Russian scientist decided to create genetically modified children

One of the leading Russian specialists in the field of molecular biology techniques and genetic engineering Denis Vladimirovich Rebrikov in an interview with the journal Nature outlined plans to conduct an experiment to create children with the edited genes. He said he was willing to repeat the experience of Chinese genetics Ho Cisangkuy, which came to light twins Lulu and Nana. According to Rebrikov, he is considering to have implantation of genetically edited embryos before the end of the year, if receives the approval of three ministries, including the Ministry of health of the Russian Federation.

What is CRISPR-Cas9?

CRISPR-Cas9 is a technology for genome editing, based on the principles of the immune system of bacteria (they are able to find and eliminate viral DNA). CRISPR-Cas9 includes a guiding RNA molecule that finds a piece of a chromosome, and the enzyme Cas9 cuts the DNA. If at this point to add a normal copy of the gene, it is built in the right place. The process is similar to editing text, when part of the sentence is deleted and in its place insert other words.

Editing genes in Russia

The purpose of the experiment, a Russian biologist will be a modification of the same gene, on which a Chinese expert on genetic engineering – CCR5. In an interview with Nature of Rebrikov toldthat he was going to turn off the gene in the embryos, which encodes a protein that allows HIV to enter the cells of the body. The embryos will be subsequently implanted to HIV-positive mothers who do not respond to standard therapy. It is noted that the risk of transmission to the child in this case will be higher, but if the procedure will successfully disable the CCR5 gene, this risk will be significantly reduced.

Recall that he Cisangkuy in turn took the cells of HIV-positive fathers, and then transplanted the resulting embryos are HIV-negative mothers. It doesn’t make practical sense, which in turn among other things was another reason for criticism of the Chinese genetics global community of scientists. Work Hae caused a storm of criticism among the scientific community and led to the emergence of the open letter, in which scientists called for a moratorium on experiments on gene editing of human embryonic cells. Rebrikov claims that its method of modifying the gene will be healthier, will be less risky and more ethically justifiable and socially acceptable.

Rebrikov adds that it has reached agreement with the local HIV center, where he is going to attract women volunteers willing to participate in his experiment.

The journal Nature asked for comments regarding the planned experiment of Russian scientist to other researchers who, as expected, expressed concern about the plans Rebrikova. For example, Jennifer Doudna, a specialist in molecular biology from the University of California at Berkeley and one of the pioneers of the method of gene editing CRISPR-Cas9 says that this technology is still not fully understood and not ready for use in clinical situations.

“I’m not surprised at such statements, but this news is very disappointing and at the same time worried,” added the scientist.

Even if the experience is successful, a small risk of infection will remain. And still we don’t know exactly how it will affect human life in General. For example, in a recent study in carriers of both copies of the mutant CCR5 found the risk of an earlier death compared with carriers of the normal gene.

“Before, scientists will begin to attempt implantation of genetically modified embryos is necessary to conduct a transparent, open debate about the scientific and ethical validity of such experiments,” says geneticist George Daley of Harvard medical school.

Russian experts also expressed their disagreement with similar experiments.

“It is potentially very dangerous. The possibility of even a sick person already imposes a ban on all”, — commented the newspaper VIEW geneticist Igor Zolotovskii, commenting on the plans of the biologist Denis Rebrikov to create genetically modified children.

Molecular geneticist Konstantin Severinov, contacted the authors of the Nature noted, in Russia to receive approval to conduct such experiments will be very difficult. I will have to take into account not only the opinion of the state and the Church, which opposes editing genes. And this greatly reduces the chances of getting approval – at least in the coming years.

And yet the most important question is how real is the prospect that draws Rebrikov?

Dolatowski believes that the experiment is technically possible to carry out, but the problem lies in the ethical part of the question.

“Everything is possible, Chinese made, our scientist can also. Here the question is ethical – experiments on humans, changing human genome. And technically you can do a lot,” added Dolatowski.

According to Rebrikova to which the editors asked for comments, the ethical side of the question – least important aspect.

“The ethical side of the issue is extremely important and we would certainly need to obtain all approvals from Ethical committees and regulatory agencies. But the fact is that there are clinical situations where the ethics of such (genericactosha) approach cannot be subjected to doubt. These are cases when 100% of children have a pair of data parents will suffer a severe genetic disorder. Such situations are infrequent, but do exist. When both parents are homozygous for disruption of the same gene leading to hereditary disease (e.g., deafness),” said Rebrikov.

