The Human Antivenom Project
Since 2000, Tim Friede, a truck mechanic from Wisconsin, has endured some 200 snakebites and 700 injections of lethal snake venom—all part of a masochistic quest to immunize his body and offer his blood to scientists seeking a universal antivenom. For nearly two decades, few took him seriously. Then a gifted young immunologist stumbled upon Friede on YouTube—and became convinced that he was the key to conquering snakebites forever.
It might one day be to the world’s great fortune that Jacob Glanville, a young immunologist trying to make a name for himself in the field of universal vaccines, went online and found Tim Friede, a mechanic who had been shooting lethal doses of snake venom into his bloodstream for going on two decades. It may also prove to be yet another stroke of terrible luck for Friede.
But let’s start at the beginning. It was March 2017. Glanville, who left a principal-scientist position at Pfizer to launch a startup called Distributed Bio, had just developed a novel method for accelerating the creation of new drugs by extracting patients’ antibodies, the blood proteins vertebrates use to counteract the threat of viruses, bacteria, and toxins. He thought he’d apply the technique to cancer research. So one day, while sitting with a meditative view at San Francisco’s Japanese Tea Garden, he took to Google in search of a melanoma survivor. Chasing a thought, he typed in “repeat venom survivor” instead and found Friede.
Friede, who has spent 19 years promoting his quest to help researchers create a universal antivenom, takes up an inordinate amount of space on the internet. Glanville soon stumbled upon a newspaper story that described a YouTube video of Friede’s favorite stunt, the one he says proves his immunity to two of the deadliest snakes in existence. In the video, Friede holds the head of a Papua New Guinea taipan, one of the world’s most potently venomous snakes, against his forearm. Blood is already dripping from fang marks on his right arm, left there moments earlier by a ten-foot-long black mamba. Now the taipan bites. An attack from either snake can stop a person’s heart in a couple of hours. Other symptoms, including drooping eyelids and paralysis of the tongue, develop in seconds. But Friede calmly puts the snake back in its cage and says to the camera, “I love it. I love it. I love it.”
Glanville watched this with the appropriate mix of discomfort and grim fascination. “Jesus fuck, this is my guy,” he said. Friede’s immune system, it seemed, was able to neutralize dozens of different toxins. Glanville wondered whether he could use his new antibody-extraction method on Friede to create a universal antivenom.
Friede was driving home from his factory job building military trucks in Oshkosh, Wisconsin, when he received the first call. He remembers Glanville complimenting him on his knowledge of the immune system and explaining his interest in creating an antivenom. Soon after, they made a handshake agreement. Friede would supply his antibodies, and Glanville his science, and should they bring an antivenom to market, they’d split the profits down the middle. It was a long shot, but one that could eventually net each of them millions.
It’s now early December 2018, and Friede and Glanville are meeting in person for the first time, at Distributed Bio’s new offices in South San Francisco, in a nondescript building so close to the city’s birthplace of biotechnology sign, you could hit it with a genetically modified peach. Along with four other young immunologists and Friede’s girlfriend, Gretchen Greeley, they are drinking single-malt Scotch in an office down the hall from the lab where Glanville’s team has been studying Friede’s blood. Glanville, 38, is six-foot-two, with round glasses and a round face framed by dark, curly hair. He’s wearing designer jeans and nice leather boots.
Friede, 51, is around the same height as Glanville. He has a full head of closely shaved graying hair, wispy sideburns that drip into a goatee, and a face so thin it looks blown onto his cheekbones. He’s wearing faded jeans from Goodwill and steel-toed Keens. His voice is gravelly from cigarettes, and feeling insecure in the presence of so many Ph.D.’s, he plays the part of the dumb country boy. “That was the most terrifying few hours of my life,” he says, describing what was a fairly routine flight to San Francisco. Then he proclaims, “Today is the best day of my life.” When Glanville pulls him into a fatherly side hug, Friede seems to swell.
Glanville has ostensibly flown Friede to San Francisco to plan the next steps of their multiyear antivenom project. But really they’ve gathered here to meet me. Putting a new drug on the market can cost tens of millions of dollars, and Glanville knows that press can lead to funding. Having once survived a harrowing rattlesnake bite myself, I was curious whether, by some cosmic confluence of the ongoing technological revolution in immunology, Glanville’s skill set, and Friede’s unfathomable tolerance for pain, a mechanic from Wisconsin really was on the verge of becoming the dark angel of antivenom that for years he’d been saying he was.
A week earlier, I was buying Friede dinner in his new hometown of Green Bay and trying to figure out what triggered this obsession of his in the first place. A veteran of interviews, he took me to “the steakhouse where the Packers eat” and ordered a $50 rib eye. With an IPA in hand, Friede told me about his recent move from Oshkosh, where he’d lived for two years. “I was bagging up my mamba, a big ten-foot black,” he said, adding that he hadn’t injected that particular snake’s venom in several months. “And pop, right in the ring finger. Blood everywhere. I mean everywhere. Total accident.” This was the 100th time he’d been bitten by a mamba. “So, true story,” he said, “I walk into the kitchen and tell Gret, ‘Give me 15,’ because normally after 15 you’re pretty good to go.”
