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#047 - Dr. Paul Offit MD



Paul Offit on the incubator podcast



Hello Friends.


We are very excited to release this special episode of the podcast. We are partnering with the Eastern Society for Pediatric Research in honor of the 1st annual medical research conference, taking place March 10-12 2022. ESPR was generous enough to sponsor a giveaway and to put us in touch with Dr. Paul Offit whom we had the pleasure of interviewing for the podcast. We spoke about his most recent book (you bet your life - link below) , scientific progress and how it is perceived by the public. We also spoke about mentorship which was fitted since Dr. Offit will be awarded the Mentor of the Year award from the conference.

Enjoy


 

Bio: Paul Offit is a pediatrician specializing in infectious diseases and an expert on vaccines, immunology, and virology. He is the co-inventor of a rotavirus vaccine that has been credited with saving hundreds of lives every day. Dr. Offit is the Maurice R. Hilleman professor of vaccinology, professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania and director of The Vaccine Education Center at Children's Hospital of Philadelphia (CHOP). Offit is currently a member of National Institutes of Health (NIH) working group on vaccines, a subgroup of the "Accelerating COVID-19 Therapeutic Interventions and Vaccines" (ACTIV) comprised of experts to combat COVID-19. He is also a member of the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC). Previously, he was a member of the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices. Offit is a board member of Vaccinate Your Family, The Franklin Institute, and Autism Science Foundation. "You Bet Your Life" is his 12th book.




 

Daphna 0:00

Hello, everybody. Welcome back to the podcast Daphna, what's going on today.


I'm just I'm really excited about her interview today. You know, we had talked about having our guest


Ben 0:57

on I had mentioned that you had mentioned, give yourself credit.


Daphna 1:02

No, I think it's an interesting time to have him on even though he's been at the forefront of vaccination efforts for decades. And so I'm just glad that it came to fruition one way or another.


Ben 1:17

That's correct. So this is a special episode being released. For the first annual Eastern medical research conference that's taking place between March 10, march 12. It is sponsored by the Eastern society for pediatric research and the American Federation for medical research. And Dr. ofit, who we're interviewing today is going to be receiving an award at this conference for mentor of the year. So congratulations to him. And we're doing some cool things with the Eastern Medical Research Conference this year where we will have a giveaway of some of Dr. off its books, and a few more swag, I guess. Or this courtesy of the Eastern society for pediatric research. And basically, we will post on our Twitter account how to enter this giveaway. And the the instructions are going to be similar to our prior giveaways. I think you'll have to, quote retweet the giveaway announcement and follow the Eastern society for pediatric research Twitter account, and that should enter you into the giveaway. We will release the giveaway will be open starting today on Monday, which is when we're recording this, and we'll announce the winners at the time of the conference. So yeah.


Daphna 2:43

If you liked it, we love doing giveaways.


Ben 2:45

Oh, yeah. Yeah. So so our guest Dr. Paul Offit is a pediatrician specializing in infectious disease and an expert on vaccines, immunology and virology. He is the CO inventor of a rotavirus vaccine that has been credited for with saving hundreds of lives every day. Dr. offit is the Maurice R. Hillman professor of vaccinology, Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and the director of the Vaccine Education Center at Children's Hospital of Philadelphia. Dr. offit is currently a member of the National Institutes of Health Working Group on vaccines, a subgroup of the accelerating COVID-19 therapeutic intervention and vaccines, comprised of experts to combat COVID 19. He is also a member of the FTAs vaccines and related biological Products Advisory Committee. Previously, he was a member of the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices of it as a board member of vaccinate your family, the Franklin Institute and autism Science Foundation. He's written multiple books, his 12 and most recent book, you bet your life is now available everywhere books are sold. Dr. ofit, thank you so much for being on with us. Is it okay, if I call you, Paul?


Unknown Speaker 4:07

It's actually offered after if it was the original name


Ben 4:12

of it. Yeah. Okay.


Unknown Speaker 4:16

Everybody tries to make me Irish, right?


Ben 4:20

No problem. Thank you for being on with us. I wanted to maybe congratulate you on the recent release of your last book, you bet your life and for the people who haven't had the pleasure of picking up the book yet? Is there? Could you give us briefly a little bit about what that book is about.


Speaker 3 4:39

It's about the fact that medical innovation invariably comes with a human cost that there's a human price to be paid for knowledge that nature gives it secrets up slowly grudgingly and invariably with a human price. And so I sort of go through the nine major medical innovations that have caused us to live 30 years longer than we did 100 years ago to make the point that every Every step of the way, there was a price to be paid for knowledge. I mean, whether it's antibiotics or vaccines or biologicals, or transplants or chemotherapy, there was there was always a tragedy associated with that endpoint. I wrote it because I'm on the FDA vaccine Advisory Committee. We were considering that these vaccines, these novel vaccines, the either the mRNA vaccine strategy, or the vectored virus vaccine strategies, based on 10s of 1000s of people where we were making recommendations for hundreds of millions of people, and you knew there was going to be a prize, you knew it. The only question was, how big? How rare and how long? How serious. So and that's, that was sort of part of it, just to realize that, that everybody would like to believe that we're at a point in our era of scientific knowledge, medical knowledge, where that doesn't happen anymore, that people just think, oh, you know what, I'm gonna wait till the learning curve is over. But it's never over. And I


Ben 5:53

think the first page of the book, you have this quote by William Faulkner, where you, it's where he says the past is never dead. It's not even past. And I thought this was you look at this page, and it's almost a reminder that we forget, I feel like as a collective, we've forgotten that, don't you think? Is that why the reason why you put that quote there?


Speaker 3 6:12

Exactly. Right. We constantly are reliving our past, whether we like it or not.


Ben 6:18

Yeah, and sadly enough, the current situation in Europe is is a reminder of that as well. Sorry, definitely, we're gonna say,


Daphna 6:25

No, I mean, it's really I think, what your book represents is how much we are taking for granted of the science discoveries in the, you know, the last hundreds of years.


