THE SCIENTIST (CONTENTS PAGE + FULL ISSUE FOLLOW THIS SHORT MESSAGE) *********************

---
Master Index Current Directory Index Go to SkepticTank Go to Human Rights activist Keith Henson Go to Scientology cult

Skeptic Tank!

THE SCIENTIST (CONTENTS PAGE & FULL ISSUE FOLLOW THIS SHORT MESSAGE) ****************************************************** Dear Reader: Many of you have been accessing THE SCIENTIST, free of charge, on the Internet for over a year. We thank you for your interest. Would you please take a moment to let us have your views, suggestions, and comments about THE SCIENTIST to enable us to better meet your needs? We would particularly like to know: 1. If you are working in an academic, commercial, or government organization? 2. After you ftp each issue of THE SCIENTIST, how many others do you share it with? 3. Do you usually ftp the file or prefer searching it via Gopher or WAIS? 4. If it can be arranged, would you prefer receiving each issue, automatically, in your electronic mail box? 5. Finally, do you have any suggestions for ways of improving our file or format? Thanks and best wishes, Eugene Garfield Publisher THE SCIENTIST, 3600 Market Street, Philadelphia, PA 19104,U.S.A. Phone :(215)243-2205 // Fax: (215)387-1266 E-mail:garfield@aurora.cis.upenn.edu ================= To access THE SCIENTIST electronically: ON WORLD WIDE WEB URL:gopher://ds2.internic.net/11/pub/the-scientist ---- GOPHER : telnet ds.internic.net login : gopher terminal type: vt100 (if unknown) Choose #4, 4, and 6 from successive menus. ---- TO FTP : ftp ds.internic.net /cd pub/the)scientist login / password = anonymous / your e-mail address ================== THE SCIENTIST VOLUME 8, No:24 DECEMBER 12, 1994 (Copyright, The Scientist, Inc.) =============================================================== Articles published in THE SCIENTIST reflect the views of their authors and not the official views of the publication, its editorial staff, or its ownership. =============================================================== *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON *** *** JANUARY 9, 1995 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the U. S. : one year $58, two years $ 94 (Institutional) : one year $28 (individual) Canada : one year $82, two years $142 All other foreign: one year/air cargo $ 79 one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NEXT = next article ------------------------------------------------------------ TI : CONTENTS TY : NEWS PG : 3 ============================================================ NEWS DATABASE DISPUTE: The terms of access to a new database of complementary DNA sequences--specifically, the exclusion of commercial users--has one drug maker so incensed that it has sponsored a competing database that it says will place these cDNAs completely in the public domain PG : 1 FUTURE SHOCK: The major surprise in the predictions of scientists, sociologists, and architects researching and planning the laboratory of the future may be that--rather than a concentration on fantastic new technologies or equipment--the emphasis will be on promoting the interdisciplinary collaboration and well-being of investigators PG : 1 DUAL CHALLENGES: Tough economic times in the pharmaceutical industry are presenting its researchers with two major problems heading into 1995, observers say. Recent layoffs and R&D downsizing present a bleak employment picture, and those scientists who survive are increasingly under pressure to develop novel therapeutics PG : 1 FAMILY AFFAIR: For one new member, the announcement of the latest inductees into the Institute of Medicine holds extra-special meaning. She is the third member of her family to be so honored PG : 3 SCIENCE-POLICY FEST: The symposium honoring astronomer and space scientist Carl Sagan's 60th birthday was as much a forum on national and international science-policy issues as a testimonial to the career of the celebrated science figure PG : 4 OPINION FINDING A WAY: Much as the Heisenberg Uncertainty Principle revealed the difficulty of forecasting the position and momentum of subatomic particles, scientists and research administrators are struggling to find direction amid the intersection of societal goals, politics, and the scientific merits of the national research enterprise, asserts Argonne National Laboratory chief Alan Schriesheim PG : 12 COMMENTARY: One of the most disturbing trends in research funding, says University of Texas Health Science Center professor Naomi Kraus, is the alarming decrease in the number of young scientists being funded, reflecting the science establishment's low tolerance for controversy--and, therefore, for original thought and innovation PG : 13 RESEARCH REFINING ITS MISSION: The National Institute of General Medical Sciences recently reorganized--in order, according to institute officials, to become more efficient in its support of basic biomedical research and training and to promote interdisciplinary work PG : 14 HOT PAPERS: Medical geneticists Harry Orr and Huda Zoghbi describe their search for an unstable trinucleotide repeat; plant biologist Daniel Cosgrove reports on the extension of plant-cell walls PG : 15 TOOLS & TECHNOLOGY UPWARD MAbILITY: Though the popularity of monoclonal antibodies has ebbed and flowed dramatically over the past two decades, MAbs have nonetheless become a staple of cell biology, and numerous suppliers have emerged to facilitate researchers' access to them PG : 16 PROFESSION DAZZLING DISCOURSE: In making a successful scientific presentation, preparation as well as respect for and consideration of one's audience is key, according to cell biologist Robert Anholt, author of Dazzle 'Em With Style, excerpted here PG : 22 BEATRICE MINTZ, a researcher at the Fox Chase Cancer Center, has received the John Scott Award from the city of Philadelphia PG : 23 SHORT TAKES NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 13 NEW PRODUCTS PG : 19 (The Scientist, Vol:8, #24, p.3, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI :The Lab Of The Future: Movable Walls, 'Office Pods,' And Well-Being AU : KAREN YOUNG KREEGER TY : NEWS PG : 1 It is early morning in the year 2024. A cell biologist at a major university climbs the massive, open stairway of her research facility, heading for her "office pod," one of several clustered in a wing of the building. Donning her lab coat, mug of coffee in hand, she sets off toward the skybridge that connects the offices to the laboratory suites that dominate the other side of the facility. Along the way, she bumps into an old friend and current colleague, a radiologist with whom she shared an early-morning physics class in her undergraduate days; he is now a nuclear science professor at the school. Reliving old times and casually discussing their disparate research, they settle in a nearby alcove, one of several "interaction spaces" that dot the architecture of the building. An off-hand remark by her friend implants the germ of an idea that might crystallize a theory she is developing. Invigorated by the new concept, she rushes off to her lab. As she gazes out the floor-to-ceiling window overlooking the campus, she contemplates a quick reconfiguration of her lab, moving the walls to accommodate an armada of workbenches, instruments, and other equipment she will wheel in to test her newfound notions. What she doesn't know, of course, is that this chance encounter will garner her the 2060 Nobel Prize in physiology or medicine, its $19 million cash prize, and the adulation of millions of her colleagues worldwide. . . . Scientists, sociologists, and architects planning and researching the lab of the future have come up with predictions that some might find quite surprising. They believe that, rather than concentrating on facilitating space-age technologies, undreamed-of equipment and instrumentation, and wondrous new organisms and materials, lab designers in the next century will place a heavy emphasis on less-fantastic considerations, such as fostering interdisciplinary communication, creating highly adaptable and cost-efficient facilities, and alleviating the sense of isolation that has long been the lot of the researcher. A June 1993 workshop sponsored by the New York Academy of Sciences (NYAS) examined some of these issues. In a subsequent report distributed in October by the academy, "Research Facilities of the Future," (S. Stark, ed., Annals of the New York Academy of Sciences, Vol. 735, 1994), the participants summarized their views on the factors they see dominating the research centers of the 21st century: "The lab will continue to be the heart of the scientific workplace, requiring more adaptability, more user autonomy, and tighter control over the environment. . . . Because labs are where scientists live as much as where they work . . . more concessions to user comfort will be demanded [as well as] a reduction of barriers between disciplines." Although he did not take part in the workshop, Tom Gieryn, an associate professor of sociology at Indiana University in Bloomington, says that his research into the sociology of the architecture of university-based biomedical and biotech labs jibes with many of the conclusions drawn in the report, especially the need to relieve the isolation reinforced by today's lab design. "I think that there was a sense in the minds of architects until fairly recently that science is a very secluded activity, one where you had to have a little cubbyhole to get away," Gieryn asserts. "That's true, that's what scientists have their offices for; but much more important is the space where there are a lot of people at work." The report notes that the primary inhabitants of these new labs will probably be academic scientists, although as industrial-academic collaborations continue to grow, logistical and sociological dynamics of these facilities will also be affected. Some of the planners' theories are grounded in steel-and-stone realities of today. They point to several recently constructed facilities that have already incorporated some of these principles in their design. Prompting--and challenging--the work of these theorists is the universality of the lab as the primary scientific workplace and the issues it engenders for its inhabitants. According to Rodney W. Nichols, chief executive officer of the academy and former executive vice president at Rockefeller University, this common bond prompted the workshop. "We wanted to sponsor activities that, in the long run, would be of greater interest to a broader cross-section of the academy's community," he says. "A conference like this covers everyone in science." The purpose of the workshop was "to stimulate debate" among the research-facility designers and scientists in industry, government, and academia who attended, he adds. Two years ago, Nichols recalls, Stanley Stark, a partner and director of research facility design at Haines Lundberg Waehler, an architectural firm in New York, approached the academy to develop the workshop. Stark, an architect and urban designer who has been involved in building research facilities for more than 25 years, explains, "With the millennium approaching, that's what led me to think about what might be happening" in lab design. Fostering Collaboration Facility design that promotes interaction among diverse investigators was the basis of much of the discussion at the workshop, say its organizers. This same theme also permeates Gieryn's sociological research, which has included dozens of interviews with life scientists. Gieryn comments that to determine what scientists want in an ideal work environment, it is "key" to understand how buildings can facilitate "unexpected, unpatterned" interactions. "The trick is how to design a building so that people are going to run into colleagues that they wouldn't be expecting to run into," he observes. "That's apparently very important for cultivating the collaborative thinking that science requires." For example, he points out, the concept of promoting unplanned encounters as a design element "works beautifully" at the life sciences-oriented Thomas Laboratory of Princeton University. In this facility, bulges in the hallways--referred to by architects as "interaction spaces"--are essentially open lounges, with tables, chairs, and blackboards for informal discussions. Two scientists who spoke at the workshop--Nathaniel Heintz, a Howard Hughes Medical Institute investigator at Rockefeller, and Samuel J. Williamson, a professor in the department of physics and the Center for Neural Science at New York University--said that other public spaces, such as stairways, could be used more effectively to enhance communication among colleagues. "Instead of hiding the center stairway, make it a focal point by opening it to view," proposed Williamson. He noted: "If hotels draw tourists by such a display, would it not provide a similar sense of fun and dynamism to professionals in [a science] building?" Stark concurs: "Stairways will have to become much bigger and inviting places. Right now stairway design is [essentially] governed by life-safety codes." Form And Function In addressing issues of the comfort and well-being of future scientists, designers are examining features as seemingly mundane as adding windows. A common plea from scientists at the workshop, as well as the researchers Indiana's Gieryn has spoken with, is for facilities to have "a view of the outside, so you do not feel like a lab animal when you are trying to do your experiments," as Heintz put it in the report. "Let's face it, a room without a window is just a bad place to do science," maintains Gieryn. He says that all of the buildings that he has studied--places that have been designed from 1985 on--have emphasized natural light as part of their design. "I suspect that most scientists, if forced into a choice of having a window in their lab or in their office, would choose to have a window in their lab," Gieryn contends. The reason for this, at least in mo-lecular biology, he says, is that although scientists "might be dealing with some fundamental properties of life," the day-to-day tasks can be "tedious and repetitious." Having "the ability to look out a window to see what the weather is like and to feel that the day is changing with the passing light" is important to lab researchers, he adds. Another innovative idea discussed at the workshop is what Stark calls the "lab as a shell" concept. A lab is a "raw, utility-rich, but otherwise bare space . . . capable of accommodating many different layout alternatives, which can either be built in, rolled in, or plugged in very quickly," wrote Stark in the workshop report. Movable walls and workbenches on wheels are examples of likely contents of the shell lab. Stark says this flexibility has much appeal to scientists because they see it as "a quick way to readapt" to changing research proj-ects. But, other experts ask, is it cost-effective? "You can't really see a lab as an empty space," because a large percentage of the total cost to build a facility goes for the delivery of services--the plumbing and heating, for example, Gieryn reasons. "You can't really just sort of stop those and stub them at the walls and pretend like you have a cavern that you then can outfit," he asserts. Stark says he thinks if research- facility designers are careful in their planning, shell labs could be cost-effective. He adds that some industrial labs, which have to move quickly between a basic research function and a development function, are one example of how shell labs might work well. "You roll it [equipment] in and roll it out and just make adjustments to the finishes, but the systems must be designed to be validatable," Stark describes, referring to the fact that, especially in industrial labs, there must be a mechanism to constantly verify air and water quality and other such factors. 'Entrepreneurial Seedbed' NYAS CEO Nichols predicts that universities--funded by individual states and such private philanthropies as the Chevy Chase, Md.-based Howard Hughes Medical Institute and the Pew Charitable Trust in Philadelphia--will probably continue to be the primary constructors of scientific laboratories. On the other hand, industry, after a boom of building labs in the 1980s, has been thinning out research-and-development activities, he says. The bulk of private-sector expansion, he remarks, will most likely continue with small start-up companies. Because government funds are drying up, forcing university-based researchers to foster more collaborations with industry, Stark calls academia the "seedbed for entrepreneurial companies." In this vein, Heintz forecasted in the report that scientists may increasingly want to maintain proximity to these companies in order to retain some control over the development of their research findings. As a result of this, he wrote, "small-scale mixed research and development facilities accessible to the universities" may spring up, and these new ways to collaborate "may lead to [universities'] having a very active role in these small [business] ventures." State Of The Art According to Stark and other experts in facility design, some lab buildings constructed in the last five to eight years--Princeton's Thomas Lab; the Schering Plough Research Institute Drug Discovery Facility, Kenilworth, N.J.; and the Glaxo Research Center in Research Triangle Park, N.C., for example--do incorporate some of the design elements discussed at the academy's meeting. Another lab that "makes significant gestures toward the future," according to Stark, is the Beckman Institute for Advanced Science and Technology, located at the University of Illinois, Urbana-Champaign. "In general, one's discipline of origin plays a minor role in the [administrative] groupings" at the institute, says William Greenough, a neuroscientist at Beckman. "Instead of grouping people because their Ph.D.'s are in, say, physiology or cell biology, we group them by functional interests." Greenough's group, which studies how the nervous system processes and stores information, includes researchers in analytical chemistry, biochemistry, cell and molecular biology, physiology, psychology, physics, and electrical engineering. "If you think about how that maps to a typical college campus, these people would be blocks from each other in different buildings," Greenough remarks. Echoing Gieryn and others, Greenough, who participated in the planning of the institute, stresses that part of the goal in designing the Beckman facility was to "create a building that really emphasized interactions--getting people to-gether." For example, he says that faculty and postdoctoral offices are arranged in "pods"--a grouping of offices instead of a more traditional lab-office pairing. The effect, he says, is that "you have faculty bumping into each other in the halls all the time." Much like the hallway interaction spaces at Princeton's Thomas lab, Greenough says that open areas--equipped with tables, chairs, and wipeboards--on bridges that connect the office wing to the lab wing of the building are used for impromptu discussions of research ideas. "They're used all the time," says Greenough. "The culture here is when people are starting to work on something," they go to the meeting areas to work out the details. "Sometimes it's fun to walk past the boards filled with writing and guess what people were talking about." (The Scientist, Vol:8, #24, p.1, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------- TI : Pharmaceutical Companies Stress Innovative Research For Success AU : NEERAJA SANKARAN TY : NEWS PG : 1 As 1995 approaches, changing economic forces in the pharmaceutical industry are presenting its scientists with tough challenges, both professional and scientific, according to researchers, company officials, and other observers. Financial setbacks and shifting business dynamics, such as mergers and takeovers, have caused companies to drastically downsize their work force in recent years, they say, with more cuts anticipated. "There were some 40,000 layoffs through the entire industry in the last two to 21/2 years, and the industry will become leaner still in the years to come," predicts Robert Ruffolo, Jr., vice president and director of pharmacological sciences departments at Philadelphia-based SmithKline Beecham Laboratories. For scientists surviving the carnage, observers maintain, the pressure is on to focus on novel ideas and to increase efficiency in discovering and producing new drugs. "Innovation has to be part of everybody's job description," stresses Mary Graves, director of biotechnology of Hoffmann-La Roche Inc., Nutley, N.J. "We can't afford to do 'me-too' drugs any more," Ruffolo agrees, referring to times when companies worked on improving and refining existing drugs to make them most efficient. "In order for a company to invest research dollars into development," he explains, it "has to be a 'pioneer' drug the first to be able to bind to a novel target molecule." But so long as the focus is on novelty, many say, there is still plenty of opportunity for research within the industry. According to Michael Steinmetz, vice president of preclinical research and development for Hoffmann-La Roche, "Biotechnological innovations now allow us to understand mechanisms of disease, so that things are very different from 20 years ago, when we used blind approaches and random screening procedures for drug discovery." The Washington, D.C.