SynBio

An emerging, unregulated science now being used to create food and fiber, that was originally used to produce medicines, biofuels, and super bacteria designed to eat oil spills. It applies principles of genetic engineering to create life forms from scratch, and GMO labeling laws do not apply because of loopholes. From “spider silk,” synthetic flavors, and animal-free egg whites, Impossible’s “bleedingveggie burger, shrimp made of algae, and vegan cheeses that melt, are all making their way into restaurants and on to supermarket shelves, offering consumers a new generation of plant-based proteins that look, act, and taste far more like the real thing than ever before. Critics say that synthetic biology’s dangers lie in the potential release of gene-edited organisms into the wild, human health impacts, and disruption to agricultural communities, should engineered food or fiber displace natural products.

Whereas many genetically modified crops today contain a single engineered gene, synthetic biology makes it easier to generate larger clusters of genes and gene parts. These synthetic clusters can then be engineered by more conventional methods into plants or microbes. Generally, genetically engineered foods take desired genes from one organism and cut and paste them into another organism. Synthetic biology instead treats genes like computer code, remixing DNA sequences to create foods (and medicines and biofuels and lots of other things) that are not seen in nature. Scientists are literally printing DNA and then placing that DNA in e-coli or yeast.

“If genetic sequencing is about reading DNA, and genetic engineering as we know it is about copying, cutting and pasting it, synthetic biology is about writing and programming new DNA with two main goals: create genetic machines from scratch and gain new insights about how life works,” writes Josie Garthwaite for The Atlantic.2

The Woodrow Wilson Center’s Synthetic Biology Project says potential risks demanding more research range from the creation of ‘new or more vigorous pests and pathogens‘ to ‘causing irreparable loss or changes in species diversity or genetic diversity within species,'” notes Garthwaite.

It’s impossible to know how organisms with completely new DNA will interact with bees, soil or other species. Could artificial DNA overtake natural variations? Probably.

SynBio Food

A California accelerator, IndieBio, is helping to churn out many of these new businesses. Synthetic biology applications span from simple gene editing combined with fermentation processes, to cellular meats that culture food products from animal cells in the lab, to gene drive applications intended to change an organism’s genetics in the environment, such as a mosquito’s ability to spread malaria. For purposes of this discussion, we focus on products and processes that rely on gene editing combined with fermentation.

Synthetic biologists identify the gene sequences that give food or fiber certain qualities, like the gooiness of cheese or the tensile strength of silk. Often, it’s a protein produced by plant or animal cells that imparts the desired quality. Once identified, the gene sequence for that protein is created chemically in a lab and inserted into yeast or bacteria cells. Then, much like brewing beer, a fermentation process turns the microbes into tiny factories that mass produce the desired protein—which is then used as a food ingredient or spun into fiber. The Impossible Burger, for example, contains an engineered heme, a protein originally derived from soy plant roots, that gives the burger its pseudo-meat flavor, color, and texture.

Most of the companies using synthetic biology are still in the startup phase and may fail to gain traction, just as the earlier applications of synthetic biology for biofuels failed to reach scale. But there are billions of dollars in funding behind these products, and plenty of desire for them to succeed. And while many synbio products promise to use fewer natural resources, similar to cellular “meat,” a general lack of public information and transparency from many companies about their processes and what their supply chains will entail when brought to scale leaves unanswered questions about the safety and ultimate environmental, economic, and social sustainability of these products.

In the interest of trying to track down answers to some of these questions, Civil Eats asked six companies using synthetic biology, as well as two industry associations—including Bolt Threads, Impossible Foods, Gingko Bioworks, and IndieBio—for comment; although many declined to comment, the answers we received—plus the many questions that remain unanswered—suggest how much we still need to know about the potential impacts of this food of the future.

How it Works: Fish Food as an Example—and a Source of Concern

Each synthetic biology process is unique, but take the example of bacteria-based fish feed produced by KnipBio, the first company of its kind to receive U.S. Food & Drug Administration (FDA) approval as GRAS (“generally recognized as safe”). KnipBio uses a microbe commonly found on leaves that naturally produce carotenoids, anti-oxidants that can be vital for fish health.

Through simple edits to the bacteria’s genetic makeup, KnipBio CEO Larry Feinberg says he can “turn up or turn down the valves to make things of interest,” like variations on the carotenoids. Next, he ferments the microorganisms in a tank, feeding them methanol—an alcohol derived from methane gas—or corn waste by-products to stimulate them to reproduce and make the carotenoids. The fermented bacteria are then pasteurized and dried, which Feinberg says kills them, and formulated into a flour that is milled into fish feed. It has taken KnipBio five years to refine this process.

Rebecca Burgess, the founder of Fibershed, which last fall produced a report with ETC Group on the hazards of clothing made from genetically modified or synbio-derived materials, questions the efficacy of methods to keep gene-edited material from getting into the environment. “The concern is that they’re using base life forms that grow rapidly and transfer genes rapidly and they’re not considering the future of genetic pollution.”

