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The Crossroads of Chemistry and Biotech
Wednesday, May 1, 2002
Chaitan Khosla knows how to work a crowd. At a recent dinner hosted by the Ecology and Environment Professional Interest Council where he’d been invited to lecture, Khosla teased the audience: “I never thought anyone would want to pay to hear my life story — or worse, have me tell it to them while they are eating.”
Khosla, a Stanford professor of chemical engineering, had the group laughing for the duration of his speech. One quickly intuits that little of what he does goes off badly. At 36, Khosla has already established a family, founded his own public company, Kosan Biosciences, and amassed a tongue-tying array of distinctions. Among these are the Camille and Henry Dreyfus New Investigator Award in 1991, and, eight honors later, a Caltech Distinguished Alumni Award.

The awards in particular highlight Khosla’s impressive strides in an area of research know as microbial natural products, which straddles the worlds of chemistry, biology and engineering. In the simplest terms, natural products are complex chemicals that nature makes for its own purposes, but that have, for the last 100 years or so, also been exploited as curatives. Sometimes they become cancer-fighting drugs; other times they serve as immunosuppressive agents. Most come from fermented microorganisms whose structures and properties have been analyzed, then scientifically manipulated, such as the molds used to create Penicillin.

Khosla’s work revolves mostly around a group of mega-enzymes called polyketides. Though seemingly esoteric, it’s difficult to overstate the importance of the research. Every day, Khosla and his students attempt to better understand how bacteria and fungi make up polyketides, and how they can be rearranged to create deviated “natural” products that have enhanced uses in medicine.

So far, the group has enjoyed success in genetically engineering bacteria to make the antibiotic, Erythromycin, which is widely prescribed for respiratory tract infections. Traditionally, manufacturers have made the drug slowly, through fermentation using the soil bacterium, Saccaropolyspora erythraea. But Khosla and his researchers have found a way to speed the process by incorporating genes from a different bacterium, Escherichia coli, into a microorganism that can produce new, more plentiful amounts of the antibiotic. Further, says Khosla, by tweaking nature’s recipe, the newest bioengineered products have a better shot at combating strains of bacteria that have become resistant to overused antibiotics.

Khosla didn’t set out to become a chemical engineer. In fact, he fancied himself a chemist during his first year at Bombay’s Indian Institute of Technology, which was roughly 100 miles west of his hometown. It was when his father, an electrical engineer, voiced concern about this game plan (“Why chemistry? Don’t people go to IIT to become engineers?”), that Khosla says he “called it a wash” by obtaining a chemical engineering degree instead.

Neatly navigating life’s many intersections seems to come naturally to Khosla. Take, for example, the ways he is applying his research to both the commercial sector and academia. He still serves on the board of Kosan, which he took public in September of 2000, and whose $178-million market cap reflects some of the success it is enjoying in developing drug candidates out of — surprise — polyketides.

He spends a fair amount of time cultivating his relationships with the private sector, too. He calls his position on Kosan’s board “not a neutral one. I actively consult with companies. I work closely with senior management at many levels,” he says. “I also have extensive relationships with other small and large companies that interact with the firm. I’m pretty seriously corrupted in that regard.”

But Khosla’s first love — if only by a nose — is teaching. “If you’re in a position of influence, you can definitely get things done more powerfully in the for-profit sector than in a university environment,” he says. “When it comes to innovating new things and making new, fundamental discoveries, it isn’t like one has a decided superiority over the other.” Still, says Khosla, “I feel strongly about the ability to mentor. The power of having the opportunity to work with someone who is extremely talented and motivated, but green — the ability to help that person grow to be a world leader — is a tremendous thing. It factors more than anything into my wanting to be a professor.”

Khosla attributes his passion for mentoring to being exposed to great mentors himself, especially one Sir David Hopwood. According to Khosla, after ITT, he, “like 90 percent of ITT graduates,” decided to apply to graduate school in the States, ultimately choosing the California Institute of Technology. He soon figured out what he wanted to do, which was to find a way to merge chemical science and engineering with genetics, all in the context of understanding natural product biosynthesis.

So, after snagging his Ph.D., Khosla deferred an associate professorship spot at Stanford and moved instead to England. There, at the John Innes Centre in Norwich, Hopwood had pioneered research on the antibiotic-producing bacteria, Streptomyces, spores that are common in soil, plant debris, dung and house dust. Indeed, Hopwood’s team was the first to clone any gene involved in antibiotic production, and the first to clone a complete set of genes for an antibiotic. This opened up the idea of “designer antibiotics” being produced by a genetic manipulation.

Hopwood, now a John Innes Emeritus Fellow and Emeritus Professor of Genetics at the University of East Anglia, “was a great mentor,” says Khosla. “And his contributions to the field of [bacteriology] genetics are unparalleled.” He adds, “A scientist doesn’t get to become a knight in England for nothing.”

Ultimately, the similarities and disparities between life at Stanford and at Kosan have given Khosla a much better sense of what he can contribute to both worlds. “I know now that my early thinking, including that it was easier to control one’s future in an academic environment than in the real world, was significantly simplifying the situation,” he says.

Best of all, though, Khosla says that by weaving between his two worlds, he gets to “work with all manner of people who are extremely smart and extremely ambitious.” Considering Khosla’s professional efforts so far, those students and employees are liable to benefit a good deal from working with him as well.

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