Investigation raises questions over lack of “substantial evidence” for FDA approved antibiotic

Did new antibiotic meet the legal standard for approval? Are US drug regulatory rules being bypassed?

Peer-Reviewed Publication

BMJ

Drugs approved in the US require “substantial evidence” that they are effective. But an investigation by The BMJ into the recent approval of the antibiotic Recarbrio from Merck suggests that these standards are being bypassed.

Peter Doshi, senior editor at The BMJ, describes how US Food and Drug Administration (FDA) scientists had serious doubts about Recarbrio - a product 40 times more expensive than an existing generic alternative - but the agency approved it anyway.

Did the FDA break its own rules in approving this antibiotic, and what does this case tell us about problems within the agency, he asks? 

Recarbrio is a combination therapy made up of a new beta-lactamase inhibitor (relebactam) and a decades old Merck antibiotic (imipenem-cilastatin) to treat complicated infections. It costs between $4,000 and $15,000 for a course, compared with a couple of hundred dollars for the generic version of Merck’s old antibiotic.

In its FDA application, Merck submitted results from two clinical trials comparing Recarbrio with imipenem in adults with complicated urinary tract infections and in patients with complex intra-abdominal infections.

But FDA reviewers noted that Merck had studied the wrong patient population to evaluate the added benefits of the new drug, and said the trial for urinary tract infections showed that Recarbrio was as much as 21% worse in effectiveness than the older, less-expensive imipenem.

The FDA concluded that “these studies are not considered adequate and well-controlled.” And of a third clinical study, the FDA called it a “very small,” “difficult to interpret” “descriptive trial with no pre-specified plans for hypothesis testing.”

Yet despite all three clinical studies not providing substantial evidence of effectiveness, FDA approved Recarbrio.

“Instead of basing its decision on the clinical trials in Merck’s application, FDA’s determination of Recarbrio’s efficacy was justified on past evidence that imipenem was effective, plus - to justify the new relebactam component - in vitro (lab) studies and animal models of infection rather than evidence from human trials as required by law,” writes Doshi.

Others are concerned that Recarbrio’s approval essentially amounts to a return to a way of regulating medicines that the FDA abandoned a half century ago prior to the agency’s “substantial evidence” standard.

Doshi explains that, under specific circumstances, the Director of the Center for Drug Evaluation and Research (CDER) can waive in whole or in part the FDA’s “adequate and well-controlled studies” approval criteria. But the FDA told The BMJ ”there was no center director memo in the file” for Recarbrio.

And when The BMJ contacted Janet Woodcock, CDER Director at the time, and now the FDA’s Principal Deputy Commissioner, she said she was not aware that the clinical studies of Recarbrio did not provide substantial evidence of effectiveness.

Woodcock was also unable to confirm that approvals of new drugs require at least one clinical study of the drug itself that demonstrates substantial evidence - evidence lacking in the case of Recarbrio.

A spokesperson for CDER told The BMJ that FDA “applied regulatory flexibility” in approving Recarbrio. 

It is unclear whether this regulatory flexibility enabled FDA to conclude Recarbrio had met the legal “substantial evidence” standard without “adequate and well-controlled investigations” of Recarbrio, says Doshi. FDA declined to answer the question, saying “We have no additional information to provide.”

The decline of science at the FDA has become unmanageable, argues David Ross, associate clinical professor of medicine at George Washington University, School of Medicine and Health Sciences, and former FDA medical reviewer, in a linked commentary.

He describes Recarbrio’s approval as “shocking” and says while much of the blame must go to the FDA’s reliance on industry paid user fees for around two-thirds of its annual drugs budget, “the corruption of the FDA’s scientific culture remains the primary culprit driving the deterioration of safety and effectiveness standards.”

To address this “dismal situation” he suggests tapering the FDA’s dependence on user fees and improving public access to the information received by the FDA, its reasoning, and its decisions.

