0:00:01.200,0:00:09.080 Hello. In the lecture, we will focus on the basics of food safety, primarily in connection with GMOs, 0:00:09.080,0:00:16.040 and describe the essence and significance of GMOs and animal cloning. The lecture is part 0:00:16.040,0:00:23.760 of Module 2: Conservation and Sustainable Use of Animal Genetic Resources. The creation of this 0:00:23.760,0:00:32.360 presentation was supported by the ERASMUS+ KA2 grant within the ISAGREED project: 0:00:32.360,0:00:38.320 Innovation of Content and Structure of Study Programs in the Field of Management of Animal 0:00:38.320,0:00:48.440 Genetic and Food Resources Using Digitization. Food safety is currently one of the most important 0:00:48.440,0:00:55.400 topics in relation to animal husbandry and food production. From this perspective, it is 0:00:55.400,0:01:01.680 necessary to monitor the potential occurrence of harmful chemicals that can have mutagenic 0:01:01.680,0:01:10.400 or even carcinogenic properties. Here, we most commonly encounter the presence of heavy metals 0:01:10.400,0:01:19.520 and mycotoxins. In some countries, antibiotics may also be present in meat as unwanted contamination. 0:01:19.520,0:01:27.920 Food must have a defined composition to prevent the occurrence of naturally occurring allergens, 0:01:27.920,0:01:37.120 and in this case, consumers need to be notified of this risk. The most serious in terms of health 0:01:37.120,0:01:44.120 is microbiological contamination, especially in meat and dairy products, by bacteria such 0:01:44.120,0:01:51.240 as salmonella, listeria, or Campylobacter. Fortunately, the presence of these foodborne 0:01:51.240,0:01:59.880 pathogens can be tested using microbiological cultivation techniques, but also DNA tests. 0:01:59.880,0:02:08.120 In connection with the presence of GMOs in food, thorough testing of their health safety is carried 0:02:08.120,0:02:16.520 out during their approval. With GMOs, there is a potential risk of allergenicity, so even they need 0:02:16.520,0:02:23.120 to be tested and detected. Similar mechanisms for verifying health safety need to be applied 0:02:23.120,0:02:35.080 to potential foods made from cloned animals. Currently, the presence of GMOs above 0.9% must 0:02:35.080,0:02:42.760 be declared in food. For this purpose, several sensitive detection methods have been developed. 0:02:42.760,0:02:49.960 The diagnosis of GMOs in food can be performed by detecting the presence of GMOs through 0:02:49.960,0:02:57.560 direct identification of transgenic DNA (using polymerase chain reaction - PCR) or by detecting 0:02:57.560,0:03:06.440 transgenic protein - immunochemically using the ELISA method. In the case of using PCR, if a 0:03:06.440,0:03:13.400 transgene is present in the sample, amplification or replication of the product occurs, which is 0:03:13.400,0:03:21.320 visible as a band on an electrophoretic gel. Quantitative methods are used to determine the 0:03:21.320,0:03:27.360 proportion of GMOs in food. The most sensitive method is real-time PCR, 0:03:27.360,0:03:34.240 which is extremely accurate and sensitive. The amount of GMO in the sample is determined by 0:03:34.240,0:03:41.520 comparing the curve of the tested sample with the curves of known composition standards. The 0:03:41.520,0:03:49.960 method is also called relative quantification. In terms of the result, there is no difference 0:03:49.960,0:03:57.000 between traditional breeding and transgenesis as the main method of creating genetically modified 0:03:57.000,0:04:04.040 organisms. They have the same goal, which is to obtain individuals with desirable alleles 0:04:04.040,0:04:11.200 in their genotypes. In traditional breeding, hybridization and deliberate crossing are often 0:04:11.200,0:04:18.760 used, and it takes many generations to obtain desired combinations of genotypes. Transgenesis 0:04:18.760,0:04:26.280 is characterized by targeted and rapid changes, requiring knowledge of the gene we want to use 0:04:26.280,0:04:32.800 and transferring it to the organism using a vector, i.e., its structure, function, 0:04:32.800,0:04:40.040 and sequence. Traditional breeding work is done in the population, while transgenesis can be 0:04:40.040,0:04:49.400 seen as breeding an individual. The comparison of both approaches can be seen in the diagram. 