Speaker 1: School of Humans. Let's go back to the spike protein.
Speaker 1: Remember Jason McClellan, the guy at the University of Texas
Speaker 1: who told us about the spike protein in episode four.
Speaker 1: It's the mushroom stock shaped thing on coronavirus cells. Based
Speaker 1: on decades of literature many researchers, it was clear that
Speaker 1: the spike protein is a key component of any vaccine
Speaker 1: because Jason explained how the spike protein is, how the
Speaker 1: coronavirus attaches itself to human cells and infects us with
Speaker 1: the virus, and why we need to teach the immune
Speaker 1: system to recognize it. And that's how the Maderna Adviser
Speaker 1: and Johnson and Johnson vaccines work. All the vaccines Americans
Speaker 1: are getting, but there are some big problems with those vaccines.
Speaker 1: Not in their function. They work incredibly well and protecting
Speaker 1: us from COVID, but they're expensive. Expensive because they're made
Speaker 1: by giant pharmaceutical companies designed to make money. Expensive because
Speaker 1: they require relatively hard to get ingredients that have to
Speaker 1: be put together, and specialized factories with specialized equipment. And
Speaker 1: expensive is fine for America. It's kind of okay that
Speaker 1: these pharma companies make lots of money for providing an
Speaker 1: invaluable service, and the government is subsidizing the COVID vaccines anyway.
Speaker 1: It's that they're free of charge, but expensive doesn't work
Speaker 1: for a lot of the world. Expensive means poorer countries
Speaker 1: can't get doses because they're outbid or have no money
Speaker 1: to bid with. And if we're not protected, unless everyone
Speaker 1: is protected, that doesn't stop at the border. It means
Speaker 1: the whole world has to be vaccinated, not just the
Speaker 1: whole country. But right now that's not happening. I mean,
Speaker 1: as of this recording, only two percent of people in
Speaker 1: low income countries have gotten even a single dose of
Speaker 1: coronavirus vaccine two percent. And so a bunch of people,
Speaker 1: including Jason McClellan and its mother, top notch scientists got
Speaker 1: together and they created a cheaper COVID nineteen vaccine. In
Speaker 1: this episode, we're going to tell the story of how
Speaker 1: they did that. From School of Humans and iHeartRadio, I'm
Speaker 1: Sean Revive and this is long shot. Okay, hold on
Speaker 1: one second, sure, thank you. Yeah. This is Peter Palais.
Speaker 1: He's a microbiologist and professor and share of the Department
Speaker 1: of Microbiology at the Icon School of medicine and mount Sine.
Speaker 1: Just sorry, wind bottling the back. You know that's not
Speaker 1: the best of here. Okay, this is what he does
Speaker 1: that I have been working for really decades um ourna
Speaker 1: viruses with an emphasis on influence of us is over
Speaker 1: many many years and there I have written an anti
Speaker 1: virals on Vaccines, UM Genetics um the whole gamut. So.
Speaker 1: Peter has been working on RNA viruses and especially flu
Speaker 1: viruses since the nineteen seventies. He created the first genetic
Speaker 1: maps for three of the four types of flu viruses, A, B,
Speaker 1: and C, the three important ones as far as humans
Speaker 1: are concerned. D is mostly a cattle virus. Peter is
Speaker 1: also a pioneer in the field of reverse genetics. He
Speaker 1: said technology allows you to make changes in the genome
Speaker 1: of the virus. Reverse genetics allows you to make particular
Speaker 1: changes in a virus to sort of pick and choose
Speaker 1: which genes you want to include or exclude. Reverse genetics
Speaker 1: allows researchers to look at a gene, a basic unit
Speaker 1: of DNA or RNA, the thing that passes traits from
Speaker 1: your parents to you, and discover what it does, what
Speaker 1: its purposes, and using reverse genetics Peter was part of
Speaker 1: a team that actually brought the nineteen eighteen Spanish flu
Speaker 1: back to life, the one that killed maybe fifty million
Speaker 1: people three percent of the world back then, and they
Speaker 1: did this for science. Peter and a bunch of other
Speaker 1: scientists were able to frankenstein the Spanish flu. It started
Speaker 1: with a Swedish microbiologist named Johann Houlton. In nineteen fifty one.
Speaker 1: He traveled to Alaska to a tiny village called Brevig
Speaker 1: Mission to find a mass grave of Spanish flu victims.
