Portal de Periódicos da CAPES

Translating translational research

2006; Elsevier BV; Volume: 148; Issue: 1 Linguagem: Inglês

10.1016/j.lab.2006.04.003

1931-5244

Jeffrey Laurence,

Biomedical Ethics and Regulation

“US biomedical research [is] under siege” was the ominous title of a recent article in Cell, written by someone who should know, the Nobel laureate and President of Rockefeller University, Paul Nurse.1Nurse P. US biomedical research under siege.Cell. 2006; 124: 9-12Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar A few months earlier, a National Academies committee had admonished us all to “Ris[e] above the gathering storm” or lose our competitive edge in world science.2Broad W.J. Top advisory panel warns of an erosion of the U.S. competitive edge in science. NY Times, 2005Google Scholar Yet the 2007 National Institutes of Health (NIH) budget will be the fourth consecutive year that federal research funding has lagged behind the rate of biomedical inflation, driving it some 10% below year 2003 levels. What’s a new editor to advise? If mounting anxiety over declining levels of NIH support, difficulty in retention of post-doctoral fellows and domestic graduate students, and recruitment and training of new physicians in translational research just as university-based hospitals are under siege weren’t enough, there’s the politics of science. The U.S. Congress continues to attempt to define what we can and cannot study or implement, from human embryonic stem cells to harm reduction-based prevention strategies. Federal research funding is risk-averse. “The general strategy used by most applicants is to propose projects that are already largely completed because these will be less vulnerable to criticism,” Dr. Nurse observes.1Nurse P. US biomedical research under siege.Cell. 2006; 124: 9-12Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Not only that, but the “stop-go” cycles of funding characteristic of the NIH and National Science Foundation in recent years will be damaging to future generations of researchers, as the expansion of junior positions fails to be maintained by availability of later support for principal investigator positions.1Nurse P. US biomedical research under siege.Cell. 2006; 124: 9-12Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar There is no indication that funding of the new Clinical and Translational Science (CTS) entities, the means by which U.S. science is mandated to breech the “growing barriers between clinical and basic research … translat[ing] new knowledge to the clinic—and back again to the bench,”3DHHS. Request for applications (RFA) number: RFA-RM-06-002. Available at: http://grants.nih.gov/grants/guide/fra-files/RFA-RM-06-002.html.Google Scholar will be any less vulnerable. Traditional grant reviewers tend to find applied grant proposals less than compelling,4Kaiser J. A cure for medicine’s ailments?.Science. 2006; 311: 1852-1854Crossref PubMed Scopus (9) Google Scholar and their critiques have been resistant to change through a half-dozen NIH administrations. Even without the carrot of funding for these centers, the number of papers in PubMed with “translational research” in their title or abstract grew exponentially from 1997 to 2004. But the success rate of all clinical grants, about 18%, did not increase in that interval, lagging about 5 points behind that of their non-clinical competitors.4Kaiser J. A cure for medicine’s ailments?.Science. 2006; 311: 1852-1854Crossref PubMed Scopus (9) Google Scholar There is much debate as to how best to approach these concerns. Gerald Weissmann, Editor-in-Chief of the FASEB Journal, argues that “all research is translational.”5Weissmann G. Roadmaps, translational research, and childish curiosity.FASEB J. 2005; 19: 1761-1762Crossref PubMed Scopus (20) Google Scholar No fan of the CTS concept, he goes on to state that “we need to support the childishly curious, not the politically astute.”5Weissmann G. Roadmaps, translational research, and childish curiosity.FASEB J. 2005; 19: 1761-1762Crossref PubMed Scopus (20) Google Scholar There is a half-century of federally funded scientific discovery to bolster such a notion. But it is naive to think that such support, the freedom to follow a hunch—well, a good hypothesis—can continue without greater public enfranchisement. “Scientists need to listen to the public,” Nurse writes, and “earn the trust and confidence of the public if we are to retain our ’license to operate’.”1Nurse P. US biomedical research under siege.Cell. 2006; 124: 9-12Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar This mandate is actually quite fine, once we scientists realize that the public is usually on our side. According to a recent poll by Research!America, Americans rate health-related research (94%) equivalent to homeland security (92%) in terms of the nation’s top priorities.6Research!America. Americans say more funding for medical research vital to U.S. economic Health. Available at: http://www.researchamerica.org.Google Scholar And yet there is a 16-fold gap between per capita spending for national defense ($1600) and biomedical research ($97) in the United States.7Loscalzo J. The NIH budget and the future of biomedical research.N Engl J Med. 2006; 354: 1665-1667Crossref PubMed Scopus (58) Google Scholar Narrowing that gap will require some very creative activity. Dr. Joseph Loscalzo, chair of medicine at Harvard’s Brigham and Women’s Hospital, suggests that universities cease relying so heavily on the NIH for funding and become more entrepreneurial. He offered 4 alternatives: not-for-profit organizations, industry, enlightened philanthropists willing to provide unrestricted endowments, and sustainable pools of funds from universities involved in biomedical research.7Loscalzo J. The NIH budget and the future of biomedical research.N Engl J Med. 2006; 354: 1665-1667Crossref PubMed Scopus (58) Google Scholar In addition, some 2 of 3 (63%) respondents to the Research!America poll would be willing to pay $1.00 per week more in taxes for additional medical research.6Research!America. Americans say more funding for medical research vital to U.S. economic Health. Available at: http://www.researchamerica.org.Google Scholar One must not impede the discovery process that has worked so well in the past. But that need not mean the flow from discovery to translation, dissemination, and change will not be facilitated by novel structures and funding sources. New medical knowledge will lead to new therapeutics, diagnostics, and prevention strategies sometimes, even if, as Dr. Barry Coller of The Rockefeller University wryly suggested, “the translational component is almost always going to crash and burn.”8Coller B. Medical