“The Recarbrio approval is a sentinel event, warning of a return to an era when drug effectiveness was an afterthought,” argues Ross. “Although the FDA crowed about this approval, it would have been better advised to remember that “for a successful technology, reality must take precedence over public relations, for nature cannot be fooled,” he concludes.

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JOURNAL

The BMJ

DOI

10.1136/bmj.p1048 

ARTICLE TITLE

Investigation: Did the FDA break its own rules in approving the antibiotic Recarbrio?

ARTICLE PUBLICATION DATE

15-May-2023

COI STATEMENT

https://www.bmj.com/about-bmj/editorial-staff/peter-doshi

Porous crystals made from plant

extracts purify water from

pharmaceutical pollutants

Researchers from Stockholm University have developed porous crystals made from pomegranate extract to capture and degrade pharmaceutical molecules found in local municipal wastewater. The research is published in the scientific journal Nature Water.

Peer-Reviewed Publication

STOCKHOLM UNIVERSITY

 

IMAGE: PART OF AN SU-102 CRYSTAL. THE DARK AREAS ARE ONE NANOMETER WIDE PORES, THE IMAGE WAS TAKEN USING AN ELECTRON MICROSCOPE. view more 

CREDIT: TOM WILLHAMMAR

Researchers from Stockholm University have developed porous crystals made from pomegranate extract to capture and degrade pharmaceutical molecules found in local municipal wastewater. The research is published in the scientific journal Nature Water.

Pharmaceutical compounds affect the human body to improve our health, but they can also have unintentional adverse effects for the wellbeing of wildlife. Hence wastewater treatment plants are facing the challenge of removing emerging organic contaminants (EOCs) such as active pharmaceutical ingredients, and therefore new materials and technologies are required.

One strategy for removing pollutants from water is by using porous materials that behave like sponges. Metal-organic frameworks, so called MOFs, are a type of nanoporous material that are made of metal ions and organic molecules. Most MOFs are made using synthetic organic molecules. But now researchers from the Department of Materials and Environmental Chemistry, Stockholm University, have managed to develop new porous MOFs using a naturally occurring molecule found in plants – ellagic acid. 

“Ellagic acid is one of the main building units of naturally occurring polyphenols known as tannins, which are common in fruits, berries, nuts, and tree bark. By combining ellagic acid, which was extracted from either pomegranate peel or tree bark, with zirconium ions, we developed a new highly porous MOF which we named SU-102,” says Erik Svensson Grape, PhD student at the Department of Materials and Environmental Chemistry.

In order to test the performance of SU-102, water that had already been purified at a local wastewater treatment facility was further treated with the new MOF. The results showed that SU-102 removed many of the pharmaceutical pollutants that were not fully removed by the wastewater treatment facility. In addition to capturing the pharmaceutical pollutants, SU-102 was also used to break down pollutants using light in a process known as photodegradation.

“This has been a very exciting project as we got the opportunity to work directly with water samples from the treatment plant, thereby finding an application where our material could be put to use towards a very pressing environmental issue. We hope one day that SU-102 will be used on a bigger scale and also for other environmental applications,” says Erik Svensson Grape at Stockholm University.

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JOURNAL

Nature Water

DOI

10.1038/s44221-023-00070-z 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Removal of pharmaceutical pollutants from effluent by a plant-based metal–organic framework

ARTICLE PUBLICATION DATE

15-May-2023

Dementia study reveals how toxic proteins spread through brain

Peer-Reviewed Publication

UNIVERSITY OF EDINBURGH

Fresh insights into the spread of damaging proteins that build up in the brains of people with Alzheimer’s disease could hold the key to stopping the condition progressing, a study says.

Researchers have discovered that synapses, which send essential signals through the brain, are also transporting toxic proteins known as tau around the brain.

Large clumps of the protein tau – called tangles – form in brain cells and are one of the defining features of Alzheimer’s disease. As these tangles spread through the brain during the disease there is a decline in brain function.

