San Francisco’s Dogpatch neighborhood, with its converted canneries and warehouses, is a long way from Iowa’s farm fields, where tens of billions of bushels of corn are harvested every year, and farther still from the smallholder farms of Uganda and Kenya, where one acre of corn and a few vegetables might be the sole source of livelihood for a family.
With its farm-to-table eateries and quick light-rail connection to the medical research that congregates around UC San Francisco, Dogpatch is a once rough-and-tumble neighborhood by the bay, where recently rehabbed Victorians sit alongside high-tech shared workspaces and new condo developments rise across the street. There, a seven-person start-up has used synthetic biology to develop what cofounder Travis Bayer (PhD ’07) hopes will transform the lives of sub-Saharan farmers and industrial agriculture alike.
Bayer set out trying to use plant hormones to outsmart a weed that cripples agriculture in parts of Africa. In the process, he and his colleagues created what is arguably a whole new class of treatment for crops, alongside pesticides, herbicides, and fungicides. They have seen the results of their work in the lab, and Bayer regularly stalks the rows of the company’s test plots in Iowa, alongside two agronomists looking at the effect of their treatment on stalks, leaves, ears, and ultimately harvest yield. Field trials have shown their treatment to make crops more resilient in times of drought—essential as traditional growing regions become hotter and dryer—as well as under irrigated conditions. More significant, their treatment could increase crop yields 5 to 20 percent stateside; on more marginal sub-Saharan land, by 50 percent or more.
So, what is it? AB01 is the working title of the first product developed by Asilomar Bio. It was initially developed to make plants more resilient during drought. Field tests showed it could do far more. And it was essentially discovered by accident.
Bayer, 36, is chief technology officer of Asilomar Bio. In a building full of biotech start-ups, his office might be mistaken for the spare digs of a software innovator—save for a few plump ears of corn resting on the windowsill. Downstairs, the company occupies a long alcove for lab space. A Wednesday morning finds him dressed in jeans and an untucked button-down shirt. Dark-haired with a couple days’ growth of beard, he comes across as quietly on fire, fueled by the sense that he’s part of a synthetic biology moonshot.
“I’ve always enjoyed being both a scientist and engineer,” he says, “to think about what we can learn about the natural world and then what we can use from that knowledge to rewire it, reprogram it—some people call it hacking the natural world.”
Bayer chose Caltech for his graduate studies because of its reputation for scholarly rigor. “I’ve studied, taught at, and visited a number of excellent universities around the world, and I haven’t been anywhere that matches the intensity of science and engineering at Caltech,” he says. “It’s a great place to dig into one’s particular field and passion.” When Bayer was completing his doctorate at Caltech, synthetic biology was in its infancy—but that was already his focus. A postdoc at UCSF focused on metabolic engineering and biofuels. He was recruited by a new center for synthetic biology in London, lectured at Imperial College, then was appointed associate professor of biochemistry at Oxford.
Bayer grew up in Texas, just outside of Austin, with no real connection to farming. It was in London, through conversations with a postdoctoral student from Zimbabwe, that he got interested in how to increase productivity and efficiency in farming. One problem afflicting agriculture in Africa is the weed striga, or “witchweed,” which one UN report estimates cuts yields by an average of 40 percent.
Bayer and crew created a synthetic strigolactone—a hormone that could be applied to fields and induce germination of striga. With no host to feed on, the parasite dies.
One member of that team was Bayer’s friend Eric Davidson, also from Texas. They wondered about commercial possibilities. “So we started the company to get the technology from the lab out into the world,” Bayer says.
They christened it Asilomar, after the historic conference center on the rocky Monterey Coast. The name means “refuge by the sea.” In the mid-1970s Asilomar hosted a landmark conference laying out the ethical boundaries of future work in biotechnology. Bayer attended a conference there in 2010 looking at what he describes as “radical blue sky thinking ideas for increasing and enhancing the efficiency of photosynthesis, the output of photosynthesis, and how that could affect crop systems, bio fuels, etc.” In the work with Asilomar Bio, photosynthesis remains an interest.
