Reading and writing our DNA-code: does this improve human life? Good evening. The question is: does reading and writing our DNA code improve human life? That is a comprehensive question. Human life, humanity… Such a big question, who am I to answer this? Yet, it is an important question So how do deal with this? I will minimise this question for you. Would it make me happy to know my DNA code? And would I make changes by myself or a future child, if I had the possibility If I approach the question like this, a lot of things cross my mind that will probably cross your minds too. So… This is me This me a couple of months ago, on the 1st of April 2017 A date I will never forget I was chosen as the national Teacher of the Year A big ceremony. There is a familiar face applauding in the corner of the picture This means that teaching is my job And tell about DNA That is what I do in the education track Biomedical Sciences in Utrecht I teach mainly first year students In a course that I use most of my time and energy for It is called ‘Genome’ And it is about DNA: How it works; how DNA influences our cells and the human body I learned the basics for this knowledge here, in Wageningen I studied Biotechnology, my academic roots are here And during this time, genetic modification was a much-discussed topic Back then, I did not realise the technological view I had on my discipline I was being trained as a DNA expert And… I took all the possibilities for granted And when people ask questions like: “do we really want this?, it made me a little uncomfortable I recognise this in my students, they are studying Biomedical Sciences to learn about the human body And if I ask them: Do we really want to do everything we are capable of? Then, it takes a lot of effort to keep them focused. Not because they are uninterested, because it is still about the human body, but because these kind of questions make them feel a little uncomfortable. My job is to encourage them to think about it, And I try to involve also other people in questions like this, like you today The weird thing is that I have a lot of knowledge about genetics, But when I look back, I never really questioned if I really want to know what my DNA looks like. It has always been a theoretical exercise “We researchers can sequence and read DNA” But the question whether you want to know more about your own DNA code only got relevant last week When one of my colleagues said… “You can participate in our research program” They have developed a research programme in which they have the permission of volunteers to sequence their full genome And it will give you a hard disk with one terabyte of data In which you are allowed to search for whatever you want. So suddenly, the question becomes reality, and actually I do not know what to do The most important reason for the fact that I never questioned all this, is my family history, that never gave me a reason to think about it. As far as I know, hereditary disorders do not occur in our family We do not have any hereditary cancer in our family, no other diseases… I have no reason to think that my DNA provides useful information about my health That is because I am not ill while I am standing here at this moment, while most hereditary diseases give reason for direct action Most of these diseases are directly visible or can be tested by a newborn child. This does of course not apply for all diseases, but a very familiar example is Huntington’s disease A very severe disease with complaints that look like dementia in the beginning, but will eventually lead to death, and there is no cure But this disease only occurs at the age of around forty, and until this time, it looks like you are fine But still, I do not presume that I have this disease, because then, I would have seen it before in my family The heredity patterns of this disease reveal in most cases if it runs in the family We need a short biology lesson for this, by the way Most of you will probably know this, but you should realise that different diseases have different heredity patterns There are dominant heredity patterns, this means that one of the parents suffers from the disease and can transfer it to the children Those are patterns that are easy to recognise in families There are also recessive heredity patterns, which means that both parents are not ill, but carrier of the disease and if they give this affected gene to their children, a child with the disease might be born. In addition, there are also congenital abnormalities that are not directly hereditary, but where something went wrong in the production of the sperm cell or ovum or in the first phase of development of the child Down’s syndrome is an example of this: not directly hereditary because of parental transmission but something else goes wrong. And that is an important distinction to remember. So, if you look at my life, I was never really concerned with my own DNA Of course, we know that some things run in the family and you might recognise some aspects of your parents, At the same time, I knew that a lot of things that we call characteristics or maybe even some other tendencies I will not call myself mentally disturbed, but sometimes I do things that make you think: ‘Is that normal?’ But then, I look at my parents and think… Well, never mind. Maybe you recognise this a little bit. The thing is… That there was one moment in my life that suddenly made me think Or actually it were two moments, as you can see here. The moment I became Fabian’s dad, he is 3.5 years old now, and Evy, 1 year old I was really drawn into genetics Partially because I of course really hoped for a healthy child, and that starts from the first moment of my wife’s pregnancy, But also on the moment that the child is born and it is healthy and has everything included and good first test results, even then, you look forward and hope that your deepest wish for them to be healthy will come true for the rest of his or her life So you think about it yourself, but others also help you with this because before you know it, the bell rings and there goes a small needle in your baby’s foot to collect a small drop of blood This is called the heel prick As a parent, you can choose whether you want to do the heel prick You can choose not to do it but what I found striking is that I realised that the heel prick existed, and that somebody would ring the bell and do it and we did not really make the consideration. Of course we would do this! That is just how it goes. It was only later that I thought about which diseases they might have checked and what happens if something is wrong? The message was clear: if you hear nothing, everything is fine. If something is wrong, we will call you. They never called. So actually I forgot about this test, Although there is still a small drop of my children’s blood somewhere at the RIVM But they have performed this test. Most of these tests are not yet genetic, so they do not focus on DNA but on substances in the blood But still it made me question: which diseases did they check, and why these specific diseases? And when I did a little research, I found that they think about this really well in the Netherlands and whether you agree with it or not, one of the principles is that it has to involve diseases that require acute action to secure that the first years of the child’s life are healthy It has to be treatable… And there is a little doubt about whether you are allowed to make decisions for a child if it is not directly necessary at that moment. So diseases that only occur in a later stage of life for which you can test your child later, are not involved in this first test. An example of this is increased risk on hereditary breast cancer those are risks that occur at a later age, and everyone can decide for themselves whether they want to check this or not. And this brings me to an interesting part of the story, because you can easily expand the heel prick with the newest techniques. It will not take a long time before DNA sequencing will become so cheap that it might be beneficial to check the complete DNA of each child with one standardised test. Maybe even cheaper than twelve or thirteen different tests that have to be performed nowadays. It is easy to standardise, we have all the facilities, so why not? And the most important counter-argument is what I just said: The right to be ignorant. We do not want to make the decision for the child that this information is available if it is not absolutely necessary for the child’s health at that very moment. And that is why we do not automatically check on things that are only relevant in a later stage. The right to be ignorant. That is an important principle in the question what (not) to check in these screenings. Of course, we had to make some choices already before the child was born. We lived in the time before the NIPT test which meant that we had to decide whether we wanted to check our child on Down’s syndrome Nowadays, this is how it goes In the Netherlands, the majority of women have access to this test whether it is reimbursed, is still a topic of discussion even yesterday, the government had a discussion about this. But what matters, is the following. Technically, it is brilliant and I never imagined it was possible… A pregnant woman’s blood contains DNA of the premature child. I will repeat this: a pregnant woman’s blood contains DNA of the premature child. While I always thought, with my limited knowledge about what is going on in the womb, that there is always a clear distinction between the womb and placenta: this is the child, that is the mother. No, fragments of the child’s DNA come from cells that break down in the mother’s blood where it circulates, not inside a cell but as loose fragments, So you can separate the cells from the blood, and they contain the mother’s DNA But in the substance that remains when you separate these cells, that is a mixture of the mother’s DNA and the child’s DNA And if you manage to separate that properly from each other, which is a more matter of computer skills, because everything is measured and then you can puzzle what belongs to the mother and what to the child, And theoretically, you can reconstruct the complete genome of the premature child this way We are not doing this yet, but we do check whether chromosome 21 occurs three times because that is the trisomy that leads to Down’s syndrome, where this test is based on. So currently, we are using the NIPT test for Down’s syndrome and some other chromosomal abnormalities But theoretically, we could do all types of other tests on the DNA of an unborn child on a short term. One aspect of this is very interesting, so I want to discuss this with you today and it is about congenital abnormalities, that are not present in the mother’s or father’s DNA, but only in the child’s DNA, caused by so called ‘denomo mutations’, meaning that something new changed, and not something from the parents and what appears, is