The U.K. parliament is meeting soon to decide whether to allow doctors in Britain to be the first in the world to perform germ-line gene therapy. The therapy would involve performing modifications on embryos in an attempt to avoid incurable diseases that arise from abnormal mitochondria. Mitochondria are organelles in the fluid of a cell (cytoplasm), which act as the powerhouses of the cell. They have their own DNA, which happens to mutate over 100 times faster than the DNA within the cell nucleus, and therefore cause disease in about 1 in 6,000 children. These mitochondrial diseases are carried only in the woman's eggs and are passed on to all of her offspring. Depending on the percent of mutated mitochondria and the particular mutation, the children will show varying degrees of clinical problems from mild to fatal, which usually involve the heart, eyes, and muscles. These diseases can burden families from generation to generation with no current cures. Unlike many other genetic problems, reliable prenatal testing options for mitochondrial diseases are limited due to the complexity of accurate diagnosis.
The regulatory body that governs fertility treatments in the U.K., the HFEA, is considering if it should begin allowing this new genetic therapy for women who carry mitochondrial diseases, so that they may attempt to have children who are unaffected by these often fatal and devastating diseases. The success of this process, technically known as spindle transfer (ST), was advanced recently in the U.S. by an Oregon team lead by Shoukhrat Mitalipov, Ph.D., and has now been replicated by several other researchers around the world. With this technique, a donated egg cell will contribute its healthy cytoplasm and mitochondria, but the nuclear DNA will come from the mother's egg and will thus express the mother's family traits. The ability to successfully replace a part of an egg cell will likely prove to be one of the most significant advances in modern medical history.
With all novel complex medical advances, it is common to simplify the terminology in public discussion. Unfortunately, the adoption of the term "three parent IVF" is unhelpful and misleading. An egg, which was knowingly donated for this purpose from a well-informed donor, does not a parent make. The mitochondrial DNA from the donor's egg contributes only 1/1000th of the total genetic material of an individual and is not responsible for the transmission of traits or family related personal features. Using the term mitochondrial replacement is more accurate and descriptive.
Opponents to this technique speak out with a number of objections. One reflexive objection is that this step will lead directly to human reproductive cloning and eugenics. While this argument emerges in response to many significant advancements in the field of genetics, it is unfounded. As well, I would urge anyone who relies on the cliché of a slippery slope to designer babies to listen to the story of a couple who has suffered through the loss of a young child from mitochondrial mutation before passing judgment on the potential of this technique for preventing life-threatening diseases.
Another objection is that we do not have enough information to move this into human trials. Concerns exist regarding limited outcome data on offspring, as most data thus far come from human embryos which have only been grown to five or six days (known as blastocysts) and from non-human primates which have not yet bred their own offspring. Other concerns involve more technical issues, such as unknowns regarding the interactions of a cell's nuclear DNA with its mitochondrial DNA.
However, it is important to realize that a similar treatment on humans has already been completed. Over a decade ago, a team headed by Jacques Cohen at Saint Barnabas in New Jersey injected tiny amounts of donor egg cytoplasm (containing mitochondria) into the eggs cells of infertile women. This experiment led to the birth of 17 babies who are, by now, in their teenage years. The U.S. FDA stopped the procedure in 2001 stating that more research was needed. The team is currently embarking on a long-term follow-up study of the health of children that would contribute significantly to the U.K. parliamentary debate.
Deciding what weight of the published evidence might tip the scales from basic science experiments to clinical human trials certainly warrants a long and informed discussion best held by those who work in the field and comprehensively understand the science. As with the very first IVF treatment in 1978, which culminated in the birth of Louise Brown in England, there must be, at some point, a first case. In science such a first case will occur before all of the answers are in, even in the presence of controversy about the techniques and the ethics. The birth of Louise Brown has now evolved into the birth of over 5 million children around the world from IVF.
The utilization of mitochondrial replacement has the potential to eliminate incurable diseases in children and improve the human condition. It is also possible that, if it proves to be safe and effective, in the future ST-enabled advancements using mitochondrial replacement could have a more significant impact on reproduction by improving egg quality in women of advanced reproductive age and restoring their fertility.
The British approach to the novel implementation of mitochondrial replacement therapy, with extensive public involvement and careful, measured scientific review, may serve as an example for the United States and rest of the world.