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Mayo Clinic Scientists Use Chemical Analysis of Beethoven’s Hair to Determine Lead Poisoning May Have Contributed to Composer’s Hearing Loss and Other Health Ailments

Results of an earlier study in which locks of Beethoven’s hair underwent genetic analysis showed the composer ‘had a predisposition for liver disease and became infected with hepatitis B’

Here is an example of modern technologies being used with “historical biospecimens” to solve long-standing mysteries or questions about the illnesses of famous historical figures. Clinical laboratory scientists at the Mayo Clinic have used modern-day chemical analysis techniques to answer a 200-year-old question: What caused Ludwig van Beethoven’s deafness and other health problems?

In a letter published in Clinical Chemistry, a journal of the Association for Diagnostics and Laboratory Medicine (ADLM) titled, “High Lead Levels in 2 Independent and Authenticated Locks of Beethoven’s Hair,” researchers with the metals laboratory within Mayo’s Division of Clinical Biochemistry and Immunology revealed analysis performed on authenticated locks of the composer’s hair. The results indicated extremely high concentrations of lead—64 to 95 times the expected level.

“Such lead levels are commonly associated with gastrointestinal and renal ailments and decreased hearing but are not considered high enough to be the sole cause of death,” the authors wrote.

Beethoven’s death at age 56 has been attributed to kidney and liver disease, CNN reported. Even if the lead concentrations were not the sole cause, they would nevertheless be regarded as lead poisoning, lead study author Nader Rifai, PhD, told CNN.

“If you walk into any emergency room in the United States with these levels, you will be admitted immediately and you will undergo chelation therapy,” he said.

Rifai is a professor of pathology at Harvard Medical School and director of clinical chemistry at Boston Children’s Hospital.

“It is believed that Beethoven died from liver and kidney disease at age 56. But the process of understanding what caused his many health problems has been a much more complicated puzzle, one that even Beethoven himself hoped doctors could eventually solve,” CNN reported, adding, “The composer expressed his wish that his ailments be studied and shared so ‘as far as possible at least the world will be reconciled to me after my death.’” Mayo clinical laboratory scientists are using chemical analysis on authenticated locks of Beethoven’s hair to do just that. (Photo copyright: Joseph Karl Stieler/Public Domain.)

Mass Spectrometry Analysis

Mayo Clinic’s metals laboratory, led by chemist Paul Jannetto, PhD, an associate professor in the Department of Laboratory Medicine and Pathology and Laboratory Director at the Mayo Clinic, performed the analysis on two authenticated locks of Beethoven’s hair, using inductively coupled plasma mass spectrometers.

The researchers found that one lock had 258 micrograms of lead/gram and the other had 380 micrograms. Normally they would expect to find less than four micrograms.

“These are the highest values in hair I’ve ever seen,” Jannetto told The New York Times. “We get samples from around the world and these values are an order of magnitude higher.”

The researchers also found that the composer’s hair had four times the normal level of mercury and 13 times the normal amount of arsenic.

Rifai and other researchers noted that Beethoven drank large amounts of plumbed wine, and at the time it was common to sweeten wine with lead acetate, CNN reported.

The composer also could have been exposed to lead in glassware. He likely absorbed high levels of arsenic and mercury by eating fish caught from the Danube River in Vienna.

David Eaton, PhD, a toxicologist, pharmacologist, and Professor Emeritus, Department of Environmental and Occupational Health Sciences at the University of Washington, told The New York Times that high levels of lead could have impaired Beethoven’s hearing through their effect on the nervous system. Additionally, he said the composer’s gastrointestinal ailments “are completely consistent with lead poisoning.”

Rifai told CNN that he’d like to study locks of hair from other 19th century Vienna residents to see how their lead levels compared with Beethoven’s.

Beethoven’s Genome and Genetic Predisposition for Liver Disease

Additional research published in May built on an earlier genomic analysis of Beethoven’s hair, which appeared in March 2023 in the journal Current Biology.

