Japan is preparing for tens of thousands of international tourists to descend on Tokyo for the Olympic Games next year — and that includes being ready for unwanted biological visitors.
Last month, Japan imported Ebola and four other dangerous viruses in preparation for a possible outbreak at the event. The Japanese health ministry says researchers will use the samples, which include Marburg virus, Lassa virus, and the viruses that cause South American haemorrhagic fever and Crimean–Congo haemorrhagic fever, to validate tests under development.
The viruses’ arrival represents the first time that pathogens rated biosafety-level-4 (BSL-4) — the most dangerous rating — have been allowed to enter the Japanese National Institute of Infectious Diseases (NIID), the only facility in the country operating at that level.
Japan’s medical-science community welcomes the move. Although infectious-disease scientists say that the risk of an outbreak during the Olympics isn’t much higher than at any other time, access to the live viruses will boost the country’s capacity to handle infectious diseases in general — and to prepare for a bioterror attack.
Although the NIID’s laboratory in Musashimurayama, Tokyo, was built to BSL-4 specifications in 1981, it operated as a BSL-3 lab for decades because of opposition from residents. In 2015, the health ministry and the Musashimurayama mayor agreed that it could operate as a BSL-4 lab, but the decision to import the five viruses was only finalized in July.
Japan’s ability to study the most dangerous pathogens has lagged behind that of other advanced nations — both the United States and Europe have more than a dozen BSL-4 labs in operation or under construction, and China is building a network of at least five BSL-4 labs, with one already operational in Wuhan.
"This is a landmark time, a landmark event" for NIID, says Masayuki Saijo, director of the NIID department that is responsible for haemorrhagic-fever viruses.
But not everyone is pleased about the imported viruses. Some local residents have told Japanese media that scientists and the government are using the Olympics as a pretext to import the viruses. And Richard Ebright, a molecular biologist and biosecurity specialist at Rutgers University in Piscataway, New Jersey, says that BSL-4 labs can be prepared to handle outbreaks of hazardous agents without the need to bring them to the country ahead of time. Storing dangerous viruses, even in a highly secure lab, increases the risk of an accidental or deliberate release, he says.
What’s the risk?
The NIID will use the live samples to validate tests it has developed to assess whether a person with one of the viruses is still infectious, says Saijo. The tests measure whether the patient is generating antibodies that are capable of neutralizing the virus in question, which would suggest that the patient is recovering, and not infectious, he says. If there is a person with one of these viruses at the games, such a test could provide valuable information for assessing whether they can be discharged from hospital, he says.
The development of these tests will boost Japan’s preparedness for such an event or a bioterror attack, says Saijo. Other Olympic host nations didn’t have to import these viruses specially ahead of the games because they already had the pathogens in BSL-4 labs. The NIID will also continue developing more sensitive and accurate tests after the games. Saijo says that he understands opposition from local residents, but that the live viruses give Japanese researchers an important advantage in preparing against infectious diseases.
Elke Mühlberger, a microbiologist at Boston University in Massachusetts, thinks that a major outbreak of Ebola at the Olympics is unlikely because the infection is not transmitted through the air. But she says that Japan’s plan to assess the NIID’s tests with live viruses before the games makes sense, especially given the ongoing Ebola outbreak in the Democratic Republic of the Congo. “A report of an Ebola virus infection during the Olympics could have devastating consequences if the emergency responses were not professional,” she says.
But Mühlberger is sceptical about the usefulness of neutralizing-antibody tests to evaluate whether a patient can be released. She says the easiest way to determine whether a patient is virus-free is to look at the amount of viral RNA in their body fluids. “I don’t believe anybody would release a patient just because they have developed neutralizing antibodies,” she says.
Now that the NIID is allowed to handle BSL-4 pathogens, researchers there will also be able to study other dangerous viruses that might emerge in the region, says Mühlberger. The latest genome sequencing technologies are revealing that Ebola-like viruses are more common than previously thought, she says. Three in the same family were discovered in animals the last year: the Mengla virus in Chinese bats and two Ebola-like viruses found in fish in the East China Sea. "It is amazing how many animals are infected with viruses which are very closely related to very, very dangerous pathogens," she says.
It remains unknown whether these viruses can infect or harm humans, says Mühlberger. But their diversity is "pretty scary", she says. "These viruses are everywhere."
Virologist Ayato Takada at Hokkaido University in Sapporo, Japan, is also excited about being able to study BSL-4 pathogens in animals in Japan. Until now, researchers had to apply for access to BSL-4 labs overseas, which are in high demand. Takada hopes to use a second BSL-4 lab that is under construction at Nagasaki University in southern Japan and due to be completed in 2022.
But Ebright argues that the proliferation of BSL-4 labs around the world increases the chances that a deadly virus could be released in a bioterror attack. He thinks that some governments, including Japan, are using their BSL-4 labs to stockpile deadly agents to deter bioattacks from similarly equipped adversaries.
Saijo says that the NIID is operated solely for public-health research.
Nature 574, 306-307 (2019)