October 6, 2021 • 37 mins
The final episode of Long Shot travels millions of years into the past to when coronaviruses first appeared, and brings us back to the future of COVID vaccines. With a hell of a lot of vaccine milestones in between.
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Episode Transcript
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Speaker 1 (00:08):
School of Humans. This is the tenth and final episode
of Long Shot, and this time around, I want to
do something different. We've covered a lot of vaccine ground
in this series, starting thousands, even millions of years ago
and bringing it forward to the pandemic days we're still
living in. In this super episode of Long Shot, we'll
(00:31):
go over all the coolest things from the series and
fill in a few gaps along the way. It's gonna
move pretty fast, but if you're listening to this series,
your brain probably moves pretty fast too. From School of
Humans and iHeartRadio, I'm Sean Revive and this is Long Shot.
(00:51):
Let's get this party started two ninety three million years ago.
That's when Joel Wertheim, an associate professor of Medicine at
UC San Diego, estimates coronavirus has first appeared. Our estimates
put the incestor of all coronaviruses at hundreds of millions
of years old, which actually would line up with the
split between bats and birds or their divergence. Now, as
(01:16):
much as I'd like to think, in all of that
noise and all of that uncertainty, we managed to hit
the nail on the head going back hundreds of millions
of years and identifying the split between bats and birds.
I just think that that's a lucky happenstance, and nobody
knows how old they are. Okay, so he's not really
sure about that number, but it's probably safe to say
(01:38):
that coronavirus has first appeared millions of years ago. But
the practice of innoculation, the prevention of disease through contraction
of that disease, doesn't start with coronaviruses. It starts with smallpox. Yep.
Smallpox one of the deadliest diseases in human history, killer
of hundreds of millions of people. Smallpox probably predates written history,
(02:01):
but some Egyptian mummies were found with signs of smallpox.
There are written descriptions of smallpox from seventh century India,
so we know it goes back many hundreds of years
at least. But what about smallpox inoculation. There's a legend
about smallpox inoculators living unmountain in China about the millennium ago.
(02:22):
The son of a local governor got very sick from smallpox,
which by len had to plague the China for at
least a thousand the years. The governor offered the piles
of gold to anyone who could help. He's his son.
Real documentation of inoculation comes about five hundred years later
(02:44):
in a fifteen forty nine medical text by a Ming
dynasty physician. Things start getting less hazy in the sixteen hundreds.
In sixteen eighty, in an ooculator named fushang Lin is
chosen by an emperor in China to protect his children.
Lo the Conci emperor, survived the smallpox, he did not
escape it to trauma. Every time there was an outbreak
(03:08):
of small pox, he was haunted both by his fallest
death and by the isolation, and so when he grew
into an adult, the county emperor searched far and wide
for the umpire's best inoculators. Thirty five years later, in
seventeen fifteen, Lady Mary Wortley Montague, a talented British poet
(03:32):
and young aristocrat, gets smallpox, which is probably the single
deadliest disease in England at the time. Her symptoms are horrible,
a wicked fever, a rapid pulse, trouble breathing due to
the swelling of her nose and throat, liquid filled pustules
that eventually cover her entire body and face. Lady Mary
survives the pox, but her face is scarred for life.
(03:57):
The next year, she moves from London to Constantinople with
her ambassador husband. There she hears the Turkish have a
way of protecting against pox. What they do is purposefully
inject a patient with a little smallpox matter, and that
gives the patient lifelong protection from full blown smallpox. Two
years later, in seventeen eighteen, Mary has her five year
(04:20):
old son inoculated. He may be the first english person
ever to be inoculated. And when she returns to London,
she has her daughter inoculated by a surgeon named Charles Maitland.
He'd go on to perform an innoculation experiment on prisoners
in seventeen twenty two. Here's historian Arthur Boylson. So six
(04:40):
of them, all of them quite young, late teens, early twenties,
and they were all inoculated with a big public spectacle.
They had all been sentenced to hang from various crimes.
And the King agreed that he would allow Maitland to
inoculate some prisoners. And at one point somebody complained to
(05:03):
the King and said, even that's a fairly nasty thing.
To do. McKey said, well, it's better than they preferred
it to hang. Regardless of the ethics of this experiment,
all six prisoners live and are pardoned. Meanwhile, around this time,
an enslaved African brings anoculation to the United States. His
(05:25):
name is One Samous and he's owned by a Puritan
minister in Boston named Cotton Mather. And One Samous changes
the course of inoculation history in the US. When Mather
asks One Samius if he's ever had smallpox, on Samius
replies both yes and no. He shows Mather a scar
and says it's from an operation where he got a
(05:45):
small mountain of smallpox in order to protect him from
the disease. Years later, when a smallpox outbreak comes to Boston,
Mather becomes the strongest voice in favor of anoculation, and
by the time of the American Revolution, General George Washington
makes an oculation standard practice for soldiers, so he inoculates
(06:06):
the entire continent alarmy over a period of weeks. Within
the army, it prevented smallpox, and thereafter inoculation became part
of the enrollment ritual for new soldiers. They were given
a shirt and gun shoes and inoculated. It's the reason
the United States exists. A few decades after Lady Mary
(06:31):
in the UK and once Amiss in the US, a
family by the name of Sutton starts at innoculation business
in rural England, traveling around and inoculating entire towns. They're
the first inoculation entrepreneurs. It was explosive. There were villages
all over the country that adopted the Suttonian system. They
(06:52):
hire a preacher to speak of God's support for the practice.
This is the way for our escape. Reason directs us
to it. Experience proves the utility and safety. This sickness,
as caused by innoculation, is not unto death. The Sutton's
(07:13):
helped make anoculation to mainstream practice, and by the time
their work is finished, a new type of smallpox prevention
is discovered by Edward Jenner. The legend goes that he
meets a milkmaid with perfect skin and she tells him
about being exposed to cow pox, which gives her protection
from smallpox. We all know and believe that beautiful story
(07:34):
of the milk Maide and how she was gorgeous, but
it's not true. It's made up. Even if the story
isn't true, Jenner does pretty much invent vaccination with his
use of cowpox to fight smallpox. In seventeen ninety six,
Dinner makes history by testing his vaccine on his Gardner's son,
eight year old James Phipps, and the boy lives. In
(08:00):
the eighteen eighties, Louis Pasteur creates vaccines for anthrax and
then rabies, using the practice of attenuation, weakening the virus
before injecting it into the body. In nineteen eighteen, the
Spanish flu arrives and sort of takes over the entire
world for a couple of years, killing somewhere around fifty
(08:20):
million people. The next year, Maurice Hilleman is born. Well,
I'm Marie's Haliman. I had a long career in science,
about sixty years. Hilleman is the goat of vaccine invention.
He helps develop most of the vaccines that we get today, measles, rubella,
(08:41):
hepatitis A, hepatitis B, Beninjacoccus, hib streptococcus, chicken pox. That's
all him. He also accidentally helps discover ad no viruses
while culturing the cells of a dead man's trachea. And
I said, well, I'd like to have his trachia. So
I went over to the morgue and waited for him
to carve out the trachea, wrapped it up newspaper and
(09:04):
brown back the lab, cut dope and start chopping on tissue.
Some days, you know, everything just goes right. Ad No
viruses are used today as a delivery system for some
of the COVID vaccines, like Astra's ENCAS and Johnson and Johnson's.
