Table of contents
- Why are 2 doses of vaccine needed
- Also have an innate immune system
- Glycans are quickly recognized by the innate immune system
- Vaccines are perfect to use outside of a pandemic
- Virus evolution is different during a pandemic
- Hazard of a mass vaccine campaign– especially with variants
- Pressure on the virus to mutate
- Virus adapts to unfavorable conditions
- Selective immune escape.
- Analogy: Soldiers good at camouflage will survive
- Current vaccines have narrow focus on the spike, so virus just changes it to hide
- Virus adaptions can include learning to infect children
- 1918 pandemic had no vaccine, so no pressure to have variants
- Infectious rates explode when have both variants and vaccines
- Timestamps from YouTube
- Vaccination publications in VitaminDWiki
- Lots of people on the web disagree with Dr. Bossche
"Geert Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany. He held adjunct faculty appointments at universities in Belgium and Germany. After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development. Geert then moved on to join the Bill & Melinda Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior Program Officer; he then worked with the Global Alliance for Vaccines and Immunization (GAVI) in Geneva as Senior Ebola Program Manager. At GAVI he tracked efforts to develop an Ebola vaccine. He also represented GAVI in fora with other partners, including WHO, to review progress on the fight against Ebola and to build plans for global pandemic preparedness. Back in 2015, Geert scrutinized and questioned the safety of the Ebola vaccine that was used in ring vaccination trials conducted by WHO in Guinea. His critical scientific analysis and report on the data published by WHO in the Lancet in 2015 was sent to all international health and regulatory authorities involved in the Ebola vaccination program. After working for GAVI, Geert joined the German Center for Infection Research in Cologne as Head of the Vaccine Development Office. He is at present primarily serving as a Biotech/ Vaccine consultant while also conducting his own research on Natural Killer cell-based vaccines."
0:00:05.1Weinsten: Hey, folks, welcome to the DarkHorse Podcast. I have the great pleasure of sitting today with Geert Vanden Bossche. Geert Vanden Bossche: is a doctor of veterinary medicine who has specialist expertise in virology and vaccinology. He has worked in industry in the construction of vaccines. He has also worked in the non-profit sector in bringing immunity to larger numbers of people. Welcome, Geert.
0:00:37.2 Geert Vanden Bossche: Thanks, Bret, for having me.
0:00:41.4 Weinsten: You have become well-known in certain circles and controversial of late because you have deployed an argument that suggests that the current campaign to vaccinate large numbers of people in the midst of the COVID-19 pandemic may be ill-advised, and I have seen you have been accused widely of being an anti-vaxxer, which is completely preposterous in light of the career that you have participated in. Do you wanna say any words upfront about where you're coming from in deploying your warning, and then we can get into some of the biology that will be relevant to the argument that you're making?
0:01:26.7 Bossche: Well, Bret, what I could say is that, for me, the alarming point came when I realized, or we realized as a community, that all of a sudden, this was back in November last year, a number of highly infectious variants were popping up almost simultaneously. That was one thing. And the second thing was, when vaccinations started, that there were some reports that were reporting indeed about people being vaccinated and still shedding virus. So, the combination of these things, the presence, even before mass vaccination started, of highly infectious strains that were already present, and then this combined with the fact that the vaccines, as most vaccines, do not prevent against infection, and enable people who are vaccinated to shed the virus and basically to spread it. This was, for me, the alarming point.
0:02:28.1 Weinsten: Interesting. From my perspective, one of these things, it seems to me is obvious that we would see it. Essentially no matter where this virus came from, we would expect, in light of the fact of effectively a point source, we would expect a large number of variants to emerge on the basis that this virus is new to people, and it is now experiencing effectively a very large canvas on which to learn new tricks. I find nothing surprising about the idea that new variants are popping up, we should have expected that. The other point that you make is not so obvious from my perspective, that people who are vaccinated may still be shedding virus. In other words, they do not have immunity sufficient to ward off the infection and prevent them from infecting others. Is that what you're saying?
0:03:26.9 Bossche: Yeah. But this is pretty normal for conventional vaccines. There are only very few vaccines, and you would rather need to look into live vaccines, live attenuated vaccines. Most of our modern vaccines prevent against disease, and to some extent they diminish, of course, the spread of the infection. They diminish the viral load, to some extent really substantially, but they do not completely prevent infection. Yeah.
0:03:55.9 Weinsten: So, this then sets up a hazard in the form of a trade-off, that the vaccines are very good at preventing people from becoming sick, but by being narrowly focused and not preventing the shedding of virus, they open an evolutionary pathway for the virus to learn new tricks because that is to say somebody who has substantial immunity but not complete immunity to the virus will tend to shed new variants that have made use of that higher bar or that have cleared the higher bar.
0:04:37.9 Bossche: Well, if the variants are present already, which was the case before the mass vaccination really got rolled out, the mass vaccination campaigns, and of course, we are talking about the spike protein. I think everybody by now knows more or less about the spike protein. As we know, the version of the spike protein in the vaccines is not the same as on the variants. So there, there is some heterologous situation. And therefore, it's also logical that when you are vaccinated but you are exposed to a variant that has a different version of the S protein, that the S protein may not be completely recognized by the vaccinal antibodies and therefore not completely, completely neutralized, for example. So, that is pretty logical. It only becomes a problem, I guess, if you do this at a very large scale, and that is my argument, the mass vaccination in the midst of a massive infectious pressure, which is the case during a pandemic, of course.
0:05:41.9 Weinsten: Alright. Here's my suggestion. In order for people to understand what is, I think, a fairly subtle distinction, deploying a vaccine like one of the ones that we currently have narrowly targeted at the spike protein in advance of a pandemic might work very well, and in the midst of a pandemic might have exactly the opposite impact. The reason for that is clear enough to me, but I think it will be obscure to almost everyone. Let's talk a little bit about the immune system, how it functions, so that people can understand the context of your argument. I should say, my background, I did not... I have no degree in either virology or vaccine science, but I did study this many years ago in the context of... Basically, I took a course in the medical school that I was interested in, in immuno-biology, which is basically the biology of the immune system that underlies both the natural immunity that we have and the immunity that we create with vaccines. We essentially have... We can dichotomize the systems that create immunity in a number of different ways.
0:06:53.3 Weinsten: One of them is that we have something called innate immunity. These are the ability to recognize pathogens or other disease causing patterns without needing to have any exposure. And then we have what's called acquired immunity. Acquired immunity is, for example, people all will have had the experience of getting sick with something, a cold or a flu, and then a couple of weeks later they will find themselves recovered. And what has happened is that the immune system has learned the electromagnetic signature on the surface of either the viruses or the cells that have been infected, these are called antigens. And having learned that specific pattern, it is then very good at finding cells that have been infected and destroying them or triggering them to self-destruct. And once you have that, then a set of memory cells are created, so that if you ever encounter the same pathogen again, creating the same antigens, the immune system is so quick to recognize it that we very frequently don't even realize that we've been invaded. Right? So, you don't tend to get the same cold twice or chickenpox, for example.
0:08:12.3 Weinsten: Alright. So, what I want you to do, I'm going to stand halfway between what you understand and what my audience is likely to understand, and just try to paint, with a broad brush, some detail about the systems here so that people can follow. So, the acquired immunity is carried in two kinds of cells, broadly speaking. We've got B cells, which make antibodies. People will have heard the term antibodies. Antibody is basically a Y-shaped protein, and that Y-shaped protein floats freely, and it sticks to things based on the pattern of electromagnetic charge on the the pads, on the tips. And so those antibodies float around and they attach themselves to bacteria or to virally infected cells, and that has a number of consequences. And then the T cells function very much like B cells except that instead of creating free-floating antibody, the what looked like antibodies remain on the surface of the T cells, and they function as receptors. So the T cells move around, and when they encounter something that their receptors stick to, an antigen for which they're well matched, those T cells become triggered to do something. How am I doing so far?
0:09:38.7 Bossche: Yeah, yeah, that's okay. So, there is just the T cells that then can immediately destroy the infected cell because, as you were pointing out, they recognize an antigen of the pathogen on the surface of that cell. But there are also the T cells that will provide help to the B cells in order to build that memory. If there is no T help, there will be no B cell memory. There is two types of T cells that are important, the helper cells to enhance the B cell response, and the cytotoxic T cells that have the capability to immediately destroy a cell, an infected cell, provided they recognize the antigen on the surface of that cell.
0:10:21.9 Weinsten: Great. Alright. Help me remember that we wanna come back to that so people understand what it means. What I want to do is talk about the way in which acquired immunity is acquired in the first place, so that we can then understand what these memory cells are. Acquired immunity, I must say, is one of the most fascinating evolutionary processes I've ever heard of. The first time I learned of this, my jaw was on the floor. It was so interesting that such a system had evolved and existed and functioned without our awareness 24 hours a day, every day of your life. So, the system functions more or less in this way: You have an array of cells that produce antibodies which have an ability, sort of a general ability, to react to any large organic molecule. Any configuration of charges that an antigen might have is contained in the system. There are multiple cells in the system that will react to it somewhat. So, you have billions, billions... Is that the right order of magnitude? Maybe it's tens of billions of...
