#159-Peter Hotez MD, PhD.: The anti-vaccine movement, causes of autism, & COVID-19 vaccine update

1. 0:00 – 0:10

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to "The Drive Podcast." I'm your host, Peter Attia. [upbeat music]

2. 0:10 – 10:30

   The stubborn persistence of anti-vaccine sentiment;

   1. PAPeter Attia0:10

      Hey, Peter. It's really great to have you back again. Every time you and I sit down, whether it's on the podcast or just on the phone, [clears throat] I get the sense we could go on for hours. Um, I wanna really talk about a bunch of things today, but I wanna start our discussion with a broader topic than just coronavirus or SARS-CoV-2, COVID, things like that, which I know is a topic you are still front lines on, and, uh, I don't think a day goes by that you're not being, uh, sought after for your opinion on things. And, and we will certainly get to many of those things later today. But I, but again, I wanna start with a topic that was near and dear to your heart long before the coronavirus emerged in this fashion, which is the topic of vaccines and vaccine safety. Now, recently, I had Brian Deer on the podcast, and I think for many people it was an illuminating discussion, um, because, uh, you know, Brian himself is not particularly a vaccine advocate. He's very clear about that. He's just an advocate for good science. And I think his, his work, uh, uncovering the web of lies and, uh, deceit surrounding the work of, uh, Andrew Wakefield is, is really unparalleled, especially when one considers the depths to which it was scrutinized, both scientifically and even in the court of law. Um, so I think [chuckles] the first thing I really wanna understand, Peter, is why is it that after the complete, um, debunking of everything that Andrew Wakefield did, said, published, et cetera, why is this still an issue? Why is it that in a post Andrew Wakefield world, most polls would suggest somewhere on the neighborhood, correct me if I'm wrong, 20% of, uh, Americans still believe there's a relationship between vaccines and autism.

   2. PHDr. Peter Hotez2:02

      Yeah, I think what, what's happened, and it's actually a very profound question, and, and I agree Brian's work was extremely important, and, and then the scientific community came in in a big way debunking all of the assertions. And one of the things about the anti-vaccine lobby that it spawned or that it ignited, at least in the modern sense, is that they kept, from then on, they kept on moving the goalpost. So it began in its modern form, uh, 1998 with the Wakefield paper l- asserting that measles, mumps, rubella vaccine causes autism by repli- the live virus vaccine replicating in the colon. The scientific community responded in a very vigorous, robust way, publishing multiple papers, large cohort studies showing that kids who were autistic, and I got involved in it 'cause I have a daughter with autism, and, you know, kids who are autistic are no more likely to have gotten the MMR vaccine than kids who are not, and similarly, kids who get the MMR vaccines are no more likely to become autistic than kids who don't, and really sound epidemiologic studies. But then they switched. They flipped. They said, "Okay, well, it's not really MMR vaccine." They had Robert F. Kennedy and a group of people saying it's the thimerosal preservative in vaccine. And then it switched again to spacing vaccines too close together. Then it switched again to aluminum vaccines. And now what you're starting to see is even shifting away a bit from autism, saying that vaccines cause something called chronic illness, or looking at the HPV vaccine for cervical cancer and other cancers and, um, and then seeing it causes infertility, uh, or miscarriages. And, and each time the scientific community responds. And, and what they do is to, to maintain momentum, to re-energize, they keep on shifting. And, and the concern for me now is they're not even looking at this from a, a pseudoscience point of view. What they're now focusing on is the politicization of it. So with this, and we'll talk more about it, but it, it, and starting around 2014, 2015, they managed to glom onto the Republican Tea Party and to make it a politicized movement around these concepts of health freedom and medical freedom, and that's what we're dealing with today now. And, you know, that's why you've got all the craziness on Fox News the last four or five nights with Tucker Carlson going on this rant against vaccines and Laura Ingraham going on this rant against me and Tony Fauci. And, and so this is, this is a problem in that it's, that they have this adaptability, and y- they create these versions 1.0, 2.0, 3.0, uh, of the anti-vaccine movement. But the autism piece never entirely left. That's still its, that's still its legacy, uh, legacy fake assertion that, that still haunts us today.

   3. PAPeter Attia5:02

      Well, uh, uh, I mean, I think [clears throat] given how deep, uh, Brian went into the discussion specifically of MMR and autism, that relationship, I don't think anything else needs to be said on that topic. And obviously for anybody who's listening to this that still has questions around that, I would highly recommend that they go back and watch that video, listen to that podcast, read the book. And, um, you know, truthfully, and I don't say this to be, um, [tsks] uh... Y- y- you know, I, I don't know how to say this delicately, but I think if, if after all of that work, uh, if after assimilating all of that work, you still believe that there's a relationship between that vaccine and autism, there's probably nothing that can be said that can dissuade you from that. And, and I would just leave it at that and agree to disagree. But let's focus on some of the other things that you've brought up. Uh, do you have a preference for where you'd like to begin? Would you like to start with thimerosal?

   4. PHDr. Peter Hotez5:58

      Yeah, I mean, you can, but it, but it always comes down to the same Same few things. I mean, what happens is each time the scientific, and in the case of both Brian Deer and the MMR, in addition to the scientific community refuting it on the basis of large cohort studies and prospective studies, what he was able to do was show nefarious intent, and which was extremely helpful because knowing that. What's happened since then is the anti-vaccine movement has grown so much larger than, than Wakefield. Now you've got dedicated anti-vaccine groups, national anti-vaccine groups like Children's Health Defense and, and ICAN and, and those kinds of things. But then you also have, um, you have local political action committees, PACs, that are linked to far-right-wing extremism. So it's become this very complicated, uh, ecosystem or web and, and now it's even gone beyond the United States. So yeah, I mean, we could go into why thimerosal is not linked to autism, and then we could go into why spacing vaccines is not related to autism or what autism is and how it begins in early fetal brain development. But it won't stop the momentum of the anti-vaccine movement because, you know, they, they light a fire, they cause damage, and then they move on, and, and that's their modus operandi.

   5. PAPeter Attia7:20

      Yeah. Uh, I, I don't disagree with that, Peter. I guess the way I think about the role I'd like us to play in this discussion is I don't think we're here to stop the anti-vaccine movement. What I'd like to do is help parents who frankly are inundated with information and can't distinguish between signal and noise, at least-

   6. PHDr. Peter Hotez7:40

      Yeah, yeah

   7. PAPeter Attia7:40

      ... come to a, a place where we can have an honest discussion about it, because I really do want to have that discussion. And, and I think the order in which you actually just went through them is an, is a very elegant way to talk about this, right? Which is let's spend a few minutes on thimerosal. Let's spend a few minutes on some of these other claims, and then let's actually talk about autism, because there is no denying the fact that the incidence and prevalence of autism are increasing, and we should talk about what some of the plausible reasons for that are and why the scientific community has been able to rule out these claims that are being put forth. Um, because again, I, I, I have great empathy for the parent who's listening to this, who is confused. Um, w- you know, and, and that doesn't necessarily mean just the parents of children with autism, but that's the, the, the, the parent who's trying to decide, [swallows] "What am I supposed to do here? Am I, am I supposed to get my kid vaccinated? And, and am I supposed to get them vaccinated at this pace? And does m- does my kid really need three H, you know, or hep C v- or pardon me, hep B vaccines in the span of six months?" Um, and, and so, uh, I think just having an open, honest discussion about that is, is by no means going to dissuade the 20% of people who are clearly in the camp that says, uh, "Vaccines are evil." But I, but I do believe that there's a very confused group of people in the middle, and I hope we can, we can talk about that. So, um, is it safe to say that post-Wakefield, 'cause I'm trying to go back and remember the timeline. It was around 2007, 2008 that w- I mean, every claim of Wakefield had been pretty much debunked, correct? And to your point, it wasn't just debunked scientifically, but I mean, it had been made clear that, that he had lied and he had manipulated data, as had O'Leary, and this was one big house of cards.

   8. PHDr. Peter Hotez9:29

      Yeah, the, the, the, The Lancet paper was retracted, I think, in 2010.

   9. PAPeter Attia9:34

      Okay, 2010.

   10. PHDr. Peter Hotez9:35

       Uh, although, although I think there was an expression of concern-

   11. PAPeter Attia9:38

       Yep

   12. PHDr. Peter Hotez9:38

       ... put out by The Lancet a few years before then, maybe 2004.

   13. PAPeter Attia9:41

       Okay.

   14. PHDr. Peter Hotez9:41

       I can't remember exactly, so. And the basis for the retraction, um, is, you know, they didn't really spell it out that much. They basically said the results are, are no longer valid. I don't think the retraction letter issued by The Lancet, uh, went into, um, all, all of the investigation that the medical council had done and, uh, and for, for Wakefield to be struck off the register. I don't think the retraction mentioned anything about the Brian Deer paper.

   15. PAPeter Attia10:12

       Uh, yeah, I think it was Deer's reporting, and, and frankly, the most damning evidence was the lawsuits, right? It was the complete inability of Wakefield to maintain any legal argument against the people who were accusing him of fraud and, and that, you know. So, so let's put that aside and let's move forward.

3. 10:30 – 24:00

   A closer look at claims about thimerosal and vaccine spacing causing autism;

   1. PAPeter Attia10:30

      Let's start by telling people what thimerosal is and what is it doing in a vaccine.

   2. PHDr. Peter Hotez10:34

      Well, first of all, thimerosal is really not in childhood vaccines anymore.

   3. PAPeter Attia10:39

      No, but what, what was it?

   4. PHDr. Peter Hotez10:40

      Um, there is a, there, there, there is a flu vaccine. It, so what happens is if you're giving vaccines in multiple, if, if, if you have a, a multi-dose vial of vaccines whereby you've got a vial of vaccine that could be given to six or seven or 20 people, each time you're introducing a needle into that vial through a rubber stopper, potentially you're introducing bacteria. And the worry is that if you do that enough, that there could be some bacterial growth or overgrowth into the vial, so you need to put some preservative in to, um, that's non-toxic, that could be, that will kill the bacteria. And, and when thimerosal was discovered, it was considered quite an advance in terms of allowing you to vaccinate large populations. And the bottom line was it was taken out. The manufacturers, uh, took it out of the vials just because of all the, all the bad publicity swarming around it. It, there was never evidence to show that it was a problem, uh, but I think the thinking was that we don't really need it. We can give single-dose vials instead. Let's just take it off the table. And, and in fact, that was done. There are still, uh, some of the flu vaccines still have thimerosal, um, uh, in the U.S., but I think that that's about, not all of them. You can still get a single-dose vial for flu vaccine and, and take that as well. But, um, but there was never, ever any shown association between thimerosal and any untoward effect in, in terms, certainly in terms of autism.

   5. PAPeter Attia12:17

      Now, thimerosal was one of the, one of the, the big, uh, push, uh, one of the big pushes from, from, uh, Bobby Kennedy Jr., correct? Wasn't this really, um, his, his initial cause and his initial fight?

   6. PHDr. Peter Hotez12:33

      I think so. I think he got into it because, you know, he's an environmental law attorney.

   7. PAPeter Attia12:38

      Yep.

   8. PHDr. Peter Hotez12:39

      And, you know, looks at, um, toxic waste, and I think, you know, when he saw the mercury word, he probably got a link to Minamata disease, which is, remember, uh, back in Japan several decades ago, there was a lot of mercury exposure in fish, and young kids who were exposed to what's called methylmercury, um, uh, either during pregnan- I think it was during pregnancy, um, and the, the kids that were born were born with intellectual deficits, and there was a syndrome associated with it. It was called Minamata disease. And so I think, I think probably people in his camp put two and two together, and they said, "Well, you know, probably autism must be some form of Minamata, uh, disease. Even though it's not the same, maybe there's enough there, there that it could be due to thimerosal." But again, the large cohort study showed absolutely no linkage, uh, wi- with, with autism, um, and ultimately we know why. It's 'cause we know autism is associated with prenatal events, that it's this, we have... Well, we can talk about it.

   9. PAPeter Attia13:48

      Yeah, we'll come to that. Yeah.

