National Institute Of General Medical Sciences Turns 50

Convincing lawmakers of the importance of basic science can be a hard sell, but officials at the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS) have excelled at it for the past 50 years. Authorized by Congress in 1962 to support research and training in general or basic biomedical sciences, NIGMS is one of the largest institutes in terms of budget at NIH.

From the beginning, NIGMS has supported fundamental research on how life works at the most basic level. Numerous significant medical breakthroughs have resulted from that research, including new ways to detect, treat, and prevent disease. In the late 1960s and early ’70s, the institute funded the basic science on restriction enzymes that led to recombinant DNA technology and genetic engineering. More recently, NIGMS has supported studies that catalyzed the fields of pharmaco­genomics, protein structure analysis, cellular imaging, computational biology, stem cell biology, and RNA biology.

“NIGMS is the foundation on which everything else at NIH has been built and will be in the future,” NIH Director Francis S. Collins said last spring at an event on Capitol Hill to honor the 50th anniversary of NIGMS. “If you want to see that next breakthrough in Alzheimer’s, Parkinson’s, diabetes, or cancer, you have to be sure you are investing in the basic science that teaches us those fundamentals upon which we can build that future.”

In addition to supporting basic research, NIGMS is known for its efforts in preparing the next generation of biomedical scientists through various training grants and fellowships. The institute also has a reputation for promoting diversity in the biomedical workforce and for encouraging interdisciplinary research.

NIGMS has grown from 114 employees and a budget of about $110 million in 1963, to 165 employees and a budget of about $2.4 billion today. Most of its money is spent on grants—that’s been true since it was founded. Today, NIGMS spends about 60% of its budget on research project grants, 20% on grants to centers, and about 8% on training grants. The remainder goes to other research, including support for minority biomedical researchers, as well as to R&D contracts, and research management and support.

Chemistry has always been important area of research for NIGMS. The institute has funded the work of 36 Nobel Prize-winning scientists in chemistry.

“We realize that chemistry is integral to everything else we do,” says NIGMS Acting Director Judith H. Greenberg. NIGMS funds more chemistry-related research than any of NIH’s other centers or institutes, but it is hard to get a handle on exactly how much because the lines between chemistry and other sciences are often blurred, Greenberg notes.

“We do know that we are spending probably as much on chemistry research as the National Science Foundation,” Greenberg tells C&EN. “We are a big player.”

One area in particular that receives a lot of support from NIGMS is synthetic organic chemistry, notes Michael E. Rogers, director of the Division of Pharmacology, Physiology & Biological Chemistry at NIGMS. The institute also supports research on metals in biology or bioinorganic chemistry, chemical biology, bioorganic chemistry, and medicinal chemistry.

A big area of interest to NIGMS right now is glycomics—the comprehensive study of carbohydrates, Rogers says. NIGMS is also interested in chemistry associated with enzymes and enzyme mechanisms, he notes.

Through its Division of Cell Biology & Biophysics, NIGMS also supports a substantial amount of analytical chemistry, including work in nuclear magnetic resonance spectroscopy, mass spectrometry, and the development of imaging probe reagents, Rogers says. “That support has been crucial to the development and application of those technologies,” he points out.

One of the reasons NIGMS is such a big supporter of chemistry has a lot to do with Ruth L. Kirschstein, who directed the institute from 1974 to 1993. “When I first came to NIH in 1980, there was some discussion of whether NIH should be supporting chemistry in a major way,” Rogers recalls. “Ruth took a strong stance that chemistry is an enabling science for health research and that it should be supported.”

Kirschstein was the first woman to become director of an NIH institute. She also served longer than any other NIGMS director to date, and she is credited with shaping the current direction of the institute. “She really put her stamp on the institute in many ways,” Greenberg says.

That stamp included a strong emphasis on investigator-initiated research and a commitment to research training, Greenberg notes. Under Kirschstein’s leadership, NIGMS awarded training grants to institutions rather than individuals in areas such as genetics, cell biology, bioengineering, and pharmacology. NIGMS also established an institutional training program at the chemistry-biology interface.

The rationale for creating the chemistry-biology interface program was to make chemistry departments around the country feel included in NIGMS’s training efforts, Rogers says. “We wanted to make it very clear that they are part of our community.”

