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Pillar of Genomics

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Tim Hunkapiller’s a kid off the farm whose sequencing and computational biology brainstorms shaped the genomics industry

 

By Meredith W. Salisbury

 

At first, Caltech rejected Tim Hunkapiller’s application for graduate studies. He doesn’t mind admitting that, but Caltech probably would, given how much the school makes in royalties off the patented four-color sequencer he helped develop in one of its labs.

Now 48, the president and CSO of consulting firm Discovery Biosciences doesn’t even mind admitting that he had little interest in Caltech when he was looking at grad schools in 1977. “I was kind of poor at the time, and applying to grad school was expensive,” Hunkapiller recalls. “Honest to God, the only reason I applied to Caltech was because [the application] was free.”

But his well-known stubborn streak came out when he was rejected. With his environmental biology background at Oklahoma Baptist University, he didn’t have enough math and chemistry for Caltech’s program. So Hunkapiller negotiated his entry: he met individually with a professor eight hours a day during the summer to make up the course work in time to start that fall.

“He has a family gene having to do with a high level of stubbornness — but in a good sense,” says older brother Mike, president of Applied Biosystems and co-developer of the four-color sequencer. “He’s pretty tenacious about pursuing his interests.”

Straight talk

For someone who got his start by negotiating, Tim Hunkapiller doesn’t come across as a smooth talker. He’s got a tell-it-like-it-is attitude that gives away his small-town Oklahoma upbringing. On bioinformaticists, a title he loathes: “We really let ourselves get screwed by not actually doing the science with our own algorithms.” On academia: “Academics tend to seriously underestimate people in industry.” On Celera’s shotgun approach: “Craig embraced shotgun sequencing publicly. It wasn’t clever; everyone else was kind of embarrassed about it. Celera won because they just didn’t care [about] the process.”

Hunkapiller adds a caveat to almost everything he says: “I have a strong opinion on this, but I could be wrong. Even I admit that.”

Reclining in a café chair on the 24th floor of the San Diego Marriott Marina sporting a scruffy beard, denim shirt, and a plastic South Park watch — one of his many pop-culture collectibles (others include Curious George, Superman, and Star Trek gadgets) — this doesn’t look like a guy who was crucial to the birth of the genomics industry. But that’s precisely what he is.

Hunkapiller was a grad student in Lee Hood’s Caltech lab during the quest for an automated sequencer in the early ’80s. He had read about capillaries etched on silicon wafers, “and I thought, Aha!” He talked about the capillary idea with Mike, also in the lab, and the two worked with Hood, Charles Connell, and Lloyd Smith to come up with the final concept for the four-color sequencer, for which they share a patent.

Mike and Hood set out to license the technology, but no company wanted any part of it. “They went to 19 companies, including Beckman,” says the younger Hunkapiller. “They all pretty much blew them off.” As a matter of necessity, Applied Biosystems came into being, and the development of the actual instrument happened there.

‘Ahead of His Time’

Meanwhile, Hunkapiller pursued his interest in computational biology, bringing the first computers into Hood’s lab to work on HPLC. He patented work on the biological information signal processor chip, and later helped Paracel develop that into its GeneMatcher comparison engine.

“He’s obviously always been way ahead of his time,” says Marcie McClure, an associate professor at Montana State University who co-authored a paper with Hunkapiller. “He has a diverse interest in biology and computer science and he’s well versed in bioinformatics.”

Though — or perhaps because — he earns enough patent royalties to make a decent living, Hunkapiller remained primarily devoted to the academic world. He’d had the option of working for ABI, where he’s been a consultant “since ’82, even before my brother was there.” But, he says, “academics does give you a lot of freedom.” In retrospect, it was the right decision. “As an outside person I add more value and do more for [ABI] than I would internally.”

He stayed with Hood’s lab till 1992, when Bill Gates’ $12.5 million gift brought the entire lab to the University of Washington, where Hunkapiller accepted a faculty position.

He didn’t exactly cut the ties with California, though. The weekend that he moved to Washington in October of ’92, he started dating the woman who became his wife (they’re expecting their first child this month). Hunkapiller maintained a lab at Caltech for two years after he left, and between that and his consulting work for ABI, he managed to fly down nearly every weekend for five years. Since he got married, though, his travel has been mainly day trips, but he still gets to ABI for a day every week or two.

New Discovery

Three years ago, Hunkapiller finally left academia and founded Discovery Biosciences. It wasn’t an unexpected move, according to colleague Joan Goverman, a professor at the University of Washington who has known Hunkapiller since their days together at Caltech. “Tim has always had an entrepreneurial bent,” she says. “He can have a novel idea and get excited about it and have the intellectual ability to develop it.”

The idea for the consulting firm was to work for biotechs and pharmas, but it turned out that most clients are intermediaries who are themselves dealing with biotech and pharma. Among his clients are Applera, IBM, Microsoft, Deloitte & Touche, and VC groups. Hunkapiller hired David Kingsbury, a microbiologist from the US National Science Foundation and CIO of Chiron, to be Discovery’s CEO, and the company now has about eight employees. Offices are in Seattle and Foster City, and new branches are slated to open in Cambridge, Mass., San Diego, and Paris.

Harking back to his post-college days of “brown shirts and patches” running a nature center, Hunkapiller finds ways on his own and through his company to further various causes. He’s a member of the ACLU and Sierra Club, and Discovery Biosciences supports a charity called Children of Sosnovaya Street, which aims to improve conditions at a Russian orphanage.

Conflicts, Connections

Throughout his career, Hunkapiller’s been faced with conflicts of interest. He consulted for Applera and was on the books as a part-time Paracel employee when Celera bought the computing company. He had to turn down a consulting job for Hewlett-Packard because of his involvement with competitors, and only worked with that company from his academic standpoint. It’s typical for him to walk into a meeting and start off, “I’m sitting here as …” and fill in the blank with consultant, academic, or whatever else he might be at the time. “You have to really think about what ethics means to you,” he says.

At least he doesn’t have to worry about conflicts with ABI, where his connections are easy to spot. He grins. “The name kind of gives a lot of it away.”

The Scan

For Better Odds

Bloomberg reports that a child has been born following polygenic risk score screening as an embryo.

Booster Decision Expected

The New York Times reports the US Food and Drug Administration is expected to authorize a booster dose of the Pfizer-BioNTech SARS-CoV-2 vaccine this week for individuals over 65 or at high risk.

Snipping HIV Out

The Philadelphia Inquirer reports Temple University researchers are to test a gene-editing approach for treating HIV.

PLOS Papers on Cancer Risk Scores, Typhoid Fever in Colombia, Streptococcus Protection

In PLOS this week: application of cancer polygenic risk scores across ancestries, genetic diversity of typhoid fever-causing Salmonella, and more.