rom the backseat of a black sports utility vehicle, wildlife toxicology grad student Anke Krey peers out at the snow-lined arctic road ahead. A teenager on a skidoo pulls onto the shoulder and narrowly weaves ahead of a pick-up truck; two huskies run across the road as a Mack truck comes barreling down the other way. It’s a week before the winter solstice, and the temperature outside is roughly –35°C with the wind chill. Krey quietly slips on her seatbelt.

“You know you’re a foreigner when you put on a seatbelt,” laughs the unbuckled driver Michael Kwan, a local environmental toxicologist from the Nunavik Research Centre in Kuujjuaq, Northern Quebec. Erring on the side of caution over local practices, Krey, visiting from the University of Northern British Columbia in Prince George, keeps her seatbelt on.

Kwan drives down Kuujjuaq’s main thoroughfare, past the town hall, bank, post office, general store, two churches, and the half-frozen Koksoak River, to a pair of temporary trailers. With the research center in the middle of a $7 million upgrade, these propped-up, makeshift laboratories serve as the provisional epicenter for studying contaminants in Nunavik—a landmass about the size of California that comprises the northern third of Quebec.

Stepping inside one of the trailers, Kwan opens a large freezer full of bread loaf–shaped lumps wrapped in black garbage bags. He unties one bag to reveal the snarling canine teeth of a dead, skinned polar bear head. Kwan looks up, grins slyly and says: “This is the kind of opportunity that a researcher from the south can only dream of.”

Krey came to this remote Inuit village—where the boreal forest meets the arctic tundra, some 1,500 kilometers north of Montreal—in December with a singular goal: to dissect polar bear brains and look for neurochemical changes associated with low levels of exposure to the toxic metal mercury.

However, it’s not just polar bears that interest Krey and her advisor, environmental health researcher Laurie Chan. Over the past few years, Chan’s lab has measured mercury contamination in many arctic mammals—including, seals, caribou, mink, otters, muskrats, beluga whales (see page 20) and humans—in an effort to better understand how these various species deal with chronic exposure to mercury.

“It’s all different ways to ask the same question,” says Chan: “Can we have a better handle on our human activities and its consequences on the health of the ecosystem?”

The story of mercury contamination traces back to the 19th century, when the toxin was widely used in the felt industry, and hat makers often developed neuropsychotic symptoms—hence the phrase “mad as a hatter.” Researchers started to notice that food was a potential source of mercury poisoning after scores of people died or fell ill from contaminated fish in Japan in the 1960s and from tainted grain in Iraq in the 1970s. In these cases, however, people were exposed to extreme doses of mercury pollution from industrial discharge or mercury-laden pesticides, and most scientists agreed that normal background levels of mercury were safe, for the most part.

Even so, no governing body could agree on how much mercury was too much.

Drawing on research indicating that no adverse clinical symptoms were detected below a blood mercury level of 58 parts per billion (ppb), the US Environmental Protection Agency factored in a 10-fold margin of safety and recommended a blood mercury maximum of 5.8 ppb. The European Food Safety Authority, however, was less conservative and set the bar at 10 ppb, while Health Canada and the World Health Organization agreed that 20 ppb was safe for nonpregnant adults.

Yet these guidelines were put into effect without studying any neurochemical reactions at the cellular level, which is where scientists see the early signs of toxicity. Now Chan’s group is taking biochemical measurements of brain receptors and enzymes to study the close links between neuronal cell death and mercury uptake, and his team is producing some surprising—and unsettling—findings. “We see subtle changes in the brain before the onset of clinical outcomes,” says Chan.

In short, he and others are seeing biochemical changes in the brains of polar bears, mink, wild river otters, and other species. These biochemical changes could translate into physiological changes—such as defects in memory, language, attention, motor function and visual-spatial abilities—that often go unnoticed until it’s too late and the animal has suffered significant damage from mercury. As Chan’s group struggles to replicate and understand those changes, they are beginning to wonder: Is there no safe level of mercury exposure?

