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Horsepox virus creation, aimed at smallpox vaccine, stirs controversy
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Biosecurity experts have warned that a recent study detailing the replication of horsepox virus could give bioterrorists a blueprint for constructing a smallpox-causing pathogen.
However, one of the authors of the study — David H. Evans, PhD, a professor of medical microbiology and immunology at the University of Alberta — argues that scientists have already shown that they do not need guidance in recreating potentially dangerous pathogens. Furthermore, he said the study’s findings could lead to a smallpox vaccine that is more tolerable than the one currently safeguarded, as well as cancer treatment.
“There are a lot of really clever scientists out there,” Evans told Infectious Disease News, “and it seems that it’s been known that you can do this for years. There is no surprise to any of my colleagues.”
Evans said two main goals drove the research. First, Tonix Pharmaceuticals, which funded and helped formulate the study, is seeking to develop the more tolerable smallpox vaccine, a goal that other research teams are also pursuing. Second, Evans said he wants to use the research to understand the construction of more complex viruses that can lead to new cancer treatments.
Evans worked with University of Alberta research associate Ryan S. Noyce, PhD, and Tonix CEO Seth Lederman, MD, to study the horsepox virus (HPXV), which is related to the vaccinia virus strain (VACV) used in the smallpox vaccine. Given that no HPXV specimen was available, the researchers chose to see if they could reconstruct it by synthesizing certain genes.
They completed a live synthetic chimeric horsepox virus (scHPXV), with which they infected mice. The scHPXV was less virulent than VACV but also provided vaccine protection against lethal VACV in the mice, Evans and colleagues said.
Should the researchers develop an alternative smallpox vaccine for humans, it could address a variety of possible adverse effects. According to the CDC, the current vaccine “is generally safe and effective, but some people do experience side effects and adverse reactions.”
These adverse reactions include infections at the site of vaccination that can range from mild to severe. They can also include various skin infections and complications.
Rarely but often fatally, smallpox vaccination can result in progressive vaccinia, the CDC says. That occurs when the vaccination site does not heal, and vaccinia virus continues to replicate.
Although fewer adverse effects can be a desirable and marketable outcome, several biosecurity experts say the study by Evans and colleagues is a dangerous endeavor. Greg Koblentz, PhD, director of the biodefense graduate program at George Mason University, recently said the study by Evans and colleagues was the first in which an orthopox virus was synthesized and therefore offers a “new pathway” to recreate smallpox. Koblentz spoke in an interview with the news publication for the University of Minnesota’s Center for Infectious Disease Research and Policy.
Evans agreed that pathogen synthesis can be used with malicious intent but maintained that his research provides nothing that bioengineers would not already have. He further suggested that security officials should have been alarmed about the possibilities much earlier.
“The technology is advancing in leaps and bounds,” Evans said. “What does disturb me is that it’s not really been on the radar of public health people and the biosecurity people ... My sense is that [the notion] has always been, ‘Well, it’s going to happen, but it will be a number of years before we really have to worry about it.’ But that genie is out of the bottle.” – by Joe Green
References:
CDC. Vaccine Adverse Events. www.cdc.gov/smallpox/clinicians/vaccine-adverse-events5.html. Accessed February 19, 2018.
Noyce RS, et al. PLoS One. 2018;doi:10.1371/journal.pone.0188453.
Disclosures: Evans and Noyce report that they provide consultation services to Tonix Pharmaceuticals. Lederman is the co-founder, CEO and chair of Tonix. All three authors are claimed as co-inventors on a U.S. patent application for synthetic chimeric poxviruses, Application No. 62/434,794, filed on behalf of the governors of the University of Alberta and Tonix.
Perspective
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Margaret E. Kosal, PhD
In the recent article “Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments,” which appeared in PLoS One, the University of Alberta’s Dr. David Evans and colleagues report “the first complete synthesis of a pox virus using synthetic biology approaches,” specifically the extinct horsepox virus, and a potential candidate for development of a new vaccine against smallpox. The underlying research has been the subject of discussion within the biosecurity community for over a year, since Evans presented details of his work on synthesizing the virus to the WHO Advisory Committee on Variola Virus Research in November 2016.
Evans had reportedly gone through all the biosafety and biosecurity procedures required by the Canadian government and his university before starting the research. All evidence indicates that everything was done properly and more than sufficiently. So, what’s the concern?
The concern is one that has been seen before, most notably with the successful chemical synthesis of polio virus in 2001 and the reconstruction of the influenza A(N1N1) virus responsible for the 1918 Spanish flu in 2005. The concern is that the techniques and methods might be hijacked for more malicious use in the development of biological weapons. It is the dual-use conundrum of cutting-edge science, especially synthetic biology in the 21st century.
To further complicate the issue, the U.S. Congress, through the programs funded as part of the biodefense program, provided a legitimate incentive for the type of work pursued by Evans and his team. It is an incentive to create a better medical countermeasure for smallpox than the currently available vaccine.
This is another example of the ongoing tension between science and security. Biosecurity laws, as written, are insufficient when it comes to regulating the ingenuity of humans, which is something of a truism. They always will be. They are limited, and that may be for the best.
We need methods and processes to deal with one-offs and other cases that are not overly restrictive and that do not impede scientific discovery and development of new biomedical products. We need processes that do not discourage young people from pursuing science but that do reduce the threat of good science being appropriated by people, groups or nations with bad intentions.
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