Speaker 3 6:40

That's exactly right. That's exactly right. It was an education for me. I mean, that's part of why I enjoy writing these books is I learned a lot. And it helps me it helps me to put things in perspective.


Ben 6:51

So the book is divided into three parts. The first part is called risk. The second part is called oversight. And the third part is called serendipity. And so I wanted to touch a little bit ask you a few questions about about each of these different concepts. So in the first part, the first part called risk, you present three stories about the origins of heart transplant, blood transfusion and anesthesia. And you make eloquently, I think, the case for the continued risk associated with medical innovation. Now, what I wanted to ask you is that I'm a big fan of Daniel Kahneman and his book Thinking Fast thinking slow, where he's making the argument that it's not so much uncertain situations that are causing a lot of a lot of anxiety. But however, more like loss aversion that prevents us from going through with difficult decision. Now, also, what I think the the the idea you're presenting in risk is, is a form of are we are we willing as a as a collective, to, to go through delayed gratification where it may not be so, so good right now, but as a whole will be will be better? Do you think that our collective human psychology right now is robust enough to keep walking that path? Again, the same path that has been that has sorry, the same path that hasn't been walked 5060 years ago?


Speaker 3 8:10

No, I don't. I think we want to believe that we know everything we need to know right now period, either we want to, but we're always certainly in science or medicine, making decisions under uncertainty. And it's hard to convey that certainly to the patients that we take care of that. I think if you ask people that, do you think we're going to know more 50 years from now and sign this? And then we know I think everybody would say yes to that question. But when it comes to their disease or their problem, you want to believe you no need to you will know everything you need to know right now, which is why we're so drawn by the guru, you know, the people like, you know, Matt oz or, or Deepak Chopra, or Andrew Wakefield who who don't express doubt, they're certain, and even somebody like Andrew Wakefield is a perfect example. I mean, he, he raises this notion that the combination of measles mumps, rubella vaccine causes autism. I mean, you could argue in the in the the nicest thing you could say about that is that he raised the hypothesis, but he never tested. I mean, it subsequently was tested in a de different studies involving hundreds of 1000s of children in seven different countries on three different continents, involving probably hundreds of millions of dollars spent answering this fruitless, dead end hypothesis, but he still believes it, he still believes it's true. And so he still has his following because he refuses to see this as anything else other than he was right. And there's something very reassuring about that. It's the what I call sort of the bones. McCoy seduction. You know, for anybody who was a fan of Star Trek. Bones. McCoy was the chief medical officer on the USS Enterprise. And he had, he had this thing called a tricorder. And if you had signs or symptoms, he would scan you up and down. And then he would look at it and there would be a readout and that's what you had. That's very seductive, but it's not the way medicine works, or science works. And I think that's the fluidity of Science is disconcerting. You see this with the COVID pandemic, what why didn't we know this a year ago? You know, because, and you hear constantly Dr. Fauci and Dr. walensky. And others are saying, Look, we learn as we go. And that's a very, very hard message for people to buy.


Daphna 10:17

You know, we talk about this all the time on the podcast with an array of people that like, why is it so hard in our human nature to say, you know, we don't know yet. And obviously, you're speaking to this big, you know, overarching medical, pro projects, right? But But even in our own offices in our own hospital settings, one on one with patients we have such a hard time saying, We don't know.


Speaker 3 10:48

No, you're right. Absolutely. I'll be curious to hear how this plays out with the COVID pandemic, because we are much more sophisticated. I think in terms of how we understand this pandemic, I was I was on service last week of just one service up till yesterday. And I was rounding on it, there was a 13 year old boy who came in who had received two doses of COVID vaccine. He came in with mild symptoms. And that's not why he came in, he came in for another problem, but he just happened to have mild COVID. So I'm rounding on you. Here's this 13 year old boy, he says, says to me, do you know what variant strain I had? We're all we're all kids. Yeah,


Ben 11:26

at the end of the first section of the of the, of the part one of the book on risk, you have this great analogy, where you're talking about this idea of risk and scientific discovery is a bit like walking through the woods and reaching this big gorge. And you have three possibilities when it comes to how you're going to cross to the other side, then you say scenario, one is that you have a bridge that's old, but you know, it's taken many people across. Second option is there is that old bridge that you could go across. However, if you walk three miles up the road, there's another bridge that maybe is a bit safer. And you said that situation number three, which is, which is funny, because it says the same situation as scenario number two, but now you're being chased by a lion, and you may not be able to get three miles up the road. And you conclude the analogy by saying that people should make the most informed, clear eyed, most dispassionate decision using all the information available. And I was reading those words. And I was like, That's so true. And yet so unattainable. I mean, we've seen through the pandemic that we can, that's definitely I mean, I feel that it's a, it's cannot be expected of people to make rational decisions, people do not have a good grasp of statistics. And then the decisions that are needed to be made in stressful situation involving your own health is it's impossible to make and all these heuristics are going to be in place. So do you really think that's a reasonable expectation?


Speaker 3 12:55

Yeah. So here's how I would answer this. That analogy was born with Christian Barnard. Right. So what time Chris you're born, I was probably the most famous doctor in the world, a South African surgeon who was the first to do a human heart to human human to human heart transplant. The person he transplanted a man light named Louis watch cancer, he was dying. I mean, he was going to be dead in a matter of weeks at the longest. And so So what what Barnard said was, you know, if you if you come to a lake, and the lake has alligators and and you're not going across that lake, unless you're being, you know, chased by a lion, which was Louis watch Caskey story, I mean, he was willing to, to do something for which he lived there for this this successful transplant for only about 18 days. But that comes up now. Because you have about roughly roughly 30 504,000 people in a heart transplant waiting list 1300 of those people are going to die while waiting. And I predicted in this book that there would soon be and this was actually Robert actually write about this, but the what I predicted that there would be a pig heart that was going to be transferred. And that happened at the University of Maryland just recently. But it's from the person's it, which is a genetically engineered pig heart that is constructed in a way to make it so that you are less likely to reject it, that your immune response is less likely to see those MHC encoded glycoproteins that would cause you to reject it. And so and that happened at the university we have but from the standpoint of the person who got it, he was pretty sick. And so he that was an easier decision. But if you're one of the 1300 who are going to die while waiting but you don't know whether you're going to be one of those who are going to die while because you still have months or maybe a year or two years to live. Do you make that choice? And it's hard because see, the thing is, we never like to think this is true. We are always at some level gambling we are I when I was on service last week, there are children on whom you know, you're not sure whether or not they have an invasive bacterial disease. You test it. You start antibiotics and waiting to see whether or not this comes but that's a risk. That's a risk people. Seriously occasionally fatal side effects associated with antibiotic use you We're always taking risks, we always say, well, while I'm doing the more conservative thing, for example, by treating with antibiotics when I don't know others, but if they don't need antibiotics, then you're not doing the conservative thing. You're doing the radical thing, because you're not helping them. And if you're not helping them can only want to be one of two outcomes, nothing or you hurt them. Those are the only two. I just thought that we don't think about it that way. When someone's sick, we think we can't hurt them. That's not true. We can


