Okay, well welcome back,. I told you last time that in this module we're going to have a very special treat, something really special for me, to talk with Professor Erving Gottison. To be honest Erv's office is just I think two down the hall way from my own, so I do get to talk with him quite a bit, but what's really special for me is, you've had to sit through eight weeks of getting my perspective on the field and I think it'd be really nice to get someone else's, a real giant in the field, perspective on this field of behavioral genetics. Erv is, I don't want to embarrass him at the beginning here, but Erv is really one of the preeminent, if not the preeminent behavioral geneticist in the world. I just want to make, if I tried to summarize this resume, his CV, we would take all our time just doing that. So I just want to make two points, one, is Erv word got his PhD a few years ago, from the University of Minnesota. And it really shows what, that this was a very forward looking institution back then. Secondly, a scientist at the end of his or her career would loves to get lifetime achievements from the associations that they participated in and contributed in. I looked through Erv' CV this morning and I counted and I might of counted off or. But I counted ten different lifetime achievements from ten different organizations. He really is one of the most celebrated behavioral geneticists in the world. So, thanks for coming and, and sharing your thoughts with the students here today. The first thing I wanted to, to start with is something that we touched on very early in the course. We began the course with the history. >> Mm. Mm-hm. >> The early history of the field, and Gault and. Of course, you weren't around then. >> Mm-hm. >> Dalton and the, and how [INAUDIBLE] was really probably discredited by the eugenics movement. But it re-emerged in the' 60s and the' 70s. And you were there then. You were a young researcher at that time. You did your dissertation here in 1960 on the Genetics of Personality, which really must have just, I don't even know how you sold that to your advisers. And I guess it would be very interesting to get your perspective on how it is that psychology began to come back to behavioral genetics in the 60s and 70s and what it was like for pioneers like you at that time? >> I didn't know that I was a pioneer until much later but I was very lucky that I chose the U of M for my graduate training. >> Mm-hm. I came here on the GI Bill. You may not know that. >> No. >> After having served in the Korean War as a naval officer. And, during that long periods of time at sea I read psychology and psychiatry journals, and I came to the conclusion that there is no better place than Minnesota for learning about clinical psychology. >> Mm-hm. >> And I was one of the first graduates of the Child Clinical Psychology program. But early in my education here, which began in actually 1956. >> Oh. >> So in the middle of the last century. >> Mm-hm. >> I was very fortunate in taking a course in individual differences, and that changed my whole life and my perspective about clinical psychology and psychology in general. And that course which was then a two-quarter course, was taught by D.G. Patterson, another. Icon administer of psychology and Jim Jenkins, another icon, and during that course I read about twin studies of schizophrenia and other kinds of mental illness, and I thought gee it would really be cool if someday I could pull of something like that. But do it so as to avoid the criticisms that have been leveled. And the criticisms that were leveled often came from people who were well intentioned but they thought that genetics and psychology together was some kind of a fascist plot. >> Mm-hm. Mm-hm. >> And this came about because of the way the. Nazis had bastardized human genetics during that period of time from 1933 to 1945. >> Mm-hm. >> And it was very difficult to undo what they had done. >> Was it hard for you to sell your dissertation topic to your PhD committee? The PHd committee was hand picked by my advisor, my dissertation advisor was Sheldon Reid. >> [UNKNOWN] >> Who we can talk about a little bit. >> Hm, hm. >> But Sheldon Reid decided that he needed a psychologist, who can get interested genetics. He himself was a. Fruit fly Drosophila geneticist. But he was interested in some of the behavioral aspects of the fly's behavior. And he was introduced to me and vice versa by DG Patterson who was also a member of the American Civil Liberties Union. You can see that Minnesota ideas about genetics were. Very, liberal and open minded. And when I got together with Sheldon Reid, he said we really need a twin study. And because the MMPI- the Minnesota Multi-phasic Personality Inventory- had been invented here, it would be interesting if somebody could do a twin study of normal twins using a good. Personality inventory like the MMPI. And that launched me so in 1957 I started chasing around to the superintendents of schools here in the Twin