One Kid, Three Biological Parents: A New Stage in IVF

The UK Department of Health has reviewed the three person IVF technique and roundly supported its use to prevent mitochondrial disease in newborn children. A number of details must be addressed prior to sending the plans to Parliament, but this is a huge step forward towards legalizing this promising form of IVF. Hopefully the FDA will follow suit.

Among the recommendations sent to Parliament is a suggestion that each application is evaluated on a case by case basis by the Human Fertilisation Embryology Authority. This check will be in place to prevent the technique from being misused and, hopefully, will help limit the concerns about the slippery slope to "designer babies." A concern that I'll stress is, at this point, completely unfounded.

One Kid, Three Biological Parents: A New Stage in IVF

An experimental medical procedure in which a woman's eggs are combined with both donor sperm and a female donor's mitochondria has brought the eugenics debate back into 2014. Has science crossed a line with three parent in vitro fertilization?

Let's start with a quick biology lesson. Mitochondria are the powerhouses of the human cell, in charge of some basic cellular functions including converting oxygen to energy. Each mitochondria contains its own unique mitochondrial DNA. Your nuclear cell genes determine your genetic characteristics and are a split between your biological parents, but the DNA contained in mitochondria is all mom.

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Women's eggs contain hundreds of thousands of mitochondria that randomly distribute into a developing embryo. Mutations in mitochondrial DNA are responsible for a wide variety of medical conditions with varied severity depending on the mutation, where the mitochondria are located, and the proportion of mutated mitochondria.

In 1996, researchers pioneered an early version of this procedure as a means of treating infertility. A woman's eggs were injected with both sperm from a donor and cytoplasm/mitochondria from another woman's egg. There was a chance that the fetus would inherit either the biological mother's or the cytoplasmic donor's mitochondrial DNA. In the case of the first known successful birth from this procedure, no third party DNA was found in the patient's daughter. In two other cases, a third individual's DNA was found in the children's cells. The term for this is "crossing the germ line" and many scientists, ethicists, and medical professionals are wary of its potential.

There is no evidence that the cytoplasm injections actually treated infertility, but it did work for some women and that reinforced the idea that it may be a miracle cure. The premise is not unreasonable - as we age the mitochondria in our cells are less efficient and replacing older mitochondria with those from younger donors may give the eggs a jolt. In spite of that, there is no foundation for this belief - the fact that it worked with several women is anecdotal, not data. The FDA stepped in and rejected approval of use of a third person's cytoplasm as a part of IVF treatment based on a lack of evidence regarding the procedure.

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Eighteen years later, two groups are seeking approval for clinical trials for a new procedure, mitochondrial-replacement therapy. In this case, the nuclear DNA of one cell (the egg of the biological mother) is paired exclusively with mitochondria from a donor's cell. Germ lines are officially and intentionally crossed. Unlike the initial procedure, intended to help with infertility, this new procedure aims to prevent diseases caused by mutations in mitochondrial DNA. Mitochondrial diseases are incurable and can affect any organ system in our body. Scientists are hopeful that they have determined a way to insure that these heritable diseases are not passed along.

Researchers have created a viable three parent embryo, but have not yet crossed the line to implanting one into a woman. The question is whether this modification will "violate the child's right to an open future." In Britain, the national law prohibiting altering the germ line will be reviewed later this year. A few months ago, the FDA met to assess the feasibility of clinical trials in the US. This is a turning point in the field of genetics. Scientists are seeking government approval to create a child with the heritable DNA of three biological parents.

We're left with several lines of thought, reminiscent of the debate when test tube babies debuted nearly four decades ago. The first is that this is unneccesary medical intervention. There is no requirement for women to reproduce using their own nuclear DNA and women with mitochondrial disorders could easily adopt or use donor eggs. The second is that having a medical disorder does not and should not eliminate woman's desire or right to have biological children. The third is the oft mentioned slippery slope - does this lead us towards designer babies? The term eugenics has been bandied about. Are we wholesale eliminating humans who suffer from certain diseases, deciding that they have no place in our world?

Things are also tricky from a medical ethics standpoint. Any ill effects of this experimental procedure will be borne by the children resulting from the pregnancy. If the child is a girl, her future children will also face these unforeseen risks. That's a hefty decision to make for generations of offspring. Why are we potentially putting the health of future children at risk in the name of personal desire and social mores? You're enrolling unsuspecting humans in a study that could radically affect their lives. The procedure may start on an embryo but, ideally, that clump of cells is going to grow up. Then what?

At this point in time, mitochondrial replacement will not guarantee any specific traits in offspring. There is no evidence that it will confer any advantages. The sole intent of this procedure is to eliminate mitochondrial disease. Yes, it crosses the germ line and creates children with three different sets of DNA, but it does not modify their genetic characteristics. The truth is, we've been mucking around with children's' genetics on a smaller scale for years now. It's when you choose a sperm donor based on ideal characteristics. When women have babies before the age of 35 because they know it reduces risk. When we avoid certain medications during pregnancy because they may permanently alter a fetus' development.

Men and women have been taking actions to protect their offspring's development for centuries. This is a lot more complex, but conceptually I'm not sure it's really that far off. That's conceptual though. There's a world of difference between the idea and the implementation. The discussion about this procedure is, at this point in time, largely academic and ethical. We don't have enough medical evidence to really know the risks of the procedure. Should that keep medicine from moving forward?

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We are in danger of allowing the sensationalist side of popular media to construct the dialogue around these issues. Divorced from science, this story boils down to emotions, religion, and personal beliefs. That is a dangerous path that 16 years ago brought us the anti-vaccination movement. If mitochondrial transfers are found to be safe and effective, dismissing it simply because of concerns about crossing the germ line is incredibly shortsighted. Dismissing it due to concerns about future generations is not.

Embryos created through this technique are undeniably genetically modified human beings. That's in the literal sense of the term, not in popular culture's superhuman, science fiction, dystopian future use. History teaches us that when the FDA delivers its decision, the media and the public will split into camps with a focus on either the present benefits (a miracle cure for infertility) or the future ramifications (genetically curated children) of mitochondrial replacement therapy. I'll let you guess which news organizations will choose which perspective. Here's hoping some actual science will be tossed into the mix.