Case Study in Three Parent Embryos
By Brianna Bacich and Laura Rivard
Introduction
On February 25th and 26th, the FDA held a hearing to examine whether or not a new technique for replacing faulty mitochondria in embryos was safe enough to begin human trials. The media covered the story with headlines blaring "Three Parent Embryos" and the ubiquitous ethical "slippery slope". It is still unclear whether or not the procedure is safe. However, many in the media did little to illuminate the real issues at stake.
Mitochondria are membrane-bound structures within the cell that provide energy for normal cellular processes. Offspring inherit their mitochondria exclusively from their mother via the egg, since sperm are streamlined and carry little more than paternal chromosomes. Mitochondria have their own DNA, and it is separate from the mother's nuclear DNA. The nuclear genome holds the majority of genes responsible for encoding the traits we associate with people: eye color, sex, height, blood type, etc. In contrast, mitochondrial DNA makes up less than 1% of the DNA found in our cells and encodes for genes primarily used for energy production within the mitochondria. However, mutations in the mitochondrial genetic code can cause serious conditions such as muscular dystrophy, seizures, heart problems, and mental retardation. Though rare, approximately 1 in every 1,000-4,000 children in the United States are born with mitochondrial defects. A new technology, commonly referred to as "Three-Parent Embryos", is awaiting FDA approval for human trials and is in the last stages of approval in the UK. This new technology could allow women to have children without passing down mitochondrial diseases. The procedure involves combining sperm from the genetic father with an egg from the genetic mother, who is also a carrier of mitochondrial disease. Immediately after fertilization, the male and female nuclei are removed and inserted into a donor egg from which the nucleus was removed. Technically, these embryos have "three-parents", containing DNA from the intended mother and father, and the mitochondrial DNA from the donor. However, it is more accurate to refer to the procedure as "mitochondrial DNA replacement therapy" since the genetic contribution of the mitochondrial donor is minimal.
Case Study:
Bill and Rosa have always wanted a large family. They have had one daughter named Sarah, who was diagnosed with Leigh's disease a year after birth. This neurological disease is characterized by the progressive loss of mental and locomotive abilities, which results in death after a couple years. Devastated, Bill and Rosa found there were no treatments to help their daughter. They love Sarah and want to ease her suffering. They have gone to many hospitals, yet the only therapy available is a special diet and supplements that has never been shown to prevent fatality in Leigh's disease. They have always wanted to have more children, but do not want to bring another child into the world with Leigh's disease. They were excited to hear about a new technique, "mitochondrial DNA replacement therapy", that could allow them to have another child, while preventing the disease that affects Sarah's everyday. However, they read that many researchers are skeptical of the health risks that may be involved and do not want to undergo a treatment that could harm their potential new child. Bill and Rosa also read that the UK is close to approving trials of the new technique under limited circumstances. They have family in England and could make the trip easily.
What should Bill and Rosa do? Take our poll, leave a comment, and join the conversation!
References:
Smith, Matt. "FDA considering 3-Parent Embryos." CNN, n.d. Web 27 Feb. 2014
Phillips, Nicky. "Scientists grow embryos from three adults." The Sydney Morning Herald, n.d. Web 25 Oct. 2012
Woollaston, Victoria. "100 babies a year in UK will have three parents: Births as early as 2015 in worlds first." Mail Online. n.d. 27, Feb. 2014
Cheng, Maria. "UK Seeks Public Input on Making 3-Parent Embryos." ABC News, n.d. 27 Feb. 2014
Craven, et. al. "Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease." Nature 465:82-85 6 May 2010
Website: United Mitochondrial Disease Foundation
Image credit to Mile Velez (via Flickr)
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Laura~ Thank you for the explanation. Now it does make sense to me. To your original question. Wouldn't it be less controversial to do egg selection? If it is possible to discriminate between healthy and bad mitochondria, either visually using microscope or using some markers. Or maybe somehow stimulate replication of healthy mitochondria while suppressing duplication of mutated ones. Or how about to use father's mitochondria from sperm. Somehow exchange ubiqutin signal between paternal and maternal mitochondria. I do not have problem with "3 parents baby" either. 1 % DNA obtained from donor (third parent) sounds like a lot but this is because there are so many copies of mtDNA per cell. Maybe better indicator of contribution of the 3 parents could be number and type of obtained genes. A baby gets about 20000 genes from each mother and father and only 37 from the egg donor.
Marek~ You are correct that most cases of Leigh syndrome are caused by mutations in nuclear DNA. However, 20-25% are caused by mutations in mitochondrial genes. As you are probably aware, a single cell contains hundreds of mitochondria. Rosa must have both normal and mutant mitochondria. She has enough normal mitochondria that she does not show any symptoms of mitochondrial disease. By chance, the egg produced by Rosa that eventually contributed to Sarah contained a much higher proportion of mutant mitochondria. As a result, Sarah has a full-blown mitochondrial disease. Check out the second figure on this link for a very clear visual: http://mda.org/disease/mitochondrial-myopathies/causes-inheritance
I do not understand the case study. If mitochondria are affected how is it possible that mother (Rosa) is healthy or isn't she ? 75 to 80 percent of Leigh syndrome is caused by mutations in nuclear DNA and it is inherited in autosomal recessive pattern. It is more likely that parents are healthy carriers and the mutation is not found in mitochondrial but in nuclear DNA. Therefore the mitochondrial transplantation will be useless and the chances that the child will be affected by the Leigh syndrome remain 25%.
