Three months ago, Japan was recording more than 25,000 cases of COVID-19 every day - but now, in late November, the country of 125 million people has fewer active cases than New Zealand.
The stunning turnaround in fortunes has baffled scientists, but a new theory has emerged which raises hope the pandemic worldwide might eventually wane on its own.
Ituro Inoue, a professor at the National Institute of Genetics, said this week his team's research has found the Delta variant behind the massive surge of cases mutated in a way that led to its "self-destruction".
"We were literally shocked to see the findings," he told The Japan Times. "The Delta variant in Japan was highly transmissible and keeping other variants out. But as the mutations piled up, we believe it eventually became a faulty virus and it was unable to make copies of itself.
"Considering that the cases haven’t been increasing, we think that at some point during such mutations it headed straight toward its natural extinction."
Every time a virus replicates, there's a chance the genetic code of the copies is different to their parent - this is how viruses evolve. Some mutations are beneficial, such as those which increase a virus' ability to infect new hosts. Others are detrimental.
Analysis of Japan's Delta outbreak found there wasn't a lot of genetic diversity amongst cases, and they all seemed to be evolving a large number of mutations on a particular protein called nsp14, the Times reported.
That protein helps the virus correct errors in its genetic code when it replicates. If it can't do that properly, new copies of the virus are more likely to have disadvantageous mutations.
"Studies have shown that a virus with a crippled nsp14 has a significantly reduced ability to replicate, so this can be one factor behind the rapid decline in new cases," Takeshi Urano of Shimane University’s Faculty of Medicine told the paper, adding that the discovery could point the way to new treatments.
"The chemical agent to curb this protein could become a promising medicine, with development already underway.”
Whether other nations battling Delta might see a similar natural reduction in cases is possible but perhaps "too optimistic" at this stage, Dr Inoue said, with no evidence that nsp14 mutations are piling up in other countries. He said even Japan isn't out of the woods yet, with other variants likely to emerge as the pandemic continues to see millions of others infected around the world.
Prior studies have shown Asian people are more likely to have a gene called APOBEC3A, which is known to have antiviral properties. Dr Inoue said he wasn't sure if that was behind the outbreak's decline, noting that Koreans are ethnically "the same" as Japanese but haven't had the same success at quelling their recent Delta outbreak.
Dr Inoue said he hopes to formally publish their findings later this month.
