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Richard Henderson (University of Cambridge)

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About this episode

#22. In this episode of The Microscopists, we’re joined by molecular biologist, biophysicist and Nobel Laureate Richard Henderson from the MRC Laboratory of Molecular Biology, Cambridge. We’ll discuss some of his earlier career challenges in biophysics and what attracted him to biology, his pioneering work in the field of electron microscopy, his favorite comic books, and passion for electronics.

 

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Richard Henderson joins Peter O'Toole for episode #22 of The Microscopists and chats about his pioneering work in the field of electron microscopy.

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Please note that this is a Machine Transcription and may not be 100% accurate

Peter O’Toole (00:00:00):
Hello, and welcome to this episode of The Microscopists. I’m really excited today because I’m joined by Richard Henderson from the MRC Lab of molecular biology. And actually I had a very quick look, Richard at your CV, but not too much detail. So I’m looking forward to learning more. But what was amazing is you are about the MRC of Molecular Biology. You got your undergraduate in physics at the University of Edinburgh, and you’ve got the Nobel prize for chemistry. Is there anything you don’t do?

Richard Henderson (00:00:33):
Well, most things I don’t do actually, but when Joachim Frank and Jacques Dubochet, and I went to Sweden to get this Nobel prize there’s two funny stories. One is we were all told somebody has to give a two to three minutes speech thanking the king for giving us a Nobel Prize. And so I decided the best thing was to remain silent. But after about a couple of months, an email came from Joachim Frank saying, Dear Richard, I noticed one of us has to give a speech. I think it should be Jacques Dubochet. Then I sprung into action. I said, excellent idea. Why don’t you ask him? So, Joachim then asked Jacques whether he’d be willing because he was the most charismatic Frenchman to give this speech. And Jacques then replied. He said, well, he said in these Nobel prizes where there are three people sharing, he said, normally it’s the oldest person who gives the speech, which would be Joachim Frank or failing that it should be the youngest person, which is me. He said never is it the middle person? So at this point I could see these dangerous waves coming in from the side. So I sprung into action and wrote a very long persuasive email to Jacques about his character, his charming nature, his charismatic speech. How would you, you know, is he the only one who could do it and he replied with counter arguments to all of my arguments, but then in the end and this was his mistake. He said, of course, but I am a Democrat. And so, you know, since we’d already arranged it, Jacques had to give the speech. And he said, exactly what you said. He said how is it that three people from physics working in biology, get a Nobel prize in chemistry. And so when Jacques told us, this is what he was going to say, I said to Jacques , you know you’ve heard of the Peter principle, which is that in any organization, you get promoted every time you can do the job well until you get your final promotion into a job that you’re unqualified incompetent at, and then you never get promoted again so you remain in this job. So the equilibrium situation in the world is everybody’s promoted until they’re incompetent. So I suggested to Jack, this is what he should put this in his, and he did as he put it in, but then he said, no, he didn’t really agree with this. He thought that it showed that science nowadays was completely unified, which was a kind of nice way to end actually. That’s my, that, so that’s the reason is that there’s, cross-fertilization biology needs physics and the chemists are the most gregarious, outgoing, and welcoming because they’ve realized, you know, the periodic tables finished chemistry isn’t finished, you know, there’s still lots of things to do. But if you look at the chemistry department, probably in York or in Cambridge, it’s full of people doing biology or protein or nucleic acids and things like that. So the chemists are very, very good at being like the Catholic church. They welcome everyone.

Peter O’Toole (00:04:17):
Yeah. And as biologists we need chemists,

Richard Henderson (00:04:21):
Indeed. Biologists need everybody.

Peter O’Toole (00:04:23):
Yeah, it is. We kind of the end point, you know, the physics, the development of all the physics, the engineering, the chemists are all there to really help us to answer your question.

Richard Henderson (00:04:35):
That’s right. Yeah. Well, in the end of course you know, in biology 50 years ago, there were no genome sequences and possibly one protein structure. Now we have millions of genome sequences and apparently in the protein database, there’s 170,000 structures now. So pretty soon you’ll have the genomes of all the animals that people know the name of like giraffes, elephants, lions, tigers, all the genomes are done and you’ll have protein structures known, maybe not for every single protein and every single species, but at least a representative example of them. So really biology is reaching the stage where a hell of a lot is known that there are millions of untapped areas. You know, how the brain works, you know, how lots of different developmental biology of all the different tissues and organs. It’s really a big, big open book for quite a few years to come.

Peter O’Toole (00:05:34):
So I actually, I was going to ask you one of the, I’ve just got a few questions I was going to ask. And so for, you know, for the, for the none specialist, that’s actually watching or listening, why is the structure of a protein so important, actually understand?

Richard Henderson (00:05:52):
Well, it’s difficult now in the modern world to put yourself back to the time when you didn’t know protein structures, but you know, back in the thirties, there were thought of as unstructured colloids. And actually until it was shown that each protein yeah. Was unique and had a unique sequence, cause you know, 1950 when Fred Sanger was doing his insulin sequence, you know, it’s not many amino acids, many people didn’t believe it until that was done. But now of course we know a lot more than we did in 1950. And you know, that almost every reaction in biology is catalyzed by an enzyme. And they’re all enzymes are proteins apart from a few that are RNA based catalysts and they’re not very good. Capitalists proteins are much better. So basically any function in biology, chemical catalysis, mechanical work, motors recognition signaling across membrane signaling, you know, by diffusion it’s all based on the ability. Of individual proteins to do particular reactions and you, you need to know the structure and how they work for all of these proteins. And now of course we know a lot about a lot of things we know about muscle contraction, you know, oxygen in the blood, you know, about all the receptors, you know, about adrenaline and your heartbeat and you know how, how nerves work and signal and they’re all based on proteins. So each protein has its own interest actually in lots of people used to spend their whole life working on one see Max Perutz worked on hemoglobin for his whole life. And some of us tried to persuade him to be interested in other things, but in the end, he never, he developed a slight interested in Huntington’s disease from these Polyglutamine tracks when he was older, but he was still mainly focused but now you know, can determine many protein structures in their PhD thesis because of the power of the methods. But anyway, the proteins do everything in biology and you know, you, you, we need to know their structures, but once they’re known, not everybody needs to know everything about proteins. You know, you probably need an undergraduate degree. You need to know a few examples. And then the general principle of it just feeds through it to, you know, subconscious minds of the scientific community, the lay community. So, you know I, I have not worked on all that many proteins, but even now there are new ones being discovered or there are proteins that are in certain peculiar, you know, amoeba or bacteria that haven’t been found by homology and other species. So there’s still an untapped area with proteins that are popping up out of the undergrowth, but generally, we know now a lot about protein. So it’s actually not quite a closed book and it’s not like the period yeah. Table, but it’s getting close

Peter O’Toole (00:08:53):
Now, of course. So once you know, the structure, the importance of knowing it means you can then direct drugs and be more clever and smarter with how you’re developing drugs to treat different aspects of life with that. Actually I think you’re, you have a company just in that region. Yeah.

