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THE SCIENTIST VOLUME 7, No:21 NOVEMBER 1, 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 *** *** NOVEMBER 20, 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 NEUROSCIENCE CAREER OUTLOOK: Stunning research advances have swelled the ranks of neuroscientists. But tight federal funding and wariness on the part of industry about the economy in general has made job prospects for these new brain researchers sparse--at least in the short term PAGE 1 STEWART-FEDER UPDATE: The long-term future for Walter Stewart and Ned Feder, two National Institutes of Health scientific fraud investigators removed from their laboratories and transferred elsewhere in the agency, is still being negotiated, though two powerful United States senators have recently lent support to their fight for reinstatement to their former positions PAGE 1 MUSEUMS AS CLASSROOMS: The Howard Hughes Medical Institute, known for its support of productive scientists, also offers an innovative program aimed at helping to ensure the next generation's curiosity and wonderment with science--funding education programs developed by local science museums, with an emphasis on attracting young women and minorities PAGE 1 BUILDING MOMENTUM: The National Science Foundation has awarded $37.1 million to 56 colleges and universities to repair their deteriorating research facilities in an attempt to make a dent in what NSF estimates to be a $10 billion to $12 billion "problem" with such aging infrastructure nationwide PAGE 3 PATENT PROBLEMS: The patenting of scientific discoveries may be necessary in order to protect some scientists' intellectual property, says British immunologist Cesar Milstein; but he also cautions that the practice of patenting is often unfair and actually dangerous to the health of curiosity-driven research PAGE 11 COMMENTARY: A recent photo in The Scientist .MDNM/showing Hillary Rodham Clinton and Mary Lasker, founder of the Lasker Foundation's medical research awards, is symbolic of the vital role basic research can play in providing health care to all Americans, a message that should not be lost on Congress or the public, says Eugene Garfield PAGE 12 CELLULAR MECHANICS: Scientists are converging from many disciplines in an attempt to unlock the secret of "molecular motors," the complex mechanisms that drive cells. The task is daunting, and funding is described as "seat of the pants" PAGE 14 HOT PAPERS: A cancer researcher discusses her report describing an antibody that allows examination of p53 expression in solid tumors PAGE 15 DIGITAL MICROSCOPY: In many areas, film-based photography is gradually being replaced by digital imaging amenable to computer manipulation, transfer, and storage. In microscopy, especially, new digital cameras and scanners are providing ever-improving image quality, as well as ease and economy of use PAGE 19 BRAIN TRUST: Love of learning unites the prestigious membership of the American Philosophical Society, the U.S.'s oldest honor society, which celebrates scholarship in the sciences, arts, and humanities--and whose ranks include some of America's premier scientists PAGE 21 DARYL CHUBIN has been appointed division director for research, evaluation, and dissemination in the education and human resources directorate of NSF PAGE 22 NOTEBOOK PAGE 4 CARTOON PAGE 4 LETTERS PAGE 12 CROSSWORD PAGE 13 OBITUARY PAGE 22 SCIENTIFIC SOFTWARE DIRECTORY PAGE 30 (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Neuroscience Is A Booming Field--For Neuroscientists With Jobs, That Is Exciting advances in this discipline are attracting far more researchers than academic and corporate labs currently can employ AU : SUSAN L-J DICKINSON TY : NEWS PG : 1 Working neuroscientists can take heart: Their discipline is booming. Exciting advances in their field, and a rapidly broadening environment for the application of these advances, have placed their specialty at or near the forefront of life science endeavor during the past decade or so. Membership in the Society for Neuroscience has nearly doubled during recent years. At this year's meeting of the organization-- November 7-12 in Washington, D.C.--attendees will be bombarded with a packed agenda of seminars, short courses, speeches, workshops, product demonstrations, and a wealth of other events. The multiplicity of offerings attests to the high level of energy, activity, and fruitful achievement characterizing the discipline at this point, midway through the so-called Decade of the Brain. But what about the non-working neuroscientists--the advanced- degree-holding men and women who will be at the meeting primarily to find work? For them, prospects aren't all that bright. According to trends observed by the society's placement service, work-seeking neuroscientists are likely to confront the fact that their numbers are dramatically on the increase--but job availability is discouragingly on the decline. Currently, says David Bredt, who graduated from Johns Hopkins University this past May with an M.D. and a Ph.D. in neuroscience, "the job market is extremely competitive. Many of my colleagues have applied to more than 50 places." Ross Gibson, director of human resources for Cambridge Neuroscience Inc. in Cambridge, Mass., concurs. "We've had no trouble finding people we want," he says. "If we advertise nationally, we get up to 200 applicants per position; 15 to 20 percent of these meet our exact qualifications." But industry experts say that as neuroscientists spend more time copying their resume and interviewing with prospective employers, they can take heart in the knowledge that their employment prospects are better than those of their scientific colleagues in many other fields. Industry watchers say that biotech companies are still being founded to cash in on neuroscience breakthroughs, pharmaceutical firms are preserving neuro- science as they pare down their research and development budgets, and granting agencies are making a concerted effort to invest in neuroscience during the '90s' "Decade of the Brain" effort. "Neuroscience is getting lots of publicity and money, so this period is probably not as painful for us as for scientists in other areas," observes Christine Livingston, a Ph.D. graduate of the neuroscience program at the Marine Biomedical Institute in the University of Texas Medical Branch at Galveston. "The glory days of two decades ago are past," adds Jim Blankenship, president of the Association of Neuroscience Departments and Programs and director of the neuroscience program at Galveston, referring to a period of expanded hiring of scientists in general and neuroscientists in particular. "But the job market [for neuroscientists] is reasonably stable; there is no reason to panic." Market Factors Statistics compiled by the placement service at each of the past five Society for Neuroscience meetings reveal a depressing trend for those entering the job market (see charts on page 7): The number of candidates registering for interviews has increased sharply, while the number of position descriptions posted has leveled off, and the number of employers registering to interview candidates has decreased. The result is that, while the average number of interviews each employer conducts at the meeting has increased, the average number of interviews each candidate garners has decreased. Several factors--involving both the supply of neuroscientists and the demand for them--have converged to create this current tight market, observers say. The most significant of these factors is the sharpness with which the supply of neuroscientists has increased: The Society for Neuroscience reports that its membership has grown in the past five years from 11,690 in 1987 to 20,415 in 1992. A small portion of this increase can be attributed to the burgeoning number of Ph.D.'s being awarded in neuroscience. Yet it is ironic that one of the most valuable assets of neuroscience--its interdisciplinary nature--is also the primary reason there are so many scientists competing for a few jobs, neuroscientists say. "Scientists are converging from all different backgrounds into this field: pharmacology, molecular biology, protein biochemistry, immunology, and physiology," says Ted Dawson, an M.D./Ph.D. who has just garnered a joint assistant professorship in the departments of neurology and neuroscience at Johns Hopkins. "Neuroscience is probably the most interdisciplinary of any of the biomedical sciences," concurs U. Texas' Blankenship. "Molecular biologists are finding that just being able to clone genes is no longer that unusual or marketable a skill. So they are starting to focus, and the developments in neuroscience are probably more exciting, more plentiful, and more rapidly moving than in any other field of biomedical research," says Solomon Snyder, director of the neuroscience program at Johns Hopkins. "So many people are entering the field," he adds, "that NIH [National Institutes of Health] funding for neuroscience is being overwhelmed." Academic Dilemma Indeed, heightened competition for grant money--almost a prerequisite for staying in an academic department or obtaining permanent appointment--is making the academic sector of the job market tightest for neuroscientists. "Everyone is scared about the grant situation," says Blankenship, and a brief glance at some statistics from NIH reveals why. The success rate of grant applications to the National Institute of Neurological Disorders and Stroke (NINDS), the source of nearly one-third of the $1.9 billion NIH granted to Decade of the Brain projects during fiscal year 1993, has plummeted, from 39.6 percent five years ago to 21.9 percent in 1993. One reason is that the number of applications is up, from 1,583 in 1991 to an estimated 1,802 this year. And Constance Atwell, NINDS director of extramural programs, notes that the institute's annual budget increase is not keeping pace with either this increase in the number of applications or the average size of grant awards. According to students as well as professors of neuroscience, this situation is creating a lot of stress in academic labs throughout the country. And Bredt, who will be moving to the University of California, San Francisco, in January as an assistant professor of neuroscience, says that getting a job doesn't necessarily relieve the pressure: "Unless your research is successful and you are lucky enough to have it be of interest to a granting agency, then you can't even stay in a department." "You are much more marketable in looking for a job if you have a grant," Livingston agrees. She received her Ph.D. from the University of Texas, Galveston, in 1987, and it was only three months ago, after two postdoctoral fellowships, that she returned to a position on the same campus as assistant professor in the department of humanities and basic sciences. In her words, an assistant professorship in a liberal arts department is an "unorthodox position" for a scientist who wants to do serious work in the lab. She spends much of her time teaching undergraduate students, and has limited start-up funds and lab space for her own work. She says that some friends advised her against taking this position, cautioning that teaching responsibilities would swallow up her research time. Others felt that she was selling out. "But [the job market for neuroscientists] was a pretty threatening environment," she says. "And I was in a very scary position, especially as a single parent and the sole provider for my family." Now, Livingston says, she is finding her position challenging and interesting. And she is confident that, with colleagues and collaborations still in place on campus from her graduate school days, her research won't suffer. Moreover, bad as her experience has been, she agrees that in another field of research it could well have been worse. "[Undergraduate] biology departments love to have neuroscientists on their faculty," she says. "Big strides have been made in neuroscience . . . and they want to milk the field." With a job market that, at best, can be described as stable, why do many neuroscientists feel fortunate? "Neuroscience is exciting right now," says Dawson. Indeed, recent advances in molecular biology are enabling scientists to clone receptor proteins and identify subreceptors that no one knew existed a decade ago. Developments in neurophysiology are allowing scientists to record activity of a single ion channel. The gene for Huntington's disease has been identified, and it is now known that amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) is caused by the loss of a simple enzyme. "A whole new category of drugs is being developed to treat previously untreatable neurodegenerative diseases," notes Kayla Paul, director of international clinical research at Hoffmann-La Roche Inc. in Nutley, N.J. And because America's aging population is making neurodegenerative diseases more prevalent, industry's investment in neuroscience is expanding. "Since there are new tools and new avenues for therapeutic intervention, there is more money being spent in neurology and, especially, neuropharmacology," observes Thomas L. Copmann, assistant vice president for biotechnology and biologics at the Washington, D.C.-based Pharmaceutical Manufac- turers Association. "The pharmaceutical industry is having a renaissance of interest in neuroscience," adds Johns Hopkins' Snyder. "And of course, this translates into jobs." Commitment To Research Although recent layoffs and job cuts at major pharmaceutical firms have gotten a lot of media attention, several of these companies indicate that they are not backing away from their R&D commitments in the neuroscience area. Merck & Co. Inc. in Whitehouse Station, N.J., reports that it hired 18 people in the neurosciences in 1993, and plans to continue this expansion in 1994, hiring some 10 to 15 more. SmithKline Beecham, Philadelphia, won't release hiring numbers, but confirms that it has hired some Ph.D. neuroscientists in 1993, and that neuroscience continues to be one of its core programs. Warner- Lambert Co. public relations representative Lisa Wilder reports that her Morris Plains, N.J.