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 1. nature
 2. news
 3. article

Engineered bat virus stirs debate over risky research 
Download PDF
Download PDF
 * Published: 12 November 2015


ENGINEERED BAT VIRUS STIRS DEBATE OVER RISKY RESEARCH 

 * Declan Butler 

Nature (2015)Cite this article

 * 118k Accesses

 * 2 Citations

 * 9984 Altmetric

 * Metrics details

Lab-made coronavirus related to SARS can infect human cells.

An experiment that created a hybrid version of a bat coronavirus — one related
to the virus that causes SARS (severe acute respiratory syndrome) — has
triggered renewed debate over whether engineering lab variants of viruses with
possible pandemic potential is worth the risks.

In an article published in Nature Medicine1 on 9 November, scientists
investigated a virus called SHC014, which is found in horseshoe bats in China.
The researchers created a chimaeric virus, made up of a surface protein of
SHC014 and the backbone of a SARS virus that had been adapted to grow in mice
and to mimic human disease. The chimaera infected human airway cells — proving
that the surface protein of SHC014 has the necessary structure to bind to a key
receptor on the cells and to infect them. It also caused disease in mice, but
did not kill them.

Although almost all coronaviruses isolated from bats have not been able to bind
to the key human receptor, SHC014 is not the first that can do so. In 2013,
researchers reported this ability for the first time in a different coronavirus
isolated from the same bat population2.

The findings reinforce suspicions that bat coronaviruses capable of directly
infecting humans (rather than first needing to evolve in an intermediate animal
host) may be more common than previously thought, the researchers say.

But other virologists question whether the information gleaned from the
experiment justifies the potential risk. Although the extent of any risk is
difficult to assess, Simon Wain-Hobson, a virologist at the Pasteur Institute in
Paris, points out that the researchers have created a novel virus that “grows
remarkably well” in human cells. “If the virus escaped, nobody could predict the
trajectory,” he says.

Creation of a chimaera

The argument is essentially a rerun of the debate over whether to allow lab
research that increases the virulence, ease of spread or host range of dangerous
pathogens — what is known as ‘gain-of-function’ research. In October 2014, the
US government imposed a moratorium on federal funding of such research on the
viruses that cause SARS, influenza and MERS (Middle East respiratory syndrome, a
deadly disease caused by a virus that sporadically jumps from camels to people).

The latest study was already under way before the US moratorium began, and the
US National Institutes of Health (NIH) allowed it to proceed while it was under
review by the agency, says Ralph Baric, an infectious-disease researcher at the
University of North Carolina at Chapel Hill, a co-author of the study. The NIH
eventually concluded that the work was not so risky as to fall under the
moratorium, he says.

But Wain-Hobson disapproves of the study because, he says, it provides little
benefit, and reveals little about the risk that the wild SHC014 virus in bats
poses to humans.

Other experiments in the study show that the virus in wild bats would need to
evolve to pose any threat to humans — a change that may never happen, although
it cannot be ruled out. Baric and his team reconstructed the wild virus from its
genome sequence and found that it grew poorly in human cell cultures and caused
no significant disease in mice.

“The only impact of this work is the creation, in a lab, of a new, non-natural
risk,” agrees Richard Ebright, a molecular biologist and biodefence expert at
Rutgers University in Piscataway, New Jersey. Both Ebright and Wain-Hobson are
long-standing critics of gain-of-function research.

In their paper, the study authors also concede that funders may think twice
about allowing such experiments in the future. "Scientific review panels may
deem similar studies building chimeric viruses based on circulating strains too
risky to pursue," they write, adding that discussion is needed as to "whether
these types of chimeric virus studies warrant further investigation versus the
inherent risks involved”.

Useful research

But Baric and others say the research did have benefits. The study findings
“move this virus from a candidate emerging pathogen to a clear and present
danger”, says Peter Daszak, who co-authored the 2013 paper. Daszak is president
of the EcoHealth Alliance, an international network of scientists, headquartered
in New York City, that samples viruses from animals and people in
emerging-diseases hotspots across the globe.

Studies testing hybrid viruses in human cell culture and animal models are
limited in what they can say about the threat posed by a wild virus, Daszak
agrees. But he argues that they can help indicate which pathogens should be
prioritized for further research attention.

Without the experiments, says Baric, the SHC014 virus would still be seen as not
a threat. Previously, scientists had believed, on the basis of molecular
modelling and other studies, that it should not be able to infect human cells.
The latest work shows that the virus has already overcome critical barriers,
such as being able to latch onto human receptors and efficiently infect human
airway cells, he says. “I don't think you can ignore that.” He plans to do
further studies with the virus in non-human primates, which may yield data more
relevant to humans.


REFERENCES

 1. Menachery, V. D. et al. Nature Med. http://dx.doi.org/10.1038/nm.3985
    (2015).

 2. Ge, X.-Y. et al. Nature 503, 535–538 (2013).
    
    ADS  PubMed  PubMed Central  CAS  Article  Google Scholar 

Download references

Authors
 1. Declan Butler
    View author publications
    
    You can also search for this author in PubMed Google Scholar


ADDITIONAL INFORMATION

Tweet Follow @NatureNews

Editors’ note, March 2020 We are aware that this story is being used as the
basis for unverified theories that the novel coronavirus causing COVID-19 was
engineered. There is no evidence that this is true; scientists believe that an
animal is the most likely source of the coronavirus.


RELATED LINKS


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Viral-research moratorium called too broad 2014-Oct-23

US suspends risky disease research 2014-Oct-22

Biosafety in the balance 2014-Jun-25


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Butler, D. Engineered bat virus stirs debate over risky research . Nature
(2015). https://doi.org/10.1038/nature.2015.18787

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 * Published: 12 November 2015

 * DOI: https://doi.org/10.1038/nature.2015.18787


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 1. Menachery, V. D. et al. Nature Med. http://dx.doi.org/10.1038/nm.3985
    (2015).

 2. Ge, X.-Y. et al. Nature 503, 535–538 (2013).
    
    ADS PubMed PubMed Central CAS Article  Google Scholar 

Nature (Nature) ISSN 1476-4687 (online) ISSN 0028-0836 (print)


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