How the world's most poisonous death mushroom kills people

The death cap mushroom, known as the "killer of kings" for centuries, is responsible for 90% of mushroom poisonings today.

Standing 15cm tall with a yellowish-brown or green cap, the death cap is said to taste quite good, according to accounts of those who accidentally ate it and survived. However, the resulting poison can cause vomiting, convulsions, severe liver damage and death. The Roman emperor Claudius is recorded to have died from eating the mushroom in 54 AD. The Roman emperor Charles VI died from the same cause in 1740. Today, hundreds of people die from eating the mushroom every year.

When eating the death cap mushroom (Amanita phalloides), victims do not show symptoms for at least 6 hours, sometimes 24 hours. This is the reason why many people are misdiagnosed with more benign illnesses such as flu or stomach.

If the patient becomes dehydrated, the symptoms may subside, but the poison continues to spread through the body, destroying the liver. If not treated promptly and properly, the victim may experience rapid organ failure, coma and death.

According to Helge Bode, a chemist at the Max Planck Institute for Terrestrial Microbiology, alpha-amanitin in death cap mushrooms is one of the most dangerous compounds found in nature, and cannot be eliminated by cooking, boiling, or any other conventional cooking method.

After eating mushrooms, about 60% of the alpha-amanitin goes directly to the liver. Both healthy and poisoned liver cells release alpha-amanitin into the bile. The gallbladder continues to release alpha-amanitin into the intestine, along with bile salts. At the end of the small intestine, the bile is reabsorbed back into the liver. The alpha-amanitin is re-entered into the liver, repeating the cycle of poisoning.

The remaining 40% of alpha-amanitin goes straight to the kidneys, the body's waste disposal organs. Healthy kidneys extract alpha-amanitin from the blood and send it to the bladder. Until the kidneys have eliminated the last of the poison, alpha-amanitin continues to damage the liver. The kidneys can only continue to function if the victim is well hydrated.

The world's most poisonous death cap mushroom, Amanita phalloides. Photo: NaturePL — The world's most poisonous death cap mushroom, Amanita phalloides. Photo: *NaturePL*

The cure comes from the camera company

Recently, experts have discovered a potential drug that can detoxify people who have accidentally eaten mushrooms. They found the biochemical pathway needed for the toxin alpha-amanitin to enter cells and interrupted that pathway. The drug, called indocyanine, was published in the journal Nature Communications on May 16.

This is the method that has been used to combat jellyfish venom, developed by Dr. Qiaoping Wang, Qiaoping Wang, Guangzhou. First, experts used CRISPR-Cas9 gene editing technology to create a group of human cells, each with a mutation in a separate gene. Then, they tested which mutations helped the cells survive exposure to alpha-amaniti.

Scientists discovered that cells lacking an enzyme called STT3B survive alpha-amanitin. STT3B is part of a biochemical pathway that adds sugar molecules to proteins. Disrupting this biochemical pathway prevents alpha-amanitin from entering cells, preventing the toxin from completely destroying organs.

The next step in the research was to screen some 3,200 chemical compounds, looking for ones that could block the activity of STT3B. Among those compounds, they discovered indocyanine green, a dye developed by camera maker Kodak in the 1950s. The compound is used in medical imaging, to visualize blood vessels in the eye and blood flow in the liver.

After testing indocyanine green on mice, experts reported that only 50% of the animals died, much lower than the 90% of untreated animals.

Researchers are excited about the new antidote, said Jiří Patočka, a toxicology expert at the University of South Bohemia in České Budějovice, Czech Republic. They described the approach as “very modern,” and said similar experiments could identify antidotes for bacteria that cause difficult-to-treat blood infections.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved indocyanine green for medical imaging. The chemical is safe at certain doses, so Dr. Wang hopes to begin human trials soon.

According to toxicologist Félix Carvalho of the University of Porto, the key to the study is timing. Indocyanine green is effective if given to patients within four hours of alpha-amanitin exposure. However, most people who eat death cap mushrooms do not go to the hospital for 24 to 48 hours because they have few symptoms. By then, their condition may be serious.

Thuc Linh (According to Nature, Slate )

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