 Hi, everyone. My name is Regina, and I'll be talking about this for a minute. Is this working? In November 2018, so just last year, Professor E.M.Q. announced that the birth of two baby girls to which he has added their genome. He said that these two baby girls were born normal and healthy and that he had changed their DNA so that they could become resistance to HIT. No data or any paper has been published for us to be able to check what has been done. So we have very little detail on what he did, how he did it, and who knew about this experiment. The few details that we have are the ones that he gave during the talk at this conference. So, at the point of his announcement, it grew up quite a shock within the world, both the epidemic community and also the society in general. And many people said that the experiment that he gave was very premature and a bit rushed, but today I thought it is better for all of us to be on the same page that I will show you what he did, how he did it, and what are some of the technical and ethical implications of his work. So, Professor E.M.Q. said that he wanted to make babies that are resistant to HIT. HIT is a virus that can infect immune cells. Once it infects immune cells, it makes them weaker and weaker and weaker until it can no longer fight infection. And if the HIT is not treated, it is fatal. But interestingly enough, there is one percent of the world population that is immune to HIV. It does not get infected with HIV. And these people, the scientists discovered that these people have a different CCR5 receptor. This receptor, the CCR5 here, exists outside of the immune cells. And the HIV virus, it's sneaky, can recognize this receptor and infect the cell. The people that are immune to HIV naturally, they have a modified CCR5 receptor that the HIV cannot recognize and cannot use it to infect the cells. And as such, people that have a different CCR5 receptor are immune to HIV. Professor E.M.Q. wanted to use the same idea, change the normal CCR5 receptor that most of us have and change it to a form that the HIV virus cannot recognize. How do you change the receptor outside of the cell? The easiest way is to change the DNA. DNA is pretty much like an instruction manual for the cell. If the cell wants to produce the CCR5 receptor, it will go into the DNA, check the DNA, find the instruction manual for the CCR5 receptor, in this case it would be the gene of the CCR5, read the instruction manual and then produce the receptor as the manual itself. So if you change the instruction manual, you will change the product. And that's exactly what it wants to do. You change the DNA to change the receptor. How do you change the DNA? You can use gene editing technologies such as the CRISPR-CaS system. This is a system that can read the DNA, find the gene that you want in our case you want the CCR5, find the gene once it finds it, it cuts it. Once the DNA is cut, it sees easier to edit or to change. And this is exactly what it did. You change the CCR5 gene and as such, the cell will only produce this changed form of the CCR5 receptor. So the cell is immediately HIV, because HIV cannot recognize the CCR5. But how do you go from one cell to an entire body? To do that, you can think about in vitro fertilization. HIV and Q recruited couples, Chinese couples, where the mother does not have HIV and the father is HIV positive. It is known in science that the risk of transmission from fathers that are HIV positive to babies is very low. But anyways, recruited couples where the father is HIV positive he collected an egg from the mother and the sperm from the father and then he proceeded doing vitro fertilization, injected the sperm into the egg. And at the same time that he injected the sperm, he also injected the CRISPR-Cas9 system to be able to edit the cell. And I brought a little bit to show you how utero fertilization works. This is the egg. And this needle here, there is this white blood there, that is the sperm, and you will see it being injected into the cell. So the needle goes, it pushes the egg, and then collects a little bit of what's inside the egg and then releases the sperm inside. And that's how vitro fertilization works. Once the sperm is used with the egg, then you get one single cell. This cell is called cypress. And it is at this stage of the cycle when you only have one cell, that you want the gene editing to work. You already uploaded the CRISPR-Cas system, so now it can alter the CCR5 receptor and you will get one cell that has a different CCR5 receptor that is HIV resistant. This one cell will then divide itself into two, and each of these cells will divide into two, and this process will continue until you have about 16 cells. Your next step is to find out if the CRISPR-Cas system did this job and if this cell really is changed to the new CCR5 receptor. To do this, you can do a medical procedure that is called pre-eplantation genetic diagnosis. This means that after three to five days after fertilization when you have many cells, you go into the embryo and you take one cell out and you can analyze the cell to find out if the DNA has changed. This is actually a procedure that is sent nowadays if the parents suffer from a genetic disease and they want to be sure that the child will not suffer from this disease as well, you can do this procedure. And here I'll show you how it's done. You remove the protective layer around the egg and then leave it like that, that will come there. You remove, you suck