The University of Southampton

Month: March 2024

Grow yourself a backbone!

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Familiar with that phrase? Well, Scientists have given this saying a whole new meaning… A future where damaged spinal cords can be regenerated through the medical application of stem cells isn’t as far away as it once seemed…

So what is a stem cell?

Stem cells are cells produced by the bone marrow that can differentiate into a specialised cell type, and are even capable of self renewal. They can be isolated from adult tissues or grown within a laboratory. The stem cells that are isolated from adult tissues are referred to as multipotent, meaning they can only change into a particular type of cell. We also get pluripotent stem cells, which are often derived from embryonic cells. However, these can cause quite the debate, with views on ethics differing. Therefore, the use of Induced Pluripotent Stem Cells (IPSCs) is often preferred. Like embryonic stem cells, IPSCs are also pluripotent, meaning they can divide indefinitely and differentiate into almost any cell type, but they don’t raise the same ethical concerns due to originating from adult tissue.

Restoring mobility and function to those with spinal cord injuries

Therapies involving stem cells hold great promise for treating a variety of medical conditions, particularly spinal cord injuries. Stem cells taken from a patient’s skin or blood cells are used to create IPSCs. These are then coaxed into becoming progenitor cells, which are specialised to differentiate into spinal cord cells. Once these progenitor cells are transplanted back into the patient, they can regenerate part of the injured spinal cord, offering hope for recovery. Sounds great, right?

What could possibly go wrong?

Undifferentiated IPSCs pose a risk to patients, with a chance of forming tumours. This limits the therapy’s safety and efficacy, questioning the future of stem cell treatment. Luckily, researchers have developed what’s known as a microfluidic cell sorter, which you can imagine to be like a sieve. This device removes undifferentiated cells without harming fully-formed progenitor cells. It can sort over 3 million cells per minute and can be scaled up by chaining multiple devices together, sorting more than 500 million cells per minute! Plus, the plastic chip that houses the sorter can be mass-produced at low cost, making widespread implementation feasible. Cheap and cheerful!

So how does it work?

The microfluidic cell sorter operates based on the size difference between residual, undifferentiated pluripotent stem cells and progenitor cells. Pluripotent stem cells tend to be larger because they have numerous active genes within their nuclei. As cells pass through microfluidic channels at high speeds, centrifugal forces separate them based on their size. By running the sorter multiple times at different speeds, researchers are able to remove these larger cells that are associated with a higher tumour risk. Problem solved!

The future…

Although the sorter doesn’t eliminate 100% of undifferentiated cells, it significantly reduces the risk, massively enhancing the safety of stem cell treatments. Further studies including large-scale experiments and animal models are underway to validate these findings. If successful, this sorter could improve efficacy and safety, paving the way for broader applications of this revolutionary technique. The development of this microfluidic cell sorter shows a significant advancement in the field of stem cell therapy. It brings us closer to realising the full potential of stem cells and the use of other regenerative medicines for conditions like spinal cord injuries. With research ongoing and technological innovations forever evolving, the future of improved healthcare looks promising.

Looks like you will be able to grow a backbone after all…

Links:

https://stemcellthailand.org/induced-pluripotent-stem-cells-ips-ipscs-hipscs/

https://www.nhs.uk/conditions/stem-cell-transplant/#:~:text=Stem%20cells%20are%20special%20cells,cells%20%E2%80%93%20which%20help%20fight%20infection

https://www.youtube.com/watch?v=i7EN6l9wqDU

https://cells4life.com/2024/02/the-tiny-device-set-to-improve-stem-cell-therapy/

https://novavidath.com/services/stem-cell/?lang=en

https://doi.org/10.1002/path.1187

Human enhancement; how far is too far?

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In an era where scientific advancements are pushing the boundaries of what is possible, the concept of human enhancement has become a topic of intense debate. With technologies such as CRISPR, being able to edit your own genetic makeup, the possibilities for enhancements are endless.

Human enhancement is the use of technological interventions to enhance human capabilities beyond what is ‘normal’. This includes physical, cognitive or sensory capabilities, enhancing the performance and well-being of patients.

