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The Man of Steel, Myostatin, and Super Strength

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As an infant, the Man Of Steel escaped Krypton’s red sun in a rocket lovingly prepared for him by his parents. Kal-L (but more commonly known as Kal-El) arrived under our yellow sun in Smallville to eventually become Clark Kent. Since his debut in Action Comics #1 in June of 1938, Superman has accumulated a pretty long list of “super abilities”.

For me, though, I really like the list of his abilities that come from the 1940s radio serials. This was back when Superman was described as "faster than a speeding bullet, more powerful than a locomotive, and able to leap tall buildings in a single bound”. These descriptions all have to do with super-strength when you get right down to it. And with this summer’s “Man of Steel” Superman re-boot, super-strength is the focus of this post.

I have to admit I’ve always found the explanation for Superman’s powers to be, well, a bit dubious. He has his powers because of our yellow sun. That is, because he was from a red sun planet (Krypton) somehow the yellow sun of Earth unleashes some inner super power mechanism that gives Superman all his…super-ness. Of course it’s a bit pure escapist fun. But what if there actually was something to that, though?

I don’t mean something to the “yellow sun / red sun” stuff. You can just check in with our “friendly neighborhood physics” professor Jim Kakalios and his bok “Physics of Superheroes” for the real deal on that one. I mean rather the unleashing of some inner mechanism bit. What if something inside the human body could be unleashed—like removing the shackles from Hercules—and allow for dramatically increased strength?

Which brings me to two proteins with the superhero sounding names of myostatin and activin A. These are “chalones”—factors secreted by your cells to suppress excessive growth of an organ—found in your muscles. They basically work to keep the size and number of your muscle cells—and thus your overall strength—within a certain range. Since these factors work to negatively regulate muscle cell growth, removal of these factors allows muscle cells to get larger and increase in number. That’s where the “super-strength” comes from!

The Source of Super-Strength Here On Earth…

Myostatin itself has a pretty interesting history in animal husbandry and selective breeding. Although it didn’t go by the name myostatin back then, the effect of this growth factor was first described in cattle as “bovine muscular hypertrophy” by the British farmer H. Culley in 1807. Cattle that have a myostatin gene deletion look unusually and excessively muscular. So much so that the term “double muscled” is often used because of the look and the reality that such a cow has less bone, less fat and much more muscle than a “normal” cow.

This mutation, and more recently that of activin A, has been shown in many mammals so far, including rodents, dogs, pigs, sheeps, and—wait for it—humans. In fact I used this as partial basis for a genetic basis for Batman’s abilities in my first book.

The best example of myostatin gene deletions in humans was provided by Schuelke and colleagues back in 2004. The figure comes from that study and shows the image of the child at 6 days old (left side) and at 7 months (right). Arrowheads point to clear increases in muscle tissue at the hip and lower leg. The ultrasound images show the areas and sizes of the muscles (F=femur bone, VL, VI, VM, and RF are all parts of the ‘quadriceps’ knee extensor muscle group) for the child with the mutation (left) and a child of the same age without the mutation. This boy continued to develop normally but with greatly enhanced strength. In fact, at the age of 4½ this child could hold two 3 kg dumbbells with arms straight out to the sides!

But, there’s more. The story so far…your strength is a function of the number and size of your muscle cells. And the size and number of your muscle cells is regulated by myostatin and activin A. What if there was something that also guarded the guards? Well, it appears follistatin might fit that requirement. This means there could be a way to turn off the genetic switch that keeps muscle strength in check. Maybe.

Superhero Genetic Engineering… What Do We Want To Super-Charge?

Recent advances have decoded genes related to high performance in many bodily systems in humans. This gives us a kind of road map over what we want to mutate on purpose. Super-strength is a good place to start.

First of all, a note of caution. The long-term effects of deliberately inducing genetic manipulations on these growth factors aren’t known. And it hasn’t been used clinically in humans yet. But it has been done in monkeys.

That’s right. We are close to super strong monkeys. Which, in a bit of an aside, I have to admit actually scares me a little bit. That’s because of this thing I’ve had about monkeys since I first saw “The Wonderful Wizard of Oz” when I was 5 years old. It was the scene where the Wicked Witch of the West calls out her flying monkeys (okay, actually called “winged monkeys”). Those creepy monkeys defeated the Winkies, the Great Oz, and kidnapped Dorothy. When those winged primates came spilling over the rooftops to pick up Dorothy I thought it then and I still think it now—monkeys should not fly.

Instead of flight, muscle strength was on order in 2009 when research scientists at the Center for Gene Therapy at Nationwide Children’s Hospital in Ohio and at Ohio State University carried out their work. They used a virus (a viral vector) to insert the human gene for follistatin into knee extensor muscles of macaque monkeys. Remember that follistatin works to block the action of myostatin. To remove the brake on muscle growth, in other words.

This gene insertion permanently modified the muscle properties of the monkeys. The muscle grew about 25% larger and stronger than normal. This kind of experiment had been done before in other animals like mice, but this was the first time it had been successfully shown in non-human primates. It hints at possible application in humans—and beyond—yet to come.

That’s my scientific explanation for Kal-El’s super-strength under our yellow sun. Using comic book willful suspension of disbelief and assuming a similar physiology for Kryptonians and humans, perhaps the radiation from our yellow sun activated some epigenetic mechanism that eventually led to increased follistatin expression in all the muscles in Clark Kent’s body. Voila. Super-strength. Or super-strength light, I guess, since the strength gain isn’t on the order of 100 x or more that we eventually see in Superman.

But it’s a start. And, more importantly, this approach has huge potential to improve muscle mass and function in those with degenerative muscle disorders. Superman would definitely approve.

 

The views expressed are those of the author and are not necessarily those of Scientific American.

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