They called it lytico-bodig. As the Second World War drew to a close, U.S. military doctors stationed on Guam noticed many of the Pacific island’s Chamorro people were suffering from a baffling and devastating illness.
The local name for the progressive and fatal disease – said to have come from the Spanish “paralytico” – provided a label for what Islanders described as an illness that disconnects one from one’s family. It captured a constellation of symptoms, including muscle wasting, paralysis, muscle rigidity, shaking, confusion and memory loss. Doctors and researchers observed this strange illness shared characteristics of amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), Parkinson’s disease and Alzheimer’s disease, and they clamoured to try to understand it, with the hope it would shed light on other neurodegenerative disorders.
In a collection of case reports published in 1961, early investigators documented the deterioration over 12 years of their first patient, whom they described as a “Chamorro housewife.” Her initial chief complaint was of weakness in both her hands. “When last observed in August, 1960, the patient was helpless, bedridden, almost immobile and in a terminal state,” the authors wrote.
The disease was still a mystery when Canadian chemist Susan Murch travelled to Guam as a postdoctoral fellow in 2003 to study a neurotoxin researchers believed might hold the key to solving the puzzle. What she and the scientists she worked with discovered there provided not only what they considered a possible source of the illness, but may also offer clues to a new medical mystery in New Brunswick, where dozens of people have developed unexplained neurological symptoms.
Dr. Murch, working with principal investigator Paul Cox, a U.S. ethnobotanist, found that a toxin produced by blue-green algae called beta-methylamino-L-alanine, or BMAA, was present in cycad trees, a source of food for the island’s residents. They found the same toxin in the animals residents consumed, such as pigs, deer and bats that ate the seeds, fruit and other parts of the cycad plants. And they also found it in the brain tissue of several Chamorro patients who died of the mysterious disease.
Dr. Cox, together with famed British neurologist Oliver Sacks, hypothesized that neurotoxic BMAA, the amounts of which were magnified as people consumed animals at higher levels of the food chain, might offer a long-sought explanation for what was causing damage to people’s bodies and brains. Today, that hypothesis is still debated. But investigators of the new illness in New Brunswick are revisiting the work of Dr. Murch and her colleagues.
As of mid-July, 48 cases of an unknown neurological syndrome, including six deaths, have been reported in the province, mostly in the Moncton area and the Acadian peninsula. Doctors and researchers investigating the illness say they are looking into various potential causes – among them, BMAA or an algal toxin like it.
The decades-old mystery on a remote Pacific island may not have an obvious link to the new one that has emerged on the east coast of Canada. And the theory isn’t the only idea being considered. Researchers have also been probing the possibility of a prion disease, similar to the human form of mad cow disease, or some other kind of environmental toxin. Nevertheless, investigators of the illness in New Brunswick say re-examining the disease identified in Guam may provide valuable lessons for them – chiefly, that algal toxins, which are a growing concern as climate change warms waters and promotes algae blooms, have the potential to sicken people long after initial exposure.
“We’re not saying that we have that disease,” said Alier Marrero, a neurologist at Dr. Georges-L.-Dumont University Hospital Centre in Moncton, who is leading a special clinic for those affected. The symptoms of his own patients, which include pain, hallucinations, severe insomnia and visual disturbances, are not exactly the same as the ones experienced by those on Guam, he said. “But there could be a significant or similar link to an environmental factor that, if identified, it could be prevented or stopped. That’s our hope.”
In a press conference on June 3, New Brunswick’s Minister of Health, Dorothy Shephard, announced the creation of a committee to oversee the investigation of the strange neurological syndrome in her province, which has seen 48 reported cases. She also told reporters that public-health officials were conducting detailed surveys of those believed to be affected by the illness.
Ms. Shephard said it was expected to take six to eight weeks to complete those interviews with patients’ families to collect information, including about their environment, residence and travel history. Meanwhile, she said, the oversight committee would review all identified cases – a task that is expected to take four months.
