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The Innovators Issue-December, 2022

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2 6 C T I N N O V A T O R S , 2 0 2 2 And that's what he's been doing ever since. "He was clearly very inventive," says Rothberg's Ph.D. supervisor, Spyros Artavanis-Tsakonas. Now professor emeritus of cell biology at Harvard Medical School, he met the young Rothberg back in the 1980s when Rothberg was an ambitious graduate student at Yale. "He had the spark in his eye, which, aer all these years of teaching, you can recognize that." In fact, the work associated with his doctoral thesis, decoding a gene responsible for wiring the nervous system, landed Rothberg on the cover of the prestigious science journal Cell, "the Holy Grail of a graduate student," says Artavanis-Tsakonas. Rothberg continued to seek his professor's advice as he founded his first company, CuraGen. "He did it his own way," Artavanis- Tsakonas says. "It was not terribly conventional, in the sense of having a venture capitalist backing everything up." Democratization of medicine CuraGen turned out to be the sort of success most young scientists could only dream of. Rothberg's wife, physician and fellow Yale graduate Bonnie Gould Rothberg, also came on board to develop the company's pharmacogenomics program. ey took CuraGen public in 1999, and by the next year it had a market cap of $5 billion. e Rothbergs have five children, and the inspiration for his next venture came from a family emergency. When the Rothbergs' son Noah was born, he stopped breathing and was rushed to the NICU. Unable to help, Rothberg instead channeled his frustration into scientific invention. Wishing that he could peer inside his son's genome to know more about what was wrong, he began to muse on a faster way to sequence DNA. Although Noah quickly recovered, the musing led to the CuraGen subsidiary 454 Life Sciences, which eventually became the first company to make next-generation DNA sequencing commercially available, a significant step toward making personalized genomic medicine a reality. It also introduced a theme that has guided Rothberg's work ever since: e democratization of medicine, making previously complex procedures and devices cheaper and more accessible. As Rothberg puts it, "simplicity, speed and scale." He got busy applying Moore's Law — which predicts that microchips will double in power roughly every two years — to biology. His next company, Ion Torrent, would continue the innovation of DNA sequencing, putting it onto a computer chip, and eventually launching a tabletop device that promised to sequence an individual's DNA in one day for the cost of $1,000. In a nod to his scientific forebears he has sequenced the genomes of both Jim Watson, one of the people who discovered the structure of DNA, and Gordon Moore, for whom Moore's law is named. AI's impact While he was prolific even at the start of his career, it was events in 2012 that proved another turning point for Rothberg, prompting him to ramp up his entrepreneurial vision. "e world changed abruptly," he says, "because a small group showed that computers for the first time could do things that were normally restricted to humans, like understanding images." is was artificial intelligence and so-called deep learning. "And I realized that deep learning applied to biology and applied to medicine would be absolutely transformational," Rothberg says. at prompted him to replicate the processes he had worked on in earlier companies, mentoring and partnering with younger scientists to help them found new ventures. It's resulted in the birth of eight companies so far out of his Guilford-based accelerator, 4Catalyzer, including: Butterfly Network, which put an ultrasound on a chip; Detect, which makes an at-home PCR COVID test; and Quantum SI, which is sequencing proteins in the way that Rothberg once sequenced DNA. "We only work on things no one has ever done before," says Rothberg. "No interest if someone's done it." "e ideas behind all of his companies sounded far-fetched "People don't want to work anymore. They want to be on a mission." – Jonathan Rothberg Continued from page 25 Continued on page 28 Jonathan Rothberg focuses on the intersection of engineering and biology, putting processes including DNA sequencing, protein sequencing and ultrasound onto computer chips.

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