Avoiding the transmission of mitochondrial disease takes a trio, but raises a host of logistical issues.
When first used in humans in the 1970s, in-vitro fertilization (IVF) raised significant ethical, legal, and philosophical concerns. The ability to manipulate human reproduction was viewed in many circles as an attack on the traditional family and an odious attempt to assert human dominion over nature. Terms such as “designer babies” and “playing God” were commonly applied to IVF. Nevertheless, much of the scientific community touted the potential benefits of these technologies, viewing them as the start of a new era of medicine. Indeed, despite those dire predictions four decades ago, IVF is now widely accepted and has enabled infertile couples to conceive more than 5 million healthy babies.
Fourteen years ago, my Columbia University colleagues and I (JL) examined the mitochondrial origins of Dolly, the cloned sheep, and proposed the concept of a “three-parent” fertility procedure to treat mitochondrial disorders (Nat Genet, 23:90-93, 1999). The unique genetic information within mitochondria enables these organelles to function as the biochemical engines of the cell. However, sometimes deleterious mutations occur in mitochondrial DNA (mtDNA) that cause myriad human pathologies—such as heart problems, liver failure, brain disorders, blindness, hearing loss, myopathy, and in the most extreme cases, death. These mitochondrial disorders are incurable and are passed down maternally from generation to generation. One in 6,500 children worldwide is affected with mtDNA defects. (See “Power Failure,” The Scientist, May 2011.)
To prevent defective mtDNA from being passed from mother to child, scientists in the U.K. are planning to offer a “three-parent” fertility procedure. Based in part on protocols developed by scientists at the New York Stem Cell Foundation and at Columbia University Medical Center (Nature, 493:632-39, 2013), this procedure modifies standard IVF technology to create an embryo from the eggs of two women and sperm obtained from one man. Specifically, nuclear DNA from the egg of a woman carrying mitochondrial defects is transferred into the enucleated cytoplasm of a donor egg that harbors nonmutated mtDNA. This genetically reconstituted egg is then fertilized in vitro by sperm from a male partner, and the resulting embryo is implanted into the uterus of the woman with the mitochondrial disorder. This embryo will contain genetic material from three donors, but will not express any symptoms of the mitochondrial disorder.
The potential for creating children from multiple parents is not limited to the halting of the passage of mitochondrial disorders. In May 2013, Shoukhrat Mitalipov and his colleagues at the Oregon Health and Science University published a milestone article describing the use of IVF technology to transfer genetic material from any nonsperm cell into a human egg, thereby generating a pre-implantation embryo from which human embryonic stem cells can be readily isolated and maintained in the laboratory (Cell, 153:1228-38, 2013). One of many potential outcomes of this research is the ability to create a human embryo without any male genetic contribution—by transferring the nucleus of a somatic cell from one woman into an enucleated egg of another. Embryos could also be made from more than three genetic parents by merging multiple embryos into a single chimeric infant, as has already been achieved in rhesus monkeys (Cell, 148:285-95, 2012).