   10. PHDr. Peter Hotez13:49

       But that's, that, but that's the, um, that's how he got involved, and there were books about it. Um, there were a couple of books making these assertions, and it als- and then once again, it started gaining a lot of momentum, very much like the way Wakefield did a decade before. Um, and I think the first publication, which I write about in my book, uh, Vaccines Did Not Cause Rachel's Autism, um, uh, kind of points that out. I should get the book in front of me. I could, uh, read it right to you. Hold on. This, this is the book. It's, uh, the last, not this book I published, but the last one. It's called Vaccines Did Not Cause Rachel's Autism, and it's, and, uh, we, I go into it a bit, um-

   11. PAPeter Attia14:31

       And while you're looking for that, Peter, I'll just clarify for listeners the difference between methylmercury, organic mercury, inorganic mercury, uh, 'cause you made the point, um, that thimerosal is a form, it's an organic mercury, and there, there's sort of a difference between organic and inorganic mercury, right?

   12. PHDr. Peter Hotez14:47

       That, that's correct.

   13. PAPeter Attia14:48

       And most of the toxicity that we see when people are over-consuming, um, you know, fish that are high on the food chain, such as large tuna, swordfish, shark, is organic mercury. It is methylmercury, not inorganic mercury.

   14. PHDr. Peter Hotez15:04

       Right. So Minamata disease, which was, um, uh, named after a city in Japan, it resulted from a chemical plant's industrial release of methylmercury, um, which is different from thimerosal, which is a totally different compound. It's, it's ethylmercury, and it was in wastewater, and it accumulated in a bay where fish and s- shellfish lived and were consumed as seafood. And large-scale methylmercury ingestions in pregnant mothers caused a congenital syndrome causing neurologic disease in the form of gait and motor disturbances, in some cases even, uh, coma, uh, and, and death. And so there was a paper that was published, uh, at that time in a journal called Medical Hypotheses that first proposed that maybe autism could be related to thimerosal because even though it's not ethylmer- methylmercury, maybe the e- maybe it's ethylmercury doing this. And, and that was, um, uh, in 2001, uh, that the paper got published, so three years after, um, the Wakefield assertion. Uh, any- and so this was a pretty common, uh, preservative, uh, but, but then it was subsequently, uh, taken out. And what was interesting is even after it was taken out, the rates of autism never went down. Um, that, that's pretty clear. And there were, again, large cohort studies showing absolutely no link, uh, with, with thimerosal.

   15. PAPeter Attia16:32

       A- a- and all of that said, Peter, it's, uh, I, I certainly wouldn't wanna suggest that the paper in 2001 and even the work that followed was anything but reasonable. I mean, that's the purpose of medicine, right? I mean, uh, you know, you see something like autism, you look for plausible associations, and you see a neurologic disease that is associated with mercury. Uh, it's entirely reasonable to formulate a hypothesis that says this other thing that looks kind of like it could be it.

   16. PHDr. Peter Hotez17:03

       Yeah, and the, and the paper was published in a journal called Medical Hypotheses, so-

   17. PAPeter Attia17:07

       Exactly. I mean, it's, it's completely reasonable. It's the stuff that follows that's, that's challenging, right?

   18. PHDr. Peter Hotez17:13

       It's after the scientific community goes to great lengths and great attempts to s- seek the truth and publishes, you know, paper after paper after paper in mainstream scientific journals that the anti-vaccine groups refuse to acknowledge it's cling to their debunked hypothesis, and their only response is, "Well, the scientists must be paid off by the pharma companies, or the journals must be paid off by the pharma companies, or the editors m- must be paid off by the pharma companies." And so they resort to conspiracies rather than, rather than, "Okay, I get it. Let, let's move on. Let's try to figure out what really causes autism." And they've never shown that in- intellectual curiosity about what really does cause autism, and they continually discount, um, the massive amount of scientific, uh, work that's gone into really uncovering what autism is.

   19. PAPeter Attia18:17

       Before we get into kind of the deeper why, because that's a big part of what I want to understand, and there's two deep whys here, one around autism and one around this sort of latent distrust and the path that any two individuals can... You know, there's a fork in the road, right, where one person can be very influenced by [clears throat] data. They can think sort of probabilistically. They can think in terms of uncertainty. They can accept and, and reason their way through these things. And then there's another person who's going to cling to a belief in the presence, um, of emerging data that, that refute that hypothesis, and they'll continue to come up with an excuse. And I, and I, I really wanna try hard not to pass a moral judgment in either case, but, but there's clearly an anti-science sentiment, uh, that is, that is growing and that is, uh, that is fostering this. Before we get to that, let's go to the next point, which is thimerosal, I believe, was electively removed in about two, two-- like very early in the two thou- 2000s, right? It was-

   20. PHDr. Peter Hotez19:21

       I think it was actually removed two years before, um, the, the medical hypothesis paper. I think it was removed in 1999 actually.

   21. PAPeter Attia19:34

       Mm.

   22. PHDr. Peter Hotez19:34

       Or at least it was, that process was started. So, um, it, it had already been underway.

   23. PAPeter Attia19:40

       So what was the next, what was the next, uh, position of the goalpost after thimerosal?

   24. PHDr. Peter Hotez19:46

       So then it was this concept of greening our vaccines or making them more, I don't know why they used the word green, I guess making them more eco-friendly, and that the, that the li-- the third hypo- major hypothesis was that kids were becoming autistic because of antigen overload, that somehow they were getting too many vaccines at once. This was overwhelming the immune system, and somehow that led to autism, um, which again, never made a lot of sense to me how something... You know, because in a, and they say it's leading to inflammation, and I always would point out that, you know, we've seen, we've seen what the brains of kids on the autism spectrum look like. I've seen my own daughter's, you know, CT and MRI scans in her workup of autism, and we know what inflammation looks like. You can see inflammation on a s- or evidence of inflammation or at least blood on a, on a CT or an MRI and, and we know what herpes encephalitis looks like, and autism doesn't do that. It's not an inflammatory state of, of the brain, and so that one never made any sense, uh, either. Then, and then there, there were several other people who came into this, people like, um, the, the pediatrician, uh, Dr. Bob Sears started writing books about how we have to space vaccines further apart and had written a, a number of book, books about that as well. But again, it, it... Well, first it never had plausibility and, and s- but that, that's still out there today. There's-- And if you go on amazon.com and look up books on vaccinations, I think those books are still top sellers.

   25. PAPeter Attia21:25

       Now, in the case of, um, thimerosal, at least there was a plausible explanation that was put forth as a hypothesis. Um, when the hypothesis for spacing was put force-- put forth, was there some epidemiologic data that suggested this?

   26. PHDr. Peter Hotez21:41

       Uh, I, I, I'm not, I'm not aware of it. Um, and the problem was, you know, we didn't have clinical trial data to support the, the spacing of the vaccines. You know, the, the, the, the, the protocol, the, the s- the current vaccine regimen, the schedule, is based on years and years of studies confirming immunogenicity and protection. Uh, it's also based on years and years of studies showing that there's no immunological interference. In other words, if you give, pair two vaccines together, that one doesn't interfere with the other. It's a very carefully orchestrated dance, and then these guys come in with these wacko schedules, um, without any scientific basis. And then, you know, [sighs] the, it forces the scientific community to try to reevaluate whether you're still getting the same immunogenicity, uh, or not, and also the immunological interference. So in addition, so it's not just a matter of saying, "Well, what difference does it make 'cause kids are getting the same vaccines?" It's unclear whether they're going to be just as effective, uh, or safe, uh, as, as the, as that very carefully orchestrated dance that was developed jointly by the FDA and CDC.

   27. PAPeter Attia23:01

       That's a very interesting point, Peter, and frankly not one I'd ever considered. Um, I get asked not infrequently by patients, um, about vaccinating their children on the schedule, and these are not people who think vaccines are causing autism, but they do have some concern, presumably just based on things that they've read, heard, et cetera, that say, "Hey, does my kid really need to have all of these shots in the first nine months of life?" And their, um, their belief, which is not unreasonable, is isn't this just a way to ensure kids get their vaccines? Because during the first year of life, the parent is so much more likely to come in for well-baby checks and, you know, they're gonna have much more frequent contact with their pediatrician and that that's the reason that this schedule is being imposed on us as opposed to any really biologically necessary. Again, I use the example of Hep B, which, you know, most kids are really not at risk of Hep

4. 24:00 – 31:55

   The Hib vaccine: An example of the profound difference a vaccine can make;

   1. PAPeter Attia24:00

      B, right? Unless they're, you know-

   2. PHDr. Peter Hotez24:01

      Well, well, let me, let me, let me give you a different H disease as an example. So Haemophilus influenzae type b, um, it's a bacterial cause of, uh, meningitis. Back in the Pleistocene era when I was a house officer, I was a pediatric house officer at Mass General, uh, in '87, '88, um, I would be admitting a kid with Haemophilus influenzae type b meningitis to my service every couple of weeks, and Mass General was one of the oldest pediatric residencies. They called it the Children's Service. And back then, you know, the house officer did everything. You had to do the lumbar puncture, you had to look at the cerebral spinal fluid under the microscope, you had to do the Gram stain and eventually send to the lab, but to confirm it, but you would basically make the diagnosis right then and there. And when you did it, your heart sank because you knew that there was a high likelihood that kid was gonna have permanent neurologic injury or might not even survive. And it took a big emotional toll on me and, and my fellow house staff, uh, to have these young, you know, healthy infants now get Haemophilus influenzae type b, uh, meningitis. And at that time, we didn't have a vaccine that worked in infants. There was the, the capsule of the Haemophilus influenzae type b, the polyribose phosphate capsule, but it was shown that it wasn't immunogenic in infants. So it was still licensed as a vaccine for older kids to catch the few older kids that could still make an immune response, but it didn't work in infants.

   3. PAPeter Attia25:28

      Why is that, by the way?

   4. PHDr. Peter Hotez25:29

      Because you needed, it turns out, you need to haptinize it onto protein, and that's what John Robinson and Rachel Schneerson did at the National Institute of, of Child Health and Development, NIH. They figured that out and developed a conjugate vaccine that now worked in infants, which now you could start, uh, vaccinating. But until, at that time, you didn't have anything that worked in young infants. So all you could do at that time was to take a prophylactic antibiotic called rifampicin, which had the, um, unpleasant effect of turning your urine orange and, uh, reddish orange. And, and at that time, I had my f- our first son born, Matthew, and we were living, uh, uh, right a- right across the street from Mass General, and I was terri- terrified that I was gonna bring Haemophilus influenzae type b home. So I took rifampicin all the time, and I peed orange for two years practically, to the point where, uh, one of the first and only fights I've ever had with Anne was, my wife, was, um, permanent-- she accused me of permanently staining the toilet bowl orange because I was taking that, uh, antimicrobial. And then this miracle occurred. The miracle was, you know, John Robinson, Rachel Schneerson, also, uh, David Smith and Porter Anderson at, at, in Rochester, um, figured out that if they attach that polyribose phosphate capsule to protein and haptinize it, now you get T-cell responses in infants and it works. And that happened, that vaccine was licensed in 1989 as I was finishing my house officer tr- training by th- for infants, for young infants, and now it's part of that early vaccination schedule. By the time I, um, uh, finished my... And then I went to Yale for my pediatric infectious disease fellowship. I had a lab there, and then I was a junior attending at Yale Children's Hospital. By the time I started rounding as an attending two years later, um, the disease had gone, was gone. It basically, I taught the house staff about it purely for historical interest, just like, uh, you know, the old guys at, at Mass General taught me about diphtheria and, and, and tetanus. That's how dramatic it was, because we added it to the infant schedule. And I think that's, that's a good example of, you know, these infant vaccines. We, you know, we, you know, to, to get a vaccine through to be licensed by the FDA, you know, to file that biologics license application, first of all, it's very expensive. Second, it's a hi- lots of review. It has to go through the biologic license process of the FDA. It's got to go through the VRBPAC committee of the FDA for review. It then goes to the Centers for Disease Control and the ACIP, the Advisory Committee on Immunization Practices. There's a lot of smart people that are looking at all of this to say, "Do we really need this? What's the cost effectiveness? What's the benefit to society? What's the benefit to child health?" So it's, these are not decisions that are made lightly or, or, you know, th- these are, these are things which are carefully thought out.