While Bayer taught at Oxford, Davidson became CEO and employee number one of Asilomar Bio. Pursuing striga in the lab, they set up a one-off experiment in the corner of the lab, looking for possible negative effects of applying their chemistry to wheat. They dosed one plant and not the other; they watered and watched for a couple weeks. No major differences emerged. They stopped watering the plants—essentially out of neglect. A few days later, they noticed that the untreated plant was starting to wilt. “The plant treated by the chemistry was still looking healthy and robust,” Bayer says. “So we looked at that closely, and we reviewed that a couple times, and saw there was a real effect there, and started digging into both the plant’s physiology and the molecular biology of what was going on.”
Application of the hormone they had created changed the way that the plant was accessing and using water. The plant drew moisture when it was harder to get, amplifying drought resilience. This aha moment came on the heels of a year in which drought had devastated U.S. agriculture. For a hotter, drier climate, this seemed a powerful tool. “The thing that really got me was we could go into the lab, and we could apply our chemistry to a plant, and basically stop watering it.”
Bayer decided to resign from Oxford, move to San Francisco, and go full time with Asilomar. It was, he says, “two of us, basically living off credit cards and a little bit of grant money.”
They secured lab space and, through a cold call to UC Berkeley, greenhouse space across the bay. Kitty-corner to the Cal campus, the greenhouse is old-school industrial inside, which suits Bayer just fine. They don’t do tightly controlled experimentation there; that’s what the lab is for. In Berkeley, they keep a supply of corn, soy, and tobacco growing, with their biologist toting seedlings across the Bay Bridge in his Mazda sedan. Outside, they might have a few rows of corn. When they do, Bayer likes to stop by to see how things are going. “One nice thing about plants: If things work well, you get interesting visual differences.”
Case in point: the California drought of 2016. July and August were hot. At the greenhouse in Berkeley, the team treated some plants and didn’t treat others, then let them dry down. Plants wilted, and leaves curled in defense, trying to hang on to what moisture they could. “Then we irrigated and turned on a time-lapse camera, because when plants are wilted they will try to take in water as fast as they can,” Bayer says. The untreated plants recovered in about 45 to 60 minutes—the treated plants in half that.
By examining the plants in the lab, they saw the change had taken place at the molecular level: more cellular water channels, or aquaporins, that allow water to flow. Bayer concedes that the visual transformations don’t always translate into clear shifts in data—but they might, and they are satisfying.
I’ve always enjoyed being both a scientist and engineer—to think about what we can learn about the natural world and then what we can use from that knowledge to rewire it, reprogram it—some people call it hacking the natural world.
Travis Bayer (PhD ’07)
As a scientist, I’m never going to be the guy who brings the absolute hardcore analytical rigor, but I’m the guy in the seminars sorting out the crazy ideas. One in five, one in ten is going to be worth following up. That’s the genesis of this company.
Travis Bayer (PhD ’07)
AB01 can be applied as a seed treatment, before planting, or during the growing season as a foliar spray—to a crop’s leaves. Both are common methods used by farmers to apply herbicides, pesticides, and fungicides, so this new treatment can be integrated into how farmers already operate. When data from field trials began coming back a couple years ago, AB01 started to look like more than a niche product. “Originally, we were thinking about it as a drought stress-type tool, where if you had drought you would spray it, and that would rescue your crop,” Bayer says. “What we saw in 2015 was, in a lot of different locations—even places that had irrigation and good rainfall—we were seeing yield boosts. We get the biggest boost in farmland that’s hitting the median yield. But we see an even better percentage yield increase when we go down to the marginal farmland. In Africa, we see yield increases of up to 50 or 100 percent.”
For smallhold farmers, that can mean a doubling of income. “That’s more that goes to health care, to their kids’ education, and also more food security.”
In the United States, as farmers apply this new treatment, it could increase income as well. But it could also decrease the other inputs required for growing. Some 40 percent of U.S. land is devoted to farming—just under 1 billion acres. “Think about the nitrogen, the water, and the energy that goes into growing crops,” Bayer says. “If you can improve the efficiency of the agricultural system by even a little bit, you’ve really effected mass change.”
