The safety problems of human germline modification

Digital Journal has reported that the FDA is holding a public meeting this week to discuss “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease”. Although the technique being discussed does not involve altering nuclear DNA it is a form of germline genetic modification because it is creating an oocyte that is a new genetic entity consisting of the nucleus of an oocyte from one woman who desires a genetically related child implanted in the enucleated oocyte of a woman free of the mitochondrial disorder that the first woman does not want to transmit to a child. The resulting combination of nuclear DNA from woman A and mitochondrial DNA from woman B would be genetically different from any possible child parented by either woman. This new genetic combination would be then transmitted to the child’s offspring so this would be a true germline genetic modification.

Although there are other ethical concerns about the use of such a technique, the clearest concern regarding such a procedure should be the safety of the children who would be its outcome. The problem with determining the safety of such a procedure is that the adverse effects of creating a genome that consists of nuclear and mitochondrial DNA from different individuals is that the adverse effects might not be evident until later in the child’s life or might not be evident until a generation or two later. By altering inherited characteristics all the descendents of the resulting child would be affected. How can you determine that a procedure is safe if it could take generations to determine its safety?

A related problem is the difficulty of obtaining consent for the studies needed to determine the safety of a procedure that alters the genetics of future descendants of the experimental subject. The initial consent would be obtained from the parents of the child being created, but to determine if the procedure is safe the child would need to be followed for his or her entire life and consent would need to be obtained again after the child reaches maturity. However the problem does not end there because further consent would be needed for each of the child’s offspring first from the parents of the next generation and then from the next generation as they reach maturity. (This problem has been discussed in detail by Rebecca Dresser. See her article “Designing Babies: Human Research Issues” in IRB: Ethics & Human Research 26.5 (2004): 1-8.)

It is difficult to conceive a way in which the safety of procedures that alter the genetics of succeeding generations could be established. If we are really concerned about the safety of human research subjects then this type of experimentation should not be allowed. Those who advocate this type of experimental intervention should be honest that it would have to be done without regard to the future safety of the human beings who are being experimented on and their future offspring.

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Mark McQuain
Mark McQuain
7 years ago

During my residency, I performed a pilot study where I investigated the application of electrical stimulation on lumbar muscle strength and bone mineral density, hoping that positive results might be found to benefit women with osteoporosis. We had to get IRB approval, which was and still is a fairly involved task. We appropriately had to present evidence from prior peer-reviewed studies that the proposed intervention (the electrical stimulation) would not harm the study volunteers. Mechanisms were also in place to terminate the study if untoward side-effects were measured. No changes in the study design were permitted once the IRB approved the protocol.

It is mind-boggling that the FDA would bother to hold a public hearing to determine the permissibility of a technique (nuclear oocyte transfer) where there are no peer-reviewed studies of patient safety (on the actual patient – the future child and his or her progeny). Absent this data, there is no IRB that ought permit such a study to commence.

Further, there is no individual who has standing to request some type of suspension of normal IRB protections to implement a trial of this technique with a claim that their dire medical condition demands “exceptional” intervention. The technique itself allegedly prevents the very existence of such an individual. The technique does not provide benefit to individuals who already have the mitochondrial defect(s).

To whom would we be providing informed consent and subsequent intervention?