Bioethics of MRT

Mitochondrial DNA Replacement Therapy is an assisted reproductive technology that is designed to help women who carry harmful mitochondrial mutations have healthy, genetically related children. The basis of this procedure is to insert a mother's nuclear DNA into a donor egg with healthy mitochondrial DNA. This procedure has produced healthy live births in humans and is approved under strict regulations in countries such as the U.K. However, results are modest compared to IVF therapy, and the number of “successful births” is comparable. Since this is a relatively new and pioneering technology, the number of births is limited, and therefore, the data are insufficient to ensure long-term safety or efficacy. The primary ethical concern is the long-term effects and the alteration of the human germline. Many critics believe this is too invasive and could have broader implications for DNA editing. This procedure is just an extension of existing reproductive technologies that aim to prevent disease rather than cause or lead to enhancements.

            This procedure/technology is meant to be therapeutic and allow carriers to have a child without the fear of passing on harmful mitochondrial DNA. This procedure does not involve editing DNA; instead, it consists of implanting the intact nuclear DNA of the intended parents into the egg along with healthy mitochondrial DNA. (National Academies of Sciences, Engineering, and Medicine [NASEM], 2016) Furthermore, MRT only replaces mitochondrial DNA, which is less than .1% of the human genome; the donor's contribution does not meaningfully change the traits of the parents' nuclear DNA. (Klitzman, Toynbee & Sauer, 2014) This will allow parents to have a child that is genetically related without possibly subjecting them to the risk of an incurable and devastating disease. This will also have social effects, such that the costs of these diseases on healthcare networks would be reduced, allowing resources to be allocated elsewhere. However, this does set a precedent for policymakers in germline interventions; therefore, this technology must be heavily monitored, and strict boundaries must be placed. Alternative treatments such as remaining childless, donor egg without DNA transfer, and adoption are viable options that would allow these parents to have children. However, this is the only option if parents want genetically related offspring.

In conclusion, if this technology is heavily monitored, strictly regulated, and parents are given thorough informed consent, then this is an ethically justifiable therapy. This could have many benefits for society, science, medicine, and parents. Whereas this technology has no implications for a “designer baby” and does not involve DNA editing, it instead consists of the implementation of nuclear DNA with healthy donor mitochondrial DNA. I will concede that very few parents should be accepted for this procedure until efficient data have been collected on the long-term effects.

Reference

Craven, L., Tuppen, H. A., Greggains, G. D., Harbottle, S. J., Murphy, J. L., Cree, L. M., … & Herbert, M. (2010). Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature, 465(7294), 82–85. https://pmc.ncbi.nlm.nih.gov/articles/PMC7812462/

Klitzman, R., Toynbee, M., & Sauer, M. V. (2014). Mitochondrial donation: Ethical issues. The American Journal of Bioethics, 14(7), 4–16. https://pmc.ncbi.nlm.nih.gov/articles/PMC4505924/

National Academies of Sciences, Engineering, and Medicine. (2016). Mitochondrial replacement techniques: Ethical, social, and policy considerations. National Academies Press. https://nap.nationalacademies.org/read/21871/chapter/2

Tachibana, M., Amato, P., Sparman, M., Gutierrez, N. M., Tippner-Hedges, R., Ma, H., … & Mitalipov, S. (2013). Towards germline gene therapy of inherited mitochondrial diseases. Nature, 493(7434), 627–631. https://pmc.ncbi.nlm.nih.gov/articles/PMC4377089/

Wu, K., Lu, Y., Tu, Z., Wang, Y., & Wang, X. (2023). Mitochondrial transfer into human oocytes improves embryo development and IVF outcomes in infertile women. Frontiers in Cell and Developmental Biology, 11, 1101329. https://pmc.ncbi.nlm.nih.gov/articles/PMC9917531/

Zhang, J., Liu, H., Luo, S., Chavez-Betancourt, D., Xu, P., Wang, Y., … & Huang, T. (2017). First live birth using human oocytes reconstituted by spindle transfer in a mother carrying a mitochondrial DNA mutation. Reproductive BioMedicine Online, 34(4), 361–368. https://www.rbmojournal.com/article/S1472-6483(17)30041-X/fulltext