-based Pharmaceutical Research and Manufacturers of America (PhRMA), an industry trade group, reports that about 10 percent of the total cuts in the industry are in research and development. Furthermore, PhRMA records show, the industry experienced the slowest rate of growth in R&D expenditure in 22 years. What this means, Steinmetz explains, is that "researchers are vulnerable" to layoffs within a company, and that as a whole the research departments will have to "learn to live with less funds." One way the pharmaceutical industry appears to be coping with financial troubles is by moving toward consolidation, several observers note. An example is the recent buyout of Palo Alto-based Syntex Corp. by Hoffmann-La Roche's parent company, the Roche Holding Company of Basel, Switzerland. Another Basel company, Ciba-Geigy Ltd., just initiated a $2.1 billion investment into Chiron Corp., a biotech company in Emeryville, Calif. "The advantage in consolidations both alliances and buyouts_is that it helps broaden the base of innovation," Steinmetz explains. "We have better access to the latest technologies in many different fields." Researchers, however, are feeling the brunt of the downside to these mergers, he says. "Such alliances can initiate another round of head-count reduction," he acknowledges, "so as to reduce duplications." "It's like merging a basketball team you can only have 12 men," remarks Richard Stevenson, assistant to the director of preclinical research and development at Hoffmann-LaRoche. "Therefore only the best get taken." "In a way, the large drug companies today are where the big oil companies were at 15 years ago," notes an academic researcher working with a major drug firm, speaking on condition of anonymity. "Rather than go out and dig wells themselves, it was cheaper to buy the smaller companies who had already struck oil," he elaborates, drawing a parallel to the current trend on the part of large pharmaceutical companies to invest in or take over smaller, biotechnology-based start-up firms. "No company is big enough to be completely self-sufficient," Ruffolo explains, "and we are increasingly going to the outside for new ideas. We need to make sure we are scanning the horizon thoroughly so that we can jump on an idea no matter where it occurs. "Science in the research community is advancing at such a rapid pace that it's critical to keep abreast of what's happening," and collaborations with smaller firms are one way to stay current, he says. Graves does not agree entirely with the oil-company analogy. While she concurs that "no one turns a blind eye to outside opportunities," she emphasizes that "most of these collaborations come about for the licensing of one particular product," with the larger company providing the financial backing for carrying an idea through development to production. "We will go and use [small] biotechnology companies," Graves says, "not to replace our own research programs, but rather where we have gaps in a therapeutic pipeline, or to strengthen what we already have." "It is important to realize that there is a lot of innovative work going on in-house, as well," Steinmetz points out. Despite a layoff of 5,000 employees worldwide and the recent termination of the Roche Institute of Molecular Biology in Nutley, Hoffmann-La Roche officials claim, the company is maintaining its commitment to research. In October, Hoffmann-La Roche opened its new Multidisciplinary Science Building, a $100 million facility, at its Nutley location. Eye On Innovation New research ideas still abound, drug industry researchers maintain. "There will always be a need for an innovative new medicine," Graves stresses. "We have to focus on important diseases that have unmet medical needs." For example, Ruffolo notes, "the race is on [throughout the drug industry] to find LTD4 antagonists." LTD4 is one of a class of molecules called leukotrienes that are released as part of an allergic reaction during an asthmatic attack. An antagonist, he explains, would counteract the molecule and may thus be developed as a drug to treat asthma. Other promising avenues of investigation, he enumerates, include the search for insulin sensitizers_"drugs for treating type 2 diabetes, which poses a major health problem," and serotonin antagonists. "Serotonin seems to be involved in many brain disorders," and by studying it as a potential target molecule, researchers may be able to identify targets for conditions like Alzheimer's disease. At the Nutley location, investigations into therapies for inflammation, autoimmune diseases, cancer, and metabolic disorders are currently under way. "From the research perspective there are exciting times ahead," Graves says. "We have new tools and technologies for making significant discoveries." Ruffolo advises graduate students interested in entering the industry to focus on the molecular aspects of disease. "We now have the means to look into the workings of complex diseases and identify new targets at the molecular level," he points out. As the U.S. increasingly focuses on health-care issues, Steinmetz predicts, the current strained circumstances should abate. "As soon as people realize that the pharmaceutical industry is contributing to an overall cost-cutting in health care by keeping more people out of hospitals, they'll be willing to spend more money on research," he anticipates. "It's not going to happen now immediately but we should see some change over the next five to 10 years." (The Scientist, Vol:8, #24, p.1, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : PHARMACEUTICAL INDUSTRY JOB STATISTICS TY : NEWS PG : 11 The Pharmaceutical Research and Manufacturers of America (PhRMA), a trade association of research-based pharmaceutical companies, reports an almost 15 percent reduction in the overall work force in the past two to three years, with current employment totaling 266,000. Job Cuts, by year--1990-94 1990 0 1991 2,700 1992 5,950 1993 24,850 1994 12,880 Total 46,380 Job Cuts, by company--1993-94 1993 May Ciba-Geigy Corp. 600 July Marion Merrell Dow Inc. 1,850 Merck & Co. Inc. 2,100 Syntex Corp. 700 August Johnson & Johnson 3,300 September Bristol-Myers Squibb Co. 1,500 October Eli Lilly and Co. 4,000 Pfizer Inc. 4,000 Upjohn Co. 1,500 American Cyanimid Co. 2,500 (Lederle) November Warner-Lambert Co. 2,800 1994 January Bristol-Myers Squibb Co. 3,500 DuPont Merck 800 Pharmaceutical Co. April Ciba Geigy Corp. 450 June Rhone-Poulenc Rorer Inc . 200 July American Home Products Corp. 2,300 October Carter-Wallace Inc. 630 Hoffmann-La Roche Inc. 5,000 Source: Pharmaceutical Research and Manufacturers of America (PhRMA) (The Scientist, Vol:8, #24, p.11, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------- TI : Limited Access To cDNA Database Has Drug Manufacturer Up In Arms Incensed that the terms exclude industrialscientists, Merckannounces sponsorship of competing project AU : FRANKLIN HOKE TY : NEWS PG : 1 A powerful new, privately held database of human complementary DNA (cDNA) sequences has become available to researchers eager to test its capabilities to rapidly identify new genes. The proposed terms of access to the database, however, exclude pharmaceutical and other industry-affiliated scientists, angering some companies, including drug giant Merck and Co. Inc. The conditions have prompted the Whitehouse Station, N.J.-based firm to sponsor another, largely duplicative project that will deposit data into a publicly accessible database. Other terms of access have raised concerns among potential noncommercial users of the database developed by J. Craig Venter, president of The Institute of Genomic Research (TIGR), Gaithersburg, Md., a nonprofit research institute. These include the right to preview papers on resulting discoveries and to retain control of patents. The database, two years in development, currently consists of about 150,000 expressed sequence tags, or ESTs, which are partial sequences of human cDNA obtained from various tissues. Because many genes are expressed in multiple tissues, the data represent about 35,000 unique human genes, more than a third of the estimated 100,000 human genes. TIGR has a contract worth about $100 million with biotech firm Human Genome Sciences Inc. (HGS), Rockville, Md., for patent options on its discoveries; in turn, Philadelphia-based SmithKline Beecham has agreed to pay HGS about $125 million for development rights to the discoveries. Merck claims its objection to the terms is based purely in science. "We see human genes [sequences] as being essential research tools for all of drug research in the future," says Alan R. Williamson, vice president for research strategy worldwide at Merck. "And we've taken the position that research tools should be shared amongst everyone who wants to make an impact on drug research or any therapeutic application to benefit mankind. They should not be proprietary. We could have taken a private position on this [new data], too, but we decided to take a public position." The competing sequencing project being backed by Merck will be conducted at Washington University School of Medicine in St. Louis. The aim of the effort, expected to take roughly 18 months, is to sequence about 200,000 cDNA segments, with the results deposited immediately into GenBank, a publicly accessible database of sequences managed by the National Center for Biotechnology Information at the National Library of Medicine in Bethesda, Md. Venter predicts the protests will lessen over time. He notes that the Howard Hughes Medical Institute has agreed to the terms, as have a number of universities. "As people look at it closely, the issues go away, and the initial emotional responses from the publicity that's been generated by Merck and others totally vanishes, because all the data's available to academic scientists anywhere in the world," Venter says. "Over half the data has no strings attached to it at all, except that somebody be at a not-for-profit institution and that they cite the database when they publish their data." University technology-transfer officers say that the terms for use of the database by academic scientists are comparable to those of companies providing proprietary re-search materials. Genetics investigators with no plans to commercialize their research can use the database without restriction, and those who have used it praise its power and do not anticipate any limitations on their work. One point of contention underlying the picture of dueling databases is a sharp difference of opinion as to the intellectual-property value of the sequences that constitute Venter's database. The National Institutes of Health attempted to patent, and thereby control all future uses of, Venter's ESTs several years ago, when he was an intramural researcher at the agency. The move was widely criticized at the time because no basic biological knowledge of the genes' functions accompanied the partial sequences. Some critics charged that such patents, if allowed, would have foreclosed future research. Venter, however, claimed that placing the partial sequences into the public domain would have rendered full genes developed from them unpatentable, removing the incentive to work on them (R. Eisner, The Scientist, Dec. 9, 1991, page 1). After an initial rejection of the patent filings, NIH chose not to pursue appeals. "It's only the added biology that makes the DNA sequences of any value at all as far as intellectual property goes," Williamson contends. Misguided Expectations? Many scientists expected that Venter's database, when completed, would be made publicly available because he developed the EST technology in 1991 while he was a government researcher or because TIGR is a nonprofit organization. Venter acknowledges that because of the contractual ties established among TIGR, HGS, and Smith-Kline Beecham, the database is being made available with restrictions to protect and capitalize on its value as intellectual property. "I think that everyone assumed that you only needed to do this once, that it was being done by HGS and TIGR--and particularly by TIGR, which was a non-profit-making institution--and that it would be made [publicly] available," says Williamson. "The academic community backed off from generating this sort of data, because they were under the impression that this would all be made public. Once we realized that wasn't going to be the situation, then the need for this sort of database became apparent to us, and we decided to commission the production of it." According to Williamson, "many academics have said they wanted to do this sort of thing, but they couldn't get funded to do it because they were told it's being done." Officials at the National Center for Human Genome Research (NCHGR) at NIH confirm that, because of statements made by Venter early in his development of the database at TIGR, they expected the data to be publicly available and did not finance what they thought would be redundant work. "There was the anticipation on our part and the part of people who are advising us that that information would come into the public domain," recounts Mark Guyer, assistant director for program coordination at NCHGR. "And I think Craig would argue that he's putting it into the public domain now and is fulfilling those statements. So, the idea from our advisers was: This is being done, the information is going to get out, and therefore there's no point in the federal project duplicating it." Widespread expectations that the database would be made public, Guyer adds, probably were "not entirely consistent with what a private organization has to do to protect its own interests. That is, in part, where the current disagreements are based." "People can accept a certain amount of trade-secret mentality from a traditional company," says Joyce Brinton, director of the office for technology and trademark licensing at Harvard University, "But this company isn't a traditional company, so maybe people aren't as willing to accept the idea that they would act like a company." In defending his institute's contractual relationship with HGS, Venter draws a parallel between his situation and that of some of the scientists who now hope to access his database. "What I needed to do to get the funding was: I signed away rights to commercialize discoveries made by myself and my colleagues at the institute," Venter observes. "Now, because of drops in federal funding, more and more scientists are having to do that on a smaller scale at their universities. To get funding from a pharmaceutical company, they sign away all their rights to commercialize [discoveries]." Assigning Values A question confronting university technology-transfer officers and academic scientists is whether the information in the database is worth what TIGR and HGS are asking: a piece of any patents that may result. The issue becomes one of assessing relative intellectual contributions and recalls the debate over whether ESTs are tools or patentable discoveries. "It comes down to this question of how much should a provider of something get in return for it," says Brinton. "Do we--and I don't know the answer--have a distorted picture of the relative values of what our scientists would be doing vs. the [value of the] information that we got from HGS in the first place?" The agreement that HGS is asking institutions and their investigators to sign to use the database is typical, Brinton says, of so-called material-transfer agreements involving the exchange of proprietary biological reagents between companies and academic re-searchers. "But usually information has been treated in a different way than [materials], and there is a general view among people in the academic community that information should be shared," she points out. On balance, Brinton expects that arrangements will be possible allowing Harvard researchers access to Venter's cDNA sequences. The information, which is the main product of TIGR and HGS, does have value, she notes, and "a company does have obligations to its investors. It can't give away its seed corn." While the monetary worth of the database is still to be determined, the experiences of several scientists who have had the opportunity to search for genes using it suggest that its research value may be significant. "There was a yeast gene that we knew the amino acid sequence of, that was involved in a biochemical pathway of purely aca-demic interest," recalls Phillip A. Sharp, chairman of the biology department at Massachusetts Institute of Technology and a 1993 Nobel Prize winner in physiology or medicine. "And it was very laborious to think about getting the human counterpart. But by taking the amino acid sequence and looking directly in the cDNA database, we were able to find a human cDNA that encoded a related amino acid sequence, and, therefore, the equivalent protein, which we could not get by nucleic acid homology. We then just got the cDNA and cloned out the gene. So, it's going to be useful, there's no question." "The database provides a very efficient way to identify those genes for which you might be looking because you already know the sequence of some related gene or some gene with a similar function," says Bert Vogelstein, a professor of oncology at Johns Hopkins University. "Sometimes the classical approach to identifying a gene can be very difficult. It can take a long time, sometimes months, sometimes even longer, or sometimes it may not work at all. But if the gene has already been cloned and is in the