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Illustration by Errata Carmona​​

The Dual Use Problem

​A researcher in Canada with $100,000 to spend ordered bits of horsepox DNA from a commercial vendor on the Internet and introduced it to cells, successfully turning the previously eradicated virus into an infectious agent. In China, 36 people had cells removed from their bodies, which were then altered and infused back into them.

Such experiments sound straight out of a sci-fi movie, but they are being carried out with more frequency by experts worldwide—and drawing a precarious line between using the technology for noble or nefarious purposes. Fortunately, these examples were for good—the Canadian experiment is paving the way for effective vaccines and gene therapy, and the Chinese clinical trials were used to treat patients with cancer.

However, even these well-intentioned scientific experiments could inadvertently cause harm down the road. The Canadian horsepox reconstitution raised concerns that the relatively simple and legal process could be used for darker purposes—the researchers admitted that the same process could be used to bring back small­pox, one of the deadliest diseases in history.

"Have I in­creas­ed the risk by showing how to do this? I don't know," the lead virologist of the experiment told Science magazine. "Maybe yes. But the reality is that the risk was always there."

This concept is known as the dual use problem, and it's what is spurring the U.S. government to quietly increase research and spending into unrealized biothreats stemming from scientific advances that are intended to be used for good. Studies hone in on seemingly far-flung biological threats, such as antimicrobial resistance, chemical inhibitors used to pacify populations, cyberattacks on people, and nanoweapons—microscopic poisons, drones, or bombs.

"The same methods that might be used to defeat cancers could be used to destroy adversaries through virulent pandemics," notes the Lexington Institute's 2018 report, Invisible Scourge, on the danger of chemical or biological attacks. "Breakthroughs in microbiology might thus become major threats to national security."

The U.S. Department of Defense (DOD) recently commissioned a report by the National Academies of Sciences, Engineering, and Medicine to determine the top emerging synthetic biology threats. The 234-page report details high-risk technologies based on their ease of use, the ability for use as an effective weapon, expertise and resources required to carry out an attack, and the ability to mitigate an attack.

Three potential capabilities stood out to researchers as high-risk: recreating known pathogenic viruses, making existing bacteria more dangerous, and making harmful biochemicals via in situ synthesis. While the scenarios discussed in the report are unlikely or impossible today, they are expected to become more feasible as research—often conducted for beneficial purposes—continues.

"Some malicious applications of synthetic biology may not seem plausible now, but could become achievable if certain barriers are overcome," the report notes. These include knowledge or technological barriers.

"Since synthetic biology-enabled weapons might be unpredictable and hard to monitor or detect, DOD should consider evaluating how the public health infrastructure needs to be strengthened to adequately recognize a potential attack," the report states.

Michael Imperiale, a University of Michigan professor and chair of the committee that wrote the report, tells Security Management that while most of the results were predictable, there were threats that he had not previously thought of. Imperiale has studied the biology of viruses and their effect on biosecurity for more than 30 years and says that one of the highest-risk capabilities surprised him.

"Using bacteria to deliver chemical or toxins in situ—that's not something I'd previously thought of," Imperiale says. "As we discussed it, I think most of us became surprised at what the potential problems could be with that. It would be relatively easy to engineer, and how would we know?"

This capability involves a microbe that enters a person's gut and makes biochemicals out of the infected person's microbes. It is particularly sinister because it masquerades as a naturally-occurring pathogen—similar to e. coli—and would be extremely difficult to recognize as an intentional attack.

"Imagine we could engineer a bacterium to synthesize some toxic chemical, something that makes people ill, and somehow had a way to introduce that into a person's microbiome—their gut—in an organism, maybe by contaminating a food supply," Imperiale explains. "The person would get sick, and the signs and symptoms would be those of a chemical exposure, but the causative agent is an infectious agent. How do you treat that, and how do you deal with that from an epidemiological point of view in terms of preventing potential spread? And if you're looking for a chemical [in the infected person] but not finding it, what do you do? It presents a lot of problems. In effect what you've done is turned a biological organism into a chemical attack. You've blurred the lines between bio and chem."

