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Proteomics Persuader

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When Keith Williams went to the dark side, his entire lab followed him

By Adrienne Burke

 

Keith Williams, 53, is the kind of guy who could lead a cult. Standing five-and-a-half-feet tall in sneakers with sparkling brown eyes, a leprechaun-like red beard, and an infectious smile, he is an unimposing figure. Greeting a first-time visitor to his company, Proteome Systems, he bounds into the lobby, hand extended, as if welcoming a long-lost friend.

Williams peppers his discourse with well-placed expletives, their effect softened by his singsong Australian accent, as he talks about the proteomics industry, which he could be credited with helping to create. Going back five and six years, his name appeared on papers titled: “Why all proteins expressed by a genome should be identified and how to do it,” and “From proteins to proteomes: large scale protein identification by 2-dimensional electrophoresis and amino acid analysis.” Among his coauthors were other proteomics pioneers such as Denis Hochstrasser and Ron Appel, who have since founded GeneProt; Ian Humphery-Smith, who founded the Human Proteome Organization; and Andrew Gooley and Marc Wilkins, now CSO and head of bioinformatics, respectively, at Proteome Systems.

Ironically, Williams’ mission — to build the ultimate industrial-scale proteome-analysis technology pipeline — is aimed at demystifying the work of such experts. He compares the academic protein-analysis network to surgeons who obfuscate their methods in order to keep the field elite. “Our view is that this is a big deal and everyone should get access to it,” Williams says. “The real progress in this field is probably not going to come from the experts, but from the scientists.”

With Proteome Systems’ help, scientists won’t have to waste time figuring out what solutions to use. “They should be able to buy a kit and it works,” he says.

Proteomics is an “explosion” that needs tools urgently, Williams says. “This is very large, it’s very complex, and we know how to do it.” Once his team erects the platform, it will sell it in partnership with distributors and manufacturers such as Shimadzu/Kratos, Microfab, Millipore, and Sigma, as well as apply it to in-house drug target discovery.

Of potential collaborators Williams adds: “Anyone who doesn’t buy into the vision is going to be hard to work with. We have a very complete vision as to how the bits and pieces fit together, so we want to work with people who get [that] and understand the complexity and breadth of it.”

On his large Australian redgum wood desk sits a US dollar bill — to remind him of the importance of the American market, he says — and a miniature crystal globe that he toys with unconsciously. Spend an hour or two sitting across from him and it becomes clear how he persuaded a lab full of researchers to abandon the academic life and make the leap into entrepreneurship with him.

Uni or Money?

It was late 1998 when Williams, then director of the Australian Proteome Analysis Facility at Macquarie University, lost his patience waiting for additional funding for his technology development work. “I had half a dozen people but … no capacity to keep them,” he recalls.

The university, or “uni” as he calls it, was providing funds for APAF’s facility and equipment, but not for expanding the staff. BioRad, APAF’s industrial partner, was too steeped in its own cautious culture to move quickly, Williams contends. To carry on constructing the industrial-strength, high-throughput platform he envisioned, Williams needed corporate backing. When the uni dragged its feet, he picked up and left. Virtually the whole team followed him.

Marc Wilkins, for one, has been enamored of Williams since he did an undergraduate honors project under him. “The guy is brilliant and there are few people in the world with remarkable scientific minds who are also fantastic to work with,” he says. Wilkins, who went on to do a PhD under Williams and then returned to Australia from his postdoc studies at University of Geneva to join the startup, says Williams’ knack for challenging his students and staff can be infuriating, “but he gets you to do things that you might never imagine otherwise that you’d have done.”

While Wilkins counts himself among those who “get an absolute buzz out of working with Keith,” he acknowledges that it takes “a certain strength of personality” to stick with someone so strong-willed: “You have to have a lot of self confidence.” At the same time, he says, one of Williams’ greatest accomplishments as a manager has been to create a spirit of cooperation among his staff, all of whom gather for drinks and nibbles on Friday afternoons to report on “cool stuff” they’ve accomplished during the week.

Asked to characterize his venture, Williams responds: “We see ourselves as an Applera-type company.” An ambitious comparison for the head of a 70-person organization, for sure. But not entirely far-out. In Sydney and at a manufacturing facility in Boston — 20,000 square feet overall — Proteome Systems engineers are building the Applied Biosystems side of their business: With a number of instrument-maker partners, including Shimadzu and Sigma, they are developing an assembly-line-like system of integrated instruments and tools — sample prep through mass spec through informatics analysis. Williams calls it a “go-to-whoa solution,” as in “Whoa, doggie!”

Though the platform won’t be available for several more months, the company has already launched an ad campaign showing an F/A-18 Hornet breaking the sound barrier and urging proteomics researchers to “get there faster.”

Williams sees a market for several thousand of the platforms, and he sees his company capturing it. On a tour of his site, where mass spec machines, protein extraction tools, and proprietary 96-well-plate-formatted 2D-gel membranes are in stages of assembly and testing, Williams proclaims, “We want to take the space and we think the space is empty at the moment.” He all but dismisses the technologies that, a mile away, APAF is marketing (and for which he, as patent-holder, still receives some royalties). Those, he says, are now out of date.

What about the Celera part of his Applera-like business? By building and selling this platform, isn’t Williams propping up his competition in the discovery arena? He’s not worried. “You can give someone a Formula 1 racing car and put them in it, but they won’t win the race,” he quips.

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