A Human Challenge

All of them were relatively young, and all were condemned to banishment or death for their crimes. Using a technique he'd learned from an old woman in Constantinople, Maitland sliced opened the prisoner's arms and legs. Then he rubbed smallpox matter into the open wounds. This was called smallpox inoculation, a procedure meant to get the prisoners a bit sick in order to protect them from a more dangerous bout

of smallpox. Twenty five or so a well known scientists from the Royal Society witnessed the operation, and each of the prisoners were observed for weeks after to see if they developed full blown smallpox. The experiment was a success. None of the six prisoners got very sick, and in return for their participation, they were pardoned. But there were still a remaining question. Now that they had recovered from a mild bout of smallpox, were they protected from getting

the disease again. So Charles Maitland hired one of the newly pardoned criminals, nineteen year old Elizabeth Harrison. First, he had Harrison nurse a woman with severe smallpox, and when she didn't get sick, Maitland had her care for a ten year old boy with smallpox. He even had Harrison sleep in the same bed with the boy for six weeks. Considering the devastations smallpox could cause. To your mind, this was a frightening prospect. But she still didn't get sick.

Today we might call what Elizabeth Harrison went through a human challenge trial. That's when a healthy person is purposefully infected so that researchers can study a disease or a treatment or prevention for that disease. Of course, to put it mildly, in Harrison's case, there are major ethical questions about her status as a prisoner sentenced to hang and the power and balance that created about whether or not

she was a volunteer. But that aside, there are really good arguments today for infecting actual volunteers with specific diseases in order to more efficiently and quickly fight them. Infect a few to help many. And in this episode we're going to speak with someone who volunteered to do just that, a young British man who is one of the first people on earth to purposefully contract COVID nineteen From My Heart Radio and School of Humans. I'm Sean Revive and

this is long shot. In April twenty twenty, an organization called One Day Sooner was founded in order to advocate for human challenge trials. That's the number One Day Sooner. Here's one of their ambassadors to describe what they do. One Day Sooner is a global organization that advocates for the process of human challenge trials, amongst other things. We are very concerned with now because again this was like, this is not meeting Mesteing four somebody else. So I

want to be a good, you know, ambassador. That's Thomas Smiley and he is a very good ambassador for One Day Sooner. He's thirty five and he lives in Cincinnati. He works as a testing specialist. He tests medals for the aerospace industry, sometimes actual doors and propellers and seat belts and harnesses and things, and we just put them

on our machines. Exposing them too was starting amount of stress and forces and heat and just do that for hours land to verify the strength and material the failure rate, things that nature, all the material properties of it. When coronavirus started spreading around the US, Thomas wanted to help, but even though he's a smart and willing person, he knew his ability to do so was kind of limited. I'm not a virologist. I'm not a person that's going

to go out and create a vaccine. My best trait that I had was giving my time to science, giving my service to science, and being able to let people study the virus under the guise of giving my time to be part of a human challenge trial. One day Sooner was founded to advocate for human challenge trials order to speed up the development of the COVID nineteen vaccines

and to represent volunteers who want to participate in these trials. Remarkably, they've had almost forty thousand people from more than one hundred and fifty countries sign up as potential volunteers. The idea was that clinical trials in general, but especially during

a pandemic, just take too long. You need to design the studies, get approval for them, recruit thousands of people, follow them for months, if not years, and then interpret the results once enough of the participants have gotten sick and maybe after all that the trial is still a failure. But with a human challenge trial, you can give a much smaller number of volunteers a perspective vaccine, one that is believed to be safe, expose them to the coronavirus,

and see if they get sick. That could theoretically take just months or even weeks. But why would anyone actually do this? Why would they signed up to be a participant risk their own health, their life? Even Here's Thomas to explain his reasoning for doing just that. When coronavirus hit the US, there was a lot of fear, There was an incredible amount of uncertainty, and there was an incredible amount of financial and life destruction that went on.

