Decades-Long Debate on Adult Human Neurogenesis Reaches New Phase

For much of scientific history, it was widely accepted that humans are born with a fixed number of neurons and cannot generate new ones. However, this long-held belief is now being challenged by a growing body of evidence suggesting that neurogenesis may persist into adulthood, hinting at the brain’s potential for repair and regeneration.

The question has divided top researchers for decades. Arturo Alvarez-Buylla of the University of California, San Francisco, has spent years studying the topic but remains unconvinced by current data. “If someone shows it clearly, I’ll be the first to be super happy and say, well, I didn’t waste my life studying a mechanism that is not present in humans,” he said.

Hongjun Song, a neuroscientist at the University of Pennsylvania, noted that the debate involves leading figures in the field producing high-quality science on both sides. While some researchers believe the evidence is sufficient to explore therapeutic applications for neurodegenerative diseases, others argue that detection methods—mostly reliant on indirect genetic markers—remain flawed.

Gerd Kempermann of the German Center for Neurodegenerative Diseases described the field as entering a “consolidating phase,” where gaps remain but opportunities are expanding rapidly.

Challenging the Dogma

The modern axiom that adult brains do not regenerate was championed by Santiago Ramón y Cajal in the 1910s. It was first challenged in the 1960s by Joseph Altman, who observed signs of neurogenesis in rats and cats. Rusty Gage of the Salk Institute suggested that Altman’s findings may have cost him tenure at MIT due to skepticism within the scientific community.

By the 1980s, adult neurogenesis was confirmed in birds, and the concept gained broader acceptance. Standard detection methods involved injecting animals with bromodeoxyuridine (BrdU), a chemical incorporated into DNA during cell division, allowing researchers to identify newly generated cells.

The 1998 Discovery

In 1998, Gage and his team published findings in Nature Medicine suggesting that human neurogenesis occurs in the hippocampus. They analyzed brain tissue from five cancer patients who had received BrdU treatments, identifying cells that had incorporated the marker. The study was accompanied by an editorial suggesting that fears of losing a fixed neuronal quota were unfounded.

The 2018 Counterargument

Two decades later, the field was upended by a paper led by Shawn Sorrells, then a postdoc in Alvarez-Buylla’s lab. Sorrells initially set out to study the amygdala but included hippocampal samples as a positive control. He found no evidence of new neurons. Collaborating with Mercedes Paredes and researchers in Spain and China, the team analyzed 59 brain samples from people of various ages.

Their results, published in Nature in 2018, indicated that young neurons drop sharply after the first year of life and are nearly absent in individuals over age 13. Alvarez-Buylla emphasized that the findings were replicated across three independent labs.

The publication sparked immediate controversy. Kempermann criticized the uproar, noting it drained energy from the field and hindered career progress and grant funding for researchers supporting adult neurogenesis.

Evolving Methodologies

In response to the debate, scientists explored whether differences in tissue preservation accounted for conflicting results. María Llorens-Martín at the Autonomous University of Madrid reported finding abundant neurogenesis in adults aged 43 to 87 using different markers. However, Alvarez-Buylla argued that the cells lacked the morphology of true young neurons and might be remnants from infancy.

Recent studies have turned to single-nucleus RNA sequencing and gene-expression analysis. Early work by Yale University researchers failed to find neurogenesis signatures in human brain tissue, though they detected them in pigs and monkeys. Hongjun Song pointed out that different species may use distinct genes for neurogenesis.

Using human infant data as a reference and an AI model, Song’s team identified immature neuron characteristics in adults. Critics, however, argued these cells might have remained immature for decades rather than being newly generated.

Latest Evidence

Last year, a study in Science by Jonas Frisén at the Karolinska Institute addressed this uncertainty. Using single-nucleus sequencing and machine learning, his team detected dividing neural progenitor cells in adult human brains. Song described this as a significant step forward, confirming that cells with the potential to become neurons exist and can divide in the adult human brain.

As the debate moves from existence to function, researchers are now turning their attention to understanding what role these adult-born neurons play in brain health and mood regulation.