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Children With Edited DNA: First Details

A year ago, Chinese biophysicist He Jiankui shocked the scientific community with his announcement of the birth of two genetically modified children. 

There were no details about the high-profile experiment. Last week, MIT Technology Review magazine published excerpts from Jiangkui’s work. The publication added the comments of an embryologist, a specialist in genome editing and a lawyer.  

The Fight Against HIV is Just a Cover

On November 28, 2018, in Hong Kong, scientific symposium He Jiankui of Shenzhen University announced the birth of two children whose genome was edited using CRISPR-Cas9 technology. 

The DNA of the twins Lula and Nana was changed in a way to make them immune to HIV infection. He introduced a mutation into the CCR5 gene, which “opens HIV the door to the body’s cells,” which provided them with immunity to the virus that their father was infected with.

The scientist called the birth of two healthy children with altered genes “China’s historic breakthrough in disease prevention.” However, the scientific world didn’t share his enthusiasm.

122 Chinese scientists wrote an open letter in which they condemned their colleagues and asked the government to drastically limit work with human genes.

“A Pandora’s Box is open, but we can still close it before it’s too late. It’s just dishonest to those Chinese researchers who advocate hard work and innovation based on scientific ethics,” — the letter said.

Western scientists have called Jiankui’s work “an unscrupulous experiment on humans,” which cannot be justified either ethically or morally. 

A Failure of the Year

Science called the birth of children with the edited genome a failure of the year because it was “unauthorized and premature”. 

The PRC State Committee on Health and Planned Childbearing has launched an investigation. They said that the biologist’s actions violated the laws of the PRC and he will be punished. He hasn’t appeared on the public since then.

There have been no details about the procedure of the experiment and whether it turned out to be successful. The fate of the twins is also not reported anywhere. It was carried out secretly, and it was impossible to verify the words of the biologist.

Other Scientists` Studies

In February 2019, an international team of scientists published a study on how the gene removal method could influence the brain of children using the CRISPR editor. Their work showed that the absence of the CCR5 gene accelerates recovery from a stroke.

Scientists also found that the absence of at least one copy of CCR5 in the genome improves the level of education in school. This may indicate the connection of this gene with intelligence.

We are talking about people with a natural gene mutation, not acquired. 

On December 3, the Massachusetts Institute of Technology magazine MIT Technology Review published three long articles revealing excerpts from the manuscript sent by He Jiankui to Nature magazine, which declined to publish it.

It states that the experiment did not achieve the goal: only one of the four embryos had changes in both copies of the CCR5 gene, in the second – only in one. This may provide complete resistance to HIV infection, but there is no indication that it is true.

Taking into account the data on umbilical cord blood DNA cells, the umbilical cord itself and the placenta, it turns out that not all of these cells are carriers of the created “He” mutation. 

Well, even in the case of occurred changes in both copies of the gene, not a well-studied CCR5 delta 30 mutations arose in the DNA, but a gene breakdown, making it completely non-functional. How such a mutation can affect the health of a carrier is not yet clear.

In the second case, where the changes affected only one copy of DNA, another unique mutation arose cutting out a shortened gene fragment. He writes that such an embryo should have partial resistance to HIV, but it does not show any experimental evidence. 

— “This suggests that the Lulu and Nana twins come from embryos that are genetically mosaic,” — said Kieran Musunuru, a professor of genetics at the University of Pennsylvania, who wrote an editorial in the MIT Technology Review. 

The problem of genetic mosaicism when editing the genome is that different embryo cells after injection of the CRISPR / Cas9 construct can receive different mutations.

In this case, it is impossible to accurately determine the total number of non-target mutations: to do this, it would be necessary to read the DNA of each cell of the embryo, which means its destruction because the genome needs to be extracted from the cell.

Also, the scientist did not check whether HIV really can’t penetrate the altered cells of Lula and Nana. According to experts, it was not difficult to do this – you need to isolate cells from the blood of twins and conduct a standard experiment with them in the laboratory.

According to experts interviewed by the editors of MIT Technology Review, it is said that the scientist apparently chose HIV for his experiments “only to justify the use of CRISPR technology.”

It is also horrible that the twins` parents did not understand what experiment they were agreeing to. Most likely, they were sure that genome editing is the only way to give birth to their healthy children. 

However, there is already a fairly simple method of washing the seminal fluid with HIV.

Experts believe that a possible motive for participating in this experiment could be to help pay for the in vitro fertilization procedure, which otherwise would not be available to the parents.

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