The article is from the WeChat public account: Nutshell (ID: Guokr42) , OF: Barley, from FIG title: Oriental IC
On November 28, 2018, He Jiankui appeared in Hong Kong and introduced the world ’s most popular “gene editing baby” experiment.
The experimental results on the slide broke everyone ’s last chance—the news was not rumored, he really did the experiment. Two genetically edited baby girls Lulu and Nana have been born, and their gene editing results are not as expected; moreover, another participant is pregnant.
According to He Jiankui at the meeting, if it goes well, a new “gene editing baby” will be born this year | Dongfang IC
A year has passed since He Jiankui disappeared from public view, but the debate about gene-edited babies has never stopped. In June of this year, Russian scientist Denis Rebrikov announced his “Gene Editing Baby” project (Denis Rebrikov) .
Will he be the second He Jiankui?
“optimize” He Jiankui’s experiment
On June 10, the well-known scientific magazine Nature (Nature) reported on Rebrikov ’s plan—if approved He will edit the genes of human embryos and transplant the edited embryos into the womb to create a new “gene-edited baby.”
Rebrikov, 43, is a researcher at the Russian State Research Medical University in Pirogov. He also leads a genome editing experiment at the country’s largest fertility clinic, Kulakov National Medical Obstetrics and Gynecology Research Center room. Their clinics carry out about 10,000 IVF projects each year.
Denis Rebrikov | Nature
Like He Jiankui, Rebrikov plans to edit the CCR5 gene. In the European population, if the CCR5 gene is mutated and lacks 32 base pairs, people carrying this mutation may be immune to HIV (Human Immunodeficiency Virus ) infection.
Also, the technology he plans to use is CRISPR. This is the most commonly used method of gene editing, and its design and operation are relatively simple, and the target gene can be modified relatively accurately. Since its birth in 2012, CRISPR has become one of the most important biotechnology.
CRISPR usually cuts the DNA double strand first | MIT
However, Rebrikov did not exactly replicate He Jiankui’s approach. In He Jiankui ’s experiment, the mother did not carry the HIV virus, and the father ’s sperm could be “washed” by “washing” the virus. In other words, even without gene editing, such a couple can give birth to uninfected children-this is one of the academics’ doubts about He Jiankui.
Rebrikov’s plan “optimizes” this contradiction. His ideal subject is women who are infected with the HIV virus and who do not respond well to antiretroviral therapy. Such patients can easily pass the virus to their fetus if they become pregnant.
Most people are conservative
In fact, before He Jiankui broke the big news, Rebrikov had already started research in this area.
In October last year, he published his results in a Russian academic journal. Using CRISPR technology, he edited the CCR5 gene of human fertilized eggs, and discussed the success rate of the edit in his paper. However, experiments at that time were limited to fertilized eggs, and had not yet reached the stage of implanting embryos into the uterus and triggering pregnancy.
In vitro fertilization | DrKontogianniIVF / Wikimedia Commons
At the same time, he also discussed the research at an academic conference. “In the auditorium full of 500 people, he talked freely about this problem.” Egor Prokhokcho (Egor Prokhortchouk ) , surprised by this: “Everyone is interested in technical details, but no one mentions ethical issues.”
Rebrikov himself does not seem to think that research is unethical. Even when he saw academic circles and public opinion questioning and condemning He Jiankui, he did not intend to slow down his plan.
In June this year, he was interviewed by Science (Science) . In the interview, he mentioned that He Jiankui’s experiment is positive; he hopes to translate the technology into practical applications, and He Jiankui is promoting this.
“If you succeed, you are right.” When asked about the criticisms facing He Jiankui, he replied: “If he (He Jiankui ) is a lucky guy, and the condition of the baby girl has always been good, so at some point, he will be regarded as a good researcher again.
Rebrikov hopes to turn technology into applications | Sergey Ponomarev / Science
As for the voice of opposition, he felt normal. The vast majority of people are conservative, maybe only 5% Is radical. We need to wait for some time; maybe a few years later, when there are very good clinical cases, people will know that this powerful technology is safe and it can bring good results.
Rebrikov seems to value technology more. He said that if no suitable HIV carriers can be involved in the experiment, he will turn to other diseases-he needs some models for clinical practice of gene editing embryos.
Modeling for deaf patients
Rebrikov was right, he did not find a suitable HIV-infected person as a test subject.
In July, he announced that the disease he was experimenting with would turn from AIDS to deafness. He found 5 deaf couples willing to try gene editing.
This time, the target gene that Rebrikov studied was called GJB2.
Of the 23 pairs of chromosomes in our body, half come from the father and half from the mother. If the GJB2 gene inherited from the father and mother both had a base deletion at position 35, which is the so-called “homozygous”, then this person will be born without hearing.
If parents are homozygous for this mutation, the child will be born without hearing | Pixabay
The five couples found by Rebrikov are homozygous for this mutation. Without gene editing, their children will inherit this mutant gene, which is a natural deaf person.
However, the GJB2 gene is also related to other functions; if it is rashly edited, will it cause other problems? On the other hand, even if the target gene is changed from CCR5 to GJB2, Rebrikov still cannotAvoid the disadvantages of technology.
Rebrikov said he would conduct enough security checks. For example, whole-genome sequencing is performed at the early blastocyst stage and compared with the sequencing results of the parents to find “all” mutations. However, this cannot be dispelled, two safety concerns that people have been questioning since He Jiankui-off-target effect and chimera.
Off-target effects: When CRISPR is used for gene editing, genes that do not want to be modified may be accidentally mutated. At present, it is difficult to detect all off-target sites. We don’t know if the undetected mutations are harmful and will cause other diseases; but at the same time, these mutations not only exist in the body of gene-edited babies, but also can be passed on to their next generation.
