How Do We Know If a Virus Is Bioengineered?
By: Sarah Scoles
Tags: Biotechnology, Science, Disease, Pandemic, Coronavirus

The MIT-Broad team that worked on SARS-CoV-2 declined an interview. Not much is known about what’s behind their curtain, but other FELIX-funded teams were more willing to share.

Eric Young, PhD, studies yeast engineering at Worcester Polytechnic Institute, but he started thinking more about biosecurity when he noticed policy folks and government ethicists at synthetic biology conferences. They were concerned about the implications of being able to build custom organisms so easily.

“What we’re creating here are things that are going to be great for civilization,” like developing new pharmaceuticals, Young says. “But, as the history of every technology has shown, a lot of times, over the course of human history, those technological advances have been repurposed for weapons.” To date, he adds, we don’t have any examples of someone using synthetic biology to create a bioengineered weapon.

The tool Young worked on for FELIX first sequences an organism’s whole genome. Then, it delivers those letters back to the scientist with annotations, calling out which genetic parts, if any, seem to have been tinkered with. It checks for engineering by comparing the sequence against a standard list of yeast engineering sequences or a custom sequence list that the user inputs. “Future versions will use machine learning to flag DNA sequences as engineered without needing a list of parts,” says Young. For now, it works with yeast sequences.

Ginkgo Bioworks, another FELIX awardee, is coming at the problem using computational biology and its own database of known engineered sequences. The company often sits on the other side of the equation: designing and engineering organisms itself. “For this program alone, we created over 6 million simulated, engineered genomes that reflect a variety of genetic engineering techniques and design styles, across a panel of organisms chosen by IARPA and the national labs,” says Joshua Dunn, PhD, the company’s head of design.

“We really wanted to be the white-hat hackers at this table,” Dunn continues. To hack thusly, Ginkgo uses several different methods. First, they compare a sequence to known, natural reference sequences, like the MIT-Broad Foundry seems to have done for SARS-CoV-2. Then, they look for known engineering signatures in that same input sequence. A third tack analyzes the distribution of its genetic alphabet. Finally, all that information flows into a fusion engine the team is working on that assesses at all three results in tandem to come up with a final conclusion.

At the Draper Laboratory, a FELIX group led by Kirsty McFarland, PhD, has focused on a different aspect of detection: how to pick out engineered organisms from environmental samples that are chock-full of life, like soil or water. They’re developing separate methods aiming to pinpoint two sorts of bioengineering: unknown change to a known organism, and known or suspected change to a potentially unknown organism. SARS-CoV-2, being a new pathogen, falls into the latter category.

The first method works by comparing the genomes it finds to a database of gene sequences it expects to find. The second searches for sequences of interest — bits of code that might be a signature of engineering — within the genomes of previously unknown organisms. Currently, the second method can detect a single engineered being from a sample that also contains a million, or maybe more, totally natural beasts.

At Harvard, a team led by Elizabeth Libby, PhD, is working on a “biosensor”: an engineered cell that senses other engineered organisms. Naturally, the Boston group began by sketching the sensor’s basics on a Dunkin’ Donuts napkin. “It can basically vacuum up any DNA that comes nearby,” says Libby. Then, it picks up on whatever DNA signatures they’ve preprogrammed it to recognize, boosts the signal, and then lights up to say, “Got it!”

For FELIX, they’ve programmed the biosensor to react to common signatures of engineering. But the technology is broadly applicable. “What we envision, down the road, is if you wanted to detect a pathogen in, say, an air-handling system or a hospital surface or a water supply, you could have a cartridge that’s disposable and passively senses all the time,” says Libby. If it detects what she calls “the thing of interest” — whether that’s an engineering tip-off, a coronavirus, or some other genetic sequence — the cartridge lights up and sends a signal. Illumination achieved. In a pandemic like the one we’re living through now, such a technology could be useful for figuring out whether the enemy is lurking inside your office building.