Hillman even creates a vaccine from his own daughter's cells
(09:24):
in nineteen sixty three. The name of the vaccine is
the Journal and Strain. It's on all of the boxes
and package inserts that come out. I have had the
pleasure throughout my life of also being called Miss Mumps,
and usually by pediatricians. And while Maurice Hillman is doing
his thing, some other cool things are happening with vaccines.
(09:47):
By the nineteen forties, we've got new vaccines for diphtheria, tetanus,
and pertussis. In nineteen fifty five, Jonah Saut comes out
with his vaccine for polio. There's also some not so
cool stuff happening when the polio vaccine comes out. One
of the company's mass producing it cut her laboratory messes
up and creates tens of thousands of doses containing live poliovirus.
(10:12):
Fifty one people are paralyzed and five die after getting
the vaccine meant to prevent polio. And in nineteen sixty six,
a vaccine trial for respiratories and scial virus and DC
goes bad. Eighteen babies, mostly from poor black families, end
up in the hospital and two of them die. RSV
can be deadly in children, and there is still no
(10:33):
FDA proof vaccine today. We'll get back to RSP in
a sec In nineteen eighty, smallpox returns to the news
when the World Health Assembly officially declares the virus eradicated. Yes,
after thousands of years, vaccines have ridded the world of
one of humanity's greatest killers. But HIV and AIDS appear
(10:55):
around that time. They spread throughout the eighties, at first
primarily in gay men, but also in intravenous drug users
and later in countries in Africa. Virologist named Eddie Holmes
goes to Edinburgh, Scotland to study HIV spread in the
early nineties. What we were trying to do was trying
to work out how the virus was spreading through that population,
(11:16):
how it diffused, and how it got into city, and
how it spreading. In the nineties, a team at the
US National Institutes of Health creates a vaccine called rhoda
Shield to fight a deadly childhood disease called rhodavirus. Rhoda
Shield gets the nod from the CDC, but within months
some cases of a rare intestinal disorder pop up and
(11:37):
the CDC withdraws its recommendation. But all throughout the eighties
and nineties, another team of researchers is working on a
rival vaccine for rhodavirus called Rhodotech. That one gets low
from the FDA and CDC in two thousand and six,
but not before the biggest clinical trial in the history
of medicine eleven countries and nearly seventy thousand infants. Here's
(12:01):
Paul Offitt, one of the developers of Rhodotech, and it
ended in so called Phase three trial, a prospect the
placebo control, the eleven country four year, three hundred and
fifty million dollars trial to prove that the vaccine worked.
The size of that enormous trial leads to the similarly
giant trials we have in twenty twenty for the COVID vaccines.
(12:21):
Johnson and Johnson, Astra, Zeneca, Fizer, Maderna, and others around
the world are all amongst the largest clinical trials ever.
In two thousand and two, we get an outbreak of
severe acute respiratory syndrome the first stars. More than eight
thousand people in twenty nine countries get it, but by
two thousand and four it mostly dies out thanks to
(12:43):
people like Maurice Hilleman. We've got tons of vaccines at
this point. But in two thousand and six, a new
discovery leads to all sorts of advances in medicine, including
the way we make vaccines. That year, Shinya Yamanaka, a
Japanese researcher, discovers a way to reprogram mature mouse cells
into immature cells. They can then be turned to whatever
(13:05):
type of cells he wants. Here's Derek Rossi who's in
the audience when Yamanaka announces his discovery. So what he
demonstrated was that he could take any cell type, any
differentiated cell which would normally we had thought been sort
of fixed in its identity, but he discovered a way
by introducing four genes to turn back the developmental time
(13:30):
on what was differentiated cell type and reverted back to
an embryonic stem cell like state. Derek is at Harvard
in two thousand and seven and he wants to build
upon Yamanaka's work changing mature cells to immature cells. Yamanaka
is inserting strands of DNA into cells in order to
change them, but this is dangerous for humans. It could
(13:53):
give you cancer. So Derek decides to use mRNA instead,
which is kind of like skipping a step in the
way that life is made. I call it the trifect
of life. DNA makes mRNA, protein makes life. Postdoctor Othello.
In my lab, doctor Luigi Warren had the idea, very
simple idea, just saying, hey, you know, we need to
(14:15):
make these transcription factors. Let's just skip the whole DNA part.
Let's just use m rna. That turns out to be
a genius move, but he runs into another problem When
he puts RNA into cells, the cells think they're being
attacked by a virus, which caused the cell to respond
by saying, looks like a virus is coming in. Let's
(14:37):
shut down the protein production. And it really looks like
a virus is coming in, so let's kill ourselves, you know,
an altruistic suicide and cell death, which is a good
thing for the cell to do, you know, rather than
let it be hijacked by a virus and have it
make hundreds of thousands of viral particles. He finds a
workaround from a couple of researchers at the University of Pennsylvania.
(15:01):
The researchers are Catlin Corrico and Drew Weissman, and they
figured about a cloaking method for tricking cells into not
thinking they're being invaded. Derek integrates it into his own
work and lo and behold, now we can change human
cells without killing them or causing cancerous mutations. That was
the sort of technological breakthrough that led to the development
(15:23):
of modified mRNA. We called it in the lab mod RNA.
He takes this work down the street to Bob Langer,
a serial entrepreneur based at MT, and they start a
company that they eventually name Maderna. By the way, just
as a a fun fact, you know, Maderna. It comes
from the term that we used in the lab describing
the technology. We called it mad RNA. So mod RNA
(15:46):
if you put any in there, you get Maderna. That's
where the name came from. At its formation, Maderna has
exactly zero full time employees and no products. They won't
have one for ten more years. In two thousand and eight,
structural biologist Jason McClellan takes a job at the NIH
where he meets Barney Graham. Graham wants to create a
(16:09):
vaccine for RSV, which is that virus I mentioned earlier
that can kill infants. The RSV vaccine that failed back
in the sixties was made by weakening a strain of
the virus by passing it through animal tissue or human cells.
That's how Maurice Hilleman made a lot of his vaccines.
But Jason and doctor Graham have a new method in mind.
(16:29):
They want to mess with the F protein of RSV.
That's the one the virus uses to infect human cells.
Before the F protein attaches itself to a human cell,
it is in its prefusion state. If you think of
your immune system as a security guard, you want to
train your immune system to recognize the form that might
infect you, like the dangerous form, and that's the prefusion form.
(16:51):
If you train it to recognize the postfusion form, the
prefusion form can still sneak by you. Barney, Graham, and
Jason want to figure out how to keep the F
protein in this state, and in twenty thirteen they do.
They figure out a way to sort of staypule the
protein so it stays in that form. And when Barney
(17:12):
immunized mice and compared postfusion versus prefusion, the mice receiving
the prefusion form of the F protein elicited neutralizing antibodies
about ten times higher than those that received the postfusion.
This is the first time that structural biology, looking super
closely at the structure of a virus helps discover a
(17:34):
new way to stop it. But now they want to
see what other viruses they can work on using this
prefusion protein state. This is right around the time that
Middle East Respiratory Syndrome is first reported in Saudi Arabia.
MERS is a really bad coronavirus. Thirty five percent of
people infected with it we're dying. It's a real lethal virus,
(17:55):
and we thought that this would be a good target
to try to take everything we had just learned about
RSP and apply it to not just MERS, but coronaviruses
in general, because we knew the Stars coronavirus had emerged
in China in two thousand and two and it caused
an epidemic. It turns out that MERS has a protein
that works kind of like the rsv F protein. It's
(18:17):
called the spike protein, and when the merge virus attacks
human cells, the spike injects itself into them in order
to spread throughout the body. But it's not easy to
staple the spike protein. It takes tons of trial and error.
