CRISPER/Cas9 - Genetically modified or not?

MBAA Blog 3: CRISPER/Cas 9 and regulatory issues

The main goal of this technology, as far as I have understood, is to induce mutations in plants to create new traits. This has already been done for decades by traditional plant breeding, however, through a targeted mutation at a specific locus, genome editing with CRISPER /Cas9 enables researchers to observe the causal link between a mutation and the thereby resulting traits. This allows a rapid analysis of gene functions and is considered as one of many advantages of plant editing with CRISPER/Cas9. (Lawrenson et al., 2015)

Explain in your words what regulatory issues could be raised in using the CRISPR/Cas9-modified plants in the field.

Plants have to be declared as genetically modified if they contain genetic material of any other kind of organism. For many different reasons, this has stirred a lot of controversy and legal restrictions had been applied. With CRISPER/Cas9 new possibilities are at reach. Initially, all components of CRISPER/Cas9 have to be inserted into the cell of the mother plant and thus contains genetic material of a different organism. Mutations are induced and transmitted to the next generation. However, the next generation plants do not contain any components of the CRISPER/Cas9 or foreign DNA. Therefore the term genetically modified is not entirely correct anymore as these plants are transgene free and comparable to traditionally bred plants. (Lawrenson et al., 2015)

Even if these plants do not contain any transgene material, their mother plants did. Due to this fact, it depends on the point of view whether these plants must be called genetically modified or not. When new technologies arise regulations need to be reassessed and rewritten. Some regulatory issues might be:

•  It might make a difference whether the mutation is caused by CRISPR/Cas9 components which are from a different organism but the subsequent deletion or insertion is done by the cell’s own DNA repair mechanism or whether external donor DNA is inserted into the cut DNA strand.

• How could the natural spread and uncontrolled hybridisation with “normal” plants be avoided in the field?

• What would CRISPER/Cas9 plant editing mean for agriculture and the declaration of goods? What corporations can afford to do this? Would smaller seed producers be disadvantaged?

• Who gets to decide what traits are desirable and which genes should be targeted? Where is the limit?

Most likely, every country or super national organisation would have different laws. Export and import would need to be thoroughly regulated. In any case, tests need to be conducted to rule out possible negative effects on human, animal and plant health. In the study of Lawrenson et al (2015) off target effects could be observed and they speculated that higher on target Cas9 activity positively correlate with higher off-target mutation frequencies. I assume this calls for more research because the system and its effects are not yet fully understood. There are many questions that need to be answered before this technology should be legalised.

Does the current regulation in Switzerland and abroad cover the use of this system sufficiently?

It seems that plant editing by CRISPER/Cas9 is a borderline case. Due to the novelty of this technology it’s not entirely clear where to assign CRISPER/Cas9 edited plants. The definition of what exactly a genetically modified organism is needs to be reconsidered and adapted. Some countries consider such plants as not genetically modified while others do. (BFL, 2017). The current regulations cover the special case of CRISPER/Cas9 only insufficiently.

Would CRISPR/Cas9-modified plants be called GMOs according to the Swiss regulation?

The wording of the law concerning GMO’s in Switzerland (GTG, Art. 5 Abs. 2) is defined as follows: 

„Genetically modified organisms are organisms whose genetic material has been changed in a way that could not occur under natural circumstances by crossing or natural recombination. (BFL, 2017)

A fact that is unknown to many opponents of GMO and CRISPER/Cas 9 is that in traditional plant breeding radiation exposure was used to cause mutations in plants (Eisenach, 2016). As Mutations induced by CRISPER/Cas9 could also occur using traditional breeding methods, it is not clear whether this law does apply for CRISPER/Cas9 edited plants. However, at an initial stage the mother plants did contain foreign gene material which is not possible in nature and therefore tends to correspond with the text of the law. Some scientists demand an adaption of the transgene regulation which is more product than process orientated (BFL, 2017). Meaning that the GMO-classification of an organism is rather dependent on whether the end product contains transgenes and not if at some stage during the process transgenes were used to create new traits. It seems like CRISPER/Cas9 calls for a reassessment of the GMO debate in Switzerland.

A novel technology that does not introduce new genetic material would raise the question on the public acceptance of such method. Can you estimate the (Swiss) public opinion on the application of this technology to food plants? What is your personal opinion?

 

Even if no foreign components are detectable anymore in the next generation plants, in the beginning these plants were genetically modified. Also, would we look at this the same way if we initially modified a human genome? Would we consider his or her offspring not as genetically modified because no components of the originally introduced gene material are present anymore? I think that this new technology might look very promising for people who are directly involved or affected by the benefits that could result from a legalisation of CRISPR/Cas9 in plants. Some might also genuinely consider it a “good thing” to do that will help creating adaptable plants to face the agricultural challenges in the future. Nevertheless, I believe many citizens would feel uneasy and have objections to a legalisation in Switzerland. I estimate a 30 to 70 % No, if people could vote on this issue. For me it’s a plausible scenario that this technology would be turned down without presenting justified arguments, simply because of a gut feeling of the voters. CRISPER/Cas9 is said to allow very precise editing of plants and is a promising appliance in plant biotechnology (Uauy, 2015). After all, radiation exposure doesn’t sound healthy to me either. Legalisation is one aspect of the debate but what about possible influences on our health? Are the effects of CRISPER/Cas9 thoroughly known? It’s a powerful tool that can do a lot of damage in the wrong hands I suppose. Furthermore, I assume some people also lack confidence in the responsible authorities and don’t believe in an ethically correct handling of this technology. Giving big corporations lots of room for misuse. Making decisions for Switzerland is one thing, the other question is how our neighbouring countries and the rest of the world would deal with this issue. A globally harmonised regulation is unlikely and there will always be countries that peruse their own agenda. 

 

I personally would consider the insertion of Donor DNA into a mother cell as genetic modification even if the next generation plants show no traces of foreign DNA anymore. Initially foreign genetic material was introduced in the DNA strand and is therefore not transgene free for me. However, the mere cutting by an introduced protein and subsequent deletion or insertion by the cells own repair mechanism is tolerable or not worse than radiation exposure to induce mutations.

References

Tom Lawrenson1†, Oluwaseyi Shorinola1†, Nicola Stacey1, Chengdao Li2, Lars Østergaard1, Nicola Patron3, Cristobal Uauy1* and Wendy Harwood1*. (2015). Induction of targeted, heritable mutations in barley and Brassica oleracea using RNA-guided Cas9 nuclease. Genome Biology.

Neue Züchtungstechnologien. (2017). Bundesamt für Landwirtschaft BLW. Retrieved on 01.05.2017 from https://www.blw.admin.ch/blw/de/home/nachhaltige-produktion/gentechnologie/neue-zuechtungstechnologien.html

Eisenach, C. (2016). Die Furcht der Biobauern vor der neuen Gentechnik. Retrieved on 01.05.2017 form https://www.nzz.ch/wissenschaft/biologie/die-furcht-der-biobauern-vor-der-neuen-gentechnik-1.18705714

Dr Cristobal Uauy, Prof Wendy Harwood, Prof Lars Østergaard. (2015). Using CRISPR/Cas9 to genetically modify crops. Interview conducted by Rafal Marszalek 30 Nov 2015 published in Bio Med Central