SynBioBeta, which bills itself as the world’s premier forum for innovators and investors interested in synthetic biology, concluded its sixth annual conference in San Francisco earlier this month. Companies from across the country and from around the world delivered presentations on how they are finding biological solutions to human problems. The conference showcased how synthetic biology can be used to develop new drugs, protect the environment, and improve agricultural productivity.
But synthetic biology, like many other emerging technologies, is dual-use. The technological advances that fuel the amazing discoveries and products featured at the SynBioBeta conference can also be misused to cause harm.
The most recent dual-use concern about synthetic biology involves one of humanity’s oldest foes: smallpox. Smallpox was eradicated from nature in 1980, and all known stocks of the virus are located at World Health Organization–supervised repositories at the Centers for Disease Control and Prevention in the United States and at the Vector Institute in Russia.
However, a Canadian scientist funded by the American biotech company Tonix has recently demonstrated the ability to create pox viruses from scratch. In this case, it was horsepox, a once-extinct virus resurrected by stitching together fragments of synthetic DNA to create an intact viral genome. Poliovirus was the first virus created in a laboratory by assembling the chemical building blocks of life in the pattern encoded in the virus’ genetic sequence. The synthesis of horsepox virus was a significant accomplishment due to the much larger size of the virus and its more complicated biology.
Although horsepox virus itself is not dangerous, the technology and techniques used to re-create horsepox can also be used construct the closely related smallpox virus. At the Aspen Security Forum in July, Thomas Bossert, President Trump’s homeland security adviser, warned that horsepox is “not going to kill any of us, but that suggests that somebody might in the future now possess the capability to produce synthetic smallpox without the live virus. And that scares me to death. … ”
The re-emergence of smallpox would be a global health disaster. Prior to its eradication, smallpox killed an estimated 300 million people, more people than all the wars of the 20th century combined. Most of the world’s population is susceptible to this lethal and contagious disease since routine immunization against smallpox was discontinued after the success of the WHO’s global eradication campaign.
If resurrecting horsepox virus provides a roadmap to synthesizing smallpox virus, then why would anyone try to synthesize it? Because there are potentially legitimate uses for it. Tonix claims that the horsepox virus is a good candidate for developing a new, safer smallpox vaccine. Horsepox virus, smallpox virus, and the vaccinia virus that is used in smallpox vaccines are part of a closely related group of pox viruses. Vaccinia is the most well-understood of the pox viruses and is popular with scientists because it can stably integrate large segments of foreign DNA. Engineering pox viruses, such as vaccinia, could help create new vaccines and cancer therapies. But any lab that creates these beneficial applications through synthetic biology would also have the capability to produce infectious smallpox virus from synthetic DNA.
Unfortunately, the current legal and technical safeguards against the synthesis of smallpox virus are weak and fragmented. There is no clear international legal or regulatory framework to prevent the synthesis of smallpox virus. The WHO has a policy banning the synthesis of the smallpox and regulating who can produce and possess large fragments of smallpox DNA, but it hasn’t been widely adopted by states. Furthermore, there is no mechanism—at either the national or international level—for detecting or punishing violations of this policy. The 1972 Biological Weapons Convention, which outlaws the possession of biological weapons, provides a strong normative bulwark against the acquisition and use of smallpox, but without a verification system it would not present a meaningful obstacle to such an undertaking by a determined scientist, group, or state.
In addition, there is only an uneven patchwork of nonbinding regulations designed to prevent the misuse of synthetic DNA. Leading members of the DNA synthesis industry have formed the International Gene Synthesis Consortium, which oversees a voluntary system for the screening of customers and gene sequence orders. The consortium accounts for 80 percent of the global market for synthetic DNA, which is a good start, but this leaves an uncomfortably large number of companies with no legal obligation to screen either customers or sequence orders for biosecurity purposes. Some companies’ idea of screening customers is to make sure they have a valid credit card.
Unless these safeguards are strengthened soon, the capability to produce smallpox will be globally distributed and either loosely or completely unregulated. That will open the door for a disgruntled or radicalized scientist, sophisticated terrorist group, unscrupulous company, or rogue state to re-create the smallpox virus.
But there is still time to act to prevent that from happening. International organizations, national governments, the DNA synthesis industry, and the synthetic biology community all have a role to play in preventing the re-emergence of smallpox.
The first step should be making sure that this kind of research happens only at a small number of approved facilities. The WHO and the U.N. Security Council should create an enforceable international legal prohibition against the possession of smallpox virus outside of the two WHO-designated repositories, synthesis of the virus, and the use of smallpox as a weapon. In addition, governments, scientists, and private firms wishing to generate pox viruses using synthetic DNA should be required to seek the approval of the WHO.
The DNA synthesis industry should declare a temporary moratorium on the synthesis of pox-virus DNA fragments above a specified threshold until the WHO oversight system can be established. The industry should also create a mechanism to allow member companies to better share information about how they screen customers and sequence orders, conduct annual exercises to test these safeguards, and commission third-party audits of their biosecurity practices.
National governments should criminalize the unauthorized possession and synthesis of smallpox. They also need to require that any scientist receiving government funding for life sciences research can purchase synthetic DNA only from companies that adhere to strong biosecurity protocols (like those in place for members of the International Gene Synthesis Consortium). Governments should also sponsor research to increase the effectiveness and reduce the cost of the biosecurity measures adopted by industry.
More broadly, the life sciences community, particularly in the field of synthetic biology, needs to intensify efforts to raise awareness of these dual-use and biosecurity issues as early as possible in the scientific education process. The private sector, which is increasingly commercializing breakthroughs in synthetic biology, needs to be engaged as a partner in safeguarding the bioeconomy. Finally, the growing number of biohackers and citizen scientists interested in exploring synthetic biology should be nurtured in safe, secure, and transparent working environments.
These measures are intended not to prevent peaceful research on pox viruses, but to ensure that this work is carried out with the maximum level of transparency, safety, and security. The eradication of smallpox was one of humanity’s greatest triumphs of the 20th century. Synthetic biology has the potential to revolutionize public health, medicine, energy, and environmental protection in the 21st century. But to reap the promise of this technology, we need to be vigilant about its perils.
An expanded version of this article appears in the September 2017 issue of Health Security.