Here's Nanchan Wang Jason's post doc to explain how hard
it is to figure this out. We got to try
(18:41):
again and again most of the time. It's got to feel. Yeah,
it's not so too easy actually to find their mutation
that to stabilize as product, it's pretty italented. By twenty seventeen,
they figure out how to staple the spike protein in
place and use that to teach the immune system to
fight off a MERGS infection, but they don't have any
(19:03):
people to test it on. Turns out MERS doesn't spread
very easily and the outbreak is mostly over by then.
No outbreak means no human trials, no human trials, means
they can't be sure that stabilizing the spike protein really
works as a vaccine candidate. Then in December twenty nineteen,
a new coronavirus appears. Here's Derek Rossing. You could see that.
(19:27):
You know, it was really snowballing. I mean it had
everything that a good pathogen would want. It was a respiratory.
When it was first being reported, the fatality rates and
the illness rates were very very high. We didn't, you know,
it was a new virus. We didn't know how to
respond to it. So the fatality rate was around two percent.
That's pretty darn serious. In mid December twenty nineteen, a
(20:00):
worker at the Huanan seafood wholesale market gets sick with
theemmonia like symptoms. He's admitted to Central Hospital of Wuha
and he's one of the first novel coronavirus patients in
the world. Central hospital happens to be where British phiologist
Eddie Holmes and it's Chinese colleague Jan Jang Jang are
studying patients with acute respiratory symptoms around that time. But
(20:22):
what that meant was we were kind of like on site,
almost looking at the same Z syndrome in the right
tissue samples with the right technology, and so we happen
to be in the wrong place the wrong time. I
feel like when it all kind of started, and that's
gave us an open door to really to try and
look at some of the early first cases to see
(20:44):
what was going on. Late at night and January fifth,
twenty twenty, Jang finishes sequencing the virus, but Chinese authorities
are trying to keep anything related to the virus from
being made public. The Ministry of Health were controlling everything,
and they wanted They wanted to control the message, they
wanted to damp down on rumors, they wanted to be
in control of the situation. On January eleventh, Jang gets
(21:08):
on a plane in Shanghai and is about to take
off when his phone buzzes. It's Eddie. I cooled jan
very early, and I said we need to release he
stay tonight. Jang agrees, has a post duct send the
sequence to Eddie. Eddie tweets out a link. That moment
kicks off development for the COVID nineteen vaccines, and that's
(21:30):
exactly what Jason McClellan starts working on the reports were
coming out of these pneumonia clusters in Wuhan. We could
just see it following along on science Twitter and on
the news. And then it was early in January when
it was learned that, in fact, it is a coronavirus
beta coronavirus that's similar to the first stars Kobe from
(21:50):
two thousand and two. Jason's at the University of Texas. Now,
I was a snowboarding with my family in Park City, Utah,
and Barney Graham called me. He said he was in
contact with the US CDC Chinese CDC and they were
going to try and work quickly work with Maderna try
and create a vaccine. Maderna is still considered an upstart
(22:11):
company at best, and it's never brought a vaccine to market.
Anyone to know if if we were interested in continuing
our collaboration to determine the structure of the stars cope
to spike protein and use that information to create the
vaccine antigens, Jason texts has graduate student Daniel Rep. We
(22:31):
were sort of ready to go, that's Daniel, because we've
been studying these spike proteins for such a long time.
We knew how to effectively stabilize spike in the prefusion
confirmation and that acts as a really good vaccine candidate.
Within a few weeks, they figure out how to stabilize
the spike protein of the novel coronavirus. But to make
a vaccine work, they need to make sure the mRNA
(22:53):
gets where it needs to go to instruct the body
to make stabilize spike proteins. What MADERNA does is encapsulate
the mRNA in a lipid nanoparticle shell to protect the
mRNA on its way to doing its things. Here's biochemist
Thomas Madden of Acuteous Therapeutics in Vancouver to remind us
what an l enp is and does. If you wanted
(23:14):
to order a really fragile glass ornament online and you
wanted it delivered to your to your home, if you
used the equivalent of our delivery technology, then the ornament
would be would be wrapped and packaged to protect it
and noboutter how rough the journey was to your to
your house. The package would would find your house, it
(23:37):
would open the front deck door by itself and let
itself in, and then it would unwrap itself. So the
ornament is waiting for you to come along and pick
up in your hallway, so the lipidano particle delivers the vaccine,
kind of like how FedEx delivers a package. Around the
same time that the Phase one trials from Aderna begin,
(24:00):
the US starts shutting down. Rush to the grocery store
like every single other person, and you know, the meat
sections were empty, and that just kind of that was
a little eerie to see. This is Nicola Pescarilli, and
all of a sudden, I just felt like everything was
closed off, and I didn't like that feeling. And so
it's like, what can I do to get everything to
(24:21):
return back to normal as soon as possible? What can
I do? What can I do to make things better?
Because I felt just so hopeless. Tom Hanks has COVID,
the NBA has shut down, entire cities and countries around
the world shut down, and Nicola volunteers for the Phase
one trial at the Hope Clinic in Atlanta. I'm in
(24:42):
Phase one, like, I am one of fifteen people getting
the highest dosage that no one else in this country,
in this world has ever gotten. And I think for
a moment, I thought, oh God, it might crazy, Like
could I die? And then I was like, no, it's fine.
Modern medicine is great, and it is great. The phase
one trial is a success. It was a very small process,
(25:07):
and I remember afterwards they wanted me to stay to
observe me for a while after the vaccine, and it
was still just like getting used to the whole new
change in the world. Meanwhile, more than a hundred other
vaccines are in the works around the world, all sorts
of them spot Nick in Russia, Sino farm and Sino
(25:28):
vac in China, Astra Zenica in the UK, Covaccine in India,
Soberana two in Cuba. They are mr Anda vaccines, had
no virus, vaccines, in activated vaccines. There are even vaccines
grown and tobacco like plants. But in the meantime, before
the vaccines are actually rolled out, lots of people are
(25:49):
getting sick and lots of people are dying, and nearly
everyone else is stuck at home, stuck caring for people,
confused about what to do and how to live. So
happy Halloween to me. Turns out I did have COVID.
A lot of us are really lonely, unable to see
friends or family, no office to go to. Some people
(26:10):
get COVID pets. Like Marina in Sweden, I was having
a really hard time sticking to any sort of schedule
because the days were all the same and there was
nothing to do. And then when COVID came around and
I had been working from home for nine or ten months,
I was just at my wits end, like so sick
of just being by myself. So I decided, like, now
(26:33):
is the time I'll get a dog. I can be
at home and train the dog. It seemed like a
good idea, but during COVID everything is more complicated and
plans just continuously get fucked up for everyone all the time.
In a slightly different world, I would have gone all
those things I wanted, but in a COVID world, I
(26:54):
didn't get any of them. Some people get sick and
stay sick, like Dave Hockaday in Oxford. It's just getting
worse each day. And then of course the fatigue was building,
that was getting worse, and there was just generally feeling
starting to feel really unwealth inflamed hot, was getting chills
(27:15):
at night times and night sweats, insomnia, dreadful nightmares. My god,
the nightmares were horrific. People like Dave have long COVID
and even today it's unclear what exactly is causing it.
Just seeing the numbers like them, an average number of
symptoms that long COVID patients had. That's Athena Akramy, a
(27:38):
neuroscientist at University College London. She got COVID in March
twenty twenty and seventeen months later she's still sick. She
now spends a lot of her time studying long COVID.
