January 30, 20256 min readVenomous Caterpillars Are Expanding Their Range Due to WarmingThese caterpillars carry a toxic chemical cocktail and Inquisition-like delivery implements and their geographic range is expandingBy Ivan Amato edited by Gary StixThe puss caterpillar is the venomous larval form of the southern flannel moth (Megalopyge opercularis). Its hairs conceal highly venomous spines. jkntexascc/Alamy Stock Photo.Assasinations in ancient Rome, miscarriages in pregnant horses in Australia, sudden onset of arthritis in rubber tappers in Brazil: Are you ready for the common thread among these incidents? Its venomous caterpillars. And many of these larvae of the insect order Lepidoptera, along with the moths and butterflies they become, are creeping and fluttering your way at the speed of climate change. One estimate counts more than 3,600 venomous Lepidoptera species out there.I am studying venomous caterpillars because they are the most exciting area Ive ever come across, says Andrew Walker of the University of Queensland in Australia, who authored a recent paper in the Annual Review of Entomology that encapsulates much of what he and other venom researchers now know about the evolution, molecular composition and pathological mechanisms of Lepidoptera venom. This is kind of like unearthing an unexpected treasure, he says, noting how little attention caterpillars have received by the venom research community so far and how much new insight there is to unearth.Among the caterpillars Walker has studied are puss, or asp, caterpillars, whose stings can be excruciating. Some have variously described the sensation as the worst pain ... ever experienced and akin to being hit with a baseball bat or walking on hot coals.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.First, lets ease your just-triggered Lepidoptera anxiety a little. The vast majority of human encounters with venomous caterpillars result in mild and transient rashes and skin irritations that go away in a day or a few weeks at most. Such encounters, which can easily go unnoticed because of a delay in the affected persons immunological response, occur with the venomous caterpillars and moths that sport tufts of minuscule whiskers, called setae, on their surface. With a microscope, these setae look like harpoons, and theyre filled with cocktails of venom proteins that are to scientists like Walker what light is to moths. The whiskers shed onto and into your skin if you touch a setae-bearing caterpillar or moth. They can also come into contact with your body when theyre carried on a breeze like windblown pollen grains.Encounters in the more wince-and-yell category generally involve run-ins with caterpillars that wield larger and tougher venom-injecting spines. These, too, generally resolve quickly or might require standard allergy and dermatitis treatments such as antihistamines and cortisone cream. But some species can cause lethal hemorrhagic reactions. This has especially been the case with Lonomia obliqua caterpillars in Brazil. In a 2021 paper in the journal Toxins, caterpillar "accidents" in Brazil attributed to Lonomia obliqua between 2007 and 2017 amounted to 42,264 recorded cases with 248 considered severe, five of which "evolved to deaths."Those numbers help explain why Brazils So Paulobased Butantan Institute, which produces a portfolio of vaccines, antitoxins and antivenom medicines that help the immune system counter various threats characteristic of the region, got into the business of supplying Lonomia antivenom.To Walker, research into any venomous animal group promises a trove of molecular discoveries. Snakes, spiders, scorpions and cone snails have been among the natural celebrities that have garnered the most research attention so far. But it is the neglected venomous examples among the mostly nonvenomous insects that comprise the more than 150,000 species of Lepidoptera that Walker finds most alluring right now.They have never been studied using modern molecular methods, Walker points out. Lepidopteran venoms represent a barely explored opportunity for scientific inquiry and biodiscovery, he wrote in his Annual Review of Entomology article.Among Walkers favorite discoveries are those that relate to structural details of the mini proteins, or peptides, that he and others are identifying in caterpillar venoms. One example is a knotlike molecular motif embodied by many of these toxins that researchers have seen before in spider and scorpion venoms. That makes them supertough because they are resistant to proteases that normally break proteins down, and so this makes these peptide toxins inherently druglike, he says. Theres a chance many of these could become lead compounds toward the development of therapeutics, Walker adds. As an example, he notes a veterinary treatment for barbers pole worm infections, a sometimes-lethal parasitic condition that affects sheep and other ruminants in Australia.This line of research can have an impact on public health. Jan Tytgat, a toxicologist and pharmacologist at KU Leuven in Belgium, has been investigating an emerging Lepidoptera-based public health hazard due to a climate-change-exacerbated expansion of the range of the oak processionary caterpillar (Thaumetopoea processionea). The venomous caterpillars of this species of moth thrive in voracious groups. Using a bevy of techniques to analyze venom genes and proteins, he and his colleagues at KU Leuven recently identified 171 toxin components in 19 molecular categories. Among these components were small peptides, enzymes, enzyme inhibitors and molecules associated with chitin, the hard biomaterial of the caterpillars setae.Our belief is that this dataset will play a key role in paving the way for the development of a targeted medicine to treat envenomation effectively, the researchers recently wrote in the journal Cellular and Molecular Life Sciences. Tytgat says he is most excited about progress toward identifying the molecular culprit causing the allergy and inflammation responses. A leading candidate, he notes, is a protein toxin in the caterpillars venom cocktail that targets TRPV1, the same cell-receptor protein that is activated by capsaicin, the spicey chemical in foods like hot peppers. Such findings, Tytgat says, can guide development of new topical medicines for treating caterpillar encounters, among other medical products.Uncovering the detailed molecular narrative of caterpillars, grounded in the creatures venoms and the pathologic responses they elicit, is becoming more pressing as these larvaes range shifts and expands, says Andrea Battisti, a forest entomologist at the University of Padua in Italy. For example, he notes, the installation of electricity and lighting in some buildings in Nepal that lacked those amenities has attracted venomous moths.When they fly inside and against the walls and windows, their setae disperse on the floor and furniture, where people can end up touching [these whiskers] and then their eyes, Battisti says. That has led to eye infections that sometimes have progressed to blindness. In his lab now, he is hosting a student from a medical school in Kathmandu who is investigating this emerging risk from venomous caterpillars with an eye on how to counter it.We think that more and more people are likely to encounter venomous caterpillars, says Battisti, who notes that caterpillar researchers often develop allergies that make their work more challenging. Our take-home message is that we all need to be better informed so that we are primed to be cautious when we see caterpillars and to find better ways of treating caterpillar encounters.Battisti, who collaborates with Walker, says the key questions that drive his research relate to what basic mechanisms allow the caterpillar venom proteins to elicit immune responses and how these processes evolved.If we can understand why and how such a system has evolved, we can move on to finding better solutions for protection of people, pets and other animals, such as horses, which can inadvertently ingest venomous caterpillars when the larvae end up in the hay the ungulates eat, Battisti says. He adds that horse-caterpillar encounters have resulted in a costly condition known as equine amnionitis and fetal loss syndrome.Humans relationship with venomous caterpillars has a history that predates modern science. The natural threat of the caterpillars has shown up in cultural expressions as a symbolic portent of human mortality, Battisti points out. He knows about one of these because of his daughter, who is an art historian. He recounts how she excitedly sent him a photograph of the 1618 painting Et in Arcadia Ego, by the Italian baroque painter Giovanni Francesco Barbieri, better known as Guercino, from the National Gallery of Ancient Art in Rome. The allegorical painting is routinely interpreted as a message that death is always just around the corner. Near the base of a prominent skull in the painting, Battista said that to his eye it appearsThaumetopoea caterpillarthe setae of which were allegedly mixed into lethal drinks by ancient Roman assassins.