“What’s 15?” I asked.
“Minutes. If you’re not immune in 15, you’re out—dead. So I pass out. I thought, Son of a bitch, either I’m going down or fucking shock is getting me,” he said. But he had no hives. He could breathe. Five minutes later, he was back on his feet and then, wham, down again. “I hit my head on the damn sink. Made it through that one. That was two months ago,” Friede said, and then the waitress arrived with our salads.
The son of schoolteachers he never met, Friede was adopted when he was three months old and raised by a police-officer dad and a stay-at-home mom in the Milwaukee suburbs. An intense kid, he grew up hunting snakes and fantasizing about joining the Special Forces. Shortly after graduating from high school, he broke his ankle in a car accident when he flipped his VW bug. At 19, after he fractured the ankle a second time, in Army boot camp, he gave up on the military and took a job as a high-rise window washer in Milwaukee.
Still somewhat aimless at 30, he enrolled in a class on how to milk spiders and scorpions, hoping to land a career extracting venom for medical research. A few arachnid bites later, he got a pet copperhead, and it’s been all snakes ever since. That’s also around the time he first heard about self-immunization. The ancient practice involves escalating exposure to any harmful substance—toxin, bacteria, virus—that the human body produces antibodies against. It sounded smart, becoming immune to his deadly menagerie. So in 2000, Friede began shooting himself with snake venom in small doses, at one point using some syringes acquired from his best friend’s wife, a vet tech named Karen.
He suffered his first snakebite the day after 9/11. A few days before, Karen had died in a head-on collision that would also render her two young kids comatose for six months. Devastated and depressed, Friede got good and drunk and tried to milk his Egyptian cobra. The snake twisted and sank its fangs into his left middle finger. Having begun self-immunizing the year before, he’d already injected 0.26 milligrams of cobra venom diluted in saline—a dose large enough to ensure he could survive a cobra bite. Friede’s wife at the time snapped a picture of him in his living room. He looks fleshier and happy, with a smile on his face and his bloody hand pushed up against the nose of his dog, a pit bull mix, while his beaming six-year-old son hugs the animal. It’s one of two photos on his fridge. “That changed everything,” Friede said. “It was the first time I beat death.”
The second time came an hour later. The freshly cobra-bitten Friede, feeling cocky, went back to the cages where he kept his snakes and picked up a monocled cobra with his bare hands. “Naja kaouthia,” Friede recalled, using the snake’s scientific name, as he always does. The cobra perforated his right biceps. “I was scared as hell,” he said. Friede collapsed. Fully paralyzed, he could still hear when the medics arrived and discussed whether he was dead. They revived him with six vials of antivenom from the zoo, and Friede spent the next four days in a coma. “That one is hard to talk about—a fucking disaster,” he said. “I wish it never happened.” It’s also the story he uses to answer questions about his obsession. Afterward, he made it a goal to survive two venomous snakebites in a single night, this time without requiring antivenom.
To do so, Friede taught himself enough immunology to self-vaccinate more safely. When he is bitten or injects himself with snake toxins, his B cells, the body’s antibody factories, secrete thousands of different antibodies in an effort to counteract each of the many distinct proteins that make up a particular venom. At first very few succeed. Like random keys inserted into locks, they simply don’t fit. But inevitably, a few do. It’s evolution taking place directly in the bloodstream. Every time Friede receives a snakebite, his B cells make only those antibodies that address the now present toxin while at the same time constantly tinkering to improve the designs. The more venom Friede injects, the more effective his antibodies become.
What’s challenging about his approach is that each species’ venom is a combination of 20 to 70 toxic proteins and enzymes that kill or maim in their own special way. To survive bites from multiple species, Friede needs antibodies capable of turning off the deadliest toxins in the venoms injected, be it rattlesnake or cobra. He also needs a legion of them in his bloodstream at all times, although when he first began self-immunizing, he wasn’t really certain how many. Friede decided that more was better, and the process he settled on required near constant exposure to venom. So he ordered a lot of snakes.
We arrived at this part of his story almost three hours after we’d sat down to dinner. The steakhouse had closed, but after we finished our meal, Friede spotted a friend, the restaurant’s baker, a cheery, pink-haired woman who loved snakes. We joined her and the rest of the waitstaff at the bar, where Friede, who is charming and funny, had them all riveted—especially when he began explaining the work he’d lined up for his antibodies tomorrow night.
“So, when I get bit by a water cobra, the most venomous snake in Africa, it’s going to be bam—lock and key, lock and key, millions of times,” Friede said. Then he pivoted, explaining why his immunity wasn’t just a dubious party trick but could save millions of lives. “What they did in San Francisco,” he said, “is cloned all my good antibodies to mamba, rattlesnake, everything.” And that, he continued, is what would become the foundation for a universal antivenom. (As it often does, his enthusiasm for the project had him getting a bit ahead of the science.)
“Oh, you’re a hero,” the restaurant’s manager said, buying Friede a beer and a shot of whiskey in appreciation.
“Oh no, no, no,” Friede said. “I’m not. I’m just an idiot who gets bit by snakes.”
