Engaging Basic Scientists in Translational Research

Il n'existe pas de sciences appliquées, mais seulement des applications de la science. There are no such things as applied sciences, only applications of science. —Louis Pasteur “Iron Lungs” used on polio victims in Boston (1955); ©Bettman/Corbis. Q: What's missing in this picture? A: Translational research by Salk and Sabin FASEB's report, Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles (1), summarizes the proceedings of a symposium that brought together basic and clinical investigators, research administrators, funders, professional societies, and scientific publishers to examine the role of basic scientists in advancing research from the bench to bedside. Participants explored the benefits of engaging basic investigators in translational science, the challenges to their participation, and the role that research institutions, funders, professional societies, and scientific publishers can play to help them overcome these challenges. Basic research is the foundation of medical advancement and the wellspring of translatable discoveries. It is not a given, however, that basic biomedical science findings will have a near-term impact on disease treatment. Indeed, it was learning from clinicians that the thousands of papers on a genetic mutation underlying retinoblastoma had no impact on the way that patients with this form of cancer were treated that propelled Michael Dyer into translational research. NIH estimates that 80–90% of research projects fail before they ever get tested in humans (2), and despite increased public and private investment in research over the last 60 years, the number of new molecular entities developed by pharmaceutical companies and approved by the Food and Drug Administration has held constant (3). These trends have elicited concern and calls to action (4–6) from policymakers, patient groups, and the public, who expect increasing investments in medical research to yield more rapid improvement in the diagnosis and treatment of diseases that afflict themselves, their families, and their friends. Such groups have sometimes looked with envy at basic research funds and pressed lawmakers to do more to support applied research. Whereas the mission of NIH has always been to improve human health, these pressures have driven the agency to refocus its efforts on clinical and translational research. In 2004, NIH released its Roadmap for Medical Research, which set out a plan for re-engineering the clinical research enterprise. In 2006, the agency launched the Clinical and Translational Science Award (CTSA) program, which has provided funding to 60 institutions across the country to create “a definable home” for clinical and translational research. Most recently, Congress authorized the creation of the National Center for Advancing Translational Sciences. This new entity will bring the CTSA program and other NIH translational research initiatives under one roof with the goal of catalyzing the generation of new methods and technologies, which will enhance the development, testing, and implementation of disease diagnostics and therapeutics. Whereas overall funding for fundamental research at the agency has remained constant, the focus on applied research has left some investigators concerned about the place of basic science in the federal biomedical research enterprise. It is in everyone's interest to support translational science. However, we must not lose sight of the critical contributions that basic investigators make to translation (7). The stories that Dyer and other symposium participants shared illustrated that the clinical potential of bench discoveries is more likely to be realized when basic scientists have opportunities to interact and collaborate with their clinical research and clinician colleagues, support from their institutions to pursue translational leads, and training, guidance, and resources throughout the process. Unfortunately, the training, research, and funding environment at many institutions—and in the enterprise as a whole— does not lend itself to the engagement of basic investigators. A recurring theme in the meeting presentations was the cultural divide separating investigators engaged in fundamental versus applied research. Basic scientists may see their controlled, hypothesis-driven research as more rigorous than the goal-directed or descriptive research often conducted with humans in clinical research settings. On the other hand, clinical scientists may view their work as more important, insofar as it has greater relevance to human health and disease. These perceptions inhibit collaborations and deter basic scientists from pursuing translational research projects. Even when basic investigators are open to translation, they do not necessarily speak the same language as their clinical investigator counterparts. Indeed, protein chemist Daria Mochly-Rosen was surprised to encounter little interest among clinical scientists in the heart research community when she shared with them her discovery of enzymes that could change the rate at which heart cells beat in culture. Clinicians, she had been told, already had ways of managing heart rate; they were concerned with problems such as cardiac ischemia. She then discovered an inhibitor, which dramatically reduces heart damage and prevents subsequent heart failure when administered after an attack, and reached out to her basic science colleagues for help in generating industry interest in the compound. But, rather than finding support, she was discouraged from pursuing this line of inquiry and from working with industry. Translational research, she was told, “is not intellectually challenging, worthwhile, or good for her career.” Differences in training undoubtedly contribute to this cultural schism. Basic science training programs do not generally require course work in pathobiology and pathophysiology—fields that lay the foundation for understanding human health and disease processes, and basic science trainees are not typically exposed to basic concepts in medicine, systems biology, or the relationship of their work to clinical cases. Further, the physical separation of basic and clinical departments at research universities makes it difficult for basic scientists to interact with clinical researchers (and patients and clinicians), limiting opportunities for each group to counter negative perceptions of, and learn from, the other. Moreover, basic scientists interested in initiating or collaborating on human subject research projects encounter an onerous set of regulatory requirements that frustrate and deter even seasoned clinical investigators. Working with industry brings additional challenges, such as negotiating the terms and conditions of these collaborations, establishing intellectual property agreements, and