WEBVTT 00:00:17.110 --> 00:00:20.950 According to statistics published by FAO, 00:00:21.780 --> 00:00:26.540 it is estimated that on our planet about one billion people 00:00:26.540 --> 00:00:30.940 are, to some extent, undernourished, they suffer from hunger. 00:00:30.940 --> 00:00:34.147 This is especially relevant when it comes to children, 00:00:34.147 --> 00:00:36.820 and the deficiency of animal proteins 00:00:36.820 --> 00:00:41.110 that influences their physical and intellectual development, 00:00:41.660 --> 00:00:47.370 and may cause, in the long term, important deficits. 00:00:48.610 --> 00:00:54.910 Animal proteins come from farm animals. 00:00:54.910 --> 00:01:00.470 Animal breeding has historically evolved with the evolution of civilization; 00:01:00.470 --> 00:01:03.971 and today, according to FAO statistics, 00:01:03.971 --> 00:01:07.200 we roughly breed 3.5 billion animals, 00:01:07.200 --> 00:01:11.325 excluding birds and fishes, 00:01:11.325 --> 00:01:17.453 which means one farmed animal every two people on Earth. 00:01:18.330 --> 00:01:22.480 These animals also have an impact on the environment 00:01:22.480 --> 00:01:29.120 and by breeding them we generate a number of major environmental issues. 00:01:29.120 --> 00:01:32.430 A large number of these animals 00:01:32.430 --> 00:01:37.180 is located in climatically challenged areas, 00:01:37.180 --> 00:01:40.900 so the productivity of these animals is rather low, 00:01:40.900 --> 00:01:43.020 while in countries with advanced zootechnics 00:01:43.020 --> 00:01:46.880 we have less animals, but much more productive. 00:01:46.880 --> 00:01:48.340 To give you an idea, 00:01:48.340 --> 00:01:51.538 if in 1950, in the Po Valley, 00:01:51.538 --> 00:01:54.580 a Friesian dairy cow gave 4,000 kilos of milk, 00:01:54.580 --> 00:02:00.786 today with the same products, the same soil and and the same technology, 00:02:00.786 --> 00:02:02.410 but with different genetics, 00:02:02.410 --> 00:02:07.410 we can extract from these cows more than twice the amount of milk, 00:02:07.410 --> 00:02:12.989 Therefore, the selection and genetic improvement of animals 00:02:12.989 --> 00:02:15.419 for animal protein production 00:02:15.419 --> 00:02:16.850 played a pivotal role 00:02:16.850 --> 00:02:19.780 in countries with advanced zoo-techniques, 00:02:19.780 --> 00:02:22.660 while it plays no role yet in areas of the planet 00:02:22.660 --> 00:02:29.485 where animals are still raised in a, say, primitive state. 00:02:30.210 --> 00:02:37.181 What is the tool that allows us to improve the animals we breed? 00:02:38.090 --> 00:02:42.860 This improvement is brought about through reproduction technologies, 00:02:43.170 --> 00:02:46.464 From the 1950s onwards, in particular, 00:02:46.464 --> 00:02:51.100 artificial insemination has been the main tool for genetic improvement, 00:02:51.100 --> 00:02:53.600 In other words, the semen of superior animals 00:02:53.600 --> 00:02:57.620 has been distributed through on-farm insemination 00:02:57.620 --> 00:02:59.190 and this has resulted 00:02:59.190 --> 00:03:01.720 in the productive increase that I have just shown you. 00:03:02.170 --> 00:03:05.810 Other technologies were developed over the years, 00:03:05.810 --> 00:03:07.430 always with a view to speeding up 00:03:07.430 --> 00:03:09.850 this process of selection and genetic improvement. 00:03:09.850 --> 00:03:12.969 In particular, embryo-related technologies 00:03:12.969 --> 00:03:19.690 have led to an increased exploitation of the female germline: 00:03:19.690 --> 00:03:23.180 with spermatozoa we use the male; 00:03:23.180 --> 00:03:26.690 with ova, instead, we exploit the genetic value of females. 