I have a new paper out:

Wedel, M.J. 2012. A monument of inefficiency: the presumed course of the recurrent laryngeal nerve in sauropod dinosaurs. Acta Palaeontologica Polonica 57(2):251-256.

Update June 6, 2012: the final version was formally published yesterday, so the rest of this paragraph is of historical interest only. Like Yates et al. on prosauropod pneumaticity, it is “out” in the sense that the manuscript has been through peer review, has been accepted for publication, and is freely available online at Acta Palaeontologica Polonica. Technically it is “in press” and not published yet, but all that formal publication will change is to make a prettier version of the paper available. All of the content is available now, and the paper doesn’t include any of those pesky nomenclatural acts, and so, as with the prosauropod pneumaticity paper, I don’t see any reason to pretend it doesn’t exist. Think of the accepted manuscript as the caterpillar to the published version’s butterfly: different look, but same genome.

This one came about because last summer I read a review of Richard Dawkins’s book, The Greatest Show on Earth: The Evidence for Evolution. The review mentioned that the book includes a lengthy discussion of the recurrent laryngeal nerve (RLN) in the giraffe, which is a spectacularly dumb piece of engineering and therefore great evidence against intelligent design creationism. It wasn’t the first time I’d heard of the RLN, of course. It’s one of the touchstones of both human anatomy and evolutionary biology; anatomy because of its clinical importance in thyroid surgery, known for more than two millennia, and evolutionary biology because it is such a great example of a developmental constraint. (Dawkins’s coverage of all of this is great, BTW, and you should read the book.)

No, the reason the book review inspired me to write the paper was not because the RLN was new to me, but because it was overly familiar. It is a cool piece of anatomy, and its fame is justly deserved–but I am sick and tired of seeing the stinkin’ giraffe trotted out as the ultimate example of dumb design. My beloved sauropods were way dumber, and it’s time they got some credit.

But first, let’s talk about that nerve, and how it got to be there.

No necks for sex? How about no necks for anybody!

Embryos are weird. When you were just a month old (counting from fertilization), you had a set of pharyngeal arches that didn’t look radically different from those of a primitive fish. These started out quite small, tucked up underneath your comparatively immense brain, and each pharyngeal arch was served by a loop of artery called an aortic arch. What we call the arch of the aorta in an adult human is a remnant of just one of these embryonic aortic arches, and as you’ve no doubt noticed, it’s down in your chest, not tucked up next to your brain. When you were in the embryonic stages I’m talking about, you didn’t yet have a neck, so your brain, pharyngeal arches, aortic arches, and the upper parts of your digestive system were all smooshed together at your front end.

Human embryo at three weeks. From http://education.yahoo.com/reference/gray/subjects/subject/135

One thing you did have at that stage was a reasonably complete peripheral nervous system. The nerve cell bodies in and near your central nervous system sent out axons into the rest of your body, including your extremities. Many of these axons did not persist; they failed to find innervation targets and their parent neurons died. Imagine your embryonic central nervous system sending out a starburst of axons in all directions, and some of those axons finding targets and persisting, and others failing and dying back. So the architecture of your nervous system is the result of a process of selection in which only some cells were successful.

Crucially, this radiation and die-off of axons happened very early in development, when a lot of what would become your guts was still hanging under your proportionally immense brain like the gondola on a blimp. This brings us to the recurrent laryngeal nerve.

Going back the way we came

The fates of your embryonic pharyngeal arches are complex and I’m not going to do a comprehensive review here (go here for more information). Suffice it to say that the first three arches give rise to your jaws and hyoid apparatus, the fourth and sixth form your larynx (voicebox), and fifth is entirely resorbed during development. Update: I made a pharyngeal arch cheat sheet.

There are two major nerves to the larynx, each of which is bilaterally paired. The nerve of the fourth pharyngeal arch becomes the superior laryngeal nerve, and it passes cranial to the fourth aortic arch. The nerve of the sixth pharyngeal arch becomes the inferior or recurrent laryngeal nerve, and it passes caudal to the sixth aortic arch. At the time that they form, both of these nerves take essentially straight courses from the brainstem to their targets, because you’re still in the blimp-gondola stage.

If you were a shark, the story would be over. The more posterior pharyngeal arches would persist as arches instead of forming a larynx, each arch would hold on to its artery, and the nerves would all maintain their direct courses to their targets.

