The significance of 37
January 30, 2017
The significance of 37
MSc in Molecular Biology, PhD in Genetics
Masters in Bioethics, Clarkson University &Icahn School of Medicine at Mount Sinai (exp. June 2017)
It's a boy! Such a familiar statement but with somewhat peculiar and mysterious echo on the morning of 29th September, 2016. While drinking my first coffee of the day, I am wondering what is so unique about this boy to put him in the headlines of CNN, The Washington Post, The New York Times, The Guardian and every other -post or -times that exist around the world . Aha! ˝World’s first baby born with new ‘three parent’ technique. Ok, this requires a larger cup of coffee....
Even though many believe that all of our genes reside in the nuclei of our cells, it’s more complicated than that. A small part of human genome (only 37 genes compared to an estimated 20,000-25,000 genes in the whole genome) is situated outside the nucleus, in the "energy factories" of the cells called mitochondria. Mutations in one of these 37 genes might cause mitochondria failure, cell damage, and even cell death. Mitochondrial diseases are usually progressive; they manifest differently and affect those parts of the body that have highest energy demands: brain, muscles or heart. These tiny pieces of DNA are inherited only from our mothers. So, each of us inherited these 37 genes from our mother, who inherited them from hers, and so on and so forth through generations.
As a result, faulty mitochondrial genes present in the mother’s cells are always transmitted to her offspring. Mitochondrial gene transfer (MGT) is a new technique that might help us eradicate mitochondrial diseases by combining the healthy mitochondrial from one woman with the nuclear genes from another woman, resulting in baby having genes from two mothers. Despite the obvious advantage of avoiding serious hereditary conditions from abnormal mitochondrial genes, there are reasons to be concerned and cautious.
If we take a look at pure biology, some experts raise concerns that three-parent babies could be at a greater risk of severe diseases. Given how well evolution has tuned the communication between mitochondrial and nuclear genome, we might introduce risks just by interrupting this tight link. For example, in the late 1990s, fertility specialist Jacques Cohen from Saint Barnabas Medical Center in Livingston, New Jersey, tried to help women trying to conceive by adding ˝a little cytoplasm˝ containing mitochondria from another woman's healthy egg into the recipient's. However, some of the infants were born with severe genetic disorders. As a result, the procedure was banned by the FDA. Even though the mitochondrial genome represents less than 0.1% of our whole genome, the previous experience and the complexity of biological pathways indicate that this subset of the genome is very important.
The questions of parenthood
This technique also raises questions about the moral and legal parents of a child born through MGT. For example, what are the rights (if any) of the mitochondrial mother (the donor of mitochondrial genes) given the fact that she contributed such a small portion of the genome? Also, does the child have the right to know who their parents are, no matter how much they contributed to this genomic puzzle? Our current understanding suggests that mitochondrial genes provide “only” instructions for making proteins necessary for creating energy, but the complex epigenetics and interactions between nuclear and mitochondrial DNA suggest that the contribution of donor might be higher than just donating energy. Given the limits of our current understanding, the full extent of the influence of the mitochondrial genes on an individual’s development and later life are unknown.
Implications for society
There is general concern that any form of gem-line editing (including MGT) might alter human genetic makeup in a permanent way. The risks arise from the uncertainty, unpredictability, and irreversibility of germ-line modifications. However, Nuffield Council on Bioethics in the UK has examined this technology and released a summary saying that “Due to the health and social benefits to individuals and families of living free from mitochondrial disorders, … we believe that if these novel techniques are adequately proven to be acceptably safe and effective as treatments, it would be ethical for families to use them.” While some look at our genes as just another part of our body that should be fixed believing that MGT will help us to prevent serious mitochondrial diseases, the real question moving forward will be how we demonstrate that this procedure is actually “acceptably safe and effective”.
As a geneticist, I applaud the advancement of the technology, and I am amazed that the first “mitochondrial baby” is already eight months old (he was born in April, 2016). I am thinking, if science and medicine can be used as a tool to eliminate human suffering, then let's get on with it. But at the same time, the bioethicist in me can’t help but wonder if we are approaching the slippery slope to designer babies, genetically engineered to be healthier, smarter, or more beautiful than they would otherwise be?
And while I am taking the final sip of my coffee, I am staying positive and keeping my fingers crossed for the baby boy to stay healthy and have a long life. Hopefully, 37 will be nothing more than a number to him.