“Around 58,000 people are estimated to be dying of snakebite in India, and probably three times that number suffer snake bite morbidity,” says Kartik Sunagar, an associate professor at the Indian Institute of Science (IISc), Bengaluru, who heads the Evolutionary Venomics Lab at the Centre for Ecological Sciences (CES).
The country is often referred to as the snakebite capital of the world, with nearly half of the deaths by snakebite occurring here. In Karnataka alone — India’s first state to make snakebite a notifiable disease, which it did in February this year — 5,418 snakebite cases and 36 deaths have been reported to have occurred in just the first six months of 2024
Russell’s viper neonate
| Photo Credit:
Kartik Sunagar
Why neglected
And yet, snakebite, which the WHO has classified as a neglected tropical disease, is often not given the attention it deserves, possibly because it mostly affects the poor and the marginalised. “It is not the politicians and popular sports persons that are getting bitten by snakes, but poor farmers in rural areas,” says Sunagar, who has been studying snake venom for over 10 years.
The situation is compounded by a lack of awareness about treatment, inadequate understanding of the issue and the cost of treatment which can run into thousands of rupees. “Many people don’t show up in hospitals because they know it can be expensive and they can’t afford it. They go to a faith healer, instead,” he says. And worse, because the problem is underappreciated snake bite research still struggles to get adequate funding.
A 2012 article by Romulus Whitaker and Samir Whitaker, titled Venom, Antivenom Production and the Medically Important Snakes of India, lists many of the reasons for the high incidence of snakebite and resultant mortality in the country: the presence of several venomous snake species in agricultural areas, inadequate distribution and availability of antivenom serum, reliance on traditional and quack treatments, walking at night without light and adequate footwear and sleeping on ground mats and geographic variation in venom composition. “Snakebite is a medically and socially significant issue in India, but the quality of treatment and reporting protocols need to be upgraded to international standards,” they write in this article published in Current Science.
Russell
| Photo Credit:
Kartik Sunagar
What is venom?
Venom is a complex biochemical toxin produced by animals that is delivered through a bite or sting to incapacitate their prey or deter predators. “All snakes in the world, as well as a group of lizards like the Komodo dragon and Monitors, share a common ancestor that evolved venom,” Sunagar says. “It is just some of them have lost venom over time because of how and what they eat.”
Moreover, even snakes that do carry venom can be identified as non-venomous. For instance, the saliva of some tree snakes has no effect on humans even though they possess venom (and therefore categorised as non-venomous), but they are highly potent to birds, the reptile’s primary prey.
In theory, humans are never the target of this complex toxin cocktail. However, because our physiology is similar to that of the target prey—mice, for instance—the venom of some snakes also works very effectively against us. What is also surprising is how sophisticated and toxic snake venom can be (for example, it is believed that a single bite containing less than 500 mg of venom can kill twenty adult human beings).
“Many snakes produce very potent venoms, usually a consequence of what we call an evolutionary arms race,” he says. Over millions of years, snakes and their prey have been locked in a cyclical co-evolutionary conflict, with the prey evolving resistance to the venom and the snakes, in turn, producing more toxic venom, he explains.
Sochurek’s viper.
| Photo Credit:
Kartik Sunagar
Problem with antivenom
Even though humans are not the target prey of snakes, we are, as Sunagar puts it, “collateral damage”. And when we get bitten by snakes with venom that is toxic to us, the only medically approved treatment is the administration of commercial antivenoms. In India, a polyvalent antivenom is produced to treat bites by snakes referred to as the “big four”—the Indian cobra, common krait, Russell’s viper, and saw-scaled viper. It is made by milking these snakes for venom and injecting them into horses, who subsequently produce antibodies against the venom. Antivenom or antivenin is then produced by collecting and purifying these horse-derived antibodies. However, this is a far from foolproof solution.
For starters, of the 300-odd snakes found in India, around 60 are venomous, but the antivenom is effective only against these four snakes, the ones that cause the most deaths in the country. Even when it comes to these four, the dose effectiveness is low, says Sunagar, pointing out that the process of manufacturing antivenom hasn’t changed much in over a century. “Less than 10% of that vial actually contains antibodies against snake venom toxins; the rest is therapeutically redundant,” he says.
