BUILDING an understanding of our pandemic is a big challenge when we are up to our necks in a torrent of news, opinion and speculation. While most of us view COVID-19 from within our own interests as a socially disruptive disease that kills a lot of people, it can be informative to take a step back and to consider the broader scientific context of what we are experiencing.
The phenomena of epidemics and pandemics (different only in their scale) as disease outbreaks that spread through populations are manifest simultaneously as biological, historical, geopolitical, sociocultural and ecological events. Their nature has evolved as we transformed from lives as nomadic hunter–gatherers, took up agriculture and animal husbandry, and eventually came to live in large communities and travel the world. We are not unique – many other organisms are also currently experiencing pandemics for which humans are at least partly responsible – rabbits, pigs (and here), frogs, chestnut trees and other trees, for example. Ironically, spelunkers have been implicated in the spread of the fungal white nose syndrome in bats.
If nothing else, the COVID-19 pandemic has provided us with an incentive to seek a clearer understanding of our relationship with the rest of the natural world. One way to make sense of what is going on in this time of disruption, confusion and uncertainty is to explore the records of our past and the rich offerings of science.
These perspectives have an extensive literature of which the following are useful guides. Plagues and peoples, by Chicago University historian William H McNeill, was published in 1976 after the author wondered how Central and South America had been subdued so easily by the Spanish conquistadors. In 1988, Joshua Lederberg, a Nobel Prize winning molecular biologist, published Pandemic as a natural evolutionary phenomenon as one of a series of articles on the AIDS/HIV epidemic comprising In time of plague, the autumn 1988 edition of the journal Social Research. Most recently, epidemiologist Adam Kucharski produced The rules of contagion: why things spread – and why they stop.
So, how is this pandemic an evolutionary event?
First, the coronaviruses are very common in many species and include a number of human versions that we experience as the bothersome, but generally harmless, common cold. Like all viruses, they exploit the operations of the cells of their host to reproduce themselves. Whether by their nature or a lack of opportunity, most appear to coexist in relative harmony with their hosts as species-specific microparasites. Some coronaviruses, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, are able to infect more than one species.
The replication of all viruses is an imperfect process and a random array of new variants will emerge. Most new forms will be mutant duds and incapable of using any animal as a host. Occasionally, either in their original host and/or perhaps facilitated by recombination with viruses of another host, infected cells produce variants of viruses that are more virulent and perhaps even able to infect humans.
Once in a while, a single new variant coronavirus will be able to latch on to a human cell using molecules on its surface that are compatible with the surface molecules of a human cell, inject its RNA, use the new host’s molecular machinery to replicate itself repeatedly, and cause us to do things (such as cough and sneeze through a runny, snotty, virus-laden nose) that spread its countless viral offspring to other humans. If the novel strain of viruses makes some of us very sick or even dead, then it has become a newly evolved disease that can thrive until something disrupts its success.
Research undertaken soon after it appeared suggested that SARS-CoV-2 was transferred from bats to pangolins (a low likelihood event in a human-free world but plausible in an environment of exotic culinary tastes), perhaps evolved further in their new host, and was subsequently transferred to humans. If so, then SARS-CoV-2 was following a journey to human parasitism via an intermediate animal host that was similar to several other bat-derived viral infections: Hendra (horses), severe acute respiratory syndrome (SARS; palm civet cats) and Middle East respiratory syndrome (MERS; camels). More recent molecular biological studies (here and here) indicate that SARS-CoV-2 emerged naturally and unnoticed as an infection in horseshoe bats about 40–70 years ago, and may have either jumped directly to humans or passed unchanged through another species, possibly the pangolin.
We humans are not passive in our relationship with pathogenic viruses. Seen from the perspective of viruses, we are useful as a prospective substrate for their reproduction. However, our population accommodates a significant diversity in susceptibility to viral infections. Chance and our individual vulnerability to all the challenges of our world determines our likelihood of reproducing successfully. In all life forms, the variety found in offspring, and the elimination of those that are less robust or resilient in the context of the times (including, for humans, the social determinants of health), drives the evolution of species.
Almost from the beginnings of complex life, the opportunity to exploit the work of other organisms in the form of their complex molecules has encouraged the evolution of parasites. Those that were successful in the respective roles of host and parasite are our ancestors, and those of our parasites. All the while, the continuous challenges of their mind-bogglingly complex interactions drove the emergence of physical and physiological barriers to infection and infestation that comprise our immune system.
