California could become first state to mandate biosecurity screening by mail-order DNA companies

California lawmakers on Thursday will vote on a bill that would require the state’s growing gene synthesis industry to adopt screening protocols to keep dangerous DNA out of the hands of the wrong people. The proposed legislation would be the first in the nation to tackle the biosecurity risks that accompany cheap and easy DNA writing technologies.

Scientists have been making synthetic genes for decades. The process involves moving minute amounts of liquid back and forth to add the right sugary building blocks — A, T, C, and G — in the right order. More recently, several companies have figured out ways to do this at scale — producing tens of thousands of custom-built genes every day, ready to ship off to academics experimenting with things like gene editing and pharmaceutical companies developing cell and gene therapies. When SARS-CoV-2 emerged, scientists around the world raced to synthesize pieces of the virus for use in developing diagnostics, treatments, and vaccines from the first publicly posted genome sequence.

But these mail-order molecules could just as easily unleash a pandemic as fight one. The federal government keeps a catalog of regulated organisms — deadly pathogens individuals are prohibited from possessing without proper authorization. But there’s no ban on the genetic recipes for making them. Concerns over such biosecurity risks have spurred renewed discussions of regulation in Washington, including an abandoned executive order drafted by the Trump administration, but to date there’s been no action in Congress.

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“We started this pre-pandemic, but if anything, the last year has shown how dangerous a virus can be,” said Assembly member Rudy Salas, a Democrat representing California’s 32nd Assembly District, who introduced the legislation for the first time in January 2020. (That version never got a hearing because Covid-19 shut down the state capitol a few months later. AB 70 was introduced in December 2020.) “We shouldn’t be giving people building blocks to create them without guardrails for keeping people safe,” he said.

While synthetic biology might conjure up visions of garage biohackers brewing up novel pathogens from spare viral parts, a 2018 report from the National Academies of Sciences found that a much bigger biodefense risk is the ability to create naturally occurring viruses. “When you have a known program, which is what the genetic sequence for a known virus is, and you know the damage that could cause, and you have the ability to recreate it, that’s a much more pressing threat than creating something new,” said Gigi Gronvall, a biosecurity expert at the Center for Health Security at Johns Hopkins University and a co-author on the 2018 report.

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Salas had never really thought about synthetic biology until September of 2019, when he heard a story on NPR about plummeting costs of production fueling a DNA writing boom. He was troubled to learn about the lack of regulatory oversight on the industry — different companies had different standards for tracking what kinds of genes they were making, and for whom. Gronvall told the NPR reporter that one policy fix would be to require researchers receiving federal funding to order from companies that screened orders. The idea was to provide an additional incentive to take basic biosecurity precautions — not doing so would leave billions of dollars on the table. Salas liked the sound of that. So he called up Gronvall. And she helped his team draft the bill now before the California Assembly’s finance committee.

AB 70 would require any gene synthesis companies operating in California to become members of the International Gene Synthesis Consortium — a trade group that requires its 16 members, accounting for about 80% of the industry, to adhere to strict screening criteria in line with guidance issued in 2010 by the Department of Health and Human Services. They include comparing every synthetic gene order against multiple DNA databases housing the sequences of regulated pathogens and known toxins, and checking customer credentials to verify their identities and that of the purchasing organization. They won’t sell to anyone on government watch lists or ship to P.O. boxes.

While software exists to automate sequence screening, no such shortcut exists for vetting customers. Companies that have voluntarily joined IGSC and adopted its biosecurity screening standards, which add time and costs, face a competitive disadvantage against less scrupulous DNA synthesizers, according to a 2015 report authored by science policy analysts at the J. Craig Venter Institute. AB 70 simply seeks to level the playing field and create the incentives for people to do the right thing, said Salas.

Under the proposed legislation, companies will have until Jan. 1, 2025 to be certified by IGSC. Additionally, any researchers that have received state funding will be required to purchase DNA from an IGSC-certified gene synthesis provider.

“There’s so much that is hard to fix when it comes to governance of biology without hurting biotechnology, but this is a lever we can actually use,” Gronvall told STAT. Sequence screening is really the minimum that should be required, she said. “It’s really so basic. Why wouldn’t you make it just a little bit harder for someone to order something like smallpox or Ebola? It’s a matter of simple due diligence.”

“It’s hard to argue against it,” said Emily Leproust, CEO of Twist Biosciences, a Bay Area-based gene synthesis company that caters mainly to academic labs, pharmaceutical firms, and chemical manufacturers, although it also has contracts with DARPA for DNA data storage and with Ancestry for genealogy testing. Twist has been a member of IGSC since 2015. Leproust said that of the thousands of gene orders Twist processes each month, the company’s screening process usually flags less than 1% of them. And most of the time, when company representatives reach out, customers aren’t aware they’re ordering something potentially dangerous. Only very rarely has Twist received orders that warranted reporting to the FBI, said Leproust.

“It’s work to catch the extreme edge cases, but it’s worth the effort because the downside is pretty high,” she said.

While Leproust is supportive of AB 70, and has provided feedback to Salas’ team, she thinks the industry should be doing even more. Currently, IGSC requires its members to only screen DNA sequences larger than 200 base pairs. That would allow determined individuals to just order smaller sequences to stay under the radar. She said that Twist is moving toward lowering its screening threshold to capture those cases.

Another looming development the bill doesn’t address is the proliferation of decentralized DNA synthesis. Right now, it’s cheapest and easiest to order online from a supplier like Twist. A few clicks of the computer and DNA shows up at your door. But as the cost of DNA synthesis machines drops, and the technology becomes more widely available, keeping tabs on what those instruments are outputting gets that much harder. Eventually, Gronvall would love to see this screening built into the instruments themselves, she said. But for now, she’s just happy policymakers are finally paying attention.

“This has been the long-standing concern with synthetic biology, really from the very beginning,” she said. “It’s a problem that was identified in 2006, and while you don’t want to always be fighting the last war, it would be nice to not leave problems to fester.”

Not everyone is a fan, though. The California Life Science Association has been pushing for changes to the bill, and a spokesman for the industry group told STAT that an 11th-hour effort was underway to exempt life sciences companies from certain provisions. An aide to Assemblyman Salas could not be reached for comment.

Salas expects Thursday’s vote in the finance committee to be AB 70’s toughest test. If it it clears that hurdle, he has confidence it will get through the full Assembly and then pass the state Senate. He hopes it can serve as a model to other states, and maybe even catalyze long overdue national oversight. “We’d love to see this happen at a federal level, but it’s such an important issue that we can’t wait for them,” he said. “When you see a train wreck coming down the track, you don’t wait for it to get to you.”

Source: STAT