The truth about banning “dangerous gain-of-function” research

One of the greatest fears that science brings along with it is the idea that the act of conducting scientific research itself, even if it’s done with noble intentions, could end up creating something incredibly destructive and dangerous to humanity. Uncovering how to split the atom didn’t just result in the development of nuclear power, but also brought with it atomic bombs and the fear of radioactive fallout, contamination, and nuclear war. Advances in biochemistry didn’t just lead to medical treatments, but also to bioweapons that could be used in the theatre of war. And while virology and immunology are incredibly important sciences for understanding and fighting diseases, the great fear is that research in these areas could potentially lead to the creation of a deadly, human-made disease.

It would only make sense — just as we regulate nuclear weapons and their components, and just as we regulate harmful chemicals — that we regulate the type of virological research that could lead to (even the accidental) creation of a novel, deadly pathogen. However, in our attempts to do so, we have to make sure that we:

• only forbid the type of research that’s legitimately risky and potentially harmful,
• that we base any regulations on a foundation of solid science, rather than uninformed fear,
• and that we don’t step on the toes of the profoundly beneficial research that protects us from the natural pathogens that emerge in nature and spill over into the human population.

With a new bill just introduced into the U.S. Senate by first-term senator and trained obstetrician Roger Marshall, the “Dangerous Viral Gain of Function Research Moratorium Act” violates all three of these principles. While many non-experts already possess strongly-held opinions on these issues and any potential legislation concerning them, it’s important to look to the actual science for guidance. Here’s what everyone who wants to be informed should know.

Marburg virus, a deadly infectious disease, spreads through close contact with infected body fluids. It isn’t just the most popular respiratory viruses that virologists work to protect us against, but a wide assortment of afflictions for humans and animals.

To begin, there are three things we should start thinking about immediately: why is this bill being introduced, what is the actual science we need to know about gain-of-function research, and what effects will this bill — if it becomes a law — actually have?

The bill is being introduced because of a concerted misinformation campaign that asserts, incorrectly, that the virus that causes COVID-19 in humans, SARS-CoV-2, was not the result of a natural spillover event at a wet market in Wuhan, China (which the evidence shows is overwhelmingly the likeliest explanation), and instead came about because of illegal, hidden gain-of-function research performed at the Wuhan Institute of Virology that:

• created a new virus,
• failed to contain that virus by somehow infecting one of the workers there,
• and then that virus was brought to the wet market, which triggered the start of the pandemic.

That latter scenario, despite being widely touted throughout the media since 2020, is demonstrably untrue. We know this for several reasons, but the most compelling is written in the genome of SARS-CoV-2 itself: the genome tells us the history of where a virus comes from.

If it came about through laboratory manipulation, it would display a close match to one initial strain, while the (non-matching) remainder of the genome would not line up with any other strains of related (close cousin) viruses circulating in the wild.

But if it came about through frequent recombination with other naturally occurring viruses found in animals that it would contact in the wild, it would display a mix of genome segments shared between many of those “close cousin” viruses: a mosaic genome.

The central idea of the lab leak hypothesis, that the virus spilled over from the Wuhan Institute of Virology, is only possible if the virus from which SARS-CoV-2 originated was actually ever inside the institute itself. If the virus originated naturally, with parts of it found in animals that were located in a wild population in Laos, which genetic sequencing uncovered in 2021 indicates, the lab leak hypothesis is ruled out as a possibility. You cannot create something through gain-of-function research that will have an identical genetic code to something that came about in the wild through natural processes such as recombination.

The discovery that SARS-CoV-2 does indeed have what biologists call a mosaic genome makes it abundantly clear that its genome evolved naturally in bats, and was not stitched together in a laboratory setting. In other words, the scientific evidence has come in, and supports the natural spillover scenario (further supported by a whole host of other evidence), while refuting the laboratory, gain-of-function origin scenario that the other evidence also fails to support.

Yes, you can envision a scenario where there was dangerous virological research performed, and where that research led to the creation of a new, deadly virus that escapes the lab and infected others, kicking off a global pandemic. But that scenario never happened; it does not reflect reality. The bill that’s being introduced is designed to regulate an imagined scenario of potential harm; it does not regulate anything that happened in reality.

And that’s important to recognize: that virological research is already successfully regulated at both the national and international level, and that it is regulated by other experts: virologists, who understand virology and know what they’re doing. In particular, virologists don’t regulate research based on whether it uses gain-of-function or loss-of-function methods; they regulate it based on a science-based framework known as ePPP: experiments that might enhance Potential Pandemic Pathogens. This new bill, as written, would not make us any safer, as no harmful research has ever “slipped through the cracks” of what virologists already regulate.

This detailed illustration shows the molecular structure of the light-harvesting complex 2 (LH2) molecule: an important molecule in transporting incident photon energy toward the photosynthetic reaction center. These antenna proteins transport energy in a highly efficient manner: a difficult-to-explain phenomenon that relies on a specific set of structures working together to produce a unique function.

