The below is an interview with Rob Dunn (RRD), Matt Koci (MK), Sergios-Orestis Kolokotronis (SOK), David Rasmussen (DAR), and Jessica Brinkworth (JFB). Lucie Ciccone graciously lent their insights and served as additional sets of eyes.
One of the most indefatigable laws of nature is the law of natural selection. Natural selection is, at once, a simple and yet surprising law. Through a simple mechanism, it generates surprising forms. That simple mechanism is this… In any population of organisms, genetic variation exists. That variation encodes differences in the physical traits of organisms which affect their ability to survive and reproduce. Individuals with genes that lead them to have physical traits that make them less likely to survive and reproduce are “selected against.” Their genes are less likely to be passed one generation to the next. Meanwhile, the genes and traits that are left, un-winnowed by nature’s brutal sickle, spread to the next generation; by surviving, they are favored.
When Charles Darwin first wrote about the law of natural selection, he imagined that the evolution in response to selection would be slow. Humans would be left, he thought, to study the consequences of natural selection but unable to see the process in real time. It would have delighted Darwin to know that in this way that he was wrong. The good news is that the consequences of natural selection, evolution and even the origin of species can be observed in real time. This is true, for example, with experiments done on bacteria in laboratories. It is also true, with regard to the virus that causes COVID-19. Much as the finches, now called Darwin’s finches, evolved after having arrived in the Galapagos Islands, the virus that causes COVID-19 is evolving rapidly as the virus continues its global spread . In this light, I thought it would be worth sitting down (virtually of course) with a group of ecologists and evolutionary biologists who have focused their life work on viruses and the peculiar ways they change.
An important piece of information to know from the start relates to sex. In many species, sexual reproduction allows the genes from two (or more, fungi are complex) parents to come together to yield offspring that are genetically novel and also have novel physical traits. Viruses are different. They can swap genes in wondrous ways, but the far more common source of their variation results from mutations, chance changes in their genetic letters of their genes. Of course our genes mutate too, but viruses mutate at a rate much higher than in cellular life forms, such that mutation rather than the reshuffling of genes among offspring creates most of the genetic variation natural selection can act on in a viral population. Mutant forms of viruses are called variants. In some cases, the variants are genetically distinguishable but not different; their mutations have no effect on their biology. In other cases, the variants are genetically distinguishable and different in their biology. Those variants are called strains. This a subtle distinction, but an important one.
RRD: So now let’s start by talking about what happens to those viruses that have mutations that alter their biology, what I’ve described above as new “strains.” Most new, mutant strains die, or given that we are talking about viruses, which aren’t quite alive or dead, fail to spread and replicate. Let’s talk about what happens to those strains with mutations that are, despite their mutations, still capable of spread and replication.
SOK: Natural selection acts as an evolutionary force to increase the frequency of strains with beneficial mutations and decrease the frequency of strains with deleterious mutations – whether we focus at the intrahost level, i.e. within each infected individual, or the community/host population level, i.e. a viral metapopulation of sorts – according to the [dis]advantage said mutations confer to the viral variants.
RRD: So natural selection favors some mutant strains relative to others. This happens inside the host. If you have COVID, it is happening in you right now. It also happens when the virus is spreading among hosts, from you to someone else.
MK: And I think it’s important to recognize that everything we do to try and slow the spread of the virus puts pressure on the virus and could end up conferring an advantage to one of those mutants over another. I think this new strain (B.1.1.7 if you’re up on your variant lingo!) from the UK could be a good example of that. The virus spreads in coughs and sneezes and gets breathed in by its new victim. It almost certainly takes more than just one virus particle to make you sick, but how many we don’t know. For argument sake, let’s say it takes 5,000 individual viruses to make you sick. If you’re talking to someone who has the virus the closer you are to them the more virus you’ll be exposed to, especially if you both aren’t wearing masks. When you both put on masks and you back away from each other beyond 6 ft, you’re doing that to reduce the number viruses you might be exposed to. Ideally to a level below how many it takes to establish an infection in you. So now instead of breathing in 5,000 viruses, you breathe in 500.
