11 November 2021

20 facts about GMOs

Chickens with teeth, green piglets and gene therapy

Ekaterina Shutova, Alexander Panchin, XX2 century

GMO is a three—letter word that has been terrifying ordinary people for many years. Let's overcome the fear of genetic engineering together? Here are 20 facts that, we hope, will bring many closer to understanding that GMOs are not scary, and sometimes also delicious.

1. The first genetic modification appeared back in 1972. It was created by biochemist Paul Berg — the future Nobel laureate received a recombinant DNA molecule by connecting sections of the genomes of the oncogenic monkey virus SV40 and the bacteriophage lambda E. coli (Escherichia coli). However, Berg was afraid that introducing such a molecule into the cells of living beings might not be safe — and did not conduct experiments in vivo. In addition, the scientist even obliged his subordinates to donate blood for antibodies to SV40.

A year later, in 1973, thanks to biochemist Herbert Boyer and geneticist Stanley Norman Cohen, the first organism containing recombinant DNA appeared — E. coli, carrying the gene of the ribosomal DNA of a frog.

And in 1974, a GM mouse was "born", to which Rudolf Jenisch inserted a retrovirus into the DNA at the stage of embryogenesis.

2. It is believed that the organs of pigs do not take root in humans due to the fact that the cells of the latter produce molecules of sugar foreign to humans and other great apes, known as "alpha-gal" (galactose-alpha-1,3-galactose). But recently, surgeons were still able to transplant a GM pig kidney to a woman with the gene responsible for alpha-gala production disabled. The kidney took root. However, the operation was exploratory: the patient's brain was dead even before the operation began, and the vital activity of the body was maintained with the help of a ventilator.

3. In 2006, scientists introduced viral vectors with a gene encoding the regulatory protein beta-catenin into chick embryos. As a result, the embryos of chickens formed the rudiments of teeth! Thus, scientists have come closer to understanding how birds lost their teeth in the course of evolution.

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The rudiments of teeth in genetically modified chick embryos. Photo by Matthew P. Harris et al., 2006.

4. Unfortunately, there is still a fear of GMOs in society. This fear led to the fact that, for example, in 2011, a group of "greens" penetrated the territory of the Australian scientific center and destroyed all crops of transgenic wheat. And two years later, in the Philippines, anti—fraudsters trampled an experimental field of golden rice - GM rice with an increased content of beta-carotene.

5. In 2016, 107 Nobel Prize laureates signed an open letter: in the letter, scientists called on Greenpeace to stop demonizing GMOs and, in particular, to abandon their attacks on golden rice.

6. According to historical data, man began intentionally modifying organisms 12 thousand years ago. It was then that people began to select the "best samples" of corn, thereby changing its DNA.

But in general, as experience shows, traditional breeding is a less safe way than creating GMOs. For example, in the late 1960s, the Americans brought out the Lenape potato variety. However, it soon became clear that the level of solanine harmful to humans in Lenape was extremely high — consumers began to poison themselves with potatoes, and after a couple of years the product was withdrawn from the market. A similar story happened with Magnum Bonum in 1986 — this potato variety was bred by the Swedes and also with the help of conventional breeding, but it turned out that Magnum Bonum had increased levels of the same solanine and another unsafe glycoalkaloid — hakonin.

7. GMO and non-GMO DNA consists of the same nucleotides.

8. According to a 2014 VTsIOM survey, three quarters of Russians are not averse to paying extra for non-GMO products. The results of foreign surveys are also disappointing: in 2015, it turned out that 82.28% of Americans want GM products to be sold with mandatory labeling. The same American survey showed that 80.44% of US residents are in favor of labeling products "containing DNA".

9. The term "genetic engineering" appeared even before the experiments of Paul Berg — it was invented by the American science fiction writer Jack Williamson, for the first time he used this phrase in the book "Dragon's Island" (Dragon's Island, another name for "Non-people", The Not-Men). The novel, published in 1951, is about a war with a race of mutant humans created through genetic manipulation. Unfortunately, "Dragon Island" has not yet been translated into Russian.

