The Imaginations of Unreasonable Men (14 page)

Jay Keasling and Steve Hoffman have met only once, at a conference where they both happened to be giving a talk. Though they express genuine admiration for each other’s accomplishments, each is so focused that, even when prompted, neither shows much interest in the other. But when I first started visiting Keasling I could see that he was philosophically connected to Hoffman in ways beyond their shared commitment to ensuring that children didn’t die from malaria.

The first thing Steve Hoffman told me on the first day we met was that the solution to a malaria vaccine was not a matter of scientific discovery but rather of biotech engineering. Though he was overstating the point, because science played a critical role at every stage of his effort, he was trying to convey that we knew what worked, but the challenge was whether we could scale it. In leading the effort to
apply engineering principles to biology, Keasling demonstrated a nearly identical insight in terms of what it would take to make highly effective medicines available on a mass scale, the kind of scale that would ensure that children like Alima were quickly cured.

Both were producing their product in a place that literally seemed impossible right up until they did it: Hoffman using the insides of mosquitoes as his primary production facilities, and Keasling using cells as chemical factories. They not only managed to see what the naked eye could not, but also to imagine a possibility that no one else had imagined. Both were undeterred by either the complexity and unknowns inherent in such virgin territory or the skepticism of respected colleagues. The conviction that they could save lives offset the risks they would be taking.

At the end of 2004, the Gates Foundation awarded a $42.6 million grant to support Keasling’s work through a partnership between UC Berkeley, Amyris, and the Institute for OneWorld Health, the nonprofit pharmaceutical created in 2000 to help develop drugs and vaccines for neglected diseases. Keasling’s responsibility was to do the research necessary for perfecting the microbial factory for artemisinin. Amyris would develop the process for industrial fermentation and commercialization. OneWorld Health would handle the regulatory work.

It was expected to take five to ten years to develop the microbes into truly large-scale producers of the artemisinin precursor. Keasling also hoped to produce promising anti-AIDS
drugs and cancer-fighting medicines like Taxol using the same processes.

The offices of Amyris overflow like a lab flask that can’t contain the chemical reaction within.

The firm spills across a courtyard into a second building at the edge of Emeryville, California, near Oakland. There are nearly a hundred staff members, including biologists, chemists, and newly hired administrators and project managers.

Producing an inexpensive antimalaria drug is not the only project that consumes their attention. Amyris takes aim at another, very different global challenge as well, and it exploits the same pioneering technology. Close on the heels of the effort to create synthetic artemisinin, and in danger of overtaking it, is the effort to produce synthetic fuels. If the project is successful, it could reduce our dependence on oil and mitigate global warming.

Keasling’s insight, simple in concept but extraordinarily complex in the lab, is that rare and valuable plant-based substances could be grown in lab tanks. All you have to do is transplant genes from the plant into fast-growing bacteria like
E. coli
and yeast. The insight has a lot of different applications, most of which are related to medical cures. But, theoretically, it could also be used to produce a next generation of carbon-neutral biofuels.

Amyris’s founding partners, while motivated by a desire to help malaria victims, were also savvy enough to appreciate the potential for enormous profit that lay in the field of synthetic biology and the processes they were perfecting. But what animated their conversation and sustained absurdly long hours in the lab was the thrill of basic science: the prospect of discovering something never before known, of peeking behind nature’s curtain to get a glimpse of the universe’s secrets, of making real to others what once they alone imagined.

Jack Newman is the forty-something vice president of Amyris overseeing lab research. The son of peripatetic artists, he dropped out of high school at fourteen. By his fifteenth birthday, he was attending community college, and en route to a degree at UC Berkeley in molecular and cellular biology. Pursuing a doctorate at the University of Wisconsin, Newman heard Keasling guest-lecture and determined to do his postdoctoral work in Keasling’s lab

“My life is a movie,” Newman told me. “Even I can’t believe it turned out the way it did. Amyris is exactly the company that I wanted to work for from the time I was fourteen. It is everything I imagined and I’ve never wanted to do anything else. It is exactly that company in every way.”

