Lawmakers in the UK voted to approve a law that will allow 3-parent in vitro fertilization. How? Why? Does the genetic material of all three parents impact who the baby becomes? And what are the ethical implications of this new method of "playing God?"

HOW

The technique is simple. Take the nuclear DNA out of one mother's egg cell, and then fill up the nucleus with extracted nuclear DNA from another mother. Add sperm, and voila: an embryo forms. (These steps could also take place with donor and recipient embryos rather than donor and recipient eggs). These are simple words to describe an exactingly precise technological advancement!

Remember, the nucleus contains most of a cell's genetic material. But cells also have mitochondrial DNA, or genetic information encoded in the tiny mitochondria, the "power plants" of the cell that take in nutrients and produce energy*. Thus, the "non-nuclear" mother will be contributing organelles, cytoplasm, and mitochondrial DNA**; the "nuclear' mother contributes the majority of the maternal genetic material; and the father contributes his normal share of genetic material absent from cytoplasm, organelles, or anything else useful.

WHY

This pioneering method of in-vitro fertilization was developed due to a mitochondrial disorder that is relatively common in the United Kingdom (1 in 6,500 babies) and leads to symptoms such as heart disease, blindness, and muscular dystrophy. If an affected mother still wants to have her own genetically related children, she can "borrow" the egg (and thus, mitochondria) from another mother, donate her own nuclear DNA, and use sperm from her partner or desired father.

WHICH PARENTS DETERMINE "WHOM" THE BABY BECOMES?

Traditionally, we have understood that "who we are" comes from our DNA. However, we are now realizing that the way DNA translates into personality and behaviour is exceedingly complex, and is regulated and shaped by a vast number of things (including environmental experience!). So the million-dollar question is this: would the mitochondrial DNA from the donor mother impact who the baby becomes?

Many have correctly noted that the amount of mitochondrial DNA is far less that nuclear DNA. However, recent research demonstrates that, in beetles, mitochondrial DNA directly affects beetle personality. How??

Mitochondrial DNA exerts epistatic control over nuclear DNA. "Epistasis" refers to a process whereby one gene's expression depends on the presence or absence of other "modifier" genes. So, for example, mitochondrial DNA interacts with nuclear DNA in the context of aging; impaired mitochondrial DNA function can have cascading effects relating to longevity.

Similarly, mitochondrial DNA and its interaction with nuclear DNA directly affect metabolism and growth rates. In beetles, mitochondrial variation correlates significantly with personality variation (for example, how bold or shy a beetle is); again, this is because mitochondrial DNA affects the expression of nuclear DNA.

Thus, in conclusion, there is no question that all three parents would contribute to "whom" the baby becomes. The majority of DNA comes from the two primary parents, but we can't ignore the effect of mitochondria in modulating personality and behavioural development.

ETHICAL IMPLICATIONS

As with any other in-vitro fertilization technique, protesters maintain that we should not be playing God. However, does this go a step farther than past technologies by introducing a third parent, and by requiring embryo destruction?

Some would argue that this contributes in a hugely positive way to ethical debates. Most obviously, women affected by mitochondrial disorders now may be able to safely have children that are genetically their own. Perhaps in the future, same-sex female couples can have children with some elements of both of their genomes-- nuclear from one, mitochondrial from another.

But as one Wired journalist writes,

"Mitochondrial replacement IVF (mtIVF) is not a treatment for an individual with a mitochondrial disease; it is a method for creating a new person with healthy mitochondria. The only circumstance in which this technology will be used is if a woman knows that she has a mitochondrial mutation, and so chooses not to risk creating a sick child, but instead creates a different, healthy child.

That means that there would not be a single person who would otherwise have been sick, and who will, as a result of the technology, be healthy. Nor would there be anyone alive who otherwise would have died. There will simply be different people born."

The title of his article?

"Don't make a three-parent baby. Adopt instead."


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*For those who wonder why mitochondria have their own DNA, the answer is somewhat amazing: back when our tiny eukaryotic ancestors were evolving, bacteria (prokaryotes) with their own DNA probably infiltrated the eukaryote cells to filch nutrients, acting as parasites. But then the relationship evolved into one that was beneficial to both parties, so those little prokaryotic bacteria became part of the larger organism, serving important roles within our cells. In short, those single-celled bacterial parasites that invaded our ancestors were, in turn, ancestors of our very own mitochondria!

**The other great thing about mitochondrial DNA is that it is passed on only from mother to child. This means that we can do awesome ancestry studies, such as this study of domestic horses that found that all domestic horses arose from 77 ancestor mares, give or take.

Many thanks to Zak Kaplan for intriguing discussions on this topic!