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Dr. Rita R. Colwell October 20, 2003 See also slide presentation. If you're interested in reproducing any of the slides,
please contact
Thank you, Cynthia1, for a kind introduction. When Cynthia was ambassador to Holland she invited me to speak but I had to excuse myself because of a request by the President to go on Air Force One to California for a speech on science and technology. Tonight we're at quite another "meeting of the minds" at Georgetown University's Life Science Summit. I'm pleased to see that it's a meeting of such disparate minds from biology, medicine, public policy and finance, and I'm looking forward to hearing what's on your minds, after my presentation. The intersection of diverse modes of thought, and the unexpected discoveries this can generate, segues nicely into my own subject matter tonight. I plan to speak about convergence, as well as about the high-risk, the complex, and the unexpected. These words serve as some of our guideposts at the National Science Foundation. We seek out and support high-risk research at NSF, and I'll delve a bit into some mechanisms for doing that. We also identify areas of scientific convergence for special support, and I'll briefly detail these emerging, interdisciplinary research areas. I'll call particular attention to one of them—an area I call biocomplexity—which I think will be of particular interest to you because it can provide a comprehensive, 21st century context for medical and pharmacological research. Last, I will move to the unexpected—that is, how basic research traces serendipitous pathways to quite unexpected destinations. This brief overview will convey the flavor of the National Science Foundation's philosophy for investing in the nation's future. May I have the first slide, please. [Pelican Nebula with Dear Abby quote] Taking chances is an integral facet of NSF's approach to investing in science and engineering. As with almost every subject, "Dear Abby," the advice columnist, sheds some wisdom on this topic too. As she writes, "If you do what you've always done, you'll get what you've always gotten." In fact, at NSF we firmly believe that if the outcome of a particular suite of experiments or a line of research is certain, or if its purport is chiefly incremental, then NSF probably shouldn't be funding it. There is some amount of risk in everything that we support. Presumably the potential payoff will be commensurate with the risk, and we count on our reviewers and our program staff to make those sometimes-tough calls. There are at least four ways we can define elevated risk in science, engineering and education, and the categories overlap. [Slide with 4 bullets] First there are projects that are "conceptually" risky - those whose fundamental ideas are at odds with the prevailing wisdom. They may elicit review comments such as "implausible hypothesis." Then there are proposals that are "technically" risky. That is, they require equipment or techniques or approaches that have either not been tried or are assumed to be extraordinarily difficult (for example, crystallizing a membrane protein). Third, there are ideas that are risky because the investigators are proposing to work outside their previously demonstrated areas of expertise. And finally, there is risk that derives from proposals that entail unprecedented combinations of disciplines, or have criteria for success that involve viewing the results from an unfamiliar multidisciplinary perspective. Every year, NSF supports a substantial amount of research in each of those categories. I'll provide some provocative examples in a minute. But first, let's review the internal mechanisms we already have in place to encourage high-risk work. [Mechanisms Slide] One is through the discretion of our excellent program officers who continuously seek out cutting-edge science and fund novel ideas. In this regard, a continuously refreshed perspective and up-to-the-minute knowledge are provided by a large part of our staff who come to work at NSF from universities for limited periods. Another is our portfolio of priority areas, each of which is designed from the outset to promote innovative ways of thinking (and I will address these priority areas in a few minutes). A third is the roster of programs within individual directorates that are specifically tailored to support risky, unconventional ideas. An example is our Frontiers in Integrative Biological Research program, which was established to fund research on big questions that require crossing disciplinary boundaries and encourage risk-taking by making larger, longer awards. Our physical sciences area has an office with roughly similar goals. And, of course, directorates have reserves and "venture" accounts set aside to co-fund special opportunities. Finally we have a standing rule that program officers may commit up to 5% of a program's budget to "risky research," and this can be in the form of SGER awards - small grants for exploratory research - that allow us to support proposals that result from unusual opportunities or surprising new ideas. These do not require approval by external review panels. During Fiscal 2002, NSF made 278 SGER awards out of 323 applications. One of those produced pioneering insights into the structural and metallurgical phenomena that occurred during the collapse of the World Trade Center towers. [Slide of ruin] Those results drew national media attention. But not as much as one of our riskiest SGER grants ... [Taxol Slide] ...the 1992 award that allowed Gary Strobel of Montana State to pursue his hunch that fungi on yew tree bark might have learned to make taxol. As the world now knows, he was right; and in 2001 the process was licensed to a pharmaceutical company. Let me give you four more recent examples of high-risk research projects, each of which tells a different story. [BIO example Slide] Our biosciences directorate received a proposal to develop an unconventional