Today, the scientific journal Nature Methods, retracted a publication by Schaefer et al. that appeared on 30 May 2017 claiming to have found numerous unexpected mutations after a CRISPR-Cas9 experiment in vivo, in mice. The unexpectedly high number of off-target mutations reported in the study caught the field by surprise, where noone else appeared to have found similar data. However, this was a most relevant issue, should have been true, directly affecting the expectatives of the CRISPR-derived uses and applications. That publication negatively impacted in the nascent field of genome editing applications, particularly those related to biomedicine, to develop innovative gene therapy approaches. However, almost immediately, many groups around the world expressed doubts and critized the experimental design of the study and the interpretation of the observed results. Soon thereafter, several manuscripts and publications were released with more plausible alternative explanations (low number of cases analyzed, mice genetically unrelated, persisting Cas9 expression…). Anyone interested to review a timeline of events associated with this publication can visit the corresponding section of the CRISPR web at the CNB-CSIC, maintained by Lluis Montoliu.
The first phrase of the Editorial Retraction note explains this decision: “This paper is being retracted because the genomic variants observed by the authors in two CRISPR-treated mice cannot be conclusively attributed to CRISPR–Cas9.“. In other words, the most plausible explanation for the original findings were the underlying genetic differences between control and experimental mice, in principle derived from the same genetic background, but in reality selected from unrelated, and hence, genetically different, mouse colonies.
Basic information about the ARRIGE initiative can be obtained from this Presentation document (March 2014), prepared by the ARRIGE Steering Committee. This is a working document.
How to join ARRIGE?
The ARRIGE initiative was launched in Paris on 23 March 2018. However, the association does not exist yet, formally speaking. Currently, we are working hard preparing all the administrative and legal paperwork required to officially register ARRIGE as an international non-for-profit organization in France, with the great help and commitment from members of the INSERM Ethics Committee. In the meantime we have activated a communication channel, a discussion email list, where all interested individuals and organizations that would like to help and contribute to the foundation of ARRIGE, and/or to eventually become members of the association, are kindly invited to join. If you would like to join ARRIGE please send us a message to firstname.lastname@example.org and we will register your email address in the ARRIGE discussion email list.
Anyone interested in the prokaryotic origins of the CRISPR systems and their transformation into the most efficient ever known genome editing tools should consider visiting this CRISPR web page at CNB-CSIC, maintained by Lluis Montoliu. This is a most useful and regularly updated web repository of publications, information, history, protocols, procedures, talks, videos, etc… all about CRISPR and their use as genome editing tool in a variety of applications.
Yesterday, the US Department of Agriculture (USDA) issued a statement in favour of Plant Breeding Innovation. In the US, the USDA will not regulate genome-edited plants (obtained, for example, through CRISPR tools), as long as they are not pest plants or developed using plant pests, and as long as the resulting genetic alleles could have been also introduced by any traditional breeding technique. In other words, if the CRISPR-derived allele matches an allele previously existing in nature the resulting genome edited plants will not be regulated by USDA. This decision is expected to favour Plant Breeders and researchers in the field of Plant Breeding innovation and is also expected to expedite the development of numerous genome edited plants resistant to drought and diseases or with increased nutritional value.
The ethicist Mylène Botbol-Baum, from the Catholic University of Louvain, Brussels, Belgium, and member of the INSERM Ethics Committee, delivered an interesting lecture at the recent ARRIGE kick-off meeting in Paris. Her talk was on ‘Taking seriously the anthropological and societal impact of genome editing technologies’ where she presented several aspects on the conversation of genome editing with the Society. She referred to the common use of metaphores and the conflict of narratives when trying to communicate these scientific advances.
The recent ARRIGE kick-off meeting in Paris had the pleasure to have Francisco Juan Martínez Mojica (Francis Mojica), microbiologist from the University of Alicante (Spain), delivering the first keynote lecture of the conference. In his very interesting talk, Francis Mojica reviewed the origins of the CRISPR systems in prokaryotes, as part of an ancient acquired immune defense system, and their recent conversion into powerful genome editing tools. He is convinced that we are just beginning to understand the unexpected complexity of bacterial immune systems. CRISPR could be just one of many, yet to be identified and described. There is a great future ahead in the field of Molecular Microbiology for discovering new CRISPR and CRISPR-like systems that could be transformed and adapted for the efficient and safe manipulation of genomes, including the human genome.
At the ARRIGE Kick-Off meeting, participant delegates came from more than 35 countries all over the world, including most countries from Europe, and some countries from Asia, Africa and America, from North-America, through Central-America and South-America. This was a most successful event triggering the interest of a large variety of institutions, individuals and diverse stakeholders, with an interest in the responsible use of genome editing technologies.