ECDNA in Glioblastoma and a Massive Undersea Hydrogen Field

In this Science Magazine podcast episode, researchers illuminate how extra-chromosomal DNA, or ECDNA, fuels aggressive glioblastoma by carrying multiple copies of cancer genes like EGFR and forming hubs that boost expression beyond normal chromosomal inheritance. The discussion highlights Paul Michel’s rediscovery of ECDNA, the development of new bioinformatic tools to identify ECDNA across cancers, and early clinical and funding efforts, including challenges in translating this biology into therapy. The episode also reports the discovery of a massive underwater hydrogen field in the West Pacific, produced by hydrothermal reactions in subduction zones, which could account for a large share of oceanic abiotic hydrogen emissions and may inspire future energy technologies.

Overview

Science Magazine's September 11, 2025 podcast presents two frontiers in science: the role of extra-chromosomal DNA (ECDNA) in glioblastoma and a giant underwater hydrogen field in the West Pacific. The episode blends investigative reporting with expert commentary to reveal how these discoveries could reshape cancer biology and energy considerations.

ECDNA and Glioblastoma: A New Mechanism in Cancer Evolution

Freelance science journalist Ailey Dolgan profiles Paul Michel, a Stanford pathologist and cancer biologist who helped rekindle interest in extra-chromosomal DNA in tumors. In glioblastoma, many copies of the EGFR gene are located on circular DNA outside chromosomes, not on the chromosomal genome. These ECDNA circles can cluster into hubs, drive high gene expression, and pass on numerous copies through cell division, creating extraordinary tumor heterogeneity and a mechanism for rapid, non-Mendelian evolution. Dolgan describes how this phenomenon, once observed as double minutes decades ago, was largely overlooked until Michel and collaborators revisited the data with new imaging and sequencing approaches. They developed bioinformatic tools with Vanne Bafna to classify cancers as ECDNA positive, revealing that ECDNA occurs across multiple cancer types and is tied to more aggressive disease and poor outcomes.

"You really can't explain the degree of heterogeneity of the tumor." - Paul Michel

These findings point to a potential therapeutic vulnerability: exploiting replication stress and DNA repair pathways that ECDNA-heavy cancers rely on, a strategy pursued by the startup Boundless Bio and others. The field has received significant funding, including a national grand challenges grant, to map vulnerabilities and test targeted therapies. Ailey Dolgan notes ongoing debates about whether this biology is actionable in the clinic, but Michel remains cautiously optimistic that a path to treatment will emerge.

"Our job is to show them that it's actionable." - Paul Michel

Undersea Hydrogen Field: Discovery and Implications

The second story follows Wei Dong Sun, director of the Center of Deep Sea Research at the Chinese Academy of Sciences, and colleagues who identified an enormous hydrogen-rich hydrothermal system in a West Pacific trench linked to subduction initiation. The team logged hundreds of carbonate observations down to 6000 meters and documented 20 large vent pipes, the largest hundreds of meters in diameter. The hydrogen is produced by serpentinization of pyridotite in the mantle, a reaction that releases hydrogen gas as ocean water interacts with exposed rock. The field appears to contain energy quantities orders of magnitude larger than known terrestrial systems, potentially constituting about half of the world’s oceanic abiotic hydrogen emissions.

"This field is about 1000 times larger than the Lost City hydrothermal system." - Wei Dong Sun

Sun explains how these hydrogen vents could be harnessed, proposing ocean-based hydrogen production facilities rather than attempting to extract gas from natural pockets, given challenges with preservation and leakage. The scale invites new questions about geology, energy, and environmental risk, including the explosive histories inferred from breccia at vent sites and the role of oxygen-rich seawater in triggering hydrogen-oxygen reactions that could produce blasts. The researchers see potential for future collaboration and resource assessment to explore hydrogen as a renewable energy vector, while acknowledging the technical hurdles and the need for careful, responsible development.