The first genetically modified child. The first genetically modified babies were born in China. Is it possible

He Jiankui, a scientist at the Southern University of Science and Technology in Shenzhen, announced that he had implanted a genome-edited fetus into the uterus for the first time in the world. According to him, the pregnancy led to the birth of two healthy twin girls, who were named Lulu and Nana.

The purpose of this work, according to the researcher, was the birth of children with resistance to HIV. The scientist used the usual CRISPR-cas9 gene editing method. Subsequent DNA analysis showed that the editing was successful, and the changes affected only the desired gene. We are talking about the CCR5 gene: it encodes a protein that allows the human immunodeficiency virus to enter the cell. Mutations in this gene, which confer resistance to HIV to the carrier, are present at low frequency in some human populations.

In a video posted on Youtube, He Jiankui talks about how the work went: the CRISPR-cas9 molecular apparatus was introduced into the egg along with the father's sperm at the time of artificial insemination. According to him, the girls are perfectly healthy and are at home with their parents.

The details of the work have not been published in peer-reviewed scientific periodicals, and the scientist's statements have not been confirmed by an independent examination. Documents submitted to the Chinese Clinical Trials Registry. Genome editing specialist Fedor Urnov from the Altius Institute for Biomedical Sciences in Seattle, at the request of the scientific press, reviewed the submitted documents and came to the following conclusion: “The data that I have seen does not contradict the statement that the editing did take place.” However, according to him, for final conclusions, an independent analysis of the DNA of girls should be carried out.

The message of the Chinese researcher raises several questions. First, one of the unsolved problems of using CRISPR-cas9 technology is the high probability of undesirable changes at random points in the genome. To make sure that this did not happen in this case, it is necessary to conduct a complete decoding of the genomes of patients, and possibly also additionally make sure that there is no mosaicity (that is, that unwanted mutations did not appear only in the cells of some body tissues). Dr. He's statement does not indicate that such a large-scale inspection was carried out.

Secondly, when deciding on the ethicality of the use of gene editing technologies, a balance is usually considered between the possible dangerous consequences of the intervention itself and the severity of the disease that is supposed to be prevented by gene editing. If this disease is fatal or entails severe disability, then theoretically one can put up with even a fairly high risk. However, in this case, the object of intervention was a completely healthy embryo.

Currently, medical procedures have been developed that almost completely exclude the possibility of transmission of HIV from parent to child. In particular, if the mother is infected, the baby is born by caesarean section, which reduces the risk of infection to an acceptably low level. However, in the case of Lulu and Nana, the mother was not an HIV carrier. The father was infected, and in this case, the risk of infection is reduced to zero if the simplest sanitary precautions are observed. In any case, the general opinion of experts was that there was no need to resort to the expensive and dangerous method of gene editing using CRISPR-cas9 technology.

He Jiankui does not claim that the purpose of the work was to prevent HIV infection. In an interview with The Associated Press, he stated that he intended to ensure that other couples where both parents are HIV-positive, the opportunity to give birth to a healthy child.

At the same time, Dr. He claims that he considers editing the human genome only to prevent the threat of disease. In his opinion, editing the genome in order to change the color of a child's eyes or increase his IQ should be strictly prohibited. "I am aware that my work will cause controversy, but I believe that many families need it, and therefore I am ready to accept criticism," He Jiankui told Nature magazine.

Genetic editing of human fetuses is contrary to the recommendations adopted by the Chinese Ministry of Health in 2003. However, He Jiankui's work does not violate Chinese law.

Details about the work of the Chinese researcher and the opinions of various experts can be found in

Scientists around the world are competing in their developments to be the first to create a genetically modified child. They care only about technology and personal careers, and will continue to fight to remove restrictions on their work.”

China, for example, announced that they had created a new breed of genetically modified dogs "from a test tube." In terms of muscle mass, they are twice as large as their relatives, they have much greater strength and speed.

Scientists explained that the dog's genome is difficult to modify and is very similar to the human. And this means that in the future, similar manipulations can be performed with people.

Assumptions immediately appeared in the press that the goal of the Chinese was not to breed champion dogs at all, but to develop technology that would allow the creation of superhumans, soldiers with superhuman strength and not knowing fatigue, like American comic book characters.

Director of Human Genetics Alert, an organization that unites opponents of genetic experiments, David King said:

In the first experiment on cloning dogs, Chinese scientists removed the myostatin gene from them, which made it possible to create muscular monsters. It is possible that someone will want to produce superpredators or superpoisonous insects that can be used as biological weapons.