The normal fate of the aortic arches in humans. From http://education.yahoo.com/reference/gray/subjects/subject/135

But you’re not a shark, you’re a tetrapod. Which means that you have, among other things, a neck separating your head and your body. And the formation of your neck shoved your heart and its associated great vessels down into your chest, away from the pharyngeal arches. This was no problem for the superior laryngeal nerve, which passed in front of the fourth aortic arch and could therefore stay put. But the inferior laryngeal nerve passed behind the sixth aortic arch, so when the heart and the fourth and sixth aortic arches descended into the chest, the inferior laryngeal nerve went with them. Because it was still hooked up to the brainstem and the larynx, it had to grow in length to compensate.

Human laryngeal nerves, from http://www.healthcentral.com/ency/408/imagepages/19721.html

As you sit reading this, your inferior laryngeal nerves run down your neck into your chest, loop around the vessels derived from the fourth and sixth aortic arches (the subclavian artery on the right, and the arch of the aorta and ductus arteriosus on the left) and run back up your neck to your larynx. Because they do this U-turn in your chest and go back the way they came, the inferior laryngeal nerves are said to ‘recur’ to the larynx and are therefore more commonly referred to as the recurrent laryngeal nerves (RLNs).

An enlightening diversion

The RLN is the poster child for “unintelligent design” because it is pretty dumb. Your RLNs travel a heck of a lot farther to reach your larynx than they ought to, if they’d been designed. Surely an intelligent designer would have them take the same direct course as the superior laryngeal nerve. But evolution didn’t have that option. Tetrapod embryos could not be built from the ground up but had to be modified from the existing “sharkitecture” of ancestral vertebrates. The rules of development could not be rewritten to accommodate a shorter RLN. Hence Dawkins’s love affair with the RLN, which gets 7 pages in The Greatest Show on Earth. He also appeared on the giraffe episode of Inside Nature’s Giants, in which the RLN was dug out of the neck and the continuity of its ridiculous path was demonstrated–probably the most smack-you-in-the-face evidence for evolution that has ever been shown on television (said the rabid fan of large-tetrapod dissections).

Incidentally, the existence and importance of the RLN has been known since classical times. The RLN innervates the muscles responsible for speech, and on either side it passes right behind the thyroid gland, which is subject to goiters and tumors and other grotesque maladies. So a careless thyroidectomy can damage one or both of the RLNs; if one gets snipped, the subject will be hoarse for the rest of his or her life; if both are cut, the subject will be rendered mute. The Roman physician Galen memorably demonstrated this by dissecting the neck of an immobilized but unanesthetized pig and isolating the RLNs (Kaplan et al. 2009). One moment the poor pig was squealing its head off–as any of us would be if someone dug out our RLNs without anesthesia–and the next moment Galen severed the RLNs and the animal abruptly fell silent, still in unbelievable pain but now without a mechanism to vocally express its discomfort.

Galen versus pig. Figure 2 from Kaplan et al. 2009.

The name of the nerve also goes back to Galen, who wrote:

I call these two nerves the recurrent nerves (or reversivi) and those that come upward and backward on account of a special characteristic of theirs which is not shared by any of the other nerves that descend from the brain.

Like at least some modern surgeons, Galen does not seem to have been overly burdened by humility:

All these wonderful things, which have now become common property, I was the first of all to discover, no anatomist before me ever saw one of these nerves, and so all of them before me missed the mark in their anatomical description of the larynx.

Both of those quotes are from Kaplan et al. (2009), which is a fascinating paper that traces the knowledge of the recurrent laryngeal nerve from classical times to the early 20th century. If you’d like a copy and can’t get hold of one any other way, let me know and I’ll hook you up.

Share and share alike

By now you can see where this is going: all tetrapods have larynges, all tetrapods have necks, and all tetrapods have recurrent laryngeal nerves. Including giraffes, much to the delight of Richard Dawkins. And also including sauropods, much to the delight of yours truly.

Now, I cannot show you the RLN in a living sauropod, nor can I imagine a scenario in which such a delicate structure would be recognizably preserved as a fossil. But as tetrapods, sauropods were bound to the same unbreakable rules of development as everything else. The inference that sauropods had really long, really dumb RLNs is as secure as the inference that they had brainstems, hearts, and larynges.

