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Fact about three-parent babies
Preventing a disease that can be passed down for generations would be ethical as long as it proves to be safe.
-Arthur Caplan
In recent times, a majority of the population leads a sedentary lifestyle. This, coupled with problems associated with stress, food and water contamination, pollution, and addictive habits (smoking, drinking,etc), has led to the increased prevalence of issues such as infertility and genetic health disorders. These issues have had a major impact on human reproductive health. However, recent advancement in the field of medical sciences has led to the development of several novel techniques and methodologies related to human reproduction and health. Collectively, they are known as assisted reproductive technology (ART). It is used to achieve pregnancy or conception via procedures like artificial insemination, fertility medications, in vitro fertilization, and surrogacy.

In vitro fertilization (IVF) is the most commonly used method to deal with infertility and concerns related to inheritable diseases. IVF is used not only to establish successful pregnancies but also to screen the viable fetus for genetic disorders. This screening is called pre-natal or pre-implantation genetic diagnosis. It involves studying the genome of the zygote and establishing whether the offspring will develop any health disorder. In many cases, the parents often have a history of some grave genetic disease, and wish to confirm its presence/absence in the fetus. This technology helps in selecting the zygotes with the minimum chances of developing the disorder, and then implanting these zygotes in the uterus for the progression of pregnancy. However, there are a few disorders that cannot be evaded by such means. These disorders are health defects that arise due to the presence of faulty mitochondria. They are comparatively tough to resolve since genetic disorders can be evaded to a certain extent by the random selection of one parent's healthy genes over the other parent's mutated genes, but this is not so in the case of mitochondrial disorders as all progeny inherit only the mother's mitochondrial DNA (in the process of fertilization, the father only contributes his genetic material).

Hence, if the mother's mitochondria are dysfunctional, her progeny will have dysfunctional mitochondria as well, which would be exhibited in the form of myriad genetic and health disorders. To overcome this, a new technology has been developed, which is called mitochondrial donation, and it results in a three-parent baby, i.e., the baby exhibits three genetic parents.
Mitochondrial Donation
blue-mitochondria
In cases where the mother possesses faulty mitochondrial DNA, a specialized form of IVF is utilized so as to introduce mitochondrial DNA from a third party (another woman) into the zygote. Such a transfer of foreign mitochondrial DNA ensures that the offspring does not suffer from mitochondrial disorders.
Since the mitochondrial DNA is introduced in the zygote, as and how the zygote develops, each cell of the offspring's body will possess the same mitochondria, making it a germline modification. Future progeny of this offspring (if female), will also possess healthy mitochondria. This also causes the offspring to possess three distinct genetic parents. The mother and father provide the genetic material in the form of ovum and sperm, respectively, and the donor female provides the mitochondrial DNA, in a process called three-parent in vitro fertilization (TPIVF). This technique helps in averting diseases like diabetes mellitus, deafness, Leigh syndrome, etc.
Methods Involved
This process can be carried out in two ways: pronuclear transfer (PNT) and maternal spindle transfer (MST). According to research studies involving primates and mice embryos, scientists claim that PNT may exhibit an increased risk for inadvertent transfer of faulty mitochondria along with the genetic material, but MST shows an increased risk of chromosomal abnormality. This indicates that both techniques have drawbacks of their own, and it is difficult to discern which technique is better. Hence, in case of people opting for TPIVF, the technique to be used differs on a case to case basis.
Pronuclear Transfer
◆ In this method, the maternal (patient) egg with abnormal mitochondria and the donor egg with the normal mitochondria are both separately fertilized with the paternal (patient's partner) sperm. This leads to the formation of two zygotes with a pronuclei in each (fused male and female genome). Then, the donor zygote is enucleated, i.e., the pronucleus is removed and distracted. At the same time, the pronucleus from the patient's zygote is removed and is introduced into the donor zygote with the normal mitochondria. This zygote is then allowed to progress and develop as an embryo, and is transferred to the maternal uterus after cleavage of the zygote is initiated.
Maternal Spindle Transfer
◆ In this method, the spindle and associated chromosomes are removed in the form of a karyoplast from both the maternal (patient) egg with abnormal mitochondria and the donor egg with the normal mitochondria. The karyoplast of the donor is discarded, and that of the patient is introduced into the enucleated donor egg. Once the reintroduction of karyoplast is successful, the egg is fertilized via administering an intra cytoplasmic sperm injection (ICSI) using the paternal (patient's partner) sperm. Once the egg is fertilized and the zygote initiates the stages of cleavage, it can be transferred to the maternal uterus, where it develops into a healthy fetus.
Ethical Issues
► This technique involves the genetic modification of human embryos, and as such violates article 63 of the 2004 European Union Treaty, which is as follows:

In the fields of medicine and biology, the following must be respected in particular:

(a) the free and informed consent of the person concerned, according to the procedures laid down by law;
(b) the prohibition of eugenic practices, in particular those aiming at the selection of persons;
(c) the prohibition on making the human body and its parts as such a source of financial gain;
(d) the prohibition of the reproductive cloning of human beings.

► Approving such a procedure would be the critical event that initiates the descent of genetic engineering along the path of eugenics and designer/custom-made humans.

► The effects of mitochondrial manipulation are still unknown, hence it is impossible to predict the effect of the techniques. Some studies of this procedure in animals claim that no adverse effects were seen, while some others claim that the offspring exhibited accelerated aging and/or cognitive decline.

► As with any technology, there is scope for abuse, and since the technology itself is not fully understood, one cannot gauge the true scope of abuse and use. This makes it difficult to ascertain whether the technique will prove harmful or beneficial in the long run.

► The procedure of egg/ovum extraction could have an adverse effect on the patient and the donor. The risks include bone ache, seizures, ovarian damage, etc.

► Since it is a germline modification, any error during the technique would create a long-lasting effect that would be heritable in nature.

► Mitochondrial and nuclear DNA mismatch could lead to a vast range of developmental problems such as infertility and cancer.

► The transfer of nuclear DNA from one egg to another might disrupt the epigenetic programming of the genetic material, causing it to function erratically, resulting in genetic dysfunction.

► Carryover of the abnormal mitochondrial DNA into the donor egg could result in causing the very diseases the technique was meant to prevent.

► Mitochondrial DNA does not merely function as the "battery" of our cells (metabolism), but has been known to influence the expression of certain phenotypic traits. Hence this technique may introduce errors in phenotype expression in the fetus.

► The child obtained via such a procedure may have an increased likelihood of suffering from an identity disorder, since its genetic makeup is different from that of its contemporaries.

► The three-parent child may not be able to donate or receive blood, bone marrow, or organs due to its unique genetic (triad) origins.

► The technique is new and experimental, and hence would have a high cost. This could lead to the formation of a divide between the wealthy parts of society that can afford it and the poor sections of society that cannot.

► The disparity in affording the procedure could also lead to the exploitation of poor females as donors. This could also increase the difference in health status between the rich and poor.

Recently in February 2015, the U.K. Government after extensive discussion with the Department of Health and Nuffield Council of Bioethics regarding the Human Fertilization and Embryology Act of 2008 (HFEA 2008), has approved the use of this procedure to produce three-parent babies. The approval will take effect from October 2015. This decision was greeted with enthusiasm and jubilation, as the prevalence of mitochondrial diseases in the British population is quite concerning. According to population surveys, at least one in 200 live births has faulty mitochondrial DNA and almost 100 to 150 births per year risk the passing of mitochondrial disease on to the child.