Before Glanville had even heard of Friede, he was working on cures for HIV, cancer, and Alzheimer’s disease. But his real passion is the flu. As with venom toxins, the influenza virus is constantly evolving, yet with each transformation, some part of each strain remains the same.
“Evolution is ding, ding, ding, ding—all the time,” Glanville says. “Whether that mutation survives depends on whether it’s advantageous. The part of the protein that functions the same way across all species, that’s the part that’s conserved, because it’s already working.” In other words, a virus doesn’t fix what isn’t broken. This was the scientific epiphany that struck immunology a decade earlier, and it now drives all of Glanville’s work. If an antibody could be created to target that conserved portion, almost every strain of the virus could be neutralized—a universal vaccine.
Glanville grew up in Guatemala in the late eighties and early nineties, amid the country’s 36-year civil war. He’s the son of American expats, his father an “agricultural importer” (a winking euphemism) and his mother an artist whose father helped develop the engines that sent the first U.S. rockets into space. To avoid stray bullets, Glanville and his younger brother, Keith, slept on the floor of the hotel their parents owned, and to get to school they rode a boat across Lake Atitlán. Glanville was also brilliant, cooking up nitroglycerin in the family bathtub when he was nine and finishing high school math by the time he was 11. As an undergraduate at the University of California at Berkeley, Glanville studied computational bioengineering, a new field that used math and supercomputers to solve complex biological riddles. The immune system fascinated him. “So I figured out how to hack it,” he says.
Around 2008, computational bioengineering was in its promising infancy, and Pfizer hired Glanville a year out of college. Ever since human antibodies were discovered in the late 1890s, scientists have considered them immunological silver bullets—cells with the elusive power to theoretically cure any disease. Isolating and engineering them became perhaps the greatest quest in medicine. Over the past two decades, scientists compiled libraries of billions of unique antibodies that can be genomically sequenced, allowing researchers to read the DNA of each one. Once that’s known, any antibody can be grown in bacteria and modified to target a specific antigen.
The cobra perforated his right biceps. Friede collapsed. Fully paralyzed, he could still hear when the medics arrived and discussed whether he was dead. They revived him with six vials of antivenom, and Friede spent four days in a coma.
Glanville’s major contribution at Pfizer (and the reason he was promoted to principal scientist in just four years) was writing 45,000 lines of code to optimize the process of matching antibodies to antigens. Searches that once took a team of scientists ten years to complete, Glanville says, can now be done in a week by a master’s student working alone. His software taught the computer to find thousands of matching antibodies from the tens of billions in a library. None of those matches would be perfect, but by swapping various features they share, one or a few of them could be made into something close. Glanville had developed a way to dramatically cull the number of potential candidates and then engineer the most promising ones. He transformed the search for antibody drugs from a needle in a hundred hay stacks to a needle in just one.
In 2012, at 31, Glanville took his code and left his prestigious job at Pfizer. He then founded Distributed Bio while also becoming the first Ph.D. candidate in computational immunology at Stanford University. Five years later, Glanville completed his doctorate, and business at Distributed Bio was booming. He now licenses his software and antibody library back to Pfizer and each of nine other pharmaceutical giants for around $500,000 a year and typically receives 2 percent of the profit from any drugs developed using them. With those earnings, Distributed Bio has added a fleet of new hardware to help in the discovery, isolation, refinement, and cloning of antibodies, making his firm, which employs 20 researchers, a leader in the field.
Glanville’s baby was his flu-vaccine work, and important insights he gained during that quest would also apply to snakebites. As with the toxins in venom, influenza strains are incredibly diverse. We get flu shots every year because the virus mutates somewhere between 10 and 20 percent from one season to the next, rendering our defenses useless. To succeed with a flu vaccine, however, Glanville just needed to engineer antibodies that sniffed out the virus’ weak spot, that one place that doesn’t evolve even as everything around it does.
Along with his research co-lead, microbiologist Sarah Ives, Glanville bought 15 live flu viruses that were representative of the strains that had infected humans between 1938 and 2015, then locked them in cold storage. Collectively, influenza killed tens of millions of people during that span of time. Glanville wrote a computer program to identify any binding sites that were shared across all 15 viruses. And he found a region full of them, buried deep in its molecular folds. Then Glanville engineered a vaccine that would teach the immune system to produce antibodies to target that area. Back in Guatemala, at a pig farm he and his brother built on their parents’ property to save money on research trials, his team immunized 100 pigs (a common animal model for humans) with the designer vaccine. Then they exposed the pigs’ serum, the component in blood that contains antibodies, to influenza strains that the animals’ had never seen, those that went epidemic in humans between 2005 and 2015. The serum fought off the viruses. “The smart money is that this is the universal flu vaccine,” says Glanville. Indeed, the Bill and Melinda Gates Foundation invited Distributed Bio to submit a grant proposal, and the company plans to go into preclinical testing at veterinary research facilities in Iowa this fall.
Given that potential breakthrough, it’s perhaps not surprising that Glanville is so confident he can succeed with snakebites, too. “With our tech,” he told me, “because of what Tim has done—as crazy as that shit is—this is an easy problem for us to solve.”
