Hartford Business Journal

C T I N N O V A T O R S , 2 0 2 3 4 3 CREWS CRAIG Super Focus Serial bioscience entrepreneur Crews marries chemistry and biology to birth new drug discoveries >> BY HARRIET JONES When Craig Crews was growing up in Virginia, his father worked for NASA. And while that might sound exciting to most of us, young Craig wasn't impressed. "He was a researcher doing very basic things," Crews recalls. "He was looking at the strength of different wing materials. It's called fatigue and fracture. He would just simply bend things until they snapped." e fundamentals of materials science seemed tedious, theoretical and lab-bound. "I thought it was the most boring thing ever," Crews said. at all changed in 1979, when a McDonnell Douglas-made DC-10 jet taking off from Chicago's O'Hare Airport suffered a catastrophic failure. A strut supporting the le engine cracked and fell off, causing the plane to crash just a mile from the end of the runway. All 258 passengers and 13 crew on board were killed. It remains the deadliest aviation accident on U.S. soil. "My father, being the world's expert in fatigue and fracture of airplane materials, was called in to McDonnell Douglas, and he stayed there for months trying to figure out what was wrong," said Crews. "at was, for me, a really important moment where I realized one could be passionate about pure, curiosity-driven, basic science — but also have an applied bent to it." Crews himself was not destined for materials science but the interface of chemistry and biology. In uniting the two disciplines, he has carved out a stellar academic career, from undergraduate work at the University of Virginia, to a Ph.D. at Harvard, and now 28 years and counting at Yale, where he is the John C. Malone Professor of Molecular, Cellular and Developmental Biology. He's also the executive director of the Yale Center for Molecular Discovery. And that excitement to see the impact of theoretical science in the real world, first ignited during his youth, has driven him to launch four successful biotech startup companies, one of which, New Haven-based Arvinas, now employs 450 people and has a market capitalization of more than $1 billion. "ey now have three drug candidates that are in clinical trials for breast and prostate cancer," said Crews. "And it's really fun that some of those trials are actually done here at Yale. It's a nice, circular story." Collaboration drives innovation Crews' academic training seesawed back and forth between biology and chemistry. He completed his undergraduate degree in the chemistry department at the University of Virginia. "en, they did not have a biochemistry department," he says, "and so I was always exploring the biological side of the chemistry department." Aer that, during a year in Germany at the University of Tübingen, "I just went full bore into biology, which was quite an eye-opener," he says. Putting his chemical training in service of answering biological questions, "I was able to do biology that biologists could not do." It convinced him that his graduate degree, at Harvard, should be in biochemistry. e interplay between the two disciplines fundamentally shapes the way he thinks about innovation. "It's hard to be innovative as a team of one, because it requires a diversity of thought, diversity of experience, diversity of skill set," he explains. "at is reflected in my laboratory where I have half chemists, half biologists." e tension and collaboration between chemistry and biology also sparked a realization about an interface between two other worlds — academia and business. "at led me to this idea that what we're doing in my academic lab could have real-world applications in terms of drug development," he said. "Can we go one step further with my academic chemical tools in the private sector?" Billion-dollar molecule He had a model from his early career, when he worked in the lab of Dr. Stuart Schreiber, a pioneer of chemical biology, and an integral figure in the founding of Vertex Pharmaceuticals. Vertex's story was documented by Barry Werth in the book, "e Billion-Dollar Molecule," which debuted as Crews was working in Schreiber's Harvard lab. It's blurbed as "a fascinating, no-holds- barred account of the business of science." "We all read it," says Crews. He began investigating how his own research could apply to the commercial world. e story began with a failure at one of the country's biggest drug companies. Bristol Myers Squibb had identified a naturally occurring anti- tumor compound – it worked, but they didn't know how. If the Craig Crews Professor of Molecular, Cellular and Developmental Biology at Yale University Founder: Proteolix, Arvinas, Halda Therapeutics and Siduma Therapeutics Education: University of Virginia, Harvard University Age: 59 Continued on page 46

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