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Essay: Should Stem Cell Research be funded?

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Introduction

Stem cells are one the most fascinating areas of research in the field of medicine as it presents many possibilities and opens up new paths in medical treatments for diseases that currently have no known cure yet. In this essay, I am going to explore the benefits of stem cells in terms of medical advancements made using them and how they offer the possibility of treating diseases such as Parkinson’s disease. Stem cells are also the topic of many controversies in the news, so I will also be exploring the ethical issues surrounding stem cells and lastly, I will evaluate my findings in order to try and come to a conclusion to the question: is funding stem cell research really worth it?

What are stem cells?

Stem cells are defined and characterized by two properties. One: they have the ability to renew and divide themselves for long periods of time while remaining unspecialized. Stem cells are able to replicate themselves, or proliferate*. If the daughter cells remain unspecialized, they are able to proliferate like the parent stem cells; this is described as the ability of long-term self renewal. The second characteristic of stem cells that make them so special is that they have the ability to give rise to specialized cells through mitosis and differentiation; they are said to have pluripotency. Pluripotency is the ability of a cell to give rise to the more than 200 different types of cells that exist in the body.(CIRM 2016) This is also the important characteristic of embryonic stem cells, which we will explore further on in this essay, that make them so valuable. Differentiation is the process in which an unspecialized cell acquires the features of a specialized cell with a specific function. Heart muscle cells (cardiomyocytes), liver cells (hepatocytes) and brain cells (neurons) are examples of specialized cells, also known as differentiated cells. Stem cells can be categorized into groups: embryonic stem cells (ESCs) and adult stem cells.

Embryonic Stem Cells

Embryonic stem cells(ESCs) are derived from the embryo in early stages of embryo development. A point that should be made clear is that embryonic stem cells are derived from eggs that are fertilized in vitro – meaning ‘in the lab’, and then donated for research purposes after getting consent from the donors, and not from fertilized eggs in a woman. Embryogenesis* starts with fertilization between the ovum and the sperm, forming a zygote. At the stage where a blastocyst is formed, the pluripotent inner cell mass (embryoblast) inside the blastocyst is isolated; this results in the destruction of the blastocyst, which causes controversies and ethical concern of whether if embryos at the preimplantation stage have the same moral rights as embryos at post-implantation stage. Therefore human embryonic stem cells(HESCs) are constantly in the midst of all ethical debates regarding stem cell research, and it is very difficult to come up with one ultimate answer because: Who gets to decide what is morally right or wrong? A single person is unable to give a definite answer to this question. is there an authority figure in charge? Is the government going to be the one making these decisions? Another challenge faced by using ESCs is immune rejection after transplantation, called graft failure.

*Proliferation – the expansion of the numbers of cells in a population by continuous division of single stem cells to produce two identical daughter cells

Embryogenesis – stages of embryo development

Adult stem cells

Adult stem cells, also known as somatic or tissue-specific stem cells, are undifferentiated cells found throughout the body. They multiply by cell division to replenish dying cells and repair damaged tissues. They have more limitations compared to embryonic stem cells because they can only give rise to the types of cells in the organ they reside in. For example, adult blood forming stem cells located in the bone marrow can give rise to red and white bloods cells, and adult stem cells in intestines can give rise to any of the cell types in the intestinal lining. Furthermore, researchers currently are still unable to grow adult stem cells indefinitely in the lab unlike embryonic stem cells. (CIRM 2016) Although recent studies have shown that the brain and muscles have stem cells as well, they are not active in repairing injuries like other stem cells do. (Niemi 2002) However, adult stem cells are not controversial unlike embryonic stem cells because they are not derived from the embryo, but instead from adult tissue samples, therefore it does not require the destruction of an embryo.(Science Daily) Adult stem cells can be used in treatments for diseases, however so far, the only adult stem cell therapy that has been regularly used since the late 1960s is the blood marrow transplant.(Boston Children’s Hospital)

Blood forming stem cells are also called hematopoietic stem cells, and they can be found in the bone marrow, a spongy tissue found inside bones. Hematopoietic stem cells can divide to form more blood forming stem cells, or they can differentiate into one of three types of blood cells, red blood cells, white blood cells and platelets. Bone marrow transplantation can be used to treat people with sickle cell disease; this method was first discovered by an organization called St Jude Children’s Research Hospital.(National Cancer Institute 2013)