   5. PAPeter Attia28:36

      Uh, uh, so you don't think that there's, um, uh, some consideration given to this is a window in which the probability of vaccination is, is greater just due to exposure? Again, I bring up hep B just because, you know, you and I didn't get our hep B vaccines until we were adults, right? And of course, I don't know when you got yours, but for me, I think I got it in medical school. It was just on, just in time, given our exposure to hep B is enormous once you're in me- in the medical system because it's, you know, it's transmitted just like HIV.

   6. PHDr. Peter Hotez29:07

      Right. Right.

   7. PAPeter Attia29:08

      Um, and, and depending on where you trained, you might be in a population.

   8. PHDr. Peter Hotez29:13

      I think I first got mine when I was-- We, we were keeping a lab in Shanghai in China, uh, for parasitic diseases, and I think going off to China frequently, there's a lot of hepatitis B. I think-

   9. PAPeter Attia29:24

      Mm-hmm

   10. PHDr. Peter Hotez29:24

       ... that may have been when I got mine. But, uh, but you're right. Back then, you know, we weren't giving it to infants and-

   11. PAPeter Attia29:30

       And, and so I guess my question is, and again, I'm just saying this to try to take the side of the parent, right? I'm trying to put myself in the shoes of the parent who says, "This is too much." And, and again, to be clear, this is not the parent who says, "Vaccines are evil. My kid will never get vaccinated." This is the parent who's saying-

   12. PHDr. Peter Hotez29:47

       Right

   13. PAPeter Attia29:47

       ... "Is this a little too much too soon? Um, does a child really need a hep B vaccine as an infant? What is the probability that a child will be exposed to hepatitis B?" The only example I can think of is a child whose parent is in the healthcare system or frankly in the, you know, is an IV drug user who's, who's, who is themself a high risk for hep B and who is not vaccinated. But outside of that, uh, you, you could certainly make the case that a person does not need a hep B vaccine until they're, you know, an adolescent or at least a, you know, a youngster in school, correct?

   14. PHDr. Peter Hotez30:21

       Right. But let, let's take a step back. Let's look at that example of the Haemophilus influenzae type b. No doubt, no question in your mind that that, that's what we needed to do for-

   15. PAPeter Attia30:30

       Absolutely. Especially given the risk is highest to that patient. I mean, that's a, that's, that's an amazing example of that, right?

   16. PHDr. Peter Hotez30:39

       Right, and that's why I bring this. So, so the vast majority of vaccines are not given for trivial reasons, or no vaccine is given for a trivial reason.

   17. PAPeter Attia30:48

       No, no, and Hep B would not be trivial.

   18. PHDr. Peter Hotez30:50

       The, the need is, the need is more apparent for some than the others.

   19. PAPeter Attia30:53

       Yeah.

   20. PHDr. Peter Hotez30:53

       The exact reason why, uh, hepatitis B was selected for young infants, uh, you know, I wasn't, I wasn't at the table when that decision was made. It may be that there was enough at-risk populations that it's very hard to cherry-pick individuals when there's so many people who absolutely need it, that, that it just becomes easier to, um, vaccinate the whole population rather than say, "Okay, well, you're in a specific at-risk eth- ethnic group-"

   21. PAPeter Attia31:22

       Yeah

   22. PHDr. Peter Hotez31:22

       ... "or you're in a specific at-risk occupational hazard." On the other hand, when you look at what that vaccine is, it, you know, it's, it's a, uh, about as, uh, low risk a vaccine as you can imagine. It's a recombinant, and we, we make vaccines like this all the time. It's a recombinant protein vaccine produced in yeast. Um, it's been around almost four decades. It's been given to hundreds of millions of children with a really fabulous safety record. So, you know, is, are you-- What are you losing, I guess-

   23. PAPeter Attia31:54

       Yeah

   24. PHDr. Peter Hotez31:54

       ... is

5. 31:55 – 41:55

   The controversy surrounding the human papillomavirus (HPV) vaccine;

   1. PHDr. Peter Hotez31:55

      the, is, is the other way to put it, right?

   2. PAPeter Attia31:58

      Let's talk a little bit about HPV. This is-- Some people hailed this vaccine as a miracle, um, given the relationship between the human papillomavirus, uh, at least three strains of the human papillomavirus, and cervical cancer. Uh, this is not an insignificant cancer for women. Uh, s- sadly, many of us know women who have either died as a result of this disease or have been, uh, uh, who have lost their reproductive capacity as a result of this disease, so. Uh, and, and, and furthermore, I think many men might even know the anxiety that a, uh, that a Pap smear has caused their partner if, uh, it has shown one of the high-risk strains, you know, 16, 18, a number of these things. So-

   3. PHDr. Peter Hotez32:40

      Mm-hmm. Right

   4. PAPeter Attia32:41

      ... I, I, I, I think for many of us, when the HP vaccine came along, it was a really big deal. I mean, this was, this was fantastic news. Um, can you talk through some of the controversy surrounding it, both from a scientific standpoint, but also from a, a moral, ethical, religious, political standpoint? 'Cause I think that, th- to me, HPV might be one of the best examples of the intersection of all of those forces.

   5. PHDr. Peter Hotez33:07

      Yeah. So it, it came, you know, it was, it was about preventing this... So HPV-induced cancers like cervical cancer, laryngeal cancers, uh, are predominantly sexually transmitted cancers. They're-- So if you look at infectious causes of cancer, roughly about 16% of all cancers are caused by infectious disease agents like hepatitis B, like, like HPV, and the numbers go up all the time because we get better and better at discovering infectious agents that cause, uh, cancer. So in Africa, about a third of the cancers are of infectious origin. And, and this was, uh, developed by, uh, a group at the National Cancer Institute, including someone who's very dear to me, Do- Doug Lowy, um, and, and, uh, they were able to show that vaccinating against this, uh, virus would, can prevent infection of the virus and therefore will likely prevent cancer. And now new studies have shown indeed it, it's borne out that indeed it does prevent cervical cancer. And on that basis, the Australian government has now launched a program where they think they can eliminate cervical cancer from the continent of Australia by 2030. So that's really exciting to actually eliminate a, a cancer through, through the vaccination process. The issue has come up, you have to, uh, vaccine-- Originally, it was mainly focused on cervical cancers rather than the cancers in, that would develop in males. And so the recommendation was you want to th- have those girls vaccinated before their sexual debut, before they start having intercourse, uh, as they get to be teenagers or young adults. And so you wanna get them when they're nine or 10-year-old little girls in time to make certain that everybody gets, uh, gets vaccinated. And I think that, um, that did not go over well with a lot of people because they now realized, you know, their, their nice little nine, 10-year-old girl is one day gonna be a woman who is sexually active, and I think that was, that was hard for some people. Um, but in fact, it has a remarkable ability of saving lives and, and preventing cervical cancer, and that's why Australia's been implementing that. In the US, in contrast, what's happened is we've allowed, um, we have, we have-- Well, we have a couple of problems. First of all, we're a big country. The, the access to the vaccine is not everything we'd like in rural areas. It's not, uh, everything we'd like, especially among underrepresented minorities and, and, and, um, so there's a, there's an access issue. But the other big thing is this has been targeted now by the anti-vaccine lobby, and they have tried to come up with fake assertion after fake assertion that's not supported by the scientific data. So they claimed it was causing autoimmunity. They claimed it's causing mis-- They linked a lot of it to female reproductive health issues. They said it was causing infertility, it was causing miscarriage. And again, one by one, the scientific community had to do those big cohort studies to refute all of those links.

   6. PAPeter Attia36:34

      I guess this is as good a time as any, Peter, to ask the first of several meta questions, which is Why?

   7. PHDr. Peter Hotez36:41

      Wait, you didn't give me feedback, so was that convincing or [chuckles] or, or were you still unimpressed? I mean, I mean, what do you think the issue is?

   8. PAPeter Attia36:48

      No, I, I, I, I think that's a great point, and I say that as a father of a 12-year-old, right? A 12-year-old girl, which, again, I, I, I'm-- I was just sort of joking with my mom this morning. I, I, uh... You know how your iPhone will give you, it'll give you like a flashback picture or video from some time in the past and-

   9. PHDr. Peter Hotez37:10

      Oh, yeah, right.

   10. PAPeter Attia37:11

       So this, this morning it sent me a video of my daughter, uh, when she was-- well, she would've been seven and her brother, her young- her-- the next guy would've been one. So seven-year-old and one-year-old, and they're at the beach playing. And it's like the cutest thing on the face of the earth, and I probably watched the video like seven times. And then I sent it to my mom and I said, "Oh, remember when she was this little?" You know, my mom made some comment like, "Yeah, enjoy it now 'cause, you know, five, six years, [chuckles] she's gonna be in college," and blah, blah, blah. And, um, so I get that. Like, there is nothing to me that is both simultaneously amazing and sad as the, the, the, the natural, uh, loss of a game of tug-of-war that goes on between a parent and a child, right? As, as my friend-

   11. PHDr. Peter Hotez37:59

       Right. Right

   12. PAPeter Attia37:59

       ... Rick Elias described it. You're, you're playing tug-of-war and you have to lose by the time the kid's about 18. It's slow, but you gotta, you know. So, so I can see that. Like I, I, I have-- I, again, I'm trying to put myself in the shoes of the person who thinks this doesn't make sense, and I think there's an argument that they would make that would say, "Well, I don't want my child, I don't want my daughter..." Let's just, again, I, I think this, this is an important issue that we should explain why both male and female, it's relevant to both. But if we're just taking it through the lens that I think it first came through, which is, "My daughter is 12. I do not want her to be sexually active until she is..." and I come up with some arbitrary age like 18, "therefore, I am not going to have her vaccinated until she's 18." Another point of view is, "In an ideal world, I would prefer she's not sexually active until she's mature enough to handle that. I don't know when that is, but it sure as hell isn't 12, therefore, I don't want her to g- I don't want her to have this vaccine at 12." But the downside of n- of not vaccinating her in time is she could be cursed with a lifetime of, of, of asymmetry, right? There's an asymmetric bet here, and it's, it's, it's... I, I just, I, I can understand why some parents might struggle with that, even though I tend to think in terms of risk and probabilities maybe more than the average person.

   13. PHDr. Peter Hotez39:18

       Right. Right. I t- I totally agree with everything you've said. I think the problem now is that you've got these anti-vaccine groups specifically targeting, uh, HPV, including, I think now you've got children's, I forget which it is, whether it's Kennedy or this organization is now f- I, I saw it on his Twitter that he's filing some big class action suit against Merck and company, um, for the HPV vaccine.

   14. PAPeter Attia39:46

       What's the claim?

   15. PHDr. Peter Hotez39:48

       Uh, I don't remember. But you know, again, this is, this is what- what's going on right now. And, um, with-- and I'm not aware of any evidence to support all of these things like infertility or miscarriages or autoimmunity. What's really interesting also is the anti-vaccine groups have now copy-pasted those assertions onto the COVID-19 vaccine. So they could be pretty lazy. So they're just basically saying the same thing they, they would-- 'cause I guess it works for them that in, in that pyrrhic way. So, um, but, but as a result of that, our-- and like I said, it's not the only thing 'cause we have access in rural and, and underrepresented minority groups, but you know, we're going the wrong way with HPV vaccine. We're not even close to thinking about creating a cervical cancer elimination strategy.

   16. PAPeter Attia40:40

       Um, y- you mentioned laryngeal cancer as well. Um, I don't think e- enough people understand the threat of that. Uh, frankly, uh, all upper, um, um, airway cancer, right? I mean, you're, you're talking about cancers of the soft palate. You're talking about-

   17. PHDr. Peter Hotez40:57

       Yeah. Yeah

   18. PAPeter Attia40:57

       ... lots of head and neck cancers are on the rise. I can't remember exactly the stat, but I, I wanna say like the second or third largest growing cancer in young men is head and neck cancer, um, uh, on account of sexually transmitted disease.

