Mr. Chairman and Members of the Committee:
I am pleased to present the President’s Fiscal Year (FY) 2017 budget request for the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH).
NIGMS-funded scientists investigate how living systems work at a range of levels, from molecules and cells to tissues, whole organisms, and populations. NIGMS believes that, as in finance, a diverse research investment is wise because it maximizes the opportunity for breakthroughs. NIGMS supports a diverse population of scientists and a broad portfolio of science at institutions dispersed across the United States.
NIGMS has a longstanding commitment to nurturing creative thought that produces new knowledge. In turn, this knowledge grows into tangible health solutions. Again this year, two long-time NIGMS grantees won Nobel prizes in Chemistry for their groundbreaking work about basic biological processes: in this case, how cells repair damaged DNA. The work, which has led cancer researchers to develop useful drugs, explains how cells respond to DNA injuries from ultraviolet radiation or chemicals like the carcinogens found in cigarette smoke, as well as how cells fix copy errors in the genetic code that accumulate naturally during cell division. Another NIGMS grantee shared the 2015 Albert Lasker Basic Medical Research Award (“the American Nobel”) for his work on the DNA—damage response—a set of actions that cells undergo to protect their genomes against a nearly constant barrage of minor DNA damage. It is clear that seminal discoveries reflecting decades of careful study of fundamental living systems can have very practical outcomes in treating deadly conditions like cancer.
NIGMS values the time-tested practice of supporting investigator-initiated research grants that unleash the creativity and energy of investigators across the country to solve important biomedical problems essential to progress in medicine. Leaving discovery to scientists, NIGMS nonetheless charts its course guided by its strategic plan that commits to public service, careful stewardship of taxpayer funds, and a focus on efficiency and effectiveness.
NIH-funded scientists have faced increased competition to obtain grant funding over the past several years. As one step in enhancing the efficiency of this process, NIGMS developed and is currently piloting a new way to fund scientists. The Maximizing Investigators’ Research Award (MIRA) program provides support for the NIGMS-relevant research in an investigator's laboratory (via a single, five-year grant), with the goal of giving investigators greater stability and flexibility and enhancing scientific productivity and the chances for important breakthroughs. The program also aims to help distribute funding more widely among the nation’s highly talented and promising investigators. NIGMS extended its first MIRA funding opportunity to established (experienced) investigators whose grant support would expire this year or next: approximately 25 percent of the eligible pool applied, using a streamlined application that outlined a broad vision for their work and its projected significance. Peer reviewers, the Institute’s Advisory Council and NIGMS staff considered a number of criteria when judging MIRA proposals in addition to the applicants’ research vision, including their record of scientific productivity and contributions to training the next generation of researchers. The program, which the Institute is also testing with a cohort of junior investigators, has been well-received by the community: “[MIRA] appears to be more “organic” and “flexible” than the traditional R01 model, and intuitively seems more compatible with the manner in which ideas, hypotheses, and unexpected discoveries emerge from focused and sustained lines of research,” said one MIRA applicant. The Institute is capturing data to evaluate how well program goals are met.
Some areas of biomedical investigation require groups of investigators to work together to ensure synergistic, interdisciplinary expertise and a diversity of thought applied to complex problems. In addition to our programs that support single investigators, NIGMS also funds larger, team-based scientific research. These programs involve multiple investigators and can include facilities or cores, and training and outreach activities. Important areas of team-based research supported by NIGMS are the specialized Centers for HIV/AIDS-related structural biology. These Centers tackle difficult problems such as HIV interactions and viral evolution and mechanism of HIV-virus fusion dynamics with host cells. Their work has laid the foundation for the development of new AIDS drugs and possible vaccines. Other areas of team-based research funded by NIGMS that have had an important scientific impact include the National Centers for Systems Biology. By investing in these centers for over a decade, the program has funded 228 group leaders and directly supported 268 graduate students and 278 postdoctoral fellows; with an impact of approximately 2,000 peer reviewed research papers. As a testament to this program, today many universities have departments and training programs in systems biology, home to researchers whose work is now supported by investigator-initiated R01 grants. Through its strategic plan, the Institute will explore new models for supporting team science that may be more efficient ways to promote important collaborations than are current funding strategies.
