Snakebit, Part 2

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EPISODE BEGINS 

Outside Podcast Theme: From PRX and Outside Magazine. This is the Science of Survival.

(audio from Youtube video) It's not going to happen. I'm just saying. Okay, Tim, you ready?

Peter Frick-Wright (host): This is part two of our series on snake bites and it starts in a room full of the deadliest snakes on earth.

(audio from Youtube video)You don't want to take it on the hand, do you? Where are you going to take it? In the finger?

Frick-Wright: What you're hearing is from a YouTube video: it's a bunch of people gathering around a cage full of PNG taipan, water cobras, and you can hear rattlesnakes in the background. Someone is about to get bit.

On the back wall, there's this swimsuit calendar tacked up to the kind of custom installation designed to keep tropical snakes warm through a Wisconsin winter. Off camera, the crowd is pretty drunk, sniping commentary and occasionally wandering into frame. On-camera, Tim Friede, 51 years old with buzzed gray hair, wearing a Slayer tee shirt, is opening up the cage of a six foot long Black Mamba and tentatively sticking his hands in. The black Mamba is one of the deadliest and most aggressive snakes in the world. There's nothing particularly distinctive about it. No hood or intricate patterns, but it's six feet long and can be thick as your forearm. Found mostly in East Africa.

Its venom affects the central nervous system shutting down your respiratory muscles. You stop breathing. Symptoms can appear in seconds and really take hold after 10 or 15 minutes. Death often comes just a half hour after that, but Tim Friede’s friends showed up halfway to wasted, and they wanted to see it.

So now he's got the snake in a one hand grip just behind the head and he's holding it up to his left forearm right in front of the camera. When he loosens his grip just a little bit, the snake bites him twice, without making a sound.

Once it's done, he turns and calmly puts the snake back in its cage on the wall. Then what just happened finally sinks in with the crowd.

(audio from Youtube video) “This guy's a fucking beast right here”. Let me see. Let's see. “That's proof that them things went in.”

Frick-Wright: Two bites from a black Mamba and the only apparent damage is a thin trickle of blood down his arm.

(audio from Youtube video) “I Just want to know, what did it feel like?” ‘Burns.’

Frick-Wright: In part one of this two part series, we took you through the excruciating details of a rattlesnake bite that Outside writer Kyle Dickman suffered in Yosemite. When he got bit, the venom attacked his bodily systems almost immediately. He passed out, then his stomach perched itself and eventually his leg swelled up to twice its normal size. When he finally got to the hospital, he stayed eight days because the snake venom destroyed the clotting agents in his blood. He was at risk of spontaneously bleeding to death.

Inside Tim's body, there's a similar battle being waged at the cellular level. Right about now, his eyelids should be starting to droop and he should start having trouble swallowing and talking. Then his vision should blur out and he should get sleepy. Eventually he should pass out, stop breathing.  But he doesn’t, because at the cellular level, his body is winning this fight.

(audio from Youtube video) Here’s the cool thing. What’s happening is all my good antibodies are neutralizing all of the (inaudible) “Tell me why other humans don't have those antibodies and you do.”

Frick-Wright: Tim has these antibodies when other people don’t because, 19 years ago, he started injecting himself with small doses of snake venom, building up a tolerance of their effects. His goal, at first, was to be able to survive two bites from two of the deadliest snakes in the world without antivenom in a single night. But he's done that. He's immune. And now, he has bigger goals.

In his blood, he thinks, lies the key to making a universal antivenom, a treatment that could save hundreds of thousands of people around the world that get bit each year. Current antivenoms are outrageously expensive, hard to find and only effective if it was made for the exact species of snake that bit you. Not only that, but because antivenoms are made from sheep and horse proteins, when they are injected, the body tries to fight them off -- they make you sick. Tim Friede thinks his blood holds the key to a one size fits all treatment.

And in the June issue of Outside, Kyle Dickman has a story about Tim and the scientist, Dr. Jake Glanville, that thinks Tim is right. Glanville thinks he can make a universal antivenom out of Tim's blood. So Tim Friede is either on the brink of making a brilliant contribution to immunology and science as a whole, or he's just a metal head, who spent 19 years getting bit by snakes over and over again, primarily for the benefit of his friends.

