The Latest Theory That May Answer the Origin of Covid-19
By: Shin Jie Yong
Tags: Covid 19, Life, Technology, Science, Education

The Latest Theory That May Answer the Origin of Covid-19

The Mojiang Miners Passage (MMP) hypothesis explains many oddities of the Covid-19 pandemic.

Image by JohannaIris from Pixabay

In a July commentary, “A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic,” Jonathan R Latham, virologist doctorate, and Allison Wilson, a professor of biology, presented the Mojiang Miners Passage (MMP) hypothesis that provides “a plausible and parsimonious explanation of all the key features of the COVID-19 pandemic and its origin,” they stated. “It accounts for the propensity of SARS-CoV-2 infections to target the lungs; the apparent preadapted nature of the virus; and its transmission from bats in Yunnan to humans in Wuhan.” Let’s see what the hypothesis is about.

What is known about the origin of SARS-CoV-2?

First, let’s start with the known facts. The closest relative to SARS-CoV-2 is RaTG13, a bat sarbecovirus isolated from the Yunnan Province of China, with about 96% genetic identity. A recent genomics study in Nature Microbiology shows that SARS-CoV-2 descended from RaTG13, which indicates that SARS-CoV-2 came from bats without any intermediate host. “Current sampling of pangolins does not implicate them as an intermediate host,” stated the study authors.

Prior research in May also said that pangolin is not the intermediate host that passed SARS-CoV-2 to humans. The pangolin coronavirus (pangolin-CoV-2020) and SARS-CoV-2 are only 90.32% identical. “Bat-CoV-RaTG13 was more genetically close to SARS-CoV-2 at both individual gene and genomic sequence level compared with the genomic sequence of pangolin-CoV-2020 assembled in this study,” this research concluded. “Our study does not support that SARS-CoV-2 evolved directly from the pangolin-CoV.”

SARS-CoV-2 came from a bat sarbecovirus called RaTG13, not pangolin, human-made, or the wet market. How it got spread into humans is still a mystery.

Another fact is that SARS-CoV-2 is not human-made. Genetic engineering leaves a ‘fingerprint’ in the organism’s genome, which can be caught with genetics techniques. In January, the Massachusetts Institute of Technology (MIT) used the Finding Engineering-Linked Indicators (FELIX) tool of the US Director of National Intelligence to confirm that SARS-CoV-2 was never genetically manipulated from any known coronaviruses. In fact, the FELIX tool shows that SARS-CoV-2 best matches are naturally occurring coronaviruses.

In late May, the Chinese CDC ruled out the Huanan wet market in Wuhan as the source of the SARS-CoV-2 outbreak. The WHO announced the same. SARS-CoV-2 was not found in any animals tested from the wet market. And a third of early Covid-19 patients never had contact with the wet market. Therefore, SARS-CoV-2 came from somewhere else besides the wet market in Wuhan.

So the fact is that SARS-CoV-2 came from a bat sarbecovirus called RaTG13, not pangolin, human-made, or the wet market. How it got spread into humans is still a mystery. “The organizations [of the U.S. intelligence community] decided to continue investigating two alternatives,” Sarah Scoles, a freelance science writer, wrote in OneZero. “The more likely explanation that the virus jumped from an animal to a human, and the more remote possibility that it was a natural virus released in a lab accident, which still hasn’t been ruled out [by the US intelligence community].”

What happened in Mojiang Mine in 2012

In late April of 2012, six miners at Mojiang Mine fell ill with unknown pneumonia. They were brought to the Kunming University Hospital in Yunnan, which is about 250 km from the mine. Their symptoms include dry cough (all patients), sputum (all), high fever (all), difficulty breathing (5), myalgia (5), low blood oxygen levels (4), headaches (3), and blood clots (2). Treatments used were steroids (all), antivirals (5), ventilation (3), and blood thinners (2). And half of the miners (3) died in the end.

Samples (at least blood and thymus tissues) from the miners were sent to the Wuhan Institute of Virology to determine the causative agent. The conclusion made was that “the unknown virus lead to severe pneumonia could be: The SARS-like-CoV from the Chinese rufous horseshoe bat,” wrote the authors. So, the miners had a coronavirus infection.

(Please also note that the original study that detailed the Mojiang miners’ pneumonia is a Masters thesis, which is still a credible scientific source supervised by a committee of academics.)

In that same year, ZhengLi Shi, director of the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology, led a surveillance study at the Mojiang Mine. Her team collected fecal swabs from 276 bats. Using genetic sequencing, they detected nine coronaviruses species, of which six were never classified and one was RaTG13. (Recalled that RaTG13 is a bat sarbecovirus that is 96% identical to SARS-CoV-2).