Cities and learned that there were 31,000 children in grades nine through 12. And with the help of the secretaries at the various junior highs and high schools. [INAUDIBLE] Here. I was able to find all of those students who had the same last name and the same birth date. >> Oh. >> That [INAUDIBLE]. >> Boy, that's a lot of work for a graduate student. >> Oh, you haven't heard the rest of it. >> [LAUGH] >> I was a one man show in that time. >> [INAUDIBLE] >> And I was also married, and raising a child. Out of those 31,000 kids, we found 68, I found 68 pairs of twins. >> Mm-hm. >> Identical and fraternal. Same sex fraternal. >> Mm-hm. >> And then I began the chore of trying to convince them and their parents to sign off on doing the MPI and another test by factor analytically derived test. >> Mm-hm. As a backup, and we lost some people that way and 68 pair survived. And then I started to collect them on Saturdays to come to various churches, YMCAs,. What have you, libraries to sit down and take the test. I also had to convince him that I could get some blood out of them. So I was one of the very first psychologists to try to do use igocity. >> With the blood group marker. >> Blood group markers. >> That what've been very, very forward thinking back in 1957 all this. >> And I did all this without any external funding. Just by my charm and personality. And I convinced the Minneapolis war memorial blood bank that this would be a good opportunity for them to find rare blood types. And they saw the advantage right away. They did all the blood grouping for free. In addition, have one more aspect that's different. I took fingerprints from all these kids. >> Mm-hm. >> And I learned to do fingerprinting from the Minnesota Criminal Apprehension Bureau. >> Uh-huh. >> So I took their fingerprints. I drove them to the blood bank. Talked to their parents. Talked to them. And then I took their photographs. >> Mm-hm. So later on I could use their photographs to see whether or not some layman could tell the difference between identical and fraternal twins just by looking at their faces. So I had my hands full and it took me 3 years to do the dissertation. >> What was the impact of that, again, this would have been the first study. In the U.S, for sure, of behavior genetic word studies of personality. What do you think the impact of that initial study was? I think you published it in 1960? Is that, or that was the dissertation, >> Yeah. >> You published it a few years after that. >> No, I published the results. In 1963, and that has an interesting story by itself, so it fits in with your discussion. I sent the writeup of the dissertation in to an editor, a famous editor whom I won't mention by name. He rejected it out of hand, without sending it out for review, on the grounds that the nature/nurture question had been settled in the 1920s, and there was no need to revisit those issues. When my dissertation advisors here learned of that, they were even more angry than I. And they said, we're going to write a letter to that editor and get this re-reviewed. They sent their opinion. They were high powered people, as you could imagine. >> Yeah. >> And it was then sent out for review and accepted. >> M'kay. >> Finally published in 1963. I would say that the impact was close to zero. >> Oh, interesting. >> [LAUGH] that, the first text book in the Hebrew genetics have not being publish into nineteen sixty, by Fuller Thomson. And so, my dissertation came out a little bit too late to be mention there. Although it was then mentioned pretty much regularly in introductory text books of psychology, abnormal psychology, child development. And I would say probably by about 1970. >> Mm-hm. >> About ten years after I finished the dissertation, it then began to be noticed and to be cited. >> You also then, after you did your dissertation, I think, you must have gone and done a postdoc over in the University of London, is it? Maudsley, is that the university? >> The, it's the Institute of Psychiatry at the, and the Maudsley Hospital is based at the Institute of Psychiatry. In London and now it's part of King's College in London. >> And, not only, of course, did you do the pioneering studies in the genics personality, but you probably did the landmark, and I'm not just saying this because you're a friend, but you did the landmark. Twin study of schizophrenia. I think it still stands today as the most important twin study of schizophrenia. It would be interesting to hear how that was received in the field because it really did change people's' thinking about schizophrenia, did it not? >> Yeah. It was quite contentious to get involved in that area. And again, one of my goals, as I mentioned earlier, was to use my dissertation as a jumping board. But in between the dissertation, and going to London, and my post-doc, I replicated my Minnesota study during the time that I was on the faculty at Harvard. >> Mm-hm. >> And that convinced me, again, that this was not a bad area. I was in this