This article is from the public number: Husk (ID: Guokr42) < / a> , OF: Barley, from FIG title: Oriental IC
Last November, He Jiankui andHis gene-edited baby shocked society and academia; he then presented the research protocol and results at the second International Human Genome Editing Summit. However, his thesis has not been published in any academic journals or media, and people’s understanding of the research has always been limited.
On December 3, the MIT Technology Review (MIT Technology Review) exclusively disclosed the manuscript of He Jiankui’s thesis. This paper is unpublished and is entitled (Birth of Twins After Genome Editing for HIV Resistance) . The full text is 4699 words, and the corresponding author is He Jiankui.
The MIT Technology Review did not publish the source of the manuscript, only that earlier this year, “there was a resource” that sent them a manuscript version of the Microsoft document. They only published a few fragments and did not release the full text; at the same time, they recruited four experts in different fields and commented on the paper-they all thought that the research was very bad.
The snippets of the paper disclosed this time include the following two issues:
1) Experimental results
The editing of the CCR5 gene of twins was not completely successful; it was not possible to prove that there were no “off-target mutations” and “chimeras” in the embryo; it was not proven whether the twins were immune to HIV infection.
2) Research-related information
Why the parents agreed, whether the doctors knew about it, when the study was registered, where the funding came from, and what specific contributions the participants made are still unclear.
Conclusion cannot be supported by data
The MIT Technology Review published the full abstract section of the manuscript. The abstract is a brief introduction to the entire study; however, most of the content mentioned in the abstract cannot be supported by the data in the paper.
1 The CCR5 gene was successfully edited?
The abstract states: “The twins’ CCR5 gene was successfully edited.”
However, according to the results mentioned by He Jiankui in the thesis, it is not that the results are the same as those of the natural CCR5 gene mutation, but merely “similar”.
“Similar” results may not bring HIV resistance to two children. Especially in one of them, only one copy of the CCR5 gene was deleted and the other copy was not modified. This only brought up a part of the resistance-but how big and small this part is, we don’t know.
Fedor Urnov, gene editing expert at the University of California, Berkeley, said (Fyodor Urnov) , He JiankuiClaiming to duplicate a common CCR5 gene mutation is a misreading of factual data and is described in one word-a deliberate lie.
2 Is it really immune to HIV?
Has He Jiankui adopted any method to test whether the twins can fight HIV infection?
Judging from the published snippet, no.
He Jiankui mentioned in the discussion section that they will then test the twins for HIV resistance by blood. However, gene editing expert Ulnov said the test could be done-and should be done-before embryo transfer.
“They can use a currently known method: Introduce the same gene editing in immune cells in the laboratory, and then infect those cells with HIV. Only those cells with mutations in the CCR5 gene that are resistant to HIV will be able to Survive. “
But He Jiankui did not do so. While it was still unclear whether the embryos were immune to HIV infection, they transplanted the embryos into the womb, triggered pregnancy, and created a gene-edited baby.
3 No off-target mutation?
It is mentioned in the abstract that they did not observe “off-target mutations”.
“Off-target mutation” refers to genes that do not want to be modified when CRISPR is used for gene editing, and may be accidentally mutated. This is one of the biggest problems with CRISPR technology at present. In the manuscript, He Jiankui specifically explained the off-target effect-in one of the embryos, they detected a possible off-target mutation; however, they believed that this mutation should not have a substantial impact.
But the problem is that current technology is difficult to detect all off-target sites; moreover, it is impossible for us to detect all cells on the embryo.
Experimental researchers removed some cells from the embryo for genetic testing. However, because the edited embryo cannot be guaranteed, the editing results are the same for all cells; therefore, even if no off-target mutations are detected in the removed cells, it is not possible to prove that other cells on the embryo are safe-in fact, exactly It is these undetected cells that remain in the embryo and continue to develop. This is also a key issue for gene-edited babies today.
4 Are gene editing consistent?
Whether it is the manuscript of the paper disclosed this time or the speech made by He Jiankui last year, he did not discuss the issue of “chimeras” directly.
Since it is difficult for CRISPR to work at the fertilized egg stage of a single cell; in the final embryo, the editing results of the cells may be inconsistent, some cells may be edited, and some may fail. He Jiankui only wrote in the manuscript: “The CCR5 gene of all samples has been deeply sequenced to detect gene-edited chimeras.” In addition, he did not discuss specific data on chimeras.