-based company launched Cognex, the first United States Food and Drug Administration-approved drug for Alzheimer's disease, in early September. "Cognex is the most important drug in the history of our company," she says. "Neuroscience is a big growth area for us." And the picture at smaller biotech firms that specialize in neuroscience is also one of cautious expansion. Neurogen Corp. of Branford, Conn., hired 15 researchers (including six Ph.D.'s) during the past year, and estimates it will make five to 10 new hires in 1994. Regeneron Pharmaceuticals Inc., Tarrytown, N.Y., hired 25 new employees in 1993, and projects 1994 new hires will number about 50. Cephalon Inc. of West Chester, Pa., has expanded the ranks of its Ph.D.'s and M.D.'s by 20, an increase of 31 percent since last December, and plans to continue hiring throughout the coming year. Cambridge Neuroscience Inc. hired 10 neuroscientists in 1993, and has plans to hire six more in 1994. And Raymond Bartes, senior vice president of neurobiology at Alkermes Inc., also in Cambridge, has hired eight neuroscientists in the last eight months, and says that positions are still open at his company. This expansion is being fueled not only by the normal growth of young companies, but also by the unprecedented number of promising compounds these neuroscience companies are working on, according to analysts in the biotechnology research division of Merrill Lynch & Co. in New York. As a group, these firms have at least 28 neuroscience-generated products (neurotrophic factors, neurotrophins, and other neurology products) in development. Many of these, according to Merrill Lynch, address previously untreatable neurological disorders, such as Alzheimer's, ALS, Parkinson's disease, stroke, and spinal cord injuries. Despite this increased activity, all of these companies are currently operating under economic and political pressure. Consumers and investors are spending less money, and the potential results of the current national debate on health care have top managers at biomedical corporations concerned. Guarded Optimism "We are in an anomalous situation now," says John Groom, president and chief executive officer of San Carlos, Calif.-based Athena Neurosciences Inc. "We are making good scientific progress in a negative [economic] environment. As a result, I am very optimistic about our technology, but very pessimistic in terms of how to pay for it." Nevertheless, Groom says, there currently are openings for Ph.D.'s at Athena--positions that represent expansion, not just replacement. Until some of these issues are resolved, neuroscientists counsel their job-seeking colleagues to be patient. Christine Livingston recalls the advice of a professor that she has found to be true: "Just stick it out and you'll make it." Blankenship also urges calm and perseverance. "The short term looks a little spooky," he acknowledges. "But openings are there, and in the long term, things should cycle back around." Susan L-J Dickinson is a freelance writer based in Philadelphia. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : NIH Fraud Investigators Take On New Roles At Agency, But Remain Determined To Resume Sleuthing Activity Stewart and Feder, with support from senators, continue efforts to have their controversial reassignments reversed AU : FRANKLIN HOKE TY : NEWS PG : 1 Walter Stewart and Ned Feder, the two National Institutes of Health scientists whose fraud-busting investigations were quashed by forced reassignments last April, have now--after a summer-long resistance campaign--taken up their new positions. Feder is a grants reviewer in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Stewart is a science writer in that institute's Office of Program Planning and Evaluation, writing summaries of the institute's research activities. But while the pair may have acceded to their employers' demands for now, their long-running, controversial case is far from settled. Determined to resume their investigative roles, they have proposed creating an Office of Whistleblower Assistance at the institutes, to be staffed by them. They have also conducted workshops on their own time to explore sexual and racial discrimination, scientific misconduct, and retaliation on the NIH campus, offering to help attendees file official complaints. Meanwhile, two senators have taken up their cause, pressing the General Accounting Office (GAO) to investigate their reassignments as possible violations of the 1989 Whistleblower Protection Act. Sens. William S. Cohen (R-Maine) and Charles E. Grassley (R-Iowa), cosponsors of the law, are concerned that the action at NIH, within the Department of Health and Human Services (HHS), may amount to retaliation. "The two whistle-blowers are recognized experts in rooting out scientific fraud and uncovering waste of government funds," Cohen said in a statement. "This is work in which all Americans have a stake because it is their money that may be wasted. We must know all the facts surrounding the reassignment of these two scientists." `Atmosphere Of Fear' Stewart and Feder say the reassignments are certainly retaliation, an overt attempt to silence dissenting voices. "And the sad fact is that suppression sends a message to the community at large," Stewart says. "It's not necessary to shut more than a few people up before you create an atmosphere of shutting up. There certainly is an atmosphere of fear here that if anyone speaks out, they're going to be retaliated against. And I think there's an adequate basis for that belief." NIH originally reassigned Stewart and Feder to begin new jobs in early May. But the internal personnel move drew national attention, and, after a 33-day hunger strike by Stewart ended in mid-June, HHS placed the two on paid administrative leave pending a review of the case by the department's general counsel (F. Hoke, The Scientist, May 17, 1993, page 1; June 28, 1993, page 4). Several alternative job options were discussed during the review, but these were each rejected by either Stewart and Feder or the agency. These rejected possibilities included placements within HHS's Office of Research Integrity (ORI) or Office of the Inspector General (OIG) or temporary faculty positions with the Program for Cultural Values and Ethics at the University of Illinois, Champaign. Positions hardened, and HHS attorneys ended the negotiations with the late-September order for the two to return to work. The dispute between Stewart and Feder and their employers stems largely from differing characterizations of their work. The two investigators say they are involved in scientific integrity research with important implications for biomedical science, while HHS views their work as unauthorized investigations of individual scientists with the seeming imprimatur of the government. Although the investigative work was part of Stewart and Feder's formal performance assessments, HHS now says such activities are appropriate only to official investigative offices. "They profess that they're doing research, not investigation," says Michael Wald, deputy general counsel for HHS. "We find it hard to understand how they're differentiating it." He adds: "Whatever work gets done by anybody within the agency on issues of scientific misconduct--whether it's direct investigation or research as to the causes of scientific misconduct--needs to be done in an appropriate manner by people operating within the structures of the agency. And whenever an investigation is involved, the privacy rights of people who are being investigated as well as the thoroughness of the investigation, both, are important values to be protected." Stewart and Feder say they are not police but scientists, and, as such, must be allowed the freedoms traditionally accorded to scientists. Sens. Cohen and Grassley have seen sufficient merit in that view to begin asking questions of HHS officials and to call for the GAO investigation. The two senators have been involved in a number of Department of Defense whistle-blower cases in the past. "While we do not want to unjustly accuse anyone of wrongdoing in this case," Cohen said in the statement, "the circumstances surrounding the reassignment of Mr. Stewart and Dr. Feder have raised troubling questions about NIH practices." Cohen is the ranking Republican on the Subcommittee on Oversight of Government Management of the Senate Committee on Governmental Affairs. A Midwestern Alternative One employment option with appeal for all parties involved assigning Stewart and Feder to a university under the provisions of the Intergovernmental Personnel Act (IPA). The IPA allows federal employees to be temporarily assigned to nonfederal organizations for up to four years when it serves "sound public purpose," according to the federal personnel manual. The salaries and benefits of such employees continue to be paid by the federal government. The federal personnel manual also states, "Assignments arranged...to avoid unpleasant personnel decisions are contrary to the spriit and intent of the mobility assignment program." Still, after consultation with Stewart and Feder's lawyers, according to Wald, letters were sent from the HHS general counsel's office to 23 academics who had written in support of Stewart and Feder earlier, at the time of their reassignment. "We asked them whether they would take the lead in seeing whether placement was possible at their university," says Wald, "figuring that the most likely kind of placements would be where there was already somebody interested in [Stewart and Feder's] work." One of the people contacted was Robert Sprague, a professor of psychology at the University of Illinois, Champaign, and a former whistle-blower himself. Sprague received support from Stewart and Feder when he accused University of Pittsburgh psychologist Stephen Breuning of publishing false claims concerning psychotropic medication of mentally retarded people. Breuning pleaded guilty to academic fraud-related charges in United States District Court in Maryland on Nov. 10, 1988. Sprague contacted the person in charge of the university's Program for Cultural Values and Ethics, who expressed an interest in bringing the two NIH scientists to Illinois. Further consultations led to specific ideas for work that Stewart and Feder might undertake once there. One idea, Sprague says, involved Stewart and Feder using their so-called plagiarism machine--a computer system for comparing texts for similarities--to assess the plagiarism "norm" in science. "They were going to look into the base rate of plagiarism with their equipment," says Sprague. "They would take a large database and try to assess in scientific literature just how much is duplicated or copied." The arrangement foundered, however, on misunderstandings over whether the two NIH scientists would be able to maintain their homes in Washington and even their offices on the NIH campus. Stewart and Feder thought, as did Sprague, that they could fulfill their obligations with a part-time presence on the Illinois campus. Wald and HHS, however, expected them to move to the Midwest. "The purpose of an IPA is for an employee to be placed somewhere else to gather experiences and do things they couldn't otherwise do in the department," says Wald. It would "make no sense," according to Wald, for the pair to be supervised by the University of Illinois while physically working at NIH. When the terms of the IPA could not be agreed upon, Stewart and Feder were ordered back to work, in new positions chosen for them. Even in their new positions, Stewart and Feder have continued to offer ideas for ways they feel HHS could better use their talents. These include the formation of an Office of Whistleblower Assistance, to be initially staffed by them. Stewart says they have received no response to this suggestion to date. Whistle-Blower Assistance Whistle-blowers in several scientific misconduct cases indicate that such a role for them would serve an important purpose. "People who are encountering difficulties and whom the system is working over have turned to [Stewart and Feder] as a resource," says Sprague. "And they've been very, very helpful. They were very helpful to me. The government ought to have some kind of a support system [for whistle-blowers]. And, clearly, they do not have." Sprague says that young scientists often come to him for advice and counsel when they feel they have witnessed or been the victims of scientific misconduct. "Some of these people are very distraught," Sprague says. "They've spent years working, and they see it slipping through their fingers because of some misconduct." Margot O'Toole, the researcher who charged that central data had been faked in a 1986 Cell paper coauthored by Nobelist David Baltimore, emphasized the significance of Stewart and Feder's counsel to whistle-blowers in an interview with The Scientist earlier this year. "They do two very important things," O'Toole said, "and they're the only two people in science who do them. One is that they promote debate: They study cases and see how the principles of science are supposed to apply.... And the other thing they do is provide evaluation and support for whistle-blowers." A prime concern of Stewart and Feder's during their conflict with HHS has been the disposition of their files on scientific integrity cases. For now, these files remain locked up, as discussions continue. One result of the standoff over the files, perhaps unforeseen by HHS, is that the two investigators are now actively seeking new cases. They have held two workshops this fall to explore sexual and racial discrimination, scientific misconduct, and retaliation on the NIH campus. Fliers publicizing the workshops declare that "anyone seeking help in formulating or submitting an [Equal Employment Opportunity] complaint or a complaint to the Office of Research Integrity would be especially welcome." "Being deprived of our data," Stewart explains, "we're sort of wide open for business." (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : HHMI Museum Initiative Woos Youngsters To Science AU : RENEE TWOMBLY TY : NEWS PG : 1 The Chevy Chase, Md.