Evolution, the idea, is one of those beautifully simple concepts that explains so much. You’ll sometimes see it described as the “theory of evolution” - but I don’t think that’s right. For me, evolution is a consequence; an unavoidable consequence of some very simple circumstances.
If you have a few key things in place, it happens. Simple as that.
So what are those key things? You need a population that reproduces. You need there to be some potential for variation in the resultant offspring. You need those variations to be heritable. That’s about it.
The basic idea is this. Suppose some offspring have a variation that allows them to be a bit more successful in producing their own offspring. If that variation is inherited, then, over time, the proportion of the population with this variation will dominate. Eventually, this inherited advantage becomes the norm.
When you’ve got the key ingredients in place, evolution just happens. It’s a consequence of certain conditions. That’s why I don’t like to describe it as a “theory”, as such. It’s more akin to a mathematical theorem; if we have x, y, and z then A is true.
Without the adaptability conferred by evolution species would not be able to successfully respond to any adverse environmental changes and would just die off.
Of course, even though the basic principle is beautifully simple, things are a good deal more complex in practice. Evolution is like a constrained optimization process - and because the main processes by which variation occurs are essentially random you’re not guaranteed to get the most optimal variation possible for any specific environment. However, I think we could probably all agree that in many cases we do get a pretty good solution. Maybe we’d be even better off if our eyes could also see into the infra-red, but what we do have is pretty cool.
For something as complex as a human being, evolution has honed us over millions of years and, despite one or two weird and definitely sub-optimal variations having been fixed, we’re in not too bad a shape overall.
But don’t be beguiled by the simplicity of the basic principles into thinking we understand things better than we do. Newton’s 3 laws for physics are, similarly, beautifully simple, but lead to such a vast range of complex and different potential behaviours. The simple guiding principles of evolution have generated the astonishing complexity of an animal, us, who can at least partially understand how we got to where we’re at biologically speaking, and can even tinker with that through various medications, procedures and therapies.
And tinker we do. But we do so entirely at our own peril and not without a certain degree of hubris.
So our guiding principle should be this: evolution may not have given us a perfect solution, but before tinkering with those evolutionarily-driven mechanisms we’d better be darned sure we know what we’re doing
One of those evolution-driven solutions, or mechanisms, is our immune system. It’s an extraordinarily complex and adaptable system that protects us from all manner of nasty little things. It has been honed over millions of years of exposure to, and battling with, those nasty little things - things which, themselves, evolve.
Do we understand a lot about how our immune systems works? Yes. Do we understand everything about how our immune system works? I would suggest we’re not even close to that position yet. The real question is whether we understand enough about it to be able to state with certainty whether some intervention will lead to a benefit, overall.
The lessons over the last few decades from things like Marek’s disease, Original Antigenic Sin (OAS) and Antibody-Dependent Enhancement (ADE) should provide a sobering reminder that we don’t always understand things quite as well as we thought and that our well-intentioned interventions have not always gone quite according to plan.
With the basic rule-of-thumb in place that we’re going to find it very, very difficult to improve on the solutions that evolution has already provided for us, what general conclusions and concerns can we draw?
Obviously, THE hot topic right now is covid. So let’s apply our basic rule-of thumb notion and see where it leads us.
The first thing to note, and it seems somewhat paradoxical given the almost bacchanalian orgy of fear and paranoia we’ve witnessed, is that our immune system has coped rather well with the SARS-CoV-2 virus. Although estimates do vary, I think a fair central estimate is that over 99.7% of us survive infection, without vaccination. The vast majority of those who succumb are elderly or with other comorbidities. In other words, those who already have some functional impairment of their immune system represent the vast majority of fatalities.
I produced the following table some time ago in an attempt to get some sort of risk estimate. It’s not perfect - and only an estimate, based on the ONS death registration data for England & Wales by assuming a uniform infection rate across all ages. It should also be noted that assuming an overall IFR of 0.2% is actually inconsistent with the ONS data here. There could be several reasons for this but I’m going to suggest that when deaths, for any reason, within 28 days of a positive PCR test are listed as a covid death there may, possibly, perhaps, be the merest smidgeon of over-reporting of covid deaths. Whether that’s true or not is immaterial; the estimates in the chart are not wildly inaccurate.
