On August 3rd, Beijing time, Nature-Biotechnology issued a statement saying that the paper published by Han Chunyu's team on May 2nd, 20th16th was withdrawn. It is reported that Han Chunyu voluntarily withdrew his paper.
Han Chunyu, born in 1974, is currently an associate professor at Hebei University of Science and Technology. I graduated from Hebei Normal University with a bachelor's degree and graduated from China Academy of Agricultural Sciences and Peking Union Medical College with a master's degree.
In academic publishing, under the coordination of periodical investigation, the authors of widely questioned papers often take the initiative to apply to the periodical for withdrawal, so as to reduce the damage to the author's scientific reputation and prevent more researchers from continuing to cite papers.
Previously, as soon as the paper was published, Han Chunyu's team and NgAgo technology they reported got a good applause. The NgAgo technology described in this paper uses Argonaute endonuclease of Sodium Grignard to edit genes with DNA as the medium, which is called NgAgo-gDNA for short.
In this paper, Han Chunyu's team edited 100% genes at 47 loci in mammalian cell genome by NgAgo-gDNA technology, and the efficiency was 2 1.3%~4 1.3%. According to the experimental results of Han Chunyu's team, the efficiency of this technology is as high as that of CRISPR-Cas9, which is called "gene magic scissors", and it can delete and add specific sites of genes accurately.
But since July of the same year, the repeatability of this paper has been widely questioned by scholars at home and abroad. After the experiment according to the method described in Han Chunyu's paper, without exception, they didn't see any signs that NgAgo technology could edit genes.
From 2065438 to July 2006, Australian, American and Spanish scholars publicly voiced on social media Twitter, saying that they could not see the experimental results in Han Chunyu's paper. In order to avoid wasting resources, they called on researchers to stop using NgAgo technology.
20 16 10, 13 biologists from China, including Peking University, Chinese Academy of Sciences and Harbin Institute of Technology, publicly voiced in the media that they could not repeat the experimental results and called on relevant departments to start academic investigations.
In June165438+1October of the same year, 20 biologists at home and abroad jointly published an academic communication in the international journal protein and Cell, formally questioning the repeatability of the papers of Han Chunyu's team in the form of academic norms. Twenty scholars conducted repeated experiments in their own laboratories, but the gene editing caused by NgAgo technology could not be detected in different cell lines and organisms.
In the same month, biologists from the United States, Germany and South Korea published a communication article in Nature-Biotechnology, and also reported that the experiment could not be repeated.
At the same time, the editorial concern and statement of Nature-Biotechnology were published, reminding readers to worry about the repeatability of the results of the original paper (the paper of Han Chunyu Research Group), and indicating that the paper is under investigation, and it is very important for the original author to supplement information and evidence to provide the basis for the original paper.
Less than two months later, in June, 2065438+2007, a spokesman for Nature-Biotechnology issued a statement, saying that new data related to the repeatability of NgAgo system had been obtained, and it was necessary to investigate these data before deciding whether to take further action.
During the questioned year, Han Chunyu refused to disclose the experimental records, saying that his experiments could be repeated and he was constantly improving the experimental efficiency. Han Chunyu also said that other laboratories could not repeat it, and 80% of the reason was that the cells used for experiments were contaminated.
Full text of the withdrawal statement of Nature-Biotechnology:
It's time for the data to speak
A study claiming that gene editing is realized by Argonaute enzyme has been withdrawn, which shows the importance of peer review after publication in the all-weather media era.
In this issue, Han Chunyu and his colleagues withdrew a paper published in May last year. According to this paper, short 5- phosphorylated single-stranded DNA can guide the endonuclease (NgAgo) of Griffith Alcaligenes to produce double-stranded breaks and realize the editing of human genome. As soon as the paper was published, it aroused great interest from researchers and the media. But soon, with the help of Twitter, blogs and other social media, doubts about the repeatability of the study began to increase rapidly. In June last year, 165438+ 10, this magazine published "Editorial Expression of Concern" to remind the scientific research community to pay attention to these repetitive concerns. In order to finally solve this dispute, several research groups produced more experimental data within a few months. Now that the dust has settled, it proves that many laboratories around the world have spent a lot of time, energy and money to clarify the function of NgAgo.