Even if the suspect bacteria were identified, it would still be difficult to figure out where the attack originated and who was responsible. The other two high-risk capabilities pose similar challenges—the Canadian horsepox experiment was a textbook case of recreating a known pathogenic virus, Imperiale says, and modifying bacteria to make it more dangerous has a relatively low technological threshold. There are no tools in place that would deter or prevent the development of modified bacterial pathogens.

The report identifies several other potential capabilities that are of lower concern but are still notable for the type and span of damage they can cause. For example, while the current ability to develop a new pathogen is low, it can easily be weaponized—and in an especially insidious way. Pathogens can be created with never-before-seen features, the report notes, including the ability to target specific ethnicities.

"Such features include, for example, the ability to target specific tissues or cell types using genetic logic, or the ability to produce aberrant neurological effects," the report states. "Similarly, such pathogens could employ novel timing mechanisms, creating a delay between the time of exposure and the onset of symptoms."

Imperiale notes that this type of attack would be less effective in the United States due the diversity of the population. "But, obviously, there are other reasons someone might want to attack specific ethnic groups as opposed to an attack on the U.S.," he says.

While Imperiale notes that the focus of the report was emerging synthetic biology threats and not the government's ability to address them, an overarching recommendation is to build a framework to assess synthetic biology capabilities and their implications. To prepare for such threats, the government needs to strengthen its preparedness against existing, nonmalicious biological threats.

"The nation's experience preparing for naturally occurring diseases provides a strong foundation for developing strategies to prevent and respond to emerging biologically enabled threats, particularly those based on naturally occurring pathogens," the report notes.

"Even though we didn't go into mitigation capabilities, we talked about how some of the existing public health infrastructure can play a very important role here," Imperiale says. "It's primed to look for these kinds of things, and that can certainly help out."

Another recommendation suggests that the government should not rely so heavily on its Select Agents list, which notes potentially harmful bio-agents and dictates the possession, use, or transfer of them.

"Strategies based on lists…will be insufficient for managing risks arising from the application of synthetic biology," the report says. "While measures to control access to physical materials such as synthetic nucleic acids and microbial strains have merits, such approaches will not be effective in mitigating all types of synthetic biology-enabled attacks."

Indeed, the horsepox DNA used in Canada could be obtained legally because it is not on the list, and the report notes that one of the most high-risk biological capabilities—modifying bacteria—would render the list useless. "The Select Agents list and voluntary screening guidelines are not likely to be sufficient to deter or prevent the development of modified bacterial pathogens," according to the report.

"We're not telling the government to throw the lists away. We're saying it's not enough, and the question is, what do you do next?" Imperiale says. "Ideally, if I could create something, it'd be some sort of means for detecting when a DNA sequence is going to encode something harmful, and you could screen for that."

While the DOD-commissioned study focuses on emerging technology that could be used for nefarious purposes, biological warfare has been around for a long time. The Lexington Institute notes that the technology needed to deploy such weapons is readily available. "The precursors for chemical weapons—choking agents, blister agents, blood agents, nerve agents—are manufactured at thousands of sites around the world," the Lexington Institute report states. "The technology needed to edit or synthesize organisms so that they can be used to spread disabling disease is now widely available in global commerce, and inexpensive."

While international conventions have banned the manufacturing of chemical weapons, more than 30,000 chemicals can be used to manu­facture choking, blister, blood, or nerve agents—and many of those are manufactured commercially. "Sub­stances that might be turned into lethal tools of war are so commonplace in modern industry that diversion to illicit purposes is difficult to prevent," the report says. "The majority are dual-use chemicals produced at commercial sites that might be diverted to destructive ends."

The dual use problem creates a challenge for government and industry to monitor or stop the production of such commonplace substances or emerging technologies that can provide beneficial, meaningful advances in sciences. And, while many of the biological capabilities listed in the DOD-commissioned report still feel like science fiction, Imperiale says the effects may be all too real.

"It's hard to guess when someone might try to do this," Imperiale says. "On the other hand, if someone did it and were successful, you could imagine the implications of that. It's like a movie scenario, with a biological attack—and there's something about a biological attack that I think raises a special level of fear. It's something that might be able to spread and carry on, as opposed to someone blowing up a bomb. I think it is really something we need to pay attention to as a country, and as a world. I think the DOD is going to take this very seriously, and hopefully they will be able to take care of us." ​