The international team included geneticists, archeologists, and immunologists who analyzed eight locks of hair attributed to the composer. They determined that five were authentic. One, known as the Stumpff Lock, appeared to be the best preserved. They used this lock to sequence Beethoven’s DNA.

“Although we could not identify a genetic explanation for Beethoven’s hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease,” the authors wrote. “Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven’s severe liver disease, which culminated in his death.”

One surprising discovery was the likelihood of an extramarital affair on the composer’s father’s side, CNN reported. The researchers learned this in part by comparing his genetic profile with those of living relatives.

“Through the combination of DNA data and archival documents, we were able to observe a discrepancy between Ludwig van Beethoven’s legal and biological genealogy,” study coauthor Maarten Larmuseau, PhD, told CNN. Larmuseau is assistant professor, Faculty of Medicine, and head of the Laboratory of Human Genetic Genealogy at KU Leuven in Belgium.

The Mayo Clinic team used two locks authenticated in the 2023 study—the Bermann Lock and Halm-Thayer Lock—to perform their chemical analysis, CNN reported.

Beethoven’s Wishes

The earlier study noted that Beethoven wanted his health problems to be made public. In 1802, he wrote a document known as the Heiligenstadt Testament in which he asked that his physician, surgeon/ophthalmologist Johann Adam Schmidt, MD, discuss his disease after he died.

“For almost two years I have ceased to attend any social functions, just because I find it impossible to say to people: I am deaf,” Beethoven wrote at age 30, The New York Times reported. “If I had any other profession, I might be able to cope with my infirmity, but in my profession, it is a terrible handicap. And if my enemies, of whom I have a fair number, were to hear about it, what would they say?”

The authors of the Current Biology paper wrote, “Genomic sequence data from authenticated locks of Beethoven’s hair provide Beethoven studies with a novel primary source, already revealing several significant findings relating to Beethoven’s health and genealogy, including substantial heritable risk for liver disease, infection with HBV [Hepatitis B], and EPP [extra pair paternity]. This dataset additionally permits numerous future lines of scientific inquiry.

“The further development of bioinformatics methods for risk stratification and continued progress in medical genetic research will allow more precise assessments both for Beethoven’s disease risk and for the genetic inference of additional phenotypes of interest.

“This study illustrates the contribution and further potential of genomic data as a novel primary source in historical biography,” the scientists concluded.

The work of the clinical laboratory professionals at Mayo Clinic also demonstrates how advances in various diagnostic technologies can enable pathologists and lab scientists to participate in solving long-standing health questions about historical figures, especially if their hair or other types of specimens survived and can be used in the analysis.  

—Stephen Beale

Related Information:

High Lead Levels in 2 Independent and Authenticated Locks of Beethoven’s Hair

Locks of Beethoven’s Hair Offer New Clues to the Mystery of His Deafness

New Analysis of Beethoven’s Hair Reveals Possible Cause of Mysterious Ailments, Scientists Say

Beethoven May Have Had Lead Poisoning

Paul Jannetto, PhD, Contributes to Landmark Discovery of Beethoven’s Hair Lead Concentration

Beethoven Really Did Have Lead Poisoning, But That Didn’t Cause His Death

Genomic Analyses of Hair from Ludwig Van Beethoven

DNA from Beethoven’s Hair Unlocks Medical and Family Secrets

DNA Analysis of Beethoven’s Hair Reveals Health Issues—and a Family Secret

Brigham and Women’s Hospital Researchers Develop Implantable ‘Lab in a Patient’ to Test Effectiveness of Brain Cancer Drugs

Scientists reported positive Phase 1 trial results of their “intratumoral microdevice” in patients with glioma tumors

Here is an example of new microtechnology which has the potential to greatly shorten the time and improve the ability of physicians to determine which anti-cancer drug is most effective for an individual patient’s glioblastoma. As it is further developed, this technology could give anatomic pathologists and clinical laboratories an increased role in assessing the data produced by microdevices and helping physicians determine the most appropriate anti-cancer drug for specific patients.