We've evolved to a point where we at least understand that the greater good is necessary in some of these times when it's this dire. Thomas thought he'd be a good candidate for a trial, so he signed up with One Day Sooner as a volunteer in case any Human Challenge trials we're going to take place in the United States. I have no kids, I have no major responsibilities. Nobody really relies on me. I'm not in a position where I have a great deal to lose if something adverse

were to happen to me. And when I heard that I could be the subject of the study, I didn't blank. I said, of course, this more utilitarian. This is a thing that I can do to advance the masks. This is the needs of the many outwey that needs a few kind of situation. But there have not been any trials in the US. Various Powers that Be decided it would be unethical to deliberately expose people to coronavirus, even

young and healthy volunteers like Thomas. In the UK, however, medical ethics authorities approved a human challenge trial earlier this year. By then, dozens of coronavirus vaccines were being developed, and some vaccines were already being distributed worldwide, but there were still major benefits to holding a human challenge trial, and we found one of the participants. Maybe you can just quickly tell me, you know, what is your name and your age and where you were speaking to us from. Yeah,

some of my names Jacob or Jake Hopkins. I'm twenty three years old and in the Midlands in the UK, so a town called Tamworth, which is just outside to see if Birmingham, so right in the middle of the country. Should I call you Jacob, Yeah, Jacob, Jake, whatever's easier, both fine for me. Jake Hopkins is probably the first person to get COVID on purpose, and he's going to

tell us how that happened and why it happened. But first let me tell you a bit about Jake, or about Jake a year and a half ago, when coronavirus hit the UK. He's got daed blonde hair and a bunch of tattoos. Iadloads that have like kind of look a whale. Here it's a rose. They've got a rose piece just there. I have some like antners, kind of like kind of look floor things ants kind about closed

like kind of wild flowers. So when coronavirus first hits the UK, Jake is at university studying history and living with some friends, but the school shuts down around eastern twenty twenty, and he was home to live with his parents. He gets a job at a supermarket. I just got himself a job just to work, to keep himself busy, anything really tills, stocking shelves, working deliver really like just general stuff all around the store. So, like everyone else.

At the beginning of the pandemic, he's home and kind of bored. But then he reads about something called Human Challenge Trials. I remember, literally, I was just sitting at home one night scrolling through like Facebook or whatever, Instagram, whatever, and this ad popped up to be part of this clinical trial for COVID, you know, a human tryans trial.

I kind of signed up instantly, really like I had really had no idea what Human Challenge trials were other than that, like that brief description that gave when you signed up, so kind of when it's a bit blind, He signs up to be a volunteer in June twenty twenty, along with thousands of other people, including me for the record. In January, the company that actually runs the trial, h Vivo, brings them in for a pre screening at their clinic in London. The idea is to make sure Jake's healthy

enough to participate in a trial. If he's selected, he gets a full physical. They check his blood, check his heart, check his long capacity. They do you analysis test, which is awful because I knew that was coming up. So they tell us to drink a lot of water forehand, and I was in there. I did that and there was such a long way to like I actually I ended up going to fund of a nurse as being like, look, we need to do this now. But as I'm going to wet myself, like you know, like can we just

get this bit done. February twenty twenty one is one of the authorities in the UK approved the trial, but Jake doesn't know if he'll be a part of it. It's weird how passionate iually came about his trials and like how much you learned and how desil I wanted

to do them. So when they actually got a call and they're like, yeah, You're actually gonna be a part of this, I just like I was happy, weasie like I was like, oh god, I'm actually going to be part of this thing that I wanted to be a part of us so long now and then no relief is probably a bad words to mean it's COVID, but it was a bit of relief because he's like, Okay, I can actually do this now, and this his finger wanted to be part of so long. It's like happening.

So it's official. He's been selected to participate in a trial in a London hospital. But first he has to isolate at home for a few days, and he also has to do some informed consent meetings where a doctor or someone else working on the trial explains again and again what the trial is and what the risks are. There's a lot of consent meetings throughout the trial they really want to make sure Jake knows what he's getting into.

