Novel Corona Virus – Natural mutation or engineered in lab?

Prof Pankaj Chaturvedi, Dy Director, Center for Cancer Epidemiology, Tata Memorial Center, Mumbai

Dr Arjun Singh, Research Fellow, Tata Memorial Hospital, Mumbai

United States President Donald Trump said that the coronavirus may have been accidentally leaked by an intern working at the Wuhan Institute of Virology in China. He also confirmed that the U.S. Government is investigating if the Covid outbreak began due to security failure at a Wuhan laboratory. Some US news channels have quoted unnamed sources and stated that the research on this virus was an attempt by the China to prove their superiority or equality to United States. Some news articles have gone to an extent of branding this virus as a lab made bio-weapon. In this article we tried to review the information in the public domain to ascertain this theory of leak and engineering of this virus to its fatal variant.

The Wuhan Institute of Virology [WIV] located in Wuhan is a research institute on virology, administered by the Chinese Academy of Sciences (CAS). In 2015, the National Bio-safety Laboratory was completed at a cost of 300 million Yuan ($44 million) at the Institute and was the first biosafety level 4 (BSL–4) laboratory to be built in mainland China. From the beginning, the lab was involved in research of coronaviruses.

Research

In 2015, Li et al published reports linking species of bats that act as natural reservoirs for SARS like coronaviruses [SL-CoVs]. The lab was involved in research of coronaviruses and was researching on the virus responsible for SARS outbreak in 2003. They theorized genetic diversity of viruses in bats and increased possibility of them infecting the humans. During the SARS epidemic, links were established between palm civets and the strains detected in humans. This animal to human transmission happened when civets came into human contact in live animal markets. Since the pools of bat containing CoVs are limited, the likelihood of future emergence of this viral outbreak was never anticipated.

Reservoirs

But the comfort levels were disturbed when it was proven that a chimeric virus containing the SHC014 spike in a SARS-CoV backbone causes robust infection in both human airway cultures and in mice. These authors warned that that the starting materials required for SARS-like emergent strains were currently circulating in animal reservoirs. A research team in China spent five years in the caves of Yunnan province sampling from the bats. They did warn that some viral strains were circulating in animal reservoir that may cause resurgence of SARS-like situation. They also found a village nearby and warned of potential disease outbreak if precautions weren’t taken. By December 2019, the first bunch of cases was reported in China.

Lab Origins of the virus

One of the investigators from the institute even published an account of the illness and reported on a new strain of coronavirus that had bats as the “probable” source. This report along with another report shows that the onset of initial cluster of cases was December 12, 2019. All the studies of Shi Zheng Li, the lead virologist from Wuhan Institute of Virology, concerning bat related coronaviruses were centered on the southern, subtropical areas of Guangdong, Guangxi and Yunnan. But the outbreak occurred in Wuhan which is almost 900 km from Yunnan province where the Shitou Cave was located. This was the cave which yielded a natural genetic library in their researches on coronavirus.

The corona virus samples from the initial few cases in Wuhan were analyzed for their genetic composition. On comparing these genetic structures with the samples isolated from bats, none of the sequences matched those sampled from the bat cave. If not from bats, where did these come from? The Government of China conducted an investigation and reported wild life market, 10 miles away from the virology institute, as the epicenter of the epidemic. Though the Chinese government discredited lab origin based on genetic studies, the distance of epicenter from the bat caves raises questions. The theory of lab origin of the novel corona virus starts from here. Seemingly unrelated but nevertheless solid and tangible facts give credibility to this theory.

Preparedness

The Wuhan Institute of Virology in China indeed posted a job opening on November 18, 2019 asking for researches on coronavirus. On December 24, 2019, a second job opening inviting researchers for research on a large number of new viruses from bats and rodents. Within a week of these job openings, clusters of atypical pneumonia [COVID -19] started to crop up. These research posts tell us about the direction of ongoing research taking place in the labs and also underline the fact that the Chinese knew about the possibilities of novel strains even before the outbreaks. This WIV laboratory reported that the Chinese horseshoe bats were natural reservoirs for the severe acute respiratory syndrome coronavirus (SARS-CoV) which caused the 2002-3 pandemic and also generated a chimeric virus using the SARS-CoV by reverse genetics system and reported the potential for human emergence. The leak could have happened from this lab.

Theories

On February 6th, scientists from the South China University of Technology uploaded a paper on the origins of coronavirus. The report said that the intermediate host Horseshoe bat was not available at the Wuhan wet market and did not live in Wuhan area. According to them, the only place those particular bats existed locally was inside a research facility which was just several hundred yards from the Wuhan wet market. The bats carrying current corona virus were originally found in Yunnan or Zhejiang province. According to municipal reports and the testimonies of 31 residents and 28 visitors, the bat was never a food source in the city, and no bat was ever traded in the Wuhan animal market. The paper also alleges that in Wuhan Center for Disease Control and Prevention surgeries were performed on the caged animals for DNA and RNA extraction and sequencing and these were source of pathogens. They were only 280 meters from the seafood market. This center was also adjacent to the Union Hospital where the first groups of doctors were infected during this epidemic.

But curiously the lead author has now retracted the paper saying that his paper was mere speculations and not based on solid proofs. Surprisingly, other papers met similar fate. Two leading Chinese universities recently published their findings on corona virus and then removed these pages following a new policy mandating government approval for publishing academic papers dealing with Covid-19. They were posted on the websites of Fudan University and the China University of Geosciences located at Wuhan. These attempts of clampdowns bolster the theory of a leak from the lab rather than from the community.

The theory gets bolstered by the classified cables from US embassy in China in January 2020. It reported that the labs were conducting risky studies on coronaviruses from bats. The Wuhan Institute of virology has a highest level of international bioresearch safety (known as BSL-4) certificate. The officials noticed that the new lab has a serious shortage of appropriately trained technicians and investigators. There were concerns of undue risks being taken in WIV.  There are similar concerns about the nearby Wuhan Center for Disease Control and Prevention lab, which operates at biosecurity level 2, a level significantly less secure than the level-4 standard. As we can see the leaks cannot be ruled out entirely.

Artificial engineering

An Indian research paper published in January, which has now been retracted, found genetically altered insertions in the genome of novel coronavirus similar to HIV and Ebola. They argued that it is quite unlikely for a virus to have acquired such unique insertions naturally in a short duration of time. This structural change might have also increased the range of host cells that 2019-nCoV can infect. This paper was taken down as it was widely criticized but research from the Nankai University in Tianjin, China is reporting similar findings. This is seen as an evidence for the virus being manmade.

Clampdown

Lastly, the doctors who were the first responders were allegedly asked by the government not to spread rumors. Li Wenliang, the Chinese doctor who sounded the alarm on the Wuhan coronavirus on WeChat, detailed about seven people from a local seafood market who showed signs of a SARS-like illness were quarantined in his hospital in Wuhan. Li was taken to the police station where he was forced to sign a statement acknowledging his misdemeanor for spreading rumors. Sadly he succumbed to the disease later. In another report, a lawyer turned activist has also been forcibly put down after posting critical videos of the outbreak response in Wuhan. The doctors were advised by the government “not to mislead the public” and to refrain from publishing any unauthorized information. They were also told to “resist all kinds of rumors and clarify and guide false opinions and discussions”, while they were reminded to protect the privacy of patients.

Conclusion

Although it seems unethical to point fingers at this time when our efforts are required elsewhere, one cannot be entirely contended with the community origin theory put forth when the evidences say otherwise. It is imperative on the part of healthcare community to get into bottom of this in order to prevent future occurrences of man-made pandemics simply because we may never have a chance otherwise.