-based Howard Hughes Medical Institute (HHMI) has a longstanding reputation for funding high-profile researchers and their important investigations into the crucial biomedical issues of the day. But a smaller, though substantial, percentage of the Hughes budget goes toward educating the researchers of tomorrow. Amid the prestigious graduate fellowships and university-based programs the institute awards is a year-old initiative that reaches out to elementary and high school students beyond the classroom, students like Johnetta Thomas of North Carolina. Until last year, the 16-year-old Thomas was terrified of science. Normally shy, she says that having to discuss the evolution of a tornado funnel or the properties of light petrified her, until she joined an innovative, HHMI-funded program at the North Carolina Museum of Life and Science in her hometown of Durham. Now, Thomas is working as an "explainer" at the museum-- expounding on the principles behind the exhibits to visitors. "There is so much neat stuff here to see and do, and I know people want to know what's going on," says the soft-spoken high school student. "At first it was hard for me to talk to people. But then I found out that everyone else is a person, just like me, and sharing information is a way to come together." Bringing children, especially minorities and young women, into science by way of museums and similar science-related institutions is the focus of the HHMI program that last year granted Thomas's North Carolina museum $175,000 over five years. Through the museum's "Biolinks" program, dozens of disadvantaged African American students spend up to 10 hours a week at the museum, picking up job skills and scientific information by guiding the museum's visitors, many of whom are also minorities. This year, the HHMI program awarded $4.2 million in five-year grants to 22 museums, botanical gardens, aquaria, and zoos large and small across the United States. Last year, in its first round, it gave $6.4 million to 29 natural history, science, and children's museums. Small Program, Big Goals Although the museum initiative is one of the smallest of Hughes' education programs--which award-ed a total of $51.4 million in fiscal year 1993, the majority of which went to graduate, postdoctoral, and M.D. students in the form of research fellowships, as well as support for undergraduate education programs--it rounds out the institute's mandate to improve the quality of science education at all levels, from primary school to postdoctoral science. It is the largest private effort to support educational programs in science museums in the U.S., according to HHMI officials. The institute started the program to tap youngsters' inherent interest in science, says Joseph G. Perpich, HHMI's vice president for grants and special programs. "Kids have all the natural attributes of scientists. They are full of questions, and are very excited by nature. But they seem to lose that in the fourth or fifth grade if not stimulated." But, Perpich adds, the institute wants to do more than fund short-lived "gee whiz" exhibits that offer a spark of interest that dies the moment kids leave the museum. Their goal, hashed out in two years of planning, is to create well-designed educational programs, directly connected to teachers and pupils, that go beyond the museum walls to have an impact in the community. Says Perpich, "We ourselves are not able to master and run programs that support local schools. We want to fund the ones in the business of exciting kids." The institute also has a social agenda: to largely steer the programs to minority and female children. "In the proposals, we paid a lot of attention to how museums were trying to reach out to underrepresented groups and to women," he says. "It's a case of what the science rich can do for the science poor." Yvonne Merrill, education director of the Imaginarium, a science museum in Anchorage, Alaska, has already seen a payoff. After receiving a $225,000 HHMI grant last year, the small, six-year- old museum set out to reach rural Alaskans in "roadless communities." In September a small group from the museum flew in a cargo plane to Barrow, on the Arctic coast, the first of nine far-flung destinations, carrying an array of insects from around the world. They trained local teachers in the biology of the insects, and the use of interactive props such as models, puzzles, and audio devices that support the presentation. And then they left the exhibit for three weeks in the village's community room for everyone to see. "In Alaska there are a large number of insects, but only a few species, and they are dull, not showy," says Merrill. "Many of the insects brought to Barrow were from the rain forest. The whole tropical story was mind-boggling to the students." In Memphis, Tenn., the goal of the Pink Palace Museum is to reach youths in two of the city's most impoverished communities, the Foote and Cleaborn Homes public housing projects. The "Memphis Science Alliance" initiative, funded by a $200,000 HHMI grant, is a series of programs that follows students from fourth through eighth grade. One part of the program is Science Saturdays, a six-week program of highly interactive activities offered at a church in the heart of the projects. The Saturday program uses hands-on experimentation, such as building terrariums and aquariums out of plastic bottles and biological materials. Another component is a labs program offered four to six times a year in schools serving project residents. The program offers an earth sciences lab, for example, where students test for such things as the physical properties of minerals. Long-Term Commitment "Most museum programming is a one-shot visit. It is a most gratifying experience to reach a child in the community that has never gotten a chance to come here, and to maintain consistent contact," says Joyce Godfrey, the museum's programming director. Godfrey, Merrill, and other program directors say that the hallmark of the HHMI grants is its five-year funding--an unusual com- mitment for museums, which often struggle year to year for donations. "In the current economic climate, it is hard to raise money for anything but a highly visible, neat project that may last only one year," says Bonnie Van Dorn, executive director of the Association of Science-Technology Centers, which has almost 300 science museum members in the U.S. "The HHMI approach to sustained funding for five years is a real breath of fresh air. It gives museums time to develop serious projects, and to get the bugs out." Van Dorn adds that member museums were surprised that such an august foundation for biomedical research as HHMI "now wants to focus on education in the public arena for young kids," she says. "They gave a lot of careful attention to equity, to understanding what quality teacher education is. We are delighted." Teachers are equally grateful to be given some help, says Wendell Mohling, retiring president of the National Science Teachers Association. "Classrooms are generally poor. Some only get $25 a year for lab materials," he says. "The HHMI program will make sure that museums will not just give the kids a `yah-ha' field trip, but will reinforce what they learn in the classrooms." In Durham, an evolving connection between the museum and local schools and universities may succeed in providing an enriching boost to students from kindergarten through college and beyond. Program director Georgiana Searles is talking with Duke University and with HHMI investigators at its medical center to ensure that young students who thrive at the museum will have a shot at other Hughes initiatives, such as its precollege, undergraduate, and postgraduate pro- grams. As desirable as that would be, Perpich wants the goals of HHMI's museum initiative to be reachable. He says the final outcome of the funding is not to funnel kids into a lifelong commitment to a science profession, but to keep their enthusiasm for life's wonders alive. "No matter what careers the kids ultimately choose," he says, "we just want them to know more about science and nature." Renee Twombly is a freelance writer based in Durham, N.C. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : MUSEUM SCIENCE FIGURES IN EDUCATION REFORM IN NEBRASKA AU : RENEE TWOMBLY TY : NEWS PG : 18 Both content and logistics are critical to Judy Diamond, who is trying to bring the world of science to students in 982 independent, far-flung, mostly rural school districts in Nebraska. The challenge to Diamond, assistant director for public programs at the University of Nebraska State Museum: Make a difference in each district--many of which include a single K-12 school of fewer than 50 pupils--by teaching the fundamentals of science in a new and entertaining way. Adding to the challenge was the necessity do it in the midst of a statewide educational reform movement that strives to highlight a multicultural approach to science. The solution: Use a five-year, $500,000 Howard Hughes Medical Institute grant to work with Nebraska public television in producing a series of videotapes that shows real scientists talking about their love of research while performing experiments--then build curricula around it and incorporate it into the state's package. For example, one of the first of 15 "Science on the Run" kits features a female botanist talking about her life in science as she works with pollen. "This is a glimpse into the real person doing real science," says Diamond. "The aim is to bring in the minority and female perspective in role modeling while helping teach basic science concepts." The accompanying curriculum teaches students how pollen triggers the immune system. In order to make sure that the kits will be used to their full potential, the museum staff spent a year researching the needs and resources available throughout state elementary schools. Project funds will also be used to teach fourth- through sixth- grade teachers how to integrate the kits and videos into their classroom. The videos will also air on Nebraska public television station NETV. Diamond says the HHMI grant could not have come at a better time for the 122-year-old museum. Assimilation of its science resources into Nebraska schools is a major goal of the facility, and because the HHMI grant was awarded at the start of a statewide effort to draft uniform curricula, the museum had a chance to work "Science on the Run" into a future common lesson plan. --R.T. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : NSF Helps Schools Spruce Up Their Research Facilities AU : EDWARD R. SILVERMAN TY : NEWS PG : 3 The National Science Foundation, seeking to halt the deterioration of research facilities in educational institutions around the United States, has awarded $37.1 million to 56 colleges and universities for renovation work. When combined with $41 million in matching funds, more than $78 million will have been dedicated to repair and renovate laboratories and other facilities used for scientific and engineering research. This round of funding marks the third consecutive year that NSF has made monies available for this purpose. The current awards, announced in September, were the result of a competitive process in which 189 institutions submitted proposals. Schools that grant doctoral degrees must match 50 percent of the NSF award, while other institutions must match 30 percent to 50 percent. In some cases, state and local governments have contributed to the matching funds. The awards range in size from $100,000 to $2 million. Renovation projects are scheduled to vary from less than 12 months to as long as five years in duration; on average, the facilities being revitalized are 42 years old. `A Problem Out There' "There is a recorded $10 billion to $12 billion problem out there in regard to facilities needs nationwide, and it crosses small colleges and large universities," says Nathaniel Pitts, director of NSF's Office of Science and Technology Infrastructure, which administers the awards. "And there's been a lot of pressure on Congress to respond. Congress has been lobbied pretty hard. But this doesn't begin to come up against the problem out there." The amount of money that NSF is awarding for renovations is on the rise, even if it is capable of addressing only a small part of the problem. The awards given in 1992 totaled $16.5 million, and the combined total for 1990-91--the fiscal year in which NSF's Academic Research Infrastructure Program began awarding the grants--was $39 million. Next year, Pitts expects the program to hand out $50 million in funding. "We're always saying that we're concerned about attracting Americans into math, science, and engineering, and you can't do that without the proper facilities," Pitts says. "Well, this helps retain their interest." Bonnie Sherman and Howard Thorsheim would agree. They are psychology professors at St. Olaf College in Northfield, Minn., who submitted a successful proposal and received $190,000 from NSF to renovate their school's 69-year-old psychology research and training facility. "We'd be stuck without it," says Thorsheim. "We're using an apprenticeship model here, in which research is conducted with students. It's collaborative work with professors. And without the upgrade, this active learning approach wouldn't be feasible. We'd be set back." Of course, winning funds from NSF isn't a snap. Sherman and Thorsheim, assisted occasionally by seven departmental colleagues, spent well over a month preparing their proposal. "It's a lot of work, but I don't think anything was unreasonable," says Sherman. Thorsheim adds: "One of our colleagues commented that even if we [had] lost, we won, because we all worked so closely together. It was a great experience." Thanks to their efforts, the psychology department expects to be able to conduct more lab studies when the three-year renovation is completed. And by then, the animal lab, a so-called wet area because dissections take place there, will be separated from "dry" areas, where computers reside. `Crucial' Money Similarly, the chemistry and biochemistry department at Old Dominion University in Norfolk, Va., looks forward to using $870,000 from NSF to upgrade its research labs, which have asbestos problems and need electrical work. Department chairman Frank Scully says the funds have an impact beyond improvement of the physical facilities. "It's crucial money, let me tell you," he says. "We've had faculty turn down positions because of inadequate research facilities. This can only help us recruit faculty. It'll be a major overhaul, but we were in sore need of it." Indeed, the department's building, which was built 25 years ago as part of a teaching college, was never properly equipped for today's needs, faculty say. Consequently, professors who were required to develop research in order to achieve tenure have been working in less-than-ideal converted teaching labs. After a few faculty members retire in several years, the department will finally be in a position to replace them with research people because the facilities will be in place, Scully says. "This definitely came at the right time," he says. According to Pitts, the deadline for applications for the 1994 awards will most likely be in early April. For information, call the NSF Office of Science and Technology Infrastructure at (202) 357-9808. Edward R. Silverman is a freelance writer based in Millburn, N.J. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: NOTEBOOK ----------------------------------------------------------------- TI : Alzheimer's Grants TY : NEWS (NOTEBOOK) PG : 4 The Chicago-based Alz- heimer's Association has announced four competitive, peer-reviewed research awards programs for 1994. The proposals are solicited for biological, clinical, and social/behavioral research relevant to degenerative brain diseases such as Alzheimer's. One batch of grants--called Investigator-Initiated Research Grants--is designed to continue the work of established scientists; the maximum award for the grants is $50,000 per year for two or three years. Another set of grants--Faculty Scholar Awards--is intended to provide salary support to experienced junior-faculty-level investigators committed to Alzheimer's or related studies. Award recipients are funded at a maximum of $50,000 for three years. The deadline for these two programs is January 14. A third grant group, Pilot Research Grants, is designed to provide small, one-year grants for research proposals, with preference given to scientists new to Alzheimer's research. The application deadline for the $30,000 awards is June 30. Finally, Zenith Awards will go to scientists who have already made substantial contributions to Alzheimer's research. The grants are funded at $100,000 per year for two years, with a possibility for renewal. Applications must be received by next August 12. For information, contact Medical and Scientific Affairs, Alzheimer's Association, 919 N. Michigan Ave., Suite 1000, Chicago, Ill. 60611-1676; (312) 335-5779. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : NABR News TY : NEWS (NOTEBOOK) PG : 4 The October 8 edition of the National Association for Biomedical Research's Update newsletter held some grim reminders of the potential dangers facing scientists who use animals in their research; any group that, like NABR, supports such research; or, for that matter, anyone who uses animals for just about anything. According to the newsletter, a recent NABR conference at a Washington, D.C., hotel was suddenly interrupted by an anonymously phoned-in bomb threat. A District of Columbia police bomb squad cleared the hotel ballroom of conference attendees and searched it thoroughly. No bomb was discovered, and the meeting continued. But so have the threats of violence, the newsletter reported: Six mail bombs, it said, were recently discovered in a British post office--all addressed to animal sports enthusiasts in southern England. British police suspect that animal rights activists were the culprits in this case, as well. Meanwhile, revealing that NABR's heart is really in the right place when it comes to animals, the newsletter ran an appropriately mournful obituary marking the passing of canine marketing superstar Spuds MacKenzie at the age of 10 in North Riverside, Ill. Bud Light beer's "Original Party Animal," star of commercials and promotions, died of kidney failure last spring, according to the newsletter, but Stan and Jackie Oles, the bull terrier's owners, apparently had grown so tired of the constant media hounding of the long-retired Spuds that they did not release the information until recently. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Eine Kleine IQ Booster TY : NEWS (NOTEBOOK) PG : 4 Researchers at the University of California, Irvine, report that students who listened to 10 minutes of Mozart before taking a standard test of spatial intelligence significantly raised their test scores. A group of 36 students completed three tasks of the Stanford-Binet test following 10 minutes of three different listening conditions: Mozart's Sonata for Two Pianos in D major, a tape of relaxation instructions designed to lower high blood pressure, and silence. The average score after Mozart was 119, compared with 111 after the relaxation tape, and 110 after silence. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : New Uses For Old Genes TY : NEWS (NOTEBOOK) PG : 4 While hardly the stuff of which movies are made, recently discovered genes of microorganisms predating the Jurrassic period might well produce commercial "box-office hits" in their own right. The genes can redesign host cells by instructing them to make microscopic, air-filled vesicles that create a cellular flotation system. Potential applications for the newly discovered genes include bioengineering of oil-eating bacteria to clean spills, better and cheaper sewage treatment, pharmaceutical production, even improved beer brewing. Hidden millions of years ago inside a bacterium called Halobacterium halobium, they were discovered by University of Massachusetts, Amherst, microbiologist Shil DasSarma and his then-grad students John Halladay and Wai-lap Ng, while conducting basic research using as their model common Halobacterium taken from San Francisco Bay. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Dual Postdocs TY : NEWS (NOTEBOOK) PG : 4 The National Research Council and the Alexander von Humboldt Foundation have announced the opportunity to apply for linked postdoctoral fellowships to be held in Germany and the U.S. Winners of the fellowships would hold a Humboldt Research Fellowship for a year in Germany, and then take up an NRC Research Associate position at a federal laboratory for one, two, or three years. The offer is open to U.S. citizens who have held their degrees for less than five years and are under the age of 40. Applicants must apply to and be awarded postdocs from both NRC and the von Humboldt Foundation for the offer to apply. For information, contact National Research Council, Associateship Program (AvH-NRC), 2101 Constitution Ave., N.W., Washington, D.C. 20418; (202) 334-2760; Fax: (202) 334-2759; and the Alexander von Humboldt Foundation, North American Office, 1350 Connecticut Ave., N.W., #903, Washington, D.C. 20036; (202) 296-2990; Fax: (202) 833-8514. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : A Good Hair Day TY : NEWS (NOTEBOOK) PG : 4 With biotech researchers and companies feverishly working to fight devastating diseases afflicting populations around the world, two firms have teamed up to engineer a genetic solution to one of the most dreaded conditions of all--androgenic alopecia, or common baldness. Researchers at Sequana Therapeutics of La Jolla, Calif., plan to identify, map, and clone both mouse and human genes associated with abnormal hair growth and baldness. Ridgewood, N.J.-based Alopex Pharmaceuticals will then use the molecular targets identified by Sequana to discover and develop treatments for androgenic alopecia and other hair disorders. The two companies will focus on genetic disorders associated with hair follicles. Scalp hair follicles normally produce hair for two to six years and then shut down for a resting period, followed by a shedding of hair, after which the growth cycles begin anew. For those with androgenic alopecia, hair follicles grow hair for progressively reduced periods and remain in the resting period for longer times than they grow hair. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : CLARIFICATIONS TY : NEWS PG : 7 The article "University Of Virginia Appoints Biologist To Vice Provost For Research Position" in the People section of the Oct. 18, 1993, issue of The Scientist (R. Kaufman, page 22) misstated the background of Gene D. Block, new vice provost for research at Virginia. Block received his bachelor's degree in 1970 from Stanford University and his Ph.D. in 1975 from the University of Oregon. He was a postdoctoral fellow at Stanford University from 1975 until 1978, when he joined the faculty at the University of Virginia. Also, the article "Research-Scale Perfusion Systems Aid Neuroscience Studies" in the Tools section of the same issue (F. Hoke, page 18) incorrectly identified the patch-clamp perfusion system designed with the technical assistance of electrophysiologist Robert S. Eisenberg of Rush Medical College in Chicago, and commercially available from Adams & List Associates, Westbury, N.Y. The system to which Eisenberg contributed his expertise is the Whole-Cell/Patch Pipette Perfusion Kit. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Patents On Scientific Discoveries Are Unfair And Potentially Dangerous AU : CESAR MILSTEIN TY : OPINION PG : 11 Many of us still remember a time when the idea of taking out a patent was far from foremost in our minds. In those days, scientists working in universities and government-sponsored institutions were driven not by the patentability of their ideas, but rather by pure scientific considerations. Patents were rare, more an afterthought than a preliminary consideration. The advent of modern biotechnology has brought about a considerable change, so that now, even among the most curiosity- driven scientists, the question "Should I take out a patent?" becomes an issue whenever a new discovery or a new procedure becomes experimentally successful. If the scientist in question is better acquainted with current business practices, he or she may well be tempted to take out a patent even before the results of the experiments are certain. Otherwise, there is a very real risk that someone else will patent the idea, and that the experiments will be used only to validate the other person's patent. Recent developments in connection with the controversies surrounding the patenting of DNA sequences go even further. It is becoming a matter of high priority for the scientific community to take a careful look at the issues involved. A recent pronouncement of the International Council of Scientific Unions (ICSU) urging the patenting authorities to consider the danger in allowing pat-ents of nucleic acid sequences per se is a good start in the right direction. And yet the problem goes deeper. Different countries have different concepts in terms of patenting principles--for example, first to "invent" (United States) vs. first to patent (Europe); a period of grace (U.S.) vs. no disclosure rules (Europe). Worse still, lawyers and scientists do not speak the same language or use the same criteria: What is an obvious extension of previously established facts (as far as scientific judgment is concerned) can also be construed as novel (in legalistic terms), and thus merit patenting. At the other extreme, leaps in scientific knowledge that do not present any obvious practical implications today may be the foundation for further developments and lead to innumerable patents in the future. Good examples are the discoveries of somatic cell hybridization and of restriction phenomena in bacteria, both major advances in basic science whereby eventual developments could not be predicted and were therefore unpatentable. Without these advances, biotechnology would not be what it now is. So, patents are basically unfair. But perhaps they are necessary for the development of products that will ultimately benefit society. Without them (we are told) companies would not be prepared to spend the amount of money required for such developments. The new element in this equation, however, is that the complexity and multiplicity of overlapping pat-ents in the field of biotechnology is creating such havoc that the counterargument--that patents are beginning to inhibit the development of new products--should begin to be considered with the seriousness it deserves. It remains a fact that the specter of patents is not only introducing new tensions in the scientific community, but also having serious and undesirable effects on basic developments that largely rely on curiosity-driven research. Cesar Milstein is an immunologist at the Laboratory of Molecular Biology, Cambridge, England. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : ICSU STATEMENT ON GENE PATENTING TY : OPINION PG : 11 The International Council of Scientific Unions (ICSU) is a Paris- based, international, nongovernmental organization whose mandate includes the promotion of cooperation in the basic sciences, and the safeguarding of the principle of the university of science and of the free flow of scientific knowledge. The council is aware of the tremendous potential benefit of genetic research for humanity and realizes that new ethical and social dimensions arise from this. Accordingly, ICSU strongly believes that efforts to patent genetic information should not jeopardize either progress in the basic sciences or access to the information that is necessary for such progress to continue. ICSU asserts its view that information about nucleic acid sequences cannot be patented per se. Such sequences should be patentable solely within the context of their demonstrated significance and/or application (for example, regulatory signals, antisense RNAs, probes)--and not of their potential products (for example, proteins)--and provided that this can be shown to be "novel," "non-obvious," and "useful." Under such circumstances, patenting of complementary DNA sequences (cDNA) would distort the patent process, which is designed to protect applications, methods, and products, on the basis of proven facts and not mere expectations, and normally serves society by stimulating the investments and developments necessary to provide useful products and services. Any deviation from such patenting principles would run counter to the best interests of science and hinder international collaboration in such endeavors. ICSU, therefore, cautions against decisions that may be irreversible, such as those possibly emerging as a result of recent patent requests concerning cDNA sequences corresponding to portions of unknown messenger RNAs. ICSU urges the relevant authorities, particularly in countries where patent applications in this field have been or are soon to be filed, to consider such applications taking due account of the possible implications and to ensure a strict application of established patenting principles, thereby setting an example for other countries in which similar cases may arise in the future. ICSU would welcome a formal international agreement on this subject. Milstein's essay and the ICSU statement appeared previously in the March/April 1993 issue (Vol. 1, No.2) of The Immunologist, a bimonthly journal of the International Union of Immunological Societies, and are used with permission. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Hillary Clinton And Mary Lasker: A Photo In Proper Focus AU : EUGENE GARFIELD TY : OPINION (COMMENTARY) PG : 12 The front page of The Scientist's October 18 issue was graced by a photograph of two remarkable women: Hillary Rodham Clinton together with Mary Lasker. The photo accompanied our coverage of the Albert and Mary Lasker Foundation awards, given to three scientists--Gnter Blobel, Donald Metcalf, and Nancy Wexler--whose outstanding efforts in basic research over the years are likely to yield, directly or indirectly, significant gains in human health. To my knowledge, no other national publication ran a photo of these two women, bonded as they were at an event underscoring the increasingly important link between biomedical investigation and social enrichment. Since she and her husband moved into the White House last January, Clinton has gained sharp visibility for her advocacy of a new and equitable system for ensuring the good health of all Americans; for the past half-century, the Lasker Foundation has been foremost among United States organizations honoring researchers whose work ultimately is directed toward the same estimable goal. The support of basic research is fundamental to the well-being of our society, and an event like the Lasker Awards ceremony makes for, in our opinion, compelling front-page news. I find it troublesome to think that such publications as the New York Times and the Washington Post would opt to bury coverage of it in their back pages and ignore the symbolism of Clinton and Lasker's encounter. This is a moment in history, after all, when the nation's scientific community is struggling to produce, through the endeavors of basic research, remedies for AIDS, cancer, and other diseases--and while, ironically, federal support for untargeted laboratory investigation is persistently threatened. Let us hope that Clinton's appearance at the Lasker Awards gathering signifies an implicit endorsement of basic research. Although I've been a guest at many of the Lasker ceremonies over the years, I was not present at the recent ceremony. However, The Scientist's managing editor, Barbara Spector, did attend, and her report on the event is heartening in this respect. In her article ("Lasker Awards Celebrate Biomedical Scientists For Their Advances In Health-Related Research," The Scientist, Oct. 18, 1993, page 1), Spector quotes Clinton as saying in her keynote speech: "These winners join a remarkable group . . . men and women whose work has found cures for disease, who have aided the kind of breakthroughs that we've only been able to dream about in the past but now take for granted.... This is a time when the past and the present in medical research join together to point us to a new future." To me, this sounds like a strong endorsement indeed! Today, basic research and National Institutes of Health funding have become big, bureaucratic matters, not easily susceptible to influence by a single individual like Mary Lasker. But her pioneering advocacy efforts are being carried on by dozens of lobbying groups--such as Research!America--that remind Congress regularly of the high priority that medical research holds, or should hold, for most Americans. Nearly 20 years ago, I proposed in an essay (Current Contents, Jan. 23, 1974, pages 10-12) that Congress establish a National Institute for Preventive Medicine. I wrote: "With the energy crisis upon us, and the `crisis management' reaction to it, most physical and chemical scientists can look forward to another decade of generous funding. So be it; but we must make certain that it is not accomplished by sacrificing the biomedical research effort because it is now politically popular to support energy, environmental, or other forms of research." It is discouraging that Congress or NIH has still not elevated preventive medicine--and the research activity that goes with it- -to that status. On the other hand, it is heartening to see such diverse personalities as Hillary Rodham Clinton and Mary Lasker united in recognizing the value and immense importance of the nation's basic research community. The picture of them, together, is pertinent; let's hope that the prospect for basic research is as inspiring. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: OPINION SECTION ----------------------------------------------------------------- TI : Benefits Of Animal Use TY : OPINION (LETTERS) AU : CARLOS H. SCHENCK MARK W. MAHOWALD Your July 12, 1993, article (R. Kaufman, page 1) on the reasons behind biomedical scientists' choice of their experimental subjects--animals, tissue cultures, and others, including humans- -quoted sleep researcher Adrian Morrison as working "just to understand basic biological mechanisms." Such understanding is, of course, fundamental to the eventual clinical advances that allow us to help our patients. However, you missed an interesting story in not probing Morrison further, for it was his studies of a fascinating phenomenon in cats with brain damage that exhibit elaborate behaviors during REM sleep--a state when they and all mammals (including humans) are ordinarily paralyzed--that led to our understanding of a serious, dangerous sleep disorder we can now treat: REM sleep behavior disorder (RBD). Patients with RBD act out their dreams rather than remaining safely paralyzed. This can result in injury to themselves or their bed partners, which can be life-threatening, such as when cervical vertebrae are fractured. Fortunately, RBD is controlled by medication. Thus does the research that seeks to understand the basic workings of the body lead to unforeseen benefits to our patients. Clinical medicine is highly dependent on basic research, as exemplified by RBD. CARLOS H. SCHENCK Assistant Professor of Psychiatry University of Minnesota Medical School Minnesota Regional Sleep Disorders Center Hennepin County Medical Center Minneapolis MARK W. MAHOWALD Associate Professor of Neurology University of Minnesota Medical School Director Minnesota Regional Sleep Disorders Center Hennepin County Medical Center Minneapolis (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Of Morality And Animals AU : MARTIN L. STEPHENS TY : OPINION (LETTERS) PG : 12 Ron Kaufman reports that biomedical researchers tend to use science, not morality, in deciding between animal-based methods or non-animal alternatives (The Scientist, July 12, 1993, page 1). While this may be true, morality should not be ignored. Animals are more than just another research tool for scientists to pick and choose. In cases in which alternatives are not yet superior to their animal-based counterparts, the research community has a moral obligation to seek to expand the capabilities of the alternative methods. Instead, what often happens is that the available alternatives are dismissed as not as good as the animal-based methods, and no effort is made to improve them. Some non-animal alternatives are improvements over their animal- based counterparts. Where they are not, they should be advanced through targeted efforts and programs. Morality demands that we not leave the advancement of these methods to serendipity or something as vague as the inexorable tide of scientific progress. For its part, the Humane Society of the United States works closely with progressive members of industry, academia, and government to help advance the science of alternative methods. MARTIN L. STEPHENS Vice President Laboratory Animal Programs Humane Society of the United States Washington, D.C. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- Letters to the Editor The Scientist 3501 Market Street Philadelphia, PA 19104 Fax:(215)387-7542 E-mail: Bitnet: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com ===================================== NEXT: ----------------------------------------------------------------- TI : Molecular Motors Drive Multidisciplinary Research Quest AU : MYRNA E. WATANABE TY : RESEARCH PG : 14 In a major career move, molecular biophysicist Steven M. Block is leaving Cambridge, Mass., where he has been associated with the Rowland Institute for Science and Harvard University since 1987. This coming January, he'll be installed as an associate professor in the molecular biology department at Princeton University, where he'll join forces not only with other biologists, but also with physicists and chemists, in a pursuit that Block believes is as exciting as anything going on in the world of science today. Block and his colleagues will be studying molecular motors, minute energy-conversion machines that reside within cells and yield a locomotive power peculiar to living organisms. This field of investigation has dominated the 41-year-old Block's research activities in recent years, playing a significant part in his productive tenure at Rowland, where he has put out more than 20 scientific papers in the past five years, coauthoring many of them with his mentor, biophysicist Howard Berg, also of the Rowland Institute and Harvard. The lure of Princeton, says Block, is that he will hold a joint appointment with the new Princeton Materials Institute (PMI), an interdisciplinary research center, where physicists, chemists, engineers, and biologists will combine their intellectual understandings of how microscopic structures behave, with the goal of offering better approaches to the study and fabrication of materials for nanotechnology--small-scale technology in the sub-micron range. As Block notes, molecular motors are the smallest motors known to science. An `Outstanding Puzzle' "This looks to be an unbeatable combination for the future," Block says, referring to the interdisciplinary approach to the challenges facing PMI researchers. To make clear why the study of molecular motors is of great importance, Block explains that in elementary biology classes, students are taught three major qualities that differentiate living organisms from non-living matter: sensory perception, repro- duction, and movement. The biochemistry of sensory perception, he points out, is known from work that has been done on sensory transduction in bacteria. Reproduction also has been well studied, and the mechanisms for DNA duplication are now understood. But what, essentially, causes movement? "That question remains unanswered," says Block. "If you solve this, you solve one of the great outstanding puzzles of life." Once this puzzle is solved, some scientists believe, the understanding of molecular motors may foster new techniques for conducting biomedical research and fighting disease. Ambitious speculation has gone so far, for example, as to envision the introduction of microscopically tiny motors--programmed to carry out therapeutic missions--injected into the human bloodstream. Although Block agrees that "if a mechanism for molecular movement can be established, the insights that come from such a mechanism may inspire man-made molecular machines with similar mechanisms," he does not envision injectable machines for curing cancer or cleaning out clogged arteries. But some futurists, such as molecular nanotechnologist K. Eric Drexler, a research fellow at the Institute for Molecular Manufacturing in Palo Alto, Calif., suggest that such "nanomachines" are at least theoretically possible. And self-assembling, self-perpetuating biomolecular machines may be an outgrowth of this specialized research, according to Block. Myosin Vs. Kinesin Molecular motor researchers are, in the main, looking at two different motor proteins: myosin, which is present in muscle cells; and kinesin, which attaches to vesicles within the cell and moves these vesicles along microtubules. Investigators in this field are also studying the motor protein dynein, present in sperm tails, cilia, and cytoplasm, but myosin and kinesin are clearly the chief focus of current studies. All of these enzymes are referred to as motor proteins because their enzymatic activity results in energy release leading to motion. Myosin is the oldest known of these proteins, first isolated from muscle well over a century ago. Until recently, however, scientists' ability to study the molecule was limited. But with the advent of laser technology, such modern tools as optical tweezers--a laser device capable of manipulating minute objects-- and computerized video enhancement of light microscopy enable researchers to study individual molecules of myosin on a microscope slide as they hydrolyze molecules of adenosine triphosphate (ATP) to release energy. Myosin is a large molecule, its head needing approximately 890 amino acid residues to obtain movement in vitro. Kinesin's head, by comparison, needs only 350 or so amino acid residues. Johns Hopkins University biophysicist Scott Kuo likens the difference of studying them to the comparative challenges of studying an eight-cylinder Cadillac engine and studying a lawn mower. If the myosin motor is the Cadillac, Kuo says, the kinesin motor has two cylinders. The principles involved in making both engines work are the same, but the lawn mower is much easier to take apart and understand. Because of its size and relative slowness of motion, Block studies kinesin. Recently, he and fellow researchers Karel Svoboda, Christoph Schmidt, and Bruce Schnapp have focused on the size of the step the kinesin molecule takes as it moves up a microtubule, and the force generated with each step. The group recently found that one step for the kinesin molecule was equal to approximately 8 nm with a force of approximately 4 picoNewtons (pN). The team of researchers did not, however, determine how many ATP molecules are hydrolyzed per step, an important question in understanding the efficiency and molecular dynamics of the movement. Other laboratories in the U.S. are pursuing similar research with kinesin molecules. Johns Hopkins' Kuo and cell biologist Michael Sheetz of Duke University School of Medicine in Durham, N.C., have been measuring the force generated by kinesin movement. Joe Howard, a neurobiologist turned cell biologist at University of