible books are likely to be the most successful in the marketplace. Surprising as it may sound, the opposite is often true in science publishing. As William Frucht, executive director of three major science book clubs, noted in a session on science publishing at the 1993 meeting of the American Association for the Advancement of Science (Science, 260:1150-2, 1993), science titles with challenging presentations often ring up better sales than those that are "dumbed down." A second category of science books likely to command an editor's attention is made up of those written not to influence the field but to explain state-of-the-art science to an intelligent reader. As long as their focus remains on explaining science, and they do not veer off into celebrating the occurrence of some important breakthrough and the great scientist who brought it about, such books can be successful, although rarely do they have the sales potential of the first group. This is an ideal category for a first-time trade science author to think about. Third are those books that cross over from a science market to a "New Age" market. A good part of the potential market for many science books, particularly in such areas as cosmology, astronomy, evolution, and ecology, has come to be seen as including a large number of people who are often not only anti-science but also anti-rational at their core. Editors at many of the more commercial houses are looking for science books that allow for a spillover appeal to such readers--for example, a book about life on other planets. I am not. A very different group of science books is made up of those that include style elements of science fiction/fantasy. Based on cutting-edge physics and often written by cutting- edge people, they combine solid science with informed speculation. Kip S. Thorne's Black Holes & Time Warps (W.W. Norton, 1994) is an example of this kind of book. Another is The Last Three Minutes by Paul Davies, part of the Science Masters Series, soon to be simultaneously issued by 13 publishing houses worldwide. Such books are fun to read. Especially in cosmology, in which new breakthroughs now seem less likely, they may well be a wave of the future. Of less interest to most editors who maintain a serious science list are those books by scientists in one field trying to write about another field--engineers, for example, trying to write books on cosmology; books on "heroic science," best left to science writers; "Mr. Wizard" books-- that is, books explaining the marvel of certain breakthroughs in science to the lay reader. (Such books often make successful young adult books.) In science publishing, as in other publishing, the megabuck advances make the big news. But no matter how much money is being thrown at you, make the decision about whom to publish with based on a realistic assessment of the ability of the editor and publishing house to help you bring out a book that you will be proud to have authored. Susan Rabiner, whose 25-year career in publishing includes more than a decade at a university press, is a senior editor at New York-based Basic Books. She is currently under contract to write a book entitled Thinking Like Your Editor: Writing and Publishing Serious Nonfiction with her husband, Alfred Fortunato, whom she acknowledges for his help in preparing this article. (The Scientist, Vol:8, #16, pg.21, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: ----------------------------------------------------------- TI : TRADE BOOK TIPS AU : SUSAN RABINER TY : PROFESSION PG : 22 Here are a few tips for the scientist thinking of writing a science book for trade publication: * Good trade book authors are trade book readers. Before you begin to write your proposal, go to a good general-interest bookstore and read through the science titles on the shelves. Don't limit yourself to those in your own field. If you don't leave with a book or two under your arm, you are probably not destined for trade authorship. * After you have read a trade science book, go back and carefully reread the flap copy. Now ask yourself: Does the book provide the information, thesis, and analysis the flap copy suggests it will? If not, a dissonance existed between what the author attempted with the work and what the publisher thought it could sell. Note the name of the publisher and remember it. This is not a house you want to give your project to. * Title your book even before you submit your proposal. And, contrary to the general rule in most book publishing, titles of science books should beeline to the topic of the book, as in Consciousness Explained (by Daniel C. Dennett; Boston, Little, Brown & Co. Inc., 1991); The First Three Minutes (by Steven Weinberg; New York, Basic Books, 1977); and Innumeracy (by John A. Paulos; New York, Hill & Wang, 1988). Such titles suggest to an editor that the author has done the work necessary to focus the book. * Understand the distinction between a technical accomplishment and a new conceptualization. Books for the trade market require the second, not just the first. A book about a critically important breakthrough in our understanding of oncogenes would likely have limited trade book potential; embed it in a discussion of how the breakthrough could lead to reshaping what we know of a disease process and you're on your way. * In writing your proposal, envision an intelligent