Why Gain-of Function Research Should Be Banned: The Author of ‘Biotech Juggernaut’ Speaks Out on COVID-19
May 18, 2020 | Pat Thomas
Organic Consumers Association
In an interview conducted on May 7, 2020, Pat Thomas and Dr. Stuart Newman discussed the possible origins of COVID-19. Newman, Ph.D., is a professor of cell biology and anatomy at New York Medical College in Valhalla, New York. He is the co-author of the recent book, “Biotech Juggernaut: Hope, Hype, and Hidden Agendas of Entrepreneurial BioScience.” He was a founding member of the Council for Responsible Genetics in Cambridge, Massachusetts.
PT: Well good morning, good afternoon, good evening. Whatever time zone you are in, you’re most welcome here at the Organic Consumers Association. My name is Pat Thomas and our topic today is the same topic for most of us everyday. Coronavirus, Covid-19, SARS-CoV-2—whatever you call it.
It’s the conversation that changes daily, almost hourly. And in addition to some of our more forward-looking concerns like “are we ever going to get our act together on testing” and “will there ever be enough personal protection for key workers” and “will the lockdown ever end” and, in some parts of the country, “will the water ever be turned back on again,” there are now some more reflective concerns looking again at the origins of the virus and asking where did it come from?
So over the next couple of days we’re going to be talking to scientists to get their take on this. And with us today is Dr. Stuart Newman. Stuart is a professor of cell biology and anatomy at New York Medical College in Valhalla, New York. He’s the editor-in-chief of the journal Biological Theory. He writes widely on the social and ethical aspects of biological research and technology, and he is the co-author of the recent book, “Biotech Juggernaut: Hope, Hype, and Hidden Agendas of Entrepreneurial BioScience.” Welcome Stuart.
SN: Thank you.
PT: So I think we’ve got a lot to talk about. I’m going to jump right in there if I may. An increasing number of scientists, including yourself, are starting to speak up about the possibility that the novel coronavirus may actually have escaped from a lab. And that even just saying that opens up a number of different possibilities. Could you just take us through what those possibilities are about the origins of the virus, and which ones you think are most probable?
SN: Sure. Well the most suspicious looking thing is the fact that the virus was first identified in Wuhan, China, and that is the site of the only what’s called a BSL-4, that’s a biological safety lab, in China. There’s also a BSL-3 lab, and research on bat viruses goes on in these laboratories. The laboratories are not far from the wet market that is the most commonly attributed site of the origin of the virus. But I don’t think we have to even consider that market. So basically viruses of this sort were researched in the lab, and not only by Chinese scientists but also in collaboration with scientists around the world including in the United States.
The virus after it was sequenced was found to have some features that resembled earlier coronaviruses, things that were being worked on in the lab. But they also had some hallmarks of other kinds of mixtures. A chimera is something that’s a mixture of several different types of viruses, or even types of organisms. This virus is chimeric, it has bits and pieces that look like it originated from viruses in not only bats, but possibly pangolins and other organisms that it might have passed through. So it’s not like a pure virus, and no virus is. It has hallmarks of possibly having originated by manipulation, by being in different kinds of animals. The proximity to the lab is suspicious. So people have started to ask; “Could it have been partly a product of lab manipulation?”
PT: Are you saying that it could be a genetically engineered virus, or at least a part of some normal lab process?
SN: These things can be partly genetically engineered, and they could have genetic engineering in their lineage, in their history, and not be specifically genetically engineered for one purpose. So for example, scientists work on different domains of the virus. There’s something called the spike protein in the virus and that’s the protein that attaches it to cells and makes it so pathogenic, makes it so dangerous.
The spike protein of this virus has a number of hallmarks that are very unusual. So it’s very well suited to binding to something on human cells called the ACE2 receptor. That’s called a receptor binding domain and the receptor binding domain is unusually avid for the human ACE2 receptor. And then it has something else which is called a furin cleavage site. It’s a weak point in the spike protein that makes it very flexible, so the way that you assay for that weak point is you use an enzyme called furin and that will cut it. Almost no viruses in this category have that binding site, because that enzyme cleavage site, it’s something that the enzyme cuts and it’s the weak point. There are papers that show that genetic engineers working on viruses have introduced that by genetic engineering into other coronaviruses, just as an experiment. So people do these things, it’s not sinister and I don’t think that this was for germ warfare or anything like that. But scientists who are looking to make vaccines or looking to find out why these viruses are so dangerous make modifications, and they see in animal experiments if the viruses become more dangerous or less dangerous.