In a news release, researchers at Brigham and Women’s Hospital (BWH) in Boston said they have developed an implantable “intratumoral microdevice” (IMD) that functions as a “lab in a patient,” capable of gauging the effectiveness of multiple drugs that target brain tumors. In a Phase 1 clinical trial, they tested the IMD on six patients with glioma tumors.

“In order to make the greatest impact on how we treat these tumors, we need to be able to understand, early on, which drug works best for any given patient,” study co-author Pier Paolo Peruzzi, MD, PhD, told the Harvard Gazette. “The problem is that the tools that are currently available to answer this question are just not good enough. So, we came up with the idea of making each patient their own lab, by using a device which can directly interrogate the living tumor and give us the information that we need.”

Peruzzi is Principal Investigator at the Harvey Cushing Neuro-Oncology Laboratories and Assistant Professor of Neurosurgery at Harvard Medical School.

The researchers published their findings in the journal Science Translational Medicine titled, “Intratumoral Drug-Releasing Microdevices Allow In Situ High-Throughput Pharmaco Phenotyping in Patients with Gliomas.” [PHOTO OF PERUZZI HERE

“Our goal is for the placement of these devices to become an integral part of tumor surgery,” said Pier Paolo Peruzzi, MD PhD (above) of Brigham and Women’s Hospital and Harvard Medical School in an article he co-wrote for Healio. “Then, with the data that we have from these microdevices, we can choose the best systemic chemotherapy to give to that patient.” Pathologists and clinical laboratories may soon play a role in helping doctors interpret data gathered by implantable microdevices and choose the best therapies for their patients. (Photo copyright: Dana-Farber Cancer Institute.)

New Perspective on Tumor Treatments

In a news story he co-wrote for Healio, Peruzzi explained that the microdevice—about the size and shape of a grain of rice—contains up to 30 tiny reservoirs that the researchers fill with the drugs they want to test. Surgeons implant the device during a procedure to remove the tumors.

The surgery takes two to three hours to perform, and during that time, the device releases “nanodoses” of the drugs into confined areas of the tumor. Near the end of the procedure, the device is removed along with tissue specimens. The researchers can then analyze the tissue to determine the effectiveness of each drug.

“This is not in the lab, and not in a petri dish,” Peruzzi told Harvard Gazette. “It’s actually in real patients in real time, which gives us a whole new perspective on how these tumors respond to treatment.”

The Healio story notes that gliomas are “among the deadliest brain cancers and are notoriously difficult to treat.” With current approaches, testing different therapies has posed a challenge, Peruzzi wrote.

“Right now, the only way these drugs are tested in patients is through what are called window-of-opportunity studies, where we give one drug to the patient before we resect the tumor and analyze the effect of the drug,” he said. “We can only do this with one drug at a time.”

Determining Safety of Procedure

The primary goal of the Phase 1 trial was to determine the safety of the procedure, Peruzzi noted. “To be in compliance with standard clinical practice and minimize risks to the patients, we needed to integrate the placement and retrieval of the device during an otherwise standard operation.”

The trial consisted of three men and three women ranging from 27 to 86 years old, with a median age of 76. Five were diagnosed with glioblastoma and one with grade 4 astrocytoma.

“None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens,” the researchers wrote in Science Translational Medicine. They noted that application of the IMD added about 32 minutes to the time required for the surgery, equating to a cost increase of $7,800.

One drug they tested was temozolomide (TMZ), “the most widely used agent in this patient population,” they wrote. “Several patients in our trial received it systemically, either before or after IMD insertion, as part of the standard of care. Thus, although our trial was not designed to choose chemotherapy agents based on IMD data, we still could compare the observed clinical-radiological response to systemic TMZ with the patient-specific response to TMZ in the IMD-exposed tissue.”

One patient, the researchers noted, had not benefited from the drug “in concordance with the poor tissue response observed in the IMD analysis.” But in another patient, a 72-year-old woman, “IMD analysis showed a marked response to TMZ,” and she survived for 20 months after receiving the treatment “with radiological evidence of tumor response. This was despite having a subtotal tumor resection, in itself an unfavorable prognostic factor. The patient expired because of an unrelated cardiovascular event, although she had remained neurologically stable.”

