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NOT long ago, I was scanning through a recent edition of New Scientist when I noticed a report on an analysis of ancient human DNA sequencing that described the P1104A allele (variant) of a gene (TYK2) that increases human susceptibility to and mortality from tuberculosis.
Kerner and colleagues found that this allele first emerged in the ancestors of Western Eurasians about 30 000 years ago. Over thousands of years, the prevalence of P1104A has changed in response to the ways that we humans live our lives – our social evolution. Like many genes, this allele initially became more common because it provides survival benefits:
Of note, P1104A homozygotes [when both of a pair of genes are the same] have … been shown to enjoy … a protective effect against various autoimmune and inflammatory diseases.
However, in different context those same genes may also increase other risks:
Homozygotes for the P1104A [allele] … are at higher risk to develop clinical forms of [tuberculosis].
From about 10 000 years ago the frequency of this allele fluctuated, and then dropped dramatically from about 2000 years ago, after the beginning of the Iron Age. The authors attributed this decline to increased selection pressures due to the increased prevalence of tuberculosis, which “coincides with the growth of agricultural communities and anthropogenic environmental changes”. Interestingly, while they freely described the change in allele frequency, they barely mentioned that this was only because people who were homozygous for the P1104A [allele] of TYK2 were more likely to be killed by tuberculosis.
Last year, I wrote COVID-19 as an evolutionary event to focus attention on the evolutionary context of pandemics and their impact on human societies and our history. It now seems timely to revisit the evolutionary perspective on this pandemic in light of the debate about vaccines and their safety.
Until the past 100–200 years or so, and for the entirety of the hundreds of thousands of years of human history, and the millions of years of our predecessors, we had almost no agency in dealing with infection. Our only defences were our innate resistance, the response of our immune system, perhaps a few plant-based remedies, and learned and evolved behavioural measures that reduced the risk of exposure, including isolating or avoiding the sick (which we might now describe as public health measures). Every infection tested our defences, and infectious diseases were the major cause of death.
Infectious pathogens are arguably among the strongest selective forces that act on human populations.
Karlsson and colleagues, 2014
And yet, we had no idea what caused us to get sick.
The elimination of those who were most vulnerable to particular infections shaped the genetic make-up of the population of small groups, not to mention their social behaviour and culture. Across the world, survivors in groups that have been exposed to particular localised pathogens over sufficient periods of time had lower prevalence of genes that increased their risk and higher prevalence of genes that reduced susceptibility to those infections compared with populations that were meeting such pathogens for the first time (eg, cholera and malaria – for further reading I recommend Karlsson and colleagues)
This is natural selection by the elimination of the unfit: the deaths of those who, through the whims of mutation and the chance distribution of genes, offer an opportunity for pathogens; and the survival of those who carried genes that provide protection.
For most of our history, humans lived in small communities of low population density and limited mobility, and communicated only infrequently and cautiously with outsiders. Local zoonotic diseases that caused the deaths and shaped the genetics of local populations of exposed and vulnerable people could not be sustained for transmission to other groups. For example, measles did not become an endemic human disease until connected human populations reached a minimum size of several hundred thousand people in about 600 BCE (here, here and here).
Increasingly, new agricultural practices and other technologies led to environmental disruption, larger, more crowded and less sanitary communities, and networks of trade over distance. These changes created opportunities for infections by organisms that had been relatively unsuccessful in smaller, less-concentrated communities. The growth of trade supported the emergence of epidemics and pandemics of organisms that were novel (or perhaps uncommon) as infections for humans (smallpox, measles, plague and SARS-CoV-2), or had previously been geographically isolated in populations that had evolved to be less susceptible (malaria, yellow fever).
However, the context did not change the core processes of natural selection, just the nature of the consequences. The impact on human history has been demonstrated in the natural experiments of our past.
The journey of measles and smallpox and the consequences of the resulting wholesale mortality of the original inhabitants who had evolved in their absence were discussed in great detail in William McNeil’s book Plagues and Peoples (Anchor Press, 1976).
