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Three’s a Crowd: Should We Cross This Line?

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By: Tamara Litwin, Ph.D

photo credit: Mitochondria via photopin (license)

The British House of Commons recently voted to approve techniques that will enable couples to conceive children without inheriting deleterious mutations in their mitochondrial DNA1. In the United States, the FDA is considering the safety and efficacy of the same techniques, which raise a variety of medical and ethical issues because they involve manipulation of the human genome2. There are two closely related techniques, both known as mitochondrial replacement therapy, that aim to cure mitochondrial DNA disorders by combining mitochondrial DNA from a woman with healthy mitochondrial DNA, nuclear DNA from a woman with a mitochondrial DNA disorder, and nuclear DNA from a man.

Mitochondrial replacement therapy will create children who, in a sense, have three parents because the healthy mitochondrial DNA is donated by a woman who would not otherwise be related to the child3. What are the biological implications for this three parent model? Mitochondrial DNA contains less than 17,000 DNA base pairs out of the 3 billion base pairs that make up the total human genome. Therefore, mitochondrial DNA proportionally makes up a small percentage when compared to the total amount of DNA. Furthermore, mitochondrial DNA is found in mitochondria, a separate compartment of the cell from the nucleus of the cell where the nuclear DNA (all the rest) is located. While few in number, mitochondrial genes are essential to biological processes that focus on energy storage and consumption from oxygen and sugar4. When the mitochondria do not function properly, the result can be mitochondrial myopathy, a family of disorders with symptoms including muscle weakness, vision problems, heart problems, and others5. Mitochondrial disorders may also accelerate aging6.

Mitochondria are inherited solely from the mother because mitochondria from the sperm are actively degraded7. Therefore mitochondrial DNA disorders are passed down to every child (both boys and girls) conceived by an affected woman. The disorders can vary in severity among children in the same family. The potential benefits of the new mitochondrial replacement therapy to the children of mothers with mitochondrial disorders are enormous. One intervention at or before conception can prevent a lifetime of symptoms of mitochondrial dysfunction. Even better, any daughters will not have to face the same decision when they grow up and hope to start their own families, because they will pass on the healthy mitochondria to their children.

Mitochondrial replacement therapy has the potential to help specific families stop the chain of transmission of mitochondrial disorders. It is a medical technology that is not very different from traditional in vitro fertilization (IVF) techniques and does not lie on a slippery slope to ethically challenging eugenics techniques. If we have the technology to help these families, how can we withhold it on the grounds that someone may someday misuse the technology for other purposes? The technology already exists. However, it is worth proceeding cautiously because there could be health ramifications to manipulating eggs in this way. Animal studies have already shown the growth of healthy offspring for several generations with this technique8, which is very promising, but it would be wise to generate more data in animals before proceeding with human trials of this technique in the United States. The FDA can also watch the developments across the pond to help determine when and how to introduce mitochondrial replacement therapy to the United States.

  1. http://nyti.ms/1F3fM08
  2. http://www.medscape.com/viewarticle/821115
  3. http://www.ncbi.nlm.nih.gov/pubmed/24382342
  4. http://en.wikipedia.org/wiki/Mitochondrion#Function
  5. http://en.wikipedia.org/wiki/Mitochondrial_disease
  6. http://www.ncbi.nlm.nih.gov/pubmed/23965628
  7. http://www.ncbi.nlm.nih.gov/pubmed/18695671
  8. http://www.ncbi.nlm.nih.gov/pubmed/19710649

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Written by sciencepolicyforall

February 13, 2015 at 10:01 am

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