Drug Duration Limitation

One limitation of the study was that testing the device during the tumor removal procedure limited the duration of the drug treatments, Peruzzi said. The Harvard Gazette noted that following their initial study, the researchers were testing a variation of the procedure in which the device is implanted three days before the main surgery in a minimally invasive technique. This gives the drugs more time to work.

Cancer researchers have theorized that common treatments for tumors can impair the immune system, Peruzzi wrote in Healio. “One thing we want to look at is which drugs can kill the tumor without killing the immune system as well,” he noted.

Future studies will determine the effectiveness of implanting microdevices into tumors to test therapies in vivo. Should they become viable, clinical laboratories and anatomic pathologists will likely be involved in receiving, interpreting, storing, and transmitting the data gathered by these devices to the patient’s doctors.

—Stephen Beale

Related Information:

Microdevices Implanted into Tumors Offer New Way to Treat Brain Cancer

Intratumoral Drug-Releasing Microdevices Allow In Situ High-Throughput Pharmaco Phenotyping in Patients with Gliomas

Microdevices Turn Brain Tumors into Tiny Labs

Devices Implanted into Brain Tumors During Surgery May Guide Treatment

Human Brain Tumor Implant Could Guide Personalized Therapies Tiny Implanted Devices Give Insights for Treating Brain Tumors

Researchers Find That Antibiotic-Resistant Bacteria Can Persist in the Body for Years

Study results from Switzerland come as clinical laboratory scientists seek new ways to tackle the problem of antimicrobial resistance in hospitals

Microbiologists and clinical laboratory scientists engaged in the fight against antibiotic-resistant (aka, antimicrobial resistant) bacteria will be interested in a recent study conducted at the University of Basel and University Hospital Basel in Switzerland. The epidemiologists involved in the study discovered that some of these so-called “superbugs” can remain in the body for as long as nine years continuing to infect the host and others.

The researchers wanted to see how two species of drug-resistant bacteria—K. pneumoniae and E. coli—changed over time in the body, according to a press release from the university. They analyzed samples of the bacteria collected from patients who were admitted to the hospital over a 10-year period, focusing on older individuals with pre-existing conditions. They found that K. pneumoniae persisted for up to 4.5 years (1,704 days) and E. coli persisted for up to nine years (3,376 days).

“These patients not only repeatedly become ill themselves, but they also act as a source of infection for other people—a reservoir for these pathogens,” said Lisandra Aguilar-Bultet, PhD, the study’s lead author, in the press release.

“This is crucial information for choosing a treatment,” explained Sarah Tschudin Sutter, MD, Head of the Division of Infectious Diseases and Hospital Epidemiology, and of the Division of Hospital Epidemiology, who specializes in hospital-acquired infections and drug-resistant pathogens. Sutter led the Basel University study.

The researchers published their findings in the journal Nature Communications titled, “Within-Host Genetic Diversity of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales in Long-Term Colonized Patients.”

“The issue is that when patients have infections with these drug-resistant bacteria, they can still carry that organism in or on their bodies even after treatment,” said epidemiologist Maroya Spalding Walters, MD (above), who leads the Antimicrobial Resistance Team in the Division of Healthcare Quality Promotion at the federal Centers for Disease Control and Prevention (CDC). “They don’t show any signs or symptoms of illness, but they can get infections again, and they can also transmit the bacteria to other people.” Clinical laboratories working with microbiologists on antibiotic resistance will want to follow the research conducted into these deadly pathogens. (Photo copyright: Centers for Disease Control and Prevention.)

COVID-19 Pandemic Increased Antibiotic Resistance

The Basel researchers looked at 76 K. pneumoniae isolates recovered from 19 patients and 284 E. coli isolates taken from 61 patients, all between 2008 and 2018. The study was limited to patients in which the bacterial strains were detected from at least two consecutive screenings on admission to the hospital.

“DNA analysis indicates that the bacteria initially adapt quite quickly to the conditions in the colonized parts of the body, but undergo few genetic changes thereafter,” the Basel University press release states.