And then one really long one that's about two and a half hours, but basically they go through this massive, like thirty five page document which they send David to you and they read the whole thing word by word to you and you have to read it with them, and then like you to sign relevant boxes at certain points to make sure you and some that's going on as part of his self quarantine before the trial, Jake has to stop working at the supermarket for at least

a month. But his bosses are super cool about it. But thankfully they're really in his Sunday again, like really happy and willing to let me do it because I think we understood that as part of a good sort

of thing. I was like, actually, nervous is getting COVID because you know, if I caught it, it it eliminated from me even his trial, which like I just didn't want to happen to, Like I was that working, I was wearing like three masks at the same time and all that sort of stuff like that just going to like take everybody courtion necessary to make sure I didn't catch it.

So in the final days before going to the hospital, he says this goodbyes to friends, gives a few interviews to journalists, and tries to convince his family that he's gonna be okay. Oh no, no, they were. They weren't happy about it. They were like happy for me in the sense of, like you know, they know one how bad I wanted to do it, and like thad, I was getting game. But I think they were secretly hoping either the trials didn't go ahead or I would be

disqualified for some reason. The trial people don't want him using public transport too much of a risk that will contract coronavirus. So on March sixth a taxi shows up at Jake's house around five thirty in the morning. It's a long ride to London, so Jake and the driver chatted up. It turns out that the taxi driver has lost a friend and his father to COVID kind of reaffirmed the reason why I've seen it sort of thing

a lot, because it's awful. Amout of lives have been lost and like these sort of things, sort of things that I can stop it. Jake has dropped off at London's Royal Free Hospital early that morning and then I was like taken up into into that quarantine ward and then put into my room and it is like you are like a secure package, like passed around sort of thing a lot, like trying to avoid any exposure. About

forty others will also be going through this trial. All of them are between the ages of eighteen and thirty, and all are healthy. Since several vaccines like Maderna, fiser and Estra Zeneca have already been approved for use in the UK and countries across the world. This Human Challenge trial is focused on something else. They call it a dose optimization study. One of the goals is to learn how much or I guess, how little coronavirus has needed

to infect at least half of the volunteers. They also hope to learn more about COD nineteen immunity and the diseases effects on the body. By studying infected volunteers before, during, and after their infection, they can get a more granular look at the virus and that can help with future vaccine and treatment development and just generally give insight into

how the virus works. So you get into your room and by this point it's like ATM and they bring you some breakfast and then the doctor comes in and they do the same informed consent in eating V two hour one, but I did a zoom. They do that again if you but in person, and again it's just again tick up the boxes, you know, make sure you're in. Somebody getting in four and then you have your first a lot of texts and that is it. The doors are short and that's it. You don't leave. And his

new home isn't bad. It's got a TV, a PlayStation, a decent amount of space, his own bathroom and shower. The floors and walls are blue like a typical hospital room. It's got an anti chamber with an airlock type thing where nurses get into their respirators and get hours before coming in. And then luckily you have huge windows, like the main the whole wall is almost pretty much all window. You get a great view across London, like I could see the London I and all that from right from

my room, which a really nice thing to have. At around six am each day, they take his blood in a nasal swam and the rest of the day was filled with more tests. On day three they do the inoculation.

That's when they infect Jake with coronavirus. It wasn't until about half eleven in the morning where like one of the nurses came in and was like, okay, so we're going to inaculate you in about an hour and now for the un last chance now to kind of like buck out, like are you sure you want to do this sort of thing like that, And I was like yeah, like I still want to go ahead. So the nurse hands Jake a big pair of goggles and says see

you in an hour. The hour between from like half eleven to about half twelve when it came in, was like just nerves and excitement and just like I was calling Cohen being like I mean, I mean, like it's going ahead, like you know, like from my friend and stuff. Then like it was probably like the longest hour of my life. Around noon, the nurse and other staff come back into Jake's room. The experience of getting and COVID

