Should we blame Gain of Function Research: SARS CoV 2 Context

In the last few weeks, I have been receiving a lot of questions asking and challenging if the SARS CoV 2 is Gain of function (GoF) research that has gone wrong. The questions have been coming after seeing my comment on an article in nature news (Link). Considering there is a lot of media hype on the story, and a lot of public actually believe that SARS CoV 2 is a DURC (Dual-use Research of Concern) and GoF Product some clarity is needed.

Photo: Shi Zhengli. Source

So why is this even a debate? The question comes based on the earlier research by Shi Zhengli’s group where there was GoF research conducted on coronavirus to understand its transmission and pathogenic capabilities. Further, her recent disappearance has substantially pushed the debate forward (Link). Even worse, the genetic sequence of SARS CoV 2 is 96.2% similar to the virus isolated in the Wuhan lab in 2013. There was also a story published on the internet with a Hollywood movie like plot claiming that this was a biological weapon that had accidentally leaked. There are many versions of this story circulating on the internet. These claims have had so much visibility, there is an actual investigation federal level investigation into the whole matter (Link).

Genetic homology and relatedness is a great way to tell relatedness. The more is the genetic similarity, the closer are the isolates. So automatically the question comes if the virus is more than 96% similar to whats isolated at Wuhan lab in 2013, that has to be the source, right? The answer (Need not be) is slightly technical. In simplification, another SARS CoV strain from Civet has shown 99.8% identity which is perfectly in agreement with natural transmission possibilities. The SHC14-MA15 which is the chimeric virus (Lab engineered strain for GoF research) is extremely different from the SARS CoV 2 sequences (only 93% similar). In genetic terms, a change of more than 1% is considered as highly divergent and lower relatedness. I especially like the very detailed analysis published by Yuri Deigin. There is a very detailed analysis of the possibility of engineering SARS CoV 2 (Link) which considers both sides of the argument. At this point, it is not possible for any research to establish or refute the "Laboratory origin" theory of SARS CoV 2. However, the proofs available tend to indicate that it is a naturally occurring outbreak.

So let me put the question hanging in there. Assuming that the SARS CoV 2 leaked from the BSL-4 Wuhan Institute (Please note I don't imply it did), does it mean GoF research conducted at the Wuhan lab is responsible for the outbreak?

I urge you to go back and read my blog on GoF research (Link to my previous post). There is a certain way you do scientific experiments which are accepted by the international community based on years of backing research. For example, when the avian H1N1 was modified to see if it can infect human cell lines in a BSL-4 Lab, they did it to understand what mutations are required and to what extent which will make it infective to humans. This arms the scientific community with prior knowledge on what's likely to happen and how (if at all it happens). So if the strain hits, we don't start fresh from scratch in trying to understand what has happened. The reason we are ahead of the curve in this pandemic is a lot of molecular details are understood for Coronavirus is published GoF research. Indeed a bat originated coronavirus outbreak was predicted a year earlier as a clear possibility. An excerpt from the paper reads

"Fifteen years after the first highly pathogenic human coronavirus caused the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak, another severe acute diarrhoea syndrome coronavirus (SADS-CoV) devastated livestock production by causing fatal diseases in pigs. Both outbreaks began in China and were caused by coronaviruses of bat origin. This increased the urgency to study bat coronaviruses in China to understand their potential of causing another virus outbreak".

“It is highly likely that future SARS or MERS-like coronavirus
outbreaks will originate from bats, and there is an increased probability that this will occur in China”.

-Source paper

Fig 1: Polling Results from Science
Advisory Board. Data from 2015.

Coming back to the question on the light of apropos, a BSL-4 lab is highly regulated and there is a strict code of conduct on how strains are handled in it. If at any point in time, it is proved that SARS COV 2 is indeed a lab generated virus, by accident it means that they have lapsed from scientific integrity and action will be taken accordingly. But claiming that regulated GoF research is to blame and the whole world has to stop such research is "uncontrolled stupidity". 

At this point, I should answer a question. Is the GoF research a biological weapon program in context to SARS CoV 2. If SARS CoV 2 is a biological weapon detail of this virus would not have been published by the Chinese when the research was in progress. Experiments conducted for research into understanding the biology by academic and industrial scientists are very carefully planned and done at well contained biological safety labs. The results of such research are published and used to build vaccines and therapeutics. Biological weapons research is not done by academic or industrial scientists. Contrarily, they are done in military facilities only by some countries (it is assumed so), the results of which are never published. Those research are not called as GoF research (Since it doesn't follow the GoF protocol) and do not come under the control of IRBs. The logic of not communicating such research openly is obvious.

I have given you the background. In summary, the GoF research conducted on coronaviruses has helped us understand and even predict the outbreaks. There is no evidence as of yet (out of huge numbers of papers that have actually analysed the question) that it is a laboratory strain or deliberately released virus, but rather appears as naturally occurring. So consider the risk-benefit ratio and I will let the reader decide if we should blame Gain of function research.

References:

1. Michael J. Selgelid. Gain-of-Function Research: Ethical Analysis. Sci Eng Ethics. 2016; 22(4): 923–964. Link

2. Duprex, W., Fouchier, R., Imperiale, M. et al. Gain-of-function experiments: time for a real debate. Nat Rev Microbiol. 2015;13, 58–64. Link

3. Declan Butler. Engineered bat virus stirs debate over risky research. Link

4. Liu et al. No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2. Emerg Microbes Infect. 2020; 9(1): 505–507. Link

5. Fan et al. Bat Coronaviruses in China. Link