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In Their Own Words – John Hardy
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In Their Own Words – John Hardy
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[MUSIC PLAYING]
SUE NELSON: Hello. I'm Sue Nelson. And welcome to In Their Own Words, where scientists reveal their moments of inspiration and some of their influences throughout their successful careers. Joining me is John Hardy, Professor of Neuroscience at the Institute of Neurology at University College London.
SUE NELSON: John, you're most famous for discovering a mutation responsible for Alzheimer's, one of the most common forms of dementia.
SUE NELSON: What's going on in the brain with a disease like Alzheimer's?
JOHN HARDY: In the brain of people with Alzheimer's disease, two types of proteins are building up, a protein called amyloid, which goes around the cell, which forms something called plaques. And then within dying nerve cells, there are structures called tangles, which are made up of another protein called tau. And what we found, it was-- we found mutations in a few families with Alzheimer's in their amyloid protein.
JOHN HARDY: And so that really kind of settled the debate of how the disease started and suggested the disease started with amyloid.
SUE NELSON: Your discovery involved the APP gene and the discovery of something referred to as the amyloid cascade hypothesis. How would you best describe that phrase? What does it mean?
JOHN HARDY: So the amyloid-- well, APP stands for amyloid precursor protein. So this is the gene that we found - the APP gene - is the gene which makes the amyloid protein. And what the amyloid cascade hypothesis said, based upon our finding of genetic mutations, is that the problem started with the amyloid. And then that caused all the other problems in the disease process. And that's why we named it cascade, because you've got a cascade of increasingly complicated problems starting from the original problem.
SUE NELSON: Now, did this breakthrough, did it result from sort of steady years of research, or was there a sudden spark of insight that-- or a path of trial and error, in fact?
JOHN HARDY: Actually, a mixture of all three. Other people had said amyloid was important before. Somebody called George Glenner in the States and Colin Masters in Australia, they had both been working on the amyloid gene and protein before. But they had never shown mutations. So they had previously said amyloid was important. So that was in the background. So they had careful work in the background. But many other people had said many other things.
JOHN HARDY: And the beauty of genetics is that its hypothesis-free. Basically, there are many competing hypotheses. And as a geneticist, we could go in and see which hypothesis fits with the genetics. So it was built on other people's careful work. It was a very complicated process to find the gene. We made many mistakes. But in the end, when we finally understood what mistakes we and others have made-- actually the findings happened over a couple of weeks, in November and December 1990. So the final sprint, if you like, was very fast. And we understood almost immediately what the mutations meant.
SUE NELSON: That's amazing. So it's almost like you got all the bricks in place. And then it all came tumbling down.
JOHN HARDY: That's exactly right. That's exactly it. And I think it's often like that. There's a lot of background work, which you don't understand. And then suddenly one last piece of the jigsaw, and then you finally-- the picture makes sense. That's exactly what happened.
SUE NELSON: You mentioned genetics there. I know you're interested in the genetics of disease. But your first introduction to science wasn't in genetics, was it?
JOHN HARDY: No. I was originally a neurochemist. I was working on-- well, basically on the pathology of the disease, looking to see from a chemical perspective which nerve cells were killed in Alzheimer's and other diseases. So I started off as a neurochemist.
SUE NELSON: And where did that interest in chemistry come from?
JOHN HARDY: Oh, yeah, OK, the interesting chemistry came because my grandfather was a pharmacist in Colne in North Lancashire. And when I was very young, probably five or six, he would-- and, of course, in those days chemists would make their own pills or some of their pills. He had a little lab at the back of his shop. And he let me play in the lab and play with chemicals. You know, looking back I don't know what chemicals they were. I'm sure they were things like bicarbonate, and citric acid, and so on, making fizzy mixtures and changing colors of litmus and so on. I'm sure-- well, I hope that he wasn't giving me anything dangerous to play with. But I always loved chemistry after that.
SUE NELSON: It's funny because my memory of chemistry is all-- things inside test tubes exploding across the lab. Do you think-- I hate to use that phrase "health and safety gone mad." But do you think we've lost something in not allowing children to play with chemicals, so to speak.
JOHN HARDY: Yes, to some extent for sure. I mean when I got to be a little older-- actually I mean by about 7 or 8, I had a chemistry set. And I used to play with that. And I can remember melting sulfur, for example. I can remember looking at that. And I'm sure that that would not be allowed, even for A level chemistry students these days, and this sort of thing. So definitely, the things that we did then would not be allowable now. Definitely, that's true.
SUE NELSON: So how did you go from a sort of childhood interest in chemistry, sparked by your grandfather, towards biology?
JOHN HARDY: Well, both a negative and a positive really. The positive was when I was at school I had a great biology mistress called Mrs. Cox. I was at school in Hale Barns near Manchester. And she really encouraged us to be interested in biology and biochemistry. I can remember we were allowed to go in the lab without her during lunchtimes. And really that interest was encouraged. So that was the push to be more interested in biochemistry. And that led me to apply to do biochemistry and chemistry, when I went to Leeds. But the negative was I was passionately interested in chemistry at school. But when I got to Leeds and started to do my chemistry course, I couldn't stand it. I hated it. So I stopped. I quickly stopped doing chemistry and switched entirely to biochemistry.
SUE NELSON: It's interesting, isn't it, the role that a teacher--
JOHN HARDY: Yes.
SUE NELSON: --can play in your path from one to another. Was there anything else that sort of inspired you? Was a one person that you either knew of, whether-- we know a family member helped you. But was there somebody on TV, or a famous scientist, or a broadcaster that made you think, oh, I love what they're doing?
JOHN HARDY: Well, I'll just say one more thing about my teacher. The first thing is that the class of biology at school was 12. And of those, four of them are still doing biology so for a career. So she didn't just inspire me. She inspired others. I mean like everybody who's interested in biology at of my generation, and actually I suspect a lot younger-- you know, I used to watch all the David Attenborough programs.
JOHN HARDY: And that really made me really interested in biology, and genetics especially. So I can remember being got up by my parents, after me and my brother, who was much younger, went to bed. They would always get me up to watch a David Attenborough program in the evening. And that was really a big thing for me.
SUE NELSON: What about a scientist, which scientist do you admire?
JOHN HARDY: Mendeleev, I have to say. I think that the-- you know, that's obviously chemistry again, but Mendeleev. I just think that when you look at the periodic table, what you see when you read about what he knew about, for example, the atomic weights and atomic masses of elements, the data was really terrible. And yet he turned that terrible data into a systematic thing of beauty and changed chemistry really from being a mess of just things that happened, to something which could be studied systematically.
JOHN HARDY: So I would say Mendeleev is really up there.
SUE NELSON: It's interesting, the way you're crossing from biology, chemistry, biology.
