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THE SCIENTIST VOLUME 7, No:7 April 5, 1993 (Copyright, The Scientist, Inc.) =============================================================== Articles published in THE SCIENTIST reflect the views of their authors and not the official views of the publication, its editorial staff, or its ownership. ================================================================ *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON *** *** APRIL 19, 1993 *** *** *** THE SCIENTIST CONTENTS PAGE (Page numbers correspond to printed edition of THE SCIENTIST) CONTENTS Page 3 of Newspaper SCIENCE UNDER CLINTON'S PLAN: High-tech company officials, association presidents, and many leading scientists are expressing optimism as their initial response to President Clinton's proposed economic program. But other observers are waiting for more details--including specific budget figures-- before commenting, though several scientist winners and losers are emerging under the plan Page 1 STARTUP ADVICE: Despite recent setbacks in the biotechnology industry, start-up companies are forming at a steady pace, though the rules of the game are changing--especially in the area of financing. In the first of a two-part series, analysts, venture capitalists, and company officials discuss a variety of funding strategies that today's biotech entrepreneurs should consider Page 1 BIOMEDICAL SUPPORT: The National Caucus of Biomedical Science Chairs, an association of 21 university biomedical department heads, is calling on Clinton to double current spending on biomedical research funded by the National Institutes of Health, a request that association members believe the new administration will look favorably upon END OF AN ERA: The final formal activity of the full Carnegie Commission on Science, Technology, and Government was held last week as the process of shutting down the prestigious panel begins. Commission members and staffers are expressing satisfaction with the work of the body over the past five years and are hopeful that at least some of its hundreds of recommendations will be acted upon Page 3 SCIENCE EDUCATION: More than a decade ago, it was obvious-- documentably so-that U.S. science and math education was heading toward a crisis and that improvement in the system would require heavy federal financial support. However, says Bill G. Aldridge, executive director of the National Science Teachers Association, a disastrous misunderstanding by government officials and educators, among others, has misdirected the needed funding, and the crisis is upon us Page 11 COMMENTARY: Researchers must look beyond their own disciplines and even beyond the bounds of science and join with other investigators as well as with doctors, lawyers, economists, and sociologists to solve the serious problems threatening the environment, says Environmental and Occupational Health Sciences Institute director Mark Robson Page 12 CONTROVERSIAL ALZHEIMER'S APPROACH: Among the extensive research being conducted into Alzheimer's disease, one theory--that the peptide fragment beta-amyloid holds the key to a cure--is gaining popularity and support; some say too much support Page 15 HOT PAPERS: A molecular biologist discusses the effects of certain proteins on insulin-like growth factors Page 16 CLASSICS ON CD-ROM: In addition to the multitude of references, periodicals, and databases now available on CD-ROM, several publishers are making classic works from the likes of Darwin and others, as well as prestigious reference books, available on disk Page 18 Books on CD-ROM (see also Science Publishers Directory on page 31) Page 20 CHILDREN'S SCIENCE BOOKS: Some scientists are making a contribution to the fight against science illiteracy while gaining personal satisfaction through writing children's science books. Though hardly a lucrative endeavor, the effort is being welcomed by publishers because of the authenticity and excitement researchers bring to theirsubjects Page 21 Tips on writing science books for children Page 21 ROBERT W. PARRY, a University of Utah chemistry professor, has won the American Chemical Society's 1993 Priestley Medal Page 23 NOTEBOOK Page 4 CARTOON Page 4 LETTERS Page 12 CROSSWORD Page 13 SCIENCE PUBLISHERS DIRECTORY Page 31 (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Despite Chill Winds On Wall Street, Investors Continue To Place Bets On Fledgling Biotechnology Companies Stock market declines have taken their toll on established firms, but startup ventures still attract backing (Page : 1 of newspaper) BY SCOTT VEGGEBERG Launching a new biotechnology company calls for a number of key ingredients, as any wide-eyed scientist who has tested the entrepreneurial waters will attest. You need your enlightened concept, of course, and the enduring visionary force that eventually is to hammer your concept into shape as a viable product. You also need the right people--and the proper blend of them--to keep the startup's scientific and business plan exquisitely balanced, on track, and on schedule. However, those who have succeeded and those who have failed will agree that no great idea--no matter how many inspired and capable people are behind it--will succeed without adequate financial cushioning from the outset. Today, venture capitalists, while more selective than in the past, are generally willing, sometimes eager, to provide that cushion. But for some scientist-entrepreneurs--those who have nurtured their firms to the point at which they are listed on a stock exchange or are contemplating an initial public offering-- the task of maintaining the flow of investment has become daunting, thanks to the dramatically shifting winds coursing through the financial community. Indeed, if one were to judge from stock market performance alone, it would appear that the biotech sector must be anything but attractive to investors nowadays. A run of grim news about stillborn efforts to create new pharmaceuticals and poor returns on investments has made it virtually impossible for companies to grow beyond the startup phase and parlay their fortunes by selling shares in an initial public offering. And it's not clear to analysts when the IPO window will open again; some predict that it won't happen until next year. The really bad news began, analysts generally agree, in April 1992, when the United States Food and Drug Administration questioned the efficacy of Centoxin--a monoclonal antibody-based drug produced by Malvern, Pa.-based Centocor Inc.-- and requested new clinical trials. At the time, the price of the stock fell by more than 70 percent. This was disturbing news, especially from a company whose stated goal was to be a "Merck of the year 2000" (Susan L-J Dickinson, The Scientist, May 14, 1990, page 1). The deadly blow for Centoxin came on January 18 of this year, when new clinical trials were called off after preliminary data showed than those on placebo, according to Associated Press reports. A more recent disappointment came from Boulder, Colo.-based Synergen Inc., which announced on February 22 of this year that its lead drug, Antril, was barely more effective in a clinical trial than a placebo was in preventing deaths from septic shock. Synergen's stock plunged about 68 percent on the same day. Then, on February 25, Amgen Inc. of Thousands Oaks, Calif., one of the most visible and respected biotech companies in the U.S., announced that its earnings would be far lower than expected. As of late March, Amgen stock, which once had been selling for as high as $78 per share, was trading at around $35. The cumulative effect of such announcements has been to seriously depress the price of biotech stocks overall. BioWorld Financial Watch, a San Mateo, Calif., newsletter that tracks biotech financial issues, called the first 2 1/2 months of 1993 "a grim year so far for biotech stocks," noting that between January 1 and March 5, the AMEX Biotechnology Stock Index fell by 30 percent. But despite the gloom and doom prevailing on Wall Street, the biotech sector is by no means moribund when it comes to startup opportunities. This is because companies at their early stages depend not on the stock market, but on venture capital firms and individual investors for their funding. And the feeling among these investors is definitely bullish, according to a variety of analysts; as a result, they say, biotech startups are continuing to spring up at a fairly regular pace. "We believe in biotechnology," says a representative of E.M. Warburg, Pincus, & Co. Inc., a New-York-based venture capital company, speaking on condition of anonymity. "We are still actively starting up companies. I personally don't see any slackening in formation of what I'd call real companies." By "real," the representative notes, he means those startups that can gain at least $5 million of private investment, an amount that will carry forward their work for the first 18 months to two years. In biotech's early days, by comparison, about $1 million in so-called seed money, spread over the same period, was typical. But today, with more than 1,000 biotech companies in existence, the financial demands have risen. Competition is more fierce, not just to get products to market, but to attract top research. The latest startup from Warburg, Pincus is Supragen, which was founded in December 1992 in Boulder, Colo. This company is developing therapies based on the knowledge of superantigens, which stimulate the immune system. Superantigens were discovered in 1989 by influential immunologist Philippa Marrack. Marrack will be serving as a scientific adviser to the company, while retaining her position as a Howard Hughes Medical Institute investigator at the National Jewish Center for Immunology and Respiratory Medicine in Denver. The Clinton Factor Arthur Klausner, director of research at Domain Associates, a venture capital firm based in Princeton, N.J., agrees that product development disappointments and a faltering public market for biotech stocks do not pose a threat to fledgling biotech firms; in his view, the venture capital firms still have plenty of money, and activity remains strong. However, he adds, startup activity could be adversely affected by what he refers to as "the uncertainties of the Clinton health care plan." "I think any time there's uncertainty, that's going to chill entrepreneurial activity," he says. One negative effect the weak stock market can have on start-up firms is to make private funding sources--the venture capitalists and wealthy individual investors--more insistent on striking the best possible deal for themselves, says Randy Scott, vice president of research and development at two-year-old Incyte Pharmaceuticals Inc. of Palo Alto, Calif., which is heavily involved in developing new drugs based on knowledge of DNA sequences. "When the public markets dry up, the private markets start to take a vulture approach," Scott says, noting that investors are very nervous about liquidity right now. And he shares with Domain Associates' Klausner a concern about the new administration's impact. Scott perceives that there is considerable wariness among investors over what Clinton's future policy on pharmaceutical prices will do to the ability of a company to make a public stock offering, thus converting the venture capital investment back into dollars that can be invested in still other companies. "If at a cheaper price," says Scott. Meanwhile, at Domain Associates, progress on starting up companies continues despite stock market woes. This venture capital firm has helped form a number of companies, including Gensia Pharmaceuticals Inc. in San Diego. Most recently, Domain has funded a company called Trimeris Inc., based in Durham, N.C., which is tapping Duke University AIDS researcher Dani Bolognesi as a consulting scientist. Trimeris will initially focus its efforts on antiviral technologies, targeting HIV and related retroviruses. The president of Trimeris is Max Wallace, an attorney by training who, until recently, was director of Duke Management Co., which manages Duke University's assets. "We have a venture commitment from Domain, and I'm its first employee," says Wallace, who has no formal business training. He's no neophyte to biotech startups, though, having previously been a cofounder of Sphinx Pharmaceuticals Inc., also in Durham, which specializes in signal transduction mechanisms. Sphinx went public in January 1992, before the stock market began to sour in the late spring, by selling stock on the NASDAQ exchange and raising about $75 million, he says. However, shares in the company, which sold for $15 at the initial offering, were trading at 4 1/2 last month. Role Reversal If an attorney can get wise in the ways of biotech, so, apparently, can scientists become adept in the financial community. One of a growing number of scientists who have become venture capitalists is Larry Bock, a partner in Avalon Ventures in La Jolla, Calif. In addition to his MBA, Bock has a bachelor's degree in biochemistry and was in on the early days of one of biotech's oldest companies, Genentech Inc. of South San Francisco, Calif. Such a science or medical background has become increasingly common at venture capital firms that specialize in biotech startups, he says, and notes that another partner at Avalon is immunologist Kevin Gorman, who has a Ph.D., with postdoctoral experience at New York's Rockefeller University. For Bock, it's the successful pursuit of big deals on the cutting edge of science that really makes his work engaging. Says Bock: "When you're in on the cutting edge of a field, and no one else is doing that, and you know about developments that are happening six months ahead of time, and these scientists have not been approached by anybody yet, that's exciting." Bock says that after moving over to the business world, he worked for a traditional venture capital firm, but he was happy to make a move to Avalon, which is aggressively proactive in its endeavors to conceive of and launch companies. "This is in contrast to the traditional venture capital firm that passively responds to reams of ill-conceived ideas in the hope that a good one will pass over their desk," he says. Avalon, which has started seven biotech companies, such as Athena Neurosciences Inc., based in San Carlos, Calif., claims that it has never formed a company that failed--that all have advanced to the stage of going public. Avalon made a big splash in the biotech startup world in March of last year, when it and other firms not only pulled together a top-notch team of scientists but also pulled off the largest seed financing in biotech history--$48 million from venture capital firms and wealthy individuals--for Ariad Pharmaceuticals Inc. Ariad, based in Cambridge, Mass., will specialize in developing drugs based on knowledge of signal transduction pathways. The management team at Ariad includes CEO Harvey Berger, formerly the president of research and development at Centocor Inc. As vice president of R&D, Ariad tapped a well-known and highly cited researcher, molecular biologist Joan Brugge, who left her prestigious position as a Howard Hughes Medical Institute investigator at the University of Pennsylvania to become vice president of research and development. Unusual Approach In putting together this blockbuster startup, Avalon broke with biotech tradition, which calls for increments of money to be meted out as certain developmental milestones are achieved. This new approach has met with some disapproval in the biotech financing community, coming from those who fear that if one company gets such a large block of money and then ultimately falls far short of expectations, the venture