Glanville had only an inkling of how crazy it really was. Starting in 2000, when Friede set his mind to immunizing himself from nearly all snakes, he turned his basement into a venom lab. He insulated the walls to keep tropical reptiles warm in Wisconsin’s winters and used spent syringes to hang a world map and a letter from a self-immunizer he admired beside a Sports Illustrated swimsuit calendar. Every few months, new species arrived at the Milwaukee airport, where Friede would pick up the wooden crates stamped Venomous SNAKEs.
When he got home, Friede would listen to Tool and open the crates with a screwdriver. On snake hooks or in Friede’s bare hands, out came the writhing contents. Water cobras. Taipans. Mambas. He put them in cages he stacked against a wall. Friede’s rarer venom donors were wild-caught—legally or illegally, he doesn’t know—and often stressed or sick. Some died a few months after they came in. Friede loves animals, but whether his snakes survived long-term didn’t ultimately affect his work. Once he milked their venom he could dehydrate it into a lifetime supply.
He also began taking what he calls “Darwinian notes.” On December 12, 2001, he wrote, “Since dying was no fun, took off ’til December.” That day he injected himself with the venom from the same cobra that nearly killed him, and he spiked his blood every few weeks from then on. He rated pain on a numerical scale, with entries ranging from 1 to 1,000. A common symptom was “3x3 swelling”; rarer was “swelling from knee to ass,” “hives over whole body,” and “anaphylactic shock” (though he suffered the last of these 12 times). Within a year of starting, he was letting live snakes bite him to demonstrate his immunity. Over time he could distinguish how much venom they’d injected simply by his body’s reaction. He grew to like water cobras, because their neurotoxic venom blocked his nerve cells, making a bite less painful and “very easy to beat.” He hated Cape cobras and rattlesnakes, whose necrotic venom dissolved his muscles.
Along the way, Friede developed a sort of stuntman-next-door persona by posting videos online. Some were macho, like the one where a drunk friend howls in disbelief as he films a black mamba double-nipping a sober Friede. But in most of the clips, Friede tries earnestly to share how self-immunization really works. He was just your average enthusiastic guy in a Slayer T-shirt, admiring nature’s deadliest snakes by letting them bite him. He recorded the moments after a Mojave rattlesnake tagged him by surprise and after he’d solicited a bite from a black mamba to help “a girl with a school project.”
Whether he put his videos on Facebook or YouTube, haters inevitably flocked to the comments. Snake enthusiasts, leading toxicologists, and online trolls attacked his efforts as useless witchcraft and labeled Friede either a fake who’d removed the snakes’ venom glands or an idiot. Friede says he even got death threats. “What was I doing? I wasn’t hurting anybody,” he says.
Glanville studied computational bioengineering, a new field that used math and supercomputers to solve complex biological riddles. The immune system fascinated him. ‘So I figured out how to hack it,’ he says.
Before long the media discovered him, too. National Geographic filmed Friede for a TV segment in 2002. The History Channel featured him on Stan Lee’s Superhumans, and he appeared on the Science Channel and a number of YouTube shows. He was also covered in several magazines and became a regular guest on podcasts and radio. All that attention offered something he craved: affirmation. “I was a rock star,” he says. “Hell yeah, it was fun.” At one point, Friede got a lawyer and an agent to capitalize on the opportunities but has since dropped both, because “it’s never been about the money.”
What it has been about, Friede insists, is saving lives. As early as 2003, he believed that scientists could turn his blood into a universal antivenom, so he began to reach out. Friede e-mailed Nobel Prize–winning experts on the immune system, an Arizona State University professor who developed a technique for genetic immunization, and Stanley Plotkin, the author of the 1,720-page tome Plotkin’s Vaccines, which Friede used to inform his own immunization.
The scientists got back to him with cursory congratulations, but he found few who were genuinely interested in what he was doing. He got a better reception among a more amateur crowd—the burgeoning online self-immunization community. Norman Benoit, the closest thing the practice has to a historian, wrote that Friede “has almost single-handedly taken the concept of self-immunizing to where it is today.” That place seems to be a Facebook page that Friede started in 2013. It now has 3,000 members around the world and an image gallery that could be sent as hate mail to a squeamish enemy. On it, Friede generally advises caution to newcomers while supporting—though not providing advice on—their DIY immunity efforts.
Friede wasn’t exactly cautious himself. Over time his experimentation grew bolder, if not downright reckless. “You’ve got to make mistakes to get better, that’s part of it,” he says. On November 29, 2015, he filmed the black mamba and taipan double bite that led him to Glanville. The video now has 11.5 million views on YouTube. Friede described the event in his notes: “One of the worst double bites I’ve ever had. Swelling was 10" x 10". Took four days to heal.” A week later, he repeated the experiment with the same two snakes and had a similar experience. “Could not walk. Body was on fire. Fell down many times. Death was near. Learned a lot.” Friede has now survived bites from two species of rattlesnake, two species of taipan, four types of cobra, all three species of green mamba, and the black mamba.
