3-Parent Embryos, Gene Edited Babies and the Human Future

The idea of giving the best to our children, and helping them be their best, has long been a quest for parents. Today the quest for the perfect child has turned to genetic manipulation. In the past this was the realm of science fiction-think Brave New World or GATTACA-but the ability to manufacture a "designer baby" has recently taken a significant step closer to reality. Robert Edwards, primarily known for development of IVF (in vitro fertilization), said in 1999: "Soon it will be a sin for parents to have a child that carries the heavy burden of genetic disease. We are entering a world where we have to consider the quality of our children."Modern molecular genetic techniques have brought us to the brink of Edwards' consideration of the "quality of our children" and not just in terms of disease. Indeed, James Watson (co-discoverer of the double-helical structure of DNA) in 2001 also suggested opening the door to tinkering with the genomes of our children: "If we could make better human beings by knowing how to add genes, why shouldn't we?" One problem with such sentiment is that there is no direction in terms of who makes such decisions or even the meaning of what constitutes "better human beings."Human genome manipulation by adding genes actually starts first with identifying, and then screening for, specific genes. As with all of these innovations, the initial screens are designed to detect disease genes or associated mutations. All too often, such screens lead to lethal selection against those with such genetic markers. However, the screening never stops with the original intention, but moves on from definitive disease presence to carrier status or to predisposition, as well as from disease trait to non-disease trait. Whole genome screening has now been done for the fetus in utero.1 The next step, after simple screening, is the desire to prevent the disease or trait from appearing.Enter the world of 3-parent and gene-edited babies. Such genetic changes so early in life-at the embryonic stage-are termed "germline" genetic engineering, because the altered genetic traits affect not only the individual but can be passed through the germline to future generations. This is because the genetic change is made such that every cell contains the altered genetics, eventually appearing in egg or sperm.The creation of 3-parent babies was originally proposed as a way to "treat" mitochondrial genetic defects, which can be severe, even life-threatening. Mitochondria are the organelles within every cell that are responsible for generation of cellular ATP energy These small organelles contain their own small DNA genome, encoding 37 genes including 13 essential polypeptides, 22 tRNAs and 2 rRNAs. The mitochondrial proteins are complemented by nuclear-encoded proteins, to form functional mitochondria.2 Mutations in mitochondrial DNA can lead to various, often severe, diseases, all without current cure.3 Approximately 1 in 6500 individuals are estimated to have a serious mitochondrial disorder.4 Mitochondria are inherited through the maternal line, i.e., through the oocyte (the egg).However, no individual with a mitochondrial genetic disease is actually treated by the current proposals. Rather, new human beings are created with tri-parental genetic contributions in the hopes that they will not possess nor pass on the genetic mutations.5The first such experiment, done at fertility clinics, involved injection of ooplasm from a donor egg into the mother's unfertilized egg prior to fertilization in vitro. Over two dozen births attributed to ooplasm transfer were reported by clinics between 1998 and 2002. Mitochondria were transferred as part of the ooplasm, in an attempt to dilute the numbers of mitochondria containing the genetic mutation, resulting in offspring who carry genetic material from three separate individuals-the nuclear genetic mother and father, and the mitochondria/ooplasm donor; the researchers noted that this was "germline genetic modification. …