Betting on the long shots in science can be risky, but if one wants to play the odds, researchers at UT Southwestern Medical Center have a powerful track record, proving that they are the ones to bet on.

Both the “Haberecht Wild-Hare Idea Program” and the “High Risk/High Impact Research Grant Program” were established by philanthropists who were convinced that taking a chance on the “long-shot” ideas of some of UT Southwestern’s best minds may produce a spectacular payday in the health arena.

Philanthropists Dr. Rolf Haberecht and his wife, Ute Schwarz Haberecht, established the Haberecht Wild-Hare Idea Program in 1996 to foster speculative research based on innovative and controversial ideas. The program has spawned numerous visionary ideas, one of which has resulted in a novel drug that formed part of the base for establishing a new pharmaceutical company, Reata Pharmaceuticals, which has become very successful.

“I have always believed in imagination and innovation – in thinking differently and outside the margins of what is conventional,” said Dr. Haberecht. “One of the great challenges with conducting research of any kind is that it’s difficult to get funding when the research is novel and relatively unexplored. Ute and I understand that these young ideas can bring about great things, and we thought the Wild-Hare Program would be a good way to provide seed money for projects that otherwise might die before they got off the ground.”

One Wild-Hare success story stars Dr. Jay Schneider, associate professor of internal medicine, who received $37,500 in 2004 for a “High Throughput Screen for Cardiogenic Small Molecules.” Dr. Schneider proposed applying cutting-edge, high-profile technologies – differentiation of cultured embryonic stem cells and high throughput chemical library screening – to solving the fundamental problem of cardiac stem cell fate.

The chemical library screening was successful, yielding a veritable treasure chest of novel small molecules having confirmed biological activities in embryonic stem cells. This research led Dr. Schneider, along with Dr. Jenny Hsieh, associate professor of molecular biology, to create in 2008 a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture. The development might someday allow a person’s own nerve stem cells to be grown outside the body, stimulated into maturity, and then re-implanted as working nerve cells to treat various diseases.

Dr. Schneider had another brainstorm and used drug-treated blood stem cells to repair heart damage in an animal model, results that might point to methods for healing injuries from heart attacks or disease. Despite medical advances in treating and preventing heart attacks, once the heart is damaged it does not repair itself, said Dr. Schneider. “The clinical potential is enormous,” he said of the findings, which were published in Proceedings of the National Academy of Sciences.

In a similar vein, the High Risk/High Impact Program was started in 2001 by an anonymous donor to “provide seed dollars for bold unconventional projects that are not yet mature enough for federal grant submissions.”

“The idea is to fund a concept and give enough money to see if someone’s idea has potential. It is literally a ‘seed’ program,” said Dr. David Russell, vice provost and dean of basic research for UT Southwestern Medical School and a member of the National Academy of Sciences. “The National Institutes of Health expects a large amount of preliminary data – completion of 20 percent to 25 percent of the proposed research before you even submit a grant application. This has been true for the last 10 years. The desire to fund ‘sure bets’ has resulted in a shortage of funds for certain projects. The NIH is not likely to say, ‘Let’s take a flyer.’”

One of the most recent High Risk/High Impact grantees is senior faculty member Dr. Philip Thomas, professor of physiology and holder of the Ruth S. Harrell Professorship in Medical Research. He is proposing using ribonucleic acid as a sensor to follow metabolism and gene expression in cells.

“This has never been done before,” said Dr. Russell, who leads the committee that evaluates submissions. “Everyone who read the proposal was entranced with the creativity of the idea. Dr. Thomas has the necessary skills to put the idea into effect. It’s brilliantly simple; that’s the quintessential idea behind the program. When an application impresses all of the committee, it’s almost certainly a winner.

Interestingly, Dr. Thomas was in the first group of grantees for the Wild-Hare Program 16 years ago. Then he proposed developing a new pharmacological approach to the treatment of genetic diseases caused by improper folding of mutant proteins. His study yielded results that were presented at several international meetings and contributed to the development of an assay – funded by another Wild-Hare grant in 1999 – for screening compounds for effect on protein folding in a novel genetic system. Results were published in Nature Biotechnology.

“These programs are very competitive – most recently attracting 37 applicants in the biannual request for proposals – with only a few funded in each year,” said Dr. Russell, who holds the Eugene McDermott Chair in Molecular Genetics. “It’s enough money to test an idea, but not enough money to follow it up. If the idea works, it can be funded through another agency. It’s a sign of the times that we are getting lots of applications from senior faculty as well as junior faculty and trainees – all great ideas, all new ideas.”