The researchers also discovered that some of the samples, including those from different species, had identical mechanisms of drug resistance, suggesting that the bacteria transmitted mobile genetic elements such as plasmids to each other.

One limitation of the study, the authors acknowledged, was that they could not assess the patients’ exposure to antibiotics.

Meanwhile, recent data from the World Health Organization (WHO) suggests that the COVID-19 pandemic might have exacerbated the challenges of antibiotic resistance. Even though COVID-19 is a viral infection, WHO scientists found that high percentages of patients hospitalized with the disease between 2020 and 2023 received antibiotics.

“While only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, three out of four or some 75% of patients have been treated with antibiotics ‘just in case’ they help,” the WHO stated in a press release.

WHO uses an antibiotic categorization system known as AWaRe (Access, Watch, Reserve) to classify antibiotics based on risk of resistance. The most frequently prescribed antibiotics were in the “Watch” group, indicating that they are “more prone to be a target of antibiotic resistance and thus prioritized as targets of stewardship programs and monitoring.”

“When a patient requires antibiotics, the benefits often outweigh the risks associated with side effects or antibiotic resistance,” said Silvia Bertagnolio, MD, Unit Head in the Antimicrobial resistance (AMR) Division at the WHO in the press release. “However, when they are unnecessary, they offer no benefit while posing risks, and their use contributes to the emergence and spread of antimicrobial resistance.”

Citing research from the National Institutes of Health (NIH), NPR reported that in the US, hospital-acquired antibiotic-resistant infections increased 32% during the pandemic compared with data from just before the outbreak.

“While that number has dropped, it still hasn’t returned to pre-pandemic levels,” NPR noted.

Search for Better Antimicrobials

In “Drug-Resistant Bacteria Are Killing More and More Humans. We Need New Weapons,” Vox reported that scientists around the world are researching innovative ways to speed development of new antimicrobial treatments.

One such scientist is César de la Fuente, PhD, Presidential Assistant Professor at University of Pennsylvania, whose research team developed an artificial intelligence (AI) system that can look at molecules from the natural world and predict which ones have therapeutic potential.

The UPenn researchers have already developed an antimicrobial treatment derived from guava plants that has proved effective in mice, Vox reported. They’ve also trained an AI model to scan the proteomes of extinct organisms.

“The AI identified peptides from the woolly mammoth and the ancient sea cow, among other ancient animals, as promising candidates,” Vox noted. These, too, showed antimicrobial properties in tests on mice.

These findings can be used by clinical laboratories and microbiologists in their work with hospital infection control teams to better identify patients with antibiotic resistant strains of bacteria who, after discharge, may show up at the hospital months or years later.

—Stephen Beale

Related Information:

Resistant Bacteria Can Remain in The Body for Years

‘Superbugs’ Can Linger in the Body for Years, Potentially Spreading Antibiotic Resistance

Superbug Crisis Threatens to Kill 10 Million Per Year by 2050. Scientists May Have a Solution

Drug-Resistant Bacteria Are Killing More and More Humans. We Need New Weapons.

How the Pandemic Gave Power to Superbugs

WHO Reports Widespread Overuse of Antibiotics in Patients Hospitalized with COVID-19

Harvard and Google Scientists Studying Connectomics Create Massive Highly Detailed 3D Nanoscale Model of Human Neural Tissue

Ten year collaboration between Google and Harvard may lead to a deeper understanding of the brain and new clinical laboratory diagnostics

With all our anatomic pathology and clinical laboratory science, we still do not know that much about the structure of the brain. But now, scientists at Harvard University and Google Research studying the emerging field of connectomics have published a highly detailed 3D reconstruction of human brain tissue that allows visualization of neurons and their connections at unprecedented nanoscale resolutions.

Further investigation of the nano-connections within the human brain could lead to novel insights about the role specific proteins and molecules play in the function of the brain. Though it will likely be years down the road, data derived from this study could be used to develop new clinical laboratory diagnostic tests.

