Modern Prometheus
How Chinese scientist He Jiankui created the twins of the future
Alpina Publisher is publishing a book by Swedish scientific journalist Torill Kornfelt, which tells about the rapid development of genetic technologies taking place right now, about the potential consequences of these processes and new ethical dilemmas that humanity will inevitably face.
Forbes Life publishes an excerpt telling the story of the appearance of the world's first genetically modified people — Chinese twins Lulu and Nana.
November 2018, scientific conference in Hong Kong. He Jiankui is clearly nervous going up on stage. The audience is making an excited noise. The presenter has just asked the audience to "not interrupt the speaker" and "remember that we are gathered here, in fact, to hear what he has to say" — a very unusual call for a meeting of scientists.
The host, an outstanding geneticist, explains that when He Jiankui applied for participation in the conference a few months ago, the organizers did not know what he would talk about. He Jiankui is obviously proud of his own achievements, it is noticeable to everyone present.
"If it were about my children and I myself would be in the same situation, I would also try," he answers one of the questions after the report.
In 2018, on Halloween eve, 200 years after the publication of the novel "Frankenstein", Trinity College in Ireland arranges a reading of the novel. At about the same time that Mary Shelley's text sounds in the walls of the old university, twin girls Lulu and Nana, the first genetically modified people on earth, are born. Scientists have worked with the genome of human embryos before, but in this case, a particular gene was consciously edited for the first time.
He Jiankui took eggs and spermatozoa from a couple who wanted to have children and performed routine in vitro fertilization. But before the fertilized egg began to divide, the scientist used CRISPR-Cas9 genetic scissors to edit one specific gene.
This gene is called CCR5 and is responsible for an extremely small part of the immune defense. Small changes, mutations of genes are sometimes characteristic of any genome, and the child inherits a new mutated variant from his parents. As a result, different people get different gene variants depending on what they accidentally got from their father and mother. Most often, 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 option is quite common in Europe — about 10% of the total number of Europeans received the desired gene variant from one of their parents. But in order for the protection to work, you need to inherit the gene from both mother and father, and the percentage of such cases is very small.
Since people began to become infected with HIV only in the XX century, the CCR5 mutation supposedly protects not only from this virus. According to a number of hypotheses, it was she who in the course of history protected a person from other diseases, for example bubonic plague or smallpox. At the same time, a number of studies suggest that carriers of this mutation are at greater risk of contracting some other diseases, such as West Nile fever or influenza. That is, the mutation reduces the risk of contracting HIV, but otherwise scientists still do not have an accurate and complete understanding of its effect on the body.
Humans have been engaged in genetic modification of animals for about two decades, but almost all researchers unanimously believed that it was impossible to invade a human embryo, which should become a child. In order to understand the revolutionary significance of this particular genetic technology, it is necessary to realize the fundamental principle: cells are different.
The human body consists of more than 37 trillion cells: from special receptors in the eyes that catch light, and to the muscles of the rectum that are responsible for ensuring that the food we eat is where it should be. In this case, the use of genetic technologies is important to divide into two types of cells — somatic and embryonic. Almost all cells are somatic. The word comes from the Greek σώμα, which means "body". These are our own cells, our children will not inherit the cells of our nose or heart. This means that when using genetic technologies to treat tumors, blindness or liver diseases, only the patient himself is at risk. Such a risk can be great, and it should be compared with the risk from the disease that we are trying to cure. That's how Jesse Gelsinger died, it was a tragic but special case.
Serious existential questions arise when a person intends, like He Jiankui, to change the germ cells (egg and sperm) or embryonic cells, that is, the very first cells formed after the egg took the sperm and began to divide. There are great opportunities for intervention and genome modification hidden here. A person can be saved from a terrible hereditary disease or, say, guarantee a reduction in the risk of heart attack or Alzheimer's disease. But the change in embryonic cells has two serious consequences. Firstly, the genetic change will affect all the cells of the organism that will grow out of the embryo. The change made by He Jiankui, Lulu and Nana will carry through their entire lives — from birth, through adolescence, maturity and menopause to old age.
