In it for the long run

3 May 2013 by Malcolm Campbell, posted in Biology

Some people can’t figure out what I’m doing. It’s not a walk-hop, it’s not a trot, it’s running, or as close as I can get to running, and it’s harder than doing it on two legs. It makes me mad when people call this a walk. If I was walking it wouldn’t be anything. Terry Fox (1958-1981)

Imagine running a marathon every day for 140 days. Now imagine doing this with one leg amputated, a prosthesis in its place.

Many of us can’t fathom running a marathon, let alone consecutive marathons, daily, for 20 weeks straight. And yet, that is what a remarkable young man did 33 years ago. With one leg. His name was Terry Fox.

Terry Fox was 18 years old in 1977 when he lost his right leg to osteosarcoma.  A remarkable athlete, Fox accomplished an amazing rehabilitation with an artificial leg. Within two years he managed to run a marathon with what was, at that time, a fairly rudimentary prosthesis.

Frustrated by the small amount of funding dedicated to cancer research, and encouraged by his ability to complete a marathon, Fox devised a plan to raise both awareness and funding for this important cause. He would run across Canada.

Fox began his run across Canada, which he called Marathon of Hope, on April 12, 1980.  The pain of running was excruciating. Because of the manner in which he had to run, the prosthesis bruised his bone and blistered his skin. After 20 minutes of running Fox would pass a pain threshold that would enable him to continue with greater ease. He ran under these conditions for 143 days and covered 5373 km. His run was cut short by the return of his cancer.  By June 28 in 1981, Terry Fox succumbed to the cancer he had fought so hard to beat.

It is almost impossible to imagine what Terry Fox endured on a day-to-day basis during the Marathon for Hope. What keeps a person running under such conditions? How does one keep running despite adverse conditions, and continuous pain?

There are a good many of us who do not have to endure a prosthetic leg that still have a love-hate relationship with running. Our bodies just didn’t seem designed for it.  We’re flat of foot, short of stride, weak of knee, or have some other limitation that makes running a chore at best; a pain at worst. And yet we’re compelled to run. We don our runners and hit the road, heedless of rain, sleet, snow, suffocating humidity, blistering heat, and treacherous motorists. And all for what? We generally have much less compelling reasons to run than did Terry Fox, and yet we continue to run. Where does this drive to run come from? Is there an innate, hard-wired capacity to continue running, even under adversity?

The origins of running are obvious. In an eat-or-be-eaten existence, running might be your route to the next meal, or to avoid being someone else’s dinner. Simply put, running, especially running under adverse conditions, is a crucial, adaptive survival strategy.

In keeping with the need for speed, many four-footed mammals have at least three running gaits. There’s the two beat trot, the three beat canter, and the four beat gallop. The trot is a marathoner’s gait, enabling the animal to move along at a decent pace over long distances.

There’s good evidence that the manner of trotting is hard-wired. Like some other quadrupeds, horses have two trotting styles. There is the trot proper, and the pace. In the trot, feet on the diagonal strike the ground simultaneously. That is, the left fore foot and the right hind foot move in unison and strike the ground on one beat; whereas, the right fore foot and the left hind foot move in unison and strike the ground on the other beat.

In the pace, the lateral feet strike the ground at the same time. Here the left fore foot and the left hind foot move in parallel and strike the ground on one beat; whereas the right fore foot and the right hind foot move in parallel and strike the ground on the other beat. When observing the pace, the animal appears to be rocking from side to side, as the pair of legs on one side of the body move forward and then the other move forward. Consequently, the pace is said to be an ambling gate.

Trotting and pacing are distinct enough that standardbred horse racing (i.e., harness racing) has separate races for each version of the gait. This has important implications, as it suggests that some horses are natural trotters while others are natural pacers. This turns out to be the case.

While trotting is a natural gait for horses, pacing is generally not, except in some breeds. Standardbreds, Tennessee walking horses, Peruvian pasos and Icelandic horses all have natural pacing gaits. Other horse breeds do not. In keeping with this, the pace is highly heritable. If the dam and sire are pacers, the offspring are likely to be also.  Lisa Andersson, Leif Andersson, Klas Kullander, and their colleagues capitalised on this fact, and analysed the genomes of 30 Icelandic horses who trotted only and 40 who could pace. By comparing these genomes, they found that a mutation in a single gene discriminated trotters from pacers. In fact, this same mutation is found in all horses that pace.

The trotting versus pacing gene is called DMRT3.  The DMRT3 gene encodes a protein that controls the function of other genes. Crucially, the DMRT3 protein does its job in neurons. In effect, it is involved in creating the neuronal wiring that determines whether a horse is a trotter or a pacer. The normal protein ensures the horse will be a trotter. The mutated DMRT3 gene found in pacers can’t do its job properly.  If a horse has two copies of the mutated DMRT3 gene, the neuronal circuits are more permissive, and enable the horse to trot and pace.