But this gets at a deeper truth: that people have been fundamentally misinformed as to what gain-of-function research even is. One way you can test this for yourself is to find someone with a strong opinion on regulating gain-of-function research, and then to ask them what their opinion is on regulating loss-of-function research. Overwhelmingly, the response you’ll get is “what’s that,” which should alarm you: if someone doesn’t know what loss-of-function research is, they very clearly do not understand gain-of-function research at all, either in the context of virology or anywhere else. If you don’t have the necessary information, and you have a very strong opinion, you are behaving in one of the most unethical fashions imaginable.

Of course, you can fix that by becoming adequately informed, so let’s get you to where you need to be.

In the biological sciences, a “function” is any life process that an organism carries out. Your blood traveling throughout your body to provide oxygen to your cells is a function, the acts of eating and breathing and digesting are functions, plants photosynthesizing is a function, etc. Behaviors such as fighting, gathering and competing for resources, and fending off predators are all functions, too, as is reproducing. Although organisms have a variety of ways to perform these functions, every organism that performs them has an associated structure that carries out these functions.

This diagram shows the internal structure of a eukaryotic yeast cell in the process of dividing and reproducing through the process of budding. Unlike their more primitive prokaryotic counterparts, eukaryotic cells have differentiated cell organelles, with their own specialized structure and function that allows them to perform many of the cell’s life processes in a relatively independent fashion from the rest of the cell’s functioning.

Although we don’t talk about it as much as we talk about concepts like evolution, genetics, or DNA, the relationship between structure-and-function, biologically, is one of the core components of our understanding of biology. Organisms need to carry out functions in order to survive and thrive in their environments and reproduce, and unless those functions occur spontaneously for non-biological reasons, they need to have a structure that enables those functions to be carried out.

In order to transport your oxygenated blood throughout your body, performing the function of providing oxygen to your cells, we have circulatory systems and a pump (i.e., a heart) that moves that blood throughout our bodies. Our blood vessels and heart are the structures that perform this necessary function.

Structures don’t have to be macroscopic to perform functions; molecular machinery is incredibly important as well. Plants perform the function of photosynthesis because of the structure of chlorophyll molecules. Cells perform the function of letting things in-or-out based on the structure of channels in their cell walls/membranes. And pathogens perform the function of infecting host cells based on the structure of the molecular machinery that allows them to enter those cells in the first place.

The host cell, shown in yellowish-brown, contains ACE2 (in green) on its outer cell membrane. SARS-CoV-2 is excellent at binding to this molecule, allowing it to infect the cell. ACE2 behaves as a cellular doorway, and the virus’s receptor-binding domain (RBD) is what allows it entry.

When we talk about research that involves an organism’s function, in any aspect, we can divide that research into to categories:

• gain-of-function research, which results in an organism either developing a new function or making an existing function that it possesses more effective,
• or loss-of-function research, which results in an organism either losing a pre-existing function or making an existing function that it possesses less effective.

For example, if you want your organism to develop a resistance to an environmental toxin, you might consider slowly, over many generations, adding a steadily increasing amount of that toxin to the organism’s environment. If the organism (or a sub-population of the original organism) survives because it develops a way to metabolize the toxin, that would be an example of gain-of-function research, while if it survives because it loses the ability to allow the toxin to enter through its cell wall/membrane, that’s an example of loss-of-function research.

The key relationship, again, is that relationship between structure and function: where if you want it to perform a new/enhanced function or to cease to perform a function that it already performs, you are engaging in gain-of-function or loss-of-function research. They are two sides of the same coin, and both are keys to biological research. Specifically, when it comes to virology, gain-of-function or loss-of-function research is often related to infectivity and virulence of a virus, and is pretty much always related to the molecular machinery — or structure — that are produced by the proteins that its genome encodes.

This figure shows the structure of the spike protein in SARS-CoV-2. Panel A shows the spike homotrimer in its open configuration, while panel B shows the cleavage sites on the spike protein. Note how the configuration of a protein, and how it folds in its environment, controls many aspects of its functioning. Even an identically structured protein isn’t going to perform the same in different environments, which is research that would be outlawed under the Dangerous Viral Gain of Function Research Moratorium Act.

In other words, terms like “gain-of-function” and “loss-of-function” are very generic terms, and naming a bill the “Dangerous Viral Gain of Function Research Moratorium Act” should raise alarm bells in your head right away. By insinuating that:

• there is dangerous viral research being performed (there is not),
• that the dangerous part of it is that it’s gain-of-function research (which is not the dangerous part),
• and that we should place a moratorium on anything classified as “dangerous viral gain-of-function research” (which opens the door to destroying the vital, life-saving science of virology),

it’s a bill designed to prey on people’s fears, rather than what’s scientifically supported by the evidence.

So what will happen, practically, if this bill becomes a law?

In short: many things, all of which are bad for virology and humanity, and none of which make us any safer. Let’s start with the opening text of the bill (bold emphasis by me):

“To provide a moratorium on all Federal research grants provided to any institution of higher education or other research institute that is conducting dangerous gain-of-function research.”

The first thing we learn is that this bill is not designed to stop dangerous gain-of-function research, but rather, to eliminate all federal grants and federal funding to any research institute, whether at a University or elsewhere, that is deemed to be conducting gain-of-function research. It’s not just punishing any (hypothetical) researchers engaged in “dangerous” research, but rescinds funding for all research at any institute that conducts any gain-of-function research, as made clear on lines 10-14 of page three of the document.