“In the old days, we always thought there was a margin of safety that when we were exposed to a lower level of contaminants that our body could handle that and there wouldn’t be clinical observations,” says Chan. “That threshold may not be real.” If his findings prove correct, the tens of thousands of people, whales, bears, and innumerable other species living with mercury in their brains below the supposed maximum may, in fact, be experiencing toxic effects from this low-level exposure.

“Just because an animal isn’t keeling over and dying doesn’t mean it isn’t being affected,” notes Tony Scheuhammer, a wildlife toxicology research scientist with Environment Canada in Ottawa who has collaborated with Chan. “There are many more subtle biochemical and neurochemical changes that happen long before you see overt toxicity, and yet these are clearly ascribable to the effects of mercury.”

nside the trailer, Krey fires up a hand-held autopsy saw, slips on her face mask, and starts cutting a frost-covered polar bear head. She makes two half-moon incisions in the top of the head, but the bone doesn’t peel off from the brain matter below. After an hour of hacking away at the frozen head, the handsaw is dangerously overheating and the makeshift laboratory smells halfway between a butcher’s shop and a dentist’s office. The brain remains buried in the mangled ursine skull.

Kwan makes a few calls and arranges for Krey to visit the local government workshop, which maintains a more powerful, 43-centimeter band saw, usually used for splitting hefty beams of wood. Stepping out of the trailer into the arctic chill, Krey and Kwan load up the dozen bear skulls, each weighing at least 5 kilograms, into the back of Kwan’s SUV. The researchers drive over to the workshop where they meet Sandy Suppa, a local research technician, who slices each head down the middle into two equal halves. The saw’s loud buzzing drowns out the Christmas carols ringing out from the stereo in the background.

Cutting each bear head takes less than a minute, but cleaning up all the flakes of bone and gristle of pink tissue lasts well over an hour. Larry, the maintenance manager, waits around to make sure that his tool is scrubbed properly—unlike 3 years ago when Krey sliced up her first set of bear skulls, leaving behind traces of rotting flesh. “Holy smokes, did it ever stink in here,” he recalls.

Krey first came to Kuujjuaq in 2006 to collect samples from 24 bear heads then waiting for her in a freezer. Kuujjuaq is the administrative capital and largest town in Nunavik; with a population of 2,115 as of the last census count, it’s the region with the highest observed blood mercury levels among Canadian Inuit populations.

Unlike in other parts of the arctic where the bears are more abundant, hunters in Nunavik rarely seek out polar bears deliberately; rather, they encounter the animals accidentally while tracking seals—a staple of both bear and Inuit diets. “Man and bear come to the same spot, and usually the polar bear loses,” explains Kwan. The hunters, who don’t need a permit, then voluntarily submit the head to the Quebec Ministry of Natural Resources for population surveys and toxicological studies. Although blood and fur banks exist for polar bears, this is one of the first times that researchers have been able to sample inside the species’ head.

Krey isolated a handful of brain regions, and tested them for mercury levels as well as the activity of several brain enzymes and receptors involved in a range of processes including memory, movement, and learning. Chan and his former graduate student Niladri Basu had already shown that mercury disrupted GABAergic signaling, impaired components of the cholinergic system, and lowered the levels of a glutamate receptor called the N-methyl-d-aspartate receptor (NMdAR) in mink and numerous other species. In 2008, Chan also discovered a partial reason for why mercury was wreaking havoc on the brain. He showed in human neuroblastoma cells that the heavy metal bound and activated NMDARs—a commonly studied benchmark of toxicology testing that contributes to excitatory synaptic transmission and memory function—thereby causing neurons to start firing too often, and ultimately leading to cell death.¹

Specific to polar bears, last year a team led by Basu found that NMDAR levels dropped when mercury levels rose in the brain-stem region of polar bears from East Greenland.² The uniqueness of the iconic bears piqued Krey’s interest, and she set out to repeat Basu’s experiment in the polar bears from Nunavik.

