Blended Mouse Brains

I'm Sean Revived and this is long shot. Just saying diarrhea or anything related to the butt gets a laugh from me or by two year old, but it's a killer. Hundreds of thousands of kids die from it every year. There's a really serious thing that causes diarrhea, and it's called rhodavirus. Rhodavirus can give infants and young kids nausea and fever. Can also give them days of watery diarrhea,

and if those kids can't get rehydrated, they'll die. Almost every kid in the world under five gets rhodavirus at some point. It's everywhere. The question is how do you stop it. Historically, the answer has been a shit ton of research, years of trial and error, hits and missus in the nineties, a team at the US National Institutes of Health merged a human rhodavirus strain with a monkey rhodavirus strain to create a single vaccine called Rhoda Shield.

It did clinical trials in a few countries. Those went really well. The FDA approved Rhoda Shield and the CDC recommended it for every infant born in the US. This was in August nineteen ninety eight. Over the next few months, hundreds of thousands of American infants got at least one dose of Rhoda Shield, and it looked like we finally had a tool to take on this virus that was killing poor children all around the world. It was a huge deal. But then in late nineteen ninety nine, the

CDC withdrew its recommendation of the vaccine. Rhoda Shield had only been used for about nine months. There was no question that the vaccine was effective in stopping rhodavirus, but some children who got Rhoda Shield were struck with a rare and dangerous condition called into susception. It's an intestinal disorder that can be fatal in infants if not treated. There weren't many cases, just a dozen at first, but that was higher than expected based on the clinical trials,

and a deeper investigation found even more cases. Still, the risk of getting sick or dying from rhodavirus was far greater than the risks of into susception. But now American children couldn't even get Rhoda Shield. Even worse, when the CDC withdrew its recommendation, developing countries across the globe also

didn't want to use Rhoda Shield. A vaccine that could save two thousand lives per day, mostly poor children's lives, just stopped being used, and for seven years rhodavirus vaccines disappeared. When we talk about rhodavirus, one of the names you have to know is Paul Offitt. True. I think any fan of professional roller Derby knows who I am. I'm

just kidding, Yeah, I am Paul Offitt. I'm the director of the vaccin Education Center of Children's Hospital Philadelphia and a professor of pediatrics at the University of Pennsylvania School of Medicine. Paul wears many hats, doctor, researcher, advocate, writer. Maybe that's why he talks so damn fast. You could say the trajectory of his life was set when he was just five years old. Five years was rough year

for me. I actually inadvertently cut off the tip of my finger, which caused me to go to the hospital. And I also ruptured my spleen after falling from a height. And actually, frankly, the pediatritician who took care of me saved my life. I mean he was willing to come there that night to examine me. I said there is no time and put me in his car to drive me to the hospital to perform an emergency surgery was performed where a court and a half of blood was

taken out of my abdomens. And I also was born with club feet. My feet were casted as a child, and then invertently or unfortunately, a decision was made to operate on my foot, which should never have been done. I mean, the club foot surgery wasn't perfected till the mid nineties. This was the mid fifties, so we still forty years to go before we had perfected that operation, and so it was botched. Because it couldn't help it

be botched. There was no way to do that surgery. Then, after the surgery went bad, five year old Paul ended up in a chronic care facility in Baltimore. Back then it was called the James Lawrence Current In Hospital and Industrial School of Maryland for Crippled Children. So I was in that war that chronic care facility for about six to eight weeks. But that was a poly award. I mean, chronic care facilities in the mid nineteen fifties were poly awards.

