Eighteen years ago, Tim Friede began willingly injecting himself with escalating doses of venom from 16 snake species. Now, antibodies in his blood have led to the development of a three-part antivenom cocktail capable of protecting mice from the toxins of a variety of dangerous snakes.
For 13 types of dangerous snakes, the antivenom conferred full protection, while for another six the cocktail delayed death but did not save the mice. The tested venoms came from snakes in the family Elapidae, which includes cobras, taipans and mambas. All are included on the World Health Organization’s list of medically important snake species (PDF).
The results were published in Cell on May 2.
The results provide “proof of principle” that even a limited cocktail “can have very broad recognition of many, many elapids,” Peter Kwong, Ph.D., a molecular biologist at Columbia University and senior author of the study, told Fierce Biotech in an interview.
The antivenom cocktail contains two antibodies isolated from Friede’s blood and was tested against a panel of elapid venoms. Because Friede’s body has been continually exposed to the venoms over many years, his immune system has been able to fine-tune the antibodies it generates in response to snake toxins, a process akin to evolution by natural selection.
“This speaks to the power of nature and these systems and their awesome ability, with appropriate selection pressure, to produce these remarkable molecules,” Jacob Glanville, Ph.D., the CEO of Centivax and lead author of the new study, told Fierce in a joint interview with Kwong.
The two antibodies respectively target the long- and short-chain neurotoxins that make up the bulk of elapid venom. The third cocktail component is varespladib, a compound already known to block the effects of another major venom toxin, phospholipase A2.
Other experts called the study an important step forward in addressing the global health issue of venomous snakebites—which kill more than 100,000 people every year and disable many more—but said that more work remains to be done to create a truly universal antivenom.
“While there is certainly very intriguing effectiveness against some species, there are likely to be gaps in the coverage,” Bryan Fry, Ph.D., a venom expert at the University of Queensland in Australia, told Fierce.
The research “highlights the complexity of snake venoms and suggests that multiple monoclonal antibodies may be necessary for effective treatment,” Kartik Sunagar, Ph.D., a venom biologist at the Indian Institute of Science in Bangalore, told Fierce. But, Sunagar added, “none of us can take these antibodies to trials until a point when we have neutralizing antibodies for both elapids and vipers.”
Vipers represent the other major group of venomous snakes, with different toxins than the elapids. Kwong and Glanville are now working to both broaden their cocktail’s potency against elapids and expand into vipers.
The team is again “turning the crank” of its process to identify the most toxic compounds that are shared across elapid venoms, Glanville said, to see whether there’s “an advantage of putting one more agent into the cocktail to make it even broader in its full protection capability.”
The researchers are also beginning the same process for viper venoms, Glanville said, but are still in early stages.
Glanville and Kwong are planning to conduct another animal study to test the safety and effectiveness of their antivenom cocktail, this time in dog snakebite victims in Australia. The team has been in touch with a veterinary clinic that takes in many envenomated canines and offered to collaborate.
Fry, the Australian venom expert, doubts that the cocktail will prove that effective in the dog study.
“This first paper already describes the failure of the antibodies to neutralize death adder venom,” he said, reflecting the fact that Friede mainly injected himself with venoms from the U.S. pet trade, “which Australian snakes are rare in.”
The antivenom did extend the lives of mice exposed to death adder venom but did not completely protect them, according to the paper.
Friede’s effort to immunize himself against snakebites has drawn extensive media attention in the past, which is how Glanville found out about him. After the two connected, Glanville recalled, Friede said he’d been “waiting for this call for a long time.”
Friede’s self-experimentation raised some ethical concerns for Sunagar. “Self-immunization can be life-threatening and most likely negatively affects those who practice it,” he said.
“No one else should do what Tim did,” Glanville agreed. “We never gave him any guidance on what to immunize with, and he'd done almost all of it before we met him.”
“I think Tim did something remarkable, and there's a history of self-experimentation that's resulted in Nobel Prizes,” Glanville added. “But on the other hand, I don't think this experiment ever needs to be repeated.”