What we know about "genetically modified" twins



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Earlier this week, a Chinese researcher announced that he had genetically modified two embryos, giving birth to the first pair of twins with artificially modified genes in the laboratory. The news has sparked much debate, especially among geneticists, and has added new elements to the old debate about the possibilities of new techniques for genetically modifying organisms and the ethical and moral repercussions of these practices.

The story also explained why, today, we are not sure that the result announced in China has been achieved, given that many data are still missing and that the checks have been verified by others. researchers who did not participate in the experiment. Thursday, November 29, the Chinese government ordered the suspension of any activity related to this research, confirming that he had opened an investigation.

The Chinese experience
He Jiankui, a geneticist at the University of Science and Technology of China (Shenzen), said that he had artificially inseminated a woman with embryos that he had previously modified, in order to disable the mechanism that HIV (the virus that causes AIDS) exploits to infect cells. He says the two girls are doing well and that the DNA tests confirmed the presence of the artificially made modification. During an intervention held in Hong Kong on Wednesday, November 28, at a major international conference on genetic modification, he once again supported the achievement of the outcome, but did not provide some answers and data to be sure of his statements.

His statements led to two main points of comparison: on the one hand, some people wonder whether the experiment on embryos really worked and, on the other hand, question the possible ethical repercussions and the possibility of carrying out screening tests. this type, with systems of modification of DNA still at the earliest and on which more studies and knowledge are necessary.

CRISPR-case.9
To modify the embryos, he used the CRISPR-Cas9 system, which makes it possible to copy parts of the DNA from one organism to another. This technique has significantly reduced the costs of genetic experiments, as well as reduced the time required to perform experiments and verify results. CRISPR-Cas9 is considered to be the most promising frontier for DNA interventions and, from the very first days, it already offers great opportunities for the development of new treatments and treatments for serious diseases and up to the end. then incurable.

The critics
Using CRISPR-Cas9, he claims to have disabled a gene called CCR5 in embryos and contains instructions for creating a protein used by HIV to enter and colonize cells. Who has seen the documentation presented so far by He does not say that the change has been made, but only independent DNA testing of the two Chinese twins will be able to provide definitive confirmation. At the same time, harsh criticisms and accusations have been leveled against him for acting irresponsibly, jeopardizing further research with CRISPR-Cas9.

One of the first to stand out from his job was the same university where the researcher works. In a statement, the institution said that she had not been warned of the experience and that he had been on leave since last February. The university is also dissociated for legal reasons: in China, there are laws that limit research on embryos and it is suspected that it has violated some of them. However, it is unclear whether this will have legal repercussions for the researcher: Chinese research as a whole is not highly regulated and there is rarely any intervention against those who do not follow the rules.

"D & # 39; irresponsible"
More than 100 Chinese researchers have signed a document that severely criticizes God's work. He states that "going directly to experimentation on human beings is irresponsible" and asks the Chinese authorities to investigate the researcher's statements and the effects of his experience. The document also defines this initiative as "a blow to the international reputation of scientific research in China, especially in the biomedical field". Many Chinese scholars worry that the action of an individual – unauthorized and devoid of any ethical consideration – could hinder his studies and lead the government to relax and regulate a field of research who needs space and standards. opportunities for evolution.

Other criticisms have been addressed to He regarding the genetic modification performed. It is true that the CCR5 gene is involved in the spread of HIV in cells, but it is not the only point of entry for the virus. It has been shown that at least one other gene, CXCR4, encodes a protein that, in some individuals, performs the same function as that of HIV control in cells. There are people born naturally without CCR5 but who are also at risk of HIV because they could be infected with the viral strain that uses CXCR4. So technically, the two girls modified by He would not be completely immune to the virus that causes AIDS.

Safer alternatives
Then there are those who emphasize that his approach is debatable in principle. CRISPR-Cas9 offers the possibility of developing treatments for deactivating CCR5 in HIV-positive adults and not in embryos. It is considered a safer and more effective method because it is only used in people with HIV and to reduce the viral load in the body. This system, still experimental and perfected, has fewer ethical implications and especially less uncertainty about prenatal development and in the years following birth. There are also safer systems to prevent an HIV-positive mother from transmitting the virus to offspring, for example through caesarean delivery techniques, to reduce the risk of infection.

The Hong Kong conference
He's intervention in Hong Kong displeased most researchers at the conference, wanting more information about the experiment and eliminating the many doubts about the Chinese researcher's statements. He recounted his first experiments with animal testing and the subsequent decision to intervene on human embryos. He also revealed that he had at least one other pregnant woman whose embryos had been modified by him.

nature collected the impressions and evaluations of the researchers present at the conference. For their part, there was great mistrust about He's statements, some said that they were "horrified" and they described the experience as "useless," "premature" and "completely superfluous".

For about 40 minutes, he answered the researchers' questions by betraying some emotion and repeatedly apologizing for the confusion caused in a very delicate area such as genetic research. He explained that, according to him, only one of the twins is completely resistant to HIV because the change has successfully suppressed both copies of the CCR5 gene (that of the father and the mother). Due to an error, it was not possible to do the same with the other child, for which a copy of CCR5 remained. Many people asked why he decided to implant the second embryo because the procedure did not work out as planned.

He said he worked with eight couples of parents, all with HIV-positive fathers and HIV-negative mothers. She said she treated the sperm of future fathers to make sure she was free of HIV and then injected into her partner's oocytes. He obtained 30 embryos, 19 of which were vital and in good health during laboratory examinations. Two of the couple's embryos contained modifications to CCR5 and he stated that they had implanted them in the expectant mother, even though one of them still contained a copy of CCR5. It is from this pregnancy that the two girls were born that he said to have been genetically altered. The researcher did not provide information on the fate of other embryos.

Unanswered questions
The unanswered questions continue to be very numerous. For example, we do not know why He has selected future-parent couples with only HIV-positive men instead of expectant mothers, who are at a much higher risk of transmitting HIV to their offspring. One does not understand either why he chose this method that involves the removal of a gene, CCR5, certainly involved in the spread of the virus in cells, but that could also have other functions for the # 1. Organism that we do not know yet.

The scientific community has strongly criticized for not providing information on his projects before the implantation of the embryo. During the conference, he claimed to have done so at academic meetings last year, but the organizers of these events said that he had not presented anything that would indicate the choice to experience change directly on the man.

Most geneticists are worried that his work can cause considerable damage to genetic research. Systems such as CRISPR-Cas9 are considered essential for the production of next-generation therapies, solutions that could improve the lives of millions of people and help overcome serious and disabling conditions, including cancer. The debate on these systems, from an ethical and moral point of view, has been going on for years, but until now it has been kept in an open debate thanks to the self-regulation of the scientific community , which encouraged a very cautious and progressive approach to experimentation. genetics on human embryos. It has broken this mechanism and could lead governments to intervene heavily to avoid the repetition of uncontrollable experiences, but with stricter rules that could penalize the work of those who conduct more responsible research.

On the other hand, the developments and opportunities offered by CRISPR-Cas9 are enormous and require an open and informed confrontation between the scientific community, politics and public opinion. Genetic modification systems allow us to envision a future, even distant, in which each couple can personalize their child, choosing not only to exclude particular risk factors for hereditary diseases, but also to determine their physical appearance. Nowadays, something similar is already happening with prenatal diagnoses, which in many cases makes it difficult to choose whether to continue or terminate a pregnancy. In fact, a selection system already exists, but it is certainly not comparable to what can exist in a few decades and on which it is appropriate to proceed immediately to a confrontation. Check if the statements of it are true or not is just a difficult piece of conversation that will concern us all.

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