As the global Covid mortality rate has dropped to the lowest level since the first weeks of the epidemic in 2020, it could be convincing to conclude that coronavirus is getting worse. The theory is based on the widespread belief that all viruses originate badly and that they inevitably change over time.
“There has been a great story that natural forces will solve this catastrophe,” said Aris Katzourakis, an evolutionary biologist at Oxford University.
But there is no such natural law. Viral mutations often take unexpected turn and turn. For many virologists, the best unpredictable example of this is the pathogen that has been killing rabbits in Australia for the past 72 years: the myxoma virus.
Myxoma has killed hundreds of millions of rabbits, making it one of the most dangerous viruses known to science, said Andrew Read, a mutation biologist at Pennsylvania State University. “It’s the biggest killer of any invertebrate animal disease,” he said.
After its introduction in 1950, the myxoma virus began to kill rabbits, but Drs. Read and colleagues found that they changed the course in the 1990s. And a recent study by researchers, released this month, found that the virus appeared to mutate and spread more rapidly from rabbits to rabbits.
“It still finds a new approach,” he said.
Scientists deliberately introduced the myxoma virus in Australia in hopes of eradicating invasive rabbits from the country. In 1859, a farmer named Thomas Austin imported 12 rabbits from England so he could hunt them on his farm in Victoria. Without natural pests or pathogens, they multiplied by the millions, eating enough vegetation to threaten wildlife and sheep farms throughout the continent.
In the early 1900’s, researchers in Brazil came up with an Australian solution. They had discovered the myxoma virus in the South American cotton-tailed rabbit family. The virus, transmitted by mosquitoes and fleas, caused little harm to animals. But when scientists infected European rabbits in their laboratory, the myxoma virus proved to be surprisingly dangerous.
Rabbits developed skin-filled nodules of the virus. The infection then spread to other organs, usually killing the animals in a matter of days. This dreaded disease came to be known as myxomatosis.
The Brazilian scientists shipped the myxoma virus sample to Australia, where scientists spent many years testing it in a laboratory to make sure it posed a threat to rabbits only and not to other organisms. Few scientists even injected myxoma virus into them.
After the virus was proven to be safe, researchers sprayed it on a few tissues to see what would happen. Rabbits died quickly, but not before mosquitoes bit them and spread the virus to others. Soon, rabbits hundreds of miles away were dying as well.
Shortly after the onset of myxoma, Australian virologist Dr. Frank Fenner began a lengthy investigation into his murder. In the first six months alone, he estimated, the virus killed 100 million rabbits. Fenner determined in laboratory experiments that the myxoma virus killed 99.8 percent of infected rabbits, usually in less than two weeks.
However the myxoma virus did not destroy the Australian rabbit. Through the 1950s, Drs. Fenner discovered why: Myxoma viruses grew less deadly. In his experiments, most viruses killed as little as 60 percent of rabbits. And rabbits killed by rabbits took a long time to disappear.
These reforms are in line with popular ideas at the time. Many biologists believe that viruses and other parasites inevitably evolved into a more complex one – what came to be known as the law of viral decline.
“Long-lived parasites, in the process of evolution, have a much smaller effect on the host than they have recently discovered,” zoologist Gordon Ball wrote in 1943.
According to the theory, the newly discovered parasites were dangerous because they were not yet accustomed to their inhabitants. Keeping the host alive for a long time, the ideas went away, giving the parasites more time to multiply and spread new armies.
The virus reduction law seemed to explain why myxoma virus became so prevalent in Australia – and why it was harmless in Brazil. The virus has been mutating in South American cotton tail rabbits for the longest time, until they did not cause any disease.
But evolutionary biologists have come to question the logic of the law in recent decades. More gentle growth may be the best strategy for some pathogens, but it is not the only one. “There are forces that can push the virus in the other direction,” said Drs. Katzourakis said.
Dr. Read decided to return to the myxoma virus saga when he set up his own laboratory in Penn State in 2008. “I knew it as a textbook case,” he said. “I began thinking, ‘What happens next?’”
No one had systematically diagnosed myxoma virus after Drs. Fenner quit in the 1960s. (He had good reason to quit, since he had gone to help eradicate smallpox.)
Dr. Read prepared samples of Drs. Fenner was shipped to Pennsylvania, and he and his colleagues also traced recent myxoma samples. Researchers designed viral DNA – something that Drs. Fenner could not do – and did research on infection in laboratory rabbits.
When they tested the genes of the viruses that had prevailed in the 1950’s, they found that they were less dangerous than the original viruses, thus confirming the results of Drs. Fenner. And the mortality rate dropped to the 1990’s.
But then things changed.
Newer genes of the virus killed more than the laboratory rabbits. And they often did so in a new way: by installing animal protection systems. Rabbit gut bacteria, usually harmless, multiplied and caused serious diseases.
“It was very scary when we first saw that,” Drs. Read said.
Surprisingly, wild rabbits in Australia have not experienced the harsh conditions of Drs. Read. He and his colleagues suspect that the new mutation in the virus was a response to the strict protection of rabbits. Studies have revealed that Australian rabbits have undergone new mutations in genes involved in the first line of defense against disease, known as natural immunity.
As rabbits grew up with strong natural immunity, Drs. Read and colleagues suspected, natural selection, in turn, favored viruses that could overcome this defense. This arms race competition erased the benefits that wild rabbits had enjoyed for a short time. But these viruses appeared to be worse against rabbits who did not have this resistance, such as those in Dr. laboratory. Read.
And the arms race is still going on. About a decade ago, a new generation of myxoma viruses emerged in southeastern Australia. This branch, dubbed Clan C, is changing more rapidly than any other dynasty.
Infection tests suggest that the new changes allow Lineage C to perform better from host to host, according to a recent study by Drs. Read with colleagues, which has not yet been published in a scientific journal. Many infected rabbits show a strange form of myxomatosis, developing severe swelling in their eyes and ears. It is these areas where mosquitoes like to drink blood – and where viruses can have a good chance of reaching a new host.
Viral experts see some important lessons that myxoma viruses can provide as the world struggles with the Covid epidemic. Both diseases are affected not only by genetic mutations, but by the protection of its host.
As the disease progresses in its third year, people are more protected than ever before from immunization.
But coronavirus, like myxoma, has not been on the path to the inevitable path.
The Delta variant, which occurred in the United States last season, was worse than the original version of the virus. The Delta was replaced by Omicron, which caused a minor illness to the average person. But viral experts at the University of Tokyo have conducted experiments suggesting that the Omicron variant is evolving into a more dangerous species.
“We do not know what the next stage of reform will be,” he said. Katzourakis warned. “That chapter in the direction of viral evolution has not yet been written.”