The University of Southampton

Tag: ethics

Can Humans Grow Limbs? The Genetic Science of Regeneration and the Search for Limb Regrowth

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Would it even be natural for a human to regrow a limb?

When we think of animals capable of regenerating lost body parts, amphibians like salamanders and axolotls are the first to come to mind. These creatures can regrow entire limbs, a process that humans are not naturally capable of—at least not in the same way. While humans can regenerate certain tissues (like liver and skin), regrowing complex structures like limbs remains beyond our biological abilities. However, scientific research is uncovering ways to potentially change that.

The Regenerative Powers of Amphibians

Amphibians, particularly species like axolotls (Ambystoma mexicanum) and salamanders (like Pleurodeles waltl), are famous for their regenerative abilities. When they lose a limb, they don’t just heal—they regrow the entire structure, including bones, muscles, nerves, and skin. This process begins with the formation of a blastema, a mass of undifferentiated cells at the injury site. These cells revert to a more stem-cell-like state and have the potential to differentiate into all the required tissues, such as bones, muscles, and nerves, with specific types of stem cell-like cells at localized areas of the body.

The regeneration process in amphibians is regulated by specific genes and molecular pathways. One of the key players in limb regeneration is FGF8 (Fibroblast Growth Factor 8), which promotes blastema formation and tissue growth (Liu et al., 2017). Additionally, GDF11, a regenerative gene, has been shown to play a role in promoting limb regeneration by controlling stem cell activity and reprogramming cells (Blum et al., 2019). Wnt signaling is another pathway that controls the proliferation and differentiation of these regenerative cells.

https://chuckmckeever.com/post/112863213557/axolotl-appendage-regeneration-julia-moore

Why Can’t Humans Grow Limbs?

Humans, unfortunately, lack the regenerative powers of amphibians. When humans experience an amputation or injury, the body’s primary response is to form scar tissue. Scar tissue helps seal the wound but does not regenerate functional tissues like bones or muscles. Unlike amphibians, humans cannot activate the cellular mechanisms necessary for full limb regeneration. Although humans do have some regenerative abilities, such as the regeneration of skin or liver tissue (compensatory hyperplasia), these processes are much more limited and typically don’t extend to complex structures like limbs, instead simply multiplying the structures to restore the mass rather than creating various structures and mechanisms.

Evolutionarily, mammals have prioritized quick wound healing and survival over limb regeneration. The regenerative pathways seen in amphibians are not active in humans, and while we can regenerate simple tissues, regrowing complex structures such as limbs requires a much more intricate series of cellular events that humans are not biologically equipped to trigger.

The Search for Limb Regrowth in Humans

That said, researchers are not giving up. One exciting area of study involves the Lin28a gene, which plays a key role in cellular reprogramming. In amphibians like axolotls, Lin28a is activated during the early stages of regeneration and helps cells revert to a more flexible, regenerative state and is partially why axolotls retain infant features into adulthood. When Lin28a is activated in mammalian cells, it has been shown to promote reprogramming and regeneration (Zhou et al., 2018). Scientists are investigating whether activating this gene in humans could kick-start the regenerative process.

Another area of focus is stem cell technology (which I highlighted in my previous blog post as a central focus for me in this module). Stem cells are pluripotent, meaning they can differentiate into many types of cells. Scientists are exploring how to use stem cells, along with gene editing technologies like CRISPR-Cas9, to stimulate regeneration in damaged tissues. The hope is that by activating specific genes, such as Lin28a or Sox2, scientists might be able to push human cells into a regenerative state similar to that seen in amphibians (Takahashi & Yamanaka, 2006).

Would It Be ‘Natural’ for Humans to Regrow Limbs?

The question I now wish to ponder on, is whether it would be “natural” for humans to regrow limbs. While humans do not currently possess the same regenerative abilities as amphibians, nature has already demonstrated that limb regeneration is possible. If species like axolotls can do it, why not humans? Human evolution may not have favored limb regeneration, but there’s nothing inherently unnatural about the process if it can be achieved through genetic and stem cell technologies.

In the end, whether limb regeneration is “natural” might depend on one’s perspective. If it offers a chance to restore function and quality of life, it could be seen as a positive step forward for humanity—much like other medical breakthroughs that have altered the course of human health.

References:

  • Blum, J. J., et al. (2019). “Regeneration in axolotls: Mechanisms and applications.” Journal of Experimental Biology, 222(14), jeb204645. DOI: 10.1242/jeb.204645
  • Liu, J., et al. (2017). “Fibroblast growth factor 8 and limb regeneration.” Nature Communications, 8, 1313. DOI: 10.1038/s41467-017-01468-9
  • Zhou, J., et al. (2018). “Activation of Lin28a gene in zebrafish restores regenerative potential.” Nature Biotechnology, 36, 452–459. DOI: 10.1038/nbt.4145
  • Takahashi, K., & Yamanaka, S. (2006). “Induction of pluripotent stem cells from mouse fibroblasts by defined factors.” Cell, 126(4), 663–676. DOI: 10.1016/j.cell.2006.07.024

Can we sell medical waste?