Roger Ellis, who lives in Bathurst, became ill in June, 2019, initially feeling as though he were having a heart attack. Repeated visits to the hospital emergency department revealed nothing wrong, but he soon began having seizures. Doctors ruled out epilepsy. Then, when he developed delusions, aggressive and repetitive behaviour, and weight loss, they tested him for Creutzfeldt-Jakob disease, the human form of mad cow disease, but those tests showed no signs of that either.
Within three months, he lost 27 kilograms and his ability to eat and walk. Doctors believed he was going to die, said his son, Steve Ellis. But Roger bounced back, and by early 2020, he regained his ability to eat and his condition seemed to stabilize before deteriorating again this summer. He has repetitive speech, repetitive behaviours and growing atrophy in his brain, his son said, and doctors, who grouped him with the cluster of mysterious cases in June, have been at a loss to diagnose him with any known disease. “We know everything it’s not, but we just don’t know what it is,” Steve said.
Steve said he has been thinking about various factors in his father’s life that might offer clues, such as his occupation at a mine; his diet, which included a fair amount of seafood; and his upbringing and home near the water.
In a Facebook group he created, called the “Mystery neurological disease NB support group,” family members of those affected or who suspect their loved ones are affected have bandied about numerous other factors they suspect could be potential causes. But at this point, there are no firm leads. “It’s really all over the map,” Steve said.
Cyanobacteria, the blue-green algae that produce the neurotoxin BMAA, are found everywhere in the world, especially in the soil, and in lakes and oceans, said Dr. Murch, now a chemistry professor at the University of British Columbia-Okanagan. She has even collected samples from glaciers in Nunavut.
Cyanobacteria are an important part of the ecosystem, and typically, they exist at fairly low levels, Dr. Murch explained. But lately, that has begun to change. “What is happening more recently with climate change is we’re seeing much larger blooms and more prevalent blooms,” she said. Besides needing nutrients, such as phosphorous and nitrogen, algae thrive in warm temperatures.
Large cyanobacteria blooms have been reported in recent years in Lake Erie and in Lake Winnipeg, Dr. Murch noted. According to the City of Moncton, that region’s first major bloom occurred in 2017 at the Tower Road reservoir, which supplies water to the Moncton area.
It’s still unclear why and under what conditions cyanobacteria produce BMAA. But, since BMAA is just one of a multitude of compounds produced by cyanobacteria that can have harmful effects, researchers who study the algae say large blooms pose a public-health risk, whether it’s through contact (they can cause skin and eye irritation and hay-fever-like symptoms), or ingesting contaminated food or water.
In Guam, Dr. Cox and Dr. Sacks hypothesized that patients received cumulative doses of BMAA by consuming not just flour made with cycad seeds but also by consuming cycad-eating bats called flying foxes, in an effect called biomagnification. In other words, the amounts of the toxin they consumed was magnified when they ate animals that also ate parts of the cycad plants.
The trouble is cyanobacteria produce more than 1,000 different unusual compounds, and for the majority of them, the effects on human health are not yet known, said Larry Brand, a professor in the department of marine biology and ecology at the University of Miami’s Rosenstiel School of Marine and Atmospheric Science. He suggested that more often than we realize, algal toxins may play a role in long-term health problems, such as neurodegenerative illnesses, which develop over decades.
Almost all algal toxins that are known to scientists have been discovered the same way, Dr. Brand explained: A cluster of people or animals fall ill or die within minutes or hours – or at most, a few days – of eating contaminated food or drinking contaminated water, and investigators can trace the source fairly quickly.
But what researchers learned from the suspected role of BMAA in the disease in Guam was that it could take years for certain algal toxins to make people ill, he said. Since people don’t get sick right away, they may continue eating contaminated foods or doing activities that expose them to the toxin. “The point is, if you’re exposed to blue-green algae blooms, you’re going to be exposed to all these hundreds and hundreds of other compounds. And we don’t know what the health effects are going to be,” he said. “You might not see these effects until 10 or 20 years later.”
Ordinarily, he explained, the culprit in such cases would never be identified, since it would be nearly impossible to trace the illness back to consuming a specific type of fish from a specific body of water, for example. But in Guam, since scientists were studying individuals contained on a small island, they were able to home in on BMAA, Dr. Brand said.