His mother was sick and his father was always on the road for his work as a shirt salesman. So Paul spent that time when the poly award doing nothing. And I just remember sitting in that bed looking out the window which looked out onto the front door of that hospital, just waiting for somebody to come rescue me. You know, it's not like there were there was TVs there, there weren't iPads, there weren't play dogs or you know,

pet therapy dogs and stuff. So you were just lying there for all day and it was it was grim, and I just remember all seeing those children as vulnerable, helpless and alone, and I think, I think that no doubt motivated me to go into pediatrics. Paul decided to become a pediatrician. He went to med school, started doing research, and then during his residency. Well, I was a resident, I saw a child die rodavirus, so it's um that

was certainly another sort of motivator. He saw a child die of rhodavirus, so he started working on a way to stop it. Every year in the United States, before there was a roadavirus vaccine, there would be about seventy five thousand children that would be hospitalized with rhodavirus. Every year. There would be about sixty children would die of rotavirus. Everyone in this country would get rotavirus by the time

at five they were five. It didn't matter the level of sanitation in the home or the label level of hygiene in the country. It didn't matter. Everybody was infected with that virus by age five. The virus kills two thousand children a day in the world. In the early eighties, Paul was part of a team that created a rotavirus vaccine with a cow strain, kind of like how Edward Jenner used cowpox to create a vaccine for smallpox two

hundred years earlier. But after multiple trials, Paul's rotavirus vaccine didn't work well enough, and they shelved it. Over the next twenty six years, he continued working on a rotavirus vaccine,

a competitor to Rhoda shield. It took ten years to do the research to figure out what parts of the virus made you sick, would parts of the virus induce immune ten years to mix and match, test and retest different rotavirus strains from humans and cows to narrow down which strains would induce strong immune responses without making a child sick. Paul and his team took a recipe to a few pharmaceutical companies to help pay to continue the

research and test it. And it was a sixteen year research of development effort, meaning proved that each of those strange needed to be in there, proved that you had not too much or too little of each of those strains, have the right buffering agents through right stabilizing agent through right file to do all of that work, then it was phase one, Phase two, Phase three trials progressively larger and larger studies to prove that the vaccine is safe

and effective. That's sixteen more years, and it ended in a so called phase three trial, a prospect the placebo controlled the eleven country four year, three hundred and fifty million dollars trial to prove that the vaccine worked and was safe twenty six years. The vaccine that resulted from those twenty six years is called Rhodotech. It's owned by the pharmaceutical giant Murk. The Phase three trial for Rhodotech that Paul mentioned was the biggest clinical trial in the

history of vaccine development or any drug development. They tested the vaccine in eleven countries on three continents and in nearly seventy thousand infants. In January two thousand and six, they published the results. The vaccines seemed to cause no additional risk of intosusception that rare intestinal disorder. Also, the vaccine worked and worked really well. It cut hospitalizations and

r visits from rhodavirus by ninety five percent. A month later, both the CDC and FDA gave Rhototec the thumbs up. So the figure maybe at least three million children every year since two thousand and six, so certainly tens of millions, and in the world, hundreds of millions of children have received this vaccine, so it's not just in the US of getting it. All over the world, that's right. More

than a hundred countries have licensed that product. Rhodavirus vaccine is one of more than a dozen vaccines that the CDC recommends for every American kid. And what about the other thirteen? Where did they come from? Believe it or not, most of them were made by one man. It was about one o'clock in the morning when Jeryl Lynn Hilleman woke up with a sore throat. She was five years old. You know. March nineteen sixty three was when I got MOMPS.

And I do remember it, maybe because throughout my life it was made to be so important. But it was one of those moments where you wake up in the middle of the night and you go to your parents' room because you feel sick, and that's not really a big deal. But I remember waking Dad up and saying I feel sick, describing what was going on. He instantly turns on the light and grabs the Murk Manual. And the Murk Manual was a very large book, about three

inches thick. It was kind of back then what Google is today. Anything you want to look up about disease, symptoms, treatments, and so forth was in the Murk Manual. So he looks it up and he's reading about MOMPS. Because he instantly suspects I had moms, and that was of course very exciting to him because he was working very hard

