SEB Plant Symposium on New Breeding Technologies

Thanks to Iulia German from the University of York and the Warwick Integrative Synthetic Biology Centre for providing this outstanding review of the SEB plant section symposium.

At the beginning of July, Gothenburg was host to a fascinating discussion on New Breeding Technologies (NBTs), attended by scientists from 17 countries. This covered the applications of the technologies themselves, their legal status in the EU, and the rest of Europe, and the US, and Australia and New Zealand, the importance of getting the general public involved early in discussions about NBTs, and whether CRISPR-modified cabbage really does taste better than cabbage modified only through conventional breeding.

Image from Molecular Plant Pathology October 2016 issue. Pyott et al. engineered Turnip Mosaic Virus-resistant Arabidopsis and created letters in trays by infecting wildtype and CRISPR-Cas9-engineered mutants with the virus.

This Society for Experimental Biology plant section symposium was very timely given the increasing trendiness of CRISPR-Cas9 for editing plant genomes, the legal limbo of the technology in EU courts, and the lack of public awareness of CRISPR and what it can do.

From the Web of Science. While not as extreme as the overall trend, there is still a growth in published papers using CRISPR-Cas9.

While the efficiency of CRISPR-Cas9 in plants seems to be limited in comparison to animal cells, this appears to come with the unexpected benefit of fewer off-target effects. In fact the frequency of off-target mutations is even lower than that observed during chemical/physical mutagenesis. This does make for a hard time screening thousands of plants but that is worth it for people like Mariette Andersson, who is looking to bring a new variety of potato to market years faster than would be possible using conventional technologies, and Jean-Denis Faure who is generating Camelina sativa lines with different amounts of oleic acid content by targeting different combinations of FAD2 alleles in its hexaploid genome. Not to mention that it’s possible to screen for plants that have desired mutation but are CRISPR-cas9 transgene free (like in Attila Molnar’s work to create potyvirus-resistant Arabidopsis).

The variety and flexibility of CRISPR gene editing is increasing, with the possibility for nicks, double-stranded breaks, Cas9-nuclease fusions, dead Cas9-repressor/activator fusions, polycistronic systems, and a myriad of promoters and terminators to choose from.

The second point of discussion, the legal debate surrounding CRISPR is nicely summarised in this SEB article. It started with a history lesson on GMO regulation in the 70s after the ability to transfer genes from any organism to any other organism sparked safety discussions and a moratorium as laid out by the 1974 Paul Berg letter. The US was then first to develop regulations against these novel organisms. As a side note, the reason “novel” organisms are regulated rather than “risky” organisms is mainly because in a legal context it was easier to define something novel than something risky – however this has encouraged the train of thought that “novel” organisms are somehow more dangerous than “natural” organisms (another thing that emerged from this NBT meeting is how much scientists hate misuse of the word “natural”). All countries seem to have some legal variation on this “novel organism” theme, with some more lenient than others – Canada for example does not regulate plants with novel traits that do not possess an environment risk.

However, this process-based regulation is very outdated and not reflective of the current situation and advances in biotechnology. It would be better to include product-based rather than process-based rules ie plants should not be regulated based solely on the methods used to produce them (process-based) but based on the risks presented by the GM plant products.

There is no strict regulation if the technique involves mutagenesis, transfer of genes from sexually compatible organisms or non-inheritable changes. As CRISPR-edited plants fall into the “mutagenesis” category, we agreed that the same regulation should apply.
The crux of the debate surrounding NBTs: are they more like conventional breeding techniques or gene modification techniques? Image from: [1]

The world (other than Sweden and Denmark, which have declared that CRISPR-edited organisms are not GM) is looking to the EU to lead the way in making regulations, but the EU has been stalling.

As to how to present CRISPR to the public, the situation boils down to: people make decisions based on their principles and beliefs when presented with very complex information, so if scientists unite behind one success story for CRISPR that will appeal to people’s imagination and values, then the battle is half won. It’s all about planting the flag early. As Craig Cormick learned from surveying Australians, the bulk of the population is neither highly opposed to or greatly in favour of new technologies (they are penguins – image below). Given convincing arguments, they are likely to move to either side. In the case of NBTs, the public are not likely to be in favour of them without being given a context: it’s the difference between asking “What do you think of CRISPR – should it be used?” and “What do you think of using CRISPR to make X product?”

Image from Craig Cormick

The public’s attitudes towards new technologies: at polar ends of the spectrum are small groups of “polar bears” which are either highly opposed to or highly in favour of the technology. Most of the population falls into a cautious group in the middle who decides based on the risks presented and the application of the technology.

One of the organisers, Swedish Stefan Jansson, has been doing a fair bit to normalise the use of NBTs in food by growing his own CRISPR-modified cabbage and cooking up a feast with it. The recipe for tagliatelle with CRISPRy fried vegetables, along with Stefan’s blog detailing how he grew the cabbage, fought moths and ate the first CRISPR meal ever with reporter Gustaf Klarin, can be found here. He’s gone on tour with his cabbage to countries like Norway in order to start a discussion and hopefully persuade the legal authorities to pass the same laws as Sweden regarding the classification of NBTs. He is also adamant about refusing to say what has been modified in the cabbage – good luck finding a targeted point mutation amongst all the other spontaneous mutations that arise in the genome! What we do know for sure is that CRISPRy cabbage tastes delicious – especially when prepared by the culinary geniuses at Sjömagasinet.

All in all, the SEB New Breeding Technologies was a fantastic meeting, with great food and company. I’m always looking forward to the GARNet plant gene editing workshop at the University of Bristol on March 26-27th 2018!

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