capital market could be soured. Bock has ready answers for these critics. "Traditional venture capital groups would say it doesn't make much sense to give that amount of money to a start-up company," he says. "But we say good management can handle a lot of money." The problem with the incremental approach to startup financing, the next round of financing, rather than forging ahead with research, and with staying ahead of the competition. Incyte's Scott agrees that the Ariad-style financing approach is "an interesting strategy," but says it remains unproven as to whether it is superior to the incremental approach. He contends that most of the companies that do this sort of financing find themselves needing money again fairly soon, anyway. Like many of the ideas that have formed the basis of the companies Avalon has created, the Ariad concept was born out of a casual exchange between the venture capitalists and a prominent researcher. In this case it was Harvard University chemist Stuart Schreiber, who had been on the scientific advisory board of another company Avalon helped found, Vertex Pharmaceuticals Inc. of Cambridge, Mass. According to Bock, just 15 months prior to Ariad's founding, Schreiber told Avalon, "What you guys ought to be looking at is this black box of cell biology--signal transduction and protein trafficking." Besides talking to researchers and reading the scientific literature, Avalon uses citation analysis as a means of identifying the cutting-edge areas of research. For example, the researcher whose scientific expertise Avalon tapped for its next company, Neurocrine Biosciences Inc., is Wylie Vale. This Salk Institute neuroscientist, according to the Philadelphia-based Institute for Scientific Information's Science Citation Index, is the eighth most cited scientist in 1981-90; his name appeared on nearly 350 papers in this period, which amassed a total of well over 16,000 citations. In founding Neurocrine, Avalon is once again going for big money up front, this time gathering between $30 million and $40 million in a private placement, meaning that it will bring together money not only from venture capital firms but also from wealthy individual investors. Corporate Partners Another financing approach that appears to be gaining popularity is to bring in, up front, a corporate partner for a start-up company instead of using the traditional tactic of waiting until product development has advanced to clinical trials. Hal Brodersen, a partner at the venture capital firm Hillman Medical Ventures Inc. of Horsham, Pa., says that GenVec Inc., to be located near the National Institutes of Health's campus in giant Genentech. Gen-Vec will be developing simple, easy methods of delivering gene therapies. Genentech will have rights to proprietary technology as a result of the joint financing. "It's common, down the road, for a biotech company to bring in a corporate partner, but it's uncommon for a corporate partner to be in on the founding," says Brodersen. Genentech is supplying $17 million, while Hillman is putting together an $8.5 million initial investment round for GenVec, he says. Hillman Medical Ventures' style of making direct contact with the scientists and their ideas is similar to the proactive approach that Avalon prefers. But GenVec, the result of a serendipitous encounter, was a special case. Both Brodersen and an official with Genentech were invited to speak at a meeting at the University of Pennsylvania. After the meeting, the two got together for a beer and found that both companies were looking to start a gene therapy company. And both said they were interested in tapping the same highly cited researcher, medical pulmonologist Ronald Crystal. Crystal, who pioneered the use of viral vectors to administer gene therapy to the lung tissue of cystic fibrosis patients, is among the top 100 cited scientists for 1981-90. He is leaving his post as chief of the pulmonary branch at the National Heart, Lung and Blood Institute to move to Cornell Medical Center in New York City and to be chief scientific adviser to GenVec. Brodersen is another venture capitalist with a science background. He has a medical degree, with a subsequent residency at the University of Pennsylvania. Halfway into this residency, "I realized I wanted to combine business and medical interests in some way," he says. The Wharton School of the University of Pennsylvania, a highly regarded business school, was right across the street, and so it was there he ended up taking his MBA. Like many scientifically trained venture capitalists, Brodersen finds that dwelling in both worlds is uplifting. "What's exciting to me is, every day is different. I learn more medicine being a venture capitalist than practicing medicine. I'm exposed to leading scientists in every specialty," he says. alliance is Glyco Tech Corp., which, like GenVec, is setting up shop near NIH. In this case, says company president John Magnani, Glyco Tech is capitalizing on access to the abundant financial and scientific resources of Swiss pharmaceutical giant Ciba-Geigy AG. Glyco Tech, which aims to develop novel immunotherapy drugs, is so new that Magnani, when reached via cellular phone last month, told The Scientist, "I'm in the middle of construction dust"; workers, he explained, were constructing laboratories for the startup in an industrial park adjacent to NIH. Magnani formerly was a research scientist with BioCarb USA, a division of a Swedish biotech firm that failed after its sole investor went bankrupt. Following that debacle, Magnani paid a visit to Ciba-Geigy Corp.'s pharmaceuticals division facility in Summit, N.J., where the company was interested in hiring him as an employee. He told them, however, that what he really wanted to do was form his own company. Word of Magnani's entrepreneurial ardor filtered back to Ciba- Geigy's biotechnology division in Basel, Switzerland, which had expressed some interest in BioCarb when it had been seeking a corporate partnership as a financial survival tactic just prior to its bankruptcy. Magnani was invited to deliver a lecture, which led to a corporate alliance/startup deal and the founding of Glyco Tech. He finds the arrangement advantageous, and not just for the $6 million, to be spread over five years, that it is supplying. Says Magnani: "Not only do I get the financial resources to start the company, I also get a lot of [Ciba-Geigy's] guidance, not just in business matters but also in science." Magnani, who left what he felt were the stifling bureaucratic confines of NIH about three years ago to enter the biotech startups fray, says, "What's exciting to me is to build something and watch it grow. At NIH, you're almost prohibited from growing. It has its sleepless nights, but I find it very invigorating." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Editor's Note: In this first part of a two-part series on biotechnology start-up firms, scientist-entrepreneurs and venture capital investors discuss the challenging financial atmosphere in which today's young companies must function. They explore the strategies required by startups as they pursue necessary funding, and they discuss the diverse backgrounds and styles of individuals participating in today's startup arena. In the second part, to appear in the April 19, 1993, issue, scientists and others will address the prerequisites other than money that are needed to successfully launch a new biotech firm. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Biomed Caucus Members Express Cautious Optimism On Prospect For Boost In Federal Research Funds (Page 1 of newspaper) BY RON KAUFMAN Five billion dollars is not enough, according to a group pushing for the federal government to pump more money into the basic biomedical research funded by the National Institutes of Health. And with Bill Clinton now in the White House, members of the group--the National Caucus of Basic Biomedical Science Chairs-- say they are very optimistic about achieving their goal. Composed of 21 biomedical department chairpersons from 19 different United States universities, the caucus convenes annually at George Washington University in Washington, D.C., to try to educate lawmakers about the importance of increasing funding for the basic biomedical sciences and to lobby for more support. They say ripe fields for investment are molecular and cell biology, molecular genetics, immunology, and structural biology. In an editorial published last October in the FASEB Journal (6:3133-4, 1992), the caucus proclaimed that the level of NIH funding for basic research cannot be "the previous small and insufficient annual increments that were based largely on matching inflation," but rather "will require doubling current spending for biomedical research over the next few years." Clinton administration, many of the members are hopeful that funding will increase under the new president. "I think that it's not likely that there will be less money," says caucus member John Matsen, vice president for health sciences at the University of Utah Health Sciences Center. "I don't know that Clinton has defined what the budget realities are, but I think we have to be optimistic at this point." The newly elected chairman of the caucus, Robert Kelley, chairman of the department of anatomy at the University of New Mexico School of Medicine, says he is "very optimistic" that Clinton will heed their suggestions. "We were concerned that NIH was being undercut by what we saw as the increased emphasis on the funding of biotechnology for short-term gain in the previous [Bush] administration," he says. "I believe we'll now have an impact so that people in leadership roles see that the basic science community is concerned about the funding issue." Kelley says if more money were to go to basic research, it would probably come from the expected cuts in the budget of the Defense Department. Yet some caucus members are more skeptical. "Clearly, there's more hope now than there was six months ago," says caucus member Raymond Woosley, chairman of the department of pharmacology at Georgetown University School of Medicine. "Yet there's still no evidence that things are going to change. Our concern is that if Clinton's call for `sacrifice, sacrifice, sacrifice' goes on very much longer, the basic biomedical sciences are not going to be here when they're called on. There will be nobody home." For fiscal year 1993, NIH is slated to spend a total of nearly $8.9 billion on biomedical research. About 60 percent of that ($5.3 billion) will be spent on what NIH defines as basic research. To put this into perspective, what the federal government will give NIH this year for basic biomedical research is almost double the entire 1993 budget of the National Science Foundation ($2.73 billion), which also funds scientific research. NIH allocations for applied research are less then half ($2.5 billion) that of basic research and in the past year have increased only 5.1 percent, while basic research has increased 6.1 percent. However, Georgetown's Woosley disputes the numbers: "Even though they say some large percentage, like 60 percent, is `basic,' it's basic but directed research toward a disease or illness, like AIDS or curing cancer. "The basic research that's directed is not pure basic research," he says. "Scientists are finding it very difficult to get funding for basic, undirected research into the basic principles and mechanisms of biology, which could possibly have a huge potential benefit....If you stop planting seeds, the fields are dead in a few years." Former NIH director James Wyngaarden says that although he supports the general notion that increased funding would benefit basic biomedical research, the total U.S. investment in this area is equal to those of other highly industrialized countries, such as Germany and Japan. "Every field competing for the federal dollar can make the claim that there are valuable aspects of research that cannot be explored because of lack of finances," says Wyngaarden, who was NIH director from 1982 to 1989 and is now the foreign secretary at the National Academy of Sciences. "There's no question that there is potentially valuable basic biomedical research that is not being addressed because of lack of funds. On the other hand, we have put forth a very substantial effort that is comparable to many other nations." The next meeting of the caucus is scheduled to take place in the middle of April. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Science Community Is Mixed On Clinton's Economic Plan While some experts see virtue in the new president's technology policy, others warn of hidden probems (Page 1 of Newspaper) BY BARTON REPPERT High-technology company executives and association officials, along with leading scientists and others in the United States initial responses to President Bill Clinton's economic program and his ambitious effort to redirect U.S. technology policy. At the same time, several science and technology policy-watchers interviewed by The Scientist say they will need further details about the administration's science and technology initiatives, including specific budget figures, before they can offer a more thorough assessment of the Clinton plan. "I guess at this stage you could say there's a lot of excitement," says Fred W. Weingarten, executive director of the Washington, D.C.