database, it's a matter of, literally, a few seconds to find that gene." Vogelstein adds that, for his purposes, there were no problems with terms of access to the database. TIGR and HGS officials are confident that, as researchers become more familiar with the database and the terms of access, they will come to see the conditions as fair ones. William Haseltine, chairman and chief executive officer of HGS, notes that for most scientists who use the database for research purposes only, there is no cost. They are, however, obliged to show their scientific papers to HGS at least 30 days before publication for an assessment of patentability. Only when a discovery is deemed to be patentable and to have commercial potential does HGS seek to exercise its patent option, according to Haseltine, meaning that the company will be the sole developer of commercial products based on the discovery. The patent itself, Haseltine notes, is the property of the university, and the company and the school must still negotiate specific terms for development. If they cannot agree within six months, nor within a three-month extension period, the rights remain with the university. "If [a discovery] has commercial value, we've given them something of value, and we'd like something back," Haseltine says. "And that's reasonable. You don't give people the fruits of your labor for free. You just don't do it." Mapping Out Concerns Officers in TIGR and HGS note that access to the database is essentially unencumbered for most basic researchers. For those involved in mapping projects, however, rather than hunts for single genes, this may not be the case. Mapping requires the use of many sequences, and, concerned about losing control of their data, TIGR and HGS have placed restrictions on how maps derived from the human cDNA database may present information. "The people who want to construct a map have said that they want all of the data that goes into that map freely available," Haseltine explains. "Our position is we're willing to make the data available in bulk for the mapping community, provided that the points on the map get referred to the database, and the sequences go back to the database." Haseltine points out that a sequence is more than a point on a map. It is also an enabling technology, particularly for genetic medicine. Richard K. Wilson, a research associate professor at Washington University who will be directing the Merck-backed cDNA-sequencing project along with genetics department chairman Robert Waterston, cites as one of the strengths of his project the fact that the entire body of his results will be available to mappers. For these scientists, Wilson says, "our effort is not redundant, because we're going to provide a lot of sequences very quickly. These [sequences] are just going straight to GenBank from our labs, and there is absolutely no restriction on anything in GenBank." (The Scientist, Vol:8, #24, p.1, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : For One Newly Elected IoM Member, The Honor Is All In The Family AU : NEERAJA SANKARAN TY : NEWS PG : 3 For more than two decades, election to membership in the prestigious Institute of Medicine (IoM) has been a source of pride for the honorees and their families. But for the family of one of the 50 recently announced members of the institute, the occasion carried an extra- special meaning. Margaret A. Hamburg, health commissioner of the New York City Department of Health, became the third member of her family to be elected to IoM. Her parents, psychiatrists David A. Hamburg, currently president of the New York-based Carnegie Corporation, and Beatrix A. Hamburg, who now serves as the president of the William T. Grant Foundation, were elected to the institute in 1971 and 1979, respectively. Margaret Hamburg recalls that at the October annual meeting, at which she and the other new members--32 men and 18 women in all--were announced, "there was a sense of real enthusiasm and fun that the father-mother-daughter constellation had been formed." "It's a real distinction in the medical profession," adds Hamburg, who at 39 is one of the youngest people to ever be elected to IoM. She and the other new members will be formally inducted into the institute during its October 1995 annual meeting. IoM was chartered in 1970 by the National Academy of Sciences (NAS) to address issues of health and delivery of health services to society. Described by a longtime member--Mary Ellen Avery, a professor of pediatrics at Harvard Medical School--as "the medical arm of NAS," IoM conducts studies at the request of the United States government and issues reports on a wide array of policy issues related to health and medicine. Other than sharing similar operating procedures, the two organizations run independently. There is some overlap in the two memberships, although induction into one does not guarantee the other; Avery, for instance, has been an IoM member since 1981 and served as a member of the governing council from 1987 to 1993, but was not elected to the academy until earlier this year. New institute members are chosen by an electoral process within its active membership, which according to the charter cannot exceed 600 people and currently stands at 493. New honorees are obliged to volunteer their time to serve on various IoM committees engaged in various studies. Individuals aged 66 or over are transferred to the roster of senior members, who cannot vote or hold office, but serve in an advisory capacity. With this year's additions, including five individuals elected directly to senior membership, IoM has a total of 536 senior members in addition to 38 foreign associates, who also do not have voting rights. Both of the elder Hamburgs are now senior members. At the time of her election, Beatrix Hamburg held an appointment as an associate professor of psychiatry at Stanford University School of Medicine. At the time of his induction, David Hamburg, who went on to serve as IoM president from 1975 to 1980, was chairman of the department of psychiatry at Stanford. While NAS advises the federal government in matters of science and technology policy, Avery notes, "it covers all of science, and physicians have a very small piece of the action." As medicine and health care began to play a bigger role in society, she adds, it became apparent that these issues "had a dimension that was not strictly science, but social and humanistic." The input of professionals involved in the social, behavioral, legal, and administrative aspects of health issues is important for setting policy, she points out. This realization led to the establishment of IoM. Diverse Membership IoM's charter provides for a broad-based membership from within the medical community--including practicing physicians, re-searchers, nurses, and public health officials--and also mandates that at least one-quarter of the total active membership be drawn from outside the health professions. New inductee Amitai Etzioni, founder and director of the Center for Policy Research in Washington, D.C., and University Professor at George Washington University, is one such example. "I look forward to interacting with colleagues from 'real' science and medicine," says Etzioni, a sociologist who maintains a special interest in issues of medical and health ethics. He is well known as the author of the book Genetic Fix (New York, Macmillan Publishing, 1973) in which he raised several questions on the ethics of genetic engineering. Over the years, Avery points out, IoM has conducted investigations and prepared reports on crucial issues in health policy. In the 1980s, it was "the first to issue a study on the seriousness of AIDS," she notes. Two reports--AIDS and Behavior: An Integrated Approach, focusing on various behavioral and mental-health aspects of HIV infection; and Growing Up Tobacco Free: Preventing Nicotine Addiction in Children and Youths--were released earlier this year, and a third, entitled Weighing the Options: Criteria for Evaluating Weight Management Programs, was released only last week. Current projects being conducted by the institute include an assessment of HIV transmission through blood products and an evaluation of ways to bolster dental education in the U.S. As most new members have not yet attended any of the institute's meetings, many say it is too soon to know which of the specific committees and projects they will choose to work on. Instead, they identified the areas they would like to be involved in. For instance, Anne B. Young, a physician and professor of neurology at Harvard Medical School who specializes in such neurodegenerative disorders as Alzheimer's, Huntington's, and Parkinson's diseases, expresses her concern with "how to deal with the increasing numbers of people afflicted with dementing disorders." In addition, she says, "I am interested in evaluating the criteria for applying new predictive genetic tests to populations at risk for various neurologic diseases." One of the few inductees to have attended last October's IoM meeting, Shu Chien, a professor of bioengineering at the University of California, San Diego, says, "I was very impressed with the timeliness of the topics--[such as] the health aspects of violence--and the discussions were very informative." Chien says that his tenure as president of the Federation of American Societies for Experimental Biology (FASEB) in 1992-93 involved him in health research and education, and he hopes to be involved in these areas at IoM. "I still don't know what I will be involved with, though I would like to contribute to as many [projects] as possible. I am very honored to have been elected," he says. With a diverse academic background that includes medical training in Taiwan, a Ph.D. in physiology, and considerable exposure to physics and engineering through his work in bioengineering, Chien maintains multiple research interests, including studies of blood flow, such hematological disorders as atherosclerosis and ischemia, and tissue engineering. (The Scientist, Vol:8, #24, p.3, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------- TI : LIST OF NEW IOM MEMBERS TY : NEWS PG : 10 Nancy E. Adler, professor of medical psychology and director, Health Psychology Program, University of California, San Francisco Dyanne D. Affonso, dean and professor, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta Huda Akil, Gardner C. Quarton Professor of Neurosciences, department of psychiatry; research scientist, Mental Health Research Institute; director, neuroscience program, University of Michigan, Ann Arbor Bobby R. Alford, executive vice president, dean of medicine, and distinguished service professor, Baylor College of Medicine, Houston Stephen J. Benkovic, professor of chemistry, Pennsylvania State University, University Park Paul C. Brucker, president, Thomas Jefferson University, Philadelphia Patricia A. Buffler, dean and professor of epidemiology, School of Public Health, University of California, Berkeley Ann W. Burgessvan, Ameringen Professor of Nursing, University of Pennsylvania, Philadelphia Anthony Cerami, president, Picower Institute for Medical Research, Manhasset, N.Y. Shu Chien, professor and chairman, department of bioengineering, University of California, San Diego Paul D. Cleary, professor, departments of health-care policy and social medicine, Harvard Medical School, Boston Jordan J. Cohen, president, Association of American Medical Colleges, Washington, D.C. Molly Joel Coye, senior vice president for community care, Good Samaritan Health System, San Jose, Calif. Mickey S. Eisenberg, director, Emergency Medicine Service and section head, division of general internal medicine, University of Washington Medical Center, Seattle Amitai Etzioni, director, Center for Policy Research, Washington, D.C.; university professor, George Washington University, Washington, D.C. Ruth R. Faden, senior research scholar, Kennedy Institute of Ethics, Georgetown University, Washington, D.C.; professor and director, Program in Law, Ethics, and Health, Johns Hopkins School of Hygiene and Public Health, Baltimore Thomas B. Fitzpatrick, Wiggleworth Professor of Dermatology, Emeritus, Massachusetts General Hospital Elaine V. Fuchs, investigator, Howard Hughes Medical Institute Research Laboratories; Amgen Professor of Molecular Genetics and Cell Biology, University of Chicago Patricia Goldman-Rakic, professor of neuroscience, section of neurobiology, and joint appointment, department of psychology, Yale University School of Medicine, New Haven, Conn. Ann M. Graybiel, professor of neuroanatomy, Massachusetts Institute of Technology, Cambridge Margaret A. Hamburg, health commissioner, New York City Department of Health Peter M. Howley, George Fabyan Professor and chairman, department of pathology, Harvard Medical School Dean T. Jamison, professor of public health and of education, Graduate School of Education; professor, School of Public Health; director, Center for Pacific Rim Studies, University of California, Los Angeles Michael M. Kaback, professor, pediatrics and reproductive medicine; and chief, division of medical genetics, department of pediatrics, School of Medicine, University of California, San Diego Janet C. King, professor of nutrition, University of California, Berkeley Mary-Claire King, professor of genetics, department of molecular and cell biology; professor of epidemiology, School of Public Health, University of California, Berkeley Peter O. Kohler, president, Oregon Health Sciences University, Portland Robert J. Lefkowitz investigator, Howard Hughes Medical Institute Research Laboratories; James B. Duke Professor of Medicine, Duke University Medical Center, Durham, N.C. David E. Longnecker,Dripps Professor and chairman, department of anesthesia, University of Pennsylvania Medical Center Clement J. McDonald, Distinguished Professor of Medicine, Indiana University School of Medicine; chief, Computer Science Research Group; codirector, Regenstrief Institute for Health Care; associate administrator, Wishard Memorial Hospital, Indianapolis James J. Mongan, dean, Kansas City School of Medicine, University of Missouri; executive director, Truman Medical Center, Kansas City, Mo. Joseph E. Murray, professor of surgery, emeritus, Harvard Medical School; chief (plastic surgery), emeritus, Brigham and WomenUs Hospital and Children's Hospital Medical Center, Boston Hans Neurath, professor emeritus, department of biochemistry, University of Washington School of Medicine, Seattle Jane S. Norbeck, dean and professor, School of Nursing, University of California, San Francisco Kenneth Olden, director, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. Theodore L. Phillips, professor and chairman, department of radiation oncology, University of California, San Francisco Irwin H. Rosenburg, Jean Mayer Professor of Nutrition and Medicine and director, USDA Human Nutrition Research Center on Aging, Tufts University, Boston Allen D. Roses, Jefferson-Pilot Professor of Neurobiology and Neurology and chief, division of neurology, department of medicine, Duke University Medical Center F. Sherwood Rowland, Donald Bren Professor of Chemistry, University of California, Irvine Joe Leigh Simpson, Ernst W. Bertner Chairman, department of obstetrics and gynecology; professor, department of molecular and human genetics, Baylor College of Medicine Jerome F. Strauss III, Luigi Mastroianni Jr. Professor; director, Center for Research on WomenUs Health and Reproduction; associate chairman, department of obstetrics and gynecology, University of Pennsylvania School of Medicine Richard W. Tsien, George D. Smith Professor, department of molecular and cellular physiology, Stanford University School of Medicine, Stanford, Calif. Ming T. Tsuang, Stanley Cobb Professor of Psychiatry, Harvard Medical School; superintendent and head, Harvard department of psychiatry at Massachusetts Mental Health Center, Boston Stanley J. Watson, associate director and research scientist, Mental Health Research Institute; associate chairman for research and Theophile Raphael Professor of Neurosciences, department of psychiatry, University of Michigan, Ann Arbor Alice S. Whittemore, professor of epidemiology and biostatistics, department of health research and policy, Stanford University School of Medicine Jean D. Wilson, Charles Cameron Sprague Distinguished Chair in Biomedical Science; chief, division of endocrinology and metabolism, department of internal medicine, University of Texas Southwestern Medical School, Dallas Flossie Wong-Staal, Florence Seeley Riford Professor of AIDS Research and professor of medicine and biology, University of California, San Diego Tadataka Yamada, John G. Searle Professor and chairman, department of internal medicine, University of Michigan Anne B. Young, Julieanne Dorn Professor of Neurology, Harvard Medical School; chief, Neurology Service, Massachusetts General Hospital, Boston Gordon H. DeFriese, professor of social medicine, epidemiology, and health policy and administration; director, Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill Paul Nutting, director, Ambulatory Sentinel Practice Network, Denver John A. Oates Jr., professor of medicine and pharmacology; Thomas F. Frist, Sr. Professor and chairman, department of medicine, Vanderbilt University School of Medicine, Nashville Richard L. Simmons, George Vance Foster Professor of Surgery and chairman, department of surgery, University of Pittsburgh; associate dean for clinical affairs, School of Medicine; associate vice president for clinical affairs, University of Pittsburgh Medical Center Gerald N. Wogan, Underwood-Prescott Professor and director of toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology William J. Hadlow, former research veterinarian, Rocky Mountain Labs (NIAID), Hamilton, Mont. (The Scientist, Vol:8, #24, p.10, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : Sagan Symposium Spans Galaxy Of Science AU : BARTON REPPERT TY : NEWS PG : 4 As one might imagine, the topics discussed at a symposium honoring Cornell University astronomer and space scientist Carl Sagan's 60th birthday ran the intergalactic gamut, even venturing into extraterrestrial intelligence. But the two-day event on the Ithaca, N.Y., campus in October was, at times, as much a forum on national and international policy--especially space policy--as a testimonial to the career of the celebrated science figure, with Sagan himself a major contributor to the eclectic dialogue. National Aeronautics and Space Administration associate administrator Wesley T. Huntress, Jr. declared that "we need to complete a full reconnaissance of the solar system, and begin an era of surface mapping" while also striving to detect and study planets around other stars. Roald Z. Sagdeev, former chief of the Soviet Union's leading space institute, urged substantially increased U.S.