The story so far: On May 14, a group of 18 scientists, most of them from the U.S., led by David A. Relman, published a letter in the journal Science , calling for further investigation to determine the origin of the COVID-19 pandemic . Their reasoning was that in spite of a lot of scientific progress in “understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogenesis, and mitigation by vaccines, therapeutics, and non-pharmaceutical interventions”, more work needed to be done. This was necessary because the two theories on the origins — the virus could have been accidentally released from a laboratory or it was the result of a spillover from some animal species to humans — both remained valid. The novel coronavirus was first reported from Wuhan , a Chinese city hosting a laboratory conducting virus research, and the Program for Monitoring Emerging Diseases (ProMED) notified pneumonia of unknown cause in the city on December 30, 2019. The city’s Huanan wet market was associated with many of the earliest cases.
What have U.S. intelligence agencies been asked to do?
Since the call issued by scientists, U.S. President Joe Biden, on May 26, ordered an investigation by intelligence agencies into the origins of the virus. The Director-General of the World Health Organisation (WHO), Tedros Adhanom Ghebreyesus, has also acknowledged that more work needs to be done on the lab leak theory, although a WHO team that visited Wuhan thought a leak to be the least likely hypothesis . Kristian G. Andersen, a professor at the Department of Immunology and Microbiology at the Scripps Research Institute in the U.S., and his colleagues have hypothesised that the virus emerged from natural mutations.
Why has the demand for a fresh inquiry arisen?
WHO’s governing forum, the World Health Assembly, mandated the Director-General in May 2020 to conduct an inquiry into the origin of SARS-CoV-2, and a joint probe was carried out by WHO and China in January-February 2021. Since there was no conclusive evidence for either hypothesis — natural spillover or lab leak — there were apprehensions when the report leaned in favour of the animal origin hypothesis, describing it as “likely to very likely”, and stated that a laboratory incident was “extremely unlikely”.
Responding to the report, Dr. Tedros said he did not see the investigation as being extensive enough, and went along with the view that more studies were necessary. “Although the team has concluded that a laboratory leak is the least likely hypothesis, this requires further investigation, potentially with additional missions involving specialist experts, which I am ready to deploy,” he informed WHO Member-States at a briefing on the report in March this year.
One of the researchers who signed the letter to Science , Marc Lipsitch , argued that neither laboratory origin, nor natural origin had been ruled out. There was no positive evidence available from the inquiry. He was particularly concerned that the lab leak possibility had been given inadequate attention by the WHO team, and, in fact, treated as a “conspiracy theory”. Understanding the origin of the virus was important to both increase safety in laboratories undertaking biological research, and to prevent pandemics of animal origin.
What is the basis for the natural origin hypothesis?
Based on its study of possible natural origins, the Joint WHO-China study report identifies a SARS-related coronavirus in a (horseshoe) bat (SARSr-CoV; RaTG13) to which the SARS-CoV-2 virus has 96.2% genomic similarity. The novel coronavirus is less similar, by comparison, to the genome of viruses that have caused other epidemics such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Again, the higher infectivity of SARS-CoV-2 is attributed to peculiarities that it contains in the form of unique insertion of four amino acids in its spike protein that makes it more efficient than the virus causing SARS, for instance.
Kristian G. Andersen, who wrote about the Proximal origin of SARS-CoV-2 along with his colleagues in Nature (March 17, 2020), concluded that natural selection on a human or human-like host appeared to facilitate optimal binding of the spike protein of the novel coronavirus with ACE2 receptors. “This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation,” the authors wrote.
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Their arguments are based, among other things, on genetic differences between the viruses: while the RaTG13 in bats is extremely similar to SARS-CoV-2, the receptor binding domain (RBD) of the spike — the RBD protein binds to the ACE2 receptor — actually is divergent for the two, with the former appearing less efficient. Again, some coronaviruses found in pangolins in China are similar to SARS-CoV-2 in the RBD, showing that the optimised spike protein for efficient binding with human-like ACE2 may have resulted from natural selection. It could be hypothesised that while no direct link could be identified to a progenitor virus for the one that has paralysed the world, the process by which the virus could adapt itself to spread among intermediate animals and then humans was a natural one.
It is also possible that a progenitor virus was acquired by humans, and it became more efficient at transmission as it spread among humans during an undetected phase. Dr. Andersen examined the possibility that there could have been an inadvertent release of SARS-CoV-2 from a laboratory, but argues that no progenitor virus with very high genetic similarity for such an experiment has been described, and the changes to the virus to transmit efficiently would have involved its repeated passage through cell cultures or animals with similar ACE2 receptors, which have not been described either.
What does stand out in the present crisis is the emerging call for a global framework for safe biological laboratory research, and more insight into related coronaviruses, animal hosts, mutations, and pathways by which novel viruses infect humans.
