I love you very much and it breaks my heart to write this letter. For a long time, I believed that your fascination with Deadpool was just a phase. But it has driven us apart. It is clear that you believe you can regenerate limbs like Deadpool, but you are harming your physical health and it scares me.
Your belief in your power to regenerate limbs has led to some close calls. I’ve had to accompany you to the emergency room too many times, like when you almost severed your hand with a circular saw. As I don’t want see you hurt yourself, you need to learn the truth. Salamanders are the only known animals with spinal columns that can regenerate limbs in a complex, multi-step process. Because I love you, I am hoping that my explanation why humans can’t do it and the process in salamanders will help you understand and seek treatment.
Watching Deadpool 24/7 has led you to believe that your body can just re-grow any missing limbs or injures, but it can’t. Cells need to undergo a process called “differentiation”. Cells generally start the process unspecialized, similar to someone entering the job market with general skills, but have lots of “potential”. This means that they can become any cell type. In other words, they can take on any job as long as they gain the right skills; the skills are sent via messages from other cells. Cells will become more specialized over time and lose their “potential”. At some point, they will be specialized for a certain cell type and no longer have the “potential” to become any other cell type – like a tissue or muscle cell.
Salamanders are the only known vertebrates, animals with spinal columns, that can regenerate limbs post-amputation. I don’t blame you, especially after what the Deadpool movie has led you to believe. Research on the evolution of this ability shows that it has been lost many times throughout the evolution of vertebrates; both humans and salamanders belong to this group. For an unknown reason, salamander have kept the ability and they can regenerate functional limbs entirely. Humans have lost it, yet in childhood they can regrow finger tips No one really knows how salamanders managed to keep this ability, and it’s still being researched (Bely and Nyberg, 2010). Otherwise, trust me when I say that you almost lost that hand during the band saw incident.
If humans can’t regenerate limbs, fingertip regeneration in kids seems a bit contradictory. Scientists found that there are some unspecialized cells in the fingertip, which can get signals to start making new tissues. However, the cells seem to lose their regenerative abilities as humans age. Some think the cells can’t respond to regenerative signals in adults, while others think there are simply not enough cells to make new tissue (Lehoczky, et al., 2011). Either way, there are few clues as to why humans can’t be more like Deadpool.
One potential clue to this mystery is that the skin cells in humans and salamanders act differently after amputation. Both will move to the wound area and they will start to make scaffold – it’s like a support for cells. The difference is how much scaffold is made. Human skin cells end up making too much and this creates scar tissue (Muneoka et al., 2008). Meanwhile, salamander skin cells make just the right amount to form the shape for a new limb. Scientists don’t currently know why, but they’re doing research to figure it out.
All of this may be hard to swallow, but you begin to see why Deadpool’s abilities are pretty darn fictional. What aren’t fictional, though, are those of the salamander. Since you love Deadpool so much, I’ll take some time to explain the process so you can better appreciate the inspiration for his abilities. The big steps are sealing the wound, making a limb outline, and building new tissues in the right places. All of these are outlined below.
The first step of regeneration is to seal the hole left by amputation. This is done by skin cells, which get messages from the wound. (Muneoka et al., 2008). Once sealed, cells in the wound area will send messages to nerve cells to start limb regeneration. This sets off a broadcast message to be sent to cells in the surrounding area to change their cell types (Zielins et al., 2016). These cells would rewind in time and revert to earlier cell types. They are, essentially, regaining their “potential” to become a wider range of cell types. This creates a mass of less specialized cells. The mass will also send messages to muscle and skin cells to migrate to the wound area, initiating the next step (Muneoka et al., 2008).
With the wound area bustling with less specialized cells, muscle cells, and skin cells, the next step is form a limb outline. In this step, any specialized cell in the area will become a less specialized cell type. As this happens, the cells will talk amongst each other to assess the amputation damage. They will then form an outline that corresponds to the shape of the amputated limb (Muneoka et al., 2008).
With an outline and source of cells to make new tissue, the parts of the limb can be filled in like a drawing. This is initiated by communication between the wound and nerves, which results in a massive broadcast message for less specialized cells to specialize into cartilage, connective tissue, muscle tissue, and bone (Zielins et al., 2016). During this process their “potential” is lost. Scientists have long wondered whether cells would become radically different cell types during tissue regrowth – like a former muscle cell becoming a bone cell. Perhaps not. It seems that the less specialized cells can’t be bothered to become a different cell type, so they stick to their pre-amputation cell type (Nacu and Tanaka, 2011).
Now that the right tissues are being made, they need to be brought to the right places. Otherwise, Deadpool or the salamander won’t have a functional limb! Luckily for the salamander, some of the cells can easily remember their locations before amputation. These cells will start marking areas where certain cell types need to be. For example, the red coloured area will be for muscle cells, blue coloured area for bone cells, etc. Any specialized cells that don’t remember their location will recognize the marked areas and move to them will (McCusker et al., 2015). Any areas that are missing cells will be filled in via cell division, and the entire process of regeneration is complete!
I hope that you’ve developed a better understanding of why humans can’t regrow limbs and how salamanders can, and that you’re ready to get help. I’m hoping that you at least understand that you need to stop putting hands in sharp places, because they’re not growing back. I know you really like Deadpool, but you aren’t him. All you’re doing is harming yourself and I can’t stand it any longer. You can overcome this fascination, and I’ll support you during each step. Whether you agree is your choice, but you can no longer live with me if you don’t seek help. You are the most important person in my life, and seeking help means everything to me.
– – –
Bely, A.E. and Nyberg, K.G. (2010). Evolution of animal regeneration: re-emergence of a field. Trends in Ecology and Evolution, 25, 161-170.
Lehoczky, J.A., Robert, B., and Tabin, C.J. (2011). Mouse digit regeneration is mediated by fate-restricted progenitor cells. Proceedings of the National Academy of Sciences of the United States of America, 108, 20609-14.
McCusker, C., Bryany, S.V., and Gardiner, D.M. (2015). The axolotl limb blastemal: cellular and molecular mechanisms driving blastemal formation and limb regeneration in tetrapods. Regeneration, 2, 54-71.
Muneoka, K., Han, M., and Gardiner, D.M. (2008). Human limbs. Scientific American 298, 56-63.
Nacu, E., and Tanaka, E.M. (2011). Limb regeneration: a new development? Annual Review of Cell and Developmental Biology, 27, 409-440.
Zielins, E.R., Ransom, R.C., Leavitt, T.E., Longaker, M.T., and Wan, D.C. (2016). The role of stem cells in limb regeneration. Organogenesis, 12, 16-27.