Led by the University of Edinburgh, the study focused on synapses, connections which allow the flow of chemical and electrical messages between brain cells and are vital to healthy brain function. Alzheimer’s disease attacks synapses and their loss strongly predicts reduced memory and thinking abilities.

In the study, scientists examined more than one million synapses from 42 people using powerful microscopy techniques to visualise proteins within individual synapses.

The team discovered that small clumps of the protein tau – known as tau oligomers – are found within the synapses of people who died of Alzheimer’s disease.

Tangles of tau oligomers were seen inside both ends of the synapse – from the brain cell sending signals and the brain cell receiving signals.

In a mouse model of the disease, the oligomers jumped from one side of the synapse to the other, spreading the toxic tau through the brain.

Lowering oligomeric tau at synapses may be a promising strategy to stop disease progression in future, experts say.

Alzheimer’s disease is the most common form of dementia, with currently around 900,000 people with the condition in the UK. This figure is projected to rise to nearly 1.6 million in 2040. It can cause severe memory loss and there is currently no cure.

The study is published in the journal Neuron: https://doi.org/10.1016/j.neuron.2023.04.020. [URL will become active after embargo lifts]. The research team included scientists from the University of Edinburgh, the UK Dementia Research Institute, the Institut d'Investigacions Biomèdiques Hospital de Sant Pau and the Institute for Advanced Chemistry of Catalonia (Barcelona).

Lead researcher, Professor Tara-Spires Jones of the UK Dementia Research Institute at the University of Edinburgh, said: “We have known for over 30 years that tangles spread through the brain during Alzheimer’s disease, but how they spread has remained a mystery. Wherever tangles appear in the brain, neuron death follows, contributing to the decline in cognitive ability. Stopping the spread of toxic tau is a promising strategy to stop the disease in its tracks.”

For further information, please contact: Jess Conway, Press and PR Office, 07979 446 209 jess.conway@ed.ac.uk  

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JOURNAL

Neuron

DOI

10.1016/j.neuron.2023.04.020 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Synaptic oligomeric tau in Alzheimer’s disease – a potential culprit in the spread of tau pathology through the brain

ARTICLE PUBLICATION DATE

15-May-2023

Chemical exposure may raise your risk for Parkinson’s

Symptoms take decades to develop, UCSF-SFVA led study shows

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

Two years of heavy exposure to TCE, a liquid chemical that lingers in the air, water and soil, may increase the risk of Parkinson’s disease by 70%. 
 
Previous research has linked TCE, or trichloroethylene, to certain cancers, but a new study publishing in JAMA Neurology on May 15, 2023, is believed to be the first large-scale study to demonstrate its association with Parkinson’s.   
 
TCE has been used for industrial and commercial purposes for nearly 100 years, and was used as a surgical anesthetic until it was banned in 1977. More recently it was used as a degreasing solvent. Today, it is primarily used to degrease industrial metal parts. This entails heating TCE in degreasing tanks to create a vapor that dissolves the grease, but it also releases the chemical into the atmosphere. Once TCE enters the soil or groundwater, it can persist for decades.  
 
In the study, researchers led by UC San Francisco and the San Francisco VA Medical Center, compared Parkinson’s diagnoses in approximately 160,000 Navy and Marine veterans. Just over half came from Camp Lejeune in North Carolina, where TCE was used to degrease military equipment and water was contaminated; the remainder came from Camp Pendleton in California, where the water was not contaminated.  
 
Service members spent at least three months in the camps between 1975 to 1985, a period when TCE in the water at Camp Lejeune exceeded maximum safety levels by 70-fold. The researchers had access to follow-up health data on the service members between 1997 and 2021, by which time Parkinson’s might be expected to develop. 
 
Researchers found that 430 veterans had been diagnosed with Parkinson’s, and that the Lejeune veterans’ risk was 70% higher than the Pendleton veterans. On average, service members of both camps were stationed there approximately two years from 1975 to 1985. Residence began at an average age of 20, and Parkinson’s diagnosis occurred at an average age of 54 at Lejeune and 53 at Pendleton, showing that the disease took decades to develop after TCE exposure.  
 
