THE SCIENTIST VOLUME 7, No:23 November 29, 1993 (Copyright, The Scientist, Inc.) Articles

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THE SCIENTIST VOLUME 7, No:23 November 29, 1993 (Copyright, The Scientist, Inc.) =============================================================== Articles published in THE SCIENTIST reflect the views of their authors and not the official views of the publication, its editorial staff, or its ownership. ================================================================ *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON *** *** DECEMBER 13, 1993 *** *** *** ******************************************************* Subscription rates for the printed edition are: In the United States: one year $58, two years $94 Canada : one year $82, two years $142 All other foreign : one year/air cargo $79, one year/ airmail $133 THE SCIENTIST (Page numbers correspond to printed edition of THE SCIENTIST) FOR SEARCHING PURPOSES: AU = author TI = title of article TY = type PG = page NEXT = next article ----------------------------------------------------------------- TI : CONTENTS PG : 3 ===================================================================== NO EASY TASK: One of the great challenges ahead for two recently confirmed science agency directors--Neal Lane of the National Science Foundation and Harold Varmus of the National Institutes of Health--will be to advance the cause of basic science in the face of increasing pressure from Congress and the public for more directed and technology- based research PG : 1 BIOENGINEERING BOOM: The complex, multifaceted field of bioengineering is attracting throngs of life science and engineering undergraduates to academic research institutions throughout the United States. Moreover, observers are optimistic that, as bioengineering applications increase, industry will expand correspondingly to provide jobs for these students by the time they get their undergraduate or graduate degrees PG : 1 PUTTING SCIENCE IN PERSPECTIVE: NSF and the National Endowment for the Humanities are cosponsoring a program aimed at boosting science literacy through exploring the relationship of science and the humanities in everyday life. PG : 3 BUILDING A RESEARCH CONSORTIUM: Sparked by a $2.5 million grant from the Dana Foundation, researchers from Cold Spring Harbor Laboratory, Stanford University, and Johns Hopkins University are joining forces in an effort to track down the genes responsible for manic-depressive illness PG : 4 SHIFTING FOCUS: With the end of the Cold War and changing national priorities, U.S. national laboratories must narrow their focus and develop a comprehensive, long-term program of job-creating, pioneering research and development collaborations with industry resulting in technology development and transfer, and defense R&D conversion, says Roland W. Schmitt, president emeritus of Rensselaer Polytechnic Institute PG : 11 COMMENTARY: Nobel Prize-winning physicist Leon M. Lederman laments Congress' rejection of the superconducting supercollider, observing that the megaproject's termination is symptomatic, among other things, of the general public's science illiteracy PG : 12 NOBEL ENDEAVORS: The achievements of this year's Nobel Prize winners in chemistry, physics, and physiology or medicine have been well known to their colleagues for years, and citation analysis confirms the broad influence of their work on the subsequent advances of other researchers in their respective disciplines PG : 1 HOT PAPERS: An astrophysicist discusses his paper on the opacity of stellar matter PG : 16 THERMAL CYCLERS: Just as use of the polymerase chain reaction is sweeping through laboratories, an essential support tool for PCR--thermal cyclers--has gained in both popularity and sophistication PG : 17 ADJUNCT OPPORTUNITIES: Adjunct professorships serve a dual need in the world of academia. They allow scientists from varying environments access to academic life, and at the same time provide universities with the use of these scientists' skills in education and research PG : 20 RUTH F. NUTT, former senior scientist at Merck & Co. Inc., has been named director of chemistry for Corvas International Inc. PG : 22 NOTEBOOK PG : 4 CARTOON PG : 4 LETTERS PG : 12 CROSSWORD pG : 13 OBITUARIES PG : 22 SCIENTIFIC SOFTWARE DIRECTORY PG : 30 (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: NEWS ------------------------------------------------------------ TI : 1993 Nobel Prizes Honor Basic Research And Development Of Tools That Drive It Rivals share laurels for medicine, while work on pulsars and gravitation earns the big award in physics AU : DAVID PENDLEBURY TY : OPINION PG : 11 This year's Nobel Prizes in science have celebrated two types of research achievement: on one hand, discoveries about nature itself, and, on the other, inventions that have significantly aided researchers' ability to explore nature. In the first category, Russell A. Hulse and Joseph H. Taylor were awarded the physics prize for their discovery of a binary pulsar and for what it revealed about relativistic gravitation, while Richard J. Roberts and Phillip A. Sharp were given the prize in physiology or medicine for their mutual but independent discovery of split genes. In the second category, Kary B. Mullis and Michael Smith received the chemistry prize for the invention of two techniques: the polymerase chain reaction (PCR) and sitedirected mutagenesis, respectively. By its choices, the Nobel committee implicitly revealed that it values the creation of novel techniques on a par with experimental achievement. Not all in the scientific community would agree that the two types of contribution are of equal merit. A peevish comment, one that was delivered under the cloak of anonymity in the pages of Science magazine, suggested that PCR was no more than "a clever technical trick that doesn't have the intellectual content of Nobelquality work" (T. Appenzeller, Science, 263:507, 1993). That is probably not an atypical view. But as the advance of knowledge depends increasingly on investigators' ability to probe ever tinier aspects of the physical and biological world, the tools on which scientists relyand the inventors of those toolsmay find their worth more widely and generously recognized. Chemistry The 1993 Nobel Prize in chemistry exemplifies the second type of scientific accomplishment. The prize was shared by Mullis of La Jolla, Calif., and Smith of the University of British Columbia in Vancouver, B.C., Canada. Both men created novel techniques for biochemists and molecular biologists that have transformed and accelerated genetic research. The Royal Swedish Academy of Sciences recognized Mullis for inventing the polymerase chain reaction (PCR) and Smith for important contributions to oligonucleotidebased sitedirected mutagenesis. Mullis and Smith will share an $825,000 cash award that accompanies the prize this year. "The chemical methods that Kary B. Mullis and Michael Smith have each developed for studying DNA molecules of genetic material have further hastened the rapid development of genetic engineering," reads the announcement of the academy. "The two methods have greatly stimulated basic biochemical research and opened the way for new applications in medicine and biotechnology." Described variously by his colleagues as an original, iconoclastic, and even outlandish scientist, Mullis, 48, thought up the PCR technique in April 1983 during a latenight drive through Northern California's redwood forests (K.B. Mullis, "The unusual origin of the polymerase chain reaction," Scientific American, 262:56, April 1990). A description of the technique, which amplifies specific segments of DNA millions of times in just a few hours, was published in 1985 (R.K. Saiki, et al., "Enzymatic amplification of betaglobin genomic sequences and restriction site analysis for diagnosis of sicklecell anemia," Science, 230:1350). An improvement of the amplification method, using the enzyme Taq, appeared in 1988 (R.K. Saiki, et al., "Primerdirected enzymatic amplification of DNA with a thermostable DNA polymerase," Science, 239:487). Having attracted a total of some 6,750 citations by the end of September 1993, the 1988 paper ranks as the most cited article in science during the last five years. (The 1985 report collected nearly 3,150 citations by September 1993.) And, if anything, the influence of PCR is underrepresented by counts of explicit citations for at least two reasons. First, papers describing variations of PCRsuch as socalled anchored PCRare collecting citations instead of the original papers, and, second, the technique is now so well known that scientists feel it is becoming less necessary to cite the original papers, a phenomenon sociologists of science refer to as "obliteration by incorporation" (R.K. Merton, Social Theory and Social Structure, New York, Free Press, 1968, pages 279, 358). In fact, citations to the paper seem to have reached a plateau during the last several yearsabout 1,700 annuallywhile the use of PCR continues to expand. The importance of the PCR methodfor basic biochemical and genetic research, for medical diagnostics, and for forensic studieshas been formally recognized by the research community many times already and in various ways. In 1990 Science magazine named PCR (somewhat confusingly) "Molecule of the Year." In 1992, the Gairdner Foundation of Canada recognized PCR by naming Mullis a winner of its prestigious Gairdner International Award, a prize that often anticipates the Nobel committee's selection, as in this case. And last year, the city of Philadelphia presented Mullis with its John Scott Award, which honors inventions that have contributed to society in a practical way (B. Spector, The Scientist, Jan. 11, 1993, page 23). For many, then, the Nobel Prize for PCR was not unexpected. Even Mullis told reporters, "I figured it would happen eventually" (K. Carr, Nature, 365:685, 1993). Smith, 61, was honored for developing during the 1970s and 1980s a method for pinpointing specific oligonucleotides in a gene and replacing them with others. Sitedirected mutagenesis, as it is known, helps researchers understand what each nucleotide contributes to a protein's function; it also enables researchers to create tailormade proteins. The Nobel committee's announcement noted that, thanks to this technique, "protein design has already become a [wellestablished] concept." Sitedirected mutagenesis, which is said to have come to Smith during a coffee break, uses a mutated single strand of the DNA and a normal strand to which the mutated one binds to form a double helix. This altered DNA is then multiplied in a bacterium. Half of the proteins generated carry the mutation that was introduced, and the properties of this material can then be studied to learn how the alteration of a nucleotide has changed protein function. To some degree, PCR has now replaced bacteria as the medium for producing the mutated genetic material. The technique continues to find applications on many fronts, the academy noted: in attempts to create a blood substitute, to design specific antibodies to fight cancer cells, and to fashion plants that make more efficient use of atmospheric carbon dioxide, among others. In 1978, Smith and colleagues published a paper that described the successful use of the technique (C.A. Hutchinson, et al., "Mutagenesis at a specific position in a DNA sequence," Journal of Biological Chemistry, 253:6551), but the standouts, in terms of citation impact, came in the form of three papers published in the early 1980s: M.J. Zoller, et al., "Oligonucleotidedirected mutagenesis using M13derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA," Nucleic Acids Research, 10:6487, 1982 (about 600 citations by September 1993); M.J. Zoller, et al., "Oligonucleotidedirected mutagenesis of DNA fragments cloned into M13 vectors," Methods in Enzymology, 100:468, 1983 (1,000 citations); and M.J. Zoller, "Oligo nucleotidedirected mutagenesis: a simple method using two oligonucleotide primers and a singlestranded DNA template," DNA, 3:479, 1984 (650 citations). All easily qualify as citation classicspapers that, for their field, have been extremely highly cited. Unlike Mullis, Smith was reported to have been surprised by the news of his Nobel, which he learned about from a radio broadcast. Physiology Or Medicine The 1993 Nobel Prize for physiology or medicine recognized insightful and bold work by two investigators, work that revealed a previously hidden aspect of the structure and function of genes in higher organisms. The prize went to Sharp, 49, head of the Massachusetts Institute of Technology's department of biology, Cambridge, and to Roberts, 50, currently research director of New England Biolabs, Beverly, Mass., and until recently assistant director for research at the Cold Spring Harbor Laboratory on Long Island, N.Y. Roberts and Sharp will split the $825,000 prize for their mutual but independent discovery of split genes in 1977. Until Roberts and Sharp announced their finding, at the same meeting in June 1977 held at Cold Spring Harbor, it was thought that the genetic information embedded in DNA was continuous. This understanding arose in large part from work on prokaryote systems, such as E. coli. But in eukaryotes, the genetic information is, in the vast majority, interrupted by nucleotide regions that do not code for proteins. These are called intervening sequences or introns. The domains that carry proteincoding amino acids are known as exons, because their information is expressed. In these structures, the genetic information is split into pieces, hence the name "split genes." Roberts and Sharp, who knew of each other's work and were racing toward the same goal, both used electron microscopy to directly observe the activity of mRNA and DNA in adenovirus, a virus that causes the common cold. Both teams could actually see that mRNA lined up with only certain portions of the DNA, leaving large loops of the DNA unread. This showed that only portions of DNA were used by mRNA to create proteins. It also changed the world of molecular biology. Sidney Altman of Yale University, who himself won the Nobel Prize for chemistry in 1989, told the Associated Press: "Next to the discovery of the structure of DNA, this is probably the greatest discovery in genetics in the last 70 to 80 years." The finding helped start the biotechnology revolution, too, since it revealed the mechanism of gene splicing and fostered the idea of building wholly new proteins with novel functions. It also has explained about onequarter of some 5,000 inherited diseases, which turn out to result from splicing errors; as such, it has already contributed to work on gene therapy. The breakthrough was reported in two papers, both published in 1977. The article by Sharp and colleagues (S.M. Berget, et al., "Spliced segments at the 5e terminus of adenovirus 2 late mRNA," Proceedings of the National Academy of Sciences, 74:3171, 1977) collected about 500 citations by the end of September 1993. The report by Roberts and colleagues (L.T. Chow, et al., "Amazing sequence arrangement at 5e ends of adenovirus 2 mRNAs," Cell, 12:1, 1977) received about 450 citations by September 1993. Both articles are undoubtedly undercited in proportion to their influenceas is the 1953 Nature paper by James Watson and Francis Crick on DNA's structure. Most of these paradigmshattering papers have suffered the obliteration phenomenon. Sharp suspected this to be the fate of his report: "Within a few months many other labs were reporting their findings of split genes." On paper, Sharp has for some time been a good bet for winning a Nobel. He ranked 48th in