reader; don't be afraid to introduce difficult ideas. Include the chain of mental events that brought you to your special interest in the subject matter and your decision to pursue the scientific inquiry that led to the book. * Know what other science books the editor has published. (The editor's name is usually found in the acknowledgments at the front of the book.) By all means, seek out and talk to other science authors the editor has published; most will be happy to share experiences with fellow writers. * Finally, if you are unagented, don't be afraid to telephone a publishing house and ask if there is one editor who specializes in science publishing, and if you might be connected to that editor. You may not always get through on a first try, but an editor who does not return calls is not the one to whom you should be submitting your proposal. Once you reach the editor, describe your project in terms as brief as will leave it accurate. The editor will either ask you to submit a proposal or discourage you from doing so. Or he or she may direct you to another editor, possibly at another house, who might be better for your project. (The Scientist, Vol:8, #16, pg.22, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. -------- NXT: PROFESSION ------------------------------------------------------------ TI : Chemist And Mathematician Are Named Winners Of Two 1994 Kyoto Prizes AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 23 Paul C. Lauterbur, a chemist and director of the Biomedical Magnetic Resonance Laboratory at the University of Illinois College of Medicine, Urbana-Champaign, and Andre Weil, a French mathematician who is currently an emeritus professor at the Institute for Advanced Study, Princeton, N.J., have been named winners of the 1994 Kyoto Prizes in the advanced technologies and basic science categories, respectively. The two researchers will each be honored with a commemorative gold medal and cash award of about $430,000 during award ceremonies to be held in Kyoto, Japan, November 9-12. The Kyoto Prizes, considered Japan's highest award for lifetime achievement, are presented by the Inamori Foundation, a nonprofit organization in Kyoto whose mission is to recognize individuals and groups whose work has had a significant beneficial impact. Lauterbur, 65, was the first scientist to make an image using nuclear magnetic resonance (NMR). He predicted the technique's potential when he first described it (P.C. Lauterbur, Nature, 242:190-1, 1973). This work was pivotal in the development of the magnetic resonance imaging (MRI) scanner, which is now widely used in medical diagnostic imaging, providing a noninvasive method to look at the brain, spinal cord, pelvic organs, heart, and joints without surgery or X-rays. "I believe there are something like 6,000 MRI machines in hospitals around the world today," says Lauterbur. "The technique is also widely used in nonmedical types of biological research--one can now combine the anatomical information obtained from imaging with spectroscopy data [from the same region] and determine where changes are taking place in the body. One can conduct basic physiologic studies on muscle function by spectroscopic measurements of phosphorus metabolites, for example." Nowadays, Lauterbur is attempting to improve existing imaging techniques so as to facilitate various lines of research. These projects include developing techniques to obtain brain images more rapidly; attempting to obtain better resolution of microscopic MRI (which has vast applications in embryology); and synthesizing and fostering an understanding of magnetic contrast agents--particles that are not seen by NMR but affect the water around them so as to enhance details of the structures being imaged. A professor of medical information sciences at Illinois, Lauterbur received his Ph.D. in chemistry from the University of Pittsburgh in 1962 and did research at the State University of New York, Stony Brook, for 22 years before moving to Illinois. He has been a member of the National Academy of Sciences since 1985. Weil, 88, was cited by the Inamori Foundation for having influenced "the very course of 20th-century thought in mathematics." He has made major contributions in several different areas of mathematics, notably in the branches of number theory and algebraic geometry. Indeed, according to a recent profile in Scientific American (J. Horgan, 270:33-4, June 1994), colleagues describe Weil as the "last universal mathematician." A native of Paris, Weil received his doctorate from the University of Paris in 1928. He is well known for creating a theorem of a mathematical conjecture, called the Riemann hypothesis, while a prisoner in a French military prison during World War II. He provided the framework for algebraic geometry, and therefore coding theory, with his "Weil conjectures." At the Institute for Advanced Study, where he has worked since 1958, Weil has pursued a unification of arithmetic, algebra, geometry, and topology. He is currently researching the history of mathematics and helping edit the works of two great French mathematicians, Jacques Bernoulli and Pierre de Fermat. (The Scientist, Vol:8, #16, pg.23, August 22, 1994) (Copyright, The Scientist, Inc.) ---------- WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. --------

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