0:11:34.2 Bossche: Well, it's a huge amount anyway, yeah.
0:11:36.9 Weinsten: It's a very large number of these cells existing in your body that have a very wide range of patterns of antigen that they can react to, and you have these things before you're born. Now, the system will react really in principle to any sizable organic molecule, but it's very important that it not react to molecules that you yourself make. And so what happens is the system, during a critical period in development, eliminates all of those cells that are triggered by your own molecules. And the fact of being a mammal plays into this very interestingly, because there's a period before you've been exposed to the world where the only molecules you're encountering are your own. So, the system wakes up to all of the members of the this class of cells that react in utero and it eliminates them. Now what that does is it creates a system that once you've been born and you're out in the world and you encounter molecules that aren't yours, the system reacts. But when it encounters molecules that you're making, it doesn't, so it creates a self, non-self recognition system.
0:12:45.8 Bossche: Yeah. That's why we call it tolerance to the self-antigens. Tolerance.
0:12:51.0 Weinsten: Right, we become tolerant. And if you weren't tolerant, you'd have an autoimmune disorder. Your immune system would be attacking your own cells, and maybe we'll talk a little bit about what that might represent later on. But what I want to get people to understand is that the system, in its initial state, just simply reacts to anything that isn't you. Right? And what isn't you might be a pathogen or it might not. You could breathe in some pollen. Pollen isn't actually utilizing your cells to do anything, it's just an organic molecule that you've inhaled, and your system might react to it as if it was dangerous, that would be an allergy.
0:13:28.4 Weinsten: But when you are invaded by, let's say, a bacterium or a virus, you are suddenly creating molecules that your system has never seen, and your system begins to react. But at first, it reacts very weakly because it doesn't have a very good program for recognizing the specific new invader. It has a very general program that just recognizes anything it hasn't seen before. But, and this is the really amazing part, the cells that react a little bit to this new pathogenic pattern, those cells create a bunch of offspring cells that are not identical to each other. And those cells among the offspring cells that react even more strongly to the pathogen are then triggered to produce more offspring cells. And so what this does is it uses quite literally evolution to generate a recognition of this new pathogen that your body has never seen, but it learns over the course of hours, days and weeks to recognize this new pattern, and it becomes very, very good at it. At the point, it has become very good at it so it can recognize any place in the body that's making these new antigens, then it is capable of fending off the pathogen. As you point out, the natural killer cells... Actually, no. The natural killer T cells will come in and kill cells that have been infected by the virus, and the body will in many ways clear the infection.
0:15:02.0 Bossche: These are the cytolytic T cells... Or cytotoxic T cells.
0:15:06.3 Weinsten: Cytotoxic T cells, okay. Having done that... So imagine you got sick, you breathed in a virus, maybe it was a cold, it invaded some cells. Those cells started to make viral particles, those particles got recognized by the adaptive immune system, the immune system got very good at becoming specific in targeting those antigens, the affinity for the antigens went up. And then you eventually clear the infection because your system is good at recognizing it, and then your system goes and it produces memory cells. These memory cells remember the formula so that if they are triggered again they can immediately create a large army of cells that are very specifically targeted at that pathogen. Still right?
0:15:53.8 Bossche: Yeah, yeah, sure.
0:15:54.5 Weinsten: Okay, good. And then you point out that the helper T cells are actually involved in helping to trigger B cell immunity in the adaptive immune system, having discovered the formula for the particular pathogen.
0:16:15.0 Bossche: Yeah. Well, this process that you were describing, maturation and acquisition of memory, is T helper cell-dependent. It depends on the support, the assistance of T helper sells.
0:16:28.8 Weinsten: Great. And so in the context of COVID, people will have heard a discussion about whether or not the infection with the virus or the vaccination triggers a robust B cell response, they will be able to detect an antibody titer, that is the degree of antibodies that we find. A deeper question is how well, how much affinity do the antibodies have for the antigen in question, which will vary based on whether or not we're talking about the variant of the virus that the vaccine was built to recognize or a new variant, so the affinity could drop but wouldn't drop to zero.
0:17:13.2 Weinsten: And then there's a question about whether or not the system that creates the antibodies, which would create a short-term immunity, has converted over into a system of memory that would allow long-term immunity to exist. So we talk about the cellular immunity having been acquired, and that is much harder to test for. It's very easy to test for antibodies in the system, so you get the vaccine, your antibody titer goes up, we can measure that with a simple blood test. Testing whether or not you have long-term immunity based in cells that have a correct memory is tougher but still possible. Am I right?
0:17:52.2 Bossche: Yeah. But the B cells also do have memory, right? And in order to get that memory, you have to boost, you have to... You need to boost an injection for the most of the vaccines. So, it's not just the T cells that have memory, it's also to B cells, and you need that memory also of the B cells in order to recall your antibodies after the re-exposure, of course, to the virus or to the antigen. So, you have as well B cell memory as T cell memory.
0:18:22.7 Weinsten: Great. Okay. So, people can also now understand, in some sense, why some of these vaccines require two doses. Right? The vaccine is entering your cells... Let's take one of the mRNA vaccines as an example. The mRNA, which encodes the spike protein, is introduced, it is taken up by cells. And actually I'm a little unclear on why the lipid nanoparticles cause it to be taken up into cells, given that this is effectively like a synthetic virus that we introduce, and mRNA is surrounded by lipid nanoparticles. Can you explain why it is taken up by the host cells in the lipid nanoparticle coat?
0:19:10.7 Bossche: Well, these lipid nanoparticles will simply enhance the uptake of the... You could say, if you would have the mRNA as such, it would be very soluble and it could go anywhere. Whereas the lipid nanoparticle has a higher affinity, I would say, for the cell membrane because of all kinds of interactions, you would say hydrophobic interactions between the lipids and the organic phase of the cell membrane, so that will enhance the uptake of the mRNA because of the particulate structure, one, and second, because of the physical chemical nature of this particle which is now a lipid nanoparticle. And also the size, nano-sized particles are readily taken up into what we call... Well, as well antigen-presenting cells as normal cells, for example. It will promote and it will enhance the entry of the mRNA in the target cell.
0:20:12.1 Weinsten: Okay, beautiful. So, I think what I've just heard you say is that you have an aqueous environment, that is to say a wet environment of the blood and the lymph, they are primarily made of water. The cells are surrounded by fat, which is obviously not water soluble. And by putting mRNA inside effectively a globule of fat nanoparticles, the affinity for the cell, this basically drives these mRNAs into the cells, which then transcribe them because one of the things that goes on inside of cells is that mRNA is transcribed just to do the normal business of the cell itself.
0:20:51.2 Weinsten: Okay, great. What we've done so far is we've talked about the adaptive immunity system, which through a process called clonal selection actually evolves to be able to target and eliminate or control an infection once acquired. But this is not the full basis of our immunity to pathogens in the world. We also have innate immunity, that is to say immunity that does not require exposure in order to develop. Can you describe the basis of innate immunity?
0:21:29.0 Bossche: Well, I'm going to limit myself to the equivalent, the humoral, so the antibody part and the cellular part of innate immunity because that is really what is most important for this discussion. So as you were pointing out, you have the antibodies, as you described, being part of the innate immunity. Sorry, being part of the acquired immunity. Specifics are, first of all, they specifically recognize an antigen, and they can also induce memory. These T cells can have memory and therefore, produce antibodies that will readily recognize the antigen upon the re-exposure. So the equivalent in the innate immunity are what we call natural antibodies. Those natural antibodies are produced by what we call an innate-like B cell. This is a B cell that is already pre-programmed. It's already present at birth. So these natural antibodies in contrast to the antibodies produced by the B cells of the acquired immune system have no antigen specificity. They can recognize multiple antigens, and they are not recalled upon re-exposure.
0:22:52.0 Bossche: So that is the humoral part of the innate immune system. Then the cellular part is in contrast to the T cells we were talking about, not able to recognize a specific antigen that is presented, for example, on an infected cell, but the cells of the innate immune cell, of the innate immune system, we call them natural killer cells. Like you have the natural antibodies of the innate immune system, you have the natural killer cells of the innate immune system. They recognize in a non-specific way a kind of array of motifs on the surface of an infected or pathologically altered cell, like a cancer cell, for example. They will recognize motifs, a pattern of motifs, so this is not very specific for an antigen. But if, for example, a virus invades that cell, and there are some proteins that are presented on the surface or some glycans, then these glycans, for example, will build a pattern and these patterns will be recognized by the NK cells. The NK cells, again, have no memory, but they can act very, very fast. Like the natural antibodies, they are already there. They are pre-armed. They are pre-programmed, so they act immediately. This is really the first line of immune defense when a pathogen gets in.