Why are people afraid of genetic experiments?

One of the reasons why the topic of genetically modified embryos has caused such a heated debate in the international community due to the fact that if you allow such experiments now, the resulting “GM children” will grow up and be able to pass their modified genes on to succeeding generations. Scientists generally agree that the technology of gene editing will one day be able to help in complete elimination of genetic diseases such as sickle cell anemia and cystic fibrosis, however, at the moment requires much more additional research.

In addition, there are concerns about the safety of gene editing of embryos in a more General sense. Rebrikov States that his experiment in which he, as a Chinese geneticist and he is going to use the method for genome editing CRISPR-Cas9, will be completely safe. However, scientists believe that the use of CRISPR-Cas9 in the current view can cause “inappropriate” mutations in other genes, not taking need which is the goal of the editing process. Thus it is possible that the disabled can be genes, for example, responsible for growth suppression of tumors.

According to Rebrikov, he is leading the development of a method which can ensure such mistakes. The scientist plans to publish the preliminary results of this work during the month of may in the online repository of scientific preprints, or bioRxiv peer-reviewed journal.

Asked to comment on this statement our portal the author of the project said the following:

We learned how to correctly check the safety of the used the CRISPR system, pinpointing its off-target (non-specific — approx. ed.), the activity in the embryos with a known genome. This, as far as I know, yet no one in the world. And it allows us to reach a practical use consciously, and not, as did he”.

In turn, scientists that for the review asked the authors Nature, was skeptical about the claims Rebrikova about solving the problem of untargeted mutations and possible implementation of only the target under which you will edit only the desired genes and exactly as planned.

Last year in the journal Bulletin of RSMU, where he is the chief editor of Rebrikov published an article in which he argued about the development of a method capable of disabling both copies of the CCR5 gene (by removal of 32 base pairs) to more than 50 percent of cases.

However, Jennifer Doudna, a specialist in molecular biology from the University of California, Berkeley, expressed skepticism about these results.

“The data I’ve seen shows that to control the process of DNA repair is not simple,” he says.

Agree with her geneticist at the Australian national University Gaetan of Burgo, noting that in the process of editing possible deletion and insertion, which are difficult to determine.

Incorrect editing can lead to the fact that the gene is not disconnected properly, which in turn will leave the cage still unarmed against HIV, or lead to gene mutations, which will be completely different and unpredictable ways, says Burgo.

Moreover, said Burgo, neutrophase gene CCR5 has may have many useful functions that are still not fully understood. For example, previously scientists have determined that, it seems, the gene provides some protection against complications of infection with West Nile virus and influenza.

“We know a lot about the role of the gene CCR5 in the penetration of HIV into cells, but we do not know much about its other functions,” adds Burgio.

The prospects of CRISPR in Russia

Denis Vladimirovich Rebrikov (photo Nature)

We asked Denis what are the prospects of technology CRISPR-Cas9 and whether it is able to win all genetic diseases.

“Hereditary diseases do not win CRISPR-Cas9, and preimplantation genetic diagnosis (PGD). The fact that, as stated above, the edit is justified only in case of failure of all four alleles (for a given pair of parents). This is an extremely rare situation. One in a million. But the children with genetic diseases are born very often (almost 1% of newborns!) and win is very simple: for a pair of parents who have the risk of having a sick child (because we are in advance (somewhere) know their genetics) is necessary to carry out IVF and PGD to select healthy embryos. And no CRISPR-Cas9 is not needed! Somehow, few non-specialists that”.

On the question of how the General state of Affairs with the studies of CRISPR-Cas9 in Russia, and the role played in them by the state of Rebrikov said that overall so far so good.

“On the General background – normal things. Many groups working with this technology in all areas: plants, animals, microorganisms. There are developers of new-type Cas9 nucleases and modifiers available. There are exploratory studies of these new systems. Everything is fine here”.

“The state now has announced a large program of development of genetic technologies. While the money didn’t go down, but it will definitely be a plus development and CRISPR-Cas9 including”.

About how he described the technology CRISPR-Cas9, and what his attitude of Rebrikov said:

“This is another molecular genetic technology. Over the last 50 years created such a lot, and this is no steeper than PCR or sequencing (for which, given the Nobel prize, by the way). Just another technology DNA and genes. I believe, in the foreseeable future (10 years) mankind has come to directional changes of the human genome with the goal of improving (and possibly the alternation of cloning and for genome editing is most effective)”.

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