The endangered golden poison arrow frog Phyllobates terribilis lives in the rain forests along the northern Pacific coast of Colombia. Its skin contains batrachotoxin, a lethal poison that prevents nerve and muscle cells from firing properly. That substance makes muscles contract and leads to heart failure or fibrillation. Each frog contains about a milligram of the toxin, enough to kill 10,000 mice, 20 people, or two elephants. A whale might survive ingesting the frog, but anything else that eats this frog dies.

Batrachotoxin works by activating proteins called voltage gated sodium ion channels. These are specialized proteins located within cell membranes that respond to changes in voltage across the cell membrane by opening up a central pore. This allows positively charged sodium ions to flow into the cell before the pore quickly closes up again. This helps the cell reset the voltage differential across the membrane, allowing future electrical signals and messages to be propagated along the length of neurons.

The frog toxin binds to the inner pore of the channel and props it open, allowing sodium ions to continuously flood into the cell. The cell never resets, so any signal it transmits will be its last.

Part of the way we know about how these channels work is by using batrachotoxin and similar toxins to study them. But “the utility of this natural product as a voltage gated sodium ion channel activator has led to a substantial depletion in the world supply,” according to organic chemists from Stanford writing in this week’s Science. Since the frogs are endangered, collection of the toxin from them is “restricted.” Batrachotoxin is also made by three birds in Papua New Guinea and some beetles, so there are some limited alternative supplies. But being organic chemists, these scientists decided to just whip some up.

A 24 step (!) synthesis yielded two milligrams of batrachotoxin, or two frogs' worth. If it can be scaled up, then collection in the wild will become irrelevant.

But the synthesis also revealed some interesting biology. That's because, like many chemical syntheses, the protocol generated not only batrachotoxin, (-)-BTX, but also its evil twin, (+)-BTX.

Many carbon-based molecules—i.e. most biologically relevant molecules—have a handedness, determined by the way the various other atoms they contain are arranged around the carbon. Molecules can have the same constituent atoms but be mirror images of each other, just like your right and left hands. They are the same but are not superimposable one atop the other. This seemingly small difference matters. All life on Earth, for some as yet undiscovered evolutionary reason, uses exclusively left-handed amino acids to make proteins and right-handed nucleic acids for their genetic material.

As evil twins are wont to do, batrachotoxin’s synthetic enantiomer completely foils the natural product. Batrachotoxin holds voltage gated sodium channels open and lets sodium ions stream into the cell like a bouncer that doesn’t make every single girl in the bachelorette party pay. But its mirror image holds the channel closed and does not let sodium in, even after a change in voltage. It's like the strict bouncer who could not be less interested that your friends are inside and you’re supposed to meet them, you promise.

Not surprisingly, keeping the ion channels shut would be just as fatal as permanently propping them open. The only animals that can tolerate batrachotoxin are those who make it; they have specialized sodium channels in their cells. But perhaps tipping a blow-gun dart with synthetic (+)-BTX would kill them.

Science, 2016. DOI: 10.1126/science.aag2981 (About DOIs).