By David Warmflash, MD | 22 March 2017
Would you agree to genetic modification of your germline DNA, genetic edits that would get passed down to your children and their future generations? This is different from the standard kind of gene therapy. In the latter case, genes in the nucleus of selected body cells – blood forming stem cells, liver cells, or cells in the retina of the eye for example – are changed to eliminate a disease, but those changes are not passed to your offspring.
Scientists, ethicists, and others have been worried about germline modification – sometimes called heritable gene therapy – on the grounds that it could usher in an age of designer babies, or even a 21st century-style eugenics. Eugenics is concerned with genetic improvement of humanity through controlled breeding. It was a popular idea in the early 20th century, but it was embraced and perverted by the Nazis, so it fell out of favor. The concern today is that new biotechnologies would make eugenics much easier than it was in the 1940s. In one scenario, they imagine couples having the genome of their children tweaked to improve traits like intelligence, athletic ability, musical talent, and even beauty. If enough people do this, such children might be placed in special schools when they are young, leading ultimately to a two-class society.
But a recent decision by the National Academies for Science and Medicine says that maybe germline editing should be permitted – after it is proven safe – for correcting certain genetic conditions. This is a recommendation, not a law, but here’s some rationale. Consider that there are families with a genetic propensity for breast cancer, or for various disease of the nervous system. With some genetic diseases and modern medical care, it is possible to have two disease genes and no normal genes and grow up and have children of your own. It’s extremely rare, but it’s also possible for two people with the same genetic disease, both with all disease genes and no normal genes, to have children together. Let’s imagine a man and a woman with cystic fibrosis (CF), for example. Two people with CF each have two abnormal copies, and no normal copies, of the gene that causes the disease. This means that they cannot produce normal embryos, so genetic screening of embryos – a procedure that many find more palatable than germline editing – would not help such a family. If they have biological children, there is a 100 percent chance that the children will have CF – unless the germline is first modified to repair the CF gene.
From the National Academies of Sciences, Engineering, and Medicine, the list of indications for gene editing of germline DNA:https://t.co/GcD2J0JTR4
— Cecile Janssens (@cecilejanssens) December 6, 2018
The National Academies announcement did not come out of the blue. The surge in genetic technology over the passed decade has fueled a trend toward increasing intervention at the genetic level. You may have heard about the recent “3-parent babies”. This involves a technique to eliminate rare conditions involving little parts of the cell called mitochondria, and it has been in use for more than a year. Unlike the chromosomes in the nucleus of each of your cells, which come from both your mother and father, mitochondria are inherited only from the maternal line. You get them from your mother, your maternal grandmother, on and on through the maternal line, but not from your father. This means that a woman with diseased mitochondria has a 100 percent chance of passing down the disease to her children, and to her daughters’ children, and their daughters’ children. Thus, embryo screening would not help her anymore than it would help the couple with CF.
There are different approaches to the 3-parent baby procedure, but essentially a women with normal mitochondria donates most of an egg the cytoplasm, not the nucleus. Instead, the nucleus comes from a woman who wants to be a mother, but has mitochondrial disease. That nucleus contains DNA, which then combines with nuclear DNA from her male partner. The catch is that mitochondria have their own DNA (mtDNA), so the baby ends up with a father and two mothers – a nuclear mother and a mitochondrial mother. There is also a newer procedure under study that edits such a woman’s own mtDNA to create healthy mitochondria with no need for a mitochondrial donor. In either case, this amounts an altered germline, but unlike nuclear germline modification, mitochondrial modification is already happening. The situations when it’s appropriate are very rare, but it’s moving forward, and the same rationale could be applied to nuclear germline editing when a couple cannot produce any normal embryos. This means when father and mother both have two copies of a gene for a recessive condition, and also when either has two copies of a gene for a dominant condition. Yes, such situations are uncommon, just like mitochondrial disease, but show that there’s a rational for a middle ground when it comes to restrictions, and isn’t this how we handle most medical technologies?
Reprinted with permission from The Pulse.
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