00:03:26.690 --> 00:03:29.572 In particular, the production of in vitro embryos 00:03:29.572 --> 00:03:31.610 is a recently acquired technology 00:03:31.610 --> 00:03:37.428 that allows us to produce large numbers of test-tube embryos 00:03:37.428 --> 00:03:38.670 and now we’ll see how. 00:03:38.670 --> 00:03:44.040 This technology has also created the technological premises, the know-how, 00:03:44.040 --> 00:03:47.782 to develop cloning, 00:03:47.782 --> 00:03:49.940 which is the topic we are dealing with today. 00:03:49.940 --> 00:03:52.132 In turn, cloning laid the foundations 00:03:52.132 --> 00:03:55.310 that allowed us to make genetic modification, 00:03:55.310 --> 00:03:59.000 or animal transgenesis - similar to the one used for plants - 00:03:59.000 --> 00:04:02.755 a further tool in our pursuit 00:04:02.755 --> 00:04:06.990 of genetic improvement of farm animals, and not only. 00:04:08.770 --> 00:04:14.510 A few words on in vitro technology now, as it paved the way for animal cloning. 00:04:14.510 --> 00:04:16.290 Today, in a laboratory, we are able 00:04:16.290 --> 00:04:21.020 to take gametes, the ova from females and the sperm from males, 00:04:21.020 --> 00:04:24.000 and obtain fertilization in a test tube - 00:04:24.000 --> 00:04:26.982 in vitro technology is synonymous with test tube technology - 00:04:27.580 --> 00:04:31.280 obtain the first stages of embryonic development, 00:04:31.280 --> 00:04:36.948 obtain an embryo that can be at this point either implanted in a receiver, or frozen. 00:04:36.948 --> 00:04:40.387 So the value of this technology 00:04:40.387 --> 00:04:45.540 goes beyond the applications that have been used so far 00:04:45.540 --> 00:04:47.410 and the value of this technology 00:04:47.410 --> 00:04:52.800 has resulted in the awarding of the Nobel Prize for Medicine 00:04:52.800 --> 00:04:55.461 to the pioneer on humans of this technology, 00:04:55.461 --> 00:04:56.704 which has led to the birth 00:04:56.704 --> 00:05:01.170 of over four million people around the world. 00:05:01.170 --> 00:05:05.864 So, in vitro technology is crucial to achieve cloning. 00:05:05.864 --> 00:05:10.670 Now, let's examine in greater detail what we are going to talk about. 00:05:11.330 --> 00:05:15.314 The term cloning is improper, often used inappropriately 00:05:15.314 --> 00:05:19.320 and it creates ungrounded fears. 00:05:19.320 --> 00:05:20.614 Technically speaking, 00:05:20.614 --> 00:05:25.531 we talk about somatic cloning or cell nuclear transfer, 00:05:25.531 --> 00:05:28.230 because cloning consists 00:05:28.230 --> 00:05:32.080 in transferring into an egg cell the nucleus of a cell. 00:05:32.760 --> 00:05:37.380 But, before we go into further detail, what is meant by cloning? 00:05:37.380 --> 00:05:40.496 It means creating two animal organisms, 00:05:40.496 --> 00:05:44.970 that is, two living beings with the same genetic makeup. 00:05:49.776 --> 00:05:53.557 All of you, I think, know sets of homozygous twins, 00:05:53.557 --> 00:05:57.118 that is, two absolutely identical individuals. 00:05:57.118 --> 00:06:01.840 Technically, we can define them clones, so homozygous twins are clones. 00:06:01.840 --> 00:06:05.734 With cloning in the lab we create homozygous twins, 00:06:05.734 --> 00:06:08.940 although they are born at different times. 00:06:09.990 --> 00:06:13.398 But to understand cloning even better, 00:06:13.398 --> 00:06:18.600 consider that it has always been practiced in agriculture, 00:06:18.600 --> 00:06:21.681 because from a simple cutting of a plant 00:06:21.681 --> 00:06:25.610 we generate a new plant, which is therefore cloned. 00:06:25.610 --> 00:06:30.996 Most artificial forests or tree plantations, or fruit trees, 00:06:30.996 --> 00:06:33.060 are obtained by cloning; 00:06:33.060 --> 00:06:34.572 and we eat this fruit, 00:06:34.572 --> 00:06:37.940 we use these materials that are of clonal origin, 00:06:37.940 --> 00:06:42.360 but no one has ever raised any objection, as far as plants are concerned. 