The civilian population is also at risk of TCE exposure, said first author Samuel M. Goldman, MD, MPH, of the UCSF Division of Occupational, Environmental and Climate Medicine, and the SFVA, noting that between 9% and 34% of U.S. water supplies contain measurable amounts of the chemical.   
 
 TCE Production Has Increased  
 
“TCE is still a very commonly used chemical in the United States and throughout the world. Its production has been increasing over the past several years and it is widely available online,” he said.  
 
“Unfortunately, there’s no easy way to know if you’ve been exposed, unless you’ve worked with it directly. Many of us have detectable levels of TCE in our bodies, but it gets metabolized and excreted very quickly, so blood and urine tests only reflect very recent exposure.” 
 
Additionally, the researchers found that the Lejeune veterans had a higher prevalence of prodromal Parkinson’s – symptoms that are suggestive of Parkinson’s but do not yet fulfill diagnostic criteria for the disease.   
 
“Loss of sense of smell, a sleep disorder known as RBD, anxiety, depression and constipation can be early signs of Parkinson’s, but only a very small fraction of people with them will develop it,” said senior author Caroline M. Tanner, MD, PhD, of the UCSF Department of Neurology, the Weill Institute for Neurosciences and the SFVA.  
 
“The risk of developing Parkinson’s in the future can be estimated using a risk score based on these symptoms. The Lejeune veterans had higher risk scores than the Pendleton veterans, suggesting that they are more likely to develop Parkinson’s in the future.” 
 
Co-Authors and Disclosures: Please see the paper. 

Funding: This research was supported by clinical science research and development merit award I01 CX002040-01 from the U.S. Department of Veterans Affairs. Support for Veterans Administration (VA)/Centers for Medicare & Medicaid Services data was from the U.S. Department of Veterans Affairs, VA Health Services Research and Development Service, and project numbers SDR 02-237 and 98-004 from the VA Information Resource Center. 

 

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at https://ucsf.edu, or see our Fact Sheet.

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JOURNAL

JAMA Neurology

ARTICLE PUBLICATION DATE

15-May-2023

Risk of Parkinson disease among service

members at Marine Corps Base Camp

Lejeune

JAMA Neurology

Peer-Reviewed Publication

JAMA NETWORK

About The Study: This study of 340,000 service members found that the risk of Parkinson disease was 70% higher in veterans who were stationed at Marine Corps Base Camp Lejeune, North Carolina, during 1975-1985 when the water supply was contaminated with the solvent trichloroethylene and other volatile organic compounds. The findings suggest that exposure to trichloroethylene in water may increase the risk of Parkinson disease; millions worldwide have been and continue to be exposed to this ubiquitous environmental contaminant.

Authors: Samuel M. Goldman, M.D., M.P.H., of the University of California, San Francisco, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaneurol.2023.1168)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2023.1168?guestAccessKey=49157dd3-61b6-407f-b910-797c1a489b84&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=051523

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JOURNAL

JAMA Neurology

Heat-loving marine bacteria can help detoxify asbestos

Peer-Reviewed Publication

AMERICAN SOCIETY FOR MICROBIOLOGY

Asbestos materials were once widely used in homes, buildings, automobile brakes and many other built materials due to their strength and resistance to heat and fire, as well as to their low electrical conductivity. Unfortunately, asbestos exposure through inhalation of small fiber particles has been shown to be highly carcinogenic. 

Now, for the first time, researchers from the University of Pennsylvania have shown that extremophilic bacteria from high temperature marine environments can be used to reduce asbestos’ toxicity. The research is published in Applied and Environmental Microbiology, a journal of the American Society for Microbiology. 

Much of their research has focused on use of the thermophilic bacterium Deferrisoma palaeochoriense to remove iron from asbestos minerals through anaerobic respiration of that iron. “Iron has been identified as a major component driving the toxicity of asbestos minerals and its removal from asbestos minerals has been shown to decrease their toxic properties,” said Ileana Pérez-Rodríguez, Ph.D., Assistant Professor of Earth and Environmental Science at the University of Pennsylvania. 