-based Computing Research Association, which has been distributing to its members--mainly university computer scientists--information about Clinton's proposals. "They're reading it, and they're talking about it on the [Inter]net." But Weingarten adds that "there are still a lot of unanswered questions about how exactly it would be organized, what the funding would be." Clinton's technology plan--emphasizing increased government assistance for the development of advanced industrial technologies--is estimated to cost about $17 billion over the next four years. It may amount to the most far-reaching R&D policy initiative since 1954, when the Eisenhower administration directed federal agencies to help support basic research. According to White House science and technology adviser John H. Gibbons, "The nation urgently needs improved strategies for government/industry cooperation in the support of industrial technology. We cannot afford to wait for investments in defense and space to trickle down to civilian industry." Key elements of the administration's technology policy include: making the research and experimentation tax credit permanent; accelerating efforts to create a national "information infrastructure" through development of more powerful computers and faster computer networks; directing federal laboratories to undertake more R&D partnerships with private industry; increasing funding for advanced manufacturing consortia, along with creating a national network of manufacturing extension centers; providing government support to assist the development of a new generation of efficient, nonpolluting automobiles; and improving technology for use in education and training. A White House policy paper spelling out the technology plan contends that "this new policy will result in significantly more federal R&D resources going to (pre-competitive) projects of commercial relevance. It will also result in federal programs that go beyond R&D, where appropriate, to promote the broad application of new technology and know-how." The announcement of the new technology policy on February 22-- during a trip by Clinton and Vice President Al Gore to a computer firm in California's Silicon Valley and a Boeing aircraft plant near Seattle--came less than a week after Clinton, in a speech to Congress, presented his overall economic plan, including proposed funding increases for certain research programs along with cutbacks for others. According to an analysis of Clinton's plan prepared by the House Committee on Science, Space, and Technology, "S&T programs are relatively unscathed in the deficit reduction package. Of the $54 billion in non-defense discretionary reductions which are identified, less than 2 percent (net) are in the S&T area." At the same time, the committee analysis says, S&T programs are an important component of the additional "investment" spending proposed by Clinton. "Out of approximately $100 billion in spending incentives for FY [fiscal years] 1994-1997, over 10 percent are in the S&T area.... If all these investments were in fact funded, they would probably come close to restoring a 50:50 civilian/military R&D ratio by FY 1997." Currently, the civilian share of the total federal R&D budget is about 41 percent. The panel's chairman, Rep. George E. Brown Jr. (D-Calif.), said in releasing the analysis that he looks forward to working with Clinton on the S&T initiatives: "The administration clearly is committed to science, space, and technology as critical components of a long-term investment strategy aimed at job creation and sustained economic growth." However, the science committee's ranking Republican, Rep. Robert S. Walker of Pennsylvania--reflecting the views of other conservative-oriented critics in Congress, private industry, and elsewhere--says he is concerned about several aspects of Clinton's plan. "My principal concern about the package is its endorsement of overt government participation in technology development ... where we are now going to have government involved in commercial applications of one kind or another, and where you have government playing a more substantive role in picking technology winners and losers," Walker says. Also, he says, "I believe that a substantial part of the problem that we face is as a result of excessive litigation, excessive regulation, and excessive taxation in the technology field. And until we deal with those issues, we are not likely to end up with a global competitiveness posture which is satisfactory." Clinton's proposals have drawn statements of support--though not unqualified endorsement--from leaders of several R&D-intensive industries, such as aerospace, computers, and electronics, and bio- technology. But there have also been complaints from some sectors--such as the pharmaceutical industry, which is concerned over possible moves to impose government price controls on prescription drugs as part of an overall effort to deal with spiraling health care costs. J. Richard Iverson, president of the American Electronics Association--a group based in Santa Clara, Calif., that represents about 3,000 high-tech companies across the U.S.--said in a press statement that "we applaud the president's leadership in presenting a long-term, serious plan to get the economy moving again. Like everyone else, we have concerns about the impact of some of the tax provisions, especially those related to foreign tax issues. However, on balance, the package is a significant step forward." Martha Sloan, president of the Institute of Electrical and Electronics Engineers, an association with about 250,000 members in the United States, says Clinton's technology policy and its emphasis on aiding U.S. high-tech companies shows that "the whole attitude of the administration is very different from the previous one.... " Adds Sloan, who is a professor of electrical engineering at Michigan Technological University in Houghton, Mich.: "His visit to Silicon Valley was very positive. The whole [area of] high- speed computing and high-speed communication is certainly a very Don Fuqua, president of the Washington, D.C.-based Aerospace Industries Association, said in a statement that "we are encouraged by the president's statement that he will give special attention to the aerospace industry, which he singled out as one that is of critical importance." Another industry group that has come out in support of Clinton's economic package and technology policy is BIO--recently formed through the merger of the Industrial Biotechnology Association (IBA) and the Association of Biotechnology Companies (ABC)--also based in Washington. The group's president, Carl Feldbaum, said in a press statement that he believes Clinton "fully appreciates how government actions can strengthen or strangle the development of a high-technology-based industry such as biotechnology." He specifically cited Clinton's support for making the research and experimentation tax credit permanent, for active R&D partnerships between industry and government, and for what Feldbaum called "a regulatory policy that encourages innovations and achieves social objectives efficiently." At the same time, however, Feldbaum warned that "the government could destroy biotechnology through counterproductive policies such as imposing controls on the introductory prices of new biopharmaceuticals. If companies are not able to generate a reasonable return on these types of long-term, high-risk investments, then it will be impossible to attract the venture capital that has been the lifeblood of the biotechnology industry in the United States." David L. Winter, president and chief operating officer of GenPharm International, a biotechnology company based in Mountain View, Calif., says he believes it is "really much too early to tell right now" what kind of longer-term impact Clinton's initiatives may have on the biotech industry. With regard to the administration's proposal for making the research and experimentation tax credit permanent, Winter says: "Any tax credit in this area helps us, there's no question. We're just totally R&D-dependent." Overall, the GenPharm executive says of Clinton's economic program and technology policy: "We're very pleased that the administration is saying some of the right words. What we're concerned about is that the biotech industry be so wrapped into the pharmaceutical situation that it's not looked at as a high- tech field distinct from the pharmaceutical industry, with its own problems and needs." With S&T "megaprojects," the administration has decided to propose stretching out for another four years--until 2003-- completion of the superconducting supercollider, and also undertaking a fourth redesign of the space station. The SSC stretch-out will trim near-term outlays but result in raising the project's final cost from $8.3 billion to roughly $10 billion, while redesign of the space station is aimed at reducing costs of the project by $2.1 billion over the next four years. Although the administration's main focus has been on technology, it has also called for sustained federal funding of basic research. Presidential science adviser Gibbons told the House science committee at a March 4 hearing: "None of the innovations in technology proposed in our initiative will be funded at the expense of basic science. Our budget proposal ensures that support for basic science remains strong and that stable funding is provided for projects that require continuity. We will not allow short-term fluctuations in funding levels to destroy critical research teams that have taken years to assemble." To underscore this commitment to basic research, the administration is requesting a fiscal year 1993 supplemental appropriation of $207 million for the National Science Foundation, along with further budget increases for NSF--over previously projected levels--totaling $2.297 billion during the next four years. With regard to biomedical research supported primarily by the National Institutes of Health, Clinton's plan would involve spending an additional $8.182 billion in 1994-97 on HIV/AIDS, women's health, and other NIH research, along with child immunizations and other public health initiatives. No specific figures were provided on the portion of this overall amount going Shu Chien, president of the Bethesda, Md.-based Federation of American Societies for Experimental Biology (FASEB), says that "I applaud the goal of emphasizing basic research, and also the point of the need for continuity--stable funding." Chien, a professor of bioengineering and medicine at the University of California, San Diego, says FASEB will be urging Congress to provide enough additional funding to offset the $217 million cut it imposed on NIH's budget last year. As for how he views the current research funding climate on Capitol Hill, Chien says: "It's still hard to assess. I think we need to do a lot more work, because there are a lot of new members of Congress." Barton Reppert is a freelance writer based in Gaithersburg, Md. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ THE CLINTON PLAN (Page 6 of Newspaper) The Clinton administration has proposed the following new initiatives in its technology policy, as presented in a White House policy paper, "Technology for America's Economic Growth" (released on February 22): Research and Experimentation Tax Credit: The administration is calling for permanent extension of this tax credit, which would apply to qualified research expenditures paid or incurred after June 30, 1992. Performance Computing and Communications Program, to assist development of more powerful supercomputers, faster computer networks, and more sophisticated hardware; also, creating an interagency task force on information infrastructure; providing funds for networking pilot projects; and promoting dissemination of federal government information. Advanced Manufacturing Technology: To provide increased federal funding for advanced manufacturing R&D, particularly to consortia such as SEMATECH; also, supporting "agile manufacturing," facilitating more flexible production; creating a national network of manufacturing centers; and promoting environmentally conscious manufacturing. Technology for Education and Training: Includes expanding access to Internet and developing high-speed National Research and Educational Network (NREN); also enhancing programs being developed through Federal Coordinating Council for Science, Engineering, and Technology (FCCSET) to improve the teaching of science, mathematics, and engineering at all levels. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ FUNDING INCREASES (Page 6 of Newspaper) Major science and technology agencies and programs for which the Clinton administration is proposing additional federal funding (amounts listed are the requested total increases over current projected budgets for fiscal years 1994-97): NSF--including support for more "strategic research." Clinton also requesting $207 million supplemental appropriation for current fiscal year. $2.297 billion NIH--including HIV/AIDS, women's health, and other NIH research; also, immunizations and other public health initiatives. (Not yet specified how much of this total will go to biomedical research.) NIST--for Advanced Technology Program; manufacturing extension centers; other R&D to assist industry. $1.306 billion FCCSET research initiatives (climate, advanced supercomputers and networks, math and science education, materials processing, biotechnology, advanced manufacturing). $1.206 billion High-performance computing and networks (NSF, NIH, NIST, and NASA). $ 784 million "Information highways"--Commerce Department (for telecommunications demonstration projects). $ 275 million Industry/government civilian research at DOE laboratories. $ 180 million Advanced Neutron Source--for biomedical, materials, and other applied research (to be constructed at Oak Ridge, Tenn.). $ 420 million Tokamak Physics Experiment--for fusion energy research (to be constructed at Princeton, N.J.). $ 210 million (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ FUNDING CUTBACKS (Page 7 of Newspaper) Major programs in which the Clinton administration is proposing federal funding cutbacks: Space station--Undertaking fourth redesign of project in order to save $2.126 billion during 1994-97. Superconducting supercollider--Administration proposing $640 million for fiscal 1994, or $70 million cutback from previously projected budget. However, stretch-out of SSC completion over four years will raise total cost by $1.770 billion. Indirect costs--Seeking to save $1.2 billion over next four years by capping overhead costs of university research grants. Nuclear reactor research--Savings of $820 billion from phasing out advanced reactor program. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Blue-Ribbon Panel Begins Process Of Closing Up Shop (Page 3 of newspaper) BY BARBARA SPECTOR At an April 1 meeting in Washington, D.C., the Carnegie Commission on Science, Technology, and Government formally began the process of going out of business. The commission's five-year charter ends June 30. The panel was convened in 1988 under the auspices of the Carnegie Corporation of New York to assess the ways in which policymakers take science and technology issues into account when making decisions. The blue-ribbon panel is cochaired by Nobel laureate Joshua Lederberg, former president of Rockefeller University, and William T. Golden, chairman of the board of the American Museum of Natural History in New York, who formerly served as a special consultant on scientific activities to President Harry Truman. Included among the members of the commission and its advisory council are some of the United States' most prominent scientists, Republican Gerald Ford); three former U.S. senators (Republicans Charles McC. Mathias, Jr. of Maryland and Daniel Evans of Washington, as well as Democrat Lawton Chiles of Florida); three former U.S. representatives (Democrats John Brademas of Indiana and Paul Rogers of Florida, as well as Mathias, who served in the House before being elected senator); and three current or former governors (Democrat Richard Celeste of Ohio, as well as Chiles, now Florida's chief executive, and Evans, who was Washington's governor from 1964 to 1977). Winding Down Commission staff, as well as the commissioners themselves, say the five-year limit on the panel's lifespan is a positive thing. "The types of studies the commission did could continue to be done by others, or the commission could go on," says Mark Schaefer, senior staff associate and director of the commission's Washington, D.C., office. "But it's a good idea to have a defined lifetime and then go on and do other things. I think it keeps people fresh." In the five years that commission members have been working together, Lederberg says, "we all got to know each other, and personal axes to grind were all worn down. In that way, it's a shame to disband, but I think we all agree it's time. I don't think the world needs a permanent watchdog." Vital Statistics The panel's 15 committees and task forces, involving the efforts of more than 150 high-power volunteers, have made about 400 recommendations. While commissioners acknowledge that some of these suggestions are more likely than others to be put into practice, they note that several have already been implemented (for example, the recommendation that the president move quickly to appoint a science adviser--as President Clinton did when he named John Gibbons to the post in December). Yet, as Golden notes, "One can never be sure of paternity; we weren't the only ones urging such action." In addition to its eminent volunteers, the commission has eight professional full-time-equivalent staffers scattered among its three offices--two in New York and one in Washington. When the commission's charter ends, some $12 million to $15 million will have been spent on continued production and dissemination of its 18 reports. In addition, the commission has contributed to a half-dozen