The United Kingdom has taken one step closer to creating children with three genetic parents. Last week legislation that will allow fertility clinics to conduct “mitochondrial replacement” in human embryos went into effect.
“Mitochondrial replacement” (MR) is a group of techniques that aim to genetically engineer embryos to be without certain types of mitochondria disease. Mitochondria are organelles in our cells that produce energy. They have their own DNA called mtDNA. We inherit our mtDNA, which is separate from the DNA in the nucleus of the cells, only from our mother. If a woman has a mutation in her mtDNA that causes disease, she cannot help but pass that on to her children.
MR techniques essentially create embryos with the genetic material from three people – two women and one man. In one MR procedure, a donor egg is emptied of its nucleus leaving healthy mitochondria behind. The nucleus of the woman with mitochondrial disease is placed inside and that genetically-engineered egg is fertilized with the father’s sperm.
MR is considered germ-line genetic engineering because any girl conceived with this technique will pass this modification onto her offspring. Germ-line genetic engineering is illegal in the UK. Earlier this year, Parliament voted to allow MR in fertility clinics despite that ban on germ-line genetic engineering. Last week that change took effect. The Daily Mail reports:
Doctors are close to making the first baby with three parents following a historic change in the law.
Legislation that comes in force today makes Britain the first country to sanction the creation of children that effectively have two genetic mothers and a father.
It allows doctors to use a complex form of IVF to prevent devastating illnesses caused by faults in mitochondria – the tiny ‘engine rooms’ that power the cells in the body.
The technique, which was developed at Newcastle University, involves swapping a mother-to-be’s diseased mitochondria with healthy ones from an egg donated by another woman.
Supporters say it will allow families blighted by an incurable disease the chance of having a healthy child.
The regulatory body that controls the fertility industry, the Human Fertilisation and Embryology Authority (HFEA), has yet to grant licenses to perform MR, but the government has now paved the way for the HFEA to approve the procedure.
While the goal of MR is to “treat” disease and alleviate suffering, it is morally problematic. Not only is it germ-line genetic engineering that will affect generations, but this techniques shares much with cloning which we know causes major birth defects in animals.
The comments on the Daily Mail story have a disturbing theme. Those that support MR basically think anyone who opposes it is a knuckle-dragging idiot that is ignorant about basic science. Proponents argue that mtDNA is only 37 genes – tiny when compared to the rest of our genome – that are entirely separate from the DNA in the nucleus and so these genes have no effect on the traits of the individual. Supporters also insist that changing out mitochondria is just like changing out a battery. No big deal. One commenter confidently asks sceptics, “How do you feel entitled to an opinion when you clearly know very little on the topic?”
It is clear to me that it is the proponents of MR that know very little about mtDNA and the possible ill effects of this technique. Paul Knoepfler is a stem cell researcher at University of California Davis, and he is a vocal opponent of MR as it stands. He has a great blog post called Top 10 Myths about 3-Person IVF. In it, he makes a compelling case that MR is not at all what it seems. Here is a sampling:
Myth: This technology would cure mitochondrial diseases. Fact: The technology, even if proven successful and that’s a big ‘if’, would prevent some children from being born with mitochondrial diseases. It would not treat or cure them.
Myth: This technology has been conclusively proven safe in animals and would definitely produce healthy babies. Fact: Animal studies are mixed as to whether this approach is safe. Some that are limited in scope are encouraging, while others have raised serious warnings. More studies, particularly in primates, would be needed for a conclusive determination. As this technology is highly experimental it is unknown if the human babies produced would be healthy. In fact, it might put them at risk.
Myth: This technology involves transfer of mitochondria. Fact: This technology does not involve moving mitochondria. Instead it involves moving entire nuclei or so-called “spindles” that are groupings of chromosomes, from one human egg or embryo to another.
Myth: Mitochondria are just like little batteries that can be swapped out. Fact: Mitochondria are vital for energy production in cells, but there’s a whole lot more that they do as well. There is strong evidence that the mitochondrial genome, for example, “talks to” the nuclear genome, and has pervasive effects on cellular and organismal functioning. Therefore the notions that mitochondria are simply like replaceable batteries or that mitochondrial transfer would be just like transfusing blood into an anemic patient are misleading at best.
Knoepfler also brings up a great point that I have yet to see anywhere else. Yes, it is true that mtDNA only has 37 genes, but there maybe be as many as 500,000 copies of mtDNA in a cell. Now compare that number to the two copies of each gene in the nucleus, one from each parent. In reality, the “little” mtDNA genes outnumber the genes in the nucleus by 250,000. The effect of a mtDNA switch maybe much greater than we can anticipate. Knoepfler writes:
So for example to those who say that the mitochondrial genome “only” has 37 protein coding genes versus the perhaps 25,000 human genes in the nucleus, you should at least take into account that all those nuclear genes are only present at 2 measly copies per zygote whereas there might be 500,000 copies of any given mitochondrial gene in that same single cell. That’s a 250,000-fold difference.
No one wants children to suffer from mitochondrial disease, but MR is not the right approach. Because of the the invasive nature of the technique, it may put children at greater risk of birth defects or other unintended consequences. Any any ill effects will likely be passed on to future generations.
We should instead put new genetic engineering techniques to work healing existing patients with mitochondrial disease. This is an approach that will help everyone, even those already born with mitochondrial disorders, and does not put future generations at risk.