Over the course of 18 years, a truck mechanic from Wisconsin injected himself with snake venom hundreds of times. His actions were considered stunts by some over those years, but his blood has just helped lead the way toward a universal antivenom.
When you watch Tim Friede's now decade-old homemade videos on his YouTube channel, showing him getting bit by the world's deadliest snakes – and surviving – you might not instantly think of him as a pioneer in the world of immunology.
But Friede's videos are actually only the showy part of a self-immunization project he undertook for nearly two decades in which he injected himself over 800 times with increasingly high venom from a wide-range of serpents. This effectively hacked his immune system to produce some very valuable antibodies.
Those antibodies have now been harvested by a team of scientists with the goal of developing a universal snake antivenom treatment.
Human lab
In carrying out the work, the researchers isolated the antibodies in Friede's blood that countered a range of venom produced by 19 of the venomous snakes classified as either category 1 or 2 by the World Health Organization, marking them as the deadliest snakes on the planet. These included the black mamba, king cobra, tiger snake, coastal taipan, and Papuan black snake. Each antibody was given to mice, which were then injected with the snake venom. This allowed the researchers to track exactly which of Friede's antibodies countered the most neurotoxic effects in the snake venom.
That's a tricky thing to arrive at because poisonous snakes generally produce between 5-70 protein toxins each. Yet, by carrying out his snake-bite injection program over the years, Friede used his own body as a lab of sorts, allowing his biology to develop the necessary antibodies to the most potent of these toxins.
After conducting the mouse experiments, the team eventually settled on an antivenom cocktail consisting of two of Friede's antibodies along with a small molecule known as varespladib, a toxin inhibitor that is increasingly being studied as an antivenom treatment.
The mix worked, protecting the mice from the effects of venom from 13 of the 19 species and offering partial protection for the remaining six. Study first author Jacob Glanville believes that adding a fourth component to the formula could create a universal antivenom.
“By the time we reached three 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,” he said. “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?”
But even as the researchers search for that additional component, the mouse study shows that the formula they currently have may prove to be a potent tool in fighting a broad range of snakebites. If human trials uphold its efficacy, it could mean that hospitals could keep the formulation on hand instead of storing a range of fragile and expensive antivenoms that only work for particular species of snakes. In a country like India, which has roughly 60 species of venomous snakes, such a tool would be a game changer.
Human helper
Using Friede's blood also sidesteps a major issue with one of the more common ways to develop antibodies. Currently, the process involves injecting horses or sheep with snake venom and then harvesting the antibodies that develop. However, that can lead to reactions in people receiving non-human antibodies. Also, antibodies produced this way can be extremely species – and even region – specific. Starting with a range of human antibodies eliminates the compatibility concern and thanks to the range of venoms Friede exposed himself to, the specificity problem disappears as well.
The researchers now plan to move forward with their work with the goal of developing a true universal antivenom, or perhaps two of them, paralleling efforts by a team seeking to develop a synthetic universal antivenom that we reported on last year.
“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 study lead author Peter Kwong from 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.”
The study has been published in the journal Cell Press.
Sources: Centivax and Columbia University via Scimex, Outside