Wedel (2012) Fig. 1. Course of the left vagus nerve and left recurrent laryngeal nerve in a human, a giraffe, and Supersaurus. The right recurrent laryngeal nerve passes caudal to the right subclavian artery rather than the aorta and ductus arteriosus, but otherwise its course is identical to that of the left.

Giraffes have necks up to 2.4 meters long (Toon and Toon 2003), so the neurons that make up their RLNs approach 5 meters in the largest indiividuals. But the longest-necked sauropods had necks 14 meters long, or maybe even longer, so they must have had individual neurons at least 28 meters long. The larynx of even the largest sauropod was probably less than 1 meter away from the brainstem, so the “extra” length imposed on the RLN by its recurrent course was something like 27 meters in a large individual of Supersaurus. Take that, Giraffa.

Inadequate giraffe is inadequate.

One way or another

It is possible to have a nonrecurrent laryngeal nerve–on one side, anyway. If you haven’t had the opportunity to dissect many cadavers, it may come as a surprise to learn that muscles, nerves, and blood vessels are fairly variable. Every fall in Gross Anatomy at WesternU, we have about 40 cadavers, and out of those 40 people we usually have two or three with variant muscles, a handful with unusual branching patterns of nerves, and usually half a dozen or so with some wackiness in their major blood vessels. Variations of this sort are common enough that the better anatomy atlases illustrate not just one layout for, say, the branching of the femoral artery, but 6-10 of the most common patterns. Also, these variations are almost always asymptomatic, meaning that they never cause any problems and the people who have them usually never know (ask Mike about his lonely kidney sometime). You–yes, you, gentle reader!–could be a serious weirdo and have no idea.

Variations in the blood vessels seem to be particularly common, possibly because the vessels develop in situ with apparently very little in the way of genetic control. Most parts of the body are served by more than one artery and vein, so if the usual vessel isn’t there or takes an unusual course, it’s often no big deal, as long as the blood gets there somehow. To wit: occasionally a person does not have a right subclavian artery. This does not mean that their right shoulder and arm receive no blood and wither away; usually it means that one of the segmental arteries branching off the descending aorta–which normally serve the ribs and their associated muscles and other soft tissues–is expanded and elongated to compensate, and looks for all the world like a normal subclavian artery with an abnormal connection to the aorta. But if the major artery that serves the forelimb comes from the descending aorta, and the 4th aortic arch on the right is completely resorbed during development, then there is nothing left on the right side to drag the inferior laryngeal nerve down into the torso. A person with this setup will have an inferior laryngeal nerve on the right that looks intelligently designed, and the usual dumb RLN on the left.

Can people have a nonrecurrent laryngeal nerve on the left? Sure, if they’ve got situs inversus, in which the normal bilateral asymmetry of the internal organs is swapped left to right. Situs inversus is pretty darned rare in the general population, occurring in fewer than 1 in 10,000 people. It is much more prevalent in television shows and movies, where the hero or villain may survive a seemingly mortal wound and then explain that he was born with his heart on the right side. (Pro tip: the heart crosses the midline in folks of both persuasions, so just shoot through the sternum and you’ll be fine. Or, if you’re worried about penetration, remember Rule #2 and put one on either side.) Anyway, take everything I wrote in the preceding paragraph, mirror-image it left to right, and you’ve got a nonrecurrent laryngeal nerve on the left. But just like the normally-sided person who still has an RLN on the left, a person with situs inversus and no remnant 4th aortic arch on the left (double variation alert!) still has an RLN looping around the aorta and ductus arteriosus on the right.

Bottom line: replumb the vessels to your arms, swap your organs around willy-nilly, you just can’t beat the aorta. If you have an aorta, you’ve got at least one RLN; if you don’t have an aorta, you’re dead, and no longer relevant to this discussion.

Nonrecurrent laryngeal nerves–a developmental Hail Mary?

But wait–how do we know that the inferior laryngeal nerve in embryonic sauropods didn’t get rerouted to travel in front of the fourth and sixth aortic arches, so it could be spared the indignity of being dragged into the chest later on?

