Gain-Of-Function Research At The Wuhan Lab: Part 1

“Mater artium necessitas"

 A lot of news print, band width, and fevered comment has been bandied about regarding “Gain-of-Function” (GoF) coronavirus research at the Wuhan Institute of Virology (WIV). It usually has been done so with an unspoken insinuation that something was very wrong or careless with that research. People are left with visions that GoF research involves mad scientists creating Franken-viruses and that that perhaps caused the pandemic. Certainly when scientists begin fiddling around with the genomes of nasty pathogens bad things can possibly happen. In fact, bad things can occur simply by growing and culturing dangerous microbes—accidents can happen.

Did we in fact get the SARS-CoV-2 virus, which caused COVID, from scientists in Wuhan playing Russian (or Chinese) roulette with coronaviruses and their genes? Did irresponsible or careless research lead to an intentional, or, more likely, an accidental event that unleashed a virus that devastated the world for two-plus years?

These questions and rumors have floated around long enough that people now believe the premise--say it often enough and people will believe. But, hardly anyone knows what research was being done in the WIV labs. Few people even know what GoF research entails because no one has taken the time to describe it.

Let me give a shot at clarifying all this. I will do this in a two-part blog. The first blog post, which you are now reading, will explain what gain-of-function research is. It will surprise readers to learn that humans have been doing it for thousands of years and that it is going on all around us all the time. In the second blog that I will post in a few days, I will delve into what exactly was going on in the Wuhan labs and try to explain the research so non-scientists can grasp what they were doing.

My aim in these two blog posts is to give readers the ability to parse through the rhetoric and understand the reality. Here we go.

GoF research backstory: Basically, gain-of-function simply is when a mutation in an organism--animal, plant, or microbe--changes some function in it. That is what drives evolution, That is how bacteria acquire resistance to antibiotics, as an example. Microbes and cells do it all on their own via happenstance mutation followed by natural selection in an environment that favors the mutation.

Humans have been purposefully doing GoF research ever since we began farming and raising animals. We just never called it gain-of-function research. The minute we began selectively breeding animals and crops to produce better products, we were doing GoF research. Selective breeding first identifies animals or crops with desired traits that arose by chance genetic mutation and then selectively chooses the animals with those traits to breed. That fixes the genetic mutation and its desired trait into the genome of the plant or animal. Gain-of-function.

Then came recombinant DNA technology in the 1970s. We began cloning and mutating genes in the lab, and  inserting the lab-altered genes into animals and plants, thereby speeding up the long, arduous process of selective breeding. We do this all the time now in making genetically engineered crops and animals. It also is how we are now beginning to genetically treat certain diseases in plants, animals and humans. This is all gain-of-function technology. It is happening all around us all the time.

GoF technology also is a very common research tool used in almost every cell biology and microbiology lab in the world. For example, at one point in my own research lab, we studied how a change in a normal human gene might cause what was an untreatable leukemia. We took a cloned version of the normal human gene, mutated it, then put it in a virus to shuttle the mutated gene into bone marrow cells growing in tissue culture. The gene we altered caused normal bone marrow cells to become leukemia. That is how we proved the alteration in the normal human gene was sufficient to cause leukemia. From all the research that followed in many labs using that GoF leukemia model, the leukemia is now mostly curable. That illustrates the value of GoF lab research. It is done all the time in countless labs around the world to understand how genes and cells work.

What about GoF research on dangerous pathogens? Just like in the cell biology experiments above, GoF experiments on pathogens can tell us how certain viruses and bacteria become dangerous. As just one example, in the early 2000s, flu researchers at the University of Wisconsin did experiments to learn what made the 1918 Spanish flu so much more devastating than other seasonal flus. They systematically replaced genes from a mundane cloned laboratory flu strain with genes from the 1918 strain that had been cloned from stored patient samples dating from 1918. The goal was to learn which of the 1918 flu genes increased the transmission and/or virulence of the lab strain. Gain-of-function.

Bottom line: Similar GoF studies are undertaken all the time in many labs around the world that work with many other dangerous pathogens. Information from such studies has been enormously valuable for understanding how dangerous pathogens become dangerous and cause disease, and how to protect us from them. These studies have been conducted without causing major problems for the world.

Sure, GoF research can be used for nefarious purposes. A malevolent actor can use it to make terrible pathogens like anthrax resistant to all antibiotics and turn it into a weapon. It would be simple to do; a college microbiology student in a college lab could do it if he got his hands on the bacteria (which can be easily grown from soil). Ebola is a terribly lethal virus, but it is very difficult to transfer between people,  which has limited it to controllable regional epidemics. If a mad scientist manipulated its genome to turn it into an airborne pathogen, it could wreak world-wide havoc, probably worse than COVID or the Spanish flu. And so on.

Therefore GoF research on pathogens can be both beneficial and dangerous. This is called “dual purpose research.” Scientists and government officials are very aware of this dual threat from such research and sometimes science publications purposefully withhold critical data that a bad actor could misuse.

Needless to say, this is a very controversial tightrope science walks when dealing with dual purpose science, such as GoF research on dangerous pathogens. Science is entirely based on disclosing what it discovers, but it can sometimes discover things that, while enormously useful for humans and the world, can also be enormously destructive. What do you do then?

Have you seen the movie, Oppenheimer?

Now that we have established grounding in what gain-of-function research entails, the next blog post, will describe the coronavirus research that went on in the Wuhan Institute of Virology. Hopefully, these blogs will give you a clearer understanding of whether or not the lab was responsible for the virus that caused the COVID pandemic.