A Unique Drive to Genetic Parenthood: The Efficacy and Autonomous Decision Making of Mitochondrial Replacement Therapy

We were taught throughout biology that the mitochondria is the powerhouse of the cell, but did you know that faulty mitochondrial DNA can lead to diseases that are fatal? To resolve this issue, scientists have created a procedure known as Mitochondrial Replacement Therapy that utilizes DNA from three different people: the intended biological mother and father as well as donor (female). Along with this, an analysis of the drive to become a genetic parent, or the “biological imperative” to become a genetic parent is crucial. How strong is this drive? If it is solid, how can we meet this need while still using this therapy, if needed? Throughout this ethical dilemma, you will be questioning the priority of your own rights versus your potential child’s’ autonomy along with debating the ramifications of the therapy.




We were taught throughout biology that the mitochondria is the powerhouse of the cell, but did you know that faulty mitochondrial DNA can lead to diseases that are fatal? To resolve this issue, scientists have created a procedure known as Mitochondrial Replacement Therapy that utilizes DNA from three different people: the intended biological mother and father as well as donor (female). As an adolescent growing up in a society that is rapidly moving toward new technological advancements in reproductive sciences and methods, I thought that it was important to raise ethical questions around mitochondrial replacement therapy, a specific type of assisted reproductive technology that prevents the inheritance of fatal mitochondrial diseases. Along with this advanced procedure comes many ethical issues: the possibility of detrimental long term effects, different alternatives that offer various pros and cons, and making the best decision for your child and future generations. As we analyze the values and stakeholders involved with the dilemma at hand, how can we judge which procedure is the most effective and how can we value our child’s autonomy and make a just decision for them? All in all, Mitochondrial Replacement Therapy has significantly improved the quality of life of the offspring thus far; on the other hand, as we evaluate the procedure, how can we make sure that it is used ethically?  

I decided to explore the unique drive to become a biological parent and how Mitochondrial Replacement Therapy can affect genetic parenthood. In making this decision to have a genetic child, we must analyze the severity of the ramifications once the child is born. For example, when having a child without altering the mutated mitochondrial DNA, how is the child’s quality of life/lifespan affected? Conversely, if the decision is made to undergo an  mitochondrial replacement process driven by IVF, how would that affect the child, whether it be positively or negatively? Adoption is also a viable option other than mitochondrial replacement therapy or “natural” reproduction. It is imperative to analyze the ramifications for a child that does not have a biological parent versus one that does; for instance, the biological child will have access to important things like family medical history, and it is simply evolutionary understandable that we want to have a genetic child. On the other hand, the genetic child with the mitochondrial disease would pose vastly greater risks to the child.



While learning about how the therapy is implemented into reproductive sciences and its general process, it is important to first understand the true function of the mitochondria. The mitochondria, often called the “powerhouse of the cell”, is an organelle found in both animal and plant cells in which respiration and energy production (in the form of ATP) occur. This organelle is composed of many complex parts including the inner and outer membrane, the matrix, the cristae junction, and the intermembrane space. The inner membrane is home to the electron transport chain (ETC), which is a key step in cellular respiration and the formation of ATP. On the other hand, the outer membrane is the entrance to the mitochondria. Like the cellular membrane that surrounds the overall cell, it is selectively permeable to directly allow small proteins to enter and indirectly allow larger proteins to enter through the protein complexes. Next, the matrix is a gel-like material found inside the mitochondria. It functions during cellular respiration and is located specifically where the citric acid cycle takes place. The cristae junction is the small fold in the inner membrane of the mitochondria. These folds increase the area of the inner membrane and expedite the formation of ATP. Lastly, the intermembrane space is the space between the inner and outer membrane of the mitochondria. There is no significant function of this space besides for being a barrier between the two other parts. Inside of the complex mitochondria is the organelle’s very own set of DNA, which contains thirty seven genes that are completely unique to this organelle, separate from Nuclear DNA. Thirteen of these genes include instructions that create enzymes and the remaining twenty four genes provide instructions for creating transfer RNA (tRNA) and ribosomal RNA (rRNA), which both assist in the protein building process. On another note, mitochondrial DNA (mDNA or mtDNA) is heritable, meaning it is passed on from generation to generation. If there is an problem in the mDNA, it is important to fix the issue or else there is a giant risk that the mutations will be passed on to the affected organism’s offspring, causing severe repercussions including damage to the heart, other important muscles, and the brain. These mitochondrial diseases can result from either inherited or even spontaneous mutations in the mDNA which lead to altered functions of the proteins or RNA molecules that normally reside in mitochondria. We need our mitochondria in order for us to function properly because they produce large amounts of ATP, or energy, that we need to survive. For example, the mitochondrion located in our muscle cells are imperative because they require large amounts of energy to keep our bodies moving. Problems with mitochondrial function, however, may only affect certain tissues as a result of factors occurring during development and growth that we do not yet understand. Even when tissue-specific isoforms of mitochondrial proteins are considered, it is difficult to explain the variable patterns of affected organ systems in the mitochondrial disease syndromes seen clinically. Specifically, some symptoms of mitochondrial diseases include seizures, cardiac arrest, loss of motor control, visual and hearing problems, and more.