JOHN HARDY: Yeah. Yes, yes.
SUE NELSON: Has that-- crossing disciplines, it sounds like it's been a help to your career?
JOHN HARDY: Oh, I think it has. Definitely, it has. I mean, so I was doing neurochemistry before. And I thought that neurochemistry and studying the brains of Alzheimer's patients was important. But it was only telling us how the disease ended. You're only looking at the end of the disease. And when I saw the genetics-- and this was the work of Gouseller in the '80s particularly-- could help you find how a disease started, I thought this is going to be the way of the future.
JOHN HARDY: If you can study the pathology to study the end of the disease and the genetics to find out how it starts, you can really start to develop the whole picture. And so being able-- being fortunate enough, actually, to switch from chemistry to doing genetics was very important. And now, we've understood the genetics. Now, we're going back to doing biochemistry and neurochemistry again.
SUE NELSON: Would you say that's partly what sustained your interest in the brain.
JOHN HARDY: Yes, for sure. Yes, for sure. Genetics is such a-- molecular genetics is so beautiful. I mean, it really is a science where you get answers about what genes are involved. But then the fascination now especially is to take all of this information and start to make-- if you like, take all these pieces of a jigsaw and start to put the puzzle together. And that's the excitement at the moment.
SUE NELSON: Now, technology plays quite a role now in the work that you're doing. How has it changed how you do your research?
JOHN HARDY: Well, I'll start by finding-- talking about how we found the amyloid gene. The amyloid gene, we found one gene. It took a team of six of us five years to do it. And so that's 30 person years of work. Now, because of the technology, and the gene chip analyses, and the whole genome sequencing, that work would now take a month or two months for one person. And we can discover risk genes because of these whole genome technologies.
JOHN HARDY: Simply by applying a recipe, we know exactly how to do it. We just need to have the right samples and follow the right pipeline. So it's really speeded up by a factor of at least 100, how quickly you can find genes. And actually, it's applicable not only, of course, to Alzheimer's and other dementias, but across the board. It's applicable to all sorts of all conditions really.
SUE NELSON: And you don't just do research on neurodegenerative diseases. You've also been part of an ongoing study, which has been funded by The Drake Foundation, looking into the effects of concussion from specific sports, particularly rugby and football.
JOHN HARDY: Yes. I mean, of course, just to give you a bit of background, there's always been good data saying that head injury was a modest risk factor for dementia, for Alzheimer's disease. That has always been that. So I've always been involved in that and interested in that, because eventually we've got to put the genes and environment together. But I was really impressed a long time ago by a paper from somebody called John Corsellis long since dead, who described the pathology in boxers' brains.
JOHN HARDY: And boxers' brains often-- they have quite a lot of different aspects of the damage, but they have the same tau tangle protein that you have in Alzheimer's disease. So this has always interested me. And Corsellis said, and I completely agree with him, that boxing should be illegal. And I started to say this during the London Olympics.
JOHN HARDY: And that indirectly led people, particularly at Saracens-- initially at Saracens rugby club, and then with the Drake Foundation to start a study-- it's now being led by Hugh Morris, my colleague-- to look at how other sports, contact sports might lead to dementing illnesses. I mean, I think that it's absolutely clear. It's absolutely clear that firstly American-- boxing firstly, American football, and also now soccer lead to increases in the propensity for dementia, the number of tangles in the brain, and so on.
JOHN HARDY: So yes, we've been part of that study. There's a very good study headed by-- our Drake Foundation study is headed by Hugh Morris. We're working very closely with someone at Imperial called Dave Sharpe, who is looking to MRIs of people in contact sports. We're really trying to understand exactly what the relationship is. But there clearly is a relationship.
SUE NELSON: Other than MRIs, how else do you study someone, say a rugby player, to assess the impact?
JOHN HARDY: Well, our first study was-- our first study on the pathology was initiated by somebody in South Wales called Don Williams. He had been collecting and organizing the collection of brains of former soccer players. And we at Queen Square did the autopsies of the soccer players, about a dozen of them. And half of them had evidence-- these are professional soccer players-- had evidence of some of what we call now CTE, chronic traumatic encephalopathy.
JOHN HARDY: So half of the soccer players had evidence that they had had repeated head injury. There's a study published in the New England Journal by Willie Stewart subsequent to ours, which makes the same observation. So there's really no doubt that this is an issue. Absolutely no doubt.
SUE NELSON: And this should be purely from heading the ball? Or would this be from concussion from colliding with another player or a mixture of both?
JOHN HARDY: We actually don't know that really. Probably a mixture of both, but this study from Willie Stewart suggests that those who head the ball more frequently are more likely to be ill. So heading the ball does seem to be an issue, for sure. I mean, I think you have to understand, though, how soccer, professional soccer, works. We see maybe 90 minutes a week.
JOHN HARDY: But of course, these people are practicing every day for hours every day. And so during the practice sessions, some of them, for example-- a person would keep taking corners. And the center forward would head the ball in. And that would happen 40-50 times a day as part of the practice. So it isn't necessarily what we see on the TV which is causing the problem.
JOHN HARDY: I mean, it is obviously an issue. But it's also how the practice sessions are done, which could easily contribute. Let me just say, though, I loved playing football when I was a kid. And I can remember-- I must have been about 13. I can remember heading a corner into the goal when I was about 13 once and being immensely proud.
JOHN HARDY: And I wouldn't-- I think we have to be careful not to deny kids the opportunity. I mean, we don't want everyone to be couch potatoes either. We have to find the balance. And I really remember playing football with great fondness really. I loved it.
SUE NELSON: That's the worry, isn't? It's that you could be seen as the biggest killjoy out for anybody who likes sport, or professional sport.
JOHN HARDY: I mean, I do think the boxing of its nature should be stopped. I mean, really, I'm not-- that's really-- I mean, the goal of boxing is to cause your patient-- your opponent injury.
SUE NELSON: And there have been quite well known deaths from being in the ring.
JOHN HARDY: Yeah, sure. I just really think that should be banned. But the other sports, we need to look at them and minimize the damage, but keep the sport.
SUE NELSON: It's interesting. You're saying you love football, because you're from the northwest. You're born in Burnley, grew up on the Wirral. You've got Liverpool, Everton, Tranmere. I have to say Tranmere there, being from the Wirral myself. Did coming from the northwest-- it's a place known for being very talkative, very chatty, friendly, sportsmen. Did that influence your career at all in any way, that openness to talk to people?
JOHN HARDY: I don't know. I mean, I'll just say, just continuing the football stuff. I used go watch Altrincham play. That was who I used to watch.
SUE NELSON: Traitor.
JOHN HARDY: That's who I used to watch play. I don't know about-- I mean, when I was a kid, my parents were both keen on amateur dramatics. And I actually hated it. But they pushed me into it. I was in about three plays as a young teenager. And though I hated it, I think it was very good for me, because that, I think, has been very important to me.