(from Youtube video) We've developed antivenom for black widows. We've developed antivenom for bees, like Africanized killer bees, ywhich actually could end up killing you. Now you want to do the same thing with snakes…

Frick-Wright: But a room full of deadly snakes isn't really the right setting to explain just how crazy this is and how it might change the face of medicine. In fact, if you want to talk about what's really going on here, we should actually start with another video, one where Tim isn't performing for an audience, he's all business.

Kyle Dickman: There was a time when I was just Googling incessantly, venom and venom related things. And so if you do that, it doesn't take you very long before you come across Tim and his sort of outside presence on the internet.

Frick-Wright: This is Kyle Dickman, Outside contributing editor, rattlesnake bite survivor, and, ever since, a little bit of a venom obsessive.

Dickman: There was this one video that he shot that's described in the story of Tim letting, a PNG taipan and a black Mamba bite him. And those are two of the most potently venomous snakes on the planet.

Tim Friede: (from Youtube video) PNG Taipan.

Dickman: He lets them bite him and he's just sort of like, blood is dripping down his forearms -- and most people would be dead in about a half hour.

Friede: Black mamba.

Dickman: and Tim is just sort of calm, talking to the camera man about what his antibodies are doing or how he wants to develop a universal antivenom from his blood.

Friede: It's 9:30 -- the bites were at eight o'clock, back to back in five minutes. No antivenom used, no money spent. That's the point. Watch.

Frick-Wright: It's not quite as entertaining as the Black Mamba party trick, but this is the video (except technically it's two videos) that brought Tim Friede and Dr. Jake Glanville together. It's also the video that introduced Kyle to both of them. Two bites, just a few minutes apart, from two of the deadliest snakes on the planet, in the name of a universal antivenom, which at this point conventional wisdom said was pretty much impossible.

Dickman: So like the first time I saw it, I was like, this guy was a crack. There's no way that that's going to happen. This is just lunacy. And then it turns out that I go to his website and I click around on his website and there's this guy named Jake Glanville referenced and so I start looking up Glanville and it turns out that he's this highly accredited scientist, and what he was doing actually had a chance of being successful.

Frick-Wright: Jake Glanville is an immunologist, not a herpetologist who studies reptiles or some kind of venom scientist. So we're actually going to stop talking about snake bites for just a second and talk for a bit about the immune system, because if Jake and Tim are going to make a universal antivenom, they're going to have to harness the immune system in a way it's never been harnessed before and the idea that you could improve or augment the immune system is an idea that's captivated Jake Glanville ever since he was a kid growing up in Guatemala, getting asthma attacks during the rainy season. Asthma is an autoimmune response, the body attacking itself and Jake was fascinated -- and then when he was in high school, Jake's dad came down with necrotizing vasculitis, another autoimmune disorder which doctors treated with chemotherapy --

Glanville: That type of autoimmunity, you give them chemo and it wipes out the active immuno cells that are causing the autoimmune reaction and so it sort of reboots the immune system and he was able to recover

Frick-Wright: All this to say that when Jake finished high school and got to college at UC Berkeley, he was, in his words, fiercely interested in immunogenetics and genomics.

Glanville: As a hobby I was just always interested in computers and algorithms. And then the two laboratories I showed up at, that's when I was exposed to the idea that you can apply math and computers to help analyze the immune system, and, in fact, you kind of need those tools to really understand how the immune system works.

Frick-Wright: So like pretty much every other major breakthrough in the 21st century, Jake applied massive computing power to something we thought was too complex to ever really understand, because Jake says the immune is largely a numbers game. Viruses and bacteria antigens can take billions of different forms and once something gets a foothold, and the body doesn't have an antibody to fight it off, it can sometimes double itself every 30 minutes.

Glanville: An evolution solution to that is kind of beautiful, right? It's this technique to create a set of cells that are evolving in real time, huge numbers of them.

Frick-Wright: What the body does in response is to constantly evolve and change its defenses, trying different combinations and configurations of antibodies against each new threat, hundreds of millions of them.

