Countless sources are reporting on the “three parent embryo” created as a potential treatment for infertility. What has not been reported is that ther is an almost 10 year history of unreagulated human experimentation in this arena which led to a rare federal ban on specific fertility treatments. Is this hope, hype or dangerous human experimentation? Read on to see!
Background- what are mitochondria? Mitochondria are tiny primite organisms that millions of yers ago became incorporated into human cells. They exisit in every cell but have their own unique genetic material. They function as the engines of the cell providing energy for metabolism. I wrote an review of how they got there and what they do that you can read here. In short mitochondria have their own DNA (similar to that of bacteria) and reproduce independently of the cell in which it is found. We now have a symbiotic relationship with them.
First – the details receontly reported by the BBC. Diseases of the function of mitochondria exist. “About one in every 6,500 people is affected by such conditions, which include fatal liver failure, stroke-like episodes, blindness, muscular dystrophy, diabetes and deafness.” Details of their human experiment: Scientists in the UK experimented on 10 embryos left over after IVF fertility treatments. They microsurgically removed the nucleus, containing the embryo’s DNA and implanted it into a donor egg whose DNA had also been removed. The donor egg while missing its DNA still contained its mitochondrial DNA. They watched these embryos grow in the petri dish for 6 days.
Therefore the resulting embryo will have the DNA of the donated nucleus but the mitochondrial DNA of the host cell- curing and potentially eradicating – the mitochondrial illness.
This is not the first time this has been done. The fertility treatment history of human experimentation on this: While I was teaching at Yale Medical one of my partners and mentors in the fertility department (Dr David Keefe) was actively pursuing research on mitochondrial dysfunction as a cause of human infertility. At that time a few fertility doctors in the US theorized that one cause of human reproductive aging was accumulated damage to the mitochondria in the egg. They thought the genes of the egg could be healthy but the rest of the egg that supports its become faulty. They experimented with a technique called cytoplasmic transfer. Using a microscopic needle tiny drops of fluid were sucked out of a donor’s egg and injected into that of an older infertile woman hoping to breath new energy and life into it. Unfortunately most research groups found it did not seem to offer any benefit.
Reasons why it likely did not work:
- using minute drops of fluid from a donor egg into a recipient is just not enough to correct the metabolic problem or defect
- my collegues at Yale found that the mitochondria in the egg is often tightly joined to the nucleus so the cytoplasmic transfer did not move enough of them
- a huge proportion of age related egg defects are related to nuclear not mitochondrial DNA defects.
The federal government banned this treatment in 2001. Some feared that chromosomal abnormalities and birth defects could result if there were three people’s DNA in one embryo. Federal officials decided that any method involving the transfer of genetic materials without the fusion of egg and sperm requires the oversight and involvement of the Food and Drug Administration. The US legislation leading to the FDA taking jurisdiction over human eggs sperm and embryos is a whole other topic to be covered in later posts. A brief overview of this from Rodger Gosden (who I know and respect as a leading reproductive biologist) is posted here from 1999 when this treatment was at its heyday with references justifying its use from mouse research.
The next brouha using the technique in humans in 2003: Related research on nuclear transfer was again presented at the annual ASRM meeting in San Antonio in 2003. I was in the audience for the talk and remember it well. One of the researchers was an American out of NYU Dr Jaime Grifo who also used to be in my ex-department at Yale. He is also a repected researcher who I know well. Unable to perform the research in the US- the experiment was performed in China. as reported here and here
Researchers at Sun Yat-sen University in Guangzhou implanted three embryos in the womb of a 30-year-old infertile woman… A triplet pregnancy resulted, they announced at the annual meeting of the American Society for Reproduction Medicine in San Antonio, Texas this week. One of the foetuses was “reduced” to ensure the viability of the pregnancy, but the other two died anyway at 24 and 29 weeks.
With this technique, called nuclear transfer, the doctors fertilised an egg from their patient and an egg from a donor. Two embryos resulted. The nucleus of both women’s embryos was extracted, and the patient’s genetic material was inserted into the empty “eggshell” of the other embryo which, however, contained mitochondria with the other woman’s DNA. The procedure gives the infertile woman’s embryo the healthy mitochondria it needs to develop — but it also results in a child with genetic material from one father and two mothers.
Dr Grifo has maintained that he was an advisor and did not partake in the actual experiment. NYU issued a statement that if the research was performed in China their IRB did not have oversight (different than my department where all work I did anywhere fell under the IRB as a faculty member). I have never asked him his take on this but do respect him and strongly do not believe he is someone who would knowingly break the law or do what he felt was wrong.
Nonetheless- the ASRM responded with a moratorium on any future presentations on cloning (whether this was cloning is a whole other debate- many feel not).
The technique is still undergoing related research: I chair the video committe of the American Societry for Reproductive Medicine (ASRM) the largest international fertility research society. Just this past year we accepted a video presentation on how to technically perform the procedure from a research team in Japan. The paper- Embryonic Development Following the Nuclear Transfer of In Vitro Matured Metaphase-II Oocytes into Enucleated Freshly Ovulated Metaphase-II Oocytes by Tanaka and collegues investigated the possibility of repairing either mitochondrial diseases or female infertility due to ooplasmic deficiency and abnormalities. They demonstrated embryonic development following the nuclear transfer of in vitro matured metaphase-II oocytes into enucleated freshly ovulated metaphase-II oocytes and concluded it could be applied to the treatment of mitochondrial diseases or female infertility due to ooplasmic deficiency and abnormalities.
More is certainly to come.