other publications, as well as several dozen background or working papers. "Commission on Everything" because of the wide range of topics it has addressed, according to one source who requests anonymity. It has issued reports on science and technology as they relate to societal goals; international affairs; and the executive, legislative, and judicial branches of government, among other subjects. Bidding Adieu The April 1 event was the final formal activity of the full commission. After a closed session in which the panel was scheduled to approve one of its last task force reports-- "Science, Technology, and Congress: Organizational and Pro- cedural Reforms"--it hosted a meeting and reception for about 300 members of the U.S. scientific community as well as members of government and the media. Gibbons was among the invited speakers slated to address the group. At press time, the meeting had not yet taken place. The open meeting marked the release of a report noting the highlights of the commission's tenure, "Science, Technology and Government for a Changing World." Also planned is a book-length summary document on the work of the commission, now being written by Lederberg and Jesse Ausubel, the commission's director of studies. The volume is scheduled for publication in the winter of 1993-94. The purpose of the meeting, says Golden, was "to review what we have done and plot for the future--to devise ways to stimulate continued attention to the issues to which we have paid attention." David Z. Robinson, the commission's executive director, adds that another goal of the meeting was to thank the invited guests--many of whom had been sought out by the commission for advice--for their help and to get their reaction to the panel's five-year- long work. "If they agree with the conclusions [of the reports]," Robinson says, "we want them to have `ownership' of them, and use the fact that the commission has recommended them to push them." The Next Stage "There will be an enormous letdown after [the commission disbands]," acknowledges Maxine L. Rockoff, senior administrator of the commission. "But there will also be a lot that gets launched." The chairpersons of the commission's various task forces, she says, "are committed to the ideas" set forth in the reports. "There will be continued growth and flowering of seeds that the commission planted, even though there won't be a central Golden says he hopes that some of the responsibility for seeing that the recommendations get carried out will be shouldered by "other organizations that will continue more or less in perpetuity," such as the national academies of science and engineering, scientific societies, and academic entities like Harvard University's John F. Kennedy School of Government. "We hope they will use our reports and create their own." As others take over, he adds, "there'll be mutations to our recommendations--and there ought to be as the years go on. Our recommendations won't last in perpetuity, but will mutate in a Darwinian way." The Carnegie Corporation will support the distribution of the commission's reports to anyone who requests them for the next year or two, corporation staffers say. Robinson, a research physicist who was executive vice president and treasurer of the Carnegie Corporation before joining the commission staff, will return to the corporation and will work there on implementation of the commission's findings. In addition, says the commission's creator, Carnegie Corporation president David A. Hamburg, "there are some grants that [the corporation] may make over the next three years to follow up in spirit." For example, he says, funds might be disbursed to university-based groups or scientific organizations that want to pursue the commission's ideas. An important component of the follow-up process will be the efforts of the commission members themselves, commission officials say. "All of us who have been connected will be promoting these gospels as best we can as a sideline to our other activities by seizing every opportunity to bring these issues up," says Golden. Another way for commission members to keep the recommendations in the public consciousness, says Robinson, is by writing opinion pieces in journals and newspapers. The level of interest in continuing the panel's activities will vary according to the commitment of the individual commission members, Golden acknowledges: "Some will be more interested than others; that's the way of the world. All of these things have a half-life, it's true. The next few years will be very important-- attention will taper off unless we keep the attention level up." Rodney W. Nichols, chief executive officer of the New York Academy of Sciences and a member of the commission's advisory something on a pro-bono basis" will keep to their commitment after the commission has shut down. "Those of us involved will keep tracking [the recommendations] through networking and meetings," he says. "Would I be doing the same things if the commission had never existed? The answer is probably yes." Robinson notes, however, that "the value of reports goes down over time." As the years go by, he says, it is possible that "the recommendations [will be] all in place or all rejected"--or that changing times have rendered some of the items moot. "These things [recommendations] ought to be airborne," says Golden. "They'll go on their way, and in the next couple of years there'll be a need for another Carnegie Commission." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ NOTEBOOK Page 4 of Newspaper Colorado Amendment Gets Rocky Reception Members of the scientific community are starting to express their opposition to Colorado's Amendment 2, a change in the state constitution passed in November that prohibits local antidiscrimination laws for homosexuals. Although the American Chemical Society went ahead with its meeting in Denver March 28- April 2 (Barbara Spector, The Scientist, March 22, 1993, page 3), the American Mathematical Society and the Mathematical Association of America (MAA) have voted to move their joint January 1995 meeting from the originally planned site of Denver to a location yet to be determined. According to the February 1993 issue of Focus, MAA's newsletter: "The financial implications of a pull-out at this stage are not at all clear . . [but] not moving would also be costly. . . . Given the strong sentiment many felt on this issue, it seemed likely that a meeting held in Colorado . . . would be boycotted, leaving a greatly impoverished meeting." Meanwhile, the Committee of Concerned Scientists has passed a resolution stating: ". . . We express our grave concern about [Amendment 2] and strongly urge its repeal." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ This Party Could Be A Real Blast Los Alamos National Laboratory, together with Los Alamos County, N.Mex., is sponsoring a number of events, beginning next week, to mark the 50th anniversary of the Manhattan Project and the opening of the lab. A series of seminars and panel discussions on the scientific and policy implications of the lab's work is slated for April 12-16, featuring speakers such as former laboratory directors Harold Agnew (1970-80) and Don Kerr (1980- 85); Sens. Jeff Bingaman (D-N.Mex.) and Pete Domenici (R-N.Mex.); and Frank von Hippel, editor of the Bulletin of Atomic Scientists. On June 7-10, more than 900 people who worked on the Manhattan Project have been invited to Los Alamos to view an exhibit of project memorabilia, tour the project site, and dance to big-band music. On June 11-12, Los Alamos County will sponsor a "Bridge to the Future" festival, highlighting the Hispanic and Pueblo cultures of the region. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Swimming Upstream There is, undoubtedly, something fishy about this month's space shuttle Endeavor mission. An experiment on board will test whether mutations occur in brine shrimp that hatch and develop in the microgravity of space. Brine shrimp cysts will be injected into a saline solution and videotaped for seven days as they undergo their rapid growth cycles. A parallel set of Earth- hatched shrimp will be brought along as a control group. After the shrimp return to Earth, the development, swimming patterns, and breeding habits of the two groups will be compared. The experiment's researchers, from Sierra College, Rocklin, Calif., suspect that mutations in the space-hatched shrimp may be an outcome. Andy Schmidt, president of Newark, Calif.-based San Francisco Bay Brand, which manufactures brine shrimp-based fish food and supplied the brine shrimp used in the study, points out that this is an experiment that keeps on giving: "The brine shrimp cysts produced during the space life cycle will be made available to other science programs, so the research will go on." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Not Like Mama Used To Make Purdue University scientists have genetically engineered a tomato plant that they claim will produce thicker spaghetti sauce, tomato paste, and ketchup because of its 10 percent increase in soluble solids. The West Lafayette, Ind., scientists found the gene that produces the enzyme pectin methylesterase involved in ripening, reversed it, and inserted it back into the tomato plants, yielding the more solid tomatoes. Other Purdue teams are investigating using biotechnology to make rice a complete-protein food and to develop ways to produce low-fat meats. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Environmental Focus In a rare case of students demanding to be taught a subject, this fall the University of Southern California is launching several interdisciplinary degree programs focusing on the environment. Undergraduates in the USC College of Letters, Arts and Sciences will be able to earn B.S. or B.A. degrees in environmental studies; students in the School of Engineering can receive a B.S. degree in environmental engineering. USC officials say the new majors are in response to a rapid rise in enrollments in existing environmental programs at USC and nationwide figures indicating that incoming freshmen believe the government is not doing enough to combat environmental pollution. All of the tracks are highly interdisciplinary, university officials note. Social science majors must take courses in biology, chemistry, geology, and other natural sciences. Natural science majors must sample courses in environmental law, economics, politics, ethics, or sociology. Engineering students, meanwhile, will be exposed to geology, biology, chemistry, physics, and political science, in addition to civil and chemical engineering. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ The Doctor As Scientist The Yale University School of Medicine is trying to close the "bench-bed" gap. Through a five-year, $2.1 million grant from the Miami-based Lucille P. Markey Charitable Trust, Yale will train 11 of its students to combine their knowledge of patient care creators hope these physicians will learn to swiftly correlate laboratory discoveries with classical clinical treatment of human ailments. During the first six weeks of the course, the students will be exposed to advances in experimental cell and molecular biology in Yale's Life Sciences Research and Training Center. They will work on an individual research project for the next 2 1/2 years. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ A Remedy For Science Education Crisis Is Long Overdue (Page 11 of newspaper) BY BILL G. ALDRIDGE Science and mathematics education in the United States is desperately in need of reform, and any substantial remedy will demand not only the financial support of the federal government, but also a concerted effort by scientists, lawmakers, and educators. Although the current crisis has been in the making for decades, efforts at corrective action have been stymied by a fundamental and disastrous misunderstanding. In December 1981, James Shymansky, a science education professor at the University of Iowa, and I surveyed 450 teacher placement offices at U.S. colleges and universities. We also polled 1,000 high school principals to determine the qualifications and teaching assignments of science and math teachers. The results were startling: Half of the classes of newly employed science and math teachers and one-third of all science and math classrooms in the U.S. were, according to the school principals, staffed by teachers who were unqualified in those subjects. The number of men and women who had received teaching degrees and were qualified to teach science and math had dropped by a factor of four in only 10 years. These results, which were incorporated into testimony presented by the National Science Teachers Association (NSTA) to committees immediately, a flurry of other studies and commissions was created to further analyze what appeared to be an emerging crisis in science and math education. One such effort--the National Science Board Commission on Precollege Education in Mathematics, Science, and Technology-- documented defects in science and math education and showed the relationship of this emerging crisis to the nation's needs, including its ability to compete in a global economy. The fundamental finding was that the U.S. was failing to educate both its general population and its needed specialists in science, math, engineering, and technical fields--the very areas most needed for commercial innovation and efficacy. The NSB report also showed that the U.S. population was going through revolutionary changes in its makeup, with minority populations--largely underrepresented in science and technical fields--soon to become a majority. According to the report, the general level of scientific and technical literacy had to be raised in order to place a larger number of qualified people into the science and engineering job pool, while simultaneously addressing the problem of science and technology literacy for the general population. However, not to be outdone by NSB, the U.S. Department of Education, under T.H. Bell, then Secretary of Education, created a commission on excellence in education. And an April 1983 report by this commission, titled A Nation at Risk, was the spark that ignited a broad-based call for reform not just in science and math education, but in all areas of education. In doing so, the report cited dismal statistics on U.S. student achievement compared with that of students of other nations--including sharp declines in U.S. students' Scholastic Aptitude Test (SAT) and American Council on Testing (ACT) scores. However, unlike the NSB report, the Department of Education report, proclaimed a crisis in all areas of education. But it failed to provide evidence linking the statistics it cited and the reforms it recommended. Indeed, A Nation at Risk had no bibliography or citation of sources for its data. Instead, a list was provided of authors of commissioned papers--papers that were unchecked by peer reviewers and were often presented in the form of opinion. As for the lower test scores reported, they were a function not of diminished capability or quality of education, but of the significant rise during the two decades prior to the study in the number of students entering and completing high fact that when larger numbers are involved, lower average scores will result. Moreover, most of the test results cited in A Nation at Risk either were irrelevant or could be accounted for quite easily by demographic changes that had occurred in the schools studied. The truth is, except in science and math, there never was a documented crisis in education. Nevertheless, as the various reports appeared, and were picked up by the media, the documented