Glanville: And then that system is entirely predicated on combinatorics. And so to really understand it, you need high throughput sequencing or high throughput data generation and then algorithms and computers to help interpret it. That's what I specialize in.

Dickman: He's kind of a hacker and a mathematician and an immunologist and, through this confluence of all these technological revolutions and immunology -- he's basically been able to figured out how to isolate, engineer, and clone fully human antibodies. And the reason that's important is because fully human antibodies, for a long time, have been sort of thought of, in science, as the silver bullet for drugs.

Frick-Wright: When the immune system finds an antibody that works, it replicates it in it's B cells, it's antibody factory until it's eliminated the antigen.Then, it keeps those B cells on hand so it can quickly make more antibodies as a kind of quick reaction force case it ever sees that antigen again. Pharmaceutical companies do something kind of similar, searching for antibodies that solve certain problems, like cancer, Alzheimer's, or multiple sclerosis. When they find an antibody that works, however, they make a drug out of it and sell it, sometimes making hundreds of billions in profit.

So after he left UC Berkeley, Jake went to work at Pfizer, the pharmaceutical giant. And while he was there, in 2012, he developed a computer program that essentially speeds up the process of matching antibodies with antigens. He made Pfizer much better at developing new drugs, and then he left, to start his own company, Distributed Bio.

Dickman: So Jake was really good at doing this stuff and back in the winter of 2016, in the spring of 2017, he developed this new product that allowed him to isolate antibodies from hyper-immune patients.

Frick-Wright: Instead of simply speeding the random search for new antibodies, now he could take the antibodies from someone who had beaten a certain disease and copy them.

Glanville: I'm always tinkering in my lab and I developed a technology to make it easier for us to take the blood of someone who had an interesting immune response and to extract out the genetic information that encoded how to make the antibodies the recipe to provide that production to others. And I was trying to figure out cool applications where I might apply this technology in a way that would give me a cool new drug and demonstrate its power -- the sort of the low hanging fruit.

Frick-Wright: This was, and it is, brand new technology, and to prove that it worked, and could provide real results, Jake went looking for a test case, something that would show the power of this new technology to take successful antibodies and turn them into new treatments.

Glanville: I was thinking, it'd be really cool, we should go after something where it's just a slam dunk. The antibodies are definitely protecting the person and it's a straight forward problem. And that's when I was talking with my wife, who's a field biologist, and we started thinking about antivenom.

Frick-Wright: That was when Jake went online, found Tim Friede and called him up, and that finally brings us back to snake bites.

Dickman: I think the most useful analogy that I can think of, is venom is basically a compilation of 40 to 60 different viruses.

Frick-Wright: The body's process of dealing with a snake bite and fighting it off is an immune response. Basically the same system our body uses to fight off the flu or chickenpox.

Dickman: Your body, in order to fight off those venoms, your body has to produce an antibody to turn off either every individual, or an antibody capable of turning off groups of them.

Frick-Wright: The big difference between a snakebite and the flu, however, is simply volume. If you catch a virus by someone sneezing on you, you're getting, what, a few tiny droplets, most of which is just saliva, not virus, and it lands on your skin or ends up in your stomach. Only a tiny fraction of it finds a way to take hold in your body and start reproducing.

Snakes, on the other hand, deliver a few hundred milligrams of concentrated viruses, all at once, directly into your bloodstream. It will wreak havoc until your antibodies destroy every last piece of the venom -- but as long as you don't die first, your body will respond by making antibodies until it finds one that can dismantle venom proteins, then it'll make a whole bunch more. But venom works fast. So to beat a snake bite, you need really high titer levels, which means your blood is already stocked with the venom killing antibodies. And the only way to get those titer levels up is to expose yourself to snake venom without dying. And that means tiny doses of venom that you build up slowly, over time.

Glanville: This sort of approach has been used over the ages. I mean it's referenced in Princess Bride.

(audio from The Princess Bride)

Dickman: Yeah, people have been doing it forever basically. But Tim took it a lot farther than anybody else. Way back in 2000, he started injecting Cobra venom, very small amounts of Cobra venom.