one of the cells out and then this cell as previously said can be destroyed and the DNA inside analyzed. Once you find the right embryos that have been changed as it wasn't to be changed, then you let these embryos grow and develop until they form this structure that is called the plasticis. These groups of cells can be implanted into the mother. Nine months later, you have a baby in form. And because these embryos have a change on DNA, then these babies will only be able to produce the modified CPR5 receptor and as such, it is HIV resistant. And this is how the pezzanine cube made the first two babies to have a gene edited. These babies, Lulu and Anna, at the point of this announcement, this really shocked the world. But you had always two factions. You have some people, both in the science community and in the normal public, that would say that moves like this, experiments, radical experiments like this is what makes the gene editing feel moved forward, what makes us achieve better and go higher on our imagination. On the other hand, you have a group of scientists that say this experiment was done very prematurely, it was not well planned and moves like this, we fear the populations that will then lead to the condition of loss that can prevent the further development of this field. So let's take a look at what are the implications, technical and ethical of this experiment. I will not be able to go into every single implication but I will do three of each. Let's start with technical implications. Some of the technical implications are related with the use of the CRISPR-Casman system, with the gene editing technology itself. CRISPR-Casman system, although it's a fantastic system, is one of the questions that we had to edit genes, it's still very recent. It is used in the lab for about 10 years. So we are still learning the consequences of using it. And recently we have found out that even though this system is super efficient, it can also lead to some alterations on the DNA that you did not expect. So it will change the gene that you want, but it can also change some genes somewhere else that you were not expecting. These alterations can be, has non-important as a very important with the blue eye and the brown eye, and has serious as this baby being more likely to develop cancer or being born with a malformed liver. So these non-intended defects are hard to predict and sometimes they're even hard to find out, even by analyzing the DNA before the implantation was resolved. Another thing that we can think about is that the CCR-Pyroceptor exists in other bodies for a reason. Its job is not to be there to let the HIV virus in. It is there to actually protect us against the virus. So once you change the CCR-Pyroceptor to a form that you can along the word properly, then studies have found that you are more likely to suffer severe side effects and severe forms or symptoms of infections from western virus, tick-borne virus, yellow fever and Zika virus. And although these virus might all sound very tropical, it's actually not so true because a study in Spain has found that people have a change in this receptor are actually four times more likely than average to die from complications from the flu virus. Another thing that we need to think about is that because these babies have all of their cells in all of the body as a change, so even their sexual cells have no change. This means that whatever consequences good or bad come about because of the gene editing, will be passed along to the next generation and then to the next generation. So these are some of the technical implications about the work when using gene editing technologies in human areas. Let's now discuss some of the ethical implications. Professor Lee has recruited fathers that were HIV positives and we know that the risk of infection from a father to a baby is very low. And nowadays there are medicines called antivirals that are safe, cheap and a proven method of treating HIV infection. They can even protect these fathers from contaminating their baby or even the mother. So they are effective. So now the point that is about is it ethical to use an unproven treatment that we don't really know the consequences of? It's when there is a safe and cheap method to treat these children to protect their family HIV. Another ethical aspect that we need to think about is that when Professor Lee and you did this project and also the gene editing technologies came about it was agreed within the scientific community that we did not know enough about this technology to use it in human embryos for pregnancy. And it was agreed that we would not do this right now. When he did this he broke the trust of the scientific community. More importantly and maybe more concerning is that by doing it in such a secrecy he raises very serious ethical and civil rights concerns about the way that he did the experiment and if the patient or the parents in this case knew about the risks and the consequences of doing gene editing in their babies. Another thing that we need to consider and it's actually something that is being discussed a lot right now in our media is that what is the limit between making a baby better looking or that has better skills in music to treating a disease? What is the difference between enhancement and treatment? If you ask to most of the world population they will tell you that gene editing is fine as long as you are treating for a disease. But then it comes about what you define as a disease