Designing people: GMO generation

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

Many of us are born with qualities that help to better compete in society: beauty, intelligence, spectacular appearance or physical strength. Due to the advances in genetics, it begins to seem that soon we will be able to access something that was previously not subject to - to "design" people even before they were born. To ask the necessary qualities, if they are not given by nature, predetermining the opportunities so necessary in life. We do this with cars and other inanimate objects, but now that the human genome has been decoded and we are already learning to edit it, it seems that we are getting closer to the emergence of so-called "designer", "projected" children. Does it seem that way or will it soon become reality?

Lulu and Nana from Pandora's Box

The birth of the first children with a modified genome at the end of 2019 caused a serious resonance in the scientific community and among the public. He Jiankui, a biologist at the Southern University of Science and Technology, China (SUSTech) - On November 19, 2018, on the eve of the second International Summit on Human Genome Editing in Hong Kong, in an interview with the Associated Press, announced the birth of the first ever children with an edited genome.

The twin girls were born in China. Their names, as well as the names of their parents, were not disclosed: the first “GMO-children” on the planet are known as Lulu and Nana. According to the scientist, the girls are healthy, and interference with their genome has made the twins immune to HIV.

The event, which may seem like a new step in the development of mankind, or at least medicine, as already mentioned, did not cause positive emotions among the scientist's colleagues. On the contrary, he was condemned. Government agencies in China began an investigation, and all experiments with the human genome in the country were temporarily banned.

He Jiankui / ©apnews.com/Mark Schiefelbein

The experiment, not appreciated by the public, was as follows. The scientist took sperm and eggs from the future parents, carried out in vitro fertilization with them, he edited the genomes of the resulting embryos using the CRISPR / Cas9 method. After the embryos were implanted into the lining of the woman's uterus, the girls' future mother was not infected with HIV, unlike the father, who was a carrier of the virus.

The CCR5 gene, which encodes a membrane protein used by the human immunodeficiency virus to enter cells, has undergone editing. If it is modified, a person with such an artificial mutation will be resistant to infection with the virus.

Lulu and Nana / © burcualem.com

The mutation that He Jiankui tried to create artificially is called CCR5 Δ32: it is found in nature, but only in a few people, and has long attracted the attention of scientists. Experiments on mice in 2016 showed that CCR5 Δ32 affects hippocampal function, significantly improving memory. Its carriers are not only immune to HIV, but also recover faster after a stroke or traumatic brain injury, have better memory and learning abilities than “ordinary” people.

True, so far no scientist can guarantee that CCR5 Δ32 does not carry any unknown risks and that such manipulations with the CCR5 gene will not cause negative consequences for the carrier of the mutation. Now the only negative consequence of such a mutation is known: the organism of its owners is more susceptible to West Nile fever, but this disease is quite rare.

Meanwhile, the university where the Chinese scientist worked has disowned its employee. The alma mater said that they did not know about He Jiankui's experiments, which they called a gross violation of ethical principles and scientific practice, and he was engaged in them outside the walls of the institution.

It should be noted that the project itself did not receive independent confirmation and did not pass peer review, and its results were not published in scientific journals. All we have are just the statements of a scientist.

He Jiankui's work violated the international moratorium on such experiments. The ban is established at the legislative level in almost all countries. Colleagues of the geneticist agree that the use of CRISPR / Cas9 genomic editing technology in humans carries enormous risks.

But the key point of criticism is that the work of the Chinese geneticist has nothing innovative: no one has undertaken such experiments before because of fear of unpredictable consequences, because we do not know what problems modified genes can create for their carriers and descendants.

As the British geneticist Maryam Khosravi said on her Twitter account: "If we can do something, it does not mean that we have to do it."

By the way, in October 2018, even before the shocking statement of the Chinese scientist, Russian geneticists from the National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Kulakov also announced the successful change of the CCR5 gene using the CRISPR / Cas9 genomic editor and obtaining embryos that are not subject to the effects of HIV. Naturally, they were destroyed, so that it did not come to the birth of children.

40 years before

Fast forward four decades. In July 1978, Louise Brown was born in Great Britain - the first child born as a result of in vitro fertilization. Then her birth caused a lot of noise and indignation, and went to the parents of the "test-tube baby", and the scientists, who were nicknamed "doctors of Frankenstein."

