Snakebites are a major issue in many parts of the world, especially in developing countries like India, sub-Saharan Africa, and Latin America. Approximately 5.4 million people are bitten by venomous snakes annually, with 1.8-2.7 million experiencing clinical illness. Tragically, between 81,410 and 137,880 of these cases result in fatalities, while hundreds of thousands more face permanent disabilities. The most affected victims of snakebites are often rural residents, particularly breadwinners working in fields to provide for their families.

Snake venom composition varies widely between species due to dissimilar ecologies and diets. This diversity presents a significant challenge in developing effective antivenoms and treatment strategies for snakebite victims. Certain snake venoms cause paralysis and severe tissue damage that can lead to permanent disability, including limb amputation, while others disrupt blood clotting processes, resulting in fatal hemorrhages.

Currently, the only reliable treatment for snakebites is the administration of antivenoms, which work to counteract the harmful effects of venom in the body. However, these antivenoms are often ineffective against the dangers posed by snake venoms from different geographical regions. They also impose a serious risk to patients, as the animal-derived antibodies can cause severe allergic reactions and anaphylactic shock.

Antivenoms are produced by injecting venom into horses due to their large blood volume and tolerance for repeated immunizations. The horses generate antibodies in response to the venom. Blood is then drawn from the horses to isolate antibodies, which are formulated and bottled for use as antivenom. This method, which has remained unchanged since the 19th century, is laborintensive and expensive, requiring many horses to produce adequate antibodies.

Given these limitations of traditional antivenom production, there is an urgent need for novel approaches to antivenom production that could enhance efficacy and safety for snakebite victims.

Over the last few years, Scientists have developed mini-organs, known as organoids, from adult human and mouse stem cells, which can divide and grow into new tissue types. These tiny, threedimensional cultured tissues can organize themselves into structures that mimic real organs. Researchers have utilized these organoids to produce miniature versions of organs like the gut, brain, and liver for study and potential treatment development. However, little is known about the biology of adult stem cells in reptiles. This knowledge gap sparked my interest in studying one of the important reptilian organs—the snake venom gland.

Our research aims to develop snake venom gland organoids to enhance our understanding of snake venom biology and produce effective antivenoms. We harvested venom glands from Western Diamondback Rattlesnakes, a species responsible for many venomous bites in the United States. Using advanced stem cell technology, we cultured the venom gland organoids in a dish with cell culture media supplemented with stem cell growth factors.

These lab-grown mini glands produced and secreted biologically active toxins that closely resembled those made by live snakes. We then genetically manipulated the organoids to produce only the toxins associated with the morbidity and mortality following snakebites. The toxins produced were more concentrated and potent than snakes usually make.

We are currently assessing the potential of these organoid-derived toxins to stimulate antibody production in Chinese hamster ovary (CHO) cells, known for generating antibodies similar to human antibodies. This method could reduce reliance on traditional animal-based antivenom production, which often produces non-therapeutic antibodies. Our research offers a promising path toward developing faster, cheaper, and more effective antivenoms, addressing the urgent global snakebite crisis while advancing the field of venom research.