Biotechclub–2017
Human genome: edit or not edit?
Anastasia Subbotina, "Science and Life"
On October 13, the first scientific conference "Biotechclub–2017" was held at the I.M. Sechenov First Moscow State Medical University (MGMU). The main topics of discussion were personalized medicine, cancer control, immunotherapy and gene therapy, as well as bioinformatics and computational methods in the medicine of the future.
It was repeatedly said at the conference that the academic community cannot generate a commercial product, that pharmaceutical companies should cooperate with scientists, help them, including with patenting, which is traditionally not easy in the Russian Federation.
Sergey Lukyanov, Rector of the Pirogov Russian National Research Medical University (RNIMU), Academician of the Russian Academy of Sciences, spoke about the achievements of Russian researchers in the field of regenerative medicine. The N.I. Pirogov Russian National Research Medical University has developed a new method of treating diabetes mellitus – with the help of salivary gland cells, which themselves are capable of producing insulin. After some manipulations and corrections in biochemistry, they are transplanted to rats instead of dead pancreatic cells, and in animals sugar metabolism returns to normal. Now, during such operations, the dead cells are replaced by others taken from another organism – the recipient's own immunity is trying to kill them. If you use salivary gland cells, they can be taken from the patient himself.
Another development of the N.I. Pirogov RNIMU appeared in cooperation with the Institute of Bioorganic Chemistry (IBH) It is also associated with the treatment of autoimmune diseases. Usually, blood is taken from a patient with an autoimmune disorder, subjected to chemotherapy and returned to the body. After such a procedure, T-lymphocyte clones that act against the tissues of their own body cannot reproduce effectively, and the disease "falls asleep". However, this is not forever – after about four years, a relapse occurs, so the patient is forced to undergo a harmful procedure again. Researchers from the Pirogov RNIMU and IBH have developed a technology in which a malicious clone of T-cells is purposefully destroyed by specially developed antibodies that can be injected directly into the blood, without taking it and returning it.
After the speakers' presentations, interesting discussions took place at the round tables. One of the topics sounded like "The future of genome editing: where are the boundaries of what is allowed?". Most of the participants in the discussion agreed that editing the genes of embryos – what we remember first of all in connection with this topic – is not worth it yet. And it's not even so much ethical issues as methodological expediency: it's not entirely clear why we need to edit something if we can simply carry out genetic screening of embryos - similar to what is being carried out for newborns today – and select initially healthy embryos.
According to Alexander Pavlov, CEO of Parseq Lab, now in Russia newborns are being tested for six diseases with the help of genetic screening, while in other countries the number of screened diseases reaches forty. Pavlov says that if screening were more widespread, not only among newborns, but also among the adult population, many hereditary diseases could be eliminated within two or three generations. People who are carriers of diseases, but in whom it does not manifest itself explicitly (that is, the damaged version of the gene is compensated by its normal copy on another chromosome), with the help of screening, could find out about it in advance, and during the planning of children, already with the help of embryonic screening, they could prevent the birth ofa real sick child with both damaged genes.
On the other hand, is it always worth telling people the results of their genetic test? A person may have a predisposition to a dozen deadly diseases, but none of them will appear – "predisposition" does not mean "100 percent probability". Nevertheless, a person will have to live with this knowledge all his life, and some people would prefer ignorance to knowledge here.
If we talk about editing the genome of embryos for other purposes – not to control health, but, for example, to change the indicators of physical development (to get people capable of becoming outstanding athletes or "ideal soldiers"), then we are not ready for this yet. Even if today we can create a person, for example, with well-developed muscles, his cardiovascular system will remain the same as other organ systems, and in general we will have a sick person in front of us. Finally, the very idea of creating "superhumans" smacks of eugenics and inevitably raises complex ethical questions.
And we still don't understand well enough what exactly we are editing. How close will the editing result be to what we want to get ideally? To what extent will our intervention affect other processes in which we did not want to interfere? The relationship between genotype and phenotype (appearance, physiology, etc.) is very complex: most traits are controlled by several genes at the same time, and the formation of traits depends not only on genes, but also on environmental conditions.
According to Pavlov, the too complex relationship of the phenotype with genes was the reason that in the Czech Republic even abandoned the screening program for newborns for cystic fibrosis – a severe hereditary disease in which all organs that secrete mucus (bronchopulmonary system, intestines, glands) are affected. Screening revealed a huge number of genotypes with changes of dubious clinical significance – which, however, could or could not lead to the disease, the disease itself could occur in severe or mild form, and so on. The program was closed a year after its launch.
Another example is given by Oleg Glotov, a leading researcher at the Department of Genetics and Biotechnology of St. Petersburg State University (St. Petersburg State University), senior researcher at the Laboratory of Prenatal Diagnostics of the D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology (NIIAGiR) of the Northwestern Branch of the Russian Academy of Medical Sciences. He and his colleagues wanted to find out if it was possible to predict cholesterol levels using genetic analysis. It turned out that it was quite difficult to do this. (However, an interesting point was that cholesterol levels correlated most strongly with genetic data in older people – women after menopause.)
By virtue of all the above, gene therapy, when a patient is treated by introducing genetic elements into his cells that restore or suppress the functions of certain genes, works only in the case of well-studied diseases. However, according to practitioners who are ready to fight even the most dangerous side effects of some genetic drugs, we really need gene therapy – if only patients had a chance. Panelist Mikhail Maschan, Head of the Hematopoietic Stem Cell Transplantation Department No. 1 from the Center for Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, said that about 1,000 Russian children with blood cancer die every year simply because we do not have a suitable treatment for them today.
The introduction of gene therapy is also complicated by the fact that society is afraid of what it is not used to and what it does not understand. For example, many people are frightened by the fact that viruses are used to deliver drugs to cells. Of course, these are not the pathogenic viruses that infect the flu or something more dangerous. But such subtleties are not known to everyone – Mikhail Maschan told how a cargo with purchases for their laboratory was detained at the border, because the word "lentiviruses" was written on the container (they are the most popular method of delivering genetic "parcels" to the cells of the body).
An online survey of people from the audience on the subject of whether they consider genome editing to be a blessing or a "cat in a bag", nevertheless gave a bias towards the "good": thirty votes against seventeen. But more specific questions caused more confusion. The moderator of the discussion, Alexander Karabelsky, director of the Department of Advanced Research at BIOCAD, asked the audience: "If you were offered to edit the genome so that you could live up to 120 years, but at the same time you would be told that you would definitely have Alzheimer's, would you change your life expectancy?" Some raise their hands. "And if we talk about changing appearance?" "And intelligence?" No one dares to raise their hands, but they smile mysteriously. One of the participants in the discussion notes that eye drops have already been invented that change the color of the iris at the gene level, but no one needed such a technology, after all, developments aimed at specific medical tasks enjoy the greatest attention (and funding).
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