Louise Brown. In childhood and now / © dailymail.co.uk

But if that success frightened some, it gave others hope. So, today on the planet there are more than eight million people who owe their birth to the IVF method, and many of the prejudices that were popular then have been dispelled.

However, there was one more concern: since the IVF method assumes that a “ready” human embryo is placed in the uterus, it may be genetically modified before implantation. As we can see, after a few decades, this is exactly what happened.

IVF procedure / © freepik.com

So can a parallel be drawn between the two events - the birth of Louise Brown and the Chinese twins Lula and Nana? Is it worth arguing that Pandora's box is open and very soon it will be possible to "order" a child created according to a project, that is, a designer one. And most importantly, will the attitude of society towards such children change, as it has practically changed towards children "from a test tube" today?

Embryo selection or genetic modification?

However, genome editing is not the only thing that brings us closer to a future where children will have pre-planned qualities. Lulu and Nana owe their birth not only to CRISPR / Cas9 gene editing technologies and IVF, but also to preimplantation genetic diagnosis of embryos (PGD). During his experiment, He Jiankui used PGD of edited embryos to detect chimerism and off-target errors.

And if editing human embryos is prohibited, then preimplantation genetic diagnostics, which consists in sequencing the genome of embryos for some hereditary genetic diseases, and the subsequent selection of healthy embryos, is not. PGD is a kind of alternative to prenatal diagnostics, only without the need to terminate pregnancy if genetic abnormalities are found.

Experts point out that the first "legitimate" designer children will be obtained precisely through the selection of embryos, and not as a result of genetic manipulation.

During PGD, embryos obtained by in vitro fertilization are subjected to genetic screening. The procedure involves removing cells from embryos at a very early stage of development and "reading" their genomes. All or part of the DNA is read to determine which variants of genes it carries. After that, the parents-to-be will be able to choose which embryos to implant in the hope of pregnancy.

Preimplantation Genetic Diagnosis (PGD) / ©vmede.org

Preimplantation genetic diagnosis is already being used by couples who believe they carry genes for certain inherited diseases to identify embryos that do not have those genes. In the USA, such testing is used in about 5% of IVF cases. It is usually performed on three to five day old embryos. Such tests can detect genes that carry about 250 diseases, including thalassemia, early Alzheimer's disease and cystic fibrosis.

Only today, PGD is not very attractive as a technology for designing children. The procedure for obtaining eggs is unpleasant, carries risks and does not provide the required number of cells for selection. But everything will change as soon as it becomes possible to obtain more eggs for fertilization (for example, from skin cells), and at the same time, the speed and price of genome sequencing will increase.

Bioethicist Henry Greeley of Stanford University in California states, "Almost everything you can do with gene editing, you can do with embryo selection."

Is DNA Destiny?

According to experts, in the coming decades in developed countries, progress in technologies for reading the genetic code recorded in our chromosomes will give more and more people the opportunity to sequence their genes. But using genetic data to predict what kind of person an embryo will become is trickier than it sounds.

Research into the genetic basis of human health is certainly important. Still, geneticists have done little to dispel simplistic ideas about how genes affect us.

Many people believe that there is a direct and unambiguous connection between their genes and traits. The idea of the existence of genes directly responsible for intelligence, homosexuality, or, for example, musical abilities, is widespread. But even using the example of the aforementioned CCR5 gene, a change in which affects the functioning of the brain, we saw that everything is not so simple.

There are many - mostly rare - genetic diseases that can be accurately recognized by a specific gene mutation. As a rule, there really is a direct connection between such a gene breakdown and the disease.

The most common diseases or medical predispositions - diabetes, heart disease, or certain types of cancer - are associated with several or even many genes and cannot be predicted with any certainty. In addition, they depend on many environmental factors - for example, on a person's diet.

But when it comes to more complex things like personality and intelligence, here we don't know much about which genes are involved. However, scientists do not lose their positive attitude. As the number of people whose genomes have been sequenced increases, we will be able to learn more about this area.