that a lot of mental disabilities that we know, are caused by this type of mutation. So when you track the DNA of mentally disabled children, you can often bring the disability back to… …one or two mutations that originated in a very early phase of development If this is the case with my unborn child, I would want to know this. And nobody knows who is at high risk for this, because we are unable to predict it based on family history. So I can imagine that a lot of future parents want to perform such a test to know… … if such severe mental disabilities are present in the child’s DNA. And that is a very interesting viewpoint in this discussion. Because there is a lot of doubt about the Down’s syndrome test, Because we do not really know what to think of this syndrome Some people do not agree with the easy availability of this test, because of arguments like this “A Down-free society: do we want this?” But maybe the opposite can happen, when tests become available that can indicate… disabilities that are even more serious than Down’s syndrome. And that might even change our point of view about the Down’s syndrome. If you could choose what you want to know from such a test, and you can just tick a list of diseases you could pick the very severe ones, and just drop the Down’s syndrome Until now, it was a question of science what we were able to measure and what not, But now, it becomes a personal choice. It is possible, but do you want to know it? Another interesting development in this field is this one; a lot more specific than the example about mental disabilities. This is a test, based on the same NIPT technology, Where they try to indicate the type of mono-genetic hereditary disabilities that we talked about before… …in the unborn child. Also based on DNA analysis. The only thing you need for this, is the mother’s and father’s DNA Because these types of diseases are transmitted by parents. So the idea is, that if parents are possibly going to have a child with a genetic disorder, That you analyse the father’s and the mother’s DNA, and perform the NIPT test to see if the same mutations occur in the child’s DNA. If that is not the case, the disease will not occur, But if it is the case, the disease will occur. So what do you do? In all these cases, we are talking about a pregnancy of around twelve weeks, and the choice is… abortion… or birth, knowing that the disease will occur but being prepared for it, which can also be an important argument for doing such a test. So the question is not always about abortion. And these are the main dilemma’s with these tests. And this brings me to something interesting… Why not screen the risks for your child before you try to become pregnant? So check if you are at risk of transmitting a hereditary disease to your child before you try to become pregnant Like I said, this does not apply to families where a disease inherits dominantly, because these people already know they are at risk. But in case of recessive hereditary diseases, you could be totally unaware which diseases you carry with you. I know that all the people in this room are carriers of at least five recessive hereditary diseases. All of you. There are thousands of those diseases, and they only occur very rarely, So the chance of a mismatch, meaning that your partner has the same gene mutation for a certain disease, is very small. But still. You might have just walked into that person… And that is why you could perform a test for this: the carrier status test It happens in a lot of places: in Belgium, you can perform this test for several hundred euros So the Dutch decided that they should also implement the possibility for tests like this in the Netherlands and they did that in Groningen, so that is where you can go as a future parent or as a couple to do a test. And something interesting happens there. This is an overview of conditions that the diseases must meet in order to… …make it to the list of diseases that the test checks on. And that resulted in a list of fifty diseases for which they check your carrier status. And these are the conditions and considerations for the team to choose these fifty diseases. And what you see is that it is a list of diseases that occur directly at a young age And that have such a negative impact on the quality of life… …that it is justified to perform this screening. And I think this is for a reason. That we do not simply do a screening on every person for every possible disease, but I would like to hear your opinions on this. Personally, when I would have had the opportunity… …I might have done an extensive carrier status test. But the point is of course: what is next? When you are aware of the fact that you and your partner carry the same gene mutation… …that leads to a 25% chance of getting a child with a certain disease, a classic recessive genetics chance of 25%, but still, 25%. What are the options? You can do nothing, perform no other tests, get the baby and see what happens, You can test it during pregnancy with the technique I just talked about, Of course, there are a lot of other options that lead to a child that is not genetically the same as you are, for example by choosing for a sperm donor, or adoption. But a lot of people have a strong urge for getting a child with the same genetics as themselves. This is something that I recognise myself, too, and I do not know exactly where it comes from. I do not have a biological explanation for this, Because eventually, it is