As the Covid loss of life rate worldwide has fallen to its lowest degree for the reason that early weeks of the pandemic in 2020, it could be tempting to conclude that the coronavirus is turning into irreversibly milder. That notion suits with a widespread perception that every one viruses begin off nasty and inevitably evolve to develop into gentler over time.
“There’s been this dominant narrative that natural forces are going to solve this pandemic for us,” mentioned Aris Katzourakis, an evolutionary biologist on the University of Oxford.
But there isn’t a such pure legislation. A virus’s evolution typically takes surprising twists and turns. For many virologists, the very best instance of this unpredictability is a pathogen that has been ravaging rabbits in Australia for the previous 72 years: the myxoma virus.
Myxoma has killed a whole lot of hundreds of thousands of rabbits, making it probably the most lethal vertebrate virus recognized to science, mentioned Andrew Read, an evolutionary biologist at Pennsylvania State University. “It’s absolutely the biggest carnage of any vertebrate disease,” he mentioned.
After its introduction in 1950, myxoma virus grew to become much less deadly to the rabbits, however Dr. Read and his colleagues found that it reversed course within the Nineties. And the researchers’ newest study, launched this month, discovered that the virus seemed to be evolving to unfold much more shortly from rabbit to rabbit.
“It’s still getting new tricks,” he mentioned.
Scientists deliberately launched the myxoma virus to Australia within the hopes of wiping out the nation’s invasive rabbit inhabitants. In 1859, a farmer named Thomas Austin imported two dozen rabbits from England so he may hunt them on his farm in Victoria. Without pure predators or pathogens to carry them again, they multiplied by the hundreds of thousands, consuming sufficient vegetation to threaten native wildlife and sheep ranches throughout the continent.
In the early 1900s, researchers in Brazil provided Australia an answer. They had found the myxoma virus in a species of cottontail rabbit native to South America. The virus, unfold by mosquitoes and fleas, induced little hurt to the animals. But when the scientists contaminated European rabbits of their laboratory, the myxoma virus proved astonishingly deadly.
The rabbits developed pores and skin nodules full of viruses. Then the an infection unfold to different organs, normally killing the animals in a matter of days. This ugly illness got here to be referred to as myxomatosis.
The Brazilian scientists shipped samples of the myxoma virus to Australia, the place scientists spent years testing it in labs to ensure it posed a menace solely to rabbits and never different species. A couple of scientists even injected myxoma viruses into themselves.
After the virus proved protected, researchers sprayed it into a couple of warrens to see what would occur. The rabbits swiftly died, however not earlier than mosquitoes bit them and unfold the virus to others. Soon, rabbits a whole lot of miles away had been dying as effectively.
Shortly after myxoma’s introduction, the Australian virologist Dr. Frank Fenner began a cautious, long-term research of its carnage. In the primary six months alone, he estimated, the virus killed 100 million rabbits. Dr. Fenner decided in laboratory experiments that the myxoma virus killed 99.8 p.c of the rabbits it contaminated, usually in lower than two weeks.
Yet the myxoma virus didn’t eradicate the Australian rabbits. Through the Nineteen Fifties, Dr. Fenner found why: The myxoma virus grew much less lethal. In his experiments, the most typical strains of the virus killed as few as 60 p.c of the rabbits. And the rabbits the strains did kill took longer to succumb.
This evolution match with common concepts on the time. Many biologists believed that viruses and different parasites inevitably advanced to develop into milder — what got here to be known because the legislation 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 speculation, newly acquired parasites had been lethal as a result of they’d not but tailored to their hosts. Keeping a bunch alive longer, the pondering went, gave parasites extra time to multiply and unfold to new hosts.
The legislation of declining virulence appeared to clarify why myxoma viruses grew to become much less deadly in Australia — and why they had been innocent again in Brazil. The viruses had been evolving in South American cottontail rabbits for much longer, to the purpose that they induced no illness in any respect.
But evolutionary biologists have come to query the logic of the legislation in current a long time. Growing milder could also be the very best technique for some pathogens, however it isn’t the one one. “There are forces that can push virulence in the other direction,” Dr. Katzourakis mentioned.
Dr. Read determined to revisit the myxoma virus saga when he began his laboratory at Penn State in 2008. “I knew it as a textbook case,” he mentioned. “I started thinking, ‘Well, what’s happening next?’”
No one had systematically studied the myxoma virus after Dr. Fenner stopped within the Nineteen Sixties. (He had good purpose to desert it, as he had moved on to assist eradicate smallpox.)
Dr. Read organized for Dr. Fenner’s samples to be shipped to Pennsylvania, and he and his colleagues additionally tracked down more moderen myxoma samples. The researchers sequenced the DNA of the viruses — one thing that Dr. Fenner couldn’t do — and carried out an infection research on lab rabbits.
When they examined the viral lineages that had been dominant within the Nineteen Fifties, they discovered that they had been much less deadly than the preliminary virus, confirming Dr. Fenner’s findings. And the fatality fee stayed comparatively low by means of the Nineties.
But then, issues modified.
Newer viral lineages killed extra of the lab rabbits. And they typically did so in a brand new approach: by shutting down the animals’ immune programs. The rabbits’ intestine micro organism, usually innocent, multiplied and induced deadly infections.
“It was truly scary when we first saw that,” Dr. Read mentioned.
Strangely, wild rabbits in Australia haven’t suffered the grisly destiny of Dr. Read’s laboratory animals. He and his colleagues suspect that the brand new adaptation within the viruses was a response to stronger defenses within the rabbits. Studies have revealed that Australian rabbits have gained new mutations in genes concerned within the first line of illness protection, referred to as innate immunity.
As the rabbits developed stronger innate immunity, Dr. Read and his colleagues suspect, pure choice, in flip, favored viruses that might overcome this protection. This evolutionary arms race erased the benefit the wild rabbits had briefly loved. But these viruses proved even worse in opposition to rabbits that had not advanced this resistance, corresponding to these in Dr. Read’s laboratory.
And the arms race remains to be unfolding. Roughly a decade in the past, a brand new lineage of myxoma viruses emerged in southeastern Australia. This department, dubbed Lineage C, is evolving a lot quicker than the opposite lineages.
Infection experiments recommend that new mutations are permitting Lineage C to do a greater job of getting from host to host, in accordance with the newest research by Dr. Read and his colleagues, which has not but been printed in a scientific journal. Many contaminated rabbits show an odd type of myxomatosis, growing large swellings on their eyes and ears. It is exactly these locations the place mosquitoes wish to drink blood — and the place the viruses might have a greater likelihood of reaching a brand new host.
Virologists see some vital classes that the myxoma virus can supply because the world grapples with the Covid pandemic. Both ailments are influenced not solely by the genetic make-up of the virus, however the defenses of its host.
As the pandemic continues its third 12 months, individuals are extra protected than ever because of the immunity that has developed from vaccinations and infections.
But the coronavirus, like myxoma, has not been on an inevitable path to mildness.
The Delta variant, which surged within the United States final fall, was extra lethal than the unique model of the virus. Delta was changed by Omicron, which induced much less extreme illness for the common particular person. But virologists on the University of Tokyo have carried out experiments suggesting that the Omicron variant is evolving into extra harmful kinds.
“We don’t know what the next step in evolution will be,” Dr. Katzourakis warned. “That chapter in the trajectory of virulence evolution has yet to be written.”