Joint Project: Christos Ioannidis, Valentina Pena (Bugle Team) and Bernardo Milani Alvares (Guest Interviewer)
Earlier this year, our team members conducted an interview with John O’ Keefe, a professor at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour and the Research Department of Cell and Developmental Biology within UCL. Professor John O’ Keefe was, recently, listed as one of the recipients of the Nobel Prize in Physiology or Medicine for his discovery of place cells within the hippocampus.
From humble beginnings, to current and future projects, and on to the state of academia in developing countries, we ask all the hard-hitting questions. Do read on as we present to you the life, times, and opinions of a brilliant mind.
Interviewer: You’ve recently been awarded the Nobel Prize in Medicine. Did you expect your work on place cells to have such a great impact?
John O’Keefe: Well yes, at the time I did think that this could turn out to be very important. When we first made the discovery and I realised that the cells in question might be part of a spatial system providing the animal with some form of cognitive map, I thought that if this were correct and actually stood up to experimental verification testing, it would be an important finding. And the hippocampus was in fact one of the first areas of the brain which we knew would be involved in cognitive processing, so I believed it could open up an important area of research.
And how would you say single-cell recordings impacted your work on place cells? Wasn’t it a very novel methodology when you first begun your research?
Yes, you are absolutely right! One of the advantages I had was that I came to neuroscience – it wasn’t even called neuroscience in those days – from a background in engineering. I realised back in the 1960s that there were several technological advances in engineering at the time which would make it possible to record the activity of single cells in animals while they behaved more or less normally or carried out simple behavioural tasks. So I built little amplifiers that could go on their heads and used a new recording technique that required inserting very fine insulating wires into the [rat’s] brain. We also used deep anaesthesia and gave them painkillers so they didn’t suffer. This allowed us to record the activity of individual cells while the rats went about their daily business. It was those types of techniques, plus some additional knowledge brought over from engineering, which enabled us to do things that had never been done before, and there were one or two other labs that were doing similar things at the time.
Tell us a bit about your career development. How did you come to dedicate yourself to neuroscience?
That’s a good question … In secondary school, in New York, I actually studied Classics. I studied Latin and Greek, and other languages. I didn’t do very well, so at the end of that, I didn’t have good enough grades to go to college, and certainly not to win any scholarships. So I decided to work. I worked in Wall Street, in insurance companies – I worked in lots of different places. Eventually I got myself a job in an aircraft company, making airplanes. But at the same time I decided I really should try to learn more, so I studied engineering at NYU in the evenings. Even though I was studying aeronautical engineering, they had a broad curriculum which encouraged us to take courses in history and philosophy and things like that. They were mostly survey courses where you would learn broadly about a whole field, and I became very enamoured with philosophy. I started thinking about whether there were ways in which we could, given the techniques that were available, answer standard philosophical questions – the nature of consciousness, perception, the mind, and things like that. So I started to read independently on those topics, and eventually decided that this would be a good career for me to pursue. I then stopped working at the aircraft company and went to City College of New York, which was the only place in the United States which didn’t charge tuition. I started taking courses in engineering and physics at first, but eventually took courses in psychology and philosophy. At the end of that, I was lucky enough to be offered a place to do a PhD at McGill University in Montreal, where Donald Hebb was one of the few people who believed you could understand a lot about psychological processes by studying the brain. And that’s where I began to develop the techniques and do the work which enabled me to record brain cells in animals.
So basically, you aspired to solve big philosophical questions through neuroscience?
Yes, to put it succinctly. I thought that if we could look at cells in certain parts of the brain, particularly parts that were far removed from the central inputs and the motor outputs, we might see activity which related to some of the interesting things that were going on in the animals’ minds. It could even give us some idea as to how that activity might relate to human psychology, and through that, to some of the big philosophical problems.
Do you think neuroscience is getting any closer to solving those problems – or at least moving in the right direction?
Well, astonishingly, many laboratories still use the techniques we developed in the 1960s and 1970s. They’ve improved on them and they’re much more reliable, but they’re still basically the same techniques. The big-game changer now is the involvement of physics and molecular biology in developing new techniques that allow the simultaneous recording of either a small or a large number of cells in active animals. There’s also work coming out of computer science which we can use to develop much improved electrical recording devices. Thanks to these advances we’re now at the stage where we can examine network interactions, i.e. connections between lots of cells and how they talk to each other. This is particularly exciting because we think that a lot of important psychological processes like perception, memory, and emotions involve not only individual cells but also a network of cells which interact with each other. We are finally beginning to have the techniques which enable us to address some of these questions, opening many interesting new doors in terms of research.
That does sound like an exciting leap forward! On a more personal note, we’ve heard that you’re originally from the Bronx in New York, an area that has a reputation that precedes it. What would you say helped you stay focused in following such a successful career?
