Mitochondrial Replacement Therapy

I attended a highly informative and thought-provoking seminar by Prof. Adashi, a world-renowned Ob/Gyn specialist, Senior Consultant for Women’s Health in the World at US Secretary of State and a member of the Board of Directors of Physicians for Human Rights and of Population Connection. According to Dr. Adashi, MRT is the Harbinger of all things future; it is the first reproduction technique since IVF.

The most natural question that follows is "Should we be doing this?" The most recent development relating to this scientific breakthrough with the 3 parent IVF baby immediately comes to mind.

The goal of this therapy is the prevention of heritable mitochondrial diseases attributable to mutant mitochondrial DNA (mtDNA). Let's backtrack a bit -- mutant mitochondrial DNA is a genetic defect in mitochondrial DNA that affects mitochondrial function. This genetic defect is tissue-defect since organs like the heart and brain are most prone to dysfunction due to their high energy demand. We have already experienced numerous cardiological and neurological manifestations. Since mitochondrial inheritance is non-mendelian, such defects are quite unpredictable. Preimplantation genetic diagnosis (PGD), a screening test used to determine if genetic or chromosomal disorders are present in embryos produced through in vitro fertilization (IVF) is unreliable in this case. Here's a few quick details on the disorder:

1. >1 in 5000 women are affected

2. Characterized by variable failure of Oxidative phosphorylation

3. Multiple pathogenic mtDNA

4. Crippling muscular disease in patients

There is really no cure for this disorder once the children are born except supportive care. And this is the idea behind mitochondrial replacement therapy — germ-line therapy. This therapy is basically substitution of mutant mitochondrial DNA (mtDNA) in the affected oocyte (egg) with wild type/normal mtDNA from a donor.

Very quickly, questions of what really makes us human, arise. Is the Mitochondrial DNA or Nuclear DNA responsible for who we become? Although distinct from nucleus, the mitochondria interacts dynamically with the nucleus. The mitochondria is important in natural cell death (apoptosis), immune functions, energy generation, etcetera etcetera.

Keypopints of mitochondrial replacement therapy:

• 1st time scientists are crossing the germline barrier

• This actually means genetic material is being modified and can be propagated through generations to come

• Only females may transmit mitochondrial DNA, fathers mtDNA is destroyed at birth

• ​What this means is that male children will not be passing this mtDNA to their children but female children will

• 1st organelle replacement therapy: usually organs like liver, heart, etc get transplanted, but for the first time we are going sub cellular

• MRT approved by UK house of commons and Lords (Feb 3, 2015) -- Human fertilization and embryology authority /(act)

Diverse Concerns with this therapy:

• Conscience grounds (objection in principle) — Catholics, Anglicans and Protestants

• Safety Grounds

• Legal grounds

I would like to know what the public really thinks about this new reproductive intervention. Do you think this is just a case of “first in humans”? Even though this is the first time such interventions are being done in embryos and not adults or born people