In the past, prosthetics included wooden limbs with limited movement and comfort. The evolution of prosthetics has improved overtime and now with the development, integration of technology and artificial intelligence (AI), we are able to do what was only possible in science fiction.

A 46 year old male was able to regain movement in his arms with the use of AI. With plans already being made for chips to be implanted in our brains by Elon Musk, founder of neurotechnology company Neuralink, he quoted, “Initial users will be those who have lost the use of their limbs. Imagine if Stephen Hawking could communicate faster than a speed typist or auctioneer. That is the goal.” We are certainly not far from these developments.

These advancements hold the promise of improving the lifestyle and health of those effected, effectively changing their lives for the better. However it is important to think about the risks. Long term effects are currently unknown with no way of knowing until they are introduced it into society, but by then will it be too late to control. The risk of unintended consequences are always present.

Ethical implications:

Ethical questions are raised about the limits of intervention and the potential consequences for individuals and society. The notion of playing God, intervening in the natural order of things, contradicts many religious and philosophical perspectives. Moreover, informed consent are paramount as individuals must have the necessary information to make informed decisions about undergoing enhancement procedures.

Ethics and science need to shake hands - Richard Clarke Cabot

While some enhancements may address medical conditions and improve quality of life, others may be pursued for cosmetic or commercial reasons. This also raises concerns about fairness, equality, and access to these technologies. Who should have access to enhancement technologies, and at what cost? How do we define the limit?

Social & legal implications:

Human enhancement technologies could exacerbate social inequalities, widening the gap between those who can afford enhancements and those who cannot. Cultural attitudes toward enhancement, beauty standards, and even sports competitions may be profoundly influenced by these technologies. Regulatory frameworks must strike a delicate balance between fostering innovation and ensuring safety. Questions about marketing, prosecution for misuse of enhancement technologies, and setting legal limits on enhancement procedures add further complexity to the legal landscape.

Moreover, we may become a society increasingly dependent on technology to define human capabilities and identity. This challenges societal norms and values further, potentially reshaping perceptions of being human. Will we eventually lose our sense of what it really means to be a human?

Conclusion:

In conclusion, the ethics of human enhancement force us to confront profound questions about the nature of humanity, the limits of intervention, and the implications for individuals and society. While advancements in science and technology offer incredible opportunities for improving human capabilities, we must proceed with caution, mindful of the ethical, social, and legal ramifications. As we navigate this uncertain terrain, it is essential to engage in robust dialogue and ethical reflection to ensure that human enhancement technologies are used responsibly and ethically, for the betterment of all.

Ethics of growing Synthetic Human embryos

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The Ethics and laws around growing Human embryo’s and their status have been a contentious topic since the first experiments deriving stem cells in 1981. And it is an area in which the law leaves areas unclear given recent advancements in synthetic embryos. Currently in the UK embryos are not allowed to be grown outside of the womb for more than 14 days, the reasoning behind this being that it is the best guess for the last point in which an individual, instead of multiple people, could develop from a single embryo. Given these rules, and the understanding that Embryos cannot grow into foetuses outside of the womb, in many countries embryos are not legally considered people. This idea has been challenged recently in the US, where the Alabama supreme court ruled that frozen embryos used in IVF are considered children.

What are synthetic embryos

Embryos are the initial stage of development of multicellular life, starting as the blastocyst (formed from the fertilisation of the egg cell by a sperm cell) implants onto the walls of the uterus. For most of history this was the only way to form an embryo, until 2022 when a team at the Weizmann Institute in Israel manipulated mouse stem cells, which then grew into embryo like structures. This work has been continued and since then scientists at the University of Cambridge have created synthetic mouse embryos that have formed with a brain, nervous system and beating heart.

Natural (top) and synthetic (bottom) embryos side by side to show comparable brain and heart formation. Image credit: Amadei and Handford

Ethics of using synthetic embryos

Research using synthetic embryos has many touted benefits, many pregnancies fail in the first weeks when the cells that will become the embryo, placenta and yolk sac differentiate, and the hope is synthetic embryos will allow further research into this area, where current research with human embryos is limited due to the 14 day rule. It also allows research in understanding the development of the brain, as this starts developing later than 14 days and cannot be examined closely inside the womb. The rational behind these synthetic embryos being developed for longer periods of time is that they are models of the human embryo, and would not be able to develop into the foetal stage.