Washington, Seattle, demonstrated that kinesin can function as a single motor in vitro. He did this work along with cell biologist Ron Vale, one of the codiscoverers of the kinesin molecule, who is at the University of California, San Francisco. Both Howard and Vale have been investigating kinesin step size and how the molecule moves down the microtubule. Still other groups are working with the larger myosin molecule. Most prominent among these is the University of Osaka's Toshio Yanigida, who has done work on myosin step size. Yanigida's work, according to Block and other researchers, is considered to be controversial because the step sizes his group has reported--60- 600 nm with each ATP--do not appear to correspond to recent X-ray crystallographic evidence from the laboratory of Ivan Rayment at the University of Wisconsin, Madison. Rayment's group showed that the myosin head is only 16 nm long. Thus, researchers such as Block question whether Yanigida sees myosin acting as a "wind-up toy," carrying out multiple moves in succession, or whether Yanigida's interpretations of his measurements are correct. Molecular cell biologist James Spudich, a former postdoctoral student of Block's, now at Stanford University School of Medicine, also is studying step motion in myosin. These and other researchers need to clarify the size of each step, and whether less than one, one, or more than one ATP molecule is hydrolyzed per step. Duke University's Sheetz puts the work into perspective, explaining the importance of determining the number of ATP molecules hydrolyzed per step. "The reason that this is an important issue," he explains, "is not that it's stopping every 8 nm. It's that we need to understand how ATP is converted into mechanical energy in these systems with the efficiencies in muscles at 50 percent conversion." Sheetz further explains that these discoveries "will potentially help us in designing other motor systems on a larger scale." He points out that nanoscale motors currently being fabricated by silicon chip makers work at only 10 percent efficiency. Scientists agree that even the most efficient automobile engine does not work at anywhere near the 50 percent efficiency of these natural molecular motors. Supporting The Effort Although the basic research being conducted by Block and others around the U.S. may well lead to applications in microfabrication of motors, U.S. funding agencies are not agog. While the National Institutes of Health funds what Sheetz calls a "significant fraction" of this research, he adds that "NIH considers this too basic to be applied to many of the problems that are out there." Although not extraordinarily expensive as research goes--the equipment, according to Sheetz, costs between $50,000 and $100,000 --Sheetz laments, "The funding is typically by the seat of one's pants. "Almost everybody I know who has such systems got a little bit from here, a little bit from there," with NIH coming in "after the feasibility has been shown," he says. Block--whose work was fully funded by the Rowland Institute, but now, with his move to Princeton, must apply for NIH funding-- says, "The NIH has shown a certain reluctance to fund innovative research that is instrumentation-intensive." This is not what is happening in Japan, according to Palo Alto futurist Drexler. Drexler states that the Japanese Ministry of International Trade and Industry (MITI) is funding a large-scale project to develop nanotechnology. Part of this project will focus on molecular machines. Drexler points out that "on the nanoscale, we've seen a considerable amount of attention to electronics ... and we've seen microfabri- cation of molecular components." But the missing piece of the molecular machinery puzzle, he adds, is the study of biological molecular machines. Drexler sees molecular motor research leading in the short term to more efficient instrumentation for sequencing DNA, for example. In fact, Sheetz points out, the nano-scale measurement techniques established in the course of this work can already be applied in automated DNA sequencing. He also foresees molecular motor research as leading to more efficient nanoscale motors for the computer chip industry. Meanwhile, Block and his coworkers are cooperating with the National Nanofabrication Facility at Cornell University in Ithaca, N.Y., on micromachining microscope slides so that their glass surfaces will be irregular in shape and will, themselves, without use of any separate attachments, be able to hold molecules such as kinesin for more direct studies of movement and force. And at Stanford, Spudich and his colleagues are working on coating micromachined slide surfaces with myosin in order to study the interactions between actin and myosin. But no matter what the future applicability of this line of research, the basic premise, as Sheetz points out, is that "it's extremely important for us to understand whether nature has found some fundamentally different way of converting chemical to mechanical energy than we have utilized in our machines." The next step will be to apply what has been learned to make more efficient micromachines. Myrna Watanabe is a biotechnology consultant based in Yonkers, N.Y. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : HOW TO STUDY KINESIN AU : MYRNA E. WATANABE TY : RESEARCH PG : 14 Karel Svoboda and his colleagues in Steven Block's laboratory at the Rowland Institute use a technology-laden in vitro setup to study the movement of the motor protein kinesin on microtubules. They are able to visualize microtubules through a light microscope using, what Block refers to as "some tricks." The "tricks" are use of video-enhanced differential interference- contrast (DIC) microscopy, allowing visualization of structures, such as microtubules--1/20 of a light wavelength across--that are too narrow in diameter to be seen without computer-assisted enhancement. They attach a kinesin molecule to a silica bead and, using optical tweezers, deposit the bead onto the microtubule. The optical tweezers, developed originally by Arthur Ashkin and associates at Bell Laboratories check, Holmdale, N.J., in 1985 in order to study single atoms, is constructed by bringing light from a laser--in this case near-infrared--to a sharp focus. Block explains that the tweezers focuses a single beam of light on a single spot, pulling small objects into the area where the light is strongest. The silica bead that attaches the kinesin to the microtubule can be held in place with the optical tweezers. ATP is added to the system, but in order to measure the movement of the kinesin molecule and the force of that movement, a dual- beam interferometer is used along with the optical tweezers. This is called an optical trapping interferometer. Two photodetectors, Block explained in a recent product review of the optical tweezers in Nature (360:493-5, 1992), "can measure the displacement of a trapped object down to distances as small as ngstroms, thousands of times per second, using polarized light." Using this setup, Svoboda--who is Block's graduate student and the person Block refers to as "the linchpin" of this research-- and his coauthors measured an 8 nm step along the microtubule, and a force of about 4 picoNewtons. Joe Howard from the University of Washington, Seattle, and Duke University School of Medicine's Michael Sheetz explain that the 8 nm steps correspond to stopping points at the alternating alpha and beta subunits of the microtubule. The width of each subunit is 4 nm so there is one binding site per each tubular dimer. Although other researchers, such as Johns Hopkins University biophysicist Scott Kuo and Sheetz, have come up with different numbers for force or step length, they admit that there may be differences in sensitivity of their instrumentation, or differences in the way the experiment is set up. Kuo, for example, who measured a force of 2 pN for kinesin movement, says, "I think Steve is pulling it better than I can." --M.E.W SUGGESTED READING S.M. Block, Modern Cell Biology, Vol. 9, pages 375-402, eds. J.K. Foskett and S. Grinstein, New York, Wiley-Liss, 1990. K.E. Drexler, Engines of Creation: The Coming Era of Nanotechnology, New York, Anchor Press, 1986. K.E. Drexler, Nanosystems: Molecular Machinery, Manufacturing and Computation, New York, John Wiley & Sons, 1992. J. Gelles, et al., Nature, 331:450-3, 1988. S.C. Kuo, M.P. Sheetz, Science, 260:232-4, 1993. S. Ray, et al., Journal of Cell Biology, 121:1083-93, 1993. R. Taylor, Journal of NIH Research, 5:58-62, 1993. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : CELL BIOLOGY TY : RESEARCH (HOT PAPERS) PG : 15 M.J. Solomon, T. Lee, M.W. Kirschner, "Role of phosphorylation in p34cdc2 activation: Identification of an activating kinase," Molecular Biology of the Cell, 3:13-27, 1992. Marc W. Kirschner (Department of Biochemistry and Biophysics, University of California, San Francisco): "Work from several labs had shown that phosphorylation might be involved in the activation of the mitotic kinase, cdc2, or its inhibitors. The story was naturally confusing for a while until it became clear that there were two types of phosphorylation that occurred simultaneously upon binding of cyclin to the inactive cdc2 protein, one that activated and one that inactivated the protein. Initially, most attention was directed to the inactivating phosphorylation, particularly since candidate genes had already been identified in Schizosaccharomyces pombe as negative regulators of mitosis. When the activating site was identified, it was thought that it might be phosphorylated by cdc2 itself. If this were the case, the only regulation of the entry to mitosis would have been negative regulation. "In this paper Mark Solomon, Tina Lee, and I showed that a new kinase existed and could be partially purified--called CAK (for cdc2 activating kinase)--that is separate from the cdc2-cyclin- type kinases, and which phosphorylated cdc2 on the activating phosphorylation site. This finding opened up a new site of regulation of cdc2. It is likely that CAK regulation exists not only at G2/M transition but also at G1/S transition for cyclin- dependent kinases. Purification and identification of CAK and its regulation are now an active area of research in the cell cycle field." (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : BIOCHEMISTRY TY : RESEARCH (HOT PAPERS) PG : 15 R.A. Heyman, D.J. Mangelsdorf, J.A. Dyck, R.B. Stein, G. Eichele, R.M. Evans, C. Thaller, "9-Cis retinoic acid is a high affinity ligand for the retinoid X receptor," Cell, 68:397-406, 1992. Richard A. Heyman (Ligand Pharmaceuticals Inc., San Diego): "Metabolites of vitamin A (for example, all-trans retinoic acid) modulate several important life processes, including cellular proliferation, differentiation, and metabolism. These actions are thought to be exerted through specific intracellular receptors. The retinoid receptors are members of a superfamily of proteins that function as ligand-dependent transcription factors. These intracellular receptors regulate expression of their target genes after binding to small lipophilic ligands, including steroid hormones, thyroid hormones, vitamin D, and retinoic acid. "In addition to the receptors that bind to the known hormones, there are members of the superfamily for which a hormone is not known; these proteins are referred to as orphan receptors. In 1990, members of our research team published a paper identifying one family of these orphans as receptors for a novel vitamin A derivative, which was called retinoid X (D.J. Mangelsdorf, et al., Nature, 345:224-9, 1990; Hot Papers, The Scientist, Nov. 25, 1991, page 16). These retinoid X receptors (RXRs) activated transcription in cells exposed to all-trans retinoic acid but did not bind all-trans retinoic acid directly as a ligand. It was therefore postulated that in cells all-trans retinoic acid was being converted to the RXR ligand. "This observation led to a hunt for the RXR ligand, which combined the scientific efforts of researchers at Ligand Pharmaceuticals, the Salk Institute, and Baylor College of Medicine. In the present work, a novel ligand for the RXR family has been identified as 9-cis retinoic acid, making this the first hormone to be described for the intracellular receptor superfamily in more than 20 years. Interestingly, 9-cis retinoic acid is a high-affinity ligand not only for RXRs, but also for the retinoic acid receptors (RARs) (E.A. Allegretto, et al., Journal of Biological Chemistry, in press; G. Allenby, et al., Proceedings of the National Academy of Sciences, 90:30-4, 1993). "The RARs were originally identified for their ability to bind and be activated by all-trans retinoic acid. Thus, while all- trans retinoic acid serves as a ligand for only the RARs, 9-cis retinoic acid is a bifunctional ligand for members of both the RXR and RAR subfamilies. The experimental techniques developed and used to identify this new hormone provide a potential approach to identify new hormones for other orphan receptors. In addition, the identification of 9-cis retinoic acid has yielded a lead structure for the design of synthetic retinoids with unique receptor activity profiles. "Recently, we have synthesized a series of synthetic retinoids that selectively bind and activate members of the RXR subfamily and have no cross-reactivity with the RARs. These unique tools are being used to examine the physiological and pharmacological consequences of selectively activating different gene pathways and may provide novel therapeutic compounds for the treatment of disorders that involve abnormal growth or differentiation, or both." (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : CANCER RESEARCH TY : RESEARCH (HOT PAPERS) PG : 15 C.A. Midgley, C.J. Fisher, J. Bartek, B. Vojtesek, D. Lane, D.M. Barnes, "Analysis of p53 expression in human tumours: An antibody raised against human p53 expressed in Escherichia coli," Journal of Cell Science, 101:183- 9, 1992. Carol Midgley (Cancer Research Campaign Laboratories, Departments of Biochemistry and Anatomy & Physiology, Medical Sciences Institute, University of Dundee, Scotland): "The protein p53 is a member of the rapidly expanding family of so-called tumor suppressor proteins. These are present in all normal cells, and their function is linked to the control of cell division. In cancer cells, where mutation in the p53 gene leads to expression