Deadpool, the fourth-wall-breaking comic book hero turned movie star known as the “merc with a mouth,” is effectively immortal. No matter which way he gets sliced and diced, he does not die. Cursed by Thanos, one of the most villainous characters in the Marvel Universe, barring him from reaching “his lady” death, Deadpool sometimes shoots himself in the head to be with “her” for a while. But it’s always futile because he just regenerates, pops back up, and lives to fight another day. And another day. And another. 

Deadpool is a mutant who has an accelerated healing factor. He can re-grow his parts or attach them if cut from his body. He is said to have cancer, which resulted in a deformed face, but he does not die due to his heavy healing factor. All fantasy and sci-fi aside, Deadpool’s warp speed healing factor is an inspiring concept to ponder and pursue. So, what’s the science behind this superhero’s death evading abilities?

The delicate dance between regeneration and cancer

Deadpool’s immortality lies in his cancer and regeneration ability. According to the comics, cancer triggered his healing powers. As a result, the cancerous cells regenerate just like the normal, healthy ones do. The healing factor simultaneously stops cancer from killing him and prevents the cancerous cells from being killed. This manifests in the scarred, tumor-like appearance of his skin.

Cancer cells grow and grow like a snowball, pulling other cells into malignancies and tumors. Typically, cancer occurs when genes that control how cells grow and divide mutate, causing them to malfunction. When this happens, the cells’ checks and balances system for growth and division fall apart, which is a cascading process because the more of these genes that get disrupted, the greater the chance for cancer’s survival.

The genes that are the gas and the brakes of cell division and growth are called oncogenes and tumor suppressor genes. When oncogenes get mutated, the gas pedal goes full throttle; when tumor suppressor genes get mutated, the brakes go out, and cell division and growth become a runaway train that can’t be stopped.


(Source: BioNinja)

How does this apply to Deadpool? Well, one way to think about it is that when his limbs get blown off or he takes a bullet through his body, the stars align for oncogene and tumor suppressor activity such that cells grow back quickly and precisely without going overboard. In other words, oncogene activity ramps up in the damaged area, and the cancer cells start multiplying and rebuilding the limb or tissue; then, once the healing process is moving along, tumor-suppressor genes come in and stifle the oncogenes before they get too out of control.

Is this likely to work out in humans? Scientifically, cancer and regeneration are linked. It’s possible that one day we may be able to manipulate tumor suppressor genes and oncogenes in such a way to drive regeneration, but I wouldn’t hold my breath for it at this time. That being said, there’s one creature that’s figured out exactly how to do this.

Meet the axolotl: a real-life regenerator

The idea of re-growing a missing limb sounds extraordinary, but a type of salamander that lives in Mexico called an axolotl is capable of doing just that. Scientists have established that the axolotl can regenerate limbs cut at any level, perfectly and with no scarring. They can even regenerate a cut spinal cord and even parts of the brain. The axolotl uses a similar relationship to the one painted above in Deadpool between oncogenes and tumor-suppressor genes to regenerate, just not at the speed it takes to flip between the pages of a comic book or watch a scene of a film.

(Source: ​​Creative Commons Zero – CC0) An axolotl

The plasticity of the body’s healing power

Not all parts of the body regenerate equally. There are regions of constant cell growth and populations of cells with a high degree of plasticity and regenerative activity like the skin, gut, and muscles -— even parts of the nervous system.

On the other hand, hearts are notorious for being limited in terms of plasticity and regenerative activity. The key to this phenomenon is that heart cells essentially do not divide in adulthood. That is why we rarely see heart cancer (there’s no cell growth going on), but it’s also why heart failure is still the number one killer in the US (once it scars, it never heals). 

For the bits of the body we do regenerate, these abilities seem to decrease with age. Although poorly understood, these regenerative factors are presumably associated with the patterns of genetic activity and the changing cell environments.

But, with age, our genetic programs and cellular environments become less plastic and more rigid or stiff, both figuratively and literally. Perhaps the key to retaining regenerative qualities is creating a pro-youthful environment to give cells a “young” genetic status. In line with this, there is increasing evidence for the ability of terminally differentiated cells and aging stem cells to respond to “pro-youthful” signals generated by the microenvironment.

Why do humans not regenerate like some amphibians and fish?

Circling back to the heart, research has shown that cardiac regeneration is an ancestral trait in vertebrates — animals with backbones like mammals, birds, reptiles, amphibians, and fishes. There are 64,000 living species of vertebrates on our planet, and all of them have a heart. The capacity to regenerate the heart is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures and as members of certain species developmentally progress towards their adult forms.

While higher vertebrates like humans and rodents resolve heart injury with permanent scarring (fibrosis) and loss of heart function as adults, juveniles of these same species can fully regenerate heart structure and function after injury. This is not the case with lower vertebrates like certain fish and amphibians, in which the adults retain these regenerative capabilities. Recent research has elucidated several broad factors that may contribute to this loss of regenerative potential in the heart: an oxygen-rich environment, vertebrate thermogenesis, a complex adaptive immune system, and cancer risk trade-offs (see above).

Understanding how these lower vertebrates, particularly the axolotl, can regenerate limbs and even organs may make it possible to apply this to humans one day. Such regenerative medicine may provide the capability to heal previously irreparable tissues and organs and perhaps even prevent aging. Maybe we may even be able to regrow our heads like Jeebs in Men In Black based on understanding how flatworms can regrow their entire bodies from just a sliver.