crisis in science and math education was erroneously broadened into something quite unreal. What resulted were mainly solutions to nonexistent problems. For example, at the federal level, support for foreign language instruction was increased. At the state and local levels, specialized high schools were created, in which the top (usually the most advantaged) students were skimmed from other schools and excessive resources provided to prepare even more specialists, while further impoverishing the schools from which these resources had to be drawn. Although requirements for more science and math courses for graduation were imposed by some states, they were imposed without improving inappropriate courses and content. And they were imposed without providing the additional funds for teacher training, laboratories, or supplies that would make science experiences in the schools truly meaningful. Needed were incentives for more young people to go into science and math teaching; needed were massive retraining programs for current teachers of science and math. And curricula needed to be revised to make it possible for all students to learn science and math. The massive support required for dealing with the crisis in science and math education would have had to come from the federal government, since states did not have the resources. But Congress is so constituted that it cannot seem to target any problem. The only way to get votes is to provide general support. It is the shotgun approach: Throw money at every geographical area and every possible constituency. Thus, from Congress' point of view, our whole educational system had to be regarded as flawed and, therefore, the entire system had to be reformed. The right-wing conservatives in the government of the 1980s, meanwhile, saw the situation as an opportunity to dump public involvement in education, but to any government involvement--even that of local governments and their school boards. They wanted schooling to be entirely separate from government, with the task of improving education entrusted either to private schools or profit-making companies. As a result, then, of Congress' inability to target a single area of concern, compounded by the disinclination of the Reagan and Bush administrations to get government involved in addressing the concern, we find the U.S. suffering today from a crisis in science and math education that is harsher than ever. In our efforts to resolve the crisis, we must be careful not to place blame on either our teachers or our schools. Teachers are doing as well as they can with the resources provided. The so- called unqualified teachers are, more often than not, teachers who are fully qualified in one field, but are being required to teach in several fields, irrespective of their credentials. They are therefore not unqualified teachers; they are misassigned teachers. Nor can our schools and teachers be accused justly of being uncooperative, resistant to change, or hostile to the use of new and expensive technologies. What, after all, can they do to innovate or become responsive when the nation has cut its federal support for schools in half over the past 12 years, and when states are unable to provide even baseline support, having had dumped on them the financial responsibilities previously assumed by the federal government? How do teachers teach meaningful science with no labs or no money for supplies or equipment? How do we reform our schools with $5 per year per student (the national average) for educational materials for an entire course? And how do we inspire teachers who are burdened by misassignment to subjects for which they have no preparation, who are still paid far less than they would earn in similar positions in the private sector, and when they no longer enjoy even the respect and admiration that once substituted for salary? It is possible for us to leverage the problem in science and math education, but this will require a concerted effort by lawmakers, scientists, and educators. Lawmakers will have to respond to the fact that we must dedicate a disproportionate amount of federal education support to science and math. Educators, for their part, should seriously question the notion, common among them in the U.S., that most young people cannot learn real science, and that, therefore, we should focus science education on personal and applied to decision-making that they will need in their daily lives. But this is without learning the underlying science, if any, and it assumes that the methods of science are appropriate for making decisions in a wide range of areas where emotion, belief, political preference, and aesthetics often dominate. And what can scientists do? Well, there is a desperate need, for example, for university scientists to work with their colleagues in science education and with high school science teachers to address the serious problems we have. Science teachers need greater depth of understanding of the various subjects they are expected to teach, and all teachers need to pay more attention to research on how people learn. All scientists should work at the local, state, and federal levels to secure support to address the problems. There currently are serious efforts being undertaken to create national standards and to pursue reforms in science and math education. Almost all of these efforts have as a component prestigious panels of expert advisers. In addition to scientists, science educators, and science teachers, some panels include people from the social sciences or from political office. It is my observation that scientist panel members rarely attend meetings, much less offer substantive advice. As a consequence, unsupported positions, some of which I have already described, go unchallenged. When called upon to serve on these panels, scientists should lend more than their names. The need for revolutionary reform in science and math education is real. If scientists do not take this very seriously and lend their expertise as well as their names, the reform will fail miserably. Bill G. Aldridge is executive director of the National Science Teachers Association, Washington, D.C. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ COMMENTARY (Page 12 of Newspaper) by Mark Robson Interdisciplinary Efforts Are Needed As Researchers Battle Environmental Threats In an old parable, each part of the body claims superiority: The head boasts of its intelligence, the feet of their fleetness, the eyes of their vision. The respective claims don't pan out, though, the moral of the parable being that, to function most effectively, each of the parts must learn to work with the others. This is a lesson that the scientific community should heed--especially now that science and society must join in thwarting serious threats to our environment. Traditionally, it's been rare for biologists, chemists, physicists, and engineers to communicate with ease, let alone pursue cooperative research. Rarer still has been the inclination for researchers to reach beyond their hard-science disciplines in shared endeavors with economists, lawyers, public health experts, sociologists, and so forth. What we're only now beginning to understand is that to solve today's problems--especially environmental problems--we need to draw on the expertise available across disciplines, scientific and otherwise. Currently, the most successful environmental solutions are being developed by laboratory scientists, field researchers, doctors, and lawmakers, all working together. But attaining a really productive level of cooperation is far from easy. In a college environment, professors are used to sharing their results, but they balk at sharing in the research process. Communication is lacking, and, to make matters worse, the typical campus rarely sees science faculty classrooms and offices in proximity to those of the nonscientists; indeed, they may be on different campuses altogether, making informal exchanges of ideas all but impossible. Three strategies may help to overcome the factors impeding interdisciplinary endeavors: * Different disciplines should be housed under one roof. If psychologists could easily consult with toxicologists over coffee, we might more quickly gain an understanding of the perplexing syndrome known as multiple chemical sensitivities. If specialists in exposure measurement and education were in adjoining offices, we might better mobilize people to reduce analysts attended the same departmental meetings, we might devise better plans to protect the health of those living near toxic waste sites. * Granting agencies should reward interdisciplinary efforts by giving special consideration to interdisciplinary proposals. A single proposal, for example, might seek funding for research into better ways of measuring blood lead levels accurately; at the same time, it would seek support for studies on methods to assess sources of lead within the home, and it would solicit funding to support education and training for parents trying to protect their children from lead poisoning. * Institutions should consider hiring a science coordinator charged with locating areas of overlapping interest and encouraging researchers across disciplines to work together. Such a person can play a key role in organizing interdisciplinary conferences, lectures, and colloquia. At the Environmental and Occupational Health Sciences Institute in Piscataway, N.J., we are beginning to see the fruits of some of these interdisciplinary strategies. Jointly sponsored by Rutgers University and the University of Medicine and Dentistry of New Jersey, the institute houses under one roof medical doctors, toxicologists, biochemists, environmental scientists, molecular biologists, pathologists, pharmacologists, geographers, engineers, educators, and policy analysts. Additionally, there's a clinic on campus for evaluating patients who may have been exposed to environmental contaminants, a worker training center, and a resource library open to the public. Primarily because of our interdisciplinary format, we've been able to attract funding for a National Institute of Environmental Health Sciences Center of Excellence and to win grants from state and federal agencies to study pesticides, lead, and toxic waste. Certainly all has not gone smoothly. Turf quarrels have erupted from time to time as people struggle to work within a new and, to some, alien framework. Overall, however, we are rapidly learning that--as an alternative to the parable of the warring body parts- -two heads are better than one. With environmental studies, this certainly seems to be the case. Mark Robson is acting executive director at the Environmental and Occupational Health Sciences Institute, a joint project of Rutgers University and the University of Medicine and Dentistry (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ LETTERS Animal Research (Page 12 of the Newspaper) As president of Americans for Medical Progress (AMP), I am writing on behalf of our 1,600 members concerned with the radical "animal rights" movement's threat to medical progress. AMP is a nonprofit organization dedicated to ensuring the future of medical research that eases human suffering and saves human life. The article "Opponents Set 1993 Tactics For Animal Rights Showdown" (Ron Kaufman, The Scientist, Jan. 25, 1993, page 1) doesn't tell the whole story with respect to the issue of the use of animals in biomedical research. First, any discussion of the tactics planned by "animal rights" activists should include threats, distortion, and violence. To simply say that "animal rights" fanatics are going to concentrate on education is to ignore their 10-year history of criminal activity. Furthermore, their idea of education is nothing more than the dissemination of their deceptive propaganda. Those who heed the lessons of the radical "animal rights" crowd will certainly not have a proper understanding of the issue, nor will they have the opportunity to make a well-informed decision of their own. The scientific community, on the other hand, is dedicated to helping young people understand the value of biomedical research, while allowing individuals to make their own ethical decisions. protectionists" suggests a misunderstanding of the difference between "animal rights" and "animal welfare." AMP supports the concept of animal welfare. Like all human beings, scientists have an obligation to treat animals in a humane, compassionate manner. But the philosophy of "animal rights" transcends the traditional concept of animal welfare, and argues that animals have the same rights as human beings, and therefore cannot be used for any purpose, including food, clothing, and medical research. Finally, to suggest that two-thirds of the students polled support "animal rights" because of their "natural sensitivity to animals and the environment" is to suggest that to be pro- research indicates insensitivity. The two (pro-animal and pro- research) are not mutually exclusive. Those of us who are pro- research simply realize that thousands of human lives depend on responsible medical research. SUSAN E. PARIS President Americans for Medical Progress Inc. Arlington, Va. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Dissenters Suppressed? The Scientist (Notebook, Feb. 8, 1993, page 4) announced that a PBS show on Rachel Carson and Silent Spring would include "interviews with foes and friends." The interviews with "foes" were with only one person: myself. The only other opponent was Professor Robert White-Stevens of Rutgers University, who died several years ago and thus, for obvious reasons, was not interviewed. Instead, two or three selected film clips were shown, to represent him as a spokesman for the pesticide industry. Several "friends" came on camera for a total of about 30 times, plus a number of character witnesses. Topics that were not mentioned were the use of DDT by the World Health Organization, and the fact that it saved millions of lives from malaria. I had discussed such matters when I was videotaped, but these parts of the tape were not used. THOMAS H. JUKES Department of Integrative Biology University of California Berkeley (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ WHERE TO WRITE: Letters to the Editor THE SCIENTIST 3501 Market Street Philadelphia, PA 19104 U.S.A. Fax: (215)387-7542 Email: 71764, THE SCIENTIST welcomes letters from its readers. Anonymous letters will not be considered for publication. Please include a daytime telephone number for verification purposes. ======================= Controversial Theory Sparking Research On Alzheimer's (Page 15 of Newspaper) BY DIANA STEELE Research on Alzheimer's disease is one of the hottest topics in the biological sciences today. In 1992, for instance, two Alz- heimer's papers made it into the list of the top 25 cited papers Information of Philadelphia. And in 1991, one paper occupied the second-most-cited slot for that year. But despite the excitement among researchers, there remains a number of unanswered questions about the underlying mechanisms of the disease. While the most popular theory--that the key to the disease is beta-amyloid, the peptide fragment that accumulates in patients' brains--continues to gain ground, some worry that devoting all research to the beta-amyloid theory may be dangerous. "If it doesn't pan out, you take about 100 steps backward," says one knowledgeable research scientist at an East Coast biotech company heavily involved in developing drugs that target beta- amyloid production, speaking on condition of anonymity. He and other researchers say that while the beta-amyloid theory holds the greatest promise for developing a cure, if the notion