This 17-Year-Old Scientist Is Making an Acetaminophen Alternative That Is Less Damaging to the Liver
Chloe Yehwon Lee’s research could change the painkiller, known by the brand name Tylenol, for the better, ultimately reducing emergency room visits and cases of liver failure
High school senior Chloe Yehwon Lee first encountered the devastating effects of acetaminophen toxicity during her time volunteering at a local assisted living center in Plano, Texas. She struck up conversations with the residents after her school’s Ensembles for Elderly performances, and it was through these exchanges that she began to hear about a dangerous problem. Acetaminophen, one of the most widely used painkillers in the world, can cause liver damage in those who rely too heavily on it.
“I actually witnessed a resident have to be taken to the emergency room because of acetaminophen toxicity,” Lee recalls. “I was pushed to find a solution because I wanted to help the residents who I volunteer for.”
Acetaminophen, commonly known by the brand name Tylenol, is a staple in the medicine cabinets of millions of people around the world. It’s used to alleviate pain and reduce fever, but its misuse—whether through overdose or long-term use—can cause serious damage to the liver.
Studies report that acetaminophen overdose contributes to 82,000 emergency room visits each year in the United States. Meanwhile, acetaminophen toxicity is the leading cause of both acute liver injury and acute liver failure in this country.
While treatments for acetaminophen toxicity exist, many of them are either difficult to access or fail to address the underlying issue effectively. These approaches have typically involved managing the consequences of overdose rather than preventing them. For example, the most commonly used treatment is N-acetylcysteine (NAC), which helps replenish glutathione in the liver, allowing it to neutralize toxic metabolites. However, NAC must be administered within a narrow window of time after an overdose to be most effective. Other treatments, such as liver transplants, are often reserved for patients who have already suffered significant liver damage.
With a new understanding of the widespread impact of acetaminophen toxicity, Lee became acutely aware of the critical need for safer alternatives to the drug. Inspired by this, she decided to take a different approach to solving the issue, one that would allow for effective pain relief without compromising safety.
Lee’s project began with a deep dive into research. “I noticed that current solutions against acetaminophen toxicity are limited,” she explains. “Antidotal therapy, a clinical approach against toxicity, is widely inaccessible and also unreliable, and current approaches to chemically modifying acetaminophen, what my research seeks to do, are impractical since they sacrifice acetaminophen’s pain-relieving properties.”
The problem was clear, but the solution wasn’t so simple. Acetaminophen is metabolized in the liver, where about 90 percent is converted into harmless compounds that are then excreted in urine. However, the remaining portion is converted by cytochrome P450 enzymes into N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite. This is where the problem begins. At high doses or when combined with other drugs, the liver is no longer able to produce enough glutathione to neutralize all the NAPQI, leading to inflammation, oxidative stress and, ultimately, liver failure.
“If there is too much acetaminophen, the liver becomes overwhelmed, and it cannot clear acetaminophen’s toxic metabolite, which can cause liver damage,” says Robert Green, a pharmacist at Johns Hopkins Outpatient Pharmacy. “Patients with a history of alcohol abuse, hepatitis or cirrhosis are at higher risk of acetaminophen toxicity, as they already have underlying liver damage.”
Rather than eliminating acetaminophen entirely, Lee wanted to modify its structure to reduce the harmful effects of NAPQI. To start, she designed computational models to explore potential chemical modifications. She focused on altering the molecule’s benzene ring, a crucial part of acetaminophen’s chemical structure, and discovered that her modification could reduce acetaminophen’s chemical reactivity in the liver, decreasing liver toxicity. Additionally, it improved acetaminophen’s ability to bind to pain receptors, potentially enhancing its effectiveness as a pain reliever.
After completing her models, Lee moved to the lab, and to the real challenge: synthesizing the modified compound. It was a lot of trial and error for the young scientist. “When I was developing the scheme to synthesize my compound, I found that process very challenging,” she admits. “That was because the scheme I was developing was completely original and it really hadn’t been done before by researchers.”