Science has changed dramatically over the past three decades, and the amount of information available about biological systems has grown exponentially. New methods allow researchers to illuminate and investigate the inner workings of cells with unprecedented resolution (see, for example, the discussion below of cryo-EM technology), and to generate expansive datasets that monitor and measure hundreds to thousands of molecular entities in a system, in both time and space. Biomedical research is becoming increasingly interdisciplinary and collaborative, whilst the questions become ever more complex. NIGMS is working to catalyze modernization of the education and training of the next generation of biomedical researchers to meet the rapidly evolving challenges and opportunities of science and medicine. The Institute recognizes that teaching and learning are not one-size-fits-all endeavors, and that institutional context matters. To promote the necessary shifts, NIGMS is helping colleges and universities test new, innovative educational models that develop the skills required for students to become outstanding scientists who conduct rigorous and reproducible biomedical research. New training paradigms will also emphasize the essential role of mentoring in career development. The Institute hopes to promote a culture in the academic community that continually optimizes training strategies to meet the changing needs of the scientific enterprise. Toward achieving these goals, in April 2016, NIGMS is hosting a symposium on the NIH campus to convene stakeholders from the biomedical graduate education community to continue momentum for positive change and showcase innovative approaches in Ph.D. training.
One key element of research excellence is scientific workforce diversity, because capitalizing on the full spectrum of skills, talents, and experiences is essential for solving complex human health challenges. Over the past several decades, the biomedical workforce has benefited from various NIH programs aimed at enhancing diversity. NIGMS, in particular, has demonstrated a strong commitment to training underrepresented individuals through programs supporting all stages of the career development pathway. The Institute has identified a pressing need to focus on career inflection points, notably the transition from trainee to career independence. The Institutional Research and Academic Career Development Award (IRACDA) program addresses this need by combining a traditional mentored postdoctoral research experience with an opportunity to develop academic skills, including teaching, through workshops and mentored teaching assignments at a partner (typically underserved) undergraduate institution. NIGMS recently began an analysis of how well this program is achieving its goals, and the initial results are very good. IRACDA has sponsored about 400 scholars who have completed training since the program’s 1999 inception. A substantial number of these alumni (70 percent) hold academic positions at a variety of educational institutions: 35 percent of academic alumni are located at research-intensive institutions; 14 percent work at partner institutions; and the remainder are employed at other institution types. A particularly promising finding is that IRACDA scholars are considerably more diverse than either a comparable pool of NIH-funded postdoctoral fellows or the overall NIH-funded research workforce.
In addition to the creativity of the human mind, cutting-edge technology is a catalyst for innovation. However, technology resources are often not accessible to investigators because of limited supply, location, or cost. NIGMS is using a range of approaches to improve the nation’s research infrastructure, providing investigators better access to critical, shared research resources and technologies. For the past few decades, X-ray crystallography has been the method of choice to allow researchers to take three-dimensional “pictures” of proteins and other molecules important for health and disease. But recently, advances in another technique, cryo-electron microscopy, or cryo-EM, have moved it to the forefront of research into the structures of biological molecules. Unfortunately, despite cryo-EM’s advantages over X-ray crystallography and its great promise for helping scientists understanding cell function and dysfunction, state-of-the-art cryo-EM equipment is out of the reach of most of the country’s researchers because of its very high cost. To begin to address this problem, NIGMS has started a program to support the purchase and maintenance of cryo-EM technology by regional consortia, giving multiple research groups and institutions access to the equipment. NIGMS hopes to expand this consortia model into larger, regional facilities that will produce significant economies of scale and expand greatly the number of scientists who can use important, cutting-edge technologies.
Through its Institutional Development Award (IDeA) program, NIGMS provides targeted support to increase research capacity in states that historically have had little NIH funding. The IDeA program investment is catalytic and has been successfully leveraged into additional investigator-initiated grants to researchers in IDeA states. For the eight-year period spanning FY 2007 to FY 2014, this additional funding support was $12 billion, almost a seven-fold return on investment, according to a recent NIGMS program analysis. The IDeA Centers of Biomedical Research Excellence (COBRE) program supports thematic, multidisciplinary centers that expand and develop biomedical faculty research capability and enhance research infrastructure, in part through development of core facilities needed to carry out modern multidisciplinary collaborative research. While the number of COBRE-supported scientists increased only nine percent between FY 2007 and FY 2014, the productivity of those investigators in terms of scientific publications increased much more – an impressive 43 percent – suggesting that resources are integral to priming the biomedical capabilities of recipient institutions. NIGMS is also supporting the development of clinical research capacity in IDeA states through IDeA Infrastructure for Clinical and Translational Research awards and through joint management, along with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the new IDeA States Pediatric Clinical Trials Networks.
While the number of scientific publications per scientist is one metric of success, others include patents and generating interest in commercialization. The Lexington, Kentucky COBRE, for example, has launched two start-up companies to further develop potential cancer treatments identified through NIGMS-funded research. One is pursuing drug development of a substance that targets molecules that are overactive in certain colorectal and liver cancers.
In this statement, I have shared just a few examples of the remarkable types of returns received from NIGMS’ investment in fundamental biomedical research. NIGMS looks forward to the many more advances that will emerge from laboratories across the Nation.