Friede: Didn't know if it was going to work, didn't know if huge venom was going to be worse than the next.

Frick-Wright: This is Tim Friede -- in our recording studio, not on YouTube. And in the year 2000, he started ordering poisonous snakes, milking their venom, diluting it and injecting it.

Friede: Didn't know if I could maybe survive a Western Diamondback versus a Taipan versus the black Mamba versus Mojave rattlesnakes.

Dickman: Basically he had turned his body into a vaccine factory. His interest in it was that he liked venomous snakes. He was interested in venomous snakes. He wanted to be able to handle them and get bit by them and then not have to worry about dying.

Frick-Wright: He started with Cobra venom, diluted down to 1/10000th of its normal concentration, and then slowly built up from there. And Tim isn't very specific about these first few months, because he doesn't share information that could encourage other people to try this on their own. No one helped him, but he kept with it. And the first test of Tim's theory came on September 12th, 2001 on accident.

(music starts and intensifies)

Not only was it the day after the attacks and the World Trade Center in New York, but one of Tim's good friends had just been killed in a car crash. So Tim got really drunk.

Dickman: Got really drunk, picked up a Cobra, got bit by a Cobra, survived it, was totally fine. Went back like a half hour later, picked up another Cobra, got bitten by it, and nearly died, and basically did die, and had to be resuscitated by medics. After that, Tim's conclusion was that from now on, he would dedicate his life to surviving two snake bites in a single night, or really a single sitting, without any anti-venom.

Friede: And it just made sense to me that if I have these snakes, I know I should be immune to it, you know?

Frick-Wright: But the only way to test immunity really is to let a snake bite you and you pay for that in pain.

(music stops)

Friede:Oh, the pain’s intense. The pain -- you want to basically cut your own finger off. It's like smashing your finger with a hammer. You don't sleep for days on end, the swelling's terrible. It's painful. It's painful as shit.

Frick-Wright: Different species affected Tim's body differently, and because he wanted to be immune to all of it, the last two decades, he cultivated resistance to as many different kinds of snakes as he could find. He may be the only person alive who can tell you what all these different kinds of deadly venoms feel like, like a kind of masochistic sommelier.

I'm curious if you could just talk me through the qualities of different venoms. What does a black Mamba feel like compared to a rattlesnake?

Friede: Depends on what kind of rattlesnake -- like Mojave's more of a neurotoxin. It's not too bad.

Frick-Wright: In general, snakes whose toxins target the central nervous system, like black mambas, Taipans, or water cobras, aren't as painful, because part of how they work is shutting down the nerves. They don't hurt as bad. Other snakes like rattlesnakes or Vipers have proteins -- Friede calls them fractions -- in their venom that attack the tissue itself, breaking it down on contact, almost like in your blood. And that hurts a lot.

Friede: If the necrotic fractions weren't in snake venom, it’d be really, really easy to do. But because of the necrotic fractions in Vipers, pit Vipers, cobras -- cobras are really bad; Cytotoxins are really bad.

Frick-Wright: It also depends on where you get bit. If you're immune, you want lots of blood flowing to the site carrying antibodies to turn off the venom, so bites on the finger where you don't get much circulation are bad news.

Friede: Without immunity, you're going to lose a finger, lose a hand. But even with immunity it's still tough to pull through. Those are all finger bites, one on the tip of my finger, and I pulled through all three of the Western diamondback bites, and those were adults, big snakes and that's when I knew that my immunity worked.

Frick-Wright: But being immune doesn't mean they don't affect you, and being in pain and/or totally focused all the time on beating snake bites took more than just a physical toll. Tim's ex-wife has said that his snake bite project ruined their marriage. She dealt with it for a decade, the second half of their time together, and then they split up in 2010. Friede’s relationship with his kids, two sons, has also suffered because of the snakes.

