Modern Prometheus: how Chinese scientist He Jiankui created the twins of the future

November 2018, scientific conference in Hong Kong. He Jiankui is clearly on his way to the stage. The audience growls excitedly. The host just asked the audience “not to interrupt the speaker” and “remember that we are here, in fact, to hear what he has to say”, a very unusual call for a gathering of scientists.

The host, a distinguished geneticist, explains that when He Jiankui applied for the conference a few months ago, the organizers did not know what he was going to talk about. He Jiankui is clearly proud of his achievements, this is felt by all present.

“If it was about my children and I myself would be in the same situation, I would try too”, he answers one of the questions after the report.

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Halloween 2018, 200 years after Frankenstein’s publication, Trinity College Ireland hosts a reading of the novel. Around the same time, Mary Shelley’s text is heard on the walls of the old university, the twin girls Lulu and Nana are born, the first genetically modified humans on earth. Scientists have worked on the genome of human embryos in the past, but in this case, for the first time, a specific gene was consciously processed.

He Jiankui took eggs and sperm from a couple who wanted to have children and did conventional IVF. But before the fertilized egg could be divided, the scientist used the CRISPR-Cas9 genetic scissor to process a specific gene.

This gene is called CCR5 and is responsible for a very small part of the immune system. Small changes, gene mutations are sometimes characteristic of any genome and a child inherits a new mutated version from their parents. As a result, different people receive different gene variants, depending on what they accidentally inherited from their father and mother. Most of the time, such small mutations do not play a special role and the gene works properly. Sometimes a mutation causes a problem and a disease. And in rare cases, it can cause positive changes.

In some people, the CCR5 gene mutation acts as a defense against HIV. This variant is quite common in Europe – about 10% of all Europeans received the desired gene variant from one parent. But for protection to work, you have to inherit the gene from both mother and father, and the percentage of such cases is very small.

Because humans only became infected with HIV in the 20th century, the CCR5 mutation is thought to protect against more of the virus. According to some hypotheses, she was the one who, throughout history, protected a person from other diseases, for example, groin disease or smallpox. At the same time, a number of studies suggest that carriers of this mutation are at greater risk of contracting certain other diseases, such as West Nile fever or influenza. That is, the mutation reduces the risk of HIV infection, but otherwise, scientists do not yet have an accurate and complete picture of its effect on the body.

Humans have been genetically modified animals for about two decades, but almost all researchers unanimously believed that it was impossible to invade a human fetus that was to become a child. To understand the revolutionary importance of this particular genetic technology, it is necessary to understand the fundamental principle: cells are different.

The human body is made up of more than 37 trillion cells, from special receptors in the eyes that catch light to muscles in the rectum that are responsible for ensuring that the food we eat is where it should be. In this case, the use of genetic technology is important for separation into two cell types – somatic and embryonic. Almost all cells are somatic. The word comes from the Greek body, which means “body”. These are our cells, our children will not inherit the cells of our nose or heart. This means that when genetic technologies are used to treat a tumor, blindness or liver disease, only the patient is at risk. This risk can be great and must be balanced with the risk of the disease we are trying to cure. This is how Jesse Gelsinger died, it was a tragic but special case.
Serious existential questions arise when a person, such as He Jiankui, intends to change the sex cells (egg and sperm) or embryonic cells, ie the first cells that form after the egg receives the sperm and begins to divide. There are great opportunities for intervention and modification of the genome. A person can be saved from a terrible inherited disease or, say, guaranteed to reduce the risk of heart attack or Alzheimer’s disease. But the change in embryonic cells has two serious consequences. First, the genetic change will affect all the cells in the body that grow outside the fetus. The change brought by He Jiankui will carry Lulu and Nana throughout their lives – from birth to adolescence, maturity and menopause to old age.

In addition, the processed genes will be passed on to the next generation. A genetically modified girl who grows up to become a grandmother can pass on the modified gene to her grandchildren, who in turn can pass it on to their grandchildren. There is both opportunity and danger for the future of all humanity. That’s why when He Jiankui announced the birth of the girls, the audience was noisy and the cameras clicked.