Speaker 1: In nineteen eighteen, Brevig Mission had only eighty people living there,
Speaker 1: and seventy two of them died over a five day
Speaker 1: period from the flu. The bodies were buried in permafrost
Speaker 1: and marked with white crosses. Holton believes he could find
Speaker 1: traces of the virus in the bodies. He got permission
Speaker 1: from village elders to unfreeze the grave with campfires and
Speaker 1: unearthed several bodies. He took lung tissue from a few
Speaker 1: of the dead, including that of a young girl still
Speaker 1: wearing a blue dress and red hair ribbons. After all
Speaker 1: these years, he tried to preserve the samples during travel
Speaker 1: all the way back to his lab at the University
Speaker 1: of Iowa, but when he got there, he couldn't extract
Speaker 1: any virus from the tissue samples. Half a century later,
Speaker 1: he would get another chance. In nineteen ninety seven, he
Speaker 1: read about the work of a team at the Armed
Speaker 1: Forces Institute of Pathology in DC. They had extracted RNA
Speaker 1: from the nineteen eighteen virus from the preserved lung tissue
Speaker 1: of a US service member, but the sample didn't contain
Speaker 1: enough virus to collect a full genetic sequence. Holton reached
Speaker 1: out to the team and offered to go back to
Speaker 1: the Alaskan village he'd gone to forty six years earlier
Speaker 1: and find more samples. He did, and this time he
Speaker 1: was able to successfully preserve the lung tissue on the
Speaker 1: way back from brevig mission using the samples Holton collected,
Speaker 1: along with samples from two long dead US soldiers, the
Speaker 1: Armed Forces Institute of Pathology researchers had the nineteen eighteen
Speaker 1: flu fully sequenced a few years later, so they had
Speaker 1: the code to build it, like having a blueprint for
Speaker 1: a house before construction, but the virus still needed to
Speaker 1: be built. That's where Peter Palais came into it. They
Speaker 1: brought in Peter and his colleagues at Mount Sinai to
Speaker 1: create the parts that would be put together in a
Speaker 1: highly secured CDC lab to recreate the nineteen eighteen virus
Speaker 1: using Peter's reverse genetics techniques in two thousand and five,
Speaker 1: working alone during off hours when nobody else was in
Speaker 1: the lab to be extra safe in case of contamination,
Speaker 1: microbiologist Terence Tumpy made the Spanish flu virus unextinct. The
Speaker 1: Franken virus lived. Tumpy then performed experiments on mice comparing
Speaker 1: the lethality of the nineteen eighteen virus to more modern
Speaker 1: day flues. The old flu was found to be at
Speaker 1: least one hundred times more deadly than the other flu
Speaker 1: viruses he tested against. But what if the actual nineteen
Speaker 1: eighteen flu got out of the lab, would we be
Speaker 1: in for more years of quarantine? And why is it
Speaker 1: important to study a virus that hasn't been out there
Speaker 1: in almost one hundred years? What was the goal of that?
Speaker 1: To understand? I mean the first one was it? So
Speaker 1: we have anti virls against influence of ours. These are
Speaker 1: the famous humidities inhibitors, tamiflu Baloques Ofvere et cetera. And
Speaker 1: that was the first thing we want to know. Can
Speaker 1: the available FDA prooved thugs, can the inhibit the virus?
Speaker 1: And we were thank the Lord. We were very happy
Speaker 1: to see right away that these virus has behaved like
Speaker 1: any other influence of ours. Also, we learned that it
Speaker 1: is inhibitable by anti virus, It is not resisting to vaccines.
Speaker 1: We've learned how it gets transmitted, and we have a
Speaker 1: much better understanding of the nineteen eighteen virus than we
Speaker 1: had before. And I can honestly say, if that virus,
Speaker 1: the nineteen eighteen virus would emerge miraculously, I don't think
Speaker 1: it will, we would be not as helpless as we
Speaker 1: were a hundred years ago. And a lot has to
Speaker 1: do with our understanding now with the whole alimentarium of
Speaker 1: things which would prevent such a pandemic. Again, reverse genetics,
Speaker 1: the field that Peter Palaze helped create, has also proven
Speaker 1: valuable in creating new vaccines. Many vaccines today are developed
Speaker 1: by making genetic changes to a virus so they're less pathogenic,
Speaker 1: less able to make you sick, but the less pathogenic
Speaker 1: virus remains recognizable to the immune system so that it
Speaker 1: can learn to fight off the real virus when it
Speaker 1: enters the body. One type of vaccine that works this
Speaker 1: way is called a viral vector vaccine. These are vaccines
Speaker 1: that use one virus as a delivery method or vector
Speaker 1: to send instructions to the body to fight off another virus.
