How was the polio vaccine developed?

22:17But to be honest, I didn't look too much into why. I didn't look for conspiracy theories. They're so easy to find most of the time. All right. And so at this point, we have vaccines already for other diseases, right? So it must have been like on the radar, like let's get a vaccine for polio. Yeah. And so our early research into polio, unfortunately, set us on kind of the wrong track. So there was a guy named Simon Flexner at the Rockefeller Institute, and he was trying to infect rhesus monkeys to understand how the virus is transmitted. But one of the hard things about studying human diseases in other animals is that sometimes it works different in those animals.

22:54And so in the rhesus monkeys, the way you got them infected was you swabbed their nasal passage, and essentially you were sending the virus, like, really close to the nervous system. and so the rhesus monkeys got polio but if you put it in their mouth and had them swallow it they didn't and so there was this idea that the only way polio could get to people is if it went directly into the nervous system and that you couldn't get it by ingesting it and that's bad for a couple reasons so one it's throwing off your understanding of how the disease is actually transmitted which means public health measures are harder to to create and the other thing is it suggests that the virus is never passing through the bloodstream.

23:33And that is your best chance at hitting it with your immune system. So if you're going to have a vaccine, it's probably going to create antibodies that will be in your bloodstream. And if the virus is never in the bloodstream, how's your body going to attack it? All right. So now you've questioned your immune system is only in the blood or is that where most of it is or what? Your immune system is in lots of places. But my understanding is that the strongest part of the immune system and the part of the immune system that gets activated by vaccines tends to be in the blood. Yeah. And since we're doing an immune system primer, what is an antibody exactly?

24:08Is it one of these like crazy white blood cells that you see on those videos, like searching around and killing bacteria? Ah, no, not quite. So your immune system makes an antibody when it encounters a pathogen for the first time. And what the antibody does, it's like a protein and it binds to the pathogen. And one of the things that it does is it keeps the pathogen from, for example, getting into a cell. So this could keep polio from getting into a nervous system cell because it's essentially like blocking it from doing anything that it wants. Another thing that it does is it flags the pathogen so that those white blood cells can then find it.

24:43So it essentially is like, white blood cells over here, I've got something. And so you make antibodies that are specific to different kinds of pathogens. So if your body encounters the polio virus, it will create antibodies that remember the polio virus. And so the next time you encounter polio, your immune system is ready to attack it right off of the bat. And you say remember, and that makes me think of like, you know, I remember somebody's face and I have no idea how that works inside the brain. How does it work for the immune system? Is it like it builds some protein which latches on to the something on the surface of that thing?

25:16I'm totally guessing here. How does it work? Yeah. So I think you are the amount of antibodies that you have for a specific pathogen does kind of go down over time. And like you may have had the experience where you go to get a booster vaccine. And so sometimes your body does seem to sort of forget if it hasn't seen something for a while. And so you're essentially just reminding your immune system like, hey, this is a bad thing. You should be prepared. And it's not like it always has loads of antibodies for all pathogens it could possibly encounter. But there's some of them in there. And then the number of them can be rapidly increased if the pathogen is encountered again.

25:52I see. And so you're saying remember and forget. It's sort of like anthropomorphizing our immune system. Really, it's like, do you have a bunch of antibodies for this or do you not? Absolutely. Yep, that's right. Cool. All right. And so it's a big challenge to develop a vaccine for something if it doesn't go through the blood, if it just like bypasses our major defense system. So what does that mean about developing a vaccine? What else can we do? Well, so it turns out that Simon Flexner, because he had studied rhesus monkeys, he thought it never went through the blood. But he was wrong. He was wrong.

26:23He was wrong. And he was wrong because he was studying monkeys. And polio is different in rhesus monkeys than it is in humans. In those monkeys, it can only get in through the nose if you put it really close to the nervous system. But in humans, we can get it through our mouth. And then it goes into our stomach and into our lymph nodes. And then it goes into our blood before it goes to the nerves. So you do have a shot. But for a long time, we were all sort of thrown off track by this research that didn't quite get it right because the animal model set us on the wrong track. All right. So bad news for the rhesus monkeys, but good news for humans.

26:57Eventually good news when we figure it out. When we figure it out. Yeah. All right. So let's take a break. When we come back, we'll hear more of the saga of how we developed a polio vaccine. The twists, the turns, the ups, the downs. Get your popcorn and get some tissues because it's going to get emotional.

27:20Hey, everybody. It's the Jonas Brothers. This week on the podcast, Hey, Jonas, we're so excited to be hanging out with Mika Abdallah from the hit show Off Campus. Congratulations on the massive show and massive success. Got through about episode five. I left the next morning to go meet the guys. Came back, was like, cool, let's pick up where we left off. And that series had been completed without me. Oh, no. Oh, that's like the number one rule of watching something. It's literally cheating. That's crazy. We talk about what it's been like watching the show become such a massive hit. What's next for season two and just how close the off-campus cast really is.