Richard Henderson (00:09:12):
So yeah. So I didn’t, you know, obviously you can ask you why is it interesting to know about proteins, but also almost all the drugs that you take? Not all of them. They are either activators or inhibitors that are directed at one particular drug target, which is usually a protein and in the human genome, for example, putting aside pathogenic organisms, but there’s 20,000 proteins. So you could argue that a complete Pharmacopia of drugs would mean you’d have one drug that inhibited every one of the 20,000 proteins in the human, in one set of test tubes and then another drug that activated them. And usually in disease processes to cure you of say cancer, usually there are half a dozen genes or some cancers, just two or three others, 20, you might want to either block or activate more than one gene. And there aren’t, you know, there’s probably drugs against several hundred drug targets, but there are not, there is not yet a complete library of activators inhibitors for all the protein targets and of course there are other targets like viruses and bacteria, which you want to get rid of. So for example, in Corona virus, there are two drug targets that people think if we had really good drugs, which we do not have yet, that would block the activity of the protease that cleaves up the polyprotein, that’s absolutely essential for coronavirus. And there’s the RNA polymerase that copies the genome of these are the two prime drug targets. And there are hundreds of companies working on them and they all have all the companies they all have now in the lab, really good in vitro inhibitors that block the activities at both of these drugs, but it will take three or four years until they feed their way through to being approved for use. And then, you know, if all goes, well, you’ll take a pill or two pills or one pill that has both drugs in the same. Uh and then it will completely stop coronavirus dead. You won’t even need to bother with vaccination, but that’s some years off and HIV. That is the current situation. There’s, you know a multi-drug treatment that will stop HIV in its tracks and people who were dying within six months after getting HIV from aids. Now they can live forever, but they have to take the drugs indefinitely. But with coronavirus, you probably only have to take them long enough to clear you of the virus and then you can stop taking them again. So it probably needs some investment and the drug companies don’t like in terms of a business model a drug that you take one off and completely cures you forever is not a very good business model is a drug that when you get the disease and HIV is such one, you have to take it every day for the rest of your life. And so, you know, drugs against Alzheimer’s disease, they’ve got a lot of investment, but drugs against coronavirus that give you it, you know, they will need to have some government or state or world health organization’s support to create the impetus to develop them, but the companies are already in waiting to take the money. So I just had lunch today with Malcolm Weir is the CEO of the company that we started about 14 years ago, Heptares, Sosei Hoptares and they’ve got about something like 40 drug targets. And, but only one or two of them have actually reached the stage of being in humans in clinical trials, not yet in, you know, so it takes for small molecule drugs, or even for antibody drugs, if you’re putting them into people, it takes many years of clinical trials. And the great thing about the vaccines, they’ve been able to do a very fast track development of it and now in the Britain, at least in the US and some other countries the vaccines at work, it’d be much better to have drugs. And these are inhibitors in this case against proteins. In the case of coronavirus, the spike protein is on the outside of the virus and the preliminaries that makes the next virus once it’s infected the cells, those are the two prime targets and people who do proteins and drug companies that develop drugs against the proteins. They are the people or the experts who can do the development, but they need to be pushed and funded by investments either from themselves or from venture capital or from governments or from the tax-based. So it is it is it’s working. I mean let’s say before 1940, there was very little, I mean, penicillin, probably the first one that was just, just, just pre war and during the war and then all the antibiotics. And now it’s a big industry, actually, pharmaceutical industry didn’t really exist a hundred years ago.

Peter O’Toole (00:14:40):
So just, just rewind the clock back you’ve got, you’ve got a spin out company, well established company that you spun out or set up started. So that’s another, another complete dimension to your, your career. And you start to take, why, why, why as a physicist, did you choose to then go into biology? You’re not the first, I think Dan Davis was exactly the same. Did his degree in physics and then went on to become a star of immunology. Why, what attracted you to biology?

Richard Henderson (00:15:17):
All right. Well, so I can, you know, I, I I’ve told this a few times actually, but when I was in school, I really did enjoy maths and science and I couldn’t wait to get rid of the, the, the burden of having to study other things like English, French, Latin, whatever. And so when I was about 13 in high school, we were asked which subjects we would like to select for secondary education. It was, it was the highers, which is, Scotland’s like A levels in England or, you know, baccalaureate or whatever. So I filled in my form and I said, I was going to do maths science and technical subjects engineering. Yeah. And then at this point English was compulsory, but none of the others I called into the headmaster’s office age 13. And they say you know, that you won’t be able to go to university unless you have a language, a foreign language and so I said, I only 13 then from the rural parts, I hadn’t heard of university at that point. We, you know, our family, you know, we, we, universities didn’t exist. We, we live in the countryside. So I said, okay, well, that seems like good advice. So then I look at my ability in languages and I had studied age 11, 12, 13. I had studied French and Latin and in the exam just before I decided to give them both up, my score was 47% in Latin and 48% of in French and 50% is supposedly the pass mark. So I said, okay, 47 versus 48. I better to do the 40. So I chose French by 1%. So yeah, 48% in my, this is at the end of three years of second. So then I studied French for two more years and I sat my lower Scottish exams, which is equivalent of O levels are GCSE

Peter O’Toole (00:17:36):
60 years of age.

Richard Henderson (00:17:38):
And so I’d be, I’d be 15 or something like that, taking my, my O levels. And I’m the only one I failed was French. So and as the only one in the class who failed, because I was obviously the most marginal and I was only taking it because the headmaster told me I had to. So then in the sixth year, which is the final year of school in Scotland I’m in the class and it’s the teacher. And there are only two of us left me because I had failed lower French and another young girl, same age as me, but she was, she had failed higher French cause she’d picked. So we had individual tuition for a whole year, both of us, one teacher two pupils. And at the end of that year of essentially, you know, several lessons every week for the whole year, I did pass, I got a by then they changed the, the result and the grading was A, B and C. So I scraped in with a C and consequently, I was allowed to apply to university. And so but at that point I finally could give up and then I did physics and maths in Edinburgh. And then of course, the question you’re asking is how did I get from physics and maths

Peter O’Toole (00:19:12):
To biology? Well, why choose it? Yeah.

