Think All Viruses Get Milder With Time? Not This Rabbit-Killer.

As the Covid death rate worldwide has fallen to its lowest level since the early weeks of the pandemic in 2020, it may be tempting to conclude that the coronavirus is becoming irreversibly milder. That notion fits with a widespread belief that all viruses start off nasty and inevitably evolve to become gentler over time.

“There’s been this dominant narrative that natural forces are going to solve this pandemic for us,” said Aris Katzourakis, an evolutionary biologist at the University of Oxford.

But there is no such natural law. A virus’s evolution often takes unexpected twists and turns. For many virologists, the best example of this unpredictability is a pathogen that has been ravaging rabbits in Australia for the past 72 years: the myxoma virus.

Myxoma has killed hundreds of millions of rabbits, making it the most deadly vertebrate virus known to science, said Andrew Read, an evolutionary biologist at Pennsylvania State University. “It’s absolutely the biggest carnage of any vertebrate disease,” he said.

After its introduction in 1950, myxoma virus became less lethal to the rabbits, but Dr. Read and his colleagues discovered that it reversed course in the 1990s. And the researchers’ latest study, released this month, found that the virus appeared to be evolving to spread even more quickly from rabbit to rabbit.

“It’s still getting new tricks,” he said.

Scientists intentionally introduced the myxoma virus to Australia in the hopes of wiping out the country’s invasive rabbit population. In 1859, a farmer named Thomas Austin imported two dozen rabbits from England so he could hunt them on his farm in Victoria. Without natural predators or pathogens to hold them back, they multiplied by the millions, eating enough vegetation to threaten native wildlife and sheep ranches across the continent.

In the early 1900s, researchers in Brazil offered Australia a solution. They had discovered the myxoma virus in a species of cottontail rabbit native to South America. The virus, spread by mosquitoes and fleas, caused little harm to the animals. But when the scientists infected European rabbits in their laboratory, the myxoma virus proved astonishingly lethal.

The rabbits developed skin nodules packed with viruses. Then the infection spread to other organs, usually killing the animals in a matter of days. This gruesome disease came to be known as myxomatosis.

The Brazilian scientists shipped samples of the myxoma virus to Australia, where scientists spent years testing it in labs to make sure it posed a threat only to rabbits and not other species. A few scientists even injected myxoma viruses into themselves.

After the virus proved safe, researchers sprayed it into a few warrens to see what would happen. The rabbits swiftly died, but not before mosquitoes bit them and spread the virus to others. Soon, rabbits hundreds of miles away were dying as well.

Shortly after myxoma’s introduction, the Australian virologist Dr. Frank Fenner started a careful, long-term study of its carnage. In the first six months alone, he estimated, the virus killed 100 million rabbits. Dr. Fenner determined in laboratory experiments that the myxoma virus killed 99.8 percent of the rabbits it infected, typically in less than two weeks.

Yet the myxoma virus did not eradicate the Australian rabbits. Through the 1950s, Dr. Fenner discovered why: The myxoma virus grew less deadly. In his experiments, the most common strains of the virus killed as few as 60 percent of the rabbits. And the rabbits the strains did kill took longer to succumb.

This evolution fit with popular ideas at the time. Many biologists believed that viruses and other parasites inevitably evolved to become milder — what came to be known as the law of declining virulence.

“Longstanding parasites, by the process of evolution, have much less of a harmful effect on the host than have recently acquired ones,” the zoologist Gordon Ball wrote in 1943.

According to the theory, newly acquired parasites were deadly because they had not yet adapted to their hosts. Keeping a host alive longer, the thinking went, gave parasites more time to multiply and spread to new hosts.

The law of declining virulence seemed to explain why myxoma viruses became less lethal in Australia — and why they were harmless back in Brazil. The viruses had been evolving in South American cottontail rabbits much longer, to the point that they caused no disease at all.

But evolutionary biologists have come to question the logic of the law in recent decades. Growing milder may be the best strategy for some pathogens, but it is not the only one. “There are forces that can push virulence in the other direction,” Dr. Katzourakis said.

Dr. Read decided to revisit the myxoma virus saga when he started his laboratory at Penn State in 2008. “I knew it as a textbook case,” he said. “I started thinking, ‘Well, what’s happening next?’”

No one had systematically studied the myxoma…