Speaker 1: The Astrazenica and Johnson and Johnson vaccines are viral vector vaccines.
Speaker 1: The Russian Sputnik vaccine, that has been given emergency authorization
Speaker 1: in more than seventy countries, is also a viral vector vaccine.
Speaker 1: Now Peter has been involved in a new viral vector
Speaker 1: vaccine for COVID nineteen. But before we get there, we
Speaker 1: got to go back to spike proteins and chickens. Let's
Speaker 1: refresh our memory a bit more on the spike protein.
Speaker 1: The way the American vaccines work is by showing the
Speaker 1: immune system stabilize spike proteins, which the body then learns
Speaker 1: to recognize when coronavirus cells enter the body. The way
Speaker 1: the spike proteins and the vaccines are stabilized is by
Speaker 1: swapping out two amino acids for two prolleins. Really stable
Speaker 1: amino acids at a specific joint. That's called the two
Speaker 1: P mutation. The P is for prolins. That's what the
Speaker 1: vaccines use to teach the body to protect against coronavirus.
Speaker 1: And after figuring this out, Jason McClellan at UT didn't
Speaker 1: stop there, and in March twenty twenty one, with lots
Speaker 1: of trial and error in the lab, he and his
Speaker 1: p pole came up with an even better way of
Speaker 1: stabilizing the spike protein. It's not that different from the
Speaker 1: two P mutation, but this one involves using six pro
Speaker 1: lieins to stabilize the spike. In this case, using six
Speaker 1: is better than two. They name the stabilized spike protein
Speaker 1: hexapro because of the six prolleins. Hexa means six. Jason's
Speaker 1: hope was that hexapro could be the basis for the
Speaker 1: next generation of COVID vaccines, and the University of Texas
Speaker 1: arranged it so that hexapro could be used royalty free
Speaker 1: by low and middle income countries. That means these countries
Speaker 1: can theoretically make vaccines cheaply, but first they needed an
Speaker 1: inexpensive way to get the super stabilized protein into the body.
Speaker 1: At the same time that Jason McClellan was working on hexapro.
Speaker 1: An organization called PATH was trying to figure out a
Speaker 1: way to deliver more vaccines to poorer countries. Were extremely
Speaker 1: interested in ensuring at countries where health budgets are not
Speaker 1: strong have access to world class vaccines that are life saving,
Speaker 1: on the proposition that everyone deserves to have access to
Speaker 1: life saving vaccines. That's doctor Bruce Innes. He's a physician
Speaker 1: and he's been working on vaccines for almost forty years,
Speaker 1: tons of them against human papaloma virus, against rotavirus, gastroenteritis,
Speaker 1: various cella vaccine, combination, measles, MOBSTERB varius cella vaccine, influenza viruses,
Speaker 1: human papaloma virus. Bruce has been a PATH for five years.
Speaker 1: The organization is based in Seattle and aims to improve
Speaker 1: public health in lower income countries through innovation and partnerships.
Speaker 1: At PATH, Bruce has worked on vaccines against RSV, meningitis, pneumonia, flu,
Speaker 1: and now COVID. We realize that with COVID nineteen, even
Speaker 1: early in the PATH demic, that no one would be
Speaker 1: safe until everyone was safe, and that's why it was
Speaker 1: important for us to think about in showing that all
Speaker 1: countries would have access equitable access to covid vaccines. This
Speaker 1: is where chickens come back into it. Remember an episode
Speaker 1: three when we heard from the King of all vaccine inventors,
Speaker 1: Maurice Hilliman. He grew up raising chickens on the family
Speaker 1: farm and talked about how important they were to his
Speaker 1: work in the lab years later and my career, chickens
Speaker 1: were my best friend because I used them for so
Speaker 1: many types of experimentation, and then we're breakthrough experiments. A
Speaker 1: lot of vaccines are grown in chicken eggs, including lots
Speaker 1: of the vaccines invented by Hilliman. Bruce and Path had
Speaker 1: worked in the past with some middle income countries to
Speaker 1: improve their capacity to produce egg based flu vaccines. An
Speaker 1: egg based vaccine is literally one where the primary ingredient
Speaker 1: the virus to be expressed, is grown and chicken eggs.