Feinberg responded to this concern by saying that ensuring microbes are dead before release outside the lab is “microbiology 101,” like milk pasteurization. Nevertheless, “there should be, and will be, safety redundancy built into containment at an industrial biotech operation,” he adds. Furthermore, Feinberg says that research shows that modified bacteria tend to revert back to their “wild type” when they’re no longer housed in the optimized conditions created in the lab.

Piers Millet, vice president of safety and security at iGEM, a non-profit organization that runs a global synthetic biology competition, agrees. “One of synthetic biology’s biggest challenges is getting the new traits to stick past a few generations [which typically last days or weeks]. In almost every case, the alterations you’re making make those organisms less suitable for natural environments.”

That challenge leaves Michael Tlusty, associate professor of sustainability and food solutions at the University of Massachusetts, Boston, “guardedly optimistic” that synthetic biology will have beneficial applications, like the creation of alternative fish feeds to reduce the pressure on forage fish. Tlusty also notes, “we’ve been editing bacteria for a long time, medically, such as for insulin.”

Health Impacts?

Bacterial engineering processes for medicine have been established for 40 years. We’ve also been editing bacteria to create the vegetable rennet in cheeses since 1990. In fact, 90 percent of U.S. cheese today is produced with what’s known as fermentation-produced chymosin, or FPC, a vegetable rennet.

There are no reports of health or environmental impacts from FPC to date, but neither does it appear that anyone has researched the question.

The main health concern with synthetic biology products is that they add new proteins to foods, and those new proteins may be allergenic or otherwise unsafe to eat, says Dana Perls, senior food and agriculture campaigner with Friends of the Earth. “We need to understand the short- and long-term impacts before these ingredients and products enter the market or the environment,” she says of products genetically engineered to replace animal products, and stresses the need for stronger regulations for all genetic engineering.

Most consumers wouldn’t know that the cheese they buy is produced using gene modification, because it isn’t labeled as GMO. The FDA ruled that because FPC was identical to the chymosin found in animal rennet, it didn’t require labeling.

GMO labeling laws in the U.S. don’t apply to products made using synthetic biology, which makes it tough for consumers to make informed choices. Most recently, the FDA announced that labeling isn’t required for ingredients made from GMO crops if no modified genetic material is detectable.

Cell-based meat, which is grown in a lab by multiplying entire stem cells taken from animal muscle, will be regulated by both the FDA and the U.S. Deparment of Agriculture (USDA), though it’s not yet clear what that means in practice.

Synthetic biology is advancing so meteorically, regulatory schemes are hard pressed to keep up, Millet says, adding that, besides national laws, the industry follows World Health Organization biosafety guidance and other international regulations. But that guidance is updated every five years, so there can be a lag before the newest technology will be considered.

“The new wave of genetic engineering is slipping through very large loopholes,” says Perls. “People who are trying to purchase food or clothing that reflects their values are in the dark.”

Social Disruption Ahead?

As a disruptive technology, advocates fear that synthetic biology may also pose harm to the livelihoods of farmers, particularly in the developing world.

Oakland Institute’s Executive Director Anuradha Mittal is especially concerned that the rise of synthetic biology for products such as vanilla, coconut oil, and silk poses a threat to the livelihoods of smallholder and indigenous farmers if those engineered products replace their natural counterparts. Many of these farmers, like the Filipino coconut growers facing super typhoons year after year, are on the front lines of climate change, and Mittal notes that synbio alternatives could increase their vulnerability at a time when they need solid markets to help them adapt to climate change.

“These artificial solutions that are manufactured in petri dishes threaten smallholder farmers,” she told Civil Eats. “The devastation of women’s livelihoods in particular in India would be huge from these fancy silks.”

Fibershed’s Burgess worries that artisanal farmers and agroecologists could lose their sovereign rights if the synthetic biology world takes over fiber production and patents its processes.

Burgess’ concerns of farmer’s livelihoods being displaced are not unfounded, according to Todd Kuiken, senior research scholar at the Genetic Engineering & Society Center at North Carolina State University. “There are winners and losers. All of that needs to be evaluated and put on the table so people can make informed decisions,” says Kuiken, who previously led the Wilson Center’s Synthetic Biology Project. Companies need to conduct full life cycle assessments of their products, including both environmental and socio-economic impacts, he says. He knows of few companies that have done this, however.

Finally, Feedstocks

Fermentation requires carbohydrates—think barley or wheat for beer brewing—and that raises a key sustainability concern: What feedstocks will be used, and how much?

U.S. synbio companies are largely using sugar from GMO corn, because of its abundant supply, according to Bolt Threads, a leading manufacturer of Spider Silk, on its website, adding, “It is widely believed that large-scale fermentation will be possible with non-food crops … in the future.”

Some companies like KnipBio, however, are choosing to work from day one with more sustainable feedstocks, like agricultural waste or methane gas. “Feedstocks that don’t compete with humans—that has to be part of the consideration. We have to make things more efficient,” says Feinberg.