   19. PHDr. Peter Hotez41:14

       Yeah. And if you talk to, you know, the head and neck surgeons, we're, we're right next to MD Anderson Cancer Center and th- within this Texas Medical Center, it's devastating, the, the very aggressive surgeries that you have to do. It's really heartbreaking. By the way, we never finished the one thing about the autism, which was you made the statement autism's on the rise. I think it's important to clarify that. I think we're clearly getting better at diagnosing autism. I'm not convinced that the incidence of autism is truly increasing. It's, it's-

   20. PAPeter Attia41:48

       Yeah. W- and we're gonna-- we'll, we'll talk about it in detail. I, I've got... Yeah. There's, there's a lot-

   21. PHDr. Peter Hotez41:52

       Okay

   22. PAPeter Attia41:52

       ... I wanna come back to on autism. We're not, we're not abandoning that. Um, but

6. 41:55 – 1:09:10

   The growing anti-science sentiment, COVID vaccine hesitance, and the basis of the anti-vaxx movement;

   1. PAPeter Attia41:55

      thank you for clarifying that. Um, so, so yeah, coming back to this point I wanted to make, which is meta question number one: Why do, call it, 20% of the population and an entire cottage industry of, of lobbies, you know, lobbying groups, PACs, et cetera, come out so hard against this one class of drug, whereas we don't see it for antibiotics, right? Where is the, where are the 20% of people who think penicillin is evil and the companies that make Zofran or, you know, not Zofran, but, you know, pick your favorite antibiotic?

   2. PHDr. Peter Hotez42:35

      Yeah, yeah. Yeah. Yeah.

   3. PAPeter Attia42:36

      Or, or similarly, like, where are the companies that are coming out against insulin, exogenous insulin that, that all these diabetics are using? Because l- look, I'm gonna be a skeptic for a moment. I don't think there's a greater mismatch between drug companies doing wrong and profiting and spend- overcharging patients for a medication than insulin. Like, I, I think, I think the economics of insulin are an embarrassment to how pharma works. Where's the rage? Like, where are the 20% of Americans that aren't losing their mind over Novo- what Novo Nordisk is doing?

   4. PHDr. Peter Hotez43:12

      Mm-hmm. Yeah.

   5. PAPeter Attia43:13

      So, so what is it about vaccines in particular that brings out so much ire, so much skepticism, and so much anti-science rhetoric?

   6. PHDr. Peter Hotez43:24

      I think-- Well, I don't ha- know that I have all the answers, but I think part of it is the fact that you're giving vaccines to, not for all, not in all cases, but in most cases, you're giving vaccines to well individuals to prevent them from getting sick. So you're giving something that it, that's not always intuitively obvious that they need because, you know, f- as, as opposed to insulin, as opposed to penicillin, somebody is sick and somebody needs a treatment. So this is being so th- that you understand. But for a vaccine, you're preventing somebody from getting sick, and I think that simple feature is a big component of it. I think the other is the fact that so many vaccines are mandatory for school entry, so there is that kind of loss of choice that, that you feel it's being imposed on you. And so those two things become pretty easy to exploit. Uh, unless you've got really strong vaccine advocacy activities in your community, it's, it- it's pretty easy for an anti-vaccine group to cherry-pick those two things. And then, you know, we- when you have conditions like autism and people want to understand how did this happen, uh, particularly the regressive form where people, where kids seem to be developing normally and have normal milestones and then regress, this makes, this is easy pickings for, uh, an anti-vaccine group to come along.

   7. PAPeter Attia45:00

      So as an example, if-

   8. PHDr. Peter Hotez45:02

      So, so for instance, back in the 1900s in the UK, they started anti-compulsory vaccination leagues, and this extended to the US. So I think it's the, the man-- I think it's, it's a combination of the fact that they're preventative, not, not therapeutic, and the, the mandate component. I think those two are a toxic mix that get people, uh, some people upset about vaccines, particularly in this environment, which now dominates the internet. I mean, in the past, when you had an o- anti-compulsory vaccination league, you know, you could go to your physician, the physician would explain why that's all nonsense and why you should get vaccinated. Now we've got something called the internet, now we've got something called social media that dominates our lives, and you've got Amazon now as the single largest promoter of fake anti-vaccine COVID conspiracy books. So most of the information you're getting now on a daily basis is actually anti-vaccine, anti-science information.

   9. PAPeter Attia46:06

      But again, the, I still, I'm still trying to understand why the disdain for science is so prevalent. So, so hear me out on another thought experiment. If, if, if the president says, "I want to cre-" I'm using this 'cause it's the current example, right? If the president says, "Uh, uh," you know, "I have a legislative agenda that's going to propose a multi-trillion dollar infrastructure bill," you may not think that's the best idea, right? Well, y- y- y- you're going to oppose that through legislative action. You're going to oppose that through lobbying. Uh, maybe that's not a great example. Uh, I guess what I'm trying to get at is why n- if, if you're opposed to vaccines, I can at least understand the argument around medical freedom 'cause th- you could at least stand up and say, "Look, I'm opposed to being told I have to take a drug to prevent an illness I don't have." And then at, you could at least argue the merits of the individual versus society. Like, to me, that's a more palatable argument. Um, but the complete anti-science part, maybe because I'm a scientist, is just harder for me to empathize with. Like, it's harder for me to put myself in those footsteps because I can't think that way, and I, but I want to because I think it's important to be able to think that way and not be dismissive of it, if that makes sense.

   10. PHDr. Peter Hotez47:28

       Yeah. So, so here's what, here's what I think happened, which is I think, you know, maybe b- part 'cause of my activities and, uh, you know, I'm not alone, others were involved in this, there was a lot of effort to debunk the links between vaccines and autism and, and, and HPV vaccine and all the craziness that they asserted it caused. And, and I think it was taking some steam out of the anti-vaccine movement, and but you still had enough parents in places like Orange County that were scared about vaccines, the causing autism, that it allowed a measles epidemic to erupt. And, uh, and there was, and it was a pretty bad epidemic in Orange County f- twenty f- end of 2014, 2015. It was linked, I think the origins may have been Disneyland, um, w- where the epidemic came from. What happened was the California legislature responded, uh, appropriately, I think, and said, "You know what? We're allowing these vaccine exemptions, but it's getting out of hand, and now it's causing a measles epidemic." And measles is a bad actor, right? It's got a significant mortality and permanent disability, deafness, and, and other things, and they shut down the vaccine exemption. Uh, and, uh, and I think that helped re-energize the anti-vaccine movement, 'cause I think they were losing some steam around autism, and they saw this as an opportunity to rebuild, to reinvent themselves. And they reinvented themselves as a political movement around health freedom, medical freedom. And that's... And it really amplified in Texas, so it, uh, where, where I am. And it took off with, they created political action committees like Texans for Vaccine Choice. It started getting... And the PACs started getting other PAC money, and they, the PACs were giving PACs, the other PACs money. And so there was a lot of money flowing, and it, it was very powerful. And they were able to convince the Republican Tea Party in Texas, which is a very powerful group, to adopt this issue as a platform issue. And that's when it really started to accelerate. Um, and you started to see PACs form not only in Texas, but also in Oklahoma, other Western states as well. So it was more of a Western state phenomenon than, than anywhere else. And, and so your political allegiance, your identity actually became tied to not vaccinating your kid or to be skeptical of vaccines. And then it all really blew up last year because those same anti-vaccine groups then started, uh, going up against masks and social distancing, again, under this health freedom, medical freedom banner. And now it became a full-on anti-science movement. And you really saw this happen, uh, starting in around in, last summer when the epidemic moved into the Southern states, and people, uh, showed their political allegiance to the Republican Party by defying masks and social distancing. And then it went up in the upper Midwest as well. And then you had that story, that awful story of the ICU nurse in tears being interviewed, you know, talking about, uh, one of her ICU patients whose dying words were, "COVID-19 is a hoax." So you s- That's when you started to see this kind of mainstreaming of what was a fringe group around health freedom, medical freedom in 2015, had now become a major platform of the Republican Party, um, going up against science. And then you saw the targeting of scientists. That's when they began really going after Tony, uh, Dr. Fauci. They began going after Bill Gates. They be- started going after me, uh, quite a bit. And now we're on, now this thing is s- is steamrolling. I mean, you had Tucker Carlson last week going on this whole rant about vaccines and questioning vaccines, and Laura Ingraham at Fox News went after me a couple of nights ago and-

   11. PAPeter Attia51:41

       And specifically saying what? Y- I mean, you'll have to forgive me if I don't follow this stuff too closely.

   12. PHDr. Peter Hotez51:46

       Yeah, well, it's, it's pretty unpalatable stuff. I mean, they would say that, you know, we, we misled the public, that we got it wrong, that we didn't understand the epidemic, and then they would parade out all, all the Great Barrington stuff about, um, no lockdowns. Even though none of us ever said lockdowns, they, they create these straw men that say we're trying to lock everybody down and we're hurting our economy. And along with that, they're saying that what's going on with these vaccines? And, and so tying... And again, this is a throwback to 2015 when the, um, when it was first linked to political extremism on, on the far right. So what was started out as an anti-vaccine movement is now a movement against any kind of public health intervention and demonizing scientists and, you know, basically calling us the boogeyman and that. And, and, and it's continuing. Now you've got this, this was exported last summer to s- to Europe. You had these anti-mask, anti-vaccine protests, which for the first time used that same American language, um, in Berlin and Paris and Trafalgar Square in London. You had The New York Times reporting how it's linked to QAnon, um, and other far-right-wing extremist groups. And so this, this really concerns me. And then, of course, to make it all the more complicated is the fact that now you've got the US and British intelligence talking about Putin's government has been lobbying this whole program of what's being called weaponized health communication, uh, on our internet in order to destabilize the country and destabilize other democracies. And, and so what was kind of a fringe group arising out of the Tea Party in Texas is now, I don't know what you wanna call it, whether it's a anti-science empire or a confederacy that has lots of moving parts to it, but I, I'm concerned about the direction it continues to, and the fact that it continues to build.

   13. PAPeter Attia53:55

       Do you think this is just a sort of very vocal part of the Republican Party, or do you think this actually represents an entire political party? I mean, it's, it's, it seems hard to me that this could represent an entire political party, um, given, given the, given the, given the heterogeneity of beliefs that would exist across that from, you know, fiscal conservatives, social conservatives, I mean, all of these things, uh-

   14. PHDr. Peter Hotez54:20

       Yeah. And, and the fact that the Republican Party historically has not been anti-science, right? I mean, the National Academy of Sciences was started in the Lincoln administration. Uh, you know, Eisenhower launched NASA. George W. Bush launched PEPFAR. So, you know, this seems new to me. And, and I don't know how how much it's, uh, pervasive, uh, in the Republican Party. Certainly it's become now a major component of Fox News in the evening. And, and it, and as l- recently as last year, I was going on Fox News almost every day on a pretty regular basis, and, you know, I didn't... And I didn't see it until the disinformation campaign came out of the, out of the Trump White House. And when they said COVID wa- this around a year ago last year when they said COVID was a hoax or the flu and, you know, attributed the COVID deaths to other causes or you had Kayleigh McEnany say, you know, the uh, the hospital is, the hospitalizations were all elective catch up and elective surgeries and discrediting masks, and then later on in the summer, they brought out Scott Atlas. So there was no question about it, this very, um, uh, deliberate disinformation campaign coming out of the, uh, Trump White House. And I was one of the first to call it out, not because I'm so brilliant, but because I've been going up against these anti-vaccine guys for years and have become, un- unfor- by default, an expert in anti-science disinformation campaigns and could recognize it. But it's, I, I, I see it accelerating, and whether, you know, I can't say whether it's across the whole Republican Party, but it's a lot more pervasive now among Republicans than it's ever been. And, and then what's the evidence? Well, the evidence is now the, um, the PBS NewsHour and, uh, t- teamed up with NPR and Marist, and they've now, uh, found that if you look at the single most vaccine hesitant group in the United States, this was just last week, um, it's, it's what's called white Republicans. So it's around four- I think it was 41% of white Re- a significant percentage of white Republicans are saying they're not going to get vaccinated. And that's not the first poll. I mean, we did one with Te- a group at Texas A&M. I'm not a social scientist, but we teamed up with so- a group of social scientists at Texas A&M led by Tim Callahan and the School of Public Health found the same thing. I think we called them Trump voters. And, and Kaiser Family Foundation also found the same thing twice, that it's... So this is the number one vaccine.

   15. PAPeter Attia56:57

       [lip smack] Now I've seen another poll that suggested, and it didn't slice the data by race and party. It sliced it by race and party separately, and it found the greatest predictor was indeed Republican Party association, but the second was African American.