It is important to remember that our evolution, and that of all organisms, is not a journey with a destination or a goal – it is a consequence, not a response. The random chances of evolution in a dynamic environment mean that we continue to face new microparasitic threats. When we do, and leaving aside the obvious social and health risk factors, it is simply chance whether our individual prize in the genetic lottery (shaped by the selection of the genes of our parents) has provided us with an immune system that can block or overcome the particular parasite, or leaves us vulnerable to serious illness and the possibility of dying.
Contemporaneous records show that epidemics of novel parasites have on occasions killed a huge proportion of human populations – 90% mortality in some naïve communities. Those of us who die young will not have our genes reproduced, while the survivors, those with the greatest resistance to the novel infection, become the dominant members of our species. Evolution can happen quickly when selective mortality is very high: the genetics of a population of New Guinea highlanders exposed to Kuru — a transmissible prion disease related to Creutzfeldt–Jakob disease — changed very rapidly when almost all of those whose genes left them susceptible died.
There is no predicting the nature of future novel parasites that jump from other species, nor what it is that will make some of us particularly vulnerable to them. However, once a specific pandemic such as COVID-19 is underway, molecular science can start to identify the genetically determined factors that make some people far more susceptible, and develop fixes. We may find we all have attributes, some otherwise beneficial, that could be exploited by a novel parasite emerging with the means to turn our trait into an opportunity.
Long term host–parasite relationships are very complex and dynamic over evolutionary time frames, and beyond the scope of this article. However, our evolved immune systems and biological strategies such as sickle cell disease are examples of human parasite defences. We also learn behaviours (cultural evolution) that reduce the risk of being parasitised. Rules such as not eating pigs because they may carry trichinosis, and avoiding eating sick marmots (large burrowing rodents) in which plague bacteria (Yersinia pestis) are endemic, have become embedded into many cultures and are ignored at individual peril.
An outbreak of a species-jumping illness in a small and isolated community would generally burn out without spreading beyond the confines of that single group. If there were enough of them, the less susceptible or more robust survivors would pick up the pieces, and perhaps endow their successors with a diminished susceptibility to that disease.
As our technologies, farming and trading practices became more complex, humans established larger, more permanent settlements that became more socially connected with other communities. These changes opened up new opportunities for a range of microparasites more suited to the ecology of larger groups of hosts and their habitats (I will address the topic of human macroparasites, those people who exploit their own species, in a further article). While epidemics were quite common in the early civilisations and dynasties of the Middle East and China, often causing very high mortality, global spread in the known world remained limited by a lack of opportunities.
McNeill reported that descriptions of diseases such as smallpox and measles did not appear in the literature prior to a few thousand years ago. Until that time, such diseases could not be sustained as endemic within communities because they were too small. Once the population reached a minimum size, perhaps 100 000 for measles, transmission could be sustained without need for the parasite to jump repeatedly from another species. As confirmation of the historical record, a recent study of the genetic clock of measles found that its antecedent disease of cattle, rinderpest, moved into humans about 2600 years ago and became established as a separate endemic disease, a relationship that may yet evolve further (but for disruption by the anti-evolutionary phenomenon of vaccination). Our short and meaningful relationship with smallpox seems to have been a far more complicated tale of mummies, Vikings and mutations.
Other pandemic or epidemic diseases still require intermediate hosts but may be enhanced by human communal actions. Before the emergence of larger human communities, plague was restricted to local outbreaks that were self-limiting. It was not until the development of the Silk Road, and extensive maritime trade across the Black Sea and throughout the Mediterranean, that humans were able to carry plague from Asia. Once it became endemic in our cohabiting and hitch-hiking fellow traveller black rats and their fleas, it remained active as human disease. Multiple outbreaks over many centuries killed over one-third of the population of Europe and changed human social, cultural and political history.
Malaria, which had been imported from Africa by the Romans, virtually disappeared from Britain when farming culture changed. Marshes were drained and the number of cattle and horses increased. The endemic British mosquito species that transmitted malaria between humans apparently prefers the blood of cows. As cows cannot host human malaria parasites, the risk of humans developing malaria decreased.
When Columbus arrived in the Americas in 1492, he and the Spaniards who followed him brought with them smallpox and measles. Having been isolated from the rest of the world for tens of thousands of years, before pandemics became possible, the indigenous peoples of the Americas were genetically naïve to what were for them novel illnesses and, with no evolved resistance, they died in droves. Weakened, or even deconstructed, by parasites, the native American civilizations were easily overwhelmed by small numbers of Spanish and Portuguese soldiers, and subsequently by northern Europeans. On the other hand, Columbus and his crew brought home with them typhus, syphilis (although this is not universally accepted) and tobacco (perhaps a slow burn of a pandemic?). Subsequently, enslaved Africans carried malaria and yellow fever to North, South and Central America.