Chimeras: It is difficult for CRISPR to work at the fertilized egg stage of a single cell; Therefore, there may be cells in the final embryo that have not been edited, or the editing was unsuccessful. If gene-edited babies are chimeras, they may not get the benefits they expect, such as still being infected with HIV, not hearing, or even having other unpredictable defects.
Although technology has been emphasized, Rebrikov has to admit that he cannot currently detect off-target mutations and cells that have not been edited: “For technology, we always have some limitations . “
Is it worth the risk?
But once the experiment is carried out, these limitations of technology will become an unknown risk to genetically edited babies. At the other end of the scale, the benefit of these risks is-hearing.
This is another important reason why Rebrikov ’s plan has been questioned: is it worth the risk?
Deafness is not fatal, and some hearing impaired people can lead a relatively normal life. Moreover, gene editing is not the only way to gain hearing. Otolaryngologist Richard Smith of the University of Iowa, USA (Richard Smith) said that cochlear implants can stimulate the auditory nerve, and implanted this The device is able to restore some hearing; moreover, surgery is performed in childhood with a higher success rate.
Infants with cochlear implants | Bjorn Knetsch / Wikimedia Commons
Rebrikov himself also stated that On rare occasions, gene editing of embryos has more advantages than disadvantages.
In order to achieve the “pros outweigh the disadvantages”, he must find a very serious genetic disease, and only rely on gene editing to avoid inheritance, such as what he planned at the beginning-HIV infected women, Antiretroviral therapy is ineffective. However, there are too few of them, only about 30 in Russia; only a few of them have fertility needs.
Rebrikov turned to deafness, which was not fatal.
Science interviewed a deaf couple who was considering participating in an experiment. They already have a child. They didn’t know at first that their deafness would be passed on to their offspring; when they were told that their children were born with no hearing, they were very broken. They hope that their second child can hear.
This deaf couple considers genetic editing to make the second child have hearing | Sergey Ponomarev / Science
Rebrikov also responded to the question in this way: hearing has nothing to do with life and death, but perhaps parents strongly want their childrenDoes the child have hearing?
But do these parents know what risks their children will face? The bioethicist questioned Rebrikov: “What will you tell these patients? Is it all the facts, or is it only a part?”
The scientific community has also questioned He Jiankui:
Before conducting the experiment, He Jiankui must introduce the possible risks to the couples involved in the experiment and sign an informed consent form with them. However, according to He’s public informed consent document, he does not seem to be fulfilling this obligation well. Informed consent contains many unexplained technical terms, and it does not discuss the effects of off-target effects and gene editing failure.
Rebrikov told Science magazine that he would make his informed consent public later.
The experiment has not started yet
At present, Rebrikov will not be the second He Jiankui for the time being-his experimental application should be rejected.
Since the plan was publicized in June, Rebrikov has claimed that he would apply to the relevant Russian authorities before conducting experiments; he would definitely not act without permission.
Even if his plan seems to run counter to Russia ’s 2012 ban on the transfer of genetically modified embryos, he is not worried: “The law was written to change. As long as I can prove Technology security, rules can be changed. “
However, mainstream opinion is not the case. In August this year, the World Health Organization (WHO) called on all countries to stop allowing research on heritable human genome editing within their borders; they also established A registry system to collect and manage related research and programs.
WHO wants to register and manage heritable human genome editing experiments | Pixabay
In October, the Ministry of Health of the Russian Federation issued a statement announcing that “any clinical application of human embryo and germ cell genome editing technology is premature”; they agreed with WHO that genetic editing of human embryos is a trigger for pregnancy Irresponsible and unacceptable.
According to Rebrikov, he has not yet performed embryo transfer experiments.
He previously told the media that a couple was ready to enter the experimental process; but later, the couple changed their minds. They didn’t want the child yet, so they quit the experiment.
In October, Rebrikov told Nature that he had begun gene editing in eggs-but these were not the eggs he would use in his final experiment. He did this experiment to understand the potential harm of off-target effects.
Rebrikov said he was tired of the media’s crazy reports. He will not be interviewed until he is finally granted permission to transfer gene-edited embryos | Sergey Ponomarev / Science
He Jiankui hadn’t published his experiments in any academic journals or conferences before the baby was born; and Rebrikov chose to push his plan to the media-to some extent, this seems to make the situation less so Oops.
On the one hand, the relevant departments can no longer maintain a vague and ambiguous attitude. They are being forced to answer a key question as soon as possible: Is it possible to perform heritable gene editing on humans? On the other hand, with the attention, Rebrikov ’s crazy experiments have become relatively controlled; instead of after He Jiankui ’s gene-edited baby was born, like last winter,ure 570, 145-146 (2019). Russian biologist plans more CRISPR-edited babies. doi: 10.1038 / d41586-019-01770-x
[2] https://www.sciencemag.org/news/2019/06/russian-geneticist-answers-challenges-his-plan-make-gene-edited- babies
[3] https://www.newscientist.com/article/2208777-exclusive-five-couples-lined-up-for-crispr-babies-to-avoid- deafness /
[4] Nature 574, 465-466 (2019). Russian ‘CRISPR-baby’ scientist has started editing genes in human eggs with goal of altering deaf gene. doi: 10.1038 / d41586-019-03018-0
[5] Science 366 (6465), 564-565. Embattled Russian scientist sharpens plans to create gene-edited babies. doi: 10.1126 / science.366.6465.564
[6] https://news.un.org/en/story/2019/11/1045341
The article is from the WeChat public account: fruit shell (ID: Guokr42) , author: Barley