27:52We're genuinely so close. What's the group chat called? If you can say, if it's allowed to be said on the pod. That's a great question. One of them is off-campus Brazil. Okay, love it. Shout out Brazil. Shout out Brazil. And then the boys have their own group chat called Dean's ****. Our conversation with Mika Abdallah is out now. Go check it out. Listen to Hey Jonas in the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. What did Black music, food, and culture teach us about who we were becoming? 2016 was sort of that last era of monoculture where we still consumed things in community.

28:33From Beyonce and Rihanna. Everybody wanted to be Beyonce. I don't think we'll ever see another Rihanna. to soul food, memory, identity, and the stories we carry through Black culture. What does it mean to be Black and eat in America? So we were this group of people who knew how to work the land, who knew how to live with the land. We make it do what it do. Therapy for Black Girls is bringing together the conversation shaping Black life right now. You will never make me feel bad for being a Black girl, for being a Black American girl, ever. Therapy for Black Girls is bringing it all to the mic.

29:04Listen to Therapy for Black Girls on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. It's Latino USA. I'm Maria Hinojosa. I sit down with New York City Mayor Zora Mandani to talk about sports, immigration, politics, and the serious question of what makes a great New York City taco. But Mr. Mayor, as a Mexican, What have I done? What makes the best taco in New York City? Oh my God. Listen to Latino USA on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. I'm Manga Shatigular and I'm back with a new season of the podcast Skyline Drive. This time I'm diving into a rabbit hole of peptides, organoids, blood boys, blue zones, and brain replacement to try to understand what this longevity obsession is all about and what it really means to live forever for all of us.

29:56I learned about some rad science. I can make a brain for you, and then we can test what draw is the best for your brain, as opposed to his brain. Here are some hard truths. I would expect Indians to age faster, but I did not expect it to be almost a four to five year acceleration. And get myself into a world of trouble. I'd say probably start bone smashing. That doesn't work. Make it look more defined. They say it works. I don't know. Listen to Skyline Drive, How to Live Forever on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

30:47All right, we're back and we're telling a story of how we developed the polio vaccine. Kelly, what is the next step in this story? Well, you know, like so many scientific endeavors, the next step is get the money because it's expensive to do science. And the story for how the vaccine got funded starts with Franklin Delano Roosevelt, who in 1921 at the age of 39 got polio himself and his legs were paralyzed. In 1924, he hears that this person went to these nice warm springs and by going in the warm springs and moving his body around in the springs, he was able to walk again. Oh. And FDR was like, whoa, what?

31:26That's great. I'm going to go. And so he goes and he falls in love with the place. He feels like actually he can move a little bit better in the warm strings. That might have been a placebo effect. But also it's just sort of nice to have a lot of your body supported by the water. And the warm water probably felt pretty good. Hot tubs are fun. They sure are. Yes. And so he decides, you know what? I love this place. I'm going to buy it. Wait, I'm going to buy it? I'm going to buy it. Yes. He came from a rich family. So he was like, I'm going to buy it. I'm not just enjoying the hot tubs. I'm in the hot tub business now.

31:56Wow. Cool. Yeah. And so he buys it, but he buys it and tries to make it a place where lots of polio folks can go. OK. And so he will sometimes even charge people less if they have polio and they want to come to the Warm Springs, but they can't afford to. And that's great. But he's having trouble making money, one, because he's giving people all these discounts, and two, because it turns out people who don't have polio are worried about getting into the water with people who do have polio because we don't know how it's transmitted. And so this place is financially going down the tubes. Come soak in hot disease water doesn't really work, it turns out.

32:30Yeah, right. Yes, that's right. You know, for these patients, the polio had passed through their body. They were so paralyzed, but they almost certainly weren't shedding virus anymore. So it probably was safe. But, you know, stigma being what it is, people were staying away. Nobody wants to slip into polio soup anyway. Yeah, that's right. So in 1928, FDR becomes New York governor. and in 1932, he becomes pregnant. Pregnant, oh my God. In 1932, he becomes - What an accomplishment. Yeah, that's right, that's right. Who knew polio was the key? Anyway, all right. So in 1932, he becomes president and he no longer has time to run Warm Springs.

33:11And so his work colleague, Basil O 'Connor, takes over and he's trying to figure out how he's gonna take this financial disaster and turn it around. And he essentially starts a campaign that's sort of focused on FDR where he says, hey, let's start to raise money for polio by having like big gala balls. And eventually he brings in famous actors and actresses to try to raise money. And this becomes the National Foundation for Infantile Paralysis, which ultimately becomes the March of Dimes, which I think a lot of people have heard of. And this is why FDR's face is on the dime. Oh. Because this, yeah, this became like a super popular thing.

33:51Well, they raised loads of money. A lot of their money was spent on helping to care for people who were paralyzed. And so they offered a lot of support for polio victims. But they also saved a bunch of money for research. And so this is how the research is going to get funded. So if you're out there and you're a disease and you're listening, it's a bad idea to infect a white guy who becomes really important because those are the diseases that get attention. I wish that that were otherwise. But no, you're right. And in fact, there's a pretty good argument that you could make that polio in particular was getting a lot of attention because it tended to hit the middle class.

