Gosse caps decade of research into troublesome triclosan
University of Maine toxicologist Julie Gosse spent a decade unearthing the medical harm posed by the germ-fighting agent triclosan (TCS).
Manufacturers had included the synthetic chemical in soap, toothpaste, facial cleansers, sanitizer and other common products since the 1970s, when no research delved into its health and toxicological effects. Products containing the antimicrobial agent filled store shelves. By the time Gosse and her students began investigating it, 75% of Americans were exposed to it, according to the National Health and Nutrition Examination Survey.
Various studies in the past 10 years, however, have revealed problems with TCS, that it weakens disease resistance and interferes with various bodily functions. Research led and overseen by Gosse, an associate professor of biochemistry, found TCS inhibits immune cells, particularly T and mast cells, and damages mitochondria. Investigations from other toxicologists and experts also uncovered that TCS can harm human fertility, development, intelligence and thyroid function.
Growing scientific evidence from Gosse and other scientists inspired public outcry against TCS and government intervention. The U.S. Food and Drug Administration (FDA) banned TCS from bar soaps, liquid soaps and body washes in 2016; hospital soaps in 2017 and hand-sanitizer in 2019 prior to the COVID-19 pandemic.
The chemical has since been removed from almost all products. When Gosse wrapped up her TCS research with a final paper, she sent two graduate students to the grocery store to search for any goods with it. They found none.
“I think the public became aware of triclosan’s toxicity, so the decision was really made by consumers,” says Gosse, who has published eight research papers on TCS, the most recent in October 2020.
The now controversial antimicrobial agent had not entered the UMaine toxicologist’s radar until she watched a presentation by Environmental Protection Agency scientist Susan Richardson, hosted at UMaine 10 years ago.
Richardson noted that the antimicrobial agent resembled a dioxin, or toxic environmental pollutant. Despite experts producing virtually no toxicological literature for the chemical, it had become widespread, which Gosse says she and Richardson found troubling.
“Here we have a chemical to which the vast majority of Americans are exposed, and we have no idea what it does to their health,” Gosse says.
Her then graduate student, Rachel Kennedy, sprinted to Gosse’s lab to search for any medical literature about TCS. Kennedy found only a couple of studies about the chemical pertaining to its ability to disrupt cells in the endocrine system. Gosse and her students were studying endocrine disruptors at the time, so Kennedy delved deeper into TCS.
The work conducted by Kennedy, her colleagues and Gosse resulted in the UMaine researchers’ first study into the antimicrobial agent, which concluded that TCS suppresses mast cell function. The former UMaine graduate student was the first author of the paper.
“She just dove right into the research,” Gosse says about Kennedy, now a medical liaison for EMD Serono Inc. in Rockland, Massachusetts. “Ever since, we’ve been trying to figure out the exact biochemistry that causes that cellular disruption.”
The study launched a series of investigations into TCS from Gosse’s lab. Research from the UMaine toxicologist and her partners found out how the antimicrobial agent suppresses mast and T cells, particularly mast cell signaling, and that it damages mitochondria in immune and nonimmune human, rodent and other cells, as well as in living zebrafish. Mitochondria provide energy that cells need to perform various tasks, including combating disease.
The National Institutes of Health, the U.S. Department of Agriculture, Maine Agricultural and Forest Experiment Station, Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation, and UMaine provide vital funding for Gosse’s research.
Lisa Weatherly, a former Ph.D. student of biomedical sciences from the Graduate School of Biomedical Sciences and Engineering, led the first study from Gosse’s lab that revealed how TCS as a toxicant harms mitochondria. The UMaine toxicologist says Weatherly was also the first to use “super resolution microscopy in the field of toxicology,” in particular, the fluorescence photoactivation localization microscopy (FPALM) technique developed by professor of physics Sam Hess. Using FPALM, they watched TCS deform live mitochondria in real time.
Gosse says without Weatherly’s hard work, several papers may not have been produced. The former UMaine student now serves as a researcher at the Centers for Disease Control and Prevention National Institute for Occupational Safety and Health (CDC/NIOSH) in Morgantown, West Virginia.
“We wanted to continue studying this as long as people continued to be exposed,” Gosse says. “If you know what a chemical does, the causes and effects, you might be able to predict what the next chemical with a similar structure will do.”
Widespread integration served as an undoing for TCS, which is intended to slow or stop bacteria and mildew growth.
Incorporating it into numerous products for the majority of Americans to consume resulted in TCS becoming less effective, Gosse says. Bacteria had grown resistant to the chemical, making its implementation useless in many goods while still posing health risks.