There are many questions on the morality of creating synthetic embryos. If the synthetic embryo is recognised as children, much alike the case in the Alabama Supreme court, then the embryo could be seen as a clone of the person who donated the stem cells, Importantly Human cloning is banned in most countries around the world and thus would make the development of these embryos illegal.

Currently the only limit to this research in the UK is that it is illegal to implant synthetic embryos into a human womb.  This leaves a wide range of possibilities for research, and questions are being asked about what stage these embryos can be grown to before they are seen as alive. This question has yet to be agreed on regarding the development of natural foetus’ and so likely will be a long time before it is answered.

Links

Epstien, K. (2024) Alabama IVF ruling: What does it mean for fertility patients?, BBC News. Available at: https://www.bbc.co.uk/news/world-us-canada-68366337 (Accessed: 06 March 2024).

Collins, S. (2022) ‘Synthetic’ embryo with brain and beating heart grown from stem cells by Cambridge scientists, University of Cambridge. Available at: https://www.cam.ac.uk/stories/model-embryo-from-stem-cells (Accessed: 06 March 2024).

Villalba, A., Rueda, J. and de Miguel Beriain, Í. (2023) ‘Synthetic embryos: A new venue in ethical research’, Reproduction, 165(4). doi:10.1530/rep-22-0416.

The ethics of genetic engineering

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On the 26th of July 1978, Louise Joy Brown, the first test tube baby was born. Nearly 50 years on, are we any closer to editing our imperfections and what are the implications?

What is genetic engineering?

Genetic engineering is the process of modifying an organisms DNA. Aside from helping couples who are otherwise unable to have babies, recent advancements in the field ranges from the eradication of malaria to the production of synthetic human insulin to reducing the risk of genetic diseases. The benefits of genetic engineering also extends beyond humans, with the development food crops that are resistant to extreme weather, ecological and soil conditions. An example of the technology used is Crispr CAS (Clustered Regularly Interspaced Palindromic Repeats), which edits an organisms genome by removing/adding/modifying DNA. The first babies born using Crispr CAS9 edited genes was born on 25th November 2018, suggesting we are getting closer to editing our imperfections.

The ethics debate

However, despite these benefits, the question remains: Is it ethical? Indeed, these technologies are beneficial to couples who are otherwise unable to have children, however, there is potential for this technology to be misused. The ability to select for certain genes has given rise to “designer babies” where features of interest can be selected for with other undesirable features selected against. While this can be beneficial in selecting against genes susceptible to disease, the fact remains that there are multiple ethical issues?

One major issue is the potential to increase social inequality. Due to the financial cost only the rich can afford this technology, increasing the gap between those who can afford it and those cannot. Further, we may also be creating a society where certain traits are seen as more desirable, resulting in discrimination towards those without the preferred features, aswell as a loss of diversity. Another concern is the issue autonomy and informed consent as it is the embryos that are being modified, questioning whether the parents have the right to make life changing decisions of their future children, especially if they are non-medical. Further, the long term consequences are largely unknown and could have side effects in the individual and future generations.

Conclusion

The ethics of genetic engineering are complex. Indeed, the possibility of advancement and improvement to health are massive, but the side effects and potential misuse is equally big and must be considered. Nevertheless, it is important that there is a balance between allowing for innovation and protecting human right.

Links

Guardian Research Department (2011). 1978: The First Test Tube Baby. The Guardian. [online] 2 Jun. Available at: https://www.theguardian.com/theguardian/from-the-archive-blog/2011/jun/02/guardian190-test-tube-baby-1978 [Accessed 1 Mar. 2024].

Mirage News (2023). Designer Babies & Ethics of Human Genetic Engineering. [online] Mirage News. Available at: https://www.miragenews.com/designer-babies-ethics-of-human-genetic-992678/ [Accessed 1 Mar. 2024].

Rose, B.I. and Brown, S. (2019). Genetically Modified Babies and a First Application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas9). Obstetrics & Gynecology, [online] 134(1), p.1. doi:https://doi.org/10.1097/aog.0000000000003327.

