Acetaminophen poisoning is one of the leading causes of hospitalization and death related to non-prescription drugs in the United States, according to Kennon Heard, MD, PhD, a professor in the CU Anschutz Department of Emergency Medicine and the department’s section chief of medical toxicology.

Each year, an estimated 56,000 people visit emergency departments because of acetaminophen poisoning, and about 2,600 are hospitalized. The drug is responsible for nearly half of all acute liver failure cases in the U.S. and roughly 20% of liver transplants nationwide.

Heard has studied acetaminophen poisoning for more than 25 years. He is now helping to lead a long-term clinical trial that is testing a potential new way to reduce liver damage in severe overdose cases. The experimental approach uses a medication typically given to patients poisoned by antifreeze.

Heard says CU and Denver Health, which is home to the Rocky Mountain Poison & Drug Safety center, have played a central role in this research for decades. “have been the center of the acetaminophen research universe for the past 40 years. There’s been a long history of this type of work being done here, and it’s great to be a part of it.”

Why Acetaminophen Overdoses Happen

Acetaminophen is the main ingredient in Tylenol and many store-brand pain relievers used for mild to moderate pain and low-grade fever. It is also included in a wide range of over-the-counter products for colds, flu, sinus symptoms, and menstrual discomfort.

The medication has been used safely for decades when taken according to instructions. Problems arise when people exceed recommended doses, either by taking too much at once or by repeatedly taking more than advised over time.

“There are cases where people accidentally take too much acetaminophen,” Heard says. “Or maybe they have a really bad toothache, and they think if two is good, four is better, eight is even better, and so on. Or it’s someone who’s taking multiple repeated overdoses. Those are the people who get into trouble.”

Overdoses are also frequently linked to suicide and self-harm, Heard notes. “The No. 1 rule at the Poison Center is that if it’s available, people will take it, and a lot of people have Tylenol in their medicine chest.”

Limits of the Standard Antidote

For decades, doctors have relied on a drug called acetylcysteine as an effective antidote for acetaminophen overdose. When given early, it can prevent serious liver damage.

Its effectiveness drops sharply, however, if treatment begins more than eight hours after the overdose.

“The problem is that many patients don’t present with acetaminophen poisoning until after they have liver injury, at which point the acetylcysteine is less effective, and in some cases doesn’t really work at all,” Heard says.

Testing an Antifreeze Antidote

The current clinical trial led by Heard and his colleagues is focused on fomepizole, a drug approved to treat poisoning from ethylene glycol and methanol, substances commonly found in antifreeze. Exposure can occur accidentally, and in some cases people with alcohol use disorder have consumed antifreeze as a substitute for alcohol.

Fomepizole works by blocking enzymes known as alcohol dehydrogenase, stopping the body from converting ethylene glycol and methanol into toxic byproducts.

Heard says interest in using fomepizole for acetaminophen overdose dates back to the 1990s, when he was training in medical toxicology. Evidence came from individual patient case reports and animal studies, particularly in severe overdose cases.

More recently, research has shown that doctors are increasingly using fomepizole off-label to treat serious acetaminophen poisoning.

Richard Dart, MD, PhD, a professor of emergency medicine and Heard’s longtime mentor, ultimately suggested formally testing the drug in a clinical trial. Dart has served as director of Rocky Mountain Poison & Drug Safety since 1992.

A Proof of Concept Clinical Trial

The ongoing phase II trial is designed to determine whether adding fomepizole to standard acetylcysteine treatment can reduce liver damage in patients at high risk after acetaminophen overdose. It is considered a “proof of concept” study to see whether the combination shows enough promise to justify larger trials.

Participants are randomly assigned to receive either both medications or acetylcysteine alone. The study is double-blind, meaning neither the patients nor the researchers know which treatment each participant receives until the trial ends.

“We’ll compare the amount of liver damage, as measured by their liver enzymes, to see whether the fomepizole provides an added protective benefit beyond the standard treatment,” Heard says.

Patients are currently being enrolled at Denver Health, UCHealth University of Colorado Hospital, Children’s Hospital Colorado, and several additional sites. Enrollment has been slow due to the challenge of finding patients who meet the study criteria, but researchers hope to enroll about 40 participants within 12 to 18 months.

If the findings are positive, Heard expects the research to move into a larger trial that would examine longer-term outcomes, including survival and the need for liver transplants.

