An Introduction to Stem Cells and the state of research in present day
The human body contains a wide array of specialised cells which work in synergy to ensure healthy conditions are maintained. Stem cells are unspecialised or undifferentiated cells with the ability to divide and renew themselves over an extended period of time. They also have the potential to either remain a stem cell or differentiate into a cell purposed for a specialised function. Right from embryonic development to adulthood, stem cells play an integral role in the human body. They develop into specialised cells in the embryo, eventually forming different organs in the foetus. As well as that, stem cells assist the growth and repair of all organs and tissues in the human body, making their attributes ideal for regenerative medicine. Multiple types of stem cells exist, some of which currently provide treatments for diseases including Multiple Sclerosis, Leukaemia and Parkinson’s disease. The 2 main types of stem cells which are largely discussed in regenerative medicine are adult stem cells and human embryonic stem cells (hESCs). Adult stem cells, first successfully used in 1968, are capable of producing cell types from the tissues they originate from (for example, Brain Stem Cells have the potential to become neurons or glial cells).
Human embryos utilised in stem cell research are made during IVF (in-vitro fertilisation) treatment,. During IVF, a couple will typically produce embryos in excess of what is required for their treatment. Human Embryonic Stem Cells used in research are derived from these additional embryos. These stem cells are extracted from the inner cell mass of an early embryo called the blastocyst which is surrounded by trophectoderms. A blastocyst is a hollow, thin-walled structure containing a bundle of around 150-200 cells which are formed at five days into embryonic development and eventually give rise to human life. Furthermore, cells from a blastocyst can grow into any human cell type and therefore they are referred to as ‘pluripotent’
Figure 1 – simplified diagram of Blastocyst including the inner cell mass
Due to their pluripotent ability, future hESCs could facilitate clinical cures to an abundance of diseases like no other biological discovery. They could arguably become the most important aspect of medicine in the 21st century.
Human Embryonic Stem Cell lines are produced in research facilities globally. Although they have not been clinically applied yet, hESC researchers are making stellar progress to enable this. This has been through the increasing number of donors involved in hESC extraction lines such as the ISCF (International Stem Cell Forum). Founded in 2003, the ISCF are a funding body of stem cell research which consist of 21 institutions including the Medical Research Council in the UK. Their system has led to many breakthroughs in hESC research. In 2015, scientists from the University of Manchester successfully produced cartilage originating from embryonic stem cells and this holds huge importance in the treatment of osteoarthritis. It is currently very prevalent in society with an estimated 33% of people in the UK aged 45 years and over affected by the condition. They placed hESCs into a cultured solution which triggered the differentiation into cartilage cells. Another example is the search for the cure of age-related macular degeneration which has emerged in hESC research. Clinical trials for the disease have been ongoing from September 2015, pioneered by University College London. The affected cells in the retina get replaced with newly created eye cells originating from hESCs which restore the patient’s vision.
With embryonic stem cells having the capacity to produce any cell type, it is seemingly apparent that research should be extensively endorsed. However, there is a considerable issue that prevents this – ethical concerns regarding the use of embryos for hESC research. Since its inception in 1998, when the first stem cells from human embryos were grown, hESC research has rapidly grown in prominence among the media and the scientific research community. This has also garnered a large base of negative attention, especially among religious groups and divided the general public into two categories- ‘pro-life’ & ‘pro-hESC’. This essay will investigate the rationale behind the differing views between pro-life and pro-hESC in the stem cell ethical debate, while assessing if there are options that can fundamentally reconcile the two groups.
The pro-life views and reasoning
The principal argument posed by pro-life organisations is whether embryos are worth using for research and treatment. A more severe interpretation of this argument is ‘An embryo is a human being; therefore the act of stem cell extraction is murder’. This statement refers to how most individuals would strongly condemn the killing of another human being for the purpose of experimentation as done by nations of war in the past. Consequently, they argue that the use of embryos for the purpose of hESC research is ethically equivalent to this. As well as that, another particularly strong view shared by pro-life supporters is that hESC research could lead to the gradual devaluation of human life. Many pro-life supporters fear instead of using spare embryos from IVF, scientists may eventually resort to creating embryos for the sole purpose of experimentation to increase efficiency of research.