But if the virus randomly makes a small change in its spike protein so now it can bind to your lung cells more tightly, more efficiently, maybe that virus variant doesn’t need 5,000 viruses to make you sick. Maybe that one only needs 1,000 or even 500. So now that strain will spread more efficiently though the population because it can get around the selection pressure we imposed on it.
RRD: And different mutant strains might be favored within hosts versus with regard to spread among hosts. What makes you good at surviving and replicating in a particular person, might not be the same thing that makes you good at spreading among people.
JFB: Popping in to add that host environmental conditions also have a big impact on pathogen success. If you densely pack your hosts (think cities), stress them out and create conditions where they are more likely to be immunosuppressed (think modern life) and without adequate care you can simultaneously create a large host population whose adaptive immunity is somewhat hobbled, and other aspects of immunity disrupted but functioning [e.g.innate, cell-autonomous immunity (the immune tactics that a cell might have all by itself such as enzymes, restriction factors that chop up infecting viruses etc.], and create conditions beneficial to infection and replication. This increases the odds that mutations emerge that can escape immune tactics that are functioning – like cell autonomous immunity – or new virulence factors.
RRD: So, in essence, stressed out, high density human populations with poor access to health care are ideal settings for the origin and success of novel strains with novel mutations that can escape immune systems (or vaccines) and, at the same time, be more deadly. Not great news for America.
JFB: These are the conditions under which a number of pathogenic bacterial strains have emerged, including a MRSA that creates its own wounds that arose out of the New York State prison system, and E. coli O157:H7 out of intensive farming operations. Now, there are other factors in play in the evolution of those microbes, including the long half-life of antimicrobials that affect selection, and the amount of time these bacteria can be outside of a host – but the basic mechanics are the same for easily transmitted respiratory viruses. Pack your hosts close together, stress them out, deny them care and you create conditions for increased replication and change.
RRD: Yikes.
RRD: All of the natural selection we are talking about here acts on the variety that results from mutations. Jessica, you’ve noted that the duration of infections in people affect the number of mutations that might arise. What factors affect how fast a particular virus strain mutates?
JFB: Speaking from an immunological and epidemiological standpoint, the availability of hosts also affects how fast a virus strain may shift or rise to dominance. To a certain extent the rise of mutant viruses is a numbers game. The more hosts available to infect, the more likely it is that a variant with beneficial mutations will become prominent. This is a factor outside of those intrinsic to the virus itself and it matters for circulating viruses. Viral life cycles start and end with a host. In a birds eye view sense (as opposed to, say, looking at mutations arising in quasispecies inside a host), sampling a host population, lack of host availability can smother mutations that arise – even really beneficial mutations – because it limits transmission to the next host.
RRD: OK, so the total number of mutations in a virus population is larger if the population is larger. Are there other factors related to the virus population that affect the total number of mutations in a population, other than the things you’ve just mentioned plus population size?
MK: Yes, and especially for RNA viruses. RNA viruses in many ways are the best example of Darwinian evolution. For most RNA viruses the enzyme they make that copies their genome (viral RNA polymerase) can’t proofread and edit the copies they make.
RRD: So this enzyme is like a little monk in the cell copying and recopying the virus’s ancient text.
MK: A drunk monk.
RRD: Got it.
MK: Each infected cell can produce 500-60,000 daughter viruses. That’s a lot of copying so there are bound to be a lot of mistakes.
RRD: The drunk monk again.
MK: In fact there are so many errors, virologists talk about the viruses that result from an RNA virus infection as a quasi-species cloud.
RRD: Sounds like a medieval monster. But the idea, I guess, is that the monks are sufficiently imprecise that the offspring of one virus are almost like species into and of themselves, a cloud of species.
MK: Yes, but this is where the Linnaean classification system really breaks down for viruses. We use terms like genus and species, but they don’t really work the same way as they might for animals. Viruses don’t mate. Even terms like strain, variant, and isolate can mean different things depending on the virus you’re talking about and the context. In fact, the high error rate in RNA viruses is thought to be part of their evolutionary strategy. If you create 1,000s of offspring many with random mutations it increases the chances that one of them will be better suited for survival. Many of those mutations will make things worse for the virus and may even render them inert.
