Princeton University’s geoscientists discover a new cancer detection method using hydrogen isotopes

A New Way to Detect Cancer Early: Princeton researchers Xinning Zhang and Ashley Maloney are exploring an unconventional approach to cancer detection—one rooted in geosciences. Their groundbreaking study, published in the Proceedings of the National Academy of Sciences, suggests that the same hydrogen isotope analysis used to study ancient climates could help detect cancerous cells at an early stage. If confirmed, their findings could pave the way for a revolutionary, non-invasive diagnostic tool.

A Chance Discovery with Transformative Potential

For years, geoscientists have used hydrogen isotopes—regular hydrogen (H) and its heavier counterpart, deuterium (D)—to analyze past climates and biogeochemical cycles. However, Zhang and Maloney have uncovered an unexpected link between hydrogen isotopes and cancer metabolism. Their research, which shows that cancer cells process hydrogen, leaving a distinct isotopic footprint in fatty acids, could be detected through a simple blood test, is both surprising and intriguing.

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"This naturally occurring signal can help us understand health and disease," said Zhang. Unlike traditional cancer diagnostic methods that often require invasive biopsies or radioactive tracers, this isotopic signature in lipids, which is a unique chemical fingerprint left by cancer cells, could offer a much simpler and earlier detection method.

Sebastian Kopf, a co-author and assistant professor in geological sciences at CU-Boulder, highlighted the life-saving potential of early cancer detection. "Your chances of survival are so much higher if you catch cancer early on. If this isotopic signal is strong enough to be detected in blood lipids, it could serve as an important early warning system," he said, emphasizing the potential clinical implications of the research.

Hydrogen's Hidden Footprint in Cancer Cells

At the heart of Zhang and Maloney's research is the role of hydrogen in cellular metabolism. Cancer cells grow abnormally rapidly, requiring them to rewire their metabolic pathways. This shift alters the movement of hydrogen atoms, leaving an isotopic imprint in lipids—the fatty molecules that makeup cell membranes.

"Many problematic processes in cells have to do with improper hydrogen flow," Zhang explained. “Cancer cells divide rapidly and modify their metabolism to sustain that fast growth. In doing so, they turn on pathways that manipulate hydrogen in distinct ways.”

Because lipids are among the most hydrogen-rich molecules in cells and remain stable over time, they serve as an excellent record of these metabolic changes. "Lipids last longer than most other organic molecules in the body," said Zhang. “They preserve a history of hydrogen flow, which makes them an ideal medium for detecting subtle metabolic shifts associated with disease."

From Geosciences to Biomedicine: A Personal and Professional Journey

Zhang's interest in the biomedical applications of hydrogen isotopes dates back to her graduate studies. In 2009, she published a paper demonstrating how isotope ratios could reveal metabolic processes in bacteria. However, it wasn't until years later—when her father was diagnosed with terminal cancer—that she began to consider its relevance to human health.

"I kept wondering, what are the real-world applications of this idea? How could it help people?" she reflected.

A chance meeting with early-career geochemist Ashley Maloney, whose father’s work in medicine had sparked her interest in biomedical research, led to a collaboration. Maloney joined Zhang's lab at Princeton in 2018 as a Hess Fellow, determined to explore whether hydrogen isotopes could serve as a biomarker for cancer.

"I’m thankful that this work could be done at Princeton, where postdoctoral fellowships support interdisciplinary projects," said Zhang. “Most funding agencies won’t invest in ‘blue-sky research’ without proof of concept, so this opportunity was crucial.”

Testing the Hypothesis: Yeast, Mice, and Mass Spectrometry

Since working with human cancer cells required extensive approvals, Zhang and Maloney started with a simpler model: yeast. Specifically, they grew Saccharomyces cerevisiae—the same yeast used in baking and brewing—under controlled conditions to mimic cancer metabolism.

Cancer cells fuel their rapid growth by fermenting sugar instead of using oxygen for energy. Maloney fed one group of yeast glucose to replicate this, forcing them into a fermentation-based metabolism similar to cancer cells. The control group, by contrast, was given glycerol, which they used to generate energy through respiration—identical to healthy human cells.

Using isotope ratio-mass spectrometry, a standard tool in geosciences, they measured the hydrogen isotopes in the yeast's lipids. This process involves ionizing the lipids, separating the ions based on their mass-to-charge ratio, and then measuring the abundance of different isotopes. The results were striking: the fermenting, cancer-like yeast had significantly lower deuterium levels than the healthy yeast.

“We were really impressed by the difference in the hydrogen signature," said Maloney. “The signal was even stronger than we expected.”

They obtained healthy and cancerous liver cells from a former Princeton graduate student to test whether this trend held in more complex organisms. Again, the cancerous cells displayed a much lower D-to-H ratio, reinforcing their hypothesis.

The Road Ahead: Expanding to Human Applications

With proof of concept established, Zhang and her team are eager to collaborate with medical researchers to explore how this approach could be applied to human patients.

"We needed to get this work done to show that yes, there is a signal—a big signal," Zhang said. “Now we have key data to start working with the medical community to develop this tool beyond geosciences.”

A significant advantage of this approach is its potential for non-invasive testing. Since the isotopic signature is naturally encoded in blood lipids, a simple lipid panel—already a routine part of medical checkups—could theoretically be adapted to detect early signs of cancer.

"If we can refine this method and validate it in clinical studies, it could become a revolutionary tool for early cancer detection," said Maloney.

Despite the promising results, Zhang and Maloney acknowledge that more research is needed before this method can be translated into clinical practice. They aim to conduct more extensive studies, refine their detection techniques, and collaborate with oncologists to validate their findings in human trials.

A New Frontier in Cancer Research

While the journey from geosciences to cancer diagnostics may seem unlikely, it underscores the power of interdisciplinary research. Zhang and Maloney's work exemplifies how fundamental scientific principles—originally used to study Earth's history—can lead to breakthroughs in human health.

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Their discovery opens new doors for cancer detection and highlights the untapped potential of geochemistry in medicine. If successful, their research could transform cancer diagnostics, offering a simple, non-invasive, and highly effective way to detect the disease before it spreads.

“In science, you never know where a discovery will lead,” Zhang said. "Sometimes, a tool designed to study ancient rocks can end up helping to save lives." Stay tuned at Education Post News for more global updates.