Richard Henderson (00:19:15):
All right. So I always studied carefully each step in my career and in my let’s see final year of physics. So I gave up maths after two years because you had to, you know, you have to, I did physics and maths for two years, and then I, you have to choose. So I chose physics and gave up the maths. So then the final two years, four year degree at Scotland, third year and fourth year was physics. And at the end of that, I thought, well, what should I do next after high school scraping through with the French physics degree doing well in physics, I have to say, no, cause I enjoyed it. I went, I thought I’d better go and see the careers advisory office in Edinburgh University. So I went along to the career advisory office and they said, oh, look at all these jobs you’ve done in the summer to earn money and physics and they looked at the grades and they said, oh, they said it’s clear that you should do a PhD. So I hadn’t really heard about PhDs either, but nevertheless, I thought, okay, I better look into this. So then the final exam came in physics at the end of the fourth year. And in Edinburgh it was six papers. So five of them are on physics, you know, optics, electronics and so on. But the the sixth paper was always considered to be a bit of fun that you had to write an essay and you’re supposed to you know, be somewhat philosophical. So my essay at the end of my physics degree, it was multiple choice. You know, they were just giving you the opportunity. So one of the topics was, would you like to write an essay for two or three hours? This was on. And I picked writing an essay on time now, you know, time normally means relativistic time and science, but I decided this was a fun thing. And because I’d been thinking about it a lot, I wrote that time consists of the past present and future. But since we know everything about the past and the present, or at least you could look it up, the only thing that’s interesting about time is the future. And so then my little essay was about what is the future of physics? So then I, the rest of my several hours of essay consisted of a little paragraph about astrophysics, which would be cosmology, gravitational waves. So a little bit about solid state physics, which would be transistors and computers. And so on. Now a little bit about single particle physics, CERN and particle colliders, a little bit about fusion research and how it’s going to produce an unlimited power. And then the final one out of about five or six areas was biophysics. And I said, okay, biophysics needs physicists to do physics in biology. And we had had a very good physics teacher at high school called Bill Cow, who is just an enthusiast. And he was keen also on biology. And he had recorded a lecture by one of the lecturers in Edinburgh University called Jack Dainty and he was in the Edinburgh University biophysics department that they would never make him into a professor. He was a lecturer or a reader, so eventually, and he was there still while I was at university. I never met him, but our physics teacher recorded Dainty, giving a lecture while we were still in high school, I played it back to us and it was Jack Dainty. He was putting an electrode down the middle of Nutella, which is a plant cell with a big cell and looking at electrical currents in a Nutella and bill said, this is the future of physics in biophysics. So I, four years later I went through all the different options and decided that he was right. And so then I said, okay, now I’ve decided on biophysics. Where can, where in Britain can I go? I didn’t want to go out of the country. So I then tried to research biophysics all over Britain and in the physics department, the medical research council, where I ended up nobody had heard of it in the physics department. I certainly heard, I hadn’t heard medical, et cetera, but in our, but there was everybody who was doing your PhD or thinking of it. It was the science research council in those days, which has now metamorphosed into six different research councils. So the SRC had a handbook, this thick, and I looked through it found biophysics, found all the biophysics departments in Britain, you know, Oxford, London, Leeds, Norwich and Dainty by then was at Norwich in my final year? So I wrote to them all and said, what do you do? Do you do PhDs in biophysics? And several of them Leeds and Norwich wrote back and said, we don’t allow anybody into our university to do a PhD. You have to do an MSC first. And I said, well, I’ve had it with exams, no more exams for me. So I went round anyway, and I went to Kings college in London and it was John Randall, Maurice Wilkins, Jack [inaudible], Jean Hanson was a really good department. So I went there and, you know, November, 1965, all the way down to London in our old car went there for a day and I thought quite a good department. So I wrote to them and said, I’ve decided I like to do a PhD in biophysics at Kings College. And they wrote back to me Struther Arnott uh saying, okay, thank you for your application. We’ll let you know. So they didn’t say I could come so I thought, well, maybe, you know, while I’m waiting for them to reply, I should go and tell the head of department in Edinburgh, the physics department who is called Bill Cochran. so I made an appointment, went to talk to the head of department, said, I am in your final year physics class. And there were only 40 of us. So he probably, he probably knew who I was. I was, I said, I decided to go into biophysics and I’m going to Kings College London. And he said, oh, he said, no. He said you mustn’t do that. So finally, I found somebody who knew about it and never taught. He said, you must write to Perutz in Cambridge. So I wrote to Perutz January, 1966 and heard nothing back. So after about six weeks, I wandering around the physics department then saying, you know, this this is the lab in Cambridge is no good. I wrote to them six weeks ago, haven’t replied yet. And they said, I said, I’m thinking of writing another letter asking them whether they, and they said, oh no, no, don’t do that. They’d been writing for references. So finally I did get a little note from Max. One line said, dear Mr. Henderson thank you for your interest. Would you, would you like to come and visit the lab? This is where I am now in the building here. So I immediately wrote back saying dear Dr. Perutz. yes. I would like to come and visit the lab. Could I come next week? So then he writes back immediately. He said yes, you could come next week, but it’d be much better if you came three weeks on Saturday when we have a special open day for students. Yeah. So I went on the train overnight. No hotels, no staying. So I got an overnight train to Cambridge, arrived at 8:00 AM at the station on a Saturday morning, came to the lab and there were about 30 students, 28 of them from Cambridge and two, one from London, one from Edinburgh, and they’re all working Saturday morning, you’re all working. And I thought this, this is better than Kings because on Wednesday five o’clock on a Wednesday afternoon, it was getting pretty quiet. And I was about the last one to leave. But in Cambridge on Saturday morning, they’re all working. So I said immediately, so I withdrew my application to King’s and applied to the lab and they accepted me about two days later, say, doesn’t matter what your degree is, you can come. So they didn’t even care whether I had a first, second, you know? So, so anyway, I ended up here and you know, it’s, I’ve been here for 53 years or something like that. So there you go.

Peter O’Toole (00:28:41):
That’s a long, long time. There’s two things I’d like to pick up the first one. It’s more, I’m just more interested. What, what was your car that you drove down to London?

Richard Henderson (00:28:51):
It had, I had time to show you I have a beautiful photograph of the car too I can send it to you. It was a Morris eight series E, 1948. And we bought it in 1962 when I was 17. So I had two friends who were also studying physics and it also came from the same class in Burmoores School, in Edinburgh. And when we, two of us were too young to drive. So one of the three of us had been taught by his father how to drive. So the three of us, we each put 10 pounds into the kitty and we a car for 30 pounds, which was about 10% of the new price. Yeah. And it was a, it was a 14 year old Morris, eight series E. And it worked actually w you know, it went wrong a lot. So we, we became very good motor car repair engineers, but the one friend who could drive taught the other two of us, how to drive, because that was our hobby. And of course, we both passed our test within eight weeks or something like that. And then we had one car between three of us and we would just share it. So we would take it to the Highlands. I took it to, I took it around Ireland with a couple of other friends once, and it broke down a lot, but we’ve got expert at fixing it in the end. And then after about a year and a half with the three of us owning it, one of the friends decided he wanted out. Yep. So we, we each gave him five pounds to buy his shares. And then,uabout a year later, my parents moved out of Edinburgh into the country into, and I needed transport. So I traded in my share as well,ufor five pounds or something like that and bought,uI bought,ua more,uVesper motor scooter because, you know, we didn’t have much money, but we lived,uin Edinburgh, but we were about to move to,uBroxburn, which is about 15 miles from Edinburgh in the countries up sort of. But I had noticed that in the back yard of our house, where we lived right in the middle of Edinburgh, there was,uan old Vesper that had been there for six months. And,uso I asked my mum who is quite well-organized, could she find out,uwhat that Vesper was doing? And she found out that it was owned by somebody who had bought it, you know, there were new, new, there, there were about, probably about a hundred pounds. So this guy who was in his twenties had bought a Vesper scooter for about 30 pounds and didn’t like it. So he tried to sell it back to the dealer and the dealer said, okay, he said, I’ll give you 10 pounds for it. He said, that’s rubbish. He said, I could make more money by breaking it up for parts. And so he wasn’t knowledgeable. He started, he cut out all the wires, you know, everything was just complete mess. And so it didn’t work. So my mom, so I bought it for seven pack. So I sold my car, my share in the car, my half share, which 15 pounds initially sold it for five pounds and bought the scooter for seven pounds and then reconnected all the wires and got it all working. And it never quite, but it worked. And then it turns out riding a motor bike or a scooter in Scotland in the winter. It’s not very clever is dangerous thing, actually. And one morning I was working on the post at Christmas and money delivering the post involved, driving from Broxburn into Edinburgh at seven 30 in the morning on my little Vesper scooter. So I’m going along 45 miles an hour. And you know, it’s very early morning, not a lot of traffic. And I had this feeling as though I was floating on air and it turned out it was black ice, a completely invisible and friction, coefficient of zero. So eventually the wheels have lost traction and the scooter swung to the side and then went back and it got, eventually I fell off and I skidded along for, you know, 20, 30 yards. Ubut it’s completely smooth. So my trousers are undamaged because I’m, I’m on ice.

