Aibolites-GMO

Diana Khomyakova, "Science in Siberia"

The GM technologies being persecuted in Russia today not only save humanity from hunger, but also open up prospects for the creation of fundamentally new drugs that can overcome many diseases, even cancer and infertility, and also probably make it possible to transplant animal organs to humans. The human body produces a lot of proteins. All of them are very important for its successful development and functioning, and if some of them begin to be produced in insufficient quantities, the disease develops. Many ailments arise precisely for this reason. The matter is complicated by the fact that human proteins, except from a human, can not be taken anywhere. Our body is a very poor source of this "building material". For example, for one therapeutic dose of hormones for one patient, you need to take blood from about a hundred people. In addition, it is necessary to conduct a thorough check of each donor – none of them should have viruses and infections, so as not to infect the patient. "Genetic engineering helps very well here. Now we can simply take a certain gene from the human genome, transfer it to another organism, and make the latter produce the proteins we need," says Nariman Rashitovich Battulin, PhD, Head of the stem cell Genomics sector of the FIT Institute of Cytology and Genetics SB RAS. – Most often, microorganisms – bacteria and yeast – act as such - they are easier to produce and cheaper. For example, insulin today is almost entirely created in bacteria; in fact, diabetics were saved thanks to the development of transgenic technologies."

In September, Novosibirsk State University launches a video course of lectures "GMOs: technologies of creation and application" on the Coursera educational platform. The lecturers will be Nariman Battulin, Veniamin Fishman and Alexey Menzorov, employees of the FIT Institute of Cytology and Genetics SB RAS.

How GM insulin is produced: scientists take human DNA – there are about 20 thousand genes, among which there is an insulin gene. In order for it to work in bacteria, it is necessary to hang special regulatory elements on this piece, necessary for the adequate functioning of the gene in the new "place of residence". For example, the promoter (the part that "tells" where and when this gene should work; for example, insulin is produced only in the pancreas and only in response to an increase in glucose levels). "That is, you need to take the coding part of insulin, discard all the "human" regulatory parts, replace them with regulatory parts of bacteria, and transfer the resulting fragment, the so–called "transgenic construct", into the DNA of the bacterium," explains the researcher. – This is a very simple procedure, and students can cope with it quite well." It needs to be done once. And then the bacterium will communicate a "new plan of action" to its daughter cells, that is, multiply in the usual way and produce insulin (the same thing happens with transgenic animals that are able to transmit modified genetic information to descendants). However, not all proteins can be made in bacteria – the problem is that we are still very distant relatives with these microorganisms. There are a huge number of modifications going on in our body that are inaccessible to them. Therefore, some GM proteins are produced only in animal cells. Also, human cells are used to create some of them – they can be cultivated in artificial liquid media in special huge tanks, where they multiply and behave, in fact, like single-celled organisms, but with a human genome. However, the nutrient medium required for this method is quite expensive, which significantly increases the cost of medicines. It was very difficult to obtain many hormones necessary for the treatment of certain diseases before the advent of GM technologies. Thus, human growth hormone was once extracted only from human corpses (the gland in which it is contained is located in the brain, in the pituitary gland). Now it is produced recombinantly. Follicle–stimulating hormone is a very important protein that regulates the maturation of follicles in women (it is now actively used in in vitro fertilization, since it is important for superovulation that there are many eggs at once) – it used to be extracted from the urine of women after menopause. Today it is obtained either in cultures or in microorganisms. Transgenic technologies are also used for the production of antibodies. These proteins are good because they can be directed, relatively speaking, to any target. And a lot of hope is associated with their use in anti-cancer therapy. "There is such a concept of a "golden bullet" – an ideal medicine that acts only on a diseased target organ and does not touch anything else. In the case of cancer, there is a problem: the pathogenic agent is the cells of the body themselves, they have the same genome as the rest of the body, so it is very difficult to kill them. There is an idea to make antibodies that would recognize cancer cells by some features and connect only with them, and sew substances to them that kill everything in the world. Then they will destroy only diseased cells with precision," Nariman says. There is a problem here: the cells that produce antibodies are specially "trained" not to recognize the proteins of their own body in order to avoid an immune reaction against their body. Several anti-cancer drugs based on antibodies have already been created. The problem is that for the production of these proteins, immunization is needed (the creation of artificial immunity by infecting the body with a small amount of virus or pathogenic bacteria), and it cannot be carried out with people, because it is unsafe and unethical. For the needs of medicine, animal antibodies are usually used, which are not always accepted by the patient's body, since they can develop immunity. Therefore, there is another direction in transgenesis: to make animals produce human antibodies. "The procedure is complicated, although at the conceptual level the idea is quite simple: to replace those genes that produce antibodies, for example in a mouse, with a human gene. And then inject her with the virus in small quantities so that the animal develops immunity to it. This is called "humanization" – to take and make the mouse more "human," explains the researcher. In addition, transgenic medicine today solves the problem of finding donors for transplanting cells, organs and other tissues. There is such a direction as xenotransplantation – transplantation not from humans, but from animals. And very high hopes are pinned on pigs here. They have about the same size of organs as we do, and according to all other characteristics they are best suited for these purposes (even now scientists say that in the future, not human heart valves, but pig valves will be placed on the cores). However, these animals produce their own proteins on the surface of the cells, which can serve as targets for our antibodies. And the task of genetic engineering is to break down everything that causes rejection in humans, to make sure that this cell surface is not recognized by our immune system. A lot of work is underway on this topic. Today, GM technologies are trying to direct to the production of substances of a non-protein nature, for example, antibiotics. "There is such a difficulty: it is very easy to produce proteins using genetic engineering. Because our whole body is a machine for their production, and genes are instructions for it. If non–protein substances are sugars, fats and the like, there are no genes for them, they are produced by proteins as a result of enzymatic reactions," Nariman says. – For example, fireflies glow because they have a special protein involved in a chemical reaction with another substance. It is called luciferase, and the substance is luciferin. You can make a mouse that will produce luciferase, but it will not glow, because it cannot be forced to produce luciferin. To do this, you will have to stuff a whole complex of proteins into her cells." However, there are already successes in this area: last year an article was published about how yeast was taught to produce opioid alkaloids contained in opium poppy. They are used as a medicine – antitussive, analgesic, and the like, but also to create drugs, which is why the field of poppy cultivation is highly criminalized. The idea arose: to make opioids not in the fields, but directly in production, with the help of yeast. In order to implement this idea, 23 new genes had to be transferred to the yeast genome and a huge number of complex manipulations had to be carried out. However, the experiment was a success. In the next five to ten years, these yeasts will be ready. Another example is related to antimalarial medications. The most recent effective of them – artemisinin – is made from wormwood. However, it grows only in a certain period, and since this disease is spread mainly in poor countries, it is important that the medicine is affordable and cheap. Scientists have created yeast that has been taught to produce substances necessary for the production of artemisinin. "It was not possible to reduce the cost of the technology, but the experience of creating GMOs of a non–protein nature has been gained," the researcher notes. "Today there is a kind of revolution in genetic engineering: new genome editing tools have appeared. The protein, discovered in 2012-2013, allows you to change the sequence of nucleotides in any pre-selected part of the genome of any organism. And now thousands of laboratories around the world have started using this method. Research on genetic engineering has accelerated dramatically," Nariman says. For example, in one of the works on turning pigs into ideal donors (these animals have their viruses in the genome, there is a danger that they will take root in humans and some new epidemic will arise, so it is important to destroy them before transplantation) with the help of this system, 20 viruses were simultaneously destroyed in the animal genome, and thus cleared it of potential dangers. "The proof that humans, animals, plants, and bacteria descended from one common ancestor is that our genetic apparatus for creating proteins, the genetic code, is the same for all living organisms. Instructions alone record the sequence of amino acids both in carrots and in the body of a great white shark. Therefore, if you understand the question, you can find a solution to almost any problem of producing proteins from one organism in another," says Nariman Battulin. Thus, by transporting virus proteins to plants, scientists create plant vaccines based on them (that is, by eating certain foods, a person will gradually acquire immunity against a particular disease).As the researcher notes, genetic modification of animals today has mainly research purposes. There are practically no transgenic food breeds (the exception is American salmon), since breeding is still working better in terms of food animal husbandry. "Animal husbandry has the following tasks: to make the animal as big as possible, eat as little as possible and grow as fast as possible. From the point of view of achieving these goals, traditional methods are more effective," Nariman comments. For example, during the XX century, people actively improved the food breeds of chickens. As a result, the rate of weight gain in this bird has increased four times. This was due to changes in the genome of the organism: it is enriched with various variants of genes that provide rapid growth (plus the cultivation technology has changed). Then they tried to use transgenic technologies – to add growth hormone. However, contrary to expectations, the weight gain of the bird turned out to be quite insignificant. "The fact is that the resources of each organism are limited. You can't create a chicken the size of a cow and grow to such parameters in one day. There is a "biological ceiling" above which you cannot jump," Nariman explains. – It turns out that breeding, which has been going on for several millennia, and in the last 100 years – very intensively, has almost reached this ceiling, and the resources for additional growth in the chicken's body are no longer available. Therefore, it is useless to solve such problems with the help of transgenic technologies."