-Russian cooperation in space exploration, while arms-control expert Georgi Arbatov of the Russian Academy of Sciences contended that the "major enemy" of both countries is now the proliferation of nuclear weapons. Other talks were equally wide-ranging in scope: current proj-ects and problems of the U.S. space program, the search for extraterrestrial intelligence (SETI), studies on the origin of life, future "terraforming" of Mars so that it might sustain living habitation, the need for better science education, improving reporting on science in the news media, and the increasingly important role of scientists in public-policy debates. The occasion drew some 350 scientists, engineers, social thinkers, government officials, diplomats, and other invited guests from across the U.S. as well as Russia and five other countries. Cornell president Frank H.T. Rhodes told a banquet audience at the conclusion of the symposium: "It takes two days and 25 speakers to merely outline Carl's work. It shows the astonishing breadth, from astronomy and public policy to education, of his interests." Sagan, David Duncan Professor of Astronomy and Space Sciences and director of the Laboratory for Planetary Studies at Cornell, has played a leading role in the Mariner, Viking, Voyager, and Galileo planetary expeditions. He is known for his research on the massive greenhouse effect on Venus, windblown dust as an explanation for the seasonal changes on Mars, organic aerosols on Titan, the origin of life, and the possible long-term consequences of nuclear war. Cofounder and president of the 100,000-member, Pasadena, Calif.-based Planetary Society, the world's largest space-interest group, Sagan is the author, coauthor, or editor of more than 20 books. Among his best-known titles are The Dragons of Eden (New York, Random House, 1977), Broca's Brain (Random House, 1979), and the novel Contact (New York, Simon and Schuster, 1985), which is currently being made into a movie starring Jodie Foster. His newest book, Pale Blue Dot: A Vision of the Human Future in Space, is to be released this month (see accompanying story). Sagan's television series "Cosmos" has won Emmy and Peabody awards, and became the most widely watched series in the history of American public television. The companion book, also called Cosmos, was on the New York Times bestseller list for 70 weeks and became the best-selling science book ever published in the English language. Although plaudits for Sagan himself were abundant, most of the speakers at the symposium eventually turned their attention to his favorite subject--space. Huntress told the attendees that "for many on this planet, Carl is the personification of science--and in particular space science and space exploration. He's reached millions of people with his articles, his television appearances, and his books." The NASA official added: "Carl realized long ago that scientists have a responsibility to participate in society. They cannot stay safely in their labs and offices any longer, divorced from the rest of the world. Carl recognized early, more than most, that science can continue to prosper only if the public can participate in its excitement--and that scientific discoveries have value only if they are shared." Surveying the field of space exploration, Huntress said that, in addition to further probes studying the solar system, "it's time to expand the purview of planetary science, and detect and classify planets around other stars, what their atmospheres are like, and whether they are inhabited or whether they are habitable. We also need to complete a map of the universe along the entire electromagnetic spectrum." O.B. Toon, a space scientist at NASA's Ames Research Center, Moffett Field, Calif., hypothesized that in the future it might be possible to utilize carbon, nitrogen, and oxygen in the soil of Mars to "rehabilitate" portions of that planet so they could sustain human or at least plant life. However, he cautioned, "terraforming Mars would be a massive project." Elsewhere in the universe, Toon added, "the most exciting development of the next few decades" would be the discovery of "habitable zones," offering conditions amenable to life, in solar systems around other stars. A Mission To Mars? Sagdeev, former head of Moscow's Institute of Space Research, and now director of the East-West Center for Space Science at the University of Maryland, College Park, reviewed the sometimes-checkered history of Soviet lunar and planetary missions. He noted that in 1988, Sagan went to Russia to discuss the possibility of a joint manned flight to Mars, but that then-Soviet leader Mikhail S. Gorbachev failed to persuade President Ronald Reagan on the merits of such a project. Looking ahead, Sagdeev said, a possibility remains for a robotic mission to Mars in 1998. The Russians, he noted, also are considering an unmanned mission to Venus; a robotic lunar landing; a mission to return samples from Phobos, a moon of Mars; and perhaps reviving efforts toward a joint U.S.-Russian manned mission to Mars. At a news conference during the symposium, Sagan confirmed about Mars exploration that "there are, in fact, 25 robotic missions that are either in the works or in the serious planning stage, between 1996 and 2005. This involves the United States, Russia, the European Space Agency, Germany, Italy, Japan, a consortium of smaller nations including Austria, and England. It's very clear that, at least as far as robotic exploration goes, we are on the threshold of an extremely exciting time in the exploration of Mars." However, a manned mission to Mars, he speculated, is unlikely: "That's much more expensive, much more difficult. It's premature to do that." Frank Drake of the University of California, Santa Cruz, described past efforts in the SETI program. Now, he said, "there is a great deal of evidence that planets like our own are abundant. It suggests modes of life are abundant in the Milky Way." Drake, director of the SETI Institute, pointed out that today, using radio telescopes such as the one at the Cornell-operated Arecibo Observatory in Puerto Rico, "SETI is capable of detecting signals anywhere in the universe." Arbatov, former director of Moscow's Institute of the USA and Canada, who served as a senior adviser to Soviet leaders, told the audience that in the wake of the Cold War "there is the need for a real revolution" in international relations, in order to overcome the "militarized mentality" of past decades. With the end of the communist system and the breakup of the Soviet Union, he said, "we deprived you of an enemy. We deprived ourselves of an enemy. Never had the powers spent as much on military power as during the nuclear era, and we were not ready. Because we don't have the United States as an enemy and you don't have us, our major enemy is the proliferation of nuclear weapons. All other nations will ask, why shouldn't we? This is the most important thing that has to be taken into account now." How the U.S. will stand up to challenges, especially scientific ones, is a cause for concern to Sagan. Commenting about the overall performance of the Clinton-Gore administration in the science and technology area, Sagan told reporters at the news conference, "There's no question that the vice president is the most scientifically literate and, in a way, gifted president or vice president in many, many years. "But on the other hand, the political muscle of this administration is somewhat dubious. So their ability to carry out well-conceived programs is not certain. It's very striking how little they've been able to do on the environment, despite the clear dedication of the vice president." Other speakers at the symposium included Edward C. Stone, director of NASA's Jet Propulsion Laboratory in Pasadena, Calif.; Richard P. Turco of the University of California, Los Angeles, coauthor with Sagan of a controversial study on the "nuclear winter" likely to follow a nuclear war (Science, 222:1283-92, 1983); William G. Aldridge, executive director of the National Science Teachers Association; Richard Garwin, a senior scientist with IBM Corp. of Armonk, N.Y.; Frank Press, White House science adviser during the Carter administration and former president of the National Academy of Sciences; and Walter Anderson, editor of Parade magazine. Barton Reppert is a freelance science writer based in Gaithersburg, Md. (The Scientist, Vol:8, #24, p.4, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : THE LATEST FROM SAGAN AU : BARTON REPPERT TY : NEWS PG : 4 Carl Sagan's latest book, Pale Blue Dot: A Vision of the Human Future in Space (to be released this month by Random House), serves as a sequel to his 1980 bestseller, Cosmos. Following are a few excerpts: On Humanity's Place in the Universe: "The Earth is a very small stage in a vast cosmic arena. . . . It has been said that astronomy is a humbling and character-building experience. There is perhaps no better demonstration of the folly of human conceits than this distant image of our tiny world [as viewed from the Voyager 1 spacecraft, while heading out of the solar system]. To me, it underscores our responsibility to deal more kindly with one another, and to preserve and cherish the pale blue dot, the only home we've ever known." On Future Settlements on Other Worlds: "Surface or underground habitats on asteroids or the Moon seem technically feasible by the middle- to late 21st century. Many resources could be supplied from the world itself. Because the gravity is so low, human-powered flight would be easy." On Settling Mars: "If we wanted to set up housekeeping on Mars, it's easy to see that, in principle at least, we could do it. There's abundant sunlight. There's plentiful water in the rocks and in underground and polar ice. The atmosphere is mostly carbon dioxide. There's a great deal of organic matter on nearby Phobos, which could be plowed out and delivered to Mars below. . . . It seems likely that in self-contained habitats--perhaps domed enclosures--we could grow crops, manufacture oxygen from water, recycle wastes." On the Search for Extraterrestrial Intelligence (SETI) Project: "SETI is one of those search programs irritating to those who want well-defined cost/benefit ratios. Whether ETI can be found, how long it would take to find it, and what it would cost to do so are all unknown. The benefits might be enormous, but we can't really be sure of that either. It would of course be foolish to spend a major fraction of the national treasure on such ventures, but I wonder if civilizations cannot be calibrated by whether they pay some attention to trying to solve the great problems." On Seeking Future Security in Space: "Since, in the long run, every planetary society will be endangered by impacts from space, every surviving civilization is obliged to become spacefaring--not because of exploratory or romantic zeal, but for the most practical reason imaginable: staying alive. . . . A cataclysmic impact on one world would likely leave all the others untouched. The more of us beyond the Earth, the greater the diversity of worlds we inhabit, the more varied the planetary engineering, the greater the range of societal standards and values--then the safer the human species will be." --B.R. (The Scientist, Vol:8, #24, p.4, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: NOTEBOOK ------------------------------------------------------ TI : Take This Grant And . . . TY : NEWS (NOTEBOOK) PG : 4 Molecular biologist John Fagan made nationwide headlines the week before Thanksgiving when he said thanks--but no thanks--to the National Institutes of Health, returning a grant of nearly $614,000. Fagan, a professor of molecular biology at Maharishi International University (MIU) in Fairfield, Iowa, returned the grant--for research on two genes that are blueprints for cytochromes P450, involved in carcinogen and toxin metabolism--to protest genetic engineering, a field he believes is progressing too rapidly and without consideration of its harmful implications. Fagan, who got his Ph.D. from Cornell University in 1977 and was a research fellow at NIH before he joined MIU in 1991, brought a measure of respect to the institution, the site of 1994 Ig Nobel Prize-winning research concluding that meditators caused a decrease in violent crime in Washington, D.C. Losing the funding is "a big hit" for the school, acknowledges Fagan, who is redirecting his work toward cancer prevention and hopes to obtain future NIH grants. Jerome Green, director of NIH's Division of Research Grants, says Fagan's ability to obtain subsequent funding "depends on how far afield he goes" from areas in which he has demonstrated "competence and experience." (The Scientist, Vol:8, #24, p.4, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : A Year On The Hill TY : NEWS (NOTEBOOK) PG : 4 Applications are currently being solicited for the 1995-96 congressional Office of Technology Assessment (OTA) Congressional Fellowship Program, in which scientists take a year off to advise Congress in its deliberations of science and technology issues affecting public policy. Salaries range from $35,000 to $70,000. Applications must be submitted by February 1. The fellowship is expected to begin in September. For information, contact Morris K. Udall Fellowships, Personnel Office, Office of Technology Assessment, 600 Pennsylvania Ave., S.E., Washington, D.C. 20003. (The Scientist, Vol:8, #24, p. , December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------- TI : The Verdict TY : NEWS (NOTEBOOK) PG : 4 In a long-anticipated report made public on November 25, the Office of Research Integrity (ORI) concluded that Thereza Imanishi-Kari, who was a researcher in David Baltimore's Massachusetts Institute of Technology laboratory in 1986, committed scientific misconduct when she "fabricated and falsified" data published in Cell, 45:247-59, 1986, as well as data appearing in a letter of correction to the paper, published in Cell, 57:515-6, 1989, and in two National Institutes of Health grant applications. The report, which found Imanishi-Kari, now at Tufts University, guilty of 19 charges of misconduct, was made available to her in September; on November 23, she requested a hearing on the findings. If ORI's conclusions are sustained, Imanishi-Kari would be prohibited from receiving federal grant or contract money or participating in cooperative agreements for 10 years. She did not return telephone calls from The Scientist seeking comment. (The Scientist, Vol:8, #24, p.4, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: --------------------------------------------------- TI : Interview With Several Bats TY : NEWS (NOTEBOOK) PG : 4 The mythical image of the bat might conjure visions of Bela Lugosi, or, more to the moment, Tom Cruise, as vampires seem to be making a comeback on the silver screen. In fact, say the Penn State University authors of a study of the nesting habits of "house" bats, the more appropriate image might be a star of a do-it-yourself home-repair show. For example, according to Lisa Williams, a graduate research assistant who led the investigation for Pennsylvania's Wild Resource Conservation Fund, female big brown bats, which use attics to communally raise their young, appear to assess external aspects of a house--such as age, height, home style, accessibility, and roofing material--in selecting roosting sites. The study is important for those who want to coax the creatures from their attic or even attract the mammals to their homestead, a tactic that Williams, who coauthored the study with Penn State associate professor of wildlife resources Margaret Brittingham, encourages. The investigators designed a box that would precisely mimic the height, decor, and ambience--such as widely fluctuating temperatures--of the attics bats find so attractive. The boxes are hung from trees or attached to the buildings themselves. (The Scientist, Vol:8, #24, p.4, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : And No Tan Lines! TY : NEWS (NOTEBOOK) PG : 4 Researchers at Boston University School of Medicine (BUSM) have developed a method to get a permanent jump on the tanning season without messy, orange-tinted "sunless tanning" products. The team, led by BUSM dermatology department chairwoman Barbara A. Gilchrest, developed a topical preparation that causes an increase in melanin pigment production and a darkening of the skin color identical to that resulting from exposure to ultraviolet light. The preparation's secret ingredient: small DNA fragments, especially thymidine dinucleotides--ask for them by name. (The Scientist, Vol:8, #24, p.4, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: OPINION ------------------------------------------------------ TI : U.S. Science Confronts A New Uncertainty Principle AU : ALAN SCHRIESHEM TY : OPINION PG : 12 Sixty-seven years ago, German physicist Werner Heisenberg informed us that we cannot determine with any degree of accuracy both the position and the momentum of a subatomic particle. This is the famous Heisenberg Uncertainty Principle of quantum mechanics. This principle revolutionized high-energy physics, taught us to think in relativistic rather than absolute terms, and has guided subsequent generations of research scientists. Heisenberg, of course, received the 1932 Nobel Prize for his trouble. Today, science in the United States faces a new uncertainty principle. This principle says that we cannot forecast with much accuracy the position, the momentum, or the probable intersection of society's goals, the nation's political agenda, and the scientific merits of our national research enterprise. Like Heisenberg's postulation, this new uncertainty principle is revolutionizing the management and the direction of America's labs, is teaching us to think in relativistic rather than absolute terms, and is guiding--and sometimes vexing--modern generations of research laboratory directors, including this one. There is an important difference, however. Our reward for planning the labs' future in accord with this new uncertainty principle will not be a Nobel Prize. Instead, our reward will be our survival in the 21st century as vital and essential American institutions. Conflicting Agendas Once, the vagaries of scientific research were acceptable in America because political, scientific, and social agendas largely coincided: We wanted national security in the face of threats from a large and well-defined enemy, we were destined to grow, and we needed energy to do it. These agendas no longer coincide. Interplay and occasional conflict among the objectives of science, government, and society are relatively new additions to the environment within which the nation's research labs function. The divergence of political, social, and scientific agendas happened slowly. It was, perhaps, the chemists who came up against it first--in the environmental firestorm erupting from the pages of Rachel Carson's Silent Spring (Boston, Houghton Mifflin, 1962) and the anger of Love Canal. The energy labs got a wake-up call from the OPEC oil embargo, smog warnings, Three Mile Island, Chernobyl, oil-soaked shore birds, and the so-called ozone hole. Our colleagues in high-energy physics encountered it somewhat more recently, in the scuttling of the superconducting supercollider (SSC). But the biggest single impetus to change in American research came when the Cold War collapsed in the rubble of the Berlin Wall. Suddenly, America no longer faced a well-armed, technologically sophisticated enemy capable of destroying us with just 30 minutes' warning. Defense research needs, projections, and budgets dropped precipitously, and are still falling. Major new challenges moved to the forefront in post-Cold War America, and the national scientific and technological establishment began to feel the pain and promise of a fundamental transformation. Nowadays, industry increasingly is seeking out opportunities to team with other R&D performers--including former competitors--in the development of new technologies. There is growing political pressure for all public investments to be tied more closely to national needs--as those needs are perceived by the Washington political establishment. Scientific latitude was greater in the past because we could presume continued national consensus on exactly what the needs were. That's no longer so. The startling results of the November elections are the latest in a series of reminders that the definition of "national needs" today is a moving target. Here's the core of the whole "New Uncertainty Principle": Science must not only determine what today's definition is, but also project--some might say divine--what the definition will be tomorrow and plan accordingly. Assuming we do that, and to further compound a complex situation, we must craft our course to recognize tomorrow's definition while not falling afoul of today's. What is already apparent is that the principles of total quality management increasingly are being applied throughout industry and government, including at research institutions. And the traditional boundaries between federal R&D agencies are getting fuzzier, as the nation seeks to provide multiagency, coordinated approaches to satisfying national needs. "Progress at any cost" is out. Fiscal accountability, environmental responsibility, and cost efficiency are in. And, in a trend likely to continue, research under way or projected is far more likely than in the past to have a strong thrust toward marketplace applications. Environmental protection, long a goal of some research, is rapidly becoming a precondition for all research. International competitiveness and job creation are only slightly below in the pecking order. >From Push To Pull We now find corporations with global competitive interests deeply involved in cooperative R&D agreements with national laboratories. At Argonne, we already work with DuPont Co. of Wilmington, Del.; Midland, Mich.