the world in terms of total citations to his papers published in 198190 (E. Garfield, A. Welljams-Dorof, "Of Nobel class: a citation perspective on high impact research authors," Theoretical Medicine, 13:117, 1992); he ranked 16th in the world in molecular biology and genetics for papers published in 198892, in terms of average citations per paper (Science Watch, 4[7]:12, July/August 1993); and he is the author of at least a dozen papers that have achieved citationclassic status. Moreover, he is a member of the U.S. National Academy of Sciences and a previous winner of both the Gairdner Inter national Award and the Albert Lasker Basic Medical Research Award, receipt of which is also recognized as a strong indicator of those who may eventually win a Nobel Prize. But it was the discovery of split genesnot a lifetime of accomplishmentthat was recognized by the Swedish Academy. That is why other researchers who are the peers of Sharp on paper have not yet won the Nobel Prize. Physics The Nobel Prize in physics was also split between two investigations this year, but unlike Roberts and Sharp, the awardees were paired as teacher and student rather than as rivals. Taylor, 52, of Princeton University, and Hulse, 43, of Princeton's Plasma Physics Laboratory were honored by the academy for "their discovery of a new type of pulsar, a discovery that has opened up new possibilities for the study of gravitation." In the mid1970s, while Taylor was a professor of physics at the University of Massachusetts, Amherst, and Hulse was there as his graduate student, the two were searching the heavens for pulsars. These superdense, rapidly rotating neutron stars, first discovered in 1967 by Anthony Hewish and his student Jocelyn Bell of Cambridge University, emit radiation like a beacon at precise intervals. Working with the 300meter radiotelescope at Arecibo, Puerto Rico, Taylor and Hulse studied many pulsars and monitored the exact timing of their radiowave emissions. But they found one object (PSR1913+16) that exhibited a slight irregularity in its pulse. What they found, in fact, was a pulsar rotating around anotherthe first binary pulsar. This was much more than a rare species, however. It offered Taylor and Hulse a kind of "space laboratory," as the Nobel committee called it, and a chance to test Einstein's theory of general relativity, which predicted that such massive bodies in close association would produce gravitational waves, ripples or warping in spacetime. After meticulous measurement over several years, Taylor reported in 1979 that the rotation of the pulsar was decreasing ever so slowly and this implied the loss of energy being given off as gravity waves. The finding accords with what Einstein predicted in 1916. "So far," the acad emy noted, "Einstein's theory has passed the tests with flying colours." The account of the discovery appeared in 1975 (R.A. Hulse, J.H. Taylor, "Discovery of a pulsar in a binary system," Astrophysical Journal, 195:L51), and has been cited in about 200 publications since then. Several years later, Taylor was able to confirm the existence of gravitational radiation at the predicted levels (J.H. Taylor, et al., "Measure ments of general relativistic effects in the binary pulsar PSR1913+16," Nature, 277:437, 1979); this paper has been cited some 150 times. Since radio astronomy papers tend to collect far fewer citations than those in biochemistry and molecular biology, it is certain that these two reports have had, like the others highlighted here, significant impact, perhaps even greater than the citation record suggests. Hulse, after earning his Ph.D. at the University of Massachusetts, left astrophysical research for the field of fusion studies. Taylor has continued to study pulsars and relativistic gravity. Teacher and student will now share the $825,000 prize for their fruitful collaboration. David Pendlebury is an analyst with the research department at the Institute for Scientific Information (ISI) in Philadelphia. He also edits Science Watch, an ISI newsletter that tracks trends and performance in basic and applied research. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : NSF's Lane, NIH's Varmus Poised To Articulate Research Priorities Now that they've been confirmed, the two Clinton appointees must cope with tough choices and political pressures AU : FRANKLIN HOKE TY : NEWS PG : 1 Mounting a defense of basic research will likely top the agendas of two recently confirmed presidential appointees, as political pressures to divert resources to more targeted work continue to grow, researchers and policy observers say. University of California, San Francisco, molecular virologist Harold Varmus, new head of the National Institutes of Health, and Rice University provost and physicist Neal Lane, director of the National Science Foundation, both will confront questions about the appropriate level of support for fundamental investigations. Varmus, confirmed by the full Senate this month as NIH director, made his position on the issue clear at a hearing November 3, in a reference to the work that led to his sharing the 1989 Nobel Prize in physiology or medicine. "As an investigator who has seen the pursuit of an obscure chicken virus create a new vision of human cancer, I will defend open-ended basic science against calls for restricted application to what we already know," Varmus told the Committee on Labor and Human Resources. Reminding Varmus of the many powerful voices that seek to influence the use of NIH resources--including several in the Senate--Sen. Dan Coats (R-Ind.) told the nominee, "You're going to need a lot of steel to resist the tremendous pressures in terms of how you administer the institutes." Committee chairman Sen. Edward Kennedy (D-Mass.), echoing Coats, told Varmus he would need a "steel backbone" to be an effective director. Physicist Neal Lane, in place as director of the National Science Foundation only since October 7, will face similar demands. Maintaining support for fundamental research while responding to calls for more applied investigations will be one of his biggest challenges, observers say. "The new NSF director faces an uphill fight, because the notion of untargeted, peer-reviewed research is unfashionable right now, particularly in Congress," says Harvey Brooks, a professor, emeritus, of technology and public policy and applied physics at Harvard University. Brooks is also a former chairman of the National Academy of Sciences' Committee on Science, Engineering, and Public Policy (COSEPUP). `Reinventing' NIH At Varmus's confirmation hearing, Sen. Barbara Mikulski (D- Md.), in whose state NIH's Bethesda campus lies, spoke of the institutes' being "adrift." Picking up on the vocabulary of Vice President Al Gore's ongoing campaign to improve government, Mikulski charged the director-designate with "reinventing" NIH for the next century. She later asked what plans Varmus had for renewing the agency. Varmus responded that a major reevaluation of the $1.2 billion intramural research program was already under way and that he would move to address the "encumbrances" of the extramural grant review system. He also noted that several important personnel searches were in progress, including one for a director for the Office of AIDS Research. Varmus later told reporters he hoped to fill the position by February 1. Several times during the hearing, Varmus touched on the importance of addressing the AIDS epidemic, perhaps seeking to allay the concerns of some early critics of his nomination. Reportedly, AIDS activists initially were worried that Varmus would not be sufficiently supportive of their agenda, owing, at least in part, to his focus on undirected research. What differences may have existed, however, between Varmus and those pressing for more attention to AIDS appear to have been settled in a meeting held since his nomination. "There isn't any opposition here," says David Barr, director of treatment education and advocacy for Gay Men's Health Crisis in New York City. "The thing I'm really most interested in is that he cooperate with the new Office of AIDS Research director, and there was some concern that he was opposed to that. But as we talked it through with him at the meeting, I didn't find that to be the case." Barr notes that Varmus's focus on fundamental research will, in fact, be critical to defeating AIDS. "Certainly, among AIDS treatment activists, the call for beefing up the basic research effort has been our demand of the year," Barr says. "Not that we're opposed to clinical research, but we've sort of hit a dead end. Clinical research is only valuable if you've got a drug to study." Varmus also stressed that he hopes to confront racial and sexual discrimination charges that have dogged NIH. As proof of this effort, he announced at the hearing that Ruth Kirschstein, director of the National Institute of General Medical Sciences, had agreed to take the position of NIH deputy director formerly held by Jay Moskowitz. Kirschstein, who stepped in as acting director following Bernadine Healy's resignation at the end of June, has long been active in efforts to correct inequities for women researchers at the institutes. A version of the strategic planning process, which became a focus of controversy during Healy's tenure, will continue under Varmus, although it apparently will have a decidedly different character. "I hope to have a member of the office of the director traveling about the country looking for ideas from the extramural community that might have some significant influence on the way we do business, the way we set goals," Varmus said. He noted that several of the constituent institutes at NIH use such a process successfully, bringing academic investigators together from around the country periodically to consider the future. "The products [of this planning process] are often obsolete by the time they're published," Varmus said, "but the process of thinking about directions often has a very direct effect on program planning." Policy Deja Vu? Contending with pressures for more goal-oriented research is something of a cyclic struggle, according to Harvard's Brooks. He recalls testimony he gave to Congress in 1970 on similar issues, the main points of which closely mirror the debate today. At that time, he says, the social welfare goals of President Lyndon Johnson's Great Society initiative were cited by those seeking changes in research funding allocations. "Today it's economic competitiveness, but there's a great deal of parallelism between the two," Brooks says. "In each case, the criticism of the NSF was that it supported research that the scientists wanted to do instead of the research that somebody--and who that should be, of course, is the big question--thought was important for society." Lane "has the task of responding to these feelings in a reasonable and plausible manner without destroying the scientific enterprise," Brooks adds. Marye Anne Fox, a professor of chemistry at the University of Texas, Austin, agrees that carrying the case for basic research to members of Congress and others will be one of Lane's principal challenges. Fox is a member of the National Science Board, which oversees NSF, and was a member of the Special Commission on the Future of the National Science Foundation. "What [Lane] faces is the difficulty in conveying the importance of basic research in a clear way, how relevant it is for the nation's competitiveness," Fox says. An aspect of the message will be how basic research should be formulated as a national goal in light of cutbacks on basic research in industry, she says. The desire to make better use of the nation's scientific leadership for social benefit is reasonable enough, according to Phillip A. Griffiths, director of the Institute for Advanced Study, Princeton, N.J. Significantly redirecting research at NSF toward strategic purposes, however, is not what is needed and is not, in fact, something that industry itself has called for, says Griffiths, who is a member of the National Science Board and current chairman of COSEPUP. "Rather, industry has indicated that the NSF should have as its primary mission to support excellence in science and engineering education and in pioneering research," Griffiths says. "Once the objective of insuring a solid foundation of basic research is being met, then special attention to basic research in strategic areas is appropriate." NSF, as a non-mission-specific funding agency, fills a unique role in United States science, observers say. "It's the only agency that is really responsible for the health of science overall," Brooks says. "With all the other agencies that support science, their support is justified by their mission, whereas the mission of the NSF is the support of science and science education." J. David Litster, vice president and dean for research at the Massachusetts Institute of Technology, expresses a similar view. "Over the past decade or so, the NSF has really become the one agency which is responsible for stewardship of the country's capability of basic research in the physical sciences," he says. Litster says that defense-related motives for basic research have declined with the end of the Cold War. Part of the pressure on science to contribute to economic goals is a reflection of this change and the overall national effort to reorient to new purposes. "There's a lot of pressure to support research which will contribute to the economic position of the country," he says. "That pressure is being interpreted as that the NSF should do more applied research and not as much fundamental research. We need a strategy for research in this country, but part of that strategy for the NSF should be making sure that we don't lose the fundamental underpinnings for the other things we do." Finding and communicating the best combination of basic and applied research for science and for the country, although crucial, will not be an easy task for Varmus or Lane, observers agree. "The whole research enterprise is a seamless web," Brooks says. "If you go too far in trying to pick and choose just those things that appear--temporarily, to the layman--to be relevant to economic competitiveness, you destroy the whole infrastructure, which is essential for economic competitiveness in the long run." (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : More Undergrads Embrace Bioengineering Discipline AU : MYRNA E. WATANABE TY : NEWS PG : 1 Prepped in the operating room, a patient may to be too uneasy or too drowsy to notice the tools of modern medicine at hand: endoscopes that transmit images of internal anatomy to video screens; computers that help analyze these data; surgical lasers; pulse oximeters; respirators; and all of the other machinery commonplace in today's surgical environment. Such immensely valuable clinical tools are, directly or indirectly, the products of biomedical engineering research. But the fruits of laboratory investigation in this field are by no means limited to the operating room. The structure of subcellular components, the development of artificial organs made of nonbiological materials--even the devising of medical information systems and methods of downstream processing for pharmaceutical manufacturing--fall within the discipline's extraordinary range of concerns. Extraordinary as well is the apparent attractiveness of the field to undergraduate students: Young life sciences, medical, and engineering students are flocking to schools throughout the United States that offer programs focused on the field, say academic officials. Graduate fellowships and faculty awards in bioengineering are now available in all of its subspecialties; and, unlike