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CRISPR is out of Pandora’s Box

crispr

Nature has a nice overview of the excitement over CRISPR. The plot above shows Google Trends, and it illustrates what’s been going on. Friends of mine who were working with Talens and Zinc-finger methods are now switching to CRISPR. For a generation genetic engineering has been an idea, CRISPR brings that idea to life. As suggested in the article a lot of the concern with how much more feasible CRISPR has made useful genetic engineering. The cost and effectiveness have gone in reverse directions; down and up respectively.

One thing to note though is that it seems ridiculous to worry about the sheer number of modifications. Conventional genetic engineering techniques and even old fashioned breeding actually produces far more mutants than CRISPR, which has more specificity. Rather, it’s the fact that CRISPR makes genetic engineering feasible for many more labs, and at a more rapid clip. With the ability to do good comes the ability to do bad. As I’ve mentioned before I’m not too worried about CRISPR being used to create genetically engineered superman. Though far better than older forms of genetic engineering, the downside risk of CRISPR is going to be too great for parents to be comfortable engaging in proactive gene editing in the near future (rather, it will be probably first be used in the case of adults with very terminal illnesses, likely of the Mendelian sort). In the Nature piece there’s an analogy to gene therapy. I think that’s a weak one, because gene therapy always had a biomedical focus and massive downsides for misfires (even then, I think there’s been an overreaction, but that’s another post). Rather, CRISPR has more general applications in areas such as GMO.

Finally, there’s the issue of “gene drive.” Basically we’re talking about distortion of Mendelian segregation, so that an allele spreads through the population via intragenomic competition. Instead of a 50% chance of transmission, it could bias it so that the transmission rate is ~100%. Segregation distorters are found in nature, and can cause problems. They could be a foreseeable path toward eliminating pests. But, there are other concerns. From the piece:

But many researchers are deeply worried that altering an entire population, or eliminating it altogether, could have drastic and unknown consequences for an ecosystem: it might mean that other pests emerge, for example, or it could affect predators higher up the food chain. And researchers are also mindful that a guide RNA could mutate over time such that it targets a different part of the genome. This mutation could then race through the population, with unpredictable effects.

This is a legitimate worry obviously. Prominent evolutionary population geneticists take this issue seriously. But, others do not. In the specific concerns above, my reaction is basically echoed below:

The issue is not black and white. Micky Eubanks, an insect ecologist at Texas A&M University in College Station, says that the idea of gene drives shocked him at first. “My initial gut reaction was ‘Oh my god, this is terrible. It’s so scary’,” he says. “But when you give it more thought and weigh it against the environmental changes that we have already made and continue to make, it would be a drop in the ocean.

Genes are not magic. We need to separate the distinctive and particular dangers inherit in genetic engineering, and CRISPR technology specifically, from the broader suite of ills and concerns which plague us. Nature is not at a perfect equilibrium, but dynamic, In addition, we are reshaping the world around us constantly, so concerns of out of control gene drive needs to be kept in perspective.

Finally, I do understand that scientists such as George Church are influential, and their concerns carry great weight. But if CRISPR is so democratizing, does anyone really think that the entire rest of the world will wait? And by the “rest of the world” I guess I kind of mean China….

For God doth know that in the day ye eat thereof, then your eyes shall be opened, and ye shall be as gods, knowing good and evil.

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