True, the only public animal cloning experiment in Europe ended in failure. Dolly the sheep, cloned by the British, was often sick and lived only six years.

At the Institute of Biological Medicine in Guangzhou, the experiment with dogs is called a scientific breakthrough, previously only Koreans managed to clone a dog. But in China, for the first time, a dog with the desired properties was cloned.

King believes there are increasing attempts to modify human embryos. This can lead to the construction of designer babies. Parents will order doctors what kind of children they want to get. In the US, this is already happening - beautiful and smart women are paid much more for their eggs.

Another US specialist, James Grifo, pioneered the transfer of the cell nucleus from the eggs of older women to young ones. As a result, children are born with three genetic parents at once. The demand for this service may well enrich genetic engineers.

Massive symposiums are held all over America where such specialists promote their technologies. Princeton biologist Lee Silver admits that ordering a child with the desired properties will be available only to a small group of the elite, that is, over time, humanity will be divided into a ruling genetically improved race and ordinary mortals working for it.

The whole scientific world, and not only the scientific one, was stirred up by the news from China. It became known that for the first time in the world genetically modified children were born - these are twins, girls. The father-grandparent, so to speak, the Chinese scientist edited the embryos so that the newborns would become immune to HIV. And claims that everything worked out.

So far, no one has seen these children, and the results have not been proven by anything. Although such experiments with people are not allowed anywhere in the world, everyone understands that sooner or later science would cross this line. It turns out that now you can literally "make" a new superman to order.

“Two beautiful little Chinese girls named Lulu and Nana came into this world crying loudly,” Dr. He tells with emotion about his experiment. He claims that he managed to edit the genes, and in the future these newborn girls will never get HIV. Babies are not shown yet, but Dr. He has already said: everything worked out.

“When the embryos were still very young, we removed the loophole in the genome through which HIV infects the body,” explained He Jiankui, a researcher at Shenzhen Southern University of Science and Technology.

Seven couples participated in the experiment. Every man in these couples is infected with HIV, while the women are healthy. All underwent artificial insemination. But only one woman managed to endure. She gave birth to two girls. According to the scientist, one gene is completely changed, while the other is partially.

“The world has advanced in gene editing. There will always be someone who will do it. If not me, then someone else,” said the scientist.

“We can now treat diseases at the gene level - that's what's important. This will help people with rare diseases, especially those with HIV, no longer be the target of discrimination,” said Lin Zhitong, administrator of the hospital.

So after all, what is it: a breakthrough in medicine or a dangerous experiment? In the world of genetics, they are skeptical: while there is not a single publication in a specialized journal, Dr. He kept the study a secret from the scientific community. Scientists study human cells in vitro, including in Russia, but before that no one dared to endure and give birth to a genetically modified child.

“One of the goals is to make these molecular scissors that cut DNA so precise that the likelihood of some side cutting of DNA in the wrong place is negligible. It seems to me that quite a few years will pass before a person appears somewhere in whose embryo something has been changed using any genetic engineering methods,” said Candidate of Biological Sciences, senior researcher at the Institute for Information Transmission Problems of the Russian Academy of Sciences Alexander Panchin.

Overseas have already condemned this experience of a Chinese doctor, they say, why open Pandora's box?

“There is still a lot of work to be done to prove that this procedure is safe. I would say that the birth of children in this experiment, with this technology, should not be allowed yet. At the moment, this is premature, ”Kiran Musunuru, a doctor from the University of Pennsylvania, expressed confidence.

“I think this is a violation of what was recommended in a communication released last year by the National Academy of Sciences. It maintained an open and transparent approach to news of clinical experiments in embryo modification. The course of these experiments should be well prepared and carried out in accordance with the standards established by the international association of scientists. I don’t think that in this case all the requirements were met, ”said Jennifer Downa, a professor at the University of California at Berkeley.

Even Dr. He's home university hastened to disown him, saying that we didn't know anything. And the Chinese authorities reacted like this.

“The official statement of the State Committee of the People's Republic of China for Health and Planned Childbirth: the media reported the birth of genetically modified babies with immunity to HIV. The Committee is closely monitoring this fact, and has already instructed the Guangdong Provincial Health Committee to conduct a thorough investigation,” the official statement said.

Genome editing technology itself is not new, to put it mildly. It has long been used in the selection of agricultural crops. And in the same China, with the help of this technology, they change the DNA of animals. Experiments with gene modification in the Republic of China are not prohibited, but even encouraged. It is not yet known what this experience of Dr. He will lead to, but it is already clear: the experiment on people here is not the last.

