Scientists comment on a new study claiming precision from CRISPR-Cas GM technique

An article in Science Daily reports on a study in the journal Nature [1] that concluded that the off-target effects of CRISPR-Cas gene editing can be reduced to virtually nothing.

Is this the ‘holy grail’ of GM – a genetic engineering technique that really is precise and predictable? We asked scientists for their views.

A summary of the feedback is as follows:

* We should not fall for the narratives and definitions of some genetic engineers. In their small, controlled and constant environment, they claim that they have had instances in which they could reduce the off-target effects to non-detectable levels. This means that they did not see them - it does NOT mean that they do not exist.

* One reason for not detecting off-target effects may simply be that the researchers did not look in the right place or do not have the necessary capacity to detect such effects even if they are in front of their eyes. To prove ‘no effect’ is difficult. It needs to be proven for all applications and GM traits, in all conditions and environments. None of that can be done in a few lab experiments.

* Increasing precision does not meaning increasing understanding or knowledge. We can, in a precise and controlled way, cut and paste a book written in Chinese and yet have not the faintest idea of what we have been rearranging. The narrative of precision = control = safety is a fallacy.

* The researchers’ protocols for looking for off-target effects must be critically scrutinized in order to see where their limits of detection are. What they consider to be 'non-detectable' may not be 'non-detectable' for others outside their controlled laboratory world.

* These researchers and other genetic engineers continue to build on the outdated central dogma of biology: “The coded genetic information hard-wired into DNA is transcribed into individual transportable cassettes, composed of messenger RNA (mRNA); each mRNA cassette contains the programme for synthesis of a particular protein (or small number of proteins)." These people appear to believe in the reductionist idea that organisms are hard-wired by their genes. However, we see at best limited (partial and exceptional) supporting evidence for that in ecological genetics.

* The capacity of these DNA-cutting “gene editing” techniques is limited to simple traits that we presume are coded in certain short stretches of DNA. In reality genes operate in complex adaptive networks which help the organism function in, and adapt to, quickly changing environmental conditions outside of cells in corporate labs. If it were so simple to tweak a few short stretches of nucleic acid molecules to adapt to and deal with complex conditions, we would long ago have been cranking out designer organisms on conveyer belts. That is obviously not happening and will likely not happen in the foreseeable future, if ever – at least NOT with CRISPR-Cas and other currently available techniques. But there is a good chance that we could cause serious problems if we fail to look for and detect the shortcomings rigorously enough.

* Currently, the chances that adverse effects could escape our attention and cause serious problems are bigger than our capacity to produce something useful. This is simply because of our severely limited understanding of how
genetics really work. We mainly know how they do NOT work –
– in a predictable (deterministic) way
– in a non-variable way
– in a reductionist fashion.
Unfortunately these are the fundamental prerequisites for genetic engineering, including gene editing.

Notes

1. Kleinstiver BP et al (2016). High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016 Jan 28;529(7587):490-5. doi: 10.1038/nature16526. Epub 2016 Jan 6. https://www.ncbi.nlm.nih.gov/pubmed/26735016