to develop a vaccine. My name is Jerry Hilliman, also known as Jerald Lynn Hilleman, and I live in Palo Alto, California, and I am the daughter of Maurice Hilleman, who was a wonderful man but also particularly known for his work developing I think about forty vaccines. Gerlin's father, Maurice Hilleman, did develop more than forty vaccines. He's the greatest vaccine inventor in history. He played a part in where single handedly developed most of the vaccines that we get today, measles, rubella,

hepatitis A, heppatitis B, Meninjacoccus hib strepped Aococcus, chickenpox. He made them all. Paul Offit crossed paths with Maurice Hillman during his work with vaccines, and he was in awe of the man and his accomplishments, which had gone relatively unrecognized considering their impact. So in two thousand and four, Paul asked if he could sit down with Hilleman and

take down his stories. In October of two thousand and four, he was diagnosed with disseminated cancer which was not operable, and he was given about six months to live and lived in fact six months. He died in April the following year. And I thought, you're hearing all this, this amazing man who has these amazing stories to tell, and

all those stories were going to die with him. And I just asked him if he would be willing to let me come, you know, at least once a week and hopefully twice a week, to just interview him, to sit in his office and interview him. I knew how hard it was to do the research and development to on one vaccine. The notion that he had essentially done that for nine vaccines was like trying to imagine kind of a different dimension. Paul wrote a book about Hillman's

life based on those conversations. It's called Vaccinated. He also worked on a documentary called Hilleman. It's directed by Donald Mitchell. Who's letting us use some clips from the many hours he spent interviewing Hilliman, who was eighty five years old at the time. So why don't we start there just to have me introduce yourself to me and just tell me, you know, briefly, you know what You've done well. I'm

Maurice Halloman. I had a long career in science, about sixty years and Maurice Hilliman was born in nineteen nineteen during the Spanish flu epidemic. He grew up working at the family farm in Montana. I think that was the luckiest thing that could happen to anyone to be born on a farm on the western frontier. We had a black smash shop, had a machine shop, plants, nursery, stock, and so forth. One of my jobs was to take

care of the chickens. Lots of vaccines are grown in chicken eggs, including the annual flu shots and a bunch of Hilliman's vaccines, so his childhood experienced raising chickens helped bring several vaccines to the world, like the measles vaccine. And my career, chickens were my best friend because I used them for so many types of experimentation. Never break through the experiments. I grew to like chickens stupid, you know, But I felt that I owed them and that Hilliman

had a twin sister who died during her birth. Two days later, his mother died from acclampsia, and Hillman told Paul that He nearly died many times as a kid from disease, drowning, dodging trains, but somehow he always recovered. In high school, he worked at a JC Penny. He thought that might end up being his career, but he was smart, and one of his brothers told him he should go to college. He got a scholarship from Montana State University and then a PhD in microbiology from the

University of Chicago. But virology, the study of viruses, was still a brand new field with more questions than answers, and I gave the first course in virology given in the United States lamb and lecture, no textbook. In nineteen forty four he went to work for er Squibb and Sons. That's where he developed his first vaccine. It was for Japanese and cephalitis, a disease spread by mosquitoes that can

cause brain inflammation. Hillman's work on Japanese and cephalitis was for the US military, which needed the work done right away. They converted a horse barn into a laboratory and production facility, and the process for creating the vaccine was pretty gross.

Skip forward a couple of minutes if you don't want to hear descriptions of dead animals, but it really and amounted to was to inoculate mice with a needle into the head and to wait about three days before when they developed an acute and kephalitis and the virus was at its greatest level in the brain. Okay, here's where

it gets really graphic. Anyway, to just take these mice and snap them around a forceps and cut the skin off and sterilize it, and pop off the sky and the scissors and scoop out the brains which then had to be chopped up. And that was done in the Fred Waring's blender. Remember he developed that for to mix his cocktails. Fred Waring was a famous singer from the nineteen twenties to the nineteen to fifties. As a side gig, he backed and promoted the first electric blenders, Jonah Salk,

famous for inventing a polio vaccine. He also used the wearing blender. Invariably, they would leak and the virus would come out through the bearing at the bottom. Thirty women spent three months blending thirty thousand mice brains a day. Altogether, they blended enough brains to vaccinate six hundred thousand American troops. Okay, no more on mice brains, but there is a bit more grossness ahead. After squib, Hillman went to work at