D. palaeochoriense has also been shown to mediate transfer of electrical charge within the iron contained in asbestos, without changing its mineral structure. Doing so might enhance asbestos’ electrical conductivity, said Pérez-Rodríguez.

Based on this observation, the bacterium could be used to treat asbestos’ toxicity through iron removal. Alternatively, the new properties of electrical conductivity could enable reuse of treated asbestos for that purpose.  

As with iron, the fibrous silicate structures of asbestos are also carcinogenic. Removal of silicon and magnesium from asbestos has been shown to disrupt its fibrous structure. The investigators tested the ability of the thermophilic bacterium Thermovibrio ammonificans to remove these elements from asbestos minerals by accumulating silicon in its biomass in a process known as biosilicification.  

T. ammonificans accumulated silicon in its biomass when in the presence of “serpentine” asbestos, which has curly fibers, but not while growing in the presence of “amphibole” asbestos, which has straight fibers, said Pérez-Rodríguez. This difference, along with the varying amounts and types of elements released during microbe-mineral interactions with different types of asbestos “highlights the difficulty of approaching asbestos treatments as a one-size-fits-all solution, given the unique chemical compositions and crystal structures associated with each asbestos mineral,” Pérez-Rodríguez said. 

Overall, these experiments promoted the removal of iron, silicon and/or magnesium for the detoxification of asbestos in a superior manner as compared to other biologically mediated detoxification of asbestos, such as via fungi, said Pérez-Rodríguez. However, further analysis will be required to optimize asbestos treatments to determine the most practical methods for the detoxification and/or reuse of asbestos as secondary raw materials.

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 30,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences.

ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.

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JOURNAL

Applied and Environmental Microbiology

Communities of color disproportionately exposed to PFAS pollution in drinking water

Peer-Reviewed Publication

HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH

Boston, MA – People who live in communities with higher proportions of Black and Hispanic/Latino residents are more likely to be exposed to harmful levels of per- and polyfluoroalkyl substances (PFAS) in their water supplies than people living in other communities, according to a new study led by researchers from Harvard T.H. Chan School of Public Health. The researchers link this finding to the disproportionate siting of sources of PFAS pollution—such as major manufacturers, airports, military bases, wastewater treatment plants, and landfills—near watersheds serving these communities.

The study will be published online May 15, 2023, in Environmental Science & Technology.

In March, the EPA proposed the first-ever national drinking water regulation for six PFAS, which it anticipates finalizing by the end of 2023. The regulation would establish maximum contaminant levels of two PFAS compounds, PFOA and PFOS, at 4 parts per trillion (4 ng/L) and limit the other four. The public comment period ends on May 30.

“Our work suggests that the sociodemographic groups that are often stressed by other factors, including marginalization, racism, and poverty, are also more highly exposed to PFAS in drinking water,” said first author Jahred Liddie, a PhD student in population health sciences at Harvard Chan School. “Environmental justice is a major emphasis of the current administration and this work shows it should be considered in the upcoming regulations for PFAS in drinking water.”

This is the first peer-reviewed study to show sociodemographic disparities in drinking water PFAS exposures and to statistically link sources such as landfills and airports to PFAS concentrations in community water systems over broad geographic scales.

PFAS—dubbed “forever chemicals” because of their extreme persistence in the environment due to their characteristic fluorine-carbon backbone—are artificial compounds widely used for their stain-resistant and water-resistant properties. PFAS exposure has been associated with numerous adverse health outcomes, including diabetes, cardiovascular disease, and cancer.

The researchers used PFAS monitoring data from 7,873 U.S. community water systems in the 18 states in which such data is widespread: California, Colorado, Illinois, Indiana, Kentucky, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Jersey, New York, Ohio, Pennsylvania, South Carolina, Utah, Vermont, and Wisconsin. Their analysis included 44,111 samples collected between January 2016 and August 2022. They also looked at the geographic locations of PFAS sources from multiple databases.