Daphna 15:24

I especially like your discussion around risk, and currently with the COVID pandemic. And for people who are choosing not to be vaccinated that they're doing nothing still carries risk. And I think people feel like only if I do something, do I have a risk, but doing nothing also carries risk? And I think you've done a really eloquent job that I'm not sure everybody's heard you. I think you've done an eloquent job of describing that that doing nothing is still a choice.


Ben 15:56

I wanted to add something there. I wanted to add something that because at the end of the book, you do say that very, very well. And you say is the sin of commission always viewed as greater than the sin of omission. But doing nothing you say is doing something? I think that's so key. So I wanted to put that in there as well. Because I think deafness question is a great one.


Speaker 3 16:15

There are no risk free choices, just a choice to take the risks. And you're exactly right. We think okay, you know, I'm not going to risk this, this vaccine B and then you can argue when the vaccine first came out, I mean, it was a novel technology, the mRNA technology, we you know, we tested in the case of Pfizer who 15,000 or 20,000 people would receive the vaccine in the case of Maderna 15,000 people receive vaccine. That's not a lot of people. I mean, you could say, You know what, let me just wait till the first the first few million doses are out there before I think they should but but by making that choice, this COVID is a highly contagious disease, it was common, you were Chote making the choice to risk that virus and which was the greater risk? That's the question because you there's always at some level incomplete information.


Ben 16:57

Do you think so what was very interesting to me during the COVID pandemic is that it was a display of all these books about psychology that I love reading, where they talk about heuristics about the duck. Nassim Taleb talks about the turkey fallacy where a turkey is being fed every single day. And so the turkey may assume that because I'm being fed every day tomorrow, I'll be fed again, when in truth, tomorrow is Thanksgiving, and this is the Black Swan effect. And I thought people were think making the decisions you're talking about, were saying, Well, I'm not gonna get the vaccines because I was fine. Yesterday, I'm fine today, I'll be fine tomorrow. And and I'm wondering if this is a product of the trend and precision medicine, which I'm not saying is bad, but I'm saying we're, we're moving towards something where we say, well, we're going to individualize your care on every level, does that, in effect is murdering public health in a way where we tend to think of ourselves as part of a society where we say we know what I'm going to want to buy in whatever society has to offer for us as a group, rather than saying, Well, no, I know, my, my DNA, I know this, and it has to be tailored to me specifically, do you do you think there's, there's anything there?


Speaker 3 18:09

I think we've always done that. I mean, I think we've always sort of considered the patient when we're moving forward in the case of, say, mass vaccination programs. Um, there are, you know, contraindications and precautions, depending on what your sort of individual medical stories are. But I'd like to know how then your, your, your the influence of Daniel Kahneman when he was clear. Risk six. That's good. I love this. He was great.


Ben 18:37

So then I think this transitions well, to part two of the book, which talks about oversight, right. And, and in part two of the book, especially in the in the early part, you mentioned how the state of the FDA and its role during the COVID 19 pandemic, and how some of the decisions had a dramatic impact on how the FDA is being viewed and on the FDA is credibility, especially when you talk about the approval of hydroxychloroquine for the treatment and prevention of COVID. And I am wondering if in the case of oversight, we tend to delegate our decisions to larger bodies and say, You know what these people should know what they're talking about. And I'm going to, I'm going to defer my decision to this body in based on two weeks because I'm a bit lazy, and I don't want to do the work. And also if something goes wrong, I can I can have something to blame and I won't be at fault. But the dramatic consequences what you're describing if if the oversight agencies lose credibility, what is how do we recover from that?