JOHN HARDY: You learn-- and I went to drama school for one summer, for six weeks. And I hated that, too. But I think one of the things you learn is to how to give a speech, and watching your audience, and understanding if you're boring your audience, and keeping-- making-- and that I think has been extremely important to my career, extremely important.
SUE NELSON: Pushing you out of your comfort zone?
JOHN HARDY: Well, yes. And also, a lot of lectures-- I mean, I might want to judge my own lectures, but I think a lot of lectures can be very boring. And keeping the audience interested is a goal of a lecture. Going to drama school and having to do this was part of the training for that.
SUE NELSON: That's right, because I've been at American universities and been to lectures. And I was always struck how the difference between, for me, American lecturers and British lecturers was that Americans saw it more as a performance, not just as imparting information from me to you-- write it down, copy it down. But they saw that almost being on stage.
JOHN HARDY: Oh, definitely. I definitely see it as being on stage. Absolutely, definitely, I see it on stage. That's no doubt about it.
SUE NELSON: So what personality then would you say best suits a neuroscientist?
JOHN HARDY: Oh, I think it's different for different disciplines. It's different for different disciplines. For geneticists, what you need to be able to do is to get hold of families. And that means talking to clinicians and persuading clinicians to work with you, talking to families and persuading them to work with you, and so on, and being engaged with both the clinician and the family.
JOHN HARDY: So it's a social-- it's definitely a social thing. And then the discipline-- in the old days, less so now, in the old days-- was a ruthless race between the different groups working on families. So engaging and ruthless are the characteristics, I'm afraid, that select for genetics. For other things-- I think, for example, I work with electrophysiologists.
JOHN HARDY: They have to be meticulous and careful. And they tend to be rather introverted. I mean, they're looking down on their rig. So it's different for different scientists. And actually, working with a variety of people, you realize pathologists tend to be rather anal. Neurologists are very observant. Each discipline has its own-- I mean, of course, they're generalizations, but each discipline has its own characteristics.
SUE NELSON: So it sounds like it's almost akin to a medical doctor, in that it's not enough to have the scientific knowledge, the academic knowledge. You have to have a good bedside manner as well.
JOHN HARDY: Yeah, no doubt. Science is a social career. No doubt, it's a social career structure definitely.
SUE NELSON: Now, you've won a number of awards throughout your career, including the Brain Prize and the Michael J. Fox Foundation Award for Parkinson's Research. Now, at the time, that award said it was given for high risk research. What was it about what you were doing then that was high risk at the time?
JOHN HARDY: In Parkinson's disease, everybody-- the background view about Parkinson's disease when we started was that Parkinson's disease was not a genetic disease. So that's why it was considered high risk. In fact, the family we worked on, which we work on with a clinician called Katrina Gwin she had not been allowed to call the family a Parkinson's family, because Parkinson's-- of its nature, "everybody knew"-- and I put that in inverted commas-- was not genetic.
JOHN HARDY: And so that, in a sense, is why it was high risk. There was no guarantee that we would find genes. I should say other people in the same era found important genes at the same time. So someone called Mitzuno in Japan found a gene. And Bob Nussbaum in the States also made very important findings. So we were not alone. I don't want to give that impression. But Parkinson's genetics was considered not to be an important area of research.
SUE NELSON: Which do you prefer? Do you prefer looking at the so-called big neurodegenerative disease, like Parkinson's or Alzheimer's, dementia, or the more rare ones that you also do work on?
JOHN HARDY: There's no separation. What happens is, often when we find mutations in a rare disease, we start to realize that the same processes are going on in a more common disease. I'll give you one very good example of that. And that is that Gaucher's disease, which is a reasonably rare lysosome storage disease of children-- the gene has been known for many years-- the same gene is a risk gene for Parkinson's disease.
JOHN HARDY: And so we see that there are often relationships between rare diseases and common diseases. I'll also say that one of the beauties of working at Queen Square is that we get both types of diseases referred through the-- because it's the tertiary referral center-- referred through Queen Square. And my colleague, Henry Houlden, at Queens Square runs the genetics clinic.
JOHN HARDY: And he is probably found more genes for more diseases than anybody else. I mean, he's a very good molecular geneticist. And he's got a wonderful patient collection.
SUE NELSON: Is this what you enjoy about your work, is that there's always more to learn, more to discover?
JOHN HARDY: Yes, of course. And I'm sure that Henry would agree with this. There's nothing better than finding a gene. Really, there's nothing better than finding a gene. It's a goal that's been scored. It's really a great, great feeling. You know that you've got it. And actually, some of the exciting things in our department-- I'm not directly involved-- is when you find a gene, sometimes it leads directly to treatment.
JOHN HARDY: We've got a very young clinician who's just started called Viorica Chelban at Queen Square. And she's found genes which are involved in ataxia, which are involved in vitamin metabolism. And you give the vitamin, and the patients get better. So sometimes-- it's rare, but sometimes a finding directly leads to treatment. And that's, of course, doubly exciting.
SUE NELSON: Now, you've just named a young researcher who's up and coming. Who have you got your eye on in terms of the field, in terms of, oh, this person or this group looks like they're going to do good things?
JOHN HARDY: I don't want to start naming my colleagues, because then I'll miss somebody. And they'll watch this video and think, oh, why didn't he mention me? But I'll just say, in Alzheimer's disease, I have been very impressed by a young woman from Leuven called Lucía Chávez-Gutiérrez who's just done some-- looked at an old problem, which is how amyloid is metabolized. This has been a problem we've been studying for 20 years.
JOHN HARDY: And she's looked at it with new eyes and made really, I think, really beautiful finding. So I've been really impressed by her work outside of our group. I'm not going to start naming my colleagues, because I might get into trouble and miss someone. But let me just say that Queen Square is a great place to be, because, if people want an academic career in neurology and neuroscience and neurodegenerative disease, they often choose to come to us.
JOHN HARDY: So we're very fortunate in who applies to come and work with us.
SUE NELSON: If you could make one more discovery in your research area, what would it be? Other than a new gene.
JOHN HARDY: I'll just say what I think about the field in general. We made all of these findings in Alzheimer's disease. But we haven't got a treatment yet. And what would, well crown my view of things definitely is if one of the treatments started-- based indirectly on our work started to work. That would really be great. And we are ever hopeful that some of these treatments will work.
JOHN HARDY: And at the moment, we're very interested in this Biogen Eisai drug aducanumab But let's see if that really pans out. If that pans out, that will be great.
SUE NELSON: Have you ever known anyone close who has unfortunately had one of the diseases that you study?
JOHN HARDY: Sure, yes.
SUE NELSON: So you've got firsthand experience.
