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August 18, 2021 26 mins

Jeryl Lynn Hilleman has the rare distinction of having a vaccine named after her, because it’s made from her cells. And her father, Maurice Hilleman, was the world’s greatest vaccine maker.  

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Speaker 1 (00:08):
School of Humans. Fair warning, this episode starts with diarrhea. Today,
we're going to hear from someone with the rare distinction
of having a vaccine named after them because it's made
from their cells. We'll also speak with a vaccine historian
who also happens to be a vaccine inventor, and who
also happens to have written a book about the world's
greatest vaccine maker. From My Heart Radio and School of Humans,

(00:32):
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

(00:53):
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

(01:14):
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

(01:36):
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

(01:58):
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

(02:20):
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

(02:42):
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.

(03:09):
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.

(03:30):
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

(03:52):
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

(04:15):
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

(04:36):
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

(04:58):
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

(05:20):
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,

(05:41):
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.

(06:01):
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,

(06:22):
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,

(06:44):
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

(07:06):
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

(07:28):
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

(07:49):
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

(08:12):
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

(08:33):
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

(08:54):
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.

(09:15):
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

(09:35):
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

(09:59):
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,

(10:22):
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

(10:43):
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,

(11:04):
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

(11:25):
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.

(11:47):
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

(12:07):
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

(12:29):
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

(12:51):
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,

(13:14):
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.

(13:35):
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,

(13:56):
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

(14:20):
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

(14:41):
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

(15:02):
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,

(15:25):
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,

(15:46):
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,

(16:08):
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,

(16:30):
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

(16:51):
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

(17:13):
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

(17:36):
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

(17:56):
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.

(18:18):
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,

(18:40):
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

(19:02):
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

(19:24):
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

(19:47):
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

(20:11):
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

(20:34):
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.

(20:57):
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

(21:17):
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

(21:41):
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

(22:02):
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,

(22:25):
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,

(22:46):
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

(23:06):
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

(23:30):
and winning a battle over these damn bugs. You know,

(23:53):
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

(24:14):
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

(24:35):
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

(24:56):
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,

(25:19):
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

(25:40):
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

(26:00):
audio mixed by Harper Harris with Tuonewelders School of Humans,
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