Orthopoxvirus Synthesis: The Implications of Publishing Instructions

Last year the science community was set ablaze with the news that Canadian researchers had synthesized horsepox virus from scratch by using mail-ordered DNA, $100,000, and several months of work. News came of the experiment prior to the official publication; however, this past week the paper was officially published. It details the “construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments.” Led by virologist David Evans, and funded by the New York City-based pharmaceutical company Tonix, the goal of such work was to create a new synthetic virus that would enable efforts to create a more effective smallpox vaccine.

Prior to publication, there were concerns within the biosecurity and biosafety community regarding the implications of publishing a “how-to” for creating an orthopoxvirus and close relative of smallpox. Although it was steeped in controversy, the study was nonetheless published; however, what does this ultimately mean for our global health security and safety?

Although there are, of course, tacit barriers to such scientific endeavors, many are concerned that this experiment not only provides x information for nefarious actors, but also sets us up for disastrous safety and security failures within the laboratory.

In addition, the experiment falls under the dual-use research of concern (DURC) umbrella, which means that although there are benefits, there are also substantial risks that such work could be misused for malevolent purposes. The publisher of the article, PLOS, stated that the benefits outweighed the risks, but many biodefense and biosecurity experts aren’t convinced. In fact, in a recent Science commentary on the study, Tom Inglesby, MD, director of the Johns Hopkins Center for Health Security, noted that it was “a serious mistake” and that “the world is now more vulnerable to smallpox”.

I was able to speak to Gregory Koblentz, PhD, health security expert, and director of George Mason University’s Biodefense graduate program, regarding the implications of this research and its publication.

The support for the project has focused on making a safer smallpox vaccine, which many medical providers can support, but how many vaccine-related adverse outcomes are we talking about in relation to the threat of misusing this research?

Dr. Koblentz noted that,

“The claim that this research was justified by the need for a safer smallpox vaccine is disingenuous. The safety issues that the authors refer to are an unexpected number of myopericarditis events that were caused by a first-generation vaccine called Dryvax during the 2002-2003 smallpox immunization campaign. The United States now stockpiles (and just announced it is buying more of) a third-generation smallpox vaccine called IMVAMUNE that does not have the cardiotoxicity side effects of earlier smallpox vaccines. The vaccine is even safe enough to give to people with compromised immune systems. Japan also has also developed and licensed a third-generation smallpox vaccine that does not have problems with cardiotoxicity. There is a weak scientific case and an even weaker business case that Tonix can turn this virus into a licensed medical countermeasure. As a result, this research is all risk and no reward. Given the known risks of this research for pioneering a technique that can be used to recreate variola virus and the questionable benefits, I think this article raises serious questions about the proprietary of a private company sponsoring such high-risk research without any oversight.”

Undoubtedly, the synthesis of smallpox poses a huge risk to the world, so just how far are we willing to go with other orthopoxviruses? The World Health Organization has recommendations that ban the synthesis of variola's whole genome, but synthesizing an orthopoxvirus in a lab is the first step to normalizing such work. Oversight and laboratory biosafety/biosecurity efforts have struggled to stay up-to-date and find the middle ground of promoting science while keeping it safe. The publication of this research was highly risky and appears to have little consideration for the precarious situation that it has not only encouraged, but also created.