RNA viruses typically make one mistake out of every 10,000 to 1,000,000 bases copied per infected cell. However, the one exception to this actually are the coronaviruses. It is the only type of RNA virus I know of that DOES have the ability to proofread.
DAR: Coronaviruses are actually pretty unique in that almost no other RNA viruses have proofreading capabilities! As the virus’s polymerase replicates its RNA, other enzymes in the replication machinery check to see if there’s been a mistake and fixes those mistakes.
RRD: Oh, well this is good news. Coronaviruses are less drunk monks, maybe careful monks even.
MK: Yes. The thought is, that based on how sloppy RNA polymerases are, coronaviruses shouldn’t exist. Their genome is big for an RNA virus, some 30,000 bases long. It is way easier to make mistakes in copying a big genome than a small one, and the way that coronaviruses go about their business in cells, details of their biology, leaves them even more prone to mistakes. So they carry an additional protein that helps them account for this, a monastic proofreader. Studies with the first SARS virus suggest its mutation rate is 10 times lower than it would be without this proofreader, and by all accounts this coronavirus (SARS-CoV-2) works the same.
This proofreading function is part of what has slowed our ability to generate antiviral drugs against COVID-19.
RRD: Wait, why is that Matt?
MK: One of the major parts of the virus we target with making antiviral drugs is the polymerase, which is to say the genes that encode the monk. Especially since RNA viruses are normally sloppy, we can treat people with drugs that look a lot like one of the building blocks of RNA (A, G, C, or U nucleosides, the RNA version of DNA nucleotides). When the viral polymerase uses the drug instead of the real thing, it causes the RNA copying to stop. So the drug blocks the ability for the virus to copy itself. However, since coronaviruses can proofread, if one of these drugs is used by the polymerase, the other enzyme will catch it and can fix the error.
RRD: Wow, so with other viruses we rely on their messiness to “trick” their system. But coronaviruses catch our fakes.
RRD: Now, what factors influence how many of those mutant strains might be expected to be more successful than their non-mutant relatives (the wild type strains)?
SOK: The now classic D614G mutation in the Spike gene was not dominating prior to the geographical expansion of SARS-CoV-2 in Europe. Now we’d be tempted to call it ‘wild type’, but in February 2020 we weren’t. Demographic expansions of the virus follow human movement and behavior in this case, given the mostly airborne transmission route. A novel variant with mutations conferring only a slight selective advantage may grow in numbers rapidly in an ecological takeover scenario because large numbers of humans congregated during superspreader events.
RRD: When we look at the UK strain of the virus that causes COVID-19, it appears that it has something like 23 different mutations. What does that tell us?
SOK: Variant of Concern 202012/01 belongs to lineage B.1.1.7. 23 mutations are indeed more than what we’d expect though evolution based on epidemiological trends.
RRD: Pausing for clarity here. You are saying that what I’m calling the UK strain should be called “variant of concern 202012/01”? Scientists should just never be allowed to name things.
SOK: Well, it was named ‘Variant under investigation’ at first when its epidemic growth was observed in SE England, and became ‘of concern’ soon after. Naming credit goes to Public Health England. We also like to abbreviate names, so you’ll see it referred to as ‘VUI’ or ‘VOC’. The Nextstrain framework proposes a phylogeny-informed classification that is backwards-compatible as time goes by and names phylogenetic clades of the virus using criteria based on time and frequency criteria (see https://virological.org/t/updated-nextstain-sars-cov-2-clade-naming-strategy/581 for info). At least, we refrain from calling it the ‘British virus’ or the ‘Kent variant’, like politicians and some media platforms. You’ll see this VOC also referred to by its hallmark mutation in the receptor-binding domain of the Spike glycoprotein, 501Y.V1 – standing for amino acid position 501 mutated to tyrosine (letter code: Y) from asparagine (N), version 1. ‘Version’, yes, because there is now 501Y.V2 that emerged in South Africa and is another VOC harboring another mutation (E484K) in the Spike protein potentially impacting neutralization by antibodies. We must come up with a nomenclature system adapted to the pathogen in question that will stand the test of time and constant revisions. Future-proof standards can be tough to invent. I guess one could start calling variants human names, like storm systems…
RRD: Yes, I think it would be easier to talk about all of this if “variant of concern 202012/01” were called Mildred.