Peter O’Toole (00:33:50):
You haven’t stopped yet. It’s still sliding. At this point, you haven’t stopped. It’s the stopping that hurts

Richard Henderson (00:33:57):
Sliding. It stopped before me cause it had metal I slid on, but I, I got up. I mean, it’s, it’s in a big Motorway road. Fortunately there were no cars coming. So I got the scooter up, got back on and then it was a bit more careful because I realized now it’s icy. But at that point I decided that perhaps it was time to trade in the motorbike scooter. So then I did by having saved up some money. I did buy an Austin 830 for 60 pounds. And then I had that for about five or six years. And then when we went to America to be post-docs, I eventually sold my 60 pound Austin 830 that I bought that I used for it. I sold it to the same friend who bought my share in the Morris eight. And I sold it to him for five pounds

Peter O’Toole (00:34:58):
Quite well, with five pounds. Doesn’t it.

Richard Henderson (00:35:01):
You can see that you know I had a lot of knowledge and expertise, but no money. So it’s amazing. What you could do with five is that no, that would be about 50 pounds. That’s who you’d be. You’d be selling a pile of old junk for 50 pounds, but you know, you can, you can easily buy a car. Now you can get beautiful cars for 50 or a hundred pounds. And as long as you’re willing to fix it yourself, if you want the garage to fix it, you bet just to spend a bit more

Peter O’Toole (00:35:34):
That’s those two things, don’t take this the wrong way, but you’re a very man. So I thought until you bought a a Vesper up in Scotland, cause that was always going to happen. That was always going to happen up there. So the other side is, you said that was your hobby. Was your car and fixing your car engineering, your car. What other hobbies do you have? You’ve gone down the LMB. You’re working six days a week. You’re working on Saturdays. What did you do outside of work?

Richard Henderson (00:36:07):
At what age? When I was a young lad, I didn’t really, I didn’t have any hobbies at all, actually. I have, I have so many hundreds of stories actually, but it’s because they, they, you know, they impressed it on me, but you know, I was brought up in rural Roxburghshire which is two or three miles north of the border,uwith England. And I, I, my mum tried to get me to read books and I did try, but I never managed to read a single book of any kind. And I had,umy mother’s family lived in Edinburgh and we visited once a year for a week for a holiday and my grandmother’s sister. So my great aunt, she owned a little corner shop in Edinburgh,uin William street. And she sold newspapers,ufirewood, firelighters, cigarettes, chocolates,uit was, it was a general store. It was like Sainsbury’s but tiny. And she had to work from 7:00 AM until 7:00 PM every day. And the onD she didn’t have any children of her own. But the great thing for me is that every week from the age of about six, she sent me every single child’s comic in the news agent shop. So every week we got this package, which came from the grandparents and the great aunt and, you know, it would have things for my parents in it, but for me it had maybe 15 comics, everyone, the Lion, the dandy, the Beano,

Peter O’Toole (00:38:04):
Your favorite, what was your favorite comic?

Richard Henderson (00:38:08):
The favorite word? Good question. I think there was one call did they didn’t have the, the one I would have liked, which was not in my aunt’s shop was the Eagle.

Peter O’Toole (00:38:22):
Okay. Yep. So I’ve heard of it at least.

Richard Henderson (00:38:25):
Yeah. But no, but I’m leading into, so that’s what I had. And then since once I’d read them, they had no further value to me, so I’d give them away. And as a result, I became quite popular for giving away free copies of one week old comics. But in our village, you know, there must have been 800 people. The school had about 150 pupils in it. Our class had 20 to 20 pupils, seven classes, 150 people. The year ahead of me, one of the people I knew was another young lad, a year older than me. And he was the son of the headmaster of the school. And I was slightly friendly with him. But one time when I’m about 12, 11 or 12, something like that, he went to the same secondary school as well. That we went on the train every day from the village where I grew New Castleton to Hawick, which is, you know, 20 miles north. So every day, morning and evening we went on the train and of course there were 20 or 30 other children and the headmaster’s son went on the same train. So I certainly friendly with him. And one time visiting his house and I noticed that he has a copy of a little magazine called boys on paper. Now you may not have heard of this, but no, it’s a very boy oriented paper, you know, with adventure stories and sort of so on. And so when I got back home, I told my mom, I said, you know, there is this very good magazine, which my aunt doesn’t send us cause she didn’t have that. She didn’t have the Eagle. Then she didn’t have the boys on paper. The ones she did have though, were things like the wizard, you know, there were, there were a lot of child’s comics. Anyway, I persuaded my mom that she should buy me once a month. The boys on paper, which is like a shilling or something like that. And in a way that was the first time I became any, any interest. So one of the issues, which is, you know, January, 1959, which is about I don’t know, 13 and a half, this was the, the issue it came and it had a center page pullout spread. It said, build your own one valve shortwave radio set. So I read this, this is really interesting. You know, we’re, we’re cut off here in the middle of nowhere. We have no contact. You, you know, we did have a TV that worked very badly, reception was very bad. There’s no transmitter for 40 miles. So I decided I would my project, which is the beginning of the first hobby, I would build this one valve crystal set, but we had no components whatsoever. So I wrote to my grandmother who lived in Edinburgh, I said, I need the following components. And in Edinburgh they had lots of shops, of course. So my grandmother would go to the electronic component shop called Browns on the mound, which isn’t there anymore. And she sent me the valve, you know, the, the tuning the coils. And there were no, there were only about eight components and I wired them all up according to the center pullouts spread and it didn’t work. So I spent months making this thing. It didn’t work. So then I had to compare the physical layout with the schematic wiring diagram, which course I’d never looked at before. And I realized that the coil, which was the official one I was supposed to use they changed the design between when they did the D the article. And when I got my version of it. So the connections were wrong on the coil. So when, when, when when I connected them, correctly it worked perfectly. So then I had a one hour radio academic loop, listen to myself without having to bother anybody else. The only thing was it was you don’t get much gain out of one valve, so you have to run it close to being a transmitter. You’re almost oscillating, it’s called the regenerative receiver. And as it went, as it crossed over from being a, you know, an amplifier to a transmitter, it would broadcast a lot of interference and our neighbor who is a next house complained that she’d been getting a lot of interference on radio reception. And that was my short wave radio. There’s all your fault being a transmitter instead of yeah. Anyway, and that was partly, and then from then on, I became interested in electronics and you know and actually, unfortunately when we went to high school on the train, we couldn’t stay. So I couldn’t go to, you know, they had to after school clubs, but because the train, there’s only one train back, I couldn’t go to any of them. So it was all, it was all self-taught hobby. And I did that probably till the age of about 20 something like that. And then when I left home to come to Cambridge, I left all my electronics and power supplies and stuff in my mum’s house. And after about a year and a half, she didn’t tell me she decided to get rid of it,