concept of "species" in microbial communities by using genomic ecotypes. Here you can see the research site, Octopus Springs in Yellowstone National Park, a sample of the microbial-rich layer, and component unicellular cyanobacteria and filamentous bacteria. It is a classic example of the sort of work in which the concepts can only be validated by carrying out the research. The multidisciplinary review panel split over the proposal. One group argued that the definition of a microbial species has always been arbitrary. The other emphasized the potential value of an entirely new "species" concept. After several animated discussions, the panel recommended a medium priority. NSF program staff, however, recognized the dispute as evidence that the current intellectual framework for describing microbial species is inadequate, and that confusion exists in the community as to how to begin to resolve the problem. Because the proposal constituted a promising way to provide such a beginning, they recommended an enabling award, which was recently made. [GEO example Slide] We faced a similar problem a few years ago when meteorologists wanted to use the signals generated by the Global Positioning System in space as a probe to reveal various aspects of the atmosphere. By monitoring how the GPS transmissions were refracted and reflected by the atmosphere, investigators hoped to reveal the pressure, temperature and vapor content of the air through which the signal passed. GPS had never been used for meteorology, and many reviewers felt that it was way too risky for NSF. But we funded it anyway. It proved to be a huge technical and scientific success. A federal interagency partnership was formed to exploit the results. In cooperation with Taiwan, which has agreed to pay 80% of the $100 million costs, the group will launch a six-satellite fleet called the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) in 2005. This slide shows existing radiosonde data sites in red, and the added coverage from COSMIC in green. The satellites will produce some 3,000 soundings per day, distributed around the globe, dramatically improving our understanding of the atmosphere. [MPS example Slide] Here's a case study from the physical sciences that is about as risky as they get. The investigators wanted to confirm - with extraordinarily high precision - one of the more exotic predictions of physics: namely, that anti-electrons orbiting anti-protons in anti-hydrogen would experience the same energy transitions as they do in everyday hydrogen. Among the numerous downsides to this proposal was a fundamental problem. No one had ever created anti-hydrogen, much less trapped it and cooled it to the point at which it could be studied. So as you might expect, reviewers were skeptical. Our staff kept examining the proposal and discussing it with reviewers. Eventually, the physics staff concluded that the science was so important that this was a risk that NSF simply had to take, even though it could take many years to achieve the experiment's goals - if they could be achieved. So far, so good. The NSF-sponsored team made worldwide front-page headlines when it created the first anti-hydrogen atoms. Now they're concentrating on cooling and trapping the anti-atoms. Will it work? Nobody knows for sure. But is it a risk worth taking? Absolutely. If we don't take risks, we don't just lose opportunities. The science community loses new knowledge that might have been gained, industry loses critical new insights, and the economy loses the potential for untold new jobs. Viewed in that context, the biggest risk we face may be in not funding enough innovative proposals. [Slide of quote] I like how one of our program officers summed up that attitude in practice, as follows: "I still feel as if I took a big chance in doing this, but in the end I made the right decision. I always feel that the worst mistake I as a Program Director could make is not to take a risk that doesn't work, but to miss taking a risk on a project that in the end should have been funded." [slide with priority areas] I'll move now to our portfolio of priority areas in multidisciplinary research. These overarching areas are: information technology research, nanoscale science and engineering, biocomplexity, mathematics, human and social dynamics, and 21st century workforce. [IT generic slide] As a tool for scientific discovery, information technology has proven as valuable as theory and experiment. Information technology has transformed the very conduct of research—helping us to handle the quantity as well as complexity of data. It enables new collaborations around the globe and lets us visualize in stunning new ways. [nano] This nanoscale image depicts a frontier at a vastly different dimension—at one-billionth of a meter. The promise of nanoscience for the inorganic and living realms converges here, the point at which the worlds of the living and non-living meet. The National Science Foundation leads the National Nanotechnology Initiative, a coalition of organizations from government, academe and the private sector. Our investment includes investigating the societal and educational implications of this new frontier. [Fractal image] Mathematics is another priority area, truly a wellspring for all of science and engineering. It is a springboard for advances across the board. A good example, pictured here artistically, is the fractal, the famous illustration of how inner principles of mathematics enable the modeling of many natural structures. Our math investment goes to fundamental research as well as interdisciplinary research linked to mathematics, to modeling complex, non-linear systems and to critical investments in math education. [stylized face and brain] We have just launched two more priority areas. Both focus on people, as this slide symbolizes. Our human and social dynamics effort will investigate the impacts of change on our lives. It will create new technology tools for social scientists. This