   16. PHDr. Peter Hotez57:14

       Right.

   17. PAPeter Attia57:14

       Uh, what's, what's the best explanation for that?

   18. PHDr. Peter Hotez57:17

       So that... And, and what's more now, it's coming down. So, uh, whereas it's still staying... So what's happened, that you're absolutely right. So about three, two, three months ago, African American groups and white Republicans were sort of neck and neck in who was the most vaccine hesitant. And, um, it's stayed up among Republicans, but it's been coming down among in the African American groups. And, and one of the things I've been going on, uh, lots of podcasts and radio shows that reach Black and brown audiences and, and I was on one last night, um, with a, with a, a Baptist church in, in Richmond, Virginia. And I asked the, the, the pastor, I said, "Are you seeing less of it now?" He goes, "Definitely. It's coming down." I said, "What do you think's happening?" Well, he goes, "Well, Doc, I think part of it is people like you, you know, reaching out to Black and brown communities, but the other is a lot of the clergy have created a sort of an informal network now and, and we're really hitting hard on the need to get vaccinated." So I think that, that may be part of it. But initially it was quite high, and I think part of... You know, what the reasons were I don't entirely understand. Um, you know, what's often said is it's around structural and historic racism and that horrible legacy of Tuskegee. I think the other thing that I've seen, though, is deliberate targeting of African American groups by the anti-vaccine lobby. And, and now I just saw on the internet there's a new, quote, "documentary" where I, you know, clicked on the, the trailer and it's got people getting the Pfizer BioNTech vaccine, then it switches right away to Tuskegee experimentation. So by it's kind of making that, that link, so I think it could do a lot of damage, so. But it seems to be somewhat resolving, but it's still really high among the, the, those group of Republicans. And you saw it, you know, when COVID-19 accelerated in the summer in, uh, uh, in the southern states and in the upper Midwest in the fall. And so how, so what's going on? And, and, and, and I'm, and I'm worried that now you've got, again, people tying their allegiance to the Republican Party or their, um, their identity to being against scientists and science, and this is not good for the country.

   19. PAPeter Attia59:36

       Yeah. There, there are a few things I wanna say and, and one thing to add. Um, the thing that we haven't mentioned yet that I think is worth mentioning is the enormous measles outbreak in Minnesota that occurred in the Somali community, um, that I think that story doesn't get enough attention because I guess it's now been enough years. But, uh, I've always found that to be an unbelievably sad story, in some ways more sad than the Orange County outbreak because this was, this was really a deliberate targeting of a community of immigrants, um, you know, not facile with the language and, um, and the measles outbreak was terrible there. And I guess that's the thing I've always struggled with. If you just put your common sense hat on, every time a community gets targeted to stop taking, in this case, the MMR vaccine, a measles outbreak shows up.

   20. PHDr. Peter Hotez1:00:26

       Yeah. And measles is sort of the, Paul Offit always calls it the canary in the coal mine, and it's, um... And I, and I think he's right. It's 'cause it's got such a high reproductive number of 12 to 18.

   21. PAPeter Attia1:00:38

       Yeah. It's crazy.

   22. PHDr. Peter Hotez1:00:38

       Um, all, all, you know, as soon as the vaccination coverage goes down, meas- measles finds it. Um- And that was really the in... That was the first time, I think, that you saw the anti-vaccine groups targeting specific ethnic, uh, groups. So, um, Lena Sun at The Washington Post back in 2017 reported that, um, Wakefield, who had kind of disappeared for a while, was at town hall meetings. I don't know if he organized them or if the Somali immigrant community organized them, but, you know, there he was piling on, and, um, and brought down vaccine coverage to over, from over 90%, The Washington Post reported, to, to 40%. Guess what's gonna happen? There was, and I think it was 21 kids that landed in the hospital. And then it happened again in 2018, 2019. They began targeting Orthodox Jewish groups, uh, in New York and New Jersey. And what they did was just so offensive. You know, they started parading around in these phony yellow Jewish stars, like the Holocaust, um, with the word "vaxx" written in it, and "vaxx" was written like Hebrew letters, and started comparing vaccines to the Holocaust. And that, uh, caused this massive measles epidemic across N- uh, both in, in Monsey, New York, by the Tappan Zee Bridge, and then in Brooklyn, and I think there were 18 people in the ICU because of that, 50 hospitalizations. So this has become the new modus opera. And then in 2019, you saw these series of Harlem vaccine forums, um, that they organized, and, um, even held one in the Riverside Church, which is on the Upper West Side in New York, near Columbia University. It's one of the iconic churches in the history of the civil rights movement, uh, the Reverend Sloane Coffin, and somehow got access there and held, held a rally there. So all of that has caused, uh, a lot of damage. Now this new documen- quote, "documentary," uh, that, that's coming out. So I'm very concerned. Um, so you've got these, as I say, these multiple facets. You've got the health freedom component expanding now across the Republican Party, now into Western Europe. You've got the Russians, uh, fueling this with their systematic weaponized health communication. And now you've got the specific targeting of, of racial or, and ethnic groups and causing a lot of damage. And, and the problem is it, it, it's takes time to explain, right? You can't... I can't give you a 30-second UNICEF commercial, uh, about this. You know, how long have we been talking? A full hour now. You kinda get it now, but it, you know, it's, it takes time to, to unfold and explain. And, um, and the problem is people... It makes people very uncomfortable. Um, it made me uncomfortable, right? I mean, I, you know, when I was going on CNN and MSNBC in, in last year at this time, I, I didn't wanna call out the White House for their disinformation campaign. I mean, you know, the me- You know, what we're told as scientists is, "Hey, Peter, just stick to the science. You know, you're not a political guy. You're not a, you're not an expert in, in, in White House Washington politics. Uh, w-what are you doing? You can't do that." And, but, uh, you know, I, I s- being ha- being an expert in anti-science disinformation campaigns by being targeted by these guys. I mean, Robert F. Kennedy Jr. calls me the, on his Instagram, called me the OG villain, the original gangster villain. So that's who you're talking to today. I had to look up what OG meant. Um, uh, so I, I, I unfortunately became a bit of an expert in anti-science disinformation campaigns and could smell one a mile away. And I saw this and I said, "I know what this is." You know, you saw Peter Navarro out there with all the Chinese conspiracies, and I said, "You know, th- we're being, we're being gaslighted here." And I, and I said to Anne, my wife, I said, "I don't know what to do. This is taking me to a very dark place. You know, I'm supposed to only talk about the science." And she saw how upset I was getting. She said, "Peter, you know, if you don't say anything and, and all, you find out all this massive lo-loss of life from COVID and didn't do all you can to stop it, you're gonna hate yourself." And that's all I needed to hear, and then I really went after it, and it was, it took me to a very dark place, and in part because you didn't, at that time, you weren't getting a lot of backing. I didn't get, um, a lot of backing from the academic and professional societies 'cause, you know, that's not what they do. And, and, um, and so I really felt out there alone. Later on, I think when it became safe, you know, other people, uh, came to my support, but in the beginning, it was a very lonely kind of thing to do. I mean, I'm glad I did it, but it took emotionally, it really knocked the crap out of me. It was very tough to, to, to do that. Because the truth is, I'm not that ideologically driven politically. I mean, I, you know, I was in Washington for 10 years, and as chair of microbiology at GW, and one thing I learned in Washington, if you wanna get anything done, you reach across the aisle. So, you know, we got a lot of neglected tropical disease legislation passed, and, you know, I would think nothing of going to Sam Brownback, who was, now he's the governor of Kansas. Back then, he was a se- very conservative senator from Kansas. He would hold a prayer breakfast meeting, and I'd go to that, and I would speak, and then I'd go across the way and talk to Senator Leahy's people, who's, you know, this very liberal senator from Vermont. And back then, nobody thought twice about those kinds of things. But it's not happening anymore. So, um, so to be able to have to, you know, tear into what was going on with the Trump White House and, and it was often perceived as I was just being, uh, somebody in, in, in the Democratic camp, which wasn't the case, but, you know, I understand why it was perceived that way. And, and now what's interesting is I, um, you know, whenever I have something with the Biden administration I think is not quite right, um, then I get then I get beat up a lot from my colleagues on the left, and there's a lot more of those who say, you know, "What are you doing after all we've been through? How can you criticize the, the Biden White House?" I'm not really criticizing. I think they're doing a good job, but there are things that need to be changed as well. So it's very tough to... It's very tough not-- It's very tough to... If your focus is only on saving lives and doing whatever you can to save lives, that, that's very tough because it means if you're sincere about that, you go on Newsmax and you go on Fox News, which I've been doing, or, and you go on, uh, radio podcasts and, that reach Black and brown audiences. That's what I've been doing. So, and hopefully at the end of it all I'll, I'll be okay, but it's, it's not easy doing this.

   23. PAPeter Attia1:07:40

       Peter, is there a, um, historical precedent for, um, such a distrust of science? I mean, that, you know, given that the scientific method has only been around for, call it 400 years, that doesn't give us a great opportunity to look for such things. But even in the last century or two, have we ever seen such massive distrust for the establishment of science?

   24. PHDr. Peter Hotez1:08:06

       I haven't seen this distrust systematically. Certainly, there's been, um, a lot of pushback or anger around certain things scientists have said. Like for instance, with, um, w- during colonial times when, uh, when Cotton Mather, uh, tried to vaccinate the, the Massachusetts colony against smallpox, uh, people were very aggressive with him, and they actually threw a firebomb into his window, uh, around that particular, uh, issue. So yeah, that's, that's gone up and down in, in American history. But I've just not seen this systematic distrust of science and scientists and the targeting of scientists and, and the mainstreaming of, of anti-science. That, that's kind of worrisome. And then of course, a lot of this is because now we have this new era of the internet and, and social media and, and, and Amazon and all those kinds of things doing a lot of damage.

7. 1:09:10 – 1:22:38

   The origins of autism, and Hotez’s personal story as a parent of an autistic child;

   1. PAPeter Attia1:09:11

      So I kind of want to pivot a little bit to something very personal for you. Um, how, how old is Rachel now?

   2. PHDr. Peter Hotez1:09:17

      Now she's 28.

   3. PAPeter Attia1:09:19

      28. So, so let's go back in time 28 years. Tell me what you remember about her birth and the, the first few years of her life.

   4. PHDr. Peter Hotez1:09:28

      So when she was-- So by the time Rachel was born, I had already had two other kids. And I remember Anne saying, always feeling that something was off, that, you know, she wasn't as huggy or clingy as the other kids were, but didn't really come to medical attention till around 19 months of age. Um, that's when the pediatrician clearly saw developmental delays and, um, referred us to special services. And ultimately, I was at Yale, which is, uh, I was an assistant professor then running a lab. And that was hard for me 'cause I was going off to China and keeping a lab in China and, and now having a child with, with a medical issue was, was really, uh, was really tough. Ultimately had to give up going to China and, and re- reconfigure our, our program. But at, at Yale, there's-- that's also the home of the Yale Child Study Center, which is, you know, the, one of the big thought leader places for autism. And she came, she was referred eventually to the Yale Child Study Center, where the world's experts on autism, people like Fred Volkmar and, uh, Donald Cohen and, uh, Linda Mayes and, and we got, um, there was a child psychiatry fellow, Wendy Levine, who, you know, really looked into this very carefully, and she was clear that she was, she was on the autism spectrum. And, and it's a little tougher to diagnose for girls than boys 'cause girls tend to be more verbal. Um, so, you know, often time boys-

   5. PAPeter Attia1:11:00

      Was she verbal at 19 months? Was she appropriately verbal?