Peter O’Toole (00:44:35):
She threw it out, quite literally. Yeah.

Richard Henderson (00:44:38):
Well, she gave it away to another teenage boy. So I don’t have any of those things anymore, but the ones that I’d kept and, and taken with me to Cambridge, when we eventually went to America, I had to get rid of those as well. And so I sold some of them to another friend that had been from school and university. And unfortunately he, he died age 60. So he’d had this stuff that he bought from me for 40 years. So I got them back. So now I ha I have in our house, I have a 1942 working shortwave radio that is 1942, that’s 58, 78 years old. And because we were locked up with Corona virus for the last year, I decided that this was the perfect time to fix all the old clocks radio and broken stuff around the house? And when I, when I switched to time, about six months ago, it didn’t work of course, because it didn’t mean it hadn’t been switched on for, so I did spend about a week replacing all of the electrolytic capacitors, which of course, you know, they’re dried out and so on. So now it works perfectly. Again, it’s almost as good as the ones you buy that have got microchips running them.

Peter O’Toole (00:46:07):
You fixed it, but it sounds like it’s going to be a new one at this point, just cause you replaced all new parts.

Richard Henderson (00:46:14):
I left all the old components. So they’re, so, you know, with electroclytics, you can just wire a new one, then they’re much smaller. You just wire them in parallel, and then you just ignore the old one. It works quite well. Actually. It’s really good. So

Peter O’Toole (00:46:30):
I’ve heard I’ve, I’ve now got to ask this question. Are you like, are you a minimalist or are you a maximist at home? Cause it sounds like you hoard a lot of stuff.

Richard Henderson (00:46:40):
Yeah. We never throw out anything. Yeah. I’m yeah, you’re hoarder. I’ve got numerous others. We have a reasonably big house, but when we moved into it 22 years ago, I thought since it’s empty, this is the time. And so we, we, we put floorboards in the attic. So our attic is full of pre-war radios, you know, TV sets, record players, and then all the old papers and files, meetings and things all up in the attic. And that idea that you can use. The attic came originally from the house we lived in, in Broxburn which was, you know, the second two years of my four year degree in Edinburgh. And my parents moved out to a less expensive house in the countryside. And it was a terraced block with about 10 houses, but each of them had an up and do it. So it was 20 houses. I don’t think it was very expensive. It had it had one room that was pretty small, which was the kitchen and the sitting room in one. And then it had two bedrooms. My parents were in one bedroom and my brother and I were in a bunk bed in the other bedroom. And that was our house. And then when I’m about 17 or 18 and in university I had noticed that there was a, a hole up into the attic, not very big. So we, we looked up there and then when you go up into the attic and these old you can look along and it was the attic for the entire block of houses and there’s nobody up there. So I asked my mom and dad, I said, do you think we could put a bigger trap door? So we, we bought a loft ladder and, and then you could get up at the light. And then we got a little skylight put in, which was, you know, very cheap, just a, a pane of glass. You could open and close it. And then this friend and I, the, one of the people who shared the car, he had, his father had a bigger car. It was an estate car. So it opened the back one day, we drove down to the docks in Edinburgh where they had a shipyard, Woodyard, So, and we bought for eight pounds. We bought an entire car load of floorboards and then took them back. And then I spent probably about a week flooring, the loft completely house, just above the bits of above your terrace. Yeah. It was a bit about our terrace, but actually, you know, you could go a little bit further into that. There was nobody else there. So then we had a loft ladder, a skylight and a floor, but no walls. And so we put two single beds up there. So one for me, and then one, I mean, so I could have a friend to visit and then my brother could have the, yeah. The proper bedroom. He had that to himself. So he was quite pleased. This is about like six months after we moved there. And then I, I probably, I was only there for, for two years, but during that time, once it became clear, it worked quite well. We added, I added walls or walls, but I left it so that you could, you could, you could remove a bit out of the wall and put stuff behind the walls, in the other, in the other people’s attics. Yeah. Well, you know, and yeah. You know, and then we’ve, we’ve continued to do that. So in our house we, we then when we came back from America, when we’re, let’s say late twenties and we’ve got children, now we did the same thing in the semi and it was before they had now they don’t do this. They have dividing walls in the attic, so you can’t go in, but we went up into the semi-detached house and it’s the same, our side and the neighbor’s side. And so we, we floored that as well. And then, so we’ve also from teenage, we’ve always had homemade floored attics, and they’re always the complete size of the whole house. So it’s an immensely. So I recommend anybody who lives in a house with an attic that they should floor it and get to get a little pull down ladder. And then it’s, it’s not only another room. It’s another room bigger than any other room, anywhere in the house.

Peter O’Toole (00:51:56):
See my father in law has, he has he’s train, track and model village, which is, you know, when you take the grandchildren down, they love it. Actually. I think we all quite like it. It’s really cool, Jeremy. Yes. Yeah. So again, he teaches part of it. It’s got a part for storage and these guys lovely bit it’s, it’s, he’s done an amazing job. I guess his hobby at the time is setting that event still running. So that’s, that’s brilliant. And actually I say grandchildren can have great grandchild not from us, but don’t put my side that, that will be enjoying that very, very soon. So it’s about the questions, Richard, because I realize time is flying past us really fast. I can ask you some quick fire questions. Do you prefer email or telephone?

Richard Henderson (00:52:48):
Well, I I’m happy either, but hardly anybody uses telephone nowadays, actually. So I have possibly, you know, I don’t know, 50 or a hundred emails a day and no phone calls and even the children now and the grandchildren, they do FaceTime or zoom or, yeah, Skype.