34:27And so there was this idea that maybe because the middle class were living in like super sanitary environments, they were more susceptible to polio. But it was this was a disease of like upper middle class white people. And that is probably part of why it got so much attention. Yeah, unfortunately, folks in government need like a personal connection to some kind of experience before they take action sometimes. It's too bad. Anyway, it's good news that there was a lot of research money towards developing a vaccine. It's a bummer that FDR had to get polio for that to happen. But then how did that research effort kick off?

35:00All right. Well, so first they had to decide what kind of vaccines they wanted to fund. And it turned out there were two competing camps that both felt very strongly. And the competing camps were live attenuated virus. So you essentially get a wimpy version of the virus and inject that into people or a killed virus where you kill the virus before you inject it into people. But you make sure that you haven't like totally destroyed it. You need your immune system to still recognize it. Okay. And did we have working examples of both in other diseases? Yes. The live attenuated virus was pretty common at the time, and it was thought that that was the best way to make vaccines.

35:40But Jonas Salk early in his career is going to get experience working on a killed version of the influenza virus. Oh. And he's one of the people who helps develop the first flu virus, and that kind of convinces him that killed viruses are the way to go. But there's a couple problems. So the live virus people argue that a killed virus will never stimulate the immune system as well. And so you might get weaker immunity or immunity that fails more quickly. And they're concerned that it's going to be really hard to be sure you've always killed all of the virus. Like if you've got a batch of virus that is alive and then usually what happens is they put formalin or formaldehyde in there.

36:23How can you be sure that it got to every single virus particle? How can you be sure you're not going to give people polio? Oh, my God. Imagine injecting polio into some kid. That would be terrible. Yeah, hang on. We're going to get there. Oh, no. And so, yeah, I know. It's a sad story. And so the problem with the live attenuated virus is that viruses mutate. And so a virus that has been made sort of wimpy over time can mutate and go back to being really bad. and when you make a live attenuated virus people shed that virus and it gets into the environment and so anywhere people are defecating you've now got this polio virus in the environment and you can't really control where it goes and what it does yeah both of these seem like bad ideas now kelly you got me almost over the end of that the lesson at the end is going to be that we have really good protocols for killing viruses now and it's been going well for like 50 or 60 years.

37:21There have been no mistakes as far as I know. All right. So what were some of the early tests? How did they go? Okay. So one of the early trials is called the Park Brody vaccine, and this is named after the two scientists who worked on it. And this was around 1934, and they essentially infect monkeys with polio, grind up their nervous tissue, and add a little bit of formalin, hoping the formalin will kill the virus. And they first give it to 20 monkeys, and the monkeys make antibodies to polio, which suggests it works. And then they try the vaccine on themselves. And it goes pretty well. They gave the vaccine to themselves.

37:55They did give the vaccine to themselves. They were pretty confident. Wow. Okay. And then they give it to 12 kids and it goes okay. Okay. And so they say, hey, we've got a safe polio vaccine. And they start scaling things up really quickly because everybody really wants a polio vaccine, right? And so as soon as there's like evidence that you've got something that works, people start scaling up. But the problem is it wasn't really safe and it might not have been protecting against polio. So but before they scaled up, they must have had some evidence that it was working. Was the evidence just that it was creating antibodies in the humans?

38:30And that doesn't mean necessarily that it's protecting against polio. Having antibodies isn't enough. One of the lessons we're going to learn from this is that there hadn't been enough basic research before they started making the vaccine. And it turns out there's three types of polio, not just one. And so you can protect against one type, but someone can still die or get paralyzed by some of the other types. I see. And so they didn't have complete protection. And then the other problem was we didn't know at the time that there's a lot of people who will have very strong immune system reactions to monkey nervous tissue.

39:02And so some of the nervous system cells were still in the vaccine and people had like massive abscesses and their whole body would be inflamed and kids were getting super sick from this vaccine. And it was because of the monkey cells. At the same time, this guy Comer is making another vaccine. But this one is a live virus vaccine with a wimpy version of the virus. This was in 1935. He also vaccinates himself. He vaccinates his two kids. Oh, my gosh. And so he must have been confident. And then he vaccinates 23 other kids. Whose kids are these kids? Right. So sometimes. Trick or treat. Jab. Jab.

39:42Well, you know, if somebody confidently told me I can protect your kid from polio, there's some chance I'd be like, I wouldn't want my kid to be the first one in line. Yeah. But I can imagine why he was able to find 23 kids. Well, it's a terrible decision to make. Like, do you maybe take this vaccine that protects your kids or do you not take it? And then they're still risking their lives. There's risks either way. Yeah, there absolutely are. But he then goes on to vaccinate 10 ,000 kids. Wow. So a pretty big trial and at least a dozen kids get paralytic polio from his vaccine and nine of them die.