0:04:49.400,0:04:56.680 First, let's define genetic modification. Genetic modifications refer to targeted interventions in 0:04:56.680,0:05:04.400 genetic information. Although the result may be similar, random interventions by mutagens 0:05:04.400,0:05:12.240 or ionizing radiation (such as the creation of wheat or rapeseed varieties) are not considered 0:05:12.240,0:05:19.680 genetic modification. Genetic modifications include intentional changes in gene activity, 0:05:19.680,0:05:26.520 changes in "site of action" (in which tissue), gene replacement with another variant, 0:05:26.520,0:05:33.880 gene blocking, and especially the introduction of foreign genes - transgenesis. A classic 0:05:33.880,0:05:40.920 example of transgenesis in plants is the use of the bacterium Agrobacterium tumefaciens, 0:05:40.920,0:05:48.080 which has the natural ability to introduce genes for herbicide resistance or insecticide 0:05:48.080,0:05:55.400 production - this is how Bt corn, for example, was created. Alongside the development of 0:05:55.400,0:06:04.400 these biotechnologies, legal regulations are emerging, such as the law on handling GMOs. 0:06:04.400,0:06:11.280 Genetic modifications are synonymous with recombinant DNA techniques. These involve 0:06:11.280,0:06:18.480 direct and targeted interventions in the hereditary material of an organism (i.e., 0:06:18.480,0:06:27.020 DNA). The most well-known method is transgenesis, also known as gene transfer between species and 0:06:27.020,0:06:34.800 the introduction of individual genes into the genome using genetic engineering methods. A 0:06:34.800,0:06:43.160 genetically modified organism (GMO) is an organism (other than a human) whose genetic material has 0:06:43.160,0:06:51.200 been intentionally altered in a manner that cannot be achieved through natural recombination. GMOs 0:06:51.200,0:07:01.400 can be microorganisms, fungi, plants, or animals. The creation of GMOs presents a few problems. 0:07:01.400,0:07:08.320 One of them is the low efficiency of insert incorporation. The integration of an insert and 0:07:08.320,0:07:16.840 its copies often occurs randomly. The product can be formed in low or high concentrations because it 0:07:16.840,0:07:23.640 is difficult to properly regulate expression of the structural gene. Incorporation of 0:07:23.640,0:07:32.400 foreign DNA is often unstable and may be lost over generations. Gene manipulations are still costly, 0:07:32.400,0:07:38.160 and the goal is often achieved with great uncertainty. The most advanced molecular 0:07:38.160,0:07:46.640 biotechnology based on the CRISPR-Cas9 system helps solve most of these problems. 0:07:46.640,0:07:52.680 The base of recombinant DNA technology (used in genetic engineering) lies in the 0:07:52.680,0:07:59.320 use of restriction enzymes, which originate from bacteria and serve as a defense mechanism against 0:07:59.320,0:08:07.680 foreign DNA. These enzymes can cleave DNA at specific sites known as restriction sites. By 0:08:07.680,0:08:14.200 using the same enzyme to open the vector and create both ends of the gene, the likelihood 0:08:14.200,0:08:23.440 of correct insertion of the gene into the plasmid can be increased. The DNA ligase enzyme is used 0:08:23.440,0:08:31.480 for this joining process of originally unrelated DNA segments, and it is called DNA recombination. 0:08:31.480,0:08:36.480 The vector can then be integrated into the genome of the host cell, thereby 0:08:36.480,0:08:44.560 transferring the sequence of the gene itself. The main problem with transgenesis is how to 0:08:44.560,0:08:50.960 effectively introduce recombinant DNA into the cell and nucleus. Many methods have 0:08:50.960,0:08:58.600 been developed, of which I will first mention the so-called biological methods. Lipofection involves 0:08:58.600,0:09:06.080 the use of lipid micelles that encapsulate nucleic acids into liposomes, which can naturally 0:09:06.080,0:09:12.800 penetrate the cell nucleus. Transfection using plasmid vectors is a relatively simple method 0:09:12.800,0:09:19.560 but with low efficiency. Viral vectors are now more commonly used in animals because they 0:09:19.560,0:09:27.640 have a natural ability to penetrate the cell and nucleus. In the case of adenoviruses, DNA enters 0:09:27.640,0:09:36.280 the chromatin, not directly the DNA, while