This is the untold story of the strange case of the child with three parents

The title of this column, which I paraphrased from a journalist who knew how to sell newspapers, is technically true, but does not tell the real story. The title should read: The Strange Case of the Healthy Child with 2.0002 Parents. If you were imagining an equal contribution by three people in a ménage à trois, you can relax. Take a deep breath!

Two older siblings of the “child with three parents” died because of defects in their mitochondria, the energy-producing units of virtually every cell. A cell needs energy, banked in a molecule called ATP, to drive its metabolism. This energy allows your heart muscle to contract and your skeletal muscles to move. An active body needs a lot of ATP— and mitochondria provide it. ATP is to your body what currency is to an economy.

Mitochondria are remnants of bacteria that took up residence in the cytoplasm of nucleated cells perhaps 2 billion years ago, long before such cells evolved into plants and animals. They still carry some of the DNA of their bacterial ancestors and this DNA can mutate in a number of ways. The mother of the children who died and the one who is healthy had abnormal mitochondria — while 70 percent of her mitochondria were normal, 30 percent harbored a mutation and did not produce energy. She had enough ATP for life, but distribution of mitochondria during cell division and egg formation is random and, by chance, her older children received a high proportion of defective mitochondria. Insufficient mitochondria lead to multi-faceted diseases with symptoms that include stroke, blindness and eventually death.

Mitochondria are inherited only from the mother. Sperm mitochondria are left behind during fertilization. Mitochondrial genetic defects are an almost biblical curse of the Genesis 3:16 variety because they go on for generations. If a female child receives a mixture of 70 percent normal mitochondria and 30 percent mutant, she may eventually have children who are mildly or badly affected and this can go on for generations. 

However, an in vitro fertilization technique exists that can solve this problem, at least in principle. First, an unfertilized egg is recovered from a donor ovary and the nucleus is removed, leaving behind 200 or so healthy mitochondria. A nucleus containing the DNA of the prospective mother (but not her troublesome mitochondria) is then inserted into the egg with the healthy mitochondria (from the surrogate mother). This now normal egg can be fertilized in vitro and implanted (in the biological mother), using well-known techniques. The resulting children should all be normal, as will their children. So far only a few children have emerged from this procedure but they seem to be normal.

How did I come up with the 2.0002 number? My colleague, Dr. Kurenai Tanji, a Columbia University neuropathologist, told me that there are hundreds of mitochondria in a human egg cell and each one has about five copies of the mitochondrial genome, which is about 16,000 nucleotides long. Nucleotides are the basic subunits of the genetic code, called A, C, T, and G. Doing the arithmetic, that is, say, 200 mitochondria x 5 genomes per mitochondrion x 16,000 nucleotides per genome, it gives 16 million nucleotides of contributed mitochondrial DNA. This sounds like a lot, but the DNA from the two real parents resides in the nucleus of the same cell and contains two copies of every gene. It amounts to 6.4 billion units of DNA. The egg/mitochondrial donor did not contribute a third of the DNA, but about 0.0002 percent, at best. Mitochondria contribute energy, but not human individuality; that stems from the real parents’ genes — and, let’s not forget, their love and care for this child.

My Department of Pathology and Cell Biology at Columbia University Medical Center is a leader in the study and diagnosis of mitochondrial diseases. Dr. Tanji is a member. These scientists and physicians analyze tissue samples and DNA from around the world, to diagnose mitochondrial diseases (which is not so easy). The Mitochondrial Diseases Group has produced an excellent brochure on mitochondrial diseases. Email me for an electronic copy.

Is this new technique available to families who carry defects in mitochondrial diseases? In the United Kingdom, Parliament approved it several years ago, against the opposition of the Church of England and the Catholic Church. It is not legal in the United States yet, and my guess is that there will be opposition, as there was years ago to in vitro fertilization. The procedure discussed in this column was performed in Mexico.

Richard Kessin is Professor of Pathology and Cell Biology Emeritus at Columbia University. He lives in Norfolk and can be reached at rhk2@columbia.edu.