In the office, on the day I first visit, he is working on a report for the Gates Foundation—which has been a backer of their work in Kenya and Uganda. Other partners of their work in Africa are the United Kingdom’s DFID (the equivalent of USAID) and the One Acre Fund, which focuses on helping smallhold farmers, cultivating an acre or two. Later in the week, Bayer has a meeting to negotiate a commercial license and before the month is out, he’ll be in Washington for a conversation with a patent official.
Back in the lab, bubbling away in a flask is a murky brown liquid known as AB09, “one of the more promising downstream compounds.” With the company’s first product slated for release in 2018, they continue to develop others for the pipeline.
This plays to Bayer’s strengths, he says. “As a scientist, I’m never going to be the guy who brings the absolute hardcore analytical rigor,” he acknowledges, “but I’m the guy in the seminars sorting out the crazy ideas. One in five, one in ten is going to be worth following up. That’s the genesis of this company.” The projects they’re working on now, like those he has tackled throughout his career, he says, “look a lot more like engineering: Can we engineer a microbe to do this? That’s really why I got involved in this field of synthetic biology early on. We’re not starting from first principles. We’re starting with something that’s evolved for a few billion years then trying to see what we can do with it.”
Farmers have always paid close attention to the weather. Climate change matters profoundly to them. “It’s going to get hotter, rainfall patterns are going to shift and largely make a lot of our prime crop growing regions dryer,” says Bayer. “We’re going to need a lot of different tools—chemistry as well as genetic engineering, breeding, smart management of water. The other big pressure point is we’re going to have more people to feed. So we both have to increase the total harvest we’re getting and increase the resilience of those systems.”
Look to the developing world—where Bayer’s team began focusing—and there are more factors to consider still. Take infrastructure: the need for good roads to get farmers’ crops to market.
“That’s huge,” Bayer says. “Probably a bigger piece of the puzzle. Thinking about global development, there’s no silver bullet, right? We think our technology could be transformative, but we acknowledge that it’s going to be part of a spectrum of solutions that people in sub-Saharan Africa can use.”
Those who come to farming from the outside often observe that farmers tend to be pretty conservative in how they manage the complexity of growing crops. There’s a lot at risk if they try something new. “As a scientist, I get to experiment every day,” Bayer says. “A farmer only has 30 or 40 seasons in their lifetime to get it right.”
But, he says, when we’re thinking in terms of the pressure points of more population and the same—or less—land to grow food, we need to get beyond thinking in terms of incremental changes to the system. “The crop breeding and crop protection industry has been thinking about gradual increases. That’s important—a few more bushels per acre. We think we can make a complete jump here. We have to.”
Bayer expects to see the company double in size, from its current team of seven. “We’d like to be the team developing new concepts, new chemistries, new inputs that are useful tools for farmers and getting those to market with specific strategies,” he says. “We have a lot of essential compounds in the pipeline. As we test them at larger and larger scales, we either advance them or we don’t. A lot of the things we make don’t work at all. A lot actually have negative effects on crop yield. We put some things out in the field last year that decreased harvest yield. We learn a lot from that, but it’s not something we would advance as a product.”
One area where they do hope to advance products: compounds that have an effect on microbes in the soil. “We’re starting to do a little bit of microbiology, which is a little bit closer to my background. It’s growing organisms on plates. We’re doing a couple different microbe physiology assays.” In the lab he points to a set of circular dishes. “That one is seeing how fast they can clear this zone of the nutrients around them. In a lot of symbiotic relationships, microbes in the soil will pass the plant nutrients, the plant will pass the microbe sugars. That’s a big part of crop yield and crop performance. Not a lot is known about that right now, but it’s starting to be a big area in crop science.”
The bigness, and the sense of possibility, seems to keep bubbling up with Bayer—whether it’s in the lab, or stalking the rows of corn alongside the greenhouse in Berkeley. “Think about environmental stress on crops. That’s cutting the harvest yield by about half. A farmer in Iowa will get 200 bushels. Without the stresses from the environment, he would get 400. We think that we have a discovery platform that’s going to come up with solutions to solve that, as big as a doubling of crop yield per acre. The way I like to think about it is: In the ’60s, the Green Revolution was the synthetic fertilizers for the crops. This type of chemistry, either built by us or others, could be a second green revolution.”
