What if humans could regrow an amputated arm or leg, or completely restore nervous system function after a spinal cord injury?

A new study of one of our closest invertebrate relatives, the , reveals that this feat might one day be possible. Acorn worms burrow in the sand around coral reefs, but their ancestral relationship to chordates means they have a genetic makeup and body plan surprisingly similar to ours.

A led by the 91̽»¨ and published in the  of the journal Developmental Dynamics has shown that acorn worms can regrow every major body part — including the head, nervous system and internal organs — from nothing after being sliced in half. If scientists can unlock the genetic network responsible for this feat, they might be able to regrow limbs in humans through manipulating our own similar genetic heritage.

“We share thousands of genes with these animals, and we have many, if not all, of the same genes they are using to regenerate their body structures,” said lead author , a 91̽»¨biology doctoral student based at . “This could have implications for central nervous system regeneration in humans if we can figure out the mechanism the worms use to regenerate.”

The new study finds that when an acorn worm — one of the few living species of hemichordates — is cut in half, it regrows head or tail parts on each opposite end in perfect proportion to the existing half. Imagine if you cut a person in half at the waist, the bottom half would grow a new head and the top half would grow new legs.

After three or four days, the worms start growing a proboscis and mouth, and five to 10 days after being cut the heart and kidneys reappear. By day 15, the worms had regrown a completely new neural tube, the researchers showed. In humans, this corresponds to the spinal cord and brain.

After being cut, each half of the worm continues to thrive, and subsequent severings also produce vital, healthy worms once all of the body parts regrow.

“Regeneration gives animals or populations immortality,” said senior author , director of Friday Harbor Laboratories and a 91̽»¨biology professor. “Not only are the tissues regrown, but they are regrown exactly the same way and with the same proportions so that at the end of the process, you can’t tell a regenerated animal from one that has never been cut.”

The researchers also analyzed the gene expression patterns of acorn worms as they regrew body parts, which is an important first step in understanding the mechanisms driving regeneration. They suspect that a “master control” gene or set of genes is responsible for activating a pattern of genetic activity that promotes regrowth, because once regeneration begins, the same pattern unfolds in every worm. It’s as if the cells are independently reading road signs that tell them how far the mouth should be from the gill slits, and in what proportion to other body parts and the original worm’s size.

When these gene patterns are known, eventually tissue from a person with an amputation could be collected and the genes in those cells activated to go down a regeneration pathway. Then, a tissue graft could be placed on the end of a severed limb and the arm or leg could regrow to the right size, Swalla explained.

“I really think we as humans have the potential to regenerate, but something isn’t allowing that to happen,” Swalla said. “I believe humans have these same genes, and if we can figure out how to turn on these genes, we can regenerate.”

Regeneration is common in many animal lineages, though among the vertebrates (which includes humans) it is most robust in amphibians and fish. Humans can regrow parts of organs and skin cells to some degree, but we have lost the ability to regenerate complete body parts.

Scientists suspect several reasons for this: Our immune systems — in a frenzy to staunch bleeding or prevent infection — might inhibit regeneration by creating impenetrable scar tissue over wounds, or perhaps our relatively large size compared with other animals might make regeneration too energy intensive. Replacing a limb might not be cost-effective, from an energy perspective, if we can adapt to using nine fingers instead of 10 or one arm instead of two.

The researchers are now trying to decipher which type of cells the worms are using to regenerate. They might be using stem cells to promote regrowth, or they could be reassigning cells to take on the task of regrowing tissue. They also hope to activate genes to stimulate complete regeneration in animals that currently aren’t able to regrow all tissues, such as .

Co-authors are Kirsten Gotting of Stowers Institute for Medical Research, and Eric Ross and Alejandro Sánchez Alvarado of both the Stowers Institute and the Howard Hughes Medical Institute.

This research was funded by the National Institutes of Health, Howard Hughes Medical Institute, the Seeley Fund for Ocean Research on Tetiaroa and a National Science Foundation graduate fellowship.

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For more information, contact Luttrell at shawnl2@uw.edu or 206-543-1484 and Swalla at bjswalla@uw.edu or 206-616-0764.

“BEACON was founded on the premise that the study of evolutionary processes not only enriches our understanding of the natural world, but also has applications in other fields, such as computer science and engineering,” said 91̽»¨biology professor , who manages the BEACON project for the university. “We want to understand evolution in biological systems better, but we also want to use evolution to improve computer software, to solve engineering problems and other projects of practical value.”

The BEACON center was founded in 2010, and the 91̽»¨received $2.5 million in funding for the first five years. This year’s renewal — $22.5 million split among the five universities — will support the center for a final five years. The majority will go to , where BEACON is headquartered. The other partner institutions — the , and the — will receive amounts comparable to the UW.

BEACON was founded in part to pursue interdisciplinary and innovative approaches to evolutionary studies. Participating faculty receive funds to begin new types of projects that fall under BEACON’s overall mission.

“These are often seed grants to professors — starter funds for getting new projects and collaborations off the ground,” said Kerr.