in the case of retroviruses and lentiviruses, foreign DNA 0:09:36.280,0:09:44.800 directly integrates into the genome. The image on the right shows the schema of a lentivirus, 0:09:44.800,0:09:52.240 which, in addition to RNA, contains enzymes for integrating nucleic acids into the host's DNA. 0:09:52.240,0:09:59.920 During transgenesis, care is taken to ensure that viral vectors are safe and modified so 0:09:59.920,0:10:08.320 that they cannot reproduce in the host cell. Physical methods mainly involve microinjection, 0:10:08.320,0:10:15.880 which is the introduction of DNA into a fertilized egg or embryonic stem cells. This method is simple 0:10:15.880,0:10:22.000 and foreign genes are effectively expressed. The method cannot be used in later developmental 0:10:22.000,0:10:31.040 stages, and the disadvantage is low success rate and random insertion of the insert. Gene 0:10:31.040,0:10:39.560 transfer using embryonic stem cells, known as ESC, is a specialized method where pluripotent 0:10:39.560,0:10:46.480 cells from a blastocyst with DNA inserted in vitro are inserted into a foreign embryo, 0:10:46.480,0:10:54.200 which is then transferred to a surrogate mother's uterus. The result is the birth of an offspring 0:10:54.200,0:11:02.240 that is a genetic chimera, meaning it has some tissues with the transgene and others without. 0:11:02.240,0:11:09.200 Other methods include transfer of DNA through various particles and shooting them into the cell, 0:11:09.200,0:11:16.840 as well as electroporation (i.e. creating pores in the cell using electrical impulses). Thermal shock 0:11:16.840,0:11:23.680 or coated magnetic particles can also be used. However, all of these methods have relatively 0:11:23.680,0:11:31.520 low efficiency (up to 5%) and their application depends on the specific species of animals and the 0:11:31.520,0:11:36.360 experience of the respective laboratory. In this scheme, we see an example of 0:11:36.360,0:11:42.040 microinjection technique used to transfer a transgene, with the aim of expressing the 0:11:42.040,0:11:49.960 transgene only in the mammary gland and producing a readily isolatable product, i.e. protein, 0:11:49.960,0:11:55.760 from transgenic milk. These genetically modified animals used to produce specific 0:11:55.760,0:12:04.640 transgenic proteins are called animal bioreactors. Various uses of microinjection can be seen in the 0:12:04.640,0:12:11.520 images here. Injection can be done into the pronucleus just before the fusion of nuclei 0:12:11.520,0:12:18.200 and the formation of a zygote - the result is a completely transgenic individual. Another 0:12:18.200,0:12:25.160 approach is the insertion of the transgene into embryonic stem cells, which are then inserted into 0:12:25.160,0:12:33.000 the host blastocyst. Chimeras are born, which can be further crossed and in subsequent generations, 0:12:33.000,0:12:39.440 a completely transgenic individual can be obtained again. The advantage of this method 0:12:39.440,0:12:45.200 is that we can culture and select embryonic stem cells, which increases the likelihood of 0:12:45.200,0:12:53.880 success in transgenesis. Another frequently used method is nuclear transfer, where a DNA 0:12:53.880,0:13:01.920 construct is inserted into cultured somatic cells (usually undifferentiated, such as fibroblasts), 0:13:01.920,0:13:09.200 and then the nucleus is removed and inserted into an enucleated egg. The zygote is then 0:13:09.200,0:13:17.520 implanted into a surrogate mother and in all cells transgenic individual can be born again. 0:13:17.520,0:13:23.680 And what is the purpose of creating GM animals? First, to increase the better production and 0:13:23.680,0:13:29.960 quality of animal food. This is also related to the production of new and better foods, 0:13:29.960,0:13:37.360 for example the lactase gene in cattle will reduce the lactose content in milk. Another example is 0:13:37.360,0:13:43.280 the replacement of allergenic proteins in milk with human proteins. There is great 0:13:43.280,0:13:49.200 potential for the production of high-quality recombinant proteins (pharmaceuticals, 0:13:49.200,0:13:57.880 etc.) or new materials in industry with the help of so-called "living bioreactors". High hopes are 0:13:57.880,0:14:04.000 placed in research on resistance to disease and the adverse effects of a changing environment, 0:14:04.000,0:14:10.360 for example, an experiment with the transfer of a gene for a protein that protects against freezing 0:14:10.360,0:14:16.760 into the genome of salmon. The use of animal models is important for research into human 0:14:16.760,0:14:26.040 diseases, and research into the use of transgenic animals for xenotransplantation is also underway. 