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NIGMS Celebrates 40 Years of Discovery, Progress

By Alisa Zapp Machalek

The year is 1962. John Glenn, Jr., becomes the first American to orbit the Earth, Sam Walton opens the first Wal-Mart, a first-class stamp costs 4 cents, and — most relevant here — NIGMS is created.

Established by Congress to support research and training in the "general or basic medical sciences," NIGMS has a strong record of supporting scientists at the forefront of their fields. In its 40-year history, more than 50 of its grantees have won Nobel prizes for their groundbreaking research.

Today, NIGMS has one of the largest budgets at NIH, coming in at more than $1.7 billion. The institute — which is almost entirely extramural — funds more than 4,000 research grants to universities, medical schools, hospitals and other research institutions. Its broad interests lie in areas such as cell, molecular, developmental and computational biology; genetics; chemistry; and pharmacology. Basic studies in these and other areas covered by NIGMS increase our understanding of life processes and lay the foundation for advances in disease diagnosis, treatment and prevention.

As part of its 40th anniversary celebration, NIGMS selected 40 topics that reflect its interests and accomplishments. Brief descriptions and illustrations of these topics are at http://www.nigms.nih.gov/ anniversary/discovery/.

The institute has a longstanding commitment to increasing the number and competitiveness of minority biomedical and behavioral scientists. Through its Minority Opportunities in Research (MORE) Division, NIGMS has helped thousands of minority students pursue degrees in science and has enhanced research and training at minority-serving institutions throughout the country. Adding to the air of celebration at NIGMS, both of MORE's branches — Minority Access to Research Careers and Minority Biomedical Research Support — are commemorating their 30th anniversary this year.

Championing Basic Research

Many NIGMS-supported scientists dedicate their careers to detailed studies of the individual molecules — proteins, nucleic acids, carbohydrates and lipids — that form living systems. This research steadily improves our understanding of how these molecules function in healthy cells and how faulty molecules can cause disease.

NIGMS grantees working in the field of genetics identified key regulators of the cell cycle. Others discovered restriction enzymes, which launched the field of recombinant DNA technology.

Two NIGMS efforts in genetics have spun off to other NIH components. NIGMS' early investment in genome sequencing spawned an initiative that grew into the National Human Genome Research Institute. The GenBank database, which NIGMS established in 1982 to meet the critical need for a central storehouse of genetic sequence information, is now managed by the National Center for Biotechnology Information. The database contains more than 20 billion nucleotide bases from over 100,000 organisms, including the nearly completed human genome.

At the Coriell Repository tank room, cells are stored in liquid nitrogen and are preserved virtually indefinitely.

An exciting new area of exploration is RNA interference, which was first described in 1998 by an NIGMS grantee. This natural process, in which small pieces of double-stranded RNA "turn off" individual genes, has tremendous potential as a research tool and as a possible therapeutic approach. For example, RNA interference has recently been harnessed in vitro to block infections by HIV and poliovirus.

True to its commitment to basic studies that are not targeted to specific diseases, NIGMS supports the bulk of NIH-funded chemistry research. Chemists supported by the institute have made seminal discoveries in many areas, including catalytic RNA, organic synthesis and chiral reactions.

Another area within NIGMS' broad mission is research on burns and other forms of trauma. Every year, more than 1 million Americans suffer serious burn injuries. One of the most significant NIGMS-sponsored advances in this area is the development of an "artificial skin" that promotes the healing of burns. This product, along with other NIGMS-supported discoveries on the body's response to burn and trauma injury, has dramatically increased survival and recovery.

Training Tomorrow's Scientists

Since its inception, NIGMS has been dedicated to teaching students how to become independent researchers. Nearly half of all NIH predoctoral trainees, and a large portion of postdoctoral trainees, receive their support from NIGMS.

Renee Hosang, a graduate student at Florida International University, benefitted from a MORE program.

Recognizing that the most significant biomedical investigations often involve and affect several different fields, the institute designed its training programs to cut across disciplinary and departmental lines. In addition, NIGMS has several programs that address areas of critical scientific need. One of these, the Medical Scientist Training Program, leads to a combined M.D.-Ph.D. degree and prepares scientists to bridge the gap between basic and clinical research. Other programs train scientists to conduct research in the rapidly growing field of biotechnology and at the interface between chemistry and biology. The institute also sponsors a Pharmacology Research Associate Program — its only intramural activity — that trains postdoctoral scientists in pharmacology in NIH and FDA laboratories and clinics.

Forging Paths into New Areas

In the late 1990s, NIGMS held meetings with leaders of the scientific community to get their advice and vision on new directions in science and the needs of researchers. A common theme emerged: Solving many of the most complex — and interesting — questions in biology requires interdisciplinary cooperation and multi-faceted approaches. In response, NIGMS established collaborative and integrative grants (better known as "glue" grants) to bring together large groups of scientists from diverse fields to help tackle these complicated research problems. The institute currently supports glue grants to investigate cell communication (including the roles of G proteins and carbohydrates), cell movement and inflammation. (NIAID and NCI also co-fund the G protein grant.) For the first 4 years of the initiative, which began in 2000, NIGMS plans to invest more than $100 million.

