How does arsenic kill?

Arsenic rose to infamy centuries ago as a nearly odorless, tasteless poison that was often used by and against the ruling classes in Europe during the Middle Ages and the Renaissance. 

But what is the history of arsenic poisoning, and how does it kill?

It turns out, an element that’s vital to life also plays a role in making arsenic lethal.

What is the history of arsenic poisoning?

Arsenic is a naturally occurring element that is widely distributed in Earth’s crust, according to the Centers for Disease Control and Prevention’s (CDC) Agency for Toxic Substances and Disease Registry (opens in new tab). Pure arsenic — which is a steel-gray, brittle solid — is typically found in the environment combined with other elements, such as oxygen, chlorine, sulfur, carbon and hydrogen, often resulting in white or colorless powders that have no smell or special taste. As such, you can’t usually tell if arsenic is present in food, water or air.

Historically, arsenic was known as both the “king of poisons” and the “poison of kings,” for its toxic power and its popularity among rulers who wanted to quietly do away with their rivals, according to a 2011 study published in the journal Toxicological Sciences (opens in new tab). 

Stories abound describing arsenic’s deadly use. For example, in biomedical historian James C. Whorton’s book “The Arsenic Century (opens in new tab)” (Oxford University Press, 2010), Whorton recounted the legend of Roman emperor Nero ridding himself of his 13-year-old stepbrother and potential rival Britannicus by slipping arsenic into his soup.

Powerful and wealthy Italian families, such as the Medici and the Borgia, were also rumored to have used arsenic to eradicate their rivals, according to the Toxicological Sciences report. The use of arsenic in murder was common until the development in te 18th century of chemical methods of detecting arsenic poisoning, which involve looking for the element in hair, urine or nails, according to Britannica (opens in new tab).

Nowadays, arsenic poisoning is more likely to be accidental than deliberate. People are most frequently exposed to arsenic through drinking water in areas where arsenic levels in dissolved minerals are naturally high, according to the CDC (opens in new tab). Other sources of accidental arsenic exposure include contact with contaminated soil or dust, wood that has been preserved using arsenic compounds, or certain foods, such as rice and some fruit juices. (Rice absorbs an unusual amount of arsenic from the soil compared with other crops, according to the FDA (opens in new tab); the agency notes (opens in new tab) that arsenic may make its way into apple and other juices due to naturally high levels of arsenic in soil and water, past use of arsenic-based pesticides in the United States and current use of such pesticides in other countries.)

What makes arsenic toxic?

Arsenic’s toxicity stems from its proximity to phosphorus on the periodic table of elements. Because arsenic and phosphorus have similar atomic structures, they have similar properties. Both possess chemical keys that unlock access to cellular function. But whereas phosphorus is essential to life, arsenic is disruptive and deadly, Mark Jones, a chemistry consultant and fellow of the American Chemical Society, told Live Science.

Arsenic’s similarity to phosphorus means that “arsenic can substitute very easily for phosphorus in many fundamental chemical reactions in biology and disrupt them,” Jones said. “This means that arsenic can act like a broad-spectrum poison against insects, weeds and pretty much every life-form.”

For example, phosphorus helps cells generate adenosine triphosphate (ATP), which is the main source of energy in all known organisms, according to the American Chemical Society (opens in new tab). Arsenic can mimic phosphorus in chemical interactions where enzymes use oxygen to help liberate the energy stored in the sugar glucose and capture it within ATP. This can lead to arsenic disrupting the vital chemical reactions in which phosphorus takes part.

“You can think of enzymes and the chemicals they act upon as locks and keys,” Jones said. “Arsenic is like a key that is not cut correctly — if it goes into a lock on a door, not only will it not unlock that door, it can get jammed in there and prevent another key from getting in to unlock that door. In this way, arsenic can block a lot of vital chemical pathways.”

By chemically jamming cellular “locks,” arsenic can harm nearly every organ in the human body. Large doses can lead to symptoms including vomiting, diarrhea, dehydration, shock, abnormal heart rhythms and multiple-organ failure, which may ultimately result in death, according to the CDC (opens in new tab). Long-term exposure to high levels of arsenic in drinking water is linked to medical conditions such as skin disorders, an increased risk for diabetes, high blood pressure, and several types of cancer, including lung and skin cancers, the CDC (opens in new tab) says.

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Individual susceptibility to arsenic poisoning varies widely; some people can tolerate doses of the element that would kill others, according to Britannica. In a 2018 study published in the journal Mammalian Genome (opens in new tab), researchers reported that people’s genes, diet and gut microbes may affect their chances for surviving an encounter with the deadly toxin.

Despite its deadly potential, arsenic poisoning is treatable if caught early, according to the Agency for Toxic Substances and Disease Registry (opens in new tab). A key medicine is dimercaprol, which was developed by British scientists during World War II as an antidote to arsenic-based chemical weapons. The drug works by absorbing arsenic and neutralizing its toxicity, according to the National Library of Medicine (opens in new tab). 

Although arsenic has a reputation for being deadly, it can also help cure disease, according to the Wellcome Library in England (opens in new tab). In 1909, German chemist and Nobel Prize winner Paul Ehrlich and his colleagues developed an arsenic-loaded compound called Salvarsan, which became the first effective treatment for syphilis, according to the Science History Institute in Philadelphia (opens in new tab). The principle behind how Salvarsan works, wherein a drug seeks out and destroys diseased cells, eventually found use in chemotherapy, Wellcome Library reported.

Originally published on Live Science.

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