(Warning: Spoilers)

2016 has been the year of disappointing comic book superhero movies such as the widely-panned “Batman vs. Superman” and “X-men Apocalypse”, but one film that received surprisingly high reviews from both critics and fans is Marvel’s R-rated action comedy “Deadpool”.  The film follows the exploits of Wade Wilson, aka the eponymous Deadpool, as he goes from wisecracking mercenary, to wisecracking cancer patient, to wisecracking superhero bent on revenge.  Many reviews have discussed the plot structure, originality, and marketing of the film.

This is not one of those reviews…

Instead, we’re going to look at the science behind the film, and ask whether –and to what degree — there is any scientific basis for Deadpool’s superhuman abilities.

Deadpool’s primary ability is hyper-regeneration. He is able to shrug off potentially lethal bodily injuries, to the point where he severs his own hand, and within a few days has regrown a new one.  But how did he gain these abilities, and how realistic might they be?

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Images adapted from Wikipedia, and full image by Barbara J

Adrenalin as a catalyst. In the movie, Wade Wilson is given his preternatural healing abilities as part of an experiment by evil scientist stereotype Ajax in order to cure his otherwise lethal cancer.  Ajax claims that in order to activate the therapy, which is based on unnamed mutagens, which are catalyzed (in the movie) by high levels of adrenalin – justifying a montage of torture scenes designed to increase Wade’s adrenalin levels.  Of course, these types of activities tend to be rightly frowned upon in any civilized society, but comic book villains don’t have to worry about ethics boards and funding agencies, so we’ll let this slide.

Adrenalin itself wouldn’t be a very good catalyst since it has no actual catalytic properties. Furthermore, it doesn’t take a scientist to realize that torture is just about the worst way of inducing an adrenalin spike.  It might work, but the results will vary between people, and one won’t be able to control the amount of adrenalin released.  Anybody who has ever seen Pulp Fiction, or is a real scientist, knows that adrenalin can be administered by injection with a needle.  If Ajax had been just a cancer scientist he could’ve activated Wade’s healing abilities by hooking him up to an IV bag with appropriate doses of adrenalin.  But then, without the torture montage, Ajax becomes more of a clinician who actually cures Wade’s cancer (albeit with some ugly side effects), and not so much a movie supervillain.  So really, Ajax isn’t just a bad guy, he’s a bad scientist to boot!

Regenerating limbs. So how might the eponymous wisecracking hero have gained the ability to regenerate such injuries as gunshot wounds and, more surprisingly, and entire hand at one point?

Loss of p21? Cyclin-dependent kinase inhibitor 1A (CDKN1A), commonly called simply “p21”, is a protein that plays an important role in cell cycle arrest.  Notably, mice deficient for p21 display enhanced regenerative capabilities and ear punctures in these mice close completely without scarring.  They also form a blastema – a structure typically observed during limb regeneration, though it is less clear whether p21-defiicent mice are capable of regrowing entire limbs.

Unfortunately, p21 plays an important role in fighting cancer incidence. P21 is one of the canonical “tumor suppressor” genes, and one of the primary targets induced by the master tumor suppressor, p53. P21, however, is also the primary effector for p53-induced cellular senescence, which promotes aging and age-related disease (see our blog:  Aging Fundamentals: Cellular Senescence).  Thus, if Ajax’s treatments mutated Deadpool’s p21, he might gain the regenerative abilities displayed in the movie, but the cancer he was being treated for would likely have gone out of control, resulting in his death, making for a very short movie.

Developmental regression? Forms of hyper-regeneration akin to Deadpool’s are seen sporadically in the animal kingdom, from hydra to planaria, but perhaps the most notable parallel to our hero’s abilities is a type of salamander known as an axolotl.  These amphibians spend their entire adult lives in a sort of semi-developed state.  However, upon injury, such as loss of limb, the cells at the site of injury undergo a form a developmental regression, de-differentiating into new stem cells, which in turn allow the regeneration of the limb.  This unique process allows these animals to regenerate from virtual destruction to their limbs, hearts, and even spinal cords.  Indeed, in this embryonic-like state, p21 levels are reduced.  Research in this area is a major focus for those studying limb regeneration.  Unfortunately, due to pollution in an already limited home environment (a single lake in Mexico City), the axolotl is now critically endangered, and possibly extinct, in the wild.

Hyperactive Immunity?  In the axolotl, limb regeneration required the presence of macrophages at the site of injury.  These immune cells clear the wound and prevent fibrosis (scarring) that would otherwise limit the ability of the limb to regrow.  Furthermore, current therapeutics that activate the immune system toward elimination of cancer cells are among the biggest recent breakthroughs in cancer therapies.  Might Deadpool have hyperactive macrophages that allow both regeneration, and also killed his cancer?  The analogy goes even further, immune cells can attack normal cells under certain conditions, a phenomenon known as autoimmunity, it’s possible that this autoimmune response is what drove Deadpool’s loss of hair and created the appearance of his damaged skin.  This hypothetical scenario seems the most plausible explanation for the phenomena observed in Deadpool.  A major caveat, however, is that adrenalin acts in part by suppressing – rather than activating – the immune system, so the treatments described in the movie would actually have the opposite effect on Deadpool’s immune system.

It’s just a story, right? In the end, Deadpool is a movie based upon a comic book character.  The scientific bases of these types of phenomena are left more to the narrative than to any type of hard science.  Speculative fiction such as that found in science fiction or even comic book movies allows for a creative interpretation for how things might be, and might inspire a scientist’s next big breakthrough.  At worst, these movies are excellent creative fodder for an amused blogger.