Speaker 3 19:37

If we don't trust the FDA and CDC in this country, we're in trouble. I mean, those we you know, the FDA is the critical regulatory agency for products. They stand between pharmaceutical companies in the American public to make sure we get what's safe and effective. And hydroxychloroquine was an example of the FDA not doing its job. I mean, it showed you the degree to which politics could influence Science. You know, I think that's there's line. Barry who wrote the book, The Great influenza said when you mix science and politics, you get politics. And that's certainly true here you saw, the Trump administration basically twisted the arm of Commissioner Stephen Hahn to approve hydroxychloroquine, a drug which had not been shown to treat or prevent this disease, which had certain serious side effects, including cardiac arrhythmias, which could be fatal. Within within a few months of that approval, you had many studies showing that it didn't work to treat or prevent the disease, and then they withdrew the product, they should have waited, there was no rush to do that. And so they lost credibility. And what ended up happening as a consequence of that, as we move closer and closer to the vaccines in December 2000 2020, that there was there was a loss of faith, and I'm on the vaccine Advisory Committee and what you saw happening where there were at least six states that formed their own vaccine advisory committees because they didn't trust the FDA. Imagine with that had played out in the United States, it's the did recommend the vaccine and states that didn't recommend the vaccine, it would have been a mess. You have to trust the FDA. And I do think they let us down, although I would say and Commissioner Hans defense, as we moved, the election was on November 3, I think that the former President Trump would have clearly benefited from a vaccine having been approved before the election day. But in order for that to happen, you would have had to have truncated the safety follow up for those trials, you really had to have at least a two month safety follow up from the last dose, which would have put those vaccines at the beginning of December. And Trump really tried to to influence the FDA to just approve them before November 3. And he then they didn't then I think Trump pulled Commissioner Hahn into the into the Oval Office and let him have it. And still, he stood tall, so that was good. I'm hearing we didn't have the October surprise. We all feared and things settle down there. But I think the same thing with the CDC, you have to trust the CDC. And I do think I mean, I think the CDC is the principal epidemiologically epidemiological study group in the United States, and I think they do a great job, but I do think they could do a better job of communicating because I think the single worst communication error with this vac with this vaccine occurred on July 4 of 2001. With the outbreak in Provincetown, Massachusetts when 1000s of men get together to celebrate July 4 79% are vaccinated nonetheless 346 men who were vaccinated, get COVID Okay, it's 346 people who were vaccinated get COVID for hospitalized. That's a hospitalization rate of 1.2%. Great, that's a win. That's a vaccine that's working well. The rest had either mild or asymptomatic disease, which we called Breakthrough illnesses. Were breakthrough was a failure. This is a win. I mean, within weeks of that, you heard that Brett Kavanaugh had an asymptomatic infection despite being vaccinated, if you watch that coverage on the media, you would have thought he was in the ICU, he had an asymptomatic infection. And this is the hardest The hardest thing right now, because and I think this all leads into the booster dosing. I mean, if our goal is to try and prevent mild illness, we're going to be boosting forever. Because this is a mucosal virus, the best you can hope from following either natural infection or immunization is, is protection against severe illness, you're not going to get protected against mild illness over the long term that can't happen. Yeah,


Daphna 23:23

I mean, I really think you've taken a truly scientific approach to the pandemic, you don't always get a lot of credit for that. And especially in your op ed, where you do discuss what can we even, you know, expect from the COVID vaccines and children and in relying on boosting to prevent mild disease. And I think you've given us some indication of some big places where we kind of went off the rails in public health messaging. But I'm feeling like our public health messaging is very much reactive instead of proactive, and I'm wondering if we're Hindsight is 2020. But if you know if we could have done things differently, how would we have been proactive with the with the public health messaging, and helping people understand what to anticipate about science as we learn? More?


Speaker 3 24:13

Great question. A few things. I think when our committee was presented with those two studies, the Pfizer moderna study in in December 2017, where you had 95% protection against mild illness and those studies, we should have made it very clear that that wasn't going to last because those were three months studies, those participants had just received their second dose, it wasn't surprising that that protection gets mild illness would be that good. But we didn't do that. We should have done that. Because what ended up happening then over the next six, eight months, is you heard about fading immunity against it against infection. And really what you were just seeing was fading immunity against mild disease and not moderate to severe disease. And that was mistake one. I think the breakthrough was was a mistake the term it's also associated with that Have a turn after he was born. The false notion again, really put out by the CDC, that if you had mild elicit you'd been vaccinated, as compared to if you had mild illness and you hadn't been vaccinated, you shed an equal amount of virus, you were equally contagious, which again, sent the message. Wait, so it doesn't matter whether I'm getting vaccinated, I'm still gonna be contagious, if I get them all those wasn't true, because they were looking at PCR testing, rather than infectious virus, that shed quantity of infectious virus, which is a research tool. But when those studies were done, you saw that you did shed less virus for a shorter period of time if you were vaccinated, yet another reason to get vaccinated. And then I think when President Biden stood up on August 18, of 2021, and said, as of September 20, we're going to have a booster dose for everybody over 16 years of age, thus sending the message that two doses weren't enough. I mean, we continue to damn this vaccine, even though it is a remarkable scientific achievement. I think it's the it's the greatest scientific achievement in my lifetime. And as you can see, I'm on your screen. I'm old. So my lifetime consists of also the development of the polio vaccine. It's an amazing accomplishment. And we just keep inadvertently damning the vaccine and the booster dose story is just getting more and more complicated. And I think we need to, we need to make it clear what you can reasonably expect from the specs. And we haven't really done that.


Ben 26:19

Do you think that so it's great that you're talking about this, because I'm wondering if whether we are inadvertently making the case that the vaccine is the end all be all, when in the book, you talk about the story of an Gods thinker, I think, I hope I'm pronouncing this right where in the in the 1950s. She gets vaccinated against polio and catches polio from this vaccination. And that was due to the Qatar I guess, quote unquote, Qatar incident where the company that was manufacturing the vaccine was was not was not following the safety protocol. Well, and what's interesting to me is that we know that with when you talk about these issues, these issues of scaling up you're going to vaccinate millions and millions of people, we know that there's going to be a little bit of a risk and a cost in terms of some people may be having adverse reactions, some maybe having I don't know, any type of reaction. Do you think that we didn't do enough of a job in preparing the population for these potential outlier cases? Because when I was reading the case, you read this case, you're like, Oh, my God, this is almost exactly what's happening today, where if somebody has one reaction to the vaccines, I Oh, you see, vaccine doesn't work this one person. And um, and you realize that this story had been there for 5060 years, and you're like, man, if maybe we should have advertised the way this person went through to show people? Yes, there may be some costs, but overall, polio eradicated, and that's what we're fighting for here today. You know, I


Speaker 3 27:48

think there were a lot of things interesting in that story in the Qatar story. So here was when Jonas Salk made his polio vaccine, five companies stepped forward to make it take the virus, grow it up and cells, purify it inactivated with formaldehyde. There were five companies made it they all had trouble in activating the virus they did. Why are cutterhead the most proud biggest problem so because they failed to fully inactivate the virus about 120,000 children were inadvertently inoculated with live dangerous poliovirus about 40,000 of those children developed a short lived paralysis 164 were permanently paralyzed for the rest of their lives and 10 were killed, I think was the worst biological disaster in this country's history. And in no sense contributed to an anti vaccine sentiment in this country. Not at all I'm imagine this happening today. Not at all.


Ben 28:36

I had not realized that.