SOK: Or my favorite: names drawn from Greek mythology and literature.
RRD: So says the guy named for a famous Greek hero.
SOK: Getting back to the main thread… Data from immunocompromised infected individuals reveal a higher number of mutations accumulating more rapidly than expected.
RRD: So people who are immunocompromised who get COVID-19 become a sort of incubator for rapid viral evolution. Good god. This is in line with what Jessica was saying earlier about stressed hosts. Immunocompromised people are, in essence, extremely stressed hosts.
SOK: Therefore, we hypothesize that this variant emerged and evolved in an immunocompromised individual presenting with a chronic infection. Eight of the 23 mutations localize in the Spike protein gene. This has an added importance due to the antigenic properties of Spike, that is the ability of our antibodies to ‘neutralize’ the virus, and the expected success of antibody treatments and vaccines.
RRD: Which is to say, the mutations are in the same part of the virus that antibody treatments and vaccines target. And if this part of the virus changes a lot, those antibody treatments and vaccines might no longer work. Yuck. Mildred is terrible.
RRD: I am struck in considering COVID-19, that the potential for evolution is very different from most other viruses. Its population sizes are huge. It is in many different regions (with different climatic conditions). Am I right that its global distribution makes it unusually likely to be a virus that begets many new strains, adapted in new ways to the global population or adapted in new ways to local conditions or human genotypes?
SOK: Local adaptation is a scenario that should be considered in public health and genomic surveillance.
RRD: So we could see locally adapted coronavirus strains, adapting to regions and people the way that Galapagos finches adapted to individual islands and resources.
SOK: Yes, but that said, human travel networks tend to homogenize the viruses in different regions by migrating variants around the country and across borders, and thus preserving the cosmopolitan character of a pandemic pathogen.
MK: I agree with Sergios that global travel helps homogenize the viruses around the globe, but I think the finches analogy takes things a bit too far. Humans in Europe and humans in Brazil aren’t different ecological niches at the level of the environments Darwin’s finches adapted to. If you force a ground finch to survive on a cactus, it’s going to starve. The variants of SARS-CoV-2 that develop south of the equator will still do quite well in the northern hemisphere.
RRD: But presumably different genes favor survival in arctic air than in Amazonian air. Or is this not such an important factor?
MK: Could some strains become more or less stable in some environments, yea maybe, possibly, but the basic architecture of a coronavirus is the same across all coronaviruses. They all have the same viral proteins on their surface, the same basic shape and volume. There may be some differences in the amino acids in those proteins that affect stability some, but it’s the lipid coat that makes them the most vulnerable to the environment and the lipid is stolen from the host cell. That’s only going to vary but so much.
Plus, I would say the virus already has one of the best things going for it. The number one trait I would pick for myself if I was a virus bent on world domination would be the ability to spread from host to host before the first host knows it has been infected. People with SARS-CoV-2 appear to be most contagious 2-5 days before the onset of symptoms. This pre-symptomatic spread is likely one of, if not the reason this coronavirus became a pandemic and the previous SARS-like viruses didn’t. If you can get in, replicate, and move on to your next host before the first host even knows it. Any other changes are just gravy.
DAR: Yes, this seems to be the winning strategy for human coronaviruses. All the human coronaviruses that have previously emerged in humans and managed to remain in the human population over long periods of time, what we call ‘endemic’ pathogens, only cause fairly mild or asymptomatic infections like the common cold
MK: Now you can and often do end up with different types of viruses circulating in different parts of the world that each would require their own vaccine. That is to say the random mutations that end up making the virus resistant to the immune response humans make are different in one region compared to the other. From a vaccine production standpoint this makes things worse than having one dominant strain everyone is dealing with. If you just have one dominant strain you can make one vaccine for everyone. If you have regional variations in serotypes you have to make lots of different vaccines, or try and make one that works against lots of them. But it does suck when that one dominant strain changes after you’ve already started your mass vaccine campaign.