40:16Oh, my gosh. Yeah. And so there's a scientific conference where the Park Brody vaccine and the Colmer vaccine are discussed. And it's a bunch of polio scientists. And at the end, essentially, Colmer gets accused of murder by one of the other scientists. And he says, gentlemen, this is one time I wish the floor would open up and swallow me. Oh, my God. He must have felt terrible. He felt horrible. And Brody dies at age 36 or something of a heart attack. There's some argument that maybe it was he brought the heart attack on, you know, purposefully. But anyway, really horrible episode for everyone involved.

40:51And the lesson they end up taking away from this is that we need a lot more basic research. And these guys were all acting in good faith, right? Maybe they rushed a little bit. Maybe they got unlucky, but they were trying to do good. Yeah. Yeah. And, you know, I think that Comer, who tested the vaccine on his kids, he must have thought he had the solution or he didn't like his kids. Wow. One or the other. I was trying to say these people are not monsters. They're not villains. But you're like, maybe he hates his children. No, I'm just joking. They're not monsters. Like they really. No doubt part of them was thinking, I will be a really big deal if I solve this polio thing.

41:28Right. I can't imagine that that wasn't on their minds. But I do genuinely believe the fact that they tested it on themselves first, they tested it on their kids, that they really – they were trying to save lives. I think their intentions were good, but they rushed into it and they didn't realize how little we knew, I think. Well, it's a tragedy either way. It is. So then we did a bunch of basic research to understand polio and the immune system better. How did that help shape the next step in the vaccine story? Yeah, so the next thing that we wanted to do was work on figuring out how many types of polio there are.

42:00So it became clear to us that that is a question we didn't really have a good answer to. And this is where Jonas Salk comes in. So I think a lot of people have heard of Salk. He's, you know, a fairly famous scientist. His family were Jewish immigrants from Russia who moved to New York City. Yay, scientists as immigrants. Yay. Oh, there's a lot of stories of scientists as immigrants here. They're like, we have a lot of immigrants to thank for protection against polio. It's almost like we should be welcoming smart, hardworking people into our country, especially if they bring expertise and want to help us.

42:29Yeah. You know, I think you and I try to not be political on the show very often. I don't think that's political. I don't think that's political. It's just common sense. I am 100 percent behind you. Yes, I agree. This is a small subset of the many immigrants who have made our country better. So, as we mentioned, Salk had some experience working on the flu vaccine, which was a killed virus vaccine. He did that at the University of Michigan with an advisor who we're going to hear about later, Thomas Francis Jr. But then he starts his own lab at the University of Pittsburgh. And when he's at the University of Pittsburgh, he meets a representative for the National Foundation for Infantile Paralysis.

43:05This is the funding agency we were talking about before. And they're like, hey, look, you're starting up a lab. You clearly need a lot of equipment and some extra space. What if we gave you a bunch of money to try to figure out how many types of polio virus there are? And he was like, I need money. I'm in. And so he starts typing polio. And he works on this for two years from 49 to 51. And he confirms that there are three types. The first type is the most common and it's the most likely to lead to paralysis. The second type tends to lead to asymptomatic cases, but sometimes it can still paralyze the unlucky.

43:40And type 3 is the most rare, but it's also the most likely to go after your brainstem and put you in an iron lung or kill you. Oh, boy. Yeah. So you want protection from all three of those. I certainly do. Yes. Okay. So around this time, there are some other really exciting advances. One of them being that we figure out how to grow the virus in monkey kidney cells in dishes rather than nervous system cells. And so now we're in a position where if we need to grow up this virus to make vaccines, we don't have to be doing it in monkey nervous systems anymore. And we don't have to worry about that horrible reaction the first set of kids had to monkey nervous system tissue.

44:19All right. That's good news. That is good news. And then a woman named Dorothy Horseman, while doing some experiments, realizes, hey, actually, polio does have a phase where it goes through the blood. At this point, we knew that sometimes it gets in through the stomach, and she figures out that sometimes it goes through the blood on the way to the nervous tissue. And she's like, hey, that's good news. We might be able to make a vaccine. This is promising. But then she stopped working on that question. But now it's in the air that you could go after it in the blood. So in 1951, Salk starts. growing the virus in the lab, and he has to pick the three strains that he wants to use.

44:57So he knows that there's lots of different, like, even if it's just type one, there's still different kinds of strains, and some of them are worse than the others. And so what he does is he puts the poliovirus into kidney cells. He gently rocks it in an incubator with nutrients. He gently rocks it? Well, not like, you know, not like with a foot on a bass and at night. Yeah, exactly. I'm sure he had a piece of equipment that was, you know, moving it around on a tray. He's whispering sweet nothings to it as it grows. That's right. Come on, babies. You got this. Okay. There is something kind of macabre about growing them up just so you can kill them and then kill all their brethren, right?

