With the latest omicron variant of Covid-19 now identified in two dozen countries, what can we expect next from the virus that causes it? Is SARS CoV-2 any more ingenious than other viruses in developing new strains, and will we be able to keep ahead of it in the race between infection and suppression? Professor Peter White is an expert in viral evolution and leads the White Laboratory at the University of New South Wales in Sydney, Australia. He spoke to David Fickling on December 1. A lightly condensed and edited transcript of the conversation follows.
David Fickling: What makes viral evolution, and broadly evolution of pandemic diseases, different from evolution elsewhere in nature? It feels like we're watching natural selection taking place in the span of days rather than millennia.
Peter White: The answer to that lies in the speed of evolution — the speed of generation of genetic diversity, or mutations if you like. The fastest of all those are viruses. Bacteria are slower and then of course we are the slowest, and you could draw a line through the mutation rates and see the correlation: If you have a small genome like viruses, you get a faster mutation. They change quickly. We don't. It will take generations, hundreds of years to change phenotypes for most mammals, but with viruses, it's very quick.
DF: And the generations themselves are ridiculously short for viruses, in terms of what we think of as a generation.
PW: If an e. Coli bacterium lands on a bit of sugar, think, "This is nice" and starts replicating, it goes from one cell to two, then four, eight, 16, 32 and it gets exponential. And you might think, "Wow, that's quick." But if a virus gets into a cell, it goes, "OK I'm in the cell now: One, 100,000, thank you very much, next cell." So within a few hours, if you're infected by a few particles, viruses can pump out billions of copies. And that takes, for most mammal viruses, about 14 hours to 20 hours. So when you sneeze, you've got a million viruses coming out your nose. When you have diarrhoea you have 10 billion viruses per gram of faeces, it's like pollen. Its job is to find the next host. That's why they evolve because if they don't, they don't exist. It's a selection of the fittest.
DF: We often talk about viral evolution as something that happens between individuals in the community, but with numbers like that, presumably, there are very important selective pressures happening within the host's body. Is one of those more important than the other, and how do the two of them interact?
PW: The virus will mutate in the host's body, and then if any of those mutations are good, they'll dominate. One thing I'm expecting with coronavirus that no one is talking about is recombinants. The strain I discovered that caused the norovirus gastro pandemic in 2012 was a recombinant of two previous strains: Half of its genome was from New Orleans and half from a Dutch virus. We know that with Covid there are five variants of concern, and they're good and efficient viruses. What happens if we take the best bits from one and the best bits from another and create a hybrid? Then we're going to get a recombinant. This happens all the time, in influenza, this is how we got the 1957 and 1968 pandemics. It's a mutation on a big scale, swapping genomes with each other, which is much better than if they tried to do it on their own. This is what scientists will be looking out for in their genomic sequencing.
DF: We've heard a lot of people surprised at the adaptive ingenuity of Covid, with the delta and omicron variants emerging. How do you look at it?
PW: I'm not surprised. I don't think it's any more agile than any other virus. It's doing exactly what a norovirus would do or influenza would do. Viruses will change and spread. This is exactly what happens to every virus that causes a pandemic. What about HIV? We don't really talk about that as a pandemic, though it's killed 36 million people. It is a pandemic, it's just a long one that's been going on since the 1980s, a three- or four-decade pandemic. And how did that virus come about? It was a recombinant of viruses in two smaller monkeys that a chimpanzee had hunted, which infected the chimpanzee efficiently but was also able to infect humans. And that is what led to the pandemic.
DF: Do the different interventions like vaccines, antivirals and social distancing have different effects on the selective pressures that the virus faces?
PW: Most interventions are selection pressure, and if it's a selection pressure on the genome then it will drive evolution. Let's start with the easiest one. If we make a drug against particular enzymes of the virus, then the virus will generate mutations because, if the virus doesn't mutate, the drug will kill it. So it's churning out a massive diversity of RNA sequences. The one that protects it from the drug will be selected, for that virus will come to dominate the population and all the rest will be dead, and then you have what we call a drug escape mutant or drug-resistant mutant. So that does happen, it's documented for every virus.