But to roughly the same degree that Tim neglected those relationships, scientists have kept him at a distance. Since the beginning, Friede has been trying to get the attention of people who might be able to make something useful out of his immunity. But he’s had better luck with cable TV shows. It wasn't until Glanville came along that someone saw how Tim's history of being bitten so many times by such a wide variety of snakes made him valuable to science. But for all his value, there are also problems with working with a guy like Tim, who’s been experimenting on himself for so long. We'll get into those after this break.

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Frick-Wright: So before the break, Tim had been trying to reach out to scientists but having no luck. Then Jake Glanville came along and said, basically, what you've done with your immune system dovetails perfectly with my company's ability to copy antibodies and I think we might be able to make a universal antivenom from your blood.

Glanville: We think that because Tim kept injecting himself or letting snakes bite him from lethal snakes from all over the world, from every major continent that has snakes, we think that he's probably trained his body to produce antibodies that cross-react against the evolved versions of toxins from many different species.

Frick-Wright: Glanville’s basic theory is that he can exploit the fact that viruses are lazy; they don't change what doesn't need to be changed, and it turns out that's also true of the proteins that make up snake venoms. A lot of them have really similar structures. Anti-bodies work sort of like a key in a lock. If they fit a protein, they neutralize it and every time the body is exposed to a new lock, it pumps out new keys, trying to find one that fits even better. With repeated exposure, it'll eventually find a kind of master key that fits more than one lock. Give it almost 20 years of nearly constant exposure to snake venom, and it'll find keys that unlock entire families of proteins.

Recent advances in genomic sequencing have shown that across all 700 species of venomous snakes, the most destructive proteins belonged to just 13 different families. And this is actually controversial because not everyone agrees this'll work, but in theory, each venom within that family could be turned off by a perfect antibody. So all your body has to do is find a perfect match 13 times and it would be able to neutralize all venoms, except technically some venoms require more than one antibody, so the number is actually probably closer to 30 perfect antibodies. The point is, it's an attainable number.

Glanville’s great insight was that because Tim had been exposed to so many snakes from so many different parts of the world, maybe his blood was already teaming with his multi-protein killing antibodies. All Glanville had to do was copy them and turn them into something that could be injected into snake bite victims, and then he'd have his universal antivenom.

The universal antivenom is something the world could use. Snakes kill between 80,000 and 130,000 people each year, and cause about 400,000 limb amputations. In June of 2017, the World Health Organization categorized snake bites as a neglected tropical disease because antivenom hasn't really progressed since it was originally invented back in the 1890s, so it's got all these problems. It costs upwards of $2,300 per vial and it only lasts two years. It also makes you sick.

Glanville: It's expensive, it's not very shelf stable. It's going to cause often pretty gnarly reactions at the injection site, and you can't give it to the same patient more than once because the second time their body has created a bunch of antibodies against the antivenom itself.

Frick-Wright: Antivenom is made by injecting horses and sheep with snake venom and then harvesting their antibodies. But it makes you sick because your body recognizes the animal proteins as a foreign substance and tries to fight them off.

Glanville: The first time it works to block the venom, but by the second time, now your body has mounted a response against the antivenom itself. So you get this thing called serum sickness.

Frick-Wright: Make an antivenom from human proteins, like Tim’s, and that probably won't happen. But the other problem with current antivenom is that it's only effective against the venom for which it was manufactured. That's not really a big deal here in the U.S., where there are basically only four different types of venomous snakes, but it's not so simple in other parts of the world.

Dickman: Let's say you're a kid in India and you get bit by a venomous snake, but because there's 60 different species of venomous snakes in India, you really don't know what kind it is. So right now what happens: that kid goes into a clinic and they look at the bite and they say, what are his symptoms? And they guess, and they give them an antivenom. And sometimes they get it right and sometimes they get it wrong. And so the consequences of that are the kid either loses a limb or he dies, right? Or they get it right, and he lives.

If Tim's blood is truly the source of a broad spectrum antivenom, that same snakebit and kid can now go into a clinic, get this broad spectrum antivenom and live pretty much no matter what. The other piece of it is that -- Jake would tell me again and again, a snake bite is relatively easy to cure. It's not as if it’s a technical deficiency. It's mostly just that nobody was willing to invest the money needed to make it happen.

