Scientific Enterprise At Critical Juncture, Say Panelists, Researchers

MISCONDUCT POLICY: University of Illinois' C.K. Gunsalus cites problems of oversight in academia. Is science in crisis? Scientists, historians, administrators, and others have debated this issue over the last few decades. The controversial topic was the impetus for a September 19 conference at George Washington University (GWU). Panelists at the day-long symposium, titled "Science in Crisis at the Millennium," think something has gone awry. Keith Yamamoto, University of California, San Francisco: "If we have a crisis, it's that the public at large really isn't educated about science." Conferees examined, among other things, purported crises in quality, knowledge, human genetics, peer review, misconduct, and morale. In addition, speakers at the meeting noted that funding simply isn't what it used to be. Funding agencies are being asked to do more with less. Competition for dwindling resources is fierce; though more research grants than ever are being awarded, they are harder to come by. Scientists' morale may be lower than ever. "We have treated the individual crises as if they were symptoms of underlying maladies [in science]," conference organizer Horace Freeland Judson said at the meeting. Judson is director of GWU's new Center for the History of Recent Science, which sponsored the conference, and a research professor of history. "If you put all of these symptoms and problems on a program, they point to what the underlying malady is." He maintains that "science will never recover that glorious situation of free-flowing research funding, and a sense of community and mentorship it had in the quarter-century after World War II." FALLING SHORT: Physics Nobel laureate Leon Lederman sees problems in the U.S.'s "robust scientific enterprise." Such claims are not new. In 1991, Nobel Prize-winning physicist Leon Lederman wrote a report to the board of directors of the Washington, D.C.-based American Association for the Advancement of Science (AAAS) titled "Science: The End of the Frontier?" In the report, Lederman, then AAAS president-elect, complained of a federal funding shortage for science. From his informal survey of some 250 academic scientists at 30 top research universities, he concluded that American science was indeed in crisis. Rising competition for shrinking federal dollars threatened the country's technological base and leading role in the world market. WHAT CRISIS? UCSF's Keith Yamamoto sees "exciting times" ahead for biological sciences researchers. As expected, many scientists challenge the notion of a crisis. "In the biological sciences, there's never been a more exciting time because the lights have come on between disciplines to see how things are linked together, from yeast and bacteria to clinical medicine," contends Keith Yamamoto, chairman of cellular and molecular pharmacology at the University of California, San Francisco (UCSF). "The opportunities have never been greater. "If we have a crisis, it's that the public at large really isn't educated about science," adds Yamamoto, who was not at the meeting. "Scientists need to communicate to citizens that having an understanding about science and scientific reasoning is not just for scientists but for the general public as well. It will be charged with making difficult decisions about all sorts of technologies." Yamamoto notes that the scientific community is making an effort to further educate the public. "Scientists have begun to wake up to the fact that for the magnitude of support we want, we'll have to get involved in the political process ourselves-educating the public and Congress about what we do," he says. Even Lederman maintains that in many ways "we have a robust scientific enterprise." However, the Pritzker Professor of Physics at the Illinois Institute of Technology in Chicago and director, emeritus, of Fermi National Accelerator Laboratory in Batavia, Ill., points out that "the 1991 screening was an indicator of troubles." He tells The Scientist that "industry has been giving up incredibly productive laboratories, universities are in financial straits, and too many Ph.D.'s in science are getting jobs in areas they were not trained in." The 16 speakers (and some 300 attendees) at the GWU conference agreed that the American scientific enterprise has more than its share of problems. Most were bullish on the science and less pleased with the process. They focused on dwindling federal funding, challenged the peer-review process, and called for universities to pay more attention to scientific misconduct. TOUGH TASK: New York Academy's Rodney Nichols wonders if the top research is adequately funded. Few scientists argue that American science is, on balance, the highest-quality research in the world. Yet judging quality is often a difficult task. Rodney W. Nichols, president and CEO of the New York Academy of Sciences, doesn't necessarily see a crisis in quality. He is concerned about a continuing dilemma of how to appropriately distribute limited funds. Ensuring that research is indeed of high quality when determining resource allocation is paramount, he