Child Conceived from the DNA of Three Parents

admin  ∼  October 27, 2016  ∼  Education Outreach Mitochondrial disease mtDNA Nuclear DNA Inheritance Research Treatment Genetics

VMP's Dr Fran Kendall Factoid Friday Blog on Rare Diseases


One, two, three makes a baby boy! I discuss the recent birth of a child conceived from the DNA of three parents, the revolutionary technique utilized, and the issues surrounding its use. 

IT TAKES THREE

The mitochondrial disease community is all too familiar with Leigh disease, a particularly aggressive and unrelenting form of mitochondrial disease that results in a neurodegenerative course and a loss of neurological functioning that systematically robs affected children of their future.

Caused by nuclear gene mutations, defects in the mtDNA, and X-linked PDH deficiency, medical science is now offering hope to women who harbor an mtDNA mutation that can lead to the birth of children with Leigh disease and other types of mitochondrial disease caused by mutations in the 37 maternally inherited genes.

On April 6, 2016 a little boy entered the world, a product of DNA from three parents. Although healthy herself, his mother carries an mtDNA mutation causing Leigh disease and had suffered four previous miscarriages and lost two children to the disease, one at eight months of age and another at six years, prior to his birth.

Seeking help to ensure the delivery of a healthy child, the woman and her husband sought help from Dr. John Zhang, a reproductive endocrinologist at New Hope fertility center in New York City.

Utilizing a three parent IVF technique, scientists can greatly diminish the likelihood that an mtDNA mutation carried by a woman is not passed to offspring.

THE SCIENCE, LEGALITIES, AND MORALITIES OF IT ALL

This procedure received widespread attention when lawmakers in the UK became the first to approve its use in February 2015 amidst heated debate in the House of Commons with concerns raised about "designer babies "and "playing God".

Although not currently approved in the US, a panel convened by the Institute of Medicine under the direction of the US FDA reported on February 3, 2016 in the journal Science that it is ethically permissible to create three parent babies in clinical experiments, as long as certain guidelines are followed.  They recommended that the procedure be limited to women with mtDNA mutations and be restricted to creating male children to prevent Germline modification of future generations because mitochondria are inherited from the mother. The procedure is now pending approval by the FDA.

To circumvent legalities in the US, Dr. Zhang performed the procedure for this couple in Mexico. The procedure, known as spindle nuclear transfer, removes the healthy nucleus from one of the mother's eggs and transfers it to a donor egg that was enucleated. The resulting egg contains the nuclear DNA of the mother and the healthy mitochondrial DNA from a donor. This egg is then fertilized by the father's sperm. The resulting embryo is a product of three separate people, the mother, the father and the egg donor.

Because only 37 out of the 19,000 to 20,000 protein coding genes found in humans are contributed by the egg donor the resulting fetus is essentially the genetic product of the mother and father since the mitochondrial genes do not contribute to a person’s commonly recognized traits.

THERE ARE ALWAYS COMPLICATIONS

In this case, five embryos were created by the spindle nuclear transfer technique but only one developed normally leading to implantation and ultimately the birth of a baby boy with no signs of disease to date. Quoted in News in Brief on October 19, 2016 during a news conference at a meeting in Salt Lake City of the American Society for reproductive medicine, Dr.Zhang relayed that the baby appears to be healthy at 6 months of age. He stated that testing on the child has detect the presence of the mtDNA mutation harbored by his mother in only 1.6% of a variety of the child's cells, a very low level of heteroplasmy not typically associated with disease.

Additional testing in the future will be required to determine whether or not this number increases over time. Of note, the child harbors some mutated DNA since mitochondria are transmitted from the mother to the donor egg during the nuclear transplant procedure. Studies suggest that in the spindle transfer technique, the carryover of mitochondria from the mothers egg to the donor egg is usually 1% or less.

But concerns about carryover of mtDNA mutations are not the only issue plaguing this technique. There is another study that suggest the mismatches between the parents' nuclear DNA and donor mitochondrial DNA could affect aging. In a study looking at two strains of mice, genetically identical except for the source of their mitochondria, researchers found that the mice age differently. Their results were recently reported in online Nature on July 6, 2016.

Even though both mouse strains had healthy mitochondrial DNA, the researchers discovered that the mice with mitochondria that did not come from the same source as the rest of their DNA appeared to show fewer signs of aging and had a lower incidence of tumors at two years of age.

However, the scientists caution that a mitochondrial transplant does not necessarily lead to a healthier life but does point to a larger relationship between mitochondrial DNA and aging raising additional questions about the long-term effects of creating three parent babies.

CONCLUSION

While many applaud the birth of this child and marvel at the power of genetic engineering, there clearly remains many unanswered questions regarding the implications of the technique and long-term outcome of children created through three parent procedures. However, as the FDA contemplates this procedure and ethicists debate the morality of genetic engineering,  women around the world who harbor mtDNA mutations are embracing the opportunity for the possibility of having a healthy child.

Sincerely

Fran Kendall, M.D.

The above blog was funded by a generous donation from the Foot Foundation. More can be learned at www.footfoundation.org

This post is not meant to be a recommendation or a substitute for professional advice and services rendered by qualified doctors, allied medical personnel, and other professional services. The responsibility for any use of this information, or for proper medical treatment, rests with you.