Humans have noted with frustration our conspicuous inability to regenerate organs, limbs, and heads. But there is an animal – a close relative -- that can do not only that, it can regenerate the entire front half of its body after bisection: head, heart, central nervous system and all. That animal is the acorn worm (This is the third time I have written about these humble and apparently vastly under-appreciated animals in just the last few months. Clearly, they need a better PR team).
Don’t believe me? Here’s a time-lapse video that shows one accomplishing this show stopping feat in a mere two weeks:
The images of regeneration go by a little quickly -- try pausing and restarting the video to slow them down.
OK, this is a cool party trick, you may concede. But why should we care? Because these invertebrates are just about as close to being a chordate – an animal like ourselves with a dorsal spinal cord -- as you can get without being one. They grow a hollow neural tube along their backs, just like us. As such, they use many of the same developmental genes we use to develop our brains to grow their heads, “brains”, and bodies.
Those shared genes means that understanding how they can regrow the entire upper half of their bodies and central nervous system from scratch in a matter of just two weeks could help unlock doors that could produce radically better treatments for people with brain and spinal cord injuries, dementia, paralysis, and amputations. I should emphasize, however, that these scientists are not suggesting humans can regrow entire heads. They are suggesting we may be able to regenerate parts of our brains, central nervous systems, and perhaps even bodies that have been damaged or lost. This could obviously help a lot of people, should it pan out. And it may not.
Regeneration is, perhaps surprisingly, not unusual among animals. “Popularized in myths, science fiction, and even horror movies, regeneration of missing and damaged tissue is a common reality in the animal kingdom,” the authors write. Unfortunately, that reality does not include us. Yet nearly every phylum of animals contains at least a few species able to regenerate. Sea stars and other echinoderms can famously regenerate large sections of their body should they be cut into pieces. Even among the chordates and vertebrates it is not uncommon. Lancelets, tunicates(sea squirts), frogs, fish, and salamanders can all regenerate parts of their bodies to one degree or another. Fish and amphibians even regenerate parts of their central nervous systems.
However, in a stroke of bad luck for scientists, the vertebrates that can regenerate have also, for unrelated reasons, had their genomes duplicated more than once. That makes it much harder to tinker with their genetics for the purposes of studying regeneration. Normally, scientists amp up production of, suppress, or knock out a gene – effectively, breaking it -- to study what the effect of that tinkering tells us about what the normal version does. But because there are so many different versions of the same gene to deal with in the vertebrates, the usual strategy is impractical. Invertebrate genomes, like that of the acorn worms, lack duplication issues.
Of course, that this seemingly magical ability exists among a group of animals so closely related to our own begs a more basic question: when did the ability to regenerate evolve? Was it an ability the first animals possessed and passed down to their descendants, or has it evolved multiple times in many different animal groups? That the earliest evolved living animals, like sponges, jellyfish, coral, and comb jellies, all have great powers of regeneration, suggests the former is true.
This matters because if regeneration was a trait present in the first animals and persisted a long time before groups like our own lost the ability, it is probable, the authors say, that humans still retain many or all of the genetic switches that control it, but they have been disabled somehow. It may be possible to reactivate these regenerative molecular pathways in us using insights we gain from studying animals like the acorn worm whose gene networks are still operational.
To that end, the scientists chose to study the acorn worm Ptychodera flava, whose regeneration you witnessed above. Before scientists can begin breaking the worm’s genes to see what they do, however, they need to know what normal worm regeneration looks like. A new study published in September in the journal Developmental Dynamics lays this out the normal course of acorn worm regeneration.
Acorn worms are, as I wrote in October, made up of a proboscis which sits in a collar attached to a tail. The mouth is inside the collar, and the proboscis is used by the worm to wriggle through the mud or sand in which it feeds.
The experiment employed a simple, if drastic, intervention: slice the worm in two. The surviving halves recuperated from this grave insult with remarkable speed – particularly the unlucky rear end. On this half, the wound sealed and healed within two days. A little round construction pod called a regeneration blastema formed within 3 days. Cells accumulated and assembled there to form a rudimentary head by 5 days post cut. Four to five days later, a mouth formed and opened. An acorn worm can actually start eating again just five days after being sliced in half! Blood vessels regenerated quickly too. This makes sense: both obtaining fuel and distributing that fuel along with oxygen to growing, energetically-needy tissues is critical for regeneration.
The worm then regenerated all the structures of the head , collar, heart, nervous system, and upper trunk, going in order from front to back. Just two weeks later, you have a shiny new acorn worm where there was only the decidedly non-business end of one before.
When the scientists closely examined the sequence of regeneration, they also made an intriguing discovery: there were differences between how the worms develop as embryos and juveniles and how they regenerate after grave injury. Small differences, but differences which nonetheless show a separate regenerative program may be operating.
An unsolved puzzle remains: from where do the cells that migrate to the regeneration blastema come? Are they genuine stem cells always present somewhere in the worm’s body? Stem cells are undifferentiated cells that can divide indefinitely or produce cells of any other tissue types. In human adults, they're found in bone marrow, fat, and blood. Or are these construction cells ex-body cells that have been de-programmed and returned to a stem-cell like state so they can be assigned a new role in the regenerating tissue?
One clue comes from the first gill slit that forms during regeneration (all original gills were removed by cutting the worm in half). The part closer to the proboscis is white, wall the part closer to the pre-fabbed worm is pigmented like the rest of the worm’s original body. That suggests the front end is being generated from new cells, while the back end is being constructed from cells recycled from old tissue that has been dissolved and its cells re-assigned.
Human cells are not normally capable of shedding their identity once they have been assigned a tissue type. If acorn worms can do this, we might be able to similarly remodel our own tissues, these scientists say. These are magical superpowers indeed. But it is worth remembering that should we come by any or all of the abilities I've described, it would be thanks not to a yellow sun or a radioactive spider bite, but to an ugly, humble but fascinating little worm, quietly digging its way through seafloor mud.