Ethics of Experimentation Using Stem Cells



Moral Crossroad signOne of the most controversial topics in cutting edge medical science is the use of stem cells. Much of this is due to two factors: 1) misrepresentation of stem cells in the media, and 2) misunderstanding of stem cells and the ethics surrounding their use. Before delving into stem cell ethics, a brief understanding of stem cells is necessary. First, stem cells are present in all humans, regardless of age! They are the source of all cells in the body and are responsible for both its healing and general maintenance. In fact, without stem cells, we wouldn’t be able to form memories. Secondly, there are many different sources and types of stem cells because they can’t just become any other type of cell. For example, stem cells present in the bone marrow, called hematopoietic stem cells, are responsible for becoming the wide variety of blood cells present in the body. They are different from stem cells in the skin, called epidermal stem cells, that are responsible for both maintaining and healing the skin. Hematopoietic stem cells cannot become cells that heal the skin and epidermal stem cells cannot turn into different blood cells, naturally that is. In addition to these adult stem cells, there has also been the Nobel Prize winning development of inducible pluripotent stem cells (iPSCs)1. Under the correct experimental conditions, cells procured from almost anywhere on a person, including cells that are not adult stem cells, can be turned into nearly any other kind of human cell. For a more in-depth discussion on stem cells, please read my article – Stem Cells: The Ultimate Cellular Blueprint.

Ethics Violation - The Case of Woo Suk Hwang

All biomedical research intended for publication and/or application in a legal clinical setting requires ethics approval. In fact, the majority of research centers worldwide require completed ethics documentation for their experiments before even starting them in order to have access to animals, patients, and sometimes even equipment. If an individual is found to be violating international ethics principles, Snuppy Afghan hound the first cloned dogit is not only detrimental to the reputation of the institution they are working for, it significantly impairs progress in the field. As a result of these high stakes, ethics in biomedical research is taken very seriously. Consider the case of South Korean scientist Woo Suk Hwang, who had successfully produced the world’s first cloned dog, Snuppy. He published a paper stating that he had successfully created a human embryonic stem cell line2. Investigation of Hwang’s falsified data brought to light the ethically dubious way he was able to get the material to work with.

In order to start a stem cell line, techniques similar to cloning are used. It involves taking an unfertilized egg, removing the half-set of DNA present in that egg, and then inserting a complete DNA set of the animal to be cloned. This is called somatic cell transfer. Dolly the cloned sheepAlthough the principle is straightforward, the process is incredibly difficult to do in practice and involves a significant amount of trial and error. For instance, Dolly, the sheep cloned by the Roslin Institute in Edinburgh, took 227 attempts in order to get a single adorable sheep3. Hwang reported acquiring 242 human eggs from only 16 female donors, meaning that these volunteers underwent hormone injections to produce 12-20 eggs per menstrual cycle instead of just one4. This number seemed suspicious within the scientific community, so his work was investigated. In 2006, he was charged with both embezzlement and bioethics law violations where it was found that he was also illegally buying human eggs on the black market for his experiments. In addition to losing his job at Seoul University, he was sentenced to two years in prison despite having close ties to the South Korean government5. This international scandal shattered the stem cell scientific community and amplified public doubts on not only stem cell research, but scientific research in general. Fortunately, such scathing ethical violations are extremely infrequent in medical science, and part of that is due to the international understanding and accountability of the scientific community. For example, since 1964, the World Medical Association adopted the Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects which acts as the ethical base for medical research centers around the world6.

International Guidelines

In addition to overarching general ethics guidelines, the International Society for Stem Cell Research has created a 30-page document on Guidelines for Stem Cell Research and Clinical Translation7. Not only does it coalesce a number of different medical and scientific ethics and principles, but tailors those ethics to working with stem cells. The fundamental principles of this document are:

  1. Integrity – advance scientific understanding by coordinating research that maintains public confidence and ensures information is trustworthy, reliable, accessible, and responsive to scientific uncertainties and priority health needs
  2. Primacy – never unduly place patients at risk. Stem cell-based interventions should be evidence-based, subject to independent expert review, and serve patients’ best interests.
  3. Respect – Exercise valid informed consent for patients ensuring adequate decision-making capability.
  4. Transparency – Researchers should promote timely exchange of accurate scientific information and communicate with public groups, including patient communities.
  5. Social Justice – Benefits of research should be distributed justly and globally where advantaged populations should make efforts to share benefits with disadvantaged populations.


