CRISPR CAS9 EDITING GMO Do you know these acronyms? Hello everybody. Well, who hasn't heard of GMO in the last ten, or even twenty years it is likely however that many of you don't know these new acronyms or words such as CRISPER written as CRISPR, or EDITING but they are already revolutionizing scientific research in biology and medicine these new technologies to modify the genome of a living organism have been invented just a few years ago. Most of the work has been made by two women Jennifer Doudna and Emmanuelle Charpentier. Keep these two names in mind because for sure they are going to win the Nobel prize, if not the next year in the following ones these new bio technologies that they helped develop spread enormously in just a few years and are potentially very powerful but also potentially cause of many discussions within a society something we are not talking about yet, we are stuck, not just in Italy but in many other countries to discussions on GMOs, on vegetable GMOs but in reality in the scientific research we are already far beyond. Briefly then, without too many technical details that are not relevant: if I want to make a GMO I extract with some bio technologies a gene of a species, which can be more or less distant from the species I want to modify it can be the same one, but from a legislative point of view it does not matter, and I insert it in the genome this is what we have normally done for 20 years or more This transfer leaves some traces and such traces, in the species I modified, allow the identification and the correct reporting, for instance on a label, of the use of a GMO product. You know that GMO are strictly regulated basically all over the world: in some countries they can be farmed and consumed, in others, such as in Italy, they can be imported and used but not farmed but anyway they are regulated everywhere. This new bio technology however which has been discovered, or actually adapted from something already existing in nature since it has been used by some bacteria to defend from a viral attack, this technology is called Editing, because exactly like a word processor it allows, instead of doing a copy-paste from somewhere else, from another genome, it allows to zoom directly on the gene I want to modify, and then to edit it, delete it or change it, as we prefer. The analogy is this: up to now to make a GMO I had to extract something, a word from a text - let's say we open two word processors, - and in my file I want to write "My little house" and for now I wrote "My pretty house". In another file I have some text and the word "little" appears there. What can I do? I can go to the second file, select the word "little", cut it, and then go to the first file, select the word "pretty", delete it and insert the word "little" This is a GMO: I took something from another file and put it in mine. It is this transfer, this copy-paste procedure, this cutting and sewing between two files, two genomes, that is regulated It is not the genetic change itself that is regulated, but the way it is made. What Editing does instead is to go directly - exactly as I would do with a word processor, I go with the cursor on the word I want to change - with the cursor I delete the letters I don't need and write what I want instead. Of course the result is the same but from a legislation point of view it is entirely different because I did not make a copy-paste from another organism to this one, I have changed, as it might happen spontaneously in nature with a mutation, the genome. The article by Doudna and Charpentier is from 2012, but already one, two, three years later the number of scientific articles exploiting this technique for a variety of things has exploded exponentially even so that in 2015 the two most important scientific magazines in the world: Nature and Science, dedicated a cover to this discovery naming it "the innovation of the year" since it will be something truly subverting, not just in this year but in the whole century. What is subverting from a legislative point of view? Well, two things: the first is that it is really cheap you can already find small kits on crowfunding platforms to make Editing with CRISPR at home, or maybe in an equipped lab These kits cost less than 200 dollars, so potentially if you already have some equipment around, you can make some types of manipulation but from the legislation perspective, what is truly subverting and will subvert is that this type of bio technology leaves no trace. If today I make a GMO in a lab, in the new genome, in the new organism I leave traces and this is because normally, beside the gene I am interested in transferring which gives for instance resistance to an insect, I transfer other sequences I need too, I insert what is called a "construction" and this can be done with something at the beginning, the "promoter" something maybe at the end, other auxiliary genes that allow me to select in the lab the plants or cells that have been really transformed, and so on. The result is that, having other information beside the inserted gene, in a lab I can effectively regulate I can verify if a food, a plant has been really modified with these techniques. Editing, among which CRISPR is the latest, but it is the most used one, has the great advantage of leaving no trace to those who analyze a product, CRISPR has no trace it is indistinguishable from a random mutation that can occur and occur constantly in nature. So if tomorrow in my lab I modify some lemons to make them violet and produce anthocyanins, and I succeed in making a violet lemon, I could theoretically do it with a transgenic process, obtaining a GMO, I could take the gene or group of genes that cause the violet tinge of anthocyanins from blueberries, insert it in the lemon, and tomorrow I hypothetically get a violet lemon. Having so transferred the gene, my violet lemon - this hypothetical GMO - would be absolutely regulated and possibly at least in Europe would never see the light. If I wake up and tomorrow a violet lemon appears in my garden through spontaneous mutation, I could with no problem sell it, use it and nobody can tell me no, it is not a GMO since it lacks the signals of a gene transfer inside. The fact is that now I can do that, for instance, with these techniques it is a hypothetical example, but gives an idea of the importance of this technique, I can do it and make a lemon that produces anthocyanins, and so becomes violet without leaving any trace. I can take it, plant it and then say: look, I found this in my garden and nobody can, by analyzing the genome of this lemon, discover that I made this modification myself and so it automatically eludes the regulation, and if we want, the political control GMO are exposed to, that created and still create discussions in these years. In this moment in Bruxelles there is a discussion that has been ongoing for years because these Editing techniques have been developed for years the so-called "new breeding techniques" these new technologies have no regulation the European directives has nothing to say about them, since they were not known. As I said, the legislation only applies checks on the way the change has been done, not on the change itself. So there are for instance plants on the market able to resist to herbicides - this is usually the bane of many people, many ecologists - that since were not obtained with a transgenic process, but with other bio technologies, do not fall under the GMO regulation, are not named GMOs, and we all have those at home and nobody is concerned. Thus, since the current legislation does not regulate this new type of technology which