Medical researchers predict 'flood of discoveries' soon

By Jeff Raymond

Published: September 14, 2007

Medical school and graduate studies in biochemistry at the University of Pennsylvania didn't prepare Dr. John Harley for his life's work.

The death of a friend with lupus did.

Fellow University of Pennsylvania grad student Jim Allen worked with Harley in the same lab. Allen's death spurred Harley to focus on the autoimmune disease, but from an unorthodox perspective.

He is a pack rat with blood.

Harley relishes the grunt work and says his work with lupus has lessons for other multi-gene diseases and their hard-to-locate homes on DNA.

What allows Harley and researchers worldwide to come closer to targeting lupus' underpinnings is the Oklahoma Medical Research Foundation's Lupus Family Registry and Repository, a decade-long, $20 million collaboration with the National Institutes of Health. It contains genetic profiles and blood samples from thousands of lupus sufferers and their relatives.

Part of making a difference, Harley said, was putting in place the infrastructure that makes scientific breakthroughs possible.

A New York team recently used the repository to determine relatives of lupus sufferers have high levels of interferon — proteins involved in immune responses. Because lupus is considered an autoimmune disorder, and many of those included in the repository don't have the ailment, high interferon levels among people without lupus was curious enough to merit publication in this month's issue of Genes and Immunity.

"It has been known for a long time that this is an issue for patients but not family members,” Harley said.

The registry has been cited in scientific publications more than 50 times since 1998. The National Institutes of Health renewed the lupus registry contract a year ago for $6.7 million over five years.

Harley went to work in 1982 at Oklahoma Medical Research Foundation as an early recruit to the Arthritis and Immunology Research Program. His interest, apart from his friend's death, was that lupus' cause was unknown, and it affected a large part of human biology.

He has asserted the Epstein-Barr virus is responsible, something fellow researchers had panned but now accept.

Fellow Oklahoma Medical Research Foundation lupus researcher Dr. Pat Gaffney predicted improving technology would unleash a flood of discoveries within six to 12 months.

The ability to analyze thousands of more genes at a time has put technological improvements at "center stage,” he said.

Imagine trying to catch a single fish in an entire lake. Now imagine knowing where the fish was hiding.

"The single most difficult thing for anyone doing genetics work is to accumulate the genetic material,” Gaffney said, complimenting Harley and his group for assembling the collection of lupus-related samples.

After 10 years at the University of Minnesota, Gaffney arrived in June at the Oklahoma Medical Research Foundation.

The importance of the registry, Gaffney said, was that lupus wasn't caused by one or two strong genes.

Instead, multiple genes contribute, and individuals will have different manifestations of the disease and different "genetic portfolios” that lead to them. It becomes a numbers game, a question of statistics.

Mailings to doctors' offices, outreach staff and presence at medical gatherings ensure participation in the registry.

Harley and Gaffney both treat lupus patients as physicians.

"In general, most physicians want to be able at some level to contribute to the scientific understanding of the diseases that they treat,” Gaffney said.

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