Speaker 3 28:39

The exit interview actually wrote a book about the veterans. But if you looked at the the exit interviews from those first few trials, the jurors wanted to find Qatar not guilty, not responsible, because they saw it for what it was, which was a problem with scale up. And I think as we scaled up these vaccines, say the mRNA vaccines, because I was fortunate to be part of a team that created the rotavirus vaccine road attack. And so which was made by Merck. And so I talked at one point with the head of the Merck manufacturing division, he said, We have never scaled up lipid nanoparticles before. You know, just he went through all the things that you would have to make sure were in place. And so I think we all held our breath when this this happened. But it all worked well. But to get to your point, what did we learn, we learned that when we gave this vaccine to hundreds of millions of people, that mRNA vaccines, which was a complete surprise was a rare cause of myocarditis, inflammation of heart muscles. We learned to our complete surprise that these vectored virus vaccines were a rare cause of so called thrombosis with thrombocytopenia syndrome, which means blood clots, including serious blood clots in the brain, which could be fatal. And and I think what we should have done right at the beginning is realize there are going to be problems with this vaccine. It's always true, they will likely be very, very rare, but the good news is we're looking for them. And, and so and so through mechanisms like the vaccine safety DataLink which where you can look very quickly in real time, you can see the Um, who's gotten the vaccine? Who hasn't. And so you can see if something comes up when it's intensive, 1000 people, hundreds of 1000s of people, millions of people who, who has a real problem and who doesn't. The problem is, is the vaccine adverse events reporting system, which is misnamed. Anybody can report to that it should it should be called. And any casual person who's not necessarily involved in this would think that this is where adverse events from the vaccine are reported. But it's not it's to be called suspected vaccine adverse events. Because people like like Tucker Carlson get on television and say 3300 deaths have been reported to the to the very system, which means that the vaccine doesn't make you immortal. That's basically what it means because there are people that will die after they've gotten the vaccine, because the vaccine is only designed to prevent SARS, cov, two infections, not everything else that happens in life. And I think people that didn't never understood that we need to do a much better job of explaining all this and telling people look, we're going to be looking. And if this is a rare adverse event, you're going to know about it as quickly as we know about it. And what ended up happening was the CDC ended up expressing a preference for the mRNA vaccines, because although both that and the vector virus vaccines had a side effect, the the side effect from the mRNA vaccines was much, much less consequential than was the vector virus vaccines. That's why that happened. So we should let people know that early on, because that had to happen. I mean, that was part of this this book You Bet Your Life was, it always happens, just


Daphna 31:26

I think that's what's such an important point about, really about transparency. It's almost like, it's almost like we're afraid to tell people like what the process looks like, and has looked like, many we've done this many, many, many, many times. But because we have the same process over and over again, that's how we that's how we keep things safe. And I wonder why we think, you know, the lay public can't can't, you know, understand that we have these processes. And maybe if we advocate for that sort of transparency in education, that, you know, again, that people would know what to expect.


Speaker 3 32:08

You're right. And I think I think it's hard to do that. It's hard to tell is the reason we were talking about right at the beginning this this interview that that, that there are often problems and but but that we're going to be looking for them, and you're going to know about them as quickly as we know about them, but to expect that there wouldn't be problems and to constantly try and defend safety as being absolute, which it's never true. I mean, as I say to friends, you know, the most dangerous aspect of getting vaccines is driving to the office together. Okay. Yes.


Ben 32:38

And I think the the issue with the with the I think it's called The Verge, right, the adverse event reporting system, is that verse is that we've allowed anyone to make the connection between any event and their vaccination, which is a scientifically extremely difficult process. And we have such a hard time doing that in our research and everything. And we've allowed anyone to say, if you felt anything in relation to the time of vaccination, then report it as a correlation. When this is this, I think this was this was very dangerous. It's very dangerous to do because it allows people to make connections that often are not there.


Daphna 33:13

I do think it's an it's an interesting system. That way we have given people have the opportunity to engage in the scientific method. But I like the way actually you describe it as as a hypothesis generating tool to allow us to look for links that we may not have looked for before. So I think there's still a ton of value. We just have to be honest about how we how we use it. Yet I


Speaker 3 33:41

think that you're exactly right. So for example, in the late 1990s, when wife made a rotavirus vaccine called rota shield, it was not a very rare cause of intussusception, which was a blockage that was actually first reported in fares and then proven by the vaccine safe. Actually, bears picked up myocarditis very embarrassed picked up this actually thrombosis with thrombocytopenia syndrome, but it's open to the public. It's incredibly misuse. I mean, I would argue it on balance, it probably does more harm than good. Just because it really scares people because they think that this is this is really meant in many ways. The one stop shop for anti vaccine activists, okay, go to there. There was somebody who was an anesthesiologist years ago reported because anybody can report reported that his son had gotten a vaccine and turned into the Incredible Hulk and then that appeared on him.


Ben 34:33

As we're talking about funny stories, I want to highlight one of the stories in the book about the rise that you talked about the rise and fall of X rays, which is a part of history that I enjoyed tremendously, but then you bring up a piece of of history that I didn't know and you talk about as the dangers of X rays were uncovered extra machines started disappearing from Opera House streets, nightstands and department stores. And you talk about that there's one area where they persisted During the 30s, the 40s, the 50s. And that was shoe stores and how cobblers used to use X rays to see if the shoes their shoe size and the fit. And that was baffling to me. I had not heard that story before. I'm wondering what was doing. I mean, this is a very well researched book. So I'm wondering, through your research, what is the one story that really caught your eye and that you enjoyed the most from the medical history side of things? Well,


