How is a baby born? Biology tells us that the father’s sperm (containing his genetic material) enters the mother’s egg cell (containing her genetic material) and upon fertilization an embryo is formed and in time the baby is born.
But note, the mother’s egg cell has one minor, but important component called the mitochondrion (mitochondria in plural; from the Greek mito meaning threadlike and chondrio meaning granular). These are bacteria-like cells that have colonized fungal, plant and animal cells since a billion years ago, and act not as parasites but symbionts. They help in taking our metabolic path to completion by oxidizing the food molecules we eat and generate energy. Indeed, without mitochondrial help, the efficiency of converting food into energy would be far less. They add the extra steps, using oxygen for “burning” the molecules and increasing energy production almost a dozen-fold. In addition, they also interact with the ‘host’ cell machinery, helping in signalling and coordinating several molecular events there. Mitochondria are thus often referred to as cellular powerhouses.
The mitochondrion comes with its own genetic material, which it does not share with the DNA contained in nucleus of the host cell that houses it. Autonomy is maintained in this collaborative living together. An important point to note here is that the developing baby inherits its mitochondria from the mother — from her egg cell which contains mitochondria.
The father simply injects his genes through the sperm. (Sperm cells do have mitochondria in their tails, powering the speedy movement of the sperm. But when the sperm enters the egg, this tail with its mitochondria is discarded). Mitochondria are thus an exclusive maternal gift to the baby.
What if her mitochondria had defects? She would then pass them on to the child. Indeed, it is estimated that one in 6500 babies born in UK (and 1 in 4000 in the US, no data in India yet) have mitochondrial disorders such as liver and heart disease, respiratory problems and so forth. How does one solve this problem? Should we repair them or replace them? With the technology currently available, it would be easier to replace than repair.
Why not remove the defective mitochondria from the mother’s egg, replace them with healthy ones from a donor lady who is willing to offer her egg cells or embryo? This way we have the genetic or nuclear mother (who passes on her genomic DNA to the baby) and the ‘mitochondria mother’ (who has donated healthy cellular powerhouses). Now when the sperm of the father-to-be enters and fertilizes the modified egg, the baby has three ‘parents’: the geno-mom, the mito-mom and the geno-dad.
How can this be done? In much the same way as the sheep Dolly was produced by Dr Ian Wilmut in 1996, or the first test-tube baby Louise Brown was born using in vitro fertilization (IVF) method of Dr Edwards in 1978.
Take the nucleus of a lady carrying defective mitochondria and transfer it to the egg cell of another lady who has healthy mitochondria, but before doing so remove the nuclear material from the egg-donor lady. This way the genetic material (genomic DNA) of the baby-to-be will be from the first lady while the egg donor simply offers her mitochondrial genes — and not her nuclear genetic material. This hybrid egg is now fertilized in vitro using the sperm (and thus the genomic material) from the father-to-be through the now conventional IVF method.
Such three-parent babies are now a reality. UK has given the go ahead a few months ago for clinical trials and is also drafting regulations covering the safety, efficacy and the ethical and societal aspects involved in such a method.
The Food and Drugs Administration (FDA) of the US has just convened a meeting to consider the biological, ethical and legal issues involved in this technology.
What are the scientific issues? Among several, let us focus on one. We are still not sure whether the imported ‘new’ mitochondria work seamlessly with the host cell machinery in the same manner as the original (albeit defective) ones did. This issue of compatibility needs to be understood. Work by Dr. Mitalipov of the Oregon Health & Science University at Beaverton, OR, USA on rhesus monkeys suggests no difficulty on this score.
These three-parent-monkeys are now four years old and healthy. Clinical trials on a few chosen humans will help us understand if this works as safely with us as well.
What are the ethical and legal issues? The Nuffield Council on Bioethics, UK concludes that if this novel technique is proven to be safe and effective, it would be ethical for families to use the method in order to help the child. It also concludes that “mitochondrial donation does not indicate, either biologically or legally, any notion of the child having either a third parent or a second mother”.
In other words, the phrase “Three Parent Baby” might be a misleading one. I wonder what Indian society has to say on this. We have welcomed IVF but banned human cloning (a decision which is both socially and ethically sound and sagacious).
A sentence in the above article read: “ … the first test-tube baby Louise Brown was born using in vitro fertilization (IVF) method of Dr. Edwards in 1968.” The year should have been 1978. It was corrected