In this picture taken on April 29, 2020, an engineer shows an experimental vaccine for the COVID-19 coronavirus that was tested at the Quality Control Laboratory at the Sinovac Biotech facilities in Beijing. Many of the techniques used to develop vaccines, including vaccines against SARS-CoV-2 and its various strains, would be illegal under this proposed new bill: the Dangerous Viral Gain of Function Research Moratorium Act.

You may wonder, then, what this particular bill defines as gain-of-function research, which it tries so hard to stamp out? According to the bill, it is any research involving:

• influenza viruses,
• coronaviruses,
• any agent or toxin on one of three federal lists,
• or “any synthetic construct of such virus, agent or toxin,”

where they genetically alter the organism to change or enhance any of the following:

• infectivity,
• transmissibility,
• pathogenicity,
• or host range (i.e., making it infectious to new host organisms, including animals).

This bill, then, if it becomes law, will effectively end much of the most important virological research presently conducted in the United States and across the world.

How?

Let’s say you’re studying influenza, and you’re looking at the dangerous H5N1 strain. Which animals will this variant of the strain infect? Cows? Pigs? Birds? Humans? What mutations will confer these various infectivities?

Under this new bill, you won’t be able to perform that research.

The SARS virus (orange) has a crown-like structure, meaning that it’s part of the coronavirus family of diseases. The novel coronavirus SARS-CoV-2, also known as the virus which causes COVID-19 in humans, is the largest, most lethal and long-term detrimental new pandemic to hit planet Earth since the dawn of the 21st century. Despite having a genetic sequence of only ~30,000 base pairs in it, this virus has killed over 7 million people since 2020, with many estimates for the true number of deaths rising into the tens of millions.

SARS-CoV-2, the virus that causes COVID-19, has mutated many times, as we’ve already seen many different strains that continue to infect people who’ve already been infected previously. We call these mutations ones that lead to the virus “escaping immunity,” as even though we’ve been infected and have developed antibodies against the strain that infected us previously, this new strain can infect us anew.

Under this new bill, studying how SARS-CoV-2 escapes immunity is research we could no longer perform.

You can’t study live viruses found in the wild, including the “close cousin” viruses of SARS-CoV-2 that are out there, floating around in the wild, mutating naturally and creating the natural viral reservoirs of future diseases, epidemics, and potentially pandemics as well.

You also can’t study “any synthetic construct of such virus, agent, or toxin,” which means you can’t study:

• The spike protein of SARS-CoV-2, which is what we use as antigens in the COVID-19 vaccines.
• Any research or clinical procedure that uses viral vectors, which would kill the entire industry of gene therapy.
• The recently developed science of deep mutational scanning, which is vital for understanding differences in structure and function that arise from protein mutations.
• The features common among different strains of flu virus that could lead to a vaccine or treatment across all of them.

But the big punitive cost isn’t limited to the individual research programs that would now be forbidden. The worst aspect is that any institution that attempts to conduct any form of research, no matter how beneficial, benign, or important it is, that gets deemed as “dangerous gain-of-function research” would lose all of its Federal funding for all of its research grants. No research institution or University would want to carry that risk, and so the most likely outcome is that this bill, if it becomes law, would signal the end of practically all virological research in the country.

This color-coded diagram represents 15 recombinant fragments of various SARS-related beta coronaviruses compared to the original genome of SARS-CoV-2 that first infected humans. Several different strains show a “best match” for a variety of these 15 fragments, indicating a recombination-based origin for SARS-CoV-2, and refuting the feasibility of a lab creation through gain-of-function research.

To recap:

• there is a bill proposed under a misleading name, the Dangerous Viral Gain of Function Research Moratorium Act,
• which cannot point to any dangerous viral gain-of-function research that has ever been performed,
• which fundamentally (and arguably, deliberately) misrepresents and misunderstands what gain-of-function research is,
• which would effectively end incredibly beneficial virology research in the United States,
• while stopping no threats, pathogens, or diseases at all.

It is a Trojan Horse of a bill: similar to Florida’s 2004 “Ban Bad Doctors” law that caused a mass exodus of doctors who specialized in obstetrics and gynecology, because the way the bill is marketed (who doesn’t want a moratorium on dangerous research? Who doesn’t want to ban bad doctors?) is very different from what the bill actually accomplishes.

This bill wouldn’t make anyone safer, but rather would bring an end to an important tool in the battle against infectious diseases. It’s another thinly-veiled government-led attack on science: similar to what DOGE is doing to government-funded science across the board, or the numerous government decisions that have triggered the abrupt retirement of many legendary figures in 20th and 21st century science. As noted virologist Roberto Burioni said back in 2016, “The Earth is round, gasoline is flammable, and vaccines are safe and effective. All the rest are dangerous lies.” Don’t fall for the latest lie; dangerous viral research is already appropriately and sufficiently regulated. Any claims to the contrary need to be backed up by hard evidence to the contrary; until that day arrives, follow what the evidence actually shows us.