0:24:19.7 Weinsten: Fascinating, okay. So you have a system that reacts more or less to the symptoms at the cellular level of pathology. The cells are behaving molecularly in an unusual way that triggers these natural killer cells, and they don't need to learn any new tricks, but they also are limited in their capacity because they are not specific. So they can recognize the pathology and react, but to specifically recognize the pathogen and its molecular consequences requires this acquired immunity. Alright. Now, I hope we haven't antagonized people by leading them through that biology, but I know from experience that listening to conversations about COVID, if you don't have this basic level, you can't understand what's being said and why it might be true. It doesn't add up. The complexity of the system is inherent to understanding how it works and what is reasonable to do in response. So alright, let us get into your argument about the hazard of our current vaccine regime. And let me say, you have made some very strong claims. You have argued that in fact, the vaccine campaign that we are currently engaged in is so dangerous that it should be halted.
0:25:44.6 Weinsten: And I will say, I don't know if you're right. I cannot determine based on what I understand if you're right, but what I can say is that you are making sense. This is frightening in and of itself, that your argument is completely coherent whether or not it is true. This is at least a question that should be engaged by those who are making policy around this because the possibility of making our viral situation with respect to COVID worse is present, and we are creating the hazard of the future that we will be confronting a year or two down the road by our actions now. And so were we to have reacted differently at the beginning of COVID, we might not be in the situation we're in now. Were we to act differently now, we will be in a different situation years down the road, and so we are always sort of setting the stage of our next battle. And it is in that context that we have to engage your argument and take it quite seriously. So what, in a nutshell, is your argument for the hazard that we may be creating?
0:27:00.6 Bossche: So my argument is, first of all, as I was always saying, these vaccines would be perfect to be used outside of a pandemic. Why I'm saying this, because if you use them, if you use vaccines before you get exposed to the virus, well, in this case, it's a virus, you can build a full-fledged immunity. As you were pointing out Bret, this takes time. Most of the current vaccines even require two doses. You have been pointing out about this clonal expansion. In the meantime, you acquire memory, you acquire higher affinity, etcetera. This is a process before you acquire the full-fledged immunity. So if you have this full-fledged immunity and then you get exposed to the pathogen, you literally have everything you need to fight off this pathogen and with absolutely no problem, and that's what I have always been saying. I'm not talking about maybe secondary effects or adverse events, etcetera. This is not my field of specialty. Other people can discuss this, so I'm not talking about really the quality of the vaccines or adverse events, but in principle, this is a correct vaccine to be used outside of a pandemic.
0:28:27.5 Weinsten: So let me just pause you there. Let's say, just hypothetically speaking, let's say that the virus had emerged in Wuhan, and the world had limited its spread. Let's say that it was kept to Eurasia, and the rest of the world had not faced the virus. Then if we took one of these mRNA vaccines, for example, and vaccinated the population, so that 80-90% of the population was vaccinated before encountering the virus, before the virus crossed any the ocean, for example, then we would expect this to work very well.
0:29:12.6 Bossche: Sure.
0:29:13.3 Weinsten: And the hazard of it would be low, even if it was true that it only produced, let's say, 80% immunity, and even if it was true that people shed... Some people who were vaccinated but then became infected did shed some virus and occasionally infected other people. Is that fair to say that this would still be a reasonable campaign?
0:29:42.6 Bossche: Yeah, the only thing I would like to add, Bret, just to be clear for the audience is that here we are talking about the original virus, about the wild virus, the original Wuhan virus, right? We are not yet talking about variants.
0:29:55.9 Weinsten: Right.
0:29:56.6 Bossche: Under that assumption, what you're saying is perfectly correct and fine because even if you don't prevent infection completely and you diminish only the viral load, as long as the virus will not have enough opportunity because the infectious pressure is so low to propagate, it will die out. So that is perfectly fine, and so you can control it.
0:30:26.5 Weinsten: So this is the thing that I think is too subtle for most people to get, and hopefully, we can help them see the difference. The vaccine, from the point of view of the patient, the patient goes, they go through whatever anxiety they have about needles and unknown hazards of vaccines, and they get their shot. That looks the same to people whether they're being vaccinated in the midst of a pandemic or in advance of a pandemic, but from the point of view of the evolutionary landscape, these two things are completely unrelated, right? Introducing the vaccine when the virus has already gotten a foothold and has started to diversify, getting a vaccine is actually... It's like showing up... Imagine that your nation was being invaded, and there's a question about how useful your rifle is when the ship, some little boat with 12 people on it, shows up on the shore, your rifle might be very useful. If you show up with that same rifle against an army of 10,000, you're gonna get shot and you may actually be in a worse position 'cause you'll give away... You're shaking your finger.
0:31:45.4 Bossche: Especially if this happens before you can completely charge your rifle. Your arm is not fully charged, and you are already under attack.
0:31:56.5 Weinsten: Right, already under attack. I mean in some sense this is very straightforward to me because I'm used to thinking in evolutionary terms, and so the idea of to me, the virus looks very different. Even though the particles may be very similar to each other, the virus looks very different when it has a huge number of individuals in which to engage in evolutionary experimentation versus a tiny number of individuals where the chances of it happening on anything useful are very small. Once you've got the huge canvas, the chances that the virus is gonna learn new tricks are 100%, and in fact it's doing it. And as I said at the top, no surprise at all that us having botched the initial reaction to the virus, which frankly, in my opinion, should have been much stronger, we should have had a much more intensive campaign to control the spread of the virus early on, then we might not be dealing with this half-assed long-term set of measures that are increasingly Draconian and having all sorts of other effects. A short, intense control effort would have been more effective.
0:33:07.7 Weinsten: In part, the reason that I say that is because it's just much easier to address. If this was an invasive species and there are 10 individuals, finding them is very effective. You could find them. You can eliminate them. You're done. Once the thing has covered the landscape, it's a whole different puzzle even if the individual critters aren't very different. So all right. We've got a difference between these vaccines and their utility in advance of a pandemic versus in the pandemic. We are in the pandemic, and now, what do you see the hazard being of a mass vaccine campaign?
0:33:52.6 Bossche: Well, so these vaccines will definitely induce an immune response. That's what we have been explaining. So what we know is that it takes time to develop an immune response. So during that time, your immune response is not optimal. It's not fully mature. That is one thing. The other thing is, we are already dealing... Before we started the mass vaccination campaign, before they got rolled out properly, ++we had already variants. So again, the immune response that you are mounting when you have been vaccinated is suboptimal towards a variant that has a spike protein, which is different from the spike protein in the vaccine__. So the vaccinal antibodies against the spike proteins are suboptimal because the S protein of the variant is not the same. So we are... When we are vaccinating people, as I was saying, you are going to war, but your arm isn't charged yet. You're already fully under attack, and you still need to mount this antibody response. And you are attacked by things that you have not learned to properly recognize, so the immune response is suboptimal.
0:35:16.5 Bossche: So now, so this creates what we call an immune pressure, a pressure. It's a pressure. It's definitely a pressure on the virus that the virus isn't happy with this immune response, but it is going to be able to adapt to that immune pressure. Why am I saying this? I'm saying this because when you have, whenever you have to adapt a virus or a microorganism, but I'm talking about viruses, to unfavorable conditions... Let's say you would like to do this in the lab. You have a virus, and you would like to adapt a virus to an unfavorable condition. That unfavorable condition could be cultivating, for example, an influenza virus on eggs instead of on a cell culture or incubating your virus on a temperature that is not ideal for the cells to grow and for the virus to produce, but it could also be, the unfavorable condition could also be an immune pressure, antibodies, for example, that are present.
0:36:21.3 Bossche: So if you would like to do this in the lab, you would like to adapt a virus to unfavorable conditions, what you would do is you would take that virus and you would put it on a saline in the presence of those unfavorable conditions. So in this case, it would be a suboptimal antibody dose, let's say, but then that is not sufficient because, of course, you have always... And that is the argument of many people, "Yeah, you have all the time, variants and mutations, etcetera." Of course. But now, you will select certain mutations that are capable of dealing with this unfavorable condition, so you will select those variants. But that is not sufficient because it's not because we have done this selection one single time that this variant is now going being to become dominant in the population. It will still have a very low, we call this a viral titer, a very low concentration. But now, if you take that virus or all these viruses and you're now going to inoculate this on another cell culture, under the very same conditions of immune pressure and then you do it again and again and again and again, then ultimately, this mutant will adapt to this unfavorable conditions and it will have a competitive advantage compared to the original viruses.
0:37:51.0 Bossche: And that is how, in the course of time, this population of these mutants that originally were only present at a very low concentration will now become predominant. So now, you extrapolate this to people what you're gonna do in order to be able to adapt a viral mutant, you would need to passage a virus from one person to the other, but in order for that virus to be able to adapt, it would be important that these people are under the same immune pressure or also experiencing a situation of suboptimal immune response. And what I'm saying is that, if you are already having variants before you start your vaccination campaign, and then you're immunizing in the heat of the pandemic where while the immune response is built up you're already under attack many, many people, of course, in such situation are going to be experiencing a suboptimal immune response. And hence, this will enable mutants that occasionally emerge, of course, to adapt and to gain a competitive advantage and to become dominant in that population.
0:39:08.2 Bossche: And then, of course, we have a problem because this is what we call selective immune escape. You select it, and you enable the virus to adapt to that situation so it becomes predominant. And that is what we are seeing right now. As soon as you have an infective variant of popping up, guess what? I mean, it takes like a few weeks, or it becomes predominant in the population.