A Caution for Medicine Cabinets Everywhere

“The message that I would want to get out,” Heard says, is that people should carefully read medication labels, avoid exceeding recommended doses, and recognize that acetaminophen may be present in multiple products at home.

“We’ve started to recognize that the number of people who die from an accidental overdose is pretty close to the number of people who deliberately take an overdose,” he says.

Heard’s collaborators on the study include Dart and Andrew Monte, MD, PhD, also a professor of emergency medicine.

The iron cloud is being reported for the first time in Monthly Notices of the Royal Astronomical Society. It forms a long strip that fits neatly inside the nebula’s inner region, which has an elliptical shape seen in many well known images, including those captured by the James Webb Space Telescope at infrared wavelengths.¹ The structure is immense. Its length is about 500 times greater than Pluto’s orbit around the Sun, and the total amount of iron it contains is roughly equal to the mass of Mars.

What Makes the Ring Nebula Special

The Ring Nebula was first observed in 1779 by French astronomer Charles Messier in the northern constellation Lyra.² It is a glowing shell of gas produced when a star reaches the end of its nuclear fuel burning stage and ejects its outer layers into space. Astronomers expect the Sun to shed its outer material in a similar way several billion years from now.³

How the Iron Bar Was Found

The iron cloud was revealed through observations made with the Large Integral Field Unit (LIFU) mode of a new instrument known as the WHT Enhanced Area Velocity Explorer (WEAVE).⁴ WEAVE is mounted on the Isaac Newton Group’s 4.2-meter William Herschel Telescope.⁵

LIFU is made up of hundreds of optical fibers working together. This setup allowed the researchers to collect spectra (where light is separated into its constituent wavelengths) from every point across the face of the Ring Nebula, covering all optical wavelengths for the first time.

Seeing the Nebula in a New Way

Lead author Dr. Roger Wesson, who is based at both UCL’s Department of Physics & Astronomy and Cardiff University, described how the finding emerged. “Even though the Ring Nebula has been studied using many different telescopes and instruments, WEAVE has allowed us to observe it in a new way, providing so much more detail than before. By obtaining a spectrum continuously across the whole nebula, we can create images of the nebula at any wavelength and determine its chemical composition at any position.

“When we processed the data and scrolled through the images, one thing popped out as clear as anything — this previously unknown ‘bar’ of ionized iron atoms, in the middle of the familiar and iconic ring.”

Competing Ideas About Its Origin

The researchers say the origin of the iron bar is still unknown. More detailed observations will be needed to understand how it formed. One possibility is that the structure preserves new information about how the dying star expelled its material. Another, more speculative explanation suggests the iron could be part of a curved arc of plasma created when a rocky planet was vaporized during an earlier expansion of the star.

Co author Professor Janet Drew of UCL Physics & Astronomy stressed that key information is still missing. “We definitely need to know more — particularly whether any other chemical elements co-exist with the newly-detected iron, as this would probably tell us the right class of model to pursue. Right now, we are missing this important information.”

What Comes Next for the Research

The team is now preparing a follow up study and plans to gather new data using WEAVE’s LIFU at higher spectral resolution. These observations should help clarify how the iron bar formed and whether other elements are present alongside it.

WEAVE is scheduled to conduct eight major surveys over the next five years, studying objects that range from nearby white dwarfs to extremely distant galaxies. One part of the project, the Stellar, Circumstellar and Interstellar Physics survey led by Professor Drew, is already observing many additional ionised nebulae across the northern Milky Way.

Dr. Wesson noted that similar structures may turn out to be common. “It would be very surprising if the iron bar in the Ring is unique. So hopefully, as we observe and analyze more nebulae created in the same way, we will discover more examples of this phenomenon, which will help us to understand where the iron comes from.”

Professor Scott Trager, WEAVE Project Scientist at the University of Groningen, added: “The discovery of this fascinating, previously unknown structure in a night-sky jewel, beloved by sky watchers across the Northern Hemisphere, demonstrates the amazing capabilities of WEAVE. We look forward to many more discoveries from this new instrument.”

