ETHICAL ISSUES IN STEM CELL RESEARCH

Give me a doctor partridge-plump,
short in the leg and broad in the rump,
an endomorph with gentle hands,
who’ll never make absurd demands,
that I abandon all my vices,
nor pull a long face in times of crisis,
but in a twinkle of his eyes,
will tell me that I have to die.[1]

No one who qualified as a doctor more than 20 years ago can be unaware of the change in the ethos of medicine since then. To tackle ethical issues in medicine, one would need to go retrospective and decide how we as doctors have changed. Simply speaking, it is useless to talk about such issues without knowing the foundations on which medicine is built on. Medicine has been an art thousands of years before the advent of systematic science, and it was then that many problems started plaguing doctors. True, science and technology has propelled medicine to perhaps one of the fastest changing field in any sense, making accurate and difficult diagnosis, offering treatment for diseases we would never even have dreamt of dealing with just short of a century ago. In 1950, the poet Auden gave a witty sketch of his ideal doctor (above). Auden’s physician is not too much concerned with resource allocation, prolonging life, achieving ideals in disease prevention, abortion or euthanasia. He is deeply rooted in a culture during which, physicians, bound deeply in the Hippocratic oath acted as almost ecclesiastical and autonomous being that held the patient’s trust in their hands from a paternalistic point of view. Most importantly, Auden’s doctor knew the patient close enough to be able to tell him with a twinkle in his eye that death is imminent and inevitable, without fear. In contrast, a generation of doctors have risen that knew not this pattern of confidence and privilege held by themselves, and so go on to strip themselves of the ethos that has been with medicine from the start. We have diluted medicine so much that it is nothing more than a business between the treating doctor and the knowing patient. The doctor no longer act autonomously in the benefit of the patient, but rather, the paternalistic relationship of trust and kindness has evolved into a business contract of agreement and fear. Lastly, instead of walking alongside the patient with care and support to death, we have scrambled in every direction trying to prolong and prevent the end of life which we now so fear and do not dare look in the eye. Harsh as it might sound, discounting the few physicians who still operate from the same ethos of the original Hippocratic oath [2], this is the general shift or ‘hollowing’ medicine has undergone. It is from this premise and background that the content of this article will proceed.


Definitions

Ethics, is a word that begs proper definition. To put it simply it is the correct way to do things. Ethical issues surrounding medicine have generally surrounded an epicenter which is “human dignity” or “the sacred human life”. All medicine and every decision made hinges upon the premise that human life is sacred and every human should live a dignified life. Every side of the debate on abortion, euthanasia, embryonic stem cell research claims they have human in their best interest, but one has to be correct. However, to talk about ethics without talking about moral values is as futile as talking about morality without bringing in God. I have to be radical here as I opine that the elimination of a transcendant being that rules with objective moral his mortal subjects will ultimately leave this discussion fruitless. Transcendence is the value that so powerfully dominates the Hippocratic Oath. Throughout history, men have seeked numerous ways to teach themselves morality, Hitler used himself, Darwin used nature, Pol Pot used power; and we later use consequence, conscience, authorities, feelings and lastly relative morality. It would be wrong for me to say that all these are wrong in themselves, but they certainly are not dependable and infallible. We have them to guide us, but what our lives and values are based on should be objective and unchangeable, someone I call God. Ethics is but the tip of the iceberg resting on a monstrous foundation of core beliefs, doing ethics ignoring all others is to float aimlessly in the sea and calling ourselves practitioners of evidence-based medicine.

The second word is stem cells, which means simply thecells from which all cells begin from. These cells have sparked endless interest, hope and debates because they possess the ability to differentiate into all the cell lines in the body, which amounts to more than two hundred. Stem cells are the reason an egg of two cells could transform into a human being with utmost complex functions. These stem cells give hope to millions who are stricken by degenerative diseases such as Alzheimer’s, osteoarthritis, patients with spinal cord trauma, diabetes mellitus, inborn errors of metabolisms, etc. Basically, researchers believe that if we can correctly stimulate the stem cells, it can transform into any tissues in the body which needs repair, a fibrillating heart, a thinning brain, a broken nerve, name it and stem cell transplant is the miracle answer. In fact, the body’s reparative mechanisms each day is a miracle in itself. Cells are dying and stem cells are metamorphosing into mature functioning cells every second in our body in every system, its regulation beautifully controlled by genes; any faster results in a cancer, any slower, in degeneration. Stem cells can be found in an adult body, in the skin, bones, heart, and more than sixty other sites identified by scientists. Embryonic stem cells are stem cells that formed after fertilization of an egg by a sperm, and it is this that give rise to ethical issues, not the adult one.

