CRISPR-Cas is a type of genome editing technology. It is used to create double stranded breaks in DNA at specific target sites. ‘CRISPR’ stands for Clustered Regularly Interspaced Short Palindromic Repeats. The associated ‘Cas’ (CRISPR-associated) protein can be easily changed to target specific sections of DNA, and to switch genes on or off without altering their sequence.
CRISPR-Cas is only one method of genome editing used in research for livestock applications. Zinc Finger Nucleases (ZFNs) and Transcription Activator Like Effector Nucleases (TALENs) are also used for livestock applications. ZFN and TALENs require two proteins that have to be assembled in order to target the correct DNA sequence. According to natural scientists this makes these technologies more specific, but also slower and more complex to develop (Nuffield Council on Bioethics, 2016; NASEM, 2017; COGEM, 2018).
According to diverse policy reports (Nuffield Council on Bioethics, 2016; NASEM, 2017; COGEM, 2018) and natural science publications, CRISPR-Cas is easier to use, cheaper, and more accessible than older genome editing technologies, and is rapidly taken up in diverse scientific fields. CRISPR-Cas appears to remove technical barriers to develop genetically modified humans, animals and plants.
Potential livestock applications of genome editing are: to increase yields (for example editing chickens to produce only female offspring for egg-laying, or beef cows to only have male offspring); to improve product quality (editing pigs to produce meat with higher levels of unsaturated fat or chickens to lay hypoallergenic eggs), to improve animal welfare (like breeding hornless cows or chickens with short blunt beaks); and to increase disease resistance (for example against avian influenza, bovine tuberculosis or African swine fever).
Some challenges for genome editing are: off-target effects, mosaicism, uncertain/unknown long-term effects, and traceability. Off-target effects refer to the possibility of the genome editing technology to alter DNA at sites that are not targeted. This can cause diverse problems for the altered organism, depending on where the extra alterations are made. A related problem with off-target effects is that these are hard to detect. Often only with complete genome sequencing can unintended edits be found. Mosaicism refers to edited organisms in which not all cells are edited. This means that not all cells have the same genetic code, which can also lead to problems.
It is also unclear what the long-term effects are for edited livestock, or what the long-term effects are in humans after consuming edited livestock. Influential reports therefore argue to be cautious and to ask the general public for input about potential applications (Nuffield Council on Bioethics, 2016; NASEM, 2017; COGEM, 2018).
Finally, the traceability of genome edited livestock and the products derived from them is an issue of concern. If no transgene is inserted it is practically impossible to differentiate genome edited livestock from traditionally bred livestock, because no marks are left behind by the genome editing technology. This is, next to a technological problem, also a governance problem in terms of how to regulate and label products derived from genome edited livestock.
Public concerns also shape the governance and development of technology. The following concerns were raised in social science studies on perceptions of other emerging technologies, and also inspire this research project:
Powerlessness refers to the public feeling as if decisions about the technology are already taken, and that there is nothing they can do about it to make a difference. Lack of trust refers to the feeling that the direction of science and technology is overly directed by private rather than public interests. Motivations and purposes of research and researchers means that the public questions why research needs to be done, and asks for alternatives for the proposed technology as well. Unnaturalness refers to the idea that editing the genome is an unnatural and hence problematic thing to do, regardless of whether or not a transgene is involved. Speed of innovation refers to the idea of technology developing too quickly to be governed satisfactorily. Finally, social distribution of benefits and costs refers to the idea that the rich will get richer, and the poor or vulnerable will bear most negative consequences of the technology.
The potential of genome editing to successfully alter livestock DNA in a particular way and for specific purposes requires careful consideration. Therefore, the question that guides this research is: How, if at all, can genome editing in livestock be responsibly embedded in Dutch society?
COGEM, 2018. CRISPR and Animals: Implications of Genome Editing for Policy and Society. Available at: https://www.cogem.net/index.cfm/en/publications/publication/crispr-animals-implications-of-genome-editing-for-policy-and-society? (Accessed 12 February 2019).
NASEM, 2017. Human Genome Editing: Science Policy and Governance. Available at: https://www.nap.edu/catalog/24623/human-genome-editing-science-ethics-and-governance (Accessed 12 February 2019).
Nuffield Council on Bioethics, 2016. Genome Editing: An Ethical Review. Available at: http://nuffieldbioethics.org/project/genome-editing/ethical-review-published-september-2016 (Accessed 12 February 2019).
CRISPR-Cas is a type of genome editing technology. It can be easily changed to target specific sections of DNA, and to switch genes on or off without altering their sequence.
Potential livestock applications of genome editing are to:
Prof dr Phil MacNaghten
Knowledge, Technogy and Innovation Group
Wageningen University and Research