Tim Friede caught the eye of Jacob Glanville, an immunologist and chief executive of biomedical firm Centivax in South San Francisco, California, back in 2017. Tim had injected himself over 600 times with the venom of some of the world’s deadliest snakes, including mambas, cobras, and rattlesnakes, and allowed himself to be bitten around 200 times by these snakes. Although Friede’s experiment is ethically off-balance, Jacob didn’t ask him to do any of this, nor would he suggest that anyone do so.
Current methods of developing snake antivenom are outdated and messy. Traditionally, snake venom is milked, and then it is injected into horses and other animals. The animal produces antibodies, which are then gathered. Each antivenom can protect only against venoms of at most a few snake species. The paper’s authors plan to make an antivenom that can safeguard against 600-plus snake species.
To start with, the team is trying to develop antivenom against the Elapidae family, which contains nearly half of those species. Elapid venom consists of peptides called short-chain neurotoxins (SNX) and long-chain neurotoxins (LNX). Both these venomous peptides bind to the same receptors on the nerve cell. As a result, communication between neurons gets impaired. This leads to muscle paralysis and respiratory failure.
Kartik Sunagar, a biologist who develops antivenoms at the Indian Institute of Science in Bengaluru, says that technological advancement calls for updated methods of generating snake antivenom.
Jacob and co-author Peter Kwong read news coverage about Friede, who injected himself with snake venom over a period of 17 years, 9 months, and took careful notes about his venom exposure. Friede and Jacob agreed to work together, and he donated a 40-milliliter blood sample to Glanville and his colleagues. Eight years hence, they have procured an antivenom to protect against bites from 19 different species of venomous snakes in mice. All of this has been obtained as a cocktail of two different antibodies from Friede’s blood, mixed with a venom-blocking drug that inhibits a snake-venom enzyme that breaks down muscle and nerve tissue called varespladib. One of the antibodies bound to toxins in the SNX family and rendered them inactive, while the other one bound to toxins in the LNX family and neutralized them.
Glanville says that exact copies of human antibodies will be less risky and will prevent adverse reactions than those based on animal antibodies. Broad-spectrum synthetic antibodies designed with computational and AI-based approaches also fall behind in safety.
While there are concerns regarding the ethics of the research, Sunagar says that the study has been well executed. The research shows that combinations of small-molecule drugs such as varespladib and monoclonal antibodies, which are copies of human antibodies, hold promise. One major question lies in whether the treatment will become affordable in the future or not.
Jean-Philippe Chippaux, a specialist in venomous-snake bites and an emeritus researcher at the French National Research Institute for Sustainable Development in Paris, says that the tough part in treating snake bites is not the efficiency of the treatments, but the fact that they are often administered too late. Glanville plans to make the therapeutic measures portable and affordable. He also plans to test the antivenom in the real world before moving on to human trials.
Centivax plans to test the experimental cocktail in dogs bitten by snakes in Australia. First, the dogs will be given the experimental treatment. They will receive the usual antivenom if it doesn’t work after a few minutes.
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