Thinking Beyond Tomorrow

Courtesy of Getty Images That discovery is fraught with unpredictability poses an enormous problem when evaluating research priorities and allocating funding. It also sends many scientists scrambling for cover when they are asked to prognosticate the future. The Scientist asked anyway. Research scientists, venture capitalists, patent attorneys, even a biomedical professor-turned-mystery author offered their opinions on what will be the hottest new technologies five years hence. Their responses varied considerably. Some say bioterrorism is an imminent threat, and some say it's an improbable one. Some say proteomics will finally bear fruit, while others say it won't. Neural cartographers, structural biologists, and nanotechnologists will witness advances, they say. Genomics will remain the foundation upon which all good things will come. "It is the means, not the end," says Charles Cantor, cofounder of the Human Genome Project and chief scientific officer of Sequenom, a high-performance DNA-analysis company in San Diego. Cantor predicts that the next five years in the life sciences will see a major trend towards more quantitative measurements as well as a qualitative way of thinking. "Biology is transitioning from an observational science to a predictive one," he says. THE PERSISTENCE OF GENOMICS Genomics looks to be a safe bet for the foreseeable future, and a fruitful one. With every new genomic sequence, researchers gain insight into the evolutionary process. "Comparative genomics will lead to many discoveries," says Carnegie Mellon University researcher Victor Weedn, an expert in forensic science, pathology, and DNA typing. "In the next half-decade, a sufficient number of species and subspecies and populations of species will be DNA-sequenced, permitting new insights into the impact of many genes." Comparative genomics uses genetic information gleaned from one species to help decipher that of another. Last summer, research scientists reported on the first large-scale comparison of the human genome to 12 other vertebrates. The National Science Foundation recently poured $100 million into plant genome research, partly to compare the complete genetic sequences of related plants. Bacteria, too, will be subjected to ever more genomic scrutiny. Jay Hinton, head of molecular microbiology at the UK's Institute of Food Research, predicts a rapid explosion in the understanding of bacterial evolution over the next five years. "Today, biologists have completed the sequencing of 126 bacterial genomes. Five years from now, that number will be closer to 600," says Hinton, who investigates bacteria that cause food poisoning. "That means we will have covered all of the bacteria that cause human and animal disease." And that information, in turn, will open a window into bacterial evolution, exposing the mechanism by which new lethal variants of bacteria arise. "We will be in a better position to combat bacterial infectious disease," he concludes. FINANCIAL CONSIDERATIONS After a painful economic lull that stalled research and the testing of new technologies, the life sciences sector is hot. The AMEX Biotech Index is up 40% this year. In the second and third quarters, the biotech sector absorbed nearly $700 million in venture capital investments, according to life sciences securities expert Bryan Armstrong, principal at Ashton Partners, a strategic investor-relations firm in Chicago. "This is approximately 10% higher than the quarterly average of venture capital investments in biotechnology since 1997," says Armstrong. "In addition, biotechnology public financing has seen a stable up-tick as well." And the trend will likely continue, he says. "The life science industry is less correlated with the broader market [compared to other industries], and the potential returns are still well above the average even when adjusting for risk," he says. "These are attractive attributes when considering a diversified investment approach, regardless if you are Joe investor or Fidelity, or if it is a bull market or bear market." Mike Hildreth, director for Ernst & Young's Americas Biotechnology practice, offers this bold prediction: "The biotech industry as a whole could reach a major milestone within five years: its first profitable year overall since the industry began more than 25 years ago." REINVENTING MODERN MEDICINE Just as the Human Genome Project reinvented the way scientists view and practice biology, Weedn predicts that "systems biology and cellomics will become the dominant research area, as we try to understand how all this information fits together" in the next five years. "It will reincarnate physiologic research." Funding agencies evidently agree. In November, the NSF announced it would spend $4 million in FY 2004 for "Quantitative Systems Biotechnology." And last year, the National Institutes of Health launched an initiative to create Centers of Excellence in Complex Biomedical Systems Research. Massachusetts Institute of Technology (MIT) received a five-year, $16 million grant in September to expand its Computational and Systems Biology Initiative as part of