Three-Parent Babies: It’s Not What You Think

Three Parent Babies

In 2016, doctors from a fertility clinic in New York City announced the birth of a three-parent baby boy. It’s not what you think. Three-parent babies have nothing to do with a ménage a trois. The technology involves genetic engineering. It is not done to produce a designer baby, but it may save a baby’s life. [1-3]

The proper term for this new technology is mitochondrial replacement therapy (MRT). MRT is a type of assisted reproductive technology. Although doctors from a fertility clinic in New York City participated, the birth of this baby took take place in Mexico. MRT is not approved in the United States. [1-3]

One Sperm, One Egg, and Mitochondria

A three-parent baby gets half of its genetic information – its DNA – from a father’s sperm and half from a mother’s egg, same as most babies. But a three-parent baby also gets a transplant of mitochondria from a donor egg. This technology is tricky, so bear with me. Let’s start with the mitochondria. [1-3]

Mitochondria are energy producing bodies that are present in almost all the cells of your body. These bodies – called organelles – are located in the cytoplasm that fills your cells and surrounds the nucleus of your cells. The nucleus of a cell is where all your DNA is located. The weird thing about mitochondria is that they have their own DNA, separate from nucleic DNA. Researchers believe that these organelles started out as bacteria that invaded cells millions of years ago. [3]

Mitochondrial DNA (mDNA) has nothing to do with how you look, what sex you are, or what color eyes you have. Those traits are all coded by nuclear DNA. But mDNA is important for keeping mitochondria healthy and functional. That is very important because over time, lots and lots of time, mitochondria developed the ability to supply energy for your cells. In fact, healthy mitochondria supply about 90 percent of the energy your cells need to survive. [4,5]

That brings us to why MRT might save a baby’s life. Just like the genes in a cell nucleus, the genes of mitochondria can develop changes called mutations. These mutations can build up over several generations and pass to a baby through mitochondria in the cytoplasm of a mother’s egg cell. Sperm cells do not have mitochondria, so mDNA defects are only passed from mothers to babies. [3,4]

There can be thousands of mitochondria in a cell’s cytoplasm and billions of cells. Some have a few mDNA defects and some have a lot. A mother may not have enough defective mitochondria to have symptoms, but she may pass enough defects off in her egg for a baby to have symptoms. If enough genetic defects are passed along, a baby can be born with symptoms of a genetic mitochondrial disease. [4,5]

Since babies need lots of energy to grow, and defective mitochondria do not produce much energy, many babies do not survive these diseases. Research shows that one in every 200 people have some mDNA mutations. Up to 5,000 babies are born each year with enough mDNA mutations to cause a mitochondrial disease. [1]

There are many types of mitochondrial diseases. They affect cells that need to produce lots of energy like brain cells, digestive system cells, and muscle cells. [5] The woman who had the three-parent baby in Mexico had two previous children die from a mitochondrial disease called Leigh syndrome. [1] Leigh syndrome is a progressive brain disease that starts in infancy or early childhood. [6]

How to Make a Three-Parent Baby

MRT is similar in most ways to other reproductive technologies that combine sperm cells and an egg outside the body – called in vitro fertilization. Here are the steps: [1-4]

  • A mother must be suspected or diagnosed of carrying a mitochondrial disease. Since these diseases are hard to diagnose, the first sign may be a previous baby with mitochondrial disease.
  • The mother has an egg removed from her ovary.
  • The father donates sperm cells.
  • A donor egg is removed from a woman who does not carry mitochondrial disease.
  • The nucleus of the donor egg is removed, leaving the cytoplasm and mitochondria.
  • The nucleus of the mother’s egg is removed and placed into the donor egg cell.
  • The donor egg now has the mother’s DNA in the nucleus and the donor’s mDNA in the cytoplasm.
  • The donor egg is fertilized with the father’s sperm.
  • The fertilized egg is placed into the mother’s womb to grow.

What Could Go Wrong?

So far, there are only a few three-parent babies. The baby born in Mexico shows no signs of mitochondrial disease. But he is still a baby. Researchers don’t know the long-term effects of MRT as children grow older. [1-3]

One problem is that some of a mother’s mDNA can still get into the donor egg. Testing after birth suggests that the Mexico baby has about 2 to 9 percent of his mDNA from his mother and the rest from the donor mother. Why is this a problem? [2]

Research in fruit flies suggests that when you transplant foreign mDNA into a cell, the natural mDNA and the foreign mDNA may start to compete. Researchers call this competition for genetic dominance “bully genomes” versus “wimpy genomes.” A few bully genomes can knock out many wimpy genomes, at least in fruit flies. Nobody knows if this will happen in three-parent babies. If it does, the baby may revert to maternal mDNA and develop mitochondrial disease over time. [3]

Another big obstacle is ethics and government policy. The United Kingdom is the latest country to approve MRT. In the United States, the FDA is prevented from even studying MRT by language stuck into a 2016 congressional spending bill blocking any research that involves genetic modification that can affect future generations. [4]

So for now, at least in America, all we can do is sit back and watch what happens in other countries performing MRT. It has great promise for families who want to have children but are at risk for passing on a mitochondrial disease. MRT may also lead to other breakthroughs. Only time will tell.

Sources:

  1. Nature/News, Genetic details of controversial three-parent baby revealed, https://www.nature.com/news/genetic-details-of-controversial-three-parent-baby-revealed-1.21761
  2. Science News for Students, How to make a three-parent baby, https://www.sciencenewsforstudents.org/article/how-make-three-parent-baby
  3. University of California San Francisco, Three-Parent Babies: The Science of replacing Mitochondrial DNA and What Remains Unknown, https://www.ucsf.edu/news/2017/01/405486/three-parent-babies-science-replacing-mitochondrial-dna-and-what-remains-unknown
  4. United Mitochondrial Disease Foundation, Mitochondrial Replacement Therapy, http://www.umdf.org/mitochondrial-replacement-therapy/
  5. Cleveland Clinic, Mitochondrial Diseases, https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases
  6. National Organization for Rare Disorders, Leigh Syndrome, https://rarediseases.org/rare-diseases/leigh-syndrome/
Christopher Iliades
Dr. Chris Iliades is a medical doctor with 20 years of experience in clinical medicine and clinical research. Chris has been a full time medical writer and journalist since 2004. His byline appears in over 1,000 articles online including EverydayHealth, The Clinical Advisor, and Healthgrades. He has also written for print media including Cruising World Magazine, MD News, and The Johns Hopkins Children's Center Magazine. Chris lives with his wife and close to his three children and four grandchildren in the Boston area.

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