Almost all the cheese we buy today is made using GMOs. Cows are ordinary, but in order to get this product, a solid substance must precipitate out of the milk. Once upon a time, when milk was still stored in the stomachs of slaughtered animals, people paid attention to an interesting fact: in the stomachs of dairy calves, it quickly folded. It turned out that a special protein is produced there that allows you to digest this product. And therefore, until the 1990s, the production of cheese was specially slaughtered calves no older than ten days old in order to extract these stomachs from them and use them in crumbled form as a starter. And then this protein was transplanted into the genome of yeast and black mold, and today they already produce the necessary component for cheese production.

However, methods of genetic modification still sometimes help animal husbandry. So, the main dairy breeds of cows are horned. They often fight, butt heads, there are injuries, bleeding. To get rid of these problems, their horns are usually cut down on large farms. An idea arose: it would be good to breed a hornless breed (there are such, but they are usually meat). With traditional breeding, it would have been necessary to cross the meat breed with dairy for several hundred years, selecting hornless animals. However, the hybrid will be worse both in meat and dairy terms, and then it will take a very long time to return all those gene variants that provide a high milk content. And with the help of genetic engineering, you can simply take a piece of the genome responsible for "hornlessness" and purposefully introduce it into the dairy breed. And all this is done during the existence of one generation of animals. "It does not mean at all that the development of GMOs will ruin breeding. Breeders cope with their tasks better. They have a more complex approach – they change a huge number of genes at once, and we act pointwise, that is, these are different tasks, and each achieves its goals," the scientist concludes.

Portal "Eternal youth" http://vechnayamolodost.ru  09.09.2016