“Three-parent babies” explained
Susan Olmstead: This is Susan Olmstead, editorial director of Contemporary OB/Gyn, and I’m speaking with Dr. Stephen Ory, who is a professor of obstetrics and gynecology at Florida International University and a partner with IVF Florida. Thank you for speaking with me, Dr. Ory.
Dr. Stephen Ory: Thank you for the invitation.
Susan Olmstead: Well I wanted to discuss this three-parent baby phenomenon that we all heard about in the news lately. My reporting ears perked up when I heard that term because I suspect that three parents are not involved in this technique. Is that an accurate term? Will babies born using this technique really have three parents?
Dr. Stephen Ory: I think you’re correct. That really is not an accurate term. It’s certainly a catchy term and it is guaranteed to garner a lot of attention, but I think that this process is more akin to maybe a kidney transplant or something like that. At least parenting as we envision it, the offspring will have mitochondrial DNA from a third individual, but that would not be expected to confer much genetic material or programming to the resulting offspring.
Susan Olmstead: I see. So if you could go into a little bit of detail about what exactly or how exactly the procedure works. It’s just the mitochondrial DNA that are extracted or how does this work?
Dr. Stephen Ory: Actually the earlier iteration of this involved just exactly what you described. Donor mitochondria were extracted and put into the recipient, what’s done now, it’s a bit more complex, but it seems to be more effective, more successful, and probably has a greater margin of safety, is a procedure where a donor embryo is created. Actually there are two techniques, but the one that’s probably used most commonly would involve creation of a donor embryo, extracting the pro-nuclear material from the donor embryo and then putting the pro-nuclear material from the parent embryo into that. So it’s really an intact embryo that receives the genetic material rather than the other way around.
The other variation of that would be at an earlier stage where the maternal spindle complex, this would be an unfertilized site, is extracted. The one from the affected parent would be injected into the donor egg that had been previously enucleated. So the remainder of the apparatus within the egg would be intact. So all of the mitochondria that was in the donor oocyte would be used.
Susan Olmstead: So what is happening is the defective portions of parental DNA are being replaced. Is that in short what’s going on?
Dr. Stephen Ory: Not exactly. It is a complex … we’re taking a new oocyte or a new fertilized zygote and replacing the nuclear material. The resulting embryo has the genetic material from the affected parent, that is the nuclear DNA, either from an unfertilized egg or from a fertilized zygote, but the mitochondria all comes from the donor.
Susan Olmstead: So this is specifically for parents who are aware that they have certain defects that can be passed genetically. Why not use pre-implantation genetic screening rather than this technique?
Dr. Stephen Ory: So pre-implantation genetic diagnosis, PGD, actually can be used for some patients with mitochondrial disease. There are two sources of abnormal mitochondrial DNA. It can be either from an inherent mutation in the mitochondrial DNA or there can be a mutation in the nuclear DNA where a mitochondrial protein is encoded and it’s taken into the mitochondria and about 85 percent of them or nuclear origin rather than arising specifically in the mitochondria.
PGD can be done for that 85 percent, patients that have the mutation in the nuclear DNA, but there are a number of technical limitations of this because the mitochondrial DNA can be so variable. The concept of heteroplasmy where some of the mitochondria are affected, some of them are perfectly normal and the procedure requires extracting a large number of cells in order to figure out the proportion of normal versus abnormal.
There’s also quite a bit of variation in terms of how this is expressed. Some individuals can tolerate quite a bit of abnormal mitochondrial DNA without any apparent effect, whereas others are likely adversely impacted by a smaller amount. So these are some of the limitations that have led the results to be a bit unpredictable. The ability to take a set of mitochondrial DNA that’s from a presumably normal donor and doesn’t have any of these issues may eliminate a number of those problems.
Susan Olmstead: I see. So from what I’ve read, this is not being performed in the United States yet and apparently is not legal. Is that right?
Dr. Stephen Ory: Well, the technique that I described at the outset where the cytoplasmic mitochondrial DNA was being extracted and this was back in the 1990s, that was being done for patients with IVF failures; not mitochondrial disease. The FDA intervened and stopped that research because of safety concerns. There’s not a specific FDA injunction that I’m aware of that specifically addresses this application, mitochondrial disease or this particular technique using either the maternal spindle or the pro-nuclear transfer techniques.
Susan Olmstead: So you don’t know that there’s any proscription against it by the FDA?
Dr. Stephen Ory: Correct. I think their earlier ruling pertained to a very narrow application of this, but I think that that experience has certainly served to make a number of current investigators reluctant to delve into this until some of these issues are sorted out. I think the process that they went through in the United Kingdom where they had periodic review of literature, which has evolved considerably over the last 10 years to permit limited applications. I think that was an ideal way to do that, I think they’ve done it in a very cautious and prudent way that it’s being monitored is particularly reassuring. We do not have an equivalent of the HFEA in the US. So I think their model may very well serve to facilitate research in this area on this side of the Atlantic.
Susan Olmstead: I see. Well that’s really interesting and we appreciate you taking the time to talk with us, Dr. Ory. Thank you very much.
Dr. Stephen Ory: You’re very welcome.