JOHN HARDY: Oh, I think almost everybody does. I mean, I have firsthand experience of Parkinson's disease, not of Alzheimer's disease, though my father was definitely growing cognitively downhill when he died. But Parkinson's disease, I've had firsthand experience, yes. And of course, they're terrible diseases. But to come back to what you said about what I would like, I'd really like to-- now, we're starting to find for all the genes, for all the diseases-- Alzheimer's disease, we know 40 or 50 genes involved; Parkinson's disease, the same.
JOHN HARDY: To be able to make sense of them and to put them together in terms of pathways-- I mean, we're partway there. But to really understand the disease in terms of pathways, that would be great.
SUE NELSON: Do you think you've got the balance right throughout your career? Because there's a lot-- currently, a lot of PhD students have been quite vocal in their work load is too much. A lot of scientists are saying it's very difficult sometimes to get the work/life balance right between family and their work. Did you get it right, do you think? Or do you think it's difficult to get right?
JOHN HARDY: Well, a couple of things-- it's difficult to get right. I do think that I definitely did too-- I'm trying to pull back now a little bit. I think I didn't get the work/life balance right. I think I did too much work. I think now it's very difficult. I was very lucky, but I got a two into a tenure track job when I was 30 years old. And Actually, that was not uncommon.
JOHN HARDY: I think I was actually a month short of my 30th birthday when I got into a tenure track position. Now, that never happens. Everybody-- all the postdocs that are in my department, they keep on temporary jobs until their mid 30s, mid to late 30s before they get a tenured position. And this is really terrible. I mean, I think it's terrible. It means they have no security.
JOHN HARDY: They don't buy houses. They don't have kids. I think it's really-- the career structure for young scientists now is really much tougher. I mean, I thought it was tough when I was younger. But I think it's much tougher now.
SUE NELSON: So what would your advice be to someone at the early stages of their career?
JOHN HARDY: Well, only do it if you like it. I mean, only do it if you like it. That is absolutely--
SUE NELSON: More than like, I would have thought. It sounds like it's a passion for you.
JOHN HARDY: Yeah, yeah, no, no, sure. You have to really want to do it. You have to really want to do it. But also, choose good-- well, I don't know about-- I was going to say choose good places to work. I'm not sure that I did that particularly. I mean, I think I didn't-- but it was easier in those days. I almost picked-- I mean, for example, I went to Sweden for two years.
JOHN HARDY: And that turned out to be a very good move. But in fact, I was offered the job walking across a car park after I'd given a lecture. And I said yes within 30 minutes, that I would take the job without thought. So though I say think about what you're doing, it isn't what I did.
SUE NELSON: Well, sometimes, it's OK to make a sideways move or a zigzag line towards a career.
JOHN HARDY: Yes, I do think that the career structure is very, very tough at the moment. And one of the problems we have in the grant system now is that the grants favor established scientists. We have these consortium grants all the time. And consortium grants of that nature favor senior scientists rather than junior people. And that makes it even tougher for them.
SUE NELSON: So how do you relax?
JOHN HARDY: I've got a house-- my wife and I I've got a house in northern France, which needs a lot of work. In fact, tomorrow morning, we're driving-- it takes us four hours door to door. So going to fix that up is a way that I relax.
SUE NELSON: So DIY, are you a good DIY--
JOHN HARDY: No, I'm terrible. My wife is very good. My wife is very good. I make cups of tea.
SUE NELSON: What would you consider, looking back, as the highlight of your career so far?
JOHN HARDY: What is the most exciting thing is for suddenly you to understand something which you know that you have not understood before. And no one else has understood before. And suddenly, over a period of an hour or two, the scales drop from your eyes. And the things-- finding amyloid mutations was like that. And that was 90-- actually it was November the 20th, 1990 that the mutation was found.
JOHN HARDY: Finding tau mutations with Mike Hutton in frontotemporal dementia, that was a period of an hour sat in his office looking at data till the penny dropped. My colleague Andy Singleton finding synuclein mutations triplications in Parkinson's disease was fantastic. This was a family we'd studied for years.
JOHN HARDY: We hadn't understood it. And suddenly, we understood it. And that was great. And then finding TREM2 mutations in Alzheimer's disease a couple of years ago was-- and suddenly-- I mean, that's over 40-- is it 40 years? Yeah, 40 years, those four things, where we've suddenly understood something. That's great.
SUE NELSON: Would you consider-- or do you think we will ever find a treatment for these diseases?
JOHN HARDY: Yes, yes. I think we'll definitely-- I think we will. I think we will find a-- think we'll find strategies. I'll say strategies, strategies to reduce their incidence for sure. Now, about reversing the disease, that I'm not sure about at all. But reducing the incidence, yes.
JOHN HARDY: And actually, I think it's worth saying, just by the way, that the incidence-- that's the age-specific incidence of Alzheimer's disease has dropped about 20% over the last 20 years. So without really knowing why, we have reduced the incidence of Alzheimer's disease. That's almost certainly because of better heart health. We don't know exactly why, but that's what we think. So definitely, we can do-- we have done something indirectly already. And I'm sure it'll get better.
SUE NELSON: And I know this is a difficult question. But if you could choose a book, or a piece of music, or a piece of art that describes or sums up you, the essence of you or what you do, what would it be?
JOHN HARDY: Oh, I don't know about that. I'll just say what I'm listening to-- I was listening to this morning and reading last night. I'm listening to an obscure Swedish singer called Monica Tornell, a song called "Vintersaga," which I was a postdoc in Sweden. And that was released then. And it's about a bridge collapse on an icy night in southern Sweden. And I really recommend it, "Vintersaga" by Monica Tornell.
JOHN HARDY: What am I reading? I'm actually reading The History of the 20th Century by-- what's the name of the BBC interview who's on Sunday mornings?
SUE NELSON: Andrew Neal?
JOHN HARDY: No.
SUE NELSON: Andrew Marr?
JOHN HARDY: Andrew Marr. I'm reading Marr's History of the 20th Century, which I'm finding, yeah, very-- well, entertaining and revealing. So those are the two things that I'm doing right now.
SUE NELSON: Well, entertaining and revealing I think sums you up. Professor John Hardy, thank you very much for joining me In Their Own Words.
JOHN HARDY: My pleasure. [MUSIC PLAYING]
Segment:0 .
[MUSIC PLAYING]
SUE NELSON: Hello. I'm Sue Nelson. And welcome to In Their Own Words, where scientists reveal their moments of inspiration and some of their influences throughout their successful careers. Joining me is John Hardy, Professor of Neuroscience at the Institute of Neurology at University College London.
SUE NELSON: John, you're most famous for discovering a mutation responsible for Alzheimer's, one of the most common forms of dementia.
