In 2012, six miners in Mojiang, a small province in southwestern China, contracted a flu-like sickness and three ended up succumbing to their symptoms. Researchers later discovered that the miners had contracted a virus directly from bats that lived in the mine. A virus called RaTG13 was later isolated from the bats and determined to be the culprit, and to this day remains the closest known relative to SARS-2 in nature.
“Aha!” you might be saying. “We’ve found bats with a similar virus in China. Case closed!”
Not so fast! We have to do a little work to understand how viruses mutate and why the emergence of the strain that appeared in Wuhan was so bizarre.
How viruses mutate
As soon as it appeared in 2019, the virus was immediately extremely transmissible from human to human. And yet, no intermediary clusters of infections between the caves in Mojiang and the tens of millions that live on the routes to Wuhan 1,000 mi / 1,500 km away have been found. An imminently contagious virus simply appeared one day in the middle of a massive metropolis and left no trace of how it got there, despite a gargantuan hunt for its origins. To fully appreciate how weird this is, we need to understand how new viruses come to infect us.
While the general idea of how viruses become infectious in humans is common knowledge (“the virus mutates and that change allows it to infect humans”) the process by which this happens is more complicated. Viruses mutate in two ways. The first way is via random mutation, a process that is happening all the time in all organisms, but in viruses happens at a rate that is orders of magnitude faster than macroscopic life. The reason why viruses mutate so much faster is twofold: firstly, viral reproduction cycles are very short (on the order of hours) and secondly, the number of “copies” viruses produce is very high. While a pair of humans can produce a single offspring per year, viruses can produce upwards of 10 trillion copies a day in an infected host. These two factors combine to ensure that viruses seem perpetually a step ahead of our immune systems’ ability to learn and our technological ability to manufacture vaccines.
The second way viruses change is via a process called recombination. When two different viruses hijack the same cell, the pieces of genetic instructions which make up the viruses have the chance of being swapped into each other in a sort of viral code sharing. Just as two cooks sharing the same kitchen might swap ingredients and create a new dish and thus a new recipe, borrowed code that ends up benefitting the recombined virus gets passed on to its descendants.
In almost every instance, random mutations or recombinations have either a neutral or deleterious effect on the infectiousness of the virus. Very occasionally, however, a change to the viral code will make the virus more suited to spreading amongst the host population. Over time, viruses are always trending toward greater spread all while adapting to ever shifting pressures like changes to the host’s immune system or behavioral patterns. Contrary to popular belief, viruses that cause the death of the host are typically not selected for, since a dead host has a greatly diminished ability to spread to other individuals. This is one of the primary reasons viral pandemics have historically become less deadly over time. An exception to this is very slow acting viruses like HIV, which do not have this same selective pressure to become less deadly.
Jumping from animal to human
When a virus jumps from animal population to human hosts it is called a zoonosis. In order for a zoonosis to occur, a virus must become adapted to human hosts. But viruses can only adapt to organisms they are continuously exposed to. Therefore, a zoonosis requires close and sustained contact between the animal hosts and a human, preferably several. This is because a single random mutation is rarely enough for a virus to suitably adapt to human hosts. Multiple mutations must occur, often some of them very substantial. The likelihood that the required combination of mutations would occur at random is thus very low. You need a “ladder” of adaptation, in which small adaptations allow some residence in human hosts, after which larger adaptations can be selected for. It’s akin to picking a lock in which all pins must be set in the perfect position simultaneously vs picking a cheap lock in which each pin can be picked sequentially.
And even once the virus has suitably mutated to infect humans, that’s still only part of the way there. This is because the first strain that manages to infect a human host will initially be very poorly adapted to inducing symptoms that cause spread amongst its new hosts, like sneezing or coughing for example. For spread to occur, there must be a second period of adaptation during which infected people are mixing with uninfected individuals and providing opportunities for the virus to jump to the uninfected.
If this sounds like a fairly difficult series of hurdles for a virus to overcome, it's because it is. For this reason, it's theorized that many zoonoses have a little help making the transmission via an intermediate species. The intermediate species acts as a bridge between the primary reservoir species and humans by introducing new adaptations that end up providing the key to infecting humans.
The reason an intermediate species is theorized in the case of SARS-CoV-2 is because of the genetic chasm that exists between the virus and its closest known relative. It’s akin to an artist’s catalog going from stick figure drawings to fully formed masterpieces with no progression in between. The bat caves where the closest relatives have been found (which, as of 2021, are now in Laos) are over 1,500km away from Wuhan. Logically, we would expect to have seen clusters of infections between the caves and Wuhan, since the process of adapting to human hosts should leave a trail of genetic breadcrumbs in the form of clusters of less infectious infections. Similarly, serological studies conducted since the initial outbreak haven’t found any evidence of Covid-19 exposure in the Chinese population prior to December 2019.(need source)
And winding the clock back further, we still haven’t found the original reservoir or intermediate species yet. Despite having tested over 80,000 animals, the closest genetic match is still missing key features of the virus that appeared in Wuhan. By contrast, reservoirs and intermediate hosts for previous epidemics of SARS1 and MERS were found in months with much less exhaustive searches (bats in Yunnan province and camels in Saudi Arabia, respectively). Even the closest relatives that have been found still lack distinctive features that scientists have still yet to discover in any natural reservoir.
Unclear origins
This is perplexing. If this virus did indeed emerge from a natural reservoir, we would expect to have found it. But we haven’t. No host reservoir. No intermediate species. No evidence of prior clusters of outbreaks in villages near the bats in Laos or anywhere in China. No less transmissible version of the virus circulating within China. No antibodies against the virus in blood samples collected earlier in 2019…
Human history is filled with examples of extremely potent viruses emerging suddenly and without apparent warning, sweeping the globe and killing millions. Are we then to assume all prior outbreaks that emerged without irrefutable genetic provenance should also be suspected as being artificial?
No, of course not. Scientists suspect the 1918 Spanish flu originated in Kansas swine farms situated next to hospitals treating casualties returning from the front lines in Europe, but can’t know for sure. The difference in the case of SARS-CoV-2 is that our current methods of tracing genetic lineage are much more sophisticated. Murky origins no longer pass the smell test in an age where our scientific tools allow such godlike insight into what were once considered divine acts. This isn’t to say that any unknowns about SARS-2’s origins are immediate cause for suspicion, just that the current number of stubborn unknowns is, well, quite strange.
In summary, the gap between the closest known natural variant and the variant that appeared fully formed in humans is currently difficult to explain by natural zoonosis. However if we do away with this assumption of a natural origin, it becomes very easy to explain.
But isn’t the scientific consensus that this virus can’t have been lab-created since the process would leave a trace on the virus’s genome?