In addition, the edited genes will be passed on to the next generation. A genetically modified girl who grows up and becomes a grandmother can pass the modified gene to her grandchildren, and they, in turn, to their grandchildren. Here lies both an opportunity and a risk for the future of all mankind. That is why, when He Jiankui announced the birth of the girls, the audience was noisy and cameras were clicking.
He Jiankui contacted an organization that supports HIV-infected people in China and asked to find a couple who wants to have children, while the father must be HIV-positive, and the mother is not. The aim of the experiment was to provide the child with protection from accidental infection from the father throughout his life and to get rid of discrimination and stigmatization that HIV-infected people in China are often exposed to. That is why the scientist was deliberately looking for a father who himself had experienced discrimination because of his diagnosis. In order for the child not to get the disease from the father, usually the sperm is cleaned, viruses are removed. So did He Jiankui.
Initially, three couples decided to experiment, but later one of them refused to participate. The parents could choose between a modified embryo, in which He Jiankui would try to edit the CCR gene, and an ordinary embryo. Both couples preferred modification. At the time of He Jiankui's report, another woman was pregnant with a genetically modified baby, who was presumably born in 2019. I will come back to the question of why the fate of this child remains unknown.
When He Jiankui demonstrated the results of his work, it became obvious that he could not get the CCR5 variant, which is believed to protect against HIV, strictly. Instead, he created new mutations that may or may not have had the same effect. In one of the girls, everything went as planned, and all her cells received a new version of the gene.
The second girl had something that scientists often encounter with genetic modification of animals: not all cells have changed. Perhaps this happened because at the time of modification, the cells had already begun to divide. This means that the girl's body is now a mosaic of modified and unmodified cells. It is not known whether this will protect her from HIV and whether it will give any other effects. He Jiankui was criticized for not interrupting his work when he realized that the mutation was different from the studied variant and not all cells had changed. In addition, there are concerns that the CRISPR scissors also worked in other places at the same time and made other changes in the girls' organisms. It is extremely difficult to detect small changes in the genome. He Jiankui claims that he was looking for such non-directional changes, but did not find anything, although there can be no complete certainty here. At the moment, there are no international laws that would prohibit scientists or states from carrying out genetic modification of the fetus. The Convention on the Protection of Human Rights and Dignity in Connection with the Application of the Achievements of Biology and Medicine, adopted 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 convention because of too strict restrictions, while Germany did not sign the document, considering that it gives too much freedom of action.
Thus, there are different points of view on genetic modification, and the attitude to the issue is determined by the legislation of each specific country. Nevertheless, in 2015, a group of the world's leading geneticists proposed a kind of gentleman's agreement. Scientists have agreed to carry out genetic modification of embryos only for research purposes, for a better understanding of the features of diseases and embryonic development. In other words, genetic modification is possible only for those embryos that will not become children. The researchers concluded that all attempts to genetically modify children are irresponsible, since all safety problems have not yet been solved, such experiments have not received widespread social approval, and the process cannot develop openly with the participation of the entire scientific community. The goals set were somewhat idealized, but sound. No interference at this stage!
In fairness, it should be noted that the main areas of activity were determined at a meeting of scientists at the end of 2015 in some haste. Genetics was still very young. Of course, everyone understood from the very beginning that a new scientific toolkit had appeared that could also be used to work with human embryos, but most experts believed that in practice this would take time. The reason was partly legislation, and partly — which is also important — the fact that science is developing in leaps and bounds.
However, this time everything happened with lightning speed. Immediately after the publication of the first materials on the effect of CRISPR genetic scissors in 2012, Chinese scientists began experiments with the genetic modification of human embryos. The first scientific article, which spoke about the fundamental possibility of genetic modification, appeared in the spring of 2015. It told about the attempts of Chinese scientists to edit the gene, a variant of which causes thalassemia — a hereditary blood disease common in Southeast Asia and the Mediterranean region. The results of the experiment impressed and caused concern, as a result of which a meeting was held in the same year, at which the main areas of activity were determined. The number of scientific articles published since then on modified human embryos is very small. But after some time, a number of countries, including the United States, Great Britain and Sweden, for scientific purposes and to understand the problems, begin to conduct experiments with editing embryos using the CRISPR method. The main results come, however, from China, where with the help of improved technology it is possible to solve some problems, but still of a purely scientific nature: there are no children yet. Not yet.
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