SUE NELSON: What's going on in the brain with a disease like Alzheimer's?
JOHN HARDY: In the brain of people with Alzheimer's disease, two types of proteins are building up, a protein called amyloid, which goes around the cell, which forms something called plaques. And then within dying nerve cells, there are structures called tangles, which are made up of another protein called tau. And what we found, it was-- we found mutations in a few families with Alzheimer's in their amyloid protein.
JOHN HARDY: And so that really kind of settled the debate of how the disease started and suggested the disease started with amyloid.
SUE NELSON: Your discovery involved the APP gene and the discovery of something referred to as the amyloid cascade hypothesis. How would you best describe that phrase? What does it mean?
JOHN HARDY: So the amyloid-- well, APP stands for amyloid precursor protein. So this is the gene that we found - the APP gene - is the gene which makes the amyloid protein. And what the amyloid cascade hypothesis said, based upon our finding of genetic mutations, is that the problem started with the amyloid. And then that caused all the other problems in the disease process. And that's why we named it cascade, because you've got a cascade of increasingly complicated problems starting from the original problem.
SUE NELSON: Now, did this breakthrough, did it result from sort of steady years of research, or was there a sudden spark of insight that-- or a path of trial and error, in fact?
JOHN HARDY: Actually, a mixture of all three. Other people had said amyloid was important before. Somebody called George Glenner in the States and Colin Masters in Australia, they had both been working on the amyloid gene and protein before. But they had never shown mutations. So they had previously said amyloid was important. So that was in the background. So they had careful work in the background. But many other people had said many other things.
JOHN HARDY: And the beauty of genetics is that its hypothesis-free. Basically, there are many competing hypotheses. And as a geneticist, we could go in and see which hypothesis fits with the genetics. So it was built on other people's careful work. It was a very complicated process to find the gene. We made many mistakes. But in the end, when we finally understood what mistakes we and others have made-- actually the findings happened over a couple of weeks, in November and December 1990. So the final sprint, if you like, was very fast. And we understood almost immediately what the mutations meant.
SUE NELSON: That's amazing. So it's almost like you got all the bricks in place. And then it all came tumbling down.
JOHN HARDY: That's exactly right. That's exactly it. And I think it's often like that. There's a lot of background work, which you don't understand. And then suddenly one last piece of the jigsaw, and then you finally-- the picture makes sense. That's exactly what happened.
SUE NELSON: You mentioned genetics there. I know you're interested in the genetics of disease. But your first introduction to science wasn't in genetics, was it?
JOHN HARDY: No. I was originally a neurochemist. I was working on-- well, basically on the pathology of the disease, looking to see from a chemical perspective which nerve cells were killed in Alzheimer's and other diseases. So I started off as a neurochemist.
SUE NELSON: And where did that interest in chemistry come from?
JOHN HARDY: Oh, yeah, OK, the interesting chemistry came because my grandfather was a pharmacist in Colne in North Lancashire. And when I was very young, probably five or six, he would-- and, of course, in those days chemists would make their own pills or some of their pills. He had a little lab at the back of his shop. And he let me play in the lab and play with chemicals. You know, looking back I don't know what chemicals they were. I'm sure they were things like bicarbonate, and citric acid, and so on, making fizzy mixtures and changing colors of litmus and so on. I'm sure-- well, I hope that he wasn't giving me anything dangerous to play with. But I always loved chemistry after that.
SUE NELSON: It's funny because my memory of chemistry is all-- things inside test tubes exploding across the lab. Do you think-- I hate to use that phrase "health and safety gone mad." But do you think we've lost something in not allowing children to play with chemicals, so to speak.
JOHN HARDY: Yes, to some extent for sure. I mean when I got to be a little older-- actually I mean by about 7 or 8, I had a chemistry set. And I used to play with that. And I can remember melting sulfur, for example. I can remember looking at that. And I'm sure that that would not be allowed, even for A level chemistry students these days, and this sort of thing. So definitely, the things that we did then would not be allowable now. Definitely, that's true.
SUE NELSON: So how did you go from a sort of childhood interest in chemistry, sparked by your grandfather, towards biology?
JOHN HARDY: Well, both a negative and a positive really. The positive was when I was at school I had a great biology mistress called Mrs. Cox. I was at school in Hale Barns near Manchester. And she really encouraged us to be interested in biology and biochemistry. I can remember we were allowed to go in the lab without her during lunchtimes. And really that interest was encouraged. So that was the push to be more interested in biochemistry. And that led me to apply to do biochemistry and chemistry, when I went to Leeds. But the negative was I was passionately interested in chemistry at school. But when I got to Leeds and started to do my chemistry course, I couldn't stand it. I hated it. So I stopped. I quickly stopped doing chemistry and switched entirely to biochemistry.
SUE NELSON: It's interesting, isn't it, the role that a teacher--
JOHN HARDY: Yes.
SUE NELSON: --can play in your path from one to another. Was there anything else that sort of inspired you? Was a one person that you either knew of, whether-- we know a family member helped you. But was there somebody on TV, or a famous scientist, or a broadcaster that made you think, oh, I love what they're doing?
JOHN HARDY: Well, I'll just say one more thing about my teacher. The first thing is that the class of biology at school was 12. And of those, four of them are still doing biology so for a career. So she didn't just inspire me. She inspired others. I mean like everybody who's interested in biology at of my generation, and actually I suspect a lot younger-- you know, I used to watch all the David Attenborough programs.
JOHN HARDY: And that really made me really interested in biology, and genetics especially. So I can remember being got up by my parents, after me and my brother, who was much younger, went to bed. They would always get me up to watch a David Attenborough program in the evening. And that was really a big thing for me.
SUE NELSON: What about a scientist, which scientist do you admire?
JOHN HARDY: Mendeleev, I have to say. I think that the-- you know, that's obviously chemistry again, but Mendeleev. I just think that when you look at the periodic table, what you see when you read about what he knew about, for example, the atomic weights and atomic masses of elements, the data was really terrible. And yet he turned that terrible data into a systematic thing of beauty and changed chemistry really from being a mess of just things that happened, to something which could be studied systematically.
JOHN HARDY: So I would say Mendeleev is really up there.
SUE NELSON: It's interesting, the way you're crossing from biology, chemistry, biology.
JOHN HARDY: Yeah. Yes, yes.
SUE NELSON: Has that-- crossing disciplines, it sounds like it's been a help to your career?
JOHN HARDY: Oh, I think it has. Definitely, it has. I mean, so I was doing neurochemistry before. And I thought that neurochemistry and studying the brains of Alzheimer's patients was important. But it was only telling us how the disease ended. You're only looking at the end of the disease. And when I saw the genetics-- and this was the work of Gouseller in the '80s particularly-- could help you find how a disease started, I thought this is going to be the way of the future.
