A brief history of antivenom
September / October 2022 | Volume 21 Number 5
By Susan Scutti
Antivenom (also referred to as “antivenin”) is an antibody therapy that can disable the toxins within a specific venom if injected quickly into a patient after a bite. French scientist and physician Albert Calmette is credited with creating the first snake antivenom.
Renowned chemist Louis Pasteur met Calmette in Paris in 1890, and, impressed by his work, invited him to organize rabies and smallpox vaccination campaigns at The Pasteur Institute in Saigon. It was there that Calmette first encountered the lethal activity of the Naja naja (Indian cobra). In 1891, he published a paper on snake envenoming and his tests of several chemical substances as possible therapies.
This research led Calmette to successfully develop an anti-cobra serum in rabbits in 1894. Calmette's work was based on that of Henry Sewall, whose publications described repeat inoculations of pigeons with sub-lethal doses of rattlesnake venom to achieve an increasing resistance to its toxic effects. In 1895, Calmette began production at the Pasteur Institute in Lille of a therapeutic serum created by inoculating horses with the venom of the Naja naja snake. This process of obtaining antivenom revolutionized the treatment of snakebite envenomation and influenced researchers worldwide.
Over more than 120 years, production of antivenom, which must be tailored to species of snakes, remains much the same. Most antivenoms are produced in horses, some in sheep; a small amount of venom is injected into the animal, causing an immune system reaction and release of antibodies, which are later harvested via bleeding. This blood plasma is then concentrated and purified into pharmaceutical grade antivenom.
While the basic production method has remained little changed, many technological advances and purification processes have been introduced to achieve higher quality products and reduce side effects. Additionally, in the 1970s, antivenom began to be administered via the intravenous route (injected into the vein) as opposed to the subcutaneous route (injected under the skin) or intramuscular route (injected into the muscle). This has helped decrease severe reactions.
Global supply crisis
By the end of the 20th century, antivenom manufacturers began to dwindle worldwide, due to complexity of production, high production expenses, and lack of a lucrative market. This has resulted in a dramatic increase in the price of some products over the last two decades. Antivenom availability has also declined significantly. Meanwhile untested, unethically produced, or fake products have entered the market. The populations hardest hit by shortages of antivenom, which is included on the
WHO’s List of Essential Medicines, live and work in rural areas of less-developed nations where highly venomous snakes are endemic.
Experts in the field suggest these changes to help increase antivenom supply: establish production in developing countries (following the example of Brazil’s Instituto Butanan); introduce new methodologies to reduce costs while further increasing the quality of products; and apply state-of-the-art technologies to abolish the use of animals in anitvenom production.
Updated October 6, 2022
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