How Do We Know If a Virus Is Bioengineered?

How Do We Know If a Virus Is Bioengineered?

Almost as soon as the coronavirus appeared in the news, so too did speculation that it was purposefully engineered, the result of experimentation at one of several Wuhan laboratories.

Almost as soon as the coronavirus appeared in the news, so too did speculation that it was purposefully engineered, the result of experimentation at one of several Wuhan laboratories. The idea that the virus, whether natural or engineered, came from a scientific facility was pushed by some politicians. The White House reportedly pressured spy agencies to look into lab links.

Most scientists agree, based on the virus’s genetics, that it probably hopped from animals to humans. On April 30, the U.S. Office of the Director of National Intelligence declared, on behalf of the 17 different organizations that make up the U.S. intelligence community, that “the Covid-19 virus was not manmade or genetically modified.” The organizations decided to continue investigating two alternatives: the more likely explanation that the virus jumped from an animal to a human, and the more remote possibility that it was a natural virus released in a lab accident, which still hasn’t been ruled out.

So, the U.S.’s spy sector “concurs with the wide scientific consensus,” as the statement put it, that the virus wasn’t created by people. But how did _its _people come to that conclusion? While the full scope of its investigation isn’t known, one program within the intelligence community, FELIX, did specifically investigate the hypothesis. FELIX’s analysis revealed that the virus hadn’t been engineered using “foreign” genetic sequences, indicating that SARS-CoV-2, the virus that causes Covid-19, was not man-made or engineered using pieces of other organisms.

But detecting “bioengineering” is a fraught task for any organism. Just as there are many ways to determine whether a virus was engineered, there are many ways to engineer a virus, leading to a constant tug of war — and a lot of uncertainty.


F

ELIX stands for Finding Engineering-Linked Indicators, and it’s run by IARPA, the Intelligence Advanced Research Projects Activity. IARPA does high-risk research and develops next-next-gen technology under the Office of the Director of National Intelligence. In 2018, FELIX began funding six external teams to develop tools that can detect the fingerprints of bioengineering. These genetic signs are clear indications that someone messed around with an organism’s genome.

A genome is the full list of genetic bases that make up an organism. In DNA, those bases are A, G, C, and T; in RNA, they’re A, G, C, and U. Strung together, they make up “sequences,” which can either refer to all the letters, in order, that describe an organism, or a smaller subset.

Within a genome, the fingerprints of engineering can take a few forms, according to FELIX program manager David Markowitz, PhD. They can appear as foreign genetic material in a given sequence, or the off-kilter duplication, insertion, or deletion of bases. Other flags, says Isaac Plant, PhD, who worked on FELIX as a graduate student at Harvard, include sequences known to encode antibiotic resistance and short sequences called “scars,” which “show a change was made to a DNA sequence.” There’s no totally comprehensive list of “engineering sequences” like the ones Plant describes, but services like Addgene, which provide the molecular tools to manipulate DNA in the lab, host big databases.

FELIX’s tools could determine whether someone has stolen biological IP from someone else — like if a custom yeast strain from one company appeared in a competitor’s lab — and investigate the naturalness of new germs. In SARS-CoV-2, an RNA virus, FELIX got its first big real-world test.

“FELIX [teams] spent 18 months developing the first working prototypes of their engineering detection platforms,” says Markowitz. “They were poised to work on SARS-CoV-2 when this biosecurity threat first emerged.”

And so in January, a team from the MIT-Broad Foundry deployed its FELIX tools to “test the veracity of online stories claiming that SARS-CoV-2 was engineered in a laboratory,” according to IARPA’s website. Though the results of that test aren’t fully public, a pop-up on the page says that the system compared the virus’s genome to 58 million known genetic sequences — including “genomes from closely and distantly related viruses.” In 10 minutes, the tool determined that the virus’s makeup matched those of naturally occurring coronaviruses better than any other organisms: “This analysis indicates that no sequences from foreign species have been engineered into SARS-CoV-2,” IARPA wrote.

It sounds definitive. “But that actually doesn’t rule out engineering,” says Filippa Lentzos, PhD, a senior research fellow at King’s College London focused on biosecurity. It just means that the virus wasn’t engineered in specific ways.

coronavirus biotechnology pandemic disease science data science

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