ML: Is this the first time that there is a sense in rich countries that it's in their interest to vaccinate the world because of the threat of mutation?

RH: I think the way you frame that question specifically, the answer is yes. The first time that a global pandemic was recognized as presenting a national security threat to the United States was with HIV. HIV was in Africa. It was destabilizing and designated a national security threat. But that was a different dynamic. It wasn’t spreading as rapidly. This is the first time that a changing, evolving disease has made this kind of a claim on the attention of world leaders.

But Covid made that claim even before mutation became a major issue and it did that obviously because of the scarcity of vaccines and then the economic impact. Even before the mutations began to demonstrate that they could generate new waves of infection—even after vaccination—we recognized that as long as the virus was circulating freely, and transmission rates were high, that there were going to be opportunities for it to mutate in ways that might allow it to evade the countermeasures that we have.

ML: This has as much to do with the nature of the virus as anything, right? With the flu, you wouldn't worry to this extent that it's going to mutate into something that's going to evade a vaccine.

RH: Actually, there are a lot of analogies with flu. You typically have three or four strains of flu circulating globally. Each of them changes over time, though they don’t seem to change quite as rapidly as Covid. With flu, every year, you have cycles of flu epidemics. They don't devastate society but there's a semi-annual review to make sure the vaccines are the right ones.

Every so often, a flu virus either jumps directly from an animal species, or you have a recombination event where two flu viruses interact and create something that looks brand-new to the immune system. Then you have a virus that has pandemic potential. These occur with the periodicity of maybe 10 years on the short side to maybe 40 or 50 years on the long side.

ML: Is the rate at which Covid seems to be evolving greater than the rate at which flu evolves? Is it just because more people are getting it and so it has more chances to replicate?

RH: You've got a virus that’s trying to optimize for this new environment that it's in. And what's interesting is the kinds of pressure that are put on the virus. There are really two important kinds of pressure that would be put on the virus in a population where nobody's been exposed to it and nobody has any immunity. The virus is racing with the other viruses in the neighborhood. And if a virus can develop an adaptation that makes it transmit faster, then it emerges from the pack and drowns out everybody else and becomes a dominant strain. That’s what delta did. Delta mutated in a way that made it super-transmissible, much more so than the virus was at the outset.

The other kind of pressure that a virus can be subject to is the one that emerges once a population begins to build up immunity. If that immunity has been produced largely through vaccination, then the virus is driven to mutate in a way to evade the immunity provided by the vaccine. The thing we don't really know is how much space the virus has to mutate before the mutations start to impose costs of their own—if it could mutate to a point where it just completely escapes the vaccine, or if there's some kind of limit on what it can do.

What's really striking about omicron is that is has 50 mutations. Delta wiped out other variants because it was so much more transmissible than its competitors, even if its competitors were potentially more lethal. This thing—omicron—looks like it's really souped up to evade whatever immune response the human population has developed. It has mutations in areas that we believe will ramp up its transmission, so it can compete with delta. The numbers that we're seeing coming out of South Africa are not reassuring. Remember, this is summer in South Africa. This is when there shouldn't be a lot of transmission, and yet omicron is exploding there.

ML: So we create these vaccines, we administer them unevenly across the global population, and it creates pressures on the virus to change in certain ways. If we were to set out to create conditions in which the virus was most likely to learn how to evade a vaccine before we're all vaccinated, how different would it be from what we've done?

RH: It would look pretty much like what we've done.