Yellow fever was also imported to the Americas as an invisible companion of the slaves transported from Africa. When Napoleon tried to start an American empire based in Haiti, his European troops died in droves from yellow fever while rebel slaves and their descendants, having evolved in Africa with yellow fever as a long term selective influence, were relatively resistant. Napoleon abandoned his plans, sold Louisiana (2.14 million km2 for $15 million) to the United States (the “Louisiana Purchase”) and eventually set his sights on Russia instead, and we all know how that ended.
Life persists because it offers variety in an uncertain and unstable world. We are all aware of diversity in the variety of our macroscopic morphology but the diversity of our genes also generates invisible differences that influence our susceptibility to microbes and parasites. Life evolves because organisms that are less vulnerable survive, and their genes become the future of their species. We are no different.
Humans will always vary in their susceptibility to new viral infections. Many of our gene variants offer advantages in some contexts, while novel pathogens, or new variants of old pathogens, can expose weaknesses in others (eg, the P1104A allele of TYK2). However, it is not possible to identify vulnerabilities in advance because they do not exist until they are created and identified by the random mutations of potential pathogens. Only once it is being exploited does a trait that is essential become a liability that may be fatal.
Viruses and bacteria are not devious, nasty, malicious or any of the other human behavioural traits that we anthropomorphically ascribe to them. They simply throw out a variety of options, most of which fail because they don’t work. Those that succeed do so because they find molecular gaps in our defensive armour that allow them in.
So, what of our COVID-19 pandemic?
It seems very clear from anecdotes that SARS-CoV-2 is no different from other pandemic organisms – only a proportion of the population are particularly vulnerable to serious illness and death. However, leaving aside comorbidities that increase risk, particularly for the elderly, we do not yet understand why some healthy younger people die very quickly from COVID-19. Or why others who initially had a milder illness are afflicted by long COVID-19, and why a small, but not insignificant, number of very young and healthy children die from multisystem inflammatory syndrome.
Our science of the 21st century is beginning to explain the variety and complexity of genetic reasons that may make some people more susceptible (here, here and here). Over the next few months and years, scientists will identify which variant or variants of which gene or genes confer increased or decreased risk of becoming infected and seriously ill with COVID-19. We will learn how SARS-CoV-2 invades our cells and causes disease, and most importantly, we will rapidly create vaccines and perhaps develop other technologies that can prevent most of us from getting sick from the virus.
At the same time, SARS-CoV-2 itself is also mutating and evolving. Science is tracking a growing range of new strains that are picking their way (hard to avoid teleological and anthropomorphic language) through the vulnerabilities of the human population and our responses. The evolution of these variants is shaped by the opportunities and obstacles created by our behaviour, be it travel, social interaction, public health measures, or vaccines.
Perhaps the most important step in the whole of the scientific journey of the past few centuries has been the acceptance of evolution as the process of change that has underpinned the success of life on an unstable planet: that evolution is the consequence of the complex processes of natural selection – the elimination of the vulnerable and the persistence of the robust – as shaped by probability, chance and the circumstances of the moment. This applies no less to us and our communities than it does to viruses.
When we view life through the lens of evolution, understanding the rest is simply working out the details – although that is not to imply that such discovery is a simple task (here and here). The power of human curiosity through science is changing forever our relationship with pathogens, or at least for as long as we can sustain a balanced relationship within the vast complexity of life on earth.
However, none of this means that we can ignore the lessons of the past and deny the limits of what we know now. From the pandemic perspective, we are part of a single global community and it seems virtually inevitable that most people in the world will be exposed to SARS-CoV-2 (and probably its more virulent descendants) in the next year or so.