Speaker 3 35:24

the story that was the most emotional for me, and it really, in many ways drove me and I'll give you some background for it. The the when I was when we approve the vaccine, for example, for the 1215. Year, we the vaccinated advisory committee to the FDA are approved for the five to 11 year old. I got a lot of hate mail. I mean, I would say before the four or five to 11 year old, I think I got not kidding. Within a few days before that vote. I got a little more than 3000 emails people's vote no, no, not in a nice way. The the the thinking was, look here, you have Pfizer that did a 40,000 person trial. Now you have for the five to 11 year old a 2400 child trial. So 2400 children when you did just 40,000 for the adults. Is that enough? And you know, it's it's a reasonable question, but the answer to it actually lies in something that I wrote in this book, which is when Jonas Salk tested his polio vaccine, he tested it and 700 children in and around the Pittsburgh area found that it was safe and effective. And as far as he was, he had I mean, he went to his home to his wife Donna that night and said, Eureka got a got a vaccine. He didn't want to do a trial that vaccine he didn't want to do a placebo controlled trial that vaccine, he could not conscience, giving saltwater saline as a placebo to first and second graders in the 1950s with with a polio knowing that polio caused 20,000 to 30,000 children to be paralyzed every year, knowing that polio killed cause 1500 children die every year he couldn't conscience that it really, really upset him. Nonetheless, the March of Dimes insisted on doing a trial and did the largest probably medical trial in history. 420,000 people got the children first and second graders got six vaccine, and 200,000 got placebo. And so the vaccine was announced to be safe, potent and effective. Those three famous words that appeared on headlines everywhere in this country. My my mother cried when I was a first and second grader in 1950s. My mother cried when that announcement was made. I mean, department stores stopped when the announcement was made synagogues held special prayer meetings, church bells, bells rang out, well, how do you know is effective, he knew was effective, the 16 children died of polio. And that study on the placebo group, he knew that it was effective because 36 children were paralyzed in that study permanently 34 in the placebo group. I mean, you know, those kids were first and second graders 1950s. So they could have lived long and productive lives. But for the flip of a coin. And so when people came to me, and they said 2400 Children, that's all you want, when when, for example, in the in the that trial, there were 16 cases of COVID people group, you know, my response was that the people who were were not, didn't you know, call me a Nazi or make references in Nuremberg Code. I mean, I wrote back and I would say, Okay, you could do 24,000 Children, in which case, there wouldn't have been 60 cases in the placebo group COVID, there would be 160. I mean, what price do you want to pay, and it's always true, it works both ways. It's not just the price that you pay for knowledge. After the vaccine is out there, it's the price that you pay for knowledge while you're doing the trials. I mean,


Daphna 38:30

I think that's such an important point, because it's hard to get people to sign up for trials. And in full disclosure, my, my school aged daughter was in the Maderna trial and, and, you know, families potentially, depending on what the trial is for sacrifice a lot to put to put themselves or a loved one and into a trial. And we don't talk really about, you know, the placebo arm, right that we think we're giving people something that will work, but half the people or 25% of the people in most of the, you know, child COVID vaccine trials, got placebo, they got something that could have worked. They they lost the opportunity to get something that could have worked. And so we don't talk about that cost. I think that's a really important point.


Ben 39:20

Ken, so since we're talking about that, in the serendipity section of the book, you talk about this story of Jesse Gelsinger, which I think is a phenomenal story because you can you tell the audience about who Jesse was and how his story is, is important in the context of the book.


Speaker 3 39:36

Right so So Jesse was a 19 year old young man from Arizona who had a genetic defect he his liver did not make an enzyme, which had the fancy name one of the TransCarbamylase that allowed him to sort of effectively process proteins and eliminate ammonia from his bloodstream ammonia just like the ammonia used to clean the floor. So he therefore periodically because of this lack of an enzyme, he would go into a coma. And so so because it was very hard for him as a as a young man as teenager and older to, to stick to this 30 pill regimen, strict diet, I mean, it was very hard for him. So he wanted to then volunteer for this trial, which is close to my heart because it occurred at the University of Pennsylvania, which is where I am. So Jim Wilson was the head of that trial. And he, it to his credit sort of slowly went forward, trying to find a way to give Jessie Gelsinger the gene that he lacked. And he did it by really the same way. We have the Johnson and Johnson or AstraZeneca vaccines, which is you take a replication defective adenovirus meeting and adenovirus common cold virus that doesn't reproduce itself, you insert the gene into there, and then that that vector serves as a Trojan horse course to bring the gene into the cell. And he showed it with lower doses, somewhat higher dose, somewhat higher doses, there was a woman just before Jesse who got the same dose he got who did well, but when he got it, he was overwhelmed. He had what looked like invasive bacterial disease. It was only later learned that the problem was he had this sort of hyperactive component of his immune system called interleukin six, which really led to his demise. Even if we'd known it at the time, it wouldn't matter if there was nothing specifically to lessen the amount of interleukin six that monoclonal antibody didn't come around till later. But but in any case, what was striking to me about that story was that when a little girl named Emily Whitehead got something called car T therapy, which is basically she had acute lymphoblastic leukemia, she had failed chemotherapy twice, she was on the road to dying. She then became an early receipt of of this particular therapy where they took out her an immune cell called T cell, they re engineer it to kill her her cancer cell. And it worked. But she had the same reaction he had now years later, they realized what it was they found out she had high levels of interleukin six, they gave her this monoclonal antibody called totalizm and saved her life. And so she then became she was she met President Obama, she was on NBC NBC morning shows and other morning shows, and she was a hero. And if you go to the car T Lab, which is Carl June's lab, at University of Pennsylvania, what you'll see is pictures of Emily Whitehead pictures of her beating Obama or being on the dateline NBC or today's show. Well, you don't see your pictures of Jesse Gelson. Because because we were much more comfortable celebrating our successes than the failures that led to those successes. Yeah,


Ben 42:31

can you? That's exactly. I mean, that's exactly what I wanted to get you. Why do you think we have such a problem showcasing and commemorating the people that unfortunately suffered and passed away for us to know a tiny bit more and get us further along? Like you said in the book, I think you said, there's no, there's no statue of Jesse like next to Rocky Balboa or something, something along those lines. And I resonated with that. It's like it's true. It's thanks to his sacrifice in a way that we Emily was able to survive. And yet, why why are we not doing more of that as a collective field?