He Jiankui contacted an HIV support organization in China and asked for a couple who wanted to have children, with the father being HIV-positive and the mother not. The aim of the experiment was to provide the child with lifelong protection from accidental infection by the father and to avoid the discrimination and stigma often experienced by people infected with HIV in China. This is why the scientist deliberately searched for a father who himself was discriminated against because of his diagnosis. In order for the child not to get the disease from the father, the sperm is usually cleaned, the viruses are removed. So is He Jiankui.

Initially, three couples decided to experiment, but later one of them refused to participate. Parents could choose between a modified embryo in which He Jiankui would attempt to process the CCR gene or a normal embryo. Both couples preferred the modification. At the time of He Jiankui’s report, another woman was pregnant with a genetically modified child, who was supposedly born in 2019. I will return to the question of why this child’s fate remains unknown.

When He Jiankui showed the results of his work, it became clear that he had not been able to obtain exactly the CCR5 variant that is believed to protect against HIV. Instead, it created new mutations that may or may not have the same effect. In one of the girls, everything went as planned and all of her cells received a new version of the gene.

In the second girl, something happened that scientists often encounter when they genetically modify animals: not all cells have changed. Perhaps this was because at the time of the modification, the cells had already begun to divide. This means that the girl’s body is now a mosaic of modified and non-modified cells. It is not known if this will protect her from HIV or have other side effects. He Jiankui was criticized for not stopping his work when he realized that the mutation was different from the variant studied and that not all cells had changed. In addition, there are fears that the CRISPR scissors worked in other places at the same time and introduced other changes in the girls body. It is extremely difficult to detect small changes in the genome. He Jiankui claims that he was looking for such misguided changes, but found nothing, although there can be no absolute certainty here. At present, there are no international laws prohibiting scientists or states from genetically modifying the fetus. The Convention for the Protection of Human Rights and Dignity in relation to the Application of Biology and Medicine, approved in Oviedo (Spain) in 1997 and signed by more than 30 countries, restricts the artificial modification of the human genome. At the same time, some countries, including the United Kingdom, refused to sign the treaty due to very strict restrictions – while Germany did not sign the document, believing it gave too much leeway.

Thus, there are different views on genetic modification and the attitude towards the issue is determined by the legislation of each specific country. However, in 2015, a group of top geneticists in the world proposed a kind of gentlemen agreement. The scientists agreed to carry out genetic modification of embryos only for research purposes, in order to better understand the characteristics of diseases and embryonic development. In other words, genetic modification is only possible for those embryos that do not become children. The researchers concluded that all attempts at genetic modification of children are irresponsible, as all safety issues have not yet been resolved, there has been no widespread social approval of such experiments and the process can not be developed openly with the involvement of the entire scientific community. The goals set were somewhat idealized, but healthy. At this stage, no intervention!

To be fair, it should be noted that the main areas of activity were identified at a meeting of scientists in late 2015 with some haste. Genetics was still very new. Of course, everyone understood from the beginning that there was a new scientific toolkit that could be applied to working with human embryos, but most experts believed that in practice this would take time. The reason was partly due to the legislation and partly – which is also important – to the fact that science is developing spasmodically.

However, this time it all happened at lightning speed. Immediately after the publication of the first materials on the action of the CRISPR genetic scissors in 2012, Chinese scientists began experiments with the genetic modification of human embryos. The first scientific paper on the potential for genetic modification appeared in the spring of 2015. It described Chinese scientists’ efforts to develop a gene that causes thalassemia, a inherited blood disease common in Southeast Asia and beyond. Mediterranean. The results of the experiment were impressive and caused concern, as a result of which a meeting took place in the same year, in which the main directions of activity were determined. The number of scientific articles published since then on modified human embryos is very small. But after a while, some countries, including the United States, Great Britain and Sweden, for scientific purposes and to understand the problems, start conducting embryo processing experiments using the CRISPR method. The main results, however, come from China, where improved technology can solve some problems, but it is still purely scientific: there are no children yet. Not yet.

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