The study found that PFAS detection was positively associated with the number of PFAS sources and proportions of people of color who are served by a water system. Each additional industrial facility, military fire training area, and airport in a community water system’s watershed was associated with a 10%−108% increase in perfluorooctanoic acid and a 20%−34% increase in perfluorooctane sulfonic acid in drinking water.

According to the researchers, about 25% of the population in the 18 states considered in their study were served by community water systems that had levels of PFAS above 5 ng/L. Per this estimate, if the EPA’s new proposed level of 4 ng/L is implemented, more than 25% of all Americans are likely to be considered exposed to dangerous levels of PFAS.

“Our findings are particularly concerning because past work on environmental disparities for other pollutants shows marginalized populations are susceptible to greater risks of adverse health outcomes compared to other populations, even at the same exposure levels,” said senior author Elsie Sunderland, Fred Kavli Professor of Environmental Chemistry and professor of earth and planetary sciences at the Harvard John A. Paulson School of Engineering and Applied Sciences and professor of environmental science and engineering in the Department of Environmental Health at Harvard Chan School. “Regulating releases from PFAS sources and ensuring that people have safe drinking water is especially important in the most vulnerable communities to protect public health.”

Laurel Schaider at Silent Spring Institute was a co-author.

This research was supported by the National Institute of Environmental Health Sciences (NIEHS) grant P42ES027706, grant R01ES028311, and an NIEHS training grant (T32 E007069).

“Sociodemographic Factors Are Associated with the Abundance of PFAS Sources and Detection in U.S. Community Water Systems,” Jahred M. Liddie, Laurel A. Schaider, Elsie M. Sunderland, Environmental Science & Technology, online May 15, 2023, doi: 10.1021/acs.est.2c07255

Visit the Harvard Chan School website for the latest news, press releases, and multimedia offerings.

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Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives—not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health.

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JOURNAL

Environmental Science & Technology

DOI

10.1021/acs.est.2c07255 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Sociodemographic Factors Are Associated with the Abundance of PFAS Sources and Detection in U.S. Community Water Systems

ARTICLE PUBLICATION DATE

15-May-2023

EPA's new PFAS rules don’t account for major source of drinking water contamination

Harvard study reveals unmonitored PFAS build up and last for centuries

Peer-Reviewed Publication

HARVARD JOHN A. PAULSON SCHOOL OF ENGINEERING AND APPLIED SCIENCES

 

IMAGE: MEMBERS OF THE SUNDERLAND LAB SAMPLING FOR PFAS CONTAMINATION ON CAPE COD view more 

CREDIT: MICHAEL SALERNO

CAPE COD, MASSACHUSETTS – Earlier this year, the US Environmental Protection Agency proposed maximum allowable levels in drinking water for six PFAS (per- and polyfluoroalkyl substances) – so-called forever chemicals. But the draft standards do not account for half of the PFAS at contaminated sites across the country.

The findings are from a team led by the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and are published in the journal Environmental Science & Technology.

PFAS are present in fire retardant foams among other products and have been building up in the environment since they were first invented by Dupont in the 1930s and manufactured widely by 3M beginning in the 1950s. Exposures to some PFAS are linked to a range of health risks including cancer, immune suppression, diabetes, and low infant birth weight.

PFAS compounds come in two forms: a precursor form and a terminal form. Most of the monitored PFAS compounds are terminal compounds. The EPA’s draft drinking water rules are for six terminal compounds that do not degrade under normal environmental conditions. Precursor compounds can be transformed through biological or environmental processes into terminal forms. There are many precursor compounds, most of which are not routinely monitored, and none are currently regulated.

The U.S. military is the largest global user of fire-retardant foams containing PFAS known as AFFF (aqueous film forming foam). For decades, hundreds of military bases across the U.S. and around the world used AFFF containing high levels of PFAS for fire training drills and fighting fires. AFFF use is one of the largest sources of PFAS contamination in drinking water.

