Introduction
There are many controversies of using animals in testing; whether this is for the cosmetics industry or the medicinal drugs industry, animals make up a crucial part of the development process, however, stem cell models could eventually make the use of animals unnecessary. Stem cell research offers a great promise for the understanding the basics of human development, and can be used for the treatment of diabetes, Parkinson’s disease and spinal cord damage. Using human stem cells, especially from embryos, raises many ethical debates, however, other methods of obtaining stem cells raise fewer ethical concerns. While attention to stem cells within medicine has been focused on potential in the regenerative side of medicine, stem cells have also been known for their ability to produce human tissues which can model diseases – which in the future could lead to the development of more ethical, efficient and economical ways of producing medicines. However, embryonic stem cell research is a very conflicting subject in the world of science; some people think that it is morally and religiously incorrect as they are ‘killing’ a human life at the first stage of life, while others think it is okay because to them, human life starts later on in the development. Embryonic stem cells are derived from embryos at a developmental stage before the time that implantation would generally occur in the uterus.
Methodology
For my extended project, I will be using a variety of different research resources to gather information that is relevant and will be useful about my topic.
I have visited my school library, as well as Exeter University library to find books and articles, however these were only useful to gain personal knowledge as they were not specific enough for my needs, as they only covered general stem cell technologies. I also used the search engine ‘google scholar’ as this filters out the search and provides many scientific advanced literature reports.
For structure, I planned certain subheadings, however these have changed slightly and are still flexible to fit with the path of the dissertation. However, I have tried to stick with a rough plan, that being; the ethical issues that come with using stem cells in research, the process of therapeutic cell cloning, the use of animals within the drug development industry and finally the argument as to which technique (using animals or embryonic stem cells) has fewer ethical issues.
Literature Review
An overview of stem cell research
I found this website useful, as it includes both the positives of using stem cells in research for medicine, but also made points about the ethical issues with using embryonic stem cells.
Animals in pharmaceutical research and development – Novo Nordisk
This was useful to an extent; Novo Nordisk is a global healthcare company which happen to test on animals. This makes me slightly distrust some of the information I gained from this website as there are potentially a few ‘false dilemmas’ within the speech. As the writer talks about the process of animal testing they only give one or two scenarios, making me think that they are withholding information about the true happenings that occur when animals are tested on, to reduce backlash.
The use of animals in testing –PETA
Originally, I looked at this website for information, but have discounted it as there is a sweeping generalisation through the text that all animals suffer whilst being tested on, also it seems as if the conclusion is drawn by hasty generalisation, meaning that it is formed without sufficient evidence. This is most likely because PETA is an animal rights activist group, that regularly have petitions to ban animal testing.
Embryonic stem cell production through therapeutic cloning has fewer ethical problems than stem cell harvest from surplus IVF embryos.
I found this article really useful for helping to balance my arguments about the benefits of using embryonic stem cells and the ethical issues behind that and whether it is justified. It had lots of backed up scientific evidence, that was made easy to understand and to fit into my title.
Ethical issues with stem cell research
This article was useful as it simplified scientific research without reducing the amount of useful content.