FOE’s Perls worries that synbio companies could simply perpetuate “unsustainable, pesticide-intensive, industrial agriculture,” by requiring massive amounts of GMO corn or sugar cane.

“If we now have to scale monoculture 2,4-D corn to feed these fermentation tanks,” notes Fibershed’s Burgess, “what does that mean for the [U.S.] Midwest or the Cerrado in Brazil?”

Until recently, life cycle assessments that could answer the feedstock question were hard to come by. Recently, Impossible Burger became the first to release an environmental life cycle analysis of its burger. Peer-reviewed and produced by independent auditor Quantis, the assessment found that the Impossible Burger requires 87 percent less water, 96 percent less land, and produces 89 percent fewer greenhouse gas emissions than an equivalent beef burger.

The heme protein that’s synthetically produced is but one ingredient of the burger, which is made from plant-based proteins, fats, oils, and binders. Spider silks or other products that are principally made from proteins produced by synthetic biology will likely have a different footprint that may or may not be as environmentally beneficial.

And while Impossible Burger has taken initiative on environmental transparency, its life cycle analysis didn’t consider potential socio-economic impacts. That’s important, says Kuiken, because “say Impossible Burger takes over the world: You’d reduce the number of animal products; you need to understand all of [the] socio-economic interaction[s]” of a reduction in demand for products from farmers and ranchers and the resulting impacts on their livelihoods.

Need for Dialogue

For those raising these questions, the lack of information and transparency on the part of most synbio companies fuels mistrust and prevents broader dialogue about the best solutions for the future of food, much like the lack of transparency on the part of cellular ag startups.

Garrett Broad’s 2017 essay in Civil Eats, “Why We Should Make Room for Debate about High-Tech Meat,” speaks to the dilemma. “I find myself with mixed feelings about the whole enterprise,” Broad wrote. “On one hand, I’m skeptical that these technological fixes will automatically lead us to some sort of agricultural utopia. But I’m also concerned that many who identify with the food movement might be missing out on the chance to shape the future of food because they’re turning their backs on food science altogether.”

iGEM’s Millet acknowledges there is some consumer distrust. “My feeling is that a lot of the leftover concerns about genetic modification has to do with the nature of power relationships, about very powerful companies controlling technology,” he says. “But that doesn’t mean we can’t have a different type of relationship.”

Dialogue with impacted communities is key, he says. Furthermore, Millet believes that synthetic biology can be used “to create a much fairer world, where people have more access to the tools they need to solve the problems challenging them, as opposed to mega-corporations selling the solution to them.” He cites an iGEM project in Sumbawa, Indonesia, where a poor community used synthetic biology to develop a genetic test to stop the pirating of its famous honey, a key revenue source for the island.

That vision of a fairer future is shared by others, like Oakland’s Counter Culture Labs, a “community supported microbiology maker space,” but not necessarily by the synbio companies remaining tight-lipped about their enterprises.

As in any industry, there are a range of players, with some more focused on sustainability than others. Whether synthetic biology can meet its promise by helping address some of agriculture’s biggest impacts and feeding the world—without causing harm—remains to be seen and will likely be project-dependent.

In the meantime, “people want real food, they want transparency, and nobody wants to be an experiment,” says Perls.

SynBioweapons

Scientists use technologies to engineer or create organisms for a variety of beneficial purposes such as treating diseases, boosting agricultural production and cleaning up pollution. But even though synthetic biology offers a number of benefits, it also opens the door to the creation of new bioweapons, the panel warned. That includes making existing bacteria and viruses more lethal, and shrinking the time it takes to create such organisms, according to the report, which was sponsored by the U.S. Department of Defense.

Weapons created through synthetic biology might be unpredictable and hard to monitor or detect, the panel’s report said, so U.S. defense officials should assess how to strengthen the nation’s public health system to recognize a potential attack from such weapons. “It’s impossible to predict when specific [weapons] enabling developments will occur; the timelines would depend on commercial developments as well as academic research, and even converging technologies that may come from outside this field,” Imperiale said. “So it is important to continue monitoring advances in synthetic biology and other technologies that may affect current bottlenecks and barriers, opening up more possibilities,” he explained.3

The real danger today is from organisms that already exist. The idea of synthesizing something worse than that, of taking bits of Ebola and other viruses to create something more deadly, underestimates how hard it is to survive in the natural world. Ebola, for example, is very pathogenic. It infects families and health workers, but it never spreads widely because it is too lethal – it isn’t in the community long enough to spread. Bird flu is not likely to spread widely until it mutates to become less pathogenic.

Smallpox, for example, is very potent, and we are not protected against it. The smallpox sequence is published, so you could recover it by synthesis if you had the lab facilities to do that. But getting the pieces of DNA to make smallpox is not a backyard experiment. You need a large lab with significant biosafety precautions.4

SynBio Shoppers Guide

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