0:14:26.040,0:14:33.280 The most significant application of genetically modified animals is in the field of pharmaceutical 0:14:33.280,0:14:39.720 production. Many important drugs, often for the treatment of genetic diseases, are of 0:14:39.720,0:14:47.720 protein nature. Proteins, as complex substances, cannot be produced chemically like simple drugs, 0:14:47.720,0:14:56.560 but synthesis must occur in biological systems. The simplest way is the production of drugs using 0:14:56.560,0:15:05.080 microorganisms, such as bacteria. Insulin has been produced this way for many years. However, 0:15:05.080,0:15:11.560 insulin is a relatively simple protein, and bacteria cannot produce more complex proteins 0:15:11.560,0:15:19.040 with specific post-translational modifications. Therefore, eukaryotes - animals such as mammals or 0:15:19.040,0:15:27.880 birds - must be used. One of many examples of drug production is obtaining human protein lipoprotein 0:15:27.880,0:15:37.920 lipase from chicken eggs. Goats or rabbits are often used for similar purposes in mammals. 0:15:37.920,0:15:43.800 Proteins have very diverse properties that can be used as materials for various advanced 0:15:43.800,0:15:51.040 technologies. For example, spider silk protein is a material that is about 7 times stronger 0:15:51.040,0:15:57.840 than high-quality steel in terms of volume and weight, and it is called Biosteel. The 0:15:57.840,0:16:06.080 source of this protein is genetically modified goats that produce this protein in their milk. 0:16:06.080,0:16:12.480 There are not many examples of genetically modified food of animal origin approved for 0:16:12.480,0:16:19.600 consumption. A well-known example is GM salmon, which grows 11 times faster than 0:16:19.600,0:16:27.200 regular farmed salmon. The approval process in the United States was very complicated and 0:16:27.200,0:16:37.880 took 20 years. To prevent the escape of GM salmon into the wild, they are bred in isolated tanks. 0:16:37.880,0:16:44.120 Genetic modification is also associated with ethical problems. Is the new product 0:16:44.120,0:16:52.920 acceptable to customers? European consumers tend to reject GMO foods. In the past, 0:16:52.920,0:16:58.480 concerns arose regarding the risk of tumor formation or neurodegenerative 0:16:59.120,0:17:05.760 diseases in transgenic animals due to the integration or expression of transgenes, 0:17:05.760,0:17:13.640 following the initial failed experiments. It is logical that side effects due to gene modification 0:17:13.640,0:17:21.000 cannot always be excluded. An ethical issue for many people may be that humans may benefit 0:17:21.000,0:17:29.720 from genetically modified animals even if the transgenic animals themselves do not. In any case, 0:17:29.720,0:17:36.840 it is necessary to ensure that GM does not cause any harm to animals. There are often 0:17:36.840,0:17:43.640 concerns that foreign genes affect hosts and whether there may be a threat to ecological 0:17:43.640,0:17:51.920 balance and species diversity. However, GM animal husbandry is usually closed, although 0:17:51.920,0:18:00.960 there is no 100% guarantee. Currently, rapidly developing genome editing as a method causing 0:18:00.960,0:18:09.760 specific and only minor changes in the genome eliminates most potential risks. Nevertheless, 0:18:09.760,0:18:20.680 all GMOs are subject to detailed verification of potential risks, so safety should be ensured. 