Main body
Ethical issues with using stem cells from embryos rather than animals
The use of embryonic stem cells as an alternative to animals in drug development has some ethical issues as many people believe that embryonic stem cells have potential to become a human life and thus shouldn’t be tested on, however, there are many restrictions on research, but many of these are questionable as they stop the development of certain techniques that could increase the chances of successful application of pluripotent stem cells in the treatment of severe diseases and producing new drugs to treat these diseases. (Hansen, 2001) Most embryonic stem cells are derived from the embryos that develop from excess eggs from IVF, these are then donated for research purposed with informed consent from the donors, these are ‘waste’ eggs that would be discarded if not used during IVF treatment. However, there are many ethical issues in regards to using stem cells from human foetuses and umbilical cords – if foetal stem cells are obtained from miscarried or stillborn foetuses, or if it is possible to obtain stem cells from live foetuses in the womb without doing any hard to the foetus, then no harm is done to the donor, meaning stem cell research can be an ethical means of developing new drugs. Human embryonic stem cell research is ethically and politically controversial because it involves the destruction of human embryos. There is no set time scale of when human life begins throughout all religions and cultures as some people believe that an embryo is a person with the same moral status as an adult or a child – therefore making the embryo a person. From this point of view, taking a blastocyst (the hollow structure that contains the cluster of cells from which the embryo arises) and removing the cell mass would be murder. Other people have a different view and believe that the embryo becomes a person later in the stages of fertilisation and growth – meaning that an embryo is just a clump of cells that can be used for research without restrictions. If stem cells are obtained by foetuses from abortion, this would be an unethical way of producing new drugs. Stem cells can also be obtained from umbilical cords, and since they are detached from the child at birth, the blood within the umbilical cord is very rich in stem cells and also an ethical way of obtaining them. With consent from the parents, blood can be collected from the umbilical cord of a new born, this does not hard the child in any way, as the umbilical cord is discarded along with the placenta (which is another rich source of stem cells) after the birth. (Bevington, 2008)The umbilical cord contains haematopoietic stem cells (the stem cells that give rise to other blood cells – the process of haematopoiesis), these are similar to those found in bone marrow. Umbilical cord blood stem cells are currently used to treat a range of blood disorders and immune system conditions such as leukaemia, anaemia and autoimmune diseases. Another type of cell that can be harvested from umbilical cord blood are mesenchymal stromal cells (these are multipotent stromal cells that can differentiate- grow into bone, cartilage and other types of tissues). Adult stem cells can differentiate into specialised cells in their tissue of origin and can also transdifferentiate into specialised cells with characteristics of other tissues. For example, hematopoietic stem cells can differentiate into all three types of blood cell types as well neural stem cells, liver cells and cardiomyocytes (muscle cells that make up the cardiac muscle). However, adult stem cells can’t be expanded in vitro and have not been definitively shown to be pluripotent. (Parham, 2009). Drugs can cause problems throughout pregnancy, this is where animals and human models cannot be used. The early stages of pregnancy are the most critical phases for the health of the foetus, which is when the main bodily systems are developing. 5-10% of congenital abnormalities in new born babies are caused by side effects of chemical compounds; therefore, the need for toxicological safety assessments of any drugs used on humans is incredibly important.
Some consider this therapeutic cell cloning to be ethically neutral; and claim that the product made is not an embryo. However, to restrict the definition of ‘embryo’ to the product of fertilization in the post‐Dolly the sheep (the first mammal to be cloned) era is a misleading anachronism. Although the purpose of therapeutic cloning is not the creation of a new individual and it is unlikely that the viability of the constructed product is equivalent to that of an embryo derived from sexual reproduction, it is not right to say that an embryo has not been created. The root of the problem is that embryos are created solely for instrumental, medical use. There are two main perspectives in general embryo research debates; a ‘foetalist’ perspective, that focuses on the moral value of the embryo, and a ‘feminist’ perspective, with the interest of women and oocyte donors. From a feminist perspective, the creation of embryos for research should be evaluated critically in as far as it may require hormone treatment of a woman to obtain oocytes for research purposes: can this be morally justified when it requires unpleasant treatment of the donor with no benefit at all, or even a detrimental outcome, for her own state of health? One objection is that women themselves become objects of instrumental use. However, an analogy can be made with recruiting healthy research subjects. The second objection is that the health risks to the women themselves are too high and the degree of discomfort disproportional. Even with both foetalist and feminist perspectives there is no overriding objection as to why embryonic stem cells shouldn’t be used for research.
Having considered the possible moral status of the transnuclear egg cell resulting from therapeutic cloning and having found that stem cell production including destruction of the blastocyst does not violate the fundamental human right to life, it may still be warranted to prohibit this technique as it may be perceived to pave the way for reproductive cloning.