Rather than banning TCS outright, however, the FDA tasked companies with proving that its inclusion provided benefits. When companies declined to demonstrate the benefits of TCS in their goods, the FDA forced them to remove the chemical.
One business, Colgate-Palmolive, however, was able to keep TCS in its Colgate Total toothpaste after demonstrating that the product can combat gingivitis better than products without the antimicrobial agent. Public pressure, however, eventually prompted Colgate-Palmolive to remove TCS from its product.
Gosse says the benefits of Colgate Total for consumers with gingivitis outweighed the risks, but likely not so for other users. The toothpaste, she says, should have been marketed only to people with the disease.
“The last triclosan product really standing was Colgate Total toothpaste,” she said.
Several companies still used TCS for their products up until Gosse published her last paper on the component, with a few products like cutting boards and baby products that are not regulated by the FDA still containing it.
After years of investigation, Gosse and her fellow researchers determined why TCS inhibited immune cell function. They knew the antimicrobial agent stifled the inflow of calcium into the cell cytoplasm, a necessary function for immunity, but lacked the findings to define how it occurred.
A team of scientists, led by former UMaine master’s student Suraj Sangroula and former UMaine undergraduate student Alan Baez Vasquez found, to Gosse’s surprise, that TCS is acidic. The chemical releases enough acid to deform the calcium channels leading into the cytoplasm in immune cells, preventing them from absorbing calcium and, therefore, from responding to various threats such as pathogens, allergens or inflammation. The finding serves as the culmination of 10 years of research from Gosse’s lab, capping its investigations into TCS.
The study also revealed new details about the biological pathway calcium follows throughout the cell. Gosse says by understanding how a chemical affects users, scientists can begin to predict how others with similar structures may act.
Sangroula, Baez Vazquez, Gosse and their UMaine colleagues were joined by former student Juyoung Shim, now an assistant professor of biology at the University of Maine at Augusta. Toxicology and Applied Pharmacology published a paper describing their fundings in its October 2020 issue.
“They really did the precision experiments to prove (their hypothesis)” Gosse says about Sangroula and Baez Vazquez. “Their experimental data replicated the exact conclusion drawn from their theoretical calculations.”
The several TCS studies from Gosse’s lab involved 12 UMaine graduate students, 19 undergraduate students, two students from the University of Maine at Farmington and University of Maine at Presque Isle, six UMaine professors and four senior research collaborators from other institutions.
Findings produced from Gosse’s lab provided knowledge that informed everyday people, assisted in government decision making and trained a new generation of scientists and other professionals, all of which the UMaine toxicologist says are crucial services from a research institution.
Many of Gosse’s former and current students use the skills they learned in their lab to excel in later academic studies and careers in pharmacology, biotechnology, medicine, teaching and other fields. Senior Bailey West, for example, will receive the Society of Toxicology Undergraduate Student Research Award at the society’s 2021 Virtual Annual Meeting in March.
After leading the final TCS study from Gosse’s lab, Sangroula graduated and now serves on the front lines of vaccine production for COVID-19. While working as a pharmaceutical validation engineer for Clarke Solutions, Bloomington, Indiana, Sangroula serves as a consultant for Catalent, which is mass producing vaccines for Moderna and Johnson & Johnson. The UMaine alumnus helps validate equipment to fill vials as part of Project Apollo.
Baez Vasquez enrolled in Harvard University’s molecules, cells and organisms program as a Ph.D. student after graduating from UMaine.
Students who succeed in Gosse’s lab prove to be naturally hard workers with the patience and dedication needed to complete challenging experiments that lead to answers to hard-hitting questions. The UMaine toxicologist says she considers her students research partners, some who unveil findings she may have overlooked while performing other duties.
Watching her students achieve milestones in their research and academic careers, and create novel knowledge, is the “the best thing in the world,” Gosse says.
“I’ve been very lucky to have several awesome undergraduate and graduate students,” Gosse says.
With the mechanism behind triclosan’s ability to weaken immunity uncovered, and the chemical effectively removed from store shelves, Gosse says there is no further need for her lab to research it.
Many of the about 80,000 synthetic chemicals in circulation contain little toxicological data and need to be studied, Gosse says. The UMaine biochemistry professor has already begun exploring another chemical with current graduate student research partners Bright Obeng and Sasha Weller, exploring another chemical widely used among the general public via personal care products.
“We are now moving on to study new chemicals of interest, to which people are widely exposed but for which there is little or no published toxicological or epidemiological data,” Gosse says. “The overarching goal of toxicology research is to protect human and environmental health.”
Contact: Marcus Wolf, 207.581.3721; email@example.com