Wednesday , April 21 2021

The problem of changing the baby's genome

Nov 26th news that there was a Chinese doctor genetically modified two embryos is resistant to HIV It shook today. In order to understand all the problems that occur when converting human embryos and being born, you need to understand how the method works, CRISPR / Cas9, and also what's going on turn off CCR5 gene, gateway to HIV.

It is also important to know ethical constraints to carry out this description of pregnancy, in addition to what is used to do it. There is no ethics committee or mediation committee behind this genetic modification, just a doctor He is jiankui and his team from South Korea's Science and Technology University (Shenzhen). Even the hospital or university they were working on knew knew that this modification was made as they commented.

You must have CRISPR / Cas9 handled

The method used to carry out genetic modifications in two small DNAs was used CRISPR / Cas9. With CRISPR / Cas9, "we can record a gene, we can change the gene's reading," he explains. Hypertext José Alcamí, Director AIDS Immunopathology Unit at Carlos III Institute. What does it mean? What can you do? modify the gene so that it is expressed as the researchers want.

This method is used in "many laboratories". "We use genetic editing in cells in the laboratory and there are my colleagues who do it in mice or flies, for example, so we can choose mutant mice, mutant flies …" says Alcami. But, even though CRISPR / Cas9 is a "very powerful" genetic editing technique that additionally "works very well" is a limitation to be taken into account when making genetic changes in human embryos: "We developed this tool to change the specific gene we want to change, but we know that it is not absolutely specific. In other words, it changes what we ask for, but in itself it can cause mutations in other areas of the genome, "says the researcher.

Jennifer Doudna / UC Berkeley

As a result, embryos are not viable, that is, the technique "duck a gene that is important and cells die, "or that, despite being able to grow and be born, its DNA has caused mutations that can lead to important changes that may take some time to see it. "This means that the instrument's specificity is still not sufficiently controlled," says Alcami.

"For example, if you want to make a mouse with a tool, You may need to take 20 mice to get one right"illustrates the Carlos III Institute researcher, the result may be that the edition works as one wants and does not change anything of importance, or" if you change other genes, the mouse is not viable. "" The tool itself still need to be cleaned do what he needs to do, and just what he needs to do, "adds Alcami.

On the other hand, the problem does not apply to the modification of human embryos, but to him implantation for their development, which should be managed by the Ethics Committee. "Embryo implantation is virtually banned all over the world, it's not," says Alcami. "Embryo modification is allowed, for example, in the UK, but always for experimental purposes, then it is prohibited to implant the embryos. There you can make changes and check if you really have loaded the gene but it is you have not caused the consequences aroundbut this can not be achieved, "explains the researcher," continuing one step further and implanting the embryo ", this situation has become an ethical problem.

The CCR5 gene is not only the opening of HIV

Idea about turn off The gene, so that it is not expressed, and avoiding the fact that young people are infected with HIV, is very good on paper, but in fact, that Modifying this gene can affect the health of both babies. This is without regard to other genes that could have been rewritten in their DNA and which could lead to other diseases.

Sebastian Kaulitski | Shutterstock

Modified gene is CCR5, which "encodes one of the recipients, a virus that causes AIDS," explains Alcamí. "In fact, less than 1% of the Caucasian population (white) with a genetic variant that does not disclose this gene expresses a defective protein, and if it does not spread, the virus can not be infected, they do not have an open door for the virus," he said. confirms the researcher.

However turn off this gene is leave flavivirus open door, such as those that produce West Nile Fever (or West nile) or even some bacteria, such as Listeria, as explained Hypertext Alcamí "This is known less people, only those of us who work with the HIV virus, and these recipients know it. We know that this receiver does not have a virus to infect it but because it has a function. "HIV has only" adapted to these doors "and used it to infect cells.

"Interesting for people to whom this genetic variant is obviously not a diseaseNo one will be with them until they are infected with Nile fever, "says an HIV expert." This genetic variant continues, it only happens between Caucasians, it does not happen in Africa or China. "And that's for some reason" he says: "This gene helps to develop an immune response against some viruses"as above West nile.

