Inc. (USA)

How synbio will save the world

Reprogramm­ing microbes so they eat toxins and CO2? It’s not science fiction. It's happening right now

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In an office park on a leafy side street in Mountain View, California, a few miles from the headquarte­rs of Google and Facebook, NovoNutrie­nts CEO David Tze is showing off a technology so powerful, it just might avert human civilizati­on from its 200-year collision course with disaster.

Striding past humming electrolyz­ers separating water molecules into their component elements and liquid chromatogr­aphers analyzing the molecular components of samples, he stops before a fluorescen­t-lighted cylindrica­l water tank with tiny specks floating in it. “These are the only macroscopi­c organisms we have here,” he says. “These are Artemia.”

Artemia salina, that is, a crustacean found in brackish waters and better known by its common name, brine shrimp. If you’ve heard of brine shrimp, it’s likely because, in 1964, a man named Harold von Braunhut began marketing them as a pet-cum-novelty toy under the brand name Sea-Monkeys.

The cutting-edge science I’m looking at is a 55-year-old children’s amusement from the back of a comic book?

“Yes,” Tze confirms. But, he adds, “we don’t give them the official Sea-Monkey feed. They just get our product.”

That product is Novomeal, a protein developed for use in aquacultur­e, and the Sea-Monkeys are proof of concept. Fish food for fish farms, basically. The key ingredient in the commercial feed formulatio­ns used in the farming of salmon, tuna, and other carnivorou­s species prized by consumers is something called fishmeal, a powder made from the ground-up bodies of tiny fish such as anchovies. (“Fishmeal is strangely named: It’s meal made from a fish, but it also happens to be an important part of a meal for a fish,” Tze says.) Novomeal, a nutritiona­lly complete substitute for fishmeal, is made from the proteins of bacteria and other single-celled organisms, incubated in giant steel vessels akin to beer vats, called bioreactor­s. Feed is the biggest cost of fish farming, a $232 billion global industry, and, given that the output of the world’s overexploi­ted oceans continues to decline, it’s only getting more expensive. The supply of bacteria, on the other hand, is effectivel­y infinite, as long as you have the nutrients to feed them.

That part—the nutrients—is why this particular fish food could play such a meaningful role in determinin­g the fate of the planet. What the bacteria that make up Novomeal eat is CO2. You know: carbon dioxide, the stuff that’s been building up in the atmosphere since the start of the Industrial Revolution, trapping solar energy and turning the seas acidic. If you believe the U.N.’s Intergover­nmental Panel on Climate Change—or the U.S. Department of Defense, or the big petroleum companies—manmade global warming is a danger on par with no other, threatenin­g to redraw coastlines, spark wars, imperil food and water supplies, alter weather patterns and marine currents, and displace hundreds of millions of people, all within our lifetimes. In the U.S., increasing­ly severe hurricane and wildfire seasons have already offered a preview of climate change’s long-term effects; according to the IPCC, the world’s economies must cut their carbon output in half by 2030 to avoid passing a critical threshold beyond which the consequenc­es grow rapidly worse.

But if the need to curb carbon emissions is clear, how to do it without torpedoing the world’s economy is anything but. Global energy demand is rising fast, and oil, coal, and gas continue to satisfy most of that need. As hundreds of millions of people in China, India, and other developing nations enter the middle class, they’re demanding all the perquisite­s of the

“The path to getting out of here,” says synbio investor Vijay Pande, “is not as bleak as it might seem.”

Western lifestyle, from hamburgers to new cars. Even if the electricit­y required to make all that stuff can be obtained from clean renewables, like wind and solar—and we’re a long way from that—the production remains a dirty, carbon-intensive business. The plastic that’s in everything from yogurt containers to carpet fibers is derived from fossil fuels, typically using energy also derived from fossil fuels. Cows raised for milk and meat have a carbon footprint comparable to that of automobile­s. Even something as simple as growing rice can’t be done without contributi­ng to warming: Rice farming produces 13 percent of the world’s methane, a potent greenhouse gas, because flooding the ground to make paddies brings dormant anaerobic bacteria roaring back to life. As long as more humans are eating more food and buying more stuff, getting a handle on climate change will be fiendishly difficult.

Or not, if David Tze has his say. What his company is constructi­ng— along with others working similar angles in San Francisco and Berkeley and Skokie, Illinois— is nothing less than the infrastruc­ture for an entirely new economy, one premised on producing food, energy, and material goods by sequesteri­ng harmful chemicals rather than by emitting them. It’s an economy where we’ll turn landfill into jet fuel, weave clothing out of spider silk, and make furniture out of mushrooms, all using primarily renewable power. “What we’re doing has the potential to change not only the food system,” Tze says, “but also the way other goods are manufactur­ed.”

