Dr Des Corrigan wonders what we can learn from animals treating themselves for injuries
Last year, I was intrigued by a story about an orangutan in Sumatra that had used a plant paste to heal a facial wound. This story did not quite go viral, but it certainly caught a fair bit of media attention as it was followed up by articles in outlets such as The Conversation and the Smithsonian Magazine describing what is meant by the term ‘Zoopharmacognosy’ — in other words, the study of medicinal plants used deliberately by animals to cure themselves.
Now, this is not a new term, dating back as it does to 1993, nor is the underlying concept new either, as Aristotle and Pliny among others highlighted the benefits to humans of observing what plants are chosen by animals when they are ill. It has also been suggested that both khat and coffee were discovered after changes in the behaviour of goats who had consumed these stimulant-containing plants was noticed by herdsmen. While that was millennia ago, those at the forefront of studies in this area believe that new life-saving drugs can yet be discovered by careful observation of animal behaviour.
The research that started the current wave of interest appeared in Nature Scientific Reports last year. It reported on a male Sumatran orangutan with a facial wound who was seen by the researchers to selectively chew the leaves of a liana (a woody vine). The animal first applied the juice to the wound and then covered it with the chewed leaves. Three weeks later, the facial wound was seen to be fully healed in what the authors claimed to be the first systematic documentation of apparently active wound treatment with a biologically active plant in great apes.
The plant in question was identified as Fibraurea tinctoria and that last part of its Latin name indicates that this plant has a history of use as a dye (yellow in colour). According to a 2008 paper in Bioorganic and Medicinal Chemistry, it is widely used in folk medicine in China and South-East Asia in the treatment of dysentery and for analgesic, antipyretic, diuretic and antimalarial (especially in Vietnam) effects. The plant was found to contain protoberberine alkaloids and furano-diterpene derivatives, known inevitably as fibraruretins. Two of these had significant anti-inflammatory activity in the carrageenan-mouse paw oedema test, whereas five others were potent nitrous oxide production inhibiters. In addition, both the alkaloids and the terpenoids are known to be antibacterial, which would also be relevant to wound healing.
The first fully documented case of an animal self-medicating with a plant involved chimpanzees in western Tanzania, who were observed consuming the bitter juice from the pith of a plant called Vernonia in order to expel worm infestations. The chimps only used this plant at times of peak worm infestation during the rainy season when they had to actively seek out the plant due to its uneven distribution. Scientific studies have shown that the plant contains bitter sesquiterpene lactones with antibacterial activity. More pertinently it has been shown to have anthelminthic, anti-malarial and tumour-growth inhibitory effects in the lab.
Not all of the research involves non-human primates, as pointed out in a 2022 Planta Medica review of 14 case studies of plant medicines inspired by observation of animals as diverse as llamas, reindeer and porcupines. In the latter case, observation by a local traditional healer of a porcupine in Tanzania eating the roots of particular plant led to the successful use of plant by that healer to treat STIs as secondary infections in AIDS patients. There is little information on this plant, but a related species has been shown to produce an antibacterial essential oil, according to a 2024 paper in Molecules.
There is another aspect to the plant — animal interaction as described in a June 2024 article in the Smithsonian Magazine. In it, the author describes how various animals consume a poisonous diet in order to defend themselves against predators. Among the classical examples of this are the Monarch butterflies, the caterpillars of which feed on Milkweed plants that are rich in digoxin-like cardiac glycosides. The adult butterflies store the toxic glycosides to deter predators and their characteristic black and orange colouring is a signal of this toxicity. Unfortunately for the butterfly, one species of predatory mouse and a bird have evolved mutations that allow them tolerate the toxins when they eat the insects.
The other classical example is of course the poisonous tree frogs from South America that are also highly coloured as a warning sign to predators. These frogs obtain their toxins from ants, beetles and termites that constitute their diet. Some species contain an alkaloid called Epibatidine that is 200 times more potent than morphine, although the lethal and effective doses are far too close for comfort. One derivative (ABT-594) or Tebanicline did get as far as Phase 2 clinical trials, but dangerous GIT effects apparently led to it being dropped from further study. However, this does show the potential of zoopharmacognosy in pointing towards new drugs with novel mechanisms of action, because the frog-derived alkaloids were found to exert analgesic effects through their role as nicotinic acetylcholine receptor agonists.
The other classical example is of course the poisonous
tree frogs from South America
Another species of South American frog contains batrachotoxin, as does the pitohui bird from the New Guinea rainforest. This is a steroidal alkaloid that is 250 times more toxic than strychnine and has both neurotoxic and cardiotoxic effects. Initially, it was believed that the toxin originated in beetles upon which the frogs fed, until it was realised that the beetles in question could not synthesise the steroid nucleus, meaning that some as-yet unidentified organism further down the food chain was the source of the toxin. As a number of authors have pointed out, most natural product research has been concentrated on the half-million or so plant species that are estimated to exist on our planet, whereas the chemistry of the several million species of insects is largely unexplored.
A 2022 review in the American Journal of Primatology notes that self-medication is best documented in African primates, but points out that the great diversity of both plants and animals in the tropics and elsewhere suggests that many medicinal species might still be discovered by studying animal self-medication and protection. I have the strong feeling that a huge proportion of drug discovery budgets are nowadays focused on large molecules, but I remain convinced that there is still potential in clinical practice for small molecules, be they synthetic or natural. So, saving the plants and the animals that could save lives continues to make sense.
Dr Des Corrigan, Best Contribution in Pharmacy Award (winner), GSK Medical Media Awards 2014, is an Adjunct Associate Professor at the School of Pharmacy and Pharmaceutical Sciences at TCD where he was previously Director and won the Lifetime Achievement Award at the 2009 Pharmacist Awards. He was chair of the Government’s National Advisory Committee on Drugs from 2000 to 2011, having previously chaired the Scientific and Risk Assessment Committees at the EU’s Drugs Agency in Lisbon. He chaired the Advisory Subcommittee on Herbal Medicines and was a member of the Advisory Committee on Human Medicines at the HPRA from 2007 to 2024. He has been a National Expert on Committee 13B (Phytochemistry) at the European Pharmacopoeia in Strasbourg and served on the editorial boards of a number of scientific journals on herbal medicine.
