The Discovery of Enkephalins: The Brain's Own Opioid Peptides

The researchers extracted enkephalin from pig brain tissue, then used two complementary analytical techniques — the dansyl-Edman degradation procedure (which reads amino acid sequences one letter at a time) and mass spectrometry — to determine the exact amino acid sequences. They then chemically synthesized both peptides in the laboratory and compared the synthetic versions to the natural brain extracts to confirm identical structure and biological activity.

This is one of the most important papers in neuroscience history. Before this discovery, scientists knew the brain had receptors for opiates but couldn't explain why — since plants make morphine, not humans. Finding that the brain produces its own opioid peptides explained why we have opioid receptors in the first place and launched the entire field of endogenous opioid research. It fundamentally changed our understanding of pain, addiction, mood regulation, and the brain's reward system.

This discovery opened the floodgates for endogenous opioid research. Within years, scientists found endorphins, dynorphins, and other opioid peptides — revealing an entire natural pain-modulation system in the brain. This knowledge has shaped our understanding of pain management, opioid addiction, and the neuroscience of pleasure and reward. It also provided the foundation for developing peptide-based pain medications and understanding why opioid drugs are both effective and addictive.

The abstract is notably brief, as was common for Nature papers in 1975. The initial characterization was limited to identifying the sequences and confirming opioid receptor binding. The broader physiological roles of enkephalins — including their involvement in pain modulation, mood, gut function, and immune regulation — would only be elucidated in subsequent decades of research. The work used pig brain tissue, though enkephalins were later confirmed across mammalian species including humans.