What are the benefits of making animal viruses capable of infecting humans?

Question

If you take an animal virus that doesn't affect the humans and you change it so it can infect humans, what is the benefit from achieving that? Other than maybe creating a potential bio-weapon

On September 20, a group of internet sleuths calling themselves DRASTIC (short for Decentralized Radical Autonomous Search Team Investigating COVID-19) released a leaked $14 million grant proposal that EcoHealth Alliance had submitted in 2018 to the Defense Advanced Research Projects Agency (DARPA).

It proposed partnering with the Wuhan Institute of Virology and constructing SARS-related bat coronaviruses into which they would insert “human-specific cleavage sites” as a way to “evaluate growth potential” of the pathogens. Perhaps not surprisingly, DARPA rejected the proposal, assessing that it failed to fully address the risks of gain-of-function research.

The leaked grant proposal struck a number of scientists and researchers as significant for one reason. One distinctive segment of SARS-CoV-2’s genetic code is a furin cleavage site that makes the virus more infectious by allowing it to efficiently enter human cells. That is just the feature that EcoHealth Alliance and the Wuhan Institute of Virology had proposed to engineer in the 2018 grant proposal

https://www.vanityfair.com/news/2021/10/nih-admits-funding-risky-virus-research-in-wuhan

Answer 1

First off; to clear a couple of things up:

Furin cleavage sites in coronaviruses are quite common - about 30-50% of human ones have them naturally¹, and these sites do NOT necessarily cause them to infect humans, it is just that we ubiquitously express furins², so the presence of a furin-cleavable site makes them more likely to be capable of infection people, but also many other organisms too.

Gain-of-function (GoF) is used all the time in scientific research, as you can cause a gene to gain a function in a bacterium or mouse with almost no risk to anything outside of that individual organism. What you are asking about is GoF in a highly pathogenic virus that has the potential to cause damage to humans.

There are quite a few benefits to so-called GoF research

You could very easily argue that the AstraZeneca/Oxford vaccine, ChAdOx1 is a GoF for a chimpanzee adenovirus, as the chimpanzee virus will not normally infect humans, yet this virus has not only been engineered to infect humans, but also to carry the SARS-CoV-2 spike protein and no-one is complaining about this research at all

You can also use it to study historical viruses, such as the 1918 H1N1 influenza virus, where the sequences are typical influenza, but the only way to find out what properties of these gene products or which combinations to look out for, involve taking those genes and putting them into a lower pathogenicity virus and seeing whether they are more transmissible, pathogenic etc and what particular parts of the protein(s) make it so. We can then look out for these properties in regular surveillance and treat them as potentially more dangerous.

You can also use it to look at the pathogenicity of the viruses: what symptoms do they produce in a model organism, how fast does it act, how lethal are they etc. This is so that we know what to look for in medical terms and likely danger for people if you see a virus with a certain combination of features.

Thirdly - as pure research, if we know the features we are looking at, then finding out exactly what happens when these are introduced to a non-pathogenic virus is of scientific interest, it lets us know how and when viruses could become zoonotic. It also lets us do things like find out what happens when you take a virus like this and passage it through an organism (i.e. infect one, allow it to infect another, which then infects another and so on). This shows us how the viruses evolve, how they adapt to hosts, whether they become more pathogenic or less and many other things.

There's a nice write-up of the risks and benefits here³ for influenza, but the concepts can equally be applied to coronaviruses or any other virus.

1: Peacock Nature Microbiology volume 6, 899–909 (2021)

2: Braun Clinical and Translational Immunology (2019)

3: Casadevall mBio Vol. 5, No. 4 (2014)