grand rounds. New York Presbyterian Hospital, New YorkJanuary 12, 2006Google Scholar When that new knowledge is generated, we must have an integrated system with a much greater capacity to disseminate it, along with ways of fostering behavioral changes in patients, the public, and physicians themselves, all based on research. This system will lead, ultimately, to improved health for all. We must also not lose sight of the misuse of scientific discoveries. I will leave the concept of “forbidden knowledge” for another writing. Here I mean that sound public policy must be based on sound science. As U.S. Representative Brad Miller (D-North Carolina) recently argued, “Scientific research needs to inform our policy choices, not justify policy decisions already made. … If we can make the manipulation of scientific research off limits, and rely on neutral research to inform our policy decisions, there’s no telling where it would lead.”9Integrity of science. Available at: http://dailykos.com/storyonly/2006/4/14/64533/6890.Google Scholar Restructuring of general clinical research centers and university laboratories into CTS entities and implementation of supporting integrated pathways will not come easily. C. P. Snow lectured almost 5 decades ago that the “gulf of mutual incomprehension” between those trained in science and those in the humanities would impede rationale solutions to the world’s problems.10Snow C.P. The two cultures. Cambridge University Press, Cambridge, UK1959Google Scholar Dr. Coller noted myriad differences between individuals of 2 ostensibly as disparate subcultures: the basic scientist and the clinician.8Coller B. Medical grand rounds. New York Presbyterian Hospital, New YorkJanuary 12, 2006Google Scholar Their training illuminates two different concepts for acquiring knowledge: the scientific method, or authority. One reserves judgment until all evidence is compelling, and the other recognizes the need for timely action regardless of certainty. One is comfortable operating in spheres with many uncontrolled variables, and the other desires to identify and control all variables. One is suspicious of expert opinion, and the other respects and expects such advice. (I leave it up to the reader to assign respective labels.) If both disciplines are difficult to represent in one person, creation of administrative homes to nurture clinician-scientists, and support collaborations with their basic science peers, to which the CTS awards aspire, should be viewed as all the more sane. NIH Director Dr. Elias Zerhouni reviews these arguments in this, my first issue of Translational Research as Editor-in-Chief. There are also other potential benefits. The fact that stop-go funding cycles are unlikely to disappear, could encourage many research groups to be smaller, with more opportunities for advancement into principal investigator positions, and principal investigators as active experimentalists for more of their careers, while recognizing the need to forge interdisciplinary alliances. Some reject these arguments outright. Dr. Andrew Marks, my counterpart at the Journal of Clinical Investigation, wrote in a somewhat dyspeptic tone that, “It was irresponsible of Dr. Zerhouni to support his new initiative before protecting … the investigator-initiated RO1 grant.”11Marks A.R. Rescuing the NIH before it is too late.J Clin Invest. 2006; 116: 844Crossref PubMed Scopus (43) Google Scholar Although we would all encourage a stable base level of funding, with inflationary adjustments, this new program deserves a chance, along with other means of maintaining research support, as offered by Dr. Loscalzo. Indeed, Dr. Eric Fearon, President of the American Society for Clinical Investigation (ASCI), quickly sent out a reminder to ASCI members that, “the views expressed [by Dr. Marks] do not necessarily reflect the opinion of the ASCI.” Full disclosure: I bought into this model a long time ago. I love science, at the bench and the bedside. My first grant, as a hematology fellow at The New York Hospital, was a Clinician-Scientist Award from the American Heart Association, providing me with 5 years of freedom to explore immune suppressive disorders and, eventually, vascular complications of HIV disease. I am now a Professor of Medicine in the Division of Hematology-Oncology at the Weill Medical College of Cornell University and Attending Physician at New York Presbyterian Hospital-Cornell. I also run the Medicine Department’s Research Residency Track and am Senior Scientist for Programs at a non-profit research-based organization founded by Dr. Mathilde Krim and Dame Elizabeth Taylor: amfAR (The Foundation for AIDS Research). Although it is with no little trepidation that I assume leadership of a journal with such a long and august history, I do have some experience at this editing thing. I was elected a Rhodes Scholar, out of Columbia University, while enrolled in medical school at the University of Chicago, and am the long-standing Editor-in-Chief of 2 clinical AIDS journals, The AIDS Reader and AIDS Patient Care and STDs. I have also assembled a great team of Associate Editors, Fife, Frohman, Garcia, Kamp, and Todd, along with a restructured Editorial Advisory Board. My predecessor, Dale Hammerschmidt, announced a focus for our journal in translational medicine in an editorial published exactly 2 years ago. He also changed the journal’s appearance and “tag line.” I’ve followed through with this concept, including a new cover design and name. I’ve also broadened the concept of “translational” to encompass health outcomes and epidemiologic research, including new members of the Editorial Advisory Board to reflect this concept. These physical changes, and the articles we hope to attract, parallel the objectives of the Central Society for Clinical Research (CSCR): correlate science with the art of medical practice; encourage scientific investigation; and disseminate this science among the members. Part of the “encourage and disseminate” goal will involve solicitation of manuscripts from young CSCR members, perhaps after their presentations at our annual meeting. Our publisher, Elsevier, has also agreed to provide free subscriptions to students enrolled in the NIH K30 award-based Masters degree programs in clinical investigation, one component of the CTS project. As a recent editorial in a journal in my subspecialty framed the argument, in calling for a greater understanding of the clinical utility of hemostatic tests, “To think out of the box, one must first get out of the test tube.”12Kitchens C.S. To think out of the box, one must first get out of the test tube.Thromb Hemost. 2005; 94: 899-900PubMed Google Scholar We do not have the luxury of not doing so.