Leading bioethics specialist & Graves Professor of Moral Philosophy at Union University, Ben Mitchell has discussed the validity of this concern and he said: ‘It is wrong to create human embryos for the purpose of experimentation and destruction. This is biotech cannibalism, consuming our young for the sake of our own potential prosperity. It does not matter whether she is 5 days old or 50 days old, a human embryo is a human being. That is just what human beings look like at that age. That us what all of us looked like at that age.’. These words convey the outright sense of fear shared by the ultra-conservative spectrum of pro-life support.
Another one of the primary disputes between pro-life and pro-hESC supporter originates from the different perceptions of when human life begins. This element is often mentioned by moderate pro-life supporters. One example is Ronan O’Rahilly, an embryologist based in the University of California. He expressed that ‘Although life is a continuous process, fertilization… is a critical landmark because, under ordinary circumstances, a new genetically distinct human organism is formed.’
Religion is a key constituent in the debate because of its ability to promote and encourage a belief onto its masses of followers. This is particularly evident with conservative Catholics, with a large section of the pro-life support consisting of this religious denomination. According to biblical scriptures human life begins at conception. One example is Psalm 139:13-16, which refers to how God has a plan for all embryos before conception and it says “Before I formed you in the womb I knew you, before you were born I set you apart; I appointed you as a prophet to the nations.” Furthermore, high-profile religious authorities in the Vatican have been calling for the use of adult stem cells instead of hESCs, compelling a large number of Christians to follow this belief.
While Orthodox Christians have distinct beliefs against hESC research, other religions have variable stances on it. For instance, Islam has no official ruling in their holy scriptures but the beliefs among its followers differ. Some argue that extraction of embryos is early abortion, while others point towards the verses of the Quran
which mention a developing embryo does not have a soul until 120 days after fertilisation. Surah al-Mu’minun V: 12-14 says ‘Then the soul is breathed into him after 120 days’. Thus, some Muslims do not consider embryos as human life.
Religions such as Sikhism and Hinduism have no specific stance on hESC research. Whereas in Buddhism, some believe hESCs research is permitted as it helps in the path of eliminating human suffering. However, others strongly argue the use of an embryo directly goes against the philosophy of Ahimsa- a key principle of Buddhism. The Holy scriptures of Judaism do not reject the moral principles behind hESC research and it is entirely accepted for therapeutic prospects.
The ethical debate surrounding human embryonic stem cells is highly philosophical as it prompts an individual to weigh the relative importance of potential human life against a breakthrough in regenerative medicine which could benefit living human beings. While the philosophical aspect of the debate is an influential factor among pro-life supporters in their hostility towards hESC research, they also largely incorporate the scientific aspect of the debate to convey their beliefs.
Pro-life supporters allude to how all humans were at that stage of development to begin with and embryos should be considered as human life. Furthermore, they argue how the size and location of the embryo is irrelevant to the rights they deserve. On the contrary, the vast majority of scientists do not consider a blastocyst as a form of life and they can be described as ‘genetically human but not a human being’. Some pro-hESC supporters believe that birth is the moment a human should have the right to life because at this point a human is free from a mother’s womb. Other supporters in this group acknowledge the most common legal criteria used when drafting abortion laws – the stage where the foetus could survive outside the womb.
Pro-life supporters mention practical aspects involved with embryos. Although there are many left over embryos in IVF, they do not necessarily have to be destroyed for hESC research. One argument posed is the adoption of unused embryos from IVF which is possible through ‘rescue surrogacy’, where they can be implanted into a womb of another woman and this could potentially be born into a healthy baby.
