A New Initiative on Precision Medicine

—— Francis S. Collins, M.D., Ph.D., and Harold Varmus, M.D.

“Tonight, I’m launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes — and to give all of us access to the personalized information we need to keep ourselves and our families healthier.”
— President Barack Obama, State of the Union Address, January 20, 2015

President Obama has long expressed a strong conviction that science offers great potential for improving health. Now, the President has announced a research initiative that aims to accelerate progress toward a new era of precision
medicine (www.whitehouse.gov/precisionmedicine). We believe that the time is right for this visionary initiative, and the National Institutes of Health (NIH) and other partners will work to achieve this vision.
The concept of precision medicine
— prevention and treatment strategies that take individual variability into account — is not new1; blood typing, for instance, has been used to guide blood transfusions for more than a century.
But the prospect of applying this concept broadly has been dramatically improved by the recent development of large-scale biologic databases (such as the human genome sequence), powerful methods for characterizing
patients (such as proteomics,metabolomics, genomics, diverse cellular assays, and even mobile health technology), and computational tools for analyzing large sets of data. What is needed now is a broad research program to
encourage creative approaches to precision medicine, test them rigorously, and ultimately use them to build the evidence base needed to guide clinical practice.
The proposed initiative has two main components: a near-term focus on cancers and a longerterm aim to generate knowledge applicable to the whole range of health and disease. Both components are now within our reach
because of advances in basic research,including molecular biology,genomics, and bioinformatics.Furthermore, the initiative taps into converging trends of increased connectivity, through social media and mobile devices,and Americans’ growing desire
to be active partners in medical research. Oncology is the clear choice for enhancing the near-term impact of precision medicine. Can-cers are common diseases; in the aggregate, they are among the leading causes of death nationally and worldwide, and their incidence is increasing as the population ages. They are also especially feared, because of their lethality,their symptoms, and the often toxic or disfiguring therapies used to treat them. Research has already revealed many of the molecular lesions that drive cancers,
showing that each cancer has its own genomic signature, with some tumor-specific features and some features common to multiple types. Although cancers are largely a consequence of accumulating genomic damage during life, inherited genetic variations
contribute to cancer risk, sometimes profoundly. This new understanding of oncogenic mechanisms has begun to influence risk assessment, diagnostic categories, and therapeutic strategies, with increasing use of drugs and antibodies designed to counter the influence of specific molecular drivers. Many targeted therapies have been (and are being)developed, and several have been shown to confer benefits, some of them spectacular.2 In addition, novel immunologic approaches have recently produced some profound
responses, with signs that molecular signatures may be strong predictors of benefit.3 These features make efforts to improve the ways we anticipate, prevent, diagnose, and treat cancers both urgent and promising.

From the National Institutes of Health (F.S.C.) and the National Cancer Institute(H.V.) — both in Bethesda, MD.This article was published on January 30,2015, at NEJM.org.1. National Research Council. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington, DC: National Academies Press, 2011 (http://www.nap.edu/ catalog/13284/toward-precision-medicine-building-a-knowledge-network-for-biomedical-research).

2. de Bono JS, Ashworth A. Translating cancer research into targeted therapeutics. Nature 2010;467:543-9.
3. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014;371:2189-99.
4. Abrams J, Conley B, Mooney M, et al. National Cancer Institute’s Precision Medicine Initiatives for the new National Clinical Trials Network. Am Soc Clin Oncol Educ Book 2014:71-6.
5. Department of Health and Human Services. Federal Policy for the Protection of Human Subjects (‘Common Rule’), 1991 (http://www.hhs.gov/ohrp/humansubjects/ commonrule).