0:39:29.4 Weinsten: Okay. So let us build on the analogy of war to see your argument more clearly. When we send soldiers to war, we send them to boot camp first. Boot camp is like the vaccine. We expose them to something that is war-like without there being an actual enemy, so that the soldiers can learn to fight that enemy in a comparatively safe context before they face the actual enemy. If you send your soldiers to the front before you send them to boot camp, not only will they be vulnerable, but they will end up training the enemy on how to exploit their weaknesses. You want to eliminate their weaknesses first. And so in effect, what you are saying, is that by deploying this vaccine in the context of an epidemic already underway, we are effectively sending soldiers to the front and we are... Yes, it is true that the soldiers will learn to fight on the front to the extent that they can survive, but they will also teach the enemy to fight even better. So you are entering an arms race at a disadvantage rather than an advantage.
0:40:45.5 Weinsten: Now, if we extend the metaphor a little bit, let's imagine... So the whole system functions based on the ability to recognize the enemy and see it very clearly, and you could imagine on the battlefield, this would make sense, too. To the extent that some enemies are very good at camouflaging themselves, those enemies tend to persist. To the extent that some enemies are obvious, they tend not to persist because they get shot. So imagine that we did some trick with the camouflage that the soldiers on the front wore where those that persisted the longest, their camouflage spread itself, and those that died early, their camouflage went extinct. So over time, the camouflage would get better and better. By exerting this pressure, you are arguing, and I think there's no question that this is accurate, we are effectively running what would in the laboratory be called a serial passage experiment. We are creating those exact conditions in a context where there's a huge landscape of virus already adapting to the inability of the immune system to see certain things.
0:41:56.1 Weinsten: And I would add one thing to your description so far, which is that the nature of these vaccines, part of the magic of them, the ability to generate them so quickly has to do with how utterly narrowly focused they are. Instead of doing something traditional like taking a virus and inactivating it and introducing the whole virus into the body, so the body sees the whole thing, we've narrowed the focus down to the spike protein itself. And not only that, we've narrowed it down to the spike protein of the original virus, and this has created a very concentrated pressure, which means that we're trying to inform the immune system of exactly what the enemy looks like and we've honed in on one characteristic. And that means that if the virus can change that one characteristic, then suddenly, it becomes invisible. And so, we are effectively setting ourselves up for an evolutionary failure by concentrating our response and introducing it on the front rather than in advance of the encounter. And again, I don't know that your argument is right, but I can say, it's very clearly plausible and the hazard is potentially immense.
0:43:14.5 Bossche: So the thing I would like to add to this, Bret, which is a very objective argument, we absolutely need, because otherwise, we, not the both of us, but the community is going to turn around in circles. And of course, I can understand that the resistance is enormous, but we absolutely need criteria that we agree upon, that would enable us to distinguish whether human intervention, whether this is mass vaccination or the mass prevention, infection prevention measures are both combined in immune escape. So what would be the criteria that would be generally acknowledged and accepted? Would this be, for example, dramatic increase of more infections variants, for example? Would this be resistance to the vaccines ultimately? Would this be that we have more and more younger age groups that become infected?
0:44:24.0 Bossche: There is a number of criteria that could be defined and that, according to my humble opinion, clearly illustrates that there is a huge impact of human intervention on the way the virus evolves and on the collective immune response of the population and the dynamics thereof. But as long as we don't agree upon this criteria, my fear is that mass vaccination will continue no matter what 'til everybody gets vaccinated. It's no longer a question of immune defense, building an immune defense. It becomes a question of vaccinating everybody, which is not the same, certainly not within the context of this complex phenomenon, the pandemic, combined with human intervention.
0:45:14.4 Weinsten: Yes. I like what you're saying very much about the criteria. I have a concern or two. Some of the criteria are likely to occur either way. For example, let's just take one. You talk about the potential for the increasing vulnerability of the young, and we have not yet described why it is that the young might be anomalously immune to COVID, which they seem to be. We'll come back to that. But one thing that is certainly true is that the young, to the extent that they do not seem to come down with COVID and when they get it don't seem to have very severe disease in general, represent an opportunity for any variant that can figure out how to bypass effectively what must be their innate immunity that is preventing the disease.
0:46:06.6 Weinsten: So, that opportunity exists whether we vaccinate or we don't. And it is, in fact, one of the reasons the argument that I would make for a very intensive campaign of behavior modification to control the virus, which the ship has sailed, but we should, very early on, have treated this much more carefully, because now that it is out in the world in such large numbers, there is nothing to stop it from discovering a pathway to infect the young. It is always hovering at the door, and it may eventually figure out how to accomplish that, just as it may eventually figure out how to spread outdoors, something that it does not seem to do well yet, but is an opportunity to the extent that some of us are using the outdoor environment effectively to engage in social behavior because the environment itself protects us, that's an opportunity if the virus can figure out how to endure UV light or whatever else it's doing. How many of your criteria will separate the natural evolution of the virus, just by virtue of the fact that we have an uncontrolled pandemic, from the evolution of the virus driven by a targeted broad scale vaccine campaign?
0:47:27.2 Bossche: Well, that is exactly what the criteria should be based upon. And I guess the only competitor we have, unfortunately, is almost like the flu pandemic 1918. Why I'm saying this is because this was clearly a pandemic of a respiratory virus where there was no human intervention. Infection prevention measures were very, very, very limited. It was war on top, so you had crowding, you had very bad hygienic conditions, etcetera, and there was no vaccine. So, there, first of all, what we have seen, we have seen no variants. The whole thing happened within one year. And people have been sampling or analyzing autopsy samples to see whether there was any variation in this range that during this pandemic appeared in several different parts of the world. And it was very homologous, so that is one thing.
0:48:26.5 Bossche: So, that is very important because this is a high infectious pressure, a natural pandemic, no human intervention. If you imagine now that we have every second or third week, we have a new infectious variant appearing. And not only is this a more infectious variant, it's very often also much more infectious, like the Brazilian compared to the UK, etcetera, and it all appears very rapidly. It's not like during evolution, of course, these things appear, and if they have a competitive advantage, they will replace the original strain. Now, all this is happening, multiple variants within a short period of time with dramatically increased infectivity. And this in parallel with the mass vaccination campaign. As I was saying, you have the same pandemic... Well, it was flu, of course, nothing happens in terms of variants. There were a few mutations, but here the mutations are very clearly targeted. They are selected at domains that enhance the infectivity. So, they are not like random... They are really selected towards parts of the spike protein that are responsible for infectivity. There is something there, right?
0:49:52.0 Weinsten: Oh, yes.
0:49:53.4 Bossche: We need to agree upon this. Say, for example, if you look... If you imagine now the situation in Chile, for example. You are vaccinating on a background of a variant that had just appeared. I mean, the Brazilian, the Brazilian variant. This Brazilian variant is, of course, pretty much different, the S protein, from the S protein of the vaccine. If you now start vaccinating people, of course this variant that just emerged is going to have a competitive advantage because it's more infectious, and what you want to do with your antibodies is to prevent infectivity. So now, all of a sudden, you see how this variant is exploding and you see the infectious rates that are dramatically increasing. All of a sudden, you have a much higher infectivity rate.
0:50:46.6 Bossche: There is other criteria as well that we could... The mutations are, of course, studied. We see more and more that they are also now converging towards domains that are targeted by the vaccinial antibodies. If you take all these things together, we should be able to compare it, as you pointed out correctly, to a natural pandemic, to observations that are really high, very, very strange, and that, according to my humble opinion, could be correlated with at least, I would say, human intervention in this pandemic.
0:51:24.4 Weinsten: If I can make that a little bit simpler, what you're saying is: A, something that surprised me the first time I heard you say it, which is that in the 1918 pandemic, there was apparently... There were no widespread variants. And we know this from the comparison of samples taken during autopsy. That shocks me. I think what it suggests is that the evolutionary experimentation took place before the pandemic, that effectively the virus got very effective at transmitting in some small population that wasn't captured in the autopsy samples, maybe it wasn't even recognized as a unique disease. And then by the time it circulated around the globe, it was already highly effective. And that in this case, we have, well, A, I would say the anomalous fact of this virus apparently having emerged in the human population already highly effective. We have no evidence for that experimental evolutionary period at the beginning, which is one of the reason that many of us believe the laboratory origins hypothesis is probably correct.
0:52:39.2 Weinsten: But in the context of this vaccine campaign, what you're arguing is that we are seeing exactly the pattern of change that you would predict if we were creating this inadvertent serial passage experiment in the human population. We are putting pressure on the spike protein in this narrow way, we are seeing change in the spike protein and in exactly the domains that would cause immune escape, and that the... Let's put it this way: I think the presumption would have to be that we are driving that change or at least accelerating that change by virtue of the very intense and very narrow evolutionary pressure that we are applying to the virus.
