Jonathan Rothberg admits he wasn’t always the best student. In elementary school he spent a bit of time in the principal’s office. But when he was in seventh grade, his brother bought him a computer.
“Until then I had difficulty focusing,” he remembers. “Computer programming taught me how to organize things. Everything I’ve done since has been around that kind of structure.”
Rothberg’s love of structure has led to a storied career as one of the nation’s most prolific inventors and commercializers of bioscience technology.
His first company CuraGen, begun while he was a graduate student at Yale, worked to develop drugs that targeted specific genes. He went on to invent a method for high-speed DNA sequencing, bringing it to market with his second venture, 454 Life Sciences.
And now, several companies later, his Guilford-based accelerator, 4Catalyzer, is launching multiple startups at the intersections of medicine, engineering and machine learning.
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Rothberg was awarded the National Medal of Technology and Innovation by President Barack Obama in 2016. He is a member of the National Academy of Engineering and the Connecticut Academy of Science and Engineering, and has been awarded the Connecticut Medal of Technology.
He’s been named a Technology Pioneer by the World Economic Forum four times, among a host of other recognitions.
Father’s footsteps
All of this started at the family home in New Haven. His parents co-founded Laticrete International, a company that specializes in innovative ceramic tile adhesives, and Rothberg credits his dad, chemical engineer Henry Rothberg, with being his earliest scientific mentor.
“I never took a car ride with my dad without having to do estimations,” he says. “We would drive by a water tank and he’d ask me how much water was in that tank.”
The family basement was also equipped with a laboratory, where the young Rothberg enjoyed creating pyrotechnics.
“Always thinking about the physical world, how to estimate, how things worked,” he says. “We didn’t use repair people. So if something was broken — from a radio to the plumbing — you fixed it.”
Academically, things started to come together for him at Amity High School where he warmly remembers some of his science teachers. Going on to Carnegie Mellon University in Pittsburgh, he dived into the rigorous world of chemical engineering. But he wasn’t following in his father’s footsteps.
“I had no interest in pursuing a career in chemical engineering, I just wanted the engineering discipline so I could bring it to biology,” he says.
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, after 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. They took CuraGen public in 1999, and by the next year it had a market cap of $5 billion.
The 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: The 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.
“The 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.”
This 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.
That 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.”
“The ideas behind all of his companies sounded far-fetched when he first conceived of them,” says Eric Kauderer-Abrams, co-founder and chief technology officer of Detect. But “Jonathan is able to see potential and put pieces together in ways that no one ever thought of before. He communicates his vision in a simple and compelling way that inspires people to join him on the mission.”
Beyond the vision, Rothberg has so much experience in the field that Kauderer-Abrams calls him “a master strategist — he has all sorts of maxims and playbooks that he’s developed for how to lead and grow a company through the various phases of the startup lifecycle.”
Detect was born out of Rothberg’s intuition in the earliest days of the pandemic that COVID-19 was about to upend science. He says what’s happened since 2020 has justified that view, calling it comparable to a world war in terms of spurring technological change.
“We made 10 years of progress in 18 months,” he says, getting people comfortable with key processes like telehealth and home testing. “It transformed the point of care. It transformed the home. It transformed people doing things themselves.”
It also prompted an influx of talent to his field.
“It brought together the most passionate people who realized, ‘do I really want to be designing computer chips or video games, or do I want to do something in health care?’ ” he says. “People don’t want to work anymore. They want to be on a mission.”
The fact that several companies in 4Catalyzer are led by young scientists demonstrates that Rothberg is paying forward the mentorship he received early in his career.
“I don’t actually do anything at any of these companies. I literally just have lunch with people,” he says, in what we should likely regard as an enormous understatement. “I find smart people, have lunch with them, and let them go.”
‘Gene Machine’
His old Ph.D. supervisor is enjoying watching it happen. Artavanis-Tsakonas says loyalty is one of Rothberg’s hallmarks.
“He cares about people. We remain very, very good friends,” says his former mentor. “I seek his advice as well, at this point.”
Throughout his stunning success, Rothberg has remained close to his roots in Connecticut, partly because it’s a great place to raise a family, but also as a strategic decision for his businesses, he says.
“Connecticut has a fantastic history of machining engineering, and engineering discipline,” he says. “All the machinists of the world were in Connecticut at the turn of the last century.”
That heritage has proved useful. He hires engineers from the state’s advanced manufacturing companies, “and I have them work on problems that at first they don’t even know are biological, but they apply their engineering principles.”
Rothberg clearly doesn’t have a lot of patience for leisure activities — he cites writing up patent outlines as his hobby. But he enjoys the lifestyle his success has brought him. He owns Chamard Vineyards in Clinton. He has also built a version of Stonehenge in the grounds of his Guilford home.
In 2013 he invested in a 55-meter luxury yacht, christened Gene Machine. He says he now spends 16 weeks each year with his family in an ocean somewhere in the world.
But he’s hardly soaking up the sun. Gene Machine is a fully-equipped research vessel.
“It has a machine shop, electronic shop and molecular biology lab,” he says.
A step up from the basement lab in Rothberg’s childhood home, but definitely a step on the same ladder.