That kind of talk sounds right at home in Dogpatch, with a change-the-world attitude. “Changing the world in a positive way is why I got into science in the first place!” Bayer says. But he points to how science has changed in the years since he first came to Caltech near the beginning of this century.
“When I started out in grad school at Caltech, we spent a lot of time cloning,” he says. “Taking pieces of DNA, cutting them with enzymes, pasting them into other pieces of DNA, moving them into cells. Now we basically open up a browser, go to a DNA synthesis company, and design out what piece of DNA we want in silicon—and hit go. Pay with your credit card and get that within a week.”
In terms of what could be done with this technology, we moved from making blinking fluorescent E. coli bacteria into metabolic engineering—to make useful drugs and fuels. “It’s time to think beyond that,” he says. “Let’s think about engineering bacteria to interphase with our gut microbiota to change our mood. Let’s think about engineering microbes or chemistry to influence plants. I’d like us as a field to approach the point where the limited resource to what we can do is our imagination.”
Asilomar Bio’s treatment could increase crop yields in the United States by 5 to 20 percent; on more marginal sub-Saharan land, yields could increase by 50 percent or more.
Travis Bayer (PhD ’07)
In North Carolina’s Research Triangle Park, Kelly Smith (PhD ’96) is fermenting bugs. She directs microbials development for AgBiome, a 5-year-old company that developed its first microbiome fungicide. This year, there is a version being introduced for turf (think golf courses), marketed by the company SePro as Zio, and a version for covered crops (think tomatoes, cucumbers, peppers), a product named Howler.
For centuries, farmers have combatted fungus. Modern agriculture relies heavily on chemical fungicides. With Howler, the active ingredient is a live bacterium, Pseudomonas chlororaphis, which both attacks fungi and colonizes plant tissue to outcompete fungi. The product passed muster with the Organic Materials Review Institute so it bears the designation OMRI Listed—the equivalent of its USDA-approved organic for food—and qualifies for organic farming. But the product was developed with broad application in mind, with comparable efficacy to chemicals. “You can rotate it in with your chemical fungicide,” Smith says, “and so maintain the efficacy of the overall program without using as much of the chemistry.”
Biologicals are a small but growing slice of the market, she notes—with an emphasis on growing. Smith and other researchers in the crop microbiome aim for breakthroughs in agriculture on par with the new frontiers that understanding the human microbiome has enabled in human medicine. Quick and inexpensive DNA sequencing is key. “Technical challenges around our products have a lot more to do with the immense volume of genomic data available now,” Smith says.
She estimates the company has the genome sequence on more than 40,000 microbes. “What do we do with all of that information? How do we turn data into knowledge? That’s a big part of what we do here, technologically.”
Smith is an industry veteran. At Caltech, she looked at the use of methane-oxidizing bacteria to clean up hazardous waste. “My first love is the fermentation of unusual microbes,” she says. With the company Pasteuria Bioscience, she created a process for growing a microbe to tackle nematodes; that company was acquired by ag giant Syngenta for $113 million.
Expect to see more development in microbiome fungicides, she says—because agriculture needs to maintain a diverse slate of chemistry to keep weeds and pests from developing resistance to individual products, as happened with the widely used herbicide glyphosate, which had been developed by Monsanto. And biologicals offer incredible diversity for controlling pests. Odds are, she says, “nature has already invented most of the new modes of action that you want.”
But she also offers this sobering reminder: “The arable land that we need to feed everyone is not increasing. How are we going to be able to feed everybody on the land that we have—or even less land? And can we keep up with the pest control landscape as the climate changes in the zones for growing particular crops?”
Along with climate instability, the ag business itself is in turmoil now as well, Smith notes. Big companies are consolidating, and commodity prices are low—which keeps growers from being able to invest in new products or equipment. “Those are the very challenging external headwinds.” But what’s at stake keeps the work compelling. “Well, feeding the world,” Smith says. A reliable supply of safe, affordable food is critical to social stability and technological progress. “Agriculture is absolutely vital to everything.”
A common refrain of scientists in agriculture: There’s no silver bullet. Mary Ollenburger (BS ’06) has done work in the African nation of Mali testing soybean varieties inoculated with microbes to increase crop yield. “It’s a pretty cheap way to get microbes into the soil,” she says.
