I found interest in the Paolo Macchiarini case, when watching ‘Bad Surgeon: Love Under the Knife’ on Netflix, described as one of the biggest frauds in modern medical history. As a biomedical sciences student and a fan of true crime documentaries I inevitably binge watched the series. Then when I attended lectures on tissue engineering and the ethics and laws surrounding the use of body parts in biomedical research, I decided to produce this blog combining what I’d learnt.

Paolo Macchiarini is an Italian born thoracic surgeon and researcher in regenerative medicine. He rose to fame in 2008, when he successfully completed a thoracic transplant in Barcelona by chemically stripping a donor windpipe and then seeding the bare scaffold with stem cells from the patient’s bone marrow (autogenic cells). (1) After his initial success Macchiarini was recruited by the Karolinska Institutet (KI) as a visiting professor and researcher in regenerative medicine and stem cell biology as well as being employed by the Karolinska University Hospital as a consultant and surgeon. Here he begins to use synthetic plastic windpipes and patient stem cells. Out of the eight thoracic transplants he performs at both Karolinska and in Russia, seven of them die within a few months or years post-op.

When reading around the ethics of regenerative medicine specifically, I found this article discussing the main ethical considerations concerned, including: patient consent, safety and efficacy, professional responsibility and, equity and fairness.

During this time, Macchiarini failed to consider any of these factors.

It was found that a proper risk assessment was never performed nor did his team seek permission from the government for the use of the plastic scaffolds, stem cells or chemical growth factors required for the procedure. Furthermore, Macchiarini was found to deliberately misrepresent his results in publications. Some papers claimed improvement in patients, however there was no record of examination. The plot further thickens when the validity of the murine studies was assessed. In the critical rat-model papers, the data collected, weight-gain data and computed-tomography (CT) overexaggerated the success of the study. (2) So where usually years of thorough pre-clinical testing is conducted to ensure the windpipe is fit for use, Macchiarini essentially publishes made up results to bypass this stage.

What I found to be especially concerning was that the misconduct was not limited to Macchiarini, but actually extends to his fellow researchers, his supervisors and the Karolinska Institutet itself. In order to carry out the transplantation, permission from the Swedish Medical Products Agency (MPA) is required due to the fact that synthetic tracheas are classed as “advanced therapy medicinal product”. Who was at fault was never clarified. Additionally, the Karolinska Hospital had deemed the operations as care interventions on the basis of so-called vital indication, (last resort treatment), but when reassessed it was found that some of the patients were actually relatively healthy, making the risk of the surgery completely unjustifiable.

After the thorough investigation of the Karolinska Institutet, an action plan was put in place to prevent future incidents. To summarise, the main initiatives include but are not limited to; strengthened ethical orientation, increased support for leaders, establishment of the council for the investigation of deviations from good research practise, review of admissions and recruitment and support systems put in place to aid incident reports. (3)

This case encapsulates the importance of ethical research and the risks associated with regenerative medicine, and is a lesson to scientists about our responsibility in producing genuine data.

What would you do if you were offered the chance to enhance your future child’s intellect and athletic abilities before they were even born?

Would you do it?

With the rapid advancements in genetic engineering, this question may demand an answer sooner than we first thought!

What is Genetic Engineering?

Genetic engineering is the process of deliberately manipulating and modifying the genetic makeup of an organism (the genetic makeup being the stuff that makes us… well… us). At the forefront of this endeavour is CRISPR-Cas, a ground-breaking technology developed in 2012. CRISPR-Cas allows scientists to target specific DNA sequences with remarkable precision and altering their function.

The potential of genetic engineering is immense, extending far beyond what you might imagine. It has been pivotal in treating human diseases such as diabetes, sickle cell disease and haemophilia.

This all sounds great, doesn’t it? Individuals grappling with diseases may not have to struggle anymore!