Kirschstein was ahead of her time with respect to increasing the diversity of the biomedical workforce. She was in charge when NIGMS inherited a program aimed at supporting minority biomedical researchers from another NIH division in 1989, and she spearheaded the establishment of the Minority Opportunities in Research (MORE) Division at NIGMS in 1991 to increase minority particpation in biomedical research and teaching.

She was also known for her ability to charm Congress. Kirschstein was well aware of who held the purse strings for NIH, and she got to know those law­makers and their staffers. “She could even talk to them about their relatives,” Rogers remarks. During her directorship at NIGMS, the institute’s budget quadrupled.

Beyond those profound influences, Kirschstein also set the culture for the institute, Greenberg stresses. She hired top scientists and instilled a strong sense of mission in them even after she left NIGMS to become deputy director of NIH. “We work together for the benefit of science,” Greenberg says. “I am happy to say, that culture has lasted all of these years.”

Another past director who had a long-lasting impact on the institute is Kirschstein’s predecessor, DeWitt Stetten Jr. When NIGMS was established, it invested more in applied than basic research. Initially, programs were established in clinically related areas such as anesthesiology, trauma, and burn research, and training was focused on bridging the gap between basic science and clinical research.

Stetten changed that. During his 1970–74 tenure as director, NIGMS began investing more in basic research through its genetics program and a program on cell biology. The institute continued that trend under Kirschstein’s leadership.

NIGMS, like the rest of NIH, experienced a period of tremendous growth from 1998 to 2002. During that time, the budgets of both NIH and NIGMS doubled. With the additional funds, NIGMS started a program in pharmacogenetics, the Protein Structure Initiative, and a program focused on the modeling of infectious diseases, as well as several other initiatives, Greenberg notes. The institute also began large collaborative grants called glue grants to encourage interdisciplinary research, and it increased funding for grants awarded to centers.

But by 2003 the NIGMS budget was beginning to flatten and “there was a mixture of hope and anxiety,” recalls Jeremy M. Berg, a chemist who directed NIGMS from 2003 to 2011. “There were attempts to try to prepare for the end of the doubling, and there was a lot of concern that things needed to be managed carefully so the best research could still be done.”

Shortly after Berg arrived at NIGMS, then-NIH director Elias A. Zerhouni launched an NIH-wide initiative called the NIH Roadmap for Medical Research to bring NIH’s 27 institutes and centers together to work on common projects. NIGMS was involved in several NIH Roadmap projects.

One of the efforts involved development of molecular imaging probes. “We tried to build partnerships between chemists, physicists, engineers, and cell biologists to push imaging probe technology to the point where we could perform real-time imaging of individual molecules in live cells,” Berg says. “That work has continued, and the goal is now becoming closer and closer to being a reality.”

NIGMS also played a key role in advancing the field of structural biology. “The focus was entirely on membrane proteins,” Berg recalls. “A lot of structural biology was moving quite well under its own power, but work on membrane proteins was an area that wasn’t as strong as everybody had been hoping.”

Huge progress has been made in membrane structural biology over the past 10 years as a result of efforts by NIGMS, Berg stresses. Many structures and mechanisms are now understood, he says.

In the years to come, NIGMS expects to continue supporting basic biomedical research. Two areas that look particularly exciting are the dynamics of microbial-host interactions and bioinformatics and computational biology, Greenberg points out.

Like all government agencies, however, NIGMS faces an uncertain future in terms of its budget. It also faces uncertainty with respect to its future leadership. The institute has been without a permanent director since Berg left in July 2011 to take a position at the University of Pittsburgh (C&EN, June 20, 2011, page 28).

NIGMS is also under pressure to move in the direction of translational research—to turn previous discoveries into treatments and cures that have a direct impact on human health. Although much progress has been made in biomedical research over the past 50 years, “it is easy to lose sight of how little we actually understand,” Berg warns.

“Continuing to invest in basic, curiosity-driven research has been the strength of NIGMS over its history, and it continues to be important,” Berg says. “I think NIGMS needs to continue to articulate and support basic research in areas that are off the beaten track, while at the same time trying to bridge between what is known and areas of translation.”

NIGMS is commemorating its 50th anniversary by holding various events this year, including a special symposium on the NIH campus in Bethesda, Md., in October. It also plans to showcase some of the work it has funded at various scientific meetings, including the American Chemical Society national meeting being held this week in Philadelphia.