So far, however, she has been unable to replicate Basu’s findings in the 24 bears she has examined because the brain tissue has degraded to the point that her assays can’t accurately detect the receptors. Consequently, Krey has turned to another indicator, the enzyme monoamine oxidase (MAO), which Chan previously showed was less active in the face of low-dose mercury in many regions of the brains of both wild river otters and lab rats. Krey found this inverse relationship between the enzyme and the metal in the bear’s occipital cortex, which processes visual signals, but she has not yet seen this association anywhere else in the brain. Part of the reason, they now realize, is that the overall mercury levels are extremely low in all parts of the polar bear brain—less than 1 part per million (ppm) on average. (However, Basu has found levels of up to 5 ppm in the Greenland polar bears’ pituitary glands, a tiny brain region that Krey didn’t study.) In contrast, mercury concentrations in the bear’s liver can exceed 100 ppm—one of the highest known mercury levels among all organisms. And Chan’s group isn’t yet looking at the cellular damage mercury can cause in the liver.

Further digging into these low-mercury brain levels, Krey coupled liquid chromatography and mass spectrometry to differentiate between two different forms of mercury in the bear brains. The first is organic methylmercury, which can penetrate lipid bilayers, including the blood–brain barrier, which is how humans and wildlife are exposed to the neurotoxic element. The other form is inorganic mercury, which is converted from methylmercury in the brain, where it effectively gets trapped because it cannot readily cross the body’s membranes. The inorganic mercury then accumulates and usually causes the most damage.

Unlike many other mammals, including humans, who have a near 50:50 split of the two types of mercury in the brain, the toxin within polar bear brains is more than 95 percent in the organic form. “That tells us that the polar bears are not at risk of neurotoxic effects of mercury,” says Krey. “That’s very good news…it’s awesome. It’s great for the bear—besides that they’re dying of climate change, but that’s something else.”

But other species are not so lucky.

han’s team is slowly uncovering unique differences in how the brains of polar bears and other arctic species take up and respond to the subtle mercury poisoning in their diet (see “Mercury gone wild”). Resolving these differences may ultimately lead to a better mechanistic understanding of how the human brain handles the toxic metal, too.

Given the neurotoxicity observed in wildlife, “we have to wonder if the same thing happens in humans—and it probably does,” says Basu, now at the University of Michigan, Ann Arbor. “The problem is that we can’t go into humans and get their brains.” Although brain banks exist at many research institutions around the world, these centers rarely carry samples from isolated populations such as the Inuit who, because of their diets rich in mercury-laden fish and fish-eating mammals, are at the most risk of unknowingly suffering from low-dose chronic exposure to the contaminant. “It’s really the people who depend on fish who are suffering most,” says Chan.

Ideally, a single animal would near-perfectly mimic the pathology seen in humans to serve as a proxy. But because the species-level diversity in the quantities of mercury toxicity is so great, none of the mammals that Chan, Basu or others have looked at is emerging as good stand-in models for deciphering mercury’s toll on human populations at risk. “Unfortunately,” says Chan, “the fact that we’re seeing more and more differences between species means it’s less and less likely that it’ll be feasible to use the results we see in wildlife to extrapolate to humans.”

Researchers continue to show the detrimental effects of low-dose mercury via regular health surveys. For example, a November study of more than 700 adults from Nunavik, who had an average blood mercury level of 10 ppb (nearly twice the US limit), showed that higher levels were linked with elevated blood pressure.³ But probing into the brains of humans is much more difficult than simple blood assays. Considering Chan and Krey’s great efforts to track down a couple dozen polar bear brains, direct neurochemical studies on Inuit brains seemed out of the question. So, Chan has been searching for peripheral neurochemical biomarkers in blood.

One early promising candidate is the protein Krey investigated in her bears, MAO—which is found both in neurons and blood platelets and has been shown to be a molecular target of mercury in animal models. MAO also controls behavior by regulating levels of dopamine, serotonin, and noradrenaline in the nervous tissue, and has been linked to many neurodegenerative disorders.

Besides the health implications, finding such a biomarker could also have great legal importance. In 1977, for instance, an aboriginal Quebec Cree group sued 15 mining and industrial companies, claiming to be adversely affected by continuous low levels of mercury pollution. The lawsuit was thrown out after a study of approximately 300 Cree adults found no correlation between mercury levels and overall neurological performance, although a later reanalysis of the data found a significant link between mercury intoxication and the prevalence of involuntary tremors. A valid biomarker could provide more definitive results that would be more quantitative and less subjective to human interpretation.