Frick-Wright: So Jake's got the technology, Tim's got the antibodies, but up to this point, it was all just a theory. If they wanted to get the funding they'd need to keep moving forward, they'd have to show people that it actually works.

What happens next? Like how does the science move forward?

Dickman: One day, Jake basically sets up a blood draw.

Frick-Wright: In July 2017, a woman came and took Tim's blood and shipped it off to Glanville’s  lab in San Francisco. Then for the next 19 days, Tim injected escalating doses, four or five different venoms. Then, on day 28, the same woman came back, took more blood and shipped it off again. At the lab, Distributed Bio’s scientists compared the two samples of blood, looking to see if the antibodies had changed, gotten better between the first blood draw and the second. Was it reacting to the venom? It was. So they started exposing it to different venoms that his body had never seen before. And then combinations of venom proteins that don't even exist in nature, and watching what happened.

Just last week as we were finishing up this episode, Jake texted me a video of the most recent test results. The Distributed Bio scientist that works on this project, Raymond Newland, put together 25 proteins specially engineered to find antibodies that would cross-react to multiple venoms. To your immune system, it would be like getting bit by eight different types of snakes at once. They're hoping to find out if Tim's blood actually contained those master key antibodies, so they started off exposing normal human plasma and the line on the graph showing how many antibodies are reacting, it's in the middle, kind of flat

Raymond Newland: (audio from video) And then I flow Tim's plasma, where we have baller antibodies, in is fricking plasma.

Frick-Wright: If you can't hear it in their voices, the line on the graph goes up. More antibodies are reacting. So it works.

Newland: God dammit Tim, you glorious bastard.

Frick-Wright: And probably right because of results like these, if you talked to Tim, he's already convinced that the universal antivenom is a done deal. He pictures three products for snake bites: a vaccine for people who work with snakes, who're at a high risk of getting bit; a human antivenom for people who get bit on accident; and the current slate of anti-venoms, cause there's no reason not to have them around.

Friede: If you use the first thing you won't need the second cause I don't need the second -- I made the second, but don't need the second -- and having the three products on the shelf is the key point of my message. The human vaccine, anti-venom, the current anti-venom -- it will save a shit load of people.

Frick-Wright: But if you talk to Jake, it's not actually that simple, because even if they make a drug that works, it's still a long road to actually treating people with it. But if their results continue looking so good, the next step is to test their drug on mice. And if that works, they'll make a drug for dogs and cats and horses, for veterinarians to give out when pets get bit by snakes. And if it keeps working, and at this point we're looking at at least three years down the road, but if it keeps working then they'll look for funding to start human trials.

Glanville: We need a sponsor. So we're hoping it's one of the U.S. military or other militaries around the world, all of whom are definitely interested in having like a single syringe that has a broad spectrum anti-venom so that when their boys are out in the bush and one of them gets bit, they don't need to go hunt the snake down. They can just grab this thing and jab it in their leg and there'll be okay.

Frick-Wright:But several things might still go wrong. Just because an antibody binds to the protein in a venom doesn't necessarily mean that it's destroying or neutralizing that protein. So they'll have to test for that, and there might be some problem recovering and copying the antibodies. Remember, this is all brand new technology.

Glanville: And the next ever-present set of concerns is funding.

Frick-Wright: When it comes to finding a new drug, there are a bunch of different things you have to pay for, but mostly you pay to prove that your drug is safe. So first you test it on primates, and if that goes okay, then you give it to healthy volunteers or paid subjects who sit around in a room with people, watching them to see if they develop any side effects. No side effects -- then you get to move on to using the drug to actually counteract the venom. But you can't actually dose anyone with venom.

So instead what you have to do is make a bunch of your drug and hand it out at clinics and hospitals and places likely to see snake bite victims and wait for them to come in. But even that's not good enough because if you have an antivenom that you know works, you can't ethically give someone an experimental drug that might not work. So you have to wait for people to come in who have snakebites for which there is no anti-venom. Tim probably said it best. T

Friede: This stuff takes a shit load of money and a shit load of time.

