Since the 1970s, both the number of molecular biology PhD scientists and the amount of biomedical research have grown rapidly, greatly expanding our knowledge of the cell.1 This explosion has led to incredible scientific achievements, including development of the polymerase chain reaction in the 1980s and completion of the Human Genome Project in 2003.2-4 The focus of research has shifted from single genes to all genes, from single proteins to all proteins. Neither scientists nor pharmaceutical companies, however, have been able to keep pace with the sheer quantity and complexity of modern biomedical research. Additionally, while the majority of medical researchers were once physician-scientists in the 1950s and 1960s, they are predominantly PhDs today.1 Questions of basic and clinical research, once addressed side by side, are now separate.
The widening gap between scientific discovery and therapeutic impact is a result of these changes. In the United States, the dramatic increase in spending for pharmaceutical research and development has been offset by a disappointing decrease in therapeutic output (Figure 1). As this paradox becomes more apparent, translational research, which aims to convert laboratory findings into clinical successes, emerges as an increasingly important endeavor.5,6
In 2006, the U.S. National Institutes of Health (NIH), the largest source of funding for medical research in the world, focused its attention on translational research by launching the Clinical and Translational Science Awards program.7,8 However, implementing effective translational research is both time- and labor-intensive. According to Dr. Garret FitzGerald, Director of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania, challenges include a lack of human capital with translational skill sets, relevant information systems, and intellectual property incentives.9
During his leadership of the NIH from 2002 to 2008, Dr. Elias Zerhouni witnessed the consequences of clinicians lacking in training on the speed of scientific advancements for patient care.10,11 Beyond the need for manpower, an open culture of communication between scientists and clinicians is necessary.
Drug development is a one-way process from benchside to bedside in which scientists identify drug targets, conduct clinical tests, and develop marketable drugs. Many argue, however, that the communication must run in the opposite direction, too; feedback from clinical trials and doctors is valuable because understanding their concerns allows researchers to improve drug development.12 The third challenge derives from current institutional practices and regulations. An investigator’s publication record rather than their efforts to advance medicine determines success.13 Research funding is also granted on an individual basis, which does not promote the collaboration necessary for successful translational research. Lastly, the regulatory and patent processes governing drug development require much expertise and time to navigate, which offer little incentive for researchers to become involved.1
To better integrate basic science with clinical science progress, countries such as the United States are building a new team of leaders in all aspects of clinical research: medicine, pharmacology, toxicology, intellectual property, manufacturing, and clinical trial design and regulation.13 Dr. Francis Collins, Director of the NIH since 2009, has called for a partnership between academia, government, private, and patient organizations to repurpose molecular compounds previously failing in their original use.15,16 Historically, Collins referred excitedly to azidothymidine, a drug originally developed to treat cancer that later treated HIV/AIDS.14 Tremendous potential lies in applying scientific developments to other contexts, and the NIH has already drafted policy for this purpose.15
However, the growing support for translational research does not diminish the importance of basic scientific research, which poses the most interesting questions. Translational biomedical research creates an efficient environment for scientists to work at the interface of basic science and therapeutic development and to help fulfill the social contract between scientists and citizens. The full impact of translational initiatives has yet to be seen because the success of drug development, which can take up to 20 years, cannot be evaluated easily or quickly. For now, we can hope that integrating the work of scientists and clinicians will benefit both the patients, who await treatment, and the researchers, who only dream of seeing their discoveries transformed into new therapies for disease.
- Butler, D. Nature. 2008, 453, 840–2.
- Smithsonian Institution Archives. Smithsonian Videohistory Collection: The History of PCR (RU 9577). http://siarchives.si.edu/research/videohistory_catalog9577.html (Accessed Jan. 15, 2013).
- National Center for Biotechnology Information (NCBI). Probe, Reagents for Functional Genomics: PCR. http://www.ncbi.nlm.nih.gov/projects/genome/probe/doc/TechPCR.shtml (Accessed Jan. 15, 2013).
- Human Genome Project Information. About the Human Genome Project. http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml (Accessed Jan. 15, 2013).
- CTSI (Clinical and Translational Science Institute) at UCSF. Translational Medicine at UCSF: An Interview with Clay Johnston. http://ctsi.ucsf.edu/news/about-ctsi/translational-medicine-ucsf-interview-clay-johnston (Accessed Jan.15, 2013)
- Helwick, C. Anticancer Drug Development Trends: Translational Medicine. American Health & Drug Benefits. http://www.ahdbonline.com/article/anticancer-drug-development-trends-translational-medicine (Accessed Jan. 15, 2013).
- National Institutes of Health (NIH). About NIH. http://www.nih.gov/about/ (Accessed Jan. 15, 2013).
- National Institutes of Health National Center for Advancing Translational Sciences (CTSA). About the CTSA Program. http://www.ncats.nih.gov/research/cts/ctsa/about/about.html (Accessed Jan. 15, 2013).
- Pers. comm. Dr. Garret FitzGerald, Director of the Institute for Translational Medicine & Therapeutics at the University of Pennsylvania.
- NIH News. Elias A. Zerhouni to End Tenure as Director of the National Institutes of Health. http://www.nih.gov/news/health/sep2008/od-24.htm (Accessed Jan. 15, 2013).
- Wang, S.S. Sanofi’s Zerhouni on Translational Research: No Simple Solution. The Wall Street Journal. Health Blog 2011 http://blogs.wsj.com/health/2011/05/20/sanofis-zerhouni-on-translational-research-no-simple-solution/ (Accessed Jan. 15, 2013).
- Ledford, H. Nature. 2008. 453, 843-5.
- Nature. 2008, 543, 823.
- TEDMED 2012. Francis Collins. http://youtu.be/spUoPC_TU_8 (Accessed Jan. 15, 2013).
- Wang, S. Bridge the Gap Between Basic Research and Patient Care, NIH Head Urges. The Wall Street Journal Health Blog. http://blogs.wsj.com/health/2012/04/11/bridge-the-gap-between-basic research-and-patient-care-nih-head-urges/ (Accessed Jan. 15, 2013).