In black jeans and a black T-shirt, with long black hair flowing behind a prominent forehead and beyond his shoulders, he looks more rock band or computer geek than Dr. Newman. Some of the company’s energy seems bottled up inside his body, which moves in awkward ways, his head
occasionally tilting then snapping back. A natural teacher whose enthusiasm is infectious, he jumped up to the white board to diagram for me their process of using chemistry to create amorphadiene and artemisininc acid.

“The chemistry isn’t simple, but it is reliable,” Newman said. “You get an outcome you can count on. Biologic processes don’t work that way. Historically biology was too complex to apply engineering to, but that is changing.” Ever faster genome sequencing has made it so.

At the time I visited Amyris, the milestones that Amyris, Keasling’s lab, and the Institute for OneWorld Health had agreed to with the Gates Foundation focused on getting the metabolically engineered microbe to produce artemisinin on the scale of 25 grams per liter. At first they were getting 0.0000000001 gram per liter. Twenty-five grams per liter would be far more than has ever been produced in a lab, and a telling indicator of future potential. They’ve been testing both yeast and
E. coli
. “Both crossed the finish line,” said Newman of the ability of yeast and
E. coli
to grow large-scale batches of the drug. “Just this morning an experiment on this came back with results that were beautiful.”

Newman didn’t use “beautiful,” to mean “great” or “cool.” He meant beautiful the way it is used to describe a Monet or a Matisse: elegant, balanced, pleasing to the senses. He looks at chemical analysis and sees art. The 25-gram mark had not yet been reached, but things looked very promising.

Keasling walked me through room after room of tubes, tanks, coils, and monitors, most of it connected to enormous
computing power, young technicians, some with arms covered in tattoos from wrist to shoulder, strove to create artemisinin in ever greater quantities.

Just as Steve Hoffman would wrestle with whether what worked via the bite of the mosquito would work when scaled into a clinical manufacturing process, Amyris faced the issue of whether what worked in the shake flask on a lab shelf would work in a 50,000-liter tank the size of a bus. Scale changes chemistry. For example, the pressure at the bottom of the tank is different from the pressure at the top. That alone can completely alter results. And there are different surface-to-mass ratios, which vary with exposure to oxygen.

Amyris’s president, Kinkead Reiling, fell in love with math and science at a young age. In blue jeans and a button-down striped shirt with a neatly trimmed goatee, he seemed like an earnest, cautious person. His eyes lit up as he described a protein that, if pulled taut, would be like a long string of spaghetti, and when let go would fold up and in on itself.

Reiling, a military brat whose father flew cargo planes for the U.S. Air Force, started out in physics at the University of California at Los Angeles, fascinated by the notion of being able to understand the world by understanding the most basic parts of which it is made. He switched to biology at Columbia University and had the chance to work with Professor Robert Stroud, whose legacy was great advances in protein crystallography. He’s been a jack-of-all-trades at Amyris, reluctantly moving farther from the science to assume business responsibilities for which he has no training. Finances, office
space, human resources, hiring, payroll—all of this is Reiling’s portfolio. Akin to the oldest child in a dysfunctional family, he had to be the responsible one.

An added undercurrent of complexity runs through this company because its investors have varying expectations and objectives, even though their interests may be aligned. When Bill Gates funded Amyris to develop artemisinin, there existed essentially no commercial market or likelihood of financial gain. But in 2006, venture capitalists Kleiner Perkins and Khosla Ventures put $20 million into Amyris and arranged for John Melo, former head of fuel operations for BP, to become president. Shortly thereafter BP committed to invest $500 million over ten years into a new Biosciences Energy Institute at UC Berkeley. BP, looking ahead to whatever might end up being the next generation’s source of energy, apparently sees the potential for profit in the development of an alternative to fossil-fuel extraction.

