For nearly 18 years, Tim Friede injected himself with doses of venom from the world’s deadliest snakes. A snake enthusiast, Friede was regularly at risk of snakebites and always kept vials of antivenom around. He began to wonder: Can I build up tolerance to snake venom?
After more than 850 injections at escalating doses and hundreds of snakebites from cobras, mambas, and taipans, he can now endure snake venom doses “that would normally a kill a horse,” Jacob Glanville, CEO of Centivax, Inc and author on a new antivenom study, said in a press release.
Friede’s risky self-experimentation could help others with lethal snake bites. Glanville and his team found antibodies in Friede’s blood that protected mice against 19 of the world’s deadliest snake toxins. Adding a previously approved antivenom chemical saved mice poisoned by 13 deadly snake species who otherwise would have succumbed to the neurotoxins.
Today’s antivenoms neutralize a few different types of poison at most. They are generally produced in horses and other animals, a practice that can lead to immune side effects. Friede’s human-derived antibodies, in contrast, are lower risk and can tackle multiple venoms at once.
To be clear, Friede did not subject himself to snake venom for the study, which was published in Cell, and the team warned people not to follow in his footsteps. His eccentric experiment led to a potential solution urgently needed for deadly snakebites, especially in underserved communities. But to state the obvious, “snake venom is dangerous,” Glanville told Nature.
The Antivenom Hunter
Globally, over two million people are poisoned by snakebites each year. Hundreds of thousands succumb to the toxins, with young people and children at greatest risk.
Granville, a computational immune scientist, is well aware. He grew up in a remote village in Guatemala hours away from a hospital. People got snakebites, but even if the patient made it to a clinic, there often weren’t medications to combat the specific type of snake poison.
Existing antivenoms have saved lives. But they also have weaknesses. Most are made by injecting a specific snake venom into horses, sheep, and other animals. In response, their immune systems create antibodies—proteins that act as antivenom when isolated and given to humans. Because of their animal origins, however, these antidotes can trigger unwanted immune responses, weakening their efficacy or even stirring life-threatening allergic responses.
There’s another problem too. Snake venoms are not all alike. Each antivenom usually only neutralizes a handful of them. Scientists, including Granville, have long dreamed of a universal treatment. One way would be to inject multiple venoms into the same subject, training that person’s immune system to fight them all off. But most people wouldn’t survive.
A Perfect Match
Friede began collecting highly venomous snakes in high school. Each of his snakes could easily kill him with a single bite. For years, he stocked up on expensive antivenom. Then he tried something radically different: He began training his own immune system to defend against venom from each species of his beloved snakes.
For nearly two decades, he injected himself with ever-larger doses of venom from cobras, mambas, and other deadly snakes—16 types in total and roughly 850 doses. He also stuck his arm out towards his snakes, inviting hundreds of bites. Early in his self-experimentation, cobra bites put him into a multiday coma. But upon recovering, he decided to continue with the goal of potentially helping other snakebite patients.
Friede’s unusual story led to some online media exposure that caught Granville’s eye. Aiming to help scientists develop a universal antivenom, he had been searching for protein structures in snake venom shared across species.
“I remember calling Friede and being like, ‘Look, I know this is awkward, but I would love to get my hands on a little bit of your blood,’” Glanville told Science.
Glanville teamed up with study author Peter Kwong at Columbia University, who develops protein-based vaccines, to collect Tim’s blood and isolate its proteins. They hoped these might include supercharged antibodies to fight snake venom. The team first focused on 19 deadly snake species—including Friede’s favorite mambas, cobras, and taipans—all of which belong to the elapid family and represent over 300 poisonous snake species across the globe.
The researchers extracted DNA from Friede’s immune cells and developed a library of roughly two billion potential antivenom antibodies. Adding various snake toxins, including those from black mambas, Cape cobras, and others, they whittled the group down to two candidates.
Snake toxins come in two main forms—one is a long-chain molecule, the other short. Both of these paralyze the nervous system, making it hard to breathe and move. Eventually, they lead to paralysis and death. One of the team’s two antibody candidates grabbed onto the long-chain protein from 22 of 24 snake venoms. The other candidate neutralized short-chain proteins. Both targeted a conserved molecular structure embedded in multiple toxins, suggesting the antibodies could potentially seed a universal antivenom down the road.
As a proof of concept, the team combined both antibodies with an antivenom drug and gave this mixture to mice. The cocktail completely protected mice poisoned with 13 types of snake venom, all of them surviving what would otherwise have been deadly doses. The treatment also boosted the length of survival for another six types of venom, although only for a few hours.
“Once [the mice] started living, that was really exciting,” Kwong told The Scientist. “I was like ‘Oh my god, we actually have something that could actually work.’”
Don’t Try This at Home
The results are only in mice, and much more work is needed before testing the treatment in humans.
For one, the antibody cocktail and venom where injected simultaneously in mice—in a way, giving them the antidote along with the poison. But snakebite victims don’t usually receive antivenom for hours or longer. A next step is to test the antivenom long after a snakebite.
Also, though the cocktail can tackle a broad range of venoms, it doesn’t neutralize toxins from the viper family. The team is already working on a separate treatment for those snakes.
“The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other,” said Kwong.
The team is testing the antivenom in dogs with snakebites in Australia. If symptoms don’t improve within minutes, the dogs will be given a classic antivenom. Meanwhile, they’re working to lower production costs and make the therapy more portable for treatment in rural regions.
As for Friede, he ended his self-experimentation after donating blood for the study in 2018. While proud of his contribution, he discourages other people from repeating his journey.
Glanville agrees. “We did not advise Friede to do this and no one else needs to do this again—we have all the molecules we need,” he told Nature.
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