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Immortal cells

I recently read The Immortal Life of Henrietta Lacks by Rebecca Skloot1; the remarkable story of an American woman whose cervical cancer was used to make the first immortal cell line, HeLa. In vitro cell research is normally constrained by the Hayflick limit2; cell lines die out after a few days. Lacks’ cancer was so aggressive that its cells could divide indefinitely, providing an invaluable biological material still used today. Incredibly, few know her name. The cells were used without her knowledge or consent, and her family knew nothing for twenty years.

This story raises important questions about human tissue ownership, notably: who owns medical waste, and can it be sold? Skloot heavily implies that the Lacks family should be compensated for Henrietta’s cells, but I’m not sure it’s so simple.

A video by Hank Green on SciShow, with further information about immortal cell lines and HeLa cells.3

Tissue ownership in the UK

My friend works for the Southampton Imaging4 group and routinely uses femoral heads, leftover from hip replacement surgery, in his research. Recently introduced to tissue ethics, I had several questions for him. My Gran had a hip replacement – are scientists experimenting on her bone? Could they extract stem cells from the marrow and make a cell line like HeLa?

Thankfully, the Human Tissue Act 20045 (HTA) restricts research on tissue to licensed labs and requires informed consent from all donors. My friend assures me that strict protocols are followed, from surgery to the lab to disposal, and that his lab must comply with the Declaration of Helsinki6.

What does this mean for Lacks’ family?

Henrietta Lacks was treated unethically. Her cells should not have been used without her consent, violating her dignity when she was extremely vulnerable. Furthermore, it’s now possible to sequence HeLa’s genome, raising concerns about Lacks’ and (her family’s) privacy. Unfortunately she died in 1951, before widespread adoption of informed consent as best practice.

Henrietta Lacks. Photo from the National Geographic7

In her book, Skloot implies that Lacks’ family should be paid for the cells. It’s important to note that HeLa cells are not full organs, nor were they healthy – if not for their scientific usefulness they would have been deemed medical waste. In the US it is illegal8 to sell one’s organs, but consent and payment law for other tissue is more permissive than in the UK, where selling human tissue is banned.

I strongly support the UK position that selling human tissue for money, regardless of purpose or usefulness, is unacceptable. Tissue derived from a person’s body deserves to be treated with more dignity than a mere commodity.

Even if the act of selling one’s own tissue were ethical, a culture that allows it is not. It would encourage objectification of the human body and provide incentive for organ theft. Nobody should have to resort to selling their tissue. Meixuan Li’ 9 wrote a post exploring this concept taken to a dystopian extreme; prisoners exchanging their organs for reduced sentences. The very idea is abhorrent.

This is why, while Henrietta Lacks was wronged, her family should not be financially compensated. Payment for human tissue, even retrospectively, is morally unacceptable.

Read my full book review on Goodreads

Sources

  1. Skloot R. The Immortal Life of Henrietta Lacks. Crown Publishing Group (2010) ↩︎
  2. Hayflick’s handy guide to immortality and cell senescence. The Genetics of Basic Things and Stuff. 30th November 2022 (cited 24th March 2025). Video: 5:13 min. Available from: https://www.youtube.com/watch?v=w5SBZOa_qAg ↩︎
  3. Immortal Cells Turn 96. SciShow. 1st August 2016 (cited 20th March 2025). Video: 4:41 min. Available from: https://www.youtube.com/watch?v=sXY6-wLesYY ↩︎
  4. Southampton Imaging. University of Southampton (cited 21st March 2025). Available from: https://www.southampton.ac.uk/research/institutes-centres/southampton-imaging ↩︎
  5. Legislation. Human Tissue Authority (cited 21st March 2025). Available from: https://www.hta.gov.uk/guidance-professionals/codes-practice-standards-and-legislation/legislation ↩︎
  6. WMA Declaration of Helsinki – Ethical Principles for Medical Research involving Human Participants. World Medical Association. 2024. (cited 21st March 2025). Available from: https://www.wma.net/policies-post/wma-declaration-of-helsinki/ ↩︎
  7. Marc Silver. A New Chapter in the Immortal Life of Henrietta Lacks. National Geographic. 2013 (cited 21st March 2025). Available from: https://www.nationalgeographic.com/science/article/130816-henrietta-lacks-immortal-life-hela-cells-genome-rebecca-skloot-nih ↩︎
  8. Can you sell organs in the United States? Donor Alliance; Tissue and Organ Donation. 2025. (cited 21st March 2025). Available from: https://www.donoralliance.org/newsroom/donation-essentials/can-you-sell-organs/ ↩︎
  9. Li M. Prisoners ‘Donating’ Organs for Sentence Reduction: Should the Punishment Fit the Crime? 12th March 2025 (cited 21st March 2025). In: Engineering Replacement Body Parts 2024-2025. Available from: https://generic.wordpress.soton.ac.uk/uosm2031-2025/2025/03/12/prisoners-donating-organs-for-sentence-reduction-should-the-punishment-fit-the-crime-2/ ↩︎

