EMBRYONIC STEM CELL RESEARCH: ALTERNATIVE METHODS & ALZHEIMER S DISEASE

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1 EMBRYONIC STEM CELL RESEARCH: ALTERNATIVE METHODS & ALZHEIMER S DISEASE BY KHYATI PATEL Word count: Approx 2300 Grade awarded June 2006: PASS WITH DISTINCTION RESEARCH PAPER BASED ON PATHOLOGY LECTURES AT MEDLINK 2005

2 Abstract The project highlights the ethical issues surrounding the use of embryos for the isolation of stem cells, and discusses other methods by which stem cells can be obtained. However, it was concluded that despite conquering some issues, it remains impossible to avoid all such ethical concerns. The current uses of stem cell therapy have also been investigated, and ideas for the future of stem cell research, using the example of Alzheimer s disease, have been proposed. Introduction At the most fundamental level, stem cells can be defined as the primitive cells from which all other body cells are derived. This basic but central concept, acting as a springboard, has initiated research into the myriad of possibilities that the existence of stem cells offers to the development of medicine. Increasing numbers of scientists have begun to investigate methods by which to manipulate this ability of stem cells to divide indefinitely and differentiate into a wide variety of specialised cells, and thus contribute to future medical treatments, including therapies involving the use of stem cells in the repair and regeneration of damaged tissue. For the purpose of this project, I have concentrated on the benefits to the neurological disorder, Alzheimer s disease. The year 1998 marked the world s initial step in embryonic stem cell research, where scientist James Thomson, from the University of Wisconsin, U.S.A, was successful in creating the first stem cell line. However, the stem cells he used were obtained from discarded embryos from fertility clinics; this factor instigated worldwide dispute about the ethics of this new realm of research. Controversy in embryonic stem cell research arises when considering the spare embryo, discarded from in-vitro fertilisation, as a potential life an unborn human being. Scientists, politicians, and religious activists alike have been forced to rethink various questions. When does life truly begin? If it does indeed begin at the moment of conception, does the unborn embryo have rights? Therefore, is the waste of an embryo equal to committing murder - taking the life of a human being? This project also aims to discuss the ethical issues surrounding the use of embryos in research, and the possible alternatives for the future. Scientists have discovered that stem cells vary in plasticity during the stages of embryonic development. A zygote is totipotent meaning it has the highest degree of developmental plasticity. However, following the initial few divisions, this level of potency is lost. A blastomere is pluripotent, meaning there is a more limited range of cell types it can form. The progression of the embryo, gives rise to cells of multipotency, and eventually specialised cells which can only form cells of a particular nature. Embryonic stem cells are therefore significant because of their unique capacity to effectively construct an entire organism made up of hundreds of different cell types.

3 When used in research, embryonic stem cells can be obtained only from the inner mass of a blastocyst (Fig.1), and once placed in a culture, they have the ability to differentiate into any type of cell. However, following the disruption of connection between the inner cell mass and trophoblast, the stem cells are no longer able to develop into embryos. They do however become immortal, and retain the embryonic phenotype. Another type of stem cell, known as adult stem cells have been found to exist in various tissues of the adult body, including the brain, bone marrow, skin, and skeletal muscle. Experiments on such cells obtained from adult mice have shown that they are less potent. Consequently, despite there being no controversy surrounding them, the disadvantages related to the use of adult stem cells lies with the current scientific evidence that they do not present with as many possibilities, and so scientists hoping to reach advances in stem cell therapy, have looked towards alternative sources of stem cells, such as cord blood. The residual blood in the umbilical cord and placenta following the birth of the baby, known as cord blood, is another abundant source of stem cells which has been utilised in existing treatments such as that for the cancer, Leukaemia. One of the more common treatments of cancer chemotherapy entails the intake of various drugs, which aim to kill cancerous cells, or reduce their activity, and in the case of Leukaemia treatment, also to restore the normal functioning of blood cell production. Where chemotherapy proves ineffective, or the cancer cells invade the body again, stem cell therapy is another option made available by doctors, where a stem cell transplant is performed. Stem cells are transfused from the cord blood of a healthy donor, in the hope that a new blood and immune system is established. Cord blood stem cells are used in preference to bone marrow stem cells, simply because those from cord blood are less mature and therefore there is the reduced likelihood of rejection.

4 Discussion When discussing the ethicality of the current methods being utilized as means to forward embryonic stem cell research, that is to say, the use of embryos as the primary source of stem cells, it becomes very difficult to draw the line for what borders acceptable, and what becomes ethically irresponsible. Thinking back to the issues highlighted in the introduction, one of the most important questions to consider is when an embryo becomes human at what point does it become a life and an individual in its own right. However, firstly we must answer what defines life. Many scientists today still following the reasoning of the Geek philosopher, Aristotle, who talked about life being in three stages: vegetative, animate and intellectual. This belief was perhaps misinterpreted, however many people believed it to be the case in the context of embryonic development. According to the theory, the unborn embryo is in a vegetative state at conception, animate during its development inside the womb, and finally, intellectual, following the birth; thus implying that the embryo is not human during pregnancy. However, claiming that a vegetative or animate state does not define life, is highly debatable. Often after sustaining severe brain injury, a person may reach what is known as a persistent vegetative state. In this state, the individual is unaware of their surroundings, is unable to respond to commands, and unable to speak. Although higher brain functions have been lost, the person continues to breathe and the circulation of blood still takes place within their body. They are also capable of spontaneous movement. In such a state, people legally cannot be recognised as being dead. Therefore, is it scientifically correct, when applying the term vegetative to an embryo, to claim that the embryo, unlike the injured person, is not a living thing? By definition, an embryo also follows the criteria of a vegetative state; it is, up to a certain stage, also unaware of surroundings, it too does not speak, it too cannot respond to commands. If the same words can be used to describe both entities how can one be claimed still living and the other claimed still not alive? Consequently, as embryonic stem cell research, in particular, remains amongst the most controversial of new biological advances, the search for alternatives sources of stem cells is imperative for the progression of research in the future. A most recent breakthrough has claimed that there may be no need for using embryonic stem cells at all. Scientists in Germany have discovered, through experimentation on mice, a way in which to create cells identical to embryonic stem cells, by using the sperm-producing stem cells found in the testicles of a male. The team of scientists at Georg-August-University of Goettingen, led by Dr. Gerd Hasenfuss, are believed firstly to have isolated spermatogonial stem cells from tissue from the testicle, and then to have moved on to determine a growth medium which could induce these stem cells to reach the same level of potency as embryonic stem cells. Tests showed that these ''multipotent adult germline stem cells (magscs) had the ability to develop into various cell types, aside from sperm cells, once injected into an early embryo of a male mouse.

