Ob/Gyn Behind Birth of Three-Person-DNA Baby Plans More Procedures

Stephanie Cajigal


October 20, 2016

Editor's Note:
In an interview with Medscape, the ob/gyn behind the team that worked to bring about the recent birth of a healthy baby boy, via a new technique that helped the infant avoid the devastating mitochondrial disease his mother carries, said that he is planning to perform this procedure in more women.

John Zhang, MD, medical director and founder of New Hope Fertility in New York City, led a team that performed a new technique called spindle nuclear transfer. This technique is a form of mitochondrial manipulation technology that involves removing the nucleus from the mother's oocyte and transferring it to an enucleated donor oocyte that is then fertilized with the father's sperm. An abstract describing this case was published in Fertility and Sterility in September. The procedure helped the baby avoid Leigh syndrome, a rare genetic disorder that is characterized by progressive mental and movement abilities. Leigh syndrome, like other mitochondrial disorders, is maternally inherited.

Medscape spoke with Dr Zhang at the American Reproductive Technology World Congress in New York City on October 13. Here's what he had to say about why he chose this technique for this patient and where else it might be applied.

Medscape: Can you start by talking a bit about your training in medicine and when you became involved in this type of reproductive medicine?

Dr Zhang: I did my clinical training at New York University Medical Center. I also did my training at Cambridge University in the UK, and the scientific background includes the training needed to make this project successful.

Medscape: Could you describe exactly what mitochondrial DNA is and how spindle nuclear transfer works?

Dr Zhang: As we all may know, mitochondrial DNA is different from nuclear DNA. It's a very small molecule but it is inherently involved with antigen production. Mitochondrial disease causes muscular and motor dysfunction. There is no treatment, so the best way is to prevent the birth of babies [with mitochondrial disease].

Medscape: Could you describe more details about this case?

Dr Zhang: This mother is a carrier of a common mitochondrial DNA disease called Leigh syndrome. She already has had two children pass away due to mitochondrial disease and also has had four miscarriages. [The family was] just desperate and a good candidate for this project.

The nuclear transplant technique is a very simple concept. [Think of it as an] egg yolk and egg white. The mitochondrial DNA stain is the egg white, and in this procedure we remove the egg white from the mom's egg and [replace it with] the egg white from the donor egg. Now you have a new reconstituted egg, which is the mom's own egg yolk and an egg white from the donor.

Medscape: Can you explain the other approaches to mitochondrial manipulation?

Dr Zhang: Sure. With medical procedures, before we start we talk about alternatives and risks. Alternatives include diagnosis and adoption. [Another is] spindle nuclear transplant, which is to change the environment of mitochondrial DNA.

Medscape: Why did you choose this procedure specifically for this case?

Dr Zhang: First of all, clinically, this patient has been suffering for 7 years. This mother had Leigh syndrome at the highest threshold, so if you bring the DNA mutation down, the baby should be absolutely safe. That's why we chose this case as the first case.

Medscape: Have you treated any other patients using spindle nuclear transfer?

Dr Zhang: We have not. We have a group of patients already lined up, and I think we can start the procedure to the next step.

Medscape: Do these other patients also have Leigh syndrome or do they have other syndromes?

Dr Zhang: Some have Leigh syndrome and some have other kinds of mitochondrial DNA disease.

Medscape: Can you use this procedure for women with other types of mitochondrial diseases?

Dr Zhang: Absolutely. Mitochondrial disease is one of the applications.

Medscape: How is this particular case different from others that have been published previously in the medical journals?

Dr Zhang: The previous studies and proposals have two things different from our technique. First of all, in most of the techniques, the nuclear transplant is performed after fertilization, so you have to create the embryos first and then you have to destroy half of the embryos. So, ethically, that's not as good as our technique. The second [technique] is [to] use a special virus to reconstitute the eggs, which also will not be the best approach. Our approach uses electronic effusion, so it's a more clean technology.

Medscape: Just to clarify: This is the first time that a baby has been born using this specific technique?

Dr Zhang: Yes. This is the first case. It's the first case to treat a patient. It's also the first case to prove that a baby can be obtained through the nuclear transplant technique.

Medscape: What other applications could this technique have?

Dr Zhang: I think the application is definitely tremendous and will be limited by our imagination. It can be used when we treat mitochondrial DNA disease. It can definitely be used to treat a certain kind of a patient with poor-quality eggs or otherwise. It definitely can be used as a gene additive and, in the future, for pharmaceutical research and stem cell research.

Medscape: When this abstract was first published, certain media outlets described this as the birth of a three-parent baby. Could you explain why that's misleading?

Dr Zhang: The eggs involved were two female eggs and one male sperm, so just like in vitro fertilization, it's a test-tube baby, and I think ["three-parent baby"] is a little bit misleading.

Medscape: Can you explain what sort of DNA information mitochondria carry?

Dr Zhang: Mitochondrial carry the DNA information and may involve antigen protection. So that's not [the information that decides] who you are, who I am, which is related to nuclear DNA.

Medscape: Would you describe this case as a medical breakthrough?

Dr Zhang: Obviously, no doubt this is a medical breakthrough. It's going to change medicine and human reproduction forever. No argument about it.


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