the waning job situation in many other science disciplines these days, there seems to be no dearth of opportunity for current bioengineering graduates. Moreover, observers are optimistic that, as bioengineering applications grow, industrial opportunities will cor- respondingly expand to accommodate the graduates' career pursuits. A Complex Field The field is so diverse that it is defies simple definition. Respondents to a 1991 University of Utah survey of biomedical industry workers defined a bioengineer as "an individual skilled in the interaction between physical and life sciences or between engineering and medical practices'" (R.A. Normann, et al., Biomedical Engineering Society Bulletin 15/4:57-60, 1991). David Katz, chairman of University of California, Davis, biomedical engineering program, terms the discipline "as much a mindset and a toolbox as it is a formal academic sector." Janie Fouke, an associate professor of biomedical engineering at Case Western Reserve University, explains that her design and mathematical skills, honed as a graduate student in biomedical engineering, are the key to her function on a team consisting primarily of clinicians. "I can design and build the measurement devices," says Fouke, "and I can write the mathematical models that try to interpret the results." The latter, she adds, is where "the engineer comes in." Those in the field agree with Fouke on the dynamic interplay required between life sciences and engineering skills. Generally speaking, biologists and medical researchers use their knowledge of anatomy, physiology, biochemistry, and molecular biology to present problems and hypotheses, while solutions to the problems may entail sophisticated understanding of design and structure, often calling electrical, mechanical, aerospace, or chemical engineering skills into play. Academic Efforts Among the growing number of bioengineering research programs in U.S. academic institutions--schools such as Johns Hopkins, the University of Washington, Duke University, Case Western Reserve, and the Massachusetts Institute of Technology--several are benefiting from a rise in funding for certain targeted efforts. One of these specialties is the relatively new field of tissue engineering, in which researchers are striving both to create human tissues by means of cellular transplantation and to regenerate human tissues that have been damaged or are diseased. Shu Chien, director of the Institute for Biomedical Engineering at the University of California, San Diego, is such a researcher. He is taking a molecular mechanics approach to tissue engineering, studying molecular models of blood cell deformation and attempting to determine the factors responsible for cell adhesion. He hopes his work will elucidate how blood vessels become clogged with leukocytes and how leukocytes function in the immune response. Using quantitative approaches to determine how tissue is structured and how it functions, scientists at UC-San Diego also are working to develop skin grafts in vitro, consisting of living cells and proteins, to aid in healing the wounds of burn victims. Other UC-San Diego bioengineering researchers are working to determine pressure-flow relationships within the heart, to develop a laser that measures the thickness of retinal nervous tissue (to diagnose glaucoma), and to create implantable glucose sensors. At another major bioengineering center, the Georgia Institute of Technology in Atlanta, Robert M. Nerem, Institute Professor and holder of the Parker H. Petit Distinguished Chair for Engineering in Medicine, is studying the endothelium--the lining of the blood vessels--and its interactions with blood flow. Nerem is reconstituting blood vessels out of living endothelial cells, muscle cells, and other components. In order to do this, Nerem says, he utilizes his background in aeronautical engineering--he received his Ph.D. in that field from Ohio State University--to study how mechanical forces alter the composition and function of blood vessels. Other studies at Georgia Tech look at biomaterials, controlled release of biomolecules, targeted drug delivery, pancreatic transplants, improved blood dialysis pumps, and computer modeling for radial keratotomy surgery. Meanwhile, the University of Utah--known for its work on the artificial heart and the bionic arm--has a strong tissue engineering research program. Building on silicon-based microelectrodes, researchers such as Richard A. Normann, chairman of the bioengineering department, are creating a system that will allow blind people with a functional visual cortex in the brain to receive stimuli from a video camera via microelectrodes implanted within the cortex. It follows that Utah also is a leading academic center for research on synthetic materials that can be used for artificial organs. Karin Caldwell, director of Utah's Center for Biopolymers at Interfaces, says that among these materials are bioerodable polymers, used in artificial organ implants, that degrade as the body's cells grow to replace them. These bioerodable polymers also are useful for targeted drug release. They must be compatible with blood, she explains, so that the molecules can stay within the bloodstream long enough to function. They also must be soluble in the body, and must not trigger its immune response. Applying The Skills According to Georgia Tech's Nerem, who is president of the Washington, D.C.-based American Institute for Medical and Bioengineering (AIMBE), approximately 160 bioengineering Ph.D.'s are now granted annually in the U.S., but an approximately equal number of degrees in chemical, mechanical, electrical, and other engineering specialties are granted to people whose training is in bioengineering. Recognizing the increasing need for reliable job-market forecasts for this burgeoning field, AIMBE is considering a manpower study to develop useful projections. Meanwhile, researchers such as UCDavis' Katz predict that "in the 21st century, a lot more [engineering] is going to be biologically oriented." James McIlhenny, chairman of biomedical engineering at Duke, says there currently are 21 accredited undergraduate bioengineering departments in the U.S. and more than 64 graduate programs. One of the largest undergraduate bioengineering programs in the U.S. is at UCSan Diego; 400 students are enrolled there this year, up 100 percent over five years ago. The University of Pennsylvania has one of the largest graduate programs, with approximately 100 students. Onethird to onehalf of bio engineering undergraduates nationally go on to medical school, an equal proportion opt for graduate school, and 20 percent to a third of them take jobs in industry, observers estimate. Master's program graduates tend to pursue their doctorates or else enter medical school, while those with doctorates most often take jobs in either academia or industry. Currently, according to Karen Mudry, an official at the Washington, D.C.-based Whitaker Foundationan enthusiastic supporter of bioengineering researchthere are relatively few academic positions available. Sources agree that the bulk of industrial jobs is with biomedical instrumentation companies; but in the past five years, according to many academics, bioengineers increasingly have been finding management jobs at biotechnology firms. As the biotech field grows, sources believe, it is expected to absorb more bioengineers. The Funding Picture Although bioengineering research is supported by the National Institutes of Health and the National Science Foundation, many investigators say that without the support of the Whitaker Foundation, the field would not have developed as rapidly as it has. Whitaker's most recent venture, according to its vice president for biomedical engineering programs, Peter G. Katona, is a joint initiative with NSF begun a year ago for support of research into costeffective health care technologies. Formed in the mid1970s by electronics industry entrepreneur Uncas A. Whitaker, the foundation has long been a source of research support for individual bioengineers (A. Martello, The Scientist, Feb. 5, 1990, page 26). In 1989, the foundation began administering development awards to universities for improvement of bioengineering education programs. The first two schools to receive awards were Johns Hopkins and the University of Washington. Two years later, a second set of awards was givento UCSan Diego, the University of Utah, and Georgia Tech. Development award grantees receive $1 million for capital investment, and $500,000 a year for four years that is not earmarked but can be used to recruit bioengineering faculty, award graduate fellowships, and run core facilities. Upon review, the award may be extended for two years. At the end of the award period, schools are given $1 million in transition funds to help phase in other funding sources. The Whitaker Foundation is not the only source of private support for bionengineering, however. The University of Pennsylvania's Laboratory for Injury Research and Prevention, for example, has received funds from automobile manufacturers and insurance companies, explains Gershon Buchsbaum, a Penn professor of bioengineering. Some researchers complain that NIH and NSF bioengineering funding levels are low, although the federal government is still the largest provider of research support for the field. Nevertheless, Katz of UCDavis contends that the NIH review panels need to have a better understanding of the relevance of engineering to research proposals. Murray B. Sachs, Massey Professor and director of Johns Hopkins School of Medicine's department of biomedical engineering, says, with regard to NIH, "Study sections sometimes don't have engineers or mathematical people on them." Myrna E. Watanabe is a biotechnology consultant in Yonkers, N.Y. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : WOMEN AND MINORITIES IN BIOENGINEERING AU : MYRNA E. WATANABE TY : NEWS PG : 1 There is agreement among bioengineers that their field offers excellent career opportunities for women. Georgia Institute of Technology's Robert Nerem, for example, says that in 199192, 35 percent of the bioengineering bachelor's degrees, 30 percent of the master's degrees, and 24 percent of the Ph.D.'s went to women. However, the Whitaker Foundation's Karen Mudry points out, these figures indicate a recent trend, since, at present, "there are very few senior women in the field." Some other frequently underrepresented minorities, however, are not well represented among the ranks of professional bioengineers, either. Georgia Tech's Nerem notes that in 199192, AfricanAmericans earned only 3 percent of the bachelor's degrees, 1 percent of the master's degrees, and essentially no Ph.D.'s in the field. Although exact figures are unavailable, it is believed, he adds, that there are slightly more Hispanic than AfricanAmerican bioengineers. Cato Laurencin, an orthopedic surgeon and biochemical engineer who is director of a polymer materials laboratory in the division of health sciences at the Massachusetts Institute of Technology, believes that current bioengineering recruitment initiatives at the late high school or college level are not sufficient to attract minorities. He says that the effort to recruit minority students must start early in high school, if not before, and suggests that universities or bioengineering departments enter into partnerships with high schools to increase awareness of the field. --M.E.W. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Joint Program Aims To Explore Links Between Science And The Humanities AU : TRACEY D. WEBB TY : NEWS PG : 3 The National Science Foundation--hoping to boost science literacy among Americans of all ages--has joined with the National Endowment for the Humanities (NEH) in a program aimed at examining the relationship between science and the humanities in everyday life. The two agencies have awarded five states $40,000 to $50,000 grants for public education projects aimed at highlighting the role of the humanities in understanding science and technology. Georgia, Kentucky, Massachusetts, New Hampshire, and Vermont are the first recipients of grants under NSF and NEH's Nature, Technology and Human Understanding program. The federal project is the result of talks that began in 1992 between former NSF director Walter Massey and former NEH director Lynn Cheney. Massey wanted NSF to increase its efforts to promote science literacy and believed examining science and technology in their cultural context was a unique way to achieve that goal, says NSF program director Rachelle Hollander. "NSF sees this program as a way to show that science and the humanities should not be viewed as two unrelated disciplines and that one doesn't understand science without understanding the human and social context in which it exists," Hollander explains. >From NEH's perspective, the project is a way to encourage thought and discussion among the general public about the human implications--good and bad--of science, says NEH spokesman Jim Turner. "There is the notion that the humanities and science have absolutely nothing to do with each other," Turner says. "But there are a lot of people who are concerned with the value judgments and human concerns surrounding science and technology. We believe the projects selected for grants are broad-based enough to allow schoolchildren to adults to understand how the two disciplines are connected and that they are not mutually exclusive." In all, 12 state humanities councils submitted proposals for grants. Turner says the five awardees will submit reports back to NEH and NSF once the projects have been completed. "The councils are all NEH affiliates, and all had impressive proposals," Turner says. "The five states awarded grants were selected by a panel of science and humanities scholars on the basis of the diversity of the projects and audience that those projects would reach." For example, Massachusetts's program--"Knowing Our Place: Humanistic Aspects of Environmental Policy Making"-- addresses environmental concerns of the public by focusing on the impact of nuclear power. "We plan on using the history of nuclear power and the controversy that has surrounded it as a case study of how public perception plays a role in environmental and energy policy," says David Telbaldi, executive director of the Massachusetts Foundation for the Humanities. Telbaldi says the project will begin in March with a series of live television broadcasts linking local studio audiences, viewers across the state, and a panel of science and humanities experts. The broadcasts will include discussions on the place of scientific expertise in forming environmental policy, the challenges of making technological decisions within a democracy, and future sources of energy. The Georgia project will connect science with the achievement of African Americans in the field. "Technology and the African American Experience" will focus on the role of African Americans in the development of science and technology with a two-day symposium and four public lectures on the topic. The theme of Kentucky's "Science in Our Lives" project is change from an agricultural to a technology-based economy. The project's intent is to examine the implications of the state's own current transition from agrarian to high-tech through a series of public lectures, readings, and discussions. The aim of New Hampshire's project is to show how science incorporates social and cultural perspectives. The program, entitled "Of Apples and Origins: Stories of Life on Earth," will include public radio and television broadcasts as well as public reading and discussion programs. The project is