Another aspect about hESCs which pro-life supporters are critical of is there are currently no treatments which it can provide for. Instead, they argue there is a more effective and ethical alternative available instead of hESC in adult stem cells. Adult stem cells are derived from tissues of organs such as muscle and bone marrow. They already provide treatments for many diseases including treatment of blood diseases such as Leukaemia. The present-day success of adult stem cells suggests that they offer immense opportunity for the enhancement of regenerative medicine and is a more proven clinical success compared to hESC.
One type of adult stem cell specifically discussed by pro-life organisations are cord blood stem cells. Originally dismissed as waste material, cord blood stem cells are now successfully used in the treatment of numerous blood diseases. They are derived from the umbilical cord and the placenta, extracted after a mother gives birth and the umbilical cord is cut. Cord blood stem cells are hematopoietic, meaning they are stem cells with the ability to produce all other types of blood cells. They have a mainstream donation system in the UK via the NHS Blood Trust, which provides services for blood cancer treatment. In the process of cord blood extraction, they check for compatibility of blood, carry out procedure of supervision of maturing blood cells and collection of cord blood. As well as that, NHS Blood Trust is the fourth largest cord blood bank globally, while being responsible for the collection of 3000 stem cell donations annually and have 18000 cord blood units banked.
Besides that, it is believed that the true capacity of cord-blood stem cells is yet to be uncovered and they could offer cures to more blood diseases in the near future. Pro-life supporters believe it would be beneficial to increase funding towards research in cord blood stem cells rather hESCs because of its difference, ethically. These alternatives arguably indicate, even though hESCs may seem to be advantageous due to their pluripotent nature and research is in deep stages in development, there are more ethical means to achieve the scientific success.
The pro-hESC views and reasoning
While viable alternatives exist, there are clear advantages to the use of hESC. The main point used by pro-hESC supporters is the fact that human embryonic stem cells are pluripotent. This offers a larger likelihood for the discovery of cures for diseases in the future unlike adult stem cells which are restricted to production of cell types from the tissue it was derived from. The analogy of a gift card and cash could be used to convey this. If one had the choice between a gift card worth £250 which is only applicable to one store or cash worth £250 that could be used to buy any item from any store, the obvious preference would be cash due to the fact its use has no limitations. Adult stem cells are rigid and lack flexibility, whereas hESCs can offer a broader scope of treatment
Figure 3 – A Diagram demonstrating the primary functions of hESCs
In addition to its relatively confined range of treatment, pro-hESC supporters also mention the flaws of adult stem cells which are typically are less efficient at self-replication, while they also have a greater risk of gradually acquiring genetic abnormalities. This is because adult stem cells are typically older than stem cells derived from a discarded embryo and therefore they are more susceptible to genetic abnormalities to due to changes in the environment, as well as discrepancies in DNA replication.
There are various options for couples who have spare embryos after IVF treatment. Firstly, they could store embryos for their future use or allow them to perish. Alternatively, they can donate embryos to other couples who have had failed IVF cycles previously. As well as that, they could donate the embryos for stem cell research which might benefit patients in the future with disease that are currently incurable. Pro-hESC supporters believe this is a high purpose, one that promotes both human health and understanding. They raise the question whether preservation of embryos is more valuable than humans who are afflicted and suffering with incurable diseases. They believe hESCs may be the solution in terms of alleviating the pain experienced by individuals affected by incurable diseases, while it may also offer a cure for them.
However, there is an ideal alternative to hESCs which theoretically have the same versatility and attributes as them – known as Induced Pluripotent Stem Cells or iPSCs. Pioneered by Japanese stem cell researcher Shinya Yamanaka, the ground-breaking discovery of iPSCs later earned him international recognition in the form of the 2012 Physiology Nobel Prize. They are originally differentiated cells (Specialised cells such as blood cells, nerve cells and neurons), which are then genetically reprogrammed to become pluripotent-just like hESCs. Induced Pluripotent Stem cells on the surface seems to provide an ethical solution for pro-life supporter, while not compromising the scientific potential the pro-hESC supporters. Although it seems this is the ideal solution to reconciling the 2 parties, it is a long way from being controlled and being utilised in a clinical environment. Until very recently, the production of iPSCs caused permanent genetic changes in a cell which would cause tumours to form. This has now been amended and conveys the progress made with IPS cells but it also clearly shows further research is required for the possibility of future therapeutic use.
