Think all viruses get softer over time? Not this killer bunny.

Like the death of Covid evaluate globally has fallen to its lowest level since the first weeks of the pandemic in 2020, one might be tempted to conclude that the coronavirus is becoming irreversibly milder. This view is consistent with the widely held belief that all viruses start out being dangerous and inevitably evolve to become milder over time.

“There was a widespread belief that natural forces would solve this pandemic for us,” said Aris Katsourakis, an evolutionary biologist at the University of Oxford.

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

Myxoma has killed hundreds of millions of rabbits, making it the deadliest vertebrate virus known to science, said Andrew Reid, an evolutionary biologist at Pennsylvania State University. “This is the biggest carnage of all vertebrate diseases,” he said.

After its introduction in 1950, the myxoma virus became less lethal to rabbits, but Dr. Reid and his colleagues found that the course changed in the 1990s. And the researchers’ latest study studyreleased this month found that the virus appears to be evolving and spreading even faster from rabbit to rabbit.

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

Scientists deliberately brought the myxoma virus to Australia in hopes of wiping out the country’s invasive rabbit population. In 1859, a farmer named Thomas Austin imported two dozen rabbits from England to hunt on his farm in Victoria. With no natural predators or pathogens to keep them at bay, they have multiplied by the millions, eating enough vegetation to threaten native wildlife and sheep farms across the continent.

In the early 1900s, explorers from Brazil offered Australia a solution. They discovered the myxoma virus in a species of cotton rabbit that lives in South America. The virus, spread by mosquitoes and fleas, did little harm to the animals. But when scientists infected European rabbits in their lab, the myxoma virus turned out to be startlingly deadly.

Rabbits developed skin nodules filled with viruses. The infection then spread to other organs, usually killing the animals in a matter of days. This terrible disease is called myxomatosis.

Brazilian scientists have sent samples of the myxoma virus to Australia, where scientists have spent years testing it in labs to make sure it only poses a threat to rabbits and not to other species. Several scientists have even injected themselves with myxoma viruses.

After the virus proved to be safe, the researchers sprayed it into several mazes to see what would happen. The rabbits died quickly, but not before the mosquitoes bit them and spread the virus to others. Soon, rabbits hundreds of miles away began to die, too.

Shortly after the appearance of myxoma, Australian virologist Dr. Frank Fenner began a thorough, long-term study of his massacre. He estimates that in the first six months alone, the virus killed 100 million rabbits. Dr. Fenner determined in laboratory experiments that the myxoma virus killed 99.8% of the rabbits it infected, usually in less than two weeks.

However, the myxoma virus did not wipe out the Australian rabbits. During the 1950s Dr. Fenner figured out why: the myxoma virus became less lethal. In his experiments, the most common strains of the virus only killed 60 percent of the rabbits. And the rabbits that the strains killed took longer to die.

This evolution was in line with the popular ideas of the time. Many biologists believed that viruses and other parasites inevitably evolved to become softer. known as the law of decreasing virulence.

“Long-standing parasites in the process of evolution have much less harmful effects on the host than newly acquired ones,” wrote the zoologist Gordon Ball in 1943.

According to the theory, the newly acquired parasites were deadly because they had not yet adapted to their hosts. Keeping the host alive longer was thought to give parasites more time to reproduce and spread to new hosts.

The law of decreasing virulence seems to explain why myxoma viruses became less lethal in Australia and why they were harmless in Brazil. The viruses took much longer to develop in South American cotton rabbits, to the point where they did not cause disease at all.

But in recent decades, evolutionary biologists have questioned the logic of the law. Mitigation may be the best strategy for some pathogens, but not the only one. “There are forces that can push virulence in a different direction,” says the doctor. Katsourakis said.

Dr. Reid decided to revisit the myxoma virus saga when he opened his lab in Pennsylvania in 2008. “I knew it like a case from a textbook,” he said. “I started thinking, ‘Well, what next?

No one has systematically studied the myxoma virus since Dr. Fenner stopped in the 1960s. (He had a good reason to refuse her, since he went to help eradicate smallpox.)

Dr. Reading organized for Dr. Fenner’s samples are to be sent to Pennsylvania, and he and his colleagues have also tracked more recent myxoma samples. Researchers have sequenced the DNA of viruses – what a doctor. Fenner could not do this – and conducted research on infections in laboratory rabbits.

When they tested the viral lines that were dominant in the 1950s, they found that they were less lethal than the original virus, which confirmed Dr. S. Fenner’s findings. And the death rate remained relatively low throughout the 1990s.

But then everything changed.

Newer viral lines killed more lab rabbits. And often they did it in a new way: by turning off the immune system of animals. Rabbit gut bacteria, normally harmless, multiplied and caused deadly infections.

“It was really scary when we first saw it,” says the doctor. Read said.

Oddly enough, but wild rabbits in Australia did not suffer the terrible fate of the doctor. Reed’s laboratory animals. He and his colleagues suspect that the new virus adaptations were a response to stronger defenses in rabbits. Research showed that Australian rabbits received new mutations in genes involved in the first line of defense against disease, known as innate immunity.

Because rabbits have developed stronger innate immunity, dr. Reid and his colleagues suspect that natural selection, in turn, favored viruses that could overcome this defense. This evolutionary arms race wiped out an advantage that the wild rabbits had briefly enjoyed. But these viruses were even worse against rabbits that had not developed resistance, such as those found in Dr. H. Reed’s lab.

And the arms race continues. About a decade ago, a new strain of myxoma viruses emerged in southeastern Australia. This branch, called Lineage C, is developing much faster than the other lines.

Infection experiments show that the new mutations allow Lineage C to better cope with host-to-host transmission, according to the latest study by Dr. J. Reed and colleagues, which has yet to be published in a scientific journal. Many infected rabbits exhibit a strange form of myxomatosis, developing massive swelling in the eyes and ears. It is in these places that mosquitoes like to drink blood – and where viruses may have a better chance of getting to a new host.

Virologists see several important lessons that the myxoma virus can teach as the world battles the Covid pandemic. Both diseases are affected not only by the genetic makeup of the virus, but also by the defenses of its host.

As the pandemic enters its third year, people are better protected than ever thanks to immunity from vaccines and infections.

But the coronavirus, like myxoma, is not on the inevitable path to ease.

The Delta variant that broke out in the United States last fall was more deadly than the original version of the virus. Delta was replaced by Omicron, which caused less severe illness in the average person. But virologists at the University of Tokyo conducted experiments suggesting that the Omicron variant evolves into more dangerous forms.

“We don’t know what the next step in evolution will be,” the doctor said. Katsourakis warned. “This chapter in the evolutionary trajectory of virulence has yet to be written.”