How does the brain know how to get our breathing right? - by Michael Parkes

Next time you tie the laces of your running shoes just before going for a run, ask yourself how your brain knows to set your breathing at the current resting level? How does it manage to set it correctly no matter how hard you run? This simplest of vital tasks still baffles scientists. The story of how scientists have spent the last hundred years barking up the wrong tree provides an interesting insight into how science works in theory and in practice.

Every school child is taught that the purpose of breathing is to deliver oxygen to tissues so that they can burn fuel to release energy and to remove the main waste product that is carbon dioxide. So the obvious (the simplest) guess about how the brain controls breathing is that the brain somehow measures the on-going rate of oxygen consumption (formally named metabolic rate). This then produces some sort of signal to the brain that enables the brain to match breathing with it. Clearly the harder you exercise, the greater should be the measured rate of oxygen consumption. Hence the bigger will be this signal to increase breathing. The result should always be breathing remaining in proportion (i.e. matching) the on-going metabolic rate. And breathing itself must not make this signal disappear, because then there would not longer be a signal to drive breathing to match the new metabolic rate.

In the late 1920s a scientist discovered by accident that if you lower the oxygen level at 2 specific sites, a region around the branch of each of our 2 carotid arteries, then this stimulated breathing. So the obvious conclusion was that he had discovered that these contained carotid chemoreceptors that these ought to form the metabolic rate sensor that controls breathing. He was awarded the Nobel Prize in 1938. It was presumed only a matter of time before somebody sorted out the fine details of how this all worked. If the carotid chemoreceptors are the metabolic rate sensor, the basic philosophy of science, as introduced by Claude Bernard and JS Mills, produces a minimum of 3 simple and testable predictions to resolve the fine details of this control theory. These should be true if carotid chemoreceptors control the matching of breathing to metabolic rate (and indeed the principles should be generally true in describing how any simple control system works):

  • between rest and maximum exercise, recording the oxygen level around these chemoreceptors should reveal that this level is always proportional to metabolic rate (with the level falling as metabolic rate rises)
  • in resting humans it should be possible to stimulate these chemoreceptors artificially with low oxygen levels to increase breathing to mimic exactly the level seen at maximum exercise
  • if these chemoreceptors are surgically removed, then there should be a devastating effect on breathing (subjects may no longer be able to get out of a chair) and breathing will no longer match metabolic rate.

If one or more are false, then carotid chemoreceptors alone cannot be the metabolic rate sensor. This article considers the difficulty scientists have in establishing whether a hypothesis is true or false. It explains how one of these predictions appeared false even before the Nobel Prize was awarded. Indeed scientists can be remarkably reluctant even to see evidence that gets in the way of a good idea, especially if nobody has come up with evidence for a better one.

Michael Parkes is a physiologist whose research and teaching has covered a wide range of big questions such as do fetal hormones control fetal growth?, do sleep and wakefulness exist in utero?, what initiates breathing at birth?, what is the threshold level of hypoxia that alters brain function? what controls the matching of breathing to metabolic rate? and what causes the breakpoint of breath-holding? He is part of a team using novel methods to help patients prolong breath-holding safely for over 5 minutes in order to revolutionize radiotherapy and medical imaging.