The sensational statement of a Chinese scientist about the birth of the first genetically modified children shocked the scientific community and caused a flurry of criticism - both from his colleagues, genetic experts, and from the official authorities of the country and international organizations.

His experiment - apparently quite successful - was called insane and even monstrous. Although Professor He himself claims that he only made newborn twins resistant to HIV infection.

At the same time, from the point of view of science, nothing special - and even more so revolutionary - did not happen. Scientists have long been able to make changes in the DNA of plants and animals to give them the desired properties, and this technology is actively used in medicine and the food industry.

Moreover, it was for discoveries in the field of directed evolution that the Nobel Prize in Chemistry was awarded this year.

So what did Professor He Jiankui do? And why did his statement immediately cause scandal and anger in the professional community?

What is the essence of the experiment?

According to Professor He himself, he took an egg fertilized by an HIV-infected father and edited its DNA, removing part of the CCR5 gene, through which the immunodeficiency virus joins the cells.

This "truncated gene" naturally occurs in about 10% of Europeans due to a natural mutation that occurred about 700 years ago.

According to one version, its carriers were less susceptible to infection with bubonic plague - and the mutation was fixed evolutionarily as a result of the Black Death epidemic, as the survivors passed on the mutant gene to their descendants.

So, if twins are indeed missing part of CCR5, they are biologically immune to the most common type of HIV infection.

Is it possible?

Undoubtedly. Experts have no doubts that such an experiment can be carried out in practice.

The CRISPR-Cas technology, developed several years ago, makes it possible to very effectively make changes to DNA, cutting out sections of the genes that researchers need.

It is quite easy to use and is widely used in biological laboratories around the world - for both medical and industrial purposes.

According to He, eight married couples participated in the experiment (all eight men are carriers of HIV infection). In addition to the already born twins, another genetically modified child should be born in the near future.

Why then do scientists doubt the words of the professor?

Firstly, it is very strange that He Jiankui talked about his experiment by posting a video on YouTube, and not in the traditional way - by submitting the corresponding article to a scientific journal, where it could be studied by genetic experts.

Secondly, he refuses to reveal the incognito of the participants in the experiment - the world has not yet been shown either the supposedly born twins or their parents.

Thirdly, at the Southern University of Science and Technology, where Professor He is listed, they said they did not know anything about the experiment, and the scientist himself has been on unpaid leave since February.

Fourth, if the stated goal of the experiment, as the scientist himself claims, is to help families get rid of hereditary diseases, then the choice of infection looks very strange. HIV is not a genetic disease, and besides, the transmission of the virus to the embryo can be prevented anyway by well-known and widely used clinical methods, without DNA editing.

What is the danger of genome editing?

In general, the idea of ​​getting rid of severe hereditary diseases by replacing a "defective" DNA segment sounds tempting and looks very promising from the point of view of the development of medicine. True, it is not known how artificial mutations can affect the body in the long term - our knowledge of our own genome is far from exhaustive.

However, the problem of such gene editing lies mainly in the ethical plane.

Making changes to the genetic code may in the future lead to the creation of "constructor children" - when parents can choose in advance the characteristics of the unborn child. Not only gender, hair color or eye shape, but also life expectancy, resistance to certain diseases, or even increased mental abilities. And he, in turn, will pass on all these signs to his descendants.

It is clear that the procedure of "individual construction" of DNA will be affordable only for fairly wealthy people - and social inequality, according to opponents of the method, is in danger of gaining a foothold at the biological level.

That is why experiments in this area are prohibited in most countries.

And even where they are allowed in principle (for example, in the UK - precisely in order to study the possibility of treating severe hereditary diseases), there are strict rules that require the destruction of all modified embryos in the early stages.

That is why the birth of the first genetically modified children - if it really happened - could mean a new page in the history of not only medicine, but of all mankind.

"Pandora's box is open. And perhaps we still have a faint glimmer of hope that it can be closed before it is too late, ”says an open letter sent to Professor He by his colleagues.

The question of the ethics of such an experiment and its value for preserving people's health in the future is being actively discussed by the world community of scientists, however, Chinese researchers, according to them, were guided not by a thirst for fame on a planetary scale, but by the most humane goals - to protect humanity from HIV.

Purpose of modification

Scientist He Jiankui revealed that he altered the DNA of embryos for several couples who were being treated for infertility. One pregnancy has ended successfully so far.