that push. "These far-sighted grants from NIH provide critical support for an evolving new approach to life science, bringing scientists, engineers, and computer experts together to develop an understanding of complex cellular systems," says Charles M. Vest, president of MIT. "The interplay of sophisticated experimental measurements with advanced computational modeling will advance our basic understanding of living systems and ultimately aid the transfer of that knowledge to medical practice." Indeed, because complex biological circuits control everything from organ development to cancer, systems biology research could have a profound impact on the future of human health and medicine. The Institute of Systems Biology in Seattle is using systems approaches to develop predictive, preventative, and personalized medicine methods. According to the Institute's Web site, within the next 10 to 15 years researchers there expect to identify hundreds, even thousands of genes that predispose to disease. Perlegen Sciences, a privately held genetics company in Mountain View, Calif., uses systems approaches to identify the gene variations responsible for disease and drug responses. The company recently agreed to use its technology to identify genetic markers for drug manufacturer Eli Lilly and Co. "Perlegen and similar companies are diving deeply into the genome to find out what the genetic variations are," says Karl Handelsman, general partner at CMEA Ventures in San Francisco. "In the next few years, diagnostics for all disease is going to change. Anything that has a genetic component will be amenable to better diagnosis and better treatment." Daphne Zohar, managing general partner with PureTech Ventures, a Boston-based life sciences venture-creation company, says a whole-system mindset will allow drug-discovery programs to move beyond the single target approaches and begin to tackle complex multifactoral diseases such as cancer, cardiovascular disease, and type I diabetes. "Concurrently, we will see the rise of personalized medicine, which takes into account an individual's genetic variations, to diagnose and treat these diseases," Zohar says. "The combination of these trends will lead to a radically different and more effective approach to medicine." EYE ON THE MIND "If I were a graduate student starting today, I'd go into neuroscience," says James Glazier, director of the Biocomplexity Institute at Indiana University, Bloomington. Researchers are at the edge of understanding the mysteries of the mind. The 1990s was the "decade of the brain," during which scientists made remarkable strides in understanding what makes the human brain tick and what triggers neurological disease; now they are deciphering the information left in the wake of that expedition. Spectacular advances in brain imaging, such as functional magnetic resonance imaging, coupled with faster and more powerful computational models, expand the realm of research and help fuel discoveries into brain function and structure. The World Health Organization says such advances provide a critical platform for the genetic analysis of human disease and will contribute to new approaches to the discovery of treatments. Experts predict major developments in neuroscience during the next five years. "We've already hit much of the low-hanging fruit in biology and in understanding disease. Now we're getting to the more difficult problems," says Rachel Levinson, assistant director for life sciences, President's Office of Science and Technology Policy (OSTP). Researchers will continue to unravel the mysterious structure-function relationship of nerve tissue, predicts Steve Chubb, CEO of Matritech, a developer of proteomics-based diagnostics in Newton, Mass. Such research will bring clinicians ever closer to effective treatments for multiple sclerosis, amyotrophic lateral sclerosis (Lou Gehrig disease), and other neuromuscular conditions, he concludes. WHITHER PROTEOMICS? Proteomics will continue to bedevil researchers, experts say. "It is unlikely that we will have a comprehensive protein map in 2008," says Chubb. Russell Garlick, CEO of Cambridge, Mass.-based Protein Forest, a life science tools company, agrees. "In 2008, we will know the individual proteins like one knows the sound of a single [musical] instrument," says Garlick. "However, we will only start to realize how proteins work together or how the symphony of interactions may sound." Mapping the structure and function of each and every protein in the human body would be a coup for drug makers, who could then harness this information in their search for personalized medicines. But even some in the pharmaceutical industry have harsh words for their potential lifeline. "By 2008, proteomics will have delivered next to nothing to the drug-development pipeline," says Vishva Dixit, vice president in the molecular oncology division of Genentech, South San Francisco. "The problem with proteomics," says Dixit, "is that the technology hasn't evolved to a level where you can sample a large spectrum of proteins, without considerable bias." For example, he says, integral membrane proteins are