First of all, such a course would require that the inferior laryngeal nerve take an equally dumb recurrent course in the embryo. Or maybe it should be called a procurrent course. Instead of simply radiating out from the central nervous system to its targets in the sixth pharyngeal arch, the axons that make up the RLN would have to run well forward of their normal course, loop around the fourth and sixth aortic arches from the front, and then run back down to the sixth pharyngeal arch. There is simply no known developmental mechanism that could make this happen.

Even if we postulated some hypothetical incentive that would draw those axons into the forward U-turn, other axons that took a more direct course from the central nervous system would get to the sixth pharyngeal arch first. By the time the forwardly-recurring axons finished their intelligently-routed course and finally arrived at the sixth pharyngeal arch, all of the innervation targets would be taken, and those axons would die off.

Also, at what point in the evolution of long necks would this forwardly-looping course supposedly be called into existence? Ostriches and giraffes have RLNs that take the same recurrent course as those of humans, pigs, and all other tetrapods. The retention of the recurrent course in extant long-necked animals is further evidence that the developmental constraint cannot be broken.

Finally, the idea that a non-recurrent laryngeal nerve would need to evolve in a long-necked animal is based on the perception that long nerve pathways are somehow physiologically taxing or otherwise bad for the animals in which they occur. But almost every tetrapod that has ever lived has had much longer neurons than those in the RLN, and we all get on just fine with them.

In dire extremity

Probably you have seen enough pictures of neurons to know what one looks like: round or star-shaped cell body with lots of short branches (dendrites) and one very long one (the axon), like some cross between an uprooted tree–or better yet, a crinoid–and the Crystalline Entity. When I was growing up, I always imagined these things lined up nose to tail (or, rather, axon to dendrite) all down my spinal cord, arms, and legs, like boxcars in a train. But it ain’t the case. Textbook cartoons of neurons are massively simplified, with stumpy little axons and only a few to a few dozen terminals. In reality, each neuron in your brain is wired up to 7000 other neurons, on average, and you have about a hundred billion neurons in your brain. (Ironically, 100 billion neurons is too many for your 100 billion neurons to visualize, so as a literal proposition, the ancient admonition to “know thyself” is a non-starter.)

Back to the axons. Forget the stumpy little twigs you’ve seen in books and online. Except for the ganglia of your autonomic nervous system (a semi-autonomous neural network that runs your guts), all of the cell bodies of your neurons are located in your central nervous system or in the dorsal root ganglia immediately adjacent to your spinal cord. The nerves that branch out into your arms and legs, across your face and scalp, and into your larynx are not made of daisy chains of neurons. Rather, they are bundles of axons, very long axons that connect muscles, glands, and all kinds of sensory receptors back to the nerve cell bodies in and around your brain and spinal cord.

Indulge me for a second and wiggle your toes. The cell bodies of the motor neurons that caused the toe-wiggling muscles to fire are located in your spinal cord, at the top of your lower back. Those motor neurons got orders transmitted down your spinal cord from your brain, and the signals were carried to the muscles of your feet on axons that are more than half as long as you are tall.

Some of your sensory neurons are even longer. Lift your big toe and then set it down gently, just hard enough to be sure that it’s touching down on the floor or the sole of your shoe, but not hard enough to exert any pressure. When you first felt the pad of your toe touch down, that sensation was carried to your brain by a single neuron (or, rather, by several neurons in parallel) with receptor terminals in the skin of your toe, axon terminals in your brainstem, and a nerve cell body somewhere in the middle (adjacent to your sacrum and just a bit to one side of your butt crack, if you want the gory details). That’s right: you have individual sensory neurons that span the distance from your brainstem to your most distal extremity. And so does every other vertebrate, from hagfish to herons to hippos. Including, presumably, sauropods.

I had you set your toe down gently instead of pushing down hard because the neurons responsible for sensing pressure do not travel all the way from toe-tip to brainstem; they synapse with other neurons in the spinal cord and those signals have been through a two-neuron relay by the time they reach your brainstem. Ditto for sensing temperature. But the neurons responsible for sensing vibration and fine touch go all the way.

If you want to experience everything I’ve discussed in this post in a single action, put your fingertips on your voicebox and hum. You are controlling the hum with signals sent from your brain to your larynx through your recurrent laryngeal nerves, and sensing the vibration through individual neurons that run from your fingertips to your brainstem. Not bad, eh?

