Traitwell's Future of Genomics Series: Gene Editing
We're continuing our discussion about the future of genomics.
We’re continuing our analysis of the future of genomics. For those who are curious, please visit Traitwell.com. Be sure to check out our free apps.
The timeliness of this post isn’t lost on us. Scientists are currently gathering for the Third International Summit on Human Genome Editing. Mississippian Victoria Gray is becoming the poster child for CRISPR. You can listen to her being interviewed by NPR here or read a rather interesting profile about her in the MIT Technology Review.
As fate would have it I’ll be in London next week meeting with investors, colleagues and friends.
Genes can be directly edited in order to eliminate defects or, what is really the same thing, improve outcomes with more favorable alleles. Known techniques like CRISPR use biochemical excision and splicing tricks from viruses to reprogram genes within a cell to a desired state. Technique here is everything, and skills are continually improving to achieve more predictable results (we will gloss over the technical details).
Editing methods can be applied to non-reproductive somatic cells in principle, but also to reproductive germ-line cells prior to conception, as say an enhancement to the gamete selection described above (as far as is known, nobody has done this yet).
A developed living individual may in principle be edited ‘in-place’ but current experience doing this is limited among human subjects. The challenge is to target the treatment accurately to only the cells of interest, to avoid unwanted side-effects. In practice, specific somatic cells are edited outside the individual and then reintroduced, resembling a drug treatment which dissipates and is not inherited.
Epigenetic expression of cells, which are ‘totipotent’ before they specialize their role can also be altered though these means, but the technology is still in development.
Applications of gene editing to plants and animals will far outpace applications to humans, because ethical concerns are either absent or just less prevalent in those cases. Sophisticated gene editing involves transferring gene sub-sequences known to be effective, often from other species. Homology between genes makes this feasible. Thus genes which produce anti-freeze properties in cold-water fish have been spliced into plants to provide cold resistance.
Gene editing among humans has so far been confined to therapy for genetic diseases, for the ethical reasons stated. However in principle there is no reason why it cannot be used in the medium-term future to optimize, say, polygenic scores for aggression or intelligence. But there is a difficulty here. Most genes are now thought to be pleiotropic—that is, alternative alleles will have an influence on multiple traits, in varying proportions. Editing a SNP in order to obtain a change on one trait may have unforeseen consequences on other traits—gaining on the ‘swings’ but losing on the ‘roundabouts’—perhaps with a negative result overall. The situation is currently unclear and is expected to vary by SNP and trait.
Advances in gene editing for real-world outcomes will for these reasons take much longer than the naive expect.
Nefarious uses of gene editing among humans also loom before us. As we have said already, ethical concerns are context-dependent, and one should different customs in other jurisdictions, over space and time. For example, extracting signatures from the genome for the purpose of identity determination, as described above, invites editing of the very limited number of (non-functional) SNPs used by standard techniques, to fool them. Government actors are more likely here. This may be counteracted by using a larger number of sites for the extracted signature, implying an arms race between the parties, with ever larger numbers of sites faked. This may lead to the use of functional positions for signatures, since those are harder to edit than the non-functional ones currently used, or it may require creation of registries at birth to detect later editing.
Likewise, ancestry may be faked by replacing mitochondrial or Y-chromosome DNA—though these elements have important functional roles, so the fakers would have to tread carefully. Given the human penchant for bodily modification—a kind of Murphy’s law—it is not inconceivable that some will be interested in altering their genes merely for the jollies of doing so, or for the visible consequences where those can be found. Perhaps we can look forward to an international industry centred around genetic body modification. A special case of this might be trans-sexual modification at the gene level—the general idea should be clear by now.