-based Dow Chemical Co.; Amoco Corp. of Chicago; IBM Corp. in Armonk, N.Y.; New York-based Exxon Corp.; and many other companies. We are collaborating on profit-oriented projects aimed at producing higher-quality fiber, stronger materials, more effective pharmaceuticals, faster computers, safer herbicides, and lower-cost gasoline. We are fully engaged in technology transfer and have even helped create spin-off companies. Ten years ago, these activities would have been exceptional. Today, they represent a major research management trend at the national laboratories. We increasingly serve as a common ground to integrate skills, capabilities, technologies, facilities, and research organizations--including partners from throughout the laboratory system, other federal agencies, industry, academia, and other nations. Clearly, we are moving from a technology-push philosophy to a market-pull philosophy. New Paradigms Increasingly, we find that proposed research must be shown to benefit social goals and political objectives as well as to advance science and technology. Whether we call that "kitchen-table impact," "sustainable development," or some other term, it is the new reality. What also makes it the new uncertainty is the fluid nature of societal goals and the political agenda--not to mention the inherent uncertainties of venturing beyond the state of the art. This new paradigm does hold promise for the nation, particularly in the short term. But it is not without its pitfalls, especially for those of us engaged in basic research, for which the industrial, economic, and environmental pay-offs are unspecified and largely unpredictable and, for the average citizen, can be so obscure as to be nonexistent. Eminent marine biologist Eugenie Clark wrote in 1969 (The Lady and the Sharks, New York, Harper and Row, Chapter 1): "Not many appreciate the ultimate power and potential usefulness of basic knowledge accumulated by obscure, unseen investigators who, in a lifetime of intensive study, may never see any practical use for their findings but who go on seeking answers to the unknown without thought of financial or practical gain." Her comment is even more apt today, as anyone involved in the ill-fated SSC will no doubt agree. Hers is a point we should remember as we strive to blend scientific potential with political reality, economics, and environmentalism heading into the 21st century. We must continue to advance science in a society where researchers will increasingly be challenged to justify their work, especially on economic and environmental grounds. Such concerns, now largely confined to North America and Europe, will expand to Asia, Africa, and other areas where they have not traditionally been a major consideration. Proposed products and processes will have to be proved environmentally benign before they receive approval to proceed. This prior-proof requirement could have one troublesome effect--shorter-term thinking in the research community. We may be tempted toward the safer course of evolving current products rather than the environmentally and economically riskier path of developing wholly new products. Most of the research projects American science undertakes from now on almost certainly will include a strong energy context, flavored with an environmental and job-creation agenda. In fact, the energy imperative will supplant defense as the main research driver in the 21st century. World population is expected to double by mid-century. Global energy demands are projected to at least quadruple (even with stringent conservation measures in place). Society's burgeoning need is apparent. Walking through a bookstore one recent weekend, I noticed a copy of Thomas Wolfe's famous work You Can't Go Home Again. Wolfe wasn't writing about research laboratories, of course, but he might just as well have been. For we can't go home again, either. That is, if "home" means the past--a time when science was apart from, or "above," society and politics, somehow entitled to the public's support yet not really accountable except to future generations. Management Principles To come to terms with the new uncertainty principle, we--like Heisenberg's contemporaries--must change our perspective and our methods. We must formulate and adopt new research-management paradigms. Here are four candidates: 1. The degree to which politics and society will support scientific research is directly proportional to perceived return on investment. We research directors must be able to articulate the return to be derived from public investments in our work. We must not only be able to, but also willing to. 2. Pre-challenge political involvement is always more effective than post-challenge involvement. The research community must become more engaged in the political world and with its denizens, preferably before projects are challenged. We must overcome our community's traditional disdain for the "soft sciences," such as politics and sociology, recognizing that ultimately politics controls the money and support we need to do our work. The extent to which we avoid the political process is precisely the extent to which others will decide our fate. 3. The more the public knows about science and technology, the more likely it is to support science and technology. Here is an important issue for the 21st century--scientific literacy. We scientists have a clear obligation to increase scientific literacy in American society. Doing so will help our fellow citizens cope with what we all know will be an increasingly technological world. Doing so will also foster greater understanding of what it is that we do. In short, working to improve scientific literacy is not only the right thing to do, but also the smart thing. 4. Finally, it is wise to remember that, when you are speaking to an audience of Greeks, communications efficiency increases markedly if you speak Greek. Scientists must do a better job of making our case in terms that politics and society understand. In hindsight, arguing for billions of dollars to build the SSC because it might help us locate the Higgs boson may go down as a textbook example of speaking Russian to the Greeks, and then being surprised when the Greeks do not understand--or do not wish to contribute to the effort. At the national laboratories, we see our role in the 21st century as that of a neutral site and a robust bridge, connecting all the country's research communities; universities; industries; and federal, state, and local government agencies in a common research enterprise geared to the needs of society, both today and tomorrow. Precisely because the national labs deal daily with the New Uncertainty Principle, we may well become the catalyst that helps our colleagues in the American research community continue the advance of science and technology. Alan Schriesheim is director and CEO of Argonne National Laboratory in Illinois. This essay is adapted from remarks he delivered at the General Motors R&D Center, Detroit, on Nov. 9, 1994. (The Scientist, Vol:8, #24, p.12, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: COMMENTARY ------------------------------------------------------ TI : Scientific World's Low Tolerance For Controversy May Be What's Excluding Young Investigators AU : NAOMI KRAUS TY : OPINION (COMMENTARY) PG : 13 The process by which research is supported is under continuous scrutiny, which is a good thing, because it means that those responsible for policy-making do care. It is also the topic utmost on the minds of scientists. For example, the National Institutes of Health recently conducted a roundtable discussion on many diverse aspects of the funding process (FASEB Newsletter, August/September 1994, page 4). And the congressional General Accounting Office this year released its findings on the peer-review system, concluding that it appears to be working reasonably well (E. Marshall, Science, 265:86, 1994). Among scientists, Joachim Messing, in his excellent commentary (The Scientist, June 27, 1994, page 13), made the case for supporting many small, rather than a few large, projects. Some excellent suggestions on improvements have also been proposed by Jose M. Musacchio, though he, too, refrains from suggesting major changes in the peer-review system (FASEB Journal, 8:679-83, 1994). Of all the information recently brought out on sponsored research, one fact is truly alarming. This is the decrease in the number of young scientists who apply for grants. According to a new report by the National Research Council (NRC), applications for National Institutes of Health funding from researchers under 36 years of age declined about 55 percent between 1985 and 1993 (The Funding of Young Investigators in the Biological and Biomedical Sciences, Washington, D.C., National Academy Press, 1994). If this trend continues, it will lead to the decline, if not the extinction, of academic research in the United States. The NRC study found that young investigators' success rate in obtaining funds "was lower than that of many age groups--a new and special disadvantage." I want to propose the thesis that this is hardly a coincidence: Younger investigators might have a lower success rate than older and established investigators exactly because of their ability to approach problems in a new and original viewpoint--the very qualities that form the basis of progress in science. When I started to observe the scientific scene, about 30 years ago, controversy was viewed as an integral part of progress, a process in which ideas and facts are sorted out and paradigms are shaped. For several years I regularly anticipated the discussions between Peter Mitchell, who presented arguments for the chemiosmotic mechanism of oxidative phosphorylation, and his opponents, who vigorously argued against it, at various meetings of the Federation of American Societies for Experimental Biology. Those arguments were exciting. The atmosphere was electrifying, and I felt that I was part of an endeavor that was not only stimulating but also open, in which the best arguments and facts eventually would win. I no longer feel this way. Controversy is no longer viewed as the warf and woof of the fabric of science. On the contrary, it seems to be perceived by the powers that be as a potential source of embarrassment, which might create problems for the public image of science. As reported in a recent article on grantsmanship (A.S. Moffat, Science, 265:1921, 1994): "The most challenging part of developing a research proposal . . . is to find a balance between something sure and something new." However, the message being sent to conveyors of the new is that not only should their work have the assurance that its support does not involve risks--namely, it will result in X number of publications--but also that it should be in line with, rather than challenge, existing views. Young investigators (and some nave, incorrigible, old investigators) might not have learned the importance of staying in the "mainstream"--which might contribute to their lower success rate. However, the way young scientists fare is the way the future of science fares. In order to arrest this trend of decline in successful young applicants, either they should be taken out of the present peer-review system and their applications considered under a specifically designated new category, or the powers that be need to reevaluate the type of research that is funded. The current emphasis on "mainstream" thinking, along with discouragement of dissent and innovation, ultimately stifles--if not entirely paralyzes--progress in science. Naomi Kraus is a professor in the department of physiology and cell biology at the University of Texas Health Science Center, Houston. (The Scientist, Vol:8, #24, p.13, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: LETTERS ------------------------------------------------------ TI : NIH Triage AU : JOSE M. MUSACCHIO TY : OPINION (LETTERS) PG : 13 Hugh Stamper's letter (The Scientist, Oct. 17, 1994, page 13) concerning my commentary "Triage At NIH: A Smoke Screen Concealing The Real Problems Facing American Science" (The Scientist, Sept. 5, 1994, page 13) contains some interesting news, but also some unsubstantiated statements. I was glad to learn that the National Institute of Mental Health (NIMH) has changed the triage procedures regarding communication with the applicants, who now will receive the unedited comments from each reviewer. We discussed a preliminary triage model in the NIMH Initial Review Groups (IRG) chairpersons' meeting of Dec. 6, 1993. The model (attachment 3, NIH memorandum No. OER 88-5) indicated that the principal investigators whose applications were deemed noncompetitive (NC) were going to receive only an abbreviated summary statement. The model attached contained about 220 words, and its brevity was considered to be an advantage and a selling point for the reviewers. It is good to know that the plans were changed, and that the applicants will receive the reviewers' full comments. The bad news is that the change will impose an even higher burden on the study-section members, who now must write their reviews in an objective editorial style, suitable for consumption by deeply disappointed applicants. In the good old days, reviewers who do not write well, like me, relied on the editorial abilities and good judgment of the scientific-review administrators. It is obvious that to write the critiques in final form will require more time and effort, no matter what Stamper says. However, this problem has been neglected, perhaps because reviewers are not paid for their writing time. Despite the reviewers' increase in work, applicants whose proposals are deemed NC will not receive a summary of the IRG discussions. This can hardly be considered an advantage for the applicants, but at least the load of the scientific-review administrators will be drastically reduced. They certainly deserve a break. I was surprised that Stamper got involved with such a small issue, but I was glad to know that triage was reinvented with a better flavor. I am also pleased with his silence on more important issues, because it may indicate that he agrees with my views in "American science in crisis: The need to revise NIH funding policy" (FASEB Journal, 8:679-83, 1994). Finally, and contrary to Stamper's opinion, I think that I do understand that the issue of triage can be logically separated from the current crisis in biomedical research funding. What I do not understand is the excessive time and effort spent in discussing, advertising, and implementing superfluous changes, instead of concentrating on drastically revising the NIH funding policy, as I proposed. Jose M. Musacchio Department of Pharmacology New York UniversityMedical Center 550 First Ave. New York, N.Y. 10016 (The Scientist, Vol:8, #24, p.13, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------- TI : 'One-Party' Science AU : PAUL EVANS TY : OPINION (LETTERS) PG : 13 I was supportive of J. Philippe Rushton until he attacked those he believes to be "politically correct" ("'One-Party' Science Poses Threat To Scientists' Intellectual Freedom," The Scientist, Oct. 3, 1994, page 13). Rushton needs to learn that some people are earnestly sensitive to the issues he is studying and are concerned about the implications of the misuse of this scientific information. He should not label all who disagree with his form of "one-party science" as politically correct. The arts and the sciences are under attack by those who do not understand them. His threatened "I'm a victim" stance does nothing to help his case and makes this black scientist question his motives. As a member of the American Association for the Advancement of Science, I am pleased that the association actually has the courage to have a dialogue on the ethical issues that are of concern to all good scientists, and Rushton as well. He would do well to get off of his soap box and listen. Paul Evans P.O. Box 1830 Boston, Mass. 02205 (The Scientist, Vol:8, #24, p.13, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: RESEARCH ----------------------------------------------------- TI : Changing Scientific Times Drive NIGMS Research Agenda AU : KAREN YOUNG KREEGER TY : RESEARCH PG : 14 >From the early days of research in molecular biology--the discovery of restriction enzymes, which paved the way for recombinant technology, for example--to pharmacologist Alfred G. Gilman's 1994 Nobel Prize-winning investigations of G proteins, scientists funded by the National Institute of General Medical Sciences (NIGMS) have been advancing the life sciences. In fact, more than half of the National Institutes of Health-supported Nobel Prize winners have received grants from NIGMS. Today the institute--which supports extramural investigators almost exclusively--funds basic research in such areas as cell biology, genetics, and biochemistry aimed at finding out how systems work, usually before the implications for specific diseases are known. Last October, NIGMS reorganized its administrative structure with the purpose, according to an institute statement, of becoming more efficient in its support of basic biomedical research and training and to reflect the increasingly interdisciplinary nature of science. Specifically, four program branches--cellular and molecular basis of disease; genetics; biophysics and physiological sciences; and pharmacology and biorelated chemistry--have been reorganized into three divisions: y cell biology and biophysics; y genetics and developmental biology; and y pharmacology, physiology, and biological chemistry. Two other NIGMS programs have also become divisions: minority opportunities in research and extramural activities. Cost-cutting measures, as part of the Clinton administration's efforts to decrease the federal work force--particularly middle management--was a secondary, but not a deciding, factor shaping the reorganization, institute officials maintain. They point out that no one at the institute has lost his or her job as a result of the restructuring; however, they say, NIGMS is meeting its goal of reducing employee numbers by not filling some open positions. "Part of the immediate incentive was the requirement to streamline as with all other parts of the federal government," explains Marvin Cassman, acting director of NIGMS. "You just can't ignore that. In addition, the [old] programs have been in place for a long time, 10 years for some and 20 for others." He says that "it was time to reconsider how we grouped our research portfolio" to reflect the way science has grown and the different directions in which it has developed. He adds that Ruth Kirschstein, NIGMS director from 1974 to 1993 and currently deputy director of NIH, was instrumental in focusing the institute's research and training programs. W. Sue Shafer, associate director for extramural activities, says that some NIGMS-funded scientists were concerned that certain areas of science would no longer "have a home at NIGMS." But because the institute solicited broadly for comment from its scientific constituents during the review phase of the reorganization proposal, she maintains, groups such as professional societies that were especially concerned did have input into the restructuring, thereby dissipating their apprehension. John Perkins, president of the Rockville, Md.