In India, a need for new antidotes to curb deadly snakebites

As far back as he can remember, Kali Chockalingam, now 53 and living in Echur, a village in Southern India, has loved snakes. He often got in trouble with his teachers for hiding them in his schoolbag. “As a young boy, I thought they looked like little dolls,” he said. Chockalingam hails from India’s Irula tribe, one of the country’s oldest Indigenous communities, known for their extraordinary ability to trace and catch snakes. From his father and grandfather, he learned the family trade.

Roughly 200,000 Irulars are spread out over three Southern Indian states—Kerala, Karnataka, and Tamil Nadu. And for the past 45 years, Chockalingam’s tribe in Tamil Nadu has run the Irula Snake Catcher’s Industrial Co-operative Society, India’s largest producer of quality snake venom, which is used to manufacture antidotes to snakebites, or antivenin.

Research has shown that antivenin made from the co-op’s venom has been effective in treating bites by the four most common venomous snakes in the country, the only snakes the Irulars are legally allowed to catch: the Russell’s viper, the common krait, the Indian cobra, and the Indian saw-scaled viper.

Still, snakebite deaths remain a problem. According to the Million Death Study, one of the largest ongoing global studies of premature mortality, around 58,000 Indians die from snakebites every year, the highest rate in the world. And a growing proportion of these bites come from less common species of venomous snakes in specific pockets of the country, for which, according to researchers at the Indian Institute of Science, available antivenin — also often called antivenom—are not very effective.

People living in India’s rural areas, who are exposed to a broad range of snakes, are particularly at risk. Treating these patients can be difficult, said Gnaneswar Ch, project leader of the Snake Conservation & Snakebite Mitigation Project at the Madras Crocodile Bank Trust Center for Herpetology, where the Irula Co-op is located.

For instance, in Tamil Nadu, data on snakebites and how to prevent them—gathered by Gnaneswar’s team since 2015—suggest that people are most likely to be bitten on their legs when they walk across agricultural fields barefoot. And they may not seek treatment at the hospital until hours after the bite, turning first to natural or folk remedies. As a result, Gnaneswar said, “we’re seeing many amputations and loss of limbs.”

The Irulars’ history with snakes traces back to the tribe’s roots as hunter-gatherers. In pre-Independent India, the tribe began to sell snakes to the British, who wanted their skins. But the tribe was thrust into poverty after India’s Wildlife Protection Act came into effect in 1972, which banned snake hunting (and later, snakeskin export in 1976).

The tribe’s prospects changed in 1978, when herpetologist Romulus Whitaker, who had formed a deep friendship with the Irulars, established the Irula Co-op. Since then, the Irulars were charged with the responsibility of catching snakes, said Gnaneswar. And “they went from snake hunters to lifesavers.”

The Irula Co-op now has approximately 350 members who, like Chockalingam, are licensed to catch venomous snakes. As a collective, they are allowed to bring in up to 13,000 snakes per year, generating an annual income between 10 and 25 million Indian rupees (between approximately $120,000 and $300,000). At any given time, the co-op has the license to house up to 800 venomous snakes. Because of the region’s immense heat, the snakes are stored in wide brimmed earthen pots, which are covered with cotton cloths and closed with a string. The snakes are protected by India’s Wildlife Act, and so the co-op is only permitted to keep individual animals in captivity for 21 days, during which their venom is extracted—or milked—four times. Venom milking involves holding the snake by its head and forcing it to bite the lip of a jar; venom drips from its fangs and collects in the jar.

The work has its dangers. Over the past 30 years, Chockalingam has been bitten five times, he said, and some of the bites have been life threatening. In 2001 on a routine snake catching operation, a Russell’s viper sank its fangs into his index finger. After stopping for a cup of tea, Chockalingam said, he went to the hospital for shots of antivenin. When he was finally allowed to go home after five days, he remembers immediately setting out to catch another snake.

Not everyone can catch snakes with the ease and expertise of the Irulars, so antivenin manufacturers across India rely heavily on the co-op. Today, just seven companies in the country produce antivenin, and all of them buy Irular-milked venom for their products.

“Manufacturing antivenin is a very technologically challenging process,” said MV Khadilkar, co-founder and technical director of Premium Serums, which makes country- and region-specific snake antivenin for India, Sri Lanka, North Africa, and Sub-Saharan Africa. The product is manufactured using horses; it’s complex and labor intensive, and the outcome isn’t always guaranteed. Small, harmless doses of the snake venom are injected into the horses, and the doses are then gradually increased (though they remain at levels that will not hurt the animal). The horses’ bodies produce proteins in reaction to the venom, called antibodies, which are then harvested from their blood and processed into an injectable antivenin. “We have to ensure the health and welfare of the animal as well as we have to maintain productivity,” Khadilkar said. “It is a very delicate balance.”