There are papers in which scientists have introduced this cleavage site, it’s a sequence of amino acids. They’ve introduced it through genetic engineering in viruses that don’t normally have it, and it becomes much more dangerous when they do that. And this virus, very unusually, this coronavirus has that site in it, and nobody knows how it got in there. So that is kind of another suspicious aspect. So it could have been that some experiment introduced it to a virus, the virus left the lab maybe through an infected worker or a discarded animal. Then it got into another animal and mixed up with the viruses in that animal and then kind of came back to bite us in an indirect fashion.
So it’s not that you have to believe that some sinister scientist genetically engineered this to be such a nasty virus, but that it could have percolated through the natural environment after being genetically engineered.
PT: It’s interesting that you talk about how the virus is constructed. There was a recent paper in Nature Medicine claiming that this couldn’t possibly be a lab-constructed virus, because of the way that it was constructed. They were talking about it not having the sort of expected viral backbone and things like that. So they were using almost the same science to say, no it wasn’t from the lab, it was from nature. So how do we as lay people make sense of this sort of thing?
SN: So, when I read that paper it raised some red flags for me, because the people who wrote that paper made a very strong assertion about it being very unlikely to have originated in a lab. And what were the arguments they used? First they said it has a very avid receptor-binding domain, but it’s not an ideal one. If scientists had designed it they would have designed it differently.
Well, that was kind of ridiculous to me because there are papers going back 20 years that say that this domain is something that is very important to look at. And they said that people should try a lot of different possibilities to see what it is that makes it bind. So the fact that this is not what other scientists have found to be ideal, by computer programs, doesn’t mean that this wasn’t manipulated. And they didn’t refer to those papers that talked about modifying those domains. I was surprised by that.
Then they [the authors] point out that the furin cleavage site is part of the spike protein, and they said this is not part of any other viruses like this. Well, that wasn’t a good argument either, because they do refer to a paper where it [the cleavage site] was inserted by genetic engineers. The last thing was that they said that the experimental backbone—that if you started from scratch to try to modify a virus you would take something off the shelf, which is called the standard backbone and you modify it—they said that this doesn’t have the standard backbone. But in fact, people looking at these viruses take them from the wild, bring them into the lab and kind of compare them to each other. They don’t always begin with the standard backbone. So they came up with this very unlikely scenario that somebody would try to make something really nasty and release it. And they said, well this doesn’t look like it happened that way.
Well I agree with that, but the fact that it didn’t use the standard backbone is not at all a good argument. It’s not only me, but a number of other people have found that although the research in that paper is very good, the conclusions that they draw from it are very speculative and really raise red flags.
PT: Imagine the frustration of average citizens who are trying to make sense of all this. Every day there’s a new conflicting opinion about where it came from, or how it was constructed. Or was it genetically engineered, was it not? It’s really frustrating I think, if I could speak on behalf of the consumer. We just want to know whether there’s any certainty around the coronavirus, and it certainly doesn’t seem like there is a lot of certainty.
SN: There isn’t, and I think that the honest conclusion is that there’s a lot of uncertainty and a number of red flags. The red flags are that it was identified in Wuhan—which was a place where they were working on this kind of virus—and that things like this have been genetically engineered in the literature. And something I came across recently, that I haven’t seen written about, is that there was a lot of controversy going back around 2010, 2012 about what are called gain-of-function experiments. Where you take a virus and you try to add factors to its sequence to possibly make it more dangerous. Maybe to use it to make vaccines, or just to investigate why it’s so pathogenic.
There are a lot of people lined up against gain-of-function experiments. They had scenarios like what we’re going through now and saying, you know, if something like this got released by accident it would be awful. So they banned gain-of-function experiments at the NIH [National Institutes of Health]. They didn’t fund them and that was in 2014, when they put in that ban. In December of 2017, they rescinded the ban, and said that as of 2018 they would begin to issue grants for gain-of-function experiments. Now here we are a year-and-a-half after that and we have something that looks like a gain-of-function. So I think that it was certainly research going on in the U.S. and in collaboration with China that was doing gain-of-function experiments after five years of not doing them. I find that very suspicious as well.
