Thread by @TRyanGregory

One of the students in my evolution course asked a great question about whether vaccination will make it more likely that resistant variants will evolve. Here was my answer. 🧵

Super short version:

No, vaccines don't cause variants. (And antibiotics don't cause resistance). That's not how mutation and natural selection work.

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Longer version:

To answer this question, we need to consider that there are two different and independent processes at work. Then we can talk about the circumstances that make for a higher risk of new variants evolving.

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The first is mutation, which is the source of new variation. A mutation is a random mistake in replication leading to a genetic change that is then potentially passed on to the next generation.

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The key here is that mutations are random in the sense that they just happen by accident, regardless of whether they will be good or bad or have no effect at all. They're just errors.

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The second mechanism is natural selection. This is the *non-random* difference in survival and reproduction of individuals because of the traits they have, and the environment in which they live.

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In other words, some individuals survive more or have more offspring because they have certain heritable traits that happen to be relevant in that environment.

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The source of new variation is random (mutation) but if these genetic differences affect the phenotype in a way that impacts survival and reproduction in a particular environment, then which ones manage to be passed on will be non-random (natural selection).

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There's another factor here, which is population size. When we're talking about population sizes in viruses, you can think of both the number of viruses out there being replicated and the number of hosts that they can infect.

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Population size matters for two reasons. First, more individuals replicating means more chances for random errors to occur. Viruses have particularly lousy quality control in their replication, so mutations happen a lot. More viruses copying means more copying errors.

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The second reason population size matters is that natural selection is stronger in large populations (basically, non-random processes exert a larger effect with larger samples, whereas chance has a bigger effect with smaller samples).

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The other thing that matters with natural selection is the environment, which is what determines whether a particular mutation is beneficial, detrimental, or irrelevant.

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Vaccines can impose a selective pressure in that some mutations make the virus much better able to spread to unvaccinated hosts (as with the Delta variant of SARS-CoV-2) or better able to "escape" the immune system even if someone is vaccinated (as maybe with Mu variant).

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So, if you have lots of viruses replicating (high viral loads per host and lots of susceptible hosts), you will have more new variation arising by chance mutations.

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Vaccinating a large percentage of people both reduces the number of hosts that can become infected and the viral load of those who do get infected after being vaccinated. This would mean fewer new mutations showing up.

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Vaccines themselves do not cause mutations -- they actually reduce the conditions under which mutations occur.

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Having a fully vaccinated population also means that most people won't be infected even if exposed. This greatly cuts down on the population size of viruses, and means that even new mutations that might escape the immune system are more likely to be lost by chance.

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What you don't want is a more virulent or resistant mutant arising by chance and then spreading easily throughout a partially vaccinated population where population sizes are large and those variants can increase in frequency by selection rather than being lost by chance.

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Also, having lots of hosts available means that even variants that are very damaging or deadly to hosts can still increase in frequency. By contrast, if it's harder for the virus to reach new hosts, there may be selection for reduced impacts on individual hosts.

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The short version, then, is that to prevent more dangerous or resistant variants from evolving, we need high vaccination rates and measures to prevent transmission -- not just here, but globally.

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For a more thorough discussion of how natural selection works (and doesn't), feel free to download this paper (it's open access):

evolution-outreach.biomedcentral.com/articles/10.10…