Not Unto Death

This sickness is not unto death. His name is Robert Holton. He's not preaching on the word of God, at least not directly. He's evangelizing about a new medical curiosity. This sickness, as caused by inoculation, is not unto death. Some in the audience believe the product Reverend Holton is selling will invite Hell to their village, but he ignores the skeptics

and rolls on. This sickness, as caused by inoculation is not unto death, is not worthy of divine vengeance or punishment because it violates no command of God and is not included under any sin that he has forbidden the practice of inoculation is justifiable. This sickness, as caused by inoculation, is not unto death. Reverend Holton's conviction comes with a cost.

He's getting paid to preach by the founders of a fast growing family business, a business that began a few decades earlier with the near death of a promising young man. The young man's name is Robert Sutton Junior, twenty three years old and finished with his apprenticeship, ready to join his father, Robert Sutton Senior country surgeons and apothecaries, setters of broken bones, dressers of wounds, letters of blood, prescribers

of medicines. Their patients are lords, farmers, millers, herders, whoever can pay. By this time, Robert Junior has learned how to heal ills, to remove piles and drain abscesses, set bones, and maybe even to amputate limbs. But before he can join his father's practice, Robert Junior has to be inoculated against smallpox. Inoculation means having someone purposefully cut open your skin in a rubbish scab or puss from an infect smallpox patient on the exposed wound. In other words, it

means giving you smallpox, making you sick on purpose. Smallpox kills roughly one out of every three people it infects at the time, and you're paying someone to give it to you. Smallpox inoculation is a sort of ad hoc predecessor to vaccination. In a roundabout way, it's the beginning of one of humankind's greatest achievements, the ability to protect from disease. But it's a young procedure. There are no clinical studies and trials, no quality controls and production, no

regulatory approvals or any other modern safety checks. By the time Robert Junior finishes his apprenticeship, innoculation has been performed in England and the American colonies for at least thirty years, and in Turkey, India, and China for many decades more. But in the mid seventeen hundreds, innoculation is still a serious risk for each individual patient and for Robert Sutton Junior, the soon to be country surgeon, it's not gonna go well.

Over the past fifty years, we've seen many new diseases emerge Ebola, hive swine flu zeka, to name just a few, but there haven't been any truly planet wide pandemics until now. Now, a virus first scene in China can be in Washington in a matter of days, and driven by this pandemic, one completely unprecedented in our lifetime, a virus that has killed our neighbors, our friends, our families. We have been witnesses to a massive international effort to create vaccines and

get jabs in arms. On this episode of Long Shot, We're going to speak to a human guinea pig, one of the first people on earth to get a COVID nineteen vaccine, and we'll hear more about the predecessors to today's vaccine makers, the first big inoculation entrepreneurs who made a killing, preventing killing two hundred and fifty years ago. We know the ruined the pandemic has brought to lives, relationships, and economies on a global scale. Vaccines have instituted a

real time revival for me and for millions. I want to know what went into these vaccines, not just the physical ingredients, but the historical ingredients. So I'm tracing the story of vaccines to their very beginning and bringing it back to today from my Heart Radio and School of Humans. I'm Sean Revived and this is long shot, a two hundred and fifty year journey to the COVID nineteen vaccines.

I can't handle needles at all. So when I have to get, you know, just a tiny bit of blood taken for like, you know, a yearly physical or something, I am the person who you know, has to start working on my breathing as I wind up having to put my head between my knees. Then I have to lay down. It's twenty twenty one, so we're speaking over zoom, so of course it kind of sus Sorry, can you give me just one more minute? I'm sorry, my printer was just acting a little funny. No problem, I'm really

nice to meet you. Can you say your name again? Yeah, it's Nicola Pascarelli. Exactly a year earlier, Nicola is led into a windowless room with cream walls at the Hope Clinic at Emory University in Atlanta. She sits on an exam table covered in that paper that crinkles with any movement. By this time, Nicola's nurse already knows how nervous she is.