Therapeutic cell cloning and how stem cells are harvested
Embryonic stem cells are taken from the blastocyst, which is the first stage of an embryo. These cells are pluripotent meaning they can divide and form into any type of cell. This is the main reason why adult stem cells cannot be used in research as they are only multipotent, meaning they are limited to what they can form into. (Chapman). Therapeutic cell cloning is another phrase for the procedure known as somatic cell nuclear transfer. Therapeutic cloning refers to the removal of a nucleus, which contains the genetic material from almost any cell of the body (a somatic cell). Fusion cell cloning involves replacing the nucleus of an unfertilised egg with the nucleus from a different cell, this replacement nucleus can come from an embryo. One of the major benefits of therapeutic cell cloning is that pluripotent cells are harvested – meaning these can be used to potentially treat diseases in the body. Another advantage of this method is that the risk of immunological rejection is alleviated because specific genetic material can be used. Another way of obtaining stem cells is by reprogramming somatic cells (any cell of the body, other than a reproductive cell) to induced pluripotent stem cells (a cell that can produce any cell or tissue the body needs). Traditionally this was done by transferring somatic cell nuclei into oocytes, which is a cell derived from the ovary which can undergo meiotic division, meaning it can replicate itself to form four copies), this reconstructed cell is stimulated to initiate development of an embryo. There are concerns about oocyte donation which are specifically for research, these are particularly serious due to the Hwang scandal in South Korea (claims made by Woo Suk Hwang, a stem cell researcher from South Korea, of deriving human Somatic cell nuclear transfer lines were fabricated. The scandal also included inappropriate payments to oocyte donors). So far, none of the approaches used on murine embryonic stem cells (embryonic stem cells derived from the preimplantation stage of mouse embryos) can give 100% yield of cells with the required phenotype. Methods such as FACS (fluorescence-activated cell sorting, Fluorescence activated cell sorting (FACS) of live cells separates a population of cells into sub-populations based on fluorescent labeling. Sorting involves more complex mechanisms in the flow cytometer than a non-sorting analysis. Cells stained using fluorophore-conjugated antibodies can be separated from one another depending on which fluorophore they have been stained with. For example, a cell expressing one cell marker may be detected using an FITC-conjugated antibody that recognizes the marker, and another cell type expressing a different marker could be detected using a PE-conjugated antibody specific for that marker. First, Individual cells are “interrogated” by the laser as in a normal flow cytometer. The machine is set up so that each individual cell then enters a single droplet as it leaves the nozzle tip. This drop is given an electronic charge, depending on the fluorescence of the cell inside the drop. Deflection plates attract or repel the cells accordingly into collection tubes. Then, Sorted cell populations are then analysed to ensure successful cell sorting. And then the sorted cells can then be cultured) or MACS (magnetic-activated cell sorting – The objective of magnetic bead cell isolation is to enrich a specific cell type from a mixed population. The technique is also be used to isolate proteins, DNA, and RNA for further research or therapeutic purposes. Magnetic Bead Sorting generates a simple method for cell sorting, as unlabeled cells without attached beads separate from those treated by beads.) allow such purification using fluorescence or magnetic microbead-tagged antibodies recognizing a surface marker selective for a desired cell lineage. If this is not available, ES cells can be transduced with a lineage-specific promoter that can drive the expression of a marker, such as green fluorescent protein or an antibiotic resistance gene. This allows for preferential selection of cell subpopulations defined by the cell type specificity of the promoter utilized. This type of approach has been used to select neural and cardiomyocyte phenotypes.