JOHN HARDY: If you can study the pathology to study the end of the disease and the genetics to find out how it starts, you can really start to develop the whole picture. And so being able-- being fortunate enough, actually, to switch from chemistry to doing genetics was very important. And now, we've understood the genetics. Now, we're going back to doing biochemistry and neurochemistry again.
SUE NELSON: Would you say that's partly what sustained your interest in the brain.
JOHN HARDY: Yes, for sure. Yes, for sure. Genetics is such a-- molecular genetics is so beautiful. I mean, it really is a science where you get answers about what genes are involved. But then the fascination now especially is to take all of this information and start to make-- if you like, take all these pieces of a jigsaw and start to put the puzzle together. And that's the excitement at the moment.
SUE NELSON: Now, technology plays quite a role now in the work that you're doing. How has it changed how you do your research?
JOHN HARDY: Well, I'll start by finding-- talking about how we found the amyloid gene. The amyloid gene, we found one gene. It took a team of six of us five years to do it. And so that's 30 person years of work. Now, because of the technology, and the gene chip analyses, and the whole genome sequencing, that work would now take a month or two months for one person. And we can discover risk genes because of these whole genome technologies.
JOHN HARDY: Simply by applying a recipe, we know exactly how to do it. We just need to have the right samples and follow the right pipeline. So it's really speeded up by a factor of at least 100, how quickly you can find genes. And actually, it's applicable not only, of course, to Alzheimer's and other dementias, but across the board. It's applicable to all sorts of all conditions really.
SUE NELSON: And you don't just do research on neurodegenerative diseases. You've also been part of an ongoing study, which has been funded by The Drake Foundation, looking into the effects of concussion from specific sports, particularly rugby and football.
JOHN HARDY: Yes. I mean, of course, just to give you a bit of background, there's always been good data saying that head injury was a modest risk factor for dementia, for Alzheimer's disease. That has always been that. So I've always been involved in that and interested in that, because eventually we've got to put the genes and environment together. But I was really impressed a long time ago by a paper from somebody called John Corsellis long since dead, who described the pathology in boxers' brains.
JOHN HARDY: And boxers' brains often-- they have quite a lot of different aspects of the damage, but they have the same tau tangle protein that you have in Alzheimer's disease. So this has always interested me. And Corsellis said, and I completely agree with him, that boxing should be illegal. And I started to say this during the London Olympics.
JOHN HARDY: And that indirectly led people, particularly at Saracens-- initially at Saracens rugby club, and then with the Drake Foundation to start a study-- it's now being led by Hugh Morris, my colleague-- to look at how other sports, contact sports might lead to dementing illnesses. I mean, I think that it's absolutely clear. It's absolutely clear that firstly American-- boxing firstly, American football, and also now soccer lead to increases in the propensity for dementia, the number of tangles in the brain, and so on.
JOHN HARDY: So yes, we've been part of that study. There's a very good study headed by-- our Drake Foundation study is headed by Hugh Morris. We're working very closely with someone at Imperial called Dave Sharpe, who is looking to MRIs of people in contact sports. We're really trying to understand exactly what the relationship is. But there clearly is a relationship.
SUE NELSON: Other than MRIs, how else do you study someone, say a rugby player, to assess the impact?
JOHN HARDY: Well, our first study was-- our first study on the pathology was initiated by somebody in South Wales called Don Williams. He had been collecting and organizing the collection of brains of former soccer players. And we at Queen Square did the autopsies of the soccer players, about a dozen of them. And half of them had evidence-- these are professional soccer players-- had evidence of some of what we call now CTE, chronic traumatic encephalopathy.
JOHN HARDY: So half of the soccer players had evidence that they had had repeated head injury. There's a study published in the New England Journal by Willie Stewart subsequent to ours, which makes the same observation. So there's really no doubt that this is an issue. Absolutely no doubt.
SUE NELSON: And this should be purely from heading the ball? Or would this be from concussion from colliding with another player or a mixture of both?
JOHN HARDY: We actually don't know that really. Probably a mixture of both, but this study from Willie Stewart suggests that those who head the ball more frequently are more likely to be ill. So heading the ball does seem to be an issue, for sure. I mean, I think you have to understand, though, how soccer, professional soccer, works. We see maybe 90 minutes a week.
JOHN HARDY: But of course, these people are practicing every day for hours every day. And so during the practice sessions, some of them, for example-- a person would keep taking corners. And the center forward would head the ball in. And that would happen 40-50 times a day as part of the practice. So it isn't necessarily what we see on the TV which is causing the problem.
JOHN HARDY: I mean, it is obviously an issue. But it's also how the practice sessions are done, which could easily contribute. Let me just say, though, I loved playing football when I was a kid. And I can remember-- I must have been about 13. I can remember heading a corner into the goal when I was about 13 once and being immensely proud.
JOHN HARDY: And I wouldn't-- I think we have to be careful not to deny kids the opportunity. I mean, we don't want everyone to be couch potatoes either. We have to find the balance. And I really remember playing football with great fondness really. I loved it.
SUE NELSON: That's the worry, isn't? It's that you could be seen as the biggest killjoy out for anybody who likes sport, or professional sport.
JOHN HARDY: I mean, I do think the boxing of its nature should be stopped. I mean, really, I'm not-- that's really-- I mean, the goal of boxing is to cause your patient-- your opponent injury.
SUE NELSON: And there have been quite well known deaths from being in the ring.
JOHN HARDY: Yeah, sure. I just really think that should be banned. But the other sports, we need to look at them and minimize the damage, but keep the sport.
SUE NELSON: It's interesting. You're saying you love football, because you're from the northwest. You're born in Burnley, grew up on the Wirral. You've got Liverpool, Everton, Tranmere. I have to say Tranmere there, being from the Wirral myself. Did coming from the northwest-- it's a place known for being very talkative, very chatty, friendly, sportsmen. Did that influence your career at all in any way, that openness to talk to people?
JOHN HARDY: I don't know. I mean, I'll just say, just continuing the football stuff. I used go watch Altrincham play. That was who I used to watch.
SUE NELSON: Traitor.
JOHN HARDY: That's who I used to watch play. I don't know about-- I mean, when I was a kid, my parents were both keen on amateur dramatics. And I actually hated it. But they pushed me into it. I was in about three plays as a young teenager. And though I hated it, I think it was very good for me, because that, I think, has been very important to me.
JOHN HARDY: You learn-- and I went to drama school for one summer, for six weeks. And I hated that, too. But I think one of the things you learn is to how to give a speech, and watching your audience, and understanding if you're boring your audience, and keeping-- making-- and that I think has been extremely important to my career, extremely important.
SUE NELSON: Pushing you out of your comfort zone?
