Detoxification champions

Every day, they drink water heavily contaminated with arsenic. Yet these inhabitants of Bolivia's Altiplano don't seem to suffer... An enigma investigated by epidemiologist Jacques Gardon, who reveals how they have adapted to this poison.

Jacques Gardon

Arsenic, an almost romantic-sounding word for a substance that had its hours of glory, both at the court of Louis XIV and in the Borgia family. A poison, however, that is still sadly relevant today: "The consumption of arsenic-contaminated water is a public health problem that affects around 140 million people worldwide ", says Jacques Gardon. For over 5 years, the epidemiologist from the HydroSciences laboratory has been studying the effects of arsenic on the health of Bolivian populations, more specifically the Urus who live on the shores of Lake Poopó.

There, the researcher found arsenic levels in the water up to 80 times higher than WHO standards. " The limit is set at 10 micrograms per liter. In some wells we measured up to 800 micrograms per liter ", he explains. But where does this arsenic come from? " It is naturally present in the earth's crust and in ores in many regions, and can contaminate groundwater as a result of soil erosion," explains Jacques Gardon. In some regions, this natural process is exacerbated by mining operations, as is the case in Bolivia, where miners crush arsenopyrite to extract the metals, releasing arsenic that contaminates sediments, rivers, water tables... and wells.

Shallow wells

" Local populations obtain their drinking water from traditional shallow wells or tube wells. Unfortunately, Bolivia does not have a chemical water quality map for arsenic, and the local population consumes water containing sometimes worrying concentrations ", explains the doctor.

With what consequences for their health? " Chronic ingestion of arsenic causes cancer, damages the cardiovascular system, damages the kidneys and can lead to diabetes," answers Jacques Gardon. Arsenic also causes characteristic lesions on the hands and feet: a thickening of the skin or hyperkeratosis, typical of arsenicism, which can develop into cancer. Jacques Gardon took a good look at the hands of the Urus of Lake Poopó. Surprisingly normal hands. " They don't show these skin manifestations ".

How can we explain the absence of this characteristic symptom despite so much arsenic? " A team of Swedish researchers studied a similar situation in certain villages in northern Argentina, and hypothesized that it could be a question of adaptation to the poison ", explains the researcher. Over the generations, the inhabitants would have become increasingly able to eliminate arsenic.

Eliminating arsenic

To verify this theory, Jacques Gardon, accompanied by Swedish and Bolivian colleagues, measured arsenic and arsenic derivative levels in the urine of 200 women living in ten villages scattered around Lake Poopó. " We focused on women because men, who often leave the village to find work elsewhere, are not subject to the same exposure to arsenic ", explains the doctor.

And, unsurprisingly, the researchers did find arsenic in their urine. What was surprising, however, was the chemical form of the arsenic identified. "Arsenic exists in several distinct forms (see box), one of which is less toxic and easier to eliminate than the others. In the general population, the least toxic chemical form accounts for an average of 60% of arsenic found in urine, but in Urus women this proportion rises to 80% ", astonishes Jacques Gardon. This means that their metabolism is particularly efficient at eliminating the poison.

Adapting to poison

To explain this extraordinary efficiency, the researchers looked at the inhabitants' genomes and found a mutation in a gene that controls arsenic detoxification. " Normally this mutation is found in around 20% of the population, but we found it in 80% of the Andean people", explains the researcher. This mutation is probably selected over time, with the Urus becoming increasingly capable of eliminating arsenic from generation to generation. " This is the first documented example of human adaptation to a toxic agent", enthuses Jacques Gardon.

A researcher's enthusiasm is quickly tempered by the doctor's concerns: "Understanding the relationship between the exposome and the genome is fascinating, but the most important thing is to promote access to drinking water for all populations ". Filtration, ion exchange, oxidation, dilution... many effective techniques exist to remove arsenic from water. " Arsenic has no color, flavor or odor, andmost people drink contaminated water without knowing it. It's a real public health problem, and our role is to remedy it .

Effective detoxification

If we take in water containing dissolved arsenic, it is chemically modified in our liver to facilitate its elimination by the kidneys. This modification involves a process called "methylation", which transforms elemental arsenic into either monomethyl arsenic or dimethyl arsenic. While the former is poorly eliminated by the body, the latter is more easily eliminated, and is therefore less associated with severe symptoms. It is precisely this dimethyl arsenic that the researchers found in the majority of Urus urine. The cause: a mutation in the gene coding for the enzyme involved in this methylation process, called arsenic methyltransferase, which favours transformation into dimethyl arsenic and would explain the efficiency of the arsenic detoxification process in Urus.

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