And so, to our choices …
On the one hand, COVID-19 has devastated many nations, so far killing one in 578 Americans, one in 532 British, one in 542 Brazilians, and no one yet knows how many in India – worldwide over 3 million deaths from at least 144 million cases, and a long way to go in a global population of almost 7.9 billion. For an account of what dealing with rampant COVID-19 means for clinicians and patients (sometimes the same person), I suggest reading Breathtaking: inside the NHS in a time of pandemic.
On the other hand, so far, the risks from any of the various vaccines seems to be very low. Even the most talked about — the risk of death from the complication of severe thrombosis after the AstraZeneca vaccine (and perhaps some others) — seems to be about 4 to 6 per million of those vaccinated, with about 1 in 4 of these people dying – approximately one death per one million vaccinations. At that rate, and assuming no effective treatment is found, if everyone in the world received the Astra Zeneca vaccine a global total of about 7900 people would die from this adverse effect. Anaphylaxis following COVID-19 vaccination affects about one to two per 100 000 people (here, here, and here) and has been managed successfully by following standard guidelines.
Our choice in this pandemic is not simply whether or not to be vaccinated. In 2021, it is whether we will embrace the science of the past 200 years (including the rational calculation of risk) and accept the measured risks of vaccination, or regress to the uncertainties of evolution by natural selection and take our chances with the unknown vulnerabilities that may be written into the genes that were bequeathed to us by our parents.
Pick one!
Dr Will Cairns is Associate Professor at James Cook University and is Consultant Emeritus in Palliative Medicine at Townsville University Hospital.
The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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It is heartening to see the intelligence expressed in this “discussion”, but if the last 6 years have taught us anything, it is that “intelligence” and “facts” are of lesser importance than intent and cognitive bias. As blasphemous as that may sound, it is accurate, and I fear for our future if we cannot overcome our biases; and hopefully eliminate even the memory of alternate facts. From personal experience I can tell you that we all have a frightening “power” for self-deception. Here is a good place to start (although understated) How the Self-Serving Bias Protects Self-Esteem ( I have no affiliation)
https://www.verywellmind.com/what-is-the-self-serving-bias-2795032
This article connects human genetic evolution, population growth on Earth, from isolated communities to global interconnection, to the reality of inevitable exposure to evolving opportunistic pathogenic organisms. A key point was that survival of the fittest are the consequences of behavior and adaptation which includes how human intelligence and medical science impact social behavior. Vaccines are a great example of intelligent human adaptation and social behavior that is directly related to our survival in our environment on planet Earth. Climate Change is Earth’s reaction to human activity, destruction and exploitation of pretty much everything that makes life on Earth possible. But will intelligent vaccinated humans out-survive unintelligent unvaccinated humans and realize behavioral changes in relationship to our environment on planet Earth? Is the theory of human subspecies reverse evolution too eccentric? As a species, human beings will not only be divided by science and politics (or religion), but also by survival of the fittest (scientific) and a subspecies of humans characterized by the phenomenon of reverse evolution, which describes a shrinking population of generations of, for example, narrow-minded, short-sighted, greedy right-wing political or religious extremists who stopped using their brains for anything intellectual – abstract thinking, deductive reasoning, social or global collaboration, and of course no legislation. In reverse evolution, the higher, executive functioning regions of their brains (pre-frontal cortex and cerebellum) shrinks, and, eventually disappears. With only a basal ganglia brain, this creature will no longer be a political threat.
Natural selection does not have prevision, planning or conscious intention – it is amoral and non-rational, there is no guiding ethical or moral reasoning. Science and natural selection informs us about WHAT IS but does not inform us of what SHOULD BE, it does not tell what is obejctively good or bad, and importantly, what is right or wrong. In order to address these meaningful questions and to assign some order of moral priority to the burning questions of self-interest, communal and global interests for us as humans in a world of diverse biology, we need to step beyond the impersonal and ground morality and rationality in a coherent worldview. Having a vaccine is one thing, how we should use it and importantly, the broader issue of how we (as individuals, communally and globally) look after each other and our planet requires us to look beyond ourselves to something (or someone) greater. For too many of us, we have not subjected our personal worldview to rigorous reflection and our conversations in this area are often much too glib. Our focus needs to be more than survival, it needs to focus on an objective basis of how to live well. Objective truth about morality, meaning and purpose of life should inform us about what our subjective response should be, and not the reverse.
