The deadliest mushroom, the death cap, is still concocting new poisons

Death cap mushrooms are back in the news. Amanita phalloides has once again been linked to poisonings, this time lacing beef Wellingtons served at a family meal in Leongatha, Australia, which resulted in three fatalities. Such incidents inevitably reignite public fear surrounding this deadly mushroom – and mushrooms in general. The fact that death caps look so innocuous only adds to their malevolent mystique. With their pale yellow cap and white gills, they can be mistaken for several edible fungi – which might explain why they are responsible for almost all mushroom-related deaths. Just half of one is enough to kill you.

Headline-grabbing as it may be, the death cap is only one of many remarkable fungi. More closely related to animals than to plants, they form an entire kingdom of life, with an estimated 5 million species. Although just 5 per cent have been described formally, those we know of include some that are truly surreal. Cordyceps mushrooms (Ophiocordyceps unilateralis), for example, erupt from the bodies of ants that have been infected and zombified, while stinkhorns (Phallus impudicus) secrete a foul-smelling slime that mimics rotting flesh, and dead man’s fingers (Xylaria polymorpha) emerge from forest floors as eerie black appendages.

In comparison, death caps appear nondescript. Nevertheless, their toxicity makes them the subject of active scientific research. And the results are fascinating: recent studies reveal a rapidly evolving species, generating novel toxins, thriving in new environments and spreading across the globe. These insights aren’t just reshaping our understanding of the death cap, but of the entire fungal kingdom. What’s more, they have the potential to shift public perceptions of fungi from fear to informed appreciation.

History is marked by a series of suspected death cap poisonings. The Roman Emperor Claudius may have been killed by a dish containing them in AD 54, possibly orchestrated by his wife Agrippina the Younger. The death of Pope Clement VII in 1534 has also been linked to death cap poisoning. Likewise, that of the renowned composer Johann Schobert. These are just a few from a catalogue of fatalities. Even when the evidence is unclear, A. phalloides is often the prime suspect, demonstrating how its deadly reputation has persisted over time.

Today, the death cap is responsible for approximately 90 per cent of mushroom-related deaths. “As little as 0.1 milligrams per kilogram of body weight can be fatal,” says James Coulson, a clinical pharmacologist and toxicologist at Cardiff University in the UK. “Survival depends on the amount ingested… and the physiological reserve of the patient.”

How death cap mushrooms kill

At least we now know how A. phalloides does its damage. Its most lethal toxin, alpha-amanitin, acts by blocking the enzyme RNA polymerase II, which is needed for transcription, a step in the process of protein production that is essential for the survival of almost all cells. If death cap mushrooms are ingested, alpha-amanitin is absorbed through the intestines into the bloodstream and travels to the liver. From there, it hides out in the gall bladder, a small organ nearby that contains the digestive fluid bile. The person who has been poisoned then begins to feel better and may decide to eat again. But that is when their problems multiply. When food enters the digestive system, the gall bladder releases bile into the intestines and, with it, the toxin. Alpha-amanitin is reabsorbed into the bloodstream and begins circulating through the body again. Each cycle like this causes further organ damage, especially of the liver, and can ultimately be fatal. “Apparent improvement is often followed by features of acute liver failure, hypoglycaemia, coma and clotting disorders,” says Coulson.

Why the death cap needs to be so deadly is more of a mystery. Solving it isn’t helped by the fact that it is extremely difficult to study. “The challenge in working with A. phalloides is that we cannot grow them… so a lot of genetic tools are off the table,” says Yen-Wen Wang at Yale University. We do know that alpha-amanitin is a secondary metabolite, meaning it isn’t essential for the fungus’s survival. However, producing secondary metabolites requires energy and resources, so the toxin almost certainly confers some advantage; otherwise, it would probably have been eliminated through evolutionary processes.

Some scientists think that poisonous fungi evolved toxins as a form of chemical defence against being eaten before the mushrooms mature and release their spores. If so, then at least for death caps, humans are collateral damage: symptoms take many hours or even days to appear, which isn’t quick enough to prevent the mushrooms from being consumed. Instead, alpha-amanitin probably serves the more immediate purpose of deterring mushroom-munching insects.

