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Three Parent Babies

In this series of articles, medical students from across the country will discuss a range of topics from medical ethics to the NHS to public health to medical conditions to clinical governance.

The world’s first ‘three-parent’ baby was born in 2016 to treat a couple’s infertility issues. This controversial technique allows parents with rare genetic mutations to have healthy babies and has only been legally approved in the UK. This technique is widely used to ensure mitochondrial myopathies aren’t passed down from mother to offspring.

When do we use three-parent baby IVF?

The basic principle of this procedure is that a mother who has passed on a mitochondrial disease can have a child, free of mitochondrial cytopathy if healthy mitochondria from another female are used. This means the child would have 3 parents and so, the procedure is also often referred to as 3-person IVF. These diseases are caused by mutations in mtDNA (mitochondrial DNA) and usually, the most impacted organs are those that use high amounts of ATP such as muscle and nerve tissues. These diseases are inherited in a non-Mendelian fashion. This is because an offspring only inherits their mother’s mtDNA found in the cytoplasm of the egg cell. This mode of inheritance is known as matrilineal i.e. it does not follow any of the autosomal/sex-linked inheritance patterns. These diseases, can therefore, only be passed down by the mother, and are passed down to all offspring, regardless of sex. Note that the offspring of an affected father will be normal since the sperm does not contain cytoplasm and by extension doesn’t contain mtDNA.

What is the three-parent IVF process?

There are various methods by which three-parent IVF is made possible. The one legalized in the UK is known as pronuclear transfer. It involves fertilising both the mother’s egg and a donor egg with the father’s sperm. Before the fertilised eggs start dividing into early-stage embryos, each nucleus is removed. The nucleus from the donor’s fertilised egg is discarded and replaced by that from the mother’s fertilised egg.

However, in the first application of this technique, the parents were Muslim and were opposed to the destruction of two embryos. So the doctor took a different approach, known as spindle nuclear transfer. In this process, the nucleus from the egg with faulty mitochondria is removed. It is then inserted into the donor mother’s anucleated egg. This new egg cell will now have the nucleus from the original mother, and healthy cytoplasm from the donor mother. The egg cell is then fertilized by the father’s sperm in vitro and implanted in the original mother. In this way, the embryo will be free of any mitochondrial disease.

The Ethics Behind Three-Parent Babies

One of the main arguments against this process is that it isn’t well-tried enough so we don’t yet know any future risks that the procedure may pose. The last time we tried to make three-parent babies was in the 1990s when mitochondrial DNA from a donor was injected into another woman’s egg, along with sperm from her partner. Two of the fetuses developed genetic disorders, and the technique was halted by the US Food and Drug Administration. The problem may have arisen from the fetuses having mitochondria from two sources.

Further, the new egg cell will contain 99% mother’s DNA and 1% donor DNA - which may seem like a small amount - but will be passed down generations. Altering one person’s mtDNA may alter their DNA and cause other genetic diseases and may also change characteristics of entire lineages. Changing an embryo in this way could pave the way for ‘designer babies.’ That is, children could be selected for particular prized features such as blue eyes, blonde hair or high IQ. In fact, scientists in Sweden recently began using a powerful genetic cut-and-paste tool known as CRISPR to edit healthy embryos. Those researchers did not let the embryos mature past an early stage of development, but similar techniques could, in theory, be used to design babies that have particular traits.

However, proponents of this technique quote the medical ethics pillar of beneficence i.e. the health care provider’s duty to benefit the patient, as well as to take positive steps to prevent and to remove harm from the patient. By preventing fatality due to mitochondrial myopathies, proponents claim they are saving lives which should be regarded above all. Further, the first doctor to conduct this procedure also implanted a male embryo so as to prevent any further mtDNA inheritance to make this procedure as ethical and safe as possible - even for future generations.

Summary

Three parent IVF is used to prevent the inheritance of mitochondrial cytopathies (through mtDNA) from mother to child.
Pronuclear transfer and spindle nuclear transfer are 2 ‘three-parent IVF’ methods currently being used.
Three parent IVF involves the nucleus of the mother’s egg, cytoplasm from the donor’s egg and sperm from the father.
There are various ethical issues that arise from three-parent IVF. Some of these include the future of genetic editing, its safety, and the doctor’s ethical duty of beneficence.