This intriguing topic is a follow-up on previous CRISPR/Cas9 articles in GEITP, in which “bioethical issues” were discussed. The Chinese scientist (Dr. He) who edited the genomes of twin girls (very early during pregnancy, in utero) in an attempt to “make them resistant to HIV” — might have inadvertently shortened their life expectancy. It has been known that humans having two defective alleles (copies) of the CCR5 gene (encoding C-C motif chemokine receptor-5, which allows HIV virus to enter immune cells) — protects against HIV infection. However, it has now been discovered that such patients/persons are 21% “more likely to die before age 76” than are people with at least one functional allele of the CCR5 gene [see attached ‘Brief Communication in Nature Medicine & editorial in Nature].
The reason for this (slightly early risk of mortality) phenomenon is unknown, but — as with most endogenous receptors and other cellular proteins used for numerous critical life functions — there is always the strong possibility that blocking a key cellular function might have long-term effects on other critical life processes, not yet understood by any scientist.
This [Nat Med article] analysis was based on genetic and health data from nearly 410,000 people enrolled in the UK Biobank research project. Dr. He (biophysicist at Southern University of Science and Technology, Shenzhen, China) faced widespread condemnation of the experiment he performed on human fertilized eggs, because he had not gone through required bioethics board approval for doing such research. It was reported (Nov 2o18) that Dr. He had used CRISPR/Cas9 technology to “create the first human babies with edited genomes.” Scientists and bioethicists are still grappling with the implications of altering a person’s genes in ways that can be passed on to future generations (especially genes about which ‘we don’t know everything’, with regard to their function).
This latest finding (in a study of ~410,000 subjects) casts further doubt on the wisdom of disabling the CCR5 gene. If a patient has an extremely serious disorder — in which the prognosis is clear that the child won’t live beyond age 2 or 3 years, and that blocking the single gene responsible for that disorder by CRISPR/Cas9 technology might extend the patient’s life to age 20 or 60, then that might be one justifiable reason for using this technology (i.e. ablation of that gene ‘might be worth the risk’). However, blocking the CCR5 gene to prevent AIDS — [a] presumes the patient might be exposed to HIV during her/his lifetime, and [b] nothing is known about other “off-target” effects of such gene ablation. ☹
DwN
Nat Med June 2o19; 25: 909-910 & Nature 6 June 2o19; 570: 16-17