But after months of experimentation, Lee succeeded in producing a modified acetaminophen molecule that showed promise in reducing liver toxicity. According to her results, Lee’s molecule is 2.74 times less reactive with the liver than the original form of acetaminophen. The next step? Testing.
“Once we have enough of the compound, we can move on to testing it on liver cells,” Lee says. “But that’s the stage I’m working on right now. I’m trying to synthesize enough of the molecule to get into that next step.”
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With testing in the near future, Lee is optimistic about the potential of her work. She believes that if the modified acetaminophen proves effective, it could make a significant difference for those who are at risk of liver damage.
“I want to continue working on the research and hopefully apply it to the world,” Lee says. “The molecule I synthesized, and my work, is a very necessary and promising step to creating safer and more effective forms of acetaminophen.”
In addition to addressing toxicity, Lee’s research also holds promise in overcoming another challenge of acetaminophen: the ceiling effect. She explains that, beyond a certain dosage, increasing the amount of the drug no longer enhances its analgesic effects.
“Basically, when you’re taking acetaminophen, at some point, no matter how much more you take, it won’t give more pain relief,” she says. “I found that my modification allows acetaminophen to bind to its pain receptors better, thus enhancing drug efficacy.”
Lee’s innovative research on acetaminophen not only demonstrated the potential for more effective and safer pain management, but it also garnered significant recognition in the scientific community. Her work earned her a spot as a finalist in the 2025 Regeneron Science Talent Search, the most distinguished science, technology, engineering and math competitions for high school seniors in the U.S. Representing 39 schools across 16 states, this year’s 40 finalists were selected from a pool of 2,471 entrants, the largest number of applicants since 1967. Lee and her fellow finalists were competing for more than $1.8 million in scholarships, with a top prize of $250,000. This recognition places Lee among a group of exceptional young scientists who are on their way to make lasting contributions to their fields.
“I think this modification can reshape the future of the medicine,” says Lee’s mentor, Junha Jeon, a chemist at the University of Texas at Arlington. As her mentor, Jeon guided Lee through critical aspects of her research, teaching her how to break and make chemical bonds, as well as how to develop sustainable synthesis processes in his lab.
Green is a little more tempered in his review. “An approach like Chloe’s sounds very promising,” he says. “I believe it has the potential to have an impact for patients with liver disease or a history of alcoholism, as it would allow health care providers to be more confident recommending acetaminophen for pain relief.”
However, Green also points out some challenges. “Currently, acetaminophen is very low-cost, and any advancements or new patents could potentially increase those costs considerably,” he says. “Patients would still choose the lower-cost, generic and easily accessible ‘original’ acetaminophen.”
When asked about the potential costs, Lee acknowledged that the drug development process is very costly, rigorous and time-consuming. To modify acetaminophen, she used expensive transition metal catalysts, which are chemical compounds made from metals like iron, copper and platinum that help speed up chemical reactions without being consumed in the process. “My research is not cost-effective, as it increases the cost of acetaminophen, so that is the biggest limitation,” she says.
Insurance providers, patients and health systems bear the financial burden of liver failure caused by acetaminophen, not drug manufacturers. Green believes that in order to bring safer versions of acetaminophen to market, pharmaceutical companies must be encouraged through incentives like government funding, pressure from the Food and Drug Administration or other mechanisms. “The manufacturers would have to know that this is going to be a sustainable endeavor,” he adds.
Green also expresses concern that if a modified version of acetaminophen is viewed as entirely safe, patients might overuse it, despite the fact that some risk could still remain.
Looking ahead, Jeon says they plan to run toxicity tests on the modified compound. These tests will assess how the modified acetaminophen affects liver cells and whether it causes any harmful reactions in a biological setting. If the tests are successful, they will need to find a collaborator to help move the research forward. Jeon has already contacted hospitals that are willing to assist with testing using mouse models.
As her research progresses and the testing phase unfolds, Lee remains hopeful that her work will not only contribute to advancing pain relief but also encourage further innovation in the pharmaceutical industry. Lee’s story is a powerful reminder that the next generation of scientists is already paving the way for groundbreaking discoveries that will improve global health.