The average number of symptoms is more than fifty. Just
like seeing that number that like one person I can't
(27:58):
experience fifty different symptoms was kind of, I don't know, shocking,
and it seems like long COVID it will be a
huge problem for years to come. We are just like
accumulating so many long covides down like in a year,
probably each country will have millions of people, most of
(28:20):
them again previously young and faith that now they are
just like really struggling to go back to semi normal life.
That I really don't know what we'll how. It's a crisis,
it's a health crisis. But on a positive note. By
(28:41):
early twenty twenty one, three vaccines have gotten emergency authorization
in the US and they start making their way to
healthcare workers and the elderly. There are major hiccups at first.
I mean, it's damn near impossible for some people to
get appointments because there's no central system to do that.
It's a goddamn free for all instead of an orderly line.
(29:02):
At first, I was not successful at finding a vaccine.
That's Stanley Plutkin, one of the world's top experts on vaccines.
Even the guy who literally wrote the book on vaccines,
has trouble getting an appointment at first. He's eighty eight
years old and really vulnerable if he gets COVID. What
do you mean you weren't successful, even like you were,
(29:24):
You couldn't get an appointment at first? Yes, well, yeah,
I think initially of finding it was not easy. Initially
there was a lot of uncertainty about where vaccines were available,
how much was available, etc. That's how chaotic it is
(29:46):
in the beginning of twenty twenty one, and so it
became a You still have to navigate systems that are
largely fragmented and by the way, all online in order
to secure an appointment. And guess what, the very populations
that were favored is early beneficiaries of New York States
(30:09):
vaccine program are precisely the populations who can't be on
the internet all day or are not on the internet,
so the elderly, restaurant workers, grocery store workers, taxi drivers.
That's s Metro Khalita, whose organization Epicenter NYC helps get
people vaccine appointments in Jackson Heights, Queens back when it's
(30:29):
super hard to do it if you aren't really Internet savvy.
But eventually there's so much vaccine out there in the
US that anyone who wants a shot can get one.
Of course, not everyone does. One way to get vaccines
made and distributed faster for the next pandemic is to
use human challenge trials. That's where people get a disease
(30:52):
on purpose so that doctors and scientists can study it.
The first human challenge trial for COVID begins in the
UK in March twenty twenty one, and Jacob Hopkins is
one of the participants. Speaks of getting and COVID is
the most surreal thing in the world, Like it's intimidating.
This is him describing how they infect him during the trial.
(31:15):
It's like Jesus Christ, like this is like intense, and
they get this huge p pair. It's like almost like
a turkey basis, Like it's a massive pair they have.
They pick it up, they start counting down, So they
count down from twenty, which is adds to the suspense really,
and then they kind of like drop up in each nostrils,
so they kind of drop it around the outside of
the one nostril and then did the other and then
their way and they count not from twenty again and
(31:38):
then they repeat. You're kind of just sit like you're
kind of just laying there in silence, like just thinking,
oh my god, I've just been infected with coronavirus, and
like it kind of obviously kind of hits in at
that point. And while the UK and US and other
wealthy nations are overloaded with vaccines, poorer countries can't get
(31:58):
enough to vaccinate even small portions of their people. Even
with donations trickling in from miserly nations like the US,
low incombinations are still only two percent vaccinated on average,
And so a bunch of researchers get together and create
a new vaccine that can be produced cheaply and easily.
Here's Bruce Innis from the organization PATH. We're extremely interested
(32:22):
in ensuring that countries where health budgets are not strong
have access to world class vaccines that are life saving.
On the proposition that everyone deserves to have access to
life saving vaccines. PATH has helped coordinate the development of
(32:42):
this new vaccine, which is called ndv HXPS. It uses
a new stabilized spike protein called hexapro developed by Jason
McClellan and his colleagues at UT and then also starting
to make a second generation spike protein that was even
more stable than the two protein form. The engineered protein
(33:02):
is carried into the body by Newcastle disease by, which
is an avian virus. Here's Peter Palaze, a microbiologist at
Mount Sinai who helped develop the vaccine, and so we said, okay, right,
don't we put the sous coronavirus spike protein into Newcastle
disease bows and thens what we did, so we have
a vector ven vaccine. The big difference between this vaccine
(33:28):
and the ones we've gotten in the US is that
it's cheaper to make because it's grown in chicken eggs
just like most flu shots, and it's being piloted in Vietnam, Brazil,
and Thailand. Already here's Bruce again. They've made multiple lots
of vaccine, initially at pilot scale, which might involve a
few thousand eggs, and we're getting typically about seven to
(33:51):
eight finished vaccine doses per inoculated egg. You can think
of the egg as a mini bioreactor, each one self
contained bioreactor. And now they're in the process of manufacturing
the investigational vaccine at full commercial scale. Some phase one
clinical trials have already finished and the results are promising,
(34:14):
but the new vaccine still needs to go through the
big phase three trials. If they go well, ndv HXBS
may end up being, at least for some countries, the
future of coronavirus vaccines. That brings us to the end
(34:37):
of this podcast. We started millions of years ago and
finished still in a pandemic with no clear end. Variants
are here, people are still getting sick and dying, and
life is still weird and annoying even if you're healthy.
I'm personally super impressed with all the incredible researchers and
volunteers and historians we heard from and about. I mean,
(34:58):
how the hell the first human being figured out that
giving someone a little bit of a disease to protect
from a lot of it hundreds, if not thousands of
years go, is just mind blowing to me. But just
a reminder. This is not the entire story. It's just
what I've been able to cover in this relatively short
ten parts series. There are a ton of people who
have made important contributions to so many vaccines, lots of
(35:21):
names that have gone unsaid by me and by others,
lots of people whose work has helped save hundreds of
millions of lives, and also hundreds of millions of lives
that have been lost along the way. As of today,
four point seven seven million people have died of COVID,
and they include, just to name a few, Darlene Ray, Rose,
(35:42):
Marie Fazzio, Ron Kieran, Adel Cercelli, Kenny Cassina, Doctor Ferkin,
Ali Sadiki, Patricia Francis Prescott, Mark Dvorschak, and my aunt Rifka.
A COVID vaccine could have saved almost all of those
four point seven seven million people, just like a smallpox
vaccine has saved who the hell knows how many people.
(36:05):
My hope is that when the next pandemic. Hits will
be able to create a vaccine even faster and get
it to more people faster, but that'll depend on more research,
more domestic and international cooperation, and more agreement in the
world in general. There's just no way to protect the
world unless the whole world is protected. Now, let's end
(36:26):
this thing with another dip into the recent past. March
twenty seven, twenty one, the first Boutanese person is about
to get her first shot of a COVID vaccine. Her
name is Ninda, which roughly translates to the Sun and
the Moon. She's thirty years old and was born in
the Year of the Monkey. The nurse who will administer
her shot is also thirty years old and also born
(36:49):
in the Year of the Monkey. After being picked to
be the first person in her country to be vaccinated,
Ninda says, let the small step of mind today help
us all prevail through this illness. She sits with her
back to her room full of massed healthcare workers and monks,
and they pray together until she gets her shot. Long
(37:20):
Shot is a production of School of Humans and iHeartRadio.
Today's episode was produced, written and narrated by me Sean Ravie.