The data to generate the model came from Google’s use of artificial intelligence (AI) algorithms to color-code Harvard’s electron microscope imaging of a cubic millimeter of neural tissue—equivalent to a half-grain of rice—that was surgically removed from an epilepsy patient.

“That tiny square contains 57,000 cells, 230 millimeters of blood vessels, and 150 million synapses, all amounting to 1,400 terabytes of data,” according to the Harvard Gazette, which described the project as “the largest-ever dataset of human neural connections.”

“A terabyte is, for most people, gigantic, yet a fragment of a human brain—just a minuscule, teeny-weeny little bit of human brain—is still thousands of terabytes,” said neuroscientist Jeff W. Lichtman, MD, PhD, Jeremy R. Knowles Professor of Molecular and Cellular Biology, whose Lichtman Lab at Harvard University collaborated on the project with researchers from Google. The two labs have been working together for nearly 10 years on this project, the Harvard Gazette reported.

Lichtman’s lab focuses on the emerging field of connectomics, defined “as understanding how individual neurons are connected to one another to form functional networks,” said neurobiologist Wei-Chung Allen Lee, PhD, Assistant Professor of Neurology, Harvard Medical School, in an interview with Harvard Medical News. “The goal is to create connectomes—or detailed structural maps of connectivity—where we can see every neuron and every connection.” Lee was not involved with the Harvard/Google Research study.

The scientists published their study in the journal Science titled, “A Petavoxel Fragment of Human Cerebral Cortex Reconstructed at Nanoscale Resolution.”

“The human brain uses no more power than a dim incandescent light bulb, yet it can accomplish feats still not possible with the largest artificial computing systems,” wrote Google Research scientist Viren Jain, PhD (above), in a blog post. “To understand how requires a level of understanding more profound than knowing what part of the brain is responsible for what function. The field of connectomics aims to achieve this by precisely mapping how each cell is connected to others.” Google’s 10-year collaboration with Harvard University may lead to new clinical laboratory diagnostics. (Photo copyright: Google Research.)

Study Data and Tools Freely Available

Along with the Science paper, the researchers publicly released the data along with analytic and visualization tools. The study noted that the dataset “is large and incompletely scrutinized,” so the scientists are inviting other researchers to assist in improving the model.

“The ability for other researchers to proofread and refine this human brain connectome is one of many ways that we see the release of this paper and the associated tools as not only the culmination of 10 years of work, but the beginning of something new,” wrote Google Research scientist Viren Jain, PhD, in a blog post that included links to the online resources.

One of those tools—Neuroglancer—allows any user with a web browser to view 3D models of neurons, axons, synapses, dendrites, blood vessels, and other objects. Users can rotate the models in xyz dimensions.

Users with the requisite knowledge and skills can proofread and correct the models by signing up for a CAVE (Connectome Annotation Versioning Engine) account.

Researchers Found Several Surprises

To perform their study, Lichtman’s team cut the neural tissue into 5,000 slices, each approximately 30 nanometers thick, Jain explained in the blog post. They then used a multibeam scanning electron microscope to capture high-resolution images, a process that took 326 days.

Jain’s team at Google used AI tools to build the model. They “stitched and aligned the image data, reconstructed the three dimensional structure of each cell, including its axons and dendrites, identified synaptic connections, and classified cell types,” he explained.

Jain pointed to “several surprises” that the reconstruction revealed. For example, he noted that “96.5% of contacts between axons and their target cells have just one synapse.” However, he added, “we found a class of rare but extremely powerful synaptic connections in which a pair of neurons may be connected by more than 50 individual synapses.”

In their Science paper, the researchers suggest that “these powerful connections are not the result of chance, but rather that these pairs had a reason to be more strongly connected than is typical,” Jain wrote in the blog post. “Further study of these connections could reveal their functional role in the brain.”

Mysterious Structures

Another anomaly was the presence of “axon whorls,” as Jain described them, “beautiful but mysterious structures in which an axon wraps itself into complicated knots.”

Because the sample came from an epilepsy patient, Jain noted that the whorls could be connected to the disease or therapies or could be found in all brains.