5 Although similar discoveries have been made before (research conducted by John Gearhart s team, into the harvesting of primordial germ cells, at the John Hopkins University, 1998), the procedure adopted by the German scientists has shown development such as the purification of the sperm-producing stem cells, and also the discovery of the growth medium which has led to greater plasticity of the cells. The next obvious step following on from this new advance in stem cell research would be to obtain similar sperm stem cells from adult human males and to repeat the procedure to test its effectiveness in human embryos. The investigation has proved successful in finding an alternative source of stem cells, but equally the scientific world has also taken another step towards determining what factors exactly trigger the differentiation of stem cells. Therefore, based on factors such as the properties of the growth medium, and the conditions under which they were used by the German scientists, it may be possible to find similar growth mediums to be used in methods of directed differentiation which result in an increased range of cell types. One of the areas of medicine that will gain the greatest benefit from the development of stem cell therapy is the treatment of neurological disorders such as Alzheimer s disease, and Parkinson s disease. The primary cause of such disorders is the damage or loss of nerve cells, which becomes irreversible as mature nerve cells are unable to self replicate to replace those that are lost. Alzheimer s disease, specifically, results following the disruption of the cytoskeleton of neurones, resulting in the formation of a tangle the in the cerebral cortex, an area of the brain that is vital for cognitive function. The disturbance to the cytoskeleton eventually causes the axons of neurones to waste away, meaning normal flow of information to and from the damaged neurones can no longer take place, and vital connections cannot be made. Due to the intense complexity of the cytoskeleton, the resulting damage to brain function is devastating. The disease leads to progressive loss of memory, language, and also the ability to recognise family and friends a lasting damage that occurs gradually over the space of 10 years or so. However, despite the intensity of problems caused, the possibility of finding a treatment for the disease has increased following a recent discovery which took place within the last year. A finding that has disproved the belief that adult brain cells cannot be regenerated and replaced. Scientists came across the existence of neural stem cells in a particular part of the brain. So how can stem cell therapy become involved treatment? When thinking back to the original definition of stem cells as the cells from which any other cell can develop, it is possible to gain a vision of how stem cells can be utilised for the purpose of treating Alzheimer s. From current knowledge of stem cells, there are two primary options available. Firstly, to continue the investigation into what growth factors are needed to promote the differentiation of stem cells in a culture. Secondly, developing the research into the already existent neural stem cells, and focussing future research on how the signals controlling the specialisation of these stem cells can be identified, and thus how scientists can manipulate stem cells, already in our body, as and when necessary, for the treatment of diseases such as Alzheimer s.

6 Through both methods, the outcome is promoting stem cells to differentiate into the healthy cells of the brain, and thus regenerate the damaged or lost tissue. Some of the problems with growing stem cells in cultures have already been outlined when describing the ethical issues surrounding the use of embryos. Of the two methods, the latter provokes fewer ethical concerns as the procedure to be used in research is unlikely to involve the need to isolate stem cells from embryos, as scientists need only to work with the body s own adult stem cells. Having said that, as the brain is so integral to the functioning of the human body, any potential damage that could result from experimentation within it would most probably be irreversible, and therefore when the time comes for research to be conducted on human test subjects, who can define whether or not it is ethically responsible to put a life, already suffering or otherwise, in the position of danger, even though the long term effect on stem cell therapy may be beneficial? Therefore, although scientists have built a solid foundation for the progression of stem cell therapy, ethical issues are bound to crop up at each stage when considering how unwise it would be to hope that positive results from tests on animals will prove true for humans. Consequently, the involvement of humans in actual experimentation cannot be avoided, and whether concerning embryos, or adult humans, ethical debate will always remain. Conclusion In truth, this project gives only the essence of the multitude of questions that have arisen since Thomson s first stem cell line was established in Not only are the questions numerous, they are also highly subjective, and therefore reaching a definite conclusion about the ethics of embryonic stem cell research is near impossible. I believe that this fact will always prove one of the limiting factors, hindering some aspects of the development of embryonic stem cell therapy. However with advances in stem cell therapy continually taking place, there is a very good chance that scientists may one day come across an alternative route of achieving the same end perhaps using the body s existent stem cells to regenerate damaged tissue, and in the case of Alzheimer s, be able to reinstate the connections which are lost during the withering of the neural axons, and thus reverse the damage to cognitive functioning of the brain.

7 References ary_definition&ct=title unce_stem_cell_advance/ Joseph Panno Ph.D, The New Biology series - Stem Cell Research; Medical Applications and Ethical Controversy Mark F. Bear, Barry W. Connors, Micheal A. Paradiso (2001), Neuroscience Exploring the Brain, Philadelphia, Lippincott Williams & Wilkins

8 Dr Anna Tilley (2006), General Science: Stem Cell Research. In Biomedical Scientist.