   6. PHDr. Peter Hotez1:11:04

      Well, she wasn't always appropriate, but she was always verbal. I mean, she would repeat. There was a lot of echolalia. She would repeat things. But, um, she, you know, she had reason-- And to this day, she's got reasonably normal language skills. It's just her performance IQ is really, really low. And, and so that's, and that's one of the big issues with Rachel. It's the, um, it's the, uh, intellectual disabilities that go with aut- in her case, that go with autism. And in fact, that's a very interesting side story a- about Rachel is the whole sys- ecosystem of girls and women on the autism spectrum because, you know, the older literature says it was 10 to one boys to girls, and that's because boys are so flawed in their, their presentation and symptoms. Girls can camouflage it better. They can mask it better. They are often verbal. Um, but they have very high rates of comorbidities like obsessive-compulsive disorder or ADHD, attention deficit hyperactivity disorder, or, um, even, uh, a lot of the teenage girls with bulimia and eating disorders now, many of them may be on the autism spectrum. So we're getting better at it. So it used to be 10 to one. Now I think it's moving closer to three to one boys to girls, and some say it may even approach parity or something close to parity, like 1.5. But, but it's, it's, it's way underdiagnosed. And, uh, Alison Singer heads the Autism Science Foundation, has been supporting efforts to really call great... 'Cause she has a daughter o- on the autism spectrum, to look at this in more detail because it is so underdiagnosed and... But in Rachel's case, it finally came to, to diagnosis at 19 months of age. And I got very interested in that because- When you look back then at the CDC definition of autism, um, it's, uh, I don't think it's on the website anymore, but I guess of a couple of years ago it was still there. It said most kids on the autism spectrum are diagnosed between 18 or 24 months of age. And, and I got very interested in that because there was a, a research group at the University of North Carolina Chapel Hill run by this guy named, named Piven, P-I-V-E-N, who was able to show that that clinical expression of autism coincided with a big increase in brain volume expansion. So you could actually follow this on serial MRI, and, and that's important because a lot of parents will remember when their kid was diagnosed with autism, especially the regressive form, because that's so dr- not just a slowing of milestones, but actually loss of milestones. They'll remember that their kid got vaccinated, you know, maybe with measles or, or something else around that time and want to link the two. But now this group at UNC Chapel Hill can go back much earlier, you know, back to infancy, and show that there's already those changes happening, uh, in the brain. And now, of course, we can show prenatally. So Eric Courchesne's group at UCSD, um, and multiple groups now, the Broad Institute at Harvard and MIT, has identified about 100 genes linked to autism spectrum disorder, all involved in early fetal brain development. Uh, many of them involved in neuronal communication, so a lot of neuronal cytoskeleton genes, for instance. So we did whole exome sequencing on Rachel, and Anne and I at, um, at the, at Baylor Genetics, and identified a neuronal cytoskeleton gene, a non-red cell spectrin, a neuronal spectrin, which, you know, makes a lot more sense in terms of understanding neuronal communications and, and that sort of thing. So I think what happens is you see the activation of genes in early fetal braid, brain development, and that sets into motion a progression, but that full clinical expression of it doesn't happen till around 18, 19 months of age often. And that's not unusual for neuropsychiatric conditions. Uh, right? I mean, look at schizophrenia, for instance, which, um, oftentimes, you know, kids with schizophrenia are not diagnosed to adolescence or even young adults. And, um, so this is how the brain works, I think. I'm not a neuroscientist, but that's, that's my take on this.

   7. PAPeter Attia1:15:30

      Um, what-- I mean, just on a personal level, how, how did you cope with this realization, um, and did it ever cause you to question anything that you were doing? Um, or was it very clear-- Like, were you able to sort of distance it or think about it through kind of a, a scientific lens, even though it was something very personal and, and it, you know, it became, it went from being, you know, "This is the scientific literature in its entirety," to, "This is my daughter."

   8. PHDr. Peter Hotez1:16:01

      Yeah. Well, back in the '90s, we knew a lot less about autism than we know now, um, and all the things that I told you about, a lot of it has only come to light in the last few years. And then the Wakefield paper came out, and I remember that because I think Rachel was about five years old at the time, and, um, you know, and, and it was all over the papers. And of course, Anne was asking me about it. And to me, it never made sense. I said, "How can it be that..." I mean, I mean, they called it pervasive developmental disorder back then for a reason, because it was indeed pervasive. And, and you could see that sh- you know, that a lot of these kids were macrocephalic. They had enlarged heads. Um, and, uh, um, and so this was clearly a neuroanatomical condition. I mean, you knew that there were shifts in Purkinje fibers and, and, and, and there were structural alterations in the brain of kids with autism. How can it be that a vaccine you give at one year of age would, would cause that? It just never made any sense to me. There was never an-- So for me, there was never the plausibility, but the full weight of scientific evidence wasn't there. I mean, that was my opinion more than any... And it turns out more or less to be true. And, um, and, but so that's why I was one of the early adopters of saying, "There's no way in hell it's gonna be MMR vaccine," and, and it just doesn't make any sense.

   9. PAPeter Attia1:17:39

      This is gonna sound like a strange question, but was there a part of you that almost wished it was so that you might be able to say, "This would be amazing if we knew this"? 'Cause again, at the time Wakefield proposed this, he wasn't even saying that all vaccination was bad. He was simply saying they should be separate vaccines. "Don't put measles, mumps, rubella in one shot. Give them separately." This was his first thesis. And so even wearing your hat as an infectious disease physician, if, if, if you could have believed that the answer was MMR combined causes autism, and while it won't save my daughter, to know that I could spare every other parent, 'cause clearly, you know, you, you, you, e- you exude the ethos of wanting to help everyone. Um, all we have to do is separate these vaccines, and we could solve it. I mean, was there, was there a part of you that just wanted this to be true?

   10. PHDr. Peter Hotez1:18:34

       Not necessarily. I mean, I, I, I-- You know, if, if it made sense to me and, and, um, uh, if, if there was a logical explanation, and yeah, if we knew there was a simple intervention, sure. But it was just so outrageous at the time that it j- that wasn't even on my, on, on my radar screen at that time to think in that way. I just knew that it had to be genetic or maybe an epigenetic basis. And, and by the way, that's a real treat trying to explain epigenetics to, uh, lay audiences. Uh, start talking about microRNAs and histone, uh, deacetylation, uh, that one I'm still working on. But, you know, th- so the epigenetic component is, is an- another one that's important. But again, all of that had to be prenatal. Um, and, and I remember having some conversations with, um, some of the anti-vaccine people, um, and then saying it had to be prenatal, and then they said-- And I said, "And we, yes, we do give some prenatal vaccines like, um, flu vaccine." And then they s- the immediate response was, "Aha." And I said, "No. I mean, you know, again, I don't see how, uh, an immunization during pregnancy could be linked to that." And now the scientific data supports, shows there's no link.

   11. PAPeter Attia1:20:00

       So, so let's, let's talk a little bit about the, uh, autism is still such a complicated thing in terms of people even understanding what it means. So the definition has, uh, uh, has morphed a little bit. So today, we talk about ASD being a spectrum, um-

   12. PHDr. Peter Hotez1:20:14

       Right. And, and it's gotten very complicated because, you know, there's this whole concept out there of neurodiversity. And so there are many in, in the autism community who bristle if you even try to describe it as a pathologic condition. They say, "No, this is just an example of neurodiversity. People are, are different." And, and, and I understand that. And so the-- what I try to emphasize with Rachel, it's, it's the au- not the autism per se that's incapacitating. It's, it's, it's the, in her case, you know, she's got clear and profound intellectual disability. Um, she can barely read. She can't count num- she can't do simple math. She can't... You know, when she goes to the store to buy something, she will hand them a fistful of single dollar bills and say, "Here," because she doesn't know how to count the money. She, no matter how hard we've tried to train her to do that, she doesn't understand the value of things. And so she depends on the goodness of the, you know, merchants in our local Montrose neighborhood have been great, you know, and they kind of know Rachel. Um, um, so it's, in her case, it's the intellect- profound intellectual disabilities that make it tough and make us worry because, you know, the other piece to this is now she's an adult with autism and intellectual disabilities, and the special services and all that kind of stuff really falls off the radar screen because we have no plan for her right now. We don't know, um... You know, we've tried to, uh, have her in a residential facility, which, you know, I think did an okay job, but she was just too-- her be- her behavior was too uncooperative, and finally they had to kinda kick her out. And so now she's with us, and what worries me is I don't know what's gonna happen after, you know, Anne and I are no, are no longer here. Um, we don't-- There's no roadmap for what you do with an adult with dis- with intellectual disabilities, and that, that really worries me, especially in Texas. It's just not strong with s-services of those kind, and maybe it's better up in the Northeast, and, you know, we've heard New York and Massachusetts, but trying to work that is a huge, huge,

8. 1:22:38 – 1:41:30

   The challenge of diagnosing autism, increasing prevalence, and a potential parallel to Alzheimer’s disease;

   1. PHDr. Peter Hotez1:22:38

      heavy burden on us.

   2. PAPeter Attia1:22:40

      How is the diagnosis made today? So if a, if a parent today or a pediatrician today suspects that something is not normal, you know, whether it be language delay, uh, you know, changes in behavior, emotional regulation, eye contact, all, all the things that would, you know, flag someone, what is the actual process by which a diagnosis is made? And w- how, d- does-- Is this something that shows up in the DSM? I mean, how-- What is the, what is the criteria for diagnosis?

   3. PHDr. Peter Hotez1:23:08

      Yes. It, it, it's still in the DSM. The DSM is still not as strong as it could be, especially for girls, especially for little girls. But, um, presu- presumably, it, it, you get, the child gets referred to something called Birth to Three, which is an early intervention, uh, program. And at some point, they get medical attention, typically to a behavioral pediatrician, maybe a child psychiatrist, only there are only about six of them left on the planet. Um, there's a huge need for more child psychiatrists. Um, I, I tell all my medical students to go into child psychiatry with the hope that one of them goes, goes into it. There's a, it's a, it, that's a real crisis as well. Um, but, uh, and, and then the diagnosis is made along s- along the way of, uh, limited social interactions, in some cases, uh, lack of speech, although again, with girls and women, it's different. So there are a list of criteria that you can look at.

   4. PAPeter Attia1:24:09

      What's on the differential diagnosis? Like, what are, what are they trying to-- Is it a diagnosis of exclusion, where they're just basically saying, "Here are a bunch of things that could present with this pattern, and we're gonna rule them all out, and that which remains is ASD?" Or, or, you know. 'Cause when you think about so many of these things-

   5. PHDr. Peter Hotez1:24:27

      Well, well first-

   6. PAPeter Attia1:24:27

      ... like, it's not like Down syndrome, where there's such a clear-

   7. PHDr. Peter Hotez1:24:30

      Right

   8. PAPeter Attia1:24:30

      ... uh, phenotype and genotype, right? Like, it's unmistakable. Uh, this is much more nuanced.

   9. PHDr. Peter Hotez1:24:37

      Well, I think in, in out years, in future years, you know, we'll make whole exome sequencing so much more available that I think any time you have a child like that, you'll get whole exome sequencing, and we'll actually be able to potentially target it to a specific gene. In some cases, that may be useful because there's could be pharmacological intervention in case there's something that, um Uh, is impairing, um, abilities and, and can be, can be targeted. Um-

   10. PAPeter Attia1:25:09

       Can you explain why that's important, why whole exome sequencing is relevant versus just, quote-unquote, "a genetic sequence"?

   11. PHDr. Peter Hotez1:25:15

       Well, because with whole exome sequencing, you're getting the gene of every-- You're getting the full sequence of every expressed gene, and what that does for you is, um, identifies rare mutations, uh, that you wouldn't pick up just by looking at, at chromosomes. And so it's a very powerful technology. At this point, it only picks up around 40% of-- So if you're-- have autism and you do whole exome sequencing, my understanding is you'll only see a mutation maybe 30, 40% of the time, 'cause there's other things going on, including the non-expressed genes. So exome sequencing just looks at the expressed genes, but if you do the whole genome, potentially you could pick up, um, uh, addit-additional ones as well. So we're still in the early stages of that, and what's very interesting in that was some children's hospitals are looking at the possibility of doing whole exome sequencing on every child they admit for whatever cause, because we're learning so much about, um, the genetics and epigenetics not only of autism but, but so many other conditions. Right now, you're left with what I consider to be a somewhat rudimentary list of criteria from the DSM, and I'll, I'll never forget, Peter, I once had a, a lecture from a, from a child psychiatrist in-- when I was in medical school at, at Cornell, and, and I remember him saying, "You know, we're gonna look upon the DSM as such a, uh, anachronistic or out-of-touch document for child psychiatry. It just doesn't cut-- It just really falls down for child psychiatric disorders." And that was, you know, in the 1980s. You know, maybe it's moved on since then. I'd be curious to hear from a child psychiatrist today what they think about the DSM, but that-- I'll never forget that, that comment. And, and when you look at the DSM criteria, they're just not really robust for so many, uh, childhood conditions. And again, this whole concept of neurodiversity is not reflected in the DSM like, like it needs to be. It'll get refined, and I think that combining with whole exome sequencing and that combining with all the developments in neuropsychiatric medications, I think th-this-- things will look very different 10 years from now and then 10 years again from, uh, from then.

