The paper at a glance
What if I told you that a bacterial treatment could destroy tumors in patients with severely compromised immune systems—the very patients who need help the most, but for whom most treatments fail? Our recent paper in Nature Biomedical Engineering describes exactly that: a newly discovered tumor-derived bacterial consortium we call AUN (pronounced “Ah-oon”, meaning “harmonious breath” in Japanese) that defies decades of scientific dogma by working precisely where it shouldn't.
[https://www.nature.com/articles/s41551-025-01459-9]
The accidental breakthrough that changed everything
Science rarely follows the script we write for it. When we first isolated what would become AUN from tumor tissue in July 2022, we had zero expectations. After all, every textbook told us that bacterial immunotherapy needed a robust immune system to function—so testing it in immunodeficient mice seemed like a guaranteed dead end.
Then the impossible happened.
The tumors didn't just shrink—they disappeared. In mouse models where almost nothing works, AUN delivered results that made us question everything we thought we knew about cancer treatment. That single moment transformed our entire research trajectory and set us on a path filled with scientific surprises that still give me chills.
When mistakes reveal breakthrough potential: The "Double Shot" discovery
Sometimes the best discoveries come from the most unexpected places—including a student's mistake. One of our most significant findings emerged when a particularly struggling student (let's call him Student X) botched what should have been a routine injection. Having difficulty with tail vein injections, he accidentally gave a mouse a low dose of AUN, then—rather than starting over—concentrated the remaining bacteria and injected again.
What happened next defied all logic: instead of killing the mouse with this "accidental overdose," the tumor completely vanished—and the effect was dramatically more powerful than our standard single-dose treatment.
This serendipitous error led us to discover the "Double Shot" protocol, which proved significantly more effective than single dosing in our preclinical models. The initial low dose strategically reduces neutrophils, creating an optimal window where the second, higher dose can work with enhanced safety and dramatically improved efficacy. What started as sloppy technique became a powerful research tool that revealed AUN's full therapeutic potential.
While the double-shot approach represents the peak performance we achieved in our laboratory studies, the remarkable thing about AUN is its flexibility. Even single doses show substantial antitumor effects, suggesting multiple pathways for future clinical development—from intensive protocols for aggressive cancers to simplified regimens for broader patient populations.
The moment that brought me to tears
Science is often portrayed as cold and clinical, but some moments hit you at an emotional level that transcends data and statistics. One such moment came when we co-cultured AUN with cancer cells and watched something extraordinary unfold under the microscope.
One component, A-gyo, began transforming into fibrous, snake-like structures that moved and swirled across the dish with an almost purposeful grace (Figure 1a). It looked alive—because it was alive, reshaping itself into a weapon against cancer.
That night, overwhelmed by the beauty and implications of what we'd witnessed, I cried. This felt like a gift from nature itself—a living drug that knew exactly what to do.
The most remarkable part? This transformation only occurred when A-gyo encountered cancer cells, not healthy ones. The bacteria had somehow evolved to recognize and respond specifically to their target. Later, we identified the molecular triggers: cancer-specific metabolites like fumaric acid, lactic acid, and spermidine that signal the bacteria to activate their tumor-hunting mode.
The science behind the magic
What makes AUN special?
AUN isn't just one bacterium—it's a perfectly orchestrated duo:
- A-gyo (Proteus mirabilis): The aggressive tumor hunter that transforms into fibrous "living spears" (Figure 1b)
- UN-gyo (Rhodopseudomonas palustris): The regulatory partner that keeps A-gyo in check
Figure 1. The remarkable transformation and tumor-hunting behavior of A-gyo. (a) Microscopic evidence of A-gyo's dramatic metamorphosis: After 24 hours of co-culture with Colon26 tumor cells, these bacteria undergo a striking transformation from their normal form into elongated, snake-like swarmer cells. The transformation is so dramatic that it's visible even at low magnification (left), with intricate fibrous details revealed at higher resolution (right). (b) A-gyo in action: Real-time imaging captures a motile swarmer cell actively penetrating tumor tissue—like a living spear seeking its target with remarkable precision. (c) Vascular destruction in real-time: Direct observation of AUN's devastating effect on tumor blood vessels in live mice. Within hours of intravenous injection, the bacterial consortium systematically destroys the tumor's vascular network, cutting off its vital blood supply and leading to tumor collapse.
The key discoveries:
- Tumor-specific activation: A-gyo transforms when it encounters cancer-specific metabolites, ensuring precise targeting
- Vascular disruption: AUN attacks tumor blood supply, causing internal blood clots and cutting off the tumor's lifeline (Figure 1c)
- Dynamic optimization: Inside tumors, the bacterial ratio shifts from 3:97 to 99:1 (A-gyo:UN-gyo), automatically optimizing for maximum effect
- Built-in safety: UN-gyo acts as a biological safeguard, suppressing pathogenicity while amplifying antitumor activity
- Immune-independent action: Unlike conventional bacterial therapies, AUN works even in immunocompromised patients
The name's deeper meaning: "AUN"（阿吽）represents a fundamental Japanese concept—the harmonious balance between opposing forces. Like the temple guardian statues that inspired the name, A-gyo and UN-gyo work in perfect synchrony to protect against disease.
Why this matters now
Cancer treatment has long been constrained by a cruel irony: the patients who need help the most—those with compromised immune systems—are often the ones who can't receive the most effective treatments. AUN breaks this barrier.
This isn't just another cancer drug. It's a self-regulating, tumor-seeking, living therapeutic system that represents an entirely new class of medicine. Imagine treatments that evolve and adapt inside the patient, becoming more effective over time rather than less.
The bigger picture
Our journey with AUN reminds us that science's greatest breakthroughs often come from embracing the unexpected. A lazy student's mistake became a revolutionary protocol. An emotional moment watching bacteria transform became a key insight into tumor selectivity. What seemed like a hopeless experiment became a paradigm-shifting discovery.
As we continue developing AUN for clinical applications, we're not just advancing cancer treatment—we're opening the door to a new era of living medicines that could transform how we think about therapeutic intervention.
About the author
Eijiro Miyako is a Professor at the Japan Advanced Institute of Science and Technology (JAIST), where his laboratory develops cutting-edge biomedical technologies. He believes that the best science happens when rigorous methodology meets open curiosity—and when we remain emotionally connected to the profound implications of our work.