Reproductive Technology: How Far Do We Go?Resources to Learn More
Mitochondrial Transfer
Nobel Conference Presenter: Alison Murdoch, Newcastle University.
Overview of the Topic
Mitochondrial replacement therapy (MRT) is a recently created technology that promises the possibility of preventing genetic mitochondrial DNA (mtDNA)-related disorders being passed from parent to embryo. Of the 20,000 genes in the human nuclear genome, only 37 are found in the mitochondria. Furthermore, although mitochondrial DNA is prone to mutation, birth defects occur only above a certain threshold of mutations. MtDNA replacement therapy could prevent the roughly 4,000 birth defects that occur each year due to such mutations. Presently, two methods of MRT exist: the maternal spindle technique or MST, and the pronuclear transfer technique or PNT. Both techniques focus on separating the nuclear DNA from the faulty DNA in the mitochondria. After separation, the faulty mtDNA can be replaced by a donor’s healthy mtDNA. The use of this technique is sometimes described as producing “three parent babies,” because it requires mitochondrial DNA from a third individual.
A team of researchers at the Center for Embryonic Cell and Gene Therapy in Portland is credited with discovering the therapy. In March of 2017, Newcastle University was given authorization to begin a clinical trial of MRT.
Despite recent success with animals, there is still heated debate on whether the procedure should be used in humans. MRT presents several safety concerns, including the following: Given that mtDNA is passed to the child from the mother, any female children born using this procedure would be passing down the donated mtDNA to future generations, which could lead to unforeseen complications. Some argue that this concern could be eliminated by using the procedure only on male embryos. This solution comes with its own ethical quandaries, however, since it would require practicing sex selection on embryos. Finally, there is the concern that MRT represents a step onto a slippery slope that ends with babies being “designed” for superficial cosmetic characteristics.
MRT was used in 2016 to enable a U.S. medical team led by John Zhang, to assist a Jordanian woman with a mtDNA disorder to give birth to a healthy boy in Mexico (where regulations presently do not prevent the technology). The woman had previously lost seven children to mitochondrial disease. Justifying his action in the New Scientist, Zhang noted, “To save lives is the ethical thing to do.”
Questions to Consider
- Children born using this technique might become curious about the donor or their background. Should they have access to information about the egg donor?
- Likewise, would the donors be able to know anything about the child?
- This technique was developed as a way to help women with mitochondrial disease, but has been used to treat infertility in general. Given that the ethics and laws concerning the procedure are not yet well worked out, does using the procedure for general infertility seem like a good idea?
Resources Recommended by Nobel Speaker Alison Murdoch
HFEA Public Consultation on Mitochondrial Transfer
Nuffield Council Report on Mitochondrial Transfer
Nuffield Council Report on Donation
Wellcome Trust Information on Mitochondrial Transfer
Works Consulted and Resources for Further Reading
3-Person IVF: A Research Page (Center for Genetics and Society) (8 pp.)
The article outlines the MRT procedure, research on it, laws governing it, and examples of patients who have undergone it.
First UK baby with DNA from 3 people could be born next year (The Guardian, 2016) (4 pp.)
Clinics in the UK will now be able to apply for permission to perform MRT (as of December 2016) by submitting applications to the Human Fertilization and Embryology Authority (HFEA). A team in Newcastle, for example, plans to apply immediately and could offer the therapy as soon as early 2017.
First UK licence to create three-person baby granted by fertility regulator (The Guardian, 2017) (3 pp.)
The article details the decision by the Human Fertilisation and Embryology Authority (HFEA) to grant licensure to Newcastle University to begin clinical trials of the technique.
Mitochondrial DNA disease: new options for prevention (Human Molecular Genetics) (7 pp.)
The article describes the MRT procedure in detail, and discusses its purpose and potential benefits.
Mitochondrial replacement therapy: the UK and US regulatory landscapes (Journal of Law and the Biosciences) (10 pp.)
This article details the legislation regarding MRT in both the UK and the US. It also discusses some of the other assistive reproductive procedures that have been employed thus far.
MRT can circumvent mtDNA based disease transmission (Cell Metabolism) (4 pp.)
This article explains the two existing types of MRT: pronuclear transfer (PNT) and maternal spindle transfer (MST). The main difference between the two is that unfertilized eggs are used in spindle transfer, while early-stage embryos are used in pronuclear transfer.
Mitochondrial replacement techniques: ethical, social, and policy considerations (Institute of Medicine of the National Academies of Science, Engineering and Medicine) (184 pp.)
The report concluded that the procedure would be ethically acceptable if it were shown to be safe. Limitations to future clinical trials include: 1) the procedure should only be performed on women with a serious risk of passing a mtDNA disease to her offspring, and 2) only male embryos should be used.
Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review (Nuffield Council on Bioethics) (2 pp.)
A report published by the Nuffield Council on Bioethics on research regarding the safety and efficacy of MRT. One major conclusion was that if the procedure were shown to be sufficiently safe, it would be ethical for families to use it.
Unexpected Risks Found in Replacing DNA to Prevent Inherited Disorders (National Public Radio) (8 pp.)
Some scientists are concerned that the flawed mitochondria will resurface later in development. It is possible that it will be necessary to pair transplanted and original genomes, in order for the two to be as genetically similar as possible. Part of the danger lies in mitochondrial DNA being starkly different than nuclear DNA, given that the mitochondria originally arose from free-living bacteria.
US Panel Greenlights Creation of Male 3-Parent Babies (Nature) (2 pp.)
In the US, human trials of MRT are currently not allowed due to safety concerns. Because mitochondrial DNA (mtDNA) is passed down to offspring from the mother, only female children would pass down the donated mtDNA. One safety precaution that is being considered is performing MRT using male embryos only.
World's first baby born from new procedure using DNA of three people (The Guardian, 2016) (4 pp.)
LEARN MORE ABOUT CRispr and gene-editing
LEARN MORE ABOUT reproductive technology and social justice
LEARN MORE ABOUT male contraception
Special thanks to Gustavus students Greta Engen and Olivia Niles for compiling these resources.