0:53:24.5 Bossche: Well, frankly speaking, Bret, if you would ask me, set up an experiment where you adapt a variant to immune pressure, but do it in humans or do it in a mammalian population, what would you do? You would, of course, first of all, make sure you have a high viral load. You would make sure that as many people as possible, or in the same situation of a suboptimal immune response, and if you have already, if you can already start with variants where the match is already suboptimal, then it's even better. Right? That is exactly what you would do, that is exactly what you would do to adapt to variant. And what is worrisome, Bret, is the kinetics of all of this. This is all going very, very fast. The appearance, the emergence of all these variants, and as I was saying, there is probably a whole series of variants that have not been identified yet, but it's not like any variants. Many of these variants are selected towards, for example, a higher infectivity. And when we come now more and more with antibodies, etcetera, we see already that some of these mutations are abolishing the effect of certain antibodies within the polyclonal serum of the vaccine antibodies.
0:54:53.1 Bossche: So, it is very well-directed, it is fast, it is pretty huge, because as I was saying, if there's a mutation just by an antigenic drift, for example, and that mutation happens to be a little bit more infectious than the original strain, then in the course of time it will take over. But this will be pretty slow, evolutionary speaking. Here, these things are like accelerated, enhanced, and it is difficult to deny that this is not really in parallel with the mass vaccination campaigns or with human intervention. Because, as I was saying, during the flu pandemic, nothing was seen... And you could argue as well, people must have mounted antibody responses during the flu pandemic. It was not like there was no immune response.
0:55:43.9 Weinsten: You have said, if you were gonna set up an experiment to induce the, effectively, gain of function here, it would look more or less like this campaign. I would say evolutionarily, we can describe this very simply that effectively we have given the virus a gentle evolutionary slope for which it can discover high infectivity and escape from immune surveillance. That's all quite frightening, that not only does the pattern in the wild seem to match the fears of somebody who is well positioned to say, "Here's what you would expect to see if my hypothesis is correct about immune escape." That raises a number of different questions. It raises the question about what should we be doing vaccine-wise?
0:56:53.0 Bossche: Well, Bret, I'm a little bit hesitating if for a second we should come back to the innate immune response.
0:57:01.2 Weinsten: Oh, and the connection to the young.
0:57:02.4 Bossche: Because... You could say, "Well, if there is an immune escape, worst case scenario is that the vaccine won't work anymore." And that is then the other argument, "We will produce new vaccines." But my main argument, really that is my key argument, is that even though the antibodies may no longer neutralize the virus, they will still be able to bind to the spike protein. And all this is science because people have been showing that, for example, antibodies against the common cold virus, they do not neutralize or cross-neutralize COVID-19, for example, or SARS-CoV-2. But they do bind, they do bind to the S protein, but they do not neutralize it.
0:57:58.2 Bossche: So, if antibodies are no longer completely functional in the sense that they can neutralize the virus, they can still bind, bind to the S protein. And there comes my big argument, and therefore, we need to come back to these natural antibodies. By binding to the S protein, this antigen-specific antibodies are capable of out-competing natural antibodies, and that is the disaster. Because, as we were saying at the beginning, the natural antibodies, they are not antigen-specific. They have the capacity to broadly neutralize not only all kinds of COVID variants but even all types of coronaviruses. And maybe you want to jump in at this point to make it a little bit clear to the audience.
0:58:50.5 Weinsten: Sure. Yeah, this is such a fascinating point, but what we have is the possibility of antibodies that are ineffective at preventing the spike protein from binding the receptor, and therefore, ineffective at preventing infection, that would nonetheless attach themselves electromagnetically, they would just simply stick to the spike protein, and they would block the innate immunity that we all have some degree of, and that young people appear to have a great deal of, and therefore take the immunity that works best and neutralize it without creating a new immunity that would take its place. Again, it's a wild argument, but I see nothing wrong with it logically. Logically speaking, this makes a great deal of sense.
0:59:39.5 Bossche: Well, you know, Bret, I'm going to be very open with you. The field of natural antibodies is not well recognized or known in the field of vaccinology. It is well-known by immunologists. Frankly speaking, there are dozens of papers on these natural antibodies and how fascinating they are. As I was saying, they are a little bit in parallel to the NK cells, they recognize patterns, they recognize patterns of antigens, but this field is so neglected, so underestimated. I'm sure that many vaccinologists don't even really understand what natural antibodies are about and what they can do, because there is a lot of documentation of this. And there is even documentation... I will tell you, the nicest documentation is... You know about the blood groups, A, B, O, etcetera?
1:00:37.2 Weinsten: Mm-hmm.
1:00:39.1 Bossche: These blood groups, these are glycosylated structures. Glycans, sugars, for the people who don't understand what glycans are. And so, for example, if your blood group is O, for example, you will have antibodies, natural antibodies, all documented, all in papers, in publications, you will have natural antibodies against, for example, the blood group A. Blood group A is a sugar, N-acetylgalactosamine. And so now, interestingly enough, if the virus is now grown in a cell, in a mammalian cell, in a target cell that belongs to somebody who has blood group A, then as the virus is budding, when the virus is leaving, it's released from the cell membrane, it has an envelope, of course. That envelope, because it's partly part of the membrane of the target cell, it will also have this blood group A antigen. And when such a virus is encountered by somebody who has blood group O and who has natural antibodies against blood group A, the virus will be destroyed. And this has been proven not for SARS-CoV-2 but for SARS-CoV-1, that these natural antibodies will prevent the virus and the S-antigen from interacting with the ACE2 receptors.
1:02:20.3 Bossche: It's not like there is no evidence, there is no points. Also the binding forces between the multimeric natural antibodies and the S-specific antibodies are completely different. The type of chemical bonds, the one is the multivalent interaction which is much weaker than the S-specific binding, for example. There is many, many things documented. There is also very well-documented that natural antibodies can prevent influenza infection against a whole range of variants. All this is in the literature. So, it's not like I'm the crazy guy just inventing some stuff and making... Putting pieces of a puzzle that doesn't exist in reality together to make a fancy story. It is really highly likely that if you have S-specific antibodies binding but not neutralizing your virus, that they can prevent the natural antibodies from acting on that virus. And that is, as you pointed out, your specific antibodies are no longer functional and you have no substitute for it because you put your natural antibodies out of business.
1:03:37.7 Weinsten: So, this potentially puts the young at risk, who are largely protected, because it is presumably their innate immunity that is functioning to keep them safe. I wanna clarify a little bit in here. A, it is a very familiar pattern that medicine and medical science will ignore the parts of the system that work well without intervention. In other words, the idea that we are much more familiar with adaptive acquired immunity and it just so happens that there are lots of interventions that we deploy that depend on it and that we are largely ignorant of this alternative kind of immunity because effectively it just simply functions without largely our awareness of it is... It's a classic pattern. And the fact... Members of my audience will remember, when Heather and I started doing our livestreams about COVID, we were struck many times at the accumulating evidence, not unlike for other pathogens, but there's a piece of evidence that suggests that whether or not you get sick is heavily dosage-dependent. That effectively, even if you are in a room with an infected person and you are there very briefly, that you don't tend to pick up the virus.
1:05:02.5 Weinsten: But if you talked... If you were were there for five minutes, you effectively fill some kind of bucket and that once that bucket overflows, you're likely to get the virus. On the one hand, this creates a whole landscape of advice that we can give about how to behave to reduce your risk, like opening windows and being in large volume environments, etcetera. But effectively, that piece of evidence implies the innate immunity system, that basically you have a system that is capable of recognizing, in a not very specific way, a wide range of particles, and it can deal with them until it is overwhelmed. That is to say, when you have just simply too many viral particles so that your entire innate immunity that is capable of dealing with this virus is occupied, then that leaves some of these viral particles unhindered. Right? So...
1:05:57.0 Bossche: Yeah, sorry. Go ahead, go ahead.
1:06:00.1 Weinsten: No, so all I'm saying is that, it's interesting. We have seen patterns here that are suggestive of the importance of innate immunity in the COVID-19 story in a way that is underappreciated. And the idea that now, we're talking about rendering that immune system, the innate immune system, ineffective. At the same time, we are failing to create proper immunity in the adaptive immune system, that is... It's a perfect storm at some level. We're taking the thing that works and upending it without creating the thing that would replace it, and it does seem a very frightening prospect.
1:06:41.2 Bossche: So the error comes from the fact that, as I was saying, normally, adaptive immunity is a fantastic thing. It's a fantastic thing because it's very quick, it's very, very specific, it's really up to target. But for example, if you have... Let's say, you would have adaptive immunity, let's say, against influenza. And all of a sudden, Bret, all of a sudden, you have a dramatic change in the antigen, we call this an antigenic shift. Then the adaptive immunity will not work anymore. But the innate immunity will still work, and many, many people have never been vaccinated, they will simply deal with influenza, no problem. So this adaptive part that has now been subverted, so to say, by the virus, by the antigenic shift, you will have an outbreak, of course. And what is happening here with immune escape is that we are also creating an antigenic shift, but it's not static, it's dynamic. The more we vaccinate, the more it's gonna change, so we can never solve this.