45:35But all right. Anyway, go ahead. So you grow up all these polio vaccines in these monkey kidney cells. You're growing up all these polio viruses, right? I got to say, I don't feel bad for them. Yeah. So then you filtrate out as much as you can to make sure you're just left with viruses. And viruses are really tiny, so it's pretty easy to filter them out. But remember, some nervous system cells got through the last time, so you got to be careful. And now he tries to kill the viruses with formaldehyde. Formaldehyde is a super nasty chemical, and it's hard to do because you need to be absolutely sure that every time you do this procedure, you kill all of the virus.

46:13Yeah. Any free living virus can really cause some trouble because one of the types that he picks is a super virulent strain called the Mahoney virus. And he picks it because it would be really good to have resistance against this particular strain. It's very common. It's very lethal. So he decides to go with it. But you got to be sure you kill it. And so they worked really hard on this procedure. And one of the things you got to be worried about is if at any point your vial sits for too long, stuff can sort of accumulate at the bottom and form like clumps. and virus particles in the middle of that clump can stay alive and kill things.

46:48And so at this point, he's using what seems like an established procedure. You take the virus, you mix it with formaldehyde, you have a killed version of the virus. There's no innovation yet, right? That's 100 % right. That's a really good observation. And that is going to continue throughout a lot of this story. Salk didn't really do anything 100 % new. He was taking procedures that other people had used and he was the first one to sort of put them together and get it right, that's important. Other people had not established a protocol that definitely killed all the virus every time. But Salk manages to do that.

47:21Wow, interesting. Yes, and so he eventually gets something that's worth trying, and he tries it on monkeys, and it goes well. And after the break, let's talk about how he starts his human testing.

47:41Hey everyone, it's the Jonas Brothers. If you haven't heard, our new podcast is called Hey Jonas. And this week we're hanging out with someone we're really big fans of. Millie Bobby Brown. That's right. Eleven herself. We talk about her new movie, Enola Holmes 3, Family Life, and all the amazing things she has going on right now. This blew my mind when I saw this, Millie Bobby Brown. You have over 60 animals. First of all, how do you even keep track of everybody? And second, do you have favorites? Who are they and why? Yeah, I need to know about this. Okay. I don't know where the number's 60. I've really got to figure that out.

48:13And I could actually have over 60. I just need to really know that number. There have been plenty of sheep in my bed. It's a big bed. In the bed. Literally sleeping in the bed. Yeah. Plus, we find out what she really feels about Stranger Things ending. five seasons, almost 10 years of your life. I could have never have guessed it. I started when I was 10 years old. Our conversation with Millie Bobby Brown is out now. Go check it out. Listen to Hey Jonas on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. What did Black music, food, and culture teach us about who we were becoming?

48:462016 was sort of that last era of monoculture where we still consumed things in community. From Beyonce and Rihanna. Everybody wanted to be Beyonce. I don't think we'll ever see another Rihanna. To soul food, memory, identity, and the stories we carry through Black culture. What does it mean to be Black and eat in America? So we were this group of people who knew how to work the land, who knew how to live with the land. We make it do what it do. Therapy for Black Girls is bringing together the conversation shaping Black life right now. You will never make me feel bad for being a Black girl, for being a Black American girl, ever.

49:23Therapy for Black Girls is bringing it all to the mic. Listen to Therapy for Black Girls on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. It's Latino USA. I'm Maria Hinojosa. I sit down with New York City Mayor Zora Mandani to talk about sports, immigration, politics, and the serious question of what makes a great New York City taco. But Mr. Mayor, as a Mexican, what makes the best taco in New York City? Oh my God. Listen to Latino USA on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. I'm Manga Shatikula, and I'm back with a new season of the podcast Skyline Drive.

50:03This time I'm diving into a rabbit hole of peptides, organoids, blood boys, blue zones, and brain replacement to try to understand what this longevity obsession is all about, and what it really means to live forever for all of us. I learned about some rad science. I can make a brain for you, and then we can test what draw is the best for your brain, as opposed to his brain. Here are some hard truths. I would expect Indians to age faster, but I did not expect it to be almost a four to five year acceleration. And get myself into a world of trouble. I'd say probably start bone smashing. That doesn't work.

50:46Make it look more defined. They say it works. I don't know. Listen to Skyline Drive, How to Live Forever on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

51:09Okay, we're back and we're talking about the development of the polio vaccine. And so far, Salk has discovered there are three kinds of polio virus. He's grown them up, whispering sweet nothings as he incubates them in monkey kidney cells and then he's mixed them with formaldehyde to kill them. And you said this was successful in monkeys. But we've seen that before, right? Yep, we've seen that before. And so it's important to note that at this stage, Salk also injects his vaccine into himself and his children because he's confident that it's going to work. But then he goes on to find a larger community that he can test it on.

51:44And here I feel a little bit uncomfortable. So he found the D.T. Watson Home for Crippled Children. Crippled is the word they were using at the time. He also reaches out to the person running the Pope School for Mental Defectives. Wow. Really, you know, from today, that is a pretty insulting name for the facility, but it was basically children who had some intellectual disabilities who were getting cared for there. And there was this general feeling in the community that this was a good population. So there was a sort of condescending attitude that this is some way they can contribute to society by essentially being these guinea pigs.