said at the conference. "If there is a crisis in quality, it's [over the question of] deciding what is a fair amount of money to bet on [a scientist's] future potential," Nichols tells The Scientist. "They [funding agencies] seem to support a lot of things a little bit, rather than focusing on the 10 [percent or] 20 percent that is demonstrably the best. We tend to have our fights over the last 10 percent to get funded. "You're always faced with these resource-allocation questions," Nichols says. "Looking back, maybe 90 percent of the most highly cited work in the last few decades [has] come from 10 percent of scientists. No one knows which research that will be in advance. On the other hand, you're better off investing in the areas of higher quality [that], in the long run, will pay off. "What worries me is that the top 10 percent are probably getting funded now, but the issue is, are they getting enough support to do what they want to do?" he comments. "They are probably doing the safer type of work to ensure that funding." That in turn might curtail innovation, he maintains. "The crisis in funding comes here-do those who judge [research funding proposals] have the guts to pick the best and concentrate on that?" "There's pressure on the peer-review study groups, with so many research universities out there, to award funding [to as many as possible]," Judson notes. However, he adds, "the distinction between research judged in the 89th and 90th percentile in ranking makes it increasingly difficult for study-section members to choose." With such heated competition, Judson says, some scientists question the appropriateness of billions of dollars set aside for research on AIDS, which has a limited impact on public health in relation to other problems such as cancer, heart disease, and improving child and maternal health. "We know we need a cure-a vaccine for AIDS-but what amount [and return on the investment] is appropriate?" OVERWORKED: Conference organizer Horace Freeland Judson worries that the peer-review process is strained. Nichols favors investing research dollars in people rather than in projects, and giving higher consideration to past performance rather than future potential. However, he concedes, that is not a solution to the funding problem, particularly in cases of judging proposals by scientists who switch fields or pursue interdisciplinary research. Nichols also argues for mission-oriented research over curiosity-driven work. "There's always some very deep issues that might take a long time to solve and require a fundamental approach before you can complete the mission. Many mission-oriented research projects have resulted in very rich gains at a deeper level." He cites the National Institutes of Health's mission, setting up institutes around diseases and organ systems, as a successful example of such an approach and the accompanying discoveries in basic and clinical research. Some research investments, however, result in unexpected findings. Cancer and AIDS research, for example, offer windows to the developmental processes of the immune system and the cell. Such work has longer-term benefits, Nichols contends. Though few scientists seem to agree, one journalist believes that the quality of scientific research is so high that science itself has hit a wall, resulting in a "crisis of knowledge." One conference speaker, John Ziman, an emeritus professor of physics at the University of Bristol, England, concluded that "science cannot go on growing exponentially." He referred to the inevitable slowdown in growth as a "transition to a steady state." A scientific slowdown is neither a new nor a surprising notion, given this century's incredible growth in the number of scientists and in science itself, agrees John Horgan, senior editor at Scientific American. Borrowing from science historian Derek de Solla Price, he notes that some 85 percent of the world's scientists who have ever lived are alive today. And, as he contended in his recently published book, The End of Science: The Limits of Knowledge in the Twilight of the Scientific Age (Addison-Wesley, New York, 1996), all of those scientists have been busy. The book, which includes a series of interviews with renowned scientists as well as Horgan's own observations, is a discourse on why he believes there are no great scientific theories left to be discovered-at least none that are provable. Horgan claims that the scientific establishment is a victim of its own success: Astronomers have seen all of the universe they will ever see; physicists have probed the nature of matter as far as practically possible; and Charles Darwin's theory of evolution is the ultimate for biology. Will scientists ever answer questions about the underlying nature of matter and the origin of the universe? How would anyone really ever know?, he contends, calling such work untestable. He uses neuroscience as an example. He says that the science of the mind has become much more empirical since the days of Sigmund Freud. He thinks neuroscience will one day be able to correlate specific physical and mental states of the brain, which will have profound practical impact