Speaker 1: That's the most common way to make the flu vaccines
Speaker 1: you get or can get every winter. They are really
Speaker 1: inexpensive to make, and if you can make a covid
Speaker 1: vaccine the same way, then you can theoretically just convert
Speaker 1: a flu vaccine factory into a covid vaccine factory, and
Speaker 1: we asked Mount Sinai. That is, they asked Peter Plais
Speaker 1: and his colleagues at Mount Sinai if there was a
Speaker 1: way to make a covid vaccine using a virus that
Speaker 1: would replicate in eggs. They said, yes, We've done this
Speaker 1: before with an avian virus called Newcastle disease virus virulent.
Speaker 1: Newcastle disease or simply Newcastle disease, is an avian disease,
Speaker 1: a bird flu. In other words, it can infect humans,
Speaker 1: but rarely produce the symptoms in people. The disease is
Speaker 1: caused by the appropriately named Newcastle disease virus, and it
Speaker 1: spreads from bird to bird through their poop and other
Speaker 1: bodily secretions. It's a big problem for commercial chicken factories
Speaker 1: that squeeze a lot of chickens into densely packed spaces
Speaker 1: amorally in my opinion, but that's neither here nor there.
Speaker 1: Newcastle disease can spread on a factory farm and sicken
Speaker 1: or kill their chickens. So the commercial chicken companies spray
Speaker 1: Newcastle disease vaccines into their factories and vaccinate all the
Speaker 1: chickens at once. Here's Peter to give a somewhat apocalyptic
Speaker 1: visual in these big, big factories, and Newcastle disease virus
Speaker 1: is put in canastus on the back of people and
Speaker 1: they go into these factories. In spray life Newcastle disease virus,
Speaker 1: chickens can also get flu viruses, and the factories didn't
Speaker 1: want them getting that either. So Peter had worked on
Speaker 1: a Newcastle disease vaccine that could also stop chickens from
Speaker 1: getting the flu. Newcastle disease has also been explored as
Speaker 1: a vector for carrying an ebola gene and for carrying
Speaker 1: cancer killing viruses. And so we said, okay, why I
Speaker 1: don't put the a saus coronavirus spike protein into Newcastle
Speaker 1: disease burs And that's what we do at Mount Sinai.
Speaker 1: Peter as colleagues, including Fluorine Cramer and Adolpho Garcia Sastre,
Speaker 1: engineered a Newcastle disease virus that could carry hexapro into humans.
Speaker 1: So the Newcastle disease is the vector for the hexapro
Speaker 1: stabilized spike protein. They call the vaccine NDV HXPS NDV
Speaker 1: Newcastle Disease Virus h XPS hexapro spike instead of using
Speaker 1: super specialized machinery. They're making this vaccine and chicken eggs.
Speaker 1: They've made multiple lots of vaccine, initially at pilot scale,
Speaker 1: which might involve a few thousand eggs, and we're getting
Speaker 1: typically about seven to eight finished vaccine doses per inoculated egg.
Speaker 1: You can think of the egg as a mini bioreactor,
Speaker 1: each one self contained bioreactor. And now they're in the
Speaker 1: process of manufacturing investigational vaccine lots at full commercial scale.
Speaker 1: Clinical trials and humans for NDVHXPS are already underway in Vietnam, Thailand,
Speaker 1: and Brazil. In Vietnam and Thailand they moved on to
Speaker 1: phase two after phase one trials show that the vaccines
Speaker 1: are safe and produce an immune response in people. In Thailand,
Speaker 1: they're also onto phase two and expect to produce twenty
Speaker 1: million or more doses of the vaccine per year starting
Speaker 1: in twenty twenty two. Brazil has entered phase one, and
Speaker 1: if all three country trials proved successful, they can produce
Speaker 1: vaccines fairly quickly since they already have functioning flu vaccine
Speaker 1: production facilities. I can't tell you our quick clin Nicola
Speaker 1: and animal challenge experience, how compelling. I can't take I
Speaker 1: can't protect every mouse and every hamstand the world against
Speaker 1: any sauces. It works beautifully in the animal systems we had.