is the most surreal thing in the world. The doors open and like there's like five people in these big hoods, you know, respirator things like like a horde almost walking towards you, sort of thing like that maybe they're wheeling behind him. This like its trolley like this big red, big red box in it that you know, with by

a hazard all over it, which contains the coronavirus. The virus solution comes in a chilled plastic bag kind of like a blood beg and didn't ask you to lie on your back with your head hanging out edgy bed, which you do, and then obvious people are standing over you and it's like it's intimidating. It's like Jesus crying, like this is like intense, and they get this huge pet it's like almost like a turkey basis, Like it's

a massive pet they have. They pick it up and they get the solution side, and then like they start counting down. So they count down from twenty, which adds to the suspense really, and then they kind of like drop out 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 then they repeat. It's a

long count. It really builds up the tension, and like you can feel the solution going right back to the nostril and mean like down your throape ethically as well. And then was it's done. You have to lay there for ten minutes, your head hanging back and they're just there.

They're just talking amongst them. Sounds really like checking much they did over the prostigures, right like 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. They put a clip on Jake's nose like something a beginning swimmer might use, and he has to wear it for

twenty minutes, so nothing drops out. So Jake's sitting there in his room with a clip around his nose, and then everyone realizes it's a pretty big moment because it was the world's first. Though kind of like excited about it as I was kind of like a lot of like high fives, like whoa, you just got COVID, like like you know, really excited like that, and then made meeve and like and then that's it. You kind of

like infected with coronavirus. And at that point you're going nowhere for at least two weeks because you can't leave a quarantine unit until like you're obviously testing negative. The next few days are filled with more tests, nurses and doctors checking his blood and taking nasal swabs, that kind of thing. The interaculation was on Monday, Tuesday, Wednesday, and

most of Thursday. Jake feels fine. Since one of the points of the study is to see how little coronavirus one needs to get infected, Jake starts wondering if he didn't get enough virus, if he didn't get infected at all. But on Thursday, after his third nasal swab of the day, he gets news being the first person ever and part of the first group. I was getting the smallest, like in the most diluted dose they have, so like I wasn't sure whether'll even catch an affection because because they

dropped them and I didn't mean it was actually gonna take. Yeah, And they came to my room and like they were like, so you've tested positive two times in a row now and we're going to start you on rumdzivia. Rumdzervie is a drug originally developed to treat heppatatis C, which became a part of some treatment programs for COVID nineteen. But Jake still didn't feel sick when they started the treatment.

Even though I knew I was technically positive, I didn't feel any side effects of it, Like I still felt fine. On Thursday night, he starts feeling cold. At first he thinks the air conditioning is just too strong. Then he wakes up feeling a lot colder. And I woke up ten times colder. I had full body eggs. I felt really run down, rough over, like really high temperature, but

like feeling really cold at general thieverish stuff. And then he gets even sicker because the mine was kind of like abnormal and a bit too wrong, and my temperature was too high and my vestory or it was too high, and they actually moved me to hourly vitals. It's like they're coming in every hour to do more of just to keep monet for me, because like I was a bit like upper charts. The symptoms, just the things smiling.

The symptoms just came on like a cliff dive, Like I went from having like nothing a thing fine to literally like brick wall hitting me, like really ill. They're less about two days and then it went away to quick, like you know, I went to bed on Saturday night feeling really rough, and I woke up the Sunday it was like a healed almost straight away, like you know,

I woke up feeling fine as it was before. One of his daily activities is a smell test, basically a scratch and sniff book filled with pictures of things that you scratch and smell, like an onion or wood or gasoline. But then a week after his first COVID symptoms, he

loses his sense of smell. At this point, I've been working to the books for like over a week by at this point, you know, I knew the answer before I even synapped it, because like it was the same books every time, and that's what really actually let me name it. My son was gone, because like I've scrapped it, but I'll already know why it is, and I'm just not on it, and that'd be just nothing there at all, like not a thing. His smell doesn't come back until