“Many PFAS precursors present in AFFF are difficult to measure. This work shows that they are slowly transforming into PFAS of health concern at AFFF-contaminated sites and contributing to downstream contamination” said Elsie Sunderland, Fred Kavli Professor of Environmental Chemistry and Professor of Earth and Planetary Sciences at SEAS and senior author on the new paper.

Much of the PFAS at military sites consists of precursors that are omitted from standard analytical methods. Using a method previously developed in the Sunderland lab that captures all precursors in AFFF, the Harvard team modeled the expected duration and contribution of those precursors to groundwater contamination. The study finds that contamination of two of the newly regulated PFAS chemicals (perfluorohexane sulfonate: PFHxS and perfluorbutane sulfonate: PFBS) at one military base on Cape Cod, Massachusetts are sustained by microbial precursor biotransformation in the soil. These precursors are retained in the soil where they leach into groundwater in terminal form at concentrations thousands of times greater than the safe levels established by the EPA.  

The researchers projected using a computer model and field data that, without remediation, widespread PFAS contamination of drinking water supplies near military facilities is likely to persist for centuries. Despite contamination of nearby aquifers that may already pose a risk to human health, the majority of PFAS are still sitting in the soils surrounding these contaminated sites, emphasizing the urgent need for advances in remediation technology that are effective at cleaning up both terminal and precursor compounds. Since regulations focus only on terminal compounds, the effectiveness of current remediation technologies at cleaning up precursors is not known.

The researchers concluded that elevated PFAS exposures downstream of more than 300 U.S. military facilities that used the fire-fighting foams could similarly persist for centuries.

“The role of PFAS precursors in sustaining hazardous levels of contamination at Joint Base Cape Cod raises concern about whether exposure risks are underestimated near hundreds of other sites where they are not measured” said Bridger Ruyle, the first author of the study and former doctoral student in Sunderland’s Lab.

The public comment period for EPA’s draft PFAS drinking water regulation closes on May 30. While a step in the right direction, there are thousands of PFAS chemical structures, several hundred of which have already been detected in the environment, Sunderland notes.

In related work also published in Environmental Science & Technology today, Sunderland’s group also has shown that the number of military fire training areas within a watershed is a good predictor for PFAS contamination in a community’s drinking water supply. But some groups are at higher risk than others; a forthcoming publication by the Sunderland lab documents marked sociodemographic disparities in exposures to PFAS and proximity to PFAS sources across the country. 

Additional authors include Colin Thackray and Chad Vecitis of Harvard; Craig Butt of AB Sciex LLC; and Denis LeBlanc and Andrea Tokranov of the U.S. Geological Survey.

Funding for the research was provided by the Department of Defense Strategic Environmental Research and Development Program (SERDP ER18-1280) and the U.S. National Institute for Environmental Health Sciences Superfund Research Program (P4ES027706). Additional support was provided by the U.S. Geological Survey Toxic Substances Hydrology Program.

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JOURNAL

Environmental Science & Technology

METHOD OF RESEARCH

Observational study

ARTICLE TITLE

Centurial Persistence of Forever Chemicals at Military Fire Training 2 Sites

ARTICLE PUBLICATION DATE

15-May-2023

Chile’s mining royalty bill heads for final vote

Cecilia Jamasmie | May 11, 2023 | 

Andina Transfer station sits at 3,500 metres above sea level. (Image courtesy of Codelco | Flickr.)

Chile’s senate has approved an amended mining royalty bill, in the works for almost two years, passing it back to the lower chamber for a final vote expected to come as early as next week.


The proposed law, first introduced in 2018, originally called for a flat-rate ad valorem tax of 3% on large-scale copper miners that extract more than 50,000 tonnes per year.

Following the collapse in support for the right-wing President Sebastian Piñera and the social unrest in late 2019, the bill was modified.

The amended proposal imposes a flat-rate ad valorem tax of 1% on copper companies that produce more than 50,000 tonnes per year.