of an altered mutant p53 protein, the suppressing activity is lost, contributing to the uncontrolled growth of the tumor. In normal cells, p53 protein is present at too low a level to be detected, but it has recently become apparent that many tumor cells contain high levels of mutant p53 because the mutant form of p53 protein is far more stable (J. Bartek, et al., Oncogene, 6:1699-1703, 1991; Hot Papers, The Scientist, May 3, 1993, page 16), thus providing us with a new marker for tumor development. "The importance of this paper is that it described the first antibody (a polyclonal antibody called CM-1) that is capable of staining p53 protein in the fixed paraffin-embedded samples used by most clinical researchers. This opens up a whole spectrum of conventional tumor preparations and archive material to analysis. Our paper described a system for making bacteria produce p53 protein in quantities that were previously unavailable and has provided an excellent immunogen that has allowed us to produce not only CM-1 but also a whole panel of monoclonal antibodies with similar properties (B. Vojtesek, et al., Journal of Immunological Methods, 151:237-44, 1992). As a result, we have also developed a technique for the quantitative detection of p53 in tumor samples using an immunoassay format (B. Vojtesek, et al., British Journal of Cancer, 67:1254-8, 1993). "The availability of these reagents has generated enormous interest among clinical researchers and has allowed us and collaborators to examine the pattern of p53 expression in many types of solid tumors. Overall, p53 staining corresponding to mutant p53 protein is seen in 70 percent of malignant lesions, and there is evidence that p53 staining is a marker of poor prognosis in certain tumor types, such as gastric and breast tumors (D.M. Barnes, et al., Human Pathology, 24:469-76, 1993). Essentially, it seems that the accumulation of mutant p53 is the most common change detected in tumor cells. Perhaps even a proportion of p53 `negative' tumors are in fact mutants that have lost the ability to make any p53 at all, which would also result in a loss of growth control. Important developments are now taking place in our understanding of the underlying mechanism of normal p53 function. The accumulation of mutant protein in tumor cells not only may provide us with diagnostic and prognostic data, but also may represent a target for chemotherapy. We may even be able to find drugs that can alter the mutant p53 protein sufficiently to restore some of its growth-suppressing properties (T.R. Hupp, et al., Nucleic Acids Research, 21:3167-74, 1993)." (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Digital Imaging In Microscopy Offers Greater Control, More Options AU : FRANKLIN HOKE TY : TOOLS & TECHNOLOGY PG : 19 For researchers who have traditionally worked with photographs, the conversion of images into digital forms has been gradually, but steadily, replacing film over the past decade and more. In microscopy, the cameras and scanners that capture digital images- -based on the semiconductor technology of charged couple devices (CCD)--have put scientific imaging within reach of computer manipulation (image analysis, most prominently), communications, and archiving. Neuropathologist Lauren A. Langford at the University of Texas M.D. Anderson Cancer Center in Houston, for example, now keeps her indexed digital-image files on a hospital network and carries prepared presentations to meetings on a disk. "After years of work," Langford says, "I have filing cabinets filled with Kodachromes, and I get tired of sorting and labeling and filing. Once they're digitally captured, I don't have to do any of that. And if I want to go somewhere--to another university to give a lecture, for example--I just take my digitally captured images on a disk. They provide me with a Macintosh and a projector, and that's it." Langford consults, via computer lines, with colleagues at other hospitals using the same images of brain and spinal cord biopsies--especially important to her because there are fewer than 500 practitioners in her subspecialty. She also writes interactive training programs incorporating digital images. "And you don't have to have a darkroom," Langford says, "you don't have to have a technician, and you don't have to run a photography lab." A recent addition to her laboratory toolkit is the Kodak Professional DCS-200 digital camera from Eastman Kodak Co., Rochester, N.Y., which carries a list price of $9,995. Langford's camera is only one of a number of new digital-imaging products--some originally designed for professional publishing and other nonscientific uses--that can make such image acquisition easier and, sometimes, cheaper for researchers. Other high-resolution cameras also are available that, like hers, mount on most microscopes and facilitate direct capture of digital images nearly indistinguishable from photography. And scanners can be purchased that allow the user to convert existing 35 mm slides into a digital form for transfer to a computer system. The advantages for the researcher are clear enough, but for the institution, too, digital miscroscopy has benefits. Not having a "wet darkroom" means that disposal of photographic chemicals is no longer an issue, according to Michael Berke, service engineer for the Kodak DCS-200 camera. Some of the effluents from traditional darkroom chemistry--the thiocyanates in fixers, for instance--can be toxic, he says. Especially in localities with stringent environmental laws, digital technologies can obviate a difficult problem. Johns Hopkins University School of Medicine in Baltimore has moved almost entirely to a digital-image acquisition and management system. According to Raymond Lund, an assistant professor of pathology and director of photography at Hopkins, researchers and physicians now integrate images with text for presentations and publications, and images are transferred routinely from place to place via the hospital network. His department supports laboratories throughout the school and hospital, he says. Lund just purchased a Nikon LS-3510AF digital scanner, from Nikon Inc. in Melville, N.Y., for his department. The full-color scanner, which lists at $9,535, has a resolution of 3,185 pixels- -the tiny square visual units that make up the image--per inch; each pixel is 8 microns on a side. The scanner also provides an autofocus feature and, with an accessory, unattended batch- scanning. Full-featured, institution-wide systems such as the one Lund has helped build at Hopkins are not inexpensive, he notes. While high-quality digital-acquisition cameras and scanners are becoming more affordable, once the accompanying microscopes, computers, and output devices are factored in, the system costs can easily exceed six figures. Still, given the greater control over acquisition and manipulation of the images, this is the direction in which many researchers and their institutions are headed, according to Charles Berger, president of Image Systems Inc., a Columbia, Md.- based dealer of digital-imaging accessories and Nikon microscopes. "Over the years, I've watched as electronic imaging has slowly crept into traditional photography, to the point where now it's virtually replacing it," says Berger. Most manipulation of images--whether adding something to them or taking something away --can now be done electronically, he says. "You used to have to do that in a darkroom. It was very time-consuming, and it was more art than science." He adds: "Scientists now have far more control over the visual medium that they're going to use to communicate to their fellow scientists." Acquisition By Silicon Key to digital microscopy is semiconductor-based CCD acqui- sition technology. CCD devices capture images in arrays of pixels, the digital information units of the image. "If you were to look at film at very high magnification, you'd see grain," says Michael M. Kersker, national technical marketing manager for microscope manufacturer JEOL USA Inc. in Peabody, Mass. The grain, he says, is derived from actual silver halide or other particles in the film emulsion, and the resolution of the image cannot be finer than the size of those grains. "Those are essentially the pixels of film. Each one represents a little packet of information. Now, you can create packets like that in a very orderly fashion using semiconductor technology, using CCDs." When light hits the active silicon areas of a CCD, Kersker says, it will create a charge. The charge level depends on the amount of light hitting the silicon and is converted to a so-called gray scale--although the scale can be displayed in any color. Color images are created with multiple CCDs sensitive to different wavelengths in register with each other. Typically, gray scales resolve 256, 1,024, or 4,096 levels, Kersker says, even though the eye can perceive only about 70. But the large number of scale levels is important for successful image enhancement and analysis. An overexposed image might appear black to the eye, but electronically discernible contrast can be converted to a visually discernible contrast using computer software. The success of the procedure is directly related to the number of scale levels present in the apparent blackness. Despite the growing advantages of digital imaging, some microscopists will continue to use film for their documentation for some time to come. This is because the image quality of film is still superior, according to Kodak's Berke. But even for microscopy systems based on film, CCD technology is playing a part. Microscope manufacturer Olympus America Inc. in Lake Success, N.Y., for example, offers the automated PM30 Photomicrographic System, which uses a CCD with 400 individual detectors to calculate precise exposures. The system's special emphasis, according to the manufacturer, is fluorescence. Integrated Systems Some microscope manufacturers offer integrated digital-image acquisition and analysis systems. Their capabilities and costs, depending on available options and user needs, can include image processing, analysis, and archiving. For example, Carl Zeiss Inc. of Thornwood, N.Y. introduced the AxioDoc Image Archiving Workstation in October, to complement the company's Axioskop, Axioplan, or Axiovert microscopes. The system runs on a 486-processor personal computer under the Windows 3.1 operating system and is intended to be a comprehensive image- processing, measurement, annotation, archiving, and retrieval system. Using a coding accessory, the AxioDoc system automatically references the magnification that was used to create the image. Additional dimensional and statistical information can be linked to the image and other data. "So, a digitized image will be stored with all its pertinent data," says Seth Miller, marketing representative for Zeiss. "Then, using computer technology, you can go through, sort, and find anything related to that topic." Leica Inc. in Deerfield, Ill., offers the Quantimet 570 Image Processing and Analysis System, which provides many of the same features for users of its microscopes. For researchers working in smaller laboratories, who may be daunted by the costs and complexity associated with such full- scale systems, there are lower-cost, easier-to-use options. Nikon, for example, offers the Coolscan, or LS-10, film scanner, a version of which can be mounted in a personal computer disk drive bay. With a minimum of technical expertise required from the user, Coolscan converts color or black-and-white 35 mm slides to a digital format at a resolution of 2,700 pixels per inch. The disk-drive-bay version lists for $2,300, while an external version is available for $2,600. Despite its relatively low cost, Coolscan provides many of the advantages of more expensive digital-image-acquisition devices, accord- ing to Stan Schwartz, confocal imaging manager for Nikon. "And slides can fade," Schwartz adds. "But once the image is digitized, the numbers are incorruptible." (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : DIGITAL IMAGING IN MICROSCOPY TY : TOOLS & TECHNOLOGY PG : 19 The following companies are among those supplying digital cameras, scanners, integrated digital-image handling and storage systems, and/or microscopes that support these products. Products, capabilities, and costs vary, depending on available options and user needs, and manufacturers should be contacted directly for details. Eastman Kodak Co. Advanced Imaging Technology Group 901 Elmgrove Rd. Mail Code: 35405 Rochester, N.Y. 14653-5405 (800) 242-2424 Fax: (716) 726-9868 Image Systems Inc. 8835 Columbia 100 Pkwy., Suite A Columbia, Md. 21045 (410) 995-0748 Fax: (410) 995-1335 JEOL USA Inc. 11 Dearborn Rd. P.O. Box 6043 Peabody, Mass. 01961-6043 (508) 535-5900 Fax: (508) 536-2205 Leica Inc. 111 Deer Lake Rd. Deerfield, Ill. 60015 (800) 248-0123 Fax: (708) 405-0147 Nikon Inc. 1300 Walt Whitman Rd. Melville, N.Y. 11747-3064 (800) 52-NIKON Fax: (516) 547-0299 Olympus America Inc. Precision Instruments Div. 4 Nevada Dr. Lake Success, N.Y. 11042 (800) 446-5967 Fax: (516) 222-7920 Carl Zeiss Inc. One Zeiss Dr. Thornwood, N.Y. 10594 (800) 233-2343 Fax: (914) 681-7446 (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Elite Society Celebrates Scholarship In All Disciplines AU : STEVEN BENOWITZ TY : PROFESSION PG : 21 Not every club can boast a membership that has included such scientific luminaries as Marie Curie, Charles Darwin, Thomas Edison, and Albert Einstein. The American Philosophical Society can. In the true philosophical spirit--the term actually means "love of learning"--the organization celebrates scholarly achievement in the sciences, arts, and humanities. Last spring, when the elite organization--the United States' oldest honor society--turned a robust 250 years old, it threw itself a four-day fete, paying homage to founder Benjamin Franklin's ideal of "promoting useful knowledge." It even invited a king--Juan Carlos I of Spain--to keynote the anniversary bash at its Philadelphia headquarters next to Independence Hall. While the society prefers a low public profile, its talented membership needs no introduction. Its eclectic roster includes more than 200 Nobel laureates, nearly half of whom joined before winning the prize. The list has swelled to an all-time high of 711 members (126 foreign), and includes British physicist Stephen Hawking, former Surgeon General C. Everett