Tapping the Superpowers of Biology

When the world needs a new superhero, instead of looking to bulked-up hulks like Thor and Aquaman, Hollywood might do better to go small. Microbe-small. Plants and microorganisms have always been at the heart of the planet’s healthy functioning, but in recent years, advances in bioscience have supercharged them.

Today, biology is the engine of a rapidly expanding economic sector collectively known as the bioeconomy. Bioeconomy products, processes, and services typically share a focus on using renewable biological resources to solve the world’s biggest, most pressing problems: producing sustainable energy and medicine, ending hunger, minimizing waste, and mitigating climate change. Superhero stuff.

In real life, that can look like mushroom packaging, microbes that break down garbage, plant-based meats, drought-resistant and carbon-storing food crops, and new biofuels to support the transition away from fossil fuels.

Definitions across countries, agencies, or institutions can vary. Does the bioeconomy include pharmaceuticals? Exclude traditional agriculture? However it’s defined, the term is now integral to the global economy, serving as an umbrella category for a quickly-expanding segment of the U.S. economy. “Safeguarding the Bioeconomy,” a 2020 National Academy of Sciences (NAS) report, valued the U.S. sector at nearly a trillion dollars, or 5.1% of the GDP, based on 2016 data. The Congressional Research Office’s 2021 “Bioeconomy Primer” estimated global growth of up to $4 trillion per year in the coming decade.

While such growth might be seen as a boon, “The idea of the bioeconomy is not new,” says David Zilberman, agricultural and resource economics professor and a reviewer on the NAS report. “This is one of the oldest industries in the world,” he says. “Wine, cheese, bread, kimchi—the old bioeconomy all came from fermentation,” he says, referring to the basic metabolic process in which microorganisms such as bacteria or yeast, when sealed off from oxygen, convert carbohydrate molecules to acids or alcohols.

But in the last 20 years, tools like genomics, CRISPR gene editing, and artificial intelligence have amplified the power of plants and microorganisms, making fermentation more precise and helping organisms perform new functions or produce desired characteristics.

“Plants are the most powerful chemical factories in the world,” says Zilberman, who won the 2019 Wolf Prize in Agriculture, an international award often referred to as the Nobel Prize for agriculture. “This is an incredible set of capabilities that can allow us to increase agricultural productivity, reduce land use, move from a nonrenewable economy to a renewable one, and help solve climate change,” he says.

Circular Systems

Plant and microbial biology (PMB) professor John Coates, who leads Berkeley’s Energy & Biosciences Institute (EBI), says the bioeconomy can include any products or processes that have a biological component. Chemistry and engineering, for example, can be used to upcycle agricultural wastes from food production into animal feed, fertilizers, and biofuels.

What’s key, Coates says, is creating circular, sustainable systems that take carbon out of the atmosphere, then put it back into products and services, all without the planet-harming impacts of fossil fuels.

“We can still have a bioeconomy that’s not sustainable,” he cautions. For example, he says, ethanol-dedicated cornfields require carbon-intensive farming inputs—tilling, fertilizing, irrigating—and use land and resources that could be used for food crops. Many analyses find this practice cancels out ethanol’s carbon benefits and creates waste-disposal issues and food versus fuel land-use concerns.

“Sometimes the technology is not the important thing,” Coates says. “It’s the entire lifecycle.”

Addressing such lifecycle concerns, PMB professor Sabeeha Merchant is developing a sustainable process for producing a “designer oil” that can be used to make jet fuel. Plants can be engineered to produce the oil using their own sugar from photosynthesis, she says, but her lab is trying to make it with green algae, an aquatic organism that grows quickly. “Getting algae to make the oil using its own sunlight-produced sugar is a circular system that’s also more economically viable,” she says, “and it avoids competition between biofuels and food crops.”

Genomics and CRISPR have been critical tools. “Genome sequencing is at the center, because we need to know what an organism is capable of doing, and all of that information is in its genome,” she says. While genes for the photosynthesis protein are well known, Merchant says, her lab focuses on how environmental influences affect the process. CRISPR’s precision editing accelerates the search for beneficial genes that, for example, protect against light stress or adapt to iron deficiency. Then, she says, “We can take all those genes and put them into our production organism.”

Merchant—together with PMB professor Krishna Niyogi and researchers Jeff Moseley and Melissa Roth—recently won an $11.6 million grant from the Department of Energy (DOE) supporting this work.

Reduce, Reuse, and Upcycle

Circular systems can also clean up messes that are already here, such as hazardous waste (which often includes contaminants like heavy metals) and biowaste, the organic detritus left from food, lumber, and agricultural production.

PMB assistant professor Norma Cecilia Martinez-Gomez works with microorganisms that take up rare earth metals present in medical waste and e-waste like batteries and old smartphones, which can then be upcycled into other products.

Coates has identified bacteria that convert perchlorate, a potentially toxic chemical used in everything from herbicides to rocket propellant, into a harmless compound. He’s also working to reduce the cost of producing bioplastics, which are still four times more expensive than petroleum-based plastics.

“There are plenty of microorganisms that will eat organic waste matter and will make bioplastics,” he says, but he’s seeking microbes that can make production efficient at a commercial scale. As with much of biotech, he says, the big challenge is making new manufacturing processes economically competitive with established, fully-optimized systems like plastic production.

Getting to the Marketplace

Such scale-up hurdles must be overcome to reap the benefits these new technologies can bring, experts agree.