In biology the survival of species or groups is not the real game or issue but it is the consequence. The success of a gene whether it be in RNA or DNA form depends on its ability to replicate. So for any virus, gene or set of genes to be highly successful they should keep their host alive long enough for their reproduction.
As Bruce has observed, the fundamental immediate issue facing ‘Mother Earth’ from a biological standpoint is not really the amount of gaseous carbonaceous material that our species has deliberately freed into atmosphere but the billions upon billions of carbon molecules trapped inside the bodies of our ever expanding numbers on earth. We truly are the champion apex predator of world history and make T. Rex look positively pedestrian.
However, fortunately we do seem to have an innate self-limiting mechanism that will likely deal with us eventually. It’s called greed. The rise and dominance of this mammalian subspecies may well be short lived teleologically.
Thanks for your thorough discussion of the issues. Natural selection provides a lens through which we can view human development, pathogens and their effects on society over the centuries, but is not a useful basis for developing social policy or responding to the health needs of vulnerable people.
Dr Will Cairns’ paper highlights whats known about evlolution of natural immune response of human species against multitude of pathgens over centuries to its current state in the midst of Covid-19 pandemic in parallel with continuous adapatation of infective pathogens for thier own survival. Yes I agree Astra Zeneca vaccine administered to more than 2/3rd of total popuaton barring contraindication, in Australia is likely to make public at large less vulnerable future Covid or related virus infection but there is every possibility of more severe panademic engulfing the world unless human species across the globe can adapt and limit relentless desire to live better at the expense fast diminishing natural resources and species towards a more equitable sustanable living without harming fellow human beings and other species all round us within the bounds of nature. This can never be easy but Australia , vast country with a poulation of 25 million can acheive a lot towards that end it but it will require dtermined effort , commitment and scarifice by all concerned.
Thank you for the article Will. I notice your lack of objectivity at the end when posing the question of whether we should choose vaccination or ‘regress’ to the whims of evolution. Naturally, you support our human capacity to continue to survive the processes and consequences of evolution. The recent human capacity defy the planet’s evolutionary attempts to fight off the human plague has seen lus suddenly reach even greater plague proportions with a population of 7.9 billion, itself a pandemic. Such over-population has put enormous pressures on our planet’s capacity to survive. Over-population of the planet with unthinking, anthropocentric and destructive organisms like us have severely stressed the planet’s natural evolutionary defences. The planet itself is under serious threat as we all know. Climate change, accelerating species extinction and destruction of the planet’s seas and waterways are a few examples of the results of the human plague’s threat to the planet’s survival. Clearly the planet will respond as all life does and perhaps viral plagues are parr of the evolutionary process to fight off overpopulation and ensure the planet’s survival.
Choosing vaccination may be best for humanity to continue to multiply and thus place the planet under even more extinction pressure. But is that strategy in the long-term interests of the planet and even the human species?
Human survival on earth requires action born from a much larger perspective than our own immediate interests.
The horror, beauty, and resilience of evolution is that there is no way we can circumvent its progression. Natural selection hasn’t stopped and it won’t no matter the choices we make. Our species though does not have the same guarantee.
Thanks Will, Darwin and Russell succinctly updated for today. Truly appreciate your research and clarity.
It is a dilemma and always has been. To allow natural selection for the greater good of future generations or protect everyone in the current generation to the detriment of future generations.
The matter, fortunately, has been taken out of our hands by politics. No politician is going to risk his or her reselection now for the sake of future generations later.
Indigenous Australians have a living history of genocide through biological warfare. This historical truth and impacts on Indigenous Australians must always be considered especially when trying to understand vaccine hesitancy in this this population.