Keasling has little time for what goes on outside of Amyris. At a 2007 Harvard School of Public Health conference at which he presented, he encountered—but did not really meet—“the vaccine guys.” He not only doesn’t know Steve Hoffman from Sanaria and Rip Ballou from GlaxoSmithKline, but doesn’t seem to focus much on what they are up to. They are the other side of the ideological wall: the hopeless idealists pursuing a total victory over malaria while losing countless small wars in the meantime. Keasling is busy fighting the small wars: “They’ve been at it for fifty years and there has still never been a vaccine to reach the
market, while meanwhile millions of kids die each year. So we better get some medicines to those kids.”

His schedule could compete with that of any other driven person I’ve ever met: “I wake up every morning at 4:30, it’s the most magical time of the day, and I go to the gym from 5 to 7. Then I’m at Berkeley, teaching.” He has about fifty students. “And in the afternoon I get over to the lab, and a couple days a week to Amyris. There is some complaining about not being able to get on my schedule, but I don’t want things on my schedule.”

He said teaching is the most important thing he does, but also admitted, with a somewhat pained expression, that he may not be teaching forever. It depends on the grants he gets.

Describing the decision to take VC money and then BP’s investment, and what it meant to give up control, he was clear: “If the question is, Do you want to own 100 percent of zero, or 20 percent of something really big, I know what I want.”

Everyone I spoke with at Amyris sounded a bit defensive about the dual mission of combating malaria and inventing biofuels, but they all also went out of their way to praise John Melo, who came in as Amyris’s CEO after a career at BP and Amoco. Reiling described him as “the least oily oil guy” he knew. “He really gets what we’re doing. Doesn’t totally understand the science, but respects it.” And he also made the point that all interests are aligned. “Amyris only works if our work with artemisinin is a success,” Reiling said.

Both Keasling and Amyris were in discussions with the U.S. Department of Energy about grants that would further
their work. And like Hoffman at Sanaria, Keasling’s team was giving some thought, even though it is technically beyond their sphere of influence, to how the medicine will actually be distributed in Africa. “Everyone here is motivated by seeing the science actually used,” Keasling told me.

The example of Amyris makes a compelling case for nonprofits embracing the disciplines of science rather than fixating only on the need for MBAs to secure the “entrepreneurial” label. The team at Amyris is trying to solve almost unimaginably complex social problems through biotech engineering. They are trying to scale up proven solutions and to lower their cost.

Scientists bring proof and precision to their efforts. Clinical trials guarantee predictable results. By March 2008, Amyris had formed a new partnership with Sanofi-Aventis, a leading pharmaceutical company based in France. Achieving the goal of mass-producing low-cost, microbial-based artemisinin would require greater fermentation capacity, and Sanofi could provide that capacity. Less than a year later, in February 2009, Amyris published an article announcing the achievement of their milestone: the production of 25 grams per liter of amorphadiene through
E. coli
fermentations, proof that commercially viable levels of artemisinin could be produced through Keasling’s process.
⁹
And Keasling intends to continue to explore strategies for increasing the yield.

It’s hard to imagine anything more valuable than a new medicine that would save the lives of more than 1 million children a year. But what about the new model that led to
that medicine? It is the model itself, combining science, philanthropy, and market economics, that may prove to be the lasting legacy of both Keasling and Hoffman. What’s more important than the fact that they may succeed in developing ways to cure or prevent malaria—as important as that is—is that they have eliminated the market gaps that so often undermine social solutions.

It is no accident that both Jay Keasling and Steve Hoffman have worked closely with and been funded by an innovative organization called the Institute for OneWorld Health. Founded in 2000, it is the world’s first and only nonprofit pharmaceutical. It is also a mechanism for market making. In some cases, it finds drugs whose patents have expired. In others, it gets pharmaceutical companies to donate the intellectual property from research and development efforts for drugs they’ve abandoned because they lack the potential for profit. Either way, OneWorld Health aims to pick up the pieces, produce the drugs at relatively low cost, and make them available to the world’s poor. Since OneWorld Health doesn’t need to make a profit, it can concentrate on fulfilling a mission that is purely altruistic.