52:24And the implication there being that they weren't contributing in any way otherwise, which upsets me. Or that they're somehow less valuable because if something goes wrong, it's not as big a deal or something. Exactly. Yes. Yikes. Right. Also, you know, they are in one place and will stay in one place for a long time. So you can go back and test them and you know who they're interacting with. So there's a lot of things you can control with this population. So for better or worse, he gets permission to work with both of those communities. Now, the D.T. Watson Home for Crippled Children, most of those children who are disabled are disabled because of polio.

52:58And so what he does is he figures out by looking at antibodies in their blood what kind of polio they encountered. And then he gives them a shot of the same type of polio that he killed in his lab. And he thinks this should be a pretty safe way to test things because if I didn't kill all the virus, it's not going to be bad for them because their immune system is going to be able to respond. And I can see if they start making even more antibodies when I give them the vaccine. So they shouldn't get hurt, but they'll give us some information about whether or not we're stimulating the immune system.

53:29All right. So they have like natural immunity already because they've been exposed to the disease itself. That's right. OK. And how did that go? That went great, actually. And it went so great that they moved on to the other community. And when they moved on to the other community, this time, you know, these kids had no expected immunity to polio. They didn't have polio. You could check that with blood tests initially. and they are not sick after they get the vaccine and they start making antibodies and those antibody levels stay good for months. And these are some really good results. So he's super excited.

54:01Do you think by the way that they got parental approval to test it on these kids? Do you think the parents were like, yeah, go ahead and test it on my kid and I put it in the institution? Or do you think they just sort of did it without asking the parents? So in the interest of time, we skipped another vaccine story where Hilary Kaprovsky did not get good parental consent. And The Lancet even jokes about his use of the word, quote unquote, volunteer. And so there are some questions about consent that are raised earlier in the vaccine story. And so Salk had this on his mind. He contacted a lawyer to make sure he had insurance to cover him in case he got sued.

54:40And he worked with the state to come up with parental consent forms that were very clear about all this stuff. Yeah. So some lessons were learned there, which is good. And so he goes to write up his results to publish them in the Journal of the American Medical Association. But word gets out before his article is published that there is a polio vaccine that could start saving kids before the next polio season. Oh, my gosh. And so Salk is freaking out because everybody is like, oh, you got to give us the vaccine. And he's like, no, I'm not ready yet. This was like a small scale study. This is not ready for large scale distribution.

55:14And we learned a lesson from earlier rapid scale ups that we need to be careful. Yes, exactly. Right. And so he goes on a radio show and essentially tells the nation, look, we don't have a vaccine yet. We have some good results, but like I don't think we're going to have something for the next polio season. So we're working on it. But but now the ball is rolling. Right. And the National Foundation that's paid for his research is like we need to do a massive national trial. and Salk sort of gets pulled along. And so they give the protocol for making this vaccine to some drug companies and they say, okay, start making this vaccine.

55:50And now this debate starts about how do you design this nationwide experiment that's about to happen? And the big debate is about whether you want observed controls or double blind injected controls. So here's the difference. For the observed controls, they wanted to open enrollment to second graders and any second grader who wanted the shot could get it. And then they would compare polio rates in the second graders who got the shots to first and third graders. So similarly aged kids who were probably engaging in the same activities and then compare how much those two groups got polio. And I guess it's an issue there because there could be a bias because people are selecting, right?

56:30And there could be some confounding factor with that selection. Yes, exactly. There's a concern that the higher income families whose risk is a little bit higher might be more likely to enroll their kids in the trial. And low-income populations were less likely to get paralytic polio, again, for reasons we don't totally understand. But those two confounding factors made this experimental design not ideal. And so there were people who were pushing for signing up a bunch of kids who want the vaccine and giving half of them the vaccine and half of them the placebo. All right. So the first plan was observed controls, but this is the other plan, the double-blind study.

57:06Yeah, and Salk is pretty hard against this initially because he believes his vaccine works and it's not ethical to randomly not vaccinate a bunch of kids whose parents want them to get the vaccine. And in the human way that we often find imperfect solutions to our problems, what they ended up doing was in some places they use observed controls and in other places they used this double-blind placebo situation. So you end up with both kinds of data. And this lab at the University of Michigan collects and analyzes all the data. It was a massive record-keeping fiasco because, you know, you couldn't let the doctors or the kids know who was getting placebo and who was getting the actual virus.

57:47Because, like, if you give a doctor a vial and you say this has the actual vaccine, they're going to vaccinate their family like they're humans, you know. And maybe they're not going to give anyone the placebo. And so you have to actually make sure nobody knows. And then someone's job was to track down every kid that died that was part of the study and figure out, did they die of polio or could they have died of something else? So very depressing. And this is before computerized records. So this is like literally a lot of paperwork and scraps of paper. And oh, my gosh. It was a massive, massive undertaking.