One hugely important thing to note is that out of nearly 22 million people under the age of 30 in England & Wales, only 220 died with covid listed as a contributing factor on their death certificate up to April 9th 2021. Even if all of these actually died from covid that’s a very small number.
This means that if you’re under 30 your evolution-driven natural immune system is working very well indeed to protect you from fatally succumbing to an infection with SARS-CoV-2.
One might be tempted to pose the following question. If we all lived in the world of Logan’s Run, where people are euthanised when they reach 30, would we even know there was a pandemic? Would there be such a universal clamour for vaccination against this pathogen? I suspect not, but perceptions have been sufficiently warped over this last 20 months that I don’t feel as confident as I used to in accurately predicting a public response.
From this we can infer that SARS-CoV-2 is not a virus that incapacitates, or impairs, the immune system. If it did, we would see a much higher incidence of death in the young. Covid19, the disease caused by SARS-CoV-2, is a disease that predominantly preys on those with an existing impairment of their immune system. Perhaps a stronger conclusion we can draw from the very small number of deaths in the young is that the root cause of severe covid19 is not the virus itself, but rather a function of a maladapted or sluggish immune response.
If your immune system is working as it should, then the virus will be dealt with quickly with few symptoms. If the virus is not adequately dealt with at this stage, because of a sluggish immune response, it will multiply exponentially in the body. By the time the sluggish immune system catches up there will be too much virus and the body will have to unleash a massive counter-offensive killing all the infected cells. The virus will be killed, but so will you.
This explains why the elderly, who have a higher chance of being immuno-senescent or otherwise compromised, have a much higher risk of a serious outcome from infection with SARS-CoV-2. By the time the impaired immune response gets going, there’s just too much virus to deal with.
Now, let us consider what our natural response to infection is. It’s very complex, but in broad terms if we are hit badly enough to produce antibodies, the level of these antibodies wanes over time. That makes sense. After all, when the disease has run its course and the threat has gone, we don’t need this high level of protection. All entirely predictable from an evolutionary perspective; why waste valuable energy on resources when they’re not needed?
Putting this another way, our own evolution-driven solution is NOT to have high levels of specific antibodies circulating in our bodies at all times. One of the “selling points” of the covid19 vaccines is that they induce very high levels of antibodies to the spike protein. Sounds good, perhaps. Yet our current recommendation with the booster programmes is effectively to keep this high level of antibodies circulating permanently. This might be the right thing to do - but pause for a moment and ask why evolution did not select this as an optimal method for protection? With the prospect of boosters as a recurrent and permanent state of affairs we’re getting the body to do something that was never “programmed” in by evolution. Evolution did not produce a state for us in which antibody levels are permanently high.
What other solution to infection by respiratory viruses did evolution give us? One thing it didn’t give us is protection generated from a muscular immune response. Our natural immunity to respiratory viruses derives primarily from mucosal immunity. And this makes a difference. Our first line of defence is tied in with our respiratory system itself - and again this makes very good sense from an evolutionary perspective. If the respiratory virus gets beyond this and starts to infect other organs, then we have to up the ante and bring in bigger guns; guns which might cause a larger amount of collateral damage.
This also highlights the critical importance of early treatments. The last thing you want to do with covid19 is to send your patient home and tell them to only bother you when their lips have turned blue! This is like a plumber telling you to wait until that small leak has got so bad it’s completely undermined the foundations of your house.
So it seems obvious that a better strategy would be to develop vaccines that can generate an efficient mucosal antibody response. Instead we mostly have vaccines, for a respiratory virus, that stimulate a muscular generation of antibodies. Evolution did not select for us a muscular antibody generation as its first line of defence against a respiratory virus.
Evolution is a wonderful thing. It has given us an almost miraculous system to protect us from disease. Sometimes it needs help; it’s not perfect. But whatever help we give it we need to work in tandem with it. Solutions that evolution has not chosen for us need very careful consideration indeed, otherwise we run the risk of doing more harm than good.
I’ve written the above based on my current understanding of things. I’m not a virologist or immunologist and may very well have several things a bit wrong. Please do let me know - I’ll be very grateful. It’s important to get stuff right, particularly in this crazy post-covid world. I’ll try to write more stuff over the weeks - somewhat new to this. Please subscribe if you’d like to hear more