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  • How physicist John Quackenbush found a home in cancer biology

    John Quackenbush, PhDJohn Quackenbush, PhD: "These aren't trivial challenges. It's an enterprise dedicated to making people's lives better." 

    In 1990, a PhD in physics freshly on his resume, John Quackenbush was packed to leave California for a postdoctoral fellowship at the Los Alamos National Laboratory in New Mexico when his new advisor called with some bad news.

    "The director of the program told me the project's funding had been cut and my position eliminated," says Quackenbush, now director of Cancer Computational Biology at Dana-Farber. "Suddenly I had to find a job."

    The jolt to Quackenbush's plans prefigured what would be a common tale among physicists in the early 1990s. During the Cold War, the United States had invested heavily in basic physics research, regarding it as vital to maintaining a defensive lead over the Soviet Union. As the Cold War wound down, that funding contracted drastically, leaving many physicists — highly trained and, in many cases, hoping to live out childhood dreams of a life in science — with a giant void where their career used to be.

    Like many of his similarly situated colleagues, Quackenbush began scrambling for other opportunities in his field. One of the few bright spots in fundamental physics research at the time was a plan to build a Superconducting Super Collider beneath a tract of desert scrubland in East Texas. A 54-mile-circumference ring of superconducting magnets and scientific instruments, the Super Collider was to be the biggest particle accelerator in the world, smashing tiny bits of matter together so researchers could study some of the fundamental forces of the universe.

    After his fellowship at Los Alamos evaporated, Quackenbush joined a group that would be using the Super Collider to study kaons, combinations of elementary particles called quarks and antiquarks.

    "One of the ways that kaons decay is thought to violate some of the fundamental symmetries of nature," Quackenbush explains. "My group's job was to design, build, and test a detector that would look for evidence of such decay in Super Collider experiments."

    The group had teams at Fermilab near Chicago and Brookhaven National Laboratory in New York. Quackenbush had just returned to UCLA from the Thanksgiving shift at Fermilab in 1991 when the main investigator invited him to lunch. Quackenbush could be forgiven a sense of deja vu.

    "The investigator told me that some copper used to stop particle beams at the Brookhaven lab had been stolen," Quackenbush recounts. "The thieves had caused a quarter million dollars of damage to particle detectors; they would need to be replaced. Department of Energy budgets — which funded our research — were tight. The project managers were looking for places to reduce expenses. One place they found was my salary."

    The elimination of this second job brought a reckoning that Quackenbush had anticipated but hadn't wanted to concede: "physics was in trouble." Confirmation came a short time later when the entire Super Collider project was shut down.

    In the coming months, Quackenbush would embark on a career transition that many physicists of his generation — and those graduating more recently — would make: from a field that concerns itself with the fundamental forces of the universe to another where the ability to analyze vast sets of data is equally prized.

    For many physicists, that meant finding opportunities in finance, computer science, banking, or government. For Quackenbush, it meant discovering — and convincing others — that his skills were a perfect fit for biology, especially at a time when genomics was beginning to generate unheard-of amounts of data in research.

    The career choice that Quackenbush made by necessity two decades ago is one that more recent physics grads are making voluntarily. Many newly-minted physicists are attracted to biology and medicine by the opportunity to use their data-analysis skills in a way that helps others. Though he hadn't planned it this way, Quackenbush has become something of a trailblazer for physicists working in cancer science — and at Dana-Farber. The Institute's Department of Biostatistics and Computational Biology now includes several former physicists.

    Though Quackenbush didn't have the luxury of a leisurely reflection on his career goals when he decided to enter biological research nearly two decades ago, he had been quietly laying the groundwork for a potential career change, should one prove necessary. He had joined a graduate-level discussion group on evolution at UCLA and taken biology courses and seminars and read extensively, so that when the time came to leave physics, it wasn't as jarring as it might otherwise have been.

    "I learned on a Friday that my first job was going away," he remembers. "Saturday morning, I called a biology professor at UCLA who I had helped with some analysis, and learned in the process that someone with mathematical skills and little biological knowledge could have a big impact in the life sciences."

    Quackenbush wrote a one-page description of how his quantitative skills equipped him to tackle fundamental problems in biology and set out to convince others. Learning that the National Institutes of Health was offering fellowships to people from computer science, math, physics, and engineering to work on the Human Genome Project (a massive effort to identify and map all the genes in human cells), he applied and was one of the first two people accepted to the program.

    His work in genomics and computational biology brought him in 2005 to Dana-Farber, where he has focused on the genomics of several types of cancer.

    Remembering his initial thoughts as he pondered a future outside physics, he says, "I thought, what do I really like about physics? Problem solving: I like the exhilaration of knowing something no one else in the world knows. In biology, there is a different set of problems, but I am still trying to find answers to compelling, unsolved questions.

    "Biology was an opportunity to do science that has a potential to impact people's lives: to unravel who we are, how we came to be, to explore our relationship to other forms of life, to tease apart the nature of human disease," he continues. "These aren't trivial challenges. It's an enterprise dedicated to making people's lives better."

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