00:06:44.680 --> 00:06:49.710 The issues, when it comes to animals, are different and more complicated, 00:06:49.710 --> 00:06:52.550 which is understandable. 00:06:52.550 --> 00:06:56.158 The first historical example of cloning 00:06:56.158 --> 00:07:01.060 appears in the Bible, with the story of Adam and Eve. 00:07:01.060 --> 00:07:07.460 As you may remember, Eve was obtained from a rib taken from Adam while he slept, 00:07:07.460 --> 00:07:11.333 so that is possibly the first example of mammal cloning, 00:07:12.150 --> 00:07:17.640 but it didn't work very well, clearly, as they were not exactly the same, 00:07:18.410 --> 00:07:20.630 indeed they were of different sexes. 00:07:20.630 --> 00:07:24.953 Later on, the first examples, or at least attempts, of cloning 00:07:24.953 --> 00:07:27.460 were made with simple animals. 00:07:27.460 --> 00:07:32.250 Here on your left you can see an example, dating back to 1928, 00:07:32.250 --> 00:07:35.836 when researchers tried to recreate in a lab 00:07:35.836 --> 00:07:40.120 what happens spontaneously in nature when monozygotic twins are formed, 00:07:40.120 --> 00:07:44.380 that is, monozygotic twins originate from the bisection of the embryo, 00:07:44.980 --> 00:07:48.940 but the number of clones we can produce this way is rather limited. 00:07:48.940 --> 00:07:54.200 Instead, in these experiments on frogs, in the '50s, 00:07:54.760 --> 00:08:00.640 they worked with nuclei taken from adult animal, 00:08:00.640 --> 00:08:03.108 which meant every cell is enucleated, 00:08:03.108 --> 00:08:07.900 with all the genetic information it takes to create an individual. 00:08:08.140 --> 00:08:14.120 These researchers introduced these nuclei into frog eggs. 00:08:14.120 --> 00:08:17.578 However, they never succeeded in obtaining adult animals, 00:08:17.578 --> 00:08:18.670 but only tadpoles, 00:08:18.670 --> 00:08:21.670 which are the stage before metamorphosis. 00:08:22.190 --> 00:08:25.800 The same experiments were carried out unsuccessfully on mice, 00:08:25.800 --> 00:08:28.536 so, in 1983 some researchers claimed 00:08:28.536 --> 00:08:32.822 that it was impossible to clone animals 00:08:32.822 --> 00:08:35.766 starting from adult cells. 00:08:36.290 --> 00:08:40.130 In 1986, the first clones of domestic animals 00:08:40.130 --> 00:08:44.140 were obtained using cells taken from the embryo 00:08:44.140 --> 00:08:46.544 just a few hours after fertilization, 00:08:46.544 --> 00:08:51.162 when the few cells that make up the embryo 00:08:51.162 --> 00:08:54.710 are still undifferentiated. 00:08:56.980 --> 00:08:59.900 Briefly, how do we go about it? 00:09:01.540 --> 00:09:04.305 As you will have understood, we need the genome, 00:09:04.305 --> 00:09:06.610 which is to be found in nuclei of cells. 00:09:06.610 --> 00:09:10.262 So we start with a biopsy taken from an adult animal, 00:09:10.262 --> 00:09:13.184 which can also be an animal that has just been slaughtered 00:09:13.184 --> 00:09:14.790 or even a dead animal. 00:09:14.790 --> 00:09:18.770 These cells can be multiplied in vitro, so in a laboratory, 00:09:18.770 --> 00:09:21.734 or they can also be frozen in liquid nitrogen, 00:09:21.734 --> 00:09:23.410 and preserved for decades. 00:09:23.910 --> 00:09:28.820 Then, since we are not dealing with plants, we need an oocyte, 00:09:28.820 --> 00:09:32.398 because we have to put the genome in its natural environment, 00:09:32.398 --> 00:09:34.530 so that it may develop, 00:09:34.530 --> 00:09:39.830 and we use, just like everyone, oocytes taken at the slaughterhouse. 00:09:40.820 --> 00:09:46.480 As the 20th-century naturalist who coined the motto “Ex ovo omnia” used to say, 00:09:46.480 --> 00:09:50.160 everything originates from the egg, which is quite evident. 00:09:50.160 --> 00:09:55.380 Since we work with farm animals which eventually end up being slaughtered, 00:09:55.380 --> 00:09:57.811 we find plenty of oocytes for our experiments 00:09:57.811 --> 00:09:59.000 in the slaughterhouse. 