However, in the “Supplements” section of the manuscript, there is a result chart that provides some information.
After the twins were bornHe Jiankui used their umbilical cord blood, umbilical cord, and placental cells to detect potential off-target mutations. According to the results of the DNA sequence, the cells in these three parts do not have exactly the same DNA sequence; that is, the gene editing in the same embryo also produces different editing results.
Kiran Musunuru , a gene editing expert at the University of Pennsylvania, said that these embryos are chimeras. This means that only a portion of their cells may be HIV-resistant; at the same time, there may be undetected off-target mutations that could cause other health problems.
He Jiankui doesn’t know anything about the mosaic problem. In last year’s presentation, he discussed the results of chimera analysis in monkey experiments. However, why he did not perform this test in human embryo experiments; or why the results of this part are missing is still a big mystery.
5 Controlling the HIV epidemic?
He Jiankui mentioned in the abstract that the treatment strategy of human embryo gene editing is expected to “control the HIV epidemic.”
The manuscript of the paper mentions the situation of HIV infection in China
However, Rita Wassena, Scientific Director of Eugene Group (Rita Vassena) describes this idea as “ridiculous”: Public health initiatives, education, and widely used antiviral drugs have been shown to control the HIV epidemic. “Similarly, according to data released by the National Health and Medical Commission, the proportion of infected people eligible for antiviral treatment in China is receiving treatment. 86.6%, of which 93.5% can be successfully controlled.
Compared to human embryo gene editing whose risks are still unclear, these seem to be better means to prevent and control AIDS.
The mystery remains unsolved
In addition, other snippets published by the MIT Technology Review also reflect some of the problems in the experiment.
1 Why do parents agree?
Is the gene editing in order to prevent parents’ HIV from being “herited” to their children?
No.
He Jiankui mentioned in the manuscript that only the father of the couple involved in the experiment was HIV-infected; and that the HIV virus had been removed by washing sperm thoroughly before in vitro fertilization. In other words, cleaned sperm can be used to create embryos that do not carry the HIV virus, as long as they undergo conventional in vitro fertilization.
He Jiankui’s experiment was designed to protect two children from HIV infection in the future. This is not a direct and clear benefit, and the price paid is an unknown risk. So, why would the parents agree?
The MIT Technology Review speculates that one reason may be that He Jiankui provided assisted reproduction for the couple. According to China ’s assisted reproductive technology management measures, HIV carriers cannot implement assisted reproduction; He Jiankui ’s experiments provided them with the possibility.
Similarly, in January, Nature, a sub-issue of Nature, published a discussion on He Jiankui ’s experiment, which also mentioned that the couple may have been “over-induced”: He Jiankui They provide all the costs,Estimated as high as $ 40,000; such benefits may also affect their decisions.
2 Is the doctor aware?
According to the manuscript, there were always ten authors involved in the experiment-but the reproductive doctors treating the patients and the obstetricians delivering the babies were not among them. Concealing this information may be to obscure the identity of patients and protect their privacy; but it also raises the question: Do the participating doctors really know the entire plan?
In the survey results announced earlier this year, the investigation team mentioned that He Jiankui’s team had planned another person to take the blood test of the couple. Earlier, the Wall Street Journal and other media also made similar disclosures. They suspected that some doctors might be deceived, and they may not know that they were involved in the experiment of gene editing babies. The doctor’s opinion was not mentioned in the manuscript when discussing which embryo to transfer.
It is mentioned in the manuscript that after being informed of the genetic information of the embryo, parents chose to transfer both edited embryos
If doctors do not know it, then it is very difficult for them to understand all the conditions and to make the best choice for the patients.
3 Is the birth time of the baby accurate?
The
manuscript states that the twins were born in November 2018; however, according to the media and people familiar with the study, the twins should have been born in October. The MIT Technology Review speculates that this may be to protect the information of the twins from being easily found.
4 When was the trial registered?
According to the MIT Technology Review, the ethics discussion in the manuscript is extremely brief. It was mentioned that the study had been registered at the China Clinical Trial Research Center.
However, Henry Greeley, a professor of law at Stanford University, (Hank Greely) mentioned that this was on November 8, 2018 Registered late. At that time, twin baby girls are likely to have been born, and research is about to be made public; registration may be just to increase the assurance of publication of the paper, rather than the normal registration process.
