On March 4, 1990, during a game with UC Santa Barbara, Hank Gathers, All-American basketball player at Loyola Marymount University, suddenly collapsed on the court. Gathers, 23, died shortly thereafter.
For a moving description of these events, see https://www.youtube.com/watch?v=vcD5XUXfr1Y.
How could a young athlete, presumably in superb condition, experience sudden death while doing what he loved?
It turned out that Gathers had hypertrophic cardiomyopathy (“HCM”), a condition characterized by thickening of the walls of the left ventricle, the heart chamber that pumps blood to the rest of the body. HCM is the commonest cause of sudden death in otherwise healthy young athletes. The mechanism is often a dysrhythmia, an abnormality in the rhythm of the heart impeding its ability to pump effectively. HCM is also associated with heart failure. In patients who have been diagnosed, HCM may limit activity for fear of sudden death.
HCM also engenders genealogical concerns: a mutation in a gene called MYBPC3 can cause this disorder, and a patient can pass the mutation on to the next generation. For each gene, of course, we have two copies: one from our mothers, and one from our fathers. The HCM genetic defect is referred to as an autosomal dominant mutation, meaning that inheritance of but one copy can result in disease. A patient can develop HCM, then, if he inherits one disease-causing version of the gene and one healthy one. Physicians have long wondered whether it may be possible to prevent HCM by detecting it early enough in embryonic life. A recent paper suggests the answer may be yes.
Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park, et al., “Correction of a pathogenic gene mutation in human embryos,” Nature (2017), http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23305.html?foxtrotcallback=true reported recently that by using gene-editing techniques (referred to colloquially as “genetic scissors”) in a human egg fertilized (“zygote”) in a petri dish, they were able to cut out the HCM gene, originating in this case from the sperm used to create the zygote through in vitro fertilization; cause the healthy, normal gene from the mother to be copied; and replace the newly-deleted abnormal gene with the new copy of the healthy one. The result: the zygote no longer had the abnormal gene that leads to HCM. Of particular scientific interest, the zygote did the repair with healthy maternal genes exclusively, not with “external DNA” — a stranger’s healthy genes, also provided by the investigators. It was as if the zygote looked for a blueprint to learn how to solve the defective gene problem and found it in the healthy gene inherited from the mother. Across the board, the zygotes studied used genetic material from their mothers, not the exogenous DNA that the scientists had provided.
This suggests that, in at least some in vitro fertilization cases, it may eventually become scientifically possible to correct at least some genetic errors in embryos before they are implanted in the uterus. In theory, this could avoid the birth of infants with genetic defects. It also suggests that there may be lower risk than had been feared of inserting abnormal genes into the genome.
What’s not to like?
It is beyond debate that hypertrophic cardiomyopathy is a terrible disease; Hank Gathers is far from its only victim. Conceptually, there is no reason why the method described could not be applied in other genetic disorders as well. Many of these are debilitating; some are fatal. And preventing disease, as we do with vaccination, for example, is consistent with medicine’s highest ethical principles.
Nor can it be denied that the scientific acumen needed to accomplish the feat that Ma et al. describe in their paper is spectacular. Similar work had been done in 2015 in China, but that does not detract from the brilliance of the technique.
Moreover, if in future research the zygotes’ preference for normal parental DNA over exogenously supplied DNA is confirmed, that would be reassuring for at least two reasons: First, it suggests that “off-target” errors may be relatively uncommon. That is, the technique might not be likely to either modify healthy genes or to insert abnormal genes into the embryo’s DNA. Second, it suggests that the probability that parents will be able to bring “designer babies” into the world–babies whose heights and eye colors and IQs and so on have been chosen in advance by their parents–is likely to remain in the realm of science fiction for some time to come. We are not likely to be forced to sing the Horst Wessel Lied any time soon.
But we must not be blasé about these developments.
First, we are doing research here on fertilized eggs. To mature into a neonate, a zygote needs only some time and a chance to grow undisturbed. The polite word for the treatment of zygotes not implanted into the womb is that they are “discarded.” Among the zygotes and embryos discarded, how many Einsteins were there? How many Mothers Teresa?
Second, while existing methods seem to make “designer babies” a fantasy, the very existence of “genetic scissors” is a reminder of the power of human ingenuity. What is impossible today may not be tomorrow. And the prospect of rejecting an embryo because the parents prefer one with a genetic makeup better suited to performing some day at Carnegie Hall, or simply because they wanted a son and are destined to have a daughter (or vice-versa), is both terrifying and reprehensible.
Our Supreme Court has taught that parenting decisions “concerning education, religion, and procreation are constitutionally protected interests because they involve the most intimate and personal choices a person can make.” Planned Parenthood of Southeastern Pa. v. Casey, 505 U.S. 833 (1992), https://supreme.justia.com/cases/federal/us/505/833/. But it has also held that “many of the rights and liberties protected by the due process clause sound in personal autonomy do not warrant the sweeping conclusion that any and all important, intimate, and personal decisions are so protected.” Washington v. Glucksberg, 521 US 702 (1997), https://supreme.justia.com/cases/federal/us/521/702/.
Are there ethical limits to the pursuit of knowledge?