did not exist at the time we are literally in a Far West. So, the battle ongoing now in Europe is: on one side some countries and associations say: no, the new technologies might be new but are still doing genetic modification and quite heavy ones, so we should consider them GMOs for every intent and purpose. Another group of countries, and other associations say: no, from a scientific point of view are indistinguishable from natural mutations; if I can sell a violet lemon I find in my backyard why should I be prevented from selling by the same rules the same violet lemon that I instead produced with a mutation in my lab? You see that the matter is not scientific, but rather political and this is why for a few years they have been discussing in Bruxelles, but to no avail however there has been a small change in attitude because if earlier everybody was against GMOs, now, for instance, they are starting to make a difference as it is correct to do, looking at products on a case-by-case basis. So for instance if Greenpeace already took a side by saying "no, absolutely, Editing is evil too, and we will keep making fools of ourselves with the white overalls because we are against it" others that were earlier, and even now against the "traditional" GMOs are more open or even made positive statements for these new technologies. They could be used, but some people are already trying, to reduce the impact, for instance, of the usage of copper salts in viticulture copper is a toxic metal, it is used both in conventional viticulture and in biological viticulture and also in some other agricultural sectors, this caused some declarations in favour for example I heard them directly from Slow Food but congressman Martina also made declarations in this direction: he promised that in Europe he will vote for a lack of regulation for Editing. However this risks being a completely pointless discussion, because as I said, even in the worst case where they start regulating in a very rigorous way these new bio technologies, since there is no way to analyze the edited product as it is done e.g. to stop a product developed abroad during import, how can we stop this? This is usually done, for instance, with rice there is some experimental GMO rice used in China it is not yet on the market, but apparently it was so attractive to some rice farmers that they started even to farm it without authorization. This is sometimes found in rice imports from China but since it is a GMO it leaves, as mentioned, a trace in the genome, it is identified and usually they block its spread in our domestic market. But if tomorrow somebody really makes a violet lemon through Editing, and imports it, what can we do about it? we can say "we don't want it", but we have no way to verify and separate natural mutation that still happen and those obtained with new bio technologies. If you now see, for instance in supermarkets, some orange cauliflowers. Well, know that they are caused by a genetic mutation that happened spontaneously in Canada in 1970, so the day before yesterday or pink grapefruit is the result of some genetic modification that were created by exposing grapefuit seeds to radiations years ago, we can talk about that in another video there is no regulation on pink grapefruit, since it is not considered a GMO the fact that it is not identifiable, together with the low cost and the ease of producing suc changes, even just for vegetables, is going to create a really big disruption. For example in the US they already produced a champignon mushroom that no longer blackens these techniques have been used to "turn off" the gene producing polyphenol oxidase that makes the mushroom blacken after it is chopped. This happens also with an apple made in Canada, the Arctic apple, for this apple, with the traditional techniques of genetic engineering, they turned off the gene that makes them black this apple is a GMO for all intents and purposes, because genetic engineering has been employed to get this modification. For the mushrooms, no, Editing was used and so it is practically indistinguishable from a spontaneous mutation. The US have already declared, in this case but with others too, that such products won't be regarded as GMOs and therefore can be introduced on the market, subject to rules applied to any other new product introduced. What is going to happen in Europe? We do not know the politics, but it risks being completely irrelevant. I like making a comparison, forgive me if it is old-fashioned, a bit vintage, with what happened in the 1970s. I was a kid, and know that in the 70s, at the beginning of the 70s, you turned on the radio and could only find Rai [national radio and TV company] or, if you switched to AM you could find other stations, maybe foreign ones...Radio Monte Carlo for instance but there was not the huge amount of radio transmissions, of stations you have nowadays it was illegal to transmit a radio signal, all the radio stations were under the tight governmental control, so political control. Well, in the 70s however the cost of transmission equipment and the desire of many people to be heard, even to broadcast simple music, or to broadcast stuff Rai did not want or censored and therefore evading the political control - Rai has always been, and is still under tight political control - illegal local radio stations started to appear illegal because lacking authorization, and sometimes, when they appeared, the government sent the gendarmerie, the postal police not sure which one at the time, to block, close down the installations but they could be enclosed in an apartment room at the time they were called "free radios": I know it is funny today because we live in a time where anybody can start broadcasting, anybody can have their voice out, as I do myself through YouTube but those were the times, they were called free radios because they had no authorization, evaded any check and anybody could have their voice heard. Why do I make this comparison? Because they were completely impossible to stop as it happened in a few years the government gave up and gave to common citizens the permission to broadcast their voice and I think the same thing is going to happen here there will be those that will try to regulate Editing, for sure like some myopic politicians are now trying to regulate Internet, which is intrinsically not prone to regulation, or at least not on a large scale. Somebody might have already made a violet lemon and maybe they are just registering it saying a violet lemon just popped out of their garden and would like to sell it like it happened, as I said, for the cauliflower and several other things. The true political and ethical battle is going to be on the modifications you are allowed to do and that are already being done on embryos because this is a powerful technique and in theory it is hoped it could be used to cure some genetic diseases I really invite you, if you are interested, to go and watch the recording of the presentation Alessandro Tavecchio did on the link4universe channel a few weeks ago I'll put the link in the description, a book is about to be published, if you want to read some published article that appeared on "Le Scienze" it will be in the description too as somebody said "we live in interesting times". Goodbye. Or better, as usual Peter and I bid you goodbye I have been long-winded this time, but it was important to me to tell you a few things not so much on the technology itself, but on its outlook and its disrupting behaviour you can ask all the questions you want below and I will try to reply in one of the next videos so see you in another video.