just a bunch of DNA cells that work more or less the same… Anyway, if you do want a child with your own genes but you do not want to transmit a disease, that brings us to what we call the pre-implantation genetic diagnostics, which means you have do to a IVF treatment. And this means you cannot become pregnant in a natural way, but realise the fertilisation in a laboratory, take one cell of the embryo in this way, and test this cell. This happens with more than one embryo, and the one that does not have the disease will be placed back in the womb, and hopefully, this will lead to a healthy pregnancy and healthy child. Embryo selection. This happens quite a lot in the Netherlands, for people that are in risk groups so people that have performed a test and are aware of the fact that they are at risk of transmitting diseases With dominant diseases, it is very clear, but it can also happen with recessive hereditary diseases for example when they already have a child with that disease. Cystic fibrosis is an example of such a recessive hereditary disease, for which people consider techniques like this. And this brings me to the final part of my story, and I deliberately paid a lot of attention to the full story, and only a little bit to this last part, This is not an image of an egg cell that gets attacked, or well, fertilised by a lot of sperm cells, that swim all around it, No, this is an sperm cell that gets injected in an egg cell, which is at the same time also the injection of a lot of small scissors that we call the CRISPR-cas technology. Small scissors that can recover the gene in exactly the right place where it needs correction. Actually, this is embryo repair. This first step is not exactly science fiction, Recently, an American team showed that this really works… and that there is a very limited amount of side effects. Because you might wonder if the scissors does not cut the wrong places of the DNA, it was very carefully tested and it seems to be not the case. It seems to be very precise and safe. but what does not happen, and will certainly not happen in the short term, …or well, you never know… But in principle, no human being was born out of this process. So these embryo’s are used for science, but they are not placed back into the womb to grow further. A lot of people say that this will happen in the future. I do not know. Not in the Netherlands, by all means, because it is forbidden here, In the Netherlands, it is even forbidden to use this technique for research, so we cannot create an embryo in this way to perform research, They are however looking for ways to adjust legislation to make this possible, But what actually comes along with this, is the idea that it is not only possible to… …correct errors that cause diseases, but also the possibility to intervene in different ways, that cause an enhancement of human life through changing characteristics… that bring something positive that you would not have missed when it was not changed, So… It brings up the image of what we call a ‘designerbaby’ or ‘superhuman’. The reason that I would like to end with this unelaborated part of the story, is that, in my opinion, it requires a lot from parents to make the choice to get involved… …in a medical process like this. To do an IVF treatment, which is a serious medical process, Personally, I would never choose such a process, just from my own thoughts and experiences, I would never do this based on… …pretty blue eyes… …or nice curly hair… or even choosing the gender would not cross my mind. This is of course something personal, and you have to look at it from the perspective of the society, so this is not about me, but it is important to indicate that… It is a big deal… …to medicalise the natural process of pregnancy and getting a baby, if there is not a direct reason for this. We can talk about this later What became really clear for me, is that I only started to realise the meaning of genetics, also emotionally, when I wanted to have children. That you really identify with your child and hope that you transmit a good set of genes, And at the same time I think, when I would have had the possibility, I would have used a few of these techniques, because I would have liked to know more. The carrier status… Of course, you silently hope that it will turn out to be nothing, which is quite weird, actually, I felt the same about this combination NIPT test, ‘It will be fine, it will be nothing’, just to be sure. That is a weird way of thinking about tests like these. What I have also learned, that I turned out to handle this situation way less rational than I expected. And I think that is important to involve in your ideas about this discussion, what kind of choices people make. It is not only about facts, but mainly about relationships, trust, and gut feeling, And it is of course very hard for a scientist to approach the subject like this and to see that the impact of this technology is also very emotional: how you feel and think about it. Now, it is easier for me to understand people who say: I do not really want to know all this… But I make different choices. The question is: What would you do? And even more important: what would all of us do? Because it is also about laws and rules about what is allowed. It involves all of us, and I hope I have made you think about this And I would like to hear your views on this. My ideas on this topic have become clear to you all now, but I would like to hear what you think. Thank you.