   12. PAPeter Attia1:27:43

       Do you have a sense, ballpark, how many children that are born today-- What, what will be the incidence of autism in the cohort of kids born in 2021?

   13. PHDr. Peter Hotez1:27:55

       Well, I think one is, you know, the, the number that's thrown out there now, what is it, one in 62? I, I can't remember the latest-

   14. PAPeter Attia1:28:03

       It's surprising

   15. PHDr. Peter Hotez1:28:04

       ... number.

   16. PAPeter Attia1:28:04

       Yeah, I mean, it's, it's-- seems remarkably high.

   17. PHDr. Peter Hotez1:28:07

       Well, remember, it's-- could come close to doubling 'cause we're not-- we're way undercounting all the girls-

   18. PAPeter Attia1:28:12

       Yep

   19. PHDr. Peter Hotez1:28:12

       ... w-with girls and women with autism. So it wouldn't surprise me that it would go down to something like one in 30 or-

   20. PAPeter Attia1:28:18

       Now, what do we think that was in 1980, for example?

   21. PHDr. Peter Hotez1:28:22

       Yeah, I don't even know, but v-very rare because, you know, the criteria changed. You know, before there was a very, um, strict criteria about non-verbal boys with certain repetitive behaviors, and then we've enlarged it so much. And then it's gonna get very murky, right? Because we're gonna go, you know, now with this whole picture of neurodiversity, at what point is it a, um, condition that warrants criteria under D-- under the DSM, and what is it just being neurodiverse? Um, and, and, and I don't know that there's gonna be a cutoff, right? It's always gonna be that, that gray zone. So I talk to my, my, my oldest daughter a lot, who's an assistant professor at UCLA. She has a PH-- Emily, she's got a PhD in developmental, uh, psychology and works at the Center for Disabilities, and this is, this is a real struggle and a, and a, and, and difficult to get your arms around, but I think we still need a lot of brilliance around the, around these points. At what point is it something that you diagnose in the DSM, and at what point is it not? And I, and I, and I don't have the answers to that right now.

   22. PAPeter Attia1:29:34

       When you consider something like Alzheimer's disease and you look at the change in prevalence, um, uh, over the last 50 years, it's-- You know, there are many factors involved, right? People are living longer. The diagnosis is, uh, much more-- We have many more tools to make the diagnosis. Um, and then there are also factors that many of us, myself included, believe are actually increasing the incidence. So the prevalence is higher because people live longer, because we diagnose more, but because the true incidence is increasing.

   23. PHDr. Peter Hotez1:30:06

       And, and why do you think-- And by that, I'm just curious, why, why do you th- why do you think that is?

   24. PAPeter Attia1:30:11

       Uh, because I think many of the risk factors for Alzheimer's disease are increasing dramatically. So vascular disease, uh, medi- metabolic disease being the two among them.

   25. PHDr. Peter Hotez1:30:19

       Oh, okay. Obesity, yeah.

   26. PAPeter Attia1:30:21

       Yeah. As we see insulin resistance increase, as we see dyslipidemia increase and all of the things that accompany it, I think we're actually creating more, uh, neuropathology.

   27. PHDr. Peter Hotez1:30:33

       We're actually working with a group at, at Baylor, um, because, you know, we make vaccines. There's a, a group at, at Baylor, uh, College of Medicine run by David Corey, who also has a collaboration with Europeans that have shown some evidence of, uh, fun-fungal involvement, um, even candida, um, because there are some of the, some of the plaques that you see in the beta amyloid, um, has got fungal, fungal sequences as well. And so, you know, what is the role of Aspergillus and, and other f- and, and yeast-forming fung-fungi, and this is getting very interesting.

   28. PAPeter Attia1:31:08

       Yeah. I, I, I, I, I I think that Alzheimer's disease is probably the, the, for lack of a better word, the final common pathway of many-- There are many roads to it.

   29. PHDr. Peter Hotez1:31:18

       Right. Right. Many different-

   30. PAPeter Attia1:31:19

       Yeah.
9. 1:41:30 – 1:53:45

   Comparing the various COVID-19 vaccines and the impact of emerging variants of the virus;

   1. PHDr. Peter Hotez1:41:30

      it.

   2. PAPeter Attia1:41:31

      So let's pivot to a little bit of, um, the current around, uh, COVID. Um, as we stand here today, Peter, um, we're well on the path to most Americans who want to be vaccinated are getting pretty close to being vaccinated. Um, by the way, what's the latest on the vaccination of children? Um, where is the CDC on that? What do we know about the vaccine? Uh, how, how many of the, um, current vaccines as we stand here today, really there are three that are used in the US, correct? Uh, I think the AstraZeneca one is not used in the United States.

   3. PHDr. Peter Hotez1:42:09

      That's right. It hasn't, uh, gone through emerge-- They haven't applied for emergency use authorization. I'm worried about that vaccine for reasons that we can talk about. But, um, then there's the, the Novavax vaccine, so and there could be as many as five, uh, by, by the spring. Um, the-- In terms of kids, Pfizer just released data, uh, showing high levels of efficacy-

   4. PAPeter Attia1:42:32

      Oh, that's right. Yeah

   5. PHDr. Peter Hotez1:42:33

      ... in adolescents 12 to 15. Um, but there were small numbers. There was around 1,200 in the vaccine group, 1,200 in the control group, uh, and there were 18 cases of COVID in the, in the control group, none in the vaccinated group. And on that basis, in their press release, they said 100% efficacy. I, I'm sure that won't hold up.

   6. PAPeter Attia1:42:53

      Right.

   7. PHDr. Peter Hotez1:42:53

      I mean-

   8. PAPeter Attia1:42:53

      Yeah, it's too small a number.

   9. PHDr. Peter Hotez1:42:55

      One of the interesting things about the, about the kids though, in those, those adolescents, the virus neutralizing antibody titers are really high, like 1,200, so higher than older adults. So that may be a factor as well. And they're-- We're now starting to get our arms around correlates of protection that really high levels of virus neutralizing antibody seem roughly to correlate with efficacy. Um-

   10. PAPeter Attia1:43:20

       Is that consistent with your belief, Peter, that this would be more B-cell mediated than T-cell mediated?

   11. PHDr. Peter Hotez1:43:27

       Well, I think T-cells have a role. I mean, I think in, uh, virus neutralizing antibody may not be everything, but if you don't have high levels of virus neutralizing antibody, you're not gonna get, uh, protection. And the problem with look-- comparing those virus neutralizing antibodies is, uh I- is when you look at the actual papers, uh, they compare it with convalescent serum titers, and they're all over the map. And so, uh, so now there's a paper up on MedArchive that does something very simple, which is rather than just give the absolute value for the geometric mean titers, um, whether it's against pseudovirus or whether it, whether it's against, um, [lips smack] uh, plaque reduction nu- n- neutralization titers, uh, what they do is they do a ratio of the virus-neutralizing antibody titers against the vaccine versus the virus-neutralizing antibody titers on the convalescent to kind of normalize it. And there's this very nice curve that's been generated that shows you need to get it, that the v- level of virus-neutralizing antibodies has to be at least as high as the convalescent, and preferably about 1.5 or two to, to get really high levels of protection, and I think that's probably what we're, we're looking at. So it's not quite a, a true correlative protection, but I think we're, we're moving in that direction. And the adolescents get really high levels of virus-neutralizing antibody.

   12. PAPeter Attia1:44:56

       And did that Pfizer study give two shots or one?

   13. PHDr. Peter Hotez1:44:59

       I think it was two.

   14. PAPeter Attia1:45:00

       Okay.

   15. PHDr. Peter Hotez1:45:00

       I think it was two.

   16. PAPeter Attia1:45:02

       So now that we're out of the gate and millions of people have been vaccinated, do you, um, have any preference or concern over any of the vaccines? You obviously mentioned AstraZeneca, which I want to hear about, but let's start with the US vaccines. Any reason to believe that one is better than the other? Uh, in fact, I'll share with you something that I found very interesting, which was the J&J vaccine, which is a single, uh, vaccine, and that, um, [lips smack] uh, that vaccine, while the headline is lower efficacy, if you actually look at the, um, absolute risk reduction as opposed to the relative risk reduction, is at least as efficacious as Pfizer and Moderna. Um, I found that to be very interesting, and I'm surprised how that was sort of omitted from all the press.

   17. PHDr. Peter Hotez1:45:48

       Yeah, and I, and I also think it's hard to compare because it's a single dose. It's being given in a single dose versus the two doses. And I'm-- And it wouldn't surprise me if that J&J vaccine ultimately becomes a two-dose vaccine down the line because you may wanna give a booster for one of the variants as well. And in two doses, the virus-neutralizing antibody titers is really, really high, and it'll be as good or, um, in terms of protection as, as Pfizer or Moderna. Certainly, I think the single-- to me, the single-dose J&J looks better than the single-dose Pfizer and Moderna, not by much. The bottom line is they're all good. They're all good vaccines. And I also think don't be surprised if later on we're gonna need a boost for all of them. So y- there'll be a third dose of the Moderna or Pfizer vaccine or a second dose of the J&J. And what that will do is it'll, it'll, uh, elevate virus-neutralizing antibody titers higher. It'll create more durability of protection, uh, I think. Um, and that boost will be reconfigured, uh, for the South African or the, and the Brazilian variant, uh, which are not here in a big way in the US but may become a bigger problem down the line. Right now, it's the UK variant, the B.1.1.7 variant, that's accelerating. All of the operational warp-speed vaccines work really well against the UK variant.

   18. PAPeter Attia1:47:14

       That's because that variant has not mutated through, um, its spike protein?

   19. PHDr. Peter Hotez1:47:20

       Well, it has. So the UK variant has a single amino acid substitution, um, in, in, in an aromatic amino ac- creating an aromatic amino acid, and that seems to reduce the level of virus-neutralizing antibody. I don't know if I have a mechanism to show you pictures.

   20. PAPeter Attia1:47:38

       Yeah. Do you know how to share a screen on Zoom?

   21. PHDr. Peter Hotez1:47:41

       Yeah. I have a really cool, uh, graphic. It's a little bit of molecular biology, but not, but not much. I, I just showed this at a, at a pediatric grand rounds at Columbia this morning. And to me, it, it ex- it helps people understand it, but it's, you know, as I often like to say, it's not a 30-second UNICEF commercial. So this is a, a paper that's up in BioRxiv, a pre-print server, and looking at the B.1.1.7 variant. And so looking, and what, and in the spike protein, what there is, there's an amino acid substitution, um, in the 501 position where it went from as- an asparagine to a tyrosine. And a tyrosine is an aromatic amino acid. It has a ring to it. And they're able to show, model it with the receptor, the angiotensin-converting enzyme.

   22. PAPeter Attia1:48:34

       It's got a nice strong bond there.

   23. PHDr. Peter Hotez1:48:36

       Yeah. There's a r- ring, ring interaction. So it's these pi, pi ele- these pi electrons that circulate in aromatic rings that are interacting with each other. In addition, there's a hydrogen bond. And the reason I love this so much is, um, you know, all of, all we're talking about with this big acceleration of cases going up in Michigan and affecting younger people and higher mortality and morbidity, it's a bit of a simplification, but then again, it's not. It's all coming down to pi-pi interactions between, um, uh, between two aromatic, um, rings in, in, in two tyrosines.

   24. PAPeter Attia1:49:18

       Right. It, it's actually kind of-- Le- let's just make sure people understand this because not everybody understands biochemistry, right? Each amino acid, um, is coded for, um, by... It, it basi- there's, there's a code, right? So you have three nucleotides that code for an amino acid and, um, if y- you know, so it sounds like one of those gets changed and it changed the amino acid. Uh, and I can't remember, did you say it started at threonine or which w-

   25. PHDr. Peter Hotez1:49:47

       Yeah. It was-- So this is the wild type or the original lineages.