about five days later. Human challenge trials have been used a lot in the past, some ethical, some not. Edward Jenner created the first ever vaccine for smallpox and tested it on his gardener's eight year old son. He deliberately exposed the boy to smallpox, but he didn't get sick. There have also been challenged trials for flu throughout the past eighty years, and as recently as the late two thousands, and there have been challenge trials for cholera, malaria, typhoid,

and Danae fever. It's not a new thing. Among the arguments against human challenge trials is that they expose healthy people to unacceptably high risks. But in normal life, non pandemic life, we're happy to have people exposed to risks. Think about volunteer firefighters running into burning buildings, EMTs doctors and nurses just at the beginning of this pandemic alone, and how much they risked. We don't tell them all to stay home because we know the benefits of their services.

We also know the benefits of human challenge trials, and yet for COVID, at least in the US, we just didn't do them. I spoke with a bioethicist named near Ayal at Rutgers University. He was a co author on the first paper suggesting that human challenge trials should be used to test coronavirus vaccines. That was back in March

twenty twenty, right at the beginning of the pandemic. Remember, people were talking about risings of five years yeast one and a half years for developing vaccines, and we thought that human challenge trials would expedite the process. That was the main benefit of arriving at vaccines at the and the potential end of COVID, which is a very important

thing obviously to reach. Nier says that the reason we haven't done human challenge trials is that the powers that be simply haven't properly weighed the risks versus rewards, not even close. He says, overall, we had a skewed, excessively precautious approach to the risk in these challenge trials compared to our actual approaches in many other areas of life. We're talking here about thousands, millions of lives. How can this be regarded as too risky? With an adult participants

fully informed and comprehending consent. Nier also believes that even though we have vaccines now, it doesn't mean there's no reason left for challenge trial else, particularly when it comes to future pandemics. Here he gives a hypothetical example of what we could have done to get vaccines faster for COVID nineteen and what we should do for the next virus outbreak. Our chances of having the next pandemic are

just as high now as they were before COVID. COVID did not spare us of the next thing, and it's just a proof that those things can happen. If I

could advise people what now, what to do? I would say the minute you hear that there is a pandemic, so back in January, before we even wrote, back in January twenty twenty, start growing virus, Start preparing a protocol, start working just in case it will be needed, so that you know, if we did that in January, then a month or two after we wrote one could have started a human channel draw and gotten a very reliable read on the impact of these vaccines on infections, information

about the so called core protection the duration of immunity, long before the trials that authorized the vaccines took place. Nier also says that challenge trials can run alongside the more standard clinical trials. It's smart to run both, to basically throw all of our spaghetti pieces at the problem. There's so much value in getting any piece of information quicker and more reliably on a pandemic. So many human lives are going to be lost if we get things inaccurately,

or if we get them later. Jake went into the trial with the intention of getting a lot done while he was quarantined in the room, like he wanted to take a sign language course, but there are so many tests every day that he doesn't have big chunks of time. Instead, he watches a lot of Netflix and zooms with friends

and family. He's not allowed to leave until at least two weeks after the day he was inoculated with the virus, but even then they're testing him to see how much virus has left in his system, and he's got a bit too much, so they keep him a couple extra days. Then on the nineteenth day in the hospital, around four in the afternoon, they tell Jake he can go home. He's got an arrow to pack up and get ready.

He was so rushed because yes, for everything you way you introduced by your hazard bags, because like everything can be effecto technically, he said, Like you know, you can't pack the same way you're packed ting because you can't fold your close into the case because it just dumped into these big red bags they give you to the end up leading to all these bags, and like you have to shower to get everything, wash everything off you.

