Synthetic biology could enable bioweapons development

Synthetic biology, including DNA synthesis and gene editing, increases the number and the severity of threats from potential bioterrorists, according to a report ordered by the U.S. Department of Defense.

The report, released today by the National Academies of Sciences, Engineering, & Medicine, identifies a dozen ways that synthetic biology could be used to create biological weapons to harm humans. Its conclusions diverge from some previous suggestions that synthetic biology doesn’t change the landscape of threats posed by traditional biological warfare using nonengineered viruses and bacteria.

“Synthetic biology has the potential to enable new types of weapons,” says Michael J. Imperiale, a microbiologist at the University of Michigan Medical School and chair of the committee that authored the report. The committee identified three concerns of highest priority, including recreating pathogenic viruses such as Ebola, SARS, or smallpox. The second is engineering bacteria to make them more dangerous, which could be easily accomplished by inserting genes to confer antibiotic resistance. “Capabilities to do either of those have been around for a long time. They are only becoming more readily available,” Imperiale says.

The third major concern is engineering microbes to produce and release toxic biochemicals. “The effects could resemble a chemical weapon or food poisoning,” says Patrick Boyle, head of design at Ginkgo Bioworks and an author of the new report. That scenario is particularly worrisome because it is unclear how long it would take scientists to detect that a maliciously engineered microbe was at play rather than a natural pathogen.

“The report was extremely well done and delivered something that has potential to be useful for policy-makers,” says Margaret E. Kosal, a chemist by training and currently a professor of international affairs at Georgia Institute of Technology, who reviewed a draft of the report. In particular, Kosal applauds the committee for prioritizing potential threats, “because if everything is a problem, then nothing gets addressed,” she says.

The report highlights one recently published scientific study that illustrates how easy it might be for people with ill intentions to obtain the DNA necessary to recreate pathogenic viruses.

A small team led by virologist David H. Evans at the University of Alberta recently detailed the construction of a horsepox virus, thought to be extinct in nature (PLOS One 2018, DOI: 10.1371/journal.pone.0188453). The project, which was funded with about $100,000 from a pharmaceutical company called Tonix, was controversial because horsepox is a close relative of smallpox, a virus that’s been eradicated in nature for decades. Only the U.S. and Russia retain copies of the virus.

The purpose of the research was to consider using horsepox as the basis of a new smallpox vaccine, but many experts have since warned that the recipe for horsepox could be abused. “Synthetic biology has provided the tools necessary to recreate the smallpox virus,” says Gregory Koblentz, a biodefense expert at George Mason University. “Safeguards against the misuse of those tools are weak and fragmented.”

Currently, some synthetic biology companies choose to run their own safeguards. Twist Bioscience uses computer programs to scan its DNA orders, and James Diggans, director of bioinformatics and biosecurity, says the company would have easily detected the horsepox DNA due to its similarity to smallpox. “That would have triggered internal review,” Diggans says. That virus is “not something we would be comfortable manufacturing,” he adds.

Diggans, who also reviewed a draft of the report, applauds the “balanced treatment of the incredibly positive impact of synthetic biology and its risks.” However, he thinks that synthetic biology doesn’t actually make building biological weapons easier. There are hurdles to manufacturing, weaponizing, and delivering a biological weapon—all without killing oneself in the process—that synthetic biology doesn’t address, he says.

Kosal concurs. “Making ineffective biological weapons is easy,” she says. “Making effective biological weapons is not easy.”

Koblentz also agrees, but he adds that CRISPR gene editing in particular “creates myriad new opportunities for mischief,” due to its low cost and ease of use. “Our current approach to biodefense is heavily focused on a short list of well known biological warfare threats,” Koblentz says. “Genome editing has the potential to significantly expand the range of biological threats that need to be defended against.”

Ginkgo’s Boyle says that CRISPR, DNA synthesis, or another technology alone isn’t responsible for increasing biosecurity risks. It is the combination of these technologies, along with data science, computation, and software, that together could enable creation of biological weapons, he says.