also sponsoring a public conference on computer technology and artificial intelligence. Vermont's "Mother Goose Asks Why" project is targeted toward increasing science literacy among the state's schoolchildren. The key part of the program includes educating parents on how to help their children perform simple science activities at home. While NSF's main goal is still promoting and funding basic science research, Cora Marrett, assistant director of the agency's social, behavioral, and economic sciences division, says the NSF-NEH program should be encouraging to the science community because it provides a two-fold benefit. "This program will not only help foster science literacy, especially among young students, but could also help in advancing humanistic science research," Marrett says. She says the science agency hopes to fund and award more grants under the joint project in the future, although no concrete plans exist to continue the program until it is evaluated. For more information on the Nature, Technology and Human Understanding program, contact NSF at 1800 G St., N.W., Washington, D.C. 20550 or call (202) 357-9498. Tracey D. Webb is freelance writer based in Philadelphia. (The Scientist, Vol:7,#23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Consortium Of `Best Minds' To Seek Manic-Depressive Illness Gene AU : NEERAJA SANAKARAN TY : NEWS PG : 4 Funded by a $2.5 million grant from the Charles A. Dana Foundation, scientists from three of the United States' premier research institutions--Cold Spring Harbor Laboratory, Johns Hopkins University, and Stanford University--are joining forces in a consortium to search for the genes responsible for manic-depressive illness (MDI). In an effort the foundation is calling a new model for collaborative research, the Dana Consortium for the Genetic Basis of Manic-Depressive Illness is bringing leading researchers from disciplines as diverse as genetics, psychiatry, and informatics together toward a common goal. "Some of the best minds from the pure sciences and clinical sciences are coming together," says David Mahoney, chairman and chief executive officer of the New York City-based Dana Foundation and chairman of David Mahoney Ventures, also of New York. Mahoney, a businessman, serves on the board of advisers of the David Mahoney Institute of Neurological Sciences at the University of Pennsylvania and as chairman of the governing council of the Harvard Mahoney Neuroscience Institute at Harvard Medical School. "Researchers from these different universities are collaborating--not competing for the funds--to get to the results," says Stephen Foster, executive vice president of the Dana Foundation. "Scientists with their unique areas of expertise at the different institutions need each other to find all the answers." Each of the three institutions will be concentrating on a different aspect of the investigation. Trained clinical psychiatrists at Johns Hopkins in Baltimore will be identifying families who show strong evidence for a genetic origin of MDI. Geneticists at Stanford in Palo Alto, Calif., will be doing the actual genetic analyses--examining the DNA from these patients, searching for markers or "signposts" that will point to the genes that cause the disease. The Cold Spring Harbor Laboratory on Long Island, N.Y., is forming a new Dana-Cold Spring Harbor Laboratory Center, headed by Cold Spring Harbor director James Watson, to serve as the central facility for the project. It will house a database to integrate clinical and genetic data from the two other institutions. "[What] makes this collaboration unique is the role played by Cold Spring Harbor and Watson," says J. Raymond DePaulo, a professor of psychiatry at Johns Hopkins University, and head of the MDI project there. Watson, a Nobel laureate who recently stepped down from the directorship of the Human Genome Project, will help in the acquisition of resources and data management for the project. Recently, he was also appointed chairman of the executive committee of the International Science Foundation for the Former Soviet Union, an organization founded by investor George Soros to aid Russian scientists (B. Goodman, The Scientist, Jan. 11, 1993, page 3). In addition to setting up the database, Cold Spring Harbor Laboratory will function as a conduit for information on MDI, coordinating basic research with studies on social and ethical consequences of the disease, and organizing periodic meetings among scientists to discuss advances made in the field. The first of these meetings, scheduled for December of this year at the laboratory's Banbury Center, will address critical issues concerning MDI, with an emphasis on diagnosis. The consortium also plans to educate health and public policy- makers about MDI through briefings. One of the biggest problems about working with manic- depressive disease, says DePaulo, is that there is no established pathology to aid in its proper diagnosis. Finding the genes that either cause or increase the patients' susceptibility to MDI will enable doctors to diagnose the disease in the early stages. MDI, which afflicts about 2.5 million Americans, is a leading cause of suicide among both adults and adolescents. According to Kay R. Jamison, the clinical director of the Dana-Cold Spring Harbor Center, early diagnosis will go a long way in prevention efforts among people at risk and is thus one of the most important reasons to find the genes. "We chose MDI because [the] tools seemed to fit the goal," says David Botstein, a professor and chairman of the genetics department at Stanford University, where he leads the consortium's team of geneticists and molecular biologists. In 1986, Botstein, along with Eric Lander, a professor of biology at the Massachusetts Institute of Technology, published some landmark papers on the identification of complex genetic diseases; that is, diseases caused by defects in more than one gene (E.S. Lander, D. Botstein, Cold Spring Harbor Laboratory Symposium on Quantitative Biology, 51:49-62; E.S. Lander, D. Botstein, Proceedings of the National Academy of Sciences, 83:7353-7). They developed a "simultaneous search" theory that could identify up to five genes involved in causing disease, provided a complete map of the chromosomes was available. The lack of any consistent patterns of inheritance of MDI indicated that perhaps multiple genes were involved here. "The project is very exciting because it allows us to test out this theory," says Chris Clark, a postdoctoral fellow who will be working on the project in Stanford. "Thanks to the genome project we now have available a complete map with markers or `signposts' to identify genes on all 23 chromosomes." Using these markers, scientists can trace the genes to different lineages and hope to identify the mutant genes responsible for MDI. Since more than one gene is involved, the genetic analysis requires a significant number of samples to properly locate all possible culprits. The team at Johns Hopkins is responsible for identifying 50 families with at least three afflicted members. Compounding the search is the criterion that the disease be inherited from only one side of the family. If both families have a history of MDI, the identification of the responsible genes would not be possible. So far, the team has selected 25 families. Cold Spring Harbor's Tom Marr developed the special software for the MDI database. "Ultimately, we hope to go beyond published papers and have the database include all the background information," says Jan Witkowski, a geneticist and director of the Banbury Center. "One could be able to trace information through it, to see how others got it and what they are doing with it." For administrative purposes, the grant money is being dispensed as three separate awards to the institutions. Roughly $1.5 million is being channeled to Cold Spring Harbor and the remainder to Stanford and Hopkins. Earlier this year the Dana Foundation announced a commitment of $25 million toward neuroscience, and the MDI project alone is receiving a tenth of this amount. "The initial investment is $2.5 million over three years," says Mahoney. "If the project is working--and early results show every sign of significant progress--we expect to add and increase to this original amount." Neeraja Sankaran is a science writer at the Cancer Research Institute in New York City. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: NOTEBOOK --------------------------------------------------------------- TI : SissBoomBarium! TY : NEWS (NOTEBOOK) PG : 4 On a cold, rainy, blustery November 6, some 52,000 football fans huddled in East Lansing, Mich.'s Spartan Stadium to see Michigan State square off against Big 10 rival Northwestern. By all accounts, the game turned out to be a sloppily played affair, with MSU winning, 3129. For some in the standsthe scienceminded, especiallythe best moments came at halftime, when 109 marchers, each carrying a 28 x 44inch placard, congregated at midfield to form a "Living Periodic Table." What compelled these hearty souls to brave the elements, so to speak, in such fashion? According to Michael Kenney, a visiting lecturer in MSU's chemistry department, the intention was to remind people that chemistry affects everyone, every day. The event was Kenney's idea to promote National Chemistry Week, November 713. The volunteers including Michigan State president Peter McPherson, representing neilsbohrium (Ns)paid $100 each for the privilege of shivering with their favorite element, with proceeds going to the MSUbased chapter of the American Chemical Society. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : MegaLibrary TY : NEWS (NOTEBOOK) PG : 4 A library documenting the development of U.S. infrastructuretransportation, communications, and physical structuresthat may eventually comprise more than 100,000 volumes is in the process of being digitized in a joint project spearheaded by Cornell University Library and Cornell Information Technologies. The material to be incorporated into "The Making of America" project is part of Cornell's collection and spans the period 1860 to 1960. Many of the books and papers in the collection are currently too brittle to be handled by the public. The Cornell effort is designed to complement similar preservation initiatives, such as the U.S. Library of Congress' "American Memory Project," which will convert archival collections in American culture and history to electronic form; and Yale University's "Open Book" project, which will create digital images from microfilmed versions of 10,000 books. Cornell has already digitized more than 1,000 books and demonstrated the ability to gain access to them on Internet. Advisory panels of scholars from various institutions will decide which works will be preserved in "The Making of America." (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Testing The Waters TY : NEWS (NOTEBOOK) PG : 4 Scientists at Woods Hole Oceanographic Institute in Massachusetts and Penn State University have tested two prototype acoustic "thermometers" off the coast of Bermuda as part of an experiment aimed at measuring ocean temperatures on a global scale. A pair of surface suspended acoustic receivers (SSARs), large buoys attached to thousands of feet of cable equipped with various sensors and underwater microphones, use electronics and signalprocessing techniques to map global oceans. The buoys will be used as part of the Global Acoustic Mapping of Ocean Temperature (GAMOT) program. The techniques used in GAMOT differ from conventional ocean temperature measuring methods because they use loosely moored sound sources and the SSARs, rather than fixed sound sources and receivers. Another test of the SSARs is planned in the Pacific next year. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Chemistry For Kids TY : NEWS (NOTEBOOK) PG : 4 The American Chemical Society has testlaunched a program designed to bring the excitement of chemistry to children. "Kids & Chemistry" provides children, ages 912, with handson experiments that relate chemistry to everyday life. The experiments are contained in lunchbagsized kits holding enough experimental materials for four children. For example, the "Acid Rain" kit will show the effects of acid rain on various surfaces, and "Chemical Reactions" gives kids insight on how their body digests food. Other components of the program are classroom programs, penpal arrangements with scientists, and a schoolbased mentoring program to promote gender equity in math and science. Kids & Chemistry is being tested for a year in Irvine, Calif.; Baytown, Texas; Minneapolis; and Arlington, Va. If successful, the program will go national through ACS's local chapters. For more information, contact ACS, 1155 16th St., N.W., Washington, D.C. 20036; (202) 8724450. Fax: (202) 8724370. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Challenging Einstein TY : NEWS (NOTEBOOK) PG : 4 Stanford University has subcontracted Lockheed Missiles and Space Co. of Sunnyvale, Calif., to build a $100 million spacecraft that will transport Gravity Probe B, a physics experiment designed to test two crucial predictions of Einstein's general theory of relativity. Stanford is developing Gravity Probe B under contract from the National Aeronautics and Space Administration. The experiment will measure how space and time are "warped" and "dragged" by the presence of Earth and its rotation. To conduct the experiment, four superround gyroscopes will spin on gas jets within a quartz block so that they touch nothing while spinning. By freezing the environment surrounding the gyroscopes to near absolute zero, the Stanford researchers will be able measure the minute changes in spin. If the experiment confirms Einstein's theory, astrophysicists will be more confident in applying the theory to new star systems. If not, prevalent views of the structure and origin of the universe would be radically altered. Gravity Probe B is slated to be tested aboard the space shuttle in 1995, and sent into polar orbit around Earth in 1999. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Who's Fooling Whom? TY : NEWS (NOTEBOOK) PG : 4 The third annual Loebner Prize competition is scheduled for December 8 at the National University Technology Center (NUTEC) in San Diego. In the competition, administered by the Cambridge Center for Behavioral Studies in Massachusetts, human judges interface with a bank of computers to determine which terminals are controlled by humans and which by computers. Using a scoring system that ranks the terminals most humanlike to least humanlike, the author of the software given the highest score by the judges receives $2,000. Robert Epstein, chairman of the National University psychology department and coordinator of all three contests, notes that in the previous two competitions some of the judges were completely fooled by the software programs. This year's competition was supposed to be held in September at Cambridge, but was postponed and moved to NUTEC after a July fire razed the Cambridge center. Epstein says that the competition is open to the public, but that space is limited. For information, contact Epstein by phone at (619) 4364400 or by fax at (619) 4364490. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: OPINION ----------------------------------------------------------- TI : National Labs Have Vital New Role To Play In The 1990s AU : ROLAND W. SCHMITT TY : OPINION PG : 11 Editor's Note: In a recent speech at Lawrence Livermore National Laboratory in California, Roland W. Schmitt, president emeritus of Rensselaer Polytechnic Institute in Troy, N.Y., candidly explored the vast changes in global and national affairs that are having significant impact on the mission of United States governmentoperated labs. Schmitta former General Electric Corp. executiveaddressed the traditions and achievements of these research centers; he discussed the pattern of governmental financial support for their endeavors over the years; he reviewed the traditional balance among federal, industrial, and academic involvement in supporting and influencing their activities; and he made clear his feelings concerning the ways in which the national labs must adjust their mode of doing scientific business in response to the demands of a rapidly changing set of international concerns. Following is an excerpt from his speech, in which he addresses the conceptual reconfiguration of the national labs in response to a politically and economically reconfigured global environment. National Labs Have Vital New Role To Play In The 1990s ------ My concerns about the national labs have focused on the tradition of "chuck wagon technology," where you cook up whatever technical goodies fit your talents or interests, and then yell "come and get it." This is plainly an ineffective way to approach technology transfer to the commercial sector, since a hungry client may not always be able to digest what's served. And yet the national labs still use it distressingly often. For the last four decades, three primary themes have characterized federal science and technology policy: maintaining a strong technology base for defense, developing technologies for missionoriented federal agencies, and supporting fundamental and exploratory research. Defense technology has been dominant. It spawned a huge infrastructure that includes federal laboratories, universities, and industry and it currently accounts for about onethird of the United States' total R&D expenditures. Now, however, the nation's scientific and technical community must respond to lightningquick changes: the end of the Cold War, our altered defense needs, international economic competition, shifting domestic prioritiesall these factors have thrown science and technology into the same turmoil that is roiling the rest of society. New Goals Recently, the Committee on Science, Engineering, and Public Policy of the National Academies of Sciences and Engineering and the Institute of Medicine proposed a new basis for federal science and technology policy. The committee suggested two goals: leadership in all major areas of science to which the nation can quickly apply and extend advances; and, beyond this, leadership in additional selected areas of science identified according to criteria, including national objectives, that are external to the field of research. The committee also urged the federal government to maintain leadership in technologies that promise major and continuing impact on broad areas of industrial and economic performance. In particular, the government should pursue this goal in areas in which U.S. firms have shown they can convert the technology to marketable products or where the areas of emphasis are based on national strategic considerations. As a result, there is increasing pressure on scientists to be more motivated byand move faster onthe nation's problems and less by their own curiosity. This pressure is exemplified by California congressman George Brown, Jr., who has lamented the failure of science and technology to make the U.S. a leader in infant health, life expectancy, worker productivity, or the efficient use of resources. A Carnegie Commission reportLinking Science and Technology to Societal Goalshas called for setting tangible, longterm science and technology goals in many policy areas, among them the environment and natural resources, health and social welfare, food production and distribution, and the public infrastructure. To respond to these challenges, science and technology policy in the 1990s should add several new themes to those of the past. These are: * longterm job creation through the exploratory and pioneering efforts that launch new industries, products, and services; * technologies for selected social issues; and * defense R&D conversion. The last two are, I believe, widely accepted by the political leaders. The first, I fear, is being overlooked at present. But I believe that the most promising targets of opportunity are jobcreating, pioneering, and socially oriented R&D endeavors, especially those that center on the fields of environment, waste cleanup, and infrastructure. Until now, little pioneering work in nondefense areas has emerged from the national labs. However, scientists and engineers at those labs are eminently capable of such work if motivated and supported with the right programs. The key is to design programs to generate discoveries and inventions in areas relevant to industry and to ensure that these breakthroughs are linked with entrepreneurial firms, large or small, that can turn worthwhile inventions into profitmaking enterprises. Two kinds of organizations develop and convert pioneering technology into jobcreating businesses: startup firms and newbusiness or newproduct subgroups within existing firms. The national labs can help both by reducing their risks. National labs should choose their research initiatives by charting their courses with help from industry. Each lab could build on its present expertise and identify industries that most closely approximate its research skills. With help from people in these industries who know where the barriers and opportunities lie, the lab could identify areas in which fundamental knowledge is lacking and in which new discoveries or inventions could make a difference. Once these areas are identified, the lab's best and brightest should be set loose to address these concerns. Dollar Support Such work could be funded initially from directors' discretionary funds, which amount to 10 percent of each lab's total budget. In time, considerably larger portions of the lab's budget could be devoted to successful efforts. Technology transfer also is a key. The transfer of information, services, equipment, and people to entrepreneurial firms most likely will take place regionally. To succeed, businesses need seed money and, later, venture capital. Many states now have programs designed to encourage these enterprises. The national labs would need close alliances with these regional economic activities as well as all the private infrastructure that nurtures new ventures. The objective should be to transfer resources, especially equipment and people. By assuming major responsibility for the early coststhose associated with the pioneering work of discovery and demonstrationnational labs would help minimize risks to those seeking to develop new industries, businesses, and products. The federal government's return on investment would be highquality jobs, in either startup or existing firms. The deal between the riskreducing national labs and the entrepreneur should spell out the jobcreating milestones on which continuation of the project would depend. Providing A Link To transfer technology successfully to new business divisions of existing firms, the labs and firms must participate in programs that link people as well as ideas, knowledge, discoveries, and inventions. Team forming across organizational interfaces is essential. The paradigm that works best is a process in which people work together early, often, and over long periods through successive experiences of successful innovation. For the past decade, the government has encouraged the national labs to promote technology transfer through legislation and various executive orders. Each of these actions has sought to remove constraints and barriers that have stymied technology transfer. But removing constraints, although necessary, is not sufficient. For national labs to contribute significantly to U.S. industrial strength, their relationships with industry must be based on a longterm strategic vision, not on projectbyproject improvisation. In narrowing the focus to what I'm proposing as a major targetjobcreating, pioneering worklegitimate questions emerge: Can such concrete goals fuel the creative juices of lab scientists and engineers? Will such research evoke the best, most innovative contributions of the scientist? Or will heavyhanded, topdown direction undermine the commitment of scientists who are often motivated by an intense personal desire for knowledge? History is on our side. Research aimed at addressing practical needs often has sparked pioneering efforts that, in turn, have fueled knowledge and cleared the way for new realms of inquiry. Time and again, scientists have examined realworld problems and contributed to both society and science. You know who some of these scientists are: Louis Pasteur, who started with sour wine; Irving Langmuir, who started with blackened light bulbs; Karl Jansky, who started by listening to static. Today, from Pasteur, Langmuir, and Jansky, we have bacteriology, surface chemistry, and radio astronomy. Practical problems don't detract from the work of creative scientiststhey enrich it. National lab scientists who participate in these downtoearth programs must be willing to cast their nets into the streams of industrial barriers and opportunities. The wider they cast for places where the scientific and technical mind can work, the more challenges, opportunities, and creativity they will find. To what extent are the national labs prepared to pursue the course I've outlined? Some labs already have forged programs to promote entrepreneurial spinoffs. Many have research programs motivated by other goals that could be transformed into the kind of effort I'm suggesting. Solutions lie in fostering government/industry research teams that expose scientists and engineers to ideas for relevant, pioneering research and development. Solutions lie in policies that make job creation an explicit goal and that allow labs to carry out programs that represent riskreducing subsidies for commercial activities. And solutions lie in policies that encourage the transfer of people, equipment, discoveries, and knowledge to target organizations. If successful, such programs will boost an ailing economy, downsize the national labs in an orderly and productive manner, and leave them larger than they otherwise would bebecause they will have learned to do something new and important for the nation. Roland W. Schmitt is president emeritus of Rensselaer Polytechnic Institute in Troy, N.Y. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: COMMENTARY ------------------------------------------------------------ TI : What Can We Learn From The Supercollider's Demise? AU : Leon M. Lederman TY : OPINION (COMMENTARY) PG : 12 A stunned subset of the scientific community, the particle physicists, is wrestling with Congress' recent rejection of the superconducting supercollider. It becomes intensely important to try to understand what this episode means in the broad sweep of United States history. Science has many fronts, each making its justifiable claim to passion and to the power to illuminate. However, the quest to discover the primary building blocks, the particles and fundamental laws of nature, has a unique objective. Although these laws are not useful to cure the common cold or understand the turbulent progress of hurricanes, they provide a solid base for the pyramid of understanding. The U.S. grew rich by exploring and settling its frontiers. We learned that the bolder the thrust, the greater the returns. Isn't the supercollider a sort of wagon train into the frontier of our comprehension of the universe? How could we not continue? What does this tell us about the state of America's mind? What does it augur for the future? We cast about for reasons. Maybe we can blame our failed educational system, which produces those legislators who, looking for the approbation of their constituents, proudly announced that they lack the vaguest idea of what the supercollider is all about. Maybe we can blame the unhelpful testimony by colleagues in other science fields, stressed as they are by their own difficulties in securing adequate research support. (In fact, we particle physicists would feel infinitely better todayin this winter of our discontentif the money saved would appear in the other science budgets. Unfortunately, we do not believe this will happen.) This brings us to the general state of science in the nation. Across the board, biological, medical, chemical, and physical research are increasingly under stress. Young investigators are spending up to 40 percent of their time seeking research20funding. Bureaucratic and regulatory requirements eat up time and research funds. Creationists, animal rights extremists, and congressional fraud hunters hardly cheer up the environment in which research must flower. And there are increasing pressures from policymakers who insist that research must be more targeted to immediate goals and must not, above all, be curiositydriven. Superimposed on the litany of troubles is the fact that American industry is giving up on research. One after another, once proud and productive research labs are being either closed or reduced to shadows of their former splendor: RCA, IBM, Bell Labs, Westinghouse, GE, DuPont, and so forth. At the same time, the great research universities are experiencing financial difficulties impacting the vigor with which their research is carried out. Thus, the SSC decision may be viewed in the context of a national mood that is obsessed by immediacy at the expense of longterm investment. The inertia with which America is addressing the crisis in educationso intimately woven into the future of scienceis surely a related issue. The questions raised here are, of course, open. We need the benefit of perspective and, although I identify many of the concerns we have as scientists, I remain optimistic. I cannot remember ever seeing so many bright young scientists, eager to practice their skills. The promise of science has never been greater, and I don't believe anyone seriously questions the notion that science and technology are essential to survival and evolution of humankind on this planet. What must be understood is that vibrant and productive science is a tapestry of many threads, and each, in its proper balance, plays a vital role: applied science and engineering, basic research, big science and small science, neurophysiology and cosmology. We need to kindle the sparks of curiosity in our future scientists. Every child is a candidate, and every young aspirant is sensitive to the messages that emanate from our political and social leaders. We are in a tough period and, incidentally, our colleagues in many other industrial nations are facing similar difficulties. We obviously need to intensify efforts at international collaboration. The federal government and Congress must establish a sane research policy so that never again will the support of three administrations and four Congresses lure thousands of young scientists, engineers, and technicians into a project that can so casually be canceled. Most important, scientists must rededicate themselves to a massive effort at raising the science literacy of the public. Only when citizens have reasonable science savvy will their congressional servants vote correctly. Leon M. Lederman, a Nobel Prizewinning physicist and director emeritus of Fermi National Accelerator Laboratory, is a professor at the Illinois Institute of Technology in Chicago. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: LETTERS ------------------------------------------------------------ TI : Fetal Tissue Opposition AU : KEITH A CRUTCHER TY : OPINION (LETTERS ) PG : 12 I find it ironic that The Scientist, which states on its contents page that "one of its most valued aspects is its commitment to open discussion of controversial topics," would publish the kind of article that appeared in the October 4 issue on the federal funding of research using aborted fetal human tissue (M.E. Watanabe, page 1). Of greater irony is that the same issue contains a story on the establishment of a new ethics institute (R. Kaufman, page 3), in which we find an expert profoundly stating that "there are lots of ethical issues facing scientific researchers" and a dean observing that making students aware of ethical questions "is part of doing science right." But scanning the article on funding of fetal tissue research reveals no discussion of the ethical issues. Who is surprised to learn that the advocates (read "recipients") of federal funding for fetal tissue research "breathed a collective sigh of relief" when the ban was overturned? If readers were interested in exploring the ethical debate that erupted (and continues) around this issue, no clues for further exploration are given in the article or the suggested reading list. Such readers might be surprised to learn that objections have been voiced within the scientific community regarding the clinical efficacy of fetal tissue transplantation. They would certainly have a hard time finding support for the conclusion that such transplants "have been used successfully in individuals with Parkinson's disease, diabetes," and the other diseases listed. That politics have played an inordinate role in the determination of ethically sound science is unquestionably true. However, dismissing the issues as nothing more than politics misrepresents the underlying questions and polarizes the discussion. As a scientist with some familiarity with the scientific and ethical issues related to the use of aborted fetal tissue, I remain opposed to the federal funding of any research that depends on the systematic and intentional destruction of innocent human life. There are other scientists who hold similar views. Rather than ignore the controversy, The Scientist would do a greater service to its readership by fulfilling its goal of promoting open discussion and explore all sides. At the very least, the advocates of fetal tissue research should be given the opportunity to establish the ethical foundations of their position by demonstrating the weakness of the arguments made on the other side. Because it ignores such arguments, readers may rightfully wonder if The Scientist is displaying the same tendency exhibited by the lay media, in which appearance is more highly valued than substance. KEITH A. CRUTCHER Department of Neurosurgery University of Cincinnati Medical Center (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : Grad Student Support AU : ROBERT V. SMITH TY : OPINION (lETTERS) PG : 12 Thank you for the fine article on dilemmas faced by academic scientists as a result of funding constraints (B. Spector, The Scientist, Sept. 6, 1993, page 1). I would like to offer a correction and clarification of an item referred to in that article. First, graduate tuition at Washington State University (WSU) increased 35 percent during the past five years and is now about $10,000 per year for nonresidents and $4,000 for residents, not double and not $15,000 as indicated in the article. The clarification is related to my comments on the "hiring" of graduate assistants vs. technicians and postdocs. We encourage faculty to hire graduate students on grants, but with increasingly competitive stipends (about $15,000 per year), the cost of resident tuition (outofstate tuition is waived at university cost for students appointed onehalf time or greater), and statemandated health insurance benefits (averaging $1,000 per student), the "total package" for a halftime graduate research assistant is close to $20,000 per year. WSU faculty increasingly report that it is difficult to justify the support of graduate assistants when fulltime technicians and postdocs can be hired for a little more than the cost of the graduate student "total package" alluded to previously. This situation does not bode well for people aspiring to graduate study in the sciences. ROBERT V. SMITH Vice Provost for Research and Dean of the Graduate School Washington State University Pullman (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: HOT PAPERS ------------------------------------------------------------ TI : NEUROSCIENCE TY : RESEARCH (HOT PAPERS) PG : 16 L.R. Berkemeier, J.W. Winslow, D.R. Kaplan, K. Nikolics, D.V. Goeddel, A. Rosenthal, "Neurotrophin5: A novel neurotrophic factor that activates trk and trkB," Neuron, 7:85766, 1991. Arnon Rosenthal (Department of Neuroscience, Genentech Inc., South San Francisco, Calif.): "Development of the vertebrate nervous system is controlled by multiple diffusible factors. These factors regulate the proliferation of pluripotent neuronal precursors, the transition to postmitotic differentiated neurons, and the growth of nerve fibers to their specific cellular targets as well as neuronal phenotype and neuronal survival. The bestcharacterized polypeptides that control the survival of neurons are members of the nerve growth factor (NGF) protein family collectively designated neurotrophins. This family includes NGF, brainderived neurotrophic factor, and neurotrophin3. "The structural similarity of these three proteins enabled us to identify a fourth mammalian neurotrophin that was designated neurotrophin5, or NT5. (The same mammalian protein was subsequently designated NT4 or NT4/5.) "NT5, a 13 Kd secreted polypeptide that is 50 percent identical to NGF, was recently found to be a potent survival factor for several distinct populations of embryonic neurons in culture. These include spinal motor neurons, which degenerate in ALS disease (C.E. Henderson, et al., Nature, 363:26670, 1993); sensory neurons, which may degenerate in peripheral neuropathies (A. Davies, et al., Journal of Neuroscience, in press); midbrain dopaminergic neurons, which degenerate in Parkinson's disease (M. Hynes, A. Rosenthal, in preparation); and nonadrenergic locus coeruleus neurons, which degenerate in Alzheimer's disease (W.J. Friedman, Experimental Neurology, 119:728, 1993). The finding of a novel survival factor for neurons may help to explain the mechanism by which the number of mature neurons is epigenetically regulated in vertebrates. Furthermore, NT5, which promotes the survival of normal neurons, may prevent or ameliorate the death of neurons in prevalent neurodegenerative disorders like Parkinson's disease, ALS, and Alzheimer's." (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : BIOCHEMISTRY TY : RESEARCH (HOT PAPERS) PG : 16 C. Dingwall, R.A. Laskey, "Nuclear targeting sequences a consensus?" Trends in Biochemical Sciences, 16:47881, 1991. Colin Dingwall (Wellcome Trust Cancer Research Campaign, Cambridge, U.K.): "Our understanding of protein accumulation in the cell nucleus has progressed from the `entry by diffusion and retention by specific binding' model to our current appreciation that this is a highly selective active transport process mediated by a nuclear localization sequence (NLS) in the transported protein. However, despite a detailed earlier analysis of the SV40 large T antigen NLS, it was not possible to identify an NLS with any confidence by sequence comparison. "Early in 1991 we published our studies of the NLS of the Xenopus protein, nucleoplasmin (J. Robbins, S.M. Dilworth, R.A. Laskey, C. Dingwall, Cell, 64:61523, 1991). This analysis allowed us to define a bipartite NLS, in which two `patches,' or `clusters,' of basic amino acids constituting the recognition elements are separated by a `spacer' segment of 10 amino acids, the sequence of which is not important in nuclear targeting. We found a matching sequence in almost half the nuclear protein sequences in the database, but in less than 5 percent of the nonnuclear proteins. This immediately identified candidate sequences for investigation, and the analogy with Xenopus nucleoplasmin predicted the properties of these candidate sequences. Since then, the number of nuclear proteins in which bipartite NLSs have been mapped has increased steadily, and the function of a bipartite sequence has been shown to be regulated by the phosphorylation of adjacent amino acids (T. Moll, G. Tebb, U. Surana, et al., Cell, 66:74358, 1991). "One remarkable feature of the bipartite NLS is that longer spacer segments do not abolish nuclear localization. Perhaps the spacer segment is looped out to present the basic clusters to a receptor molecule in a precise orientation. It is clear that other classes of NLS exist, but the importance of this research is that one class is now clearly defined and provides a precise tool in the search for receptor molecules." (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : PHARMACOLOGY TY : RESEARCH (HOT PAPERS) PG : 16 A. Petros, D. Bennett, P. Vallance, "Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock," Lancet, 338: 15578, 1991. Patrick Vallance (Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London): "Endo theliumdependent vasodilatation was first described in 1980. Seven years later the mediator of this phenomenon was identified as nitric oxide. We have been interested in exploring the role of nitric oxide in the regulation of vascular tone in humans. Initial studies examined the effects of the nitric oxide synthase inhibitor NG monomethylLarginine (LNMMA) on human arteriolar and venous tone in healthy volunteers. "The finding that LNMMA substantially increased arteriolar tone indicated the importance of the L arginine:nitric oxide pathway in the control of blood flow and pressure in humans. Inevitably, overproduction of nitric oxide was then implicated in a variety of diseases associated with excessive vasodilatation. Studies in vitro and in animals demonstrated that products of infection (such as endotoxin) or inflammatory mediators (such as cytokines) caused expression of an inducible isoform of nitric oxide synthase in the blood vessel wall and the increased nitric oxide production accounted for the vasodilatation and hypotension associated with experimental models of inflammatory shock. "In order to assess the relevance of these observations to the clinical situation of septic shock, we gave low doses of LNMMA to two patients with severe sepsis complicated by profound hypotension refractory to conventional vasoconstrictor therapy. Inhibition of nitric oxide synthesis produced a dramatic increase in mean arterial blood pressure and systemic vascular resistance consistent with an important role for nitric oxide in septic shock. As a result of these studies, the possibility of using inhibitors of nitric oxide synthesis to treat septic shock is currently being explored. A fundamental mechanism of vascular changes in sepsis has been identified, but it remains to be determined whether the increased vascular tone produced by LNMMA is beneficial in terms of tissue perfusion and damage or patient survival." (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : ASTROPHYSICS TY : RESEARCH (HOT PAPERS) PG : 16 F.J. Rogers, C.A. Iglesias, "Radiative atomic Rosseland mean opacity tables," Astrophysical Journal Supplement Series, 79:50768, 1992. Forrest Rogers (Lawrence Livermore National Laboratory, Livermore, Calif.): "Opacity is a measure of how strongly matter impedes the flow of radiation. It plays an important role in determining the internal structure and observable properties of stars. Its quantification is essential for stellar modeling. In general, the more bound electrons an ion possesses, the greater its opacity. As a result of nucleosynthesis, the matter available to form young stars is richer in heavy elements than was the matter that formed old stars. Consequently, young stars have higher opacity in temperaturedensity regions where the heavy elements are only partially ionized, which affects their evolution. "Our paper provides extensive tables of the opacity of stellar matter. Prior to our work, most astrophysical modeling was done using tables produced at Los Alamos National Laboratory. Those tables were quite successful in explaning the main features of stars. Nevertheless, a number of observational properties of stars resisted theoretical explanation. For example, some of the largest and most luminous stars, known as b Cephei, are observed to vary in both size and luminosity over periods of a few hours. The mechanism responsible for this variability was sought unsuccessfully for more than 30 years. "We showed that, contrary to earlier estimates, a detailed treatment of the atomic physics of heavy elements provides an important source of opacity. This increases the mean opacity by factors of three to four at temperatures near 3 x 105 K and is just what was needed to cause pulsational instability in the bCephei stars. "The new opacity has led to several other successes. Using the earlier opacity data in astrophysical models of classical Cepheids and RR Lyrae stars, the mass could be adjusted to give the correct luminosity or the correct pulsation period, but not both. With the new opacity calculations this socalled mass discrepancy disappears. The predicted nonradial acoustic oscillation spectrum of the sun and the Liabundance in the Hyades cluster stars are now in better agreement with observation." (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: TOOLS & TECHNOLOGY ------------------------------------------------------------ TI : Supporting PCR, New Thermal Cyclers Find Diverse Laboratory Uses AU : CAREN D. POTTER TY : TOOLS & TECHNOLOGY PG : 17 Thermal cyclersor automatic temperature cyclershave not been around very long, but, having ridden to popularity on the coattails of the polymerase chain reaction (PCR), they are fast becoming essential laboratory instruments for many biological researchers. PCR is the DNA amplification process introduced in the 1980s that has revolutionized geneticsrelated research. PCR replicates a small amount of DNA in a series of heating and cooling steps and has been used in diverse research applications, including molecular biology, epidemiology, and paleontology. Reflecting the importance of the innovative process, PCR's inventor Kary Mullis was awarded this year's Nobel Prize in chemistry (see story on page 1). Thermal cyclers, for their part, have cut the time needed to run PCR by as much as twothirds. "In the 2 1/2 years I've been in this industry, I've seen the uses for PCR and the market for thermal cyclers expand dramatically," says Karen StuderRabeler, director of new product development at Coy Corp., a thermal cycler manufacturer located in Grass Lake, Mich. "PCR is used in anything from the study of fossil ambers to genetic engineering of corn." Thermal cyclers allow the PCR process to proceed automatically by subjecting the reagentsDNA nucleotides and a heattolerant polymerase, among othersto a userspecified heating and cooling sequence. In PCR, a thermal cycler heats samples to open the double helices of DNA, lets the temperature drop to bind primers, increases the temperature somewhat to build new strands, then heats up again to begin a new cycle. The development of thermal cyclers lagged behind that of PCR itself because the first enzymes used for PCR were thermolabile (unstable when heated, and therefore unusable after one cycle), explains Simon Foote, senior research scientist at the Whitehead Institute for Biomedical Research in Cambridge, Mass. PCR had to be done manually by placing sample tubes in water baths set at various temperatures, then adding new enzymes to the tubes after each heat