-based American Society for Pharmacology and Experimental Therapeutics (ASPET), concurs with Shafer's assessment, noting that ASPET officials were involved in an external review of the reorganization and pronouncing ASPET "comfortable" with the scheme. "We're still funding the same constellation of projects. What we hope is that the new organization will stimulate new interactions and perhaps new connections between areas of research that we support," stresses Cassman. One area that is new is an initiative to fund projects that contain risky or unorthodox ideas and methods (see accompanying story). Getting Inside The Cell James Cassatt, division director of cell biology and biophysics, says this division "brings together the cellular aspects of biomedicine--how the cell is organized and how things happen within the cell--with those programs where people are trying to explain these same things but in molecular terms." He adds that the division's programs also dovetail with initiatives that look at "the detailed three-dimensional structures of many of the molecules that are involved" in cellular processes. Among many "exciting" areas of research in the division, Cassatt cites projects elucidating the three-dimensional structure of such mo-lecular motors as the muscle protein actin; studying the proteins embedded in cellular membranes; and determining the structure of various G proteins and nucleic acid-binding proteins. In biophysics, Cassatt remarks, "we're supporting a lot in the area of protein folding. If you're working for a biotech company and you make a protein, you have to make sure it folds properly. "Recently it's been discovered that there are helper molecules called chaperonins that help in the folding process. Ultimately what one would like to do is to look at an [amino acid] sequence and deduce from that sequence the structure of the folded protein. Nature, of course, does this very well and the information is there, we just don't know how to interpret it completely." Cellular Processes Judith Greenberg, director of the genetics and developmental biology division, comments that "one of the extremely hot areas" of research in her division has focused on cell-cycle regulation. Scientists in this field, she explains, study what causes cells to divide, what stops cells from dividing, and how cells proceed through the process of replicating DNA to undergoing mitosis. "In the last several years, cell-cycle regulation has really been taking off in a big way," she elaborates. "There have been a lot of discoveries in what appear to be disparate areas of research that have all been coming together and causing just an explosion of information. A lot of this feeds into cancer research, also." She mentions that the study of cell-cycle regulation is also important to determining what genes regulate very early development in embryos. "It will have an impact, I think, on understanding birth defects," Greenberg predicts. Another "explosive" research topic, she reports, is "the whole area of homologous recombination, better known these days as gene targeting." This basically entails coming up with a way of substituting one gene for a very similar one in a cell, which is useful in creating transgenic mice, among other applications. "A big breakthrough a number of years ago was the ability to get a specific piece of DNA into the right location on a chromosome. These cells are put back into a mouse, so you can create a mouse that is lacking a specific gene or one that has a gene that's in some way been modified from the norm." She says two NIGMS grantees originated some of those gene-targeting technologies, which eventually led to the development of the mouse model for cystic fibrosis. "Another area that we have just been moving into is transcriptional regulation--what turns a gene on and makes it active," adds Greenberg. "This [field of study] has now moved beyond what I would consider genetics into structural biology. What's happening is that scientists refine certain protein-DNA interactions, such as transcription factors, in the genetics program. This work then moves over into the realm of structural biology as people start to look at [molecules involved in transcription] with X-ray crystallography and NMR [nuclear magnetic resonance imaging]." Molecular Keys Michael Rogers, acting director of the newly formed pharmacology, physiology, and biological chemistry division, says that research in his section covers a number of areas, including molecular pharmacology; the molecular basis of the action of anesthetics; and understanding the pathogenesis of septic shock and the molecular basis of wound healing in burn victims. Specifically, he notes that biochemistry-related projects that fall under the aegis of this new division "look at basic problems of how proteins are handled in the body--how they actually carry out their catalytic function." This division also has a large program in synthetic chemistry, which is primarily directed towards drug synthesis, namely learning how to produce drugs that come in only one chemical configuration. "You can have drugs that are the same [substance], but exist in different configurations [isomers], sort of like your two hands, which are the same, but they don't fit on top of each other," Rogers explains. "Working out ways to prepare just one molecule is very important right now to the drug industry." Rogers likens this scientific conundrum to finding the right molecular key to fight diseases: "Sometimes those drugs--the right-handed key vs. the left-handed key--might have very different effects on the body. But most chemical reactions will produce both the right-handed and the left-handed forms, and most drugs on the market today are an equal mix of both forms. Sometimes one of those is the active drug and sometimes the one that's inactive may be involved in some of the [drug's] side effects. So there's been a push to develop new medicines that only have one of the isomers," so as to minimize the harmful side effects. For more information on NIGMS programs, contact W. Sue Shafer, associate director for extramural activities, National Institute for General Medical Sciences/National Institutes of Health, 45 Center Dr., MSC 6200, Natcher Building, Room 2AN-32C, Bethesda, Md. 20892-6200; (301) 594-4499. Fax: (301) 480-1852. E-mail: wst@cu.nih.gov. (The Scientist, Vol:8, #24, p.14, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------- TI : HIGH RISK, HIGH PAYOFF AU : KAREN YOUNG KREEGER TY : RESEARCH PG : 14 In a Nov. 7, 1994, letter, Marvin Cassman, acting director of the National Institute of General Medical Sciences (NIGMS), informed NIGMS grantees that the institute is "making special efforts" to fund applications that contain risky or unorthodox ideas or methods. Specifically, these would be applications that contain ideas that challenge current dogma; include experimental approaches that have inherent or unavoidable elements of risk; propose experimental models that are not fully developed or whose utility is not adequately shown; and/or are lacking data to establish the feasibility of the proposed ideas. "A lot of people in the field don't seem to know that about a year ago the institute and our council recommended that we take 5 percent of our competing research dollars and set it aside to support 'risky' research," Cassman says. These types of grants are typically funded for two years for a total of $120,000 in direct costs. "These are applications that would have gone through the normal peer-review process, not a separate [call for proposals]," and would likely have been denied, he explains. "These would be applications where the [study section] said: 'This is really a terrific proposal. It has exciting possibilities. But the preliminary experiments aren't done yet. But we're not sure that it's going to work. But the investigator hasn't had much experience in this area.' "It's all of these 'buts' that are so damaging in peer review. We're looking for applications where the reviewers themselves said: 'If it works, it's potentially very important.' And it's those [proposals] that we're taking a flyer on." "We're trying to subtly influence [grant applicants'] behavior," maintains W. Sue Shafer, associate director for extramural activities. "We want scientists in the field to be a little less conservative and put some of their riskier ideas that they feel would really have a high payoff into their applications. We're not asking for any special treatment in the review process, although DRG [NIH's Division of Research Grants] is encouraging reviewers to note--regardless of how they are scoring the applications--where they think there is something that is risky but if it panned out would be very important." Judith Greenberg, director of the genetics and developmental biology division, adds: "In my own view, investigators are so conditioned by the system that they need to submit a safe application. Even though they have novel ideas, they often keep them to themselves." In the long run, however, for the progress of science, these applications need to be funded, she asserts: "You never know what's going to turn up [in conducting science]. It could be a bomb, but on the other hand, the payoff could be enormous. If it turns out to be correct it could really result in a whole paradigm shift." Greenberg maintains that NIGMS is actively driving to change at least part of its funding strategy because "although scientific research is in the midst of an era of tight budgets, [researchers] still need to push science." --K.Y.K. (The Scientist, Vol:8, #24, p.14, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: HOT PAPERS ------------------------------------------------------ TI : MEDICAL GENETICS TY : RESEARCH (HOT PAPERS) PG : 15 H.T. Orr, M. Chung, S. Banfi, T.J. Kwiatkowski, Jr., A. Servadio, A.L. Beaudet, A.E. McCall, L.A. Duvick, L.P.W. Ranum, H.Y. Zoghbi, "Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1," Nature Genetics, 4:221-26, 1993. (Cited in 114 publications through October 1994) The subject of this paper, the genetic basis of the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1), has been the focus of an ongoing collaboration between the laboratories of Harry Orr at the University of Minnesota, Minneapolis, and Huda Zoghbi at Baylor College of Medicine in Houston. "It demonstrates that the DNA mutation that causes SCA1 is the expansion of an unstable trinucleotide--CAG, in this case--repeat in the coding region of the gene for a protein called ataxin 1," explains Orr, who is a professor of laboratory medicine and pathology and a member of the Institute of Human Genetics at Minnesota. "A normal genome can have anywhere from six to 39 repeats of the CAG unit. When the trinucleotide is transmitted from parent to child, it can grow in length, and this expansion causes the disease." Zoghbi, a professor of molecular and human genetics, pediatrics, and neurology at Baylor, notes that "SCA1 was the fifth disease to be correlated with a trinucleotide-repeat expansion, which confirmed the theory that unstable repeats may represent a common mutational mechanism. We may have, in fact, discovered a unifying mechanism for late-onset neurodegenerative diseases." Other disorders associated with CAG repeats include Huntington's disease, spino-bulbar muscular dystrophy, and Machado-Joseph disease. While the reason for the association of this mutation with nervous-system disorders is not known, Zoghbi speculates that it may be partially due to the inability of nerve cells to regenerate: "The appearance of the expanded repeat unit in the genes may be causing an accumulation of a faulty gene product, for instance, which could eventually result in the death of a nerve cell." Currently, her laboratory is working on defining the function of the normal ataxin 1 protein, which is defective in SCA1, and on determining the nature of the disruption caused by the mutation. "We hope that by finding out the mechanism we will have a greater ability to treat this group of diseases," adds Orr, whose current line of research involves modeling SCA1 in transgenic mice, to "understand how the disease develops." Both Orr and Zoghbi point out other reasons for the widespread interest in their paper. "It was the first to show the correlation of the size of expansion with severity and age of onset of the disease," comments Zoghbi. "We can more closely predict the age of onset by the number of repeats for SCA1 than in the case for Huntington's [disease], for instance," says Orr. "However, because of ethical concerns [regarding genetic testing] and since we do not yet fully understand all the factors involved in determining age of onset, no information regarding age is given based on the SCA1 repeat number." The research detailed in the paper is also unique in that it was the first time investigators used a focused strategy to find an unstable repeat, according to Zoghbi. Since then, other investigators (R. Koide et al., Nature Genetics, 6:9-13, 1994; S. Nagafuchi et al., Nature Genetics, 6:14-18, 1994; Y. Kawaguchi et al., Nature Genetics, 8:221-27, 1994) have used a similar targeted approach to detect mutations in other neurodegenerative diseases. (The Scientist, Vol:8, #24, p.15, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : PLANT BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 14 S. McQueen-Mason, D.M. Durachko, D.J. Cosgrove, "Two endogenous proteins that induce cell wall extension in plants," Plant Cell, 4:1425-33, 1992. (Cited in 21 publications through October 1994) Daniel Cosgrove, a professor of biology at Pennsylvania State University, University Park, says that this paper breaks new ground in that it gives the first insights into "the biochemical basis of one of the key processes in plant-cell growth; namely, the extension of the cell walls. "We identified proteins that make cell walls grow in surface area," he adds. Plant-cell walls are composed of large units of polysaccharides (such as cellulose fibers), held together by hydrogen bonds, with different proteins embedded in this matrix. The newly discovered proteins, explains Cosgrove, "act on the polysaccharide component of the cell wall to cause slippage between units so as to enable extension. "For more than 50 years, people had hypothesized the presence of such 'wall loosening' proteins, but they had remained elusive until now. Our lab identified the first of this class of proteins." The discovery of these proteins--now referred to as expansins--and the elucidation of their mode of activity in a subsequent paper (S. McQueen-Mason, D. Cosgrove, Proceedings of the National Academy of Sciences, 91:6574-8, 1994) have caused considerable excitement among the community of scientists interested in cell growth. Based on the finding that these proteins acted on hydrogen bonds between polysaccharide units, these scientists are able to better explain how plant cells grow in volume and surface area up to 10 times their original size without disrupting the integrity of the cell wall (L. Taiz, PNAS, 91:7397-89, 1994; S.C. Fry, Current Biology, 4:815-17, 1994). "The fact that a protein acts in a nondegradative fashion on pure cellulose, for instance, caught many people's fancy," Cosgrove observes. Since expansins act on the polysaccharide without disrupting the backbone, many re-searchers are speculating as to the potential uses of these proteins in the recycling of paper, he adds. (The Scientist, Vol:8, #24, p.15, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: TOOLS & TECHNOLOGY ------------------------------------------------------- TI : Monoclonal Antibodies Find Utility In Cell Biology AU : RICKI LEWIS TY : TOOLS & TECHNOLOGY PG : 16 In its short lifetime, monoclonal antibody (MAb) technology has experienced more ups and downs than a yo-yo. As this brilliant invention has evolved into a difficult technology, numerous suppliers have emerged to facilitate researchers' access to the new antibodies. Today, MAbs are partners in such cell-biology staples as fluorescence microscopy, flow cytometry, and affinity chromatography. Investigators use these antibodies to track cells as they communicate and interact, respond to various stresses, turn cancerous, and die. But, just as antibodies are finding increasing utility in cell biology, a new Food and Drug Administration classification for those products with clinical utility may affect researchers' access to the important technology (see accompanying story). Monoclonal History MAbs were born in 1975, when Georges Kohler and Cesar Milstein at the Medical Research Council Laboratories in Cambridge, England, fused two types of cells to form a hybridoma. Part antibody-secreting B cell, part myeloma cell, a hybridoma combines the talents of each constituent, continuously releasing a single type of antibody when cultured in ascites fluid in a mouse's abdomen. This secretion of a monoclonal (single-type) antibody is in contrast to the response of an animal's challenged immune system, which is termed polyclonal because several types of antibodies are produced against a single type of foreign antigen, each zeroing in on a different portion of the target. Hybridoma technology, the research community thought, would finally provide a way to isolate and at the same time mass-produce a single antibody type, harnessing its exquisite specificity. But capturing that quality did not come easily. "When Kohler and Milstein made the first hybridoma, everyone started making them. But by the mid-1980s, hybridoma technology fell out of favor," says Krishna Balakrishnan, vice president of research and development at Richmond, Calif.