I get this fear of needles from my dad. He once went to a safety class for his work, and there was like some I think it was you know the importance of wearing safety goggles video and he wound up feeling white headed after watching the video, so he went off to the bathroom to like compose himself and wound up passing out, hitting his head on the toilet, and they found him in a pool of blood. That is,

you know my family line that I come from. Next to the table is a wheeled cart that holds one of those rubber tubes so they tie around your arm to help find a vein, and eighteen glass vials ready to be filled with Niccola's blood. And I just kept counting and being like, eighteen, hold on, count again, it can't be eighteen. That's verty too many. Like I don't have eighteen vials of blood in me. That's what really

Like that made me a moozy. Just every time I looked over at the table, I was like, oh gosh, she's about to be one of the first people in the world to get them maderna vaccine. Though it's believed the formula is safe, it's still a risky move for Nicola. This type of vaccine is made with a strand of messenger rabu nucleic acid or mRNA surrounded by a fatty lipid nanoparticle bubble. No vaccine of this kind has ever been approved by the FDA. Ever, it's brand spanking new,

and it's about to be injected into her body. Throughout the history of vaccines, going back centuries, there have been test subjects, guinea pigs, the first people to get the first shots. Not all of them have been willing participants, like Nicola, who knows exactly what she is getting into. Nicola has been chosen because she's young and has a clean medical history without any worrisome conditions. She is, as

her nurse tells me, the healthiest of the healthy. She's passed a detailed physical and filled out questionnaires about her health, medications, and lifestyle. She's had her temperature and blood pressure checked over and over again. She's been assured she can drop out of the trial at any time. Despite her needle phobia and in all but genetically inherited fear of seeing her own blood, She's volunteered for this. You've already started this. I'm gonna just ask you straight up, what was your

motivation for joining the trial? Initially just fear and helplessness like I felt like I needed to to do something. Um I felt very small and all of a sudden, you know, just kind of, you know, I felt. This is March twenty twenty, a couple of weeks after the entire country has shut down practically overnight. Tom Hanks has announced he has COVID. The NBA has canceled all games indefinitely after a member of the Utah Jazz tested positive.

Soon after that, schools are shutting down, offices are closing. Ppe is suddenly hard to find. Nobody knows how long this is gonna last. Things have just gotten really real in the US for everyone, including Nicola. You know, rushed to the grocery store like every single other person, and you know, the meat sections where empty, and that just

kind of that was a little eerie to see. I've never been in a situation going to a grocery store that's always you know, completely stopped to realize, Wow, you know, I can't even buy ground beef. I can't buy even cuts of beef that I don't want. There's nothing here. You know, that was when it really started to sink in. But at that point I still thought, this is just

two weeks. You know, we're being crazy for two weeks and then it's going to be over and everything's gonna be fine, 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 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. NICOLEA here's about the phase one trial on Facebook from a friend

who works at Emory and signs up. The first phase of a clinical drug trial is when the drug, in this case, a vaccine, is first given to humans, generally after lab studies and testing in animals. Nicola will be one of the first forty five or so people in the world to get a COVID vaccine. It's kind of shocking to think that while most of us in the US are just starting to feel the impacts of coronavirus on our lives, not only has a vaccine already been created,

but a clinical trial is already underway. This is eight months before the FDA will approve any vaccine for the general public. At this time, many experts are still wondering if it's even possible to get an effective vaccine produced in a year's time, much less three months. For the Phase one trial, the researchers at Emery are mostly interested in dosage and safety. The vaccine has already been tested in mice, but this is the first time they're testing

it in people. They want to know the amount to give an adult so that elicits a strong antibody response without causing overly harsh side effects. Nicola is one of the participants slated to get the highest dosage to fifty micrograms of vaccine. That's only two hundred and fifty millions of a gram, but it's ten times higher than the lowest dosage group. It's a lot of vaccine. I remember the day that I went in for the vaccine. At

that point, I was all excited. I put on makeup and I had, you know, mascara and stuff on, and I had my face mask on. And in the time that I had to sit there and wait for the vaccine to be ready, because they have to defrost it and then mix it all up and get it all prepared, I got so progressively more nervous about the needle itself that I was sweating so badly that my mascara had gone all the way down my face. My mask was

all black on top, my hair got frizzy. That was I remember just being so distinctly worried about I have volunteered for this trial and what if they give me the vaccine and I pass out, Like they're going to kick me out of this study. I think maybe I once had this like momentary, you know, Okay, I'm in 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. Like, you know, I think I had that one moment and then I didn't let myself. I just remember thinking, do not pass out, Do not pass out. The Maderna Phase one trial is a big deal. The first humans are getting shots of a vaccine meant

to protect them against the novel coronavirus. Though by this point there are more than a hundred coronavirus vaccines in the works, Madernos is the furthest along even with billions of dollars at stake in the race for a vaccine, it seems like a minor miracle to already be jabbing it in humans. Historically, vaccine development has taken years, if not decades, to get to phase one, and before clinical trials were even practice in any real signific sense, inoculation