Koop, Harvard University ecologist E.O. Wilson, and Nobel physicist Leon Lederman. Scholarship And Relevance Although the group's members wield a great deal of practical influence over the affairs of society and state, the organization, as a body, has none itself. Whereas the National Academy of Sciences serves as a national scientific advisory board, the philosophical society's mission is to "assemble the top people in a wide variety of disciplines in sciences, humanities and arts and set the standards of excellence in those areas," says 80-year-old executive officer Herman Goldstine, a retired Princeton University mathematician and holder of the National Medal of Science as one of the inventors of the electronic computer. "This is one of the few places in the world where scientists and humanists meet on equal grounds and discover that scholarship is scholarship, whether in nuclear physics or history," said former philosophical society president Eliot Stellar in an interview just before his death last month at age 73. Stellar said he especially enjoyed the semiannual meeting in Philadelphia, when the society holds two days of talks and lectures directed at the nonspecialist and often leading to vigorous debate. A meeting earlier this year, for example, featured talks on such topics as the Big Bang and black holes, the molecular genetics of heart disease, and the utility of pure mathematics, particularly the role of prime-number theory in banking codes. The society's autumn gathering, to take place November 11-12, will include discussions of astronomy as well as slavery and the Civil War. "That's an important aspect of the society's members," said Stellar, a one-time University of Pennsylvania provost who headed its department of cell and developmental biology at the time of his death and was known for his pioneering work in behavioral neuroscience. "Great minds coming together to talk and listen to a variety of topics." The society first drew international notice in 1769, when Philadelphia member David Rittenhouse first described the path of Venus crossing the sun, attracting the attention of scientists around the world, including the illustrious Royal Society of London, after which the philosophical society is loosely modeled. In its early days, it served as a library of Congress, national archives, patent office, and national science foundation, until special government agencies took over these roles. After its early national prominence, its influence and finances waned. A generous bequest in 1931 rescued the society from fiscal ruin and helped it regain prestige. Today it carries a healthy $67 million endowment and operates out of a three-building complex. Part of the philosophical society's charm lies in its vast library of some 6 million manuscripts, which includes librarian Martin Levitt's favorite: a handwritten 1859 letter addressed to evolutionist Charles Lyell, imploring the British scientist to review an early draft of a treatise tentatively titled "The Origin of the Species." "Imagine Charles Darwin asking Lyell to look over what many consider the second most important book ever written [after the Bible]," Levitt says, noting that the letter is part of the largest repository of Darwin papers outside of Cambridge, England. Yet for all its bluster about intellectualism, the organization is surprisingly relevant. "There are some- times advantages to having a politically powerless group with no particular axe to grind making comments about society," notes cancer geneticist Alfred Knudson of Fox Chase Cancer Center in Philadelphia. In addition to April and November gatherings, the organization publishes books and monographs and hands out some $600,000 annually in grants, mostly small awards of a few thousand dollars each for scholarly research and travel. (In fact, it's the U.S.'s oldest existing private research grant program, begun in 1933, when it gave $3,000 to the second Byrd Antarctic expedition.) The society's vast Library Hall holds some 180,000 volumes, including more than two-thirds of Franklin's papers, and one of only two Thomas Jefferson-penned versions of the Declaration of Independence, congressional editing included. Most of Meriwether Lewis and William Clark's journals are housed there (President Jefferson sent his intrepid explorers-to-be to Philadelphia for crash courses in the sciences before embarking westward), as is a first edition of Newton's Principia. Exclusive Membership Getting into this highbrow club isn't easy. There are five classes of members: biological scientists; social scientists; mathematical and physical scientists; humanists; and a loosely defined fifth category for those in "the arts, learned professions, and public affairs," which was added slightly more than a decade ago to appease complaints about the group's heavy academic composition. Approximately 25 new members are elected each year by the existing members, mostly to replace those who have died. Its membership is mostly male. Although its first woman member-- Princess Dashkova, who headed the Russian Imperial Academy of Sciences--was elected to the society back in 1789, female membership has remained small, today numbering 48. Former president Stellar acknowledged as much last April when he noted in a speech that women, minorities, and Third World scholars were grossly underrepresented. Out of 27 newly elected members in April of this year, only six were women. In the interview this fall, Stellar contended that the shortfall isn't confined to his group; it's reflected in academia and society. "We need to make greater efforts to recruit women and minorities into the society," he said. "But universities have had a hard time recruiting them, as well. You see that in the lack of Ph.D.'s. Before we can elect them to the society, they need to have some standing in their fields, which takes time to develop." "It's like any other organization," says Penn biochemist Mildred Cohn, Benjamin Rush Professor of Biochemistry, emerita. "I don't think it's particularly anti-women. I think they are trying to remedy the situation, but there simply haven't been many women in the pool." Cohn, who also is a member of the National Academy, contends that the "lack of women is probably more striking" in that organization, given its public visibility. "The average age of [philosophical society] members is high--at least 60. People don't get considered until they acquire quite a body of work," says Cohn. "These things take time." Robert K. Merton of Columbia University, who specializes in the sociology and history of science, observes that the relative lack of women members has to be seen in historical perspective, and that changes must be viewed over time. "Every society, like American society, has underrepresented women in the upper reaches," he says. "The pool of potential members [in the philosophical society] has been growing, but it's still smaller than that of men." Appreciating Diversity For such a busy bunch--college presidents, Nobel laureates, international heads of state and industry, and otherwise over- committed academicians and scholars, for whom the prestige of yet another society membership means little--why bother? Knudson, like many other members, delights in the diversity of the topics discussed at the meetings and the opportunity to hear about and reflect on disciplines other than his own. The society, Knudson says, is "the one place I can go that I can contemplate the question, what is history going to say about us when we're gone? What have we contributed? "We learn in school about the grandeur of ancient Greece and Rome. They weren't about conquests--they were about human creation. We've made enormous contributions to the history of man, in science, and how to govern. I'm worried that in these modern times we sometimes get so preoccupied about immediate problems that we'll forget about the human effort on a grander scale." Steven Benowitz is a freelance science writer based in Hershey, Pa. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ NEXT: ----------------------------------------------------------------- TI : Ex-OTA Staffer Brings `Fresh Eyes' To NSF Division Director's Post AU : PHIL BECK TY : PROFESSION (PEOPLE) PG : 22 Sociologist and science policy analyst Daryl E. Chubin has been appointed division director for research, evaluation, and dissemination in the education and human resources directorate of the National Science Foundation. His appointment follows seven years at the congressional Office of Technology Assessment (OTA), which he left in the position of senior associate. The move from the legislative to the executive branch has given him a new perspective on the challenges of implementing congressionally mandated education initiatives at NSF, Chubin says, but also gives the agency a pair of "fresh eyes" in evaluating its educational programming. The responsibilities of the year-old division, Chubin says, are twofold: It administers several primarily research-based education programs and evaluates and monitors the entire portfolio of the agency's 200-plus educational initiatives, ex- ercising a sort of "quality control." One example of a program Chubin's division administers is Application of Advanced Technologies (AAT). AAT's general mission, says Chubin, is "to bring technology to bear on as many NSF educational programs as possible." On a broader scale, Chubin says, his division looks at all of the agency's education programs with an eye toward whether they fulfill performance objectives and NSF's overall educational goals. "When NSF lends its imprimatur to something that can be used in the classroom, what does that mean?" he says, as an example of a central question his division tackles. "What kind of `back-end' quality control has it received?" More specifically, he says, his division tries to determine: "What difference are the programs making? How do you measure outcomes? What have been the targeted objectives of various programs?" In taking the lead in determining science education goals and methods, Chubin says, NSF is in a "good news-bad news" position: the good news is that the agency is an "important player," in the eyes of Congress and others, in setting educational priorities; the bad news is that this is "very often done within current budget constraints." He adds: "I happen to think that Congress asks very pertinent questions. But they sometimes have unrealistic expectations of time and of magnitude. `Well, if you can do this in 10 states, why can't you do it in 40? If you can find this out in three years, why can't we do it in two?' "Education does not fit those kinds of time frames ... or scale questions." Chubin says his experience with OTA and Congress will help him in dealing with their demands, but also has given him the ability to look at NSF's programs critically. "New leadership brings new opportunities," he says. "I come here with fresh eyes.... It behooves us to take a hard look at ... what needs to be expanded, what needs to be consolidated, and what needs to be let go. We can't do everything." Because of the challenges NSF faces, Chubin says, he left OTA to help: "The central motivation for my moving into the position is that this is a critical time for the foundation ... and the work that I had done in science education and science policy convinced me that I could make a difference." Chubin, 46, received his Ph.D. in sociology from Loyola University in Chicago in 1973. He became a sociology professor at Georgia Institute of Technology in 1977. He joined OTA in 1986 as a senior analyst. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================ ----------------------------------------------------------------- TI : ELIOT STELLAR TY : PROFESSION (OBITUARY) PG : 22 Eliot Stellar, a physiological psychologist and former provost of the University of Pennsylvania, died of cancer October 12 in Philadelphia. He was 73 years old. Stellar's research focused on the physiological processes of the brain that affect human behavior, especially appetite and obesity. Stellar was the author or coauthor of numerous highly cited papers. His most cited work was "Palatability, food intake, and obesity in normal and hyperphagic rats" (Journal of Comparative Physiology, 58[1]:63, 1964), which had garnered 235 citations as of 1990. His 1954 paper "The physiology of motivation" (Psychological Review, 61[1]:5-22, 1954), which had received 180 citations as of 1992, is considered by many to be a seminal work in his field. In addition, he was the author or coauthor of several books, including Physiological Psychology (New York, McGraw-Hill, 1950), considered a standard text in the field; Eating and Its Disorders (New York, Raven Press, 1983); and The Neurobiology of Motivation and Reward (New York, Springer Publishing Co., 1985), co-written with his son James. He also edited the Journal of Comparative and Physiological Psychology (now the Journal of Behavioral Neuroscience). Stellar graduated from Harvard University in 1941 and earned master's and doctoral degrees from Brown University. After graduating from Brown, he joined the psychology department of Johns Hopkins University and moved to Penn in 1954 as an associate professor of physiological psychology in the School of Medicine. While at Penn, he served as director of the Institute for Neurological Sciences, provost during a controversially extensive restructuring of the university, and Joseph Leidy Professor of Neurological Sciences. At the time of his death, he was chairman of the department of cell and developmental biology- -formerly the anatomy department--and University Professor of Physiological Psychology in Anatomy. In addition to his research and administrative duties, he was a founder of the Society for Neuroscience, a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and a member and former president of the American Philosophical Society--the United States' oldest general learned society (see story on page 21). Stellar was an active member of NAS's Committee on Human Rights, which persuades U.S. and foreign diplomats to intervene on behalf of political prisoners, especially scientists. Russian physicist Andrey Sakharov was among the prisoners the committee helped. (The Scientist, Vol:7, #21, November 1, 1993) (Copyright, The Scientist, Inc.) ================================

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