Anesth Analg 2008; 107:737-738
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31817d865a
EDITORIAL
The Evolution of Anesthetic Sensitivity and the Evolution of a Paper
Marcel E. Durieux, MD, PhD
From the University of VA Health System, Department of Anesthesiology, Charlottesville, Virginia.
Address correspondence and reprint requests to Marcel E. Durieux, MD, Department Of Anesthesiology, University of Virginia Health System, Box 800710, Charlottesville, VA 22908. Address e-mail to durieux{at}virginia.edu.
Last year, Dr. James Sonner from the University of California at San Francisco submitted an interesting article to Anesthesia & Analgesia. It addressed the question: Why is it that essentially all living organisms, from yeast to human, are sensitive in one way or another to general anesthetics? This universal sensitivity, shown by organisms that are evolutionarily far apart, suggests that it must impart some survival benefit. In other words, there seems to be an evolutionary selection pressure for anesthetic sensitivity. The question then becomes why this selection pressure would exist. At first glance, it seems hard to imagine that the ability to be anesthetized would, by itself, offer survival benefit. This theory is not completely implausible, however; there might be endogenous anesthetic-like compounds that offer survival benefits to the organism (possibly having to do with immobilization), the effects of which are mimicked by our clinical compounds. This would be somewhat analogous to the situation with endogenous opioid receptor agonists, the actions of which are mimicked by our opioid drugs. Alternatively, it is conceivable that our anesthetics in some way interact with endogenous systems that have important survival benefits but that themselves are unrelated to the anesthetic state. In his paper Dr. Sonner hypothesized that environmental compounds which share some properties with anesthetics (such as activity at interfaces) would have affected ion channels, and that organisms then developed a coordinated response to such compounds in order to prevent channel dysfunction. Our current anesthetics would trigger this evolutionally developed response, resulting in the anesthetic state. Dr. Sonner provided some evidence for this hypothesis, and suggested a number of experimental approaches to test the theory.
The article was reviewed by four experts in the field. There was no doubt that it was a good paper, but after considering the opinions of the reviewers, I decided not to accept it for publication. There were two main reasons for my decision. First, the article stated a hypothesis, but did not provide much evidence for it, and Anesthesia & Analgesia does not generally publish such articles. Second, and more importantly, as I wrote in my letter to Dr. Sonner: "Several of the reviewers offer alternate potential explanations for the finding that anesthetic sensitivity is conserved, explanations that seem able to explain the data just as well." These viewpoints would at least have to be incorporated in the paper, and balanced against one another, which seemed almost impossible to do without data.
As usual, my letter and the (blinded) reviews were distributed to all four reviewers, and one of them, Dr. Rod Eckenhoff from the University of Pennsylvania, shortly afterwards approached me with a suggestion. He was as impressed as I had been with the quality and intellectual content of the reviews, and he wondered if it might be possible to convert the original paper by Sonner, and the four reviews, into a collection of short articles that would address the central question of universal anesthetic sensitivity from different viewpoints. It was an excellent idea, and both myself and Editor-in-Chief Steve Shafer were immediately enthusiastic about it. However, it did require some breaks with common procedure: Dr. Sonner had to agree to rewrite his rejected article in another form, and the four reviewers had to agree that their identity would be revealed to Dr. Sonner. Happily, all were very willing to cooperate on this project. In addition, I changed the review process: instead of sending each of the papers to independent reviewers, all authors reviewed each other’s papers, so that the contents could be better coordinated. The result of their efforts is the sequence of five short articles that follows.
The opening article is a shortened version of Dr. Sonner’s original article.1 This is followed by four other viewpoints. Dr. Crowder from Washington University puts the question in a broader perspective by discussing whether selection pressure is really required in order to explain universal anesthetic sensitivity.2 Dr. Eckenhoff focuses on the hypothesis that anesthetics may act on cavities in membrane proteins that allow the intramolecular movement necessary for channel or receptor activation and inactivation.3 Dr. Carl Lynch from the University of Virginia proposes a role for lipid interaction,4 while Dr. Margaret Sedensky and Dr. Phil Morgan from the Case School of Medicine approach the question from a genetic perspective.5
Don’t expect any definitive answers here! We simply do not have sufficient data to draw conclusions yet. However, the authors propose a number of experiments and approaches that can be used to study this issue and that will allow us to get closer to the answers, so that some day we may know why all organisms respond to anesthetics. Meanwhile, this series of brief articles by some of the most incisive thinkers in the specialty provides a fascinating overview of how anesthesia, a state discovered barely a century ago, connects with evolutionary processes that have been active for hundreds of millions of years.
In addition, this collection of papers is a good example of the value of openness in scientific communication. Had it not been for the willingness of the participants to be unblinded and to collaborate with each other, this wonderful collection of critical thinking might have been buried forever in the Anesthesia & Analgesia peer review archives.
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Footnotes
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Accepted for publication February 22, 2008.
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REFERENCES
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- Sonner JM. A hypothesis on the origin and evolution of the response to inhaled anesthetics. Anesth Analg 2008;107:849–54[Abstract/Free Full Text]
- Crowder CM. Does natural selection explain the universal response of metazoans to volatile anesthetics? Anesth Analg 2008;107:862–3[Free Full Text]
- Eckenhoff RG. Why Can all of biology be anesthetized? Anesth Analg 2008;107:859–61[Free Full Text]
- Lynch C III. Meyer and overton revisited. Anesth Analg 2008;107:864–67[Free Full Text]
- Sedensky MM, Morgan PG. Genetics and the evolution of the anesthetic response. Anesth Analg 2008;107:855–8[Free Full Text]
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E. I. Eger II, D. E. Raines, S. L. Shafer, H. C. Hemmings Jr, and J. M. Sonner
Is a New Paradigm Needed to Explain How Inhaled Anesthetics Produce Immobility?
Anesth. Analg.,
September 1, 2008;
107(3):
832 - 848.
[Abstract]
[Full Text]
[PDF]
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