was more about improvisation. It was more art than science. That is until the Sutton family came along. It's seventeen fifty four in Suffolk, England, and a disease called smallpox is a recurring terror in the lives of the English and people around the world. It's been that way as long as anyone can remember. One hundred miles away in London, just about everyone gets smallpox at some point in their lives. A lot of people die, succumbing to the fevered delirium

and hemorrhaging. It's an ugly and tortuous disease. The morepox you get, the worse off you are. Five hundred is considered a lucky break. Sometimes they number in a thousands, completely consuming the skin. Swelling can be so severe that patients can't see or swallow. An eighteenth century writer describes smallpox patients as creatures flayed. Still, most people who get smallpox live, though forever scarred, they're also protected for the

rest of their lives. A bit like lightning. In one sense, smallpox does not strike the same person twice. Wealthy families seeking caretakers for their children examine the skin of potential employees. It's too risky to hire someone who has never had the pox. In a way, it's reverse discrimination. Show your scars, get the job. For hundreds of years, smallpox kills and kills and kills in England. When Elizabeth the First dies in sixteen oh three, the Stewarts take over the royal family.

Over sixty years time, they lose three potential rulers to the pox. In sixteen ninety four, Queen Mary the Second dies of smallpox. The future of the Empire is altered over and over by the disease. Smallpox does not care how much gold you have. It is a part of life for all rich and poor, urban and rule. Every once in a while, a smallpox plague comes to town.

It's the way it is. But around the time that Robert Sutton Senior is ten years old, inoculation comes to England, and by the time his own son, Robert Junior is ready to be a country surgeon himself. Inoculation is a somewhat normal, if still hotly debated, totally unregulated, and frankly wild practice. Inoculators travel around and making incisions in people's arms and rubbing in live smallpox virus pus really collected

from the pox of infected patients. The idea is that if you infect a person with a small amount of smallpox on purpose, they will get a little sick, not very sick, not die covered in hideous pustules that scar them for life. They will not only recover, but be protected from further smallpox bouts and live unafraid of the disease. What's craziest of all is it usually works to protect yourself from a lot of virus, give yourself a little

of it. That's inoculation. Robert Junior knows that he can't be a country surgeon without being protected from a smallpox. He will eventually come into contact with an infected patient, but innoculation is not the Sutton's business, so they hire a neighbor and innoculator. Robert Junior's arm is cut open and a bit of a smallpox matter rubbed into it, but the procedure goes wrong. Maybe the cut gets infected. Maybe the innoculator infects him with too much virus, giving

Robert Junior a full blown smallpox. Robert Junior nearly dies. His father is devastated. Robert the elder witnesses the failure of his son's inoculation and sees opportunity. He knows that some innoculations work perfectly. The patient gets a mild sickness a few pustules near the wound, and recovers. But some go badly, as it did with Robert the Younger, and the patient gets very sick. Precisely what innoculation is supposed to prevent. Robert Senior thinks over the many inoculation methods.

Deep cuts through the entire thickness of the skin, shallow cuts that barely draw blood, insertions of thread dipped in smallpox matter, rubbing of a scab from a smallpox infected patient. He settles on a minimalist approach, an older method that

is somehow lost favor. He takes a small surgical knife, dips it in smallpox matter, holds it at a slight angle to the arm of his patient, and sticks it only a millimeter into the skin, just deep enough to draw the smallest amount of blood and get smallpox into the body. It works. Robert Sutton Junior turns his discovery into an enterprise. He opens it innoculation house and advertises his services in the local newspaper. Gentlemen and Ladies, he writes,

will be prepared, innoculated, boarded, and nursed. Fish and wine are included for only seven guineas. Farmers get Tea and Mutton with their innoculation for five guineas. And for the benefit of the meaner sort, the poor folks, the price is just three guineas, including a month's boarding for the recovery period. If you can board yourself while recovering, it's just half a guinea. For the pleasure of the knife.

Word travels fast. Six months later, Robert Senior opens a second inoculation house, and in another six months a third. Soon he's got agents in sixteen towns convincing folks to get inoculated. Robert Sutton Senior's other son, Daniel, is an even better business man than his dad. He cuts the time required for innoculation preparation, allows patients to spend time outdoors after the procedure, rather than his father's preferred method

of indoor confinement, and he lowers the price. Then Daniel uses one of the most effective mediums of his day, the pulpit, and hires that fiery Reverend Holton from a local church to help market the great Satonian system, which brings us back to that passionate sermon in October seventeen sixty six, held in Daniel Sutton's private chapel. This sickness, as caused by inoculation, is not unto death, the ravages of the smallpox. It's spreading. Infection and fatality strike with terra.

