Last updated: May 09, 2012
NHGRI's Nobel Connections
One of the winners of the 2007 Nobel Prize in physiology or medicine once received a helping hand from the National Human Genome Research Institute. But the aid didn't come on the scientific front - it came on an airplane landing strip.
The saga dates back roughly a decade when a small plane skidded off the short runway at the Airlie Center in Warrenton, Va., and ended up in the mud. The pilot, Oliver Smithies, Ph.D., faced quite a predicament. But a gaggle of National Human Genome Research Institute (NHGRI) staff, assembled for their annual scientific retreat, came to his rescue, applying their collective heave-ho to get Dr. Smithies' craft back onto the runway.
Scientific meetings rarely start with such excitement; but Dr. Smithies, who was then a member of the NHGRI Board of Scientific Counselors, made that gathering one to remember. Now, the octogenarian genomics researcher has landed something far more exciting - a feat that has all of NHGRI cheering.
Dr. Smithies of the University of North Carolina at Chapel Hill is among the trio of researchers recently awarded the 2007 Nobel Prize in physiology or medicine for pioneering work on gene targeting technologies that enabled development of knockout mouse models. In addition to Dr. Smithies, the other recipients were another researcher with ties to NHGRI, Mario R. Capecchi, Ph.D., of the University of Utah School of Medicine, Salt Lake City; and Sir Martin J. Evans, Ph.D., of Cardiff University, Cardiff, United Kingdom.
Dr. Smithies served on the NHGRI Board of Scientific Counselors - a group that previews and evaluates NHGRI's intramural research programs and provides peer review of Division of Intramural Research investigators - from 1994 to 2000. He has used gene targeting to develop mouse models of inherited diseases such as cystic fibrosis and thalassemia. He has also developed numerous mouse models for common human diseases such as hypertension and atherosclerosis.
The other recent Nobel Prize winner with NHGRI connections is Dr. Capecchi, who is currently collaborating on a comparative sequencing project with the National Institutes of Health (NIH) Intramural Sequencing Center, administratively housed within the NHGRI Intramural Program. He is also a co-author of the 2004 Nature Genetics paper that described the scientific rationale for the trans-NIH Knockout Mouse Project, in which NHGRI is a key participant. In addition to his role in developing gene-targeting technologies, Dr. Capecchi's research has uncovered the roles of genes involved in both mammalian organ development and in the establishment of the body plan. His work has shed light on the causes of several human inborn malformations.
Gene targeting, the breakthrough technology recognized with this Nobel Prize, can be used to inactivate genes in mice. The result is an animal model, called a knockout mouse, which can be used in experiments to study diseases impacting mice and humans. Gene targeting makes it possible to produce almost any type of DNA modification in the mouse genome, allowing researchers to determine the role of each gene in normal physiology and development.
Researchers are developing knockout mice as models of inherited human diseases such as cancer, heart disease, neurological disorders, diabetes and obesity. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neurodegenerative diseases, diabetes and cancer.
NIH, and NHGRI in particular, is steeped in research that benefits from the discoveries made by these Nobel laureates. A trans-NIH initiative of particular note is the Knockout Mouse Project mentioned above. NIH works closely with other large-scale efforts that are developing knockout mouse strains now underway in Canada - called the North American Conditional Mouse Mutagenesis Project (NorCOMM) - and in Europe - called the European Conditional Mouse Mutagenesis Program (EUCOMM). The collective goal is to create a mutation in each of the approximately 20,000 protein-coding genes in the mouse genome. The initiative, launched in 2006, aims to generate a comprehensive and public resource of mice containing a knockout mutation in every gene in the mouse genome.
The net impact of the Knockout Mouse Project, made possible by the discoveries of these Nobel Prize awardees, will be the rapid and efficient availability of animal models to study the underlying genetic causes of diseases impacting human health. Biomedical research and public health will receive enormous benefit from the rapid and wide availability of these knockout mouse strains.
"The selection of these researchers to receive a Nobel Prize is very gratifying for those in our field who have utilized gene-targeting technologies for their studies and can see its remarkable promise," said NHGRI Scientific Director, Eric Green, M.D., Ph.D. "It truly represents a fundamental breakthrough that is enabling a wealth of important biomedical research today."