The one thing that all organisms have in common is their general life cycle: they are born, they live, they grow old, and they die. Maybe they reproduce along the way, if they are lucky. Yet, one organism was famously discovered in 1988 that breaks this pattern. On a vacation in Italy, marine-biology student Christian Sommer gathered samples of invertebrates from the sea floor, and brought them back to his lab for culture. He later realized that some of these organisms were behaving differently than the others—instead of growing older, they were growing younger (Rich, 2012).
Years later, scientists would dub this invertebrate with the scientific name Turritopsis dohrnii. It describes a jellyfish with a tenth of an inch diameter body, a bright red stomach, and many tentacles (Martell et al., 2019). After its birth, this jellyfish goes about its life like any other. It gradually develops from a polyp, anchored to the sea floor, into a medusae, free to be pushed around by water currents and consume plankton. However, if the jellyfish detects an environmental stress or physical damage, it can revert back into its younger polyp form for safety (Devarapalli et al., 2014). In this stage of its life cycle, it is smaller, requires less food, and can regenerate any lost tissue. After a time, when the danger is gone, the polyp can transform back into an adult jellyfish. The jellyfish can also hit restart on its life cycle when its body simply gets too old. It’s like a chicken that can revert itself back to an egg, or a butterfly back to a caterpillar. This process of transforming from adult to young and back again can theoretically be performed indefinitely, making the jellyfish biologically immortal.
Of course, this fascinating ability does not make Turritopsis dohrnii functionally immortal: it can still die of predation and disease. Yet its special way of reversing the clock on its life cycle has allowed the species to propagate throughout the oceans of the entire world (Than, 2009).
The jellyfish owes its success to the process of transdifferentiation. In this rare biological mechanism, any cell in an organism can turn into any other type of cell (Martell et al., 2019). Imagine if some of your cells could be converted to neurons, or give rise to muscle fibers. In the immortal jellyfish, this is a reality. There is an important distinction to be made between “transdifferentiation” of normal somatic cells and “differentiation” of stem cells. In differentiation, stem cells (cells which haven’t yet been assigned a specific job) develop into a specialized cell type (e.g. skin cells, red blood cells, etc.) (Watt & Driskell, 2010). This is the mechanism that allows fully grown humans to form from just an embryo. In contrast, transdifferentiation involves the transformation of one specialized cell directly into another specialized cell, no stem cells required. This process is absent in all other organisms: once a cell’s job has been decided, there’s no going back. Somehow, evolution has made these jellyfish unique.
Stem cell research is so valuable because it has the potential to repair damaged tissues, or even regrow parts of the body that are absent. For example, bone marrow transplants utilize a donor’s stem cells to replace diseased marrow, helping to treat cancer and other conditions (Watt & Driskell, 2010). In the future, stem cell therapies might be able to do anything from treat neurodegenerative disorders to regrow lost limbs. However, many stem cells are produced through manipulation and destruction of human embryos, leading to great controversy in the medical community (Barker et al., 2018). Although there are some stem cells (e.g. induced pluripotent stem cells), that can be produced otherwise, these embryonic stem cells are widespread. However, application of transdifferentiation could in theory provide the same benefits as stem cell therapies, without the troubling ethics. This is why Turritopsis dohrnii is important: perhaps, by studying transdifferentiation in the jellyfish, researchers could shed light on how to replicate the effect in humans, and circumvent the need for stem cells.
Unfortunately, we currently know very little about transdifferentiation in these jellyfish. There are a few reasons for this. For one, they are incredibly difficult to culture in the laboratory. Only one man has been able to do so for long periods of time, Japanese researcher Shin Kabota. He spends hours every day just making sure the invertebrates have properly digested their food; if he missed a day, they would probably die in captivity (Rich, 2012). Also, it’s understandably difficult to secure funding for jellyfish research. Governments are wary to spend money on such a project that would most likely only show returns after decades of long research, with no guarantee for human applications.
What we do know is also very surface-level. Researchers have sequenced the genome of the species, as well as studied the expression of this DNA through messenger-RNA analysis (Devarapalli et al., 2014); (Matsumoto et al., 2019). Scientists have also examined the microRNAs of the jellyfish, which regulate gene expression in its cells (Rich, 2012). However, these analyses have only served to create more questions about the mechanisms of transdifferentiation, with no concrete answers at all.
Yet, Kabota is still optimistic about his research. He states, “I believe it will be easy to solve the mystery of immortality and apply ultimate life to human beings”. Kabota has made breakthroughs with the general properties of the jellyfish: he understands the exact conditions that inhibit and promote regeneration; he has studied the natural rejuvenation of Turritopsis dohrnii due to old age, and found that the organisms will reset their life cycles about five times a year, if undisturbed; he even has a working theory that the tentacles of the jellyfish provide the key molecular signals that start the transdifferentiation process. (Rich, 2012)
The prospects of using jellyfish to cure diseases and replace lost limbs is definitely exciting. But the research is still very young. After all, the death-defying species was only discovered 32 years ago. It will take much more application of the scientific method before humanity harnesses the power of the jellyfish. Even so, researchers such as Kabota remain confident that the secrets hidden inside Turritopsis dohrnii will be unlocked within just a few decades. Will this knowledge allow us to turn back the clock on our own lives? Only time will tell.
References
Barker, R. A., Carpenter, M. K., Forbes, S., Goldman, S. A., Jamieson, C., Murry, C. E., Takahashi, J., & Weir, G. (2018). The Challenges of First-in-Human Stem Cell Clinical Trials: What Does This Mean for Ethics and Institutional Review Boards?. Stem cell reports, 10(5), 1429–1431. https://doi.org/10.1016/j.stemcr.2018.04.010
Devarapalli, P., Kumavath, R. N., Barh, D., & Azevedo, V. (2014). The conserved mitochondrial gene distribution in relatives of Turritopsis nutricula, an immortal jellyfish. Bioinformation, 10(9), 586–591. https://doi.org/10.6026/97320630010586
Martell, L., Piraino, S., Gravili, C. & Boero, F. (2016). (Life cycle, morphology and medusa ontogenesis of Turritopsis dohrnii (Cnidaria: Hydrozoa). https://www.tandfonline.com/doi/full/10.1080/11250003.2016.1203034
Matsumoto, Y., Piraino, S., & Miglietta, M. P. (2019). Transcriptome Characterization of Reverse Development in Turritopsis dohrnii (Hydrozoa, Cnidaria). G3 (Bethesda, Md.), 9(12), 4127–4138. https://doi.org/10.1534/g3.119.400487
Rich, N. (2012). Can a Jellyfish Unlock the Secret of Immortality?. The NY Times, https://www.nytimes.com/2012/12/02/magazine/can-a-jellyfish-unlock-the-secret-of-immortality.html?auth=login-email&login=email
Than, K. (2009). "Immortal" Jellyfish Swarm World's Oceans. National Geographic, https://www.nationalgeographic.com/animals/2009/01/immortal-jellyfish-swarm-oceans-animals/
Watt, F. M., & Driskell, R. R. (2010). The therapeutic potential of stem cells. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 365(1537), 155–163. https://doi.org/10.1098/rstb.2009.0149
Written by Alex Borengasser
Edited by Devanandh Murugesan
Graphics by Tiya Shah
Group advised by Lakshmi Sriram
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