rut, and I've been in that rut ever since. >> Mm-hm. >> While I was at the Mosley I was fortunate to come under the guidance of Eliot Slater. >> A psychiatrist? >> He's a psychiatrist. I was very lucky that his brother was a statistician and trained as a psychologist. Yeah. So he opened the doors to this gold mine. >> Mm-hm. >> Of consecutive admissions to the Maudley hospital, over a 16 year period of time. >> Mm-hm. >> And so I was able to re-connect with those twins who had been admitted as patients. And track down their co-twins, whether they were living in. Australia or Ireland or wherever and try to get them to be interviewed, to have blood drawn, if it had not yet been drawn, and to talk to me in a tape recorded interview. >> Mm-hm. >> People at the Mosley said no, no English twin or no English citizen is going to sit still while you do a tape recorded. Psychiatric interview. I showed them that they were wrong. They also willingly took the MMPI and I was then in a gold mine again. >> Mm-hm. >> One of the criticisms had been made of the earlier twin studies and why they were not credible across the whole field of psychology and psychiatry. Was that the individuals who did the study also did the diagnosis of zygosity and- >> There was bias there? >> The diagnosis, there was an assumed bias. >> That was the result? >> Yeah, and in the work that I did, and I was lucky then to have a partner James Shields who had a, a fantastic career first of all as a prisoner of war in Germany. He was captured on the first day of the invasion in Europe. >> Mm hum. >> And later on after he had been released, he was one of the last adults to contract polio. >> Oh. >> So he had had a rough time. And he was Slater's research assistant. >> Mm hum. >> And Slater paired us, two of us up. [COUGH]. And I was James Shield's legs. >> Mm hm. >> And he was my computer. >> Mm hm. >> Archive. He had been through these 16 years of twin collection at the Mosley. >> Mm hum. >> I chased these twins down. I collected the information that we needed. Mm-hm. >> And then, instead of doing the diagnosis, of their psychopathology. The pro ban as we call him, or her. And the code when, we decided that we would submit case histories that were blindfolded in regard to zygosity. >> Mm-hm. >> We submitted these case histories. To a panel of six judges, who were composed of psychologists and psychiatrists, who had a lot of experience with. >> Experts in diagnosis, yeah. >> Diagnosis experts, right. >> This is before the DSM. >> This is before the, well there was a, some kind of a DSM, yeah. >> There was a DSM there, wasn't there. It wasn't, anything that we use. And we had world famous people who had themselves done twin studies, like Slater, like Essenmuller in Sweden, a, a Danish psychiatrist, some psychiatrists who were anti-genetics. We wanted to get opposition views and show that even when somebody didn't believe in genetics. Did the diagnosis. We would still come out with something that was worth talking about. And so we had a credible twin study, we should that without doubt the concordance rate in identical twins. Given that one was schizophrenic, was in the neighborhood of 50%. And given that one fraternal twin had schizophrenia. The other one had it about, 10% ro so at the time and that generated a high heritability. And it was that notion of high heritability that encouraged other people to say this was a avenue worth. pursuing. It, it flew in the face of people who thought that you could convince the audience that people that developed schizophrenia because of the way their mother raised them. >> Mm-hm. >> And that was something that made me sick to my stomach. To think that in addition to the burden of raising a child who develops schizophrenia, that you could then be blamed for having produced schizophrenia. In that child by the way you treated them, and by having a genetic orientation, which was not, of course a hereditarian view of genetics, but one that made plenty of room for environmental input whenever it was deserved. Then we had a theory, which at the time was unique. We published that idea in 1967 in the highly regarded PNAS. They all know that this is the Proceedings of the National Academy of Sciences. And the person who put forward this theoretical idea. >> Mm-hm. >> Or our ideas with, Shields and I developed a polygenic theory of schizophrenia. At that time people who believed in a genetic component to schizophrenia had the idea that it was due to a single major locus. >> Mm-hm. >> Either a dominant gene with incomplete penetrance or a pair of. Recessive genes. And our theory competed with those ideas. And our theory was put forward was put forward into the PNIS by no less than Theodosius Dobzhansky. Again, a famous population geneticist, one of the most famous in the 20th century. So with that kind of backing, we were establishing a place for genetics within psychiatry and psychopathology. >> So what you started, one of those things we, we spend quite a bit