It is very important to understand that these mitochondrial disease come from only the mother’s DNA, and not the father. The general procedure of Mitochondrial Replacement Therapy is designed to prevent the transmission of mitochondrial DNA diseases from mother to child, which can lead to a premature death. The third parent or the donor must be female in order to replace the female’s faulty mitochondrial DNA.

Although there are many different ways to undergo the therapy, the two primary methods used to replace the mitochondrial DNA are maternal spindle transfer and pronuclear transfer. “In maternal spindle transfer, the nuclear DNA of a donor egg is removed, leaving the healthy mitochondria, and replaced with the nuclear DNA from an egg from a woman with mitochondrial disease. This cell is then fertilized and implanted into the mother in the same way IVF is currently carried out. Pronuclear transfer involves a similar procedure as maternal spindle transfer, however the egg is fertilized first, then the fertilized nuclear DNA, or pronucleus, is transferred to a healthy donor egg (which has had it’s nuclear DNA removed, leaving healthy mitochondria). This egg is then implanted in the mother in the same way as in maternal spindle transfer. Research on both techniques is ongoing, and potential advantages of one technique over the other are being considered. For patients with mitochondrial diseases, this means that these two methods could prevent the transmission of faulty mitochondrial genes to children” (The New York Stem Cell Foundation Research Institute).



In making this important decision that can vastly impact a life and even a generation, identifying the stakeholders and the values that will be used to choose an outcome are crucial. The two ethical values that I zeroed in on throughout my project were accountability and autonomy. With accountability, understanding the effect that undergoing or not undergoing the procedure will have on future generations is imperative in this situation. One major question that I considered was who should or should not hold this responsibility to make the decision? Why or why not? With autonomy, thinking not only about your needs, but also the future offspring (they would not want to suffer with mitochondrial issues, or on the flip side with the potential long term effects of the procedure) is also important. The big idea in this situation is the concept of the “right to an open future”, or the idea that we shouldn’t make incredibly drastic decisions for a future generation that doesn’t have the chance to consent to such decisions or not.  Additionally, another critical aspect of this dilemma is accessibility, although it is not recognized as a key value. Accessibility is important in this scenario because the price of the therapy only gives the very wealthy access to the therapy, which is not entirely fair in my opinion. Since mitochondrial diseases are fatal, in my perspective, it is not just for only some people to have access to this therapy. In other words, everyone should have the opportunity for a quality life. This argument can drag countless values into the dilemma, which shows how relevant each and every value is in making this significant decision.

In this dilemma, there are five major stakeholders: the intended mother, the intended father, the female donor, the potential child, and the in-vitro fertilization doctor and each are affected in some different way. For example, the intended mother and father are heavily affected by the decision that they make: whether or not to have a genetic child. This decision may be influenced by the opinion of the doctor (a medical professional). He or she will eventually make the chief decision based on the safety and efficacy of the procedure. Next, the donor’s role also depends on the decision made by the parents and the medical professional, so she will only be involved if they choose to undergo mitochondrial replacement therapy. Lastly, the child’s role in the situation also depends on the situation the parents and the doctor make, so those are clearly the three most important stakeholders in the dilemma.



