It is ethical to perform mitochondrial gene transplants clinical trials and if successful transplant therapies in humans. Mitochondrial gene transplant is a type of therapy that replaces the mitochondrial DNA (mtDNA) of unfertilized oocytes with donor mitochondria. The mtDNA humans inherit comes from their mother. Two main techniques are used to transfer mitochondria, spindle transfer (ST) and pronuclear transfer (PNT). ST is a technique that occurs when a mature oocyte is completing metaphase, and the meiotic spindle is isolated and transferred to an unfertilized oocyte. The cytoplasm of the original oocyte is discarded and the original karyoplast stays with the new oocyte, which can readily be fertilized to create an embryo with no mtDNA issues. The second technique occurs after the fertilization of an oocyte. Pronuclear transfer occurs when an embryo is one cell and the pronuclei are identifiable. The fertilized pronuclei is removed from the donor zygote and discarded, while the patient zygote pronuclei is transferred to the cytoplasm of the donor embryo. This new embryo contains the pronuclei of the male and female parent and the cytoplasm of the donor. In both instances, the cytoplasm of the donor and associated mitochondrial DNA is used while the nuclear DNA of the parents is used in the implanted embryo (Mitalipov & Wolf, 2014). These techniques, while proven to be effective in animals pose many questions related to the ethics of testing and application in humans.
Some of the main ethical dilemmas that arise include the required testing on humans and human embryos, the use of a third person as the donor in the embryo, and the precedent it could set for DNA alteration. Intensive testing and clinical trials would be required for research to continue and eventually authorize these kinds of therapy. For one instance of mitochondrial gene transplant to occur, two oocytes are required to be used and potentially destroyed in the process. This issue raises ethical dilemmas about natural conception and whether testing like this can be ethical to potential unborn babies. The trials required would require the testing of oocytes, which are an extension of in vitro fertilization (IVF), a method that is already frowned upon in certain communities. Another issue is the ethical dilemma surrounding the third set of DNA that the embryo receives. Since mtDNA only codes for 37 genes, compared to the approximate 25,000 in the entire human genome, a small fraction of the DNA in the embryo comes from someone who is not the mother or father. Lastly, as technology advances and different types of germ line therapy or other gene editing tools develop, more regulations will be required to limit the extent. Allowing mtDNA to be removed from the human genome removes a known disease but could set a precedent for other less noble methods of gene transfer to be introduced and approved.
Science must progress or it will stagnate. The way to progress science is through experimentation and trials by which willing and consenting adults participate in trials. Some literature, like in the Human Fertilisation and Embryology Act 1990 from the United Kingdom authorizes additional treatment to remove disease if they are considered safe and effective. (Mitalipov & Wolf, 2014) The only way for scientists and the Food and Drug Administration (FDA) to know that these treatments are safe and effective is through ethically done clinical trials. The alternative option is to not perform the research and take away the opportunity for persons who have a mitochondrial disease to have children without passing on their disease. The parents DNA would contribute over 99% of the DNA to a child, while less than one percent would come from the donor. Now, it is possible to donate eggs, sperm, and even your uterus via gestational surrogates to help aid people in having children. Allowing this practice to occur, assuming it was verified safe and effective, allows three consenting adults to allow this exchange to occur and prevent the child from having a mitochondrial disease. Lastly, innovation is of vital importance in our continually developing society. While the ethical constraints of more extreme versions of gene therapy occur, more regulations need to be developed to set boundaries. This version of germ line therapy is providing a potentially safe pathway for parents to have children that are nearly genetically identical without common versions of mitochondrial disease present in their life. The alternative to not letting clinical trials progress in this field would mean that a mother who has a mitochondrial disease may never be able to have children spared from the same burden she faced. One potential pitfall is the struggle of a child in understanding the use of a donor oocyte cytoplasm and what effect that may have on them. If the mother, father, and donor are all willing participants then this transaction, if safe and effective should be allowed. Any additional explanation for the child is at the discretion of the mother and father, like informing a child that they were a product of IVF or adoption.
Mitalipov, S., & Wolf, D. P. (2014). Clinical and ethical implications of mitochondrial gene transfer. Trends in Endocrinology & Metabolism, 25(1), 5–7. https://doi.org/10.1016/j.tem.2013.09.001