Legislation on hESC research
Both pro-hESC and pro-life supporters pose robust arguments but the aspect that can implement their views is legislation. The USA is at the heart of the controversial stem cell debate, where its citizens are among the most divided and opinionated. Although it contains a large base in pro-life support, the USA does not explicitly have a single-minded view. Legislation has fluctuated over the last 25 years. In 1993 President Clinton made an executive order to lift a moratorium preventing federal funding of hESC research. However, in 1994 the executive order was reversed due to intense public scrutiny of the decision with thousands of letters appealing against the decision were sent. In 1995, pro-life US house representatives Jay Dickey and Roger Wicker made a proposition to ban federal funding of hESC research. This became known as the Dickey-Wicker amendment and when introduced a year later, it prohibited the federal funding of activities involving the creation of embryos for the sole purpose of research, as well as embryos that would be destroyed or discarded. In 2000, the National Institute of health (NIH) unveiled their guidelines for hESC research based on the restrictions placed by the Dickey-Wicker amendment. Their guidelines specified that hESCs must be obtained with private funding from IVF clinics that offer frozen embryo storage. They must have been originally purposed for fertility treatment. It must be more than the fertility patient’s original requirement They must be obtained with IVF patient’s consent.
Under the Bush administration hESC research was heavily compromised. Throughout his presidential terms he was notably pro-life and he firstly prohibited federal funding of any embryonic stem cell research using stem cell lines derived after August 9, 2001. When discussing hESC research policy he publicly stated the federal government should not support, ‘the taking of an innocent life’ . As well as that, in 2005 and 2007, President Bush vetoed bills that would allow more federal funding for hESC research (H.R.810, S5). However, with the election of President Obama the attitude towards human embryonic stem cells transitioned into a new era. In March 9th 2009, he issued an order named ‘Removing Barriers to Responsible Scientific Research Involving Human Stem Cells’ which would reverse the detrimental effect Bush had on hESC research. His presidency highlighted how US has moved forward in regards to embryonic stem cell research. Despite the USA’s progressive attitudes towards embryonic stem cell research at a federal level, there is still a considerably large pro-life base which cannot be ignored.
Legislation of hESCs largely varies in Europe with contrasting views between the different countries. The research guidelines in Bulgaria, Finland, Greece, Portugal and Switzerland state that hESCs can be derived from excess IVF embryos. Whereas, in countries such as Ireland and Turkey, their legislation does not cover the use of hESCs. Lithuania completely bans hESC but countries such as Austria, Italy and Germany allow imported hESC lines for the purpose research instead of the usage of home-grown hESC lines. Despite the large number of countries in Europe that restrict hESC research, there are several examples such as the UK and Sweden who have a well-established regulatory framework for Stem Cell research.
The UK in particular is a quintessential example of how stem cell research can be carried out. Its hESC research is controlled by Human Fertilisation and Embryology Authority (HFEA). All the IVF centres in the UK are licensed by the HFEA, which also oversees all embryonic stem cell research taking place in the UK. In addition to that, research is only permitted on embryos up to 14 days under HFEA authority. The main act put in place by HFEA is The human fertilisation and embryology act (1990 but later amended in 2008). Their guidelines state that hESC research is allowed in these circumstances: Increasing knowledge about serious disease or other serious conditions, developing treatments for serious diseases or other serious medical conditions; increasing knowledge about the causes of congenital diseases; promoting the advances in the treatment of infertility, increasing knowledge about the causes of miscarriages, developing more efficient techniques of contraception, developing methods for detecting gene, chromosome or mitochondrion abnormalities in embryos before implantation and increasing knowledge about the development of embryos.