of time on in this course is schizophrenia. Because from my perspective it's really the prototypical, psychiatric, genetic. Phenotype, and so we've talked a lot about the research, the twin studies. And what you really initiated back in the 60s with the Maudsley twin study has really accelerated today, in terms of how people think about schizophrenia. We're in the era of large scale GWAS. Let's find the genes. When you look at it, at the field of schizophrenia genetics now what do you think? Is it the progress you expected back 40 or 50 years ago when you started or are you disappointed? You think things are going well there? I'm certainly not disappointed. I certainly feel like, I'm not a grandfather, my children, including you, my intellectual children, move the field forward. A lot of the work that, you and I did while we were at Washington University in Saint Louis involved modelling. And modelling is remote from the biological aspects >> [UNKNOWN] a quantitative model. The quantitator modelade, right, and those notions convince people who said, well, you're not into biology yet. You still, you're only talking about modeling, talking about goodness of fit. [CROSSTALK]. >> Really into biology and. >> Exactly, exactly. This was before anybody was thinking about actually looking at, genes or at snips themselves. That came along, a few decades later. Not until about 1988, or so. And, I was, anticipating that something would happen, but that I would probably be dead by the time that came around. So, I'm happy that I've lasted long enough to see. Positive findings even though nowadays, I mean think about back to my dissertation, I had 68 pairs of twins and they were normals. If you were look, that's okay, that's okay. And if you now realize that Schizophrenia occurs in 8 out 1,000 people, between the time they are born and the time they die. You need a large sample size in order to convince people using GWAS. >> Mm-hm. >> That you have something. And nowadays they're talking about samples of 10,000 or 12,000 individual with twins and control groups of, what? 50,000 that they get from blood banks and so forth. And with those kinds of contrasts, you can get statistically reliable results, in regard to snips. But still, snips are not genes. >> Mm hm. So, you, we did talk about genome wide association studies, GWAS, in this course,. And there as you know there is a debate on the one hand there are those that feel that okay lets increase the sample sizes as large as we can make them and we'll keep finding these genetic variants but any given variant will have a small effect and there are others that think that well our money might be spent better in other ways. In trying to understand the biology of these stories, do you have a view on this particular debate, do you think it's worthwhile to keep pursing these effects of diminishing size of ever larger samples or is it time for a shift, you dont have to say what that shift would be. Are we going to go under another transformation? [UNKNOWN] and the way people approach these disorders. >> I'm encouraged by the increasing array of phenotypic and endophenotypic information that's being collected. >> Mm-hm. >> So at the time that I, that Shields and I began our work, we had no idea that brain imaging would come along. Or that it would produce results. >> Mm-hm. >> Say, if you were to do brain imaging in twins. >> Mm-hm. >> Just think of the amount of information that's generated. Which is there waiting to be tied to snips? In the near future i would say it in the next five to ten years i can see a violence of this shotgun approach of looking at every single snip. G-waz?g >> A shotgun, yeah. >> A shotgun onto these remarkable chips. And that this information will be filtered through the idea that the brain is organized into systems. >> Mm hum. >> And it's these brain systems which will give us the final steps toward understanding the biology of severe mental disorders. I think the work that's been done so far. The analogy would be to, panning for gold dust, in the, Sacramento River. >> Mm hm. >> And right now, we're getting gold dust. >> Mm hm. >> And hopefully, we'll be lucky enough, somewhere around that area, we'll find gold nuggets. >> Nuggets, okay. >> And eventually those nold, gold nuggets will result in gold bars. >> Mm hm. >> And those gold bars are the genes that are actually involved in the neuropathology of schizophrenia. >> Yeah. >> Not only the, the genes themselves, but those genes that control the genes. >> Genes, mm-hm. >> So that moves us into the field of epigenomics. >> Uh-huh. Which is the near future. >> You mentioned the, the term endophenotype which is a term that Irv introduced into the field, now true confession here. >> Sure. >> I haven't mentioned the term endophenotype before. >> Uh-huh. >> But I'll just give the students a gist of this, it's a very important idea but I was kind of maybe waiting for you to come and help me introduce it. So just give the students an idea of