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The cover of a fantasy novel in which the term "genetic engineering" is mentioned for the first time.

By the way, Jack Williamson also coined the term "terraforming".

10. Genetic engineering often appears in game and animated films, fiction, games.

In 1982, Frank Herbert (the one who wrote "Dune") published a novel called "The White Plague" (The White Plague). According to the plot, the main character — a molecular biologist — creates a pathogen that kills exclusively women. Although its carriers can also be men.

In the fictional universe of the gloomy future of Warhammer 40,000, invented in 1987 and popular to this day, which arose around a board game and includes hundreds of works of various genres, all kinds of genetic manipulations are everyday routine.

In science fiction, there is a whole direction that deals with the artistic understanding of various aspects of genetic manipulation — biopunk. Typical examples of the latter are Andrew Niccol's film "Gattaca" and Paul Di Filippo's collection of short stories "Ribofunk".

11. Genetic engineering and its fruits surround us, they are everywhere — for example, almost all the insulin that people with diabetes need is produced with the help of GM microorganisms.

12. Although opponents of genetic engineering regularly talk about the dangers of this technology, GM products are carefully studied and harmless. The fact that GMOs are safe for humans is evidenced by the WHO report, the European Commission report and a number of studies. So, in 2014, scientists analyzed about 1,500 publications about GM organisms and came to the conclusion that GMOs are not worth being afraid of. And in 2016, experts from the USA prepared a report on agricultural GM crops, they studied almost 1000 thematic scientific papers and found out that GM crops are harmless and also bring the best harvest.

13. The US Department of Agriculture does not require manufacturers to specifically label GM plants whose genome has been edited either without the involvement of genetic material from other organisms or with the involvement of genes exclusively from closely related organisms. In Japan, GM crops also do not require special labeling. American and Japanese regulators think something like this: The DNA of the absolute majority of modern food crops has been intentionally altered in many ways, from breeding to mutations caused by radiation and chemical mutagens; and, since all these products do not require special labeling, then there is no need to label products obtained by genetic engineering methods.

14. It's funny, but mandatory labeling of food products made using agricultural GM products can improve the attitude of the population to GMOs. So, in the US state of Vermont (the only one in the USA where labeling of GM products was mandatory for two years, from 2014 to 2016), researchers conducted a survey on attitudes to GMOs twice, before the introduction of labeling and after. It turned out that the number of residents of the state who are negatively related to GM products has decreased by 19 percent during the validity of the local law on mandatory labeling!

By the way, in the same year another team of scientists conducted a survey and found out that the opponents of GMOs are worse than other respondents in science, including genetics.

15. Thanks to genetic engineering, scientists have created green glowing piglets, non-darkening champignons, potatoes with reduced formation of potentially carcinogenic acrylamide during frying, tobacco that can be grown even in the desert, and tomatoes with a high content of GABA.

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Fluorescent green GM piglets.

A small digression about blue roses and tomatoes

In the media and social networks, blue (sometimes blue) roses and purple (sometimes blue or black) tomatoes are often mentioned as typical illustrations of what genetically modified organisms are. However, in reality, everything is not quite as it was written about in the news and continues to be written in blogs.

As for the "blue" rose, they usually write the truth about it, but a lie (or mistake) creeps into the illustrations: notes about this GM plant are invariably accompanied by images of frankly blue roses, but it's always either photoshop, or photos of artificially painted white roses with blue paint, or even pictures of artificial flowers made of paper or plastic.

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Such pictures are usually illustrated with notes about the blue GM rose.

In fact, the "blue" or "blue" GM rose, the fruit of a long joint work of the Australian biotech company Florigene and the Japanese holding Suntory, is not blue. It just so happened.

Yes, the idea was to create a blue rose. To do this, they took the classic garden triploid variety of the Gallic rose "Cardinal de Richelieu" with flowers of a rich purple color and made three genetic modifications on it: the first one added to its genome a gene taken from pansies that produces anthocyanin dye delphinidin, the one that gives blue-blue shades to delphinium, violets, blueberries and much more still, and the other two were supposed to suppress the expression of genes that contribute to the production of other dyes, and allow only delphinidin to manifest. However, firstly, the production of other dyes was not completely suppressed, and secondly, the delphinidin of pansies partially degrades in rose petals due to the high acidity of the latter. As a result, the "blue" GM rose in reality has a light lavender or pale purple color, which is found in abundance among roses of classical breeding (take the famous Mainzer Fastnacht, bred by Rosen Tantau in Germany back in 1964).