Plague, on the other hand, did not arrive in North America until the late 19th century. Before that time, the inescapably long, slow journey under sail across the Atlantic or Pacific oceans meant that an outbreak of plague on a ship would be burned out before the journey was completed. The invention of fast steam ships allowed importation of plague from China to the west coast of North America, where it caused short lived epidemics and became endemic in the local populations of burrowing squirrels. When ranchers saw that plague also killed burrowing rodent prairie dogs that had no prior exposure to plague, they actively transported infected animals to improve grazing lands for their cattle. Plague is now endemic in burrowing rodents across much of western North America, from northern Mexico to southern Canada. As recently as 1978, when my family and I arrived in Townsville, a new concrete slab on ground required a 600 mm deep ratwall around the edge to exclude burrowing rodents. A friend and I shared ownership of a ratwall shovel!
Massive human mortality from recurring epidemics of microparasites only subsided with the scientific understanding of diseases, their life cycles and their transmission, followed by effective public health measures and vaccination. A recent article from The New York Times shows graphically how mortality in New York City from a wide range of microparasites has declined over approximately the past 150 years. You will note on the graph of mortality from 1800 to the present that mortality at the peak of the 1918–1919 global influenza pandemic was lower than in any year of the 19th century.
Where does all that leave us?
Epidemics and pandemics occur because we – or at least the molecular structure and function of our cells, our behaviour and/or our social organisation – unwittingly offer an opportunity for organisms that have chanced upon the means to take advantage of us and spread through our population. Sometimes these circumstances have been enhanced by our progressive disruption of the dynamic world in which we have evolved (here and here).
Life on earth persists because of its variability. Species (rather than individuals) change (ie, evolve) when occasional new variants appear which are better able than their peers to take advantage of opportunities and/or avoid the hazards of new or existing threats. For novel coronaviruses of COVID-19, success was found in being able to use humans (and cats, big cats, and bats, among others) very effectively as a host that would allow them to replicate in numbers sufficient for their perpetuation.
SARS-CoV-2 is simply the latest of a large number of organisms to move from other animals to humans. We change them while they change us, as individuals, as communities and as cultural beings.
In my InSight+ article of 13 January 2020, I discussed how it is not really possible to predict the extent and consequences of the disruption of complex systems. There is so much we don’t know about how this current pandemic will play out across the diversity of our cultures, communities, environments and genomes. We do not yet know if SARS-CoV-2 will be susceptible to vaccines or antiviral medications, whether immunity from infection or vaccination will last long enough to protect us from re-infections, or if SARS-CoV-2 will evolve in ways that mean we will have to deal with new strains that might be more or less virulent.
We are all experiencing the broad impacts of the pandemic on our community and our economy, and particularly on our health care systems. The consequences of social inequality are being laid bare in the unequal distribution of poor outcomes to those infected by SARS-CoV-2. However, many are reluctant to accept that our lives are fully enmeshed in the natural world and scarcely consider the complexity of the consequences of the disruption by the human community of the global environment.
Our biological and cultural evolution in a minimally changing environment has generally unfolded so slowly as to be imperceptible in one lifespan. However, a major event that eliminates a significant subset of the population, disrupts the complex systems on which we all depend, unsettles our entrenched social order and exposes our failings as communities may induce dramatic changes that are apparent in real time.
Two hundred and fifty years ago, COVID-19 would have been yet another evolutionary upheaval like that faced by the original inhabitants of the Americas and Australia with the arrival of measles and smallpox. Communities would have had no understanding of where it came from or why it was happening; those most vulnerable due to pre-existing illness, social disadvantage and/or the chance of their genetics would die, and the genetic mix of the population as a whole would have moved on.
Over those 250 years, our world has changed a great deal. While for now we must persist with measures that reduce our risk of exposure to COVID-19, it seems highly likely that science and the power and ingenuity of modern technology will fulfil our expectations and eventually provide means for preventing and treating this disease.
In other ways, our world is unchanged. History and science tell us that, sooner or later, another pandemic, perhaps promoted by global climate change, will emerge from the vast panoply of parasites circulating on our planet and it will be different from anything we have met before. Now is the time to start using our growing scientific expertise to work out how to respond more effectively.
Dr Will Cairns is a palliative medicine specialist based in Townsville.
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.