in treating and perhaps eradicating mental illness. Yet, neuroscience currently cannot solve many riddles about the brain and the nature of consciousness. "Some observers say that unobservable and untested theories are signs of science's vitality," he pointed out at the conference. "I see it as signs of its terminal condition." Horgan contends that "science advances keep imposing limits on its own power. By far the greatest limits to the future of science is its past success." Most scientists are less than pleased to hear this. Lederman calls the notion that there are no longer scientific unknowns to conquer "nonsense," noting that particle physics, for example, has many worlds left to explore. JUST BEGINNING: NCHGR's Francis Collins sees a long road ahead to develop therapeutics for genetic diseases. At the meeting, Francis Collins, director of the National Center for Human Genome Research (NCHGR) at NIH and the Human Genome Project (HGP), remarked that the human genome contains only so many genes to uncover and just so many to sequence. But does that mean that there will be no genomics after 2005? Hardly, he argued, noting that chemistry didn't grind to a halt after Dmitry Mendeleev outlined the periodic table of elements. "The genome project is trying to generate the periodic table of genes," he says, referring to the federal government's ambitious 15-year, $3 billion plan to locate and identify nearly the entire complement of human genes. "Once you've determined that sequence of the 99.9 percent of genes that are identical in all of us, that's it," he contends. "But you've no more understood biology by having that set than you have chemistry by having the elements. You have to understand how they work together, how the genes intersect and construct a cell and an organism. Already technologies are emerging to understand the functional aspects of the genome. "It will become possible in the next few years to sample the majority of human genes in a tissue and see which genes are on or off, and manipulate that cell, and then generate some hypotheses about what's going on." Science and technology discovery frequently outpaces society's ability to thoughtfully use such knowledge, many scientists agree. Many point to the HGP as such an example. It continues to leap toward completion, at least two years ahead of its originally scheduled end date of 2005. Scientists have already begun thinking about what comes next. What Collins has dubbed "Genome 2," he believes, will be the future of genetic medicine: developing diagnostics on the one hand and, in the long run, understanding how genes and their products work, from which therapeutics for diseases will emerge. While reaching for the future, researchers must continue to grapple with unresolved issues today, Collins noted at the conference. "We have a very powerful new brand of medicine lurching into clinical practice, and no one is sure how it will be received [by physicians]." Collins points out that there will be a period, perhaps a decade or more, in which "we will have mapped and cloned the genes of diseases with genetic components, but will live in this unknown area" between sequencing the gene and understanding the basic biological defect involved, and using such knowledge to develop diagnostics and therapeutics. BRING BACK THAT FEELING: Columbia's Robert Pollack argues that scientists have lost the collegial spirit. "That's the crisis [in human genetics]," contends Columbia University biology professor and conference speaker Robert Pollack. Pollack argues that human genetics has already arrived at a crossroad. Doctors can use the new genetic medicine to determine a patient's risk for disease, but can do little to prevent or treat it. Take BRCA1, the first breast cancer gene finally isolated in late 1994 (S. Benowitz, The Scientist, Jan. 23, 1995, page 1). Tests to detect genetic mutations are available, but the question of whom should be tested, the meaning of the test results, and how they should be used remain unresolved. "We have the ability to make diagnoses without attached therapy-we have the ability to tell someone what they will die of without [being able to offer] therapy," Pollack says. "Collins optimistically-and wrongly, I think-believes it's a window that will be [only] a decade long. The technology of telling you what's wrong with you before symptoms [appear] is in place-the treatment is not." What's more, Collins points out that a significant information gap exists in current know-how among scientists and many health-care providers who aren't adequately trained or prepared for the revolution in genetic medicine. He contends that the public's knowledge is woefully lacking as well. "We [as a society] are not prepared for this," he told the GWU audience. "We're heading for real trouble if we don't have a cohort of practicing physicians who are ready to take it on." The effects of that unpreparedness are already being felt, says Collins. "We are already slipping to overstating the significance of our genes." He expresses concern that people will ascribe to genetic determinism-that human disease and behavior and practically everything is