Meanwhile, Euan Birney, director of the European Bioinformatics Institute in Cambridge, hinting that decoding the genome will not answer all questions, notes: "We must get away from the idea that your DNA is your destiny."

Conductor and orchestra

However, this is not all. For our intelligence, character, physique and appearance, not only genes are responsible, but also epigens - specific tags that determine the activity of genes, but do not affect the primary structure of DNA.

If the genome is a set of genes in our body, then the epigenome is a set of tags that determine the activity of genes, a kind of regulatory layer located, as it were, on top of the genome. In response to external factors, he commands which genes should work and which should sleep. The epigenome is the conductor, the genome is the orchestra, in which each musician has his own part.

Such commands do not affect DNA sequences; they simply turn on (express) some genes and turn off (repress) others. Thus, not all genes that are on our chromosomes work. The manifestation of one or another phenotypic trait, the ability to interact with the environment, and even the rate of aging depend on which gene is blocked or unblocked.

The most famous and, as it is believed, the most important epigenetic mechanism is DNA methylation, the addition of CH3-group by DNA enzymes - methyltransferases to cytosine - one of the four nitrogenous bases in DNA.

Epigenome / ©celgene.com

When a methyl group is attached to the cytosine, which is part of a particular gene, the gene is turned off. But, surprisingly, in such a "dormant" state, the gene is passed on to the offspring. Such a transfer of characters acquired by living things during life is called epigenetic inheritance, which persists for several generations.

Epigenetics - the science called the little sister of genetics - studies how turning genes on and off affects our phenotypic traits. According to many experts, it is in the development of epigenetics that the future success of the technology for creating designer children lies.

By adding or removing epigenetic "tags", we can, without affecting the DNA sequence, fight both diseases that have arisen under the influence of unfavorable factors, and expand the "catalog" of the planned child's design characteristics.

Is the Gattaki scenario and other fears real?

Many fear that from editing the genome - in order to avoid serious genetic diseases - we will move on to improving people, and there it is not far before the emergence of a superman or the ramification of humanity into biological castes, as predicted by Yuval Noah Harari.

Bioethicist Ronald Greene of Dartmouth College in New Hampshire believes technological advances can make "human design" more accessible. In the next 40-50 years, he says, “we will see the use of gene editing and reproductive technologies to improve humans; we will be able to choose the color of eyes and hair for our child, we want improved athletic ability, reading or numeracy skills, and so on."

However, the emergence of designer children is fraught with not only unpredictable medical consequences, but also deepening social inequality.

As bioethical scientist Henry Greeley points out, a 10-20% achievable health improvement through PGD, in addition to the benefits that wealth already brings, could lead to a widening gap in the health status of rich and poor - both in society and between countries.

And now, in the imagination, terrible images of a genetic elite, such as those depicted in the dystopian thriller Gattaca, arise: the progress of technology has led to the fact that eugenics has ceased to be considered a violation of moral and ethical norms, and the production of ideal people is put on stream. In this world, humanity is divided into two social classes - "valid" and "in-valid". The former, as a rule, are the result of the parents' visit to the doctor, and the latter are the result of natural fertilization. All doors are open to “good”, and “unfit”, as a rule, are overboard.

Still from the film "Gattaca" (1997, USA)

Let's return to our reality. We noted that it is not yet possible to predict the consequences of interference with the DNA sequence: genetics does not provide answers to many questions, and epigenetics is actually at an early stage of development. Each experiment with the birth of children with a modified genome is a significant risk that in the long term can turn into a problem for such children, their descendants and, possibly, the entire human species.

But the progress of technology in this area, having saved us, probably from some problems, will add new ones. The emergence of designer children, perfect in all respects, who, having matured, will become members of society, can create a serious problem in the form of deepening social inequality already at the genetic level.

There is another problem: we did not look at the topic under consideration through the eyes of a child. People sometimes tend to overestimate the capabilities of science, and the temptation to replace the need for painstaking care of their child, his upbringing and study with paying bills in a specialized clinic can be great. What if the designer kid, in whom so much money has been invested and who has so many expectations, falls short of those hopes? If, despite the intelligence programmed in the genes and a spectacular appearance, he does not become what they wanted to do? Genes are not destiny yet.