Broiling Base Pairs: Is It Unnatural to have a CRISPR Genome?

Experiments in China using CRISPR on nonviable human embryos has caused a stir in scientific and ethical circles. CRISPR will allow for targeted gene editing and people have raised concerns about using CRISPR to create designer babies. Additionally, gene edits made using CRISPR would affect the germline; changes made to an embryo’s genome would be passed on to their offspring. Many scientists and ethicists have expressed concern over germline changes.

While I appreciate the concerns people have expressed, I think that sometimes these concerns can arise from misunderstandings about genes and gene expression. An individual’s genome is never static completely. Each time a cell divides, replication errors can occur, even with proofreading enzymes correcting mistakes. Mutations can be replicated as well. I’ve written about these ideas in the context of human cloning before, so for the conversation at hand I will focus on genomic imprinting and epigenetics.

Genes can be affected by the environment, including lifestyle choices that a person makes. This often takes the form of methylation. DNA methylation is when a methyl group is attached to a nucleotide in DNA (cytosine or adenine specifically), silencing the expression of a gene. Methylation is a normal part of the human genome, and plays a role in genomic imprinting as well as X chromosome down regulation in women. But problems can also arise from methylation, and this is relevant for this discussion because it can affect one’s offspring.

Genomic imprinting is important for mammalian genetics and genes that are imprinted do not undergo the demethylation process that other genes go through. Sperm and egg cells are imprinted paternally or maternally but the zygote removes this imprint for most genes, allowing a new imprint to be formed matching the sex of the new individual. Genes that do not undergo this process are known as imprinted because they will retain their previous paternal or maternal imprint in the new individual. Imprinted genes make up less than 1% of the genome and only occur on 9 chromosomes, but they represent a natural form of inherited change. Imprinted genes only have one of the alleles expressed (for a maternally imprinted gene, the maternal allele and vice versa). Problems can arise then if there is a mutation in the functioning allele.

Genomic imprinting is different than CRISPR, however, because it does not affect the germline cells. Those cells strip all parental imprinting away, so the parental gene expression only carries to one’s immediate offspring, and then their offspring are affected by their imprinting. It is not a change to the human genome, but a change in expression that is transmitted a single generation.

I am not suggesting that genomic imprinting makes CRISPR a non-issue ethically speaking. I am merely trying to point out that there are other ways in which gene expression can be changed outside of human directed gene editing. It seems that people are concerned about deliberate changes to the human genome, but if the basis of concern is not wanting to influence human evolution by affecting gene expression, then people should give just as much attention to DNA methylation from lifestyle choices. Perhaps even more attention, because these changes in gene expression are ongoing currently, and not a possibility or eventuality like CRISPR once the technique is deemed safe enough for use in humans.