difficult to resolve by proteomic approaches. "I don't see this problem being solved in the next five years." Not everyone agrees. "Proteomics will yield a host of hitherto unknown or unappreciated proteins and their pivotal role, even if they haven't yet led to new drugs," says Weedn. Proteomic screening, however, is another matter. By 2008, proteomic and genomic diagnostics will have a "significant impact on medicine," says Garlick. Chubb believes that within five years there will be a number of proteins "in routine use by clinical laboratories to detect cancer earlier and noninvasively." The Food and Drug Administration has approved Matritech's urine-based BladderChek™ test kit, the only cancer-screening test available for use in doctors' offices. Several other proteomic diagnostic assays are in the company's pipeline, including tests for cervical, breast, prostate, and colon carcinomas. HOT SPOTS Other fields are poised for major advances in the coming years, such as structure prediction, a typically time-consuming, painstaking task. Approximately 22,000 protein structures reside in the Protein Data Bank, and 10 years from now scientists hope to have determined 10,000 more. The NIH-funded Protein Structure Initiative, launched in 2000, is a 10-year, coordinated effort that aims to do just that. The resulting inventory could prove to be a valuable medical and pharmaceutical research tool. Edward Maggio, CEO of Cengent Therapeutics, San Diego, says the growing availability of protein structures will "spur a revolution in life sciences that will have long-lived repercussions." Pharmacogenomics (personalized medicine) is another field on the brink. Biomedical science will use gene- and protein-expression biochips increasingly in the next five years, says Duncan Haynes, a 30-year veteran of biomedical science and the author of Pharmacology is Murder (writing under the pen-name Dirk Wyle). The fruits of that technology will spill over into the clinic, he says, in the form of patient-specific regimens (for chemotherapy, for example) based on gene-activation profiles. Experts are also bullish on nanotechnology. The federal government has a long-term vested interest in this area, particularly in relation to nanoscale manufacturing, medical advances, and bioterrorism. According to a government report,1 "The convergence of nanotechnology with information technology, modern biology, and social sciences will reinvigorate discoveries and innovation in many areas of the economy." Armstrong says nanotechnology will be "the hottest technology coming to the market in the next five years." The impact of nanotechnology and biotechnology "will have an enormous effect on biological research, drug delivery, and disease detection in the future," says Andy Watson, vice president of business development for Hayward, Calif.-based Quantum Dot, which makes nanotech reagents for life scientists. Such enthusiasm isn't universal, however. "One hears that nanotechnology holds a lot of promise, but I would be very surprised if it delivers in the next five years," says Dixit. "I just don't see it making major inroads." SHADOWY FUTURE Overall, the future for life science research looks bright. "It is an extraordinarily exciting time," says OSTP's Levinson. "We are getting to the really hard problems." But it is also a time shadowed by fear: Bioterrorism experts do not ask if a bioterrorist attack will occur, says Weedn, but rather, when. "Most would venture to guess that it will happen within the next five years." Not so, says Dixit. "I don't believe there will be any large-scale bioterror attacks in the next 5 years," he says, "as biological weapons, contrary to popular belief, are deceptively difficult to 'weaponize' for large-scale attacks." The federal government isn't taking any chances, however. President Bush's 2004 budget calls for the highest-ever level of federal funding for R&D--$122.7 billion--much of it earmarked to counter bioterror threats. The newly signed Department of Homeland Security Appropriations Act provides $5.6 billion for Project BioShield, a 10-year plan designed to speed up the research, production, and availability of effective vaccines and treatments for possible biological threats. Moreover, antiterrorism technologies will remain a special focus area during preparation of the FY 2005 budget, according to a memo from OSTP and the Office of Management and Budget to the heads of executive departments and agencies,. Yet, whatever the reality, the fear of bioterror, Weedn says, already threatens information-sharing and academic freedoms. "Laws are already on the books regarding certain microbiota," he says. "Perhaps, a reasonable ground can be forged, but science as we know it, at least in the life sciences, may be forever altered." Kelli A. Miller (kelli@newscience.tv) is a freelance writer in Atlanta. 1. "Analytical perspectives, budget of the United States government, fiscal year 2004," Office of Management and Budget, Washington, DC. function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Thinking Beyond Tomorrow

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