New Stealthy Stem Cells?

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Developments in new gene editing techniques provides stem cells with the ability to bypass the immune system offering new applications in cell replacement therapy.

There are more than 10 million people worldwide currently living with Parkinson’s disease and 3 million people recorded to be living with type 1 diabetes globally in 2017. Both of these chronic diseases are currently incurable and require regular medication and treatment to control. Due to their life-long impacts, many people can relate to the implications these diseases have on both the individuals diagnosed and the family members or friends of the individuals. The negative effects can be physical, mental, social or financial and often a collection of them all.

So if there was a possible solution would you take it?

Research has suggested a new strategy that could provide an endless supply of replacement body parts for individuals suffering from debilitating disorders and diseases. Scientists can now grow stem cells in the laboratory and engineer them into specialised cell types. Which can eventually be transplanted into humans and potentially cure diseases, once believed to be incurable. For Parkinson’s disease this could mean cultivating neurones to combat the progressive damage made by the disease over the years to different parts of the brain, or for type 1 diabetes insulin-producing pancreatic cells could completely reverse the effects of the disease and lastly heart muscle cells to could be transplanted to enhance cardiac function. These are just a few examples of the life-changing effects this new treatment could have.

In genetically modified mice predisposed to autoimmune diabetes, pancreatic cells undergo infiltration and destruction by “killer” T-cells, leading to a decline in insulin production (pictured on the left). However, administration of MOTS-c injections mitigated T-cell infiltration, consequently averting disease onset (pictured on the right).

Credit: Newcomb (2021)

How this is possible…

Utilising gene-editing techniques like CRISPR-Cas systems, stem cells can be manipulated to possess immune-evading traits, effectively bypassing recognition mechanisms. Moreover, these engineered cells can integrate fail-safe features to guarantee cells can be eliminated in the case of unforeseen issues. Consequently, such ‘stealth’ cells hold promise to support various cell-replacement therapies.
In most cases, the process starts with the disruption of at least one component of the cell’s major histocompatibility complex (MHC). This complex functions like a molecular identity card, showcasing distinct cellular information fragments that inform the immune system’s T lymphocytes, its frontline defenders, and whether the cell is hostile.
To mitigate potential susceptibility to natural killer cells (NK), certain researchers have suggested the reintroduction of genes encoding particular MHC antigens. These antigens enable the cell to modulate NK cells without eliciting T-cell responses that may induce apoptosis (cell death). NK cells serve as the effector lymphocytes of the innate immune system, tasked with regulating various tumour types and microbial infections to restrict their dissemination and consequent tissue harm. Alternatively, other strategies may involve introducing genes that produce ‘checkpoint’ proteins, specialised molecules aimed at directly suppressing NK cell activity.

Are there any downfalls to this ground-breaking new strategy?

Unfortunately, therapies stemming from stem cells require customisation for each patient, a process that is both time-consuming and costly. Alternatively, these treatments can utilise donor cells; however, due to the tendency of the immune system to reject foreign cells, such ‘allogeneic’ therapies require the administration of immune-suppressing medications alongside treatment. However, this approach escalates the risk of complications like infection and cancer.

Ultimately, the optimal safety strategy, as well as the ideal extent of gene editing required to suppress immune responses, may vary depending on the disease. For instance, pre-made cell therapy for cancer may not require the same design features as one tailored for diabetes, given the differences in the immune system’s response and the distinct risk-benefit considerations for each ailment. In essence, there is no ‘one-size-fits-all’ solution.

With the true test of human trials likely to follow soon the future of this treatment is looking hopeful.

Acknowledgements:

Dolgin, E. (2024). Stealthy Stem Cells to Treat Disease. Nature. [online] doi:https://doi.org/10.1038/d41586-024-00590-y.

Green, A. (2008). Descriptive Epidemiology of Type 1 Diabetes in Youth: Incidence, Mortality, Prevalence, and Secular Trends. Endocrine Research, 33(1-2), pp.1–15. doi:https://doi.org/10.1080/07435800802079924.