Ouwei Wang (BS ’12 Microbial Biology, PhD ’18 Microbiology) has solved—and commercialized—one scaling challenge. The precision fermentation used by industry is more engineered than the traditional process, controlling factors like pH, dissolved oxygen, and agitation rates. However, Wang says, it’s still a batch system, with lots of unproductive time repeatedly setting up the reactor with feedstock, adding a reaction agent, and waiting for the growth period.

A process called continuous fermentation breaks through these limitations, keeping feedstock continuously going in and fermented material coming out, much like a flour mill keeps grain feeding in and flour coming out. However, Wang explains, because the reactor isn’t sealed off like a closed system, dust or ambient bacteria can get in. “It can ruin the whole batch because there’s always growth,” he says, adding that the active bacteria can break down over long production times.

As a student in Coates’ lab, Wang developed an additive that can be introduced into the continuous-fermentation bioreactor to prevent and treat contamination. Coates, who also runs EBI’s incubator program, saw the immense applied value of the work and connected Wang with Berkeley’s robust entrepreneurship ecosystem.

During R&D for his new company, Wang programmed the reactors using machine learning, a form of AI that “automatically detects failure events and takes actions accordingly, much like a self-driving car corrects itself,” he says, “and it continually self-adjusts to stay in its most productive state.”

Today, Wang’s start-up, Pow.bio, has helped more than 20 companies from across the bioeconomy make products like organic acids, high-value enzymes, food additives, and probiotics, increasing their production at least fivefold while reducing their manufacturing footprint.

More infrastructure is needed, Wang says. “The science is there—we can make bioplastics, biofuel, and food products, but there simply are not enough bioreactors to do the work.” With a dearth of fermentation courses at large universities, including UC Berkeley, there’s also a lack of expertise, he says.

Even amid these challenges, Wang finds the work rewarding. “It feels like I’m actually helping to solve a problem that people care about,” he says.

New ventures like Wang’s require investors. Kulika Weizman (PhD ’16 Microbiology) a principal at a venture capital (VC) firm, applies a pragmatic lens to potential bioeconomy investments. As a graduate student in molecular and cell biology professor Jamie Cate’s EBI lab, she conceived her first startup: converting biowaste from yogurt manufacturing into a low-calorie sugar alternative.

Turning waste into a sweetener was an attractive idea, Weizman says, but the project taught her tough lessons about bioeconomy supply chains and demand, and the company soon pivoted to another product. These lessons now inform her VC work.

“Technology is a solution in search of a problem,” she warns. A self-described technologist, as an investor, she says, she takes a “market-first” perspective. “We look for problems where customers are in pain and willing to pay for solutions today, then screen for technologies that address that directly.”

And while investors generally prioritize the financial bottom line over societal problems, “the two often overlap,” she says. “A lot of burning global crises today are the driving forces that feed into the market-needs perspective.” As a case in point, her recent investments include personalized medicine and renewable construction materials.

Coates, who himself has founded four startups, says entrepreneurship and investment are critical to solving lab-to-production challenges. But to mitigate climate change, he says, the bioeconomy itself will have to scale.

“Agriculture and construction are the two main industries large enough to make an impact at a global scale,” Coates says. Research efforts, led by Rausser College faculty at the Innovative Genomics Institute, are already underway to improve carbon sequestration and crop yields in the agriculture industry. Potential in construction includes converting biowaste into building materials and seeding microbes into materials that aid in sequestering atmospheric CO₂.

If these two industries can be turned into carbon-negative cycles, “Then they can account for a lot of carbon uptake,” Coates says. “We have to start thinking about scale as something that’s going to have a global impact.”

The Innovation Supply Chain

Zilberman’s research synthesizes all these points along the trajectory from an idea to a commercial product—what he calls “the innovation supply chain.” California sets a strong example, he says, with research universities winning public funding, like Merchant’s recent DOE grant, entrepreneurial faculty like Coates and alumni like Wang, and Silicon Valley’s strong VC culture.

Both the pandemic and the Russia-Ukraine war have underscored the importance of resiliency in supply chains, he says. Just as other supply chains need multiple sources—buyers, suppliers, transport—the same is true for educating new generations of innovators. “We need to develop new knowledge and new supply chains to grow biofuel,” he says, “but you need to have people who can do it.”

Policy support is critical across the trajectory, Zilberman says, especially for R&D, including the infrastructure needed to turn research into a product. In developing countries, he notes, infrastructure may include other elements, such as improving roads that carry raw materials from a supplier to a manufacturing center.

He also calls for “sound, science-based regulation,” referencing what he considers Europe’s particularly restrictive approach to biotech, and more mechanisms for providing credit and long-term investments in new supply chains for plant-based or biotech products.

Finally, he emphasizes the need for global climate change policies. “A global carbon tax would create incentives for companies and countries to move to renewable technologies, and penalties from that system can be used for R&D for lower-carbon alternatives,” he says.

Zilberman sees Rausser College of Natural Resources at the center of the bioeconomy’s innovation supply chain at UC Berkeley because its departments are complementary. “We have people developing the most advanced agricultural knowledge and creating new biological systems and working on climate change,” he says. But the College can’t do it alone, he adds. “Because we are located in a world-class university, we can integrate advances from the top people working in biotechnology, information sciences, chemistry, and engineering.”

From what Merchant observes in her students, the will is strong. “When I was a student, most of us were just intrigued by the idea of discovering something that nobody else knew,” she says. “But today’s students want to improve the world. They want to solve problems. They want to do something that has an impact.”

The future depends on it, Zilberman says. “We really need to educate the people who will develop technical solutions, educational solutions, and policy solutions to address the challenges of the bioeconomy,” he says. “If we do that, I think we will really change the world.”