Mail-Ordering Your Way to Horsepox

The online shopping industry is booming and it looks like mail-order pathogens for scientific experiments may be following suit. In fact, Canadian researchers, led by virologist David Evans, PhD, recently announced that they had synthesized horsepox virus through mail-order DNA. Although the team is small and has little specialized knowledge, half a year and $100,000 allowed them to build a cousin of smallpox.

As you can imagine, this experiment and its results are getting a lot of attention for several reasons. Firstly, anything done with a relative of variola (smallpox) implies that the experiment would also be successful with smallpox. This fact alone is a heated topic given the debate around the safety and potential destruction of the last remaining smallpox samples. Secondly, Dr. Evans’ research underscores another ongoing debate regarding dual-use research of concern (DURC). DURC applies to research that can be reasonably anticipated to provide knowledge, information, products, or technology that could pose a threat.) Thirdly, this experiment highlights potential gaps within oversight of the life sciences.

Although Dr. Evans’ horsepox experiment has not been officially published yet, it is already drawing controversy for the aforementioned reasons. Dr. Evans’ work with horsepox is a reminder of the experiments that first drew attention to DURC, such as one in which the poliovirus was reconstituted from scratch. Not only does this horsepox experiment highlight the debate regarding the oversight of life sciences in terms of DURC, it also highlights other research that could increase gain-of-function (GoF). (The reader may remember that GoF research has come under fire after several studies showed GoF research enhanced pandemic potential, resulting in a halt to federal funding for GoF research until guidelines could be established.)

The horsepox experiment also highlights differences in terms of regulatory oversight. The World Health Organization does not permit labs to make more than 20% of the variola genome, and there are guidelines and checks through the companies selling DNA fragments; however, they are voluntary and global oversight would be nearly impossible.

Although Dr. Evans hoped that his experiment would help facilitate the development of a new smallpox vaccine, many point out that the development of a vaccine could be done with smallpox however, such work may show proof of concept for nefarious actors looking to build biological weapons.

But, perhaps the most concerning aspect of this experiment is that no discussion around the work in terms of oversight and DURC concerns seemingly took place. Indeed, Dr. Evans’ own attitude on the subject seems to be alarmingly flippant. "Have I increased the risk by showing how to do this? I don't know," he says. "Maybe yes. But, the reality is that the risk was always there," Dr. Evans’ told Science.

Not surprisingly, scientific experts from across the United States have been weighing in on this controversial new research.

Many experts, such as Paul Keim, PhD, an anthrax expert from Northern Arizona University, are pointing out that there should be some sort of international system that provides background checks and permits for researchers wishing to work with viruses that are no longer found in nature (such as horsepox).

“Bringing back an extinct virus that is related to smallpox, that's a pretty inflammatory situation. There is always an experiment or event that triggers closer scrutiny, and this sounds like it should be one of those events where the authorities start thinking about what should be regulated,” Dr. Keim recently told Science.

This DURC poses several questions on biosafety and biosecurity implications, such as, if it should be done, what safety processes are in place, what will be published, etc. Tom Inglesby, MD, director of the Johns Hopkins Center for Health Security, points to these questions and the approval process as something that needs to be addressed in the wake of the horsepox research revelations. Dr. Inglesby, like many in the biosecurity field, point to the experiment as a prime example of gaps within the review process for DURC research. Although there are rules in the United States regarding federally-funded research that reconstitutes organisms that are eradicated or extinct, the 15-agent list that is included in these regulations does not include horsepox, as it is not a threat to humans. The P3C0 policy (Potential Pandemic Pathogen Care and Oversight, or as so many lovingly call it, C3PO), does take great strides to guide policies for pathogens of pandemic potential; however, there is no international component, as Dr. Inglesby points out.

Canadian oversight applies to all DURC experiments, regardless of funding source; however, the responsibility ultimately falls on the institution to review the risk and establish a mitigation plan. Dr. Evans did talk to authorities in Canada regarding the scope of his project, but many experts are highlighting that it should not have been approved during proper review and regulations. To this end, biodefense expert Gregory Koblentz, PhD, MPP, of George Mason University points to the regulations that encompass not just special pathogens, but also research that could produce knowledge that is inherently dual-use risky. “That should have captured the horsepox synthesis. But, as far as I understand, they did not engage in a systematic review of the broader dual-use implications of synthesizing an orthopox virus. I don't think this experiment should have been done.”

Horsepox does not exist in nature and does not pose a threat to humans; however, Dr. Evans brought this relative of smallpox to life—with ingredients ordered online—and the methods used could be translated to recreate smallpox, which would be devastating given the lack of immunity since it’s been eradicated. This experiment is a pivotal moment for life sciences and global health security. In fact, even former Centers for Disease Control and Prevention (CDC) director Tom Frieden, MD, weighed in, pointing out that this experiment will also impact the debate regarding the destruction of smallpox stockpiles. Moreover, he said that Dr. Evans’ experiment should fuel a closer monitoring of DURC.

Perhaps one of the most poignant aspects of this research, and the debate surrounding it, is the gaps in review processes for life sciences and the inherent attitude of the researcher. Research is vital for growth in science; however, such experiments must be reviewed properly to ensure appropriate biosecurity and biosafety measures are taken. This experiment also brings to light how the attitudes of researchers are impacting the fallout of such research. The debate regarding DURC oversight and the processes for risk review facilitate an imperfect system that allowed research, such as Dr. Evans’, to go forward without the necessary review. Overall, the horsepox creation via mail-order products will surely change the discussion on not only smallpox, but also the future of dual-use research, hopefully for the better.