Peter O’Toole (00:53:08):
Like I should’ve, I should’ve probably said email or zoom or equivalent. It’s probably,

Richard Henderson (00:53:13):
Well, I do mainly, I, I haven’t, I’ve I’ve specifically never joined Twitter or Facebook. And actually, I remember Brian Hartley who died very recently, 95. He was one of the mentors in the early LMB building. He said, I never read the literature. He said, if something important happens, somebody will tell me about it. And so with Twitter, normally in a normal day in the lab, you know, I’d be here working and then I’d go for coffee in the canteen. And to do that, normally you walk through, you know, there’s a shared terminal room where people can go out with slightly more powerful computer. So one day I’m walking through the terminal room and one of the scientists there, Paul Emsley, he said, oh, have you seen Twitter today? I said no I don’t read. So he was telling me what he’d read in Twitter five minutes before. So, you know, it was really hot off the presses. And so there are, I would say most people do have a Twitter connection now. Yeah. 90% of the younger of the younger generation. And so they tell you what’s happening, but you know, I, I just don’t have the time to do it. You can’t do everything you have, you have to be careful and focused with your time. And one of the great things and for, you know, the bad thing about the coronavirus is you, your normal social connections, you know, going to meetings. But the great thing is no traveling and you can get a lot more work done. And if you don’t do Twitter and Facebook, that must save you hours a day.

Peter O’Toole (00:54:57):
I, I, you know, I think that the travel it’s just made life busier because you haven’t got the downside. And when he’s sitting on a plane, it’s kind of the one time we could get away from everything in a way that’s like you said, you never read a book as a child what do you prefer to do now, watch TV or read a book.

Richard Henderson (00:55:17):
Well, I mean, I, I tend to, you know, I do, I do both of these things actually, but with books, I tend to anything. I think I need to read, I, I buy it and I don’t throw them away. So we have increasing. And so often you can skim a book, you know, in a few minutes, you know, randomly read you get the whole idea of it. So there, I have quite a lot of partially read books. And then I do watch a TV and particularly over the last year, I am now very well versed in films from the fifties and sixties.

Peter O’Toole (00:56:04):
What do I watch these films?

Richard Henderson (00:56:08):
Well, I mean, there’s a lot of Hitchcock, all the Hitchcock films from 1935 onwards there, they’re very, very, very good. But let’s say of the things I’ve watched recently for something like, you know bitesize whatever. The one I can strongly recommend and I thought was wonderful. Was the series called Breaking Bad? Now you must’ve watched this. I, I

Peter O’Toole (00:56:38):
Actually I haven’t watched it, but I do know of it

Richard Henderson (00:56:40):
Okay. You must, you must watch it. And I’ll tell you my, you know, two little mini things about, I had not heard of it because, you know, I, I, you wait for things to arrive, but my son who’s now in his forties, he said, dad, you must watch Breaking Bad. And I said, oh, I will. I will, I will. But then I hadn’t watched it. So next time I visited him. He says let’s watch the pilot opening episode, which is a one hour all the other 45 minutes. And so I can recommend to you, Peter, watch the Breaking Bad pilot episode one hour. And, and then there’s the second tip. So Alister and his friends had found out about this, you know, five or six years ago. And they had bought a box set for 40 pounds and they passed it around and they watched it. But by the time he had found it, it was on Netflix. And this is the thing that made Netflix take off. My son Alistair said, if you subscribe to Netflix, it’s free for the first month and you can watch Breaking Bad for nothing. So I signed on to Netflix and it’s 64 episodes. If, if the complete series though, it’s probably about 45 hours. And I watched, you know, maybe two, two a night sometimes three, sometimes none, but I managed to watch the entire series in three weeks.

Peter O’Toole (00:58:24):
Did you unsubscribe from Netflix at the end?

Richard Henderson (00:58:27):
Yeah. And then I said, Netflix is so good. I’m going to subscribe. Okay. No both are they all the children the grandchildren they all subscribed to Netflix and it, I mean, it is still very, very good. A lot of other companies are catching up on it. So Breaking Bad. It’s about, you must have heard a story.

Peter O’Toole (00:58:49):
Yeah. I said, I quickly. I will watch it.

Richard Henderson (00:58:55):
It’s a 52 year old chemist chemistry teacher in high school. He is the main character, Walter White.

Peter O’Toole (00:59:04):
I will, I promise I will watch it. I promise that

Richard Henderson (00:59:09):
You’ll find it. If you have you know, it has a scientific underpinning and it’s terribly well-written actually, you you’ll really enjoy it,

Peter O’Toole (00:59:18):
So I will give it. Okay. So the next question is, do you have a pet hate, hate? Yeah. A pet hate certain, you just really, you don’t like mind you up just what needles you?

Richard Henderson (00:59:30):
I don’t, I, I have I don’t have any hates, but I have a lot of things that I find very amusing. And so things that I find very amusing would fall into the category of things that other people hate. For example I find it very funny how easy it is that some people can delude themselves into believing something. And for example, in science, they have some theory about biology or chemistry and to any normal person, you can tell it’s, it’s complete rubbish, but some are rather the world has come in and they’re focused on it and they are completely. So the, the two interpretations of somebody who has published a wrong paper or has a wrong idea, the two possible explanations are assuming that the wrong either they have, they genuinely believe it and they’re diluted or they’re dishonest and are doing scientific fraud.

Peter O’Toole (01:00:50):
That latter one is really bad.

Richard Henderson (01:00:52):
You know, you have to look at a particular thing and you have to ask yourself, is this a naive deluded person, or is this a devious scientific fraud person? So I find this very amusing, but you know, not every people think at , you think you’re being, you’re being wicked, but no, I, I, it’s just funny actually.

Peter O’Toole (01:01:13):
Yeah. Okay. So I’ll get a challenge know. Do you think people thought you might’ve been a fraud when you told everyone that x-ray was no longer the way forward and they still will be going towards electromicroscopy because there must’ve been a load of people in there thinking, wait a minute, this is not right. Well, you know, right. So you’ve been proved. Correct.

