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Bioengineer Stephen Quake: win “Inventors’ Oscar”

Quake has made pioneering discoveries such as a technique for sequencing an entire genome from a single cell and developed the biological equivalent of the integrated circuit.

As a Stanford undergraduate, Stephen Quake took on a ‘runt’ project in Nobel laureate Stephen Chu’s laboratory that interested no other student in the lab: using tools developed for atomic physics to measure DNA. The resulting thesis won him a national prize. 

Ever since, Quake’s career has been marked by the same willingness to take risks and to push the boundaries between disciplines, often with a similarly impressive results. It’s helped him become, at just 43 years old, a pioneer in the new field of bioengineering and led him to invent a number of practical tools that have changed how science is done.

On June 23rd, Quake – the Lee Otterson Professor in the School of Engineering – was recognized for those innovations with the 2012 Lemelson-MIT Prize, an award that’s been called the ‘Oscar for Inventors.’

The $500,000 prize honors “outstanding mid-career inventors dedicated to improving our world through technological invention and innovation.” Past winners include some of the most storied inventors of recent decades: Dean Kamen, Raymond Kurzweil, Carver Mead, Robert Langer, and Stanford researchers Douglas Engelbart and Thomas Fogarty.

It’s humbling company, says Quake, who is also an investigator at the Howard Hughes Medical Center. “They’re all just giants and some of my personal heroes,” he explained recently in his office at Stanford’s James H. Clarke Center. “That’s why it’s such an honor.”

Lauded as “one of the world’s most prolific inventors,” Quake, a professor of bioengineering and applied physics, was recognized as the originator of several technologies that have transformed science and medicine. These include an improved method for measuring the immune system, a technique for sequencing an entire genome from a single cell and the biological equivalent of the integrated circuit, an invention that has allowed for the large-scale automation of much biological research.  

A Festival of Invention

Quake received his award during the annual Lemelson-MIT EurekaFest, a four-day celebration of inventing and inventors with a special focus on inspiring young people to become inventors themselves. He was introduced by his own former teacher, Nobel laureate and U.S. Secretary of Energy Stephen Chu. Quake worked with Chu in his junior and senior years at Stanford and then again after completing his D.Phil. at Oxford University.  

As an undergraduate, Quake made the first single-molecule measurements of DNA elasticity with optical tweezers, Chu recalls. For this work, the budding scientist was awarded the Apker Prize for the best senior physics thesis in the country.

Quake remembers the work as something Chu’s graduate students wouldn’t touch. “Most people in the lab were doing work in laser cooling and trapping of single atoms, which is what Stephen won his Nobel Prize for,” he says. “Stephen was also interested in biophysics, and tried to get some projects going in his lab, but the graduate students thought it was too risky and uninteresting. I was just an undergrad. I didn’t know any better, so I got the runt project. And that ended up turning into a career.”

The fruits of measurement

If extraordinarily precise measurement was a hallmark of the advanced physics underway in Chu’s lab, those techniques had yet to be applied in biology. At Oxford Quake worked on measuring polymers and since then has developed new tools for the measurement of a variety of biological phenomena.

Typically, says Quake, “I get interested in some biological problem and I want to measure something about that. Then I get a way to measure it and then the measurement approach has other applications; broader ones and sometimes commercially interesting ones.”

Indeed, a hallmark of Lemelson-MIT Prize winners is that they have translated their ideas into inventions and innovations that have had a broad social impact.

For Quake, that has meant going beyond the lab to start a total of five companies that reproduce the instruments that he’s built for his own research – from the biological equivalent to the integrated circuit, to the first single molecule sequencer, to the first machine to analyze an entire immune system, all of which are now being employed by researchers across the world to make scientifically and clinically significant discoveries.

Working with a succession of biomedical start-ups has also been what Quake calls “a whole second education.”

“It’s been really interesting to sit in these board meetings and learn how that whole world works and what people have to do to build a company and launch products,” he adds. “I’ve enjoyed that quite a bit.”

Pushing boundaries

Trying new things and taking risks is very much part of what makes Quake tick, he acknowledges.

An avid mountain biker and ski mountaineer, he takes time to read broadly and attend seminars outside his field. “I blunder into other people’s domains without much courtesy,” he jokes. “I think it is about exploring boundaries, trying to push forward in the unknown.  That’s something that happens both metaphorically and literally.”

Every summer he escapes with his family to Europe, where he has time to think. “I sort of hide out for a couple of months,” he says, “and read and work on the things, the directions I want to grow.”

Most recently, Quake has been pushing the frontiers of immunogenomics and single cell genomics. He has been exploring the effects of vaccination and autoimmune disease on the immune system, and has created a test that can show whether a transplanted organ is being rejected by its new host without requiring an invasive biopsy.

In single cell genomics, Quake has been leading an effort to sequence entire genomes from single cells. That work has already led to the first non-invasive prenatal test for Down syndrome.

His lab’s progress in human genetics research has Quake and his students now thinking about ecology and population genetics, he says.

“If you think about it, your immune system is an ecosystem,” he explains. “Diversity is created and selection acts on it.  So we think that mathematical population genetics models could be applied to the immune system, and we’ve been measuring the data that will allow us to test that.”

Characteristically, that has Quake already looking further afield. “Cancers create a whole, huge pool of mutations and whichever grow fastest wins,” he notes. “When you apply chemotherapy, the tumors that have the resistant mutation continue growing — so genomic technologies are allowing people to ask the same sorts of questions in that regime.”