The University of Southampton

Category: Ethics and the law

GFP-The fluorescent protein. Revolutionary or hazardous?

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Green fluorescent protein (GFP) is a fluorescent protein discovered in Aequorea Victoria that I’ve found to have many fascinating applications in biological research and clinical scenarios due to its central chromophore within its beta-barrel structure. I conducted a review paper in the ‘exploring proteins’ module focusing on the structure and functions of GFP and emphasised its benefits such as in tumour recognition however, I had a perspective shift upon discovering an article click here that explored previously unknown harmful outcomes of certain GFP strains have on transgenic organisms.

GFP in hematopoietic stem cell tracing

I have a passion for neuroscience and its intricacy including glial helper cells and their functions. Microglia are intriguing as they’re the immune cells of the brain protecting from pathogens and neurodegeneration. Hematopoietic multipotent stem cells produced in the bone marrow are released into the brain and differentiate into microglia cells in response to damage. Through transgenesis, the process by which foreign genetic material is introduced into an organism, GFP has been transduced into hematopoietic stem cells enabling us to track the movement and differentiation patterns as they move to the site of injury.

The use of mutated GFP (enhanced GFPs) combined with an MSCV vector (for stability) in mice chimeras illustrated that upon damage, these stem cells with GFP move past the blood-brain barrier and increase in abundance in the brain. Passage through the blood-brain barrier is rare so this may allow us to create gene therapies against neurological disorders and allow drug delivery similar to that of nanodroplets which I was shown when visiting Southampton General Hospital in which drugs can piggyback into these droplets to the site of injury therefore, something similar could be used using microglia. I think this demonstrates how powerful GFP can be in terms of disease treatments with around 6 million individuals in the US alone being impacted by these types of disorders as shown in this review article the need for this type of research is evident.

The disadvantages of GFP strains

Several new research sources have informed me of the harm GFP expression can cause to transgenic organisms. Several GFP variants show cytotoxic, immunogenetic, and physiological changes to the cardiovascular, urinary tract, and CNS some of which cause death such as in the mice strain alpha-myHC-EGFP which develops dilated cardiomyopathy where the left ventricle of the heart is weakened. The deterioration of GFP as it fluoresces also prevents accurate prolonged tracking. This means the research gathered using GFP in development such as in microglia may not be interpreted correctly. The ASPA Act of 1986 lays out fundamental requirements fulfilled to justify transgenic research projects. GFP is complicated since we still don’t understand which GFP variants cause damage to vertebrates so the rules are less defined.

My views on GFP usage

I think GFP is an incredible protein with the potential to have large impacts on a range of disease treatments and understanding of how the components of the body function and develop however, I also feel the need to emphasise the requirement for research into the different GFP strains and the changes they cause to transgenic animals so that we can properly utilise GFP without the added side effects. GFP in stem cell research has obviously been remarkable allowing us to show the mechanism by which the immune cells develop and create opportunities for treatments that would have a huge impact on a large percentage of the population yet the unsettling amount of unknown knowledge of GFP limits what research I think should be carried out by GFP until further information is obtained.

A life for a life

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Over recent years, I have become more aware of the crisis that the NHS has found itself in, regarding organ transplants. The lack of viable donors who agreed prior to death was limited and did not cover anywhere near the number of people waiting for transplants. I know that they tried to get around this by introducing the opt out system for organ donation in 2020 which was a massive step forward, however it still has its limitations. The main thing I think affects organ donations is the disparity of the genetics between the donor and the patient, leading to the need for immunosuppressant drugs to be taken for life.

Organs commonly used in transplants.

One thing that I have seen that could aid this is the use of chimeras with human derived stem cells being used to grow human organs. This would tackle so many of the current problems, as they could be genetically identical to the patient, and not require another person to die at just the right time in a specific way to allow transplant to be safe and effective.

The ethical side of this is a bit less clear cut. Currently, there are thoughts that animal chimeras would be used, for example pigs that grow human hearts or kidneys. These would be genetically engineered to lack certain organs which would be replaced with human grown ones. I can’t help but feel that the use of animals that have higher brain functioning is unethical, as they may experience unknown side-effects and experience pain and suffering that we could not prepare them for. I have always loved animals and the thought that we just decided that we were better than them and they don’t deserve the same rights has always been something that I’ve felt uncomfortable with. They are unable to consent to the research that we would be carrying out on them which makes me thing we are abusing the power we have over them.

This is the same with smaller animals such as rodents, which are deemed ok to test on. I completely understand however that this ethical dilemma is opposed by the number of people that would greatly benefit from the organs that would save their quality and quantity of life. Almost 7000 people in the UK are awaiting transplants, and 439 people died last year whilst waiting. Is it wrong to deny them the chance of life if we could save them?

A comparison of the brain makeup of rat, pig and human brains, showing the similarities between human and pig brains.

When people push for chimeric organs, they often compare it to way we slaughter pigs every day for food, and that there is little difference between this and genetically modifying them. I do not feel this to be accurate, as we are not letting them live their lives as they would do in nature, and we could not be sure that no harmful effects would be experienced by the animals. They would likely have to spend all of their life being monitored and tested to ensure the organs were growing properly, and that they were healthy.

Overall, I think that the use of chimeric animals in organ farming is not clear cut. Laws and ethical regulations would have to be heavily regulated to ensure that the animals were not adversely affected and the organs were of a high enough standard to make the animal lives lost worth it. If implemented, it would likely save countless lives awaiting transplant and reduce the illegal trafficking of organs, leading to better outcomes for all.

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.