You have to ship everything in your room put into like all your bedding and stuff that they provided, you have to put that. Him to buy has bags as well for them to keep. And then he finally leaves

the room and the weirdest thing happens. So I leave my room pretty much the first time in like eighteen days, I've left this room, and I'm walking down this corridor on the hospital ward and all the ducts and nurses that I crafty, they kind of come out and kind of just like clap as you're walking out, which is like a really just it's mental or they not a nurse to come from there thanking you, but like you know, you're also thanking then because they took care of you

for this time. Kind of like this line of people like clapping as you're walking out, which is like why you know, I mean, that's really weird sort of thing. Jake gets one less CT scan and then has pushed through the hospital in a wheelchair all the way there was taxi. When you actually leave a hospital and you go outside, that was the first time I breathed fresh air in like three weeks, you know what I mean.

Like over that, you kind of get outside and kind of you kind of want to go for a run, you know what I mean, like enjoy the outdoors, but like you kind of put straight into this taxi and sent up home and then you just back home and like it's it's just weird, like you got from me in this huge thing when one day you've gone from being in hospital apart from this huge human kind of sharper. It's like a really significant thing to back seeding in your own bed after if after being clapped out of

the hospital. I kind of expect to really like triumphant return home and like, you know, everybody excited. I kind of got there. My mom was kind of like hi. I was like, oh Hi. I was kind of like we hugged and we said him. I was going, like I went to bed. Going home is a bit bizarre for Jake. He spent so long wanting to be part of this trial that when it's finally over, he doesn't

know what to want next. And I was like, I'm kind of dead to the world for at least a few days after that, because like just exhausted and in a way a little bit emotional from it. He goes back to work at the supermarket and his co workers get him some beers and some pretty appropriate chocolates, and we also got me a Brandonby's chocolates him that I

called Heroes. It's like a selection box. And then they got me back and we got to hobb a box up being like hero and I like, because you're over here, and I was like, oh, it's so cheesy. Jake the Hero is now fully recovered from all his COVID symptoms and the Human Challenge trial he participated in. We'll officially end some time next The trial and his work volunteering for One Day Sooner have made Jake rethink what he

wants to do with his life. He told me he's now interested in working in effective altruism, using evidence and logic to help others in the most effective way through charity. He'll continue to go in for follow up appointments until March twenty twenty two, and then his particular contribution to

coronavirus science will be over. Thomas Smiley still volunteers for One Day Sooner, but he's now vaccinated and won't be participating in any coronavirus human challenge trials even if the US does start doing them, and he still believes they should be done. We need to know more, we need to be able to kind of rid ourselves of this, and that's not going to happen anytime really, quote unquote soon. So there's a place for challenge trials. There's a place

for more vaccines. There's a place for speeding up the process of new vaccines. There's a place for understanding variants. There's a place for understanding cores of protection. There's a place for understanding some people's natural nunity to it. We need to know all these things, and Challenge trials can help that because we can narrow those factors down. We can isolate variables and really pinpoint what's good and what's bad, so we don't have to concern ourselves with what may happen.

Thomas finds a lovely comparison between his passion advocating for human Challenge Trials and his day job stress testing metals for airplanes, from a person that is literally testing unknown alloys in some points in his day. Literally, we don't know if this will hold up to this many psi. We don't know if it will hold up under this kind of heat. We have no idea if this corrosion will make the thing weaker or stronger, this coding will do you have this effect on it? Well? Can we

just put it in the air? Can we just make a plane out of this? No, of course not, that's preposterous. You have to test these things, and there's really no better way to do so than doing a live test. There are some sacrifices you're gonna have to make, and there are some trials you're gonna have to go through, and failures that might have to happen regarding those but

failure is always progress in a certain sense. On the next episode of long Shot, we'll speak with an American living in Sweden who had to do the unthinkable during quarantine. Long Shot is a production of School of Humans and iHeartRadio. Today's episode of long Shot was produced, written, and narrated by me Sean Revive. A co producer is Gabby Watts. Special thanks to Noel Brown at iHeartRadio, Aby Rowerk at One Day Sooner, and Alistair Fraser Erkett. Executive producers are

Virginia Prescott, Brandon Barr and L. C. Crowley. Long Shot was scored by Jason Shannon. The score was mixed by Vic Stafford. Sound design and audio mix was by Harper Harris with Tone Moothers. School of Humans