Drug company bets on basic research

Innovative drugs often begin in university labs, after scientists pinpoint a “target,” or a component of cell machinery that plays a key role in a specific disease. Biotech companies study molecules that interact with these targets, hoping to hit on a molecule that can be developed into an effective medicine. The successes are bought up by pharmaceutical giants.

But Big Pharma, eager to keep its pipelines stocked with new drugs, is beginning to skip the biotech step and turn directly to academia for promising targets, offering scientists grants to do fundamental research in exchange for intellectual property rights. Now Yale researchers are joining the trend.

The biopharmaceutical company Gilead Sciences Inc. announced this spring that it will grant Yale $40 million over four years—with a potential extension to ten years and $100 million—in a research collaboration aimed at finding possible targets for cancer drugs. The ten-year project, if it takes place, will be the largest corporate commitment in Yale’s history.

Under the agreement, several labs at Yale will analyze the DNA of tumors from patients at the Yale Cancer Center, then piece together how these tumors’ mutations function in the patients’ cancers. Armed with that information, the researchers hope to develop new drugs to interrupt those harmful functions. There are no guarantees, but such an approach has succeeded in the past: the drug Gleevec, for example, was developed when scientists found that it blocked an enzyme that they knew caused a certain type of leukemia.

A joint steering committee of investigators from both Gilead and Yale, including Joseph (“Yossi”) Schlessinger, chair of the medical school’s Department of Pharmacology, will choose the labs and supervise the funds. Yale will hold the right to publish all discoveries; Gilead will have first option to license new intellectual property.

Collaborations like these have their critics. “The company and the academic institution are essentially business partners, both benefiting from NIH-funded research,” writes Harvard lecturer Marcia Angell, a former editor-in-chief of the New England Journal of Medicine, in an e-mail interview. Such arrangements, she says, can distort the research agenda. On the other side, venture capitalist Bruce Booth has praised the trend, arguing on Nature.com that it will help to foster academics’ appreciation of the challenges of drug development.

Gilead, best known for its HIV and other antiviral medications, including Tamiflu, recently bought three biotech companies in another effort to develop oncology drugs. Howard Jaffe ’82MD, president of the Gilead Foundation and the company’s chief architect of the agreement, explained that they approached Yale due in large measure to Schlessinger’s track record. Yale genomics expert Richard Lifton and clinician-researcher Thomas Lynch ’82, ’86MD, director of the Yale Cancer Center, will work alongside Schlessinger in the effort.

 “We’re aiming to replicate [in oncology] what we did in the antiretroviral world, and we believe that Yossi, Rick, and Tom are the best,” says Jaffe. “We’re making a big bet, obviously, that those three will point us to druggable targets. At the very least, it’ll be great science.”