Nature Methods retracts publication that claimed to have found numerous unexpected mutations after CRISPR-Cas9 experiment in vivo

Nature Methods Editorial retraction of the publication: Unexpected mutations after CRISPR-Cas9 editing in vivo. Schaefer KA, Wu WH, Colgan DF, Tsang SH, Bassuk AG, Mahajan VB. Nat Methods. 2017 May 30;14(6):547-548.

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.

Eventually, today, Nature Methods adopted an Editorial decision and retracted this publication, with the agreement of two of its authors and the disagreement of the rest, including the first and last author of the study. This was the most logical and expected decision. Simultaneously, Nature Methods has released five different responses from five independent laboratories, experts in the field of genome editing, with alternative explanations for the original study, now retracted.

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 ARRIGE and how to join

ARRIGE Presentation document (March 2018) – Working document

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 join@arrige.org and we will register your email address in the ARRIGE discussion email list.

The CRISPR web at CNB: a web repository of CRISPR information and publications

The CRISPR-Cas system from bacteria transformed into a most efficient genome editing tool.

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.

ARRIGE in Spanish: interview to Francisco J. M. Mojica on the origins of CRISPR


In this short video interview (in Spanish), as a brief summary of a much longer text in El País newspaper, the journalist visits Francisco J. M. Mojica (University of Alicante, Spain) who shows the saltworks of Santa Pola, near Alicante, where he first described the CRISPR arrays from an archaea, 25 years ago. Francis Mojica coined the name of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) at the end of 2001 and, two years later discovered that CRISPR were part of an adaptive immune system developed by prokaryotes (bacteria and archaea) as a defense mechanism against the virus (bacteriophages) and other molecules of genetic material that infected  or visited them. Ten years later, the CRISPR bacterial immune system was transformed into an efficient genome editing tool.

ARRIGE in French: interview to Sylvain Moineau and Christian Siatka on CRISPR basics


The last (November 2017) annual meeting of the SFG (Société Française de Génétique / French Genetics Society) in Montpellier (France)  was devoted to CRISPR : The CRISPR revolution: from bacterial immunity to functional genomics. The meeting organizers (among which one of the members of the ARRIGE Steering Committee, Cyril Sarrauste de Menthière) made an interview (in French) to Sylvain Moineau (Université Laval, Québec, Canada; one of the pioneers of the CRISPR systems in bacteria) and Christian Siatka (Director of the “Ecole de l’ADN”). This video, now available from the YouTube platform is here enclosed, within the ARRIGE blog, for educational purposes

USA and plant breeding innovation: USDA will not regulate some genome edited plants

Secretary Perdue Issues USDA Statement on Plant Breeding Innovation. Washington, D.C., March 28, 2018. Press Release No. 0070.18,  Contact: USDA Press, Email: press@oc.usda.gov

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.

In Europe some hints towards a similar direction have been seen last January, with the publication of an Opinion by the EU lawyer of the Court of Justice of the European Union on a recent dispute ongoing in France. However, to date, the European Commission, through the European Food and Safety Authority (EFSA) has not yet issued a final decision on the subject.

 

The ARRIGE initiative featured in Science magazine

Image from istock.com illustrating the article by Martin Enserink in Science magazine on the ARRIGE initiative

Science magazine is featuring the ARRIGE initiative in an interesting article by Martin Enserink. The journalist talked to Hervé Chneiweiss, Peter Mills and Lluís Montoliu on the past Friday ARRIGE kick-off meeting in Paris, and also contacted Sheila Jassanoff, who had presented a similar global proposal for genome editing governance in another article published in Nature last week.

Taking seriously the anthropological and societal impact of genome editing technologies

Mylène Botbol-Baum, INSERM Ethics Committee and Catholic University of Louvain, Brussels, Belgium.

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.

Ewa Bartnik reviewed at the ARRIGE kick-off meeting in Paris the many current reports already published on the Ethics issues and global governance of genome editing

Ewa Bartnik, University of Warsaw, Poland. Former rapporteur UNESCO ICB

Ewa Bartnik (University of Warsaw, Poland) reviewed the multiple reports and documents already published on the subject, with positions from other groups, agencies, societies, associations, councils and governmental bodies on the associated Ethics aspects of genome editing technologies and their impact in human beings, animals, plants and the environment. At the ARRIGE kick-off meeting in Paris, Ewa Bartnik updated her previous presentation on this matter which she had nicely prepared for the November 2017 meeting in Paris too.

Francis Mojica delivered a keynote lecture on the origins of CRISPR systems and their applications at the recent ARRIGE kick-off meeting in Paris

Francis Mojica, microbiologist from the University of Alicante (Spain) who discovered the CRISPR arrays in archaea, coined the name of CRISPR and first proposed that this was a prokaryote acquired immune defense system.

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.

Delegates from more than 35 countries attended the ARRIGE Kick-Off meeting

Delegates from 35 countries attending the ARRIGE Kick-Off meeting in Paris
Delegates from 35 countries attending the ARRIGE Kick-Off meeting in Paris

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.

Welcome reception for the ARRIGE Kick-Off meeting in Paris

Welcome reception for the ARRIGE Kick-Off meeting in Paris

Hervé Chneiweiss, President of the INSERM Ethics Committee and member of the Organizing Steering Committee welcomes all participants attending the ARRIGE Kick-Off meeting in Paris, held at the venue of the Région Île-de-France. The reception took place on 22 March 2018.