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From trading faxes to changing lives

photo of Charles Sherr and David Beach
Former Cold Spring Harbor Laboratory (CSHL) Trustee Charles Sherr (left) compares research notes with former CSHL Investigator David Beach. Their success story shows that when you bring together the best minds in biology, lifesaving science is bound to come to the surface. Image: Paul Fetters, HHMI

Sometimes, scientific breakthroughs happen by accident. Penicillin was discovered when a British scientist left a petri dish uncovered while he was away on vacation. Other times, serendipity plays a role. Case in point: two chance meetings at Cold Spring Harbor Laboratory (CSHL) led to the development of a drug that has vastly improved patient outcomes for the most common form of breast cancer.

The first happened in 1988 at CSHL’s Banbury Center. In the mid-1980s, David Beach had been investigating cell cycle regulation at CSHL. During a Banbury meeting, another scientist in attendance encouraged Beach to think about proteins called cyclins in connection with regulatory enzymes called cell division cycle kinases. Beach listened. By 1990, he was ready to publish what would become a game-changing research paper.

At the same time, future CSHL Trustee Charles Sherr was struggling with his own research. He’d read up on Beach’s work. One night, he sat down on a bus on the way back from the Howard Hughes Medical Institute. When he looked over, he realized his seatmate was none other than Beach. “I suggested I had a gene we could work on together,” Sherr recalls. “It turned out he had isolated the same gene, although we didn’t know that [yet]. It was just fortuitous.”

Gregory Hannon, now at the Cambridge Institute, was interviewing at CSHL for a postdoctoral fellowship on the day Beach and Sherr realized they’d been working on the same thing. “I remember sitting outside David’s office, chatting with the other postdocs, as he and Chuck were faxing each other one amino acid at a time to see if they had the same gene,” he recalls. “And I thought, ‘If this place is this exciting every day, it’s going to be really cool to be here.’”

In this video from 2002, then-CSHL Trustee Charles Sherr reflects on his first meeting with David Beach in the early 1990s. By 2015, their collaboration would result in an FDA-approved treatment for the most common form of breast cancer. Video: CSHL Library & Archives

In 1991, Beach and Sherr published back-to-back papers on Cyclin D in Cell. Soon thereafter, Sherr identified the cyclin-dependent kinase CDK4, which forms a complex with Cyclin D. In 1993, Beach, Hannon, and colleagues found p16, a natural inhibitor of CDK4. “Collectively, these papers from our two labs provided the key genetic and biochemical evidence that set the stage for drug discovery,” Sherr says. In time, a new drug target would emerge.

In 2015, the FDA approved Ibrance (palbociclib) for the treatment of HR-positive, HER2-negative breast cancer. Taken in combination with hormone therapy, the drug has been shown to increase patient survival by more than two years and reduce tumor size by 50%. Other applications are in the works as well. Ibrance is in clinical trials testing its potential for treating head and neck cancers, non-small cell lung cancer, and other solid tumor types.

“What is poignant about the 2015 approval of Ibrance is the fact that it came a quarter-century after the fundamental discoveries by Beach and Sherr,” says CSHL President Bruce Stillman. “In the early 1990s, we simply did not know enough about cancer to convert their newly generated knowledge into an effective anticancer drug. Now we do.”

Written by: Jen A. Miller | publicaffairs@cshl.edu | 516-367-8455

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