Speaker 3 43:03

Because I think we see as a failure, I think we saw Jesse gunslingers a failure. And even though I would argue I'm trying to argue in this book that these, this always happens at some level. And the point is not that we're going to avoid them, but rather to learn from that to be made wise from your, your, your failures, and not nervous by your failures, so so that you don't stop doing research, which is really what happened with gene therapy research. I mean, we were so paralyzed by that event that we sort of, really, that really slowed down gene therapy research for years because of it. And I think so that's a trick to be made wise by your experiences, not nervous by your experiences. But it's very hard for us to accept I'm not I'm not just talking about us, like the public. I'm talking about us scientists, Doctor. Yeah, that we see that as a massive failure.


Ben 43:47

I think that's the quote, that's the quote that I take from the book, and then I'll talk I'll stop talking about the book, but you say humility, not hubris should roll the day. And I think that's something that like I actually wrote down in my notebook, and that's coming with me everywhere I go, because it's always should be the our moral compass. Anyway, sorry. Definitely.


Daphna 44:06

No, I, it's such a good point about how we kind of we, it's not that we try to hide the failures, but we really consider those things, even though they were they were trials, and people knew they were trials is failures. And I wonder if that's a way that given this time of distrust in our medical system and disinformation. Can we align with the public by showing our humanity and saying, I mean, we're taking this seriously because every day that passes and we see 1000s of deaths, I mean, that is like, we take that on and certainly people in public health I mean, they are they're lighting their hair on fire, because because it pains them to see people dying, especially if we have something that is, you know, for severe defeat the severe disease vaccine preventable so How, how have we missed the mark? How can we align with the public to say, you know, we were doing this not because we want to be right but because we, we were feeling desperation at the amount of lives lost.


Speaker 3 45:13

Right and to and to be perfectly willing to to show our heart and express our humility. When in the lead up to the the two mRNA vaccines, the CEOs of both Pfizer moderna started talking about how they could make when they basically done phase one trials involve, like 15 people, 25 people, we can make 10s of millions of doses, there was a real lack of humility there. I mean, don't fool around with Mother Nature, because she's going to bring you to your knees as you learn more and more. And I remember saying that on one of the CNN programs, I think it was John King's program inside politics. But I said that I said, you know, we need to have humility here. And and he loved that, which is to say, I think the public would love that notion that we are learning as we go and just set that right at the beginning. Because we all want the same thing. You had a virus, which was killing people, we have the technology to do something about that. But there will be bumps on the road. And so so we can, on the one hand extol the virtues of the fact that thank goodness, we're living in an era we can make these kinds of vaccines, but realize these are novel strategies. And we're going to learn as we go and do those things at the same time. And I think it wouldn't be appreciated. Yeah.


Ben 46:20

And I think that's because the gap between humility and honesty is very short. And people realize that if you are humble, you are also being honest. So I think that that's, that's


Daphna 46:29

no, I think you've been very brave. Right? You, you, you told us about your schedule today. And you I mean, you are if people invite you to come talk, you'll you'll come talk to people. And for example, you've been on Twitter since 2009. A lot of physicians are afraid of engaging with the media or engaging with social media. Why do you think it's so important for physicians to put themselves out there?


Speaker 3 46:55

Well, I think we're now more than ever, I think science is losing its its voice as as as a place of truth as a source of truth. There's just becoming yet another voice in the room that people simply declare their own truths, their own scientific truths, right about vaccines, or whatever. And, and because of that, and especially on social media, I think we need to really just try and do that you assume that other people are doing it that other people are communicating good science and good medicine, but they're not. And, and so get get in the game, get out there. And don't don't don't read the comments.


Daphna 47:30

Well, I mean, you you, you spoke a little bit to that right about how much hate mail, you get, and I say your Twitter feed. I mean, most of the comments are positive, but they I mean, there's right, there's commentary from I mean, all all sides. How do you deal with that? Like how emotionally when you when you've dedicated your life to this? How do you how do you emotionally deal with it, you know, when you're at home, by yourself or with your family? With getting this kind of backlash on social media?


Speaker 3 48:01

Well, the drugs help. That was a joke. segment out here. Just kidding. Um, I mean, you know to do doing the right thing isn't always an easy thing. I think that when you have to learn, and it's not an easy lesson is that I mean, as a scientist, participating in national international science means it was always about the data, you know, you're just, you're presenting your data, and then you're opening up those data to be criticized, you understand the rules of the game. Once you do this, it's not science anymore. It's politics. And that can get ugly and mean. And so then some and personal and you just, you know that you know, that that's part of this. And just I deal with it with a lot of denialism. I think especially I get threats. I mean, this is where my children actually had been threatened at one point years ago, you know, it just, I just try and think, okay, these people just want me to stop talking. This is how they're get trying to get me to stop talking. But just move forward. Don't Don't, don't just just don't, don't look back, just do what you think is right. And at some level with this sort of my stance on booster dosing, which has been a little adverse to what the public health messages, I mean, I still am waiting to see data that shows that young healthy people need a booster dose to be protected against serious illness. I never saw that we voted no to that twice on our FDA vaccine Advisory Committee. And I'm telling you, if it had come to us a third time we would have voted no again. And so so but that's that's contrary to the what's what's and so suddenly I was getting like, you know, nice emails from anti vaccine as always, you know, because you can't you can't go like even a little off that the the public health message or else you know, you're you're not on the team anymore. So just, that's all and then you're gonna be wrong. I remember when, when the virus first came into this country, march 2020. I was on Christiane Emin pours program on CNN International, right. So now just millions of people so if you're, if you're going to be wrong, don't just tell your friends something's wrong. It's all the world wrong. So so she said to me, you know, how bad is this going to be? So I looked at China, the size of that country, how many deaths had been there, I looked at Italy, the size of their country, how many deaths had been there, and Italy, which, certainly in Northern Italy didn't have the healthcare system I thought we had here. And I said, you know, I would be surprised if we had more than 60,000 deaths here. And you know, I've only off by about a million deaths. So that was about but you know, so you're always going to be, you know, just, you know, realize that you're not always going to be right.