Some of these coronavirus species had likely infected the miners, although no comparative studies have confirmed this. Such events are not at all new as bat-to-human spillovers of viruses had occurred before.

MMP hypothesis part I: Human passage

Recalled that in the surveillance study in Mojiang Mine, Zhengli Shi’s team discovered the bat coronavirus RaTG13, which is 96% identical to SARS-CoV-2. Although RaTG13 is the closest relative of SARS-CoV-2, a 4% genomic difference is still too vast, which requires 20–50 years of evolution. Hence, an intermediate host is likely involved, as was the case of SARS and MERS, because coronavirus evolution rate speeds up in a different species.

Contrary to this conventional view, the MMP (Mojiang Miners Passage) hypothesis states that RaTG13 may have evolved into SARS-CoV-2 in the miners in the Mojiang cave.

Coronaviruses usually infect the upper respiratory tract. Miners work in conditions of poor air quality, which compromises respiratory health. Thus, RaTG13 bat coronavirus might have made its way into the miners’ lower respiratory tract where the lungs reside. Lungs are a large organ, and since the miners’ pneumonia was severe enough to require prolonged hospitalization, the virus load must have been enormous. “Evolutionary change is in large part a function of the population size,” Dr. Latham and Prof. Wilson explained. “The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution.”

(The term ‘passage’ refers to a standard technique to ‘culture’ viruses in a new set of cells. As viruses can only replicate using another cell’s machinery, the passaging of viruses is required for research purposes. By this analogy, the RaTG13 bat coronavirus was passaged in humans in the Mojiang Mine.)

As mentioned above, the miners’ symptoms closely resemble that of Covid-19. “Anyone presenting with them today would immediately be assumed to have COVID-19,” Dr. Latham and Prof. Wilson remarked. And the corresponding treatments administered to the miners — steroids, antivirals, blood thinners, and ventilation — are precisely the same for Covid-19. Therefore, the patient zero of the pandemic might be one of the miners.

Why did the miners not spread the disease to others? The novel coronavirus is most contagious during the early phase of the disease, probably one to two days before symptom onset. The miners were only taken to the hospital when their pneumonia had become severe. And mask-wearing was probably widely practiced in hospital settings. Therefore, the coronavirus at that time might not get much of a chance to spread.

MMP hypothesis part II: The escape

Also recalled that samples (blood and thymus tissues) from the miners were sent to the Wuhan Institute of Virology for research purposes. As their labs were under construction at the time of sample collection, virologists may have begun experimentations in 2017 or 2018, Dr. Latham and Prof. Wilson said. Then the virus may have leaked from the lab by accident.

“The more likely explanation that the virus jumped from an animal to a human, and the more remote possibility that it was a natural virus released in a lab accident, which still hasn’t been ruled out [by the US intelligence community].”

It may be an outrageous thing to state, but unintentional lab-leaked microbes have happened many times around the world. According to USA Today, over 1100 lab accidents involving the escape of bacteria, viruses, or toxins to agriculture or humans were reported to federal regulations between 2008–2012. Even a 2009 paper in the New England Journal of Medicine admitted that the re-emergence of the 1977 H1N1 swine flu pandemic — that disappeared from the human population in 1957 — was “probably an accidental release from a laboratory source.” Moreover, SARS had escaped from labs six times — one in Singapore, one in Taiwan, and four in Beijing. So it is not surprising that coronaviruses had leaked from the Wuhan Institute of Virology as well.

“Accidents happen on a regular basis. We have seen a few cases of high-profile labs in recent years where accidents happened or mistakes were made,” Dr. Filippa Lentzos, a biosecurity expert at King’s College London, stated. “For instance, in 2014 at the CDC there were safety lapses involving Ebola virus, anthrax and bird flu, and there have been lapses at the NIH [National Institutes of Health] involving variola virus which causes smallpox.”

Not to mention that the Wuhan Institute of Virology received two official warnings from American embassy officials in 2018 concerning inadequate laboratory safety measures. Chinese national team has also found that the Wuhan lab did not meet federal standards in five categories. There were also reported accidents that lab workers got wounded from bat’s attack or exposed to bat urine, according to VOA News.

Still, this narrative is not to blame research. There is no doubt that science is the cornerstone of human civilization. It is just that sometimes unfortunate accidents happen.

MMP hypothesis in a nutshell

“We suggest, first, that inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans,” Dr. Latham and Prof. Wilson said. “Second, that the [Zhengli] Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2­, that escaped from the WIV [Wuhan Institute of Virology] in 2019.”