Sickle cell anaemia is a recessive genetic disease, and it causes the sufferer to have red blood cells that contain the abnormally shaped haemoglobin S. The shape of the haemoglobin causes the red blood cells to turn into a “sickled” shape when they are deoxygenated. When red blood cells sickle, they break down easily, this can lead to anaemia. Furthermore, the shape of the red blood cells makes it easy for them to be trapped in blood vessels, blocking the flow of blood and decreasing oxygen delivery. (NIH 2012) This can happen in any part of the body and causes severe pain, called a crisis that can last for hours up to days.(WebMD)

During bone marrow transplantation, first, chemotherapy is used to destroy the patient’s bone marrow, stem cells and weaken the immune system so that the patient’s body will not reject the donor’s blood cells. Then, the blood is transfused using an IV tube and the blood forming stem cells from the donor replace the patient’s bone marrow. This means that the new blood forming stem cells produce red blood cells that are healthy as they do not contain haemoglobin S. Currently, bone marrow transplant is the only cure for sickle cell disease, and in transplants where the blood forming stem cells are from a matched related donor, there is 85% success rate in curing the disease. (St Jude Children’s Hospital 2009)

Bone marrow transplant is a very beneficial and important treatment as it saves nearly 20,000 people aged 0-74 years every year.(8 HRSA) Solely focusing on sickle cell anemia alone, it is the most common inherited blood disorder, and an estimated 90,000 to 100,000 people in America are afflicted with the disease.(Shiel Jr. 2016). The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.(Genetics Home Reference) On top of that, bone marrow transplant is used to treat other diseases such as leukemia, lymphoma and myeloma.(Be the Match) These diseases affect an estimated combined total of 172,910 people in the U.S. in 2017.(Leukemia and Lymphoma Society) This gives us an idea of how useful stem cells could be in the future as they can potentially save many lives if research is successful and stem cell treatment becomes widely used.

Induced Pluripotent Stem Cells

Induced pluripotent stem cells(iPSCs) are adult cells that have been ‘reprogrammed’ by introducing the specific genes needed for maintaining the characteristics of embryonic stem cells, which turns the adult cells into a stem-cell like state. An area of consideration is that iPSCs could replace ESCs as the production of embryonic stem cells raises a lot of ethical issues, but this does not apply to iPSCs. Furthermore, a great benefit of iPSCs is that tissues can be taken from patients and then used to generate stem cell lines to give a copious supply of pluripotent stem cells to the patient. These stem cells would not have problems when injected into the patients because they are immune-matched and so there is no risk of rejection; which has been an area of concern when trying to use embryonic stem cells in treatments.

Organ regeneration

Organ transplantation dates all the way back to 1954, where the first successful kidney transplant using a kidney from a living donor, which is the patient’s identical twin.(organdonor.gov) According to the statistics shown on the U.S. government information on organ donation and transplantation website, as of March 2018, there are more 114,850 men, women and children who are listed on the national transplant waiting list. As of March 15th 2018, only 5,448 were able to have an organ transplant performed on them (UNOS), which is about 4.7% of those who are in need of an organ transplant. Furthermore, although 95% of all adults in the U.S. support organ donation, only 54% have actually registered as donors, and the total number of donors from January to February 2018 is only 2,663. This accounts for only 2.3% of the people who are in need of a organ transplant. It is estimated that every 10 minutes, someone is added to the waiting list for a lifesaving organ transplant, and every day, 20 people die waiting for a transplant.(organdonor.gov)

As of March 2017 in the UK, the total number of people listed on the waiting list for organ transplants was 6,388, and the number of transplants performed was 4,753 according to NHS Blood and Transplant. (NHS Blood and Transplant) This means that 74% of patients were able to successfully get organ transplants in this year, which seems to be a much higher statistic compared to the U.S, and the NHS reports that 50,300 people are now alive due to organ transplants in 2017. (NHS 2017)

These statistics highlight the problem of insufficient supply to the vast numbers of organs that are sought. It is highly unlikely than 100% of the population would register to donate their organs, and only 3 out of 1,000 people die in a way that their organs can be used for organ transplant (organdonor.gov), therefore solely relying on organ donors will not be sufficient in providing the number of organs demanded. Furthermore, transplanted organs will need to be replaced within 10 years after implantation, and when it comes to the time, there might not actually be an organ available for transplantation; this means that even with one transplant, the problem is not completely solved but rather just prolonged. However, researchers have found a way that we could potentially use to solve this problem, which is by using stem cells.