The other is the immune selection pressure. Everyone has been given vaccines based on the alpha strain, and we're now up to delta or worse. We know that there are 20 to 50 amino acid changes between the variants — they've made the transmission of the virus better but none have really escaped from the vaccine. So the worry we all get is, let's say 100% of the world is vaccinated against alpha and then the virus mutates. The antibodies our body has made to bind to the spike protein of alpha will no longer bind to the spike protein of the new variant, and that becomes what we call a vaccine escape mutant, and then the vaccine becomes not as good. That will happen in the future, but the boosters can easily be changed, so we should be able to stay ahead of it.
Then you have selective pressures like social distancing, and that would probably select for a more transmissible coronavirus.
DF: Some people make the argument that we're better off making more boosters available in richer countries where older populations are more at risk, rather than sending first and second doses to emerging countries with younger populations. What's your view on that, from the perspective of variant emergence?
PW: We should absolutely be doing everything we can to give the vaccine to developing countries. It's pretty clear we haven't done enough of that with South Africa at 25% double-dosed. The more we vaccinate, the more chance we have of stopping more variants from emerging. And we should be doing that anyway because it's the right thing to do. It's not that difficult and for the benefit, it's not even that expensive. It's going to be way more expensive if you don't.
DF: Most pharma companies seem pretty confident about their ability to reformulate the vaccine fairly rapidly. Can you explain why that is?
PW: Basically in the mRNA vaccine, there's only two things: a lipid nanoparticle, which contains a piece of RNA. The lipid bit's easy, they don't have to change that between variants. And then the RNA is, let's say, 2,000 nucleotides. Now with a new variant, we have to change that sequence. So we change, say, 100 base pairs in that sequence, and we're just going to re-do the computer, add slightly different ingredients, and off you go. The only problem would be FDA approved, but they'll probably say yes quite quickly because it's not likely to be very different harm-wise. The delivery system and everything else are the same and it shouldn't do too much in terms of poisonous side-effects. It might do something different in terms of immune response and that's what they'll look at.
DF: You often hear a question about whether epidemic diseases naturally evolve toward milder forms that we're going to crack down on less. Is that the case?
PW: As a virus evolves with the host, does the disease lessen? And why? Most of the time the evidence is probably yes, it does. I like to use bird flu H5N1 as an example. It's got a 50% mortality rate in humans, but to get that virus you need a very high viral load. You need to be handling birds with the virus. The disadvantage for the virus in that situation is, if the virus is killing the host very quickly, it's never going to get a good chance to get into the population. What a virus wants to do is kill the host damn slowly and make tons of it before the host dies. The less obvious it is that it's causing any damage to the host, then the longer it will survive. Even so, there are circumstances we've seen with rabbit viruses where if you kill quickly you'll spread better and evolve toward that form, and others where if you kill slowly you'll spread better and evolve toward that form instead.
DF: The humbling thing for us is the virus doesn't care whether we live or die. It just cares about how easy it is to reproduce. Our life or death is incidental to that!
PW: That's the only thing it exists for. There's so much of the virus produced that it will always find the best way. It's got plenty of choices.
DF: Has medical science changed the way viral evolution works, now that we do impose this new form of selective pressure that didn't exist in nature?
PW: It does change the evolution of the virus a bit. Whatever virus you look at, you get things that pop out like vaccine escapes, but it's never as bad as no vaccine. It wouldn't even put much of a dent in how well the vaccine has done in dealing with the disease. Rubella was killing 20,000 babies a year in the U.S. before that vaccine. People forget that with polio, with rubella, even in the late 1960s, people were dying massively. Then, bang, 99% of it stopped. But this is stopping people from dying, it's not stopping the spread. Given that we're only nearly two years into Covid, even the best scientists wouldn't have predicted how well, in terms of vaccines, we've responded.
DF: So your point is, we're probably not going to eradicate this, but if we can get a stalemate where it's not killing people in these numbers, that's a good endgame.
PW: This virus is always going to be with us, like influenza, and it's probably going to kill more people than influenza for quite a few more years. But the only way to get on top of that is to vaccinate.
David Fickling is a Bloomberg Opinion columnist covering commodities, as well as industrial and consumer companies. He has been a reporter for Bloomberg News, Dow Jones, the Wall Street Journal, the Financial Times and the Guardian.
Disclaimer: This article first appeared on Bloomberg. It has been edited and published by special syndication arrangement.