By Brian Owens

Mercury, especially in its organic methylmercury form, is well known to cause severe problems in the brain – famously, Alice in Wonderland’s Mad Hatter is thought to be a victim of mercury poisoning.

Because mercury in the environment – both from natural sources and from pollution – can find its way into the food we eat, particularly fish, there are warnings and regulations around how much fish people should eat. But Graham George, a toxicologist at the University of Saskatchewan, says we don’t actually have a good understanding of the long-term effects of the levels of mercury typically seen in our food. “There is a lot of discussion about how mercury in our diets might affect us, but it is almost all extrapolated from animal studies of acute exposure,” says George.

So George and his colleagues set out to study exactly how mercury from different sources acts in the brain, using powerful synchrotron light. They obtained brain samples from four people. Two had suffered acute mercury poisoning: a child who ate contaminated pork, and a researcher who was accidentally exposed in their lab. The other two were from people in the Seychelles who were exposed to long-term, low levels of mercury through their diet rich in fish, but who had no symptoms of mercury poisoning. “They were eating fish up to 12 times per week throughout their lives and showed no obvious adverse effects,” says George.

Using advanced X-ray absorption spectroscopy, the team looked at what chemical form the mercury took in the brains of each group. They found that the molecular fingerprint of the mercury was different for people who had been poisoned than for those with low-level chronic exposure. The results were published in ACS Chemical Neuroscience.

In the poisoning cases, the mercury took two main forms: small particles of mercuric selenide, a highly insoluble and essentially benign form; and inorganic mercury bound to two thiolates, which George believes may be a marker of acute toxicity. In the fish-eaters, however, they saw methylmercury bound to some kind of thiolate – the same molecular form that is seen in fish themselves.

That doesn’t necessarily mean that it is safe to eat fish with high concentrations of mercury, George cautions – personally he would stay away from swordfish, shark, or other top predators where mercury can bioaccumulate up the food chain. But if we want to understand how low-level chronic exposure affects us, we need to look at data about low exposures, not high ones. “Because the molecular outcomes of the two types of exposure are so different, we probably can’t extrapolate from one to the other,” says George.

Matthew Rand, an environmental toxicologist at the University of Rochester, says getting this kind of fine detail about how mercury behaves at the molecular level in the brain is important to understanding its toxicity. The study sheds some light on the sometimes elusive chemistry of mercury, suggesting that the toxicological targets may be different in acute poisoning than in chronic long-term exposure. But he is not going to change his fish-eating habits just yet. “Before drawing this forward to meaningful physiological, or even medical and clinical implications, there’s still several degrees between them that need reinforcement,” he says.

For one thing, the experiments were done on just four samples, which had been preserved for some time, during which they could have undergone some chemical changes. Rand would like to see the work repeated on a wider array of samples in order to make a more concrete case.

That is easier said than done, says George, who also would have preferred to have more samples. But both synchrotron time and samples of brain tissue, especially from the tiny number of people who have suffered acute mercury poisoning, are not easy to come by. Even so, he is confident in his interpretations because the contrast between the two groups was so profound. And the advanced synchrotron methods used offer one big advantage: “Nothing can hide from our X-ray eyes,” he says.