Adult vs Embryo

The complexity of the ethics surrounding this is far less compared to that in euthanasia and abortion. Proponents who are labeled ‘pro-life’ oppose only the embryonic stem cell research holding on to the premise that life begins at conception, that is when an ovum is fertilized by a sperm. To use stem cells from embryos even at this primitive stage of life is tantamount to destroying a sacred human life, which the institution of medicine seek so carefully to preserve. They have never had any case against adult stem cells research; in fact, they are themselves doing active research and enthusiastically promoting the use of adult stem cells for medical purposes. The exciting prospect and results currently surrounding stem cells have mostly been the result of research on adult stem cells. Encouraging results have enabled us to catch a glimpse into how to harvest and stimulate these cells to differentiate into the type that we desire.
Having said this, it is important to know that the stage of use of stem cells to treat diseases is still at its infancy, and the prospect of cure is still a long way off. We will then have to assess the impact that stem cell therapy have in the long run on its recipients and the risk of malignancies and a whole spectrum of other considerations before we can truly call this special cells as our miracle cure. The pro-life group therefore see no real meaning in embarking on the destruction of thousands of embryo which will yield results of cure that is so elusive and tread on moral grounds so dangerous and dark. They have not left this debate with their arms crossed snugly, but they have themselves proved in many ways that in the presence of adult stem cells, the use of embryo is truly redundant.

On the other side are those who feel no qualms in using embryos for stem cell research, for to them, the embryo is not truly alive yet. Another reason is that they believe that if the sacrifice of a few lives of much lower value could result in the saving of millions and alleviate the suffering of tens of millions, then the effort is truly justified. They are called consequentialists, and perhaps possess the most seemingly logical and most powerful voice in ethical issues, and is also the main logic used in parliaments in the United Kingdom regarding this debate. The question one would superficially ask is then, ‘Are embryonic stem cells better than adult stem cells?’ The striking advantage that embryonic stem cells have, as claimed by its proponents, is its ability to differentiate into all cell lines in the body whereas adult stem cells only possess limited ability to differentiate. Embryonic stem cells can be grown relatively easily in culture. Adult stem cells are rare in mature tissues, so isolating these cells from an adult tissue is challenging, and methods to expand their numbers in cell culture have not yet been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.[3] The battle over stem cells intensified throughout 2004 becoming a major issue in the US election won by Republican George Bush on 4 November. Much of the controversy centred around different views on the status of the human embryo, and the fact that embryos have to be created and destroyed to produce stem cells. Bush's policy was to restrict federal funding to research on the 78 embryo stem cell lines in existence since 9 August 2001, banning both the use of all new human embryos and the creation of cloned human embryos through cell nuclear replacement. Democrat candidate John Kerry supported funding the use of embryo stem cells, cloned and otherwise, to develop treatments for heart disease, Alzheimer's, Diabetes and Parkinson's.[4]
The emotional intensity of the debate was raised considerably by the involvement of celebrities who threw their weight behind Kerry. Back to the Future star Michael J Fox, who has Parkinson's disease, made a television advert supporting Kerry's campaign in October.[5] Superman actor Christopher Reeves, who was paralysed in 1995 after falling from a horse, campaigned tirelessly for the Democrat candidate, believing that his only hope also lay with embryo stem cells. He died just before the election on 10 October.[6] Nancy Reagan claimed that the life of her husband former US president Ronald Reagan, who died in June from Alzheimer's, could have been saved by embryo stem cell research. The Washington Post hailed this 'Reagan-inspired tidal wave of enthusiasm' as 'an example of how easily a modest line of scientific inquiry can grow in the public mind to monumental proportions'. [7]Ironically Alzheimer's, in contrast to spinal injuries and Parkinson's, involves widespread diffuse neuronal and synaptic loss, and is most unlikely to benefit from stem cell treatment.
The scientific community on both sides of the Atlantic have not been quick to dispel the myths or counter the claims. In the UK, the British media and public have been consistently misled into seeing cloned embryos as a panacea for treating degenerative diseases through the Government's failure or unwillingness to highlight the dangers and to rectify misconceptions about the properties of the more ethical alternative of adult stem cells propagated in the now seriously dated 2000 Donaldson report Stem Cell Research. Such selective interpretation and presentation of scientific data is both irresponsible and dangerous because it falsely raises the hopes of vulnerable people. Honest and balanced reporting of the facts should always take precedence over the prestige and profit motives of the government and biotech industry.
Assessing the peer-reviewed evidence catalogued in great detail on the Christian Medical a Dental Association (CMDA) [8] they conclude that:
1. Embryonic stem cells have yielded only very limited and/or questionable success in animal models and no therapeutic application whatsoever in human beings:
• Human embryonic stem cells are difficult to obtain, develop and maintain and are unstable and mutate in culture.
• Differentiation protocols for many cell types have not been developed and cell types that have been differentiated often act abnormally.
• When embryonic-derived cells have been placed in animals, cancerous tumours have formed.
• Cloned cells, used to address the problem of immune rejection, are not normal.
• At a cost of over $200,000 per patient, only the very wealthy could afford the procedure.
2. Adult stem cells are ethically obtainable from multiple sources in human beings and research over the last three years has made great strides:
• 'Adult' (non-embryonic) stem cells have been found in cord blood, placenta, bone marrow, fat, teeth and other sources.
• Adult stem cells found in one type of tissue can repair damage in another tissue type and can be harvested from each patient, multiplied in culture and transplanted back into the patient.
• Since adult stem cells require limited, if any, manipulation, and are readily available from a number of sources, the cost for their clinical application will be far less.
• There are no ethical concerns in their use, making them acceptable to virtually all patients and healthcare providers.
• Adult stem cells are already providing cures in animals and clinical human trials.