Dr. Brand’s own research on algal blooms in the south of Florida has led him to find BMAA in local fish, crabs and shrimp and in the brains of dolphins that died mysteriously. The concentrations of BMAA, he said, were as high, and in some cases, twice as high as those found in the flying foxes that the Chamorro people ate in Guam.
Scientists disagree about how BMAA causes neurodegeneration, Dr. Murch said. And she noted much more research is needed to understand what happens when the toxin gets into the human body.
But, she explained, one hypothesis suggests that when the body synthesizes proteins, which are essential for it to function, BMAA may become erroneously inserted in place of one of the amino acids that form a protein.
Normally, there are 20 amino acids that join together in a chain to form a protein. But in neurodegenerative diseases, these proteins misfold and lose their structure and shape, she said. An erroneous insertion of BMAA is believed to cause this protein misfolding, she said.
Still, not everyone who is exposed has the same likelihood of developing a neurodegenerative disease. Such disorders are believed to arise from a combination of genetic and many environmental factors – cyanobacterial toxins being just one, said Stephanie Bishop, a postdoctoral associate at the University of Calgary, who has spent four years studying cyanobacteria and has worked with Dr. Murch. With the right mix of genetic and other factors, an accumulation of cyanobacterial toxins may put a person at higher risk of developing neurotoxic effects, she said.
In an e-mail, Dr. Cox, the U.S. ethnobotanist with whom Dr. Murch worked in Guam, said scientists’ best understanding of the symptoms of chronic dietary exposure to BMAA comes from the Chamorro people – that is, symptoms with aspects of ALS, Parkinson’s disease and Alzheimer’s disease. Laboratory animals that were exposed to BMAA in their diets developed neuropathology consistent with the disease seen in Chamorro people, he wrote.
But Peter Spencer, a professor of neurology and occupational health sciences at Oregon Health and Science University, said the effects of BMAA are far from clear-cut. A different toxin unique to cycads, called methylazoxymethanol, or MAM, is also believed to play a role – and perhaps a dominant one – in the disease in Guam, he said. To this day, he said, BMAA and MAM are both contenders as culprits for causing that disease.
Even though the presence of BMAA has been reported in fish and shellfish in numerous papers, Dr. Spencer said he doesn’t believe anyone can claim to have pinned any particular neurodegenerative disease to the presence of BMAA in seafood.
Nevertheless, he, too, cautioned that climate change has the potential to make harmful algal blooms more common. And people could increasingly be sickened from seafood contaminated with other kinds of algal toxins. For example, he noted a neurotoxin called domoic acid, produced by algae, caused a major outbreak of illness in Canada in 1987 that killed three people. That outbreak, which caused vomiting, abdominal cramps and diarrhea, was eventually traced to contaminated mussels from Prince Edward Island.
The threat of algal toxins is caused not only by warming bodies of water, which encourage algal growth, but also by the runoff of nutrients from the human use of chemicals and from agriculture, Dr. Spencer said. In other words, regardless of whether they’re responsible for the illness in New Brunswick, algal toxins that contaminate fish and shellfish could pose a big, and growing, problem.
The lack of definitive answers about BMAA and its role in the disease in Guam points to the long road ahead for investigators of the neurological syndrome in New Brunswick.
Dr. Edouard Hendriks of Horizon Health Network, one of the co-chairs of the committee appointed to oversee the New Brunswick investigation, said investigators are looking at all possibilities, and he hoped, over time, their probe would narrow the scope to one or two potential causes. Alternatively, he said, they may find these cases are an unusual presentation of a disease that is already known.
“I know some people have put on the table, ‘Well, could it be this? Could it be that?’ At this point in time, we don’t know,” Dr. Hendriks said. “Everything is on the table.”
Whatever the cause of the syndrome in New Brunswick, Dr. Murch said there’s another important lesson to be learned from Guam. That is, to ensure all of the research and attention directed to solving the mystery doesn’t add to the distress of the communities that are affected. After all, it’s stressful enough being ill, she said.
“One of the things I know from Guam is that people got very tired of being studied by everybody,” she said. “I think it’s important that we treat patients with kindness.”
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