As might be imagined, Friede’s obsession has taken a toll on his personal life. His ex-wife has said that Friede’s self-immunizing ruined their marriage. Friede doesn’t argue the point. Though he still considers his ex-wife a close friend, he says with remorse that for long periods he hasn’t had a good relationship with his sons, who are now 11 and 22. “I mean, I was working to save the world. I traded my life for all those people that snakes kill every year,” he says. After a strained 20 years, he and his wife split in 2010. Friede moved out and transferred his snake lab to a property in nearby Fond du Lac, where he slept in a tent. “I figured out how death works, then beat it,” he says. “That’s the only thing I’ve ever been good at.”
By the spring of 2017, divorced and estranged from his kids, Friede felt that he’d had enough. “I was done,” he says. “I was tired of the bites, tired of the pain, tired of not getting anywhere.” So even while he kept posting on Facebook, he planned to wind down his self-immunizing.
Then Glanville called. In as much time as it took him to explain his intentions, Friede’s dream was revived. Glanville reaching out was “everything,” Friede says. “Ev-ery-thing.”
Around the time Glanville and Friede connected, their cause got a publicity boost. In June 2017, after intensive lobbying by physicians, the World Health Organization categorized snakebites as a neglected tropical disease, an upgraded classification with the heft to shake loose vital funding. Every year, snakes kill between 80,000 and 130,000 people and claim 400,000 limbs through amputation.
Dozens of teams around the world are now trying to improve upon the antivenoms first developed in the late 1890s by Albert Calmette, a French immunologist who also developed a vaccine for tuberculosis. Calmette made an antivenom to cobras by doing to rabbits what Friede has done to himself. Since then sheep and horses have become the antibody donors of choice, largely because of their abundant blood supplies. Otherwise, antivenom production has changed very little. Serums can expire in less than two years and are expensive ($2,300 per vial and sometimes more), and the antibodies they produce work only against select types of venom. While that last flaw is acceptable in places like the United States, which is home to only four appreciably different venomous snakes, it isn’t in a country like India, which has 60.
As Glanville soon learned, none of the researchers working on a snakebite cure expected to engineer a truly universal antivenom. Doing so would require an antibody to turn off every toxin in every known snake venom, a financial improbability for a drug that Glanville forecasts will earn just $30 million a year. Yet, as Glanville also discovered, advances in genomic sequencing have revealed that across all 700 species of venomous snakes, the most destructive proteins belong to just 13 different families. “Not all toxins are equally bad. We just need to cure the nastiest ones to save lives,” Glanville says.
Like some of the other teams working on antivenom, Glanville hopes to target the protein-binding sites shared among each of those 13 families. If he can find antibodies to lock onto those vulnerable sites, a so-called broad-spectrum antivenom wouldn’t need to contain several thousand distinct antibodies. An effective number, he says, could be closer to 30.
Of the half-dozen toxicologists and antivenom experts I spoke to, not one had heard of Glanville. He hasn’t published any scientific papers on venom, though he’s published more than 30 in other areas. The most heralded work in the field is being conducted by Andreas Laustsen, a young researcher in Denmark who has dubbed himself Snakebite Jesus. Last summer, using some of the same tools as Glanville’s lab, Laustsen engineered human antibodies that when injected into mice could neutralize dendrotoxins, among the most potent ingredients in black mamba venom. But his work underscores just how difficult the challenge is. Because of the sheer complexity of venom, his antibodies were effective only when injected directly into the mice’s brains.
Glanville believes Friede is the solution. His theory is that Friede has done with his syringes and snakes what Glanville had done in the lab for flu: created antibodies to sniff out the shared sites of extremely diverse proteins. “The immune system is as lazy as the rest of us,” Glanville says. “Why make a bunch of different antibodies if you can just make one that does many jobs?”
Laustsen, who is supportive of any researcher working on antivenom, is nonetheless skeptical that Friede’s antibodies are anything special. Before beginning his experimentation on dendrotoxin, he worked with a self-immunizer from London. Laustsen found that his patient’s immunity was barely above background—not worth the effort or expense to extract antibodies, and certainly not worth the headache. Danish media had taken Laustsen to task for using a self-immunizer to develop a potentially profitable drug. “The promotion of such work carries the risk that others will start doing something crazy to get the interest of scientists. It might be a little slower to do it in the lab, but at least nobody gets hurt,” Laustsen says.
Medicine’s history of human experimentation is dark enough already. But Glanville doesn’t believe he’s made Friede into a human lab rat. Friede, he says, is the rare case where scientific curiosity drove someone to voluntarily do extreme things to their own body.
Not long after Glanville connected with Friede, on a muggy July morning in 2017, a woman in a little blue car showed up at Friede’s house in Oshkosh, drew 20 milliliters of his blood, and shipped it to Distributed Bio in South San Francisco. Then Friede grabbed a syringe and a vial of taipan venom from the fridge and shot it into his thigh. For the next 19 days, he injected escalating doses of western diamondback, black mamba, and taipan venom, following his normal immunization schedule. On the 28th day of the experiment, the woman in the blue car returned, retrieved more blood, and again shipped it to Distributed Bio.
