Man who injected himself with venom hundreds of times could revolutionize snakebite treatment

Immunologist Jacob Glanville came across media reports in 2017 of a man who had injected himself hundreds of times with the venom of some of the world’s deadliest snakes, including cobras, mambas and rattlesnakes — and allowed himself to be bitten. “The news articles were kind of flashy. ‘Crazy guy gets bit by snakes,’” Glanville said. “But I looked, and I was like there’s a diamond in the rough here.” Glanville’s diamond was Tim Friede, a self-taught snake expert based in California who exposed himself to the venom of snakes over the course of nearly 18 years, effectively gaining immunity to several neurotoxins. “We had this conversation. And I said, I know it’s awkward, but I’m really interested in looking at some of your blood,” Glanville recalled. “And he said, ‘Finally, I’ve been waiting for this call.’” The pair agreed to work together, and Friede donated a 40-milliliter blood sample to Glanville and his colleagues. Eight years later, Glanville and Peter Kwong, Richard J. Stock Professor of medical sciences at Columbia University’s Vagelos College of Physicians and Surgeons, have published details of an antivenom that can protect against bites from 19 species of poisonous snake — at least in mice — based on antibodies in Friede’s blood and a venom-blocking drug. “Tim, to my knowledge, he has an unparalleled history. It was different, very diverse species from every continent that has snakes, and … he kept rotating between (the snake venoms) over a 17-year, nine-month history, and he took meticulous records the entire time,” Glanville said. “However, we strongly discourage anyone from trying to do what Tim did,” Glanville added. “Snake venom is dangerous.” Friede gave up immunizing himself with snake venom in 2018 after some close calls, and he is now employed by Glanville’s biotechnology company Centivax, Glanville said. Glanville is CEO and chairman of Centivax. The research was published Friday in the scientific journal Cell. CNN contacted Friede, but he did not respond to an interview request. The snakebite problem If you’re unlucky enough to have a poisonous snake sink its fangs into you, your best hope is an antivenom, which for the most part has been made in the same way since Victorian times. Traditionally, the process involves milking snake venom by hand and injecting it into horses or other animals in small doses to evoke an immune response. The animal’s blood is drawn and purified to obtain antibodies that act against the venom. Producing antivenom in this way can get messy, not to mention dangerous. The process is prone to errors and laborious, and the finished serum can result in serious side effects. Experts have long called for better ways to treat snakebites, which kill some 200 people a day, mainly in the developing world, and leave 400,000 people a year with disabilities. The World Health Organization added snakebite to its list of neglected tropical diseases in 2017. Glanville, who grew up in rural Guatemala, said he had long been aware of the health problems posed by snakebites and immediately recognized that Friede’s experience presented a unique opportunity. Exposing himself to the venom of snakes for nearly two decades, by injecting venom and allowing himself to be bitten, Friede had generated antibodies that were effective against several snake neurotoxins at once. ‘Revolutionary’ potential The researchers isolated antibodies from Friede’s blood that reacted with neurotoxins found within the 19 snake species tested in the study, which included coral snakes, mambas, cobras, taipans, kraits and others. These antibodies were then tested one by one in mice poisoned by venom from each of the 19 species, allowing scientists to understand systematically the minimum number of components that would neutralize all the venoms. The drug cocktail the team created ultimately included three things: two antibodies isolated from Friede and the small-molecule drug varespladib, which inhibits an enzyme that is present in 95% of all snakebites. The drug is currently in human clinical trials as a standalone treatment. The first antibody, known as LNX-D09, protected mice from a lethal dose of whole venom from six of the snake species. The addition of varespladib granted protection against an additional three species. Finally, researchers added a second antibody isolated from Friede’s blood, called SNX-B03, which extended protection across 19 species. The antivenom offered the mice 100% protection against the venom for 13 species and partial protection (20% to 40%) for the remaining six, the researchers noted in the study. Steven Hall, a snakebite pharmacologist at Lancaster University in the United Kingdom, called it a “very clever and creative way” to develop an antivenom. Hall wasn’t involved in the research. And while the cocktail has not been tested in humans, should it be approved for clinical use, Hall said the human origin of the antibodies would likely mean fewer side effects than antivenoms made the traditional way using horses or other animals, which can often result in allergic reactions. “It’s impressive for the fact that this is done with one or two antibodies, plus a small-molecule drug, and that increases the number of species, versus a regular antidote. And I think it does a good job of highlighting the potential utility of combining a small-molecule drug with an antibody,” Hall added. “If it makes it into clinic, makes it into people in the long run, it would be revolutionary. It actually would completely change the field in terms of snakebite (treatment),” he said. Columbia’s Kwong said that the published research focused on a class of snakes known as elapids. It did not include viperids, the other major group of venomous snakes that includes rattlesnakes, saw-scaled vipers and additional species. However, the team is investigating whether additional antibodies identified in Friede’s blood or other agents might offer protection against this viperid family of 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,” Kwong said. The team also wants to start field research in Australia, where there are only elapid snakes, allowing vets to use the antivenom on dogs bitten by snakes.