   26. PAPeter Attia1:49:50

       Yeah.

   27. PHDr. Peter Hotez1:49:50

       Now it's switching over to a tyrosine and it's basically-

   28. PAPeter Attia1:49:53

       Yeah. So it went, it went from, from, from threonine to tyrosine and then all of a sudden that changes, literally changes the shape but also creates, um, uh, kind of an electrochemical attraction that wasn't there before. And so all of a sudden this spike protein has a greater, um, uh- Uh, basically a greater, uh, uh, attraction to the ACE2 receptor

   29. PHDr. Peter Hotez1:50:18

       Right, which, which, which presumably translates into better virus entry-

   30. PAPeter Attia1:50:23

       Yeah
10. 1:53:45 – 2:08:54

    Global vaccination challenges and “vaccine diplomacy”;

    1. PHDr. Peter Hotez1:53:45

       neutralizing antibody to begin with.

    2. PAPeter Attia1:53:47

       Um, t-tell me why you think the AstraZeneca, uh, takes the biggest hit here then.

    3. PHDr. Peter Hotez1:53:53

       Yeah. So the AstraZeneca started out with, you know, in some cases not as high levels of virus neutralizing antibody, and the, a study was done in South Africa showing only 10% basically ineffective against South, the South African variant. But, you know, talking to the Oxford people, one of the things they say is it's a little unfair because they only tested it against mo- moderate and mild disease, and they feel that if you were to test against severe illness, it would still be very effective. And they counter that the J&J results were mostly looking at severe illness, and if they had, if they, if, if they, like J&J, had looked at severe illness, they would have come up with similar numbers. But, you know, I guess we have to wait and see what, what happens with that. The bigger issue with the AstraZeneca vaccine is, is just public perception around the cerebral thrombosis that is being reported out of Europe, and I think that's causing a lot of, a lot of damage. Um, you know, and, and it's, and it, and it goes back and forth. You know, the German government, um, through their Paul-Ehrlich Institute pointed out you had six, I think it was six cases of, of sinus venous thrombosis, which is a rare condition in the vaccinated group, and they suspended it, and then several other European countries did. And that had big ramifications, especially for Africa. You know, Francophone Africa listens to what's going on in, in France and et cetera. And I was going on a number of, uh, uh, podcasts, not podcasts, but, uh, Zoom conferences with groups in Africa, and they were very concerned about the AstraZeneca. That was supposed to be a workhorse-

    4. PAPeter Attia1:55:36

       Right

    5. PHDr. Peter Hotez1:55:36

       ... vaccine for low and, uh, low and middle income countries. The European medicine agencies came along and said, "No, no, it, it looks okay. It's, you know, it's, it-- We think, you know, this is not related to the vaccine." But then, uh, in Science Magazine, two excellent science journalists, Gretchen Vogel and, and Kai Kupferschmidt, looked at this and, you know, have identified about thir- you know, they wrote about 31 cases of cerebral venous thrombosis and, you know, clearly, you know, more clearly showing it, it could be linked to the vaccine. It's a very rare event, but, um, uh, but still that, that- can really alter public perception, especially in light of all of the very aggressive anti-vaccine activities that are happening. So I don't know what the US is gonna do at this point. I hope they do, um, authorize it for emergency release, even if they never use it in the US, and the reason is if the US declines or if that derails, I think it could have a chilling effect on Latin America and Africa because we don't have a lot of vaccines out there. That's, that's why we came along with our recombinant protein vaccine because there are not a lot of options. The big issue is for, um, the, uh, Astra... You know, if you look at what's gonna be made for low and middle income countries, there are not a lot of choices out there. I mean, the two mRNA vaccines, it's still a new technology. We're not gonna be able to scale that up in, in a big way for Africa and Latin America. Yes, I mean, it's great they... You know, Pfizer donated 230,000 doses to Rwanda. It was fantastic, but look at the numbers. There's 1.1 billion people in sub-Saharan Africa, 650 million people in Latin America. We're gonna need four billion doses of vaccines. Where's that gonna come from? It's not gonna come from the mRNA vaccines.

    6. PAPeter Attia1:57:28

       Is the refrigeration also a problem?

    7. PHDr. Peter Hotez1:57:31

       Yeah, the fact that you have the, that onerous freezer requirement, and then the, you know, the J&J is having, you know, some issues in scaling up production. The, you know, part of the problem was when the science policymakers were looking at this, they went so heavy on the innovation, and they wound up producing a lot of really cool vaccines that are highly effective, but in terms of durability for scale-up to make four billion doses, I don't think that was high enough on their radar screen and didn't realize that when you use a brand-new technology, it's really hard to move to four billion doses. And that's why I'm hoping our vaccine comes along, you know, which is, you know, in, in part, you know, a couple of donors came to me after your, after one of the podcasts I did with you, and that was game-changing for us because it allowed us to, uh, a-adapt our coronavirus program for vaccines we were making for SARS and MERS to this recombinant protein vaccine for COVID-19.

    8. PAPeter Attia1:58:30

       What's the, what's the vehicle?

    9. PHDr. Peter Hotez1:58:32

       It's recombinant protein in, in yeast, just like the hepatitis B vaccine, and, um, you could produce a ton of it. Uh, they c- they have capacity for dr- producing 100 million doses a da- uh, a, a month, and it's looking really good in clinical trials and in non-human primate trials. I, um, I can't talk about it yet, but it should be out soon. Um, and hopefully, that will come in and, and m- and make a big difference 'cause I'm really scared that we have nothing for Africa and Latin America. I mean, what's amazing is how I had to, you know, struggle for funding. I mean, I was spending, you know, a good part of last year just trying to keep the program going because it was so hard to get funds for what was so obviously needed, which is a low-cost, unfussy, durable vaccine for low and middle income countries. And, you know, because of your podcast, groups like, you know, the, um, um, uh, Tito's Vodka came through with some funding, n- you know, they're based in Austin, and an anonymous donor and, and, and a couple of others. So the... And now the Kleberg Foundation is helping us in a big way. They're a Texas foundation and, um, and the JPB Foundation and a, and a few others. So that, that was game-changing.

    10. PAPeter Attia1:59:46

        So Peter, based on everything you're saying, it sounds like the biggest concern right now would have to be Brazil followed by Africa. Um, you didn't, unless I missed it, did you, um, explain the mutation in Brazil and the efficacy that any of the current vaccines would have against it notwithstanding the scale-up limitations?

    11. PHDr. Peter Hotez2:00:06

        Yeah, a couple of things. So the P1 variant in Brazil has those same two amino acid changes in the South African, so I kind of think of them as brother-sister issues. Um, so we're gonna have-- So dealing with South Africa will also have, will, will hopefully take care of, uh, Brazil, uh, as well. One other thing I wanted to mention is, you know, the, the global policymakers did a good job of creating this COVAX sharing facility. It's really quite brilliant in its design. I think that's not the issue, you know, 'cause they were really worried about equity. The equity issue, I think, was more of the fact that we didn't ensure there was enough vaccine available for the COVAX sharing facility, and that's, that's really the problem right now, and hopefully, we can come in and address it and, and, um, and, and take care of this because if we don't s- figure out a way to vaccinate the rest of the world, if we only vaccinate North America and Europe, it's gonna be a catastrophe. This virus is gonna continue to circulate and cause tremendous humanitarian destruction, but also, um, who knows what other variants could evolve as well as a consequence of allowing that to go unfettered.

    12. PAPeter Attia2:01:22

        What, what, what drives the evolutionary pressure here of this, of these mutations? Um, is it just standard Darwinian behavior where enough mutations occur and they're escaping? Because these mutations... Like how does the mutagenicity of this virus compare to influenza? It seems far less than influenza. Is that safe to say?

    13. PHDr. Peter Hotez2:01:41

        Yeah. And so a lot of us were surprised by, by the variants. We thought that, um, we hadn't really seen this as much in coronaviruses. What some people speculate is it happened because of an immunocompromised individual, um, who, uh, you know, had a lot more virus replication in their system and that combining even possibly with receiving plasma convalescent therapy that put some kind of selective pressure on it, and that's kind of an, um, a hypothesis that's out there but, you know, it's not strong. I don't think we really know that, um, for certain at this point. Um, the good news is The way I see it is a lot of the viruses are converging to the same mutations. So my hope, and it's only a hope, and there's by no mean consensus in the scientific community, is that if we make a booster to this South African/P1 Brazil variant, um, we might be done at that point, that there won't be this continual evolution for totally something different. But, but I don't, I don't think we know that for certain. So the good news also is it looks like our vaccine seems to, um, give pretty good levels of virus neutralizing antibody to the South African variant as well. So we're making the booster for it, for the South African just in case, but we may not need it. We'll see.

    14. PAPeter Attia2:03:09

        And we don't know how often we would need the booster. It could be every six months, every 12 months, every 18 months. It's too soon to tell, obviously, until we have longitudinal data looking at the neutralizing antibodies.

    15. PHDr. Peter Hotez2:03:20

        Yeah. I mean, my dream situation is we give this one boost, um, beyond the original vaccine series later this year or next year, and then we're done, that it won't have to be every year. But like anything else, we'll just have to monitor and follow it. But, you know, people say, "Is it gonna be like flu where you have to vaccinate every year?" And at this point, I don't think so, but I can't say for certain.

    16. PAPeter Attia2:03:43

        Because in the case of the flu, that's driven more by the mutagenicity than the lack of B cell response, isn't it?

    17. PHDr. Peter Hotez2:03:49

        Well, in the case of the flu, you're getting these wholesale antigenic shifts.

    18. PAPeter Attia2:03:54

        Yep.

    19. PHDr. Peter Hotez2:03:55

        So it's a really, like a totally different virus, and there's this careful s- carefully orchestrated dance where you, that we have in place to monitor flu virus strains, you know, maybe coming out of Asia, and then quickly transmitting the message to the pharmaceutical manufacturers who make a whole different vaccine e- every year. It's really quite extraordinary. I don't think we're gonna need to do that for coronavirus vaccines. Um, at least that's my hope, but we'll, we'll see how this unfolds. But one thing's for certain, if you look at the o- if you look at what's available for Africa and Latin America right now, it's, it's not good. And so I've been, uh, talking to a colleague, uh, Patrick Soon- Shung Chin, who's, um, in, in Los Angeles, and he's really interested to see can we build out vaccine development capacity in, in Africa or maybe Latin America, because right now there's no vaccines made on the African continent. Um, and very f- not enough in Latin, not nearly enough in Latin America, not much in the Middle East. And we've learned that if you only rely on the multinational companies, even with that great COVAX sharing facility, they're, they're not gonna make co- they're not gonna make new vaccines for the world, at least in rapid timeframe. I mean, they still-- It's amazing they do what they do. I mean, Gavi, the Gavi Alliance for Vaccinating the World's Children, depends heavily on the multinational companies. They do a great job, but we, we need parallel mechanisms in place, like new vaccine development, uh, production facilities in, locally in Africa and Latin America, and that's something I'm very int- that we've been working a lot on this concept of vaccine diplomacy and, and building that out.

    20. PAPeter Attia2:05:42

        Well, Peter, I know that we have a real hard stop in time because you've got another, um, obligation, but I'm really happy that we were able to spend a couple hours together. Um, we covered a lot of ground, and, uh, we actually got through half of what I wanted to talk about, so I consider that a win.

    21. PHDr. Peter Hotez2:05:57

        It was at only half? Okay. Well, I'm, I'm always happy to come back. You know, uh, I lo- I love, uh, being on your podcast, one, because I learn so much from you, and, and the thing I really appreciate is you, you ask questions that I just never would have thought of on my own. And, you know, after you ask it, I say, "Why don't I know that? I should have... I mean, that's so obvious that's, that I should know that because it's the right question to ask." So you have this amazing talent for asking the right questions, and I appreciate that.

    22. PAPeter Attia2:06:27

        All right. Well, thanks very much again for everything, Peter, and, uh, I'm sure we will be talking again soon.

    23. PHDr. Peter Hotez2:06:32

        Okay. Thanks so much.

    24. PAPeter Attia2:06:35

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Episode duration: 2:08:58