The 91̽»¨researchers involved in BEACON projects include faculty from traditional fields such as biology to unexpected ones such as electrical engineering. The experiments they have pursued include new approaches to biofuel production, flower pollination by insects, chemical communication among bacteria and the evolution of multicellular organisms. At other institutions, BEACON projects include robotics, evolution of computer programs, algorithms for facial recognition software and cancer detection, the origin of new species and computational techniques to understand the genetics of complex diseases.

BEACON researchers also benefit from annual meetings at Michigan State University to share research updates and hold courses and tutorial sessions on new techniques and experimental approaches. Kerr and several 91̽»¨colleagues attended this year’s meeting in August shortly before the NSF announced that the center would receive five more years of funding.

“We’re thrilled that this has happened,” said Kerr. “We’ve another five years, so let’s see what more we can do in that time.”

91̽»¨faculty and staff also use BEACON funds for public outreach and education. Using BEACON seed funds in conjunction with a grant from the Howard Hughes Medical Institute, Kerr and biology department lecturer are developing a laboratory module for introductory biology courses where students can design their own evolution experiments with bacteria, such as seeing how quickly the microbes evolve resistance to antibiotics. BEACON funds have also been used to develop new courses at the UW’s in the San Juan Islands and hold outreach events at the Seattle Aquarium, the Pacific Science Center, Seattle Town Hall and local schools.

In addition to Kerr, 91̽»¨faculty in BEACON leadership roles include biology professor , who is BEACON education coordinator for the UW, and affiliate professor of biology at the , who coordinates efforts to enhance participant diversity with the center.

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For more information, contact Kerr at 206-221-3996 or kerrb@uw.edu.

The published May 21 in Nature are based in part on analysis and work done at UW’s Friday Harbor Laboratories including research accomplished by 91̽»¨undergraduates and graduate students who spent intense quarters in 2008, 2010 and 2012 living at the lab and collaborating with visiting and 91̽»¨faculty on this specific endeavor.

The students worked under the direction of Swalla and of the University of Florida, who is the lead author of the paper, and seven former undergraduate students and teaching assistants for the research apprenticeships are co-authors.

Comb jellies are found throughout the world’s oceans and range in size from just millimeters long to nearly 5 feet. They rely on cilia – fine hair-like projections that sweep in unison – to move through the water and are the largest animal using cilia for locomotion. Almost all are predators with prey ranging from larvae to small crustaceans.

The study focused on the comb jelly Pleurobrachia bachei, about the size of a marble and commonly known as a Pacific sea gooseberry, many of which were collected from the waters at Friday Harbor Laboratories in the San Juan Islands. 91̽»¨biologist , a co-author on the paper, is considered one of the world’s top experts on comb jellies.

In a remarkable evolutionary twist, the gooseberry jelly and 10 other comb jellies appear to have independently developed complex organs, muscles and behaviors that are far more sophisticated than sponges, which previously were viewed as the earliest lineage of animals.

The findings would reclassify comb jellies, reshaping two centuries of zoological thought, and imply that there are many ways to “make an animal” with neural and muscular systems, Moroz said.

“For years, textbooks have started discussions of animals with sponges,” Swalla said. “Then studies published in 2008 suggested that comb jellies might be at the base of the animal tree of life. It became a priority to sequence one of these species.”

The result: The Pacific sea gooseberry is now the first Friday Harbor Laboratories animal to have its entire genome sequenced.

The classes of students helping with the project worked on such things as compiling gene lists and spent much of their time doing bioinformatics and laboratory experiments with Swalla and Moroz. For example, they collected embryos in the lab so researchers could examine neurotransmitters and genes that were expressed at different times. Students also used jelly catchers to collect comb jellies from the waters around Friday Harbor for research purposes.

The students were part of a research apprenticeship program that’s been underway at the labs since 1999. Instead of taking several classes as they do during a typical quarter, the students are immersed in current research projects by 91̽»¨faculty and visiting scientists.

It gives students a chance to really see what marine science is about and learn team work, Swalla said. Along with working on the overall project, Swalla has students develop their own research projects that further the common goal. Some students also worked summers with funding from the National Science Foundation’s BEACON For Evolution in Action program.

Co-authors on the paper include former undergraduate apprentices David Girado, Joshua Swore, Alexander Fodor, Rachel Sanford and Rebecca Bruders, four of whom have gone on to graduate school, and two of the teacher assistants for the apprenticeships Kevin Kocot and Matthew Citarella.

Along with reconfiguring the tree of life, the novel neurogenic and signaling molecules and receptors the researchers found also have implications for synthetic and regenerative medicine, they said. The findings could lead to new ways to investigate neurodegenerative diseases such as Alzheimer’s or Parkinson’s.

“Some ctenophores can regenerate an elementary brain – also known as the aboral organ or gravity sensor – in three and a half days,” Moroz said. “In one of my experiments, one lobate ctenophore – Bolinopsis –  regenerated its brain four times.”

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For more information:
Swalla, 206-616-0764, 206-616-9367, bjswalla@uw.edu

Portions of this article were adapted from a from University of Florida.