Regenerating organs using stem cells promises to eliminate the problems with organ transplantation using donor organs such as the shortage of donors and tissue rejection, as well as provide better quality organs. By using organs generated from the patients stem cells, there would not be any immune response after transplantation because glycoproteins on the surface of cell membranes are necessary for cell recognition and so the immune system recognises the cells as its own. This would be an improvement compared to conventional organ transplantation because patients would need to take immunosuppressant drugs for the rest of their lives, putting them at a higher risk of infectious diseases.

Will stem cells be able to help treat Parkinson’s disease in the future?

What is Parkinson’s disease?

Parkinson’s is a neurodegenerative disease where there is a progressive degeneration and death of neurons in the human brain. Although the disease can occur to people in their teenage years, it is much more common in people aged 50 years and above.(Professor Schapira 2011) It is unsure of what exactly causes Parkinson’s, however most experts agree that it is caused by both genetic and environmental factors. Like other neurodegenerative diseases such as Alzheimer’s and Huntington’s, Parkinson’s disease is incurable.

The disease primarily affects the dopamine-producing(dopaminergic) neurons in a specific area of the brain called the substantia nigra. Dopamine is a neurotransmitter- a chemical released by neurons to transmit signals to other nerve cells- responsible for movement, memory, pleasurable reward and more. The basal ganglia is an area in the brain that regulates movement, and to do so it requires a certain amount of dopamine in order to carry out its function. In individuals with Parkinson’s, the dopaminergic cells break down, resulting in dopamine levels that are too low and continue to fall. Because the body has no way or replacing damaged neurons, people with Parkinson’s progressively have falling dopamine levels and symptoms become more severe. (Dr Mandal 2017) Patients with Parkinson’s suffer from symptoms such as tremor, bradykinesia and rigidity. Bradykinesia simply means the slowness of movement, and rigidity of the muscles results in greater difficulty in moving around and it can also cause pain due to muscle cramps. (NHS choices 2016)

In the USA, approximately 1 million adults suffer from Parkinson’s; and the economic toll it has is about $25 billion annually, according to the Parkinson’s Disease Foundation. On average, the medication of an individual with Parkinson’s is between $2,500 and $10,000, annually.(MNT Editorial Team 2016)

How can stem cells be used to treat an individual with Parkinson’s?

The basic idea is that the stem cells are programmed so that they will differentiate into neurons and then they implanted into the the patient so they can replace the damaged neurons. A recent study published on August 30th, 2017 by Ole Isacson and his colleagues involved turning human induced pluripotent cells into dopamine producing neurons, and then injecting them into a group of monkeys in an attempt to improve the symptoms of Parkinson’s disease in the monkeys.

Firstly, skin or blood cells were taken from 7 human subjects, of which three have Parkinson’s disease and four do not. These cells were used to generate eight iPSC lines and then reprogrammed so the scientists could graft them into the brains of male cynomolgus monkeys aged 2-3 years. The monkeys were treated with the neurotoxin MPTP, which was used to kill the dopamine producing neurons in the brains of the monkeys in order to imitate Parkinson’s disease. The results of the experiment showed that the monkeys had 40%-50% improve in symptoms – the number of tremors have decreased and there was increase in movement. This trial was successful in two ways, firstly, the transplanted cells were able to survive in the brains of the monkeys for an extended period of time of two years. A group of researchers at Stanford University School of Medicine tried to inject mice with human embryonic stem cells, however this triggered an immune response and all the transplanted stem cells were dead within a week. Therefore, this study done with the monkeys showed to have a much longer lifespan compared to normal implanted cells. The second success in this trial was that there were no signs of developing tumors, which is another area of concern when trying to transplant stem cells into the body. After 12-24 months, the monkeys were sacrificed in order for the researchers to be able to dissect them to see if the cells have integrated into the brain. Through histological examination, the researchers determined about a third of the implanted cells expressed tyrosine hydroxylase, which is an enzyme that acts as a marker of dopamine production. 18F-DOPA PET scans done periodically showed a trend of gradual increasing dopamine uptake over 21 months up to half the dopamine levels in normal monkeys.

An ethical issue in this investigation is how the monkeys needed to be killed at the end of the study in order to dissect their brains and look at the effects of the implanted stem cells. Although animal testing is common because any side effects needs to identified and also to look at the effectiveness of something before doing trials on humans, such as drug testing and also in the cosmetic field, some people will argue that animal testing is unacceptable and there has been movements to stop animal testing.