In a 2006 study of blood platelets from 127 fish-eating humans living along the Saint Lawrence River in Quebec, Chan found that people with more mercury in their diets had lower MAO levels, even though they had no overt symptoms of mercury poisoning⁴—suggesting that this low-level exposure might be impacting their brains by causing a decrease in MAO activity, which in turn affects the neurotransmitters. This work builds on previous studies showing that Aboriginal children and adults with elevated blood levels of mercury had impaired motor ability.

Thus, Chan figured, measuring MAO in blood platelets might offer clues into human brain chemistry without having to bust open heads.

hen I visited Prince George as part of a journalism travel grant funded by the Canadian Institutes of Health Research, Chan and the 11 members of his lab group sat around a windowless basement conference room, munching on pizza and apricots, and discussing their next step with MAO.

Discouragingly, after collecting blood samples from more than 1000 Inuit, Chan and his graduate student Alyssa Shaw had found no clear relationship between blood mercury levels and platelet MAO, although more sampling is still ongoing. Yet even if MAO doesn’t ultimately live up to its early promise, “it’s not as though there is no clinical value of measuring platelet MAO in at-risk Inuit populations,” says Shaw, noting that reduced platelet MAO is associated with alcohol-abuse and schizophrenia, while elevated levels are linked to depression, Parkinson’s, and Alzheimer’s Disease. Thus, it’s a good signpost for impaired brain function generally, but “whether or not it’s a surrogate biomarker of effect for mercury, well, that’s still up for discussion,” she says.

The uncertainty surrounding biomarkers of low-dose mercury reflects how little scientists understand about all of the metal’s effects in the body. Most researchers have focused on the neurotoxic effects of mercury on the brain, but Ellen Silbergeld, an environmental health researcher at Johns Hopkins University in Baltimore, Md., has shown that low doses of the metal can interfere with the body’s immune system, too.

In December, Silbergeld, together with her former postdoc Jennifer Nyland, reported that low concentrations of mercury in human blood cells affect immune function by disrupting cytokine signaling pathways—elevating the levels of pro-inflammatory cytokines and decreasing the release of anti-inflammatory cytokines.⁵ Those findings dovetail with Silbergeld’s previous whole organism studies with mice and humans that linked mercury with hyper-autoimmunity.

“Somehow mercury is changing the threshold of activation for these auto-reactive cells so that less of a stimulus will put them over the edge,” says Nyland, now at University of South Carolina School of Medicine in Columbia. “The toxic effects of mercury on the immune system have been neglected, pure and simple,” adds Silbergeld.

What’s more, mercury’s neurotoxic and immunotoxic effects might be inextricably linked. Silbergeld has found evidence that mercury inhibits the migration of neurons in mouse brain cells by disrupting the cytokine-mediated communication between neurons and specialized immune cells in the brain called microglia. Chan’s lab is also now starting to investigate mercury’s effects on the brain’s immune system.

Working out all these mechanistic mysteries still fascinates Chan, but his main passion involves translating his basic research findings into public policy decisions. “That, to me, is the most interesting part.” Among the many hats he wears, Chan sits on the Canadian Interagency Advisory Panel on Research Ethics, he serves as the scientific director for the First Nations Environmental Health Innovation Network of Canada, and he often has the ear of lawmakers in Canada and throughout the world. For example, in January he presented evidence to the World Health Organization on the risks and benefits of fish consumption.

But Chan, who himself eats sushi around once a week, never preaches that people should not eat fish and fish-eating mammals altogether—particularly Inuit and first nations communities, for whom these traditional foods are an important dietary staple, both for nutritional and cultural reasons. Rather, he recommends that they choose to eat primarily those species with the lowest and safest mercury concentrations.