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This is what the "blue" rose, developed by the biotech companies Florigene and Suntory, actually looks like.

Work on the "blue" rose went on for thirteen years. In the process, scientists have learned a lot about the genetics of roses and plants in general, and this work is very important, and the "blue" (actually not) rose is not only a visible result, but also a symbol of this work. However, the media crave sensations, and therefore do not want to illustrate the news about the GM rose with photos of flowers of quite ordinary color. Hence all these ultramarine misunderstandings in the photo. I would like to have such roses, but they are not there yet.

The situation is different with blue or anthocyanin tomatoes: they are just there. However, the idea that all tomatoes whose fruits are stained with blue anthocyanin dyes are products of genetic modification is erroneous. Often in social networks you can find arguments that, they say, a few years ago there was news about blue or black-purple GM tomatoes, but they sell seeds of the same, but it says on the package: "Without GMOs." Where is the truth? Everywhere.

In the fruits of wild tomatoes, blue-purple flavonoids anthocyanins were found, but over the centuries of agricultural cultivation, only varieties in which these substances were found only in stems and leaves, and even then rarely, were fixed as cultural. In the XIX and XX centuries, many varieties were bred (good and still in demand today; for example, "Cherokee purple", "Kumato", "Black Prince", "Black Crimea"), which were sometimes called black, purple and even purple and blue, but in fact they were rather brown or red-green and could, with a stretch, give the impression of dirty purple only under certain lighting conditions. All these varieties contained the so-called green pulp gene, which prevents the normal cleavage of chlorophyll in ripening fruits and promotes its transformation into the brown pigment pheophytin. There were no anthocyanins in these fruits. It was possible to call them blue or black only from a great desire to see them as such.

Perhaps the only exception with real anthocyanin in the fruit was the Purple Smudge variety bred in 1963 by Texas A&M University (known in Russia as "Purple smog" or "Blob"). He had yellow-orange fruits with small anthocyanin "blots" in the area of the peduncle.

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Purple Smudge tomato. Photo — World Tomato Society.

Since the middle of the XX century, breeders from different countries have been trying to breed anthocyanin tomatoes. But the team of Jim Myers, a professor of horticulture at the University of Oregon, approached this issue most consistently. They crossed cultivated varieties with wild-growing ones, in the fruits of which anthocyanins were preserved, and then for years they selected the darkest purple fruits for further work. Finally, in 2012, they presented the first real anthocyanin tomato variety — "Indigo Rose", with a black-purple skin due to anthocyanin petunidine. Myers emphasized that the variety was obtained by traditional methods of slection and hybridization and that genetic engineering was not used in its creation. Curiously, the goal of Myers' team was not the actual color of tomatoes, but their saturation with antioxidants, which, in particular, are including anthocyanins.

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Tomatoes of the Indigo Rose variety. Photo — D. Yatsutko, "XX2 century", 2020.

The variety was immediately presented as commercial, seeds began to be sold. And soon successes with varying degrees of purple tomatoes overtook other breeders. So today both "Indigo Rose" and dozens of other anthocyanin varieties of traditional breeding (for example, "Amethyst Jewel", "Black Sun", "Red Coal", "Smurfinka", "Steak Marsha", "Blueberry", "Kryptonite") are ripening in vegetable gardens around the world. And none of them is related to GMOs.

However, when the blue tomatoes of Oregon breeders were growing only on experimental plots and did not bear the beautiful name "Indigo Rose", at the British John Innes Research Center in Norfolk, something from the snapdragon genome was added to the tomato genome, forcing the fruits to produce and accumulate anthocyanins simply in frenzied quantities. As a result, tomatoes turned out to have purple not only the skin, but also the pulp, and the content of anthocyanins is about the same as in blackberries or blueberries and a hundred times more than in anthocyanin tomatoes of traditional selection. By the way, everything was also started for the sake of antioxidants.