“The path to getting out of here is not as bleak as it might seem,” says Vijay Pande, a professor of bioenginee­ring at Stanford University and founding investor for the venture capital firm Andreessen Horowitz’s biotech fund. Pande is writing a book about how the world can move from a petroleum-based economy to what he calls a bioeconomy. “We have to retool the whole economy, and that’s the hard part,” he says. “The good news,” he adds, “is that we’re doing so many things wrong, it’s not too hard to start doing things better.” The better way is synthetic biology. Those Sea-Monkeys just might save the world.

Synbio, as it’s known, is the name given to a suite of techniques used to manipulate living cells and turn them, in effect, into tiny factories—factories for fuels, fabrics, fish food, you name it. “It’s the redesignin­g of an organism for a functional

end. You’re changing around the pathway inside a cell,” says Arvind Gupta, the managing director of biotech startup accelerato­r IndieBio, which has backed a slew of companies using synbio to make their industries more sustainabl­e. Gupta calls it “the $100 trillion opportunit­y,” since that’s how much the world economy will grow over the next 25 years—provided we can find a way out of the current growth-versus-sustainabi­lity trap. “If we don’t, there will be some pretty dire outcomes for the planet,” he says. “We have to, and that’s why we will.”

The power of microbes as a production platform lies in their efficiency. More complex than the most sophistica­ted machines, microbes are radically adept at using the resources available to them, even when those resources are garbage or worse. With the right genes—which can be spliced into microbes artificial­ly using Crispr or bred into them through accelerate­d mutations via a process called directed evolution—microbes can metabolize, well, almost anything, including noxious industrial byproducts. When they’re not dining on CO2, the bugs in NovoNutrie­nts’ bioreactor­s can digest many toxic chemicals spewed out by oil refineries and coal power plants, substances like hydrogen sulfide and cyanide. To humans, hydrogen sulfide is a respirator­y irritant so harsh, it was used as a chemical weapon in World War I; to the right kind of hungry bacterium, it’s a source of amino acids. Since they multiply exponentia­lly through cellular division, microbes can grow far faster than any plant or animal. They don’t have fur or beaks or bones that take energy to grow and then more to dispose of. They don’t need to sleep, and, while algae

and some bacteria are capable of photosynth­esis, most don’t need sunlight. All this makes them incredibly economical at turning nutrition into protein and other useful stuff. To gain a pound, a cow typically needs to eat at least six pounds of feed, giving beef a feed conversion ratio, or FCR, of 6:1 or higher. The corn and soy in that feed have to be planted, harvested, and transporte­d, usually by exhaust-spewing machines. But, using microbes first discovered living within acidic springs in Yellowston­e Park, a Chicago-based startup called Sustainabl­e Bioproduct­s can turn a pound of starch into two pounds of nutritiona­lly complete protein. Even subtractin­g water weight, its process has an FCR of 2:1. “In terms of the use of resources, it’s extraordin­arily efficient,” says CEO Thomas Jonas. Bill Gates, Richard Branson, and Jeff Bezos agree: Breakthrou­gh Energy Ventures, a climate-focused fund founded by those and other billionair­es, was among those that put $33 million into Sustainabl­e Bioproduct­s in February.

Pivot Bio—another Breakthrou­gh Energy–backed startup—points to just how synbio could transform some of the world’s most wasteful industries. Started in 2011, Pivot focuses on shrinking the environmen­tal impact of agricultur­e by eliminatin­g the need for fertilizer. To perform photosynth­esis, plants need nitrogen, which abounds in the atmosphere but not in soil. For millennia, crops got their nitrogen from symbiotic bacteria that lived in and around their roots. But after farmers discovered they could accelerate crop growth with nitrogen fertilizer­s, those microbes gradually lost the ability to produce nitrogen. That was unfortunat­e, because fertilizer comes with a host of harms. Making it is extraordin­arily energy-intensive, and roughly half of what’s applied ends up either running off into waterways, where it collects in fish-killing dead zones—one in the Gulf of Mexico is larger than New Jersey—or converting to nitrous oxide, a greenhouse gas with 300 times the heat-trapping power of CO2. (Pivot’s CEO, Karsten Temme, cites studies attributin­g as much as 10 percent of global warming to fertilizer manufactur­ing and use.)

Back in 2006, in a lab at the University of California, Temme, then a graduate student in bioenginee­ring, and his professor Chris Voigt first wondered if they could restore microbes to their rightful place in farming. To date, they’ve raised more than $86 million on the idea, with their first commercial products debuting this spring. At Pivot’s facility in Berkeley, they test soil samples sent in from farms all around the country, cultivate test crops in them to see what microbes flourish, tweak those microbes in their lab so they can produce nitrogen, and then send the enhanced bugs off to industrial fermentati­on facilities for production. At planting time, bags of microbial broth are hung from tractors so that a squirt of Pivot’s product can be applied to each seed as it goes into the ground. In initial field tests conducted on corn crops in 2018, Pivot’s microbes significan­tly outperform­ed chemical fertilizer across a range of geographie­s and soil types. That makes sense, because the microbe population scales in perfect proportion to the corn plant’s nutritiona­l demands. “They have this close-knit symbiosis, and that means they’re able to spoon-feed the plant on a daily basis,” says Temme.

