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These birds carry a toxin deadlier than cyanide

These birds carry a toxin deadlier than cyanide

New Guinea is home to some of the world's most toxic birds. Why they contain poison, and how they withstand the it is still a source of scientific mystery. The variable pitohui, a poisonous bird, captured in mist net on the outskirts of Wanang Village in Papua New Guinea in 2018. Photographs By Knud Jønsson
In the summer of 1989, Jack Dumbacher was a fresh-faced ornithologist-in-training on his maiden expedition to the lush rainforests of Papua New Guinea. One sticky afternoon, he noticed an unusual bird with gaudy black-and-orange feathers entangled in his mist nets. But as Dumbacher tried to set it free, the hooded pitohui scratched him.
'They're jay-sized birds with needle-sharp claws and bills,' says Dumbacher, who instinctively put the cut to his lips. 'My mouth started to tingle and burn, and then went numb, lasting until the night.'
When Dumbacher consulted his local guides, they nodded knowingly, telling him how villagers would avoid the 'rubbish birds,' eating them only if they were 'skinned and specially prepared.' Curiosity piqued, the then-graduate student at the University of Chicago spent the next year collecting pitohui samples and searching for a chemist back home who could pinpoint the source of the peculiar sensations.
In 1992, Dumbacher and his collaborators announced their astonishing findings: hooded pitohuis carry batrachotoxin. The toxin is deadlier than cyanide and is among the most lethal substances in the animal kingdom. It's the same substance found in certain poison dart frogs halfway round the world.
Since then, at least a dozen other avian species, out of more than 10,500 known to science, have been identified as toxic. Some members of this select group—such as the European quail, North American ruffed grouse, and European hoopoes —are found outside of New Guinea and contain different toxins. The majority, however, are batrachotoxin-carrying and endemic to the world's second largest island, including at least five other pitohui species and the blue-capped ifrit.
But 35 years on from Dumbacher's serendipitous discovery, much remains a mystery about New Guinea's poisonous birds. 'There's a ton that we don't know—from the ecology of the birds to how they use batrachotoxin for defense and where they get it from,' says Dumbacher, now California Academy of Sciences' curator of birds and mammals.
He last visited the island in 2011, and another team of scientists—led by ecologist Knud Jønsson from the Swedish Museum of Natural History and evolutionary and community biologist Kasun Bodawatta at the University of Copenhagen—are continuing Dumbacher's research. Already, they've made inroads, identifying two new toxic bird species in 2023, the first discovery in nearly two decades. They plan to visit Papua New Guinea annually until 2028.
They hope to answer a key question: where does the toxin—believed to protect the birds from predators and parasites—come from?
One theory for the origin of this poison is the birds' diet.
'It's been put forth that they eat these Choresine beetles and that's how they get their toxin,' says Jønsson. 'But in reality, we don't know.'
Dumbacher—who, in 2004, was the first to describe how batrachotoxin is present in both birds and beetles—doesn't believe the toxin originates in the tiny rice-sized insects.
'Most of the information suggests that beetles can't produce such steroidal alkaloids,' he says. 'So it's very possible that the beetles are getting it from some other source like soil mites or even a plant.'
To track batrachotoxin's origin, the researchers plan to collect poisonous birds and compare their stomach contents to insects caught in nearby traps. 'The idea is to try and home in on potential prey items that have the toxin,' explains Jønsson. 'It's very much looking for a needle in a haystack, but that's the very first step that we can take.'
They've also teamed up with Christine Beemelmanns, a chemist at Germany's Saarland University to pinpoint batrachotoxin and molecularly similar toxins in the samples already collected.
Tests have shown that poisonous birds contain a mixture of toxic derivatives—Beemelmanns' lab has identified six so far—which can vary in concentration between individuals and species. The hooded pitohui is one of several poisonous birds that have been documented in Papua New Guinea. While poisonous birds have been documented in North America and Europe, the majority known to science are found in the this South Pacific region. Photographs By Knud Jønsson How do birds remain immune?
Another enduring mystery is how the birds protect themselves from the deadly toxin they carry.
Batrachotoxin binds to sodium ion channels in nerve, muscle, and heart cells, resulting in numbness, convulsions, paralysis, and even death. 'It sits on these channels and keeps them open, so the nerves just go on twitching,' says Jønsson.
Poisonous birds contain far less toxin than the golden poison frog, which carries enough batrachotoxin to kill 10 grown men. The hooded pitohui—the most toxic avian species—isn't lethal when handled or consumed.
The longstanding theory that explains how the birds 'aren't killing themselves' is that they, like poison dart frogs, contain mutations in their sodium channels, which prevents the toxin from binding, says Daniel Minor, a biophysicist at the University of California, San Francisco, who's not involved with Jønsson and Bodawatta's upcoming research expeditions.
The same trait is found in the fugu pufferfish, blue-ringed octopus, and other poisonous animals that remain impervious to the toxins they carry.
Indeed, when Jønsson and his collaborators compared the genomes of six toxic bird species with their non-toxic cousins within the same families, they discovered that poisonous birds contained multiple mutations in a gene encoding a specific sodium channel.
However, when Minor's team conducted electrophysiological tests on genes cloned from the southern variable pitohui in a separate set of experiments, they 'were distraught' to discover that the sodium channels remained sensitive to batrachotoxin—despite their mutations.
Minor now believes that the birds' resistance lies in an as-yet-unidentified protein which acts as a 'toxin sponge,' binding to batrachotoxin and sequestering it. He and his colleagues' work on saxitoxin, another protein that binds to sodium channels, provided this insight.
'Our lab showed that saxiphilin, a protein found naturally in poison dart frogs, can scoop in and bind to saxitoxin with high affinity,' he explains. 'So maybe it's the same for batrachotoxin.'
Jønsson and Bodawatta think the two mechanisms might be complementary. 'Birds, anyway, need to transport batrachotoxin from the gut to the skin,' says Bodawatta. 'So they must have a transporter protein that facilitates this.' Are there more?
Scientists' are keen to know whether more toxic birds exist.
Jønsson thinks it's highly likely. "New Guinea's poisonous birds belong to the Corvides super-family of birds, which comprise roughly 700 species worldwide,' he says. New Guinea is home to 140 of them, and his team has so far studied just a fifth of them.
Starting this November, his team will collect 'as many Corvides samples as possible' from different parts of the island and screen them for batrachotoxin. They also plan to sequence as least one individual per species to identify sodium channel mutations.
A more comprehensive genomic dataset will also allow scientists to identify possible toxin sponge proteins, adds Bodawatta.
More broadly, the researchers want to study 'the super cool and crazy convergent evolution' that's allowed for this special toxin resistance in both frogs and birds, as well as unrelated avian species within New Guinea and elsewhere in the world, Bodawatta says.
'Understanding convergent adaptations by natural selection is a central goal in evolutionary biology,' adds Jønsson.
The more scientists learn about what exists, the more questions they'll be able to ask about why they do.
'Maybe in two to three years, we'll have some new insights to share,' says Bodawatta. 'This is just the beginning.'

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