ultimately fails to pan out, little has been done to test other approaches, forcing scientists in academia and industry to go back to the drawing boards in developing new approaches to treating this disease. The beta-amyloid peptide contains approximately 40 amino acids and is the primary constituent of the distinctive plaques that accumulate in the brains of Alzheimer's patients. It's not clear what the normal function of beta-amyloid is, much less its role in the pathogenesis of the disease. Beta-amyloid is a derivative of a much larger, membrane-bound protein called the amyloid precursor protein (APP), and there have been some tantalizing clues discovered in the course of research as to how the larger protein might be broken up to produce the peptide fragment, but the enzymes involved have not yet been found. Biotech and pharmaceutical company researchers are vigorously working to characterize these enzymes and developing compounds that block their action. They see this approach as the fastest route toward developing drugs that will halt the disease's progress. Beta-amyloid's role in the pathogenesis of Alzheimer's disease-- whether it's a primary cause of the disease or a secondary symptom--continues to engage scientific debate. But Dennis Selkoe, a noted Harvard University neuroscientist who is one of the chief proponents of the beta-amyloid theory, says its role is becoming more firmly established. "In the last five years there's been a steady drumbeat of support for the notion that beta- amyloid deposition can initiate the disease," he says. Others are still not convinced. Robert Terry, an Alzheimer's "Everybody thinks beta-amyloid is the key, and I don't." Terry has correlated the degree of dementia in Alzheimer's patients with the loss of synapses in the brain. The proponents of the beta-amyloid hypothesis say that beta-amyloid causes the loss of synapses, but he says, "I don't see the evidence." He says "amyloidophiles" still have to answer the question why the amount of beta-amyloid deposits in a patient's brain doesn't correlate with the severity of the disease. "After all, it's the dementia we care about--we don't care about plaques and tangles if they aren't doing any harm," he adds. "But if they're right, so much the better. Truth will out--that's the great thing about science." Harvard Medical School neuroscientist Kenneth Kosik, who does research on Alz-heimer's neurofibrillary tangles, says the amount of research on beta-amyloid is out of proportion to other areas of interest in the field. But that's not because there's too much research on beta-amyloid, he says, just not enough on other aspects. "Beta-amyloid is extremely interesting," he says, and when it comes down to divvying up the limited resources, decisions about what gets priority need to be made. But, he cautions, "we need to keep an open mind about other things that may be happening in Alzheimer's disease." Those "other things" include investigating the role that the tangles play in the disease, since plaques without tangles don't produce Alzheimer's dementia. The tangles are composed primarily of an abnormally overphosphorylated protein called Tau, whose normal function in the brain is to help sculpt the shape of neuronal processes--axons and dendrites. How it becomes phosphorylated to such an extent and what causes it to form tangles are unclear. Funding Unclear The funding outlook for Alzheimer's research is uncertain, especially with a new administration in the White House, says Zaven Khatchaturian, the National Institute on Aging's associate director for the neuroscience and neuropsychology program. Given the federal budget crisis, he says, "under the most optimistic scenario, the funding will not go down." Kosik says simply spending the same amount on Alzheimer's research is insufficient. "When you weigh the costs incurred by Alzheimer's patients, and the emotional and financial costs to families," he says, "the amount of research is still very small." Selkoe says potential funding cuts in the federal budget will have to be made up by private sources, like nonprofit fund- raisers, philanthropists, and pharmaceutical companies. While the media can be an ally in calling attention to the need for more funding, he likens Alzheimer's research today to working in a "goldfish bowl," and adds, "I think the scrutiny of the press is understandably a double-edged sword." Selkoe says the press leaps on every paper with the word "Alzheimer's" in the title. "While it's exciting to follow the pace of research," he says, "the public should understand that none of this translates into a treatment today." Beta-amyloid Advances Recent developments tend to shore up the theory that beta-amyloid plays a pivotal role in the disease. The discovery in 1991 of a genetic mutation that ties APP to Alzheimer's disease was the first real indication of a link between beta-amyloid production and the pathology of the disease. Alison Goate and her colleagues, then at St. Mary's College in London, made an exciting discovery--a link between an inherited version of Alzheimer's disease and a genetic defect on chromosome 21. That paper, "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease," which appeared in Nature, was the second-most-cited paper for 1991, and to date has been referred to about 250 times in other publications (A. Goate, et al., 349:704, 1991). The point mutation results in a one-amino-acid substitution in a region of the APP protein just outside what ends up as the beta-amyloid fragment. That discovery was followed by other research reporting similar abnormalities. Harvard's Selkoe says: "That linkage is so clear, even the naysayers agree that in those cases APP appears to be causal." More recently, genetic defects on chromosomes 14 and 19 have also been linked to familial Alzheimer's. Goate and Selkoe say if beta-amyloid is central to the disease process, then in all likelihood, the genes on those two chromosomes are involved in the processing, transcription, or regulation of APP. Goate says finding out what the gene on chromosome 14 does will either confirm that hypothesis or prove it's caused by a completely different mechanism. The next key step is to identify how the genetic mutations on all this end, Goate, now at Washington University in St. Louis, is trying to incorporate the defective APP gene into the genome of a mouse. If the mouse develops Alzheimer's-like plaques as a result, that would be a clear indication. "Human genetics can only give you a statistic," she says. "You need to demonstrate that the mutation is sufficient to cause the disease." She's battling difficult odds to create an animal model, however. Two of three recently published papers, purporting to show Alz- heimer's-like pathology in transgenic mice, were withdrawn after the data were questioned (D. O. Wirak, et al., "Deposits of amyloid beta protein in the central nervous system of transgenic mice," Science, 253:323, 1991; and S. Kawabata, et al., Nature, 356:23, 1992). And rodents don't normally produce plaques, aged or not; whereas humans, even in the absence of Alzheimer's disease, accumulate beta-amyloid plaques in old age. That's not necessarily an indication that the animal model won't work, just that if it's a negative result, it can't be interpreted as meaning the defect doesn't cause the disease. In estimating her chances of success, Goate says, "you can pick examples on either side." Other recent findings that lend credence to the beta-amyloid theory are the papers published last fall in the same issue of Nature, by Selkoe and his collaborators, which show evidence that beta-amyloid can be detected in the spinal fluid of both "normal" individuals and Alz-heimer's patients, and is a normal cell product (C. Haass, et al., "Amyloid beta-peptide is produced by cultured cells during normal metabolism," 359:322, 1992; and P. Seubert, et al., "Isolation and quantitation of soluble Alzheimer's beta-peptide from biological fluids," 359:325). What causes it to form the brain deposits and its role in causing dementia still remain important, but unanswered, questions. But the discovery is important because researchers had previously postulated that some sort of injury or genetic defect was necessary to start the cascade of events which produced the beta- peptide. More important, says Selkoe, now researchers have a way of identifying drugs that could inhibit beta-amyloid production, by testing them in cultured cells. Before, the only place beta- amyloid was seen was in post-mortem Alzheimer brain deposits. The researchers also found that some animals, like guinea pigs, have measurable amounts of beta-amyloid in their cerebrospinal fluid. "Now there's a way of getting to proof of concept," Selkoe says. amyloid production in the brain, or in the circulatory system, retard the progression of Alzheimer's disease?" Of course, he acknowledges, that's a leap of faith. "There's plenty of room for healthy skepticism that inhibiting beta- amyloid production would ever help an Alzheimer patient," he says, "and I can't tell you if it will or will not." Biotech companies, like Athena Neurosciences Inc., based in San Carlos, Calif., which Selkoe helped found, are targeting the enzymes that may liberate beta-amyloid from APP. Although the specific enzymes have not yet been identified, general protease inhibitors are being tested for their ability to reduce the production of beta-amyloid. Dale Schenk, Athena's director of immunochemistry, says his firm's scientists aren't ignoring other possibilities, and are continuing to develop drugs based on nerve growth factors, which may extend the life of neurons. But these don't get at the essential mechanism of the disease. That's where APP and the beta-peptide come in. "You have to take risks," he says, "and as long as the beta-peptide is the best approach out there, we'll continue to take it." Indiana University's Merrill Benson, who discovered one of the mutations in the APP gene, says the metabolism of APP is very important in understanding Alzheimer's disease. But the field is getting overcrowded, and he feels there are a lot of extraneous papers published on Alzheimer's. He says the key discoveries thus far are finding the beta-peptide, cloning the gene, finding mutations that predict the disease, and discovering the linkages to chromosomes 14 and 19. The hundreds of other papers out there, evidence of the popularity of Alzheimer's research, he says, "clog up the literature." But, he adds, they may add useful insights. "Only after you get to the top of the hill and look back," he says, "can you tell what steps were important along the way." As for the future, Selkoe says it may be seven, 10, or even 15 years before we understand fully what causes Alzheimer's disease. But, he adds optimistically, "we don't need to understand the whole picture to treat the disease." He estimates that drug trials of a credible candidate that block the early mechanism of the disease could be as little as three to six years off, and possibly even less. Diana Steele is a freelance writer based in Takoma Park, Md. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ HOT PAPERS Page 16 of the Newspaper PHYSICAL CHEMISTRY D.E. Manolopoulos, "Proposal of a chiral structure for the fullerene C76," Journal of the Chemical Society<197>Faraday Transactions, 87:2861, 1991; P.W. Fowler, D.E. Manolopoulos, H.C. Batten, "The higher fullerenes<197>A candidate for the structure of C78," J. Chem. S.F., 87:3103, 1991. David Manolopoulos (Department of Chemistry, University of Nottingham, England): "The summer of 1991 was an exciting time to study the fullerenes. The beautifully symmetric structures of the C60 and C70 molecules had recently been confirmed by infrared and 13C NMR spectroscopy, and preliminary spectroscopic results had been reported for C76, C78, and beyond. These latter results suggested that the larger carbon clusters were also likely to be fullerenes, but they were not sufficiently resolved to characterize their precise structures (F. Diederich, et al., Science, 252:548, 1991). Our two papers addressed the question of these structures by using a simple computer program for generating fullerene polyhedra in conjunction with qualitative molecular orbital theory. "The results were unexpected and interesting. C76 was found to have just two isolated-pentagon fullerene isomers, one with cubic Td and the other with chiral D2 symmetry. Huckel molecular orbital calculations revealed that the Td isomer would be open- shell, however, with a comparatively modest bonding resonance energy. Since the lower- symmetry D2 isomer was found to be closed-shell, with a larger resonance energy, it was proposed as the most likely C76 structure. This prediction seemed to fit the experimental results of Diederich and associates, but with one important exception. Whereas the proposed structure should have given rise to 19 13C NMR lines of equal intensity, the preliminary experimental report was of 16. The discrepancy was missing lines in a better-resolved 13C NMR spectrum, providing conclusive confirmation of the proposed D2 symmetry structure (R. Ettl, et al., Nature, 353:149, 1991). Thus D2 C76, the first higher fullerene to be characterized and the first chiral fullerene to be found in nature, was something of a triumph for elementary molecular orbital theory. "Of the five isolated-pentagon C78 fullerene isomers reported in our second paper, three have also since been discovered experimentally, giving valuable new insights into fullerene synthesis and stability (F. Diederich, et al., Science, 254:1768, 1991; K. Kikuchi, et al., Nature, 357:142, 1992). "Further progress has been made since this C76 and C78 work was completed. The experimental C84 product is now thought to consist of an entropic 2:1 mixture of isoenergetic D2 and D2d symmetry isomers, for example, and numerous other experimental, semi- empirical, and theoretical studies of the higher fullerenes have been published. Much of this new work is summarized in a book scheduled to be published this year, An Atlas of Fullerenes (P.W. Fowler and D.E. Manolopoulos, Oxford University Press, in press)." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ MOLECULAR BIOLOGY S. Shimasaki, L. Gao, M. Shimonaka, N. Ling, "Isolation and molecular cloning of insulin-like growth factor-binding protein- 6," Molecular Endocrinology, 5:938, 1991. Shunichi Shimasaki (Whittier Institute for Diabetes and Endocrinology, La Jolla, Calif.): "There are two types of insulin-like growth factors: IGF-I and IGF-II, which act on a wide variety of target cells to regulate growth and cytodifferentiation. The IGF ligands interact with plasma membrane receptors, and the interactions are transduced into signals that evoke the biological responses. Physiologically, most of the IGFs do not exist as free ligands, but rather are bound to specific proteins called the IGF-binding proteins (IGFBPs). At present, the precise function of the IGFBPs is unknown. However, there is an increasing body of evidence demonstrating that the IGFBPs can modulate--either enhance or suppress--the biological responses of the IGF ligands. Thus, the determining the cellular responses to IGF-I and IGF-II. "As described in this paper, we undertook a comprehensive purification scheme to isolate all of the IGFBPs present in porcine follicular fluid. During this research, we isolated three novel IGFBPs and completed their structural characterization by molecular cloning of their cDNAs in both the human and rat. We named them IGFBP-4, -5, and -6. This paper, concerning IGFBP-6, is the last one in the series of the cloning of the amino acid sequences of all six IGFBPs in both human and rat, which is undoubtedly one reason so many researchers have cited the paper. "As a result of our efforts to characterize these IGFBPs, our cDNA clones are now used in more than 150 research groups throughout the world to study structure/function aspects of the IGFBPs and to produce recombinant molecules. I anticipate that the structural information of these molecules will provide the insight into how the six types of IGFBPs are intertwined with the actions of the IGFs in both physiology and pathophysiology." