Researchers at the Pasteur Institute in Paris working under strict biosafety conditions recently opened an old box that contained a virological time capsule: four poliovirus samples, each with a handwritten label on the vial, sent to the institute more than 60 years earlier by Albert Sabin, a giant in the field of poliovirus research.
The viruses had to be destroyed, as part of a global campaign to get rid of old poliovirus samples. But first, the Pasteur team would sequence them to preserve their genetic information.
Now, a paper about those sequences, published in Virus Evolution in July, has raised an unexpected and troubling possibility: A poliovirus that infected a 4-year-old child in China in 2014 may have originated in a research laboratory or a vaccine production facility.
The exact source of that virus is unclear, as is the route by which it infected the child, and the authors are careful not to point fingers. But the paper underscores the fact that accidental releases of poliovirus are remarkably common.
“It is an interesting detective story,” says Mike Famulare, a systems epidemiologist at the Bill & Melinda Gates Foundation who has studied polio but was not involved in the work. And because the child’s virus was analyzed at the Wuhan Institute of Virology, the finding has, inevitably, become politicized: On social media and in conservative outlets, advocates of a lab-leak origin of the COVID-19 pandemic have seized on it to suggest WIV had “another” lab release — even though there is no evidence the virus came from that institute.
Polio was one of the most feared childhood diseases in the first half of the 20th century, paralyzing hundreds of thousands of children every year. Cases plummeted after the development in the 1950s of the injected, inactivated polio vaccine by Jonas Salk, followed by a live, attenuated vaccine given orally by Sabin.
Today, the disease is on the cusp of eradication: Two of the three original poliovirus strains are already gone, and the third one is circulating only in Afghanistan and Pakistan.
To reduce the risk of future outbreaks, researchers have committed to destroying the untold numbers of poliovirus samples held in labs around the world, and even old stool samples that might harbor the virus. Often, the viruses are sequenced before destruction, especially historic strains that were studied before genetic sequencing was available.
Sabin sent the four samples to Pasteur virologist and 1965 Nobel laureate André Lwoff back in 1960. They had been adapted in the lab to grow at temperatures below that of the human body, and Sabin thought they might be a good basis for vaccines. Lwoff was investigating what effect fever might have on pathogens. The samples are “an important legacy for science and public health,” the institute wrote in an email to Science.
Researchers at the Pasteur Institute recently sequenced four poliovirus strains, stored in vials with handwritten labels, that Albert Sabin sent to the institute in 1960.Chesnais et al., Virus Evolution
Now, Maël Bessaud, a poliovirus researcher at Pasteur, and his colleagues have found that one of the strains, called Glenn, is very similar genetically to a poliovirus called Saukett A, one of a group of polioviruses called Saukett that were isolated in the United States in the 1950s and are still used today to produce inactivated polio vaccine. But surprisingly, Glenn is also close to a virus isolated in 2014 from a 4-year-old child in central China.
WIV researchers had already sequenced that virus, which they named WIV14. In 2017 they reported it was closely related to a strain named Sabin 3, which is used to make oral polio vaccines. The live virus in oral vaccines can continue to circulate and mutate, and the WIV team concluded that a Sabin 3 virus used for immunization ultimately evolved into WIV14.
To better understand what had happened, the Pasteur team also sequenced Saukett A, whose genome was only partially known. They discovered that WIV14 differed from Saukett A in only 70 nucleotides, versus more than 800 nucleotide differences with Sabin 3. That means WIV14 does not derive from Sabin 3, “but rather from a strain very close to Saukett A or from Saukett A itself,” the paper says.
It’s possible, the authors write, that the child’s sample was somehow contaminated with Saukett A in the lab or elsewhere. But if the child was really infected with WIV14, it could have remained so similar to Saukett A only if it lay dormant for decades, either in a natural reservoir like the permafrost or — more likely with a strain known to be used in vaccine production — in a freezer at a facility handling this virus. Then it was somehow released. If such an accident happened, it didn’t necessarily occur in China, the authors write: The release could have happened “anywhere in the world,” before the virus was detected in China.
“At this point, the authors do not favor any of those scenarios because they consider there is no scientific argument supporting one versus another,” a Pasteur media officer wrote in an email to Science.
Famulare agrees, but other researchers lean toward the leak theory. A mistake at a testing lab is always a possibility, says Adam Lauring, an evolutionary virologist at the University of Michigan who edited the paper at Virus Evolution. But it seems more likely that the virus leaked from a production facility, he says: “I am pretty convinced.”
Roland Sutter, who headed polio research at the Global Polio Eradication Initiative until 2020, agrees a lab leak seems more likely, but not necessarily at a vaccine production facility. Saukett polio strains are used to manufacture inactivated polio vaccines in Europe, but manufacturers in China, Japan, and South Korea all use attenuated Sabin strains in their inactivated polio vaccines, he says. There are other potential sources, Sutter says, such as universities that teach virology. The Saukett poliovirus strain, one of the easiest to handle, “is probably still being used in many places for that purpose,” he says.
It’s “terribly important” to get to the bottom of any leak, he adds, saying he wouldn’t be surprised if the paper had already triggered an investigation in China. “Of course, the outcome of such an investigation may never see the light of day.”
The Wuhan institute, where WIV14 was sequenced, is at the center of allegations that the COVID-19 pandemic was the result of a lab leak. But there is no evidence that WIV14 originated at WIV, Lauring says. “Unfortunately … people will speak of this as a ‘lab leak’ and jump to conclusions,” he says. “All they did here was isolate a virus and sequence it and upload it.” Any lab leak would have occurred before that, and probably elsewhere. WIV did not respond to a request for comment.
Perhaps because of the sensitivity, many virologists and polio experts contacted by Science declined to comment or did not respond. Pasteur answered questions by email but did not make the paper’s authors available for an interview.
If the virus did escape from a lab or a vaccine manufacturer, it would hardly be the first time. In the 2000s, a lab strain was suspected of causing disease in several children in India.
In 2014, a vaccine production facility in Belgium accidentally released billions of poliovirus particles into the sewage system, but no human infections were found. In 2017, a worker at a vaccine production facility in the Netherlands tested positive for poliovirus after an accidental leak in a vaccine production room. (He did not get sick but was isolated until he no longer shed the virus.) Another employee at the same facility became infected in 2022.
Vaccine plants grow large amounts of virus, boosting the chances of escape, Lauring says, and the virus is hardy. “So lots of virus, a little gets out, and it can persist,” he says.
Lauring says he was often worried himself when he studied poliovirus evolution, despite the many safety precautions. “When I had my first child, prior to his receiving his vaccine,” he says. “I even used to strip my clothes at my front door and not wear my shoes inside.”
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