The impact of the DMRT3 gene suggests that a single gene can wire an individual for a particular running style. Well, at least in horses. This said, these findings suggest that analogous genes in humans could determine why running is such a chore for some of us, and not others. It remains to be determined if genes controlling gait exist in humans, but it is not a far stretch to imagine that there are genes that control aspects of human anatomy or neurogenesis that may predispose some individuals for easy running relative to others.

While such genes may make us more amenable to running (or not), they don’t say why we keep running. For that, we have to turn from horses to ferrets.

Ferrets turn out to be a relatively good model for a species that are relatively inactive – at least as far as long-distance running goes.  David Raichlen, Andrea Guiffrida and colleagues took advantage of this fact to contrast the activity of ferrets’ internal “reward system”, with that of equivalently-treated dogs and humans, all after strenuous running. The reward system in question was that related to endocannabinoid signalling.

Endocannibinoids are compounds that we all synthesise in response to neuronal stimuli. Endocanniboids elicit a variety of neurological effects, including the so-called “runner’s high”. The runner’s high occurs at times of strenuous activity, and results in a number of effects, including feelings of euphoria and the ability to work past normal pain limits.  Runner’s high is associated with elevated levels of a particular endocannibinoid, anandamide.

When endocannibinoid levels were examined before and after running on a treadmill, the researchers made an intriguing find. While dogs and humans had elevated levels of anandamide, ferrets did not. What’s more, in keeping with a runner’s high, the human participants in the study reported feeling happy after the exercise. Unfortunately, it was not possible to determine the ferrets’ and canine states of mind. This said, as the endocannibinoid system operates in ferrets, it is unlikely that it was stimulated by the vigorous run. The researchers hypothesise that evolution linked the endocannibinoid reward system to strenuous activity, like running, in those animals where running was a key survival strategy. In this manner, runners are motivated by the run itself, even when the activity itself is painful.

Raichlen has recently taken this hypothesis one step further, suggesting that the evolution of human brain size might be linked to aerobic activities like running. As aerobic physical activity generates and protects new neurons, thereby increasing brain volume and improving cognition in humans and other mammals, it is proposed that increased demands for this aerobic activity might actually have contributed to brain size evolution.  It may be that, from a neurological perspective, we are not only wired to run, but that we are wired by running.

Terry Fox was certainly wired by running. It made him who he was, and it served as inspiration for others. He raised awareness of cancer, and the desperate need for research to battle this disease in its various configurations. In addition to the donations he received during the Marathon for Hope, the foundation created in his name has raised hundreds of millions of dollars, with 84 cents of every dollar raised going directly to cancer research.

Aside from this, Terry Fox has served as an inspiration for people to strive to make the world a better place for others. I have my own story in this regard. In the sweltering summer of 1980, I was in the backseat of my parents’ car in the Canadian province of Ontario when the highway traffic came to a dead stop. Everyone got out of their cars.  Moving north on the highway was a young man with a bobbing gate, running down the highway. He was accompanied by another young man (his brother) and a yellow camper van. It was Terry Fox. The honking of horns, the cheering, the clapping, and the passing of cash to the donation bucket were unforgettable. But even more so was the determination on the face of that young man. It is something I will never, ever forget. In the face of profound adversity, he was doing something incredible. Not for himself. For others.

Terry Fox’s Marathon of Hope was motivated by his desire to make a difference – using his running as an example, as an inspiration. He achieved his aim through his own determination, while making use of an evolutionary innovation that rewards running, even when it is difficult to endure. We should all take heart that we share with Terry Fox the legacy of being able to keep running through tough times. Like him, we have within us the ability to capitalise on our own internal reward system to benefit the lives of others. It is fitting that a runner’s high has the capacity to elevate the prospects for those with whom we share this world.


Andersson LS et al. (2012) Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature 488: 642-646

Raichlen DA et al. (2012) Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’. The Journal of Experimental Biology 215: 1331-1336

Raichlen DA & Polk JD (2013) Linking brains and brawn: exercise and the evolution of human neurobiology. Proceedings of the Royal Society B: Biological Sciences 280: (in press)


Opening Terry's Cause Run in October 2012, with Darrell Fox, Terry's Brother.
Credit: Ken Jones

[Note: This post was inspired by a number of charity runs that I have participated in over the last year. Until a year ago, I would never have described myself as a runner. Now I describe myself as a bad runner. This weekend I will run my first half marathon. I am running it for the Heart & Stroke Foundation, in honour of my brother-in-law, Darryl Verbiski, who suffered a  stroke at the end of the 2012. Tweets of support during the run most welcome!]

2 Responses to “In it for the long run”

  1. Sean McCann Reply | Permalink

    A really great story about a fellow student at SFU. I was only 4 when he made his run, but the story has loomed large in my consciousness since then. Thanks for writing this!

    • Malcolm Campbell Reply | Permalink

      You are most welcome, Sean! Terry Fox's story is such an amazing one, isn't it? His spectacular inspiration continues to resonate with people like you and me, despite the fact that we were younger than him at the time of his run. An amazing legacy.

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