Within the umbrella topic of mitochondrial replacement therapy, there are three specific ways to complete the procedure: maternal spindle transfer, pronuclear transfer, and polar body transfer.

Maternal spindle transfer is the most common method when it comes to mitochondrial replacement therapy. The nuclear chromosomes that are grouped in a spindle formation would be removed from both an eff provided by a woman with non pathogenic mDNA and the intended mother’s egg. The intended mother’s egg, containing mutated mDNA, would be discarded. The offspring would be genetically related to the donor the procedure goes on. Pronuclear transfer is a bit different, because both an oocyte provided by a woman with the non pathogenic mDNA and the intended mother’s oocyte would be fertilized with sperm in vitro, creating two zygotes. Lastly, the most uncommon method is polar boyd transfer, which includes polar body transfer one and polar body transfer two. In PB1T, the intended mother’s first polar body would be transferred to an oocyte provided by a woman with non pathogenic mtDNA from which the mtDNA had been removed. The reconstructed oocyte would then be fertilized, grown, tested, and transferred. In PB2T, both the intended mother’s oocyte and an oocyte provided by a woman with non pathogenic mtDNA would be fertilized.

Additionally, other alternatives to in-vitro fertilization include adoption or surrogacy. Although some may not feel this unique drive to become a genetic parent, it may still be out of the question for some families based on accessibility and finances. It is important to consider the cost of the mitochondrial therapy versus the cost of adoption or surrogacy, because in some cases it can be more expensive.



Three Parent Babies are almost exactly the same as they sound– combining three different pools of human DNA, one male and two female, through MRT and in-vitro fertilization (in-vitro meaning in the lab). The majority of the DNA comes from the original mother and father, but a female donor’s mitochondrial DNA is used to replace the faulty DNA in the original mother. It is imperative to screen the mitochondrial DNA donor carefully because the quality of this genetic information is a huge deciding factor in the quality of the child’s health.

Although the answer may be apparent for some families, there are many various pros and cons of mitochondrial replacement therapy. One of the obvious positives in a healthy baby post therapy. One the other hand, since the therapy was just recently legalized and implemented into reproductive sciences about two years, are there are possible long term effects that are negative? This one major question restrains many people from undergoing the therapy. As an advocate for the procedure, I believe that altering the mitochondrial DNA and increasing the longevity of the child’s life (with possible detriments) is better than allowing them to die prematurely, having a non-biological child, or not having a child at all. Another important factor in this decision making process is finance. For instance, should wealth, money, and/or status dictate your right to quality healthcare? Since this procedure is quite recent and definitely more expensive than typical in-vitro fertilization (15,000 dollars per cycle in New Jersey), is it fair that only an elite group of people can access this therapy?

The title of this group of three people has been under a lot of debate- should they be called “three parent babies” or “three person babies”? This argument brings a lot of legal issues into the picture; for instance, the label “three parent babies” implies that the female donor/”third parent” may be legally involved with the child after he or she is born. Conversely, the name “three person babies” can almost devalue the third donor, making them somewhat irrelevant to the equation. In my perspective, I believe that this group should be called “three parent babies”, considering that the donor’s genetic information is passed on to the child, technically making them a genetic contributor and to some, a parent.