No one is secure for infection rides on the wings of the wind, and the air is incorporated with malignant vapor. The danger the fatality of the smallpox, when received by natural infection, clearly evinces the efficacy and safety of inoculation. What does inoculation mean more than self preservation? The fire and brimstone delivery works on the back of the preacher's words. The Suttons become the standard bearers for inoculation. They franchise

the Setonian system. Anyone who pays one hundred pounds can inoculate under their name. Their services spread around England and as far as France. Canada and the American colonies. The method works. Very few of the thousands of people inoculated die, compared to the thirty percent of smallpox patients who end up in the grave. It's also so easy that anyone can do it. You don't need to be a doctor, even by the standards of doctors back in the eighteenth century.

All you need is a night smallpox matter from an infective patient and an arm to jab it into The Suttons are not the first inoculators, far from it, but they may be the first to turn it into big business, to draw mass competition for arms to inject. The Setonian system of innoculation becomes so popular that copycats are inevitable inoculators, selling the Sutton name and method without sharing the profit.

One of their rivals is a doctor named Thomas Dimsdale, who learns of the Setonian method of inoculation, sees that it works better than his own method, and embraces it himself, albeit without paying a fee to the Suttons. Dimmesdale is older than the upstart Daniel Sutton, his Uppercruss family, his own land in Essex. For centuries. He's got a reputation as an inoculator and physician. He even writes a book

on his co opted innoculation method. The book spreads his reputation throughout Europe, lending him in the court of Russian Empress Catherine the Great. Dimmesdale earns fame and fortune on the back of the country bred Sutton family, whose contributions are all but forgotten. By the end of the century. He's named a baron of the Russian Empire and is spoken about all over London. The wealthy want to be inoculated using the Setonian method, but Dimmesdale offers the comfort

of being a peer of his upper class patients. Two businesses selling the same life saving innoculation, Dimmesdale's and the Suttons, with many other innoculators on their tails, a battle to jab the most arms, make the most money, and protect the most lives. It sounds familiar. What inestimable advantages do

the public reap from innoculation? Tis most certainly a happy discovery, a blessing of the most weighty concern to this kingdom, whose strength, happiness, and fecundity consist principally in the number of its inhabitants. The promoting of the practice of innoculation is therefore consistent with our best policy, and should be encouraged as much as possible. All all are saved by innoculation, but thousands, through neglect of it, are every year cut

off in the prime of youth and manhood. Let any man seriously reflect what an immense loss this must naturally be to the nation. Despite the aristocratic competition, the Suttons become rich. In seventeen sixty five alone, Daniel Sutton inoculates more than four thousand people and earns the equivalent of more than a million dollars today. A couple of years later, the Suttons inoculate fifty five thousand people. They travel the

English countryside inoculating entire towns. It was explosive. There were religious all over the country that adopted the Setonian system. By seventeen sixty seven he had fifty partners. Somebody in Virginia, there was somebody else in Canada. They were scattered all over the country and they advertised themselves as practicing the

Setonian method. That's Arthur Boylston, an American pathologist. He went to Harvard Med School in the sixties and then came to the UK for what was supposed to be a three year grand period back in nineteen seventy two, and I married my boss's secretary and I'm still here. For a few decades, he was a professor in London and Leeds. Now he's mostly retired, though he's a senior teaching fellow in the Department of Pathology at Oxford University, and I'm

a governor of the Oxford University Hospitals. The rest of the time, putter in the garden. You have become British. Okay, very, it's been a long time. Twenty five years ago, Arthur Boylston fell down in innoculation rabbit hole and he began scouring archives for records of the first inoculators, not just in North America, but also in England. Once I've discovered what inoculation was, I wanted to see how it had developed, because it's been almost completely forgotten even in the history

of medicine. He ended up writing a book about innoculation called Defying Providence. Boyleston's research helped resurface the story of the Sutton's as innoculation pioneers, and he became convinced that in the story of vaccines and of the history of the United States. The innoculators have been overlooked. More I looked into anoculation, the more interesting. In God, it's the reason the United States exists, it's the reason Canada isn't

part of the United States. We'll get into those claims in later episodes, and then ultimately the most interesting thing I think for most people is finding how Jenner really learned about Copas Boylston is talking about Edward Jenner, a doctor living in Gloucestershire, England, at the same time as the Suttons. Here's his story. As a thirteen year old boy and already an apprentice to a country doctor, Jenner

met a milkmaid with a lovely, unscarred complexion. She told them she would never get smallpox because she had had cow pox. Apparently it was common country knowledge that having the latter meant protection from the former. Later, Jenner studies under a surgeon named John Hunter, whose catchphrases why think do the experiment? Jenner listens. When he becomes a doctor himself,

