Born a Creationist, Merck’s Schadt Leads Open Source Effort to Unravel Genome

3/13/09Follow @xconomy

One of the world’s brightest minds at analyzing human DNA was born into a family of creationists. When he was 17 and graduating from high school in a rural area of southwestern Michigan, Eric Schadt couldn’t even imagine going to college.

“My parents were very religious,” Schadt told me on a visit to his office last week. They didn’t emphasize education, and neither did the community, he says. “Higher education just wasn’t something that people looked forward to there. I didn’t really know what college was.”

Schadt, now 44, and an executive scientific director at Merck’s Rosetta Inpharmatics division in Seattle, has traveled on a truly remarkable journey. One of his mathematical mentors at UCLA, Ken Lange, said Schadt reminds him of no less than the world’s leading mathematician who turned his curiosity to the riddle of the human genome—Eric Lander of the Broad Institute in Cambridge, MA.

“Eric Schadt is a real leader in the field of computational genetics,” Lange said in an e-mail. “He has published many seminal papers. He sees the big picture better than the vast majority of geneticists and inspires his co-workers to tackle critical problems.”

Whether Schadt inherited a gene or not for missionary drive from his parents, he’s going to need it. His most audacious goal yet, one that we described in this exclusive story for Xconomy last week, is to make biologists collaborate through an open-source style movement with an ultimate vision of helping develop more effective drugs. This is taking shape in a nonprofit organization, called Sage, which was seeded with $5 million in donations this month.

Through numerous publications in prestigious scientific journals like Nature, Schadt has played a key role at Merck’s Rosetta operation in the years since Lander and his peers sequenced the entire 3 billion letter string of human DNA in the genome in the 1990s and early 2000s. Schadt and his colleagues have worked on the immensely complex next step of trying to help explain what all those data points mean. The concept is about connecting the dots between faulty DNA, which gets transcribed into bad RNA, which can be linked to proteins that actually cause a disease like cancer. There has been lively debate raging among scientists online since we wrote this original story, about where it is all headed, and whether it’s worth all the money.

I decided I wanted to get to know the kind of person who would try to lead an open source biology movement, cutting against ingrained professional norms that keep biological ideas proprietary, not open. So I went to meet Schadt at his office in Seattle’s South Lake Union neighborhood.

On first impression, you would never guess Schadt is the guy behind all those scientific papers. He is legendary for wearing the same trademark rumpled white polo shirt, khaki shorts, and sandals, to work every day (except when it’s below 30 degrees Fahrenheit outside, he says). Schadt has curly brown hair that hangs off to the right side, lively eyes, and a chubby midsection. If Hollywood were to make a movie of his life story, the lead role would go to Jack Black.

This unusual life story begins in Schadt’s hometown of Stevensville, MI—population 1,100 or so—just off Interstate 94, about a half-hour from South Bend, IN.

He grew up as one of seven children in the family. His mother stayed at home, and his Dad was a barber until Eric was in sixth grade, when he became an insurance agent, Schadt says. His parents were devout Baptists until he was in 9th grade, then switched to an evangelical free church. They were “extremely conservative” and stressed the Biblical story of creation, he says. The family didn’t have much money. “It was a hard road,” Schadt says.

His school didn’t recognize his academic abilities either, so Schadt channeled his energy into sports like cross country, gymnastics, and wrestling. He scored a 27 on the ACT college entrance exam—probably good enough in the early 1980s to get into a prestigious college like Northwestern University—yet no guidance counselor urged him to go to college. Instead, he joined the Air Force. “It’s a striking failure of the education system,” Schadt says.

In the Air Force, he joined an elite rescue program that pushed his physical stamina to the limits. “It was like Delta Force or the Navy SEALs, but not in a combat role, but for rescues,” he says. One day during drills, he severely dislocated a shoulder, and that was the end of that career. Then he took intelligence tests to see what else he could do, and the results were “off the charts,” he says.

Schadt was stationed at Vandenberg Air Force Base in southern California at the time and still had service obligations to fulfill, so that meant college had to be nearby for him to attend. He chose California Polytechnic State University, where he got a bachelor’s in applied math and computer science. At the tail end of his undergraduate experience, as the Cold War wound down in the late 1980s, he was introduced to some CIA signal processing teams that worked to ensure secure communications. If he ever wanted to understand the algorithms that made such work possible, he knew he had to go to graduate school.

So he went to UCLA to study pure mathematics, but quickly got tired of the theoretical nature of the field. “I really wanted more than 50 people on the planet to understand what I was doing,” he says. It was around that time, the early-to-mid 1990s, that momentum was building for the Human Genome Project, that relied on mathematicians. UCLA had a “hard-core” bio-mathematics program at the time, which drew him in. But pursuing this field would mean colliding head-on against everything he had been raised to believe. “Biology says we evolved, but my background says we were created. How can this be?” he wondered.

He got uncomfortable when I pressed him on how he resolved this conflict. He doesn’t subscribe to his parents’ religion, or attend church. But even with everything he has learned about evolution, he says he is awed by the complexity of nature and wonders if something else besides natural selection is at work. “I think there’s something more out there,” he says.

When he finished up his doctorate in bio-mathematics at UCLA, he chose a career in industry. Academia just couldn’t afford the big-time computing horsepower needed to make sense of all the genomic data, he says. After an initial stint with Roche in Palo Alto, CA, he came to the Seattle area to join Rosetta during its independent heyday in 1999, before it was acquired by Merck for $620 million in 2001.

Schadt has had a productive run at Merck, according to the published literature. Stephen Friend, who founded Rosetta and continued his career in the Merck executive ranks, raves about him. “There are brilliant people who can quickly come to the next logical decision with lightning speed,” Friend says. “What sets Eric apart is that his solutions cannot be mapped to what others would consider logical next steps. To the rare few of these I like to use the term of transformers.”

But all good runs come to an end sometime. Merck announced last fall it is closing its Rosetta division in Seattle with 300 employees. Even without that extra nudge, Schadt and Friend say they have been talking about the idea of splitting off into a nonprofit since 2007, because they realized pooling data from academic scientists around the world in an open database has more potential than what they can do strictly inside a corporate wall. “If we get a glimpse of 1 percent of the data, it costs a lot of money. To get the kind of data we want is beyond the scope of what any one company can afford,” Schadt says.

Schadt says he wants biologists around the world to see this new project as a true collaborative, not something locked up inside a powerful institution like the Fred Hutchinson Cancer Research Center, or the Broad Institute. The more open Sage is, the more successful it will be, he says.

Schadt says he would like to stay in Seattle for this next chapter of his career—he snowboards in the winter, and wakeboards in the summer. But if he needs to move his family somewhere else to make Sage a success, so be it, he says. “I’m mission-driven. And we have a big mission.”

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