Frick-Wright: And it would all be for a drug that Glanville estimates might make $30 million a year. A lot of money to you, me and Tim Friede, but not for big drug companies. So while there are other scientists trying to improve anti-venoms, the big pharmaceutical players with the money to conduct these kinds of trials, they aren't touching it. But money might not be the only reason why.

Dickman: So I also just wanted to make clear that like that ethically, it's been a very complicated story, because it's weird ethically from the medical side of things, but it's also weird ethically from my side of things, as a journalist.

Frick-Wright: When Kyle first reached out to Tim, Tim offered to get bit by a snake for the story. Kyle could see it, write about it, it'd probably be the lead. Kyle said, that sounds great. But then he had second thoughts. Tim has demonstrated that it's possible to become immune to steak bites, but he doesn't stay immune. The body only keeps antibodies on hand for so long. So Tim needs booster shots if he wants to maintain his titer levels and sometimes things go wrong -- he might inject too much and be stuck in bed for a month, which happened after the History Channel came to film him. Or he might have an allergic reaction, go into anaphylaxis. That's happened 12 different times.

Dickman: You know, I don't need to see this. Like I don't want to be involved with it. If there's blood on my hands, if something does happen, I don't want to be involved with that.

Frick-Wright: Kyle told Tim he didn't want him to do it. No booster shots. No snake bites. You could watch it all on YouTube, but Tim did the booster anyway. Then when Kyle showed up, he brought out a water Cobra.

Dickman: Tim would be like bite me, bite me. Don't bite me. You're not going to bite me. You're not going to bite me, are you?

Frick-Wright:  But he couldn't get it to bite him in front of Kyle. So Tim milked its venom, drew it into a syringe, and stuck the needle in his arm. He was bound and determined to stick himself with a venom, but also he was doing it because Kyle was there. So how much was Kyle to blame if something happened?

How did that go? Was he okay?

Dickman: He was fine. Yeah.

Frick-Wright: I bring this up only because something similar played out whenever Tim would reach out to a scientist. Tim's experiments on himself have led to something that might be a huge breakthrough. But using those results, depending on how you look at it, might also be unethical, because throughout the history of medicine, there've been all sorts of breakthroughs from experiments on prisoners, soldiers, unknowing populations.

But the scientific community has finally, for the most part, moved away from that as an acceptable practice.

Is Tim the man we need now, for these major breakthroughs, like who's willing to kind of just like sacrifice his body?

Dickman: And that is exactly what they would say is some people would say is the ethical dilemma. So simply by doing what Jake has done with Tim's blood, you could then be encouraging other people to do what Tim has done.

Frick-Wright:  As you might imagine, Tim sees it differently.

Friede: There is no dilemma and I've wanted this conversation exclusively before the interview came out. Would I talk to the FDA? Dr. Charles Maplethorpe -- many years ago, we discussed this. He's the lead medical scientist at the FDA. We talked about this, and here's his position on it and it comes from the horse's ass: the government cannot stop me from doing anything to myself. The government only comes into play when you make a product. Are we going to make a product? Yes. Then the government comes into play. Self experimentation, the medical history, like I said, 15 Nobel winners. What does that tell you? That pretty much answers that question. I am not training nobody. None of the scientists I've ever worked with have told me what to do. I was doing this before they met me. That's something I chose on my own and they had no say in it. And that's the agreement that we have to this day. They don't tell me what to do. I do it to myself. And if they want the blood, they get it. They cannot stop me from doing that.

Frick-Wright: And as long as that's really what's happening --Tim is injecting himself on his own accord for his own reasons, and Glanville is just harvesting the data -- there is an ethical route through this.

Glanville: It's the same kind of research structure that people would use if they're doing HIV research where you definitely want to look at people at the period where they may be getting HIV. The ethics there gets a little scary. You're like, do you want to look at someone who's an intravenous drug user or a a sex worker or something that might be scary -- but the answer is that no, you can create good bioethical frameworks to do that appropriately. For like HIV research or hepatitis C or whatnot, what you do is you do these non-interventional studies where you go identify a group of people and you say, listen, I'm not going to ask you to change your behavior in any way; I'm just asking you to take some samples along the way, so you've kind of watched the process. And that way you're not exposing them to any additional risks.