Viruses are transmitted by mosquito bites and causes this disease, which is "not usually fatal". However, as seen this year in Europe or happened in the United States in 2012, There are people who die when they get sick. And why? Only the CCR5 mutation is the culprit. "After the pandemic in the United States, it was seen those who died had a mutation in this gene. This is where this mutation makes you more sensitive to death if you get a virus West nile"says Alcami Hypertext. This is the reason why there was no mutation in either Africa or China: "Those who died it thousands of years ago." Yes, this mutation happens, for example, in India, which also makes them sensitive to this flavivirus.

Influenza is another disease that seems to be associated with this gene, although "it has been less clear." People with this mutagen gene go through "More Serious and Sophisticated" and, moreover, "you also saw that you have protection of the Listeria"says Alcami.

So, by changing the CCR5, you not only close access to HIV but also open it to many other illnesses. "This defect, which is good because you do not get HIV it weakens you because you may have a serious infection West nile or possibly other pathogens. It is a problem that inactivates a non-disease-causing gene. Because if it causes you, for example, muscle disease, and that's what's up, what you do is that your muscles are good, but the gene that's it to protect you from the infection, at the same time it there are other functions and you let it in, you are loading the functions of this gene. It does not mean those we probably do not know, and we will do it now, when there are mutants that have this variant introduced with genetic engineering"he says.

Without ethical confirmation and with many lies

When making these changes, pay attention to two other problems. On the one hand, lie to justify this genetic publication and, on the other hand, absolute lack of ethics with which it has been implemented, as, as already mentioned, there is not even an ethics committee that will review all future activities. And that's why there was no need to change the genome to make the girls healthy.

Dr. He was looking for pairs in which a man was infected with HIV and, moreover, had antiretroviral therapy, but the woman should not be infected. "If the father who is infected is treated with antiretroviral drugs, which is also one of the conditions he has chosen, we know that he does not transmit the virus to his wife, we know that his sperm will be free of viruses and we know that girls will not be infected"According to the researcher, the idea that without this genetic change girls would be infected" is not true "because "under no circumstances" would not be infected. "It's a bit complicated to say that he has improved them so they do not get infected because that's not true," he says.

Credit: Oregon University of Health and Science.

On the other hand, if there is no ethics committee and mediation committee, the protocols have been violated. "I have submitted a proposal to families with whom we call" a " instability or weaknessbecause this is a family member who is disturbed. Father is infected with HIV, and his wife is not always and fear infect your partner and that it can infect girls. "But" it must be the ethics committee that confirms it, must be informed consent. It can not be a researcher who directly suggests something to parents, it must be a mediation committee that You have to study the circumstances, that is, He has adopted a very attractive case, but it has not been presented ethically, "says Alcami.

The most complicated part of ethics is the researcher at the Carlos III Institute. "He has suggested non-therapeutic therapy but a genetic modification because it does not cure any disease, that is, it's not that you tell your parents that there is a gene that can prevent fatal paralysis at birth and you go to change it so that Your baby was born healthy. No. They are girls who are ready to be healthy and not infected and have done so. improvements genetics " Hypertext on the other side of the phone. "Improvement, if everything goes well," he says. In addition, one of the girls is "only one gene deactivated," she says, but it's necessary turn off two copies of it "You can get infected like everyone else"he explains.

Genetic modification "is a debate that the public will need, but it's not the right time, because the tool is not safe enough"

"After this genetic change, they are more likely to have more, and we will have to answer the question: What is ethical improvement and what is not? The color of the eye is it? Is my son stronger, longer or smarter?" We only cure genetic diseases? " This is a debate that society will need, but this is not the right moment the tool is not secure enough"Alcam says:" All these questions are being asked "is to open a sophisticated Pandora box," in particular given that CRISPR / Cas9 This is not a "verified human tool", at least not for the moment.

In addition, he has two companies dedicated to these issues, so "we do not know if it will be business interests"because it is clear that there will be" rich "people who" say: "I want a child who is protected against the HIV virus" regardless of the price. "The open bar has begun," he says, on the other hand, as a Chinese researcher, "He has not published data," and he does not have his university or hospital "We do not know exactly what he has done". "Ethically, we are all scared that someone has crossed so much red lines"concludes Alcamí.

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