The poison behind the killing of Alexei Navalny
The “tree frog toxin” has less to do with amphibians than the Kremlin’s secret assassination program.
Last month, five independent laboratories in Britain, France, Germany, the Netherlands and Sweden published analyses of biosamples taken from the late Russian opposition leader Alexey Navalny. The outspoken critic of President Vladimir Putin died in prison two years ago in Russia’s far north, aged 47. Officials stated that his death was caused by natural causes. Navalny’s team members said they were able to collect his tissues and pass them on for examination.
You may have seen headlines announcing that all five labs discovered a lethal tree frog toxin. Given that European governments are suggesting Putin’s assassins were responsible for Navalny’s death, that might sound bizarre. But despite news media reporting, one shouldn’t be imagining Russian agents carrying hundreds of slimy amphibians from Ecuador to Siberia—the story has very little to do with frogs, much more with very well-equipped Russian labs and a strongman leader.
Some 50 years ago, a scientist at the National Institutes of Health outside Washington named John Daly collected dozens of specimens from a frog in the cloud forest near the town of Santa Isabel in Ecuador. He injected extracts from the frog’s skin excretions into lab mice, looking for unusual reactions. One sample, labelled 208/210, produced a particularly striking response. Daly recorded “agitation, labored breathing, rigid, strongly elevated tail, running convulsions, rolling convulsions, arching back, extending hind feet…cannot locomote.”
He did all that for a reason. The amphibians he was studying are called dart frogs because Indigenous people used to rub darts against the skin of some frog species to use for hunting small animals. Today, scientists know of hundreds of active molecules present on the skin of various species of dart tree frogs, including some that could have potential as medicines.
Back in the ’70s, Daly suspected that the samples he had taken contained a previously unknown substance with strong painkilling properties. He named it epibatidine and went on to study it further for possible practical use.
But he soon ran into an obstacle. Several frogs were required to yield a sufficient amount of epibatidine to achieve any noticeable effect on mice; hundreds would be needed to act on a human. More often than not, wild-caught frog skin didn’t yield much toxin at all.
That’s because, as we’ve since learned, dart frogs derive their poison through a diet of ants, centipedes and mites. Specialized glands concentrate the toxic alkaloids and secrete them onto the skin surface.
Captive-bred dart frogs denied their normal diet don’t produce the toxins. Even in the wild, as Daly documented, frogs taken from a banana plantation that probably feasted on fruit flies produced no toxin at all.
So epibatidine could be studied further only if scientists took a next step: lab synthesis. Since then, there’s been no need to extract the toxin from frogs. That’s what makes last month’s headlines seem strange. We don’t call aspirin “a chemical from willow bark” or atropine used to dilate your pupils a “deadly nightshade toxin.” Once synthesis has been mastered, you forget about the substance’s origins and focus on its use.
Epibatidine proved to be 200 times more active than morphine as a potential pain killer. But it also proved just too toxic; no one was able to develop it for practical use.
Well, no one, it seems, except for chemists working at the Russian State Research Institute for Organic Chemistry and Technology in Moscow. Twelve years ago, they published a paper on their own lab synthesis of epibatidine. Although it describes the toxin’s painkilling potential, that idea has long ago been abandoned by mainstream science. So it’s quite likely their real interest was in a different property, that of a chemical weapon.
Here’s why experts think that’s probably the case: The same institute was responsible for the creation of Novichok, a nerve agent used in the failed 2018 assassination attempt in the United Kingdom targeting Sergei Skripal, a spy who defected from Russia, but took the life of a bystander named Dawn Sturgess instead. A UK court proved Russian special forces were behind the operation, for which Putin’s direct order was named as a cause.
When Navalny was first poisoned in 2020, he was taken for treatment to Germany, where chemists were able to determine he was also attacked with Novichok. The substance is known to have been involved in several more botched assassination attempts.
I called the doctor who treated Alexei Navalny in Moscow back then. His name is Alexander Polupan. He found it strange at the time that he wasn’t allowed to wear his own scrubs while caring for Navalny; anyone in close proximity to the opposition leader was asked to wear a disposable uniform and gloves, a sign the intelligence services probably knew a toxin was present and that it was highly dangerous to anyone in its vicinity.
That’s why Navalny’s second, fatal poisoning may have been carried out with a different toxin. Unlike Novichok, epibatidine has no known antidote and doesn’t harm bystanders.
So, again: This story has very little to do with frogs and more with the moral choices Russian scientists make when they work for the state.
Ilya Kolmanovsky is host of a science podcast named The Naked Mole Rat, where he covers research into synthetic biology and evolution.
Specialists of this caliber are extremely rare — there can’t be more than a few of them. Their names should be public knowledge.