In any bioethical dilemma, autonomy can be seen as one of the most important values because of how many ideals it encompasses- from basic human rights to tiny personal decisions. Throughout my project, I decided to focus on an analysis of rights between the mother and the potential child (and even future generations). Which right truly takes precedent over the other? The mother with a mitochondrial disease has three basic options for laboring a child without the same mitochondrial disorder: first of all, the mother could decide to have no biological children and adopt or use a surrogate instead. She could also undergo in-vitro fertilization with a  donor’s egg, meaning that the child would not be biologically related to her. Lastly, the could undergo in-vitro fertilization with a screening and a selection of the embryo with the lowest amount of or with the lowest probability of developing major problems. The mother has to consider a lot of different factors before making a solid decision whether or not to undergo mitochondrial replacement therapy. Although she has to consider the economics of the procedure such as the coat (over fifteen thousand dollars per cycle) and the effects that will have on her family, she also needs to think about what will be the best for her child. This may mean putting her child’s needs before hers. For instance, if having a biological child is important to her but having this child creates an unhealthy lifestyle for the offspring, is it really worth it to have that child? It is also important to consider that some of these defects due to mutations in the mitochondrial DNA may be fatal. Furthermore, the child’s rights are almost parallel to the mother’s rights. The child has a right to a quality life– if the mother decides to undergo the therapy, the child will not inherit the mitochondrial disease and be free of the symptoms that come with it. If the mother does not undergo the therapy, the child will inherit the disease and based on the severity of the symptoms, the child will either die during childbirth, very early on in his or her life, or suffer from an adult onset disease (something comparable to Huntington’s Disease). Lastly, the viable option of adoption also poses a few pros and cons; for example, if this biological imperative is especially strong for the parents, then this may not be something they want to do. On the other hand, it would eliminate the health risks that are linked to mitochondrial disease.



For some parents, there may be an instantaneous answer to this dilemma depending on a certain drive found inside of us, named “the biological imperative”, in this case, to have a child who is genetically related to you. The purely scientific definition of the biological imperative is “the needs of living organisms required to perpetuate their existence, or to survive”, and living organisms that do not attempt to follow or do not succeed in satisfying these imperatives are described as maladaptive; those that do are adaptive. For others, it may not mean anything to have a genetic connection to your child. Conversely, for many this motivation to naturally produce offspring is thought of an inherent, innate action that has been integrated into society; that people don’t think about it sometimes, it is just what is natural. This can spark a question: what do we consider natural or normal? Is mitochondrial replacement therapy or alternatives such as adoption or surrogacy considered not normal? In my opinion, with today’s rapidly changing society, nothing is considered “normal” anymore. The means in which you take to conceive a child are and should remain completely individualized, meaning they should not be based on social norms or what a majority of other parents are doing. I think that this so-called “biological imperative” potentially creates an unnecessary pressure on parents to undergo a certain conceiving method. For example, if some people frown upon adoption or surrogacy, would that affect your decision at all? Another important question to  bring up is- how was this imperative implemented into our society in the first place? This says a lot about humans and how difficult it is to make a universal change within our society. For instance, since conceiving naturally was the first means to birth a child, it was been set in stone as the “norm” since humans first walked the earth. This can implicitly say a lot about us as humans: although our world is changing quickly right before our eyes, there are still some behaviors that we practice that have been around since the beginning of time.



Overall, Mitochondrial Replacement Therapy is an up-and-coming procedure that will have a profound impact on future generations by eventually eradicating mitochondrial disease in humans. In weighing the most extreme alternative to the therapy, which would be to have a biological child with two parents, I have come to the conclusion that it is very ethical to undergo mitochondrial replacement therapy based on the principle of beneficence. The principle of beneficence states that we must do good through all of our actions and do our absolute best to prevent harm. This “absolute best”, in this specific case, would be to ignore this powerful biological imperative and push aside the significance of having a genetically-related child.

With the procedure being recently legalized in the United Kingdom on December 15 of 2016, our society seems to be rapidly moving forward with new in-vitro fertilization and other reproductive technologies. According to the UK Human Fertilisation and Embryology Authority (HFEA), “mitochondrial replacement therapy ‘can be used cautiously for risk reduction treatments in certain cases where alternative treatments would be of little or no benefit to mothers at risk of passing mitochondrial disease onto their children’” (Jama Network).

In this ethical dilemma, it is imperative to prioritize certain values over others. Although there were numerous factors that could potentially influence the decision for or against the therapy, zeroing in on the future child’s versus the parents autonomy is most important. In making this decision to put others before ourselves, we can see other values being followed and implemented as a result.


By Hannah Abere

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