Since Parkinson’s disease is prevalent in the older generation, and an aging population is becoming a problem in countries such as China, Japan, Italy and more, I think that it would be beneficial to invest in stem cell research that can help treat Parkinson’s, especially since China has such a large population so there is also a greater number of older people. The study done on the monkeys showed positive results and if stem cell treatment actually becomes successful, it will be able to benefit a great number of people whose lives and families have been badly affected by Parkinson’s and other severe diseases. In my opinion, although it is cruel to be testing on animals, it is necessary in order to further research and it is the standard procedure before human trials in order to make sure the treatment is effective and there are no harmful side effects such as development of tumours or cancers as it is often the case with stem cell transplants. I think when it comes to stem cell research, to come to a conclusion on which side a person stands, one must really put themselves in another person’s shoes and look at the situation in the light of, for example, someone with Parkinson’s or a relative of someone with Parkinson’s and I feel that a person initially opposing stem cell research could possible change their minds if their circumstances changed and stem cell treatment was able to help them. Therefore, I think that no one could be completely against stem cell research, proving that it is necessary and stem cell research should continue to be funded.

What are the problems with stem cell research?

Ethical issues

This is the main problem which is associated with using embryonic stem cells. By retrieving the inner cell mass, the embryo is subsequently destroyed. For this reason, embryonic stem cell research is highly debated about and although both sides argue about protecting human life, one side believes that human life begins as soon as the egg is fertilised and argues that destroying the embryo is equivalent to taking a human life, while the opposite believes that the there is a large number of lives that could be potentially saved using stem cells and the stem research has a much more significant purpose. So the fundamental question this debate is based on is when does a human being starts to exist?

The side that is against the use of embryonic stem cells in research argues that a human embryo holds the same ‘value’ of human life as a human being. By destroying an embryo, you take away its potential future life; this is referred as ‘The Loss of Future Life Problem’ in a book titled “Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues”. (Monroe et al. 2008) Furthermore, the embryo is not able to give consent, therefore if it were to be regarded as a human being, then its rights would be violated by exploiting them for research.

Supporters of stem cell research provide the counterargument of how great the overall benefit of stem cell research if it were to become successful and widely used for medical treatments because theoretically, it would offer cures for an unlimited range of diseases and save millions of lives. But decisions cannot be made solely based on the outcomes and consequences of an action, as most would debate that destroying human life to save another human life is not ethical. An example given in the book was that if we were to take the case of organ trafficking, and by killing someone we would allow another person live for longer.(Monroe et al. 2008) This is, by most, if not all people’s standards, morally impermissible and it is also illegal to do so. Therefore, we cannot simply justify destroying the embryos by arguing that more people can be saved in this way. Going back to the basis of the argument, some people have the belief that human embryos do not have the same moral status as a human being since it is not self aware and has no memories, which makes them feel like it is more acceptable to use them for research purposes. This argument then depends on the beliefs of a person which is very subjective and impossible to come to an absolute answer on which belief is right.

The Catholic Church opposes research involving HESCs because it requires the destruction of an embryo in order to retrieve embryonic stem cells, conflicting with catholic teaching is about respecting the equal moral worth of every human, and that applies to embryos as well. The church favors adult stem cell research as it is ethically acceptable, and the breakthrough with iPSCs further reduces the need for using ESCs. Since the goal is to save lives through stem cell research, all lives must be protected at all times and it is unacceptable to destroy some human lives now under the pretext of saving more in the future. However, the Catholic Church isn’t completely against stem cell research, and very much supports ethical stem cell research using adult stem cells, and have invested very much into it in many cases. In October 2005, the Catholic bishops of South Korea said that they would donate $10 million to advancing stem cell research, and in Australia, a grant of $50,000 given by the Catholic Archdiocese of Sydney helped the breakthrough demonstrating the capabilities of adult stem cells in March 2005. (United States Conference of Catholic Bishops)

However, the fact is that the many embryos used for stem cell research are actually from a pool of frozen embryos made for in vitro fertilisation(IVF) in fertility clinics. These embryos are never implanted, and embryos are not able to start developing unless it is implanted, so there is no loss of future life as the embryos wasn’t on the way to developing into a human being to begin with. (Monroe et al. 2008) Therefore, it would make more sense that these frozen embryos are better off being used in research so they can help people rather than left in storage and then eventually thrown away.

It is difficult to come to a clear conclusion because the answer to these questions are always very subjective. How an individual perceives the value of an embryo compared to a human being could be influenced by religion and their own morals, feelings and knowledge.

Are there problem associated with increased life expectancy?

