NIH Funds Further Study of Manganese Exposure, Neurological Health
Researchers at Barrow and collaborating institutions have received an R01 grant to study whether environmental exposure to manganese is linked to neurodegenerative disease—just as demand for this mineral is poised to soar.
The National Institutes of Health (NIH) has awarded a $2.9 million R01 grant to Barrow Neurological Institute Chair of Neurology Brad Racette, MD, and his team to continue their research into the neurological impacts of manganese exposure.
The five-year grant will allow Dr. Racette and his collaborators to test their overarching hypothesis that environmental manganese exposure two orders of magnitude below the typical occupational exposure is associated with the progression of parkinsonism and cognitive dysfunction. They further hypothesize that manganese induces this neurodegenerative disease process by promoting inflammation in the brain.
Society has long relied on manganese for the production of steel and other alloys, making the inexpensive and abundant mineral a staple of the construction industry. Now, manganese is drawing a renewed interest due to its appeal in a burgeoning market: electric vehicle batteries.
Dr. Racette is collaborating with epidemiologist Gill Nelson, PhD, of the University of the Witwatersrand in Johannesburg, South Africa; epidemiologist Susan Nielson, PhD, and environmental engineer Jay Turner, DSc, of Washington University in St. Louis; and biostatistician Lianne Sheppard of the University of Washington in Seattle. The researchers hope this work will ultimately inform environmental regulations for manganese worldwide.
But first, they aim to address an environmental justice concern raised by individuals who often lack representation in health research.
20 Years and Counting: Extracting the Neurological Effects of Manganese
Residents of Meyerton, South Africa, a town situated in an industrial valley about 30 miles outside of Johannesburg, contacted the country’s environmental enforcement officials with worries about the smelter in their community. At the time, the smelter was the largest manganese producer in the world and had been operating for more than 50 years. The environmental agency, commonly referred to as “the Green Scorpions,” reached out to Dr. Racette and Dr. Nelson to investigate these concerns.
“I’ve been conducting manganese research for over 20 years,” said Dr. Racette, a neurologist who specializes in movement disorders, like Parkinson’s disease. “Initially, we looked at the neurologic health effects of manganese in welders, with the goal of trying to understand whether manganese exposure in welding rods was a potential cause of Parkinson’s.”
Within a few years of embarking on that project, Dr. Racette became lab partners with Dr. Nelson while the two were taking a class at the London School of Tropical Medicine and Hygiene. At the time, Dr. Nelson worked for the National Institute of Occupational Health in South Africa, where she oversaw the research component of a heart and lung autopsy program. Through this government program, families of mine workers can receive compensation if the worker’s autopsy reveals signs of diseases known to affect miners, such as silicosis and mesothelioma.
“I was interested in whether we could get brains from manganese miners, because about 5% of the mining workforce in South Africa is in manganese mining and my studies in welders had always been clinical studies,” said Dr. Racette, who holds an honorary professor appointment at Wits University’s School of Public Health.
That idea sparked the development of a grant-funded brain autopsy program, through which Dr. Racette has received brain donations from over 90 manganese miners in South Africa for his research.
Airing Grievances: Community Questions Smelter Emissions
A little over five years ago, Dr. Racette and Dr. Nelson launched a pilot study to address the concerns of the Meyerton citizens. This led to an NIH-funded study of more than 800 Black South African residents—about 700 of whom had exposure to emissions from the Meyerton smelter. The study recruited the remaining participants from a non-exposed community about 50 miles away for comparison.
The researchers performed clinical exams on the participants, measuring their motor and cognitive functions as well as their mood. They observed a pattern: the Meyerton residents performed poorly in all three areas compared to the non-exposed population. These findings aligned with those of Dr. Racette’s welder studies.
The study also measured the amount of manganese polluting Meyerton’s air, linking these neurological health effects to concentrations that are consistent with other manganese point sources throughout the world.
“Typically, environmental exposures are several orders of magnitude lower than occupational exposures because a stack distributes the pollution into the air,” Dr. Racette explained. “But it can be more continuous because, as opposed to the occupational setting where you’re working eight hours, people live in those communities and potentially have chronic exposure.”
Answering the Call: R01 to Bring Project Full Circle
With this R01 grant, Dr. Racette and his team will revisit that same cohort in South Africa to determine whether the participants’ motor and cognitive symptoms have worsened over time. The researchers will also expand their assessments to include loss of smell, a possible early indicator of Parkinson’s disease, and non-motor symptoms of the disease, such as bladder and bowel dysfunction.
To better understand how manganese exposure may be wreaking havoc on the brain, the researchers will also scan the brains of about a quarter of the participants using magnetic resonance imaging (MRI). The scans will include sequences designed to specifically assess neuroinflammation, which emerged as a likely disease mechanism in the preliminary data.
“Whether the source is a manganese battery plant or a smelter, we still need to determine the safe exposure levels. Understanding the lifecycle of these metals is important so that we understand all the effects of our attempts to de-carbonize the environment.”
Brad Racette, MD
The team will again measure the amount of manganese in the Meyerton air using more sophisticated environmental modeling techniques than were previously available.
Interestingly, the smelter shut down right around the beginning of the COVID-19 pandemic. Nevertheless, after 50 years of operation, the smelter seems to have left an indelible mark on the community—between the abandoned waste piled as high as the factory and the black manganese dust that has settled into the soil over five decades.
“Last time we performed air measurements, after the smelter shut down, we found that the people in the community were still exposed to high levels of manganese,” Dr. Racette said. “So we’re able to look at the legacy effects of the smelter as well, and part of the study is trying to understand how much exposure we anticipate going forward for Meyerton residents.”
The study will culminate in developing and disseminating culturally appropriate materials to communicate the results to Meyerton residents. “It really brings it full circle to the community,” Dr. Racette said. “They brought the question to us, and we’ll report back to them.”
Between a Rock and a Hard Place: Considering the Lifecycle of Manganese
Dr. Racette said the story of the Meyerton smelter represents a common theme in occupational and environmental research: the communities harmed by a particular industry often benefit very little, if at all, from that industry.
“Very few people in the Meyerton settlements we studied actually worked at the smelter,” Dr. Racette explained. “The people who have been poisoned with decades of pollution probably have received very little economic benefit from this company. It’s a serious health equity and environmental justice issue.”
And Dr. Racette fears history will repeat itself with the manganese battery industry. “The virtue of the electric vehicle goes away completely if we’ve poisoned a developing country in the process of trying to manufacture a clean-energy vehicle,” he said.
The electric vehicle battery industry also brings new forms of exposure to investigate, from the molten manganese in the battery plants themselves to the unprecedented challenge of disposing of these batteries, which weigh over 1,000 pounds on average, at the end of their lifespan.
“Whether the source is a manganese battery plant or a smelter, we still need to determine the safe exposure levels,” Dr. Racette said. “Understanding the lifecycle of these metals is important so that we understand all the effects of our attempts to de-carbonize the environment.”