working with technology transfer offices. Investigators who do succeed in launching a translational research program may conclude that the rewards do not justify the effort expended. Compared with mechanistic studies, translational projects—particularly those involving human participants—tend to take longer to conduct, which could result in fewer publications. Investigators may find it difficult to publish their work in journals that favor hypothesis-driven research over goal-directed or applied science, and they may suffer at the hands of promotion and tenure committees, which do not attribute the same value to translational research as they do to basic research. Whereas Dr. Mochly-Rosen persevered, formed her own company, and launched a clinical trial, these challenges are enough to dissuade many promising investigators from venturing beyond their disciplinary domains. Although strides have been made in creating a research environment that supports the translational science ambitions of basic investigators, much more can be done to maximize their potential. Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles provides a realistic set of recommendations for providing basic scientists with translational research training, resources, and support; fostering collaborations with clinical researchers, clinicians, and industry partners; and recognizing and rewarding the contributions basic scientists make to translational research. A summary of these recommendations is provided below. Public and private funders must continue to support basic science so that there is a reservoir of new knowledge ripe for translation. They are also key to ensuring that basic scientists are part of the process of translating those discoveries. Funders should provide support for basic scientists' proposals of individual investigator-initiated and team-based translational research projects, and review panels should have the expertise to review these proposals fairly. Funders should also continue to support the infrastructure, resources, and training programs that basic scientists will need to move into the translational domain, and they should use their convening power to bring basic and clinical scientists together. Collectively, funders have a wealth of information about the outcomes of translational research programs and policies. They should work together to evaluate these data to identify and replicate successful efforts. Research institutions must encourage and engineer a cultural shift toward greater collaboration, cooperation, communication, and respect between basic and clinical scientists. They should provide didactic and experiential translational research learning opportunities for basic scientists and trainees; create opportunities for basic and clinical investigators, clinicians, and industry partners to interact; and facilitate access to myriad resources that investigators need to initiate and sustain translational research programs, including expertise in human subject regulations, clinical trials, and intellectual property. Research institutions should also examine their appointment, tenure, and promotion policies to ensure that basic scientists who make valuable contributions to translational, team-based, and interdisciplinary research are recognized and rewarded for these accomplishments. Professional societies also have a role to play in encouraging and supporting basic scientists' participation in translational research. Annual meetings provide a great opportunity to stimulate interest in translation and to connect scientists to the tools and expertise that they need to establish translational research programs. Societies should consider creating a translational research meeting track, offering workshops to build practical translational research skills, or organizing “speed” networking sessions to facilitate interactions and even spark collaborations between basic and clinical researchers. Professional societies can also support summer research programs to expose students to translational research, provide trainees with information about translational science careers, recognize successful translational scientists through awards, and create databases that facilitate the identification of potential collaborators. Scientific contributions are measured, in large part, by the number of publications an individual has. As translational research is often conducted in large, multidisciplinary teams, it is important for scientific journals to establish a mechanism to identify the roles each author played in producing a publication. Publishers should also seek opportunities to raise the profile of translational science among their readers, such as by highlighting the potential contributions that basic research findings make to public health through articles and editorials. Whereas research institutions, funding organizations, scientific societies, and publishers all play a part in facilitating the engagement of basic scientists in translational research, scientists themselves are ultimately responsible for advancing their research programs. To succeed in translation, basic investigators must learn to define health problems with the same precision as a basic science hypothesis. They should seek the perspectives of scientists from different disciplines, as well as opportunities to acquire translational research training, mentorship, funding, and resources. To ensure that they have the support of their institutions, basic scientists should be aware of tenure expectations with regard to the balance between conducting basic and translational research, clearly articulate their research and career goals to their department chairs, and negotiate between and across departments or centers so that expectations are clear. When soliciting tenure review letters, they should seek reviewers who understand and value the contributions they make to translational research. Translational investigators at FASEB's symposium detailed the satisfaction and inspiration that came from working to translate discoveries into treatments and diagnostics for human diseases. For some, advancing the clinical applications of their work led to deeper insights into the biological mechanisms that they were investigating, sparked new research ideas, and enabled them to bring new research methods into their laboratories. One participant even noted that his translational work improved his publication rate. To be sure, translational research is not for everyone. The enterprise needs a cadre of scientists dedicated to the pursuit of purely basic research. However, fostering the creation of an environment that encourages basic scientists to consider the translational potential of their work and facilitates their ability to apply their knowledge and expertise will improve human health and accelerate the treatment of disease.