what an endophenotype is. Correct me if I'm wrong. But the notion is, is that because things like what, that we study, disorders like schizophrenia or IQ or general cognitive ability, are going to be remote from the primary gene products, proteins. That the, that we shouldn't necessarily expect large genetic effects there for any specific variant. And that's what we're finding in GWAS of course. And the idea you introduced was the notion that what we should do is try to identify phenotypes that are intermediate between the primary gene products, the proteins, and the behavioral phenotypes we're studying and that that might magnify these genetic effects for us and help us better identify the development genetic variance and you call these intermediate phenotypes, and a [UNKNOWN] types, right? Is that. >> Your, your definition is exactly right. >> Oh good, I'm not just in the ball park. >> Yes. Perfect. You, you again get an A+. >> Oh, thank you Erv. >> But, but there is some risk that people don't appreciate in the phenotypes because they are aware of this idea of biomarkers. And, bio-markers are very important. Bio-markers, however, can be things that aren't on the face of it, biological. >> Mm-hm. >> For example, Personality test scores or IQ test scores or sub-tests of those kinds of tests. >> Mm-hm. Endophenotypes are themselves biomarkers. >> Okay. >> But all biomarkers are not Endophenotypes. Endophenotypes for me can be defined at least at this stage of development as characteristics that are not visible to the naked eye. Will work to the naked ear. >> Mm-hm. >> They require some kind of processing. Say, with a PET scanner or with a brain scanner however you want to do your brain imaging. Functional MRIs. That kind of thing. They have to be heritable, and that means that there's still room for doing twin and family studies using in the phenotypes. Mm-hm. >> Because amongst all these biomarkers there will be a subset that will pay off and put a, pointing us toward the neurological neurotransmitter systems that make the brain go awry. >> Mm-hm. The the, the, maybe the last question that I'll ask you, [INAUDIBLE], the last topic I'll touch on. >> Mm-hm. >> Is. So we're, we're coming to the end of the course and the students probably have various motivations for taking a course like this, but hopefully some students have gone through the eight weeks and they're kind of intrigued and they're thinking well, is this something I want to pursue further. And the question along those lines I have is. Is, behavioral genetics has really established that almost any behavioral trait is heritable. Is that something that's just going to get incorporated into psychology, and behavioral genetics is, will, will go away? Or is there a real future to this field, from your perspective? Is this this something. That is going to be there 20, 30 years for now. It's behavior to that is still going to be an important part of psychology? Or how we made are point, is an important point and we should move on? >> You could of ask the same question a number of years ago, about statistics. >> huh. >> In statistics are now taken for granted as being part of all kinds of research in the, in the neuro science. However you want to, to look at them and I see behavioral genetics as having the same fundamental location. >> Mm-hm. >> Within the education of all people moving into the scientist. >> Mm-hm. >> And that means that we may not even talk about it as behavioral genetics. It'll just be. Incorporated with other fundamental courses and hopefully it'll be a required course in the curriculum. It isn't yet. >> In Minnesota it almost is. >> It almost is. >> I teach the course in behavioral genetics. >> Yeah. >> Erv started in. >> 66. >> 66 [INAUDIBLE]. >> Yeah. >> I'm teaching it. Yeah, yeah. But they didn't used to teach ethics in medical school. >> Yeah, that's right. >> And, now that's a mandatory course. And it's a refinement of those kinds of things that will last. >> Mm-hm. >> I, I see this field as being so exciting. I wish I were 50 years younger so that I could be involved more actively in, in the kinds of and the phenotype research that is happening as we speak. >> Yeah. I, I think that's really a good and positive to fall, to end on. I agree with you. I think it's extraordinarily exciting time. For people in this field. And I do, you get an A-plus for your answer. >> [LAUGH] >> Because, I, I think of the, what, what genetics has to offer the psychologist is an extraordinarily powerful set of tools for understanding behavior. And with, when that, those tools are going to be coupled with the developments in imaging and neuroscience, is really going to be a powerful force in our field. And I think you're right. I think it'll be more and more incorporated into the field. So I want to thank you for coming over here today and talking with the students and, and it's been a great time Erv. So thanks a lot. >> Thank you. It's a pleasure. >> Okay, great, thanks. [BLANK_AUDIO]