58:18So Thomas Francis Jr., who was Salk's advisor, was the one who undertook this work. And it was like, you know, years of what his lab did was crunching these data. But right before this vaccine trial was about to roll out and they were about to start, you know, giving the kids the vaccines, some of the monkeys in some of the labs where they're testing the vaccine to make sure it's safe get polio. Oh. And it looks like it was just one monkey, maybe two, that actually got polio. And the system of checks worked, right? So they did say, okay, there's some monkeys that got polio. We need to pull those vaccine lots.

58:54There was something wrong with them. But it gets out. And this celebrity gossip show has a host named Walter Winchell, and he announces that seven out of 10 tested batches contain live virus. It's been killing monkeys. He starts a rumor that coffins for kids are being made and distributed around the world in advance of the release of the Salk vaccine. Sorry, not around the world, around the United States. But, you know, a lot of what he said wasn't wrong. There were monkeys dying of the vaccine. But that had been our way of catching a mistake in the vaccine process. But the word was out, and it's estimated that 150 ,000 children were pulled from the trial due to this broadcast.

59:35And in response to the monkey incident, they now have a protocol where companies have to submit 11 consecutive lots of the vaccine that they made. And every single one needs to pass testing before any are cleared for use. So if in a batch of 11, one monkey dies, then all of that has to get thrown out and you've got to start again. Yeah, they're trying to be extra super careful about it. So the vaccine trial happens. It's like the biggest vaccine trial in the history of the United States at the time. And it turns out, if you look at the data where we had that placebo, like the best quality data, the vaccine is 80 to 90 percent effective against paralytic polio.

1:00:19It's 60 to 70 percent effective against type one and 90 percent or more effective against type two and three. That is amazing. That's incredible. Yeah, that's incredible. And so the vaccine starts getting made in massive quantities. Six different drug companies start making it. And this is where we have a problem. So it was announced that like, hey, look, we're probably not going to have enough vaccine for the oncoming polio season. We'll have it for the year after. But parents really wanted it. Right. And so companies started scaling up production and some mistakes were made. And this is where I can imagine there could be some anti-vaxxers today that remember stories that their grandparents told them because there was a company called Cutter Labs from Berkeley, California that had some batches of vaccine where not all the virus had been killed.

1:01:08Oh, no. And so as these cases start getting reported, Cutter vaccine gets completely taken off the shelves. They actually stop all vaccines for a while until they can re-look at all of the different drug companies to make sure everything is OK. Cutter never ends up making more vaccine. The rest of the companies are given permission to go ahead. But now there's much stronger controls for what kind of tests the vaccines need to pass before they can go public. And in the last 50, maybe even 60 or 70 years, this problem has not happened again. So now that we've got these appropriate controls in place, we're good.

1:01:48And this is when the government started stepping in. So you probably couldn't get a vaccine trial run by a foundation that isn't government run again. And so this is part of how like the CDC and the National Institute of Health sort of grew in response to this situation. So let's real quick get to – so Salk sort of famously said something to the effect of you can't patent the sun. I won't patent this vaccine. But as you pointed out, Daniel, he actually hadn't produced any new procedures. He was very clever about taking preexisting procedures and being like absolutely anal retentive and creating a protocol that was fail safe.

1:02:24but he actually probably could not have patented his vaccine anyway because there were no new novel procedures. And he did talk to patent lawyers and they were like, yeah, you're right. This probably isn't patentable. So it's not just that he was like a really great guy, although he was a really great guy, I think. But it also was just that like there wasn't really anything to patent there. But at the same time, there was a competing vaccine. So Sabin is a scientist who was born in Poland in 1906. He ends up at the University of Cincinnati. He's also getting funded by the National Foundation. And he makes a vaccine with virus that he has run through animals multiple times until the virus is super weak.

1:03:04And he does this with all three strains. But the National Foundation just finished doing this national trial for the Salk vaccine. They're not going to do it again for a new vaccine when they've got one that works. And so he goes to Moscow. Oh. And the Soviet Union in 1959, they're like, this vaccine looks good. We like it. We're going to vaccinate 10 million kids. Wow. And so they vaccinate 10 million kids, and they essentially say, you have to show up at the school on this day or the factory on this day, and they all get vaccinated. They decide that actually went pretty well, and so they now decide they're going to vaccinate everybody who's under 20 years old.

1:03:43So 77 million people get vaccinated. Oh, my gosh. And so the Sabin vaccine starts making its way back to the United States. And this is after, you know, the Qatar incident where people are like, oh, maybe the Salk vaccine isn't safe anymore. And that starts to be on people's mind. And Sabin sort of capitalizes on this fear. And Sabin and Salk didn't like each other at all. They were definitely like not necessarily racing, but definitely competing. and the Sabin vaccine ends up becoming a lot more popular. And eventually at some point, people stop getting the Salk vaccine and they get the Sabin vaccine instead.