The seven Indian companies that produce antivenin make 8 million vials a year, most of it derived from the Irula Co-op venom. But in spite of the Irula co-op’s efforts, and the availability of antivenin across the country, many challenges persist.

First, producing antivenins for India’s different regions is difficult. Some snakes aren’t considered medically important: Though their bites may cause severe pain, disability, neurological issues, and paralysis, they are not life-threatening. Other snakes that are lethal are restricted to specific areas of the country. In the end, producing the antidotes must be affordable without compromising on quality.

“The problem of snake venom is a problem of poor people,” Khadilkar said. It involves hard labor in manufacturing, but the profits aren’t high, he said, and “that’s why you don’t find many big pharmaceutical companies who are in this field.”

“Despite this,” he added, “there’s always a demand from different corners of India.”

The antivenin that is made isn’t always well-distributed. According to Gnaneswar, while the country produces adequate venom from the big four snakes, the antivenin may not always reach the places that need it the most. Stocks may be inadequate, especially in rural hospitals and small health care centers, because they are not distributed to places that see the most snakebites.

And the antivenins that are produced and distributed won’t treat every snakebite, even from related species. “The problem is that venom varies between species and geographically as well,” said Whitaker, who is now the Indian head of the Global Snakebite Initiative. While the Irula Co-op pulls venom from the four species that cause the most fatal bites across India, there are also four species of cobras, seven species of kraits, and two species of saw-scaled vipers, he added, and the co-op venoms may not work as well “for bites of the same or related species in other parts of the country.” And venom also changes over different seasons, even within an individual snake.

Then there’s the issue of quality. How well an antivenin works depends on the potency of the venom—a mixture of biological substances including amino acids, carbohydrates, fats, nucleic acids, peptides, and proteins. The best practices for venom extraction, which were created by the World Health Organization, “are hard to achieve in India, considering our existing wildlife laws and drug manufacturing laws, but more importantly, the necessity to keep the venom production costs to the minimum,” said Gnaneswar. For instance, the best practices dictate that snakes should be held in a controlled environment with appropriate nutrition and low chances of stress. This goes against Indian laws, where snakes are protected and can’t be held indefinitely in captivity.

There are also issues with venom storage. Once milked, the venom must quickly be stored at minus 20 degrees Celsius, or minus 4 Fahrenheit, to retain the highest quality; otherwise, its biological components could degrade. The Co-op’s current methods involve extracting venom from up to a hundred snakes in quick succession, which means the earliest collections don’t immediately go into a freezer. “It’s evident that venom loses its potency,” said Gnaneswar. “However, we are not sure how much potency it loses.”

To help make the antivenin that can treat a wider range of India’s many snakebites, there are two possible approaches, according to Khadilkar. The first is to manufacture region-specific antivenin dedicated to a particular area where there is strong demand—individual antivenins for each species of snake. If venom was collected from diverse snakes across India, a “cocktail” of those from the same species could then be used to immunize the horses, he said. The antigenic variation “can provide more diverse antibodies and the antivenin becomes effective over a wider geographical area.” But the costs for this approach would be high.

The second is to make a more diverse antivenin that can effectively act on a spectrum of snakebites. This would entail catching and milking snakes from different parts of India, not just the big four, and making a mixed antivenin. The biggest drawback is that there isn’t enough skilled labor to achieve this.

Still, on a smaller scale, there are such efforts underway. Gnaneswar’s employer, the Madras Crocodile Bank Trust Center for Herpetology, is working with the Tamil Nadu government to set up a new state-of-the-art venom collection center. The hope is for the facility to get permission to permanently house snakes from all over the country. If approved, it could be operational as early as August 2025. For Chockalingam and the other Irulars—should they get the government’s permission to catch more species of snakes beyond the big four — the serpentarium could translate to more work, more venom, better infrastructure and safety protocols, and richer rewards. “It gives me a deep sense of joy when I think of the lives we’re saving by doing this work,” said Chockalingam. “It makes every struggle worth it in the end.”

Another possible solution may be to produce antivenin in a way that doesn’t rely on injecting horses with venom and collecting antibodies. Some labs are experimenting with such an approach: oral antidotes, which target proteins in venom that are most toxic to humans. These antidotes can also withstand higher temperatures and produce fewer allergic reactions. One such company, the U.S.-based Ophirex, has recently completed a Stage 2 clinical trial on its product.

“If that drug proves out to be effective,” Gnaneswar said, “it would be a huge, huge jump for antivenom in India.”