A. phalloides may also use poisons as a form of chemical defence underground. It is an ectomycorrhizal fungus, meaning it forms a symbiotic relationship with tree roots, to which it provides nutrients such as nitrogen and phosphorus, while the tree supplies carbohydrates. Such partnerships have played an important role in the success of many fungi – they also help explain why many are difficult to cultivate under laboratory conditions. So, alpha-amanitin may have evolved to give A. phalloides a competitive advantage in colonising and maintaining access to tree roots by suppressing rival fungi and killing soil microbes and invertebrates that could cause it harm.

Alpha-amanitin is just one of a cocktail of toxins produced by death caps, and recent research has revealed that these poisons are still evolving – right now, and rapidly. This makes A. phalloides a model for studying adaptation and genomic innovation in fungi. “It informs us how toxins evolve and the ecological roles of these toxins,” says Wang.

The first clues of this came when people started finding death cap mushrooms in new and diverse habitats on every continent except Antarctica. At first, researchers thought they might have been wrong to assume the fungus was native to Europe. But this idea was proved incorrect in 2009 when Anne Pringle, now at the University of Wisconsin-Madison, and her colleagues used historical records and DNA analysis to show that A. phalloides had been brought to North America from Europe on the roots of imported trees and became established once these were planted. What is particularly striking is that, as the death cap has spread from its native Europe to the US and the rest of the world, it is sometimes found associating with trees it would never have encountered in its original habitat – a sign of adaptation.

This is where the toxins come in. In 2023, a group of mycologists, including Pringle and Wang, published a paper showing that each mushroom carries a slightly different mix of toxin genes. Crucially, these variations aren’t random: the genes are under strong natural selection, meaning they are being actively shaped by the environment in which the mushroom is growing. “In new habitats, Amanita phalloides may be encountering unfamiliar soil organisms or microbial competitors, and it seems to be evolving its chemical arsenal in response,” says Wang.

But there’s more. Pringle, Wang and their colleagues published another paper later that year reporting their discovery of an unprecedented reproductive strategy in A. phalloides. Typically, fungi reproduce sexually through the fusion of two genetically distinct individuals, a process that requires compatible mating types. However, a genomic analysis of death cap populations in California revealed that some individuals were reproducing unisexually, forming mushrooms from a single, unmated nucleus. These individuals were able to produce generation after generation of spores and persist in the environment for decades, sometimes spreading across entire forest patches.

Death cap invasion

This discovery challenged assumptions about how fungi in general reproduce. Until then, all wild mushrooms were thought to reproduce sexually; unisexual fruiting had been observed only in the lab under artificial conditions. “It is possible that most fungi can do both,” says Wang, “but invasive populations provide a specific opportunity for us to observe them.” Such flexibility would give fungi an advantage when adapting to a new environment because unisexual reproduction allows a single spore landing in a suitable environment to establish a self-sustaining colony. “If an organism can reproduce without a mate, it will be more likely to establish in the new range,” he says. Indeed, this reflects a strategy seen in many successful invasive plants and animals: those that can reproduce both with and without a partner tend to colonise more quickly and spread more widely.

This reproductive flexibility, combined with the diversification of its toxin genes, helps explain how A. phalloides has adapted so rapidly to new environments across continents. It reframes the narrative from passive spread to active evolutionary change, which makes this global expansion a fascinating real-time case study in fungal evolution. “Studying the evolution of Amanita phalloides can reveal how these fungi spread and impact local ecosystems, allowing us to develop models to understand biological invasion,” says Wang.

The idea of a deadly mushroom capable of colonising the globe, reproducing in multiple ways and evolving its toxin profile to remain lethal in new environments may sound alarming. Indeed, there have been cases of mistaken identity in areas where the death cap has only recently been found and where foragers are unaware of the level of caution required. And death cap poisoning is unquestionably serious. As yet, there is no widely available antidote – although in 2023, researchers in China found that a commonly used medical dye has the potential to be one. Early intervention is essential, and that can be problematic because the initial gastrointestinal symptoms subside when alpha-amanitin hides away in the gall bladder.