1:08:00.9 Bossche: Normally, if you have an antigen, you will have an outbreak. And then again, the collective immunity of the population can deal with this. But here, we are always changing the antigen, so the adaptive immunity can not cope, it can not deal with this. And that is why here, in a kind of exceptional situation, the innate immunity becomes so important. When people talk about herd immunity, I'm always saying the real herd immunity that we have here is innate immunity. 'Cause if you have this infection, 80% of the population, in some populations depending on age and the demographics even 85% of the population, eliminates the virus and doesn't have any symptoms. Isn't that fantastic herd immunity? This is due to innate immunity. We know in the elderly, the innate immunity is weakened due to aging, and these are the guys who first get severe disease. So the herd immunity is here due to innate immunity and that is the complete misunderstanding.
1:09:07.0 Weinsten: Yep, now this tracks perfectly with what I understand of this system and it does raise the specter that our intervention is actually not only going to become ineffective, but render things far worse than they are. That in fact, we take the immunity of the young to COVID-19 as somehow God-given and permanent, and it is anything but. It is dependent on a system we know not enough about and that system is capable of being disrupted by a ham-fisted intervention in the adaptive immunity system. That strikes me as all too plausible.
1:09:46.2 Weinsten: And I would actually point out, it occurred to me when you were speaking earlier that there are lots of familiar examples where the same kind of overly simplistic logic has failed us for exactly the same reason. So people who have been prescribed an antibiotic by a doctor for an infection know full well this counterintuitive advice that even after you've gotten better, you should finish the course of antibiotics, and most people know why you are advised this. And that's because you will surely feel better before you've completely eliminated the pathogen. And if you withdraw the antibiotic before you are done with the course, what you have then done is trained the remaining members of this population to... You have selected for those members of the population of the bacterium or the fungus that were most resistant to the bacteria. You have selected for those and then if you withdraw the antibiotic, then that population regenerates. And what you've done is you've induced resistance.
1:10:54.3 Weinsten: And so, we now know that we have a population level problem with induced resistance, and we've seen the same thing with pesticides. Where we think, "Oh, this pesticide is going to eliminate malaria or it's going to eliminate this pest from the crop," but effectively, we've entered an arms race we're incapable of winning and made things worse in many cases.
1:11:14.0 Bossche: Yeah, so people say... Yeah, I know that many people think what I'm saying is crazy because it has never happened before. But never ever, in the whole history of mankind, have we been doing a thing like this. We massively intervene in this pandemic through infection prevention measures worldwide and pretty stringent. And then on top of this, mass vaccination in the midst of the pandemic, we have never ever been doing a thing like this, and then saying, "What you're saying doesn't make sense because it has not ever happened before."
1:11:46.9 Weinsten: Right.
1:11:47.1 Bossche: And then I'm saying, "Well, the situation... We have never generated, we have never created a situation like this."
1:11:54.1 Weinsten: It's novel, either way. Alright, so I would like to talk a little bit more about, if you are correct about the hazard here, my guess, I think as you have already said, is that there's no stopping this campaign. That is in some sense, politically inconceivable that people would change course, even if it made perfect sense for them to do so. And so, the criteria you suggest might tell us that your model is correct, standard hypothetical deductive science. You've put out a hypothesis, here are the characteristics that you would expect to indicate that it's right. If it turns out it's right, what do we do next? Do you have a sense?
1:12:37.9 Bossche: Well, yeah... Do you mean in terms of to remedy the situation? I mean my point is the best thing that can happen to somebody is to be seronegative, right? Because if you're seronegative, certainly, certainly, if you are in good health and you're seronegative, you have good natural antibodies. Again, this is no fantasy. There are studies, scientific studies where even natural antibodies are defined or used as a benchmark for good health, right? So, if you're seronegative, you don't suffer from any antibodies that could block your natural antibodies, and you can be fully exposed. I mean, of course the problem is gonna be the more you vaccinate people, the more people are gonna be sitting on long-lived... On long-lived antibodies, right? And even if those antibodies decline and they get re-exposed to the virus, I mean these antibodies will be immediately recalled. You were pointing out, you were educating people on what is memory and how antibodies get recalled after re-exposure, right?
1:14:02.5 Bossche: So then you have, of course... Well, being seronegative is not gonna be easy, and I tell you why because if we continue to breed these highly infectious variants, the likelihood for somebody who is seronegative to become infected is gonna become higher and higher, of course. So at the end of the day, you can turn it the way you want. For me, there is only one solution at this point in time. Maybe not at the beginning where it was wild, it's just a wild... But at this point in time, there is no resolution but to intervene. And for me, the only intervention that makes sense is really to eradicate those variant strains, because nobody is telling us how you're ever gonna get rid of those, right? Herd immunity, well, I mean that's not gonna happen obviously, because we have all...
1:15:00.0 Weinsten: It's not gonna happen because people will have been exposed to different variants, and therefore, it's a family of viruses, not a single one.
1:15:11.5 Bossche: Yeah, yeah. But remember, this was the final target. This was the endgame of the mass vaccination, is to have herd immunity, right?
1:15:19.2 Weinsten: Sure.
1:15:19.9 Bossche: So you could, of course also, and I'm not the expert, but let's assume an antiviral would work, and this antiviral could even be things like Ivermectin. You don't hear me advocating for Ivermectin, but let's assume some kind of antiviral drug would work. You could imagine to treat also people with this antiviral but doing this in a prophylactic way, you're gonna have the same problem as with antibiotics that some people will have low concentration, be confronted with the virus, and it will induce resistance, I think at the end. So you can use this for early treatment, that I think it's very very useful, but to get rid really of all these variants and to reduce the infectivity and control the whole thing, I really see no other way but to have a vaccine that induces... You can maybe explain this to the audience, sterilizing immunity, which is really to completely kill the virus, no matter what the antigenic constellation is of the virus, whether it is a variant or not.
1:16:27.5 Weinsten: So maybe I don't know well enough to explain it to the audience. I'd like to understand better. I certainly see that there is a hazard... A vaccine is not a vaccine, right? A vaccine is a very general technology. And in this case, the narrow targeting of the vaccine seems to me, it was a blessing in the sense that it allowed the vaccine to be generated very quickly, but it's a curse in the sense that it informs the immune system only about the one characteristic. And that if we were to use something like an inactivated virus that the immune system could discover various antigens, and therefore, the evolution of a single antigen would not create the kind of escape that we're seeing, but you tell me whether that adds up.
1:17:21.1 Bossche: No, no, it doesn't. I think it's a very logical reasoning, but unfortunately, it does not apply. The reason is if you target the S protein, what most of these vaccines do, you prevent... You can prevent the virus from entering into the cell. So that is basically, that is sufficient if... The problem is if you... Well, let me put it the other way around. Instead of an inactivated virus, I thing that might make sense because by the way, that is the way we eradicated smallpox, that's also the... Well, the biggest strides in the eradication of polio. Polio is not fully eradicated but almost, but the biggest strides we have made were the oral polio vaccine which was also a live attenuated vaccine. And there, of course, you induce innate immune responses, as well as of course, adaptive immunity, etcetera.
1:18:24.9 Bossche: And that would be, I think in my humble opinion, much more efficient, but of course, it would not be a solution for people who have already been vaccinated because as I was saying, if you re-vaccinate them with the oral polio... With an, let's say, an attenuated Coronavirus, you're gonna recall their original antibodies first because those have memory, and there is something like we call this antigenic sin. If you are re-challenged with an antigen that is similar to the one to which you got originally primed, then your original antibodies are gonna be recalled and those are not gonna match with the variants, so you are gonna even promote again immune escape if you re-vaccinate people who have previously been vaccinated with the current vaccines. But they help for those who are seronegative, the attenuated.
1:19:21.6 Weinsten: So you're arguing... So the attenuated virus is one that functions to transmit between cells?
1:19:33.7 Bossche: That function to transmit... Well, it's live attenuate, so it's going to be excreted, right, to some extent.
1:19:40.6 Weinsten: Right, yeah.
1:19:42.3 Bossche: Some people will say it was also the problem with oral polio. At the end of the day, you put this in the environment, it gets again, in people, it can recombine, etcetera. But still, as we have seen with oral polio, it has dramatically, dramatically reduced viral load. But my understanding is because of this antigenic sin, that you could not use it in people who have already been pre-primed with the current vaccine, right?
1:20:11.2 Weinsten: So this is yet another argument against the current regime, is that the current vaccine regime actually eliminates what might be our best weapon going forward because it will induce a kind of immunity that will react to this alternative type of vaccine.
1:20:28.3 Bossche: This, Bret, is something people need to understand, in contrast to a drug. You have a drug, when that gets eliminated from your blood or you have the the halftime of the... You need the minimum concentration for the drug to be active. If you are below that concentration, it doesn't work anymore, it's eliminated, and you're fine, it's done. There is no... There is no consequences, so to say. A vaccine is something that educates your immune system, for God's sake, for the rest of your life, right? So, that is not a simple thing. That is something which has serious consequences. I mean, we were talking about the memory, but what is memory? Well, memory means that if you see this antigen again or something alike, your antibodies, your original immune response will be recalled, right?
1:21:22.5 Weinsten: Yes, it's...
1:21:24.8 Bossche: And so that is a serious thing.
