Getting to Know You

Shakespeare once wrote “The course of true love never did run smooth”. Relationships between individuals and even between species require time to settle down. Over long periods of time the relationship between different species in an ecosystem can shift from predator and prey, to parasite and host, to mutualistic symbionts (and back again as circumstances change). Within species evolution can change the relationship between individuals of the same species from solitary to social (and back again).

In many ways relationships are arms race between partners as they seek a balance between exploitation and mutual assistance. For example the plant milkweed once evolved potent toxins that made it resistant to a wide range of herbivores. That advantage was interrupted when monarch butterfly caterpillars cracked through the defences and found themselves with an exclusive food source. Over time the plants and caterpillars would have refined their poisons and remedies until they developed a beautiful monogamous and codependent ecological relationship. The caterpillars took enough to prevent the milkweed from becoming too attractive a target for a different insect to learn to eat. The milkweed provide a reliable food source for the caterpillars with little competition (and even provide the caterpillars with protection from their own predators since they collect the milkweed toxin in their bodies). The arms race slows as the cost of producing extra toxins gives the plants too little extra benefit to be worthwhile. Beyond a point the plant would be expending ten leaves worth of resources to save ten leaves.

When the milkweed first evolved its toxin it likely became out of balance with its ecosystem, outcompeting other plants that had their own herbivores to bear. When the caterpillar first evolved milkweed toxin resistance it likely also had a short lived population boom as it feasted on the over abundant milkweed. Humans and their infectious diseases experience a similar pattern when large leaps are made in the relationship between species. Pathogens that evolved alongside humans over long periods of time tend to be better at living in balance with their hosts and may even bring benefits. Hookworm and other intestinal worms now appear to be essential in regulating the human immune system and their absence contributes to autoimmune diseases. External parasites like lice are also suspected to serve a similar role in preventing allergies. Under conditions of malnutrition, crowding and the resulting poor sanitation these old symbionts can become out of balance and cause “disease”. Kind of like having twenty pet dogs crammed in your house will end with ruined carpets. By contrast infectious diseases that have more recently formed a relationship with humans tend to be more severely out of balance with the populations they infect.

Novel coronavirus is just the latest in a long line of such organisms to jump into the sprawling human populations. Like the milkweed that had recently evolved poison that allowed it to become over abundant in the environment, humans are an attractive target for any organism given our sheer abundance. Humans now make up 36 % of mammalian biomass on the planet, while our domesticated animals make up 60 % and also represent an attractive target for species to exploit, though it is split between a range of different species. Humans also tend to live in very crowded conditions, with 55 % of the population living in cities, and those cities are tightly connected by extensive travel. Most of the diseases capable of causing pandemics evolved after the spread of agriculture and most were acquired recently from animal livestock living in close quarters with humans, much like the novel coronavirus is believed to originate in bats.

Pandemic diseases like measles require a minimum size of connected human populations in order to not die out. New naïve hosts in the form of children need to be born and grow rapidly enough so that the disease can continue spreading without running out of hosts. Measles needs a population with 5000-10 000 new births every year to not die out for example. Diseases that kill their hosts before they can spread to others tend to become extinct, meaning that any variations in the disease that allow it to spread more and kill less are usually favoured over time. Diseases that regularly experience increases in fatality rates tend to be those that can continue to receive genetic diversity from wider sources, such as influenza and its ability to readily incorporate new genes from related viruses in wild birds. This hybridisation of strains is particularly easy for influenza since its genome is naturally fragmented into regions that can be mixed and matched between strains. Bacteria are also good at swapping short segments of DNA that can carry optional functions like antibiotic resistance. Novel coronavirus appears to be closely related to a bat virus, but a crucial region is very similar to a virus from a pangolin, so it is possible that the novel human virus emerged from the swapping of information from two animal adapted strains. Over time pathogens tend to become less disease causing and eventually join the human microbiome. Just with viruses we have recently learned for every dramatic pathogenic virus in the human population there are hundreds of others living on and in our bodies. Some viruses are even permanently incorporated into the DNA of human cells and passed on to future generations. This can provide novel genes or change the function of existing genes, often causing cancer in the individual but also providing novel functions for the entire species. For example it has recently been discovered that the evolution of the mammalian placenta was driven by the acquisition of novel viral genes provided by retroviruses. Even further back the very nucleus of our cells probably originated from a viral invader that decided to move in and spruce up the place.

