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Forbes Magazine - Gene Machine (Part 4)

On The Cover/Top Stories

Gene Machine

Matthew Herper, 12.30.10, 05:20 PM EST 
Forbes Magazine dated January 17, 2011

Page 4 of 6

Behind the swagger lies a serious mission. Rothberg's 14-year-old daughter, the oldest of his five kids, has a mild form of an inherited disease called tuberous sclerosis complex, a relatively rare disorder (50,000 or so Americans have it) that can cause benign tumors in the heart, kidney, skin, lungs, eyes and brain, where seizures can occur. Gene scanning might help nail the causes so that drugmakers can find a cure. "All motivation forever has been personal," Rothberg says, "because we all want to affect the people we love," adding: "If it [were] just intellectual, I would have a company now doing artificial life . . . making non-DNA."

Rothberg grew up in New Haven, Conn. in a family of science-oriented entrepreneurs. His father, a chemical engineer, owns a company that makes high-performance adhesive for tiles. As a kid Jonathan went on sales calls with his dad. In college at Carnegie Mellon, where he majored in chemical engineering, he idolized Steve Jobs and went to hear him speak. He still has a 1982 Time magazine cover story on the Apple founder.

He founded his first company, Curagen, in his basement in 1991 soon after getting a doctorate in biochemistry from Yale. It was one of the first biotech firms to automate the search for new genes with robots and easy-to-repeat experiments.

The timing was great. Just a few years later Craig Venter started making headlines for his gene-sequencing work--giving biotechnology a lofty place alongside the dot-com boom. Curagen went public in 1999. By the next year it had a market cap of $5 billion, bigger than American Airlines. In 2001 Curagen notched one of the biggest biotech deals of its time, a $1.5 billion agreement with Bayer to develop drugs for obesity and diabetes.

Like most of its high-flying genomics peers, Curagen was soon in Icarus free fall. Its lead drug to treat chemotherapy side effects failed, and the Bayer deal yielded nothing fast. Investors started to bail. Rothberg got pushed out in 2004. In 2009 drug developer Celldex Therapeutics of Needham, Mass. bought the remnants of Curagen for just $95 million.

While still at Curagen Rothberg realized that better technology was needed to make genetic medicine a reality. When Noah, his second child, was born in 1999, he had to be sent to the neonatal intensive care unit because of breathing troubles. Noah turned out to be fine, but Rothberg was frustrated that doctors didn't have a rapid test to ensure his son didn't have an inherited disease. Sitting in the hospital waiting room, he thought about the similarities between gene sequencing and microelectronics. Existing DNA sequencers, he reasoned, used clunky technology akin to computers based on vacuum tubes. He thought he could do better. He infuriated his wife by spending most of his paternity leave working on the new technology that used firefly enzymes to read DNA with light.

The idea evolved into 454 Life Sciences, a Curagen subsidiary Rothberg created to commercialize the new machine. He clung to 454, even after he left Curagen, announcing with dramatic flair in 2005 that he would use the machine to decipher the genome of DNA codiscoverer James Watson for only $1 million, far lower than anything before. The project finished on budget in 2007. By that time Rothberg had lost control of 454. Curagen sold it to Roche for $140 million in 2007 to raise cash; Rothberg's creation is still on the market but has been crushed by machines from rival Illumina.

Rothberg himself is indestructible. It's a little hard to tell whether the 8-foot-high slabs, made of 700 tons of Norwegian granite, he recently installed in his back yard is a monument to Stonehenge--or to his own obstinacy. His neighbors in Guilford hate "The Circle of Life," as the sculpture is known. "I don't do anything out of spite," says Rothberg.

A conversation with his son Noah in 2007 led to the founding of Ion Torrent. Acting the precocious 8-year-old he was, Noah asked his dad to invent a machine to read minds. Rothberg, addressing the boy as he would a peer, told him the best way to do that would be to create a tiny chemical sensor that could read electrical signals passing between brain cells. It slowly dawned on Rothberg that a sensor like that could be used for DNA sequencing.

Retta Beery posted on January 09, 2011 Article Rating