Losing An Arm and A Leg

London Zoo - Animal Adventure - Donkeys - Danger signImagine that you are working on a home improvement project and, being a bit of a klutz, something goes horribly wrong: a slip of the saw and you’ve lost the tip of a finger. Is there any hope of regaining your lost digit?

While there young children reportedly have the ability to regrow amputated fingertips, in adults it’s possible with special medical treatments (or maybe not even that). Cut off your whole finger – or (stars forbid) an entire arm – and unless it can be reattached, it’s gone for good.

While lobsters can regenerate their claws, and many lizards can regrow their tails, humans and other mammals have notably poor limb regeneration abilities.

The notion  that such an “animal” ability could somehow be transferred to people has been a part of science fiction since its early years.  A good example of this is Romeo Poole’s 1926 short story “A Hand from the Deep”, which has a Doctor Whitby experimenting with crayfish extracts on an unsuspecting patient:

“The theory is nothing very new. As early as 1906 it was observed that when a limb is amputated at the middle of a bone, the bone starts to grow out again, but increases only about one-fiftieth of an inch in length before it is halted by some other influence. You know also, of course, about the little warts of so-called ‘proud flesh’ that apparently try to replace the original muscular tissue in case of injuries, but which are misshapen or misplaced. What Whitby was trying to get at, as I see it, was to so control these misdirected efforts of nature as to produce a new and perfect limb.
“The human body is already able to repair damaged bones by rebuilding small particles of the bony tissue; it is also able to replace muscle, nerve and even finger-nail tissue, although in somewhat imperfect forms. Whitby was trying to induce it to build a lost member in perfect form.
“It seems that Whitby has been experimenting for years with the ductless and other glands of shellfish in pursuance of this theory of regeneration, and we have upstairs the living proof that he was able to prepare a glandular extract that changes the bodily cell-structure as well as influencing the building-up processes of nature; but it appears that he near succeeded in isolating the one influence from the other, both being present in his preparation.

Of course there are terrible side effects to the treatment; quite improbably the patient starts turning into a crustacean himself.

Later science fiction tales usually assume as a matter of course that “autodocs” and other advanced medical treatment technology will make limb regeneration almost routine procedure, albeit often a slow and painful one.

California Tiger Salamander, Ambystoma californiense IIBut wouldn’t it be better for future humans to be able to do that on their own?

The only vertebrates able to regenerate entire arms and legs as adults are some species of salamanders.   After a limb is amputated, cells are mobilized to to start healing the wound.  In humans, scar tissue forms.  In newts, on the other hand, cells migrating to the wound site form a structure called the apical epidermal cap (AEC) . Cells under the AEC begin to proliferate and create a tumorlike mass called a blastema which eventually will grow into the newt’s new limb.

If humans could be given that ability,  you could create a superhero (or supervillain) or a super soldier. It’s no surprise that some research in limb regeneration is funded by the US Department of Defense.

But the exact molecular signals that direct salamanders limbs to regrow are still being sorted out.  And it’s not at all known whether similar mechanisms would function the same way in mammals (like humans) if they were somehow transplanted.

There was an interesting paper last year that suggested the removal of a single gene in mice can stimulate scarless wound healing. But despite the wildly speculative headlines, the study did not actually even try to look at whether the mutant mice could regenerate digits or limbs. Mouse limb regeneration – let alone human limb regeneration – is still firmly in the realm of science fiction.

Red on SaleAre there aspects of limb regeneration that haven’t been fully fictionally explored?  What would be the implications if all ordinary people had that kind of wound healing ability for society and medicine?

The wound healing ability in axolotls has also allowed scientists to surgically induce the formation of extra limbs.  What if humans had that ability as well?

Additional Reading and Watching

Video: Newt Limb Regeneration from the HHMI 2006 Holiday Lectures — Potent Biology: Stem Cells, Cloning, and Regeneration

Video: Superhero Science: Limb Regeneration

Gardiner David M and Bryant Susan V. Regeneration Basics. UC Irvine Limb Regeneration Lab.

Interview with Jon Mogford, Program Manager of the Defense Sciences Office at DARPA (2009) [Military projects on wound healing]

Whited Jessica L and Tabin Clifford J. “Limb Regeneration Revisited” Journal of Biology 8:5 (2009)

Bedelbaeva Khamilia et al. “Lack of p21 expression links cell cycle control and appendage regeneration in mice” Proc Natl Acad Sci 107(13): 5845–5850 (2010)
[note that the "appendage regeneration" refers to closure of a hole punched in the mouse's ear]

Illingworth, Cynthia M. Trapped fingers and amputated fingertips in children. J. Ped. Surgery 9:853-858. (1974)

Top Image: London Zoo – Adventure Animal – Donkeys – Danger Sign by ell brown on Flicker
Middle Image: California Tiger Salamander, Ambystoma californiense II by marlin harms on Flickr.
Bottom Image: “Red on Sale” by Artiii on Flickr

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