research will improve our understanding of large-scale change, such as globalization, and of how people make decisions and take risks. In parallel is our workforce investment, which emphasizes broadening the participation of US students in science and engineering, including women and other underrepresented groups of our population. [Biocomplexity] The final emerging area drawing special NSF investment is biocomplexity, symbolized by this hierarchical spiral. The reality is that the simple questions in biology, and in many other fields, have been answered. Now we need a systems approach, and at last have the tools to support it. Bioscience has evolved to become the locus of convergence for many disciplines, drawing in such disparate threads as the physical sciences, information technology, and the social sciences. Biocomplexity is a way of thinking about the relationships between life and its environment. Ecosystems do not respond linearly to environmental change, nor do the pathogens that live in them. Here I use the form of a spiral, so evocative of life at every level, to underscore the point that understanding demands observing at multiple scales, from the nanoscale to the global. The spiral of complexity begins to unfurl at the most minute scale of the atom, and curves up through successive levels of life, through the cell, the organism, the community, the ecosystem. Complexity principles emerge at each level. The spiral curves both ways—outward, integrating the levels of life, and inward, back to the center. With the perspective of biocomplexity, disciplinary worlds, formerly discrete, intersect to form fuller, more nuanced viewpoints. Biocomplexity is a 21st century term, and the tools it employs--optics, sensors, remote sensing, nanotechnology, information technology and mathematics, among them—let us take the measure of the breadth and depth of life on our planet. Such understanding will open the new frontiers of environmental prediction. The infrastructure and approaches developed to understand the earth will also help us to understand the role of the environment in infectious disease, and can even help us to confront the threat of bioterrorism. After all, interactions between health and environment, whether natural or nefarious in origin, span scales of space and time. For example, the earth's climate acts on a global scale, while decisions on human health are made locally. Integration of these scales is critical to understanding how medicine is really part and parcel of ecology. As travel and the threats of bioterrorism increase, monitoring for pathogens, diseases and climate variables becomes all the more critical. If we do not understand the natural fluctuations in our environment, we will not be able to spot signals that are human-induced. A bioterrorism attack could appear, in the beginning, like any other natural outbreak. There are feedbacks, too; smallpox, once an infectious disease problem, has become a bioterrorism threat partly because of success with public health eradication programs. All of our insights into the environment and health are buttressed by basic research. This points to my final theme, that such research so often leads down unexpected pathways and produces unexpected results. [squid] Fundamental research in ecology, for example, has shed new light on human disease. Shown is a bobtail squid from Hawaii, which exudes a ghostly blue glow on moonlit nights. Its secret is this: The squid ingests quantities of luminescent bacteria, which glow inside the squid and cause its shadow to disappear—perfect camouflage. The real secret, however, is the whispers that animate this community of glowing bacteria—whispers of communication that take place through chemical secretion. Only when enough chemical builds up—indicating that a critical number of bacteria are present—do they light up. [chart of all bacteria that have "signaling gene"] Bonnie Bassler of Princeton University and others have discovered that this bacterial communication governs a wide variety of bacterial pursuits. E. coli and other bacteria responsible for human diseases use similar signaling. Discovery of the "signaling gene" could lead the way to foiling drug-resistant bacteria. Here's a case in which the study of marine bacteria's luminescence—once considered "incredibly arcane, with no application at all"—produces a fundamental insight for human health. [Adaptive optics: Blue Neptunes and cones in the eye] One more very striking example of how advances in one field today often resonate in another: adaptive optics, a new tool invented for a precise purpose in astronomy, has actually found service in vision science. Adaptive optics sharpens astronomers' vision from ground-based observatories, as we see here in "before-and-after" pictures of Neptune. When used to look at the human eye, adaptive optics produced the first images—shown in red, green and blue—of cone arrangements in the living eye. As an optometry scientist at Indiana University, Larry Thibos, put it, "The real breakthrough is the work of these clever astronomers. All we have done is steal their ideas and try to put them to use for vision science." To conclude, I've touched upon some of the principles that guide the development of policy at the National Science Foundation. Having the vision to take risks, understanding that creativity often results from disciplinary convergence, perceiving that the life sciences are really about all of life on our planet, that ecology and medicine are inextricably intertwined—these are perspectives that I hope might animate and give context to your discussion at the summit. Speaking of perspective, I'll close with one more bit of wisdom from "Dear Abby"—and it happens to be that "The less you talk, the more you're listened to"—so now I will be very pleased to take your comments and questions.
1 Ambassador Cynthia P. Schneider, Associate Professor, Georgetown University.
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