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Stone knew that the combination of genetic material, family pedigree, and clinical history he had in hand could prove invaluable in a search for the Best disease-causing gene mutation. Working with Sheffield for the first time, they spent the next two years looking for that gene; they found its chromosomal location in 1992 and, in 1998, they identified the mutation responsible for the family's condition.
The two scientists have continued searching for genes responsible for other inherited eye diseases and related genetically derived conditions. “The lesson was clear from the start: Pay close attention to what patients are telling you,” says Stone.
But, as Sheffield points out, “The goal is that information won't just come one way. Patients don't just provide us with resources to do research. We'll give back to them. If we have information about carriers, for example, we can educate them about the diseases and help them with marital and family-planning choices. And the ultimate hope, of course, is that the basic science will lead to treatments.” [See sidebar: Bridging the Gap]
Patient advocates play an important role in driving biomedical science to find cures, often by helping scientists interested in fundamental biological mechanisms to see that their work has important clinical applications. Consider, for example, HHMI investigator Thomas M. Jessell at Columbia University's College of Physicians and Surgeons, who studies the assembly of neural circuitry in the central nervous system. Within the last few years he began experiments to turn mouse embryonic stem cells into motor neurons (which connect to muscles for movement and locomotion) to study the course of their normal development. It turns out that this research has also been fruitful for better understanding neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and spinal muscular atrophy (SMA), both of which cause fatal loss of neuromuscular control. Jessell now works closely with Project ALS and the SMA Foundation to study stem cells as potential treatments for these diseases, in conjunction with HHMI investigator Douglas A. Melton at Harvard University.
Jessell's turn toward finding clinical applications for his basic-science studies came about because individual philanthropists and disease advocacy groups began seeking him out. At their urging, after building a career largely devoted to basic science, he has found himself increasingly thinking about the relationship between his research and its potential for clinical applications. “It's not that the work in the laboratory has changed to become clinical,” he says, “but with the perspective such alliances bring, it's easier to think about applications.”
To deepen the connection between basic and clinical research, Jessell helped to set up the Motor Neuron Center at Columbia University—funded with large gifts from Leonard Tow, a New Yorker whose wife has ALS, and the SMA Foundation—to bring together and support 40 different laboratories, both basic and clinical, in potentially productive collaborations. “This has changed the way I think about the science we do,” says Jessell.