The Search for a Unifying Theory of Anaesthesia

Claude Bernard’s Great Experiment  

Anaesthesia as we know it today evolved from a series of early experiments and breakthroughs. The discovery of ether and chloroform in the 1840s revolutionised surgery, yet their mechanisms of action remained a mystery. Physicians and scientists were uncertain whether anaesthesia affected the brain, the nervous system, or another part of the body entirely. 

In the mid-19th century, Claude Bernard, a pioneer of experimental medicine, conducted a series of intriguing experiments to understand anaesthesia. Among his observations was the effect of ether on the Mimosa pudica plant, whose characteristic movement ceased when exposed to the agent. Bernard’s experiments contributed to early theories on anaesthesia, shaping discussions on its fundamental mechanisms and broader implications for physiology. 

Bernard, a physiologist ahead of his time, was obsessed with one fundamental question: What is the essence of life? His answer lay in a peculiar concept—protoplasm, a colloidal substance he believed was the universal fabric of all living beings. Bernard proposed that anaesthesia worked by abolishing protoplasm’s ability to respond to stimuli, effectively suspending the excitability of living tissue. For Bernard, volatile anaesthetics distinguished living organisms from ‘dead’ organised matter. According to him: ‘What is alive must sense and can be anaesthetised, the rest is dead.‘¹ In effect, anaesthesia affects the ability of cells to react in response to a stimulus. In other words, anaesthesia was not just a physiological trick but an existential phenomenon, a temporary suspension of life’s essence. 

Fast-forward to 1901, when the Meyer-Overton rule was introduced. The rule proposed that an anaesthetic’s potency was directly related to its lipid solubility, meaning that the more an agent dissolved into fatty tissues, the more effectively it induced unconsciousness. Decades later, in the 1960s, Edmond “Ted” Eger II refined this understanding by introducing the concept of Minimum Alveolar Concentration (MAC)²—a practical and standardised way of measuring anaesthetic potency. While Bernard might not have known about lipid bilayers and receptor interactions, his vision of a unifying principle wasn’t far off. He saw anaesthesia as a universal effect, impacting a shared biological property across all forms of life

The Case of the Sleeping Plant 

One of Bernard’s most intriguing experiments involved the sensitive Mimosa pudica, a plant famous for its rapid leaf movements in response to touch. To Bernard’s amazement, when exposed to ether, the plant’s movements ceased—an effect he interpreted as proof that anaesthesia suppressed responsiveness at a fundamental level. If a plant, with no nervous system, exhibited a similar reaction to anaesthetised animals, Bernard reasoned that the effect must act on a universal physiological property. Though modern scientists debate the exact implications of this experiment, Bernard saw it as proof that anaesthesia wasn’t just about neurons and synapses—it affected life at its most basic level. 

Bernard’s theories dominated discussions on anaesthesia for years, laying the groundwork for future research into excitability and responsiveness in living tissue. Of course, modern science has since replaced the protoplasmic theory with a more sophisticated understanding of how anaesthetic agents interact with molecular and neural structures. We now know that anaesthesia isn’t just about “opacifying” protoplasm but about modulating ion channels, receptors, and synaptic transmissions in the central nervous system. 

Yet, in many ways, Bernard’s vision of a unifying principle still holds water. His curiosity laid the foundation for generations of anaesthesia research. Perhaps if Bernard were alive today, he’d be fascinated by the way MAC, receptor binding sites, and lipid solubility continue to shape our understanding of this mysterious and essential medical marvel. 

So, the next time you induce anaesthesia, take a moment to appreciate the long and fascinating history behind it. And maybe, just maybe, spare a thought for that little Mimosa pudica plant, slumbering peacefully in Claude Bernard’s laboratory. 

References

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC4091246/
2. The Meyer–Overton hypothesis – Physics, Pharmacology and Physiology for Anaesthetists

Authors

• Arta Leci
• Chinemerem Onuorah
• Marie-Hélène Lattes