Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.50143
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Funding
- National Institutes of Health [K08 GM123317, R01 GM124023, R01 GM088156, R01 GM107117, T32 GM112596]
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Traditionally, drug dosing is based on a concentration-response relationship estimated in a population. Yet, in specific individuals, decisions based on the population-level effects frequently result in over or under-dosing. Here, we interrogate the relationship between population-based and individual-based responses to anesthetics in mice and zebrafish. The anesthetic state was assessed by quantifying responses to simple stimuli. Individual responses dynamically fluctuated at a fixed drug concentration. These fluctuations exhibited resistance to state transitions. Drug sensitivity varied dramatically across individuals in both species. The amount of noise driving transitions between states, in contrast, was highly conserved in vertebrates separated by 400 million years of evolution. Individual differences in anesthetic sensitivity and stochastic fluctuations in responsiveness complicate the ability to appropriately dose anesthetics to each individual. Identifying the biological substrate of noise, however, may spur novel therapies, assure consistent drug responses, and encourage the shift from population-based to personalized medicine.
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