Chan “continually sees the people behind the work that he’s doing,” says Donna Mergler, an emeritus professor at the University of Quebec at Montreal who studies the neurotoxic effects of pollutants. “He not only focuses on the toxicological aspects of exposure, but also what are the benefits one is getting from traditional foods and how that fits in with the risks.”

ack at the workshop, the researchers have created an assembly line: Local research tech Sandy Suppa carefully pushes the bear heads across the whirring band saw, hands them off to Kwan, who then puts them back in the garbage bags for Krey to label. All the while, everyone wears latex gloves to protect them from a parasitic worm that infests nearly every tissue in the polar bear.

Krey pulls out the next head—the largest one she’s ever seen—and mutters an expletive under her breath. Larry, who is trying to pry a canine tooth out of a hacked-up head, rebukes Krey. He explains that according to Inuit legend, if you swear in front of a polar bear, dead or alive, “the spirit of the bear will come and get you.” Erring this time on the side of local practice, Krey seals her lips. Now, the only sound is the band saw cutting another polar bear head.

Correction (May 4): when originally posted, the article misattributed the historic sources of mercury poisoning in the 1960s and 1970s. The Scientist regrets the error.

Elie - in the article you note

"Researchers started to notice that food was a potential source of mercury poisoning after scores of people died or fell ill from contaminated fish in Japan in the 1960s and from tainted grain in Iraq in the 1970s. In these cases, however, people were exposed to extreme doses of mercury pollution from industrial burning of fossil fuels..."

In fact, neither the Minamata, Japan, nor the Iraqi exposure were due to mercury from burning fossil fuels. In Minamata, a plant of Nippon Chisso was producing aldehydes from coal and produced methylmercuric chloride as a byproduct of the processing. They dumped this directly into the Minamata river where it flowed directly into the Bay used for subsistence fishing; hence the severe onset of Minamata Disease (just now settled out of court, more than 50 years after the fact). In pre-Sadam Iraq, the **United States** shipped grain to Iraqi villages for crop planting to relieve a drought; we thoughtfully had the grain sprayed in Mexico, before shipping, with a red-dyed solution of mercuric chloride as a fungicide. The grain bags were labeled with do-not-consume warnings in English and Spanish, not much help in rural Iraq. The poisoning ensued when the grain was instead ground for bread and other foods instead of being planted.

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Dear Robert,

What studies have proven that thimerosal (mercury) does not cause autism? I can't find any that actually study what mercury does to the developing brain. If you mean the Danish epidemiological studies produced and paid for by the CDC, one of the lead researchers has taken off with 2 million bucks of the CDC monies and most of the research materials (Paul Thorsen), rendering his integrity, and any research he did, in serious jeopardy.

Mercury is a poison at any dose. It does not matter if you inhale it, ingest it, or inject it. It is a poison and will have an effect on the individual.

Sean, the preponderance of evidence from numerous studies does not support thimerosol in childhood vaccines as a cause of autism:

LINK

Furthermore, thimerosol has not been used in childhood vaccines (possible exception is flu vaccine) for many years.

Unless I missed it as I scanned the article I saw no reference to the use of mercury as a preservative in vaccines. In particular the use of mercury in baby vaccinations commonly thought to be the cause of infant neurological problems and more specifically Autism.. According to a recent report about 10% of American women of child-bearing age are at risk for having a baby born with neurological problems due to in utero mercury exposure (statistically representing about 375,000 babies/year). The fact that amalgams are most likely the major contributor to the mercury levels in American citizens should be clearly presented to the public. Yet all the American public hears is concerns about mercury in fish. Mercury poisoning is also strongly suspected of being the root cause of Alzheimer suffering in the adult population. The findings in your article would be very damning in that respect and needs to be highlighted.

Today it is known, that the blood-subtype of Apolipoprotein Type 4 plays an important role in the sensitivity to mercury exposure.
In all studies this phenomenon should be one of the parameters in any studies of mercury.
If pharmaceutical companies know about it and eliminate all the test-persons, who have this genetic aberration, they get great results for the safety and sideeffects of medications containing mercury (Thiomersal etc.)
All those generalizations of fishconsumption for example are disasterous.
If one doesn't have the mercury sensitivity, he can eat fish without any problem and those, who are sensitive, can eat fish, which lived in a mercury free environment (not from the Amazon for example).
Mercury is a, maybe the major Problem of our society and we still have a long way, to make people understand, how serious todays situation is.