The effort invested in the UK into producing a clear and stable structure for hESC research is admirable, while it is very promising that a country with the right resources is focusing on hESC research. It is the embodiment of a country which has managed to achieve an impressive balance between adopting an ethical procedure for hESC research which its citizens agree with and maximising the success of research carried out. However, the UK’s effective system raises the question – why can’t other countries achieve this?
Perhaps, it is due to the greater degree of influence that pro-life organisations have in countries such as the USA. Their profound impact is a factor that could impede the development of hESC research. The USA has a
large amount of Christian pro-life organisations that fund millions of dollars annually into lobbying against laws that allow the enhancement hESC research, while promoting their pro-life cause. Well known pro-life organisations include: The National Right to Life Committee, Susan. B. Anthony List, Texas EAGLE forum and Live Action. Their views and agendas in the past clearly gained stronger recognition under the Bush administration but since 2009 that has predominantly changed. While the federal funding increased after Obama’s executive order, it did not change the fact hESC research is competely banned in 8 states- Arizona,
North Dakota, South Dakota, Florida, Michigan, Maine, Lousiana and Pennsylvania.
Figure 3 – A map of the USA indicating the legislation regarding hESC research in each state (striped grey identifies states with no hESC legislation in place)
Even with the emergence of pro-hESC legislation, their campaigning funds and number in support are growing and it is unlikely their presence will simply diffuse away from the political stratosphere over time. It is essential that their concerns are dealt with by the current US government.
Conclusion
Pro-life organisations have a strong resentment towards hESC research and they are a major obstruction to what I believe is likely to transform regenerative medicine. It is plausible that in few generations time our descendants would not even fathom the thought of having to endure cancer without being provided with an immediate cure. Human embryonic stem cells are the catalysts to allow this thought to become a reality.
The future use of hESCs therapeutically could alleviate the government and private institutions of huge sums of money that they invest into maintenance of patients afflicted with diseases and conditions. This is because hESCs could completely cure these individuals and instead the money could be invested into other aspects of healthcare such as advancement of hospital technology, accommodation of more patients and bringing in more pharmaceutical drugs. The benefits which hESCs offers are invaluable and exceedingly overshadow the issues which surround it. I believe it is fair that a compromise is made between pro-life and pro-hESC supporters by the means of adjusting legislation in the upcoming years.
Greater restrictions could be imposed on Fertility and Embryology departments worldwide by governments to accommodate this compromise. IVF clinics could establish a new system where greater limitations on IVF donations of excess embryo towards hESC research could be placed and instead embryos would be given in preference to future fertility patients. This should be examined by governments as a matter of urgency.
Furthermore, countries which do not contain hESC research guidelines in their legislation must address this issue with the increasing prominence of hESCs among society. Without guidelines in place, unethical exploitation could easily happen. For example, pro-life supporters are against the creation of an embryo with the sole purpose of experimentation and most hESC legislated countries prevent this by only allowing excess IVF embryos to be used. Whereas, in a hESC unlegislated country like Ireland this could take place without any implications
However, with the recent election of President Donald Trump, the outlook for hESC research in the USA is unlikely to be positive. His cabinet includes vocal pro-life members such as Vice-President Mike Pence and forthcoming Attorney General Jeff Sessions, who may largely influence his choices when it comes to hESC legislation. While Trump has not explicitly expressed his views on Stem Cell research, he is a staunch anti-abortionist, he has said in a presidential debate ‘I am pro-life, and I will be appointing pro-life judges’. This likely aligns his beliefs towards anti-hESC sentiment. An American presidency has a maximum shelf-life of 8 years and if Trump were to remain in office for this time it would likely harm the rate of progress in hESC research but not arrest its development completely. After all, there are many institutions based in other countries which are committed to stem cell research.