JOHN HARDY: Well, yes. And also, a lot of lectures-- I mean, I might want to judge my own lectures, but I think a lot of lectures can be very boring. And keeping the audience interested is a goal of a lecture. Going to drama school and having to do this was part of the training for that.
SUE NELSON: That's right, because I've been at American universities and been to lectures. And I was always struck how the difference between, for me, American lecturers and British lecturers was that Americans saw it more as a performance, not just as imparting information from me to you-- write it down, copy it down. But they saw that almost being on stage.
JOHN HARDY: Oh, definitely. I definitely see it as being on stage. Absolutely, definitely, I see it on stage. That's no doubt about it.
SUE NELSON: So what personality then would you say best suits a neuroscientist?
JOHN HARDY: Oh, I think it's different for different disciplines. It's different for different disciplines. For geneticists, what you need to be able to do is to get hold of families. And that means talking to clinicians and persuading clinicians to work with you, talking to families and persuading them to work with you, and so on, and being engaged with both the clinician and the family.
JOHN HARDY: So it's a social-- it's definitely a social thing. And then the discipline-- in the old days, less so now, in the old days-- was a ruthless race between the different groups working on families. So engaging and ruthless are the characteristics, I'm afraid, that select for genetics. For other things-- I think, for example, I work with electrophysiologists.
JOHN HARDY: They have to be meticulous and careful. And they tend to be rather introverted. I mean, they're looking down on their rig. So it's different for different scientists. And actually, working with a variety of people, you realize pathologists tend to be rather anal. Neurologists are very observant. Each discipline has its own-- I mean, of course, they're generalizations, but each discipline has its own characteristics.
SUE NELSON: So it sounds like it's almost akin to a medical doctor, in that it's not enough to have the scientific knowledge, the academic knowledge. You have to have a good bedside manner as well.
JOHN HARDY: Yeah, no doubt. Science is a social career. No doubt, it's a social career structure definitely.
SUE NELSON: Now, you've won a number of awards throughout your career, including the Brain Prize and the Michael J. Fox Foundation Award for Parkinson's Research. Now, at the time, that award said it was given for high risk research. What was it about what you were doing then that was high risk at the time?
JOHN HARDY: In Parkinson's disease, everybody-- the background view about Parkinson's disease when we started was that Parkinson's disease was not a genetic disease. So that's why it was considered high risk. In fact, the family we worked on, which we work on with a clinician called Katrina Gwin she had not been allowed to call the family a Parkinson's family, because Parkinson's-- of its nature, "everybody knew"-- and I put that in inverted commas-- was not genetic.
JOHN HARDY: And so that, in a sense, is why it was high risk. There was no guarantee that we would find genes. I should say other people in the same era found important genes at the same time. So someone called Mitzuno in Japan found a gene. And Bob Nussbaum in the States also made very important findings. So we were not alone. I don't want to give that impression. But Parkinson's genetics was considered not to be an important area of research.
SUE NELSON: Which do you prefer? Do you prefer looking at the so-called big neurodegenerative disease, like Parkinson's or Alzheimer's, dementia, or the more rare ones that you also do work on?
JOHN HARDY: There's no separation. What happens is, often when we find mutations in a rare disease, we start to realize that the same processes are going on in a more common disease. I'll give you one very good example of that. And that is that Gaucher's disease, which is a reasonably rare lysosome storage disease of children-- the gene has been known for many years-- the same gene is a risk gene for Parkinson's disease.
JOHN HARDY: And so we see that there are often relationships between rare diseases and common diseases. I'll also say that one of the beauties of working at Queen Square is that we get both types of diseases referred through the-- because it's the tertiary referral center-- referred through Queen Square. And my colleague, Henry Houlden, at Queens Square runs the genetics clinic.
JOHN HARDY: And he is probably found more genes for more diseases than anybody else. I mean, he's a very good molecular geneticist. And he's got a wonderful patient collection.
SUE NELSON: Is this what you enjoy about your work, is that there's always more to learn, more to discover?
JOHN HARDY: Yes, of course. And I'm sure that Henry would agree with this. There's nothing better than finding a gene. Really, there's nothing better than finding a gene. It's a goal that's been scored. It's really a great, great feeling. You know that you've got it. And actually, some of the exciting things in our department-- I'm not directly involved-- is when you find a gene, sometimes it leads directly to treatment.
JOHN HARDY: We've got a very young clinician who's just started called Viorica Chelban at Queen Square. And she's found genes which are involved in ataxia, which are involved in vitamin metabolism. And you give the vitamin, and the patients get better. So sometimes-- it's rare, but sometimes a finding directly leads to treatment. And that's, of course, doubly exciting.
SUE NELSON: Now, you've just named a young researcher who's up and coming. Who have you got your eye on in terms of the field, in terms of, oh, this person or this group looks like they're going to do good things?
JOHN HARDY: I don't want to start naming my colleagues, because then I'll miss somebody. And they'll watch this video and think, oh, why didn't he mention me? But I'll just say, in Alzheimer's disease, I have been very impressed by a young woman from Leuven called Lucía Chávez-Gutiérrez who's just done some-- looked at an old problem, which is how amyloid is metabolized. This has been a problem we've been studying for 20 years.
JOHN HARDY: And she's looked at it with new eyes and made really, I think, really beautiful finding. So I've been really impressed by her work outside of our group. I'm not going to start naming my colleagues, because I might get into trouble and miss someone. But let me just say that Queen Square is a great place to be, because, if people want an academic career in neurology and neuroscience and neurodegenerative disease, they often choose to come to us.
JOHN HARDY: So we're very fortunate in who applies to come and work with us.
SUE NELSON: If you could make one more discovery in your research area, what would it be? Other than a new gene.
JOHN HARDY: I'll just say what I think about the field in general. We made all of these findings in Alzheimer's disease. But we haven't got a treatment yet. And what would, well crown my view of things definitely is if one of the treatments started-- based indirectly on our work started to work. That would really be great. And we are ever hopeful that some of these treatments will work.
JOHN HARDY: And at the moment, we're very interested in this Biogen Eisai drug aducanumab But let's see if that really pans out. If that pans out, that will be great.
SUE NELSON: Have you ever known anyone close who has unfortunately had one of the diseases that you study?
JOHN HARDY: Sure, yes.
SUE NELSON: So you've got firsthand experience.
JOHN HARDY: Oh, I think almost everybody does. I mean, I have firsthand experience of Parkinson's disease, not of Alzheimer's disease, though my father was definitely growing cognitively downhill when he died. But Parkinson's disease, I've had firsthand experience, yes. And of course, they're terrible diseases. But to come back to what you said about what I would like, I'd really like to-- now, we're starting to find for all the genes, for all the diseases-- Alzheimer's disease, we know 40 or 50 genes involved; Parkinson's disease, the same.