Newcomb, B. (2021). Small Protein Protects Pancreatic Cells in Model of Type 1 Diabetes. [online] USC Leonard Davis School of Gerontology. Available at: https://gero.usc.edu/2021/08/12/mots-c-mitochondria-type-1-diabetes/ [Accessed 5 Mar. 2024].

Parkinson’s Foundation (2024). Statistics | Parkinson’s Foundation. [online] www.parkinson.org. Available at: https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=Parkinson.

Vivier, E., Tomasello, E., Baratin, M., Walzer, T. and Ugolini, S. (2008). Functions of Natural Killer Cells. Nature Immunology, 9(5), pp.503–510. doi:https://doi.org/10.1038/ni1582.

Where do cochlear implants fit in Deaf culture? 

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After watching the film ‘The Sound of Metal’, I realised that my previous perceptions of hearing loss didn’t consider the personal nuances and complexities that are integral to the Deaf community. The film follows a drummer who suddenly loses hearing in both ears. It is a highly personal portrayal of the different perspectives on hearing loss and the difficulties of adjusting to cochlear implants. What struck me the most (spoiler alert!) was the main character’s initial disappointment when getting fitted with a CI and the reaction of the deaf community he lived with to his decision. Following a fascinating lecture from Nicci Campbell, I decided to explore the perceptions of cochlear implants within Deaf culture further. 

What Are Cochlear Implants? 

Diagram of an in-situ cochlear implant. (NIDCD, Cochlear Implants).

Cochlear implants are small electronic devices that aid hearing acquisition and sense of sound in profoundly deaf or hard of hearing individuals (NIDCD). The instrument picks up sound through the microphone. Sound is then arranged by a speech processor and transmitted as an electrical signal to the electrode array, which sends the electrical impulses to various regions of the auditory nerve (NIDCD).

Concerningly socioeconomic status can influence outcomes of cochlear implant surgery, particularly in children (Sharma et al., 2020). I was unpleasantly surprised to learn that adults are only entitled to one CI on the NHS. It seems that whilst just one CI may provide sufficient access to auditory stimulation, this could intensify the socioeconomic divide in treatment for hearing loss and may prevent a significant increase in quality of life of individuals who can’t afford a second implant. One reality star, Daisy Kent, spoke about her hearing loss and stated that since she had the implant she doesn’t have ringing in her left ear, but “in my right ear, I have a ton of ringing”. I think this helps illustrate how only having one CI can prevent a much more desirable outcome for those who can’t afford two. 

Deaf Culture 

Prior to watching ‘The sound of metal’, I perhaps wouldn’t have considered that cochlear implants could be such a controversial topic. However it is clear that individual perspectives, particularly within the Deaf community, vary quite dramatically (Li et al., 2024). In the film, the main character joins a deaf school, and is told to leave once he secretly pays for cochlear implant surgery.

Some members of the deaf community see CI as a threat to Deaf culture. I think this highlights the rich history of communication and adaptations of people with hearing loss. To understand this further I have included a brilliant Ted Talk by Glenna Cooper.

I particularly enjoyed her statement that deaf people tend to have a much greater appreciation for the exchange of information, and I think this enhances her point that deaf people should not be considered as disabled, rather that they “have a different language”.  

You can read more about Deaf culture here.  

A Middle Ground

Sign language is perhaps the most obvious facet of Deaf culture. However, I was horrified to learn that not too long-ago many doctors told parents to discourage their deaf children from signing – and this is just one of the reasons why I can appreciate the sensitivity of assuming all deaf people may benefit from auditory aids, which may lead to a decline in the use of sign language. However, it is important to appreciate experiences where cochlear implants have created a unique path between both ways of life – Heather Artinian, a lawyer who was born deaf and to deaf parents, decided to get a cochlear implant surgery at age 10, against her parents initial wishes. She describes how she operates in the ‘Heather world’ where her upbringing amongst a deaf community, and her implant, allows her to enjoy aspects of both the hearing and the deaf world. I would highly encourage listening to her engaging and positive perspective on being in ‘not the hearing or deaf world.’ https://youtu.be/jhm5OaXJVMQ?si=TU_DSGcD-m-fEeqq

In an ideal world, we would all be more accommodating of Deaf culture, and more people would aim to learn sign language.  