It was Anthony Fauci’s institute that issued these grants and rescinded the ban, so he kind of has an interest in minimizing the possibility that this is a gain-of-function experiment. I think that one thing that we found—and this is actually a theme of the book, “Biotech Juggernaut,” that I wrote with historian Tina Stevens. We were looking at the prospect of human genetic engineering and all the kind of soft-pedaling that was done. To say that if we did germline genetic engineering of human beings it wouldn’t be so bad, that we could cure diseases and we wouldn’t get any downside to it. And we found that very unconvincing. But scientists—particularly scientists that are backed by corporations, by patents, by business interests—have a strong stake in doing these things, trying them out even though they might have adverse effects.
PT: I think that’s something a lot of people haven’t realized—when they read in newspapers about the research, the latest genetically modified whatever— that doesn’t necessarily mean that it exists. It often means that the scientists are looking for funding. So they’re boosting it [this type of research] up all the time, to say look at how great this is, if we can just get this going we can solve all the world’s problems. So that creates confusion within the public mind and in the media about how useful something is. And why if our scientists are saying this is safe, why is it suddenly not looking very safe?
SN: I think one thing that people should really understand is that there’s this idea that’s been hanging around for 50 or more years. That we know how genes behave because we know how to sequence genes, and we know how to study genes in a test tube. And we think that what genes do in an organism is simplistic. But in fact, these are very complex systems, and if you put something simple into a complex system that wasn’t there before—like genetic engineering the crops for example—you can get all sorts of poisons being unleashed that weren’t there before but are induced by the new engineered form.
Let me give you an example of this. In the year 2000, there was an experiment in Australia. They were trying to develop some kind of birth control gene therapy, some gene manipulation that would cause infertility. They genetically engineered a mouse virus, and this mouse virus was innocuous, it basically made the mice slightly sick. But then they put an extra protein in this virus, an extra gene that was already present in the mouse genome. They didn’t add anything that they didn’t know about. Then this virus killed every mouse that it encountered, it became absolutely lethal for all mice. So they stopped that experiment very quickly. They had no idea that was going to happen, they put a known gene into a known virus and they got something completely unexpected.
PT: If the evidence about coronavirus is circumstantial all around, really we’re all sort of grasping at where it came from. But what if it does turn out to be something that is genetically engineered? There doesn’t seem to be any particular protocol for genetically engineering a virus. It feels sometimes like scientists working in that area are just flying by the seat of their pants, which isn’t something you want to do with something potentially lethal.
SN: That’s right. I think that’s why a lot of people turned against this gain-of-function protocol. Because even though there was a recognition that it could be useful and you could develop vaccines with it, you could find certain principles by doing it, it was just too dangerous to try. And this is where we may have messed up. I can’t say that this is the way the virus came about, but it’s as plausible to me as any other thing I’ve seen.
PT: So I’m interested in the state of play in terms of viral research. You made the point earlier, but I think we need to underscore it—it’s not just China, it’s global and it is growing. The number of laboratories that are doing this kind of work is also growing. My question is, as the number of laboratories engaged in this work on viruses grows, doesn’t that also increase the risk of another even more catastrophic breach from a lab? Where are we in terms of biosecurity?
SN: Well, labs know what to do to contain these things, but since it’s a living thing and it’s invisible, things can be breached. So it’s not airtight. About 99.9% of the time these containment protocols work. But if you have something that could be extremely dangerous, one hundredth of a percent of the time when it might not work feels too risky. So I would say that it shouldn’t just be at the point of potential release that it should be controlled, but also at the point of design of the experiments. That’s why I would be an advocate for banning gain-of-function experiments. And it’s a little bit ambiguous because as I said, we don’t know what a gene is going to do when it’s in a new context. So one person’s gain-of-function is another person’s ordinary manipulation. So we just have to be super careful, have to do things on a small scale, and we have to maybe increase containment when we’re working with things like coronaviruses and other kinds of viruses that have caused problems in the past.
PT: But that doesn’t seem to have happened this time, does it? I mean we’re looking at the possibility that the Wuhan Center for Disease Control, which was the closest to the market, didn’t necessarily have the security clearance that it should have had to be working with coronaviruses, isn’t that right?
SN: Well they did have a BSL-4 facility (Biosafety Level 4) and there’s an international standard for what that is, and the containment is very high.
PT: I understood it was a BSL-2 facility closest to the market?