Since Han Chunyu's paper was published last year, its influence cannot be underestimated, especially in its birthplace, China. China media reported in succession, announcing the discovery of a brand-new gene editing system with headlines. This is undoubtedly the most reported paper in China last year; According to the data of Meltwater, a media monitoring company, there were nearly 4,000 China news reports in the first two months after the publication of the paper.
NgAgo's sensation focuses on the fact that it may supplement or even replace CRISPR/Cas9 gene editing system. NgAgo expects to use the target sequence for gene editing (Cas9 needs not only the target sequence, but also another proximity recognition (PAM) sequence). In addition, the initial data also showed its advantages in other aspects, such as more stable primers (DNA relative to RNA used in Cas9), enhanced specificity, reduced genome editing miss-target, improved the activity of GC-rich regions of genome, and made the reagents used easier to synthesize and handle.
If all this sounds too good to be true, then since last summer, with more and more laboratories unable to repeat the genome editing function reported in this paper, doubts began to appear. This paper has become one of the hottest topics in various genome editing meetings, news discussion groups and emails. This quickly attracted the attention of the media, and the positive and negative voices about the effectiveness of the initial report began to conflict. Our internal image integrity screening found no obvious abnormality in Han Chunyu's paper, and three external reviewers who reviewed the data also held the same view.
During this period, Nature-Biotechnology has kept in touch with the scientific research community, paying attention to all kinds of papers that have been repeatedly read. Finally, under the coordination of the editors, the results of three independent groups formed a rebuttal paper, which passed the peer review (NAT. Biotechnology. 34,768,773,2016). With these data, we have every reason to remind readers of the possible problems in this article. We published the official "Editor's Concern" on the website where this paper is located, which was supported by two authors including Han Chunyu.
We also asked the authors if they could answer why it is difficult for the scientific community to repeat their results. Therefore, in June 5438+February last year, Han Chunyu and his colleagues, as well as several other independent research groups in contact with this journal, provided new data, saying that NgAgo gene editing activities were repeated.
Now, it has been more than a year since the original paper was published, and it is understood that the independent research team that reported the experimental results successfully was unable to strengthen the original data so that it could be published. Similarly, after seeking feedback from expert reviewers, it is concluded that the latest data provided by Han Chunyu and his colleagues are not enough to refute a lot of evidence that contradicts their initial findings. Now people think that Han Chunyu's decision to withdraw the manuscript is the best way to keep the integrity of published scientific research records.
The publication of this paper in NgAgo is not the end of the scientific research process, but the beginning. Like any other published report, it is the vast number of researchers who have tested the related methods, identified the potential error sources, verified the reagents and optimized the experiments. In this case, many dedicated researchers personally tested various details of the published experimental methods, and completed well-documented and refuted research with the control group (protein cell 7, 9 13, 2016; Cell Resolution 26, 1349 1352, 2016; PLoS One， 12，e0 177444，20 17)。
This NgAgo paper also shows the advantages and disadvantages of social media. Obviously, these platforms have played an important role in quickly reminding the scientific community of possible problems in this paper. However, they also raised people's expectations that the problems related to this paper are simple and can be solved quickly. However, there is a reason why various questions about NgAgo cannot be clarified in a few weeks or months. Even simple experiments take weeks to prepare, implement, analyze and solve problems. In addition, those who conduct repetitive research are often not rewarded for their efforts, which is useless-such work is monotonous, without financial support and thankless.
No wonder, in the eyes of all-weather media and the public who want a quick and clear answer, the peer review process after publication seems frustrating. However, when it comes to biology, there is often no clear answer. One thing we know when studying repeatability is that it takes time to do it. As far as this paper about NgAgo is concerned, it is time for the data to speak.