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Genetically modified anthocyanin tomato from Norfolk in the section. Photo by Levon Biss for NYT.

Inspired by their scientific success, the creators of the thoroughly anthocyanin GM tomato organized the Norfolk Plant Science company under the wing of the Innes Center - to commercialize the purple tomato. However, although inventors/manufacturers are, as they themselves write, in close contact with regulators of various countries, unfortunately, their GM variety has not yet entered the market. But we are waiting. In the meantime, its creators receive well-deserved awards, other scientists are trying to finish the tomato genome so that there are even more anthocyanins in it (200-400 times), and the world is slowly being conquered by "blue" and "bluish" tomatoes, bred in the usual way. So not every blue tomato is GMO, most are not.

16. The first GM food crop approved for sale was tomato Flavr Savr (can be translated as "storing taste"). Scientists have blocked a protein in tomatoes that "softens" the fruit when it ripens. This allowed GM tomatoes to be stored well and not deteriorate during transportation, although they were collected fully ripened. Delicious, well-stored and having an attractive presentation, Flavr Savr went on sale in 1994 in the USA and at first were in great demand among buyers. In 1996, tomato paste from tomatoes Flavr Savr appeared on sale in the UK. However, alarmist protests, boycotts, threats by courts and speeches in The mass media of public figures opposed to GM products influenced public opinion and consumer demand: in 1997, Flavr Savr ceased to be sold in the USA, in 1999, pasta made from them in the UK.

17. The first GM animal allowed to be eaten was AquAdvantage salmon, developed by AquaBounty Technologies. It grows all year round and gains weight faster than its relatives. How did scientists create AquAdvantage? We took an ordinary Atlantic salmon and added to it a gene responsible for the production of growth hormone in the large Pacific salmon chinook.

Although AquAdvantage was created back in 1989, and scientists and regulators have repeatedly noted that its consumption could not be any more dangerous and in general fundamentally different from the consumption of ordinary Atlantic salmon, its sales in Canada began only in 2016, and in the United States — in May 2021.

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Genetically modified salmon (more) in comparison with the usual Atlantic.

18. In 2019, American scientists grew a miniature model of a human liver based on GM cells. Over time, such experiments may lead to the creation of fully functional bio-artificial organs that can be implanted in humans.

19. Thanks to genetic engineering, there are various methods of gene therapy that help people with various serious diseases. The essence of gene therapy is that various changes are made to the genetic apparatus of patients' somatic cells — for therapeutic purposes. So, in 2016, gene therapy was started in Europe for patients suffering from severe combined immunodeficiency, and soon the FDA approved gene therapy for patients suffering from acute lymphoblastic leukemia. In 2017, doctors edited the genome of an adult for the first time. The patient was a man suffering from Hunter syndrome.

In 2019, scientists from CRISPR Therapeutics and Vertex, who tried to cure patients with hereditary blood diseases using genetically edited cells, claimed two victories. As a result of gene therapy, the patient (with beta-thalassemia) stopped needing blood transfusions, and the other, with sickle cell anemia, stopped suffering from vascular blockage.

Over time, genetic modifications will be used more widely in medicine — scientists are constantly conducting research in search of new promising techniques. For example, recently American scientists tested a method of treating rheumatoid arthritis using genetically modified stem cells on mice. What did the researchers do? Using CRISPR/Cas, they "trained" induced pluripotent stem cells to recognize inflammation and, most importantly, to produce an interleukin 1 receptor antagonist. Then the scientists injected genetically modified stem cells subcutaneously into several rodents. In parallel, the authors of the experiment treated two other groups of animals with antiarthritis medications. As a result, it turned out that genetically modified stem cells are more effective for rheumatoid arthritis than standard medications. At least on mice.

20. The famous anti-fraud Irina Ermakova in 2016 became an honorary academician of the Liar Academy of Pseudoscience (LIAR). According to the jury, the anti-GM movement causes great damage to the development of science and the economy of Russia.

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