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.

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

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.