The two samples gave Glanville and his team before and after snapshots of Friede’s immune system. By comparing them, Glanville could tell if Friede’s antibodies were actually evolving to better neutralize the toxins—and if they were, how well they were doing that job. Determining that would take Glanville and his team more than a year.
Glanville offered to host Friede at his family’s farm in Guatemala, but Friede owed so much money in child support that he couldn’t get a passport. ‘Obviously, it hasn’t worked yet,’ Friede says of the antivenom project. ‘Will it? Yes, it f—king will.’
Glanville was aware that Friede was injecting himself throughout the four weeks between blood draws. I asked him if he was concerned that his subject might be taking too many risks during a period when he was technically participating in a Distributed Bio study. Glanville was adamant that he’d never asked Tim to inject venom and that their research was strictly passive. “Our conclusion was that Tim was continuing his routine practice of boosting that he’d be performing whether or not we had run the study,” he wrote to me in a long e-mail explaining the rigorous biomedical-ethics considerations he thought through in advance of the study. “We just took blood samples during his process. We asked him what his schedule was but did not influence it. Thus our study never exposed Tim to any new risk.”
Glanville also pointed out that he’s taken steps to ensure that Friede doesn’t become antivenom’s Henrietta Lacks, the never compensated source of one of the most significant cell lines in medical research. From the outset, Glanville said he’d make certain that Friede would have a significant stake in any future profit from his cells, and he made that legal in April 2019 when they signed an official contract.
Although he and Friede are partners there’s a vast disparity between what they each have riding on the research’s success. For Glanville, the work on a broad-spectrum antivenom is something of a side project that, even if it yields a marketable product, won’t generate anything close to the profit his work on influenza, cancer, and HIV might someday generate.
Friede, meanwhile, has gone all in. Within weeks of Glanville’s first blood draw, Friede found reason to quit the $50,000-a-year truck-assembly job he’d held for eight years. “There are things I know on paper that are pretty sweet,” he told me. “Vaccine wise. Money wise.” He said he thought his partner had already invested “probably in the millions” and that Glanville was “banking on stuff he knows is going to work. Otherwise he wouldn’t do it.” (Glanville estimates his costs so far at closer to $30,000, compared with $300,000 he’s put into influenza.) The bulk of Friede’s income between November 2017 and October 2018, when he took a job delivering pizzas, was $6,680 that Distributed Bio paid him for “research funding.” After Glanville discovered Friede was broke, he offered to host him at his family’s farm in Guatemala, but Friede owed so much money in child support that the U.S. government wouldn’t issue him a passport.
“Obviously, it hasn’t worked yet,” Friede says, betraying a hint of remorse before washing it away with his familiar optimism. “Will it? Yes, it fucking will.”
When Friede and I first talked, I had my own ethical dilemma to work through. A couple of months before meeting him in Green Bay, we discussed him being bitten by a snake for this story, something he said he was happy to do. But as we got closer to the interview date, I began to have second thoughts. What if something happened? So, the morning after we’d closed out the bar at the steakhouse, where I’d heard him boast about his big plans for a water cobra bite with me as a witness, I asked Friede not to go through with it. There was plenty for me to watch on YouTube, I explained. Friede seemed to understand and agreed.
That attitude changes over the course of our second day together. We’ve just finished a late-afternoon lunch at a diner near his home, accompanied by Friede’s girlfriend of four years, Gretchen Greeley. An animal lover with a sharp intellect, Greeley works as a cook and has become something of a stabilizing force for Friede. He calls her “the most fun part of my life.”
Last fall they went through a rough patch. After a year in Oshkosh, the couple moved to Green Bay, where Greeley grew up and Friede’s ex-wife lives with their two sons. They were unable to find a rental willing to take their pit bull, however, so Friede and Greeley lived at a Motel 6 for a month with their two dogs and a polydactyl cat named Wednesday Absinthe Adams. A couple of weeks ago, they moved into the 400-square-foot attic apartment where we’ve been watching YouTube videos of the “most brutal” snakebites of Friede’s career.
And we’re drinking. A pile of empty Steel Reserve tallboys and white-wine minis crowd the garbage can. An industrial-metal band that Greeley and Friede like plays on an antique-looking radio. By the kitchen sink, in a black crate that Greeley pulled out almost two hours ago, are a pair of water cobras. Wednesday Absinthe Adams and another cat are wrestling on top of the crate, and I can sense Friede, now splayed out on the couch, plotting his move.
For ten minutes, Friede pokes and prods the cobra to elicit a bite. A week ago, after 11 months without a booster shot of cobra venom, he injected a lethal dose an hour before he and Greeley were supposed to be at her parents’ for Thanksgiving dinner.
He takes another nip of whiskey and then stretches out his arms. At some point tonight he put on my down jacket, which is much too small for him, and he’s now making noise about keeping it in exchange for showing me what I’d asked him not to show me.
“You didn’t come all the way out here to see nothing,” he says.
I’ve had a few drinks myself, and curiosity is getting the better of me. “I do want that coat back,” I say. Greeley silently fetches the crate and places it at Friede’s feet.
