The Feeling of the Need to Breathe

What a tragedy in the history of space travel tells us about the respiratory system.

On March 19^th, 1981, three NASA technicians entered the aft engine compartment of the Space Shuttle Columbia. Unknown to the three men, the compartment had been intentionally filled with nitrogen to reduce the risk of an explosion. To humans, nitrogen has neither odor nor color, so the technicians remained unaware that they were breathing pure nitrogen, rather than a mix of oxygen, carbon dioxide, and other gases, as one would under normal conditions. In short order, the lack of oxygen caused them to pass out. Tragically, two of the three would ultimately die from the accident.

When I first read about this incident—I came across it in the excellent book, The Disappearing Spoon by Sam Kean—my first thought was obviously for the victims. It’s a reminder that the dangers of advancing space travel are vast and often difficult to foresee.

My next thought was to puzzle about why the human motivational system in this case had failed. It seemed to me that a very natural way to design the respiratory system would be to include a way to measure how much oxygen one had in one’s blood—which fuels cells throughout the body—and motivate appropriate action when this level was declining or critically low. Why didn’t the lack of oxygen motivate escape?

Respiration

You probably remember from your high school biology that when humans breathe, we take in air that contains nitrogen, carbon dioxide and, importantly, oxygen. Our lungs draw out some of the oxygen, which gets absorbed into the blood stream and delivered to cells all over the body. At the same time, carbon dioxide comes out of the blood and is exhaled.

Cellular respiration is the process by which oxygen is used to produce usable energy (ATP), leading to the production of carbon dioxide. Because our cells need oxygen to function continuously, we tend to breathe continuously. But we can also go for a little while without breathing, which is helpful when we want to fetch oysters from the bottom of the sea or change a diaper. This ability creates a need for keeping track of how urgent it is to breathe again. An oyster diver needs to know when to turn back because the need to replenish oxygen is getting dire.  

Because of the way breathing works, there is, under nearly all conditions, a very straightforward relationship between the amount of O₂ and CO₂ in the blood. If you want to read all about partial pressures of gasses and so on, feel free, but the key piece is that they are very closely—and inversely—related. As you hold your breath, your cells are using up O₂ and producing CO₂, so the level of CO₂ goes up and the level of O₂ goes down, right in sync. For this reason, if—again, under normal conditions—you know the amount of CO₂ in the blood, you can closely infer the level of O₂.

So, while there are probably a number of ways that evolution could have engineered the need to breathe in organisms with lungs, the two obvious ones are 1) to measure the amount of oxygen in the blood and motivate breathing when this level gets low and 2) to measure the amount of carbon dioxide in the blood to motivate breathing when this level gets high.

Before reading The Disappearing Spoon, I figured evolution would have settled on measuring oxygen. After all, that seems the most obvious and direct method. But, of course, because of the way that evolution by natural selection works, the design won’t necessarily be what is obvious to me. There were two ways it could have gone—equally good, in terms of the function—and the one that won out was, as it turns out, the second one.

Humans, like other mammals—not to mention birds, amphibians, and reptiles—have lungs and a system that measures CO₂. That feeling you get when you hold your breath is the result of this CO₂-measuring system. There are receptors in, among other places, a structure called the medulla oblongata (brain stem) that measure the partial pressure of CO₂ (PaCO₂) in the blood. As CO₂ levels increase, the pH of the blood declines, which can be detected by chemoreceptors designed for this function.¹

This is why you feel the urge to breathe when you are underwater. Eventually, in fact, this motivational system is so strong—not that surprising, given what’s at stake—that you will try to breathe even if you are underwater. This will have the unfortunate effect of water filling your lungs and, if not corrected, death.

As a complete aside, there is no reason, in principle, that the cells in lungs can’t remove the necessary oxygen from a liquid instead of a gas. As dedicated readers know, I have an affinity for science fiction, which is how I know that in the 1989 movie The Abyss, there is a sequence in which a rodent is put into a liquid that is very rich in oxygen and, after a bit of a struggle, the little guy appears to breathe in the liquid. It looked pretty incredible. I remember puzzling about how the movie creators did this—it seemed to me beyond the special effects of the time—and it turned out that this wasn’t a fancy visual effect. It was real: the rats were taking in oxygen from a fluid. Six rats were used to shoot the sequence and all survived.

Back to Columbia

So, to return to the NASA technicians, what was going on?

Normally, when we breathe in, we are taking in air that is about 21% oxygen, 78% nitrogen, and small amounts of other gasses, including carbon dioxide. The exhale contains about 16% oxygen, the same amount of nitrogen, and four or five percent carbon dioxide. The reason that we exhale some oxygen is that the lungs can’t pull out all the oxygen from each breath, so we exhale the unabsorbed oxygen. This fact explains why mouth-to-mouth breathing is effective for resuscitation. If there were not residual oxygen in our exhale, breathing into the mouth of someone who needed oxygen would be ineffective.

