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Baptism By 2D Gel

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Ben Herbert had a woolly way to learn electrophoresis — and has woven a proteomics career around it

 

By John S. MacNeil

 

At his first job out of high school in a New Zealand government food-testing laboratory, Ben Herbert decided to try a new method of dissolving proteins extracted from canned fish. His previous attempts to verify a fish’s species of origin by analyzing its proteins using conventional techniques had failed to make the proteins water-soluble, and Herbert thought adding cyanide to the solution might do the trick.

Unfortunately for Herbert, who now serves as executive vice president for new technology at Sydney-based Proteome Systems, the lab wasn’t well designed. With the door closed, ventilation was inadequate. “He had a massive headache when he went home that night. He almost got cyanide poisoning,” says Jeff Plowman, a senior scientist at the Wool Research Organization in Christchurch, who supervised Herbert at the time.

But Herbert’s near-poisoning points to a trait that has served him well, say those who know him. “He had a lot of drive to be different, and there was always a willingness to try new things,” Plowman says. After all, initially blowing off university to concentrate on playing tennis and field hockey — as well as on drinking heavily, Herbert says — hasn’t put him far behind scientific peers who might have followed a more scholarly regimen. At 34, Herbert directs a team of four researchers in Sydney responsible for developing Proteome Systems’ sample prep, fractionation, separation, blotting, and staining technology.

The Road Less Taken

Instead of going straight to university — “I would have just failed,” he says — Herbert followed his mother’s suggestion to obtain a certificate of science in chemistry. Lab technician training involved learning how to do “endless boring repetitive things like titration until you could do them in your sleep,” Herbert says. But it did land him an internship under Plowman at the New Zealand Department of Scientific and Industrial Research food lab.

Through Plowman, Herbert discovered electrophoresis. The two established their own food analysis outpost, where they managed to avoid the tedium of routine experiments like analyzing fat content in milk by playing around with isoelectric focusing to analyze proteins, with the goal of verifying the origins of meat and fish products. Herbert also experimented on his own with some new gel-casting methods, and got turned on to gels with immobilized pH gradients — a cutting-edge electrophoresis technology at the time. As an added perk, Herbert says his analyses required only a small sample of the meat or fish — leaving the rest to take home for dinner.

After five years at DSIR, Herbert decided to “get off my lazy behind” and pursue a PhD. (Perhaps further incenting his return to school, Herbert ruptured the same ligament in his left knee twice between 1991 and 1992, effectively ending his competitive sports career. He complains that the injury sealed his fate to become a “fat lazy bastard.”) To prepare, he began studying for a post-grad diploma at Lincoln University outside Christchurch, and took a job across the street as a lab scientist at the Wool Research Organization.

Meanwhile, Herbert’s wool lab was the first in New Zealand to acquire an LKB Pharmacia apparatus for running immobilized pH gradient gels. “It seems like a joke that the Wool Research Organization bought the first IPG 2D gel unit in New Zealand” instead of a large university, he says. He knew of only a few other groups engaged in any sort of gel electrophoresis. “New Zealand was pretty small in that sense.”

So in 1991 Herbert persuaded his superiors to send him to Sydney to enroll in a short professional course on gel electrophoresis. There he met Keith Williams, who at the time was a biologist at Macquarie University. When Williams and other course organizers recognized Herbert’s prowess in electrophoretic analysis, they invited him to teach a course. “He came to my lab working on wool, and anyone who can dissolve wool proteins has got to be a genius,” says Williams.

Australia Beckons

By 1995, Herbert was finally ready to enroll for a PhD, but Williams had a better idea: Why didn’t Herbert leave New Zealand to pursue one in his lab at Macquarie? The Australian government had just awarded Williams about $3.8 million to purchase equipment and lab space for the Australian Proteome Analysis Facility, and Williams wanted Herbert to help set up the 2D gel electrophoresis lab.

Though his wife, whom he met in the food lab, “hated” the idea at first, working with Williams at APAF would give Herbert the opportunity to join one of the world’s first teams to plow full speed ahead into proteomics. Ultimately, it also led to his co-founding Proteome Systems with Williams, Andrew Gooley, Nicolle Packer, and Marc Wilkins. “I wouldn’t do anything differently because it’s turned out to be a fantastic thing to have moved to Australia and been part of the whole proteomics thing,” Herbert says. “To have been lucky enough to be one of the founders of Proteome Systems is like a dream come true.” And now that their two sons are in Australian schools, Herbert’s wife has moderated her stance, he says.

Since the company’s founding in 1999, Herbert has busied himself designing and improving the 2D gel technology that Proteome Systems is selling as part of its protein separation and identification platform. As other groups have attempted to move protein separation technology away from traditionally user-unfriendly 2D gels, Herbert has remained fixated on electrophoresis — both because he believes the technology is still extremely valuable, and because he enjoys the challenge of making 2D gels easier. Plus, he jokes, “I’m only really good at one thing!”

In a way, Herbert’s work with gel electrophoresis has come full circle. When he first started working with the technology at DSIR, he discovered a series of papers authored by Pier Righetti, a physicist at the University of Milan and an early pioneer of IPG gels. Herbert read his work voraciously, and soon Righetti became one of his heroes in the scientific community, according to Williams.

Now, Herbert collaborates with Righetti on developing new instruments and sample prefractionation protocols. Says Righetti, “We have published a number of papers together, he visits me a couple times a year, and I’ve been sending kids from my lab [to Sydney] to work on common projects. It has been a very prolific collaboration, with great satisfaction on both sides.”

 

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