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Budny 4:00 R09 STEM CELL ETHICS: AN IMPORTANT CONSIDERATION IN TISSUE ENGINEERING ADVANCEMENTS Andrew Sassani ([email protected]) INTRODUCTION: THE ETHICAL DILEMA OF TISSUE ENGINEERING: Tissue engineering is a relatively new concentration in the medical field that focuses on all aspects of tissue growth and regeneration [1].The field is not limited to tissues though; many engineers focus on the development of organs via stem cells and biological scaffolds [2]. The results of tissue engineering can be helpful in many applications in the biomedical field. Such applications include surgical replacement and testing of new drugs [3]. The practical uses of tissue engineering are numerous and more are bound to be discovered with continual research. Working as a tissue engineer, I have been given a new project. Doctors at University Pittsburgh Medical Center (UPMC) need an engineered bladder for a patient with bladder cancer. The patient doesn’t have an immediate threat of dying, but is experiencing discomfort from treatment. Also, the patient has been battling cancer for almost a year and has exhausted all other forms of treatment with no positive results; this is his last hope for survival. As project leader, I will be responsible for various steps in the process of developing tissues including ordering supplies and equipment. I will have to face an ethical dilemma over the stem cells needed to be ordered: Should I order stem cells from a certain company that harvests stem cells through the destruction of embryos? Recently, researchers have developed a method to create stem cells from patient skin cells (the process will be described later). Or should I find stem cells that have been formed skin cells despite their low availability, possibly delay the project and inadvertently discomfort the patient? As the lead engineer, I must consider both sides of the debate and make my own decision on how to act. By reflecting on personal values and engineering codes of conduct, I must make a decision that will greatly impact this project. THE BASICS: HOW TISSUES ARE DEVELOPED The process of engineering a tissue/organ is a relatively standardized process. For most laboratories, engineers start with stem cells that can be obtained from multiple sources. Stem cells have the ability to form mainly any type of cell in the human body (heart, liver, nervous, etc.). Engineers manipulate these cells to form the desired cell of the tissue/organ they are developing. However, developing organs is not as easy as letting cells divide in the lab. Cells rely on interaction with neighboring cells for complete University of Pittsburgh Swanson School of Engineering 2013-10-29 function. As a solution to this problem, engineers have developed extremely small biological scaffolds that allow physiological connection between cells [4]. Blood vessels are also grown with extreme accuracy to encompass every cell in the organ [3]. Without this precision, tissue cells could not function, ultimately making the organ useless. After development, these organs can have a multitude of uses. USES FOR ENGINEERED TISSUES Surgical Replacement Tissues are the building blocks of all organs in the human body. Therefore, when a large tissue or entire organ becomes damaged enough, the organ can lose all function and eventually die. On June 9, 2011, doctors had implanted a labgrown trachea into a patient that had been battling cancer for almost a year. An artificial trachea mold, resembling the patient’s trachea, was created and then covered in stem cells from the patient. The stem cells were manipulated in the lab so they could grow into the appropriate cells for the trachea. Once the trachea was covered in cells, it was implanted into the patient; the surgery was successful. The total time for an organ to be developed using this process takes about 10-12 days [5]. The patient I am working for will undergo a similar surgery. Knowing that he has been fighting cancer for so long, I do not want to delay the project by ordering ethically derived stem cells, but I cannot simply ignore the rights of the embryo. This is another factor that must go into my final decision. ETHICS OF TISSUE ENGINEERING Clearly, the work of tissue engineers has led to exponential advances over the past decade, but what sacrifices should be made in the name of progress? How far should we continue with medical development before we consider our knowledge too great? These are key questions that engineers and scientists must face in the development of tissues. The main issue that affects the development of tissues is the use of stem cells and how they are obtained. The popular method for harvesting the stem cells is extraction from a fertilized embryo. A fertilized egg cell can contain up to 250 stem cells five days after conception. These cells can divide and form more even after they are extracted. The stem cells are vital in a developing embryo because they have the ability to form any cell in the body. Therefore, upon extraction, the embryo will die and the possibility of creating a child with that cell is impossible. Although one life is taken, should it be deemed paramount despite the enormous benefits of developing tissues? That is, are the needs of many more Andrew Sassani important than those of an individual? It surely seems tempting to agree with this tenet, but many, including myself find this unethical. The main driving force behind this argument is the possibility of life the embryo possessed. The central reason the embryo was fertilized was to bring a new life into this world, so it rightly seems researchers are not entitled to take that gift away [6]. Another ethical argument that arises is about the “moral status” of the embryo. The moral status mainly refers to the status of “personhood” so to speak. Proponents