Welcome back this is the second module in the final unit of this course on behavioral genetics. And as I told you last time what I'm going to do is kind of go off on maybe a little bit of tangents a little bit of speculative I'll give you some data. But I think there's some in, some interesting issues being raised, in genomics now, that relate to behavior. Things that are I think are worthwhile bringing up, worthwhile thinking about. In this first module in this, in this vein, is going to be about genomic medicine. When the human genome project was started back in 1990, the goal wasn't just to sequence a human genome of course, it was to try to produce genomic information that would improve our health. Genomic medicine, sometimes called personalized or individualized medicine, was really the underlining motivation. For engaging in this massive human genome project. What genomic individualized personalized medicine is, is the notion that we can customize our medical interventions or preventions to each individual depending upon his or her genome type. And really the, the human genome project was really meant as a foundation to launch this new area of medicine. It certainly didn't exist in 1990. But is only really beginning to exist today. So what will it take to actually successfully launch a field of genomic medicine? From my perspective, three things. One is, well have to be able to actually accurately predict genetic risk. Hopefully, before somebody develops a disorder. So that we are not treating genetic disorders but rather trying to prevent them. Secondly. Given that we can predict risk, presumably we have some way of intervening, and that intervention differs depending upon our gen, genotype. That really is the essence of individualized medicine. And that's really based on the notion of gene-environment interaction, another reason why people get very excited about the notion of gene-environment interaction. And finally, the last area which to me is actually the most exciting because we know so little about it and it's an area where I think actually psychologists could help a lot. How are people going to process this new genetic information? How are they going to act on it. ? We'll know very, very little about this last area. Genetic counseling and behavioral medicine. So I want to say a little bit about each of these three here in this module. First, let's talk about genetic prediction. And maybe some of you are thinking, well, if genomic medicine is going to require that we're- we can accurately predict whether or not an, an individual is going to develop a disorder based upon their genotype, then what, what reason do we have to be optimistic at all given what I've been telling you, right? Given that most of the heritability of, of all the disorders we've been talking about in this course is missing, that is, we don't know the genetic variance today- Why do we think we could ever begin to predict? Well I think there are several reasons to be optimistic here first of all those we can't predict for schizophrenia today bipolar or cognitive ability there are some diseases for which we can begin to predict non Mendelian diseases. Complex diseases. Age related macular generation is one. It's in, It's in fact now become the, the kind of standard example of a, of a trait where GEWAS is actually identified enough variance that you could predict with a fair degree of accuracy with a small number of variants. It's exceptional but there are a few diseases like that. Like macular degeneration. The second thing to note, in this regard, is that even though overall we can't genetically predict, for most diseases, there are some individuals that we can probably even begin today to predict that, and say that they are at elevated risk. So think back to the 22 or 25 genetic variants that have been identified for schizophrenia. Those 22 or 25 aren't going to help us much predict at the whole population level, but if you're carrying 20 or 21 of those risk factors, then we're probably pretty certain even today to say that your at pretty high risk or your at a substantially elevated risk of developing schizophrenia and maybe if you don't carry any of those we might feel fairly comfortable that in saying that you have a fairly low risk. So even though, for the vast majority of the population, we can't really accurately forecast risk. Even today, we can begin to forecast at the extremes. This person seems to have a higher risk for schizophrenia, hypertension. Cancer, heart disease. This person seems to have a low risk. And the last reason I think to be optimistic is I think, from my perspective, and maybe I'm a little bit over optimistic, is that it's only going to get better. And it's really going to get better for, I think, you out there. Soon we're going to be awash in genetic data. And this is actually one of my favorite slides. It's maybe not the most beautiful slide in the world, but it actually one of my most favorite slide. Maybe many of you know about Moore's Law. Oh boy, Moore's, Gordon Moore. Gordon Moore, was the founder of Intel. It has nothing to do with Genetics Moore's Law. It has to do with the capacity of integrated circuits, computers. it, back in 1965, somebody asked Gordon Moore to project the increased capacity of computer circuits, over the next decade or so. And what Moore did back in 1965 with virtually no information or data. To do this, what he said is that, well he predicted that every two years integrated circuit boards would double in their capacity. Another way of thinking about that is every two years your computing power would double. Actually I think it's every 18 months, but that doesn't matter too much. He turned out he predicted this back in 1965. 