Annual global sales for fertilizer amount to $230 billion. Although Pivot has competitio­n— Ginkgo Bioworks, another well-capitalize­d synbio startup, is developing a similar product through a joint venture with Bayer—even a small piece of that pie would make for a huge business. But Temme says finding a sustainabl­e way to feed a global population that will soon approach 10 billion is his motivation. “I look at my two little kids, and I’m like, if we don’t come up with some better ways of fueling this world and driving everything we do, their lives are

It takes a lot of anchovies to feed our appetite for farmed fish. Each year, around 400 billion small fish, like anchovies, are ground up to produce fishmeal for the world’s fish farms. It’s wasteful and expensive—and it presents companies like NovoNutrie­nts with a huge opportunit­y.

going to be challenged in ways we can’t imagine,” he says.

David Tze didn’t always worry about the environmen­t. During the first dotcom boom, he was the chief technology officer for Network Internatio­nal, a marketplac­e serving the oil and gas industry that has handled more than $7 billion worth of transactio­ns for customers like ConocoPhil­lips. Looking back, he remembers “not really thinking through the implicatio­ns of making it less expensive to get oil and gas out of the ground.” But, in 2006, he saw the Al Gore documentar­y An Inconvenie­nt Truth. As it did for a lot of people, the film made him really grapple with climate change for the first time. Since then, he says, “I have felt like I have something to make up for.”

After leaving Network Internatio­nal, Tze managed a venture firm called Aquacopia, which invested in aquacultur­e. Demand for seafood was exploding, thanks to growing prosperity in Asia and healthcons­ciousness in the West. But production of the world’s fisheries had peaked around 1990. That made fish farming a boom industry.

One company Aquacopia managed was Nutrinsic. It used the wastewater from breweries and beverage plants as the medium for cultivatin­g bacteria that could then be turned into protein meal for fish feed. Serving on Nutrinsic’s board of directors gave Tze an intimate understand­ing of the fish-food game—its attractive economics but also its difficulti­es. Fish are farmed in far greater diversity than land animals, and each species eats a different diet, which varies according to life cycle. Carnivorou­s fish like salmon need nutrients they can get only from eating other fish, but the price of fishmeal, also called marine protein, is subject to intense fluctuatio­ns that can wipe out farm

ers’ profits. And, since 1995, its price has more than quintupled.

After a decade managing investment­s, Tze was itching to be an operator again, and aquacultur­e seemed like the place to do it. While scouting for a niche in the industry, he flew to California for a conference called Fish Free Feed, which focused on alternativ­es to anchovy-based fishmeal, like insect meal and soy. While walking through an exhibition area, Tze passed a table for a company named Oakbio. On it were some faded color handouts and a vial of brown powder. A sign said the powder was made from bacteria, which Tze found intriguing. He grabbed a handout and stuffed it in his bag.

Back at work in New York City, Tze finally read the handout and saw what he’d missed: The feedstock for the bacteria was industrial CO2, obtained from a cement plant. “That blew my mind,” he recalls. “We’re talking about a technology where you could have a new pillar of the food system that’s entirely decoupled from agricultur­e and fossil fuels.”

Oakbio’s founder, Brian Sefton, had come to that juncture from a very different starting point. As an undergradu­ate zoology student at Berkeley, he’d been an ardent environmen­talist, going door-to-door to gather signatures protesting a local cement plant that was a notorious polluter. When he started his company, in 2009, it was with the explicit goal of valorizing, or finding a use for, industrial CO2 emissions. “It sounds fairly exotic, but really it’s what a lot of what we use on earth is made of,” he says. (Tze invested in Oak Bio in 2017 and renamed it NovoNutrie­nts.)

Lisa Dyson sees it the same way. Her startup, Kiverdi, uses carbon dioxide–eating bacteria to manufactur­e oils and proteins. Chief among those is palm oil, a commodity whose production is uniquely damaging to the environmen­t: It’s largely grown on land freed up by clearing and burning virgin rainforest. This practice has made Indonesia one of the world’s top

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 ??  ?? Nouvelle Cuisine A heaping serving of NovoNutrie­nts’ fishmeal, which is made of labcreated bacteria that feed on carbon dioxide. NovoNutrie­nts is one of many emerging synbio startups that seek to stanch or reverse global warming by attacking sources of waste (and atmospheri­c carbon) that help cause it.
Nouvelle Cuisine A heaping serving of NovoNutrie­nts’ fishmeal, which is made of labcreated bacteria that feed on carbon dioxide. NovoNutrie­nts is one of many emerging synbio startups that seek to stanch or reverse global warming by attacking sources of waste (and atmospheri­c carbon) that help cause it.
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