You can follow this link to find out how to start learning sign language. You can also learn how to sign your own name, and other words here.

 

Celebrating diversity and appreciating different ways of experiencing the world enhances new perspectives and solutions of healthcare. Following utilitarian beliefs that aim to serve the majority threatens minority cultures, such as Deaf culture, which could be excluded when attempting to ‘fix’ what many people consider a significant part of their identity. I believe that whilst the development of CI has provided many people with access to a better quality of life, reduced social isolation and discomfort, we shouldn’t immediately assume that anatomical differences need to be universally ‘fixed’, rather than accommodated and respected, whether that be through learning BSL or providing equitable access to assisted hearing technology.

Links

NIDCD https://www.nidcd.nih.gov/health/cochlear-implants#:~:text=A%20cochlear%20implant%20is%20a,the%20skin%20(see%20figure).

Sharma et al (2020) https://doi.org/10.1016/j.ijporl.2020.109984

Li et al (2024) https://doi.org/10.1038/s41598-024-55006-8

The Aesthetics of Prosthetics

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When designing prosthetics, it is evident that the most important consideration is their function. After all, what use is a prosthetic leg if it cannot be walked on? Other considerations, such as comfort, lifespan, and the impact of use on the rest of the body, are also included, but one factor is often left out of the conversation: visual appeal. It goes without saying that a primitive peg leg lacks the full range of function and motion of the human leg, and thus, over the past several hundred years, the function of the prosthetic leg has been developed to not only work more like the lost limb but in many ways look like the lost limb. However, some people note that more recently increasing the functionality has lessened the visual relationship of prosthetics and the human body. In some ways this feels like a regression in progress: historians and prosthetis specialists are unsure if archaeologically recovered early prosthetics, such as the Egyptian Toe, were primarily designed for function or appearance.

Image of prosthetics from the past 100 years from Caulfield Hospital in Melbourne.

When a person loses a limb, not only their physical health is altered, but a patient’s mental health undeniably takes a toll. Feelings of depression, anxiety and low self-esteem in regards to body image are often experienced by amputees, and these are feelings that can be exacerbated with time; in a study of 207 lower-limb amputation patients, patients who had been amputated 4-6 years ago had the lowest body satisfaction. There are distinct feelings of loss of independence and bodily autonomy, as well as the aforementioned poor body image, which contribute to this. Feeling ‘other’ is common among those with physical disabilities as a result of self-sourced insecurity and insecurity due to social exclusion and discrimination. Many efforts are made in the post-operation treatment of patients to rehabilitate them both physically and mentally by psychologists, physiotherapists and occupational therapists, but often these negative self-perceptions persist.

These negative self-perceptions may go beyond the general physical insecurities and contribute to fashion insecurities. Social pressure to fit in is worse than ever with the dissection of fashion trend cycles into microtrends and the rise of social media. Trying to conform a part of you that does not fit society’s idea of ‘perfect’ into trends that demand perfection can feel demoralising and therefore trying to adapt your prosthetic to your own journey of experimentation with fashion can be a frustrating experience. These sentiments were echoed by Chinese fashion model Xiao Yang, who has worn a prosthetic leg for over 25 years and is one of several in the fashion and art industries who have ventured to add individuality and personality to prosthetics by using accessories such as patterned leg covers or shaped knee caps, developed in collaboration with jewellery brand YVMIN.

Xiao Yang wearing a prosthetic cover from her collaboration with YVMIN.

Though Yang’s collaboration with the YVMIN was temporary and specifically for Yang, another company, Alleles Design, had a similar concept and continues to provide custom-manufactured prosthetic covers with thousands of possible designs with the aim of ‘giving the power of self-expression back to [prosthetic wearers]’. You can even design your own using their design tool.

Demonstration video from Alleles Design LTD

With companies aiming to fill this gap in the market, personalised prosthetics are likely to become more common as knowledge of these accessories grows and the costs decrease. Personalised prosthetics have the potential to reduce body image and self-esteem issues amongst limb-prosthetic users and are a step towards prosthetics that feel more like man than machine.