Stephen: Thanks for alerting me to the paper showing the potential reproductive benefits of low dose mercury exposure in mallards (Environ. Toxicol. Chem. 29, 650-653; 2010). A peculiar result of this study is that the reproductive success of the control group was unaccountably low -- the hatching rate was just 58%, whereas 70-80% is more typical. So, the fact that the mercury-fed ducks had an offspring hatching rate of 72% only puts these animals into the 'normal' range.

Thus, it's a bit premature to say whether the metal confers any added benefit, says Tony Scheuhammer, a wildlife toxicology research scientist with Environment Canada in Ottawa who is quoted in the article. "I think the study, or one similar to it, needs to be repeated before any hard and fast conclusions are made."

In addition, I put the the first commenter's question about the safety of the parasite worms on the well-being of the polar bears to Lorry Forbes, a veterinary parasitologist with the Canadian Food Inspection Agency in Saskatoon who has worked at the Nunavik Research Centre in Kuujjuaq. Here's what he told me:

There is no evidence to indicate that Trichinella infections are harmful to bears or any of the numerous other carnivore hosts for this parasite. This is due in part to the life cycle of this nematode - the adult life span in the intestine is very short (generally less than a month) and by 2 months the larvae are encysted in musculature and benignly reside there until consumed by a new host (or die of old age). In addition, exposure under natural conditions is likely to low numbers of worms. In cases of massive exposure, there may be transient enteritis and associated intestinal discomfort as the large numbers of adults burrow into the intestinal wall, reproduce and die, followed by transient muscle pain as the resultant larvae migrate into the muscle and encyst. That said, clinical signs are rarely observed in high dose experimental infection of carnivores and if they are observed, they are short lived and usually reported as transient loss of appetite and muscle stiffness followed by a quick return to normal. I hope this is helpful.

(Incidentally you can safely handle raw muscle tissue containing encysted Trichinella larvae without gloves. Infection is by ingestion of live cysts in raw or undercooked meat, not by contact. However, there are a number of other reasons for routinely wearing gloves while doing autopsy work so it is usually standard practice.)

Congratulations on the courage and enthousiasm of these researchers working in not easy conditions and environment. Thank you.

Elie I wonder if there are any thoughts on your behalf about the possibility of some low level methylmercury effects being potentially positive. In this regard I point to the recent Environmental Toxicology article entitled:
Enhanced reproduction in mallards fed a low level of methylmercury: An apparent case of hormesis.

In response to the first commenter's question, the parasitic worm mentioned near the end of the article is the nematode roundworm Trichinella, which is also found in raw pork and other tainted meat. A majority of polar bears are infected and parasite concentrations in some tissues can be quite high, but infections are not normally fatal. Like mercury neurotoxicity, however, it's unclear what sub-lethal effects the parasite has on the animals.

What's more, rates of Trichinella and, indeed, mercury concentrations might be on the rise -- which touches upon the second commenter's remarks.

According to Steven Amstrup, senior polar bear scientist with the US Geological Survey's Alaska Science Center in Anchorage, "Frequencies of disease and parasite exposure, like exposure to mercury and other contaminants, is one of the things we expect to see change in coming years with increased warming of the Arctic."

When mercury is discussed, I think it's interesting that it's seemingly never noted that environmental exposure to mercury peaked in 1960 and exposures have declined since then. Nor is it mentioned that pre-1960, exposures by infants, kids, and adults were far higher due to the common use of mercury in many many products.

Until 1955, the "pink" disease from mercury over-exposure was common in infants due to the use of mercury-based calomel as a teething cream, mercury-based diaper powders and the like. The organic mercurical Mercurochrome was commonly applied to the open wounds of kids of all ages. Until the 1960s, organic mercuricals were the most effective diuretics. The good old days - they were terrible.

Fortunately, modern science has done much to reduce both environmental as well as consumer exposure to mercury.

Does someone know if the worms mentioned in the article, but not identified, are harming polar bears?