The official survey results also mentioned that He Jiankui falsified the ethics review papers by others.
5 Where does research funding come from?
These papers usually state who funded the research or what economic benefits the researcher could gain from the results. However, this manuscript is not covered at all.
In his speech last year, He Jiankui stated that a small part of the research used the school’s funding and all the medical costs of the clinical trials were borne by him personally; none of his companies provided funding, equipment, and so on.
6 What have the participants contributed?
The other part missing is about the contribution of each author to the research.
In particular, Michael Tim, the only non-Chinese author, (Michael Deem) . He is a professor at Rice University and a tutor during the doctoral period of He Jiankui; Rice University investigated him after the genetic editing baby incident.
The MIT Technology Review also mentions another researcher Craig Mello (Craig Mello) . He is a biologist at the University of Massachusetts School of Medicine and a 2006 Nobel laureate in medicine. He Jiankui mentioned a type of “HEU syndrome” in the manuscript: In Africa, when a mother is infected with HIV and her child is not infected, it is easy for children to develop this syndrome. And in a previously disclosed e-mail from He Jiankui to Merlot, he thanked Merlot for his advice on this issue-so, has the Nobel Prize winner proved the validity of this research for He Jiankui?
Should the paper be published?
According to the MIT Technology Review, He Jiankui tried to publish the paper.
Before it became the focus of the media, He Jiankui had submitted a manuscript to the well-known academic journal Nature; later, he also tried to submit a manuscript to BioRxiv, a website that can publish preprints of the paper, and another authoritative journal, the Journal of the American Medical Association. No successful publications.
Some scholars believe that such a paradoxical study, if successfully published in academic journals, may encourage the emergence of the next He Jiankui. (Rudolf Jaenisch) says: “There is no self-respecting journal Post it. “
He Jiankui at the 2nd International Human Genome Editing Summit | Dongfang ic
However, although it should not be published in academic journals, many scholars believe that this manuscript should be made public. In this way, experts, governments, and anyone else can read it on the Internet, thereby deepening the understanding of this research.
“This is to give the scientific community a full picture of the twin babiesWhat happened and a good time to avoid repeating the same mistakes. Commented on gene editing expert Musunulu. For example, Russian scientist Denis Rebrikov, who also proposed to create a gene-edited baby this year, (Denis Rebriko) , he claims that he can optimize experiments and solve safety concerns; but if we do n’t understand He Jiankui ’s experiments, how can we know whether Rebrikov ’s statement is true or false, what risks his genetically edited baby may face What?
In January of this year, the Guangdong Province “Gene Editing Baby Incident” investigation team released preliminary findings.
He Jiankui, an associate professor at Southern University of Science and Technology, pursues personal fame, raises funds by himself, deliberately evades supervision, and organizes relevant personnel in private to implement human embryo gene editing activities for reproduction purposes that are explicitly prohibited by the state.
The relevant person in charge of the investigation team stated that He Jiankui and the personnel and institutions involved will be dealt with seriously according to laws and regulations, and those suspected of crimes will be transferred to the public security organs. For born babies and pregnant volunteers, under the guidance of relevant state departments, Guangdong Province will work with relevant parties to do a good job of medical observation and follow-up.
—— Xinhuanet “Guangdong Preliminary Identification of” Gene Editing Baby Incident “
In the past year, whenever we mentioned gene-edited babies, we always asked: Where did He Jiankui go? What about the twins?
The manuscript does not answer these two questions; it even raises questions for us. But at the same time, it also acts as a warning, Respect life, don’t take others’ lives to challenge the red line of technology and ethics.
References
[1] https://www.technologyreview.com/s/614764/chinas-crispr-babies-read-exclusive-excerpts-he-jiankui-paper/
[2] https://www.technologyreview.com/s/614761/nature-jama-rejected-he-jiankui-crispr-baby-lulu-nana-paper /
[3] https://www.technologyreview.com/s/614762/crispr-baby-twins-lulu-and-nana-what-happened/
[4] http://www.xinhuanet.com/local/2019-01/21/c_1124020517.htm
[5] http://www.xinhuanet.com/politics/2019-12/01/c_1125295336.htm
[6] Sheldom Krismky. Ten ways in which He Jiankui violated ethics. Nature Biotechnology. 2019 (37): 19-20.
This article is from the public number: husk (ID: Guokr42) , author: Barley