That’s the bad news. But once death cap poisoning has been diagnosed, there are several effective treatments. “Options include supportive care – fluids to correct hypoglycaemia – oral activated charcoal [to soak up toxins in the intestine] and benzyl penicillin to reduce liver uptake,” says Coulson. Even without an antidote, the survival rate after ingesting death caps is now around 90 per cent. What’s more, despite the mushroom’s fearsome reputation, poisonings are extremely rare. “Between 2013 and 2022, the UK’s National Poison Information Service received enquiries regarding 1195 suspected mushroom poisonings,” says Coulson. “Only 28 of these were reported as relating to Amanita species.” That’s around three a year – and A. phalloides isn’t the only toxic member of the Amanita genus.

Besides, if research on death caps tells us anything, it is that they didn’t evolve to harm humans – they are simply part of a broader evolutionary arms race for survival. “Mushrooms are not dangerous in themselves; they are only dangerous when treated in a specific way – when we eat them,” says Iona Fraser, a field mycologist and educator, who is a council member of the British Mycological Society. “Fearing fungi does us, and them, a disservice.” Most mushrooms aren’t poisonous; in fact, many are beneficial. “It’s hard to overstate how integral fungi are across medicine, biotech and the environment, both historically and now,” says mycologist Daniel Henk at the University of Bath, UK.

How fungi improve our lives

For a start, fungi play a central role in scientific research. “Yeasts are the models for eukaryotic biology,” says Henk. This is a reminder that as fellow eukaryotes – organisms whose cells contain a nucleus – we are more closely related to fungi than we often think. In biotechnology, they are invaluable. “Fungi are a fantastic tool,” he says. They have a wide and expanding repertoire, such as the fermentation of foods, the mass production of key chemicals such as ethanol and citrate, and sustainable building materials. Their ability to produce antibiotics to kill bacteria has been harnessed by the pharmaceutical industry since the discovery of penicillin, and fungi continue to be a potential source of new antibiotics in an age of drug resistance. Recent research has even identified alpha-amanitin as a possible revolutionary cancer treatment.

Fungi are also vital components of ecosystems. “They drive a lot of nutrient cycling through microbial communities and their often-symbiotic interactions with plants,” says Henk. They can be used in ecosystem regeneration and can signal broad environmental shifts, including those driven by climate change. “Fungi are agents of change in ecosystems,” says Fraser. Yet they are often ignored in ecological studies and conservation efforts, which leaves a major blind spot in our understanding of the natural world. And there is a darker reason why they warrant our attention, according to Henk: chemicals used to protect crops against fungal diseases are contributing to the emergence of resistant strains of fungi that can infect and kill humans. “Over a million deaths a year are attributable to fungi,” says Henk, and only a few hundred of these are from eating toxic mushrooms.

We may feel helpless against the power of agribusiness, but at least we can control the personal risks stemming from poisoning. Around the world, many cultures respect and value mushrooms, combining traditional knowledge and ecological understanding to identify and avoid dangerous species. Fraser thinks foraging is a good way for anyone to educate themselves about the fungal kingdom and to appreciate it. She points to research showing that foraging also develops environmental awareness and a stronger connection to nature. Even for people who have no intention of eating fungi, there is immense value in observing them and “joy in interacting with mushrooms in nature”, she says.

With more knowledge, perhaps the death cap will instil fascination rather than fear. The complex biology of this mushroom provides a window into the diversity, adaptability and ecological significance of an entire kingdom. It is evolving and, argues Henk, so must our attitudes. Compared with some disease-causing fungi, A. phalloides poses little threat; we should instead be concerned about the real dangers and benefits this branch of the tree of life can bring. “The fungal kingdom cannot be overlooked,” says Henk.