1:21:25.4 Weinsten: I've been trying to call my audience's attention to this, that we are inherently intervening, not just in a complex system, right? Complex systems are tough enough, but you're intervening in a complex system, within a complex system, within a complex system, right? The narrowest one being the immune system, which you are educating, the immune system existing inside the body, which is itself an adaptive system and then it exists inside a population. And so, all of these things interact, and what they do is they mean that any action that you take, because it sounds like the right thing to do, risks creating a cascade of consequences you did not anticipate. This being one such consequence, that there is a tool that would take longer to develop that you will take off the table to the extent that you have educated people's immune systems, such that effectively, you've warned them about a pathogen, your next vaccine might be attenuated and effectively, the immune system would have the equivalent of post-traumatic stress disorder, where it would react to the attenuated vaccine, which is potentially life-saving... It would react to it as if it were a pathogen and it would prevent the effectiveness, is that what you're saying?
1:22:42.1 Bossche: Well, it will recall your original antibodies, and these are the S antibodies of the current vaccines, right? Which we know, they don't do the job essentially... Let's assume, you make this vaccine and you start vaccinating with it in half a year from now. In the meantime, you will have further evolution of course, of your variants, so they will even be more different, the S protein, from the one that was originally in the vaccine. So now when you recall the original antibodies in one, in half a year from now, yeah, for sure, they will match much less with the S protein of the variants that will be circulating in half a year from now, right? So it's further driving immune escape, basically. So for me and yeah, I start, Bret, to hate to say this because people think that I'm selling my business or whatever, but asymptomatic people, asymptomatic people, they clear the virus. Thanks to natural antibodies in combination with NK cells. Again, this is science. There's publications were very compelling, very, very compelling, show that the combination of the natural antibodies...
1:24:00.3 Bossche: The natural antibodies, so to say, as you were saying, they evacuate part of the virus, so that the concentration, so to say, diminishes, and so that the chances that you're gonna get severe disease are diminished. So they evacuate part of the virus and they bring it, they... Into the NK cell pathway, so that the virus can be destroyed by the NK cells and but NK cells normally, that's how we started the discussion, have no memory. So now, there are tricks and we know that to some extent NK cells can acquire memory. It has not been proven for Corona, but I think this is really a pathway to work on because if we know the motifs that the NK cells recognize, we can use them in a vaccine, and of course, we need to do something about the memory. But I'm always giving the example, maybe you have heard about the streptococcus vaccines, the polysaccharide vaccines against strep pneumonia, for example, otitis media, etcetera, that you get during childhood.
1:25:04.5 Bossche: Normally these antigens, polysaccharides, sugars, they induce antibodies but without memory, so that's not good. So what we have been doing, we have been making a conjugate vaccine, and we have taken the polysaccharides and we have conjugated them to a T helper protein, a T helper protein. And now, with this synthetic construct, this is not a natural construct, this is something man-made, I think the biggest invention ever in vaccinology, we have now managed to induce an immune response that not only recognizes the polysaccharides, but that also has memory, thanks to this conjugate. So in other words, even though natural immune responses do not have memory, we can educate immune system in a way that it can get, acquire memory against this particular patterns, I would say.
1:26:00.2 Weinsten: Oh, that's fascinating.
1:26:01.5 Bossche: Yeah, because this is non-antigen specific, so that means there cannot be immune escape. Escape against what? Selection of what? It's non-antigen... It's ant... Yeah, antigen non-specific, that's the right way to say it.
1:26:17.0 Weinsten: Alright. That's very interesting. I did not know about that construct, but the idea of creating, basically hacking the system to trigger memory in a case where memory would not ordinarily be developed, that's fascinating. So I had a thought here, likely wrong, but when triple drug cocktails emerged against HIV, I had this moment where I had the sense that it was obvious that we should have done something like this from the beginning, because effectively, by taking three different drugs and challenging the virus simultaneously with them, we eliminate the pathway by which we would train it against whatever our best drug was because you've pushed it to three directions at once, and it can't adapt.
1:27:08.5 Weinsten: So evolutionarily speaking, I thought this was straightforward, that something like this would work. It doesn't have to be three, but pushing it in more directions than it can go makes sense. So, by analogy, if you were to set up conditions where... Or some sort of competition, where somebody had to increase their capacity to high jump at the same time they increase the amount of weight they could lift and conserved the maximum number of calories, all those things push in different directions. So the point is, there's no way to game any of these systems, you have to just compromise, which makes you low-quality at all of them. So I'm wondering if there's not a vaccine style solution here that involves, instead of pushing the virus in one direction and creating the immune escape pathway that you describe, is there not some way of formulating a challenge that pushes it in simultaneous, mutually exclusive directions so that it cannot move?
1:28:25.0 Bossche: Well, of course I've been torturing my brain for many years, not because of this Corona thing. As you can imagine, we could have other pandemics as well to which we are not prepared at all. So in another sense, what has been the focus, in fact, of my attention of my research in the last eight years has been universal vaccines. And universal doesn't mean one vaccine for all kinds of diseases. No, it means one vaccine for a number of like... For example, natural antibodies as I was saying or in K-cells, recognize a pattern of motifs that may be shared by several different pathogens when they infect cells. That's like, a cancer cell at the very beginning, the first alteration of the cancer cell, no matter what cancer it is, it's an alteration of cells. That's a kind of common denominator. So it's a pattern that is shared amongst several different pathogens or pathogenic agents. And so how can you make such vaccines?
1:29:37.7 Bossche: This is very challenging, but frankly speaking, to cut a very long story short, that is why I started to concentrate in K cell-based vaccines, because the innate, as we were saying, the innate immune cells that we need to provide them with memory, of course, are in fact the only cells that have this capacity to recognize a wide array of several different changes on the surface cell, and another important thing is, at a very, very early stage of infection. That's a very important thing because we were talking about the T cells and the cytolytic T cells. We know when people get a disease, for example a severe disease, and then they cure it out, it's to a large extent thanks to cytotoxic T cells, but they come way too late. What we need is the cell that... The virus gets into the cell. There's an alteration of the membrane before even you have the progeny of the virus, before you have replication and production of new virus particles. So at the very beginning you have an alteration of the cell, of the cell membrane, at the very early stage, that's where you need to kill this cell.
1:30:52.5 Bossche: And I'm not aware and I don't think it exists, that you could use multiple immune interventions at the same time, combine them to cut, let's say, several different pathways for the virus to generate a progeny and to propagate. Because as soon, Bret, as soon as you come with several different immunogenic agents, you will have competition as well. You will have competition. One will be more dominant than the other, and will take advantage of the immune system and use its full capacity. And other immunogens, they will barely generate an immune response because they are not dominant. So there is one thing that I've learned in immunology that does not apply, which is the more, the better. That doesn't apply to immunology.
1:31:48.7 Weinsten: Right.
1:31:49.5 Bossche: The more, the better. That does apply to drugs very often. It does not apply to immunology. People always think, "Oh, wow, this vaccine doesn't work. We give double dose, or we give another dose after three weeks and then one month and etcetera. So the more the better." That doesn't work in immunology. That doesn't work in vaccinology. It's the message that you convey to the immune system.
1:32:13.6 Weinsten: Yes, for multiple reasons, it doesn't work. So to the extent that you have informed your immune system about a particular challenge, it's informed. Sending it a thousand emails that share the same piece of information doesn't inform it better. Then there's also the problem of autoimmunity and leukemia. So the point is, it's not just a question of the information, the value of which a single email will do or a single vaccine that is effective at creating memory will do, but there's also the problem that this system is very tightly managed for health. And that at some level, I'm pretty sure we don't know what the result of continuing to trigger it in various ways is. And unregulated production of B cells, for example, would be a known type of tumor, it would be leukemia. And autoimmunity would be the reaction of the immune system to things that you yourself make. And so the point is, messing with this system when you don't know what you're doing carries all kinds of potential hazards, and we have to be very careful with it.
1:33:38.3 Weinsten: And unfortunately, I think the political environment in which we find ourselves makes it very hard to behave rationally, that there is a demand on people who are in a position to govern that they do something. And the problem is very few appreciate just how delicate this system is and how marvelously it's working on their behalf already. I mean, yes, COVID is frightening, but the degree to which most of us have not gotten it is owing to the effectiveness of the system before you make any intervention at all.
1:34:14.0 Bossche: Yeah, the immune system is extremely sophisticated, and for example, I posted on my website a number of maybe 15, maybe 20, but 15, let's say, questions that are really fundamental questions, things we don't understand in the pathobiology of COVID-19. And a number of questions surrounding, of course, the immunology and the immune defense. And I think if you cannot answer to these fundamental questions, it becomes very, very tricky to intervene in the immune system. And certainly, if you intervene at a very, very large scale, knowing that the message we were talking about will stay with you for the rest of your life. So that is something really, I think there we should have done a much better homework because massive intervention in something which is so well-tuned, so sophisticated. Either you have a fantastic effect or, if you do this on a massive scale, or it's all but good. And that is really my fear right now with what is happening and the way in which, seemingly, we will not be able to stop anymore.
1:35:39.6 Weinsten: Yes, I think in some sense to continue with the military analogy, this is a live-fire exercise in which we're all in, unfortunately.