A sampling list has shown the examples of breakthrough of adult stem cell research in various institutions
• Researchers at Harvard Medical School say adult stem cells may eliminate the need for embryonic ones. The researchers experienced a permanent reversal of Type 1 diabetes in mice by killing the cells responsible for the diabetes. The animals' adult stem cells took over and regenerated missing cells needed to produce insulin and eliminate the disease. The results hold promise for rheumatoid arthritis, multiple sclerosis, lupus and more than 50 other ailments.
• At the University of Texas MD Anderson Cancer Center in Houston, a man with a rare, potentially fatal skin disorder that was so severe that he could no longer eat, is now symptom-free after receiving a transplant of his own adult stem cells.
• Doctors at Northwestern Memorial Hospital in Chicago extracted the adult stem cells from the blood of two Crohn's patients and successfully used them to rebuild their faulty immune systems.
• Dr. Edward Holland of the Northern Kentucky Eye Laser Center in the greater Cincinnati metropolitan area, is using adult stem cell transplants as part of a treatment to dramatically improve the eyesight of his patients.
• New research in the UK on rats indicates that transplants of adult stem cells can help stroke victims regain movement, senses and understanding. They also show that the adult cells were more effective than cells from aborted babies.
• The Albert Einstein College of Medicine in New York came to similar conclusions.
• A study by the Institute for Stem Cell Research in Milan, Italy showed that certain cells from the brains of adult rats can be used to generate muscular tissue.
• Researchers at the University of South Florida in Tampa have found that adult stem cells from the umbilical cord blood may be able to help repair damaged brain tissue after a stroke.
• Scientists at the University of Medicine and Dentistry of NJ have found that bone marrow cells may be converted into replacement nerve cells, able to treat brain and nerve injuries. Dr. Ira Black and his team were able to convert 80% of the bone marrow cells into nerve cells.