00:09:59.000 --> 00:10:02.380 However, we must remove from the oocyte its genetic information 00:10:02.380 --> 00:10:03.518 and we must replace it 00:10:03.518 --> 00:10:06.652 with the genetic information of the animal that we want to clone. 00:10:07.120 --> 00:10:09.695 So we introduce the nucleus, 00:10:09.695 --> 00:10:14.360 we have the activation of the embryo thus formed, 00:10:14.360 --> 00:10:18.150 and this embryo is implanted in the uterus of a surrogate mother, 00:10:18.150 --> 00:10:23.600 giving life to a genomic copy of the original animal. 00:10:23.600 --> 00:10:27.080 So I have proved that it is possible to get twins 00:10:27.080 --> 00:10:30.530 that are different ages because they are born at different times, 00:10:30.530 --> 00:10:34.004 but from the genomic point of view they have the same DNA. 00:10:35.240 --> 00:10:38.730 This is the first bull we obtained in Cremona in 1999, Galileo. 00:10:39.630 --> 00:10:40.631 These are embryos, 00:10:40.631 --> 00:10:43.580 just so you see what they’re like when they're put in utero, 00:10:43.580 --> 00:10:45.266 they are still undifferentiated, 00:10:45.266 --> 00:10:48.980 you can’t distinguish the parts that will form the animal yet, 00:10:48.980 --> 00:10:53.810 and anyway there are no major differences between one species and the other. 00:10:53.810 --> 00:10:57.006 This is Prometea, the first colt obtained with this technique, 00:10:57.006 --> 00:11:01.970 She is the first filly, the first equine clone in the world, 00:11:01.970 --> 00:11:04.148 and if I did not tell you that it is a clone, 00:11:04.148 --> 00:11:07.300 you would consider it a normal animal, 00:11:07.300 --> 00:11:11.850 without any particular problems, 00:11:11.850 --> 00:11:14.368 and even if the efficiency of the technique, 00:11:14.368 --> 00:11:15.826 in terms of animals born, 00:11:15.826 --> 00:11:17.741 is lower than natural reproduction, 00:11:17.741 --> 00:11:21.090 these animals are born absolutely normal 00:11:21.090 --> 00:11:23.259 and the proof that they're normal is, 00:11:23.259 --> 00:11:29.833 they are able to have a normal offspring, when they grow up. 00:11:29.833 --> 00:11:31.725 Here, on the left, you can see Prometea 00:11:31.725 --> 00:11:35.469 and her son Pegaso behind, 00:11:35.469 --> 00:11:39.613 obtained by artificial insemination. 00:11:40.180 --> 00:11:42.500 The same can be done with cattle. 00:11:42.500 --> 00:11:45.820 We have cloned several specimens of superior bulls. 00:11:45.820 --> 00:11:47.810 This picture represents the clones 00:11:47.810 --> 00:11:50.890 of a very important reproducer for the Friesian race, 00:11:50.890 --> 00:11:52.600 which died several years ago, 00:11:52.600 --> 00:11:55.338 and shows the genetic potential of this animal 00:11:55.338 --> 00:11:59.738 that could be distributed, I think, in a future perspective 00:11:59.738 --> 00:12:03.840 to those areas of the world that do not have our advanced genetics, 00:12:03.840 --> 00:12:07.101 allowing them to quickly benefit from reproducers like this, 00:12:07.101 --> 00:12:11.300 that would normally come at unaffordable prices. 00:12:12.260 --> 00:12:16.600 A number of mammals have been cloned with this technology. 00:12:16.600 --> 00:12:20.970 The technique is reproducible and certainly perfectible. 00:12:20.970 --> 00:12:25.420 Here is Dolly, the first adult somatic cell clone obtained in 1996, 00:12:25.710 --> 00:12:29.830 and then a number of other mammals ending with the camel cloned last year. 00:12:32.660 --> 00:12:36.410 Besides allowing us to reproduce genetic copies of animals, 00:12:36.410 --> 00:12:41.530 cloning has opened up another perspective: genetic engineering. 