50 years later, it's still going on. And that's why your computers are much cheaper today than they were 30 years ago or you have more power in your telephone than whole countries had in their computer in the 1960s. What's plotted here in this straight line is Moore's law. It's actually plotted here as cost per computing unit. So,. It's declining, and it's on this logarithm scale, so it's climbing linearly as function of, of, of time here. What's plotted here in the yellow is the cost to sequence a human genome. This is the first human genome sequenced. That cost $100 million. That was that massive International effort consortium. Today, and this is actually not even today, this is a few years ago, the cost is down to, I don't know I can't read it, but it's probably on this graph about $10,000. The, the declining costs of sequencing genomes is beating Moore's Law. Which is increasing our computing power. It's getting really cheap to sequence a genome. Certainly within the very near future, it's going to cost $1,000 and take a few hours to sequence someone's genome. Your children and maybe many of you, maybe most of you,. Are going to have your genome sequenced. And we're going to be awash in all this genetic data. And people are going to mine that data, and we're going to know a lot more about the genetics of disease because it's actually going to become very cheap, very efficient to get that genetic data. I tell my Danish colleagues. That within a very short period of time, every baby in Denmark is going to have their genome sequence. And then they are going to cross reference that data with all of the wonderful medical health data that they have in there data base's. Genetic prediction maybe not great today, it's going to get better in the future. The second thing though is this notion that we have to have. Treatments that are tailored to genotype. Otherwise we're treating all the people the same anyway so what does our genotype matter? We might be able to forecast risk but it doesn't really differentiate you from me how our doctors should treat us. Individualized medicine is based on the premise that your genotype matters in the way you should be treated medically. Do we have examples of that today? Well, we do have some examples of that today. It's, It's really just starting. The field of pharmacogenomics is really, what pharmacogenomics is is to try to identify genetic factors that predict how you react to a drug. To a pharmacological agent. And it's giving us very hopeful, and certainly very important examples already. And I think there may be about 100 examples that exist today. I mean examples that are actually being used in clinics. We know that individuals differ markedly in how they react to treatments. Some for some treatments some people it's efficacious, for others it's not. Some people have toxic reactions, others don't. How do doctors deal with this? Well many times they just tried various treatments and see how you react to it, and if that doesn't work or if you're sick from taking the drug they'll try something else. We know that the way we react to a drug is actually heritable, so there must be genes regulating that. In fact we know many of the genes that do regulate our drug metabolism, and reaction. And we've begun to identify using strategies like g was genetic variants. In these genes that effect how people react, whether or not. The drug is going to efficacious for me or toxic for me, not efficacious for you, toxic for you. Some of you might now of the example of Warfarin and which is an anticoagulant. Which actually is treated based upon your geno type today. That's what one example. These are going to become much more prevalent in the future. This the whole point of the genome project, to provide a foundation for pharmacogenomics. Now a reasonable question to ask is well are they being used now? Is, are, do we know about these types of interactions for psychiatric treatments? Pharmacological interactions for psychiatric treatments today. I look at this literature, I don't work in, in this area but I look at this literature pretty frequently and the last time I looked, which is very recently, I don't know of any examples today of these types of interactions for psychiatric treatment of psychiatric disease. I full expect though, within the next three or four years, we will begin to see those. That's pharmacological interventions. An interesting question no data on this. But an interesting question that needs to be explored. Is will the same thing happen for psychosocial interventions? There are some intervention researches that believe it's likely. That is take alcoholism. Will this particular person suffering from this disorder be better treated by motivational therapy, cognitive behavior therapy, an AA approach, and alcoholics anonymous approach. Maybe that will depend upon the genotype of that individual. That's and exciting question, in the research over the next, probably decade in this case, is going to begin to answer or should answer to that question for us. The last thing in this Genomic medicine question is, well, okay. Most of the reasearch here is really being done by geneticists they're not psychologists. And I apologies to the geneticists out in the audience but geneticists sometimes have a naive view of behavior how people will process information and I think there's a real need for psychologists to get involved in this area. When I teach, I teach this course here at the University of Minnesota, and when I teach this course, I always have people from genetic counseling teach the course, and I always have some people who get really excited about the area and go into genetic counseling. Hopefully some of you will see, will be excited about that as well. These are very important areas that we need in order to take full advantage of the Human Genome Project. Well what do I mean? Take it as an example. Huntington Disease, and probably many of you know about Huntington Disease. It's a devastating neurological disorder. It's autosomal dominant, it's a [UNKNOWN] disorder, it's not a complex disorder. A neurodegenerative disease. Usually you have an onset in early adulthood, maybe about age 35 on average. And what, what people with this disorder, what happens to them, it's initially a movement disorder, they have uncontrolled ticks or body spasms. But eventually over a course of about ten to 15 years their personality will disintegrate. The will suffer dementia. They'll end up in a vegetative state. And they die because of they're in a vegetative state. Things like aspiration pneumonia. Another reason they die is that 15% of people with Huntington Disease commit suicide. And, which is an extraordinarily devastating rate of suicide. And the reason they, they commit suicide is that it, because it's an autosomal dominant disorder, if you have the gene