Additional royalties would be assessed at rates fluctuating from 8% to 26% based on miners’ operating margins, rather than being adjusted according to the price of copper as was originally proposed.

Depreciation, as well as supply and work costs, would be taken into consideration in calculating operating margins.

“This has been a tremendously important step” for raising funds on a regional level, Minister of Finance Mario Marcel told reporters after the vote late Wednesday. Pending approval in the lower house, it will also provide the industry with “a clear panorama to make decisions.”

Miners in Chile, the world’s top copper producer, currently have a tax burden of 41% to 44%. The tax ceiling for units of giant mining companies, including BHP (ASX: BHP), Anglo American (LON: AAL) and Teck Resources (TSX: TECK.A | TECK.B) (NYSE: TECK), has been the focus of debate for months as President Gabriel Boric’s administration attempts to increase its take of copper earnings, without undermining Chile’s competitiveness.

Earlier this week, the government said it had reached an agreement with senators to cut the top tax rate to 46.5% from 47% for companies that produce over 80,000 tonnes of fine copper a year, and 45.5% for production in the 50,000-80,000 range.

According to official figures, the new mining royalty would inject about $1.5 billion a year into the state’s coffers, from which $450 million will be distributed to regional governments for social spending.

Minister of Mining Marcela Hernando told MINING.COM on Thursday she was satisfied with what the bill looks like.

“As a ‘regionalist’ at heart, I am very happy to see the bill will direct an important injection of resources not only to those areas where mining happens, but also to the poorest communities,” Hernando said.

Chile’s main competitors in the copper sector, such as Peru, have a tax of 41% to 44% over large producers’ operating profit.

 

Controversial Barge for Migrant Housing Arrives in UK

File image courtesy Bibby Marine

PUBLISHED MAY 9, 2023 3:14 PM BY THE MARITIME EXECUTIVE

 

An aging accommodations barge has arrived in Falmouth, UK for inspection, and after any needed repairs, it will soon begin housing Channel-crossing migrants as part of a government plan to make emergency housing less welcoming. 

The 50-year-old floatel Bibby Stockholm was built to house project workers at undeveloped ports, but in recent years it has been repurposed for temporary housing for the homeless and for asylum-seekers in the EU. Under charter to the UK government, it will be moored alongside in Portland Port, Dorset, where it will house up to 500 single male migrants at a time. 

The local government in Dorset is concerned that the presence of this many migrants in a concentrated facility will require extra policing, and local officials have asked the Home Secretary for funding to cover the additional law enforcement costs. Some officials are altogether opposed to the idea of locating the barge in their harbor.  

"We still have serious reservations about the appropriateness of Portland Port in this scenario and we remain opposed to the proposals," Spencer Flower, leader of Dorset Council, told Express. "We still have unanswered questions which we are waiting for the Home Office and the barge operator to respond to."

The barge has enough space to house about one percent of the 50,000-plus asylum seekers currently staying in hotels across the UK. The $7.5 million-per-day cost of these hotel rooms has prompted the government to look for cheaper (and less attractive) alternatives. 

"Being housed in a hotel with all the amenities that that gives is not appropriate for people coming here illegally. . . . We must end, if you like, this perverse incentive through the hotels and in a broader sense the hospitality that this country gives [to migrants]," UK Justice Minister Dominic Raab said in March. 

The previous administration of former Prime Minister Boris Johnson considered cruise, ferry or barge accommodations for migrants in 2022, but set the plan aside when officials warned that it could be costlier than hotels. In addition to the charter costs, port fees and security could impose additional expenses, according to Bloomberg. (Dorset is said to be in line to receive about $4,000 per migrant housed aboard Bibby Stockholm.) 

Despite these concerns, more barges are coming to other UK ports soon, the Home Office told media on Monday. In the long term, the government hopes to pass legislation allowing expedited removal of asylum seekers to willing third countries; Rwanda has agreed to be an early participant in the program.