00:12:41.710 --> 00:12:45.610 This instance of genetic engineering has nothing to do with cloning 00:12:45.610 --> 00:12:47.112 but gives you an idea 00:12:47.112 --> 00:12:51.310 of how much powerful - and even scary - this technique could be. 00:12:51.310 --> 00:12:53.330 These are two mice, two brothers. 00:12:53.330 --> 00:12:59.022 The rat growth hormone was inserted in the embryo of one of the two, 00:12:59.022 --> 00:13:01.450 so it grew the size of a rat. 00:13:01.860 --> 00:13:08.660 Of course doing this kind of manipulation on farm animals is much more complicated, 00:13:08.920 --> 00:13:13.164 which is why the idea of working in this direction 00:13:13.164 --> 00:13:17.380 was only acted upon once cloning became available. 00:13:17.380 --> 00:13:20.271 I already shared the technique, so where's the difference? 00:13:20.271 --> 00:13:25.140 Nowadays, using fairly reproducible and safe techniques, 00:13:25.140 --> 00:13:26.976 I can engineer somatic cells 00:13:26.976 --> 00:13:30.960 taken from an animal and being cultivated in a laboratory. 00:13:30.960 --> 00:13:33.001 I do my genetic engineering operation: 00:13:33.001 --> 00:13:36.730 I can insert genetic characteristics that interests me, 00:13:36.730 --> 00:13:39.136 or I can remove negative characteristics; 00:13:39.136 --> 00:13:43.300 or I could intervene on genetic defects or mutations. 00:13:43.300 --> 00:13:45.299 I then take these cells, 00:13:45.299 --> 00:13:47.580 I follow the process I already described to you 00:13:47.580 --> 00:13:50.971 and the animal that is born is no longer identical to the original - 00:13:50.971 --> 00:13:52.660 or better, it resembles it closely, 00:13:52.660 --> 00:13:56.120 but in addition, it will have the feature I introduced and modified. 00:13:56.940 --> 00:14:01.140 As I was saying, thanks to these systems, we can now engineer large animals, 00:14:01.140 --> 00:14:03.910 which could not be engineered previously. 00:14:03.910 --> 00:14:08.230 By way of example, here is a line of pigs in which we produced a marker, 00:14:08.970 --> 00:14:13.041 which is a protein taken from a marine jellyfish, 00:14:13.041 --> 00:14:16.310 that makes them fluorescent under blue light. 00:14:16.310 --> 00:14:20.172 This is an example of a line 00:14:20.172 --> 00:14:23.277 that serves for research and experimentation, 00:14:23.277 --> 00:14:25.560 as we can trace the cells, 00:14:25.560 --> 00:14:30.660 but above all, if instead of using green 00:14:30.660 --> 00:14:33.658 I use a genetic disease, or something else, 00:14:33.658 --> 00:14:36.010 I can create animal models. 00:14:36.010 --> 00:14:39.220 In particular, we are working to engineer the pig genome, 00:14:39.220 --> 00:14:44.370 so that pig organs may become compatible with human organs. 00:14:44.370 --> 00:14:48.040 This means that pigs in the future will no longer be bred only for ham, 00:14:48.040 --> 00:14:54.258 but may also be used as a source of organs for transplantation in humans. 00:14:54.920 --> 00:14:59.980 There are also applications in the field of animal husbandry. 00:15:00.680 --> 00:15:02.645 For instance, Canadian researchers 00:15:02.645 --> 00:15:08.780 have engineered pigs that can assimilate phosphorus. 00:15:08.780 --> 00:15:11.026 As you know, when it comes to pig breeding, 00:15:11.026 --> 00:15:12.540 pollution is a major problem, 00:15:12.540 --> 00:15:16.230 because pigs release large amounts of phosphorus in their droppings, 00:15:16.230 --> 00:15:19.320 which ends up in the sea, eutrophicates the environment 00:15:19.320 --> 00:15:21.370 and results in the proliferation of algae. 00:15:21.370 --> 00:15:26.030 This pig has been engineered so as to produce an enzyme in its saliva, 00:15:26.030 --> 00:15:31.160 enabling it to digest organic phosphorus, thus making it less polluting. 00:15:31.160 --> 00:15:36.690 Or this other example of a pig rich in Omega 3 acids. 