“The closest known relative to SARS-CoV-2 is a virus sampled by Chinese researchers from six miners infected while working in a bat-infested cave in southern China in 2012. These miners developed symptoms we now associate with Covid-19. These viral samples were then taken to the Wuhan Institute of Virology…,” agreed Jamie Frederic Metzl, an author and senior fellow at the Atlantic Council. “If the virus jumped to humans through a series of human-animal encounters in the wild or wet markets, as Beijing has claimed, we would likely have seen evidence of people being infected elsewhere in China before the Wuhan outbreak. We have not. The alternative explanation, a lab escape, is far more plausible.”

What the MMP hypothesis explains

For one, SARS-CoV-2 binds to the human ACE2 receptor with remarkable efficiency. “Such exceptional affinities, ten to twenty times as great as that of the original SARS virus, do not arise at random, making it very hard to explain in any other way than for the virus to have been strongly selected in the presence of a human ACE2 receptor,” Dr. Latham and Prof. Wilson noted, such as in the workers in Mojiang Mine. And the bat sarbecovirus RaTG13 can indeed bind to the human ACE2 receptor. A study published in May in The Lancet Microbe has also shown that SARS-CoV-2 does not replicate efficiently in cultured (in a lab dish or plate) kidney and lung cells of bats — suggesting that SARS-CoV-2 probably evolved in a human host rather than bats.

“In short, the MMP theory is a plausible and parsimonious explanation of all the key features of the COVID-19 pandemic and its origin. It accounts for the propensity of SARS-CoV-2 infections to target the lungs; the apparent preadapted nature of the virus; and its transmission from bats in Yunnan to humans in Wuhan.”

Second, viruses usually undergo rapid evolution when they replicate in a new host. For instance, when MERS and SARS first adapt to humans, phylogenetic analyses revealed numerous mutations and recombinations in the viruses’ genomes. But such rapid evolution was not observed with SARS-CoV-2 genomes at the beginning of the pandemic. Yet SARS-CoV-2 has infected far more people than SARS and MERS did. “That is to say, its evolutionary leap to humans was completed before the 2019 pandemic began,” stated Dr. Latham and Prof. Wilson. “It is hard to imagine an explanation for this high adaptiveness other than some kind of passaging in a human body.”

Third, the MMP hypothesis complements known facts about the origin of SARS-CoV-2 — that it evolved from a bat sarbecovirus called RaTG13; it does not come from pangolin or the Huanan wet market, or by human design.

A complementary theory to the MMP hypothesis

Another convincing theory regarding the origin of SARS-CoV-2 concerns gain-of-function research. Laboratories around the world had intentionally made microbes adapt to different species — through serial passaging experiments — to study the possibility of epidemics. Hence, a possibility exists that SARS-CoV-2 was cultured (or passaged) in laboratory settings to improve its binding affinity to the ACE2 receptors.

This ‘gain-of-function lab escape’ has been theorized by some research groups to explain the uncanny rapid adaptability of SARS-CoV-2 to humans. One is a peer-reviewed research paper in Bioassays in August, titled “Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?.” Another example is the commentary of Birger Sørensen, a Norwegian virologist specializing in HIV vaccine research, and his colleagues.

This ‘gain-of-function lab escape’ theory does not contradict the fact that SARS-CoV-2 is not genetically manipulated. Serial passaging mimics natural evolution in an accelerated fashion in the lab, so it does not count as direct genetic engineering or human-designed virus. It also does not contradict the MMP hypothesis, but rather complements it: RaTG13 or SARS-CoV-2 isolated from the Mojiang Mine may have undergone gain-of-function experiments in the Wuhan Institute of Virology before its accidental escape.

Short abstract and closing

The MMP hypothesis states that the bat sarbecovirus RaGT13 infected workers in the Mojiang Mine in 2012. This RaGT13 then underwent rapid evolution upon the encounter of a new organism, evolving into SARS-CoV-2. These infected miners also had pneumonia signs that were indistinguishable from Covid-19. The miners also underwent treatments used today for Covid-19. Samples from the miners were taken to the Wuhan Institute of Virology for research purposes. SARS-CoV-2 may have then leaked from the lab by accident. In between sample collection and viral escape, a possibility exists that gain-of-function experiments were done.

The MMP hypothesis (maybe plus the gain-of-function theory) explains many facets of the pandemic — such as its ability to infect the lower respiratory tract (which is uncommon of coronaviruses), its unusual adaptability to humans within a short timeframe, and its mysterious zoonotic transfer from bats in Yunnan to people in Wuhan. This hypothesis also does not contradict known facts that SARS-CoV-2 came from bats, not pangolin, human-designed, or the Huanan wet market in Wuhan.

Lastly, note that the MMP hypothesis is only a possibility and not proven yet. The WHO announced in August that they will conduct epidemiological investigations, with the help of China, on the early source of SARS-CoV-2 in Wuhan soon.