Arguably, the most effective way of ensuring the progression hESC research continues in the USA would be through state-level referendums. With 8 states currently banning any undertaking of hESC research whatsoever, it is pivotal this is overturned if hESC research is to further advance. The US constitution does not allow referendums at federal-level but with enough signatures gained for a proposition such as making hESC research legal, citizens of a state can vote to change legislation. The state-level ballot results could determine the majority in hESCs and pro-life views across the country. With the importance of stem cell research increasing, the number of people who support hESC research is on the rise. An online poll conducted by Gallup.com based on the views of an American cohort strongly conveys this with 60% affirming hESC research as morally acceptable in 2016, with 32% who viewed hESC research as morally wrong. State-level ballots would be beneficial towards hESC research as the vote would truly represent the public’s view and it is highly likely to be on the winning end. This would undoubtedly that end the greater number of disputes, especially with population growing with more open-minded individuals. Trump has the power to change federal laws but he would not be able influence the outcome of the state-level legislation in this scenario.
Figure 4 – A graph based on the views of American volunteers on hESC research asked about how they felt about the morality of ‘using stem cells obtained from human embryos’
The pro-life and pro-HESC debate can largely come to an end with legal compromises but ultimately this would still lead to a section of the general public still discontent with the use of hESCs. The adjustment of legislation will not lead a complete reconciliation as the ethical issue is just being superficially dealt with. This would not lead to pro-life supporters changing their beliefs regarding hESCs.
I believe induced pluripotent stem cells could effectively resolve the ethical debate and it is critical they receive further attention. Shinya Yamanaka’s discovery could certainly become the true breakthrough of 21st century because of its scientific promise and its equally ethical nature. It hypothetically has the same potential as hESCs and does not involve the use of embryos. Furthermore, Konrad Hochedlinger’s group from Harvard University conclude that “human embryonic stem cells and iPS cells are molecularly and functionally equivalent and cannot be distinguished genetically”. Bearing in mind hESC research has not yet been able reach the stage of clinical application, an argument that could be embraced by both pro-life and pro-stem cell supporters is that research should be focused on iPSCs. With increased resources and funding, this ethical breakthrough could be successfully used in clinics. There are trials taking place in Japan in attempt to cure blindness and this could be the gateway to other successful uses in iPSCs. If this is the case, iPSCs could receive a large amount of attention in research.
Despite this, I believe it is crucial that all types of stem cells are further researched, especially iPSCs and hESC. At this moment, it is unclear which option offers more in terms of the feasibility in their clinical use and the true extent of their capabilities. In addition to that, pro-life supporters originally may not be fully satisfied with a legal compromise but nonetheless it is a positive outset to have in the journey toward reconciling pro-life and pro-hESC.
It could act as a temporary form of legislation until the stem cell research community realise if iPSCs is a viable option. It truly is a matter of time before stem cells pioneer the way people are medically treated and improve the overall well-being of the human population. The general public must be educated by the governments and research institutions so they can have a greater understanding of stem cells and avoid any misconceptions. In fact, I managed to interview Professor Daniel Brison from the University of Manchester, a leading figure in hESC research in the world. When asked about the future of stem cell research, he said
“the greatest hurdles to overcome are not scientific. Researchers are going to need strong backing from the pharmaceutical industry and governments for the widespread emergence of Stem Cell therapies. They must be patient. With iPS cells or any new discovery, it still takes a long time. However, I think we will seriously begin to see the profound impact of stem cell research within 20 years”
It may take 20 years, large amount funding and many clinical trials to evaluate whether Induced Pluripotent Stem Cells or Embryonic Stem Cells offer a better solution. When this eventually happens, governments should alter their federal funding to fit what they believe both options can achieve. Induced Pluripotent Stem Cells, the option which would truly reconcile pro-life and pro-hESC supporters may emerge as a backup to hESCs or it could even become the forefront of Stem cell research.
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