In the spring of 2002, in a shared lab on the University of Michigan’s (UM’s) North Campus, a biomedical engineering graduate student named Dr. Zhen Xu was running out of ideas. She had spent weeks firing ultrasound pulses at pig hearts suspended in water tanks, trying different combinations of amplitudes and frequencies, looking for a way to mechanically destroy small sections of tissue without cutting into them. Nothing worked. The pig hearts came from a local slaughterhouse she had found in the yellow pages, five dollars each, that she collected bare-handedly in a trash bag. The experiments were unglamorous by any standard. And the amplifier she used was so powerful that her lab mates had started complaining about the noise.
Instead of giving up, Dr. Xu tried something different. To push the sound above the range of human hearing, she increased the pulse repetition frequency and fired super-short bursts at a pig heart using much higher amplitudes than anyone in the lab had attempted. Quickly, she noticed something: A hole appeared in the pig heart. She repeated the experiment twice more, then ran to show her adviser, Dr. Charles Cain. As Dr. Xu later recalled, they had found that ultrasound could somehow generate those holes. Their team spent the next 10 years trying to discover just how this worked.
That lab accident—part persistence, part improvisation, part annoyance from neighboring researchers—marked the beginning of histotripsy, a technology that uses focused ultrasound to mechanically destroy targeted tissue inside the body without a single incision. No scalpel, no thermal ablation, no radiation. Cavitation, an array of tiny vapor-filled bubbles that expand and collapse with enough force to liquefy a tumor, breaks apart the tissue at the cellular level.
In February 2026, the Sony Women in Technology Award with Nature recognized Dr. Xu as one of three recipients, granting her $250,000 in research funding. Around the same time, Time selected her as one of its 100 most influential leaders in health. Back in 2002 however, she could not remotely foresee the accomplishments that lay ahead. What she had was a hole in a pig heart and a result that nobody could quite explain.
Dr. Xu had arrived at Michigan in 2001 after completing her undergraduate degree in biomedical engineering at Southeast University in Nanjing, China. She joined the lab of Dr. Cain, a distinguished professor who had spent years investigating the therapeutic potential of ultrasound and whom colleagues generally consider the father of histotripsy. Dr. Cain envisioned what he called a knifeless surgical approach, the idea that sound waves could someday replace the scalpel for certain procedures. His team had originally explored heat-based ultrasound to treat heart tissue but had begun shifting their attention toward cavitation, the mechanical effect that would become the basis for histotripsy.
The original project, notably, had nothing to do with cancer. A pediatric cardiologist had asked the lab to find a noninvasive, nonthermal way to perforate the atrial septum, a membrane separating the chambers of the heart, in young children. Dr. Xu’s own reflection on this period captures something essential about how her discovery happened: She did not know enough about the field to recognize that what she was attempting was considered practically impossible, and she did not know enough to be afraid. So, she tried parameters outside the range of what more experienced researchers would have considered reasonable. That combination of inexperience and nerve turned out to matter.
Even with a striking result, the path forward proved difficult. Medicine has long relied on a familiar set of treatment logics: Cut the tumor out, burn it, poison it, irradiate it. A technology that could noninvasively destroy targeted tissue by using focused sound sat awkwardly outside those categories. It sounded improbable, even to people working close to the science. Dr. Xu and her collaborators spent years refining the approach, building evidence, and answering the doubts that greeted histotripsy at every stage. This is the less glamorous truth about medical innovation: A discovery can be genuinely important and still take years to earn broad trust because medicine rightly demands proof before it changes how physicians treat patients.
In 2009, Dr. Xu, Dr. Cain, and a small group of Michigan engineers and physicians cofounded HistoSonics to commercialize the technology. They did not make a big deal of it at the time—just had dinner and drinks at a nearby restaurant. In October 2023, the FDA authorized marketing of the company’s Edison System for the noninvasive destruction of liver tumors, including tumors that surgeons could not remove. The agency classified it as a nonthermal, mechanical process, a designation that underscored just how different histotripsy was from anything else in the treatment landscape. In 2025, a consortium of investors that included Jeff Bezos acquired HistoSonics for more than $2.25 billion. Today, roughly 100 Edison systems operate in medical facilities worldwide, and nearly 3,000 patients have received treatment.
The story carries a particular weight because of what happened to the man who started it. Dr. Cain died in 2020 from prostate cancer, the very type of disease that histotripsy aims to fight. He did not live to see the FDA authorization, the thousands of patients treated, or the acquisition that valued the company at over $2 billion dollars. Dr. Xu speaks about his absence plainly: She notes that Dr. Cain’s early contributions proved crucial and acknowledges the sadness of knowing that he did not live to see the technology treat patients or potentially his own illness.
Nonetheless, the science he pushed forward keeps advancing. In 2025, researchers at UM’s Michigan Medicine reported that histotripsy may do more than destroy a tumor at its original site. Their work indicates that mechanically destroying tumor tissue could stimulate the immune system to recognize and attack cancer cells elsewhere in the body, essentially teaching the body to identify which cells are cancerous and to mount a broader defense. Researchers continue to study the mechanism, and appropriate scientific caution applies, but the implication is significant. A technology designed as a precise local intervention may also function as a catalyst for the immune system. If that line of research holds up, histotripsy would not merely replace the scalpel: It would accomplish something a scalpel cannot do at all.
Dr. Xu’s work now extends well beyond the liver. Her research addresses challenges across cancer, neurology, and cardiovascular medicine, with trials underway or in development for kidney and pancreatic tumors and exploration continuing into breast, brain, and thyroid cancers, as well as into treatment of strokes and blood clots. Not every application will succeed (medicine has a way of humbling even the most promising technologies!), but histotripsy has moved well past the stage of being a curiosity. It provides a platform for expanding clinical ambitions, and Dr. Xu has chosen to remain at Michigan, continuing the research even as the commercial side of the technology scales.
Her story fits the “breakthroughs that almost weren’t” framing of this series in a specific, almost literal way. Histotripsy did not emerge from a well-funded initiative or a neat hypothesis that the field stood ready to receive. It came from a graduate student trying parameters that more experienced researchers would not have tried, using an amplifier that was too loud, and working on pig hearts purchased for five dollars from a slaughterhouse. The ideas that change medicine are not always the ones that sound right immediately. Sometimes they are the ones that require someone to keep working through a long stretch of doubt, someone just inexperienced enough to try something that nobody else thought would work.
Natasa Billeci, MSN, is a nurse practitioner and PhD candidate in Biobehavioral Sciences at the University of South Florida. Her research explores how reproductive aging, circadian disruption, and genomic factors contribute to Alzheimer’s disease risk across the aging continuum. She uses large-scale data and predictive modeling to advance early risk assessment and prevention. Billeci joined AWIS as a member in 2025.
This article was originally published in AWIS Magazine. Join AWIS to access the full issue of AWIS Magazine and more member benefits.