Embryonic Stem Cells: A Revolutionary Science Caught in Ethical Debate

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Embryonic stem cells (ESCs), derived from the inner cell mass of a blastocyst, are pluripotent stems cells which give rise to all somatic cell types in an embryo. Therefore, making them an invaluable tool in the understanding of complex processes involved in the production of specialised cells and the building of organ structures. The First ESCs were derived in 1981 by two scientists, M. J. Evans and M. H. Kaufman, in which they took 3.5 day old blastocysts from mice and grew them in a cell culture containing mouse embryonic fibroblasts. It was only 8 years later for the first human ESCs to be isolated!

Although, ESCs have high scientific potential, the method of isolating them raises many ethical concerns as they are typically harvested from surplus embryos from vitro fertilisation procedures (IVF)

Applications of Embryonic Stem Cells

The pluripotency and the indefinite self-renewal ability of ESCs has allowed for the in-vitro generation of a limitless number of distinct cell types. This has proved extremely useful in studies relating to early human development and regenerative medicine for degenerative diseases.

Applications of ESCs include but are not limited to the following:

  • Germline Modification – Correct potential genetic disorders by making genetic alterations on the ESCs but this raises many ethical issues.
  • Knockout Mice – Genetically modified mice, in which a specific gene or genes are selectively switched off. This enables studies of gene function and the modelling of human diseases and thus substantial advancements have been made in both genetic research and therapeutic development.
  • Treatment of Degenerative Diseases – ESCs have the capability to treat diseases such as Parkinson’s disease, Alzheimer’s disease and heart disease. This is due to ESCs being able to replace damaged tissues, for example, ESCs being directed to differentiate into dopamine-producing neurons to treat Parkinson’s disease. The added bonus of using ESCs is that there is a reduced risk of immune rejection due to their immature state.
  • Future Prospects of Organ Transplantation – As ESCs have furthered our understanding of how cells differentiate into specialised cells it provides hope for the potential of growing whole organs for transplantation.

The Ethical Debate and the 14-Day rule

Although there are many benefits to the pluripotency of human ESCs, there are also numerous ethical issues around how ESCs originate. This is because ESCs are extracted from human embryos therefore research on human ESCs correlates to human testing. Additionally, areas of research like Germline Gene editing on human embryos has many ethical implications around the breaching of human rights and the unknown consequences of gene editing in people.

To balance scientific progress and ethical considerations, the 14 day rule was established in 1990 under the Human Fertilisation and Embryology Act. This international guideline and key governing bodies like the Human Fertilisation and Embryology Authority (HFEA), restricts researchers from growing in-vitro human embryos for longer than 14 days. However, in recent years many scientists have called for an extension in the limit to enable further studies into early human development, provoking ongoing ethical debates.

Human Embryonic Stem Cells have the capability to transform medicine, whether it’s deepening our understanding of genetic disease and early human development or regenerating damaged tissues. However, the shroud of ethical debates regarding embryo destruction and the 14-day rule restricts their use as a potential source of regenerative medicine. Ultimately, finding and establishing a consensus that allows for both further scientific research and strong ethical standards is key to unlocking the full potential of human Embryonic Stem Cells.

Sources:

Eurostemcell (2018). Parkinson’s disease: how could stem cells help? | Eurostemcell. [online] Eurostemcell.org. Available at: https://www.eurostemcell.org/parkinsons-disease-how-could-stem-cells-help.

Hscn.org. (2023). Why Are Embryonic Stem Cells Useful For Medicine? [2023]. [online] Available at: https://www.hscn.org/post/why-are-embryonic-stem-cells-useful-for-medicine [Accessed 11 Mar. 2025].

Hyun, I., Wilkerson, A. and Johnston, J. (2016). Embryology policy: Revisit the 14-day rule. Nature, [online] 533(7602), pp.169–171. doi:https://doi.org/10.1038/533169a.

Lancs.ac.uk. (2023). Is it time to revisit the 14-day rule? [online] Available at: https://wp.lancs.ac.uk/futureofhumanreproduction/14-day-rule/.

McConnell, S.C. and Blasimme, A. (2019). Ethics, Values, and Responsibility in Human Genome Editing. AMA Journal of Ethics, [online] 21(12), pp.1017–1020. doi:https://doi.org/10.1001/amajethics.2019.1017..

National Research Council (US) and Institute of Medicine (US) Committee on the Biological and Biomedical Applications of Stem Cell Research (2002). Embryonic Stem Cells. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK223690/.

Vazin, T. and Freed, W.J. (2010). Human embryonic stem cells: Derivation, culture, and differentiation: A review. Restorative Neurology and Neuroscience, 28(4), pp.589–603. doi:https://doi.org/10.3233/rnn-2010-0543.