“Fear is kind of a fucking weird thing,” he says. He removes the lid, and two water cobra heads levitate above the rim to investigate, each banded black and gold. “Naja annulata,” Friede says, pausing for effect. “The most venomous snake in Africa.”
Friede thrusts his hands into the crate and comes up holding the two snakes, each about six feet long. One cobra then slides with remarkable speed and very little aggression up the baffles of Friede’s jacket—my jacket—toward his neck. He grabs it and moves his hands beneath its belly like he’s pouring sand from one hand into the next.
“It’s almost like we know each other,” he says. “See how gentle I am with these animals?” And he is, until he starts tapping one snake’s head against his wrist. “You’re not going to bite are you?” he whispers.
For the next ten minutes he pokes, prods, pats, and pets, all to elicit a bite. If he’s afraid, you’d never know it. A week ago, to prepare for this interview, he injected a lethal dose of water cobra venom. It had been 11 months since his last booster shot, and he administered it an hour before he and Greeley were supposed to be at her parents’ for Thanksgiving dinner.
“Fuck you for that, by the way,” Greeley says, reminding Friede that no antivenom exists for water cobras. She says that when she saw what he’d done that night, she cried and nearly passed out.
“Come on, hon,” Friede responds. “I just wanted to know what would happen.”
With the recent booster, Friede is confident that he can survive a bite from each of these cobras, but they don’t seem interested. “Come on, bite me. Bite me,” he says. Their jaws stay shut.
“Get me a cup,” he tells Greeley, moving to plan B. She heads to the kitchen and rummages through the empty cabinets. The scales, glass vials, and insulin syringes he usually uses when shooting venom are still locked in storage, so Greeley makes do. She grabs a plastic bag and winds it tightly around a NyQuil measuring cup. Then she gets the dirty needle Friede requested. “It’s more hardcore,” Greeley explains, passing it over the cobras to Friede.
Friede pushes a snake’s head against the bag. Fangs puncture plastic, clear venom gleeks into the cup. He repeats the procedure with the other snake, then places the cobras back in the crate. His routine thrown off by Greeley’s improvised venom receptacle, he spends the next three minutes wrestling the tightly wound bag off the NyQuil cap. “It’s not a fucking bomb, honey,” Friede admonishes, his showmanship overwhelmed by childlike frustration. Venom finally flows into the syringe. “Oh yeah, that’s enough to kill me,” he says.
The needle goes in just behind the round bone on the inside of Friede’s left wrist. And that’s about it. Twenty minutes pass without incident. Three cigarettes go into Friede. His pit bull curls up with him on the couch, and he starts chatting about how water cobra venom is simple to beat. “It’s really easy for him,” Greeley says, pleased with the results.
I’m suddenly overcome by that special fatigue that follows an adrenaline overdose, feeling as though the three of us have just survived something profound. Reluctantly, Friede returns my coat. Then I lower myself down the attic stairs and head into snow that has just started to fall.
In the parts of the day when Ray Newland, the 27-year-old scientist who Glanville appointed to the antivenom project, wasn’t panning Distributed Bio’s antibody libraries for clients, he worked with Friede’s blood. First he segregated ten million antibodies sequenced from it, an elevated amount for a normal adult and a possible indication that Friede really had done something special to his immune system. Newland arranged these into a searchable library and then began analyzing it for venom-specific antibodies.
One morning in April 2018, about a year into the project, Glanville and Newland pulled on biohazard suits, fitted themselves with rebreathers, and mixed saline into seven different types of dehydrated venoms that Newland had ordered online from a lab in France. Some were venoms Friede had immunized himself against and some were not. The varied sample would tell Glanville if Friede’s antibodies were working against any of the venoms present, and also if they were working to neutralize a venom his immune system had never seen before. The latter scenario would suggest the type of broad-spectrum reactivity necessary to build a new class of antivenom.
Ten million is an enormous number, so to cull the herd, Newland magnetized each of the seven venoms, then mixed them with Friede’s antibodies in a test tube. After ten minutes, he stuck a magnet against the side of the tube to pull out the venom toxins along with any antibodies that were sticking to them. Over the course of the next two weeks, Newland repeated this process three times, using DNA sequencing to count and clone some 1,200 of Friede’s antibodies that had stuck to the venom. To further clarify which of these were actually targeting toxins, he then dipped them all into a cocktail of venom and other chemicals. If the antibodies formed a true bond to the toxins, that area of the plate would turn blue. Newland’s first plate did so. So did his next 12. Newland let out a scream, prompting a Distributed Bio tech to shoot footage on her phone that captured Glanville and Newland in lab coats dancing something like the Macarena.
Within a week, Newland weeded out 282 binding antibodies and had hits on all seven venoms, including ones Friede hadn’t immunized against. “Tim’s blood is the best chance the world has at a broadly reactive antivenom,” Newland says. “We are light-years ahead of the competition.” Instead of a single antibody that worked against one toxin but not the whole venom, they had 282 that worked, in the lab, against many toxins in whole venoms—and millions more to look through for an even better fit.