because if I ask you do you consider blindness or deathness a disease your answer might be yes but maybe if I ask a death person if he feels like he's safe he might certainly not. So where do you define the disease? These are not so easy questions and we don't have them right now but the truth is, CRISPR babies exist this is not something that you can ignore and pretend that it will never happen again this is not true there are already people claiming that they want to have the next participation so we need to face the fact that this is happening and it will happen so right now there is a large discussion all around the world which I believe that all of us need to participate on because right now there are discussions all over the world about what rules, legislations, laws need to be applied to protect the future patients so that no more ethical problems arise from this and that people know the risks and the need for this alteration on their genome but we also need to be careful that when applying these laws to protect the people that we are also not preventing the development of this research because for HIV we know the gene that can have an impact but for many other diseases we don't really know what causes them and how we can prevent them using this technology so this will need to be for the development and it's not by creating very restrictive laws that we will be able to do this and as Carl Singer said the world is so great today about the pros and cons of CRISPR instead of a paranoid ban on the technology and it is with this sentence that I want to leave you to have a proper conversation about the CRISPR thingies and gene editing technologies and I put together a file full of some documents and some links for interviews that I think will be good for you to learn more about this technology is it good some testimonies from mothers that have genetic diseases and how they feel about having their babies both with gene editing technologies for example so take a look if you are interested in learning more and that's it, thank you very much Hi it's Gina Microphone there is a long microphone here and I want to go in there there is this one there is it in me bringing the microphone thank you very much so what do you think an appropriate level of oversight and control of the thing in general would look like how do you keep the gene involved? okay so you are asking me the question to solve the world problem yes, lovely that we are protecting the people and that we have the best interest of the people in mind but they also need to be set up in a great area because what, for example, not the rest but for some others I am doing gene editing technology but for some others we don't and these risks that I tell you they are not 100% you might do it one time and it goes perfectly and then the second time you do it it goes horribly so you cannot prevent everything from happening but you should try your best to make sure that everyone does it as safely as you can but this is a very very hard question and it's not so easy to answer okay, more questions? more tricky, there is another question in the centre please don't tell me to pick four, please thanks very much anyway, it's all right, we've got let's assume that this the development of the 45% of the 5% is going to be set around the future at some point 10 or more percent of the population will have 45% of the 5% won't the high growth bias adapt to this new 45% and then everyone is actually affected? would you make a repeat because I mean it was not very well yes, so if we start doing this then everyone will have the different CCR5% will the 5% adapt to then use something else instead of this receptor the answer is most likely because the virus has an incredible capacity to adapt to different things and the CCR5% is actually the most common way that the age-riding B virus gets in but there are some other forms of the virus that can get in through other ways so it's not so good and I think or right if the virus feels like it's dying then it probably will change something to find somewhere else to go in I think it's very interesting I think it's a very good point to add that this should be considered in discussion as well what are the risks of applying this for a specific case are there more questions ready right now? or yes? so is there a way to do gene editing on the person who is already born or so far there are technologies only do gene editing on every older cell? it's exactly the year they're leaving from so right now gene editing is used as a medical treatment for some cases of some diseases such for example people that the bubble babies the babies that are born without an immune system then you can do some gene therapy and techniques to help these people develop an immune system and right now there are a bunch of studies coming out of people doing gene editing to solve genetic problems but it has always been done in adults because then you change your cells and you do not pass them on to the next generation so the entire thing of doing gene editing in embryos and why this is so shocking is because you are affecting the next generations but gene editing is actually a very good technique and it's used today for medical purposes thank you now I'm afraid of the back people really feel that it's a smell and they get nervous so I invite you all now to the break please ask more questions to the liana and to our other speakers here in the break enjoy it fast, don't make a mess and thank you liana again