Complex venom varieties make snakebites hard to treat: study

An evolutionary “arms race” with their prey has left rattlesnakes with an ever-shifting arsenal of venom varieties, which may be one reason why snakebites are so hard to treat, a new study has found.

Drew Schield, lead author of the study published Monday in Nature Ecology and Evolution, said understanding the constantly shifting nature of snake venom could help scientists design more effective treatments.

“We found these rattlesnakes had a more diverse venom repertoire, more genetic tools in the toolkit, than their venom composition alone might suggest,” Schield, a postdoctoral fellow in Ecology and Evolutionary Biology at the University of Colorado Boulder, said in a statement.

Serious snakebites are treated with antivenoms, which neutralize the toxins injected by the bite. They are purified versions of the compounds that prey animals generate to protect themselves against snakebite.

Antivenoms are made by injecting relatively large mammals — like horses or goats — with small amounts of venom milked from snakes, according to the Smithsonian Institute.

That causes the mammals to produce defensive antibodies to neutralize the venom, which can then be extracted, purified and injected into snakebite victims. 

Unfortunately, these are the very sorts of natural defenses that rattlesnakes’ venom evolved to evade.

In order to successfully hunt a wide variety of prey — each with its own actively evolving defenses — the snakes keep a broad genetic “toolkit” of venom varieties, which allows them to constantly adapt to new conditions or habitats, the study released Monday found.

That means there’s no guarantee that two rattlesnake bites contain the same deadly proteins.

“Venom composition within the same species but in different geographic regions might be totally different,” Schield said.

Researchers attribute this to a long-running evolutionary strategy. For millions of years, venomous snakes have kept copies of genes that allow them to produce venom varieties that they aren’t currently using.

That packrat strategy has helped keep the scaly predators out of an evolutionary dead end, researchers found.

That contradicts how scientists had long assumed snake venom had evolved: by a process of increasing specialization, in which old and unused venom genes were pared away as their prey — largely rodents, birds and other reptiles — developed resistance.

Instead, the snakes kept those old variants in reserve, coiled in their genome for when they would be useful again.

“It turns out that the arms-race between snakes and prey ends up favoring the constant re-shuffling of venom variants,” co-author Todd Castoe of the University of Arlington said in a statement.

Schield said that by understanding the broad range of possible toxins hidden in venomous snake genomes, scientists will be better able to develop effective treatments.