of stem cell research claim that the embryo has no moral status because it has no properties of a human (emotions, physical properties, etc.). Based on that theory, they are correct and the embryo should be utilized to help someone how actually is a living human being. Those with opposing views claim that trying to pinpoint an exact point of “personhood” is only an inaccurate guess. Development of an embryo into the final stage of an infant is a continual process, so the question of when life begins is something we cannot fully answer. Also, it should not matter because life is supposed to develop fully and should not be abruptly ended [7]. Looking at the moral status from a scientific standpoint can bring up a new viewpoint. The genetic makeup of the embryo clearly identifies it as a human being. Although the fertilized egg does not have the ability to think or feel (the qualities of “personhood”), it is still technically a human being. Therefore, this human being, along with other human beings, is granted basic human rights for living, one of the rights being the right to live [8]. The decision I make as an engineer must be based on the debate issues that arise over stem cells. However, much of the ethical considerations should be based on public opinions of the issue. As an engineer in charge of making the decision, I must also look at professional engineering ethics, biomedical engineering ethics, public opinions and personal values including my religion. embryo will die which would be a direct violation of this cannon. Another tenet from the Professional Engineering Code of Ethics states, “Engineers shall at all times strive to serve the public interest” [9]. If the engineers should act in the public interest, do most people approve of stem cell research? The answer is yes. According to one survey, 68% of the population approves of embryonic stem cell research [10]. Therefore, in the public’s interest, it seems that the utilization of embryos for their stem cells is acceptable and should be done. However, 68% is not exactly an “overwhelming” majority of the population. The Professional Engineering Code of Ethics seems too general and vague to draw a complete conclusion on how to act in this situation. The Biomedical Engineering Society has their own code of ethics developed to center around their unique medical work. Although no specific canons address the controversy over stem cells, a few can be interpreted to help make a decision for the scenario. Canon 4 states, “[Biomedical Engineers shall] Consider the larger consequences of their work in regard to cost, availability, and delivery of health care”. To comply with this ethical statement, before I decide where to order the stem cells and ultimately consider the consequences. Should I be content with knowing an embryo was destroyed and receive stem cells on time and continue with the project? Or should I risk a delay in progress just to get ethically formed stem cells? Another canon directly related to research states, “[Biomedical Engineers in research shall] Comply fully with legal, ethical, institutional, governmental, and other applicable research guidelines, respecting the rights of and exercising the responsibilities to colleagues, human and animal subjects, and the scientific and general public”. I must respect human test subjects which includes the embryo itself. So even if it delays the project, it might be more beneficial to ethically acquire the necessary stem cells for the project to act in accordance with this cannon [11]. PUBLIC RECEPTION OF STEM CELLS AND ETHICS Religious Views Despite many outside deciding factors, much of influence on a decision will come from internal values and morals. Being a practicing Catholic, a considerable portion of decision I make will based on religious teaching. Catholics oppose stem cell research because they feel it is immoral to destroy an innocent embryo that would have formed into an actual person. Some Catholic bishops claim that embryo research will lead to a “domino-effect” where we will begin to test on living humans because we have crossed a “moral line”. They claim that stopping testing on embryos will deter future testing on other subjects [12]. Although I do not necessarily agree with the domino-effect philosophy, I understand the moral objection to destruction of embryos. Many Catholic officials do not completely disregard the importance of stem cells though. In fact, there is much attention given by Catholics to ethically harvested stem cells. Professional Views Engineers are held to high standards which are listed in the Professional Engineering Code of Ethics. This code tends to be more general guidelines because most engineering disciplines have their own codes unique to their profession; however, some canons from the professional code can be applicable to this situation. Cannon II.1 states that, “Engineers shall hold paramount the safety, health, and welfare of the public” [9]. This tenet can justify both sides of the argument. If engineers are to hold the health and welfare of the public at upmost importance, then it seems that stem cells should harvested to develop tissues to help the public in need. However, when harvesting embryonic stem cells, the human 2 Andrew Sassani In fact, in 2005, Catholics in South Korea raised $10 million into advancing adult stem cell research [13]. However, adult stem cells are not as versatile as embryonic stem cells because they can only form certain cells based on where they were found. For example, bone marrow is responsible for large amounts of blood and blood cell production. Many stem cells can be harvested from marrow, but they would only be able to form blood related cells. Since I am trying to engineer a new bladder, I would need to find stem cells from the patient’s bladder [10]. It isn’t the most efficient way