A Co producer is Gabby Watts. Special thanks to Noel
Brown and iHeartRadio. Executive producers are Virginia Prescott, Elsie Crowley,
and Brandon Barr. Fact Checking for this episode is by
(37:42):
Adam Shadow. Long Shot was scored by Jason Shannon. The
score was mixed by Vick Stafford. Sound design and audio
mixed was by Harber Harris with Tune Welders School of
Humans
School of Humans. This is the tenth and final episode
of Long Shot, and this time around, I want to
do something different. We've covered a lot of vaccine ground
in this series, starting thousands, even millions of years ago
and bringing it forward to the pandemic days we're still
living in. In this super episode of Long Shot, we'll
(00:31):
go over all the coolest things from the series and
fill in a few gaps along the way. It's gonna
move pretty fast, but if you're listening to this series,
your brain probably moves pretty fast too. From School of
Humans and iHeartRadio, I'm Sean Revive and this is Long Shot.
(00:51):
Let's get this party started two ninety three million years ago.
That's when Joel Wertheim, an associate professor of Medicine at
UC San Diego, estimates coronavirus has first appeared. Our estimates
put the incestor of all coronaviruses at hundreds of millions
of years old, which actually would line up with the
split between bats and birds or their divergence. Now, as
(01:16):
much as I'd like to think, in all of that
noise and all of that uncertainty, we managed to hit
the nail on the head going back hundreds of millions
of years and identifying the split between bats and birds.
I just think that that's a lucky happenstance, and nobody
knows how old they are. Okay, so he's not really
sure about that number, but it's probably safe to say
(01:38):
that coronavirus has first appeared millions of years ago. But
the practice of innoculation, the prevention of disease through contraction
of that disease, doesn't start with coronaviruses. It starts with smallpox. Yep.
Smallpox one of the deadliest diseases in human history, killer
of hundreds of millions of people. Smallpox probably predates written history,
(02:01):
but some Egyptian mummies were found with signs of smallpox.
There are written descriptions of smallpox from seventh century India,
so we know it goes back many hundreds of years
at least. But what about smallpox inoculation. There's a legend
about smallpox inoculators living unmountain in China about the millennium ago.
(02:22):
The son of a local governor got very sick from smallpox,
which by len had to plague the China for at
least a thousand the years. The governor offered the piles
of gold to anyone who could help. He's his son.
Real documentation of inoculation comes about five hundred years later
(02:44):
in a fifteen forty nine medical text by a Ming
dynasty physician. Things start getting less hazy in the sixteen hundreds.
In sixteen eighty, in an ooculator named fushang Lin is
chosen by an emperor in China to protect his children.
Lo the Conci emperor, survived the smallpox, he did not
escape it to trauma. Every time there was an outbreak
(03:08):
of small pox, he was haunted both by his fallest
death and by the isolation, and so when he grew
into an adult, the county emperor searched far and wide
for the umpire's best inoculators. Thirty five years later, in
seventeen fifteen, Lady Mary Wortley Montague, a talented British poet
(03:32):
and young aristocrat, gets smallpox, which is probably the single
deadliest disease in England at the time. Her symptoms are horrible,
a wicked fever, a rapid pulse, trouble breathing due to
the swelling of her nose and throat, liquid filled pustules
that eventually cover her entire body and face. Lady Mary
survives the pox, but her face is scarred for life.
(03:57):
The next year, she moves from London to Constantinople with
her ambassador husband. There she hears the Turkish have a
way of protecting against pox. What they do is purposefully
inject a patient with a little smallpox matter, and that
gives the patient lifelong protection from full blown smallpox. Two
years later, in seventeen eighteen, Mary has her five year
(04:20):
old son inoculated. He may be the first english person
ever to be inoculated. And when she returns to London,
she has her daughter inoculated by a surgeon named Charles Maitland.
He'd go on to perform an innoculation experiment on prisoners
in seventeen twenty two. Here's historian Arthur Boylson. So six
(04:40):
of them, all of them quite young, late teens, early twenties,
and they were all inoculated with a big public spectacle.
They had all been sentenced to hang from various crimes.
And the King agreed that he would allow Maitland to
inoculate some prisoners. And at one point somebody complained to
(05:03):
the King and said, even that's a fairly nasty thing.
To do. McKey said, well, it's better than they preferred
it to hang. Regardless of the ethics of this experiment,
all six prisoners live and are pardoned. Meanwhile, around this time,
an enslaved African brings anoculation to the United States. His
(05:25):
name is One Samous and he's owned by a Puritan
minister in Boston named Cotton Mather. And One Samous changes
the course of inoculation history in the US. When Mather
asks One Samius if he's ever had smallpox, on Samius
replies both yes and no. He shows Mather a scar
and says it's from an operation where he got a
(05:45):
small mountain of smallpox in order to protect him from
the disease. Years later, when a smallpox outbreak comes to Boston,
Mather becomes the strongest voice in favor of anoculation, and
by the time of the American Revolution, General George Washington
makes an oculation standard practice for soldiers, so he inoculates
(06:06):
the entire continent alarmy over a period of weeks. Within
the army, it prevented smallpox, and thereafter inoculation became part
of the enrollment ritual for new soldiers. They were given
a shirt and gun shoes and inoculated. It's the reason
the United States exists. A few decades after Lady Mary
(06:31):
in the UK and once Amiss in the US, a
family by the name of Sutton starts at innoculation business
in rural England, traveling around and inoculating entire towns. They're
the first inoculation entrepreneurs. It was explosive. There were villages
all over the country that adopted the Suttonian system. They
(06:52):
hire a preacher to speak of God's support for the practice.
This is the way for our escape. Reason directs us
to it. Experience proves the utility and safety. This sickness,
as caused by innoculation, is not unto death. The Sutton's
(07:13):
helped make anoculation to mainstream practice, and by the time
their work is finished, a new type of smallpox prevention
is discovered by Edward Jenner. The legend goes that he
meets a milkmaid with perfect skin and she tells him
about being exposed to cow pox, which gives her protection
from smallpox. We all know and believe that beautiful story
(07:34):
of the milk Maide and how she was gorgeous, but
it's not true. It's made up. Even if the story
isn't true, Jenner does pretty much invent vaccination with his
use of cowpox to fight smallpox. In seventeen ninety six,
Dinner makes history by testing his vaccine on his Gardner's son,
eight year old James Phipps, and the boy lives. In
(08:00):
the eighteen eighties, Louis Pasteur creates vaccines for anthrax and
then rabies, using the practice of attenuation, weakening the virus
before injecting it into the body. In nineteen eighteen, the
Spanish flu arrives and sort of takes over the entire
world for a couple of years, killing somewhere around fifty
(08:20):
million people. The next year, Maurice Hilleman is born. Well,
I'm Marie's Haliman. I had a long career in science,
about sixty years. Hilleman is the goat of vaccine invention.
He helps develop most of the vaccines that we get today, measles, rubella,
(08:41):
hepatitis A, hepatitis B, Beninjacoccus, hib streptococcus, chicken pox. That's
all him. He also accidentally helps discover ad no viruses
while culturing the cells of a dead man's trachea. And
I said, well, I'd like to have his trachia. So
I went over to the morgue and waited for him
to carve out the trachea, wrapped it up newspaper and
(09:04):
brown back the lab, cut dope and start chopping on tissue.
Some days, you know, everything just goes right. Ad No
viruses are used today as a delivery system for some
of the COVID vaccines, like Astra's ENCAS and Johnson and Johnson's.
Hillman even creates a vaccine from his own daughter's cells
(09:24):
in nineteen sixty three. The name of the vaccine is
the Journal and Strain. It's on all of the boxes
and package inserts that come out. I have had the
pleasure throughout my life of also being called Miss Mumps,
and usually by pediatricians. And while Maurice Hillman is doing
his thing, some other cool things are happening with vaccines.