00:15:36.690 --> 00:15:37.996 Everyone knows 00:15:37.996 --> 00:15:43.220 how beneficial these acids are, how good for our health, 00:15:43.220 --> 00:15:47.380 and it is possible to get a line of this type. 00:15:47.380 --> 00:15:50.849 Or let’s take cattle: for example, 00:15:50.849 --> 00:15:55.535 the cow you see in the picture is cloned 00:15:55.535 --> 00:16:00.170 and was obtained by inserting an antibacterial, 00:16:00.170 --> 00:16:04.085 so this cow has in its milk a natural antibacterial, 00:16:04.085 --> 00:16:06.870 which makes it resistant to mastitis. 00:16:06.870 --> 00:16:13.560 Mastitis is the main cause of infections on dairy farms, 00:16:13.560 --> 00:16:17.910 and tons of antibiotics are needed to treat the animals suffering from it, 00:16:17.910 --> 00:16:21.910 with repercussions on animals’ health. 00:16:21.910 --> 00:16:25.533 Thanks to this operation it is possible to solve the problem, 00:16:25.533 --> 00:16:29.035 or at least significantly reduce the use of antibiotics, 00:16:29.540 --> 00:16:31.916 which is also beneficial for us 00:16:31.916 --> 00:16:37.090 since it causes resistance to antibiotics in humans, 00:16:37.090 --> 00:16:42.430 which means doctors no longer have means to treat us when we actually get sick. 00:16:42.430 --> 00:16:44.560 Another example is that of being able 00:16:44.560 --> 00:16:47.380 to produce drugs in genetically modified animals, 00:16:47.380 --> 00:16:49.250 this is already a commercial product: 00:16:49.250 --> 00:16:52.390 a goat, obtained by means of cloning and genetic engineering, 00:16:52.390 --> 00:16:58.450 which produces a substance that controls the buildup of blood clots. 00:16:58.450 --> 00:17:01.524 This means, that patients who need this molecule 00:17:01.524 --> 00:17:05.110 can now get it in larger quantities and at lower prices, 00:17:05.110 --> 00:17:09.267 since by producing it in animals, in goats, 00:17:09.267 --> 00:17:13.520 it is possible to produce larger quantities, 00:17:13.520 --> 00:17:18.650 and especially for certain drugs containing complex molecules 00:17:18.650 --> 00:17:21.580 that bacteria are unable to synthesize. 00:17:22.410 --> 00:17:27.970 To sum up, I would say that regardless of the implications of the research, 00:17:27.970 --> 00:17:30.367 cloning has opened up new perspectives, 00:17:30.367 --> 00:17:34.330 new ways of perceiving and approaching basic biology, 00:17:34.330 --> 00:17:37.770 which, unfortunately, I don't have time to go into now. 00:17:38.150 --> 00:17:39.681 Anyway, even limiting ourselves 00:17:39.681 --> 00:17:44.794 to the potential impact for us ordinary people, 00:17:44.794 --> 00:17:47.447 I can tell you that there are two applications, 00:17:47.447 --> 00:17:51.000 in the zoo-technical and biomedical fields. 00:17:51.000 --> 00:17:53.654 So cloning is important not only for agriculture, 00:17:53.654 --> 00:17:56.260 but also for our health. 00:17:56.260 --> 00:18:00.689 Obviously it raises a number of ethical issues, 00:18:01.440 --> 00:18:04.536 mainly in developed countries. 00:18:05.426 --> 00:18:07.386 Maybe other countries are less concerned 00:18:07.386 --> 00:18:11.630 because they need new technologies and new opportunities. 00:18:13.930 --> 00:18:18.180 But there is an ideological stance when it comes to these new technologies, 00:18:18.180 --> 00:18:20.240 therefore often a groundless stance, 00:18:20.240 --> 00:18:24.230 and I think that being able to explain, with the utmost transparency, 00:18:24.230 --> 00:18:26.343 to the general audience, 00:18:26.343 --> 00:18:28.553 the opportunities brought by science, 00:18:28.553 --> 00:18:31.960 is definitely a thing to do 00:18:31.960 --> 00:18:34.596 and can help change, I think, among the general audience 00:18:34.596 --> 00:18:38.340 the perception of this technique. 00:18:38.940 --> 00:18:40.510 Thank you. 00:18:40.510 --> 00:18:42.830 (Applause)