SN: Well I think the one closest to the market might have been, but the one that was doing the most exacting work was also in Wuhan, and that was a BSL-4. The thing is that the market may not even be relevant. It may not have passed through the market at all. When they tried to identify the first patient, they don’t find that there was a connection to the market. So I don’t know about the market. I think in some ways when I started looking into the market scenario it sort of became like a xenophobic trope. Like this is part of Chinese culture that we don’t like or something.
But I think it’s more likely to have originated in a lab, and was maybe inadvertently released. When you say released, it’s not like somebody opened the door and the virus flew out. It’s that somebody touched something, and walked out with it on part of their skin or something. Or it might have been an animal that somehow got discarded incorrectly or something like that. A leak could take many different forms. But I think that the fact that there was this high containment research going on in the same city is very suspicious to me.
PT: I have a couple of questions left for you and they’re difficult questions. How do we weigh the risks versus the benefits of this kind of research, whether we’re talking about creating chimeras or genetically engineering viruses? The people who are involved in this research will say, we’re doing it so that we can prepare and we can protect people. How does this research prepare us and how does it protect people? Or is that just the line?
SN: Well I think that we have benefited from bacteriological research and virus research. I don’t think there’s an easy answer to it. I think that the research needs to go on, I think possibly it has to go on in a more careful way. I think that the kinds of gain-of-function experiments that have been permitted—at least in the United States for the last three years—are going to be revisited. We certainly have to keep looking into why viruses do what they do. I don’t think that we can stay away from that kind of work. Maybe lower-level plagues affecting many many people, like Lyme disease and things like AIDS that we don’t have vaccines for. It would be wonderful if we could get vaccines for these things.
In the case of Lyme disease, we’re talking about a bacterium, that’s not a virus. You can look at bacteria with an ordinary microscope. You don’t need an electron microscope. There is a kind of research that goes on for Lyme disease where isolates from patients are taken into laboratories, and then they’re looked at and compared to see which ones are the most harmful and the most disease-causing. Now there’s a case where you’re not using a standard isolate, you’re not using a standard backbone, you’re using things from the wild, from patients. There’s a fair amount of virus research that goes on that way also, just isolates from animals and isolates from patients. So this idea about starting with one backbone and modifying it just doesn’t happen typically.
PT: I was struck by an article this week in The Economist that was looking at the amount of research that has been published since the identified beginning of the coronavirus pandemic. About 7,000 papers have been published on the pandemic, and they said something like a fifth of them published in the past week. We’re looking to science. The mantra is follow the science, let the science lead us, let the science tell us what is right. How can scientists possibly keep up with that amount of information and come up with a coherent way forward for us?
SN: Well, you’re not going to read 7,000 papers in the space of a month. That’s not the way it happens. But things get shaken out. What happens is there’s a kind of a kind of a crowd-sourcing aspect to it. Where somebody posts it pre-print, and if it seems to have something new, then it kind of spreads virally itself. You know on Twitter and on social media. As a scientist I look at Twitter to find out what other scientists are talking about, even before they publish papers on it.
So something came out in Science magazine just this week saying that this particular coronavirus has a lot of sites on it’s spike protein that have numerous glycans, sugar groups attached to them. And these sugar groups both help it to bind to the human cells, but also protect the virus from being seen by the immune system. So it’s kind of like a perfect storm, there’s something about the spike protein of this particular virus that’s similar to other ones. But it’s much worse, it’s more protected and more avid. That paper, not just because it was published in Science magazine, very quickly spread through the scientific community because it has something new to it.
So a lot of these other papers that are going to appear are going to be built on that foundation. But I don’t think there are going to be that many fundamentally new findings, rather variations and refinement of existing papers. So there’s a kind of screening process that scientists have that certainly doesn’t involve reading through huge numbers of papers, rather this kind of crowd-filtering process that takes place.
PT: Okay, science by social media. We’re looking to you guys to solve this thing. Stuart, thank you so much for talking to us. It’s been absolutely fascinating. We hope to keep in touch and maybe have you back.
Pat Thomas is a journalist and author of several books on health and environment including “Complete Wellness and What Works, What Doesn’t – The Guide to Alternative Healthcare.” She is also the editor at Natural Health News in the UK. See more on her website. Thomas frequently writes for the Organic Consumers Association. You can sign up here for OCA’s news and alerts.