Speaker 1: Based on the animal studies, you can feel like it's
Speaker 1: a really very good sign, no doubt, no doubt. So
Speaker 1: Pete is very confident that the Hexa pro Newcastle hybrid
Speaker 1: vaccine will work well in people, and let's hope that
Speaker 1: it does. Not only is it really cheap and easy
Speaker 1: to produce, there's another benefit to this vaccine. One of
Speaker 1: the reasons if fives are in well, the end of
Speaker 1: vaccine also expensive. You know what. One of the reasons
Speaker 1: is stability. They have to have the binus foody and
Speaker 1: minus eighty degree freezers explorinly expensive. All of vaccine is
Speaker 1: stable at kitchen refrigeration temperatures two to four degrees four weeks,
Speaker 1: so it is very very stable. That's one of the
Speaker 1: biggest issues with modern medicine in developing countries. It's not
Speaker 1: always possible to keep it cold enough. Ndv HXPS helps
Speaker 1: with that a ton by staying stable at refrigerator temperatures,
Speaker 1: and the manufacturers that Path is working with can make
Speaker 1: a lot of vaccine in big bunches. Here's Bruce. A
Speaker 1: typical lot size involves more than five thousand eggs that
Speaker 1: are inuculated and harvested three days later. And when I
Speaker 1: say innoculated and harvested, you put a small amount of
Speaker 1: seed virus into the egg. It propagates in the embryo
Speaker 1: when it's incubated at thirty seven degrees. Then the eggs
Speaker 1: are chilled overnight at the end of a seventy two
Speaker 1: hour period and the egg fluids the whites of the
Speaker 1: egg are harvested and from that you can purify the
Speaker 1: virus inactivate it formulated for administration. So the Southeast Asian
Speaker 1: countries will have a typical lot size of around fifty
Speaker 1: to forty to fifty thousand eggs per lot, and each
Speaker 1: manufacturer can initiate multiple lots in a given week. Vietnam,
Speaker 1: for example, as of this recording, is still instituting a
Speaker 1: severe nationwide lockdown because only seven percent of their population
Speaker 1: has been able to get fully vaccinated, so being able
Speaker 1: to produce their own vaccine would be huge. Is a
Speaker 1: middle income country, relatively wealthy by world standards. Seven percent
Speaker 1: is high compared to low income countries, which, like I said, earlier,
Speaker 1: are only two percent vaccinated. Right now, the US and
Speaker 1: other wealthy countries maybe doing okay with vaccination, but we're
Speaker 1: doing a shit job as a planet. The Newcastle hexapro
Speaker 1: vaccine could help change that. Our aspiration, and we shared
Speaker 1: this with the manufacturers, is that this would be one
Speaker 1: of the most affordable vaccines possible. The starting material is
Speaker 1: an embryonated egg, a fertile egg and a small bit
Speaker 1: of seed virus, and the cost of eggs for production
Speaker 1: for vaccines is somewhere between twenty five and thirty cents
Speaker 1: an egg. And I told you that there's seven to
Speaker 1: ten doses per egg, so that's only pennies per dose.
Speaker 1: Of course it has to be mixed with a bunch
Speaker 1: of other ingredients first, but you can imagine the NDVHXPS
Speaker 1: vaccine ends up pretty cheap. If the main thing doing
Speaker 1: the work in it only costs a few cents, that's
Speaker 1: a good way to get the world vaccinated. This is
Speaker 1: a grand experiment. The inactivated Newcastle disease virus vaccine has
Speaker 1: never been administered to human subjects before. It's brand new technology.
Speaker 1: It's very very exciting, and the preclinical data were astonishing.
Speaker 1: We think that the covid pandemic won't abate until everyone
Speaker 1: has access to vaccine. There are many countries that have
Speaker 1: been left behind. We hope that the ndv hxp S
Speaker 1: vaccine will have an important impact on helping to abate
Speaker 1: the epidemic and will be used in years to come
Speaker 1: for controlling endemic covid disease which is likely to continue
Speaker 1: to circulate them on human populations. The next and last
Speaker 1: episode of long Shot is going to be a little
Speaker 1: different than the others. We're going to go over everything
Speaker 1: we've talked about in a series and put it all
Speaker 1: together into one story and then fill in some gaps
Speaker 1: from the history of vaccines that's next week on long Shot.
Speaker 1: Long Shot is a production of School of Humans and iHeartRadio.
Speaker 1: Today's episode was produced, written, and narrated by me Sean Revive.
Speaker 1: A co producer is Gabby Watts. Special thanks to Noel
Speaker 1: Brown and iHeartRadio. Executive producers are Virginia Prescott, Elsie Crowley,
Speaker 1: and Brandon Barr. Fact Checking for this episode is by
Speaker 1: Adam Shadow. Long Shot was scored by Jason Shannon. The
Speaker 1: score was mixed by Vic Stafford. Sound Design and audio
Speaker 1: mixed was by Harper Harris with Tunewielders School of Humans