“Given the scale and complexity of the dataset, we expect that there are many other novel structures and characteristics yet to be discovered,” he wrote. “These findings are the tip of the iceberg of what we expect connectomics will tell us about human brains.”

The researchers have a larger goal to create a comprehensive high-resolution map of a mouse’s brain, Harvard Medical News noted. This would contain approximately 1,000 times the data found in the 1-cubic-millimeter human sample.

Dark Daily has been tracking the different fields of “omics” for years, as research teams announce new findings and coin new areas of science and medicine to which “omics” is appended. Connectomics fits that description.

Though the Harvard/Google research is not likely to lead to diagnostic assays or clinical laboratory tests any time soon, it is an example of how advances in technologies are enabling researchers to investigate smaller and smaller elements within the human body.

—Stephen Beale

Related Information:

Researchers Publish Largest-Ever Dataset of Neural Connections

A Petavoxel Fragment of Human Cerebral Cortex Reconstructed at Nanoscale Resolution

Ten Years of Neuroscience at Google Yields Maps of Human Brain

Groundbreaking Images Reveal the Human Brain at Nanoscale Resolution

A New Field of Neuroscience Aims to Map Connections in the Brain

Patient Rights Group Says Too Many Hospitals Are Not Complying with CMS Price Transparency Rules

Only about a third of the hospitals surveyed are in full compliance with giving public access to prices, the watchdog group contends, but the AHA disputes its methodology

It’s been almost four years since the Centers for Medicare and Medicaid Services (CMS) enacted its Hospital Price Transparency rule which requires hospitals—including their medical laboratories—to make their prices available and easily accessible to the public. But according to a 2024 report from (PRA), just 34.5% of reviewed hospitals are fully compliant with the transparency rule. That’s a slight decrease from the 36% compliance rate the PRA listed in its 2023 report, the watchdog group stated in a blog post.

Released on Feb. 29, this was the group’s sixth semi-annual hospital price transparency report since the CMS rule took effect in 2021.

The rule “requires hospitals to post all prices online, easily accessible and searchable, in the form of (i) a single machine-readable standard charges file for all items, services, and drugs by all payers and all plans, the de-identified minimum and maximum negotiated rates, and all discounted cash prices, as well as (ii) prices for the 300 most common shoppable services either as a consumer-friendly standard charges display listing actual prices or, alternatively, as a price estimator tool,” the report states.

The required viewable prices are to be for, among others, medical imaging, clinical laboratory testing, and outpatient procedures such as a colonoscopies, etc.

“With full transparency, consumers can benefit from competition to make informed decisions, protect from overcharges, billing errors, and fraud, and lower their costs,” the report states. “Employer and union plans can use pricing and claims data to improve their plan designs and direct members to lower cost, high-quality facilities. However, continued noncompliance impedes this ability.”

At any time, the US Department of Justice (DOJ) could decide to file charges against a hospital or a clinical laboratory for not posting their prices on their websites in compliance with the federal rule. Such an action by DOJ officials would be to specifically put the entire industry on notice that there will be consequences for non-compliance.

The PRA’s report provides hospitals and clinical laboratories with a reminder that consumer watchdogs are also monitoring compliance.

“Our comprehensive study of 2,000 hospitals indicates nearly two-thirds (65.5%) of hospitals reviewed continue failing to fully comply with the rule, yet the Centers for Medicare and Medicaid Services (CMS) has only fined fourteen hospitals for noncompliance out of the thousands found to not be meeting all of the rule’s requirements. When hospitals don’t post their prices, they can charge whatever they want,” wrote PRA Founder and Chairman Cynthia Fisher (above) in a letter to President Biden. Hospital medical laboratories are also required to post their prices for tests. (Photo copyright:

Increasing Penalties for Non-compliance

In a March 18 Health Affairs blog post on price transparency, two healthcare policy experts—David Muhlestein, PhD, JD, Chief Research Officer at Leavitt Partners, Washington, DC, and Adjunct Assistant Professor of The Dartmouth Institute (TDI) at the Geisel School of Medicine at Dartmouth College; and Yuvraj Pathak, PhD, Associate Director at West Health—argued that CMS should increase penalties for non-compliance, so the dollar amounts are greater than the cost of compliance.