Even the 10%, which contains antibodies specific to the snake venom, does not target the toxin you need to neutralise. “The amount of relevant antibodies you want to neutralise the toxic effects of snake venoms is really low, which means conventional antivenoms have very low dose efficacy.”
Also, since these are horse antibodies injected into humans in vast quantities, there is a chance that our immune system will recognise them as intruders and respond accordingly. “Obviously, it can be unsafe because your immune system will recognise them as antigens and may mount an antibody response against the antivenom,” says Sunagar. “You could die because it causes something called anaphylaxis, which could kill you much more quickly than the snake venom.”
Specificity of venoms
Even more sobering is that venoms—and therefore antivenoms produced from them—are remarkably specific, a function of numerous factors, including geographic differences in prey and predator dynamics, environmental conditions, and distinct evolutionary histories of snakes.“They mostly work against the populations they are produced against,” says Sunagar, whose research on snake venom is inherently interdisciplinary, using insights and tools from evolutionary biology, molecular genetics, and ecology to understand this complex substance.
Sunagar elaborates on this problem of venom specificity. Nearly all the anti-venom produced in the country comes from only one source, the Irula Snake Catcher’s Industrial Co-operative Society in Tamil Nadu, and is manufactured in a handful of labs in the country. “A venom collected in South India isn’t going to be as effective for treating snakebite in North India,” he says.
Even the venom collected from the snakes on one side of the Western Ghats may not be effective in treating a snakebite from the same species that has occurred on the other side because it is likely that their evolutionary histories will be different. “That is where our work on understanding the ecology and evolutionary histories and biogeographic histories comes into the picture,” he says.
Vine snake.
| Photo Credit:
Kartik Sunagar
Recent insights
A new study from Sunagar’s lab titled From Birth to Bite: The Evolutionary Ecology of India’s Medically Most Important Snake Venoms, published in BMC Biology, adds to the growing literature on the factors that shape the biochemical complexity of snake venom. The paper shows that in the Russel’s viper, the venom of newborns was more toxic than that of adults, but such an age-dependent influence is not seen in the venom of the Indian cobra. The results suggest a role for the kind of prey each snake species encounters at different stages of its life in determining venom toxicity. “We wanted to understand how life history and ecology influence venom,” Sunagar explains.
Sunagar feels that understanding the different factors that contribute to variation in venom biochemistry is crucial in our quest to make snakebite treatment more effective in India. And they are already making headway in this direction. “One of the things that we are doing to address this immediately is to make regional antivenoms,” says Sunagar.
His lab is working with manufacturers to produce regional antivenoms targeting medically important snake species in western India. They are, at the same time, attempting to develop a single antivenom that could work against all snakebites in the region. “Snakes don’t follow political boundaries, of course. But we are trying to see if different pockets need different antivenoms or if a single one can work,” he says. He adds that the antivenoms are currently being validated using mouse models. “If it works, it will be the first major change to Indian antivenoms in over 100 years.”
Puff adder.
| Photo Credit:
Kartik Sunagar
Cutting-edge research
More cutting-edge research is on the horizon. “We are discovering many promising monoclonal antibodies (proteins made in labs by cell lines that mimic natural antibodies) capable of neutralising snake venoms from different corners of India,” he says. And while there is a long way to go—they still need to be validated in human clinical trials—he believes that the next generation of snakebite treatment in India would involve the use of a combination of two to three monoclonal antibodies produced by cell lines, rather than horses.
Sunagar is also excited about a new development to combat snake bites: a first-of-its-kind facility called the Antivenom Research and Development Centre is being established in Bengaluru’s Electronic City with support from IISc, the Institute of Bioinformatics and Applied Biotechnology (IBAB), and the Government of Karnataka. This facility for snakebite research is expected to have a serpentarium to further both education and research, space to house startups involved in venom research and several state-of-the-art labs, among other things. “Once this facility comes up, I’ll be able to do a lot more work,” he says.
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