Notes

1. 1 See e.g. https://www.ucl.ac.uk/news/2023/aug/second-james-webb-image-ring-nebula-hints-dying-stars-companion https://www.cardiff.ac.uk/news/view/2739414-astronomers-spy-structures-that-no-previous-telescope-could-detect-in-new-images-of-dying-star
2. The Ring Nebula is also known as M 57 — the 57th listing in Messier’s catalogue of ‘Nebulae and Star Clusters’. John L E Dreyer also included it in his New General Catalogue, first published in 1888 by the Royal Astronomical Society, where it appears as NGC 6720.
3. Once a star like the Sun runs out of hydrogen fuel, it expands to become an extreme red giant and sheds its outer layers, which then coast out to form a glowing shell. A shell created in this way is known in astronomy as a planetary nebula. The leftover stellar core becomes a white dwarf, which, though no longer burning any fuel, continues to shine as it slowly cools over billions of years. The Ring Nebula is a planetary nebula located 2,600 light years (or 787 parsec) away, that is thought to have formed about 4,000 years ago. Planetary nebula ejection returns matter forged in a star to interstellar space and is the source of much of the Universe’s carbon and nitrogen — key building blocks of life on Earth. Stars more than about eight times the mass of the Sun age differently, ending life abruptly in a powerful explosion called a supernova as they collapse to form a black hole or neutron star.
4. Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONACYT through INAOE, the Ministry of Education, Science and Sports of the Republic of Lithuania, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania. The WEAVE Survey Consortium consists of the ING, its three partners, represented by UKRI STFC, NWO, and the IAC, NOVA, INAF, GEPI, INAOE, Vilnius University, FTMC — Center for Physical Sciences and Technology (Vilnius), and individual WEAVE Participants. The WEAVE website can be found at https://weave-project.atlassian.net/wiki/display/WEAVE and the full list of granting agencies and grants supporting WEAVE can be found at https://weave-project.atlassian.net/wiki/display/WEAVE/WEAVE+Acknowledgements.
5. The William Herschel Telescope is the leading telescope of the Isaac Newton Group (ING), which in turn is part of the Roque de los Muchachos Observatory on La Palma, in the Canary Islands. The ING is jointly operated by the United Kingdom (STFC-UKRI), the Netherlands (NWO) and Spain (IAC, funded by the Spanish Ministry of Science, Innovation and Universities).

Interactions between phages — viruses that infect bacteria — and their hosts play an integral role in microbial ecosystems. Often described as being in an evolutionary “arms race,” bacteria can evolve defenses against phages, while phages develop new ways to thwart defenses. While virus-bacteria interactions have been studied extensively on Earth, microgravity conditions alter bacterial physiology and the physics of virus-bacteria collisions, disrupting typical interactions.

However, few studies have explored the specifics of how phage-bacteria dynamics differ in microgravity. To address that gap, Huss and colleagues compared two sets of bacterial E. coli samples infected with a phage known as T7 — one set incubated on Earth and the other aboard the International Space Station.

Analysis of the space-station samples showed that, after an initial delay, the T7 phage successfully infected the E. coli. However, whole-genome sequencing revealed marked differences in both bacterial and viral genetic mutations between the Earth samples versus the microgravity samples.

The space-station phages gradually accumulated specific mutations that could boost phage infectivity or their ability to bind receptors on bacterial cells. Meanwhile, the space-station E. coli accumulated mutations that could protect against phages and enhance survival success in near-weightless conditions.

The researchers then applied a high-throughput technique known as deep mutational scanning to more closely examine changes in the T7 receptor binding protein, which plays a key role in infection, revealing further significant differences between microgravity versus Earth conditions. Additional experiments on Earth linked these microgravity-associated changes in the receptor binding protein to increased activity against E. coli strains that cause urinary tract infections in humans and are normally resistant to T7.

Overall, this study highlights the potential for phage research aboard the ISS to reveal new insights into microbial adaption, with potential relevance to both space exploration and human health.

The authors add, “Space fundamentally changes how phages and bacteria interact: infection is slowed, and both organisms evolve along a different trajectory than they do on Earth. By studying those space-driven adaptations, we identified new biological insights that allowed us to engineer phages with far superior activity against drug-resistant pathogens back on Earth.”

In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/4q4S9AO

Citation: Huss P, Chitboonthavisuk C, Meger A, Nishikawa K, Oates RP, Mills H, et al. (2026) Microgravity reshapes bacteriophage-host coevolution aboard the International Space Station. PLoS Biol 24(1): e3003568. https://doi.org/10.1371/journal.pbio.3003568

Author countries: United StatesFunding: This work was supported by the Defense Threat Reduction Agency (https://www.dtra.mil/) (Grant HDTRA1-16-1-0049) to S.R. C.C. was supported by a graduate training scholarship from the Anandamahidol Foundation (Thailand). The sponsors or funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.