Richard Henderson (01:01:35):
But yeah, no, but you have to realize, you know, I never, I came from fairly non-academic rural background. So for me, every step is a step forwards and upwards. So I’ve never, ever had any doubts about this thing, but I can tell you one interesting story is actually there are many related to this, but the reason that I said that I wasn’t looking to do it, but what happened was we all assumed that everybody knew that radiation x-rays or electrons, did radiation damage. And from about 1980 or 1990 onwards, you know, it was clear what it was. And I thought everybody just knew this. The first thing was when Ada Yonath who, you know, as a Nobel prize for the ribosome work, she was one of the first people with Håkon Hope to freeze crystals and put them in a synchrotron. And she said at a Gordon Conference, New Hampshire. She said, you know, when you freeze a crystal to liquid nitrogen temperature the defraction lasts forever. There is no damage. And of course we’d been doing electron microscopy your years. We knew when you put the beam on, it lasts for a few years seconds. So we said that must be wrong. And so one of the first things that I compared in 1990 x-ray and EM. And showed that in order to find x-ray damage in 1990, you need three days eradiating in synchrotrons then to find the damage or five years on an x-ray source and just nobody had done it. So that was a paper that was published in 1990. I’m sure nobody knew that. But the people who are running the European Synchrotron facility that was being built in Grenoble, we’re trying to build different beamlines. And they had a meeting to discuss x-ray microscopy. And was it was Carl Branden and Andrew Miller, the director and designate director and acting director. And so they said, would I come here along to the meeting and give a talk about radiation damage in x-rays so I thought, I’m fine. You know, this is common knowledge. So I went along to this meeting and there are 50 x-ray microscopist who think x-rays is like best thing since sliced bread. And I stand up and I explain that electrons do 1,200 times less damage than x-rays. And there were really angry because they wanted 5 million euros to build a beamline. And I’m telling them that it’s rubbish. And I almost got lynched actually. And so that was the reason I decided I better write if this 50 intelligent people the best in the world, x-ray. Yeah. I didn’t know this. Then somebody needs to raise the profile. So I started to write a review. It was comparing x-rays and electrons. But during that time, a journal called Neutron news, it’s still published three times or four times a year, came with all the cross sections for neutrons. So in the end, I wrote this article, neutrons electrons, and x-rays, you know, which ones are the ones you should do in theory. And it turns out not only the electrons a thousand times less damaging than x-rays per useful scatter demand. There are three times less damaging than neutrons, which are thought to have no damage. And so I wrote that review and then we, and then I was having written it. I was then personally, so convinced that we stopped all our work and then decided to focus on single particle, electronic microscopy. And Howard Hughes once had a meeting? I went along and Michael Rossmann who was here in the lab when he was a post-doc with Max, went to Purdue, died about a year ago. I was asked to give a topic, Howard Hughes. And Michael was in the audience listening to this. And after I’d given my talk, 1000 for year, Michael stood up and said, well, he said, this is not what I’ve been teaching my students, you know, for the last 30 years, he said, must be wrong. And then, but what he hadn’t realized is that it is true, that electrons are actually a hundred thousand times more damaging in terms of their cross section. But if you look at the ratio of scattering to damage, it’s a thousand times worse than an x-ray. So it was just a learning experience. And so everybody then accepted it and then we went on. So, no, we didn’t have, I never had any trouble convincing people because all you have to do is write down the facts. And eventually there’s this review, which is now, it wasn’t cited much at the beginning. So it’s, it’s a paper that we call, you know, when you publish a paper, you may have seen this yourself, you publish it in a journal. And the journal has an impact factor. Number of citations on average in the following two years. And it has a half-life because normally when you publish in Nature, it gets cited for the next year. And then the case the second year, and the half-life is usually about one to two years. But if you have a really good paper, that’s what they call seminol, it has no citations in the first year. And then it just grows linearly with time. So actually it has a negative half-life. So we think that the best papers have a negative half-life and then, you know, they have their own momentum and they grow,

Peter O’Toole (01:07:44):
Okay. It’s also because others aren’t doing it. And if it’s a technology, there’s not many people can cite to new technology until they’ve done something with it. And then it will grow obviously massively in the case of our structural and Cryo EM itself,

Richard Henderson (01:08:03):
DNA sequencing, cloning, all those papers they’ll be in that, they’re all in that category because there were new ideas that then everybody cites until they get tired and then cite a textbook or something,

Peter O’Toole (01:08:16):
I cannot believe we’ve been talking for over an hour and these are meant to be an hour long. And I’ve got so many questions I still want to ask you. So do you know what I hope? No one minds, if you just go on just a little bit longer.

Richard Henderson (01:08:31):
No, I’m happy to do. I can do 10, second answers as well. I just wasn’t.

Peter O’Toole (01:08:35):
Okay. Do you know what, what’s your favorite music?

Richard Henderson (01:08:39):
Good question. I wasn’t a very big music fan, but I did decide I needed to it. So bach’s cello, concertos. Okay.

Peter O’Toole (01:08:52):
What’s your favorite food?

Richard Henderson (01:08:55):
Well, I had sausage and mash for lunch today

Peter O’Toole (01:09:02):
With onion gravy. Yeah, of course.

New Speaker (01:09:05):
With Lincolnshire sausages with you know, it’s really good. Okay. And also what, you know, when I was young, we had a, at the bottom of our street in Tweedmouth, which is the opposite shore of the tweet from Berwick fish and chips is very good. Oh yes. That’d be bad for you. But anyway,

Peter O’Toole (01:09:24):
In the right place at the right time in the right place. What about this is an odd question. What is your favorite item of clothing?

Richard Henderson (01:09:32):
Good question. Well, I have never changed my tastes and I’ve worn sports shirts and sweaters in my entire life, but that’s a perfect, I’ve never had a beard except for two weeks when the children wanted me to grow one, I cut it off. So I, I, I I’m afraid. I, I, I’m not mine. I don’t really change. I’ll tell you one thing that might be interesting. When we were children, we were always asked, what is your favorite color and what is your favorite number? And I always said it was purple and seven. And later on, when I was about 25, I started to work on purple membrane. Of

Peter O’Toole (01:10:24):
Course, with a sad

Richard Henderson (01:10:26):
Couple of years later, we discovered it had seven trans membrane. Yeah, pretty good.

Peter O’Toole (01:10:34):
It was fate. It was fate. I did not. I was going to mention, I know you like hillwalking do you still kayak.

Richard Henderson (01:10:46):
Yeah. We have two in the garage. Don’t go so often. Now it’s a little bit, it’s amazing. Actually the same friend who had the part ownership of the car. Last time he visited Cambridge, we kayaked from one of the villages into Cambridge. You always paddled down the key thing about kayaking. You always go downstream. And then if, even if you get tired, you just wait and the river takes you to where

Peter O’Toole (01:11:13):
I thought you were going to say that your friend came down and bought it off you for a fiver. It’s amazing. So many scientists that I’ve talked to for the microscopies kayak, Jennifer Lippercotch Swartz, still kayaks to work. Oh, it’s Janelia research campus. Alison North, still kayaks on a holidays. It’s amazing. Just the number of kayakers.

Richard Henderson (01:11:37):
I bet. I bet you, Jennifer Lippercotch Swartz, Of course doesn’t kayak in both directions. So she probably lives up stream and kayaks in, in the morning and then takes it back on her car roof rack. No,

Peter O’Toole (01:11:49):
I think she goes both, I don’t know, I think she might go both ways. It’s difficult.

Richard Henderson (01:11:54):
Well, unless it’s a very, it, there is a river right there.

Peter O’Toole (01:11:58):
So she’s the river Seldin and she’s going across a Seldin island isn’t. So yeah, so that’s quite entertaining to listen to that when it gets too dark is maybe not the best thing. There was a, there was a few with that.

Richard Henderson (01:12:12):
Anyway, all our, all our best kayaks have been, have been taken by the children. So we only have the ones that are not terribly exciting left.

