In 1997, Gattaca – a title derived from the four main nucleobases found in the nucleic acids: guanine, adenine, cytosine, and thymine- brought us a dystopic future where people could decide whether to prune their babies DNA to prevent them from genetic diseases in the future -although the idea quickly degenerated into tailoring a new generation of flawless robot-like humans. The idea is not new -see, for example, Miles’ origin in the Vorkosigan saga (Lois McMaster Bujold)- and could probably look like a good thing, only … what happens if you are not tailored to perfection? if they knew from birth you’d develop a serious disease, could you get a good job? buy a house? get married and have kids? In the movie, the answer is a clear “no”, although it does not account for human determination and endurance. And we are not even going into “A brave new world” territory -where lower castes are deliberately handicapped by the introduction of toxins during gestation and development to have low cost labour- nor raising similarities to eugenics, if only to avoid the Godwin’s Law.
However, wouldn’t you avoid genetic diseases in our progeny if you could? Because, at this point, technically you could. Sort of. Only maybe you shouldn’t.
The best known technique to do so is the so called CRISPR (clustered regularly interspaced short palindromic repeats). Francisco Juan Martinez Mojica in 2005 found a number of DNA fragments in bacteria and archaea genome that had been previously observed by Yoshizumi Ishino, but whose function was unknown. CRISPR was usually found in company of specific genes that were labelled “CRISPR associated” (Cas) genes. Martinez Mojica explained that CRISPR derived RNA combined with Cas proteines were part of a defense system against viruses: it searches for the attacking virus genetic material using the RNA as a reference and Cas slices it to render it harmless. Furthermore, Cas preserve some virus fragments to add them to the host genetic code so they already have a reference for future attacks (sort of a genetic vaccine, for -extreme- simplification).
Further research showed the potential of CRISPR for gene edition. Jennifer Doudna and Emmanuelle Charpentier re-engineered a Cas9 endonuclease into a two-component system that could find and cut the DNA target specified by any guide RNA.
Source: Alkhnbashi, Omer & Costa, Fabrizio & Shah, Shiraz & Garrett, Roger & Saunders, Sita & Backofen, Rolf. (2014). CRISPRstrand: predicting repeat orientations to determine the crRNA-encoding strand at CRISPR loci. Bioinformatics (Oxford, England). 30. i489-i496.
Simplifying in extreme, if you want to cut a DNA sequence from a gene, you need to create the corresponding guide RNA in the lab, combine it with Cas9 and send it to do its job. Afterwards, you can just leave the hole in the target chain (indel process) or even replace the cut fragment with a chosen one.
Voila! If one could “cut” all the genes associated to diseases and/or replace them with disease resistant ones, resilient population achieved! Obviously, as soon as it was stated that this process could be used on humans, yet another patent war was unleashed.
However, the process had not been applied to humans yet for several critical reasons. First, the specificity of RNA guides is not perfect, meaning that Cas9 may cut fragments we do not want it to and provoke who knows what (mutations). Also, it can not be granted that every single cell of an organism is edited (genetic mosaicism). This uncertainty should be more than enough to stop tests with humans, specially since we are contemplating inheritable genetic modification, i.e. when babies grow up and reproduce, they’ll pass these modifications to their own descendants even if effects are totally undesirable … unless one is thinking of sterilization. Like in a Brave New World. Only there are countries more lax than others where ethics are concerned.
It turns out that in 2018 He Jiankui, a chinese researcher, decided to edit the genome of two embryos to reproduce a mutation known as delta32. In cells with this mutation, gen CCR5 lacks 32 nucleotids and can not produce a protein that VIH uses to invade lymphocytes. All in all, he wanted to produce kids inmune to HIV. Bad news are that not only did he not achieve that delta32 mutation, but also provoked other mutations in gen CCR5 as well as in other parts of the genome, plus not all cells were edited. As expected. The consequences in medium/long term of this experiment are unpredictable. At the moment, China denies any official involvement, He’s lab has been closed and He is (apparently) missing.