that causes this disorder, one of your parents had the disease. And so you saw at, the, the height of their life, them develop this disorder and then end it in this vegetative state. It's it's not that common but it's not uncommon about one out of 10,000 individuals of European ancestry it's somewhat lower in other ancestor groups suffer this disorder. There's no treatment for it. What's interesting about Huntington Disease, in the regard here where I'm in this talk about genomic medicine, is it was the first genetic disease where predictive genetic testing became available. And so in thinking about how people deal with genetic information, it's the, it's the area where we know the most about. So some of the lesson, it may not be the perfect example for schizophrenia, because it is fully [INAUDIBLE] on its [INAUDIBLE]. But it is lead to some kind of interesting results. The first thing we might ask, well, you could write, the onset is 30. So let's say mid 30s on average. So now we can genetically test. An individual at any stage in his or her life whether or not they're carrying the gene that will ultimately lead them to die from this devastating disorder. And we can ask, well okay, given that possibility, how many people actually, get the test, are tested for the Huntington Disease Gene? In the abstract if you ask people if a genetic test is available will they get that test a very high percentage will say they will. If you say I have a test for schizophrenia genetics. And, and you ask relatives of, of someone with schizophrenia if they would get the test, 60, 70, 80% will say yes. If you ask people with Huntington Disease before the test became available, would they get the test, 70, 80% said they would. But how many actually followed through and got the test? About ten to 15% of people with Huntington Disease actually get the test. Now, one of the reasons for that is, right, it's untreatable, there's nothing you can really do. There are still reasons to get the test, it helps you plan your life, it might help you with reproductive decisions. Whether or not you should be saving for retirement or taking that nice vacation today. But it doesn't really tell you anything that can be treated. But one of the things that really came out of this was that we really didn't understand whether or not if tests are available. How people will think about those genetic tests whether or not they will actually take the test. That's still today is a completely open question. A question, I think, that really psychology needs a part of, to be a part of answering. Another thing about, that came out interesting as people began to be tested here. Is what were the psychological consequences of a positive test result? Right, it's a death sentence if you get the test result. There's no treatment for this, and it's not a pleasant death. It's this neurodegenerative disorder. Not unexpectedly what we saw, or what the researchers saw in people that got a positive test result is that immediately afterwards. Their level of anxiety and depression increased. But with in six months they adapted, and it fell back down. And based upon that initial research, the belief was well people kind of adapted to this like we adapt to many things in life, and there wasn't much to worry about. But as the people with the positive test results were followed over time. Maybe not surprisingly three, not six months out. But three four years later, their depression levels, their anxiety levels begin to increase. The second thing we really need psychologist to work on in this area of genetic consulting, is how people will react to this test. Not only test for Huntington Disease or Schizophrenia. Or breast cancer genes or everything. This is a very important area of research that needs more psychological input. The last thing I want to talk about genomic medicine is okay now you've got the results what are you going to do with them? This is Francis Collins, we talked about him earlier in this course, he's the head of the national institute of health, he was the head of the, the Human Genome Project in the United States, and this is based upon a very famous lecture he gave in 1999. When the point of the lecture was to talk about how the Human Genome Project would impact genomic medicine. And, in this article or in this talk and then the published an article associated with it, it was completely made up. He talked about a fictitious pa, patient. I think his name was John and he was 23 year old man. Who had he was overweight he smoked he has a high cholesterol level and they ran panel of genetic tests and after they ran the panel of genetic tests and again this is just made up. But this is how we envisioned genetic information will be uses as a consequence of the Human Genome Project. What John got the results that came back, that said, he was carrying genetic variance that for example increase risks for long cancer and cardio vascular and coronary artery disease. But lowered his risk for Alzheimer's disease. This is the apple e. The polymorphism we talked about earlier in prostate cancer. So this is how Collins thought in, in indeed this is probably how the Human Genome Project will impact genomic medicine, in part, we'll be getting information like this that said for some diseases our risk will be increased. For others,our risk will be decreased. The reason I'm printing this out now is what Collins, an eminent, extremely eminent geneticist, said John would do when he got these results. He said, again, it's fictitious, but he said, what John will do when faced with these results is. He'd quit smoking, he'd exercise, he'd lose weight, he'd eat a better diet. Now, if you task a psychologist, the likelihood that John, when faced with these results, is going to go out and do all those things, is almost nil. We need much more input as to how people will, are going to understand genetic information. How they are going to act on it to try to prevent these chronic diseases we don't know that today. We are going to get this information but we really don't know how people will use it. That's going to be very important if genomic medicine is going to be successful. So thank you and next time I am going to talk about another spec, speculative area I guess behavioral genetics and the law.
