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A new era of medicine is underway.

“With the completion of the Human Genome Project,” says Richard K. Wilson, PhD, professor of genetics and director of the Genome Sequencing Center (GSC) at Washington University in St. Louis, “medical scientists have begun applying genomics on a wide scale to help understand disease and improve people’s lives.”

The Human Genome Project, completed 50 years after the discovery of DNA, is arguably one of mankind’s greatest achievements, and scientists at the School of Medicine were at the project’s forefront. Today, those researchers, in conjunction with physician-scientists from many departments across the university, are leading the way toward reaping the potential of this powerful genetic database.

Already, the genome sequencing effort has helped to spur discoveries about breast, colon and prostate cancers, cystic fibrosis, Huntington’s disease and Parkinson’s disease. And while mapping the complete genomes of organisms remains the focus of the Genome Sequencing Center, it is the next step—the application of the genetic code—that holds the potential to change medicine. Using the map of the human genome, physician-scientists can “finger” the genes that cause disease. Now begins the detective work that may someday change, and even save, lives.

“The human genome sequence provides a place for researchers to begin if they are interested in correlating specific genes to specific disease,” says Wilson. The GSC already is working with a handful of investigators Wilson labels as “visionary” in their attempts to incorporate genomics into their research. His goal for the GSC is to connect with as many like-minded School of Medicine physician-scientists as possible.

One such researcher is Timothy J. Ley, MD, the Alan A. and Edith L. Wolff Professor in Medicine and professor of genetics, who is leading a study designed to identify genetic changes associated with adult acute myeloid leukemia (AML). Ley began assembling a team more than two years ago to study specific genes found in patients with AML, with the ultimate goal of looking at every gene in the map to find all those involved in causing leukemia.

Ley, who also is associate director of basic research at the Alvin J. Siteman Cancer Center, along with colleagues Wilson and GSC co-director Elaine Mardis, PhD, from the Genome Sequencing Center, and John F. DiPersio, MD, PhD, Daniel C. Link, MD, Michael Tomasson, MD, Timothy A. Graubert, MD, Howard L. McLeod, PharmD, Hanna J. Khoury, MD, Kathryn M. Trinkaus, PhD, Mark A. Watson, MD, PhD, William D. Shannon, PhD, and Jeffrey D. Milbrandt, MD, PhD, all from the Siteman Cancer Center, designed an initial study that examined a dozen genes in 47 AML patients. Data generated in that pilot study showed interesting sequence changes—possible mutations—that warranted further research. On the basis of that work, Ley, Wilson and colleagues recently received a four-year, $11 million program project grant from the National Cancer Institute that will allow the research team to scale up, eventually looking at thousands of genes from 140 AML patients.

According to Ley, functional genomics research is not so much a collaboration between researchers as it is a joint agreement among many people who share the same vision. “It doesn’t just take a sequencing center to do this research, it takes a group of people who understand the disease they are studying and the nuances of treatment,” Ley says. “We have the critical mass at Washington University to launch these projects.”

That “mass” includes the expertise of the GSC, physician-scientists, human and experimental geneticists, computational biologists, pathologists, cell biologists, mouse modelers, clinical data managers and statisticians. “It takes a mix of people to do a project correctly—it can’t be done in one lab,” says Ley. “We all pull together to solve problems.”

The potential benefits of such collaboration are enormous. “Getting to the genetic roots of disease one patient at a time will rewrite how we deal with disease,” says Ley. “Even thinking about getting at the molecular roots of disease will change our understanding and approach to individual therapy and give us new drug targets. It’s revolutionary and will affect how we ultimately treat patients.”

Ley is not alone in his enthusiasm. Several other scientists at the university also approached the GSC early on to propose projects using sequencing information.
How will the new field of applied genomics affect the health and life of the average person? Most likely, genetic data will lead to a precise personalization of individual health care. Today’s scientists are just beginning to explore where such knowledge may lead.

While beneficial, some people may find the prospect of such detailed genetic analysis unsettling. “Any technology that we humans inflict on ourselves carries its risks along with its benefits,” says Wilson. “This is one technology where, applied the right way, the benefits far outweigh the risks.”

By Darrell Ward and Holly Edmiston