The surprising real genetics behind the X-Men
The X-Men – everyone’s favourite mutants –
are hugely popular, thanks to seven feature films since 2000, with more on the
way, and to the enormously successful comics that have been running for over 50
years. With that kind of exposure, they can have a real influence on the public
perception of genetics, grounded as they are in ideas of mutation and evolution
of the “next stage of humanity”. So, is there any real scientific basis
underlying these stories? Well, to a geneticist, most of the supposed mutant
abilities of the X-Men and their mutant brethren are frankly ludicrous. No
matter how mutant you are, the laws of physics will still apply! (Except for
Entropy Man of course). But some of them are less far-fetched, reflecting the
strange and wonderful world of real-life biology. And underlying them all is a
much deeper mechanism that has, in the real world, a profound effect on how
mutations contribute to evolution.
The X-Men were created in 1963 by Stan Lee at
Marvel comics. He had already done the Fantastic Four and the Hulk and
Spider-Man but wanted to create a new team of superheroes, with a bunch of
different powers. And when it came to their origin story, he was, by his own
admission, just being lazy. He realised he couldn’t have everyone exposed to
cosmic rays or gamma rays or bitten by a radioactive spider – you’d quickly run
out of radioactive animals to bite people that would be in any way cool – Mosquito-Man
or Bed Bug-Man just don’t sound that awesome (though The Tick has always been a
personal favourite).
So, he decided he would simply make them
all “mutants” – they were all just born that way. That way he could have one have lasers coming out of his eyeballs and
another able to control the weather and another able to turn into ice and just
say it was all down to mutation.
He actually wanted to call the comic
The Mutants, but he was over-ruled on the basis that no one at the time really knew
what mutants were – the word was in the air, perhaps, linked to the
ever-present threat of radiation that loomed large in the public consciousness
during the Cold War, but it wouldn’t have been widely understood. And it seems
from looking at some of their abilities that Stan Lee didn’t really know what
mutants are either, because a lot of those powers are just absurd.
I mean, some animals can manage a dim
glow that you can see in the darkest depths of the ocean but lasers out of your
eyeballs like Cyclops is a bit of a stretch. Where would the power come from? And while
we’re at it, how is he supposed to see anything?
Or controlling magnetism like Magneto –
again, some animals can emit very weak electromagnetic fields – duck-billed platypuses
do that to detect their prey, for example – but the idea that a mutation could
let you lift an aircraft carrier is just silly. (It’s inspired silliness, but
still). On the other hand, if you want an origin story for a character with the
ability to manipulate magnetism, I suppose it beats being bitten by a
radioactive platypus.
Many of the other abilities also require
suspension of the laws of physics (a big ask for a little change in your DNA),
but a few of them actually have some grounding in real biology.
Let’s take everyone’s favourite mutant,
Wolverine. His main power is his super-healing ability, which actually is quite
plausible (in kind anyway, if not in degree). There are, in fact, strains of
mice called “super-healing mice” (AKA Murphy Roths Large / lymphoproliferative
mouse strain!) where something very similar has been
found. These strains were initially of interest because they are prone to
autoimmune disorders. Their super-healing ability was discovered quite by
accident when researchers noticed that the ear punches they used to keep track
of individual mice were healing over completely! These mice show increased
wound healing generally, with much reduced scarring and even more rapid healing
of broken bones. It’s still not really known why this is or which genes are
responsible, however.
Wolverine is also ferocious (a
berserker, in fact), and something like that can also be caused by mutations.
In fact, there are many mutations that affect aggressiveness, (having a Y
chromosome certainly does), but the ones with the biggest effect in mice are in
a gene called NR2E1, which is involved in brain development. A line of mice
with mutations in this gene are called “fierce” because they’re so aggressive,
with both males and females viciously attacking other mice or even anyone
foolish enough to put their hand in the cage.
Beast is another mutant whose abilities
are not completely ludicrous. There are mutations that
can make you
super-strong, in genes called myostatin or activin, which normally act to
restrict muscle growth. When these genes are mutated, in cattle, mice or
humans, muscle growth can increase by two-fold or more, with concomitant
increases in strength. And there are also mutations that can make you grow hair
all over your body (a condition called hypertrichosis, or, less
sympathetically, werewolf syndrome).