From October to December 2004 three independent reports of patients showing recovery from spinal injuries after adult stem cell transplants surfaced in Russia [9] and later in Korea and Portugal; and a group in Innsbruck have reported success in using the same technology to treat stress incontinence. We will have to wait and see if these so-far small studies are confirmed; but it seems that Christopher Reeve's hope may have been misplaced. Either way we will get far more answers through following the wise injunction to 'enquire, probe and investigate'.
Hybrids
Just two years ago, a raging debate sparked in the United Kingdom medical ethics scene when scientists proposed the use of hybrid embryonic stem cells for research. Because of the lack of embryonic cells and difficulties in harvesting them, they try to push a bill that will enable them to use cytoplasmic human cells ‘fertilised’ with animal gametes. This is a whole new facet in which opponents of hybrids believe this to be a heinous crime against nature, and that God’s creation should not be tampered with in this manner. Last May, Prime Minister Gordon Brown welcomed animal-human hybrids as 'a profound opportunity to save and transform millions of lives' and expressed his commitment to this research as 'an inherently moral endeavour that can save and improve the lives of thousands and over time millions of people'. The measure was supported in a heavily whipped vote as part of the Human Fertilisation and Embryology Bill.
Now it appears, before the new Act has even come into force, that stem cells from animal-human hybrids are seen as a poor investment and almost certainly won't work. In January, the two leading UK researchers who had been granted licences for this work, Stephen Minger of Kings College London and Lyle Armstrong at Newcastle University Centre for Life, were denied funding by the Medical Research Council. The British Medical Journal [11] reported that the grant applications had been turned down because the reviewers considered that they were not competitive in the face of the lack of overall funding for medical research in the United Kingdom. Minger himself admitted that he believed the distribution of research funding should be competitive, based on assessment of scientific value and cost, and noted that induced pluripotent stem cells are cheaper to set up than human-animal hybrid stem cell research. No one it seemed wanted to invest money in the new research, given the low likelihood of it ever yielding results and the emergence of cheaper ethical alternatives.
Less than three weeks later, in a landmark paper in Cloning and Stem Cells, Robert Lanza and colleagues from Advanced Cell Technology, Massachusetts, demonstrated that animal oocytes lack the capacity to fully reprogramme and activate adult human cells, and specifically the pluripotency-associated genes needed for stem cell production. [12] The hybrid embryos from mouse, cow and rabbit eggs looked microscop-ically normal but were genetically flawed. Journal Editor Sir Ian Wilmut, the British cloning pioneer involved in the 1996 creation of Dolly the sheep, concluded that 'production of patient-specific stem cells by this means would (now) be impracticable'. [13]

Conclusion
Debate is good, but only when we know and truly believe the direction we are coming from and the direction we are heading towards. In the midst of heated arguments, it is easy to lose our heads proving and disproving that we forgot the core of the problem. The epicenter of the problem surrounding medicine is now, I believe, the loss of ‘Auden’s doctor’. With the paradigm shift and change in ethos, healthcare and medicine are now married, and with this marriage sprung numerous problems such as issues on life prolongation, government fundings, public concern, the greater good, etc. We cannot turn back time. But what we can in fact do is to remember that in the centre of good research going on to prolong a patient’s life and give a cure to their problems, it is much more precious and important for us to be able to cry with the patients, empathise with their suffering, hold their hands and walk with them when we know that no cure is in the near future, and finally to be beside them when they need courage most to face the ultimate enemy, death. Medicine is not about the cure, but about the person. We should not cease to embark on studies that will find answers to problems for our patients, but we must never neglect rooting ourselves so deeply in the humanity of medicine and be involved in our patients who are each of them sacred in the utmost sense.


References
1) Poem Hunter. Give Me a Doctor by WH Auden. http://www.poemhunter.com/poem/give-me-a-doctor-2/. Accessed 7/4/2010.
2) The Hippocratic Oath. The Hippocratic Oath (Original version). http://www.members.tripod.com/nktiuro/hippocra.htm. Accessed 7/4/2010.
3) Stem Cell Information. What is the similarities and differences between adult and embryonic stem cells?. http://stemcells.nih.gov/info/basics/basics5.asp. Accessed 6/4/2010.
4) Tanne JH. Slugging it out over healthcare, stem cells and abortion. BMJ 2004; 329:592 (11 September).
5) BBC News. Michael J. Fox Makes Advert news.bbc.co.uk/1/hi/entertainment/tv_and_radio/3724296.stm . Accessed 7/4/2010.
6) BBC News. Actor Christopher Reeve Dies news.bbc.co.uk/1/hi/entertainment/film/3732310.stm. Accessed 7/4/2010.
7) Weiss R. Stem Cells an unlikely therapy for Alzheimer's, say experts. Washington Post 2004; 10 June.
8) www.cmdahome.org/index.cgi?BISKIT=1471444487&CONTEXT =art&art=2702
9) Free Republic. Doctors in Russia Prove that Non-Embryonic Stem Cells can be Used in Treating Spinal Cord Injuries. http://www.freerepublic.com/focus/f-news/1295924/posts.
10) Life Issues Institute. Embryonic versus Adult Stem cells. http://www.lifeissues.org/cloningstemcell/bradsarticle.html. Accessed 7/4/2010.
11) Lack of Funds slows human-animal stem cell research despite legislation in favour.
BMJ 2009; 338 :194-5
12) Lanza R et al. - Reprogramming of Human Somatic Cells Using Human and Animal Oocytes.
Cloning and Stem Cells 2009; 11(2):1-11
13) Animal eggs not suitable substitutes to produce stem cells.
Genetic Engineering and Biotechnology News 2009; 2 February
www.genengnews.com