Wedel (2012) Fig. 2. The longest cells in the bodies of sauropods were sensory neurons that connected receptors in the skin of the extremities with interneurons in the brainstem, a pattern of neural architecture that is present in all extant vertebrates. The nerve cell bodies would have been located in the dorsal root ganglia adjacent to the spinal cord. The diagram of the neuron is based on Butler and Hodos (1996: fig. 2–1B).

Getting back to big animals: the largest giraffes may have 5-meter neurons in their RLNs, but some of the sensory neurons to their hindfeet must be more like 8 meters long. I don’t think anyone’s ever dissected one out, but blue whales must have sensory neurons to the tips of their flukes that are almost 30 meters (98 feet) long (subtract the length of the skull, but add the lateral distance from body midline to fluke-tip). And Supersaurus, Amphicoelias, and the like must have had neurons that were approximately as long as they were, minus only the distance from the snout-tip to the back of the skull. I could be wrong, and if I am I’d love to be set straight, but I think these must have been the longest cells in the history of life.

Oh, one more thing: up above I said that almost every tetrapod that has ever lived has had much longer neurons than those in the RLN. The exceptions would be animals for which the distance from brainstem to base of neck was longer than the distance from base of neck to tip of limb or tail, so that twice the length of the neck would be longer than the distance from base of skull to most distal extremity. In that case, the neurons that contribute to the RLN would be longer than those running from brainstem to tail-tip or toe-tip. Tanystropheus and some of the elasmosaurs probably qualified; who else?

Parting Thoughts

In this post I’ve tried to explain the courses that these amazingly long cells take in humans and other vertebrates. I haven’t dealt at all with the functional implications of long nerves, for which please see the paper. The upshot is that big extant animals get along just fine with their crazy-long nerves, and there’s no reason to assume that sauropods were any more troubled. So why write the paper, then? Well, it was fun, I learned a lot (dude: axoplasmic streaming!), and most importantly I got to steal a little thunder from those silly poseurs, the giraffes.

Department of Frivolous Nonsense: yes, I titled the paper after those TV ads for Chili’s hamburgers from a few years back. If you never saw them, the ads compared mass-produced, machine-stamped fast-food burgers with restaurant burgers painstakingly built by hand, and concluded with, “Chili’s Big-Mouth Burgers: monuments of inefficiency!”

Update: All of the following is out of date now that the paper has been formally published. Department of Good Karma: since the paper is at the “accepted manuscript” stage, I still have the chance to make (hopefully minor) changes when I get the proofs. As is always, always, always the case, I caught a few dumb errors only after the manuscript had been accepted. Here’s what I’ve got so far, please feel free to add to the list:

• Page 1, abstract, line 3: pharyngeal, not pharyngial
• Page 1, abstract, line 8: substitute ‘made up’ for ‘comprised’
• Page 6, line 12: substitute ‘make up’ for ‘comprise’
• Page 9, line 5: citation should be of Carpenter (2006:fig. 3), not fig. 2
• Page 10, line 7: “giant axons of squid are”, not ‘ares’
• Page 12, entry for Butler and Hodos should have year (1996)
• Page 12, entry for Carpenter has ‘re-evaluation misspelled
• Page 16, entry for Woodburne has ‘mammalian’ misspelled

(Notes to self: stop trying to use ‘comprise’, lay off the ‘s’ key when typing bibliography.)

References

• Butler, A.B., and Hodos, W. 1996. Comparative Vertebrate Neuroanatomy: Evolution and Adaptation. 514 pp. Wiley–Liss, New York.
• Kaplan, E.L, Salti, G.I., Roncella, M., Fulton, N., and Kadowaki, M. 2009. History of the recurrent laryngeal nerve: from Galen to Lahey. World Journal of Surgery 33:386-393. DOI 10.1007/s00268-008-9798-z
• Toon, A., and Toon, S.B. 2003. Okapis and giraffes. In: M. Hutchins, D. Kleiman, V. Geist, and M. McDade (eds.), Grzimek’s Animal Life Encyclopedia, 2nd ed. Vol 15: Mammals IV, 399–409. Gale Group, Farmington Hills.
• Wedel, M.J. 2012. A monument of inefficiency: the presumed course of the recurrent laryngeal nerve in sauropod dinosaurs. Acta Palaeontologica Polonica 57(2):251-256.