So yes, a more broadly distributed virus is going to lead to more variants, and since this is a random process the variants that happen in one place aren’t necessarily going to be the same ones in another place. There will likely be different selection pressure on However, I have a hard time seeing things evolve into genotype specific variants.
If you really want my nightmare scenario, it’s less about adaptation to local human populations, and more adaptation to different wildlife populations. Whether that’s mink, deer, bats, cats, gulleillas, monkeys, or God forbid all of the above. This virus came from nature and now humans have spread it all over the place. If different humans in different parts of the world start giving it to wildlife and/or farm animals we could set up a situation where we create multiple different new animal reservoirs for this virus. Each of those animal reservoirs will push the virus in very different directions as it adapts to that new animal. If it still retains its ability to jump back to people…that might be time to pack for Mars.
RRD: If we are seeing five strains of novel coronaviruses, how many might there really be? Walk me through the math. How many individual virions are there right now? What proportion have we sampled?
SOK: Many strains could emerge and become established in circulating in humans. Out of the 93,765,725 cases worldwide only 0.004% has been genome-sequenced, which is indicative of the limits of genomic surveillance.
RRD: Give me a guess. More like ten strains right now? More like 1000?
Note: Here, no one was willing to hazard a guess.
MK: No one is going to guess, because it’s an impossible question. We can hazard a guess as to the numbers of genotypes out there, but how many of those genotypes are actually functionally different viruses (for example produce more or less virus per infected person), you might as well ask what the final score of the Super Bowl is going to be in 2030.
DAR: I won’t hazard a guess either for the same reason as Matt. But perhaps more interestingly, we’re starting to see some of the same mutations, especially in the Spike protein, pop up repeatedly in different strains. To the mind of an evolutionary biologist this suggests that there are a limited number of ‘pathways’ the virus can use to increase its fitness, and we may have already seen the virus evolve along the most easily accessible pathways, that is, the combinations of one or two mutations that selection can easily find to increase fitness.
RRD: Sometimes it is useful to think from the perspective of the virus. What sort of release of vaccines makes the evolution of viruses that are resistant to the vaccines most likely? Which behavior by humans leads the virus to evolve to escape vaccines rather than to herd immunity?
SOK: We would release a vaccine with low-to-moderate efficacy, so that the evolutionary potential of this coronavirus would not be hampered.
MK: I’d do what we’re doing in the US. Allow the virus to run more or less unchecked. Then save what few antiviral therapies you have for just the sickest people with the most comorbidities, who likely have the highest viral load and therefore more variants that have evolved within their bodies.
RRD: Then you’d give them the antiviral therapy. And because they have so many variants, the odds that one of them has mutations that allow the virus to survive the therapy is higher.
MK: Yes. And first let me say I’m not advocating to not treat the sickest people, but most of the therapies we have work best when used before people are really ill. By the time they are really ill, you have one of two situations. In some cases, probably a lot of cases, the virus is mostly gone and it’s their immune system that’s doing the damage and so therapies against the virus probably aren’t that helpful. Alternatively, there is so much virus there you can’t get enough drugs into the patient to really make a difference and you end up selecting for new variants that can evade the therapies.
Actually this is why the immunocompromised have been identified as the source of many of the variants. It’s not because they are/were immunocompromised, it’s because they were infected for weeks to months and in the hospital receiving convalescent plasma therapies and/or monoclonal antibody therapies for weeks to months to try and save their lives. It’s just like the use of antibiotics for bacterial infections, overuse of a drug that does not completely inhibit growth will very efficiently select for new variants.
In the lab, if I want to make an antibody or drug escape mutant virus I take high titer virus and pass it on cells in the presence of low levels of neutralizing antibodies, or low levels of antiviral drugs and wait for evolution to spit out a resistant variant. It seems to me that’s what we’ve set up here.
RRD: Would we know if there were already strains of the virus that were resistant to the vaccines?
SOK: It’s too soon to know the efficacy of vaccines in the wider population.