Now it’s not usually blue hair, like
Beast’s, but there is another mutation that does cause shockingly blue skin
coloration, in a condition called methemoglobinaemia. It is famous from a
particular kindred from the wonderfully named town of Troublesome Creek in the
Appalachian mountains of Kentucky. They are known as the “blue Fugates”, that
being the most common last name in the clan, and they really do have skin close
to the colour of Mystique or Nightcrawler. No signs of shape-shifting or teleportation,
though (although you never know with people from Kentucky – they’re tricksy…)
Let’s see, how about Professor X? He’s
a telepath, of course, with an ability to read minds and manipulate people. As
crazy as it sounds, there is a genetically distinct group of people who are
much better than the rest of the population at reading minds – they’re called
women. On average, women score higher than men on measures of empathy and
performance on tasks like “reading the mind in the eyes test”. People with
autism tend to do very poorly on such tests, but so does a sizeable proportion
of the general male population. Whether there are people at the other end of
the spectrum, with really heightened abilities – super-empathisers – remains
unknown, though it seems plausible enough.
So, overall, most of the X-Men
abilities are completely nuts but a few are only wildly exaggerated, like
super-strength or super-healing or being blue or hairy. But here’s the thing – all
those things arise from mutations in different genes while the X-Men are all supposed
to have inherited a mutation in the same
gene – the “X gene”, yet they have very different abilities. So how could
that be?
Despite not actually knowing anything
about genetics, Lee stumbled onto an idea that actually exists and that, in
fact, plays an important role in evolution. There really is a gene that, when mutated,
causes all kinds of different effects in different individuals.
This gene is called Hsp90 and it
encodes what’s known as a “heat shock protein”. Heat shock proteins are turned
on in cells when they are under stress – like when you suddenly raise the
temperature. Their job is to help the cell deal with that stress and in
particular to help other proteins in the cell to fold into the right shapes.
We have about 20,000 different proteins
in our cells, each one encoded by a different gene. Each protein is made from a
string of subunits called amino acids – there are twenty different kinds that
are strung along in a specific sequence encoded by the DNA sequence of that
gene. As each protein is being made, that string of amino acids folds back on itself in a kind of molecular origami, making a complex three-dimensional structure,
the shape of which depends on all the forces between all the atoms in those
amino acids. The particular 3D shape of each protein is crucial for it to do
its job.
Now, when the temperature goes up, this
distorts those forces and it disrupts the folding, so that many proteins become
non-functional (which is very bad for the cell or organism). The job of Hsp90 and other heat shock proteins is to help them to fold into the right shape – it
(almost literally) grabs hold of them and shakes them up and gives them a
chance to make the right structure.
So, Hsp90 can help a cell deal with
sudden stress by detecting and correcting wrongly folded proteins. But the
other thing that can make a protein fold wrong is if it has a mutation in it. If
you mutate the DNA sequence of a gene you can change the instructions so the
wrong amino acid is inserted into the protein at a particular position and that
can stop it from folding properly. But if it’s given a good shake by Hsp90,
then it can snap out of it and pull itself together.
That sounds great – Hsp90 can protect
the cell from the effects of mutations that alter protein folding. But there’s
a dark side – the result is that those kinds of mutations then start to
accumulate in a species, because Hsp90 is there to make sure they don’t have
any effect. Indeed, all of us have mutations in all kinds of genes that aren’t
having any effect because of Hsp90 and genes like it.
Now, do you see where I’m going? What
happens when Hsp90 gets mutated? Suddenly all those other mutations – whichever
ones were in the background in any particular individual – can have an effect.
And that’s exactly what people saw when they mutated the Hsp90 in fruitflies –
they started seeing flies with all kinds of different phenotypes: deformed or
missing eyes, misshapen wings, altered pigmentation, extra bristles, duplicated
body parts.
All kinds of freaky stuff, just from
mutating that one gene – all the genetic variation that was being buffered and
not having any effect was suddenly released. And not only that, when they put
the animals under stressful conditions (high temperature) it got even freakier.
Which is another central part of the X-Men mythology – the idea that, while
they are born mutants, their abilities often lie latent for years and only come
out at times of high stress. Often this is when they’re teenagers, because, as
well know, being a teenager is, like, OMG, sooooo stressful!
In evolution, this kind of mechanism is
hugely important – it allows so-called “cryptic genetic variation” to
accumulate in a population without affecting the phenotypes of the individuals.
But if the environment changes (or the organisms move to a new environment),
the stresses associated with that may “release” some of that genetic variation,
so that it starts to affect the traits of individuals. And somewhere among that
pool there may be some changes that are adaptive to the new environment. Those
differences may be selected for in the new environment so that the species
(though not all the individuals in it) can adapt more rapidly than they would
have if they came in with a clean slate, as it were, and had to wait for new
mutations to arise. The cryptic genetic variation is thus a source of evolutionary potential.
So, despite the fact that Stan Lee
seems to have known very little about genetics, the central premise of the
X-Men isn’t that far-fetched after all and actually reflects a mechanism that
is central to how species evolve and adapt to new conditions.
Still doesn’t mean we’ll have laser-beams
shooting out of our eyeballs any time soon, though…
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