Walter Reed Army Medical Center. One day he was sent out to an army base in Missouri to investigate a flu outbreak. For whatever reason, he couldn't get live throat samples, so he did the next best thing. He went to the morgue and I said, look, I got this all phone problem. And fellow said, well, he said, I have a body here from a soldier who died four hours ago. What do you want, I said, well, I'd like to

have his trak. Yeah. So I went over to the morgue and waited for him to carve out the trachia, wrapped it up newspaper and brown back. The lab cut it open and started chopping on tissue. Some days, you know, everything just goes right. Hilliman cultured cells from the recently dead men's trachia and grew virus from them, and in the process he helped discover adnoviruses, a family of viruses that we all get and that have become very relevant today.

Adnoviruses are used as a delivery system for some of the COVID vaccines like Astra Zeneca's and Johnson and Johnson's. After Walter read Hillman went to the re lab at Murk, the pharmaceutical giant. When he arrived at Murk, a man named Vanavar Bush was a chairman of the board. He was one of the people who started the Manhattan projects. He said, you know, I got an idea that one day these things called viruses are going to be important.

I really believe that. And he said, I wanted to set up a laboratory there will be second and none in the world to study of virology. And my vision was that, first of all, I wanted to conquer the pediatric diseases of children, measles, mumpster of vella, chicken pox, to discover the viruses of hepatitis, hepatitis A and Hepatatis B. And then I was interested in cancer for its cause

and control. And there was a late entry of the bacterial diseases, vaccines against new Macoccus and nin Jaccacus hem offless influence. The years after World War Two are known as the Golden Age of vaccinology, but as one writer put it, and might be more accurate to call it the Hilliman period. Hillman's vaccines saved millions of lives every year. He also made vaccines for animals. Hilliman was amazing and

making vaccines, particularly live attenuated vaccines. They're made by weakening a pathogen by passing it through chicken eggs or live animals or tissue culture. The idea is to give the virus to some other living thing and hope it comes out on the other end with less potency. Paul Offit, Hillman's biographer, explains, and it's not like there was a book on how to weaken viruses. You just kind of

made it up. You tried to pass viruses in cells which the virus normally didn't grow in, so that that kind of introduced a series of blind genetic alterations in that virus, so to making it weaker and weaker to

grow in the cells it normally grows in. So you would try it, you would pass it a certain number of time in these other cells where there was human kidney cells or monkey kidney cells or monkey testicular cells or whatever was being used chick embryo fiber blass cells or mouse embryo fiber blass cells, and then you would go back and put it into adults and then younger adults, and then older adolescents and then children to make sure

that it was weak enough but not too weak. And there was always a just a trial and error thing. And he had a real green thumb for that. I mean to make the measles vaccine, to make the mumps vaccine, to make the first German measles vaccine, to make the chicken box vaccine. That was all Maurice, and he just had a green thumb for retenuating viruses. Maybe the most amazing green thumb story goes back to nineteen sixty three

when Hillman's daughter Jeryl Lynn got sick. So he looks it up and he's reading about momps because he instantly suspects I had moms And that was of course very exciting to him because he was working very hard to develop a vaccine. You know, when you're going after to this attenuation or weakening of the virus, you go and you take a specimen from a patient. Now, those viruses that are traveling around in the human population are not

all alike. There are many different what are called clades, and you have to find the right clade that is going to allow you to attenuate appropriately. The word clade can be a bit confusing, but it's basically one step down from a strain. Two clades of a virus come from the same ancestor, and the right virus was right in my house. My daughter, Gerald Lynne came in one night and she just looked at Oh my god, yeah, I wrote like this, So I said, get back into bed.