cycle. "There was no way to automate the process with a device such as a thermal cycler until thermostable enzymes became available," Foote says. Such enzymes are now available, making the use of thermal cyclers a significant improvement over the manual method. The most significant benefits of thermal cyclers are unattended operation, faster throughput (since thermal cyclers are designed to reach target temperatures as quickly as possible), and enhanced temperature control to provide uniform heating and cooling over the entire body of samples. Capacity Range One of the most striking ways in which the thermal cyclers now available differ from each other is in the number of samples they are designed to process at once. At one end of the spectrum is a small, lightweight model called the MiniCycler, from M.J. Research in Watertown, Mass., that has a capacity of 16 0.5ml tubes or 25 0.2ml tubes. At the other end is what is commonly known as "the waffle iron" because the honeycomb pattern of its large well plates resembles the surface of that appliance. The official name of this instrument is the TC 1600 Thermocycler, and it is made by IAS Products Inc. of Cambridge, Mass. Depending on the configuration chosen by the researcher, it can process simultaneously up to 3,072 samples (16 microtitration plates times 192 wells). "The waffle iron was spun out of a custom project we did for the Whitehead Institute to help them automate their work on the Human Genome Project," says Steven Gordon, president of IAS Products. This thermal cycler is the most expensive on the market at $45,000, but, as Gordon says, "It's costeffective if you need that kind of throughput." The MiniCycler, by contrast, sells for $2,795. Four waffle irons equipped with sixteen 96well plates are in constant use at the Whitehead Institute, supporting the institute's work of mapping the complete human genome. "We average three runs per waffle iron per day," says Foote. The Whitehead lab is in the process of converting to well plates for even greater capacity, he adds. Some thermal cyclers, the waffle iron included, offer researchers the ability to divide the instrument's capacity into independently cycling sections. For example, the waffle iron can process four different heating and cooling profiles, one for each quadrant of the device. A smaller, more affordable model called the TwinBlock System from Ericomp Inc., San Diego, has the ability to run two different cycling programs simultaneously. David Brown, a research coordinator who works with a TwinBlock in a University of Georgia in Athens genetics lab, praises this feature. "Aside from the confidence that the instrument reliably produces the temperatures you expect from a particular program, the ability to run two independent programs was a real selling point," he says. "Often two people in our lab run different programs on the TwinBlock. If you had another machine with the same capacity but only one cycling program, others would have to wait until the first person was finished." Heating And Cooling Thermal cyclers must reach appropriate temperatures quickly and provide a uniform temperature over all samples. To achieve these objectives, manufacturers of thermal cyclers have turned to different technologies for heating the samples and then cooling them down. Most, but not all, use an electrically heated element to deliver heat to a metal plate (usually aluminum) that surrounds the sample tubes. For cooling, several approaches are used. Some models do not offer active control when it comes to cooling, they simply let excess heat escape into the ambient air. "These are the cheapest to manufacture, but they can have uniformity problems," says John Hansen, director of special projects at M.J. Research. Another method of cooling is that used by PerkinElmer, the largest manufacturer of thermal cyclers. This approach relies on a vapor compression heat pumping, which is similar to a typical refrigeration unit. Other devices such as the waffle iron use water for cooling the samples. "You can get much more efficient cooling out of water because there is a physical mass that absorbs the heat and pulls it away," says Gordon. Efficient cooling is a must for a unit that generates as much heat as the waffle iron. Because it handles such a large number of samples, this device requires a tremendous amount of power. "When you start multiplying things by 16 [the number of microtitration plates in the waffle iron], you start getting to numbers like 200 volts times 70 amps," says Gordon. "This becomes a potentially dangerous device." (Compare this with the requirements of a clothes dryer or oven, about 10 amps each.) IAS Products built five redundant safety systems into the waffle iron, Gordon adds. Another technology used in thermal cyclers is an electronic process called the Peltier effect. Depending on the direction of the electrical current in a Peltier unittwo ceramic outer layers sandwiching an inner layer of semiconductor materialit can actively transport heat either into or out of a sample block. As current passes through the semiconductor material, electrons migrate from one surface of the sandwich to the other, dragging a small amount of heat with them. This effect can cause a temperature differential between the top and bottom of the unit of as much as 70 degrees C. Reversing the flow of the current reverses the flow of heat as well. Discovered in 1834 by Jean Peltier of France, this electronic means of pumping heat remained a lab curiosity until the 1930s, when Maria Telkes, a solidstate physicist at Westinghouse Research Laboratories, discovered how to use a crystal instead of a bimetallic junction in the device, according to Hansen of M.J. Research. "Telkes's findings increased the efficiency of Peltier units an order of magnitude." Today's Peltier units are efficient semiconductor heat pumps that involve no moving parts or chlorofluorocarbons. M.J. Research and Coy Corp. introduced thermal cyclers based on the Peltier effect in 1988. Thermal cyclers from M.J. Research have bidirectional Peltier control (that is, the Peltier effect is used for both heating and cooling); models from Coy use the Peltier effect only for cooling. Initially, the materials used in Peltier units proved problematic for thermal cycling applications. "They were designed for steadystate conditions where the temperature doesn't vary," says Hansen. "If you put these modules into a thermal cycler they wouldn't last very long, which is why many manufacturers have shied away from them. We've devoted years of research to building better Peltier units specifically for a temperature cycling process." Using the Peltier effect for both heating and cooling makes thermal cyclers from M.J. Research highly adaptable to field conditions. One research team took MiniCyclers to the McMurdo Sound region of Antarctica to investigate genetic diversity in moss. "Preliminary isozyme and morphological studies gave no conclusive clues, but with our little MiniCyclers we were able to conduct DNA amplification at two sites in the field," says Dieter Adam, principal investigator from the University of Waikato in New Zealand. "A little gas generator could run both a MiniCycler and a gel box simultaneously and the speed of the machine allowed us to run several amplifications a day." In Situ Amplification DNA amplification was, until recently, always performed in tubes. Although this method is unquestionably a powerful tool for molecular biologists and related researchers, those who deal with whole organisms often need to know the location within the cell of the DNA sequence of interest. With traditional DNA amplification procedures, they may know that there was at least one template in the tube when they started the process, but not where it came from. With in situ DNA amplification, sections of tissue are put on glass slides and the process is carried out while the DNA is still inside the cell. "This technique has not been perfected, and there are some who doubt its ultimate validity, but others consider in situ DNA amplification to be the most significant breakthrough in molecular biology since the development of PCR," says Hansen. Since in situ amplification still requires temperature cycling, thermal cyclers can automate the procedure in much the same way they automate the process when it takes place in tubes. Several vendors have already adapted their instruments to handle slides. With these devices, PCR can now be performed in morphologically intact cells, making the process more useful in applications such as clinical diagnostics, particularly virology, histopathology, and detection of genetic mutations. For a detailed protocol for in situ amplification, see O. Bagasra, et al., Journal of Immunological Methods, 158:13145, 1993. Also, Coy Corp. offers a technical brochure on the procedure. Even before these in situ units became available, innovative researchers were taking matters into their own hands and modifying their traditional tube thermal cyclers with aluminum foil to accommodate slides. Caren D. Potter is a freelance science writer based in McKinleyville, Calif. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ------------------------------------------------------------ TI : THERMAL CYCLER VENDORS TY : TOOLS & TECHNOLOGY PG : 19 The following suppliers are among those offering thermal cyclers for use in PCR related experiments. Applied Biosystems Division of PerkinElmer Corp. 850 Lincoln Center Dr. Foster City, Calif. 94404 (415) 5706667 Fax: 5722743 (800) 5457547 (for sales information and ordering) Coy Corp. 14500 Coy Dr. Grass Lake, Mich. 49240 (313) 4752200 Fax: (313) 4751846 Ericomp Inc. 6044 Cornerstone Court West Suite E San Diego, Calif. 92121 (619) 4571888 Fax: (619) 4572937 IAS Products Inc. 142 Rogers St. Cambridge, Mass. 02142 (617) 3543830 Fax: (617) 5479727 M.J. Research Inc. 149 Grove St. Watertown, Mass. 02172 (617) 9242266 Fax: (617) 9242148 (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: PROFESSION ------------------------------------------------------------ TI : Adjunct Science Faculty Contribute Valued Expertise To Universities AU : RICKI LEWIS TY : PROFESSION PG : 20 Why would a scientist take an adjunct faculty positiona job that pays little, or sometimes even nothing at all? Why would an academic institution, already burdened with keeping track of its own faculty, reach out to industry to solicit the participation of corporate researchers as adjunct professors? Scientists and academic administrators say that both the researcher and the institution have a lot to gain from such appointments: Adjunct professorships allow a university to make the most of scientists' skills and knowledge, while giving researchers from a range of workplaces access to the academic life. "Adjunct appointments give scientists much broader areas in which to work, so that expertise is spread out," says geneticist William H. Stone, a distinguished professor at Trinity University and an adjunct professor at the University of Texas and the Southwest Foundation for Biomedical Research, all based in the San Antonio area. "Being an adjunct allows versatility, expanding your horizons, specifically if you are at an undergraduate institution where there is only one immunologist, one physiologist, one geneticist[not] a megauniversity, where there might be 20 people specializing in one area," says Stone, who was a professor of biology at the University of Wisconsin, Madison, for 32 years before coming to Texas. >From a university's standpoint, adjuncts fill gaps in course offerings. From a scientist's stance, a change in routine from a fulltime industrial, government, or museum workplace is often most welcome. "There's the possibility of having students, and of associating with a group of people engaged in teaching and research," says William Culberson, a professor in the botany department at Duke University in Durham, N.C., and former chairman of the department. Most adjuncts teach at this second home, but some agree to an adjunct association to make use of the university's research resources. An individual scientist like Stone may have adjunct ties to more than one institution. Stone says he chose San Antonio "because it gave me the opportunity to wear three hatsteaching at a very sophisticated, elegant undergraduate institution, and [doing] research at the medical school and foundation." Often an adjunct professor network weaves together a scientific community. For example, academic institutions in the capital district of upstate New Yorkthe State University of New York in Albany, Union College in Schenectady, and Rensselaer Polytechnic Institute in Troybenefit from the expertise of adjuncts from Albany's Wadsworth Center for Laboratories and Research (part of the state department of health), General Electric's Research and Development Center in Schenectady, and Virogenetics Corp. of Troy, among others. Assignments Vary The degree of commitment that comes along with the title of adjunct can vary greatly. An adjunct may be a professor in name only, lending the prestige of name recognition, but requiring no inclass time. This is the case for the National Institutes of Health's Robert Gallo, who is an adjunct professor at Cornell University in Ithaca, N.Y. Gallo "is listed as an adjunct professor of veterinary microbiology, immunology and parasitology, and . . . has an assigned office in the Veterinary Research Tower here, but a phone number that probably rings at the NIH," says Roger Segelken of Cornell's News Service. Another example of a situation in which an adjunct doesn't teach is Stone's affiliation at the Southwest Foundation for Biomedical Research, which is strictly researchoriented. K. Douglas Nelson, a professor of geology at Syracuse University in New York, is an adjunct associate professor of geological sciences at Cornell, where he is continuing research begun as a graduate student and postdoc at Cornell's Institute for the Study of the Continents. "When he does something interestinglike obtain a profile of the mountains of Tibetwe public relations types claim him as one of our own, and mention in tiny type that he is also connected to another institution," says Cornell's Segelken. Many adjuncts are industry, government, or museum scientists who teach occasional courses at nearby colleges or universities, usually on a topic that the regular faculty do not wish to teach, or do not have the precise expertise to teach. Still other adjuncts are scientists in between permanent positions, or those accompanying a spouse who has a faculty appointment. They might be in search of something to do while job hunting, or may regard an academic connection, albeit temporary, as a foot in the door to a more permanent position. These faculty standins may carry quite a loadtwo, three, or even four courses a semester. Adjunct affiliations also help define the work of scientists whose expertise doesn't neatly shoehorn into traditional departments. This is the case for Douglas R. Hofstadter, an expert in cognitive science at Indiana University in Bloomington, who is currently on sabbatical in Spain. At Indiana, he is a professor of computer science, a professor of cognitive science (although there is no such department), and an adjunct professor in the departments of psychology, philosophy, and the history and philosophy of science. Students taking his courses receive credit in whichever department the course is listed in. Hofstadter's numerous titles reflect the fact that his field, cognition, is part psychology, part computer science, and part philosophy. Such an arrangement regular faculty with adjunct status in related departments within the