(09:47):
By the nineteen forties, we've got new vaccines for diphtheria, tetanus,
and pertussis. In nineteen fifty five, Jonah Saut comes out
with his vaccine for polio. There's also some not so
cool stuff happening when the polio vaccine comes out. One
of the company's mass producing it cut her laboratory messes
up and creates tens of thousands of doses containing live poliovirus.
(10:12):
Fifty one people are paralyzed and five die after getting
the vaccine meant to prevent polio. And in nineteen sixty six,
a vaccine trial for respiratories and scial virus and DC
goes bad. Eighteen babies, mostly from poor black families, end
up in the hospital and two of them die. RSV
can be deadly in children, and there is still no
(10:33):
FDA proof vaccine today. We'll get back to RSP in
a sec In nineteen eighty, smallpox returns to the news
when the World Health Assembly officially declares the virus eradicated. Yes,
after thousands of years, vaccines have ridded the world of
one of humanity's greatest killers. But HIV and AIDS appear
(10:55):
around that time. They spread throughout the eighties, at first
primarily in gay men, but also in intravenous drug users
and later in countries in Africa. Virologist named Eddie Holmes
goes to Edinburgh, Scotland to study HIV spread in the
early nineties. What we were trying to do was trying
to work out how the virus was spreading through that population,
(11:16):
how it diffused, and how it got into city, and
how it spreading. In the nineties, a team at the
US National Institutes of Health creates a vaccine called rhoda
Shield to fight a deadly childhood disease called rhodavirus. Rhoda
Shield gets the nod from the CDC, but within months
some cases of a rare intestinal disorder pop up and
(11:37):
the CDC withdraws its recommendation. But all throughout the eighties
and nineties, another team of researchers is working on a
rival vaccine for rhodavirus called Rhodotech. That one gets low
from the FDA and CDC in two thousand and six,
but not before the biggest clinical trial in the history
of medicine eleven countries and nearly seventy thousand infants. Here's
(12:01):
Paul Offitt, one of the developers of Rhodotech, and it
ended in so called Phase three trial, a prospect the
placebo control, the eleven country four year, three hundred and
fifty million dollars trial to prove that the vaccine worked.
The size of that enormous trial leads to the similarly
giant trials we have in twenty twenty for the COVID vaccines.
(12:21):
Johnson and Johnson, Astra, Zeneca, Fizer, Maderna, and others around
the world are all amongst the largest clinical trials ever.
In two thousand and two, we get an outbreak of
severe acute respiratory syndrome the first stars. More than eight
thousand people in twenty nine countries get it, but by
two thousand and four it mostly dies out thanks to
(12:43):
people like Maurice Hilleman. We've got tons of vaccines at
this point. But in two thousand and six, a new
discovery leads to all sorts of advances in medicine, including
the way we make vaccines. That year, Shinya Yamanaka, a
Japanese researcher, discovers a way to reprogram mature mouse cells
into immature cells. They can then be turned to whatever
(13:05):
type of cells he wants. Here's Derek Rossi who's in
the audience when Yamanaka announces his discovery. So what he
demonstrated was that he could take any cell type, any
differentiated cell which would normally we had thought been sort
of fixed in its identity, but he discovered a way
by introducing four genes to turn back the developmental time
(13:30):
on what was differentiated cell type and reverted back to
an embryonic stem cell like state. Derek is at Harvard
in two thousand and seven and he wants to build
upon Yamanaka's work changing mature cells to immature cells. Yamanaka
is inserting strands of DNA into cells in order to
change them, but this is dangerous for humans. It could
(13:53):
give you cancer. So Derek decides to use mRNA instead,
which is kind of like skipping a step in the
way that life is made. I call it the trifect
of life. DNA makes mRNA, protein makes life. Postdoctor Othello.
In my lab, doctor Luigi Warren had the idea, very
simple idea, just saying, hey, you know, we need to
(14:15):
make these transcription factors. Let's just skip the whole DNA part.
Let's just use m rna. That turns out to be
a genius move, but he runs into another problem When
he puts RNA into cells, the cells think they're being
attacked by a virus, which caused the cell to respond
by saying, looks like a virus is coming in. Let's
(14:37):
shut down the protein production. And it really looks like
a virus is coming in, so let's kill ourselves, you know,
an altruistic suicide and cell death, which is a good
thing for the cell to do, you know, rather than
let it be hijacked by a virus and have it
make hundreds of thousands of viral particles. He finds a
workaround from a couple of researchers at the University of Pennsylvania.
(15:01):
The researchers are Catlin Corrico and Drew Weissman, and they
figured about a cloaking method for tricking cells into not
thinking they're being invaded. Derek integrates it into his own
work and lo and behold, now we can change human
cells without killing them or causing cancerous mutations. That was
the sort of technological breakthrough that led to the development
(15:23):
of modified mRNA. We called it in the lab mod RNA.
He takes this work down the street to Bob Langer,
a serial entrepreneur based at MT, and they start a
company that they eventually name Maderna. By the way, just
as a a fun fact, you know, Maderna. It comes
from the term that we used in the lab describing
the technology. We called it mad RNA. So mod RNA
(15:46):
if you put any in there, you get Maderna. That's
where the name came from. At its formation, Maderna has
exactly zero full time employees and no products. They won't
have one for ten more years. In two thousand and eight,
structural biologist Jason McClellan takes a job at the NIH
where he meets Barney Graham. Graham wants to create a
(16:09):
vaccine for RSV, which is that virus I mentioned earlier
that can kill infants. The RSV vaccine that failed back
in the sixties was made by weakening a strain of
the virus by passing it through animal tissue or human cells.
That's how Maurice Hilleman made a lot of his vaccines.
But Jason and doctor Graham have a new method in mind.
(16:29):
They want to mess with the F protein of RSV.
That's the one the virus uses to infect human cells.
Before the F protein attaches itself to a human cell,
it is in its prefusion state. If you think of
your immune system as a security guard, you want to
train your immune system to recognize the form that might
infect you, like the dangerous form, and that's the prefusion form.
(16:51):
If you train it to recognize the postfusion form, the
prefusion form can still sneak by you. Barney, Graham, and
Jason want to figure out how to keep the F
protein in this state, and in twenty thirteen they do.
They figure out a way to sort of staypule the
protein so it stays in that form. And when Barney
(17:12):
immunized mice and compared postfusion versus prefusion, the mice receiving
the prefusion form of the F protein elicited neutralizing antibodies
about ten times higher than those that received the postfusion.
This is the first time that structural biology, looking super
closely at the structure of a virus helps discover a
(17:34):
new way to stop it. But now they want to
see what other viruses they can work on using this
prefusion protein state. This is right around the time that
Middle East Respiratory Syndrome is first reported in Saudi Arabia.
MERS is a really bad coronavirus. Thirty five percent of
people infected with it we're dying. It's a real lethal virus,
(17:55):
and we thought that this would be a good target
to try to take everything we had just learned about
RSP and apply it to not just MERS, but coronaviruses
in general, because we knew the Stars coronavirus had emerged
in China in two thousand and two and it caused
an epidemic. It turns out that MERS has a protein
that works kind of like the rsv F protein. It's
(18:17):
called the spike protein, and when the merge virus attacks
human cells, the spike injects itself into them in order
to spread throughout the body. But it's not easy to
staple the spike protein. It takes tons of trial and error.