-based Berkeley Antibody Company (BAbCO). Researchers found it exceedingly difficult to create hybridomas, select a youthful one, and culture it successfully enough to provide ample antibodies, he explains. But as MAb research nears its 20th anniversary, it is experiencing a resurgence. "In the early 1990s, hybridomas came back into fashion because many people realized that there are a lot of specialized applications that only a MAb can do," notes Balakrishnan, referring to MAbs that zero in on chemical groups small enough to be specific to one molecule. Finding A Niche Many researchers agree that nurturing a hybridoma to secrete a desired antibody is technically challenging. First, the animal providing the B-cell part of the hybridoma must be immunized against the appropriate antigen, then B cells isolated and fused with myeloma cells to provide them unlimited cell division, or immortality. Next is the onerous task of selecting hybridomas whose antibodies suit researchers' needs. Obstacles are everywhere in the long process--cells won't fuse, hybridomas die or won't propagate. Antibodies may be produced in too low a yield, may bind to their targets with poor affinity, or may bind to target regions (epitopes) that different molecules have in common, drastically reducing specificity and making cross-reactivity possible. These technological hurdles have opened a wide niche for dozens of companies that MAbs have overcome these obstacles and nurture for researchers. Such vendors offer extensive lists of monoclonal and polyclonal antibodies, partial antibodies, and antibodies conjugated to various marker molecules. Firms that grow hybridomas and scale up production of desired antibodies report that such contract services are extremely popular. "Lately we have been providing mostly customized products. Some people want special forms of antibodies, such as without preservatives or with a certain conjugate, or just a FAb fragment [the portion of an antibody that binds antigen]," says Bret G. Wien, president of Research Diagnostics Inc. in Flanders, N.J. Richard Plante, associate scientist at the Robert Wood Johnson Pharmaceutical Research Institute in Don Mills, Ontario, works in drug discovery and doesn't have time to create monoclonals. "We work with the glucocorticoid receptor, for which there is no good clone available," he explains. A colleague had been supplying MAbs, but the hybridoma died. "So Affinity BioReagents [Inc. of Neshanic Station, N.J.] has been a good source of the antibodies I'm interested in." Sharon Devereaux, a research scientist at Abbott Laboratories Inc. in Abbott Park, Ill., is another satisfied hybridoma customer. BAbCO grew her MAbs. "They were very cooperative, everything was documented well, and they gave timely results and feedback," she says. Backbone Of Biological Research MAbs are powerful tools in cell, molecular, and developmental biology. They have helped researchers dissect the complex pathways of signal transduction, cell adhesion, the stress response, carcinogenesis, and cell death. In short, MAbs reveal life at the biochemical level. And investigators are finding that their small, individual glimpses into the lives of cells are connected, through signaling pathways. "The whole cell biology area has taken off, and signal transduction is at the core of that. A lot of the signal-transduction work is antibody-related," comments Wesley Russ, immunodetection product manager and senior scientist in research and development at Life Technologies in Gaithersburg, Md. Geneticists are using small MAbs to identify proteins. "We're finding more and more molecular biologists working with recombinant DNA turning to monoclonals as tools to isolate molecules. For example, a researcher with a partial gene sequence reconstructs the corresponding peptide, then uses a monoclonal to fish out the gene product," notes BAbCO's Balakrishnan. "You couldn't do that with polyclonal antibodies--you need a highly specific signal." Researchers can use generic antibodies to obtain gene products via an approach called epitope tagging. To do this, a scientist attaches a synthetic oligonucleotide encoding six to 10 amino acids to a fragment of the gene of interest. The oligonucleotide specifies a "peptide tag," an extra bit of protein attached to the gene's product. BAbCO supplies MAbs that are attracted to such tags. "Then you express the gene product as a fusion protein, and use the universal antibody to detect the fusion protein. The epitope tag antibody purifies the gene product from a mixture," Balakrishnan explains. "It is very powerful because of its universal use." An antibody's specificity allows developmental biologists to isolate and highlight individual steps of differentiation. This is the case for anti-agrin MAbs, a product of StressGen Biotechnologies Corp. of Victoria, British Columbia in Canada. Agrin is a protein found in the basal lamina (the connective tissue boundary between tissues) that, early in development, stimulates receptors for the neurotransmitter acetylcholine to cluster at the tip of a muscle fiber--a prelude to formation of a neuromuscular junction. "Agrin is released into the space [between a nerve and muscle cell] and it clusters the receptors to increase the signal. We offer a group of five monoclonals to different regions [epitopes] of agrin," notes Henry Rodriguez, director of StressGen's biochemical division. The anti-agrin antibodies became available last month. Many companies offering MAbs also supply polyclonal antibodies, which, when purified by affinity chromatography, are specific enough for many research needs. "Affinity-purified peptide polyclonals have specificities similar to those of monoclonals, with the advantage of multiple clones to the same epitope, which provides higher affinity. A lot of people are going this way, because it's easier than going through the process of screening for monoclonals," according to James Stiehr, president of Affinity BioReagents. Big sellers are polyclonal antibodies to nitric-oxide synthase, the enzyme that catalyzes formation of nitric oxide, a messenger molecule that takes part in vasodilation, neurotransmission, and cytotoxicity. Antibodies In Biotech Monoclonal antibodies are key components of several biotechnologies. They are conjugated to other molecules so that they can be detected, such as to a fluorescent dye for fluorescence microscopy, or to an electron-dense marker for electron microscopy. Antibody bound to an inert matrix forms an affinity column, with the antibody pulling out its target molecule from an extract passed over the column. An antibody's signal can be amplified by binding it (at a region other than the antigen binding site) to a second antibody, which is in turn bound to a label. In another popular approach, an antibody is bound to the vitamin biotin, which then binds a labeled form of the bacterial protein streptavidin. Labeled MAbs are also used in Western blots to detect peptides or proteins separated on a polyacrylamide gel by electrophoresis. In an enzyme-linked immuno-sorbent assay (ELISA), a primary antibody binds to its target antigen as well as to a secondary antibody. The secondary antibody is bound to an enzyme, such as alkaline phosphatase, that catalyzes a reaction whose products are easily detectable. Because one enzyme molecule is used over and over, catalyzing thousands of reactions, a single primary antibody, via its linkage to a single enzyme, gives off a very powerful signal. Jaspreet Sidhu, a senior fellow in the Department of Environmental Health at the University of Washington, Seattle, is evaluating a new ELISA kit for Life Technologies. "We're field-testing an ELISA to measure levels of the second-messenger cyclic AMP [cAMP], looking at stimulation of intracellular cAMP in various cells, such as human smooth muscle and rat hepatocytes," he reports. Fluorescently labeled MAbs are also used in flow cytometry, a method of separating cells or their components in a device called a fluorescence-activated cell sorter. In the technique, up to four groups of cells are labeled with MAbs coupled to different fluorescent dyes. The cells are propelled through a stream of water. A vibrating crystal breaks the stream into droplets, which pass through a laser that excites the dyes linked to the MAbs marking cells. The cell sorter, programmed to recognize specific combinations of dyes, emits pulses of electricity that deflect droplets carrying different types of marked cells into separate fractions. Life Technologies offers several MAbs specific for cluster-of-differentiation (CD) cell-surface antigens, con- jugated to fluorochromes for use in flow cytometry. "A fluorochrome-labeled antibody recognizes an epitope on a cell, such as CD4 marked with fluorescein," explains the company's Wesley Russ. "A certain percentage of cells will be selected because they have that protein exposed. Then add an antibody to something else on the cell surface, labeled with phytoerythrin, such as CD8, and then get the percentage of cells marked with CD4 and CD8. Add a third antibody, and get additional information." Specific Applications: Cancer: Antibodies can be used to follow the many ways that cancer cells depart from normalcy. Directed by expressed oncogenes or dampened tumor-suppressor genes, cancer cell surfaces and shapes grow more fluid, and the cells secrete biochemicals that enable them to invade and travel through healthy tissue. Antibodies that target any biochemical implicated in carcinogenesis or metastasis are valuable tools for basic research as well as in the clinic, as the basis of diagnostic tests and for evaluating response to therapy. Such antibody targets include variants of normal molecules, altered patterns of cell-surface antigens, or normal proteins in abnormal places. Consider cathepsins. Inside a cell, these enzymes are confined to lysosome sacs, where they degrade old proteins. But invading tumor cells release cathepsins instead, and they chew through the basal lamina. As a result, the cancer grows and spreads. Calbiochem-Novabiochem International Inc. of La Jolla, Calif., offers polyclonal antibodies to cathepsins, enabling researchers to detect the leading edge of a tumor. Monoclonal antibodies--from Minneapolis-based R&D Systems Inc.--to a cell-surface glycoprotein called CD44 are also being used to probe carcinogenesis. Because CD44 pokes out onto the cell's surface, extends through the cell membrane, and has a tail portion emerging on the membrane's inner face, it probably plays a major role in signal transduction--and disrupted relay of messages into a cell can lead to cancer. The link between CD44 and cancer is that certain types of cancer cells have characteristic combinations of CD44 variants--but there's only one CD44 gene. The variants arise from expression of different exons (protein-encoding sequences) of the gene. R&D Systems' MAbs to CD44 correspond to portions of the protein that different subsets of exons encode, allowing users to further follow this glycoprotein's role in carcinogenesis. Multidrug Resistance: At Immunotech Inc. in Westbrook, Maine, the cancer focus is on multidrug resistance (MDR). On a cellular level, MDR is an adaptive response to protect the cell from toxins--such as the botanical biochemicals that are the bases of many cancer drugs. The MDR response derives from a transmembrane protein called permeability-glycoprotein, or P-gp, which pumps drugs out of the cell. Immunotech sells a MAb that is specific for a portion of P-gp that protrudes from the surfaces of cancer cells resistant to the commonly used chemotherapeutic drug adriamycin. "If a patient's cells have the MDR marker, this indicates that response to adriamycin will not be great," says product manager Linda Diou, adding that the monoclonal is for research use only. Steroid hormones such as estrogen diffuse into a cell, then bind to receptors. The hormone-receptor complex then binds to DNA, activating certain genes whose action produces the hormone-associated effects. MAbs to estrogen receptors are very useful in studying breast cancer. Affinity BioReagents markets a monoclonal that targets a nuclear steroid receptor called the anti-retinoid x receptor b, or RxRb. This receptor binds to other steroid receptors as well as to DNA. "The RxRb antibody is licensed from NIH. It forms heterodimers with other steroid receptors to differentially control gene expression in different tissues," says Affinity president Stiehr. The antibody can be used to show which genes the RxRb receptor binds to in different cell types. Apoptosis: Cell death is at the forefront of cell biology research. Two general mechanisms are recognized. In necrosis, a passive process, the cell membrane deteriorates. In apoptosis, an active process, a specific sequence of events culminates in the cell synthesizing endonucleases that cut its own DNA into recognizably sized chunks. Apoptosis is important in the programmed cell death that forms the embryo; in establishing T- and B-cell populations in the immune system; and in the normal degradation of worn-out tissue. In pathology, apoptosis is linked to graft-versus-host disease, viral hepatitis, and cancer. PanVera Corp. of Madison, Wis., offers a MAb, called anti-Fas, that induces apoptosis in vitro. "Certain cell lines have the Fas antigen. The anti-Fas antibody binds to the antigen on the cell surface, and cross-links other proteins. This disturbs the membrane, which leads to downstream events," according to Alex Vodenlich, technical services manager. The cross-linking occurs because the antibody is a pentamer, he adds. PanVera distributes antibodies developed at two Japanese companies, TaKaRa Shuzo Co. Ltd. in Kyoto and Medical and Biological Laboratories Co. Ltd. in Otsu, Shiga. Cellular Stress Response: Heat shock proteins are part of a larger group of stress proteins, which increase in abundance in response to viral infection, cancer, toxic exposure, ischemia, or oxidation, in addition to heat. "Stress proteins interact in many different systems. They are ubiquitous and conserved from one species to another, which leads people to speculate that they are essential for life," says James Stiehr of Affinity BioReagents, which recently added anti-stress protein antibodies to its product line. Interest in heat-shock proteins has mushroomed in recent years because they have been identified as molecular chaperones. They assist protein synthesis by controlling transcription factors and protein kinases, then folding peptides as they form and escorting the maturing proteins along the secretory network. The long list of antibodies so many companies offer may taper off, but MAbs continue to meet their potential as envisioned in 1975, to provide highly specific tools with which to dissect events within and between cells. Ricki Lewis, author of several college biology textbooks, is a freelance science writer based in Scotia, N.Y. (The Scientist, Vol:8, #24, p.16, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ------------------------------------------------------ TI : REGULATORY ROADBLOCK AU : RICKI LEWIS TY : TOOLS & TECHNOLOGY PG : 16 As cell biology and clinical medicine increasingly overlap, antibody suppliers are finding themselves in what many people in the field fear may turn into a regulatory hell. On October 21, antibody-industry representatives met with several pathology organizations and Food and Drug Administration (FDA) officials for the "Hematological and Pathological Devices Panel Meeting," at which the convened panel recommended that antibody-based products that pathologists might use be regulated as class II medical devices. Many such products have not been regulated by FDA because they are used for research purposes only, but that is changing as more and more antibodies find clinical utility. Class II designation requires the manufacturer to provide various "special controls" (such as postmarketing surveillance and restricting use to in vitro applications) and to file a premarket notification, commonly known as a 510(k). The pathologists, wishing to avoid a more restrictive class III designation but still desiring assurance of consistent safety and efficacy, pushed for class II status. But a recently formed coalition of antibody suppliers, the Joint Council of Immunohistochemistry Manufacturers, argued for less-restrictive class I status. The recommendation, if approved by the FDA commissioner following a review period, may have drastic effects on the research community, especially concerning availability of products with markets too small to justify the cost of complying with regulations. Delores Graham, manager of regulatory affairs at antibody supplier Dako Corp. in Carpinteria, Calif., and cochairwoman of the joint council, said at the October 21 meeting: "In considering the costs of getting an antibody cleared through the 510(k) process [$23,000 to $40,000], we have estimated that only 10 percent of the 300 antibodies determined to be clinically useful would have the sales to justify submission. When we evaluated our product line, 60 percent of the products fell below a liberal sales cutoff of $10,000 for submission consideration, and 20 products below this cutoff could be found on the pathologists' list of clinically useful products." Some antibody manufacturers fear that they may eventually be required to keep track of which researchers are using a particular product for basic research and which for diagnosis, says James Stiehr of Affinity BioReagents Inc., Neshanic Station, N.J. This will raise costs even more. However, Carolyn Jones, director of technology regulatory affairs at the Health Industry Manufacturers Association in Washington, D.C., does not feel that the new classification will stifle researchers' access to antibodies. Instead, she predicts, the industry will fragment somewhat, with product lines shrinking as only the larger firms remain able to afford to market low-demand research antibodies with clinical applications. FDA regulation could be in place sometime in 1995, just as monoclonal antibody technology celebrates its 20-year anniversary. Concludes Stiehr: "This new classification will have a fairly major impact on the industry." --R.L. (The Scientist, Vol:8, #24, p.16, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: NEW PRODUCTS ------------------------------------------------------ TI : NEW PRODUCTS TY : TOOLS & TECHNOLOGY PG : 19 PRO Scientific Introduces Laboratory Homogenizer The PRO250 is a hand-held or post-mounted homogenizer reportedly capable of processing sample volumes as small as 0.03 ml. The unit features a 3/4 -horsepower motor and built-in variable speed control up to 30,000 rpm. It is capable of homogenizing with the full line of PRO quick-connect generators, safety-sealed chambers, and ST series assemblies. PRO Scientific Inc., Monroe, CT Circle No. 100 on Reader Service Card New Water Objective Available From Zeiss The C-Apochromat 40X/1.2 water objective for high-resolution imaging of specimens in aqueous media is designed to eliminate refractive index mismatch and the effects of temperature changes on image quality. It reportedly minimizes spherical aberration in the imaging of live tissue or cells. Carl Zeiss Inc., Microscope Division, Thornwood, NY Circle No. 102 onReader Service Card Worthington Releases New Cardiomyocyte Isolation System The Worthington Neonatal Cardiomyocyte Isolation System, a new kit utilizing purified enzyme preparations, contains all the necessary materials for five separate tissue dissociations of up to 12 hearts each. Separate vials each contain Hank's Balanced