Three parent babies

credits:geneticliteracyproject.com

This past February, after a year long debate the United Kingdom became the first country to legalize mitochondrial replacement therapy (MRT), also known as mitochondrial DNA replacement, which can be used to make “three-parent babies.”

Three parent babies have caught much attention in the year 2015 and Britain’s first such baby will be born as early as 2016.

The procedure has been developed by scientists at Newcastle University.

Advocates of the new procedure say around 2,500 women could benefit from mitochondrial donation in Britain, equating to around 150 births a year as one in 200 children born in the UK have some form of mitochondrial disorder.

Prof Doug Turnbull, Professor of Neurology, Newcastle University, said: “This is very good news for patients with mitochondrial DNA disease and an important step in the prevention of transmission of serious mitochondrial disease".

In this technique the nucleus of an affected woman's extracted egg is removed and is put into the enucleated egg of another woman, which contains her mitochondria. The child would thus be genetically related to three people, which is why the media often refers to "three-parent babies" or "three-parent in vitro fertilization."
 These techniques have been referred to with several terms, including "mitochondria replacement," "mitochondrial manipulation," "oocyte modification," "three-person embryos," "three-parent babies," and "nuclear genome transfer" (the most technically accurate).

Photo courtesy- The telegraph

The disease primarily affects children, but adult onset is becoming more and more common.
Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.

Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infectio.

It takes about 3000 genes to make a mitochondrion.  Mitochondrial DNA encodes just 37 of these genes; the remaining genes are encoded in the cell nucleus and the resultant proteins are transported to the mitochondria.  Only about 3% of the genes necessary to make a mitochondrion (100 of the 3000) are allocated for making ATP.  More than 95% (2900 of 3000) are involved with other functions tied to the specialized duties of the differentiated cell in which it resides.

The procedure can be carried out in one of the two ways.
1) maternal spindle transfer (MST).
2) pronuclear transfer (PNT).

Credits: The Guardian

The simpler of the two is called maternal spindle transfer (MST). First, doctors use standard IVF treatment to collect eggs from the mother. They then remove the nucleus from one of the mother’s eggs and transfer it into a healthy donor egg that has had its own nucleus removed. The reconstituted egg holds all of the mother’s healthy nuclear DNA, or 99.8% of her genes, plus the donor’s healthy mitochondria. This egg is then fertilised with the father’s sperm and the embryo is implanted into the woman like any other IVF embryo.

The second procedure is very similar. In pronuclear transfer (PNT), both mother and donor eggs are fertilised with the father’s sperm. Before the eggs have time to split into early-stage embryos, the chromosomes inside them are removed. Those from the donor egg are discarded, and replaced with the chromosomes from the mother’s egg. The resulting egg is fertilised and ready to grow into an embryo in the mother’s womb.

Critics of three-person IVF called this techniques as Slippery slope toward “designer babies " because of  the potential for in vitro fertilized eggs that are genetically engineered to have, for example, blonde hair, more intelligence, more increased athleticism.

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Little is known about the legal, psychological, and social ramifications for the child of three genetic parents.
Other Experts however, aren't convinced the leap from mitochondrial transfer to genetic trait modification is so direct.

Meanwhile, at the Salk Institute for Biological Studies in La Jolla, California, scientist have developed a gene-editing technique that may prevent mutated mtDNA from being passed down from mother to child.

This technique has been shown to be a success in animals it works by using DNA-cutting enzymes to delete mutated mtDNA, leaving healthy mitochondria intact. By reducing the amount of faulty mtDNA, it aims to restore the balance in favour of healthy mitochondria, reducing the amount of faulty mtDNA passed down to offspring to the point where it does not result in disease.

Debate among British and American scientists has just started.

References:

1. http://www.telegraph.co.uk/news/science/science-news/11386151/Three-parent-babies-the-arguments-for-and-against.html
2. http://www.popsci.com/uk-one-step-closer-using-dna-3-people-make-babies
3. http://www.theguardian.com/science/2015/feb/02/three-parent-babies-explained
4. https://www.geneticliteracyproject.org/2015/06/02/three-parent-babies-parent-3s-impact-may-go-beyond-mitochondria/
5. Britain is on the brink of a perilous vote for 'three-person in vitro fertilization', Marcy Darnovsky and Jessica Cussins, Los Angeles Times, February 8, 2015
6. Marcy Darnovsky, The New York Times, February 23, 2014