Peter O’Toole (01:12:23):
That’s it? I do. I re maybe we’ll do another one of these and come back to more questions in the future, because this has been so brilliant. I’m going to ask today. What do you think is the biggest challenge going forward? Scientifically

Richard Henderson (01:12:40):
What’s a big science challenge, a lot of the young students. And post-docs ask that question. And so the biggest challenge going forward, or at least the one you might want to work on, depends on how old you are. Okay. So if you’re 75, this is not the time to start on a project. It’s going to take 30 years. But when I was a first year post-doc at Yale, I thought I should simply having worked on an enzyme from my PhD. I thought I’ll just pick another enzyme slightly more interesting than the first one and work on that. And then there’ll be plenty more. But when I told my postdoctoral sponsor this, he was a very clever Chinese professor in the chemistry department, actually chemistry department at Yale is where I did a post-doc without any background whatsoever in chemistry. We stopped with inorganic aged 14 in high school, but he said, oh, he said, no. He said, I don’t think you should work on an enzyme. He said there are thousands of enzymes in the world when you’re 25 years old, you should pick a topic to work on that will come to fruition in 20 years. And so I said, this is very good advice. So I stopped working on enzymes and started to work on membrane proteins, which in 1970 was very, very badly understood. So now, I mean, I think the big, big, big frontier is the neurosciences and how, how memory and learning works in the Brain. But I would say there, there, isn’t really a big rush to get into that just at the moment, because the techniques that exist at the moment are not powerful enough to get to the bottom of it. You can make progress and eventually there’ll be a breakthrough, but what you really need is one micron and one millisecond resolution on the entire human brain, you know, and of course you’ve got, you know, 15 centimeters. So that’s 150 millimeters, 150,000. That’s nearly a million pixels in each direction. That’s 10 to the 18th pixels. And if you, if you were to record every millisecond activity, yeah. You’d be talking about 10 to the 20 ones, one numbers per per second. And this, this is beyond any capability at the moment. And so you have to, you know, dissect it down into more digestible lumps, and that’s why everybody’s a lot of people are working to soften the brain. There’s only 300,000 sales or the nematode brain only 300, but the human brain, it will be, it’s not that it will never be the last frontier because you can always invent things, but understanding, learning yeah. Memory and how we think and work. That is an actually I remember having a chat with Colin Blakemore, who is a neuroscientist who worked on cat vision and was the head of the MRC for a while. And I sat beside him in a lecture. I said, you know, this neurobiology is very interesting and obviously many things I learned, but how long do you think it’ll be before we understand learning and memory? And after a lot, hi, we bought the site. It’s at least 30 years in the future. So, you know, there’s no hurry. If you, if you spent five years doing something else and you’re a young scientist, you can easily get into it five years from now. There’s no rush. In fact, it might be better. Cause one of our favorite things is, you know, if you’re wrestling with some technology, one solution to solving the problem, instead of working hard at it and killing yourself, you could just go on holiday for two or three years, come back and all the problems you there’ll be solved by someone else. And then you can just slot back in at a much more advanced state of development of the field. So there are two strategies. One is to delay getting into something until the time is right. And Fred [inaudible], I did this with nucleic acid sequence here. He was studying it for 15 years before the methods. And then since they were available, he jumped in and he was then in the lead.

Peter O’Toole (01:17:10):
I am going to plug at Jeff Lichtman and I know you’ve listened to Eric. So Eric Betzig, microscopists, this podcast. And interestingly in your, how he actually doesn’t like electronica, who’s quite controversial. And he says electromicroscopy is not, yeah, it’s all got to be like microscopy. And then actually what you’ve just been saying, you then got the other extreme that Jeff Lichtman is working on, looking at the brain 3d electromicroscopy through that. It’s interesting how you’ve got all these various aspects, but you’re absolutely right. We need to do it live and it needs to be there. And, but we need these other techniques to keep informing us so we can make sense when we get there, that will help us make sense of your one micron per microsecond for the full volume. So it’s not work in vain.

Richard Henderson (01:18:03):
Do you can do magnetic resonance imaging of the whole body and the whole brain, but the resolution’s about a millimeter. So to go from a millimeter to a micron it’s 10 to the ninth, you know, it’s, it’s off the horizon at the moment. So although, you know, Eric Betzig, they’re all terribly enthusiastic about what they do. They’re all just scratching at the surface. Really. I mean the, the power of the methods you need is just so much further in the future. I think, I think it’s but you know, one area that’s interesting, which I, you know, th the synchrotron people are building x-ray microscopes now. So there is 3d x-ray tomography, and there’s a fantastic video now from a group in London called Peter Lee. And they go to Grenoble and Grenoble, synchrotron has just been upgraded to, and then all the synchrotrons in the world are planning upgrades. And so it’s not, you can’t get angstrom resolution because of the electrons being better than x-rays, but you can do no. Jennifer lippen lippen Lippercotch Swartz works at Janelia on this type of a plastic section inbedding and so on. And they can get 20, 30, 40 nanometers or even two, three, four nanometers. They can get resolutions sub-cellular that you can see organelles, but only have one or two cells, but the x-ray 3d tomography. You can do the entire body. You can do. So there’s a, if you look at Peter Lee, who’s a Professor at University College, London, they’ve got a lung of a normal person and a lung of a Corona virus person, and you’ve got a complete x-ray and of course, it’s a dead person. You can’t do it live it’s dead. So you, so, you know, you could donate your brain after you die. And then that could be analyzed by this method and they can zoom. They can’t do the whole thing at one micron, but they can zoom in on sub areas. They do the whole thing at low resolution, then they can do very finally. Yeah. So, I mean, there are things coming along, but they’re still nowhere near powerful enough,

Peter O’Toole (01:20:32):
Then arguably where you started and you know, the innovations you’ve come through with over the last 30, 40, 50 years is exactly what you’re saying. So the next 20, 30, 40, 50 years it could get there. Could. There’s always a way there’s always a solution. It just takes time and money

Richard Henderson (01:20:52):
Together, but it’s time and money. Exactly. But you know what? One of the things that I studied in 1960 was fusion research. And I decided against it because everybody said, oh, it’ll be 30 years. Okay. So 1965 plus 30 years, 1995, you ask, how is fusion research getting along in 1995? They say, oh, it’s going to be about another 30 years. So now here we are in 2021. And they’re building, you know, fusion, demonstration, reactor in Japan and so on. And they said it would be about 30 years. And then what are we saying about memory and learning? We’re saying 30 years. So that basically means you can’t predict it. Things go faster. So, you know, computers and DNA sequencing went faster than we predicted.

Peter O’Toole (01:21:41):
So in 30 years time, we have to come back to this podcast. People have to hear you quoted that 30 year mark and go, how wise, how wise, even then into that point, Richard, we are up, I mean, we ought to stop at this point because podcast, thank you so much. I’ve got to say it’s been enlightening. I didn’t realize you were such a Wheeler dealer with it, which has just been amazing throughout all your career. And outside’s in there. Yeah. If you are getting rid of anything, I always have a five pound note on the side, Richard, thank you very much for your time.

Richard Henderson (01:22:19):
Great fun to chat.

Peter O’Toole (01:22:22):
Thank you everyone for listening. And if you’d like to hear more, do go to The Microscopists podcasts or Spotify, YouTube, iTunes. Anything else? You can hear, Eric. You can hear Jennifer, but this has just been so brilliant today. So thank you very much for listening. Thanks.

 

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