the story of the beautiful milkmaid returns to Jenner. He does the experiment by exposing people to a small amount of cow pox and seeing if they develop immunity to smallpox. They do. That's the myth behind the invention of the world's first vaccine and the origin of the word. The Latin word for cow is vacca and the Latin word

for cowpox is vaccinia. Jenner called his process vaccination. He would become known as the father of immunology, and Jenner is undoubtedly one of the most important scientists of any time. There's just one problem with this wholesome origin story. But it's not true. It's made up. Okay, here's what really happened with Jenner. As the Sutton's expanded the reach of their innoculation business, one of the many partners they took on was John Fuster, a doctor who opened an innoculation

house in the town of Buckover. In Buckover, Fuster found that some patients who came in failed to get inoculated. That is, these unsuccessful patients showed no smallpox symptoms whatsoever, a sign that the inoculation hadn't taken They wouldn't get sick at all and would have no pustules show on their skin near the site of the jab. One farmer came in times for innoculation and had failed every time.

The farmer had never had smallpox, but he told Fuster he had suffered a similar disease he called cow pox, which he literally caught from his cows. The cowpox had given him temporary immunity to smallpox. Fuster told this story of the farmer during a meeting of his local medical society in seventeen sixty eight. The society met at an inn called the Ship. At that time, Edward Jenner was only nineteen and an apprentice to a surgeon who happened to be a member of the very same medical society.

Boylston believes the true origin of vaccination begins there at the inn. That Jenner learned of cowpox's power against smallpox via Fuster, not the milkmaid, and that means the work of the Suttons led directly to the first vaccine. Without the innoculators, which led to the discovery of vaccines, Nicola Pascarelli might not be getting her Phase one shot in April twenty twenty. I managed to make it through and

it was a very smooth process. And I remember afterwards, you know, they wanted me to stay to observe me for a while after the vaccine, and you know, it was still just like getting used to the whole new change in the world. Four weeks after the first shot, Nicola gets the second. She has some minor side effects, but nothing too bad. She hears the results of the Majerna Phase one trial just like everyone else on the news. Yeah. So, the funny thing is is my friend Jess who got

me involved in the study in the first place. She is much more of an early riser than I am. So I woke up one morning to like, oh, my gosh, you know, the study has been published in a scientific journal, and like, look at the result. It's an incredible success. All of the participants show immune responses from the vaccines, and no big safety concerns are identified. I feel a

lot of responsibility for my dissipation in it. And so, you know, to be able to read about the modernist study and these huge newspapers, the Wall Street Journal and you know, stuff like that, you know, and be like that's me, Like that's me in there, Like that wasn't really exciting, and no, efficacy isn't the focus of this trial. The results on that front are also very promising, but

maybe most promising of all for Nicola. She doesn't pass out Nicola got her first shot in April twenty twenty, just over three months after the genetic sequence of coronavirus was posted online. On the next episode of Long Shot, we'll hear from a guy who spent twenty six years creating a single vaccine, and we'll speak with a woman who has a vaccine made from her own cells. But before we finished this episode, let's go back to the

Sutton's hired preacher. There ordained Megaphone, his sermon two hundred and fifty years ago could be describing today. The danger, on one hand, is manifestly great. The extreme safety, on the other, is experimentally proved and universally known. There, death triumphantly walks the streets, seeking whom he may devour. Here he has banished from our habitations and deprived of all

power to approach and hurt us. Let us not meanly and cowardly submit to death, when we have disarmed him of his sting and obtain this victory over the grave. This is the means, this is the way for our escape. Reason directs us to it. Experience proves the utility and safety.

Men by the light of providence, I'll presume to say, have discovered inoculation and brought it to its greatest perfection, so great indeed, as to repel and subdue every dangerous symptom, and to have gained the most complete victory over this dreadful enemy of life, so that we may exclaim, in the language of Scripture, we triumph over death. This sickness, as caused by innoculation, is not unto death. This sickness is not unto death. Today's episode was produced, written and

narrated by me Sean Revivee. A co producer is Gabby Watts. Juda Andrews is our fiery British preacher. Executive producers are Virginia Prescott, Brandon Barr and L. C. Crowley. Special thanks to Noel Brown and iHeartRadio, Nadine Rufael and Mary Bauer at the Hope Clinic Virginia and Joe Pascarelli and Doris Green. Long shot was scored by Jason Shannon. The score was mixed by Vic Stafford, Sound designed and audio mixed by Harper Harris with Tuonewelders School of Humans