1:04:18Oh, wow. Both of these vaccines contributed in bringing the levels of polio down massively. But a problem with the Sabin vaccine, which we mentioned earlier, is that that vaccine is a live virus. And even though it's a weak version of the virus, there are parts of the world where when people get polio, what they're getting is this version that's in the vaccine. The Sabin vaccine causes polio in one out of a million doses. So this is the problem with having a live vaccine. And so at some point, the United States said, look, we have so little polio, but for one out of a million people who get this polio vaccine, there's a chance they're going to get polio.

1:04:57We're going to switch back to the Salk vaccine. So after doing the Sabin vaccine for a while, we switch back to Salk, And now everybody gets the killed virus version, which has been safe for 60 years. So some parts of the world still have polio, like Pakistan. But we are incredibly lucky in the United States to not have to worry about it. As we mentioned at the beginning of the show, you know, I get frustrated when I hear this quote, the good thing about science is that it's true whether or not you believe it. And it's like such a condescending attitude to give to people when there have been mistakes in the past, right?

1:05:33And I still think we have a right to say, hey, you know, if your kid wants to go to public school or if you want to be a health worker, you have to get these vaccines. I think we have a right to like mandate that kind of stuff. But I also feel like we have this massive responsibility to be super open and transparent about like what we're doing and how we made these decisions because we've made mistakes in the past. And I think it's reasonable for people to like want to be convinced and to, you know, and for you to need to make a good argument for it. Not that I think all the anti-vaxxers are anti-vax because they are familiar with this history.

1:06:06You know, the like 5G from a vaccine is kind of crazy. But anyway, I think these things are complicated. What do you think? Yeah, I think it's important that we share the process, that people understand how scientists come to these decisions, and also that science informs policy but doesn't dictate it. Like the questions of how do you develop a vaccine and the questions of should we inject this into children are different questions. One is science and one is policy. And I do think that it's important that people out there are educated in how science works so they understand where these decisions come from.

1:06:40Because, yeah, nobody wants to be told this is the truth and that's not the truth and we can't explain it to you. Shut up. That's not the way it should work. Science is by the people, for the people, and of the people. And that's one reason why I think it's great we do these episodes to show people how we learn this stuff and what we know, what we don't know. We've got to be honest about all of that because that's what's going to convince people. It's the process that people should trust, not any individual answer or result. And so we've got to include people in that process. Absolutely. Yep. Amen.

1:07:10And also, hooray, I never had to worry about my kids getting polio. Yeah, me either. How terrifying. Yep. And so, as I said at the top of the program, like, I am so grateful to scientists and to doctors and to everybody who's made our lives so much better and safer. Agreed. Thank you. All right. And thanks to everybody out there who's interested in learning about how the scientific process works, how peer review works, how discoveries are made, how we develop some of these life-saving vaccines and the things we learned along the way. And thanks to Kelly, as always, for your patented research deep dive.

1:07:44And thank you to the Extraordinaries for giving me the opportunity to read loads of stuff about topics I find fascinating. And apologies to anybody who heard the phrase fecal oral while you were having breakfast. All right. Thanks, everyone. Tune in next time.

1:08:25We really mean it. We answer every message. Email us at questions at Daniel and Kelly dot org. Or you can find us on social media. We have accounts on X, Instagram, Blue Sky, and on all of those platforms, you can find us at D and K Universe. Don't be shy. Write to us. Hey, everyone. It's the Jonas Brothers. If you haven't heard, our new podcast is called Hey Jonas. And this week, we're hanging out with someone we're really big fans of. Millie Bobby Brown. We talk about her new movie, Enola Holmes 3, Family Life, and all the amazing things she has going on right now. Plus, we find out what she really feels about the Stranger Things ending.

1:09:00You have over 60 animals. I don't know where the number's 60, and I've really got to figure that out. There have been plenty of sheep in my bed. It's a big bed. Literally sleeping in the bed. Listen to Hey Jonas on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. It just came out. Jeremy, what did you just do? You just set yourself up for failure. I've never heard you tell this story. I've never told this story. This must have been tucked deep, deep in the Jeremy Lin file. My name is MC Jin. I'm excited to tell you about Laugh But Not Lease. I'll be chatting with guests from all walks of life about the power of humor when it comes to facing difficult times.

1:09:34These will be conversations that remind us all life is hard. Laugh harder. Listen to Laugh But Not Lease with MC Jin on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. It's Latino USA. I'm Maria Hinojosa. I sit down with New York City Mayor Zora Mandani to talk about sports, immigration, politics, and the serious question of what makes a great New York City taco. But Mr. Mayor, as a Mexican, what have I done? What makes the best taco in New York City? Oh my God. Listen to Latino USA on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. I'm Mange Shachigular, and I'm back with a new season of my podcast, Skyline Drive.

1:10:15This time I talk to scientists, biopunks, curmudgeons, blues owners, super seniors, and Goa's top cryotherapy lab to try to understand this obsession with living forever and what it means for all of us. And I get into a bit of trouble along the way. I'd say probably start bone smashing. That doesn't work. Make it look more defined. They say it works. I don't know. Listen to Skyline Drive, How to Live Forever on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is an iHeart Podcast. Guaranteed human.