CRISPR cancer warning

August 2018

An inescapable and potentially catastrophic weakness in all forms of the genomic molecular manipulations currently fashionable in science, is that healthy cells don't tolerate interference.

Biotech scientists have devised a plethora of clever tricks to force unwanted changes on the cell. The tricks range from ballistic missiles, to pathogenic microbes, to viruses, to chemical- or electrical-disruption, to weird nucleic acid* constructs, and are all designed to by-pass the mechanisms which keep a cell whole, functional and viable.

Techniques for genetic manipulation involve targeting a large number of cells, and then extracting the few surviving transformed individuals which are then developed into whole plants, whole animals or whole tissues. All the unaltered 'rejects' will have either fixed themselves, neutralised the change, or elected to die: these are healthy cells doing what's needed to preserve the integrity of the species. The GM 'successes' are the unhealthy cells which couldn't protect themselves.

GM crop scientists use further breeding over several generations to remove or dilute obvious collateral damage. Whether the resulting plants are actually the reinvented healthy, resilient ones they intended to create, only time will tell, especially when multiple artificial genes are stacked into a single crop.

In the case of animals and humans, which are also being targeted by genetic engineers, the 'breeding out' of imperfections isn't, of course, an option. Scientists in these fields are being a bit more careful and much more honest.

A lot of energy is being devoted to correcting 'faulty' human genes using CRISPR-Cas9 gene editing [1]. However, recent publications have made it clear that, when the DNA in a cell is snipped, the (healthy) cell reacts by repairing or neutralising the damage, or by making itself history. The scientists might find themselves with a bunch of 'corrected' cells, but these will have some underlying fault in their DNA's immune system.

To their great consternation, more than one team working in this field realised that, for CRISPR-Cas9 to work successfully, the gene which triggers our cells' fix-it-or-kill-it mechanism must be dysfunctional: this is the same mechanism which prevents cells becoming cancerous.

These reports come on top of evidence that CRISPR isn't anything like as precise as our model suggests [2]. However, scientists are still up-beat that they have enough clever tricks up their sleeves to get around the problems.

OUR COMMENT

The cancer danger doesn't apply directly to plants but the risk of an intrinsically weakened food supply which can't heal itself and is vulnerable to stress certainly does.

Some very weak links in the way science is being applied are also highlighted by these CRISPR projects. In particular the pervasive concept of the living cell as a molecular machine absent its global fluidity and networking [3].

There are lots of sustainable ways forward for our agriculture to follow, but clever GM tricks isn't one of them.

Background

[1] CRISPR/Cas9 GENE EDITING - March 2016
[2] MISSED MOLECULAR SCARS - January 2018

(Note that one of the references used in this article, Schaefer et al., has been retracted due to questions about the validity of the experimental mice used. However, the other two references used also describe extensive unexpected changes caused by CRISPR)

[3] HOLISTIC GENE REALITY - August 2018

* Nucleic acids are the 'NA' in DNA and RNA

SOURCES:

• Robert J. Ihry, et al., June 2018, p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells, Nature Medicine Letters
• Emma Haapaniemi, et al., June 2018, CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response, Nature Medicine Brief Communication
• Sharon Begley, A serious new hurdle for CRISPR: Edited cells might cause cancer, two studies find, www.statnews.com 11.06.18, reproduced in Scientific American 12.06.18
• Genome-editing tool could increase cancer risk, www.sciencedaily.com, 11.06.18

Photo Creative Commons