All things are poison, and nothing is without poison. It is the dose that does in, the quantity that makes the poison! A team of scientists headed by Prof. Csaba Szabo of the University of Fribourg has described the mechanisms that cause our cells to naturally produce hydrogen cyanide. This gas is toxic in doses that are too high yet plays a major role in the normal functioning of our body. Potential therapeutic benefits and applications of this discovery are considerable.

Considered toxic, hydrogen cyanide not only is a gas produced naturally within mammalian cells, it also plays a fundamental role in normal cell function. Such a straightforward, even overly direct claim would be simply impossible if not for the work of Prof. Csaba Szabo and his international team. In a 3 March 2025 article published in the journal Nature Metabolism, the scientists reveal the mechanisms behind the production of this gas as well as the health consequences when the chemical builds up too much or becomes too scarce.

A smidgen of cyanide
Thanks to experiments carried out on both human cells and living mice, Prof. Szabo and his colleagues were able to observe that hydrogen cyanide was systematically present in the cells and organisms. “We managed to demonstrate that this gas is produced there naturally without intervention or contamination from the outside,” Prof. Szabo explained. Already known in plants and bacteria, the phenomenon had not yet been shown to exist in mammals.

Like any self-respecting pharmacologist, Prof. Szabo then sought to determine what exact elements were responsible for producing this hydrogen cyanide.

Adding glycine to cell cultures, Prof. Szabo and his colleagues noted an increase in the production of hydrogen cyanide. “That’s how we demonstrated that glycine, an amino acid present in our bodies, stimulates the production of hydrogen cyanide in certain cells, like those of the liver,” Prof. Szabo said.

The importance of just the right amount
For the research team, one question remained. How does the body regulate production of the chemical and avoid any toxic accumulation? In this context, the scientists looked at rhodanese, an enzyme that is well known for its role in detoxifying hydrogen cyanide.

The University of Fribourg pharmacologist colorfully metaphorized the process, “As with glycine, several series of in vitro and in vivo experiments enabled us to demonstrate that rhodanese is a kind of bomb disposal specialist able to deactivate the hydrogen cyanide. The enzyme changes it into a nontoxic form (thiocyanate), which protects cells from potential poisoning.”

Therapeutic implications
Prof. Szabo is sure that the discovery of these mechanisms for producing and regulating hydrogen cyanide and understanding how they play out have important medical implications. Two examples illustrate this potential.

In lab experiments, the research team noticed that cells have a greater chance of surviving a shortage of oxygen (hypoxia) when there is a minute amount of hydrogen cyanide present. For Prof. Szabo, this realization could help provide better care for victims of stroke. “During a CVA, brain cells are affected precisely by a shortage of oxygen. Since we now know that hydrogen cyanide protects cells, it’s not at all hard to imagine that it may help to limit cell damage following a CVA.”

The research team also discovered that certain diseases like nonketotic hyperglycinemia (NKH) cause the body to produce excessive amounts of hydrogen cyanide. The accumulation of the gas in this case poisons cells and disrupts their metabolism, having a negative impact on health, which can include serious neurological disorders. Understanding the role played by glycine and rhodanese may lead to new therapies.

Major discoveries
As a nod to the famous historical Swiss physician Paracelsus, a group of pharmacologists based in Fribourg confirms then that “all things are poison, and nothing is without poison.” It is only ever a question of quantity. This rule, going back five centuries, also applies to cyanide, whose well-known toxicity makes it a byword for poison!

The author of many scientific publications, ranking him repeatedly among the most-cited researchers in the world, Prof. Szabo nonetheless sees the latest publication as a real milestone in his career, “I am convinced this is one of the greatest discoveries I have ever made and that it will fundamentally change the way we think about cell biology and metabolism.”

Source:
Szabo, C. (2025) et al. Regulation of mammalian cellular metabolism by endogenous cyanide production. Nature Metabolism. https://doi.org/10.1038/s42255-025-01225-w