DAR: We know from the vaccine trials run last year that the Moderna and Pfizer vaccines were very effective at providing protective immunity. But some of the new strains we’re seeing this winter harbor antigenic escape mutations which allow the virus to escape antibodies generated against the vaccine. But fortunately, our antibodies target many different regions of the virus and it’s unlikely that any single mutation would allow for complete escape. And while there haven’t been comprehensive studies, it does appear that current vaccines offer a lot of protection against these new strains.
JFB: We know that at least one vaccine is not effective, for its indication of preventing severe infection, against the SA strain. I think if we take the approach of precautionary principle, we should assume, given the sheer number of infections worldwide, that there will be strains for which particular vaccines (there are a little over 30 approved worldwide, and 170-ish in development) will not be effective. There are a lot of technologies being used here – mRNA vaccines, Adenovirus vaccines, traditional antigen-based vaccines. Not all of them are targeting the same structures and some of them are going to be more sensitive than others to changes in virus structural composition not just in terms of stimulating appropriate host recognition, but also in terms of vaccine manufacturing protocol adjustment to different viral targets as strains arise. Moreover, we know that at least some aspects of immune memory against Beta-coronaviruses die off after a couple of years. So I think the safest thing at the moment is to assume that vaccine development and distribution and timing is going to be a long-haul effort, regardless of resistant strains circulating.
RRD: What is going on with this virus in five years? Are you altering your personal life with the long-term trajectory of this virus in mind?
SOK: If the vaccines confer medium-lasting immunity, it could become yet another seasonal coronavirus causing local and seasonal epidemics. As biomedical innovation will add to the arsenal of antibodies, antivirals, and drugs to control cytokine storms, we’ll be able to claim we have a handle on the situation. In 5 years we will be in a better position to understand and potentially treat the long-term effects of COVID-19.
RRD: But what about your own actions?
SOK: I am no longer thinking of travel the way I used to. Childcare is organized chaos! By the time it’s safer to congregate again, it’ll be a couple of years at least that we won’t have seen most friends and family.
MK: Wow, you know I’ve not really thought about that yet. Certainly, time will tell, so I reserve the right to disavow everything I’m about to say should Nature lob another grande at us, BUT at least as it relates to SARS-CoV-2 I see light at the end of the tunnel. So far most of the vaccines provide complete protection from death and severe disease caused by all of the variants, even those that seem to be able to evade the antibody response. So the vaccines that do a good job of inducing both antibody responses (B-cells) and T-cell responses give you the 1, 2, punch the immune system is designed to provide. And if the pathogen mutates to evade the right-hook, you’ve still got the upper-cut. I don’t see SARS-CoV-2 mutating so much so quickly that it completely evades our immune system. And, it is amazing how much we know about this virus in just 13 or so months. I suspect in the next 6 months we’ll know exactly what epitopes confer the best protection and our vaccine development will be able to keep pace with those changes if needed.
So for me, after I’ve gotten both shots, I’ll be comfortable getting on a plane and going back to normal, albeit maybe a little more guarded, for the first year or so. And unless I see evidence that we’re not keeping up with it’s mutations, I suspect, 3-5 years out I’ll be back to more or less normal.
But how “normal” will the future be? The one variable that’s the hardest to predict is what do the rest of the humans on the planet do? The history books always say the “Roaring 20s” were a response to WWI. But the 1918 pandemic killed more than WWI. I would not be surprised to see another “Roaring 20s” in response to this pandemic.
JFB: I came to terms with a few things last February – that I wouldn’t be able to go home. That I’d probably lose two years or more with my family etc.. Shortly thereafter I realized that there are goals I had that won’t be met in the next 5 years, including traveling to particular destinations with my kids etc.. I’m at risk, and I’m from another country so things are a bit different for me. I’m also still working to get tenure. Figuring out how to make the grade and homeschool and work in safe conditions has been a trip. It’s been a year and we are still troubleshooting how to do our immunological work, which had been structured as 12-14 hour experiments completed in shifts by teams of 2-3 people. That’s not practical in just about any cell culture room as they tend to be small. We are working it out. Hopefully, it’s ironed out before 5 years pass 🙂
Five years, though, from now I think we will have found some acceptable number of annual infections and deaths…like we have with flu. I feel a bit more upbeat about a global vaccination effort at the moment, than I did last year – but for many reasons this isn’t like smallpox. Polling right now indicates large numbers of people in the wealthiest nations in the world do not want to be vaccinated. That’s just one of many wrinkles.