To compile their report, PRA analysts examined the websites of 2,000 US hospitals between September 3, 2023, and January 13, 2023, and found that 1,311, or 65.5%, were not in full compliance, mostly due to “missing or significantly incomplete pricing data,” the report states.

More than 6,000 licensed hospitals operate in the US, the report notes. The group said it focused on hospitals owned by the largest US health systems.

Among the notable findings:

  • The 2023 report found that 98% of Kaiser Permanente’s 42 hospitals were in full compliance with the rule, but in the 2024 study, none were compliant because the hospitals began posting multiple files instead of a single file.
  • In total, 103 hospitals rated as noncompliant in the previous report were found to be compliant in the new analysis. Conversely, 135 hospitals previously rated as compliant were listed as noncompliant in the 2024 report.

The report lauded three hospitals for posting “exemplary files” that were “easily accessible, downloadable, machine-readable, and including all negotiated rates by payer and plan.” Those were Cape Cod Hospital in Hyannis, Mass.; Christus Santa Rosa Medical Center in San Antonio; and UW Health University Hospital in Madison, Wis.

In its discussion of the findings, PRA called on CMS to step up enforcement of the pricing transparency rule. The group also wants the government to close what it describes as the “estimator tool loophole,” which allows hospitals to list non-binding price estimates and price ranges instead of concrete prices.

“Price estimator tools do not achieve the goals of price transparency policy and fundamentally undermine the intent of the regulations,” the PRA’s report contends.

AHA Pushes Back on PRA Assessment

The American Hospital Association (AHA) took issue with PRA’s methodology, as Dark Daily reported in “CMS Proposes New Amendments to Federal Hospital Price Transparency Rule That May Affect Clinical Laboratories and Pathology Groups.”

In response to the 2023 PRA report, AHA Group Vice President for Public Policy Molly Smith issued the following statement, “Once again, Patient Rights Advocate has put out a report that blatantly misconstrues, ignores, and mischaracterizes hospitals’ compliance with federal price transparency regulations. The AHA has repeatedly debunked point-by-point Patient Rights Advocate’s intentionally misleading ‘reports’ on price transparency.”

Citing CMS data, Smith said that as of 2022, 70% of US hospitals had complied with two key federal rules:

  • One requiring hospitals to post machine-readable files with pricing information.
  • The other mandating a list of prices for at least 300 “shoppable” services.

More than 80% of hospitals had complied with at least one of the rules, she contended in an AHA press release.

Speaking to the New Orleans Times-Picayune, PRA Founder and Chairman Cynthia Fisher said her group performs a more in-depth study of pricing data compared with CMS.

“They did not do a comprehensive review,” she told the publication. “We do a deep dive for full compliance.”

The PRA study came on the heels of a January report from Turquoise Health that offered a rosier assessment of hospital compliance, albeit with different criteria. According to the Turquoise report, as of Dec. 15, 2023:

  • 90.7% of 6,357 US hospitals had posted machine-readable files,
  • 83.1% posted information about negotiated rates, and
  • 77.3% posted cash rates.

The Turquoise Health end-to-end price transparency platform uses a 5-point system to rate the quality of hospitals’ machine-readable files and said that more than 50% scored five stars. Clinical laboratory managers and pathologists may find it timely to review their lab organization’s compliance with this federal price transparency rule.

—Stephen Beale

Related Information:

Just 34.5% of Reviewed Hospitals Fully Compliant with Federally-Mandated Price Transparency Rule

Sixth Semi-Annual Hospital Price Transparency Compliance Report

Improving Hospital Compliance with Price Transparency Rules

Only Half of LA Hospitals Publish Prices as Required by Law, Hindering Patient Choice

34.5% of Hospitals Complying with Price Transparency Rule, Report Says

Little Progress Made with Hospital Price Transparency Compliance

CMS Releases Tool to Validate Price Transparency File Compliance

Hospital Price Transparency Compliance Dips: Report

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