From Snake Venom to Billions: How Toxins Became Life-Saving Drugs

Researchers in the 1990s discovered a protein in the venom of the Gila monster, a desert lizard, that mimics a human hormone regulating sugar and appetite. This discovery led to the development of the first drug based on this protein, approved by the FDA in 2005, and has since spawned a multi-billion dollar pharmaceutical market. The effectiveness of venom in drug development stems from its molecules' ability to precisely target specific bodily functions.

Several life-saving drugs have originated from animal venoms. Capoten, a widely used cardiology medication, was developed from the observation that the venom of Brazil's jararaca pit viper causes blood vessels to dilate, leading to the creation of ACE inhibitors in the 1980s. Two other drugs, Aggrastat and Tirofiban, derived from the venom of the southeastern pygmy rattlesnake and the saw-scaled viper respectively, prevent blood clots and are crucial in treating heart attacks and angioplasties. Additionally, Prialt, approved in 2004 for severe chronic pain, is based on a peptide from the venom of the cone snail, a marine predator that paralyzes fish.

Despite the success in developing venom-derived drugs, the treatment for venomous bites has seen little advancement since 1894. Albert Calmette's antivenom, produced by injecting animals like horses or sheep with small doses of venom to stimulate antibody production, remains the standard method. However, this technique has significant drawbacks: it is effective only against specific snake species, requires constant refrigeration, is expensive, and can cause severe immune reactions in patients due to foreign proteins. Furthermore, in about a quarter of bites, snakes do not inject venom, leading to unnecessary administration of the antivenom.

The World Health Organization estimates that around 5.4 million people are bitten by snakes annually, with 1.8 to 2.7 million experiencing envenomation. This results in 81,000 to 138,000 deaths and approximately 400,000 permanent disabilities each year. In 2017, the WHO classified snakebite envenoming as a neglected tropical disease and set a goal to halve mortality and disability by 2030.

The economic viability of producing antivenom for developing countries is low, as the affected populations are often rural and cannot afford Western prices. This market failure led major pharmaceutical companies like Sanofi to withdraw from producing essential antivenoms, such as Fav-Afrique, which was the only antivenom effective against a wide range of sub-Saharan African snakes. Its discontinuation in 2014 led to significant increases in mortality rates in clinics that switched to cheaper alternatives.

Three promising avenues are being explored to replace traditional antivenom. One involves human monoclonal antibodies, with research showing a mixture of antibodies derived from a person repeatedly bitten by snakes provided significant protection in animal models. Another approach uses artificial intelligence to design novel proteins from scratch that can neutralize key toxins. The third method aims to replicate the snake's own defense mechanisms by identifying and synthesizing inhibitory proteins found in snake blood that protect the snake from its own venom. In Israel, where nine out of 41 native snake species are venomous, the classic antivenom production method is still employed by Kamada, relying on a 130-year-old technique.