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ IMMUNOLOGY E.L. Berg, M.R. Robinson, O. Mansson, E.C. Butcher, J.L. Magnani, "A carbohydrate domain common to both Sialyl Lea and Sialyl Lex is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1," Journal of Biological Chemistry, 266:14869, 1991. John Magnani (Glyco Tech Corp., Rockville, Md.): "A greater understanding of the physiological functions of carbohydrate structures is currently being pursued by an exciting new field of research termed `glycobiology.' My coauthors Eugene Butcher and Ellen Berg at Stanford University have pioneered the study of lymphocyte recirculation. The first step in the extravasation of these cells from the bloodstream is their binding to the vascular endothelium of the blood vessel wall. Binding proteins classified as `selectins' recognize unique cell surface carbohydrate structures, thereby selecting specific cells from the blood for extravasation. Transfected mouse L cells expressing human E- selectin on the cell surface were used in cell binding studies with purified complex carbohydrates chemically linked to nonglycosylated proteins. "This paper first showed that human E-selectin bound not only to the known carbohydrate ligand sialyl Lex but also to its structural isomer, sialyl Lea. To determine the common three- dimensional domain shared by these two structures, hard sphere exoanomeric (HSEA) calculations were used to compute bond angles at the minimal energy conformation. By comparing these structures, we first demonstrated that the minimum epitope for E- selectin is the positioning of the Neu5Aca2-3Gal to the fucose residue. These results explain the binding of many sialyl Lex negative cells to E-selectin. "The structure of sialyl Lea was first elucidated in 1982 as a tumor-associated antigen. Likewise, the expression of its structural isomer, sialyl Lex, on cell surfaces was shown to be positively correlated with the presence and stage of cancer. Thus, it is likely that tumor cells expressing high concentrations of sialyl Lea/sialyl Lex surface carbohydrates have a distinct advantage in extravasating from the bloodstream and forming metastases by a similar selectin-mediated pathway used by normal leukocytes. "Determining the chemical structure of this functional carbohydrate sequence has great potential in the design of a new class of pharmaceuticals for the therapy of inflammatory and metastatic disease, which is currently reflected by the enormous academic and commercial interest in this field." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ TOOLS & TECHNOLOGY Classic Scientific References And More Becoming Available On CD-ROM (Page 18 of Newspaper) BY FRANKLIN HOKE Tempted by the enormous data storage capacities of CD-ROM disks and spurred by recent drops in their production costs, scientific publishers are making available to researchers an increasing Among these is a geological reference work that includes original mineral spectra data sets on a CD-ROM accompanying the printed text. Also available is a disk containing several of Charles Darwin's full texts with maps and illustrations in facsimile--as well as audio recordings of the songs of bird species Darwin encountered on his travels. In addition, several other classic scientific reference works are being considered or actively prepared for release in CD-ROM versions, including The Merck Index (11th ed., S. Budavari, et al., eds., Rahway, N.J., Merck & Co., 1989) and Mendelian Inheritance in Man (10th ed., V. McKusick, Baltimore, Johns Hopkins University Press, 1992). For the most part, these new tools build on the searching software and other strengths of the CD-ROM bibliographic databases that have proved so valuable in scientific literature searches. But now, they can include the full text--with full-text searching capability--or complete images of the original printed pages with the photos, graphs, and charts accompanying the text. "What everyone in publishing has realized in the last few years is that the mastering costs have just plummeted," says Richard O'Grady, science editor with Johns Hopkins University Press. "Only a few years ago, it was almost $10,000 [per CD-ROM]--now, it's less that $1,000. And unit costs afterwards are only about $2 to knock off copies." "Mastering" a CD-ROM refers to the process of creating the prototype product from which the copies are then made. The work O'Grady shepherded through production last year was Infrared Spectra of Minerals, by John W. Salisbury and associates (Johns Hopkins University Press, 1992). The printed book contains about 500 spectra of characterized minerals plotted on X/Y graphs, along with analysis of the information. In a pocket at the back of the book is a CD-ROM disk containing the raw spectral data upon which the graphs are based, so that scientists can work directly with those data if they need to do so. Because of the approximately 600 megabytes of available storage capacity on a CD-ROM, the raw data could be provided in both Macintosh and MS-DOS formats. In fact, the data take up only about 50 megabytes, even with the doubling to accommodate the needs of those two groups of users. The book and disk are designed to complement each other, according to O'Grady. "It's not as if we're replacing books--it's just value added, this product," he says. "It allows you to do more with the information the book communicates." Joy Crisp is a National Aeronautics and Space Administration volcanologist with the Jet Propulsion Laboratory in Pasadena, Calif., using spectral data collected by remote sensing satellites in her research. She worked closely with O'Grady as a reviewer of the book to ensure that it would be as useful as possible for researchers. After an early look, she recommended that the data be included in some form along with the printed text and graphs. "The book is almost useless to me as a scientist if I don't have the raw data so that I can, using my computer, plot up the data and compare it against spectra that I take off my own rocks," she says. Crisp explains that the graphs in the book, which represent a library of the spectra from "perfect" minerals, are helpful but not precise enough to help her work with a typical specimen. "If you grab a rock in the desert," Crisp says, "some rock that has a mixture of minerals, and you're trying to interpret it, you need to go back to the raw data to compare." According to press representative Judy Adkinson, another CD-ROM project under way at Johns Hopkins University Press aims to put Victor McKusick's classic genetics reference, Mendelian Inheritance in Man, on disk. The disk version should be finished in time for the October 5-9 meeting in New Orleans this year of the American Society of Human Genetics, she says. In addition, the text will be fully searchable--once a search program has been decided upon. "The most complicated thing has been trying to figure out what would be the best search program to use," Adkinson says, "because there are a lot out there." pages, she says, and the CD-ROM will include both Macintosh and MS-DOS format files, there still will be storage capacity on the disk for other uses. "We have a nice core of genetics reference books," Adkinson says. "I want to start adding some of those other references to the McKusick CD-ROM, because there will be plenty of room." Adkinson anticipates that purchasers of the McKusick CD-ROM will include some individuals, departments, and research groups as well as academic libraries. One reason for this may be the low cost: Adkinson expects to release updates to the work every six months, with one year's pair of disks starting at $250. Among the growing number of scientific references now available on CD-ROM is ALDRICHEM Data Search, containing data on 50,000 chemicals drawn primarily from The Aldrich Catalog Handbook of Fine Chemicals (Milwaukee, Aldrich Chemical Co., 1992). Another is The Physicians' Desk Reference, containing the complete text of the print volume of the same title (47th ed., Montvale, N.J., Medical Economics Data Inc., 1993.) And others are likely to follow in the next few years. According to a company spokesperson, for example, a CD-ROM version of The Merck Index also is under consideration. Even the venerable Charles Darwin is now available on CD-ROM. In fact, Darwin is available in several versions. The general-interest reader may want to have the full texts of Darwin's The Origin of Species and The Descent of Man on a CD-ROM product called Library of the Future from World Library Inc., Garden Grove, Calif. That reader will also be able to enjoy the other 900-plus full-text titles available on that disk, including many of the world's more prominent religious, philosophical, historical, and literary--as well as scientific--titles. A scholar of Darwin, on the other hand, is now able to work with the complete texts and original illustrations of those titles, along with original maps from the surveying voyages of the HMS Beagle and the HMS Adventure, sound recordings from the Cornell University Laboratory of Ornithology, and an array of supplemental study materials related to Darwin's work and life. San Francisco. Back Issues On Disk For scientists, reference to primary research literature, usually journals, is paramount. Discipline-specific bibliographic databases on CD-ROM and in other formats have eased the task of tracking down references to needed articles, but it has still been necessary to then find a copy of the article. But now, a growing area of CD-ROM science reference publishing is providing full image files of journal articles along with the bibliographic reference. These files are, for the most part, scanned images of the journal pages themselves, complete with charts, graphs, and other illustrations. According to Andrew Berks, a research chemical information scientist with American Cyanamid Co., Pearl River, N.Y., such products are used analogously to a microfilm collection. "But the copies are better," he says, "and it uses off-the-shelf computer hardware that's less expensive than good-quality microfilm readers." One CD-ROM image product, called ADONIS from a company by the same name located in Amsterdam, is especially targeted for biomedical researchers. Articles, letters, and abstracts from 497 biomedical journals published by Blackwell Scientific Publications, Elsevier Science Publishers, Pergamon Journals, Springer Verlag, John Wiley, and others are included. The Persistence Of Books Many of those involved in developing CD-ROM versions of works more familiar in their text forms note that the printed page will still retain its appeal for some time to come. One editor, mulling the possibility of creating a CD-ROM version of a respected, century-old scientific reference, who requests anonymity because of company restrictions, puts it this way: "If you're a lab scientist, and you have a single-volume book that sits on your shelf in your lab, and you need to look something up quickly, it's right there at your fingertips--vs. your CD-ROM player, which is probably attached to your computer back in your office. If you're familiar with a book, and it's sort of an old friend, and you're looking up a specific item, then do you really need electronic search capabilities?" This editor adds: "Everybody still learns from books right now, so it's habit, also. There is persistence to the book--we would not give up the book in favor of a CD-ROM product." Perhaps because students do still learn from books, primarily, scientific textbook publishers do not seem to be in a great hurry to bring their products out on CD-ROM. For example, a spokesperson for Worth Publishers Inc. in New York City, publishers of Principles of Biochemistry, 2nd ed., by A. Lehninger, D. Nelson, and M. Cox, says there are "no plans in the works" to bring the text out on CD-ROM. Andrew Berks of American Cyanamid agrees that books will hold their places in a researcher's reference collection, although the use of CD-ROM publications will continue to grow. "A CD-ROM is really not as convenient as opening a book," Berks says, "if a book is conveniently available." (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ SCIENTIFIC REFERENCES ON CD-ROM (Page 20 of the Newspaper) Further information about CD-ROM titles discussed in the accompanying article is available from these publishers: ADONIS NL-1000 Amsterdam, Netherlands 020 6842206 Product: ADONIS ALDRICH CHEMICAL CO. P.O. Box 355 1001 W. St. Paul Ave. Milwaukee, Wis. 53233 (800) 231-8327 Fax: (800) 962-9591 Product: ALDRICHEM Data Search JOHNS HOPKINS UNIVERSITY PRESS 2715 N. Charles St. Baltimore, Md. 21218 (410) 516-6960 Fax: (410) 516-6968 Products: Infrared Spectra of Minerals, Mendelian Inheritance in Man (in press) LIGHTBINDERS INC. 2325 Third St. Suite 320 San Francisco, Calif. 94107 (415) 621-5746 Fax: (415) 621-5898 Product: DARWIN MEDICAL ECONOMICS DATA, INC. 5 Paragon Dr. Montvale, N.J. 07645 (201) 358-7200 Fax: (201) 664-1902 Product: The Physicians' Desk Reference WORLD LIBRARY INC. 12914 Haster St. Garden Grove, Calif. 