Here's Nanchan Wang Jason's post doc to explain how hard
it is to figure this out. We got to try
(18:41):
again and again most of the time. It's got to feel. Yeah,
it's not so too easy actually to find their mutation
that to stabilize as product, it's pretty italented. By twenty seventeen,
they figure out how to staple the spike protein in
place and use that to teach the immune system to
fight off a MERGS infection, but they don't have any
(19:03):
people to test it on. Turns out MERS doesn't spread
very easily and the outbreak is mostly over by then.
No outbreak means no human trials, no human trials, means
they can't be sure that stabilizing the spike protein really
works as a vaccine candidate. Then in December twenty nineteen,
a new coronavirus appears. Here's Derek Rossing. You could see that.
(19:27):
You know, it was really snowballing. I mean it had
everything that a good pathogen would want. It was a respiratory.
When it was first being reported, the fatality rates and
the illness rates were very very high. We didn't, you know,
it was a new virus. We didn't know how to
respond to it. So the fatality rate was around two percent.
That's pretty darn serious. In mid December twenty nineteen, a
(20:00):
worker at the Huanan seafood wholesale market gets sick with
theemmonia like symptoms. He's admitted to Central Hospital of Wuha
and he's one of the first novel coronavirus patients in
the world. Central hospital happens to be where British phiologist
Eddie Holmes and it's Chinese colleague Jan Jang Jang are
studying patients with acute respiratory symptoms around that time. But
(20:22):
what that meant was we were kind of like on site,
almost looking at the same Z syndrome in the right
tissue samples with the right technology, and so we happen
to be in the wrong place the wrong time. I
feel like when it all kind of started, and that's
gave us an open door to really to try and
look at some of the early first cases to see
(20:44):
what was going on. Late at night and January fifth,
twenty twenty, Jang finishes sequencing the virus, but Chinese authorities
are trying to keep anything related to the virus from
being made public. The Ministry of Health were controlling everything,
and they wanted They wanted to control the message, they
wanted to damp down on rumors, they wanted to be
in control of the situation. On January eleventh, Jang gets
(21:08):
on a plane in Shanghai and is about to take
off when his phone buzzes. It's Eddie. I cooled jan
very early, and I said we need to release he
stay tonight. Jang agrees, has a post duct send the
sequence to Eddie. Eddie tweets out a link. That moment
kicks off development for the COVID nineteen vaccines, and that's
(21:30):
exactly what Jason McClellan starts working on the reports were
coming out of these pneumonia clusters in Wuhan. We could
just see it following along on science Twitter and on
the news. And then it was early in January when
it was learned that, in fact, it is a coronavirus
beta coronavirus that's similar to the first stars Kobe from
(21:50):
two thousand and two. Jason's at the University of Texas. Now,
I was a snowboarding with my family in Park City, Utah,
and Barney Graham called me. He said he was in
contact with the US CDC Chinese CDC and they were
going to try and work quickly work with Maderna try
and create a vaccine. Maderna is still considered an upstart
(22:11):
company at best, and it's never brought a vaccine to market.
Anyone to know if if we were interested in continuing
our collaboration to determine the structure of the stars cope
to spike protein and use that information to create the
vaccine antigens, Jason texts has graduate student Daniel Rep. We
(22:31):
were sort of ready to go, that's Daniel, because we've
been studying these spike proteins for such a long time.
We knew how to effectively stabilize spike in the prefusion
confirmation and that acts as a really good vaccine candidate.
Within a few weeks, they figure out how to stabilize
the spike protein of the novel coronavirus. But to make
a vaccine work, they need to make sure the mRNA
(22:53):
gets where it needs to go to instruct the body
to make stabilize spike proteins. What MADERNA does is encapsulate
the mRNA in a lipid nanoparticle shell to protect the
mRNA on its way to doing its things. Here's biochemist
Thomas Madden of Acuteous Therapeutics in Vancouver to remind us
what an l enp is and does. If you wanted
(23:14):
to order a really fragile glass ornament online and you
wanted it delivered to your to your home, if you
used the equivalent of our delivery technology, then the ornament
would be would be wrapped and packaged to protect it
and noboutter how rough the journey was to your to
your house. The package would would find your house, it
(23:37):
would open the front deck door by itself and let
itself in, and then it would unwrap itself. So the
ornament is waiting for you to come along and pick
up in your hallway, so the lipidano particle delivers the vaccine,
kind of like how FedEx delivers a package. Around the
same time that the Phase one trials from Aderna begin,
(24:00):
the US starts shutting down. Rush to the grocery store
like every single other person, and you know, the meat
sections were empty, and that just kind of that was
a little eerie to see. This is Nicola Pescarilli, and
all of a sudden, I just felt like everything was
closed off, and I didn't like that feeling. And so
it's like, what can I do to get everything to
(24:21):
return back to normal as soon as possible? What can
I do? What can I do to make things better?
Because I felt just so hopeless. Tom Hanks has COVID,
the NBA has shut down, entire cities and countries around
the world shut down, and Nicola volunteers for the Phase
one trial at the Hope Clinic in Atlanta. I'm in
(24:42):
Phase one, like, I am one of fifteen people getting
the highest dosage that no one else in this country,
in this world has ever gotten. And I think for
a moment, I thought, oh God, it might crazy, Like
could I die? And then I was like, no, it's fine.
Modern medicine is great, and it is great. The phase
one trial is a success. It was a very small process,
(25:07):
and I remember afterwards they wanted me to stay to
observe me for a while after the vaccine, and it
was still just like getting used to the whole new
change in the world. Meanwhile, more than a hundred other
vaccines are in the works around the world, all sorts
of them spot Nick in Russia, Sino farm and Sino
(25:28):
vac in China, Astra Zenica in the UK, Covaccine in India,
Soberana two in Cuba. They are mr Anda vaccines, had
no virus, vaccines, in activated vaccines. There are even vaccines
grown and tobacco like plants. But in the meantime, before
the vaccines are actually rolled out, lots of people are
(25:49):
getting sick and lots of people are dying, and nearly
everyone else is stuck at home, stuck caring for people,
confused about what to do and how to live. So
happy Halloween to me. Turns out I did have COVID.
A lot of us are really lonely, unable to see
friends or family, no office to go to. Some people
(26:10):
get COVID pets. Like Marina in Sweden, I was having
a really hard time sticking to any sort of schedule
because the days were all the same and there was
nothing to do. And then when COVID came around and
I had been working from home for nine or ten months,
I was just at my wits end, like so sick
of just being by myself. So I decided, like, now
(26:33):
is the time I'll get a dog. I can be
at home and train the dog. It seemed like a
good idea, but during COVID everything is more complicated and
plans just continuously get fucked up for everyone all the time.
In a slightly different world, I would have gone all
those things I wanted, but in a COVID world, I
(26:54):
didn't get any of them. Some people get sick and
stay sick, like Dave Hockaday in Oxford. It's just getting
worse each day. And then of course the fatigue was building,
that was getting worse, and there was just generally feeling
starting to feel really unwealth inflamed hot, was getting chills
(27:15):
at night times and night sweats, insomnia, dreadful nightmares. My god,
the nightmares were horrific. People like Dave have long COVID
and even today it's unclear what exactly is causing it.
Just seeing the numbers like them, an average number of
symptoms that long COVID patients had. That's Athena Akramy, a
(27:38):
neuroscientist at University College London. She got COVID in March
twenty twenty and seventeen months later she's still sick. She
now spends a lot of her time studying long COVID.
