Snake venom can be remarkably diverse in composition and potency, not only between one species and another but also within the same species. Because of biogeographic variation, commercially available antivenom in India may neutralise the effect of snakebite in one region but be ineffective in another region, even if the bite has come from a snake of the same species.
The variation, however, is not biogeographic alone. In a new study that may have implications for snakebite treatment, researchers have shown that the toxicity of venom from two of India’s deadliest snakes, Russell’s viper and spectacled cobra, can also depend on ontogeny, or the stage of life the snake is in. For example, a newborn Russell’s viper’s venom is more potent than that of an adult against mammals, and even more so against reptiles.
The study, published in BMC Biology this week, was led by the Evolutionary Venomics Lab under the Centre of Ecological Sciences, Indian Institute of Science (IISc). Researchers maintained 194 Russell’s vipers and 32 spectacled cobras in captivity, among which the adults had been collected from Hunsur, Karnataka, and the younger ones were born in captivity.
They drew their venom every three months, examined its composition, tested its effect on mice, lizards and insects, and also observed how antivenoms worked against it. In the process, they helped fill part of a knowledge gap in our understanding of the evolutionary ecology of snake venom.
Venom at different stages
The results were a study in contrast. Newborn Russell’s vipers carry venom that is twice as potent as the venom of their adult mothers against mammals, and up to 10 times more potent against lizards. The venom of a young Russell’s viper is potent against both mammals and lizards, while that of an adult kills mammals but not lizards.
The toxins in spectacled cobra venom, on the other hand, remain largely unchanged over the snake’s lifetime.
The reason why stage-specific changes were observed in viper venom but not in cobra venom, the authors conclude, could lie in the differing predatory strategies and habits of the two species. The spectacled cobra is an opportunistic feeder that hunts various prey animals, including lizards, frogs, toads, snakes and rodents throughout its lifetime, so there is no reason for its venom to change.
The Russell’s viper, on the other hand, is predominantly an ambush predator that probably hunts specific prey at various developmental stages, the authors write. For example, lizards survived beyond 24 hours even when injected with 20 mg/kg of venom from an adult Russell’s viper, but it took very little venom from newborns and juveniles to kill them. When it came to frogs, newborns readily accepted them in captivity, even wiggling their tails to attract the prey, but the adults did not show such behaviour.
“Based on our findings, we theorise that the adults may switch to feeding on large mammalian prey. Young snakes may be feeding on small lizards or frogs and may eventually switch to rodents, which correlates with our toxicity results too. It is unlikely that adults feed on lizards in the wild as they may be too little to catch or meet their appetite,” Kartik Sunagar, who heads IISc’s Evolutionary Venomics Lab, told HT.
Younger Russell’s vipers did not accept rodents in captivity, while adults in the wild are known to feed predominantly on rodents. One reason could be the smaller gape size of younger snakes, which would prevent them from feeding on large mammals. What then, explains the fact that the venom of newborn vipers is 2 to 2.5 times as toxic against mammals as that of their mothers?
“Venom is used for both predation and self-defence. So, while they may not be feeding on rodents when they are small, they would soon be switching to a mammalian-rich diet,” Sunagar explained. “The increased potency of neonate venoms against mammals and lizards is, perhaps, because of the minute amount of venom they produce. They would still need to kill prey and deter predators with this limited venom.”
Implications for treatment
The study also looked at how commercially available antivenoms worked against the venom from these two snake species at different stages of development. In vitro (outside of living targets), the antivenoms recognised the venom of younger and adult snakes, but it was poor at neutralising the venom when injected in mice.
The study acknowledges that it is not clear if this lack of antivenom efficacy stems from the changes in venom that were observed at various stages of development. It could also stem from geographic variation in venom, given that the effect of antivenom is already known to vary across regions.
All antivenoms in India use venoms sourced from the coastal regions of Tamil Nadu. They are known to act poorly against venoms from several spectacled cobra populations. Antivenoms to treat Russell’s viper bites, too, have poor neutralisation potency against viper venom in some regions while neutralising the lethal effects of venom from other viper populations.
Earlier this year, Sunagar’s lab, in collaboration with Scripps Research in California, published a study describing the development of an antibody that neutralises toxins in the venoms of a number of snake species (HT, February 27, 2024). A universal antivenom based on that antibody, however, remains a long way away.
The new study stressed the importance of developing region-specific antivenoms and also makes a case for assessing the efficacy of antivenoms against venom at different stages of the development of snakes. A question to ponder is: Will there be any difference if the venom of young snakes is added to the antivenom mix?
“Biogeographic venom variation stems from ecological differences, e.g., prey, predator types, etc. Whether we should worry about ontogenetic differences in venoms, and whether we should include the venoms of younger snakes for antivenom manufacture, will depend on how many people get bitten by younger snakes,” Sunagar said.