92640 (800) 443-0238 Fax: (714) 748-7198 Product: Library of theFuture, 2nd ed. (See also the Science Publishers Directory on page 31.) (Copyright, The Scientist, Inc.) ================================ PROFESSION Scientist Authors Lend Expertise To Kids' Books (Page 21 of Newspaper) BY RICKI LEWIS One way to combat future science phobia and illiteracy is to bring children closer to scientists, educators say. And because scientists often have many stories to tell, publishers have found that using them as authors of children's science books can help bring the excitement of research to youngsters with an authenticity and perspective that nonscientist-authors cannot easily convey. Because scientists with riveting children's stories to tell and the talent for writing them are rare birds, publishers track them down, in contrast to typical fledgling writers, who generally need to seek out publishers for their work. But why would a busy scientist invest the time to write and nurture a book for kids? The benefits, though rarely significant from a monetary standpoint, can be substantial, say those who have done it. Telling Stories If a new book series called Face to Face with Science (New York, Crown Books for Young Readers) is as big a hit as its publisher expects, demand for scientist-authors may grow. This series showcases scientists at work, in their own words. The first three volumes were published late last year. The series debuted with two favorite children's topics--space and dinosaurs. Voyager was written by Sally Ride and Tam O'Shaughnessy, and Digging up Tyrannosaurus Rex by John Horner and Don Lessem. Ride, the first female astronaut, and Horner, curator of paleontology at the Museum of the Rockies at Montana State University in Bozeman, are well-known scientists. O'Shaughnessy knows Ride from their national junior tennis Diego Community College. Lessem is the founder of the Boston- based Dinosaur Society, a nonprofit organization to promote dinosaur science. The third volume, Elephants Calling, was written by Katharine Payne, a research associate at Cornell Laboratory of Ornithology at Cornell University, Ithaca, N.Y., and best-known for discovering the poetic quality of humpback whales' songs. But it was her discovery of elephants' use of infrasound to communicate that led to Elephants Calling. It is uniquely told from the point of view of an elephant. The simple and true story, captured by Payne's camera, follows the lives of a family of elephants on the Amboseli plain in Kenya. While the elephant elders are distracted by two battling males, four-year-old Raoul wanders off, finding a hole into which he pokes his inquisitive trunk. Out jumps a startled warthog, and Raoul yelps. The response of his clan is a fascinating study in animal communication. The Face to Face with Science series was a response to complaints about children's books from scientists, who cited inaccuracies and datedness. "We thought it was a good idea to go to some people and give them the opportunity to write for children, to give kids the sense of what doing science is like, as opposed to just giving them information," says Simon Boughton, the editor at Crown who created the series. The intimate perspective of Elephants Calling is due to Payne's ability to think like a child. "There are a lot of things one can't say through the voice of the scientist," she says. "What I love to do is to just notice--and children are the best observers. The big thing is being undistracted. You can see this in a one- or two-year old, those moments of intense attention in simply examining something. We lose that ability later on." Payne was steered off the Ph.D. track by the arrival of four children. Before that, she had trained with noted ethologists Thomas Eisner of Cornell and Edward O. Wilson at Harvard University. But lack of a Ph.D. didn't stop her from doing extensive fieldwork. mainstream because he enjoys the humanistic side of science. He relishes writing children's books "mostly because there were some things I wanted to express that I couldn't in the scientific literature," he says. Myers is an assistant professor at Western College, an interdisciplinary arm of Miami University in Oxford, Ohio, where he teaches courses on ecology, evolution, the imagination, and technology. Myers and his wife, Lynne Born Myers, penned McCrephy's Field (Boston, Houghton Mifflin Co., 1991), a tale of ecological succession. The Myerses weren't well known enough to be asked to write a children's book, as the Face to Face authors were. After they wrote their book in 1989, they sent it to three companies. Houghton Mifflin signed them immediately, and they've been writing ever since. Mark Chartrand, another eclectic scientist who has attracted publishers, puts his finger on just how and why a scientist brings a special ring of authenticity to a children's book. "I consider writing a science book a little like [working in] a museum, and, having done both, I can see parallels," he says. "In a typical major museum, only 2 to 5 percent of the collection is on display. So it is with an author. The museum director must know the other 96 percent so that he or she can know the proper 4 percent to choose to display." Today, Chartrand spends about half his time writing and half as a private consultant, giving seminars on satellite technology and telecommunications. Chartrand became interested in writing from a man who influenced many science writers--the late Isaac Asimov. While working on a Ph.D. in astronomy at Case Western Reserve University, Chartrand heard Asimov speak. "I thought, well, if he can do it, so can I," he recalls. Realizing that he preferred explaining to researching, after grad school Chartrand took a position as director of education at the Hayden Planetarium in New York City. Three years later he was promoted to chairman of the planetarium, and also taught astronomy at nearby Fordham University. Chartrand's first book was an astronomy textbook written with Franklyn M. Branley, also a Hayden planetarium astronomer. Their text fell into a black hole when the publisher was sold, but Chartrand's prolific work soon attracted attention at Western him to revise its Skyguide and other how-to astronomy books. Chartrand "cut his teeth" on these projects, viewing the requests to update them as "being asked to revise the Bible." But revise he did, so well that he was soon asked to revamp guides to the planets and space exploration. Teachers' Turf Research is the scientist's niche; designing easy-to-do projects demonstrating scientific principles taps a teacher's expertise. A pro at this type of book is Janice VanCleave of Otto, Texas. Since 1989, she has written three series of hands-on science books for John Wiley & Sons Inc. of New York--six volumes of Science for Every Kid, six of Janice VanCleave's Spectacular Projects, and her current effort, for high school students, A+ Projects. VanCleave accumulated her material from 26 years of teaching science in the sixth through 12th grades, having to make do with very little. "When I was teaching, most of the time I was designing something for the kids to do," she recalls. "It was a real rarity to be in a school that had money to buy science equipment. Indirectly, all that training of not having anything to work with, well, that's what I do in the books now." Recognizing that her readers probably have limited resources, too, she designs her projects to involve commonly found, cheap, or free materials. VanCleave calls her entry into book publishing "a Cinderella story." When she was teaching at a grade school in Fort Smith, Ark., she shared her classroom approaches to teaching science with other instructors in workshops called "Teacher to Teacher." Someone from a local junior college heard of her workshop and asked her to teach an enrichment class. This program, "The Magic of Science," was described in the college's catalog, which caught the attention of an editor at Prentice-Hall Publishing Co. Inc. of Englewood Cliffs, N.J. But when the publisher asked her to send a prospectus, VanCleave recalls, "I didn't have the foggiest idea what that was." So the editor sent her an outline on how to write a prospectus. Later, after she had signed a contract, she confessed that she didn't know how to write a book. "So they sent me a book on how to write a book," she says. That original editor moved to John Wiley, which continued publishing VanCleave's books. Money Matters "For most scientists who write children's books, it's not the only thing they do," says Chris Myers. An exception is VanCleave, who supports herself by writing many children's science books as her sole occupation. But a children's book best-seller is not as lucrative as a top-flight novel. "If a book is very successful, it could make $5,000 over its lifetime. And it takes at least a year to write it," says Chris Myers. A writer usually receives a small advance against royalties, and the royalty is generally 10 percent of the cover price. But Boughton of the Face to Face series points out that for scientists writing about their own work, not much effort is required to translate it for children: "We don't ask anyone to do research, we ask them to write about what they have already done and probably already written about." Despite the lack of financial reward, writing a children's science book can be very satisfying. Says Boughton of his best- known Face to Face author: "Sally Ride did not need to do this book; she has plenty else to do. She just really enjoys it. She feels she has something to say." Adds Chartrand, "Like teaching, writing science books for children is very rewarding, when you see the light go on in somebody's eyes." Ricki Lewis, of Scotia, N.Y., writes college biology texts. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ SEVEN STEPS TO WRITING A CHILDREN'S SCIENCE BOOK (Page 21 of Newspaper) The secret of good writing is for the final product to look effortless. But writing a successful book requires a great deal of planning, even if the final product will be only a few dozen, liberally illustrated pages. Here are some tips on how to write a children's science book from those who have done it. 1. Identify a topic. Start in the children's section of a library. If you hope to write yet another book on the weather, planets, dinosaurs, or warm, fuzzy creatures, decide how yours will differ. If your topic is hot in scientific circles but hasn't quite made it to the Berenstain Bears set yet--such as anything pertaining to molecular biology--think about how you will make the material exciting and understandable. 2. Know your audience. Mark Chartrand, astronomer and author of numerous star and planet guides, says that writing at an appropriate level is difficult, because one must deal with science illiteracy without talking down to the reader. 3. Choose an approach. If you plan to write a how-to project book, be sure to test the projects on real kids. Fact-based books tend to deal with the familiar (recent books describe the seashore, a telephone, and the digestive system) or the unfamiliar (moon rocks or superconductivity). A popular type of children's science book follows a scientist at work, such as The Triumph of Discovery: Women Scientists Who Won the Nobel Prize by Joan Dash (New York, Simon & Schuster Inc., 1991). Says Rachel Cassidy, a senior at Watervliet High School in Watervliet, N.Y. "The peek at the personal lives of these women made the reading more interesting because the reader could see the scientist as a real person, rather than just some name from a textbook." 4. Organize. "Knowing the way you will organize and select topics is three-quarters of the way there. Like in science, a well-posed question is three-quarters of the way to the answer," says Chartrand. Like a scientific paper, a children's science story needs a planned unfolding of events. 5. Sell yourself. Why would you, a scientist, be better able to handle the topic than an educator or writer? Consider what Alan Harris, supervisor of the earth and planetary physics group at the Jet Propulsion Laboratory and Paul Weissman, a research scientist with JPL's earth and space sciences division, had to Voyager Adventure in 1990. "Working at the Jet Propulsion Laboratory," they write, "we were privileged to be able to watch it grow from the drawing board to reality, and then to be there as the spacecraft sent back their incredible photographs and scientific data." Children's publishing is highly visual, which may explain why pachyderms, volcanoes, and asteroids far outnumber viruses, biochemicals, and quarks in books. If you are an artist or photographer, or know someone who will work with you, so much the better. 6. Find your voice. Style is hard to define, but Katharine Payne, author of Elephants Calling (New York, Crown Publishers Inc., 1992), captures it well: "Think back to your childhood, and be that child again." 7. Send it off! You don't necessarily have to send a completed manuscript, but at least dispatch an introductory letter, a prospectus (a detailed outline), and some sample of your writing style to a publisher of children's books. If you've never written anything other than a scientific paper or a grant proposal, say so. If you have talent and expertise, an interested publisher will guide you along. Compile a list of publishers from books in the library, and make some phone calls to get the names of appropriate editors. Consult Writer's Market, an annual compendium of publishers by Writer's Digest Books of Cincinnati, which lists requirements of specific publishers. Tailor your idea to a publisher's needs, and you may be in business. --R.L. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ PEOPLE (Page 23 of Newspaper) Entomologist To Get Wolf Prize In Agriculture John Casida, a professor of entomology and director of the Pesticide Chemistry and Toxicology Laboratory at the University of California, Berkeley, will receive the 1993 Wolf Prize in Agriculture. Since 1978, the Israeli-based Wolf Foundation has been granting four $100,000 prizes annually for individual achievements among the five fields of agriculture, chemistry, mathematics, medicine, physics, and the arts. No prize in medicine will be awarded this year. The prizes will be presented on May 16 by Israeli President Chaim Herzog at the Knesset building in Jerusalem. Casida, 63, is being honored by the Wolf Foundation for his research into the mode of action of insecticides, other pesticides, and toxicants. The award citation highlights his "unique contributions to basic science and to the development of safer pesticides for agricultural use." Casida's lab, which is supported by a grant from the National Institutes of Health, investigates the fundamental underlying mechanisms that are the basis for modern pest control. "For example," Casida says, "we recently completed discovering the mode of action for a chemical inside a blister beetle called cantharidin" (Y.M. Li, et al., "Cantharidin-binding protein-- identification as protein phosphatase-2A," Proceedings of the National Academy of Sciences, 89[24]:1867-70, 1992). The blister beetle can be lethal to farm animals if swallowed. Casida's lab team put tritium in a molecule of the toxic chemical and tracked it to locate a binding site. Using the liver as a model, he says, "we discovered a single protein that cantharidin seemed to bind to in correlation to its toxicity. It turned out to be protein phosphatase-2A." This enzyme is probably also the target for the action of a related compound, endothall, as an herbicide. Casida received his B.S. in entomology (1951) and his Ph.D. in biochemistry (1954) from the University of Wisconsin. He was on Wisconsin's faculty from 954 to 1963 before moving to Berkeley in 1964. (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================ Utah Researcher Receives ACS's Priestley Medal (Page 23 of Newspaper) Poring over textbooks is fine, but real science education happens through lab work, according to Robert W. Parry, a chemistry professor at the University of Utah and winner of this year's Priestley Medal, presented by the American Chemical Society (ACS). The Priestley Medal, the highest honor awarded by ACS for lifelong service to the field, was given to Parry March 30 during the society's annual meeting in Denver. Noted former winners include Nobel laureates Glenn Seaborg (who received the Priestley Medal in 1979) and Linus Pauling (who received the medal in 1987). Parry, 74, who has taught at the Salt Lake City campus since 1969, is a strong proponent of increased laboratory work in high school and college science classes. In the early 1960s, he worked with Seaborg and the late chemist George Pimentel (a 1990 winner of the Priestley Medal) on the CHEM (Chemical Education Materials) Study. This government-sponsored program was charged with the task of developing a new thematic approach to teaching high school chemistry. "The product of the CHEM Study program was a book [ed. G.C. Pimentel, Chemistry: An Experimental Science, New York, W.H. Freeman & Co., 1963] showing that science is the result of laboratory observations, which today is called `hands-on chemistry,' " Parry says. "So instead of memorizing paragraph 37 in one of the common books of the day, we tried to show people how knowledge is obtained in the lab." Parry received his B.S. in soil chemistry from the Utah Agricultural College (1940). The research for his Ph.D., which Parry received in inorganic chemistry in 1946, was directed by John Baylor (who won the Priestley Medal in 1961) at the University of Illinois, Urbana-Champaign. He taught at the --Ron Kaufman (The Scientist, Vol:7, #7, April 5, 1993) (Copyright, The Scientist, Inc.) ================================


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