Embryonic Stem Cell Research Guidelines

But what about embryonic stem cell research? This type of stem cell that has caused the most controversy and misunderstanding. There is an entire section dedicated to any research using human embryonic stem cells that emphasizes (by putting in bold) these experiments “shall be subject to review, approval, and ongoing monitoring by a specialized human embryo research oversight (EMRO) process capable of evaluating the unique aspects of the science”. The very first stipulation on working with these materials emphasizes that “appropriate scientific justification for performing the research using the specified materials is required”. This means that if there is any other available method or material that would allow scientists to come to the same conclusion, then their research using embryonic stem cells is not to be approved. Thankfully, the development of inducible pluripotent stem cells (iPSCs) has significantly influenced this clause by decreasing the need to use embryonic stem cells to study something that iPSCs can be used for.

Concerns regarding research using embryonic stem cells stems predominantly from how they are procured. Materials are donated by patients who have given informed consent to use their tissue for research, which is the case for all tissue acquired from patients used in biomedical science. The majority of embryonic stem cells are donated from couples who visit in vitro fertilization clinics to assist them in getting pregnant8. In vitro translates to a process that is performed or taking place in a test tube, culture dish, or elsewhere outside a living organism. Essentially, sperm and oocytes (eggs) acquired from the prospective parents are placed together in an artificial environment to encourage the sperm to fertilize the egg. As this is a very expensive procedure with room for error, many eggs, and of course billions of sperm, are used to increase the chance of in vitro fertilization occurring.in vitro fertilization culture dish with sperm and egg As very few mothers are interested in carrying multiple babies simultaneously to term, only one or two successfully fertilized eggs, called blastocysts, are implanted and the rest of the blastocysts are discarded. It is at this point where couples are given the opportunity to consent to donate their un-utilized blastocysts for use in biomedical research. Interestingly, the stage that the blastocyst is implanted in the mother during in vitro fertilization is the exact same stage when the blastocyst would attach to the uterus in in vivo (occurring in a living organism) fertilization. In fact, it is impossible to tell if a female is pregnant until the blastocyst attaches itself to the uterus because that is when hormones from the blastocyst can be detected in the mother using a pregnancy test. Essentially, it is impossible to safely evaluate if a female is pregnant until the blastocyst attaches to wall of the uterus which occurs at the same time in both in vitro and in vivo pregnancy. Surprisingly, this material is not too hard to come by as it is estimated that 1 in 60 babies born in America occurred as a result of in vitro fertilization and as many as 1 in 25 babies born in countries like Denmark, Israel, and Japan9.

Additional Precautions for Egg Donors

It is also possible to procure un-fertilized eggs for stem cell-related research. The scientific community recognizes that “women carry more burdens than men during the procurement of their [eggs], women’s efforts should be acknowledged fairly and appropriately[…] Precaution is needed to avoid the potential for exploitation”7. There is a comprehensive list of standards outlined in the ethical guidelines for stem cell research regarding female involvement, including:

  1. Ensuring no socially disadvantaged individuals are disproportionately encouraged to donate their eggs.
  2. Strict regulations on payment so that it does not exceed out-of-pocket expenses. This clause is to prevent bribery and is common in most ethical guidelines for clinical research.
  3. Collection of eggs must be performed exclusively by qualified and experienced doctors.
  4. Women should undergo a limited number of hormonally induced encouragement treatments to increase the number of available eggs is being used. This is irrespective of whether the treatment is to donate eggs for research or for assisted reproduction.


Conclusion

Medical science is an ever-evolving field that pushes the boundaries of possibility, while figuring out how to approach novel technologies in an ethically conscious society. There are a variety of international organizations that ensure accountability of research at a global scale, whose ethical mandates are enforced at an institutional level. Publications are the currency of a research scientist, where the number and/or impact of their research is largely determined by their publication record. Publications are evaluated when pursuing jobs, applying for funding, and earning awards. In order to publish, all peer-reviewed scientific journals in biomedical research require a clause indicating which specific ethical guidelines were followed to perform the research. This is traditionally the very first sentence under Materials and/or Methods in a primary science paper. This article summarizes the extensive ethics documentation used by researchers all over the world. Check out the references section for links to complete ethics documentation.

References/More Information

  1. Takahashi K and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
  2. Cyranoski D. Rise and Fall: Why did Hwang fake his data, how did he get away with it, and how was the fraud found out? Nature News 11 January 2006.
  3. Campbell KH, et al. Sheep cloned by nuclear transfer from a cultured cell line. Nature 1996; 380:64-66
  4. Cyranoski D. Korea’s stem-cell stars dogged by suspicion of ethical breach. Nature 2004;429:3.
  5. Disgraced cloning researcher convicted in South Korea. CNN 26 October 2009.
  6. WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. World Medical Association 9 July 2018.
  7. Guidelines for Stem Cell Research and Clinical Translation. International Society for Stem Cell Research 12 May 2016.
  8. Bethesda, MD. Stem Cell Information: Stem Cell Basics III. National Institutes of Health 2016.
  9. The Fertility Business is Booming. The Economist 8 Aug 2019.