When one holds one’s breath, the fraction of oxygen in the lungs and the blood gradually decreases, as the cells use the oxygen. The level of carbon dioxide in the blood goes up for the same reason. As your level of carbon dioxide increases, you increasingly feel the need to breathe. The measurement of CO₂ is motivating inhaling.

Now, when one starts to breathe in pure nitrogen, remember that one is exhaling both the CO₂ in the lungs and remaining oxygen in the lungs. The body’s cells are, of course, still producing carbon dioxide with the oxygen that they have from prior breaths. For this reason the level of CO₂ in the blood will remain relatively stable as cells metabolize oxygen to CO₂, which then goes from the blood to the lungs and is expelled with exhalations.

In contrast, the level of oxygen in the blood decreases rapidly because oxygen is being expelled from the lungs but not replaced. (Recall that the exhale is 16-17% oxygen when breathing normally; when one is holding one’s breath, your lungs can make use of the residual oxygen.)

In summary, when you’re holding your breath, oxygen goes down slowly and carbon dioxide rises slowly. When breathing pure nitrogen, oxygen goes down quickly but carbon dioxide does not rise as precipitously as oxygen falls, because there is less oxygen to produce carbon dioxide. Since there is no quick rise in carbon dioxide, the technicians experienced none of the discomfort that normally accompanies the need to breathe. The table below summarizes this pattern.

This difference explains why the engineers lost consciousness due to lack of oxygen to the brain before they experienced the discomfort associated with the motivational system designed to motivate breathing, leading to their peril.

This case illustrates a point that Josh has been making, especially in his recent pieces on technology, but in his writing on emotions as well. Here, the modern world has given rise, due to technological change, to a danger which our ancestors, it is safe to say, never faced. We are not descended from ancestors who regularly marched into nitrogen-filled engine blocks. If we were, it could be that evolution would have given rise to a system to counter this threat, a way to measure oxygen and motivate escape of places that lack it. But it didn’t.

Evolution Finds a Way

Ok, so that returns us to the question posed above: why is our primary tool for measuring the urgency of breathing CO₂-based instead of O₂-based? As the nitrogen case illustrates, it seems better to go with O₂, the gas that’s actually needed, rather than the one we’re trying to get rid of.

The short version is that I don’t know, and probably no one else does or ever will. This “choice,” if you will, was made millions and millions of years ago, as respiratory systems were evolving in our ancestors. (See footnote 1, above, for one possibility.)

Evolution, of course, isn’t forward-looking. Genes are selected because of how they fare in the environment in which they exist, not future environments. You know that feeling you get with the level of dangerous ionizing radiation increases? Of course you don’t, because our ancestors didn’t face the adaptive problem of fleeing from meltdowns of nuclear reactors. If we did, maybe we would have systems on board that measure radiation and motivate escaping it. But we don’t. Evolution acts on what it has to work with, so we’re left with no defenses against harmful radiation.²

Related, evolution can get stuck in a rut. Among vertebrates, such as humans, the optic nerve in the eye is on the "wrong" side of the retina: The nerves and blood vessels are in front of the retina rather than behind it. This arrangement leads to a blind spot where the optic nerve exits the eye, as there are no photoreceptors in that region. (You can find your blind spot, if you’re so inclined.) It’s not like the other way isn’t possible at all. Our cephalopod friends, such as octopuses and squids, have their optic nerve the proper way round.

The design of this aspect of the eye constitutes an excellent example of what’s called path dependence. Once the initial design evolved, there was no incrementally favorable path to improvements with the optic nerve behind, rather than in front, of the retina. It’s very much like the QWERTY keyboard. The key layout might not be optimal, but that’s how they started and new designs follow the old. The initial design of the eye constrained future evolutionary pathways. 

In the case of determining when to motivate inhaling, evolution “found,” if you will, something it could measure—a proxy for carbon dioxide—and stuck with it through the generations.

To the detriment of the brave souls lost on Columbia.

1. There is some redundancy in this system and there are some cells that respond to reduced levels of oxygen in the blood, but this system operates only under particular circumstances. In terms of the question about the evolutionary question, here is one possibility, which takes us back to The Disappearing Spoon, a book about chemicals. As CO₂ levels increase in the blood, carbonic acid (H₂CO₃), is formed—you’ll see in that formula that you have H₂O (water) plus CO₂—which dissociates into hydrogen ions (H⁺) and bicarbonate ions (HCO₃⁻). For this reason, small increases in CO₂ levels lead to all those hydrogen ions and, in turn, changes in blood pH which, voila, can be detected.

2. I mean, we do have systems in our skin that detect energy from the sun in the sense that the sun’s rays heat our skin and we have specialized nerve endings that detect changes in temperature, which motivate some of us to seek the shade. Or sunscreen.