The geneticist explained that his goal was not to cure or prevent a hereditary disease, but to try to give children an ability that few people naturally have - the ability to withstand a likely future infection with HIV, the AIDS virus.

The essence of the experiment

The Chinese researcher has been practicing gene modification in mice, monkeys and human embryos in the lab for several years. The scientist plans to patent his method.

The choice of HIV for gene correction He Jiankui explained by the fact that this disease is a serious problem in China. He was looking for a way to block the CCR5 gene, which allows the immunodeficiency virus to enter the cell.

All the men in the project were HIV-positive, but the women were not. The gene change was not intended to prevent a slight risk of transmission of the virus - in fathers it was already deeply suppressed by standard drugs, and there are easier and safer ways to avoid infection of the offspring than correction at the DNA level.

The intention was to offer couples living with HIV the chance to raise a child protected from the virus.

The scientist recruited participants through a Beijing-based group called Baiualing. Its leader, known by the pseudonym "Bai Hua", noted that it is not uncommon for people with HIV to lose their jobs or have problems accessing medical care.

Modification algorithm

The change in the genome began during IVF - in vitro fertilization. First, the sperm was "washed" to reduce the likelihood of HIV being introduced into the embryos. One sperm was placed in one egg. Then a substance was added that affects the genes.

At the stage of development of embryos at the age of 3 to 5 days, several cells were removed and checked for changes. The couples had a choice - to use embryos modified or avoided by third-party interference in the DNA structure for conception. According to He Jiankui, 16 out of 22 embryos were modified, 11 were used in six implantation attempts to achieve a double pregnancy.

Tests showed that one twin had a pair of modified genes, the other only one, with no evidence of an effect on the others. People with one gene change are still susceptible to HIV infection, although some research suggests that the disease is likely to develop more slowly if such a person is infected.

The scientists analyzed the materials provided by He Jiankui. Their conclusions were not unambiguous, as at the moment there is not enough information to say how beneficial or harmful the modification will be.

The ethics of the experiment: the opinion of scientists

Kiran Musunuru of the University of Pennsylvania questioned the ethics of such use of embryos in an attempted fertilization, as Chinese researchers said that they assumed with great certainty that only one child would be affected.

Dr. Musunuru noted that the partially altered twin has little to no additional defense mechanisms against HIV, and yet he was exposed to an unknown risk. The scientist believes that the use of the embryo betrays the main task of researchers - testing the modification, and not searching for the possibility of avoiding the disease.

Even if the gene fix works, people without the normal CCR5 genes face a higher risk of getting certain other viruses, such as West Nile or a lethal variety of the flu. Since there are many ways to prevent HIV infection, the increased risk of getting and developing other deadly diseases is not a problem, but, on the contrary, puts a person at even greater risk.

There are also questions about why the leader of the experiment officially notified the scientific community in China after the start of clinical trials.

It is not entirely clear whether the participants of the experience fully understand its purpose, potential risks and benefits. For example, the consent documents for the trial refer to the experiment as the "AIDS Vaccine Development Program."

This type of gene modification outside of clinical laboratories is banned in Russia, the United States and a number of other countries because they can cause unforeseen DNA changes in future generations.

Scholars are divided. Someone considers the risk justified, and human experiments ethical, but many have recognized such tests as immoral. The experience was called unscrupulous, premature.

However, renowned geneticist George Chech of Harvard University has come out in support of such research, as he sees HIV as a serious and growing threat to society. The head of the ethics group also spoke in defense of the compatriot. He stated, "We think it's ethical."

Pre-Experiment Research

In recent years, scientists have discovered a relatively simple way to correct genes. The substance, called CRISPR-cas9, allows you to influence DNA to make the necessary gene work or suppress the one that causes problems.

This method has only recently been tested on adults in an attempt to cure deadly diseases. Changes in this case are limited, only one person is exposed to them. Experiments on eggs and sperm are prohibited in almost all countries, as they can provoke hereditary mutations.

Responsibility of scientists and awareness of parents

He Jiankui is confident that he made clear to the participants of the experiment the purpose of the study and advised that changing the genes of embryos has never been tested before and carries potential risks.

The scientist promised to provide insurance coverage for all children conceived as part of the project, and plans medical supervision until they are 18 years old, and, subject to consent, beyond. Part of the contract was free infertility treatment for the women involved in the experiment.

Further attempts at such fertilization are suspended until the safety of the process can be analyzed and confirmed.