Since the global covid mortality rate has dropped to its lowest level since the first week of the epidemic in 2020, it may be tempting to conclude that the coronavirus is becoming irreversibly mild. This idea fits in with the widespread belief that all viruses start out nasty and inevitably become more mild over time.
Aris Katzorakis, an evolutionary biologist at the University of Oxford, said: “There is an impressive description that natural forces are going to solve this epidemic for us.”
But there is no such natural law. The evolution of a virus often takes unexpected twists and turns. For many virologists, the best example of this unexpected is a pathogen that has plagued rabbits in Australia for the past 72 years: the myxoma virus.
Andrew Reed, an evolutionary biologist at Pennsylvania State University, says Myxoma has killed millions of rabbits, making it the deadliest vertebrate virus known to science. “This is by far the biggest killer of any spinal disease,” he said.
After its introduction in 1950, the myxoma virus became less lethal to rabbits, but Dr. Reed and his colleagues discovered that it took the opposite direction in the 1990s. And a recent study by researchers published this month found that the virus seems to be evolving to spread more rapidly from rabbit to rabbit.
“It’s still a new strategy,” he said.
Scientists deliberately introduced the myxoma virus into Australia in the hope 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 keep them trapped, they have multiplied by millions by eating enough plants to threaten local wildlife and sheep farms across the continent.
In the early 1900s, Brazilian researchers proposed a solution to Australia. They discovered the myxoma virus in a species of South American cotton rabbit. The virus is spread by mosquitoes and flies, causing little harm to animals. But when scientists infect European rabbits in their laboratory, the myxoma virus proves to be surprisingly deadly.
Rabbit skin nodules filled with the virus. The infection then spreads to other organs, usually killing animals within a few days. This terrible disease is known as myxomatosis.
Brazilian scientists sent samples of the Myxoma virus to Australia, where scientists have been testing it in laboratories for years to make sure it is only a threat to rabbits, not other species. Some scientists even injected themselves with the myxoma virus.
After the virus was proven to be safe, the researchers sprayed it with a few warrens to see what would happen. The rabbits died quickly, but not before the mosquitoes bit them and spread the virus among others. Soon, hundreds of miles away, rabbits were dying.
Shortly after the introduction of Myxoma, the Australian virologist said. Frank began a cautious, long-term study of Fenner’s assassination. In the first six months alone, he estimated, the virus killed 100 million rabbits. Dr. Fenner’s laboratory tests determined that the Myxoma virus killed 99.8 percent of the rabbits it infected, usually in less than two weeks.
Yet the myxoma virus has not been able to eradicate Australian rabbits. In the 1950s, Dr. Fenner discovered why: Myxoma virus has become less deadly. In his experiments, the most common strains of the virus killed about 60 percent of rabbits. And the rabbits that were killed by the strains took longer to commit suicide.
This evolution is in line with popular thinking at the time. Many biologists believe that viruses and other parasites inevitably evolved to become milder – known as the law of perishable viruses.
“Chronic parasites, by evolutionary processes, have far less harmful effects on hosts than recently acquired ones,” zoologist Gordon Ball wrote in 1943.
Theoretically, newly acquired parasites were deadly because they did not yet adapt to their host. To keep a host longer, the thought is gone, giving more time to the parasites to multiply and spread to the new host.
The law of perishable viruses seems to explain why myxoma viruses have become less deadly in Australia – and why they were harmless in Brazil. The viruses developed over a long period of time in South American cotton rabbits, to the point that they did not cause any disease.
But evolutionary biologists have questioned the logic of the law in recent decades. For some pathogens, mild growth may be the best strategy, but it is not the only one. “There are forces that can push horror in the other direction,” said Dr. Katzorakis.
When Dr. Reed started his lab in Penn State in 2008, he decided to revisit the story of the myxoma virus. “I knew it was a textbook case,” he said. “I started thinking, ‘Well, what’s going on next?'”
No one has systematically studied the myxoma virus since Dr. Fenner stopped in the 1960s. (He had good reason to give up, because he helped eradicate smallpox.)
Dr. Reid arranged for Dr. Fenner’s samples to be sent to Pennsylvania, and he and his colleagues also tracked more recent myxoma samples. Researchers have sequenced the DNA of the virus – something that Dr. Fenner could not do – and have carried out infectious studies on lab rabbits.
When they examined the dominant viral lineages in the 1950s, they found that they were less lethal than the early viruses, confirming Dr. Fenner’s results. And the death rate was relatively low in the 1990s.
But then, things changed.
The new viral breed has killed more lab rabbits. And they often did it in a new way: shutting down the animal’s immune system. Bacteria in the intestines of rabbits, usually harmless, multiply and cause life-threatening infections.
“It was really scary when we first saw it,” said Dr. Reid.
Surprisingly, Australian wild rabbits did not suffer the horrific consequences of Dr. Reed’s laboratory animals. He and his colleagues suspect that the new adaptation to the viruses had a strong immune response in rabbits. Studies have shown that Australian rabbits have acquired new mutations in genes involved in the first line of immunity, known as congenital immunity.
As the innate immunity of the rabbit became stronger. Reed and his colleagues suspect that natural selection, in turn, favors viruses that can overcome this defense. This evolutionary weapon competition has erased the advantage that wild rabbits enjoyed for a short time. But these viruses proved to be worse against rabbits that did not develop this resistance, as in Dr. Reed’s laboratory.
And the arms race is still unfolding. About a decade ago, a new strain of Myxoma virus emerged in southeastern Australia. This branch, known as Linus C, is growing much faster than other clans.
According to a recent study by Dr. Reed and his colleagues, which has not yet been published in a scientific journal, infection testing suggests that new mutations are allowing the inherited C to work better from host to host. Many infected rabbits exhibit a strange form of myxomatosis, with extensive swelling in their eyes and ears. These are exactly the places where mosquitoes like to drink blood – and where the viruses may have a better chance of reaching a new host.
Virologists have seen some important lessons that the Myxoma virus can offer when the world is battling the Kovid epidemic. Both diseases are affected by the host’s defenses, not just the genetic makeup of the virus.
As the pandemic continues for its third year, people are more protected than ever before because of their developed immunity to vaccines and infections.
But coronavirus, like Myxoma, did not go the way of mildness.
The Delta variant, which grew in the United States last fall, was more deadly than the original version of the virus. Delta was replaced by Omicron, which caused less serious illness for the average person. But experiments by virologists at the University of Tokyo have shown that the Omicron variant is evolving into a more dangerous form.
“We do not know what the next stage of evolution will be,” Dr. Katzorakis warned. “That chapter on the evolution of virulence has not yet been written.”