RRD: How likely is it that in the next ten years we see another virus just as bad or worse than the virus that causes COVID-19?
SOK: Very likely. Pathogens with tissue tropism for the respiratory system find great potential for demographic expansion in urban centers, and urbanization is growing – it is projected that 68% of the world’s population will live in urban areas by 2050. Influenza virus subtypes, like H5 and H7, emerge and re-emerge in wildlife with sporadic spillovers in humans.
MK: 10 years? We will certainly see more near misses like MERS, SARS-Cov-1, NIPA, Zika, and the various H5, H7, H9 influenza viruses, plus probably new players we’re not paying attention to right now or even know about. Will we see something at the level of COVID-19 or worse in the next 10 years? I certainly don’t rule it out. All the conditions that gave us SARS-CoC-2 are still in play, but we don’t even know the number of things that have to go wrong in just the right order to create a COVID-19. The right mutant is formed in the right animal, at the time the right human is walking by. That human has to have enough contacts with other humans, and so on. Again I won’t be surprised but I don’t want to make some version of the gambler’s fallacy. In either direction. Just because the last coin toss came up heads doesn’t mean anything about the next coin toss.
JFB: another virus just as bad as SARS-CoV-2? New pathogens emerge annually. With increasing frequency we see spillover of totally novel pathogens into human populations. It would be easy to say, “well our surveillance is so much better now – of course we see spillover” – but we are a much more invasive species than we were even 20 years ago. We are rapidly reducing non-anthropogenic zones across the world. That there will be another novel pathogen that leads to severe infection is without doubt. There are bound to be multiple.
The likelihood that another that is just as contagious – I don’t know. It seems less likely. But so much of what we can estimate here is based on what we have traditionally valued as important questions in health and science. There are questions we have long considered not valuable enough to ask – like how many new cold viruses emerge every year? Not that valuable from a mortality or morbidity standpoint most of the time, so we don’t prioritize it for funding and, therefore, we don’t ask. Before 2002….and even after, to a certain extent, coronaviruses were kind of an eccentric area of study. I think if we want a better estimate of what will happen in the next 10 years, the way we fund science and think about what is valuable to know has to change. Over the last two decades devastating cuts have been made to the agencies charged with funding people asking these questions. There has been a big emphasis on pigeonholing funding via agency and section for decades so that interdisciplinary approaches to these problems are increasingly harder to pitch. The last 8 years has seen a Congressional push to make projects funded by the NSF immediately financially accretive. This has been intended to push money away from evolutionary biology, social sciences (except economics) and related fields, into the maths and engineering. Maths and engineering can’t solve such problems alone. They require the basic research of these other fields. I guess the short version of this is 1) I don’t know and 2) I don’t think there is the political will or, possibly, understanding of how this work works, to know 3) …but I really hope that changes.
Who We Are
RRD is Rob Dunn: Rob is a professor at NC State’s Department of Applied Ecology who studies the often observed, but poorly understood, world around us – from foot fungus to sourdough microbes.
MK is Matt Koci: Matt is a virologist and immunologist working on host-microbe interactions in birds. He is based at NC State University and has also contributed to A High School Q&A About Covid–19 and A Primer On and Conversation About the Biology and Evolution of SARS-CoV-2, the Virus That Causes Covid-19.
JFB is Jessica Brinkworth: Jessica is an evolutionary immunologist and biological anthropologist. She asks “Why do some people get sick and others do not?”, focusing on variation in host factors and social conditions contributing to severe infections, including sepsis. She is based at The University of Illinois Urbana-Champaign’s Department of Anthropology.
SOK is Sergios-Orestis Kolokotronis: Sergios-Orestis is an evolutionary biologist who studies infectious disease systems and biodiversity of conservation concern. He is an assistant professor of epidemiology and infectious diseases at the School of Public Health, SUNY Downstate Health Sciences University, and a research associate at the American Museum of Natural History.
DAR is David Rasmussen: David is an infectious disease biologist at North Carolina State University.