Cost is critical in agriculture, especially in the developing world. But more broadly, completing research for a doctorate at Wageningen University in the Netherlands, Ollenburger examined farming systems—and how changes there affect land use. “The stuff that agronomic scientists do is only one small part of the whole problem. It matters. But a lot of times, you see these projects that say, ‘We‘re going to end poverty by improving maize yields in Africa,’ and it’s just false.” Instead, she says, “I think about it as almost an engineering design problem. A farm consists of people, animals, crops, soils—all these things. I try to model those systems and look at how they work now—and how they could work better in the future.”
No surprise there; at Caltech, Ollenburger studied mechanical engineering. A formative experience was ME 105, a course taught by Ken Pickar that began as a straightforward engineering design class and, with Ollenburger serving as teaching assistant, became focused on design for the developing world, with a partnership in Guatemala.
She volunteered with Peace Corps in Ecuador, working on an irrigation project built by the World Bank near a mountain village. It suffered from poor repair and management. Lesson: Not all solutions are technical. She became intrigued with agriculture. In Mali, she notes, the challenges in agriculture might have to do with safety—for instance, in the use of pesticides. But a bigger challenge is infrastructure.
“Just straight-up roads that are passable all year round,” she says. Without them, “farmers don’t have any control over prices, because they have to sell to whichever person can get to their village, at the price that person decides to pay. It’s a markets issue, but you can‘t do any of the market solutions if you don’t have a road. There’s no one thing that is going to fix the world—or fix agriculture in Africa, or in Mali,” she says. “It’s going to be an ensemble, and it’s going to be different in different places.”
Sometimes making a system work hinges one small idea—like a cheap, efficient solar-powered pump to power irrigation systems. That's what Katie Taylor (BS ’13) developed for farmers in eastern India. With two fellow students from MIT—where she finished her master’s in engineering as a Tata Fellow—she cofounded Khethworks, where she currently serves as CEO.
In a roundabout way, she’s also there thanks to Ken Pickar’s engineering design class. During Taylor’s studies at Caltech, the class developed projects with Kerala in southwestern India. That was Taylor’s first foray into agriculture and into product design for the developing world.
What brought her back to India was a grad school assignment to design a low-pressure, one-acre drip irrigation system. Farmers said, “‘Yes, drip irrigation—very cool, saves lots of water, and improves yields.’ But the big barrier is affordable, year-round irrigation,” Taylor says. “That’s it. The first hurdle has not been crossed for the majority of small plot farmers in India.”
Some farmers do irrigate using diesel- or kerosene-powered pumps. But fuel is expensive; most farmers instead rely on the monsoon rains, cultivating once a year, and otherwise do migratory labor—perhaps working in the diamond mines or textile factories, “less dignified than tending their land and staying at home with their families,” says Taylor. A solar-powered pump removes fuel costs. But to keep solar panel costs down, the pump must be ultra-efficient. Taylor couldn’t find one to suit the farmers’ needs, so her team designed it. In 2015 they piloted the pump with seven farmers—the first time these farmers cultivated a dry season crop. The benefits were social as well as economic. “They were staying home with their families,” she says. “They got higher prices at market during the dry season.” With the proof in the pumping, Khethworks was born, and Taylor moved to India full-time.
Look forward a few years: India will soon be the world’s most populous nation. “Food production has to increase,” Taylor says. “Increase in the productivity of Eastern India and its 30 million small plot farmers is absolutely the way to go.”
But for those farmers, climate change has made the monsoon rains less predictable; rains will come and then stop. “If farmers don’t have access to any irrigation then they lose that entire crop.”
The average size of a farm in India is under 3 acres—versus 440 acres in the United States. That leads Taylor to a familiar refrain: "When you talk about agriculture across the world, agriculture solutions need to be geographically and climatically specific. You need to tailor solutions. For instance, with pumps, there’s no one silver bullet pump."
Dan Lieberman and his team are working to bring oxygen to children at risk of dying from pneumonia in the developing world.
“Venturing out in the dead of night, mastering the steep slopes of Mt. Lee, dangling 45 feet in the air, the incurable pranksters of California Institute of Technology struck again,” the Los Angeles Times reported on May 19, 1987.
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