1:35:50.2 Bossche: Experiment. It's an experiment.
1:35:51.0 Weinsten: Yes, it's an experiment and a very poorly controlled one, which is frightening. Alright, where can people find you?
1:36:03.8 Bossche: Well, people can find me best on my website because, unfortunately, although I try to distribute scientific information and only scientific information, it gets increasingly blocked on all kinds of channels and media. So my website is geertvandenbossche and then dot org, O-R-G.
1:36:36.6 Weinsten: Okay, geertvandenbossche.org. I know that you're also on Twitter, and that your website can be found through your Twitter bio. I will say, to the extent that platforms are taking down the material that you're putting up, this is madness.
1:36:55.8 Bossche: Yeah, I know.
1:36:56.3 Weinsten: Right. This is madness. You are a domain expert. You are clearly motivated by concern. What you're saying is, whether or not it is correct, it is perfectly rational, it is highly logical, and can be interpreted by anyone who has the scientific training enough to follow such an argument. That the idea that you are somehow a hazard by virtue of engaging in very serious questions on which a great deal of human well-being rests is preposterous. These platforms are in no position to evaluate what you're saying, and that means we have to be able to discuss it in public.
1:37:50.9 Bossche: Well, that is what I'm calling for since many, many weeks, because the way the discussion is conducted right now is that, well, some fact-checkers reach out to some experts, and then you have some one-liners in their report, some one-liners that, so to say, contradict what I'm saying. And then the fact-checker confronts me with this contradictory statement, so to say. That is not a discussion, and I'm asking all the time for these experts to start a debate like we are discussing. Then things can be clarified and arguments... And we could... I would love to see a consensus on what is going to be the criteria that we all agree upon to say whether or not human intervention is driving immune escape, right? Because if there is really immune escape driven by human intervention in the way we have been discussing, then I think everyone will agree that this is not a good thing. This is really very problematic. But if we don't have criteria and if we don't agree upon, I mean, the only thing will be vaccinate everybody, right? Unless everybody's vaccinated, it's not over. And that cannot be according to my interpretation.
1:39:21.1 Weinsten: No, and the pressure to vaccinate everybody is incredible. The number of young people that I hear are being vaccinated is preposterous in light of the fact that there's really almost no reason to do it. Even if the vaccine is safe and good as it's being portrayed, the fact is young people are already immune and there's no reason to intervene in the...
1:39:46.2 Bossche: Well, the only caveat, Bret, is this was certainly the case when the wild strain came in. And I told my kids, "Okay, if you're obliged to because you have to wear a mask in the store, for example, you have to do this, but don't do it when you are with friends etcetera, and they are not... " They were not participating in mass gatherings anyway, but now, the problem now is with these highly infectious variants, the likelihood is increasing that... Well, this is something we didn't discuss, but it's important to understand. When you are an asymptomatic, asymptomatically infected, so you got infected with the virus without developing symptoms, during a short period in time, you will be developing antibodies. These are antibodies that are not very mature, and I'm not saying in all asymptotically affected people, but in a fair extent, a fair number of asymptomatically infected people, they will develop antibodies that are not fully mature and that are short-lived.
1:40:55.3 Bossche: So as we discussed, these antibodies will be able to bind to this protein, not neutralize it, but out-compete your innate immune response. So now with a highly infectious variant circulating, the likelihood that as a young guy or lady, you get hit by the virus during the time where you are sitting on your immature antibodies becomes increasingly higher. And that is how we now also see how younger age groups, without underlying diseases, people in perfect health, get severe COVID. So you see, these are criteria for me that are really important to analyze and to further discuss and to agree upon. If that is not done, and the only criterion is we go on until everybody gets vaccinated, young or old, no matter what, no matter whether they are in good health or whatever, whether they are serapositive or seranegative. I mean, then it's yeah, it's really a war situation.
1:42:03.4 Weinsten: Well, that's very frightening. Alright, well, this has been a fascinating discussion. I look forward to hearing how this develops, and I do hope that people... I know people are taking your argument seriously, privately. I think there's a lack of courage in, especially in and around academia, where people won't necessarily say what they understand because they're afraid of consequences. And in this case, the consequences for humanity are so immense that I think it is incumbent on people to at least point out that this is an argument that needs to be taken very seriously.
1:42:40.7 Bossche: Well, there are top experts, much more famous than I am, who I know and who write me, that I'm right. But if you're really a top expert, of course you are working in some of these communities that are now deeply involved in driving these vaccination campaigns. So unfortunately, these people cannot speak up, and I think it's really, given what is at stake, it is... Yeah, for me it's a moral obligation. I could be employed, I could be whatever. I mean, this is so frightening to me, I have spent weeks and weeks and nights to understand what is going on. And so having done my homework, the moral obligation to react is such that, this is for me the absolute priority, no matter what.
1:43:44.5 Weinsten: Well, I agree with you about the moral obligation of it. It's, of course, not entirely safe for me to put you on my channel either. I feel that same moral obligation. And I would just point out, that I think we've lost track of how much risk people have taken through history when something was important, and to the extent that people may have fears about what happens career-wise to them if they speak an important truth, they need to recognize that lives are on the line. This is an argument that must be engaged, and it's time for them to step up. And I would say to the extent that there are people who privately acknowledge that what you're saying is sensible, people who believe you are right and are in a position to change public opinion, I open this channel to them. If they'd like to come on and tell us what you've got right, what you've got wrong, what they think we ought to understand, I'm more than happy to host that discussion.
1:44:46.7 Bossche: Well, I much appreciate that, Bret. I really do, and yeah, I'm also very much hoping for people ultimately because it's really more than time to do so. Because as you will realize, right now things start to be very fast, to evolve very, very fast. If you see in some countries because that is the only... The other thing, every country is looking at its own situation. When I hear the news, for example in Belgium, it's like the only country where we have a COVID pandemic. And the world is closing in on this. And it's like... I mean if there is a double mutant in India that is resistant, for example, that is also my problem, that is your problem, that is everyone's problem. And it's like, "Oh, let's put the figures down. Let's try to put the figures down in Belgium or in Germany or in UK."
1:45:45.0 Weinsten: If there was ever a situation in which we should put politics aside, put national boundaries aside, and team up to address a problem, this is it.
1:45:54.6 Bossche: Yeah. Pandemic is per definition a global thing, and our strategy is not global at all. Yeah. Well, we could go on forever with is, but I much appreciate you doing this and at least giving me an opportunity to talk about this. And frankly speaking, I think, Bret, we have been very scientific about this, right? I mean...
1:46:17.4 Weinsten: Yep.
1:46:18.4 Bossche: So yeah. Okay.
1:46:21.0 Weinsten: I think we have to continue to have this discussion. And I must say I greatly appreciate your courage and your insight. I think you're a force for good, and I am so glad that you chose to come on DarkHorse.
1:46:37.4 Bossche: Yeah, thank you so much for having me, really.
1:46:39.8 Weinsten: Alright, thank you.
1:46:41.1 Bossche: Okay.
1:46:42.1 Weinsten: Be well everyone.
1:46:43.4 Bossche: Yeah.
- 00:00 Welcome
- 01:28 Basic argument around vaccines
- 03:57 Trade off of vaccines
- 06:16 How adaptive immunity works
- 16:28 COVID immunity
- 18:42 How mRNA vaccines work
- 21:11 Innate immunity
- 25:30 Geert's argument
- 39:30 War analogy
- 47:33 Comparison with 1918 pandemic
- 56:44 Immune escape
- 59:41 Natural antibodies
- 01:03:47 Dose dependent COVID
- 01:06:40 Herd immunity is innate immunity
- 01:09:46 Arms race
- 01:11:12 Is Geert crazy?
- 01:12:01 What can we do next?
- 01:23:35 The next COVID vaccine with Natural Killer (NK) cells
- 01:26:32 Triple drug cocktails against HIV metaphor
- 01:32:32 Auto-immunity and leukemia
- 01:34:15 Fundamental things we don't understand about COVID
- 01:36:02 Censorship of Geert.
- 01:40:22 Asymptomatic infection
- 01:46:41 End
- COVID-19 vaccines look good in the short term, but probably not good for the long term
- COVID-19 vaccine adverse reactions reported 6X more often in Europe than in the US – March 29, 2021
- Worrisome New Evidence That Vaccines Are Less Effective Against Variants - March 2021
- Risk of dying from AstraZeneca vaccine higher than of COVID-19 - Norway April 23, 2021
- Vaccines Are Pushing Pathogens to Evolve – May 2018
- Vaccinated children had more chronic diseases - Sept 2018
- Vaccinations might be improved with vitamin D booster – March 2015
- Vitamin D Effective in Preventing Flu if not vaccinated - June 2018
- 10X reactions to flu vaccine when vitamin D deficient
- Geert Vanden Bossche Stokes Fear of COVID-19 Vaccine To Promote His Own Flawed ‘Solution’ Snopes
- The Doomsday Prophecy of Dr. Geert Vanden Bossche McGill University Office for Science and Society
- Mass Covid-19 vaccination will not lead to ‘out of control’ variants AFP Factcheck
- *Note: I did not find any virologists disagreeing