To improve vaccine, researchers create cousin of smallpox virus
Scientists have used commercially available genetic material to piece together the extinct horsepox virus, a cousin of the smallpox virus that killed as many as a billion human beings before being eradicated.
The laboratory achievement was reported Thursday in a news article in the journal Science.
The lead researcher, David Evans, a molecular virologist at the University of Alberta, told The Washington Post that his efforts are aimed at developing vaccines and cancer treatments. There is nothing dangerous about the synthetic horsepox virus, which is not harmful to humans.
Evans has not yet published his findings in a scientific journal — how to report this kind of research is necessarily fraught for the editors of such journals — but he did discuss them at a meeting on smallpox research last November at the World Health Organization in Geneva. A report on the meeting published by the WHO noted that Evans had received approval from regulatory authorities for his work, but the report added that those authorities may not have fully appreciated the need for regulation of the steps involved in synthesizing a virulent pathogen.
Evans said he has applied for a patent and is collaborating with a commercial company, Tonix Pharmaceuticals. In a news release, Tonix said it hopes to use the horsepox virus to develop a new vaccine for smallpox that is safer than the one available, which can have serious side effects.
Smallpox, the deadliest disease in human history, was formally declared eradicated in 1980. Government officials and virologists have long debated whether to destroy the existing samples of smallpox, kept under close guard at the Centers for Disease Control and Prevention as well as in government facilities in Russia. One argument against doing so, advanced by Evans and others, is that destroying them would not conclusively get rid of smallpox, because there could be unknown caches hidden somewhere, and that, in any case, modern techniques would be able to synthesize the virus based on already published genetic sequences.
Evans’s experiment, according to Science, required about $100,000, a relatively modest sum, and used commercially available genetic material. Companies sell scraps of cloned DNA that scientists stitch together. Laws restrict access to smallpox genes, however, and Evans said that even a highly credentialed researcher would not be able to obtain such material: “You’d probably get a call from the FBI if you tried.”
Evans said he was not seeking publicity and wished that news organizations would not make a “fuss” about his work. “The fact we’re talking about it is, to some extent, increasing the risk.”
Tom Frieden, former head of the CDC, said the breakthrough highlights the need to monitor more closely “dual-use” experiments — research that could be used for protective purposes or, in theory, to create a deadly pathogen. “It is a brave new world out there with the ability to re-create organisms that existed in the past or create organisms that have never existed,” said Frieden, who favors limiting the number of such experiments and institutions where they can take place.
The broader story here, Frieden said, is that the United States and other countries need to be prepared for emerging pathogens, which can and will appear naturally — no laboratory necessary.
That sentiment was echoed by Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases. “The danger of naturally evolving microbes — like Zika, like pandemic influenza, like Ebola — that naturally evolve, are much more of a threat to civilization than the possibility that someone might be able to synthesize a microbe,” Fauci told The Post. “People should concentrate on what we’ve been talking about for a long time: getting ourselves prepared for the natural emergence in nature of microbes that could threaten us.”
Smallpox vaccination programs ceased decades ago after the virus stopped circulating widely. Today, a majority of Americans have never been vaccinated against it, one motivation for researchers to study the virus in case it returns.
“We are still struggling with how to manage the dual-use dilemma. How do we get the benefit of the research without the risk of it being turned against us?” said Alta Charo, a law professor and bioethicist at the University of Wisconsin.
Peter Jahrling, director of NIH’s Integrated Research Facility, praised Evans’s work. “I think he did a terrific service. You had a lot of people saying this can’t be done. And he said ‘Yes, it can.’ ” Jahrling said this kind of work could be replicated by other researchers. “Maybe not some guy in a cave,” Jahrling said. “But a reasonably equipped undergraduate microbiology lab could repeat this trick.”
Still, restrictions are in place to prevent smallpox DNA from falling into the wrong hands. In the United States, experiments that are identified as Dual Use Research of Concern go through an additional round of review by funding agencies and must include a risk mitigation plan in their design. Last year, the WHO recommended that no institution be allowed to possess more than 20 percent of the smallpox virus’s genome. Companies that produce DNA for research are required to screen orders for matches against known pathogens.
Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, said similar work is probably occurring around the planet.
“The question is: How many other people have done it? We never thought or expected it to come from a place like Alberta,” he said. “It’s not one of the leading universities in the world for microbiology and synthetic biology.”
Osterholm said the U.S. government is unprepared to handle an emergency involving a synthetic pathogen — particularly given that many senior positions have not been filled by the Trump administration.