In the last year there has been a push in both the United Kingdom and the United States for permission to create children with three genetic parents. This technique, often called mitochondrial replacement (MR), is presented as a simple switching out the mitochondria in the eggs of women with mitochondrial disease. We inherit all of our mitochondria from our mother, so a woman with mitochondrial disease cannot help but pass that onto her offspring.
In reality, the technique is far from simple. The nucleus of a donor egg is removed and replaced with the nucleus of the woman with mitochrondrial disease. This creates a genetically-engineered egg where the mitochondrial DNA (mtDNA) in the cytoplasm of the egg is from the donor and the nuclear DNA, the chromosomes we all learned about in biology, is from the woman with the mitochondrial disease.
The embryos created with IVF using these genetically-engineered eggs have the nuclear DNA of a woman and a man, like all other embryos, but would also have the mitochondrial DNA of the woman who donated the egg. These children would have the genetic material from three individuals.
In addition, these genetically-engineered children, well at least the girls, could not help but pass this engineering onto their offspring. This is a modification that would affect generations.
In the UK, the Nuffield Council on Bioethics, the Medical Research Council and the Wellcome Trust all came out in favor of pursuing the technique saying that because the chromosomes were unaltered, mitochondrial replacement was analogous to “replacing batteries in a camera” and would have no effect on other traits in the children.
Also, there are suggestions that sex selection be used in conjunction with MR. If all the female embryos are tossed out and only male three-parent embryos are transferred to the womb, then the modification will not be passed on to further generations because only women pass on their mitochondria. This is would be a fail-safe in case some defective mitochondria hitch a ride with the nucleus into the donor egg or something else goes wrong.
During all of this debate, I have wondered where is all the data to suggest that this technique is safe. There is a delicate balance of signals between mtDNA and nuclear DNA. Where is the evidence that replacing mtDNA has no ill effect? How can we even be discussing moving forward with this kind of human genetic engineering unless it has been shown to be safe in generations of animal studies? Where are those studies?
A recent paper in Science exposes the reality that there is little data on this technique and the data we do have suggests that MR is not just like “replacing batteries.”
So far the only primates created with this technique are four macaques that have only reached 3 years of age. Other animal models show that in males, a mtDNA-nuclear DNA mismatch has some serious effects that may not be apparent until adulthood:
Studies on model organisms, ranging from mice to fruit flies, indicate that MR can profoundly change the expression profiles of nuclear genes and affect a range of important traits such as individual development, cognitive behavior, and key health parameters. These studies also suggest that males of reproductive age are particularly sensitive to MR-induced effects….
Altered respiratory metabolism and reduced performance, learning, and exploratory capacity in males were reported when mitochondrial-nuclear genomic interactions were experimentally mismatched….
Two points may deserve careful consideration prior to any change in legislation. First, studies in humans have only tracked health through to the blastocyst stage and in macaques to 3 years of age. The results from mice and invertebrates suggest that many deleterious effects of MR would not be revealed until adulthood.
So here is the reality: many are willing to move forward with this technique in humans when 1. there are no primates created with this technique that have reached adulthood or even had another generation and 2. it is clear that mtDNA does have an affect on the nuclear DNA and a mismatch between the two could have serious effects that may not be apparent until later in life.
CLICK LIKE IF YOU’RE PRO-LIFE!
This would be pure human experimentation with little or no regard for the people who are being experimented on.
So I ask: When will it be enough?
At what point will we stand and say, “No more unethical experimentation on the next generation!”
When will we turn to parents and say, “Sorry but your desire for a child does not trump the health and safety of that child.”
When will we turn to academics in their Ivory Towers and ask them why they have such little regard for the health and well-being of future children?
I would say now is a good time.