controlled and hard-wired by DNA. "Even when we completely understand all of the genes, what happens to us will be a result of interactions of genes, environment, and free will, which won't go away as a consequence of understanding our biology," he maintains. While no one seems able to accurately gauge the incidence of scientific misconduct in recent years, several cases involving renowned scientists have been in the headlines. The academic research community has not responded effectively to such cases, according to C.K. Gunsalus, associate provost at the University of Illinois. As a result, the government is attempting to legislate solutions where academia failed. The congressionally mandated Commission on Research Integrity (CRI), headed by physician Kenneth Ryan, a professor, emeritus, of obstetrics, gynecology, and reproductive biology at Harvard Medical School, is one such government attempt to legislate misconduct rules. It issued a report last November on ways to improve the Public Health Service's response to scientific misconduct. The report's controversial conclusions, including its definition of misconduct, are under consideration by Health and Human Services Secretary Donna Shalala (B. Goodman, The Scientist, July 22, 1996, page 3).Gunsalus, who was a member of the 12-member CRI, cited inherent problems in the structure of academia: A well-run research university shields researchers from the nuts and bolts of running an institution. "The paradox is, these scientists say there are few problems because they don't see them," she says in an interview with The Scientist. "If there is a crisis of misconduct, it's in the academic community's denial. [Universities] have to deal with it to develop effective procedures to handle it [misconduct]." She contends that government intrusion and regulation is scandal-driven. "Informal rules don't handle [misconduct cases] very well," she states. The peer-review system has also been under government scrutiny. More than three-quarters of scientists who apply for federal grants are rejected. NIH has been examining ways to improve the process and appointed an internal committee to suggest improvements in the system. The Committee on Improving Peer Review has already issued recommendations, which are under discussion at NIH and among institute councils, which make the final funding decisions. Judson worries about the grant reviewers themselves. He points out that with increasingly high-quality proposals not getting funded, grant reviewers find it more and more difficult to differentiate between research proposals that merit support and those that just fall short. Scientists become weary of serving on such panels: "The peer-review process is wearing out," he says. Peer-review problems extend beyond funding issues, Judson contends. With the proliferation of journals, he says that scientists don't have enough time to adequately review manuscripts. Journals accept fraudulent papers that don't get filtered out by the peer-review process. This in turn leads to increasing incidences of misconduct. "There's a double crisis," he says. And "these crises interlock. The crisis of peer review, of too many journals-it's been said that anything can get published if you shop around-reflects the crisis in quality." Pollack, a molecular biologist, addressed what he perceived as a crisis in morale. After some 25 years of running a laboratory, Pollack decided to leave the bench five years ago. He found that spending his time writing grants for research that would merely serve as a means of getting a chance to write more grant proposals for further funding was simply too much time wasted. He argued that today's scientists have lost the collegiality and social structure that made the endeavor fun. Scientists no longer interact socially, lack a team spirit, and suffer isolationism more and more. Some scientists measure their self-worth through the research support they receive, he notes. Other factors affecting morale include rising competition among colleagues as well as graduate students and postdocs. Nobel laureate Phillip Sharp, head of the department of biology at the Massachusetts Institute of Technology, doesn't see crises in either science or morale, though he concedes that "science has real problems." Sharp, who didn't attend the meeting, acknowledges that funding and competition for jobs are high on the list. Beyond the funding difficulties and the fact that the scientific enterprise itself has grown so large, Sharp wonders, "are we attracting quality [students] as we did 20 years ago? "I'm not sure the appeal of a career [in science] is as strong as it once was," Sharp says. On the other hand, "science is faster-paced today. Life is more hectic and less collegial. The scientific operation has grown, and in molecular and cell biology, for example, biotechnology has added another dimension to the careers of scientists. "Science is a cultural activity," he observes. "We'll continue to redefine what's exciting. There will be no lack of frontiers."

Scientific Enterprise At Critical Juncture, Say Panelists, Researchers

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