This was the breakthrough Friede had been seeking for almost 20 years. You could imagine him printing Glanville’s results, chewing the pages up into wads, and blowing spitballs into the faces of his naysayers. How good were his antibodies? In a $500,000 screener called the Carterra LSA that tests how strongly an antibody binds—a good indicator of whether it’s neutralizing its target—Newland found one that hit a toxin in black mamba venom with, he says, “about three times higher affinity than any drug on the market.” It was a tighter bond than any Glanville had seen or been able to manufacture.
In December, Newland hosted a meeting with a consultant Glanville had hired to help Distributed Bio secure funding for more research. The company had a proposal in with the National Institutes of Health for $400,000, which included a full-time salary of $80,000 a year for Friede. It promised to do what had never been done before in antivenom research: use whole antibodies, first isolated from a human donor, to shut down black mamba and western diamondback venom in live mice. The venom of those two species contain proteins from most of the 13 deadliest toxin families that Glanville decided would need to be neutralized by a broad-spectrum antivenom. The antibodies would be Friede’s—fully human and unlikely to induce serum sickness, a problem with most existing antivenoms. And they could be dehydrated into a thermostable powder, so they wouldn’t need to be refrigerated. Glanville’s team was pitching the idea that the product could be carried by American soldiers anywhere they traveled and stocked in the rural clinics where it’s needed most.
Still, Distributed Bio’s scientists knew that landing a grant would be just the start. Drug development has notoriously low odds of success, and despite the recent surge in antivenom research spurred by the World Health Organization’s reclassification of snakebites, drug companies aren’t exactly clamoring for a new antivenom. In fact, the current single-species products on the market have earned so little revenue that Sanofi Pasteur, the industry giant, stopped producing its antivenom in 2014, leaving those snakebitten in large swaths of Africa to seek cures from traditional healers.
And there was that other issue hovering in the background: the murky ethics of exploiting Friede’s self-mutilation, a factor that could scare away potential investors. It’s a point Glanville still struggles with. “If the cure really is in Tim,” he asks, “why should 130,000 people have to die every year from snakebites?”
The day after Friede first met Glanville in South San Francisco, he shows up at Distributed Bio’s offices around 2 P.M. looking rougher around the edges than usual. Following dinner and sangria at a tapas joint the night before, Glanville took Friede and me to his favorite kava bar, where we sucked down several coconut shells of mildly stimulating mud. Glanville went home, but Friede kept the party going. On the Uber ride back to his hotel, he had the driver stop at a liquor store. Now, suffering a brutal hangover, he spends the afternoon with Outside’s photographer having his picture taken with Glanville. (“Not my favorite thing,” Friede says.)
Later that evening, he and Greeley sit on the sidewalk in front of Distributed Bio’s offices. They’re taking a break from the company’s holiday party to smoke a cigarette. Rush hour is ramping up, and the sun is setting. Friede’s mood, full of optimism the night before, seems to have deflated all at once. Just before they’d come to San Francisco, he’d been fired from his pizza-delivery job because he’d failed to pay a ticket for a seatbelt violation. Worse was the situation with their two dogs. They’d kenneled them before they came to California, and now they’re worried they can’t afford to get them out.
‘Tim’s blood is the best chance the world has at a broadly reactive antivenom,’ Newland says. They had 282 antibodies from Friede that worked against whole venoms—and millions more to look through for an even better fit.
“I’m just glad you got to see the ass part of this whole thing and the rock-star part,” Friede tells me. “I wish I had my job, my house, my kids, my life, but guess what? I don’t. And if it took that to get this done, maybe it was all worth it.”
He presses his cigarette into the sidewalk and goes back inside to a Christmas party full of scientists and millionaires. Glanville, wearing an ironic holiday sweater, is chatting with an immunologist who is working to cure cancer. Friede orders a vodka cocktail from the bar and steps off to one side of the room with Greeley. It’s the last time I see them.
When he got back to Wisconsin, Friede sold his self-immunization kit and snake cages so he could afford to get the rest of his stuff out of storage. One day in January, he announced on Facebook that he was quitting self-immunizing. Hundreds of people liked the post or wrote encouraging comments. An era had ended. After an estimated 200 snakebites and 700 lethal injections, self-immunizing’s brightest star had retired.
Friede, now doing maintenance work at the steakhouse where we ate and still waiting for Glanville’s grant to go through, no longer has to punish his own body to save the snakebitten. With his antibodies in the hands of reliable scientists, he could do no more. When I reached him by phone in the spring, he told me he was making an effort to spend time with his kids. He would continue to do interviews for snake-themed websites, but only to promote the antivenom project and talk about how he’d move beyond self-immunizing. Life was starting anew, and it felt good.
But then, on March 13, he backslid when Greeley suffered a non-venomous bite from a python they were pet-sitting for a friend. “Wasn’t going to post this. But had to,” he wrote on Facebook. “My GF gets nailed by a ball python. I laughed. Then I get hit by a water cobra twice.” Old habits die hard.
Contributing editor Kyle Dickman wrote about surviving a rattlesnake bike in the June 2018 issue.
Correction: The original version of this story misstated when Sanofi Pasteur stopped producing its antivenom. The story has been updated to reflect that the company ceased production in 2014. Outside regrets the error.