Frick-Wright: But that's kind of a gray area because when Glenville reached out to Tim, Tim was trying to get away from self immunizing, hanging up the syringe because snake bites suck. No one was paying attention.

Friede: I gave up -- I don't know how many times I gave up -- just cause I couldn't take it no more.

Frick-Wright: But when Glenville called and he got right back to it, not because Glenville asked him to, but just because he called. So it's murky waters.

But you could also make the same argument that it's unethical to -- because Tim has done this, with a couple of years of research and applying the right tools to the job, you could then save 125,000 lives a year. Like you could argue that the other side, that it’s unethical not to embrace this thing that Tim has done.

Dickman: Yeah, I agree. I'm sure Jake and Tim would tell you the exact same thing.

Frick-Wright: And do they talk about it as kind of an altruistic project?

Dickman: Yeah, I mean absolutely.

Frick-Wright: Kyle says Jake's childhood in Guatemala is part of what's motivating this work, but it's also simply the fact that this is an interesting problem that he can solve.

Dickman: I think he'll talk about it from very altruistic terms and I believe him, but I think his interest in this was mostly like solving a complex riddle.

Frick-Wright: Tim also felt like if we know how to do this and no one else is doing it, I guess it should be me.

Friede: But like I said, every time I either talk to somebody or turn the net on, somebody’s dying from snake bites and I have the cure and I'm like, okay, I'm not doing my job good enough. I have to do a better job.

Frick-Wright: What makes you good at this? What does it take to be good at this?

Friede: What does it take to be good at this? I have a switch in my head that I can shut off. I call it a fear switch. Like, before I get bit by certain stuff, I kinda black out.

Frick-Wright: if a universal antivenom does get made, that'll be on the back of Tim's effort, Jake's knowledge and a whole lot of luck -- luck that the technology to copy antibodies came along while Tim was still injecting himself; luck that someone with the proper expertise was interested enough in tropical diseases in the developing world to find a way through the ethical minefield; and luck that Tim didn't actually die, even if he was willing to sacrifice everything.

(to Friede) Would you do all of this again?

Friede: Absolutely. Yeah, I won't change. My passion and my love for humanity and try to make a difference in this world is my driving passion. It's not money. I have the ability to use my body to make a difference. This is all I do. This is all I know. This is all I'm good at, so no, I have no regret. I have zero regrets. Zero. My ex wife and I talk about it and we're fine. My kids and I talk about it and it's fine. My girlfriend and I talk about it, it's fine. My friends and I talk about it, it's fine. I didn't try to intentionally hurt anybody regardless of the effort I put into what I love to do.

Frick-Wright: Of course, it still may not work. Tim, in the end, may just be a metalhead with a high pain tolerance, but it's rare that a story of brutal suffering in the name of scientific progress is something that pretty much everyone involved can be proud.

Dickman: It just seems like it's such a strange -- it really just seems like this singular case where there's this one guy who got really obsessed with this strange thing and had the idea that his antibodies could be made into a universal antivenom and then for some strange confluence of technology and another --like brilliant scientists -- it actually seems to be happening. But I don't think that this is something that's going to be repeated often in the history of the world.

People do dangerous stuff and put it on YouTube every day. There's not a lot out there that's quite so dangerous as getting bit by a black Mamba or quite so selfless as spending two decades in pain for the benefit of people.

(audio from Youtube video)

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OUTRO

Frick-Wright: This piece was written and produced by me, Peter Frick-Wright, with music and sound design by Robbie Carver. It was based on a ton of reporting and research and an article in the June issue of outside by Kyle Dickman. It was brought to you by Bob's Red Mill making ingredients that are the backbone of proper nutrition for athletes. I know more at Bobsredmill.com

Thanks to Adam Hose in Cool Blue Studios in Appleton, Wisconsin. This episode of the science of survival is supported by the Alfred P Sloan foundation, enhancing public understanding of science, technology, economic performance and self immunization. More at sloan.org

Outside Podcast is a production of Outside Magazine and PRX.