Gain-Of-Function Viral Research: What’s The Big Deal?

Senator Rand Paul and many others have raked Dr. Anthony Fauci, long-time director of the National Institute for Allergy and Infectious Diseases (NIAID), over the coals for supporting research at the Wuhan Institute of Virology, and especially for supporting “gain-of-function” (GoF) research at that facility.

This needs some ‘splaining.

First, Senator Paul and the anti-Fauci crowd need to give us their definition of GoF research and then explain why it is bad. If they mean research that gives viruses new capabilities, then most labs seeking to learn how a virus functions is guilty. For example, University of Wisconsin flu researcher, Yoshi Kawaoka, did research that exchanged genes from the 1918 H1N1 Spanish flu virus with less virulent H1N1 viruses in order to learn why the Spanish flu caused so much death back then. That is classical gain-of-function research and it was done under strict quarantine and safety conditions (disclaimer, your blogger was on the safety review committee that vetted and approved Kawaoka’s Spanish flu research). It is legitimate and important research.

The Wuhan Institute of Virology had a small bit of indirect funding from Fauci’s NIAID to support a genetic registry of coronavirus sequences that is freely available to all researchers around the world. As new coronaviruses were discovered and their genomes sequenced, the lab investigators cataloged them. They also inserted the new spike protein genetic sequences into incipient, harmless viruses to see how well the new spike proteins allowed a virus to infect mammalian cells in tissue culture. This was done to help assess how much of a risk a new coronavirus was for spreading among mammals. Strictly defined, this research gave the engineered test viruses new capabilities—they acquired new spike proteins and gained the new functions that came with that. This is legitimate research and not some nefarious plot to weaponize coronaviruses that Rand Paul, et al., dishonestly allude to in their allegations.

Furthermore, there are the thousands of other labs around the world, including mine at UCLA and the University of Wisconsin that use viruses as tools for gene transfer in order to study the activity of newly discovered genes. For example, my lab discovered an aberrant gene that was associated with a particular human leukemia that used to be untreatable. We wanted to learn how the abnormal gene affected blood cells, so we cloned it and inserted it into a virus that could infect mouse cells. We then gave mice leukemia by infecting them with a virus that expressed a human cancer gene. That recombinant virus gained the function of the human cancer gene. Rand Paul, et al., would call that sinister gain-of-function virus research. However, from that and other research, that incurable leukemia now is 95% curable. Sinister?

Sure, using modern molecular technology, a minacious actor could help a pathogen gain super-lethal function and develop a super-pathogen, or a weaponized bug, like antibiotic resistant anthrax or super-spreading Ebola virus. It would be pretty easy to do. But, by far, the GoF research routinely done in labs around the world is done for learning not for killing.

When Paul accuses Fauci of supporting GoF research, that accusation is attached, without evidence, to an implicit accusation that the Wuhan labs are creating more virulent pathogens for nefarious reasons. So, why does Paul not go after Kawaoka or me for using NIH money to create viruses that might be able to kill people (Kawaoka’s flu construct) or that could cause cancer (my virus expressing a human cancer gene)?  

Could it be for political reasons?