Another area that benefits from NIGMS' emphasis on collaboration is pharmacogenetics, the study of how genes affect the way people respond to medicines. Already, more than a dozen NIGMS-sponsored research teams have begun unraveling why the same dose of a drug can help some people, have no effect on others and harm a few. This knowledge can allow physicians to tailor the doses of certain medications and save lives.

In 2000, NIGMS spearheaded a trans-NIH initiative in pharmacogenetics. It now commits more than $10 million each year to the effort. At the heart of the program is a shared online resource called PharmGKB, where participating researchers deposit their data. This knowledge base, which does not identify study participants, is accessible to scientists worldwide.

To further advance the field of molecular structure determination, NIGMS funds such cutting-edge equipment as the powerful NMR magnet shown above.

The institute recognizes that vast scientific treasures are hidden within the burgeoning masses of genome sequence and other biological data. To mine these will require quantitative tools and approaches. Beginning in 1998, NIGMS created a set of initiatives to encourage mathematicians, physicists, computer scientists and engineers to apply their expertise to biomedical research. In 2001, to serve as the focal point for such activities, NIGMS created its newest component, the Center for Bioinformatics and Computational Biology.

NIGMS has also capitalized on advances in genome sequencing through its Protein Structure Initiative. Launched in 2000, this project builds on the institute's significant investment in structural biology. The goal is to solve the structures of 10,000 genetically unique proteins in 10 years, enabling scientists to produce an inventory of all the shapes that proteins can take in nature. This, in turn, will help make it possible to predict the structure of any protein based on its sequence. The institute expects to commit at least $220 million to the project for its initial, 5-year pilot phase.

To further advance the field of molecular structure determination, NIGMS funds the cutting-edge equipment and facilities necessary for these studies. In recent years, the institute has supported construction of the most powerful NMR magnets available (900 MHz) and, together with NCI, it is funding the design and construction of three beamlines at Argonne National Laboratory's Advanced Photon Source, the newest and most advanced synchrotron in the country.

A Bright Future

"The most important biomedical questions today — how genes are regulated, how cells and organisms develop and function and what causes cellular processes to go awry — have not changed much in the last four decades," says Dr. Judith H. Greenberg, acting director of NIGMS. "But the level of detail at which we can answer these questions has changed dramatically. This progress not only helps us understand the biological basis of life, it has also been translated into new approaches to treating and preventing diseases."

For 40 years, NIGMS has been at the leading edge of supporting this progress. As it continues to champion basic research, to train future scientists and to forge paths into new areas, its future promises to hold even more exciting and significant advances.

Commemorating Through Symposia To mark its 20th anniversary, NIGMS established an annual DeWitt Stetten, Jr. Lecture, which is named for the institute's director from 1970 to 1974. This year's lecture — in Masur Auditorium, Bldg. 10 from 2 to 4 p.m. on Wednesday, Oct. 23 (see story) — will feature a trio of speakers who will discuss a blossoming area of research that NIGMS is actively promoting: computational cell biology. For details, click on the "40 years of discovery" icon in the purple color bar at http://www.nigms.nih.gov. Throughout 2002, NIGMS is taking its anniversary commemoration to the scientific community by sponsoring symposia at the annual meetings of eight professional societies whose missions align with its own. The events were designed to introduce meeting participants to investigations at the vanguard of their fields. For example, the symposium at the Society for Developmental Biology meeting was titled "Dealing with Complexity" and highlighted genome-wide studies, rather than investigations of individual genes. The symposium at the American Society for Biochemistry and Molecular Biology meeting focused on "Proteomics and Drug Discovery." For the agendas of all the symposia, see http://www.nigms.nih.gov/anniversary/symposia.

Banking on Cells This year, NIGMS also celebrates the 30th anniversary of the Human Genetic Cell Repository, which plays a vital role in genetics research. Maintained by the Coriell Institute for Medical Research in Camden, N.J., the repository houses the world's largest collection of human cell cultures. It contains nearly 8,000 high-quality cell lines and DNA samples from people with various genetic disorders, their family members and unaffected people whose cells can be used as controls. (Strict policies ensure informed consent and confidentiality.) Every week, the repository ships about 100 cell lines and 1,000 DNA samples to scientists from any of 60 countries. Cell cultures from the repository have already aided discovery of the genes associated with hundreds of diseases, including cystic fibrosis, Huntington's disease and retinitis pigmentosa. Repository materials are used extensively in studies of gene expression and mutagenesis, as well as in studies such as the HapMap project, which seeks to identify patterns of human gene variation. Information on the repository is available at http://locus.umdnj.edu/nigms.