Gradually building up his tolerance, Tim Friede, a former construction and factory worker and self-taught herpetologist endured 200 direct snakebites and self-administered 700 doses of venom. His immune system adapted to withstand venom from cobras, black mambas, taipans, rattlesnakes and more. Shown above, a rattlesnake. (iStock)
Scientists have gone to extraordinary lengths to prove their ideas. Isaac Newton inserted a needle into his eye socket. Australian scientist Barry Marshall won a Nobel Prize after drinking a culture of H. pylori for his stomach ulcer research.
Now, there’s Tim Friede, a former construction and factory worker — and self-taught herpetologist — from Wisconsin, who allowed himself to be bitten by venomous snakes more than 200 times.
Those bites, along with hundreds of additional venom injections over 18 years, have put scientists on the path to a breakthrough: a potential universal antivenom.
Though researchers say human tests are probably at least two years away, mouse studies involving an antivenom derived from Friede’s antibodies fully or partially neutralized the venom of 19 of the world’s deadliest snakes, including the black mamba, king cobra and taipan, according to a study published in the journal Cell this month. Tens of thousands of people die of snakebites every year.
“It’s an overwhelming feeling knowing that what I’m doing someday can change — it already has — medical history,” said Friede, who is listed as director of herpetology at Centivax, the biotechnology company leading the antivenom research.
A deadly toll
The World Health Organization has identified snakebites as a neglected tropical disease expected to get worse as climate change brings more snakes and people into contact. Nearly 3 million people suffer venomous snakebites each year, resulting in almost 138,000 deaths and three times that many amputations or other permanent disabilities, according to WHO.
In the recently published study, researchers injected mice with a cocktail of Friede’s antibodies and an additional toxin inhibitor. Remarkably, some of the venom tested came from snakes that had not come into contact with Friede, yet his blood still contained antibodies effective against their venom — pointing to a broad immunity and bringing researchers closer to a universal antivenom.
The research included a genetically diverse range of snakes — known as elapids — a large, highly venomous family of reptiles found primarily in tropical and subtropical regions, including Africa, Asia and Australia. The snakes cause tens of thousands of deaths annually. Their venom can kill within hours as their potent neurotoxins target the nervous system, rapidly paralyzing the muscles needed for breathing.
The mice in the study were fully protected from venom from 13 snake species and partially protected from all 19.
“These are the most poisonous elapids out there that kill horses, and we can handle 13 of them,” said Peter Kwong, a structural biologist and vaccine researcher from Columbia University, and lead author of the study. Kwong also serves as an adviser to Centivax.
With 650 venomous snake species and most deadly snakebites occurring in poor nations, there has been little economic incentive to develop snake-specific antivenins.
“The market’s fractured into 30 to 40 products, which makes it really tiny markets, which are not attractive to innovation,” said Jacob Glanville, a study co-author and the CEO of Centivax. “For that reason, antivenom hasn’t really changed in the last 125 years.”
Patients also don’t always know the type of snake that bit them, forcing doctors to guess which antivenom to use or to not treat at all. And because of genetic differences in snake populations, antivenom might be less effective outside the region where the original venom was collected.
But although there are hundreds of venomous snake species, their venoms contain different combinations of just 10 core toxin types — making a universal antivenom that targets those toxins theoretically possible.
‘Herping’ from an early age
Friede is a lifelong snake enthusiast who once boasted an extensive collection of venomous snakes at his home in Two Rivers, Wis.
Nearly 20 years ago, Friede began exposing himself to small, controlled doses of snake venom to build immunity and to protect himself from a potential snakebite. Gradually building up his tolerance, Friede endured 200 direct snakebites and self-administered 700 doses of venom. His immune system adapted to withstand venom from cobras, black mambas, taipans, rattlesnakes and more.
Growing up in Milwaukee, Friede spent his free time “herping,” or searching for garter snakes with his friends. When he was 5, he was bitten by one of the nonvenomous snakes. That first bite set off a lifelong fascination with snakes and venom.
As an adult, Friede started milking scorpions and spiders “as a hobby,” he said, and began importing the most venomous snakes he could find in 2000 — captivated by the sheer potency and danger of snake venom.
A year later, in March 2001, he began injecting himself with highly diluted venom, gradually increasing the doses over time. Most of his envenomations were deliberate, but he said there were instances where he miscalculated his dose or tried to milk a snake and it bit him.
His first intentional snakebite came from an Egyptian cobra. With no adverse reaction at first, he followed up with a second bite from a monocled cobra an hour later — which landed him in an intensive care unit with damage to his peripheral nervous system. He woke up from a coma four days later.
“When I started with mambas, as I started too fast, I screwed up. ... It looked like I had leprosy after a black mamba bite,” he said. He once felt throbbing pain from a western diamondback bite for a month, he added.
A scientist takes note
It occurred to Friede that his experiments might have scientific value, and he began posting about them on social media.
“I was more concerned about protecting myself and surviving first,” he said. “And then I realized that I’m beating death, and it’s great, but how do you get it out to the rest of the world?”
In 2017, Glanville contacted Friede after the latter was featured in a video being bitten by a black mamba and a taipan.
“If anybody has these broadly neutralizing antibodies, it’s going to be in this guy’s blood, right?” Glanville recalled thinking. “The secrets of a universal antivenom could be pumping through this guy’s blood.”
The snake enthusiast was ready: “I’ve been waiting years for this phone call,” Friede recalled saying.
Two years later, Glanville attended a dinner hosted by the Gates Foundation where he ended up sitting at the same table as Kwong. The pair quickly realized they had shared interests. Kwong was a pioneer in the understanding of how broadly neutralizing antibodies work against viruses. After speaking to Glanville, he was interested in applying the same approach to snake venom.
“He was interested in my technology. I was interested in the antibodies that he had pulled out,” Kwong recalled.
Kwong said Friede’s immune system had nearly two decades to adapt to repeated venom exposure, enabling his cells to evolve and produce antibodies capable of neutralizing venom from many different snake species.
“One of the reasons why we have a huge advantage is that Tim taught his immune system over 18 years to really, really recognize these [toxins],” Kwong said.
The team is now working on expanding coverage of the antivenom to include Viperidae snakes, like pit vipers and rattlesnakes, which are the snakes most commonly found in the Western Hemisphere and North America.
Glanville has contacted veterinarians in Australia, where elapids are the dominant family of venomous snakes. Centivax hopes to deploy the antivenom within about nine months to treat snakebites in Australian dogs. Clinical trials for humans could begin in roughly two years.
Friede retired from self-immunization in 2018. The last time he envenomed himself was in 2018 with a water cobra, one of the most venomous snakes in Africa. It was a risky one, he said, because “there’s no antivenom for it. None. Except in my blood.”
Friede still goes snake-catching with his girlfriend in Wisconsin and keeps a crossbred eastern-western diamondback at home. He hopes his efforts will ultimately result in a universal antivenom.
“Fangs crossed,” he said.