JOHN HARDY: To be able to make sense of them and to put them together in terms of pathways-- I mean, we're partway there. But to really understand the disease in terms of pathways, that would be great.
SUE NELSON: Do you think you've got the balance right throughout your career? Because there's a lot-- currently, a lot of PhD students have been quite vocal in their work load is too much. A lot of scientists are saying it's very difficult sometimes to get the work/life balance right between family and their work. Did you get it right, do you think? Or do you think it's difficult to get right?
JOHN HARDY: Well, a couple of things-- it's difficult to get right. I do think that I definitely did too-- I'm trying to pull back now a little bit. I think I didn't get the work/life balance right. I think I did too much work. I think now it's very difficult. I was very lucky, but I got a two into a tenure track job when I was 30 years old. And Actually, that was not uncommon.
JOHN HARDY: I think I was actually a month short of my 30th birthday when I got into a tenure track position. Now, that never happens. Everybody-- all the postdocs that are in my department, they keep on temporary jobs until their mid 30s, mid to late 30s before they get a tenured position. And this is really terrible. I mean, I think it's terrible. It means they have no security.
JOHN HARDY: They don't buy houses. They don't have kids. I think it's really-- the career structure for young scientists now is really much tougher. I mean, I thought it was tough when I was younger. But I think it's much tougher now.
SUE NELSON: So what would your advice be to someone at the early stages of their career?
JOHN HARDY: Well, only do it if you like it. I mean, only do it if you like it. That is absolutely--
SUE NELSON: More than like, I would have thought. It sounds like it's a passion for you.
JOHN HARDY: Yeah, yeah, no, no, sure. You have to really want to do it. You have to really want to do it. But also, choose good-- well, I don't know about-- I was going to say choose good places to work. I'm not sure that I did that particularly. I mean, I think I didn't-- but it was easier in those days. I almost picked-- I mean, for example, I went to Sweden for two years.
JOHN HARDY: And that turned out to be a very good move. But in fact, I was offered the job walking across a car park after I'd given a lecture. And I said yes within 30 minutes, that I would take the job without thought. So though I say think about what you're doing, it isn't what I did.
SUE NELSON: Well, sometimes, it's OK to make a sideways move or a zigzag line towards a career.
JOHN HARDY: Yes, I do think that the career structure is very, very tough at the moment. And one of the problems we have in the grant system now is that the grants favor established scientists. We have these consortium grants all the time. And consortium grants of that nature favor senior scientists rather than junior people. And that makes it even tougher for them.
SUE NELSON: So how do you relax?
JOHN HARDY: I've got a house-- my wife and I I've got a house in northern France, which needs a lot of work. In fact, tomorrow morning, we're driving-- it takes us four hours door to door. So going to fix that up is a way that I relax.
SUE NELSON: So DIY, are you a good DIY--
JOHN HARDY: No, I'm terrible. My wife is very good. My wife is very good. I make cups of tea.
SUE NELSON: What would you consider, looking back, as the highlight of your career so far?
JOHN HARDY: What is the most exciting thing is for suddenly you to understand something which you know that you have not understood before. And no one else has understood before. And suddenly, over a period of an hour or two, the scales drop from your eyes. And the things-- finding amyloid mutations was like that. And that was 90-- actually it was November the 20th, 1990 that the mutation was found.
JOHN HARDY: Finding tau mutations with Mike Hutton in frontotemporal dementia, that was a period of an hour sat in his office looking at data till the penny dropped. My colleague Andy Singleton finding synuclein mutations triplications in Parkinson's disease was fantastic. This was a family we'd studied for years.
JOHN HARDY: We hadn't understood it. And suddenly, we understood it. And that was great. And then finding TREM2 mutations in Alzheimer's disease a couple of years ago was-- and suddenly-- I mean, that's over 40-- is it 40 years? Yeah, 40 years, those four things, where we've suddenly understood something. That's great.
SUE NELSON: Would you consider-- or do you think we will ever find a treatment for these diseases?
JOHN HARDY: Yes, yes. I think we'll definitely-- I think we will. I think we will find a-- think we'll find strategies. I'll say strategies, strategies to reduce their incidence for sure. Now, about reversing the disease, that I'm not sure about at all. But reducing the incidence, yes.
JOHN HARDY: And actually, I think it's worth saying, just by the way, that the incidence-- that's the age-specific incidence of Alzheimer's disease has dropped about 20% over the last 20 years. So without really knowing why, we have reduced the incidence of Alzheimer's disease. That's almost certainly because of better heart health. We don't know exactly why, but that's what we think. So definitely, we can do-- we have done something indirectly already. And I'm sure it'll get better.
SUE NELSON: And I know this is a difficult question. But if you could choose a book, or a piece of music, or a piece of art that describes or sums up you, the essence of you or what you do, what would it be?
JOHN HARDY: Oh, I don't know about that. I'll just say what I'm listening to-- I was listening to this morning and reading last night. I'm listening to an obscure Swedish singer called Monica Tornell, a song called "Vintersaga," which I was a postdoc in Sweden. And that was released then. And it's about a bridge collapse on an icy night in southern Sweden. And I really recommend it, "Vintersaga" by Monica Tornell.
JOHN HARDY: What am I reading? I'm actually reading The History of the 20th Century by-- what's the name of the BBC interview who's on Sunday mornings?
SUE NELSON: Andrew Neal?
JOHN HARDY: No.
SUE NELSON: Andrew Marr?
JOHN HARDY: Andrew Marr. I'm reading Marr's History of the 20th Century, which I'm finding, yeah, very-- well, entertaining and revealing. So those are the two things that I'm doing right now.
SUE NELSON: Well, entertaining and revealing I think sums you up. Professor John Hardy, thank you very much for joining me In Their Own Words.
JOHN HARDY: My pleasure. [MUSIC PLAYING]
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Spacebar: Play/Pause Toggle
I: Info Menu,
O: Tools Menu
T: Transcript Tab,
S: Segments Tab
F: Forward 15,
R: Rewind 15
L: Languages,
P: Playspeed
M: Mute Toggle,
V: Volume Bar
N: Video Only Toggle,
B: Full Screen Toggle
C: Captions Toggle
Escape: Closes dialogs and menus / Exits Player
Z: Next Transcript Chapter
X: Previous Transcript Chapter
Q: Next Transcript Paragraph
W: Previous Transcript Paragraph
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Embed Size
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You Size - Responsive
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We Size - Responsive
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Picture Overlay Popup
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400 x 225
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512 x 288
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400 x 700
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768 x 1024
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1024 x 512
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1280 x 608
Form Title Cite
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Info
Segments
Related
Thumbnails
Exit Clip Mode
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Click OK to switch to the full video or click if you would like to stay inside the clip. You can always go back to the clip with Tools and Clip Mode