Mitochondrial Replacement: The Issue isn’t Mitochondria

My parents sent me a link today and it really got me thinking. It was about the meeting the FDA is having regarding whether or not to allow human trials for mitochondrial replacement. The U.K. is working on drafting regulations that would be put to a vote in 2015. I’m not sure how fast things would happen in the United States if the FDA ruled favorably this week, but this would be substantial news. I thought some of the wording seemed off in the link they sent, but when I found a link from a local news site, they were using the same AP piece from a health writer who uses “nucleus DNA” and not “nuclear DNA.” I thought perhaps the terminology had changed since my undergraduate degree in genetics, but that doesn’t seem to be the case, at least in general practice. But I digress.

You may be wondering what mitochondrial replacement is and why this is a big deal. I’ll try and fill in some of the information, but to be honest, my head is spinning right now with differing views. Mitochondrial replacement is not new; researchers in Oregon, according to the news article, have been working with monkeys for four years and would like to move to human trials. Mitochondrial replacement is taking the nuclear DNA (what people typically think of as DNA, the chromosomes) from a woman and place it into a donor egg. Why would this be done? There are organelles called mitochondria that produce the chemical energy that our cells use (ATP) and these organelles have some genetic material known as mitochondrial DNA (mtDNA). mtDNA is a small amount roughly 16,500 base pairs and 37 genes versus the 3 billion base pairs and approximately 20,000-25,000 according to this NIH site. Although mitochondria are fascinating and have an important history, I can’t really take the time to go into that here. Needless to say, there can be mutations in these 37 genes and there are genetic diseases that are linked to mitochondrial genes. The problem is that only the egg cell passes mitochondria onto the resulting embryo. The sperm’s mitochondria are in its tail and only the sperm’s nuclear DNA enters the egg. So if a woman has a mitochondrial genetic disease, it will be passed on to her offspring. Mitochondrial replacement would allow affected women to have a child that is genetically related to them, but not inheriting the genetic condition.

Why is this a big deal? It depends who you ask. I think it is a big deal because I wrote about the possibility of using mitochondrial replacement as motivation for utilizing reproductive cloning in an article published in 2011. There are some people who are upset because they argue the child would have three parents. The two parents who provided nuclear DNA and the donor who supplied the egg containing mitochondria. Others are concerned because changing mitochondrial DNA would be the first recorded instance of germ line therapy. In other words, the changes made in this instance would be genetic changes made by humans that would pass on to any offspring the children resulting from these trials would have. I am unsure how many countries currently ban germline changes, But according to this website, Australia, Canada, Germany, Switzerland, and the Netherlands appear to have laws against it. There is also worry from people that allowing these kinds of changes is a slippery slope to designing children.

I will say there is probably very little new about ethical concerns around the ethics of reproductive technologies presented by this case. These kinds of concerns have existed with assisted reproduction, human cloning, and stem cell research. There are a few things, however, that I would like to mention.

The first is that when digging to find multiple sources to back up the FDA’s meeting to discuss this I came across a post in Nature. What I found most disturbing in this post was the following statement: “The FDA, unlike the HFEA, does not consider ethics, and that worries Marcy Darnovsky, executive director of the Center for Genetics and Society, an advocacy group in Berkeley, California.”

If this statement is true, that the FDA does not consider ethics, how did I not know about this? It seems far too big to not know this is the case. I imagine this is editorial and not factual. I find it very hard to believe that the FDA would not take ethics into consideration at all. People may be displeased with specific outcomes, or disagree with decisions they have made, but I have to believe that ethics play a role in their decision making process.

In the original article there is this quote: “We want to replace these mutated genes, which by nature have become pathogenic to humans,” says Dr. Shoukhrat Mitalipov, who will present on Tuesday. “We’re reversing them back to normal, so I don’t understand why you would be opposing that.”

I find it disconcerting that there is no reflection on what normal means in this case. The degree I’m working on is in ethics and social theory, and I’ve read enough medical sociology (though by no means am I an expert) to say that what medicine considers “normal” is not necessarily objective fact. Normal and healthy are things that we often take for granted, but we are already seeing normal used two different ways in this case study. People are arguing that mitochondrial replacement is not normal because it would produce embryos with three biological parents. While on the other side, experts are claiming to restore normal function to these mitochondrial genes. Even as a theological ethicist who believes in a normative understanding of human nature, I will need more convincing from experts as to how they define normal in this case.

Related to the discussion of normal, there is the consideration of people who are differently abled. Transhumanist Evan Reese in disagreeing with the position of the Center for Genetics and Society wonders whether society should do everything possible to help people with help problems and that children born with mitochondrial problems could be upset that they were denied the chance to not have these conditions.

I will also say that mitochondrial replacement also would affect genealogical studies using mitochondrial DNA. This is not an argument against the procedure per se, but this was something that came to mind when I was thinking through the implications.

In principle, I am not opposed to mitochondrial replacement itself. If the numbers cited in these articles are correct, then this would only affect 1000-5000 births per year (I’m assuming that number is in the United States alone). Although you cannot draw a hard line between health and enhancement, I do think there is a difference between this case and choosing particular traits for nonmedical reasons. In regards to affecting the germline, the number of genes affected would be so small and the population that would have the replacement done is so small, that the overall impact on humanity’s gene pool is likely small. There could be unforeseen consequences and there are other ways to have children (or adopt children). I would not mind us taking our time in making a decision about making substantial germline modifications, even though according to a speaker at a transhumanism conference I attended recently, any restraint on life extension research should be criminalized.


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