0:18:20.680,0:18:27.960 And now a few words about animal cloning. Cloning, in this sense, is a reproductive technique for 0:18:27.960,0:18:34.800 creating genetically identical offspring. However, it is often also used for techniques related to 0:18:34.800,0:18:41.440 genetic modification. Cloning techniques in mammals include microsurgical embryo 0:18:42.040,0:18:49.200 dissection, isolation and proliferation, or aggregation of individual blastomeres, 0:18:49.200,0:18:56.440 and especially nucleus transfer, which may or may not be modified. Cloning in mammals 0:18:56.440,0:19:03.280 can be divided into reproductive, where a new genetically identical individual is created, 0:19:03.280,0:19:11.120 and therapeutic for the purpose of treatment. The first type applies exclusively to animals, while 0:19:11.120,0:19:20.120 the second has great potential in human medicine. The first successful cloning of a mammal from 0:19:20.120,0:19:27.360 an adult cell was carried out by Professor Wilmut of the Roslin Institute in Scotland, 0:19:27.360,0:19:37.760 when the sheep Dolly was born in 1996. The nuclear transfer technique was used by cell fusion. Dolly 0:19:37.760,0:19:45.120 was genetically identical to the sheep from which the nucleus was taken from a somatic cell of the 0:19:45.120,0:19:52.080 mammary gland epithelium. Interestingly, Dolly had three mothers: the first donated 0:19:52.080,0:20:01.440 the genetic information, the second provided an empty egg, and the third carried the offspring. 0:20:01.440,0:20:08.240 A number of problems have arisen in connection with animal cloning. Low pregnancy rates, 0:20:08.240,0:20:16.120 developmental defects such as early miscarriage, stillbirths, early deaths after birth, short 0:20:16.120,0:20:23.040 lifespan, obesity, malformations of various organs, and poor immunity have been observed 0:20:23.040,0:20:30.720 in many animals. Cloned animals are generally not accepted by breeders - for example, horses 0:20:30.720,0:20:38.840 are not included in studbooks. Legislative and ethical problems arise. Regarding food products 0:20:38.840,0:20:45.760 from cloned animals (also known as "cloned meat"), the U.S. Food and Drug Administration 0:20:45.760,0:20:53.720 (FDA) states that consuming meat from cloned animals is without risk. However, economically, 0:20:53.720,0:21:00.360 this breeding is currently highly inefficient due to the high costs of cloning. The European Food 0:21:00.360,0:21:09.680 Safety Authority (EFSA) also declared products of animal origin from clones to be safe, but there 0:21:09.680,0:21:18.360 are concerns about the welfare of surrogate mothers and the cloned animals themselves. 0:21:18.360,0:21:24.840 A large number of different animal species have been cloned, from model organisms such 0:21:24.840,0:21:33.680 as mice and rats to most livestock. The picture shows 6 clones of one mare, which the owner rode 0:21:33.680,0:21:41.000 during horse polo. Interestingly, although the mares are highly similar, they are not 0:21:41.000,0:21:48.000 genetically identical in terms of coloring. The distribution and size of color markings in this 0:21:48.000,0:21:54.680 case are not directly genetically determined. It can be said that cloning is often done for 0:21:54.680,0:22:06.160 money or for entertainment or publicity purposes. I see the main significance of cloning techniques 0:22:06.160,0:22:11.800 primarily in the potential for so-called therapeutic cloning, which could enable the 0:22:11.800,0:22:18.240 treatment of previously incurable diseases. The mechanism of this treatment involves 0:22:18.240,0:22:25.240 replacing damaged cells with genetically identical cells from the patient's own body, 0:22:25.240,0:22:31.920 or cells with corrected genetic information (in the case of treatment of genetic diseases). The 0:22:31.920,0:22:39.280 use of embryonic stem cells and, especially, induced pluripotent stem cells (iPSCs) created 0:22:39.280,0:22:46.280 directly from the somatic cells of a specific patient, appears promising. 0:22:46.280,0:22:53.040 Unlike GMO foods, food from cloned animals is more acceptable as it does not contain 0:22:53.040,0:23:00.760 anything foreign. However, both biotechnological approaches require improvement in procedures, 0:23:00.760,0:23:07.200 especially with regard to the welfare of the lives of these created animals. Neither the 0:23:07.200,0:23:16.680 consumer nor a perfect laboratory analyzer can discern the differences between these pieces. 0:23:16.680,0:23:22.880 The issue of GMOs and animal cloning is controversial, and everyone must form 0:23:22.880,0:23:28.680 their own opinion on these techniques. The aim of this short presentation was 0:23:28.680,0:23:37.120 to provide objective information to help form that opinion. Thank you all for your attention.