However, while the prospects of genetic engineering may seem promising, there looms a shadow of ethical uncertainty. The fact we can modify human cells to change their function means we can also target and modify human embryo cells.

We can basically design a human.

You may think this idea is far-fetched, and I wouldn’t blame you! The concept of designing human traits to align with our preferences may sound like the plot of a science fiction film, but it’s a reality within reach. This power to tailor human traits come with ethical risks and concerns that cannot be ignored.

Societal Implications

The societal implications of genetic engineering are vast and complex. The ability to shape human traits could worsen existing social inequalities as access to genetic enhancements may only be available to the wealthy. Additionally, there are significant concerns about eugenics, which involves altering genes to improve human traits. These actions could potentially redefine the very essence of humanity. It begs the question: Is it ethically okay to attempt to ‘play god’?

“The cloning of humans is on most of the lists of things to worry about from Science, along with behaviour control, genetic engineering, transplanted heads, computer poetry and the unrestrained growth of plastic flowers.”

– Lewis Thomas

Conclusion

Given the exciting potential of genetic engineering, we need to be careful. While it could help reduce human suffering and improve medicine, it also brings up ethical questions and societal issues that we need to think about. As the possibilities of genetic engineering are being explored, we have to make sure we’re guided by ethics and a concern for everyone’s well-being. We can use genetic engineering to make life better for everyone, not change what life is like completely.

Following the lectures on stem cells and tissue engineering, I was intrigued to learn how stem cells could be used in wound healing and specifically burn treatment. The use of stem cells for burn treatment would be amazing due to their ability to modulate the release of the chemokines, cytokines, and growth factors necessary for wound healing. Although I think this could be a really useful and interesting use of stem cells there are not yet published clinical trials on the efficacy of stem cells in burn wound care.

Pre-clinical trials have showed stem cells induce a significant promotion in healing rate of burn animals, compared with animals in control groups. Hair follicle stem cells (HFSCs) seem to be most effective at promoting the healing of burns. I was surprised to see that at this stage it appears autologous stem cells did not provide a significantly better therapeutic effect than either allogeneic or xenogenic stem cells, even though they could lead to an adverse immune reaction caused by graft-versus-host disease.

During my research I was reminded of a storyline in one of my favourite TV shows Greys Anatomy where as part of an innovation competition one doctor was looking at the use of tilapia fish skin to help with the healing of burn wounds. I was interested in finding out whether this is a reality or just fiction. I quickly found an article on a phase III randomized controlled trial looking at the benefits of Nile tilapia fish skin-based wound dressing.

Severe burns are often life altering and are a leading cause of disability-adjusted life-years especially in developing countries, such as Brazil, which may not have public health systems that can provide modern dressings developed for treating burns. Use of talapia fish skin could improve access to an effective treatment of superficial partial-thickness burns by reducing the treatment-related costs. Currently most Brazilian burn units use silver sulfadiazine cream. This is used as silver ions are antimicrobial and importantly few bacteria have been shown to develop resistance to silver. However, it has been suggested that there might not be enough evidence to suggest that burns heal better when using silver sulphadiazine.

The phase 3 randomized control study (linked above) they compared the time taken for reepithelialization, cost-effectiveness and the pain occurring during treatment with silver sulfadiazine and talapia fish skin. The mean cost per patient and number of days to complete reepithelialization was lower when Nile tilapia fish skin was used. The use of tilapia fish skin showed a reduction of approximately 50.0 percent in the mean costs for each 1 percent total body surface area ($4 vs $8). Even better news was the fact there was also a statistically significant reduction in mean pain score with the talapia fish skin treatment. Therefore, I think this treatment is a fantastic innovation.

My thoughts

Although stem cells are a fascinating area of current research, their use in treatments will not necessarily be accessible in developing countries. Simple but successful innovative treatments like the use of talapia fish skin for healing will remain important in medical research.

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

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.

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.

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 25^th 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.

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.

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.

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.

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.