Daphna 50:26

But in fairness, you you use the data you had at hand, we I think we just have to underline that we use while we could do is use the data we have in hand.


Ben 50:36

So we're getting close to the end of the show. And so I wanted to move a little bit away from the discussion on vaccines and talk about obviously, the reason why we're doing this podcast is because we're really excited that you will be featured at the first annual Eastern medical research conference sponsored by ESP RNA FMR. And you will be receiving an award for mentor of the year. So first of all, congratulations. But I wanted briefly for the time that we have left, if you could talk to us a little bit about what is your vision of mentoring? And what does what is the role? And how does a mentor mentor somebody you in a few words?


Speaker 3 51:11

It's hard question sort of like, how do you how do you be a good friend, I think, you set an example. That's where I see it. I mean, you do what you think is right. And also, I really try and equip especially with our fellows now incorporate them into when I'm asked to write a commentary piece, or whatever, to really bring them in and let them you know, let them thrive. I mean, I think the goal of failing when I had a lab for 25 years, or now I'm just you know, you you want to try and beat a path for them so that they have the biggest most chance, greatest chance of success. And don't be afraid to give give away stuff. I mean, when I had a lab, you know, there were certain projects that I that I loved, and but you know, I knew that that the graduate was going to he was going to be leaving the lab. And you know, you want to give them things so that they can succeed, which means you're taking a little bit away from yourself and you, you have to be willing to do that. Because you've had your time. Now it's theirs.


Ben 52:04

It's funny, we interview a lot of greats of medicine, and this, this idea of the tide floats, all boats is coming back again and again. Where were you by sharing everybody, everybody stands to benefit. So I'm not surprised that you would mention that. My last question then is the other side of this coin is, is if you're looking for, if you're looking for mentoring, how do we approach a mentor? And what should we expect to get out of the mentors, specifically,


Speaker 3 52:34

picking a mentor, if that's you, you want to look at talk to the people who that person is mentoring, and suggest how they perceive this person. It's just what you said, I mean, see abundance theory you want, you want to believe that that the person is enormous ly generous of their time, and of the projects, which you may be walking out of the lab with, and that they have that you have their time, you know that they're not so focused on themselves in their own career, that they see it the way you would like them to see it, which is that they're there to, to help you to help you. You know, just as you were there, you know, I have two children, at my job as a parent is the same in many ways. It's my job as mentor, which is to find the best way for them to succeed.


Daphna 53:16

I love that I love that. I, we talk a lot about work life balance on the podcast. And I mean, how how do you do it all? I mean, it's obvious that you love what you do, and you have real passion for the work. But you again, you, you were you disclosed briefly what your schedule looks like? I mean, where do you find the time to write? Where do you find the time to pick up a hobby? Spend time with your family? How do you make it all work?


Speaker 3 53:46

Right? Well, when the kids were little, I would get I get up early, generally I get up around 430 or so for 430. And so I usually write and then, you know, then the day starts, but write a research for what I'm going to be writing and then the day starts the because I just really enjoy writing. I mean that for me in many ways is a hobby. So I enjoy the process of writing. And then for the kids I mean this so my wife was a general is a general practicing pediatrician, so she would often go so I would always have the kids in the morning and and we would you know, so I always had them for breakfast and you know, we played who wants to be $1 here, you know, we also I also taught them how to play Texas no limit Hold'em, because I thought that was important for that growing up. So they both knew that and so that was I had them every morning and then you know, I was always always home for dinner, you know the and made dinner often, you know, because we both were working and that's where we're going whenever I was asked to speak in a foreign land, I would not go unless I could bring a child and so that was always the deal. So they for they've been to Japan well before my wife ever got to that was fun. So you had to incorporate them into your life but you know, it's hard it is it is hard to maintain that work life balance.


Ben 54:56

My dad taught me how to how to play Texas Hold'em poker as well. That's


Daphna 55:01

a key life skill, a key life skill. We all you've given us a lot, actually, I think for our listeners to to use in their day to day work. I did want to touch though. My last question and then I'll let Ben close out the show is that where do you think for our listeners, which are majority neonatologist, neonatal health professionals play a role in the vaccine discussion. So obviously, neonatologist has been have been advocates for things like synergis, which, of course, is not truly a vaccine. And I think we do quite well at advocating the importance of that. But for example, we're frequently the first people parents, see who may not have gotten their T dot vaccine or their flu vaccine, or now the COVID vaccine, and they're taking home a child with high risk. How, you know, how do we get into the conversation safely, comfortably, and an advocate for those parent vaccines, but also the routine childhood series, maybe it's part of our discharge, anticipatory guidance,


Speaker 3 56:08

you know, especially because you deal with children and variably. They're born prematurely. But that doesn't, and so therefore, the parents are more likely to see their children as vulnerable, and therefore, they're more likely to see them as potentially having higher problems with safety issues regarding the vaccine. And so they'll still think, okay, the better choice, the Safer Choice is not to vaccinate or to dramatically delay vaccination beyond the period that be delayed. But again, I think that where you can help is to make it clear that, you know, some of these viruses and bacteria are still out there. You know, pneumococcus, for example, that are salicylate, I mean, those those diseases are so Measles is unfortunately becoming increasingly more out there. And that they're right at some level that their children are because they're premature, somewhat more vulnerable, but they're also more vulnerable to the to the wild type virus or the bacteria. And so this is the Safer Choice. This is the better choice. I mean, here we're doing everything we can to keep your child safe by doing all these things here. This is another thing that keeps them safe.


Ben 57:08

Thank you. Well, that was that was a fantastic encounter and a chat. Paul, thank you so much for taking the time, I wanted to congratulate you again on winning the award for mentor of the year and congratulations on your latest book. Again. We'll have a giveaway set up for our listeners. We're going to win a couple of your books and a few more items sponsored by the ESP RS is the Society for pediatric research. So yeah, thank you so much for your time and good luck on the rest of your busy day, I guess.


Speaker 3 57:38

Thanks for asking me the winners get the books right just so I'm getting


Ben 57:43

it. Thank you for listening to this week's episode of the incubator.



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