How we interact with a disease greatly influences the effect it has on the population. Polio virus was a devastating pandemic that caused horrific childhood paralysis in the early 20^th century that was eventually held in check by the development of vaccines. But further study of the virus showed it had been in human populations for thousands of years while epidemics of childhood paralysis only emerged in the 20^th century. We now know that infection in infants causes a relatively mild intestinal disorder. When children are not exposed to poliovirus until they are older a percentage go on to develop a nervous system infection. The epidemics of poliomyelitis then come from partial improvements in sanitation since children were not exposed to infected faeces until later in life. In a world with perfect sanitation poliomyelitis would not exist, as would a world with very poor sanitation. Only in the intermediate state does exposure merely become delayed, leading to the worst outcome. How you treat a pathogen therefore influences how the relationship with the host expresses itself.

Small pox was one of the most feared diseases of antiquity, with a 30 % fatality rate in old world populations and up to 90 % in the new world peoples. Yet somehow people learned to cultivate the virus in a process called variolation, by deliberately scratching the dust from smallpox scabs into the skin to cause a mostly mild local reaction with about 1 % death rate. This was a better alternative to waiting to inhale droplets, leading to a systemic infection of the whole body. Through this process it was recognised that two distinct strains existed, major and minor, with the minor form causing lower rates of death. Variola minor virus was selectively cultivated for variolation, further dropping death rates. Beyond that it was recognised that the even milder cowpox was closely related enough to give immunity to small pox and it became the agent of choice. This is akin to recognising that weeds will keep growing in your garden regardless of what you do, so why not only pull out the nastiest weeds and let the nicer ones fill up the gaps in the ecosystem? If the smallpox vaccine composed of killed virus had never been developed this process of cultivating a mutually beneficial relationship with pox viruses may have continued until it became a self propagating virus too mild to cause noticeable disease.

Syphilis is caused by a bacteria but represents an excellent example of how a microbe can rapidly change its behaviour for the worse when backed into a corner. The bacteria first colonised humans in the Americas, causing a very mild skin disorder called yaws. In these small populations people came into regular contact within the tribe, but rarely came into contact with the wider human population. This drove the bacteria to form a mild but long lasting condition. When the bacteria were exported to Europe they found very different conditions. The population was huge and interconnected, so there was less pressure to be gentle with their hosts. People rarely came into close contact, making skin to skin spread difficult. Prostitutes in port cities however came into very close contact with a very large number of others, but only for a brief moment. The bacteria needed to change to become virulent enough to successfully jump hosts at every opportunity. To begin the disease was horrific, infecting every tissue of the body and leaving victims deformed, mad and begging for death. Even without effective treatment the disease eventually became less severe as it gradually came into balance with its host population. Given sufficient time it may have vanished beneath our medical radar and turned back into something like yaws.

It is possible that novel coronavirus would produce a milder disease if people were exposed via the fecal-oral route (leading to diarrhea) than the respiratory route (leading to pneumonia in some cases). Our rush to use hand washing and imperfect masks may simply be driving the virus to specialise in the more dangerous respiratory route of spread. It may even be possible to become immune to the virus by a dermal route like the variolation used in smallpox, with a similar decrease in symptoms and mortality. Novel coronavirus is not that different to the four known coronaviruses that have circulated in the population causing mostly mild colds for probably thousands of years. Some of these poorly studied viruses are known to cause up to 8% mortality in nursing homes but get little attention since they aren’t novel and nobody is counting their impact like some weird virus OIympics. Coronavirus is still rapidly mutating and adjusting to its new home. How we treat it will strongly influence how it treats us. Social distancing and intense hospitalisation may favour strains that are more effective at respiratory transmission and persist longer on surfaces, and are more effective at jumping to many new vulnerable hosts in places like hospitals, just like syphilis became a monster to transmit effectively in brothels. Or we could find a way to reward it for being gentle. The choice is ours. How you treat dynamic and responsive entities determines if they become friends or enemies in the long run.

Every plant and animal in this picture has its own host of dozens of parasites, hundreds of bacteria and thousands of viruses all living together. Each of those relationships started out as a struggle long ago before settling into the peaceful scene we see today.