The use of animals within drug development and the pharmaceutical industry
Animals have been used in medical research and development since, 300 years BC and have played a critical role throughout the history of science. To this day, the use of animals in research is essential for all companies in the pharmaceutical industry in the process of discovery, development and production of new pharmaceutical products, these companies are required to provide appropriate data in respect to efficacy, safety and toxicity from testing in both animals and humans before the authorities will approve a new product. The use of animals in research has led to many medical advances and treatment, including the use of insulin to treat diabetes; in 1921, insulin was tested for the first time in a dog with diabetes – this revolutionised the treatment of diabetes. For medical devices, the focus of animal testing is on the device’s ability to function with living tissue without harming the tissue (biocompatibility). Most devices use materials, such as stainless steel or ceramic, that we know are biocompatible with human tissues. In these cases, no animal testing is required. However, some devices with new materials require biocompatibility testing in animals.
Animals are still used to assess efficacy of new pharmaceutical products (Ani) Over the last 50 years, research and development in the pharmaceutical industry has been transformed due to the readily available advanced information and diagnostic technologies. Although there has been a substantial decline in the use of animals in the industry, pharmaceutical research remains responsible for approximately one third of the animal experiments conducted within the UK each year. (The18) Drug companies began experimenting with stem cells in 2010, now the pharmaceutical industry is increasingly adopting the use of stem cells to test for the toxicity of drugs and for identifying new therapies (Cressey, 2012).
Ethical issues with using animals in research and how they compare with using embryonic stem cells
Animal research has had a vital role in many scientific and medical advances of the past century and continues to aid our understanding of various diseases. Throughout the world, people enjoy a better quality of life because of these advances, and the subsequent development of new medicines and treatments—all made possible by animal research. However, the use of animals in scientific and medical research has been a subject of heated debate for many years in the UK. Opponents to any kind of animal research—including both animal-rights extremists and anti-vivisectionist groups—believe that animal experimentation is cruel and unnecessary, regardless of its purpose or benefit. There is no middle ground for these groups; they want the immediate and total abolition of all animal research. If they succeed, it would have enormous and severe consequences for scientific research. (Wilkinson, 2007) Many medical research institutions use animals as test subjects to gain knowledge about diseases or for testing potential human treatments. Some people argue that all animal experimentation should end because it is wrong to treat animals as tools for further knowledge. According to this view, an animal should have the same right as a human to live a life free of pain and suffering. Others argue that although it is wrong to abuse animals unnecessarily, experimentation on animals has to continue because of the tremendous scientific resource animal models provide. Testing the toxicity of pharmaceutical candidates in lab rats before the compounds are judged safe enough for human clinical trials is notoriously unreliable. Often compounds that appear safe in the rodents prove to be toxic in humans. Studying how potential drugs affect embryonic stem cells could provide a far more accurate prediction of a drug’s potential toxicity than conventional animal models can.
During normal development, embryonic stem cells produce molecules that direct cellular metabolism and differentiation. Gabriella Cezar (assistant professor of animal science at the University of Wisconsin-Madison) hypothesised that exposure to a toxic drug may change concentrations of these molecules, disrupting cell-to-cell interactions and causing a biological pathway resulting in potential developmental disorders. As a proof of concept, Cezar’s group looked at human embryonic stem cells’ response to valproate, an anti-epileptic drug that has been linked with cases of autism and spina bifida in the offspring of mothers treated with the drug. “Developmental disorders and birth defects start in utero during pregnancy, and we have no way to measure or look at mechanisms that could be participating in the onset of these diseases,” says Cezar. “With human embryonic stem cells, we can recapitulate development of the human brain and measure concrete changes of chemicals to drugs like valproate.” In the experiment, Cezar introduced various dosages of valproate, from very low to high, into three sets of embryonic stem-cell cultures, altering the dosages over different lengths of time. Control groups contained stem cells not exposed to the drug. Cezar then ran each sample through a mass spectrometer, which measured concentrations of the molecules present in culture. Compared with the control group, samples with valproate exhibited significant changes in the concentrations of two key molecules: glutamate and kynurenin. Both molecules are heavily involved in early brain development, and Cezar found that exposure to valproate caused spikes in each molecule’s concentrations, indicating that such molecules may serve as biomarkers for a drug’s potential toxicity. (Chu, 2007)
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