With improved healthcare using stem cells, it might mean that overpopulation will be a problem as less people will die from life threatening diseases. Overpopulation is the state where the human population exceed the carrying capacity of the Earth.(Conserve Energy Future) The current global population is 7.5 billion, and PRB(Population Reference Bureau) estimates that by 2050, there would be 10 billion people living on Earth, which is an increment of about 33% of the current population. The rapid growth of Earth’s population is a big concern, especially in developing countries. Pollution, decrease in availability of freshwater and food supply, depletion of natural resources, climate change and global warming, loss of biodiversity to name a few, are all anthropogenic changes which will worsen with increasing population.(Earth Eclipse)

One of the biggest problems we are facing right now is the depletion of resources. 75% of the Earth is made up of water, however only 2.5% of that is freshwater and the rest of it is ocean water. The freshwater is further divided as only 30 % of it is land surface water such as ponds, lakes, rivers and groundwater, while the rest are glaciers and ice caps.(Everything Connects 2013) Therefore, the water available to us for drinking and other everyday uses is a minuscule amount of the total water on Earth, and it is shared between all 7.5 billion individuals.

Furthermore, increased life expectancy will lead to an increase in the average age of the population. There are several problems related to to an aging population because this portion of the population are no longer able to work and therefore the government will then have to support them through pensions, which will put a big strain on the country’s economy because there is a smaller percentage of working population paying the taxes for pensions compared to the percentage of the population who are aged over 65 years.

In my opinion, although I think that overpopulation is a big problem, I don’t think that it is fair to look at human beings as merely numbers. We should not eliminate the opportunity to develop cures for many currently untreatable diseases just to control the size of the population using an inhumane method. Furthermore, over the years, most people in developed countries now prefer to have less children compared to before; according the United Nations, the average household size in Monaco and Serbia are 1.9 and 2.9 persons respectively, and in the United States of America there is about 2.6 persons per household.(EASA 2017) It is mainly developing countries where overpopulation stems from, where countries such as Senegal, West Africa has an average household size of 9.0 persons. Most of the world’s population live in poverty, statistics estimate that half of the world – over three billion people – live on less than $2.50 a day, and 80% of the world lives on less than $10 a day. Due to the poor standard of living of these families, there is a high infant mortality rate; according to UNICEF, 22,000 children in the world die each day due to poverty. Therefore, people tend to try to overcome this problem by having larger families. I think that this problem of high infant mortality rate and poverty is what we should focus on and try to improve in developing countries instead of pinning the possibility of worsening overpopulation on stem cell treatment because it is not as big of a contributor to overpopulation. If anything, this further emphasises the need for improving healthcare around the world so that families in developing countries would not need to have as many children and therefore stem cell research, in my opinion, is a justifiable necessity.

Affordability of stem cell treatment

If stem cell research was successful and stem cell treatments can then begin to be implemented in hospitals and clinics, the problem that then arises will be the cost of the treatments. There is no point in spending a lot on money on stem cell research and then only have it benefit a small percentage of the population as most people are unable to afford the costs of the treatment.

Bone marrow transplant prices depends on if the transplant is allogeneic, bone marrow taken from another person, or autologous, the patient’s own bone marrow. In the United States, the average cost of an allogeneic transplant is around $800,000(£596,524), while an autologous transplant costs $350,000(£260,979). In the United Kingdom, the cost of a bone marrow transplant ranges from £300,000 to £750,000.(MEDIGO Blog) There is an estimated 40,200 people every year who needs a bone marrow

Is using federal funds on stem cell research worth it?

Currently, global warming and climate change are very prevalent topics, would it be better to invest more in finding renewable energy sources and try to use more efficient production practices to reduce greenhouse gas emissions?

Another alternative the money can be used for is cancer research. Cancer is a very common disease and its incidence is much greater than neurodegenerative diseases that mainly affect the older population. Therefore, it would be beneficial to a larger percentage of the population if cancer research were to be successful. Both research areas are actually interlinked, and by doing research on cancer, it can help to progress research on stem cells and vice versa. Cancer is basically caused by the uncontrollable growth of cells which leads to the formation of malignant tumour. Some cancerous tumours consist of both ‘bulk’ tumour cells and cancer stem cells.(Arney 2009) Current treatment of cancer uses chemotherapy or radiation therapy to kill the bulk of cells.(NIH 2015) However, some cancers start to grow again after treatment, and this was due to the treatment targeting the wrong cells. Scientists hypothesize that cancer treatments only kill the bulk cells which are the daughter cells, when the problem lies in the cancer stem cells. By studying stem cells, it can also help scientists try to understand more about cancer.

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