Salt Solution (HBSS), Purified Trypsin, Soybean Trypsin Inhibitor, Purified Collagenase, and Leibovitz L-15 powdered media. Also included are five Falcon Cell Strainers, a phenol red color card for checking pH, and a protocol. Worthington Biochemical Corp., Freehold, NJ Circle No. 103 on Reader Service Card Bio Image Announces Band Analysis Software For Gel Scanning Whole Band Analysis Software, for use with Bio Image's gel scanner systems, automatically reads gels or films, detects lanes and bands, quantifies the amount of material present, corrects for smiling, and determines fragment sizes. The results can be compared using the Whole Band Matcher, a data-management application for creating and searching customized databases. Bio Image, Ann Arbor, MI Circle No. 104 on Reader Service Card Activated Cultureware For Cell Growth ProNectin F Activated Cultureware provides anchorage-dependent cells with a culture surface said to be immediately able to support receptor-mediated cell adhesion and spreading, initiating cell growth. The RGD cell attachment ligand of fibronectin is presented directly on the culture surface in the form of ProNectin F, a genetically engineered cell-attachment factor. The product is sterile, stable, and ready-to-use in dish and multiwell plate formats. Protein Polymer Technologies Inc., San Diego, CA Circle No. 101 on Reader Service Card (The Scientist, Vol:8, #24, p.19, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: PROFESSION ------------------------------------------------------ TI : A Successful Presentation Can Enhance A Scientific Career AU : ROBERT R.H. ANHOLT TY : PROFESSION PG : 22 Editor's Note: "For many of us, giving a scientific presentation can be stressful," writes Duke University Medical Center molecular neurobiologist and cell biologist Robert R.H. Anholt in his book Dazzle 'Em With Style (New York, W.H. Freeman and Co., 1994), a guide to presenting an effective talk. "Yet," he adds, "the ability to deliver a polished oral presentation in front of an audience of peers is an essential skill that is indispensable for a successful scientific career. . . . The skill of presenting an engaging and well-structured seminar often determines our professional reputation and future success--especially when the seminar is part of a job interview." Anholt teaches an annual seminar course in which students are required to prepare and deliver lectures to fellow students and faculty members. An excerpt from the book follows. A scientific presentation should always be prepared with the audience in mind. To blindly offer a showcase of your own accomplishments, reflecting only your interests, is a sure recipe for miscommunication and results in a poor performance from the perspective of the audience. Communication is the key. Look upon your presentation as a dialogue with the audience, not a monologue. Be sensitive to the needs and interests of your audience, and reflect on the questions: What do they expect to learn from my presentation? How can my presentation be useful to them? A presentation prepared with these questions in mind is more likely to succeed with the audience than a presentation intended from the outset solely to impress the listeners by glorifying the speaker's self-perceived accomplishments. Try to find out beforehand who might be in attendance during the presentation. Often it is possible to give credit to a specific member of the audience during the talk. Always greatly appreciated are statements such as "After we learned about the elegant experiments of Dr. Smith [in the audience], we decided to . . ." or "Since the approach developed by Dr. Jones worked so well in her system, we adopted a similar strategy," or "Our results agree closely with previous observations by Dr. Doe, who showed . . ." I once heard a speaker present data on calcium influx in synaptic terminals; he was unfamiliar with the most recent publications of one of the pioneers of his field, who happened to be in the audience! Such embarrassing in-stances can do irreparable damage to an otherwise excellent presentation and are entirely preventable. Invited speakers should always browse through a departmental brochure and try to learn a little about the organization and history of the host institution before arriving on the scene. Structure Your Material After having obtained as much information as possible about the audience and its interests, the next step in preparing the presentation is outlining the talk. A presentation is usually preceded by a brief introduction by the host and followed by a discussion period. Normally, there is a predetermined time allotted for the entire event. It is crucial for the speaker to stay within the boundaries of this time. Like hikers who go into the wilderness with a food supply just sufficient for the intended duration of the trip, people who attend a seminar anticipate the predetermined period and come equipped with an amount of listener energy just sufficient to cover this period. As soon as the speaker goes over time, the audience becomes impatient and restless. As a result, the speaker will be forced to rush through the most important part of the presentation, namely the conclusion and take-home message. When the presentation is part of the symposium, the chairperson and subsequent speakers will be greatly irritated if a speaker exceeds the allotted time, since this interferes with the next speaker and delays the entire symposium. It is also essential to leave enough time for questions. This provides a precious opportunity for the speaker to engage in a direct discussion with the audience, which is essential when you are trying to communicate information effectively. If a 60-minute presentation is scheduled, prepare a 45- to 50-minute talk. This will leave ample time for the introduction and to answer questions at the end. A good rule of thumb is to keep the presentation at a length that is 75 percent to 80 percent of the allotted time. In designing the presentation, remember the interests and expectations of the audience and put the presentation into context accordingly. Using the same set of data, for example, you can often shift the focus of a presentation from molecular aspects to cellular or behavioral aspects or from the nature and generation of a stimulus to the response of the target tissue. A strong presentation on the effects of bronchodilators delivered via inhalation as aerosols would not be structured identically for a group of physiologists interested in the effects of the drug on pulmonary function and for an audience of biomedical engineers concerned mainly with the design of the inhaler and its mechanism of drug delivery. If it is important to design your presentation according to the interests of the audience, it is essential to make the audience aware of your focus from the very outset. Suspense and mystery are excellent tools for playwrights and movie directors, but they are the nemesis of scientific presentations. To communicate scientific information effectively and maintain the attention of your audience, adhere to the old rule: "Tell 'em what you're gonna tell 'em, then tell 'em, then tell 'em what you've told 'em." An outline on the blackboard goes a long way toward keeping the audience aware of the central line of thought of the presentation. A verbal description that outlines the seminar early in the talk also guarantees that the speaker and the audience march to the beat of the same drummer--and in the same direction. Such a statement establishes a line of thought that enables the audience to comfortably make an organized mental inventory of the information that is about to follow and to apportion their total listener energy in installments that correspond to the announced segments of the presentation. Each presentation consists of three segments. (1) The introduction provides the background and perspective necessary to appreciate the remainder of the presentation. (2) The body of the presentation, usually the largest section, conveys new information to the audience; this section can often be divided into distinct, interrelated subsections. (3) The conclusion summarizes the presentation and should provide the audience with a clear take-home message. When preparing a structure for your presentation, divide the allotted time and assign a defined number of minutes to each section of the presentation--for instance, 10 minutes for the introduction, 30 minutes for the main body of the presentation, and five minutes to summarize and conclude. In many cases, the arrangement of slides or transparencies will help structure your presentation by providing landmarks along which the lecture can be organized. A good rule of thumb is to allot approximately two minutes of presentation per slide, making 20 to 25 slides a good number to aim for when preparing a 45-minute presentation. A single sheet of paper with titles or key words that identify each slide and perhaps a few small reminder notes can provide a convenient "cheat sheet" to which you can refer during your presentation. Alternatively, you can prepare a sheet that contains photocopies of all your slides in the correct sequence. A well-prepared abstract, an organized set of well-chosen slides, a concise "cheat sheet," and an outline to put on the board should all help keep you on track during your seminar. Know Your Stuff It happens often, especially in cases of novice speakers, that unjustified self-confidence leads to the belief that eloquence and style will make up for lack of knowledge, incomplete understanding, or absence of crucial data. A false sense of intellectual superiority to the audience, instilled by the assumption that no one else knows more about the topic than the speaker, frequently leads to the illusion that he or she will be able to "wing it" yet give the impression of being on solid ground. More often than not the speaker discovers too late that the audience consists of highly intelligent and insightful individuals. It takes only one knowledgeable listener to expose a lack of knowledge or data that the speaker has tried to hide behind a cloak of superficial information. Long before the question period, it will become evident even to a lay audience whether the speaker has a thorough understanding and a broad, solid command of the field. Nothing is more embarrassing to a professional than to be caught unprepared to discuss recent literature or details of important, albeit peripheral, aspects of the field. Nothing is more disappointing to an expectant audience than a speaker who, having no data or only a limited amount, spends most of the time talking about planned but not yet performed experiments. If you have no data for a scheduled research seminar, choose another topic for which solid data are available or simply decline to speak. The decision not to speak is sometimes more beneficial to a person's reputation than a lecture devoid of data. Finally, knowledge and data alone are not sufficient. Critical examination of the information is indispensable. This is perhaps one of the most difficult tasks: to stand back and critically look upon your own work. Yet those who are able to do that can prevent or anticipate embarrassing questions. Furthermore, a critical, careful presentation during which you demonstrate familiarity with pitfalls of experimental design and ongoing controversies in the literature, as well as understanding the limitations of the data presented and their statistical reliability, further instills confidence that you are truly an authority in the field. Rehearse No matter how experienced a speaker is, it is always a good idea to rehearse a presentation. Often, the same presentation can be given on a number of occasions, but not without adaptation. "Canned" seminars pose the danger of providing a product not optimally tuned in to the audience. Substantial time for preparation of the presentation should be allowed prior to the scheduled date. Frantic last-minute preparations can result in acceptable performances but seldom in memorable ones. A scientific presentation is an expression of creativity, and creation takes time. I usually start thinking about scheduled presentations weeks, sometimes months, in advance. I draw up a rough outline early on and then brood and daydream, letting the presentation go around in my mind, letting the concepts mature at their own slow pace, like a fine wine in the cellar of a French chateau. Rehearsing the presentation and going through the slides, rearranging them until I am fully satisfied with their final order, is--in my experience--best done in the evening right before retiring. A rehearsal in front of an honest and perceptive colleague is invaluable. This person should preferably be someone who could fit in as a member of the prospective audience and who does not feel inhibited about giving frank and critical feedback, with regard to both the presentation's scientific content and the delivery. For such a rehearsal to be useful, honesty must prevail over politeness. Inexperienced speakers can benefit from rehearsing their presentations with a tape deck or cassette recorder. Listening to your own voice can be very revealing and may help turn a dull, monotonous account into an exciting story. A video recorder can also be helpful. Prepare--Then Relax You have familiarized yourself with the composition and interests of your audience. You are armed with solid data, well-rounded knowledge, and a thoroughly organized presentation. You can do nothing more than confidently and quietly await the moment of truth. Relaxation is now essential. I have seen more seminars fail because of the self-destructive nervousness of the speaker than for any other cause. I always advise my students to have fun the night before their scheduled presentations, to avoid any further rehearsals or preparations, and to engage in activities that take their minds completely off the upcoming presentation. Robert R.H. Anholt is a molecular neurobiologist and cell biologist at Duke University Medical Center in Durham, N.C. (The Scientist, Vol:8, #24, p.22, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: PEOPLE ------------------------------------------------------ TI : City Of Philadelphia's John Scott Award Honors Cancer Researcher For 'Crazy Ideas' AU : NEERAJA SANKARAN TY : PROFESSION (PEOPLE) PG : 23 Beatrice Mintz, a senior member of the Institute for Cancer Research at the Fox Chase Cancer Center in Philadelphia, was presented with the John Scott Award during a reception on November 18 at the American Philosophical Society in Philadelphia. The prize was set up in the early 1800s by John Scott, a Scottish druggist, who entrusted the administration of the award--originally $20 and an inscribed copper medal--to the city of Philadelphia. Scott's intention was to reward people for their useful inventions that contributed in a significant way to the "comfort, welfare, and happiness" of mankind. Early awards went to inventors of such items as a knitting machine and door lock. Notable winners through this century have included Thomas Edison, Jonas Salk, the Wright brothers, and Kary Mullis. "This award is a paeon in praise of crazy ideas," Mintz, who was honored for her novel and creative research in the fields of developmental biology and cancer research, remarked at the ceremony. Her first "crazy idea," she says, was to attempt to fuse embryos of mice having different genotypes into a single mass during the very early stages of development, and eventually produce mice that shared characteristics from both originating embryos. One of her early published works detailing the techniques involved, which appeared in a book she contributed to (Methods in Mammalian Embryology, J. Daniel, Jr., ed., San Francisco, W.H. Freeman, 1971, pages 186-214) has been cited in almost 150 publications, according to the Institute for Scientific Information in Philadelphia. Nowadays, Mintz says, the techniques are so standard that "most people forget to cite the source." Mintz is also well-known for her experimental research in the 1970s that led to the concept of cancers arising from defects in cell differentiation and development (B. Mintz, K. Illmensee, "Normal genetically mosaic mice produced from malignant teratocarcinoma cells," Proceedings of the National Academy of Sciences, 72:3585-89, 1975). At 73, she is still actively doing research, her most recent target being malignant melanomas. Mintz received her Ph.D. in 1946 in developmental biology from the University of Iowa. Before coming to the Fox Chase Cancer Center in 1960, she served for several years on the faculty of the University of Chicago. She has been a member of the National Academy of Sciences since 1973 and of the American Philosophical Society since 1982. --Neeraja Sankaran (The Scientist, Vol:8, #24, p.23, December 12, 1994) (Copyright, The Scientist, Inc.) ================================ WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A. NXT: ----------------------------------------------------- TI : Tennessee Professor Is The First Veterinarian To Receive Award Relating Smoking And Health AU : BARBARA SPECTOR TY : PROFESSION (PEOPLE) PG : 23 Hildegard Schuller, a professor of pathology at the University of Tennessee College of Veterinary Medicine in Knoxville, has become the first woman and the only veterinarian to receive the Alton Ochsner Award Relating Smoking and Health. The nine-year-old award, presented October 31 at the annual meeting of the American College of Chest Physicians in New Orleans, honors outstanding research into the mechanisms of smoking-related lung cancer. It carries a cash prize of $15,000 funded by Marion Merrell Dow Inc. of Kansas City, Mo., and is named for the first physician to recognize that cigarette smoking is a major cause of lung cancer. Schuller, 48, points out that her work involves human lung cancer cell lines in vitro, not animals. "Most people think that because I'm a veterinarian, I do all of my research on animals," she notes. "But anyone who has a background in biological sciences could do this type of research." Her award-winning work focuses on nitrosamines, cancer-inducing chemicals found in cigarette smoke as well as beverages, foods, and cosmetics. She determined that these chemicals bind to specific lung-cell receptors that trigger the progression of cancer. Her most startling finding was that "nicotine itself is involved in the stimulation of cells involved in cancer." This went against the conventional wisdom that nicotine is not a carcinogen. "I had great difficulty over the last five years [in getting] this work published and funded," Schuller recalls, adding that the research did not gain credence until Italian and Canadian teams came out with similar findings. Schuller's paper reporting these results (H.M. Schuller, "Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines," Biochemical Pharmacology, 38:3439-42, 1989) has been cited in 17 subsequent articles. A native of Germany, Schuller received her veterinary degree in 1971 from Justus Liebig University in Geissen, Germany, and her Ph.D. in pathology in 1972 from the College of Veterinary Medicine in Hannover, Germany. Prior to joining Tennessee's veterinary college faculty in 1985, she was on the staff of the National Cancer Institute. --Barbara Spector (The Scientist, Vol:8, #24, p.23, December 12, 1994) (Copyright, The Scientist, Inc.) ================================

---

E-Mail Fredric L. Rice / The Skeptic Tank