An Illegitimate Child: Parent unknown?

There is still ambiguity over origin of SARS-CoV-2. Now some experts claim as SARS-CoV-2 is like an illegitimate child whose parent is unknown……….
By Dr Amitav Banerjee

As per report, early in the Covid-19 pandemic, SARS-CoV-2 was of laboratory origin. They noted four unique insertions in the spike protein of the virus responsible for the most disruptive pandemic in the history of public health. The insertions made the virus more efficient in attaching to human cells and therefore more transmissible. This is one of the strategies of “gain of function research.”

The researchers from Indian Institute of Technology Delhi (IIT, Delhi), and Acharya Narendra Dev College, found their findings in a pre-print to share their astounding results with the wider research community. However, the impact was not what they expected. The high priest of Covid-19, Anthony Fauci, described the research and its conclusions “outlandish!” Taking cue from the influential medical dictator of his times many top scientists strongly criticized the paper. Finding no support from the scientific community, the Indian researchers were forced to withdraw the paper.

What is gain of function research?
Gain of function research (GOFR) refers to attempts to enhance the function of a naturally occurring pathogen so that it becomes more transmissible or more virulent. The method to this madness is twofold – to be one step ahead of nature in case the naturally occurring virus or pathogen mutates naturally to a more virulent strain, so as to prepare vaccine or drugs in advance, and secondly, to be ahead of a hypothetical enemy working on bio-weapons.

Gain of function research originated from controversial experiments undertaken in USA around 2011, involving mutated version of the H5N1 avian influenza virus in which ferrets were infected with the virus. The naturally occurring strains of H5N1 while very lethal with 60% fatality had very poor transmission ability among humans. Researchers in anticipation of an unfortunate natural mutation to a more transmissible variant started working on GOFR with the H5N1 and made it highly transmissible by the airborne route among ferrets. They were also found to be sensitive to some antiviral drugs. When these researchers attempted to publish their findings, the United States Science Advisory Board for Bio-Security, an advisory committee to the US National Institute of Health (NIH), did not give permission. This was due to the apprehension that groups hostile to American interests may use the findings to develop their own biological weapons. An international group of influenza researchers in 2012 announced a pause to GOFR with the viruses which would enhance transmission among mammals. This pause lasted for eight months. In the interim, the issue was discussed at various forums including the WHO, in media and scientific journals.

Several months later the research teams which conducted the gain of function research were permitted to publish their findings in Nature and Science.

While proponents of the GOFR justify it on grounds that it can enable better preparedness in case of natural mutations of pathogens to highly virulent forms, others discourage it on the grounds of it being hazardous in case of accidents like lab leaks.

The plot thickens – was SARS-CoV-2 origins a result of GOFR gone astray?
While all along, any speculation about attributing the origins of SARS-CoV-2 to a lab leak were quashed by main stream media and scientific journals and dismissed as “conspiracy theory,” recent disclosures have swung the needle of suspicion back from the forest towards the lab.

The former Head of the Centers for Disease Control, USA, Dr Robert Redfield, a virologist himself, mentioned that he was “sidelined” due to his views on the origins of the SARS-CoV-2. He was the key witness in a public hearing on the origins of the novel coronavirus. He expressed that he was excluded from discussions on the subject by Anthony Fauci and his team, because he suspected a laboratory leak. The accusation was vehemently denied by Fauci.

Many scientists still insist that there is no possibility that the virus originated in a laboratory. The White House, as usual is non-committal. It says there is no consensus among US government scientists and officials about the origins of the virus.

Cave nectar bat (Eonycteris spelaea) from Singapore.

Proponents of natural source put forth the hypothesis that the virus originated from the wet sea food and wildlife markets in Wuhan. Incidentally, or rather conveniently, the market is near the Wuhan Institute of Virology that was conducting research on coronaviruses.

Dr Redfield, however, persists that the virus originated in the lab as it is not scientifically plausible that it evolved naturally from animal source. He was leading the CDC when the pandemic was declared in 2020. He claims that he was kept in the dark since the beginning of the pandemic and excluded from meetings as his views did not find favour with Fauci, the de facto head of the Covid-19 pandemic response. Dr Redfield said that he was informed that there should be a single narrative and his views did not fit in that narrative. He lamented that debate, so essential in science, was squashed.

Dr Redfield also expressed that he was opposed to gain of function research. He suspected that this research was being funded at the Wuhan lab by US agencies.

The public hearing in the USA came shortly after the FBI announced that a lab leak was “most likely.” Before that the US Department of Energy issued a statement saying that the virus was most likely a result of lab leak in Wuhan but could only reach to this conclusion with “low confidence,” whatever that means.

The needle of suspicion swings back towards animals
Just when it was appearing that the mystery of the origins of the virus was resolving, the WHO has muddied the waters once again. It has accused China of hiding data that would establish the animal origins of the virus. There is speculation that the pandemic originated when illegally traded racoon dogs infected humans at the wet sea market in Wuhan. The gene sequences were removed from the scientific database. These data should have been shared three years ago, said Tedros, the WHO Director General.

Doubts remain about the collection of samples, what they contained, and why they disappeared. Ambiguities persist and it is difficult to come to any firm conclusions based on propositions. The new genetic data do not establish beyond doubt that racoon dogs were infected with the coronavirus. Even if they had been the possibility remains that some infected persons may have passed the virus to the racoon dogs, the coronaviruses being promiscuous viruses capable of infecting many species.

Conclusion – “Talash” continues…
In the absence of the actual animal that first spread the virus to people (the nearest bat cave is hundreds of miles away from Wuhan), trying to search for the origins of the virus would always involve weighing probabilities. Finding the source at the seafood market was rendered impossible as animals sold at the market were removed before researchers took samples in early 2020. Failure to find the virus circulating in animals around Wuhan is the weakest link in the hypothesis of natural origins. For a long time to come, it appears, SARS-CoV-2 would remain an illegitimate child – parent unknown.

(The author is a post doctoral in epidemiology who was a field epidemiologist for over two decades in the Indian Armed Forces. He also led the mobile epidemic investigation team at the Armed Forces Medical College, Pune, India from 2000 to 2004. During this period he investigated a number of outbreaks in different parts of the country. He was awarded for his work on Tribal Malaria and Viral Hepatitis E. He presently is a Professor in a Medical College in Pune.)

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