Man Injected With Snake Venom 856 Times Helps Create Universal Antivenom

Tim Friede voluntarily injected himself 856 times with snake venom from some of the world’s deadliest species. While some may call it reckless, he calls it self-immunization.

In a study led by researchers at Centivax and Columbia University, antibodies from Friede’s blood were used to create a 3-part antivenom that protected mice from the venom of 13 highly lethal snakes and gave partial protection against 6 more.

The research was published in Cell.

The human donor with 800 snakebites

Snakebites kill over 100,000 people a year and leave hundreds of thousands of people with permanent disabilities. Most victims live in rural parts of Africa, Asia and Latin America, where access to medical care is limited.

Snakebite treatment hasn’t changed much in over a century. Healthcare providers rely on polyclonal antivenoms, made by injecting horses or sheep with venom and collecting their antibodies. These antivenoms only work for specific species or regions, and they can cause serious side effects.

There are over 600 venomous snake species, and each one produces a different mix of toxic proteins, sometimes dozens per species. No single antivenom works for all of them, and no scientist has figured out how to make one that does.

Researchers have tried using monoclonal antibodies or small-molecule inhibitors, but they usually protect against just one toxin or one snake. Even if a good antibody is discovered for one toxin, putting together enough of them to cover the full range of venom types turns into an unworkable cocktail, requiring dozens of components.

Instead of building a new antivenom from scratch, a group of researchers turned to someone with a head start. Friede has spent 18 years injecting himself with increasingly lethal doses of snake venom – on purpose. His immune system has seen more venom than most snakes ever will. The team took a blood sample, analyzed his antibodies and asked a simple question: could this approach actually work?

Building and testing the antibody cocktail

The team took a 40 mL blood sample from Friede and got to work.

“The donor had undertaken 100s of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally kill a horse,” said first author Dr. Jacob Glanville, founder, CEO and chairman of Centivax.

Glanville and colleagues screened Friede’s memory B cells and used phage display to isolate antibodies with broad binding profiles – resulting in antibodies that didn’t just react to one kind of snake toxin, but to many. The team found that Friede’s antibodies had undergone extensive somatic hypermutation – a sign of years of immune system adaptation. These antibodies had spent nearly two decades evolving in response to venom from species including black mambas, king cobras and kraits.

 

Two antibodies stood out: LNX-D09, which targeted long-chain neurotoxins, and SNX-B03, which went after short-chain ones. Both toxins paralyze their victims by binding to the same nerve receptor, but Friede’s antibodies did something clever. The isolated antibodies mimicked the receptor and blocked the toxins from binding. Structural studies showed the antibodies latched onto the exact spot where the toxins used to disable nerves.

To evaluate the antibodies, the team created a test panel of venoms from 19 genetically and geographically diverse elapid species, based on the World Health Organization’s list of the most medically important snakes.

They tested LNX-D09 in untreated mice injected with venom from six elapid species, using lethal doses to assess how well each antibody or combination could protect against full envenomation.

Mice were challenged in 2 ways: with venom premixed with the antibodies (pre-treatment model), and with antivenom given 10 minutes after venom injection (rescue model), mimicking real-world bite scenarios.

LNX-D09 alone provided complete protection in mice against venom from six elapid species, including black mamba, king cobra and four cobra species.

Adding a known drug, varespladib, which blocks another major toxin group (PLA2 enzymes), extended protection to three more species.

SNX-B03 closed the remaining protection gaps, leading to full or partial survival in all 19 species tested.

Glanville and colleagues tested different combinations of antibodies and inhibitors in mice to find the smallest set that gave the broadest protection.

The three-component mix proved sufficient to address the most lethal venom types in the Elapid snake family. The cocktail offered protection across snakes from six continents, including rare or medically under-treated species.

“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” said Glanville.

“We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” he added.

The future of snakebite treatment

The idea of a universal antivenom has been floating around for decades.

“What was exciting about the donor was his once-in-a-lifetime unique immune history. Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom,” said Glanville.

As the antibodies are human-derived, they should last longer in the bloodstream and trigger fewer immune reactions than horse serum. Manufacturing would also become easier since these are recombinant proteins made in controlled systems, not harvested from animals.

However, the doses, the venom amounts and the immune response still need to be tested in humans. The cocktail also only covers Elapid snakes. Since the current mix includes varespladib, which breaks down quickly in the body, patients would likely need multiple doses unless it’s swapped for something longer lasting.

The team is now looking to start field trials in dogs, especially in Australia where snakebites are common in pets. They are also trying to build a similar cocktail for viperid venom.

“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” said corresponding author Dr. Peter Kwong, Richard J. Stock Professor of Medical Sciences at Columbia University.

“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,” he added.

Glanville and his colleagues are also trying to approach philanthropic foundations, governments and pharmaceutical companies to support the manufacturing and clinical development of the antivenom cocktail.

“This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” concluded Glanville.

 

Reference: Glanville J, Bellin M, Pletnev S, et al. Snake venom protection by a cocktail of varespladib and broadly neutralizing human antibodies. Cell. 2025. doi: 10.1016/j.cell.2025.03.050

This article is a rework of a press release issued by Cell Press. Material has been edited for length and content.