Nature's Genetic Experiments: Humans Thrive Without Key Genes

A groundbreaking study published in Nature in June 2026 has identified "human knockouts" on an unprecedented scale. Researchers found that approximately one in five of the 173,303 participants in Pakistan had both copies of certain genes non-functional, yet lived ordinary lives. This research identified such disruptions across 6,476 genes, offering natural experiments for scientists.

The study leveraged Pakistan's high rate of consanguineous marriages, where related individuals may share rare gene variants. This phenomenon makes the population particularly informative for understanding gene function and the effects of gene absence. Previous research in 2017 on 10,503 adults had already demonstrated the value of this approach.

This extensive genetic resource, analyzing over 1.7 million participants, linked genetic data with medical histories. It identified novel gene variants and provided crucial insights for medicine, including potential drug targets and warnings against ineffective therapeutic strategies. For instance, findings on the APOC3 gene supported the development of a triglyceride-lowering drug approved in December 2024.

The findings also challenge assumptions, as seen with the PRDM9 gene, where loss of function did not cause infertility in humans, unlike in mice. While valuable, these human knockout studies offer clues rather than definitive clinical conclusions, as lifelong genetic loss allows for bodily compensation unlike adult drug interventions.

India also presents a significant opportunity for population-specific genomics due to its rich genetic diversity. Efforts like GenomeIndia are sequencing genomes to create reference maps. Linking this genetic data with medical records and enabling re-contact with participants is crucial for understanding gene function in humans, moving beyond animal models and potentially preventing costly drug development failures.