same institutionis not uncommon. On Loan From Museums Adjunct professors from museums represent a good symbiosis, as museum scientists can fill gaps in an academic department and offer students diverse research opportunities. The department of botany at Duke, for example, has tapped into the expertise and enthusiasm of the Smithsonian Institution in Washington, D.C., to broaden graduate students' experience. "A number of plant biologists at the Smithsonian are very active in evolutionary biology, and we have asked selected ones of them to be adjunct professors at Duke," says Culberson. "As such, they can direct graduate students in research." One such Smithsonian scientist now very happily in front of the classroom is paleobotanist Vicki Funk. "I felt the need to be involved more with students and stay connected with the university scene," she says. "You can get isolated being in a lab all the time and only talking to people who do what you do." Funk says she was thrilled to be offered adjunct status at Duke because of the school's excellent program in plant systematics, to which she feels some departments give short shrift in their search for more molecular biologists and the funding they bring. Funk at first made the fourhour trek to Duke from Washington to give frequent seminars and serve on graduate student committees. Then, when a sabbatical leave came up, she gladly came to Durham, where she now teaches a graduate course in the systematics of flowering plants. "There was no money to start a tropical collection here at Duke, and no money at the Smithsonian for starting a graduate program," she says. But courses offered by Funk and three Smithsonian colleagues are helping to expose students to professionals in the field. "Hopefully, in the future, systematics can have more of these kinds of collaborative programs between universities and zoologists and botanists from museums," she says. Norton Miller is another museum paleobotanist who is enthusiastic about his university connection. Miller travels throughout the Northeast and Midwest to obtain millionyearold fossilized plants, which he studies at the New York State Museum in Albany. He teaches a course in plant taxonomy and morphology at nearby SUNYAlbany. "Three years ago, some undergraduates asked for additional courses on organismal biology," says Miller. "One colleague from the museum, Bob Daniels, had taught a successful course in icthyology at the university, and we were persuaded by that. It was a way to get a highly specialized faculty member there." Both Funk and Miller see their adjunct appointments as ways for graduate students to conduct research at their museums. Alternative Lifestyles An adjunct appointment can be a lifeline to academia for scientists who have wandered off the tenure track. New parenthood and adjunct stints are particularly compatible, scientists say. Beth Burnside, for example, taught undergraduate biochemistry at the University of Maryland when having children and between permanent positions in the pharmaceutical industry. "Being an adjunct is pretty amenable to a family situationI could work at home and go in to give lectures and hold office hours," she says. Burnside has just resolved her child care dilemma, and she has accepted a position as an assistant director of pharmaceutical development at Pharmavene Inc. in Gaithersburg, Md. For Alexis Burton, becoming an adjunct allowed him to maintain his university ties when he had to retire from his regular faculty appointment a decade ago for health reasons. Burton taught basic science to medical students at the University of Texas Health Science Center. He no longer teaches, but makes frequent use of the parking permit that comes with his adjunct status so he can use the library, attend seminars, and continue to interact with his colleagues. And scientists who have enjoyed successful stints as nontenuretrack faculty can maintain connections by becoming adjuncts. Industrial Links An industrial scientist can give students a taste of the real world that isn't quite the same as traditional course fare. In return, he or she networks with basic researchers in a manner that can lead to fruitful collaborations. The relationship between the Glaxo Research Institute in Research Triangle Park, N.C., and the University of North Carolina, Chapel Hill, illustrates the mutual benefits possible from an academicindustrial alignment. The GlaxoUNC collaboration began when the United Kingdombased company sought temporary laboratory space in Chapel Hill, and borrowed a UNC undergraduate lab for four years until its new facility was built. While on campus, Glaxo researchers forged important relationships with professors. "We got to know the faculty and their research projects, and can support their work if it meshes with what we do," says Dan Sternbach, principal research investigator at the Glaxo institute, who holds an adjunct appointment at UNC. "The arrangement is a pipeline to the company. University people work here in the summers, and we teach courses at the university. Other things go along with it, too. For example, Glaxo and UNC sponsor the Glaxo UNC Frontiers in Chemistry symposium, inviting speakers spanning the biological to the physical sciences." Rewards Are Not Monetary Despite their great value, adjunct professors aren't paid much, if anything. Beth Burnside says her $5,000 for teaching biochemistry was paltry compared to her former salary as a research scientist at Johnson & Johnson of Raritan, N.J., where she worked in 1991 and 1992. But actually, this is at the higher range of adjunct pay for those who do not have a concurrent fulltime position elsewhere. Percourse compensation ranges from $2,000 to $6,000, according to veteran adjunct teachers. Adjuncts on loan from industry, a museum, or government usually re ceive no extra pay. Says Funk, "I don't get paid, I just do it." One research chemist at General Electric's Research and Development Center is paid $4,000 for teaching a graduate course in inorganic chemistry at Rensselaer Polytechnic Institute, but in order to have time "off" to teach, he's agreed to turn over the check to GE. And, of course, there is no job security for a position that is semesterbysemester. An adjunct at a large state university was lulled into "real job" complacency because she had taught one or two courses a semester for six years, tackling the large, nonsciencemajor courses that many regular faculty avoid. But when the state ran into budget problems, and as a result regular faculty were given heavier teaching loads, she received a "termination notice" in her campus mailbox. The use of adjunct and other nontenuretrack faculty is a source of concern for some academics. According to a report entitled "The Status of NonTenureTrack Faculty" by the American Association of University Professors (Academe, 79[4]:3946, JulyAugust 1993), "the growth of nontenuretrack faculty erodes the size and influence of the tenured faculty and undermines the stability of the tenure system. The large numbers of faculty who now work without tenure leaves academic freedom more vulnerable to manipulation and suppression. The professional status of faculty suffers when so many are subject to economic exploitation and demeaning working conditions inconsistent with professional standards." Lack of a hefty paycheck and job security, however, are of little concern to most adjuncts, because their motivations aren't monetarythe attraction of an adjunct position is interaction with people, particularly students just beginning their scientific careers. And the regard many adjuncts have for their students is refreshing. "I love graduate students. They are so committed and interested," says Funk. Adds Stone, "I immensely enjoy stimulating work with undergraduates, training them in science. Sitting right beside me now is one undergraduate who enjoys research so much that he has decided to pursue an M.D./Ph.D. That makes me feel really good." Ricki Lewis, an adjunct assistant professor of zoology at Miami University (Oxford, Ohio) and of biology at the State University of New York, Albany, writes college biology texts. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: PEOPLE ------------------------------------------------------------ TI : Peptide Chemist, Ruth Nutt, joins Corvas AU : PHIL BECK TY : PROFESSION (PEOPLE) PG : 22 Ruth F. Nutt, a peptide chemist and former senior scientist at Merck & Co. Inc., Rahway, N.J., has joined Corvas International Inc. in San Diego as director of chemistry. In 31 years at Merck, Nutt, 53, was responsible for the development of five major drug candidates, including one now in clinical trials. In addition, she was on the first team to chemically synthesize an enzyme and led the team that first synthesized the HIV protease, preceding recombinant production of the enzyme by about a year. Much of Nutt's work at Merck involved antithrombosis and antiinflammatory research. Among the drug candidates she developed is an anticlotting drug, GPIIb/IIIa antagonist, now in clinical trials. In her newly created post at Corvas, she will help develop the new company's drug leads in those areas. She took early retirement from Merck to join Corvas, she says, because "I felt I could use some of the expertise I developed at Merck even more in a smaller setting, where a lot of people are much younger, and may not have as much experience." In the late 1960s, Nutt was a member of the Merck team that was the first to chemically synthesize an enzyme. While the enzyme had no particular biological purpose, Nutt recalls, the endeavor was an attempt to test a synthesis method developed by Merck scientists (R.G. Strachan, W.J. Palveda, R.F. Nutt, et al., Journal of the American Chemical Society, 91:503, 1969; S.R. Jenkins, R.F. Nutt, et al., JACS, 91:505, 1969; R. Hirschmann, R.F. Nutt, et al., JACS, 91:5078, 1969). She notes that a team at Rockefeller University was producing the same enzyme at about the same time, work that eventually led to the Nobel Prize in chemistry for R. Bruce Merrifield in 1984. A 1980s teamincluding her biochemist daughter Elkathat Nutt led at Merck chemically synthesized the HIV protease, an essential component of the virus that makes it propagate and become infectious (R.F. Nutt, et al., "Chemical synthesis and enzymatic activity of a 99residue peptide with a sequence proposed for the human immunodeficiency virus protease," Proceedings of the National Academy of Sciences, 85:712933, 1988). In contrast to the previous synthesis, the HIV effort was an attempt to develop inhibitors to the enzyme, and, in fact, Nutt says, at least one inhibitor candidate developed from the work has begun clinical testing. Nutt says that chemical synthesis was not her team's first option, but using the live virus was too dangerous; the group had also tried to produce the molecule through recombinant methodsa procedure that was accomplished a year after her team's synthesisbut was unsuccessful. Nutt joined Merck as an assistant chemist after receiving her bachelor's degree in 1962 from the University of New Mexico. She held senior research chemist and research fellow positions before obtaining her Ph.D. from the University of Pennsylvania in 1981, and held the positions of senior research fellow and senior investigator before becoming senior scientist in 1989. She is the author or coauthor of more than 100 papers, and her name appears on 20 patents. Nutt says that she has never felt constricted by doing science in an industrial setting: "I've gotten an awful lot out of my research in industry. I've been very lucky. I've been in many projects where you could really do some very nice basic science. That was extremely satisfying." Nutt says that women scientists have had to perform even better than their male counterparts to succeed. She says that if she had one piece of advice she could give to women researchers starting out, it would be: "You have to make sure that you do very good research to have a good basis to stand on, totally independent of who is judging you. "You have the confidence, you know that whatever you're doing, this is really good . . . your research can stand on its own under any circumstances. That really gives you a security that nobody can take away from you." Phil Beck (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: OBITUARIES ------------------------------------------------------------ TI : Severo Ochoa, TY : OBITUARY PG : 22 Severo Ochoa, a biochemist who won the Nobel Prize in physiology or medicine for his discovery of an enzyme that synthesizes RNA, died November 1 in Madrid of pneumonia. He was 88. Ochoa made his discovery in 1955, and shared the 1959 Nobel with his postdoctoral student, Stanford University biochemist Arthur Kornberg, who was cited for discovering another bacterial enzyme that synthesizes DNA. In 1956, Ochoa, collaborating with University of California virologist Wendell M. Stanley, created an artificial virus in a test tube, using RNA material. Born in Spain, Ochoa entered Madrid University Medical School in 1922 at the age of 17, and received his medical degree in 1929, the only academic degree he ever pursued. After working in laboratories at Madrid University, Heidelberg, and Oxford University, he emigrated to the United States in 1941 and worked for a year at Washington University in St. Louis before moving to New York University. He became a full professor at NYU in 1946, and was chairman of the department of biochemistry from 1954 to 1976. He was also a member of the Roche Institute of Molecular Biology in Nutley, N.J., from 1976 to 1985. A naturalized U.S. citizen, Ochoa retired in 1986 and returned to Spain. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: OBITUARIES ------------------------------------------------------------ TI : David A. Hungerford, TY : OBITUARY PG : 22 David A. Hungerford, a cancer researcher who, while still a graduate student, described the wellknown Philadelphia chromosomethe first chromosome abnormality consistently found in cancerdied November 6 in Jenkintown, Pa., of lung cancer. He was 66. At the time of his death, Hungerford was a senior member, emeritus, at the Institute for Cancer Research at Fox Chase Cancer Center in Philadelphia. He joined the institute as a research assistant in 1951, after receiving his bachelor's degree from Temple University. In 1959, working with leukemia cells provided by University of Pennsylvania faculty member Peter C. Nowell, Hungerford found that chronic granulocytic leukemia was linked to a shortened arm of chromosome 22. It is not inherited but remains throughout the course of the leukemia, even when the cancer is in remission. The Philadelphia chromosome has been linked to eight types of cancer, tumors of the brain and soft tissue, mental retardation, heart defects, and other disorders. It was first discussed in an abstract in Science (P.C. Nowell, D.A. Hungerford, "A minute chromosome in human chronic granulocytic leukemia," Science, 132:1497, 1960). Hungerford's work called attention to specific genetic changes underlying some cancers, and helped pave the way for the identification of oncogenes. He received his Ph.D. in zoology from Penn in 1961. The latter part of his career was spent studying the structure and function of human meiotic cells in males. In 1970, he described how the chromosome associated with Down's syndrome is derived. Hungerford became a senior member at Fox Chase in 1969. He retired from Fox Chase in 1982, slowed by multiple sclerosis. (The Scientist, Vol:7, #23, November 29, 1993) (Copyright, The Scientist, Inc.) ================================

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