The average number of symptoms is more than fifty. Just
like seeing that number that like one person I can't
(27:58):
experience fifty different symptoms was kind of, I don't know, shocking,
and it seems like long COVID it will be a
huge problem for years to come. We are just like
accumulating so many long covides down like in a year,
probably each country will have millions of people, most of
(28:20):
them again previously young and faith that now they are
just like really struggling to go back to semi normal life.
That I really don't know what we'll how. It's a crisis,
it's a health crisis. But on a positive note. By
(28:41):
early twenty twenty one, three vaccines have gotten emergency authorization
in the US and they start making their way to
healthcare workers and the elderly. There are major hiccups at first.
I mean, it's damn near impossible for some people to
get appointments because there's no central system to do that.
It's a goddamn free for all instead of an orderly line.
(29:02):
At first, I was not successful at finding a vaccine.
That's Stanley Plutkin, one of the world's top experts on vaccines.
Even the guy who literally wrote the book on vaccines,
has trouble getting an appointment at first. He's eighty eight
years old and really vulnerable if he gets COVID. What
do you mean you weren't successful, even like you were,
(29:24):
You couldn't get an appointment at first? Yes, well, yeah,
I think initially of finding it was not easy. Initially
there was a lot of uncertainty about where vaccines were available,
how much was available, etc. That's how chaotic it is
(29:46):
in the beginning of twenty twenty one, and so it
became a You still have to navigate systems that are
largely fragmented and by the way, all online in order
to secure an appointment. And guess what, the very populations
that were favored is early beneficiaries of New York States
(30:09):
vaccine program are precisely the populations who can't be on
the internet all day or are not on the internet,
so the elderly, restaurant workers, grocery store workers, taxi drivers.
That's s Metro Khalita, whose organization Epicenter NYC helps get
people vaccine appointments in Jackson Heights, Queens back when it's
(30:29):
super hard to do it if you aren't really Internet savvy.
But eventually there's so much vaccine out there in the
US that anyone who wants a shot can get one.
Of course, not everyone does. One way to get vaccines
made and distributed faster for the next pandemic is to
use human challenge trials. That's where people get a disease
(30:52):
on purpose so that doctors and scientists can study it.
The first human challenge trial for COVID begins in the
UK in March twenty twenty one, and Jacob Hopkins is
one of the participants. Speaks of getting and COVID is
the most surreal thing in the world, Like it's intimidating.
This is him describing how they infect him during the trial.
(31:15):
It's like Jesus Christ, like this is like intense, and
they get this huge p pair. It's like almost like
a turkey basis, Like it's a massive pair they have.
They pick it up, they start counting down, So they
count down from twenty, which is adds to the suspense really,
and then they kind of like drop up in each nostrils,
so they kind of drop it around the outside of
the one nostril and then did the other and then
their way and they count not from twenty again and
(31:38):
then they repeat. You're kind of just sit like you're
kind of just laying there in silence, like just thinking,
oh my god, I've just been infected with coronavirus, and
like it kind of obviously kind of hits in at
that point. And while the UK and US and other
wealthy nations are overloaded with vaccines, poorer countries can't get
(31:58):
enough to vaccinate even small portions of their people. Even
with donations trickling in from miserly nations like the US,
low incombinations are still only two percent vaccinated on average,
And so a bunch of researchers get together and create
a new vaccine that can be produced cheaply and easily.
Here's Bruce Innis from the organization PATH. We're extremely interested
(32:22):
in ensuring that countries where health budgets are not strong
have access to world class vaccines that are life saving.
On the proposition that everyone deserves to have access to
life saving vaccines. PATH has helped coordinate the development of
(32:42):
this new vaccine, which is called ndv HXPS. It uses
a new stabilized spike protein called hexapro developed by Jason
McClellan and his colleagues at UT and then also starting
to make a second generation spike protein that was even
more stable than the two protein form. The engineered protein
(33:02):
is carried into the body by Newcastle disease by, which
is an avian virus. Here's Peter Palaze, a microbiologist at
Mount Sinai who helped develop the vaccine, and so we said, okay, right,
don't we put the sous coronavirus spike protein into Newcastle
disease bows and thens what we did, so we have
a vector ven vaccine. The big difference between this vaccine
(33:28):
and the ones we've gotten in the US is that
it's cheaper to make because it's grown in chicken eggs
just like most flu shots, and it's being piloted in Vietnam, Brazil,
and Thailand. Already here's Bruce again. They've made multiple lots
of vaccine, initially at pilot scale, which might involve a
few thousand eggs, and we're getting typically about seven to
(33:51):
eight finished vaccine doses per inoculated egg. You can think
of the egg as a mini bioreactor, each one self
contained bioreactor. And now they're in the process of manufacturing
the investigational vaccine at full commercial scale. Some phase one
clinical trials have already finished and the results are promising,
(34:14):
but the new vaccine still needs to go through the
big phase three trials. If they go well, ndv HXBS
may end up being, at least for some countries, the
future of coronavirus vaccines. That brings us to the end
(34:37):
of this podcast. We started millions of years ago and
finished still in a pandemic with no clear end. Variants
are here, people are still getting sick and dying, and
life is still weird and annoying even if you're healthy.
I'm personally super impressed with all the incredible researchers and
volunteers and historians we heard from and about. I mean,
(34:58):
how the hell the first human being figured out that
giving someone a little bit of a disease to protect
from a lot of it hundreds, if not thousands of
years go, is just mind blowing to me. But just
a reminder. This is not the entire story. It's just
what I've been able to cover in this relatively short
ten parts series. There are a ton of people who
have made important contributions to so many vaccines, lots of
(35:21):
names that have gone unsaid by me and by others,
lots of people whose work has helped save hundreds of
millions of lives, and also hundreds of millions of lives
that have been lost along the way. As of today,
four point seven seven million people have died of COVID,
and they include, just to name a few, Darlene Ray, Rose,
(35:42):
Marie Fazzio, Ron Kieran, Adel Cercelli, Kenny Cassina, Doctor Ferkin,
Ali Sadiki, Patricia Francis Prescott, Mark Dvorschak, and my aunt Rifka.
A COVID vaccine could have saved almost all of those
four point seven seven million people, just like a smallpox
vaccine has saved who the hell knows how many people.
(36:05):
My hope is that when the next pandemic. Hits will
be able to create a vaccine even faster and get
it to more people faster, but that'll depend on more research,
more domestic and international cooperation, and more agreement in the
world in general. There's just no way to protect the
world unless the whole world is protected. Now, let's end
(36:26):
this thing with another dip into the recent past. March
twenty seven, twenty one, the first Boutanese person is about
to get her first shot of a COVID vaccine. Her
name is Ninda, which roughly translates to the Sun and
the Moon. She's thirty years old and was born in
the Year of the Monkey. The nurse who will administer
her shot is also thirty years old and also born
(36:49):
in the Year of the Monkey. After being picked to
be the first person in her country to be vaccinated,
Ninda says, let the small step of mind today help
us all prevail through this illness. She sits with her
back to her room full of massed healthcare workers and monks,
and they pray together until she gets her shot. Long
(37:20):
Shot is a production of School of Humans and iHeartRadio.
Today's episode was produced, written and narrated by me Sean Ravie.
A Co producer is Gabby Watts. Special thanks to Noel
Brown and iHeartRadio. Executive producers are Virginia Prescott, Elsie Crowley,
and Brandon Barr. Fact Checking for this episode is by
(37:42):
Adam Shadow. Long Shot was scored by Jason Shannon. The
score was mixed by Vick Stafford. Sound design and audio
mixed was by Harber Harris with Tune Welders School of
Humans
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