Butch found a clue when he checked one of his traps and found a common garter snake devouring a newt. Overcoming his mild phobia of snakes, he collected some and found that they resisted amounts of tetrodotoxin that would kill far larger animals.

While Butch focused on the newts, his son, Edmund Brodie III, became fascinated by the snakes. Together, they showed that throughout western America, places with mildly toxic newts also had mildly resistant snakes. Meanwhile, hotspots with unusually lethal newts also had snakes that withstood staggering levels of tetrodotoxin. The two species were locked in a beautifully coordinated arms race of toxicity and resistance.

But what set off the starting pistol? How did the first snakes survive their encounters with the first newts? To find out, the team needed to understand how the snakes came to shrug off the poison.

Tetrodotoxin kills by corking molecular pores on the surface of nerve and muscle cells, which act as channels for sodium ions. If these ions can’t traverse the channels, muscles can’t contract and nerves can’t fire. Paralysis ensues, breathing ceases, and death follows. In 2005, the Brodies found that garter snakes avoid this fate by changing the shape of their sodium channels, so that tetrodotoxin no longer plugs them.

At the time, they only focused on one sodium channel called 1.4, which is found in muscles. The snakes have eight others. Three are unknown. Another three are irrelevant—they’re found only in the central nervous system, which is protected from tetrodotoxin by an impermeable barrier. The final two—1.6 and 1.7—are more vulnerable: They’re found in peripheral nerves that connect the brain and spine to limbs and other organs.

When Joel McGlothlin started working with the Brodies, he showed that 1.6 and 1.7 are also resistant to tetrodotoxin, having acquired some of the very same mutations that protect 1.4. But in 1.4, those mutations are found in some snakes but not others, which makes some populations a thousand times more resistant to newts than their peers. By contrast, the resistance mutations in 1.6 and 1.7 showed up in all garter snakes. They looked like much older innovations.

To find out when they arose, McGlothlin, now head of his own lab at Virginia Tech, sequenced the genes that encode the sodium channels of 78 species of snake. And to his surprise, he found that one mutation, which makes channel 1.7 thirty times more resistant to tetrodotoxin, is at least 170 million years old. That makes it older than both newts (which arose between 40 to 50 million years ago) and snakes (which arose 140 million years ago). It originated in lizards—the group from which snakes arose.

“We think this evolutionary change happened for some other reason,” says McGlothlin. It could have altered how quickly or readily sodium ions pass through the channel, and thus how responsive or excitable an animal’s nerves are. And by total coincidence, it also made snakes partially pre-resistant to tetrodotoxin, right from their very beginnings. “Snakes were predisposed to getting into these co-evolutionary arms races,” says McGlothlin. “They had a baseline resistance, so if they ate something with a little bit of tetrodotoxin, they survived.”