I go up to the labs about one in the morning, got specimen collecting things, brought them back to throat swabs, took him back to the lab and froze them. So now I had specimens out of Jerlynne, my daughter. We isolated the virus and went into attenuation. By this one went just like that. So Hillaman created a vaccine for

mumps using the swab from little Jeraln's th roat. Actually, my other daughter, Kirsten was about one year old at the time that we had the vaccine coming along, and a picture was taken of gerald convincing her sister that she ought to take the vaccine. Gerald says it won't hurt. She's like hill here's jeral Lynn again. The name of the vaccine is to jaral Lyn strain. It's on all of the boxes and package inserts that come out. So I have had the pleasure throughout my life of also

being called miss momps and usually by pediatricians. Gerald Lynne never saw it herself, but she told me that even at the end of her father's life, he kept a list in his pocket of all the diseases he wanted to tackle. Well before vaccines, essentially one hundred percent of the children became infected with all of these measles, mumps, and essentially reubella were ubiquitous. These diseases have essentially disappeared.

That must be for you very satisfied too, well, think about those that's numbers, Well, yes it is, but you know, for a scientist, it's the winning that counts. It's my climbing mountains. You know, you get up here, and you get up to the top of this one, you got a couple more that you're trying to climb up. At the same time, looking back on one's lifetime, you say, gee, what have I done? Have I done enough for the world to justify having been here? You know that's big worry.

And I would say I'm kind of pleased about all this. I'm not smug about it, but I'm pleased I would do it over again because there's a great joy in being useful, and that's the satisfaction that you get out of it. Other than that, it's the quest of science and winning a battle over these damn bugs. You know, when Rotor Shield was pulled off shelves, it changed the way vaccine trials were run. Nobody wanted to see another rare adverse event like into susception slipped through the cracks.

The later findings questioned whether Rodo shield even caused one in any case. Vaccine safety trials ever since have become larger and more informative. That includes the COVID vaccines. Johnson and Johnson, AstraZeneca, Fiser, Maderna, and others around the world have all been amongst the largest clinical trials in history. Vaccines have come a long way since Maurice Hilliman was somehow making them with blenders and corpses and saving millions

of lives in the process. Paul Offitt, who worked with and wrote about Hillman and invented a vaccine, is also on the FDA's Vaccine Advisory Committee. That's the committee that recommended the approval of the current COVID vaccines for emergency use. Maurice Hilliman said it best. I never be the side of relief until the first three million dosars are out there. Well, the first one hundred million dosars are out there and it doesn't cause a serious side effect. It's amazing. I mean,

I can't. This is like one of the best vaccines ever made in terms of its effectiveness, in terms of its safety, and it was in terms of the speed with which it was made. It's just I keep way for the other shooted drop on these vaccines and it hasn't happened. On the next episode of Long Shot, we're going to hear from a scientist who figured out how to make a coronavirus vaccine two years before coronavirus struck, and in the process we'll learn what the hell of

spike protein is. Long Shot is a production of School of Humans and iHeartRadio. Today's episode was produced, written, and narrated by me Sean Revive. My co producer is Gabby Watts. Executive producers are Virginia Prescott, Brandon Barr, and LC Crowley. Special thanks to Noel Brown att iHeartRadio and to vaccine

inventor Stanley Plotkin. An extra special thanks to Paul author of Vaccinated, One Man's Quest to Defeat the World's Deadliest Diseases, and Donald rain Mitchell, director of Hilliman, A Perilous Quest Saved the World's Children. Fact Checking for this episode was done by Adam Schidou. Long Shot was scored by Jason Shannon. The score was mixed by Vic Stafford. Sound designed and audio mixed by Harper Harris with Tuonewelders School of Humans,