russ_watters said: As stated, it isn't clear that this concern is meaningful. Is it:

1. Selecting cells with a higher cancer risk results in an increased cancer risk in edited cells vs selecting cells with a lower cancer risk. [Meaningless because you are just selecting and measuring a pre-existing risk without actually altering the risk.]

or:

2. Gene editing increases cancer risk in general, so selecting cells with reduced ability to fight cancer makes it worse.



or something else?

Interpretation #1 is the correct one. While you are correct that this won't result in an increased cancer risk in some applications, there are others where this is a concern. Here are a few ways in which scientists envision using CRISPR:1) Packaging CRISPR-Cas9 into a virus and applying the virus to the tissue that needs to be repaired (e.g. injection into the eye to treat blindness). As you correctly point out, the concern brought up from the papers does not really apply here. The edits are more likely to go into cells with a pre-existing cancer risk, but likely aren't altering that pre-existing risk. However, these applications are probably furthest from the clinic for other technical and safety reasons (mainly surrounding delivery of the viruses). Furthermore, the fact that active p53 suppresses gene editing suggests that these methods won't be terribly efficient in most of the cells in the body.2) Scientists extract cells from the individual, edit them in the laboratory, expand them in culture, and re-introduce them into the body. Some of the first planned clinical trials for CRISPR-based therapies are based on this idea. One hopes to engineer immune cells to help them fight cancer and another looks to correct one of the genes involved in sickle-cell anemia . Because scientists select for edited cells in the lab and then grow those cells in the lab before injecting them back into the patients, the concern is that the scientists will be introducing a large population of cancer-prone cells into the patients. This is a particularly important concern when introducing edited stem cells into the body, as envisioned by the sickle-cell anemia therapy.3) Editing embryos to correct genetic defects at their source. In the process of editing embryos and selection for embryos containing the correct edits, if scientists are not careful, they are likely to also select for embryos with defects in p53. This research makes a strong argument for a moratorium on human germ-line gene editing until we understand more about these issues.