of harvesting stem cells, but at least the Catholic Church does not completely ignore the necessity of stem cells in many medical procedures. FIGURE 1 [14] Process of Developing Stem Cells from Skin Cells ETHICAL HARVESTING OF STEM CELLS Researchers at Oregon Health and Science University have developed a method that uses human skin cells and unfertilized egg cells to develop stem cells. The process begins by obtaining skin cells from the patient and an unfertilized egg from a donor. The DNA is removed from the egg and the skin is inserted into the egg cell membrane. The researchers then initiate a series of chemical reactions that allow the cells to fuse. When the cells fuse, the combined cell is basically identical to an embryo. The formed embryo can exhibit all the properties of a fertilized egg too, therefore, it can form useable stem cells. A diagram that illustrates the process can be seen to the right. The main attraction to forming stem cells this way is the fact that unfertilized eggs are used. Without a fertilized egg, no embryo (an embryo is a fertilized egg) is destroyed, and therefore there is no debate if a human being was murdered or not [9]. The diagram above outlines the process of how researchers at Oregon Health & Science University grew stem cells from skin cells and unfertilized embryos [14]. CONCLUSION: THE DECISION NEEDS TO BE MADE Approaching the final decision, there are many considerations I must keep in mind. The patient and the embryo are the two entities that will be affected by my decision. I cannot simply place the importance of one over the other. To help make the decision, I kept in mind the pros and cons of each debatable topic on stem cells, the professional ethics I work by and the personal values that define me. I feel that stem cells created from skin cells are the best way to solve the ethical dilemma. They might not be as readily available as embryonic stem cells, but they can be found and used for this project to produce desired results. Once they are received by my lab, coworkers and I will put the project at top priority and work past normal hours to complete the project on time and 3 Andrew Sassani [12] N. O’Brien. (2013). “Embryonic stem-cell research immoral, unnecessary, bishops say.” Stem-cell Research and the Catholic Church. (Online Article). http://www.americancatholic.org/News/StemCell/ [13] (2013). “Catholic Support for Ethically Acceptable Stem Cell Research.” Stem Cell Research. (Website). http://www.usccb.org/issues-and-action/human-life-anddignity/stem-cell-research/catholic-support-for-ethicallyacceptable-stem-cell-research.cfm [14] J. Koebler. (2013). “Scientists Convert Human Skin Cells Into Embryonic Stem Cells.” News. (Online Article). http://www.usnews.com/news/articles/2013/05/15/scientistsconvert-human-skin-cells-into-embryonic-stem-cells [15] “Presidential commission for the Study of Bioethical Issues.” Presidential commission for the Study of Bioethical Issues. (Website). http://www.bioethics.gov/ ultimately minimize the discomfort by the patient. I believe that issues engineers face should be solved through the most ethical and efficient manner possible. President Barack Obama once stated, “As our nation invests in science and innovation and pursues advances in biomedical research and health care, it's imperative that we do so in a responsible manner” [15]. In accordance with presidential advice, I feel this solution has provided effective medical care that is done in “a responsible matter” yielding an optimal solution for an ethical engineering dilemma. REFERENCES [1] A. Mikos, P. Johnson. (2012). “Overview.” Tissue Engineering, Parts A,B, & C. (Online Journal). http://www.liebertpub.com/overview/tissue-engineeringparts-a-b-and-c/595/ [2] R. Yang, W. Gao. (2013). “Introduction.” Generation of functional organs from stem cells. (Online Article). http://www.cellregenerationjournal.com/content/2/1/1 [3] A. Trafton. (2012) “Tissue Engineering: Growing new organs, and more.” MIT news. (Online Article). http://web.mit.edu/newsoffice/2012/engineering-healthtissue-engineering-growing-organs-1214.html [4] J. Lannutti, D. Reneker, T. Ma, D. Tomasko, D. Farson. (2007). “Abstract.” Electrospinning for tissue engineering scaffolds. (Online Article). http://www.sciencedirect.com/science/article/pii/S09284931 06001421 [5] M. Park. (2011). “Lab-made organ implanted for first time.” CNN Health. (Online Article). http://www.cnn.com/2011/HEALTH/07/07/trachea.transplan t/index.html [6] A. Siegel. (2013). “Ethics of Stem Cell Research.” Stanford Encyclopedia of Philosophy. (Online Encyclopedia). http://plato.stanford.edu/entries/stem-cells/ [7] K. Hug. (2011). “The ethical dilemma.” Embryonic stem cell research: an ethical dilemma. (Online Article). http://www.eurostemcell.org/factsheet/embryonic-stem-cellresearch-ethical-dilemma [8] R. Doerflinger. (2010). “Old and ethics in the stem cell debate.” American Society of Law, Medicine & Ethics. (Online Article). http://go.galegroup.com/ps/i.do?action=interpret&id=GALE %7CA231407923&v=2.1&u=upitt_main&it=r&p=LT&sw= w&authCount=1 [9] (2013). “NSPE Code of Ethics for Engineers.” Ethics. (Website). http://www.nspe.org/Ethics/CodeofEthics/index.html [10] “Stem Cell Facts.” Americans for Cures: Stem Cell Facts. (Website). http://www.americansforcures.org/article.php?uid=1000 [11] (2004). “Biomedical Engineering Society Code of Ethics.” 2004 Approved Code of Ethics. (Online Document). http://bmes.org/files/2004%20Approved%20%20Code%20o f%20Ethics(2).pdf ACKNOWLEDGEMENTS I wish to commend the library for providing the useful search engine to find compelling articles about stem cell ethics. In addition, I would like to recognize Cody Fannin, Andrew Sivaprakasam and Henry Phalen for proofreading my essay. I would also like to thank Daxton Scholl for providing help with formatting. 4 Andrew Sassani 5