Well, I went to Catholic school and I was taught by nuns. They were very open and they told me I was pretty intelligent, and that if I studied hard enough (laughs) I would have a future in academia. And the area I grew up in, it was a tough neighbourhood and there were gangs and some troubles, but the other kids, they thought that I was maybe one of those who could go into university. So, they gave me a bit of an easier time, I have to say, and I’m very grateful to them. This, I think, enabled me to stay focused. I also kind of foresaw that I had a future in academia but overall, I have to say I was very lucky. There were times in my career that I made the right choices and I was lucky enough to get into the right schools.
So would you say your success was due to a combination of a supporting environment and your own willpower?
Yes, I think you need to have a purpose, you have to want to do well and to succeed. And sometimes when it seems like the world is going against you, you have to say, “I’m going to put that behind me”. One of my favourite films, “Shane”, is about a retired gun fighter in the West. He keeps getting beat up by the bad guys and yet keeps coming back (laughs). So I do think you need to show a bit of resilience. When you get knocked down, you need to come back and keep trying!
A large number of developing countries like Brazil, still haven’t won a Nobel Prize. What are your views regarding the current talent and resource distribution in science? Have you seen any movement towards developing countries becoming more capable in undertaking cutting-edge research?
I’ve said on numerous occasions that one of the really important things about science is that the next Nobel Prize winner can come from any country. It is very hard to predict where people will come from to do this work. I certainly would encourage developing countries to invest in science. I do think it’s important, not only for the intellectual life of the country, but also for scientific, technological and industrial development. I think the future in industrial terms is going to be more and more dependent on a scientific base. Having said that, it is true now, that science tends to be concentrated in a small number of Western countries. On the other hand, if you look at scientists in those Western countries, they often come from developing countries. This is because you need an infrastructure and tradition that supports science. I think it is important for developing countries to develop these traditions and support their universities, to invest more.
Back to your current research – do you have any ongoing or planned projects that you could tell us a little about?
Well, aside from our work on developing new recording tools, my lab is also very interested in the use of virtual reality (VR) environments to test the function of different brain areas. For example, if we want to test spatial navigation in humans and image their brains at the same time, the obvious way to do that is to create a virtual environment where the person can navigate around and then see which parts of the brain are involved. Results from such investigations have suggested the hippocampus to be heavily involved in spatial navigation and memory in animals, while also revealing the involvement of many other areas. Personally, although I’ve spent my whole life working on the hippocampus, I’m also interested in researching other parts of the brain such as the amygdala’s role in emotional processing.
And are these VR experiments similar to the famous UCL cab driver experiments at all?
Yes! In fact our group was one the first to actually use this technology, working along with Neil Burgess and Eleanor McGuire over at Queens Square. Eleanor actually ran the experiment, and she went on to realise there were a group of very good navigators in London – the London taxi cab drivers. So she looked into whether there is something special about their brains that could explain why they are such good navigators. To get a cab license in London, you have to essentially know how to find your way around the city, which comprises 25000 streets, so you go through a rather intensive learning period in which you study how to find your way around – it’s called ‘the Knowledge’. However, Eleanor showed that the hippocampus of cab drivers is actually enlarged relative to the average lay person. And she’s also gone back, in some of her experiments, to using virtual reality and video games to test their navigational skills.
Do you think neuroscientists will ever be able to unravel the mysteries of consciousness?
That’s a tough one. Consciousness is the topic that divides neuroscience. I wouldn’t say it divides it right down the middle – I think the majority of neuroscientists still think that it’s not a topic we should try and understand, and at this stage it’s probably too early too. My own feeling is that we won’t really understand the brain until we understand what role conscious processes play in carrying out its many functions. As of yet, we’re not really sure what these processes are, though they clearly are involved in some sort of higher order processes such as memory, cognition, perception, etc. One of the biggest problems is that as neuroscientists we’re not really sure what distinguishes the conscious and unconscious operations of the brain. It looks as though the same parts of the brain may be involved in both, so it is unlikely that there is a specific part of the brain which is the ‘consciousness centre’. But I guess that yes, I do think we will be able to understand consciousness – not tomorrow, probably not next year, but eventually. And conversely, we probably won’t have an adequate theory of how the brain works until we have a role for consciousness in that theory.
Finally, what would be your advice to aspiring researchers?
I think it’s very important to tick a couple of boxes, as various different elements come together. It’s important to start off by asking what would be a good area of research to go into. I think a lot of people go into science without ever asking themselves this key question. They just follow along the standard tram lines. But it is one of the most important things, to ask yourself which area is perhaps less mature than others, and where you can actually make a contribution. Importantly, it also has to be something you’re interested in. You shouldn’t go into an area of research you find boring because it’s going to let you down when you have to get through the hard patches where nothing’s working out. Aside from interest, you also need to be good at it. There are several people who are working in areas they are very interested in, but they’re just not very good at it for all sorts of reasons. Finding the “right area” is probably most important, yet I think you have to tick all of those boxes.
John O’Keefe and Christos (Bugle Team)
We are grateful to Professor O’Keefe for taking the time to support the Bugle, and for being interested in helping younger students with finding their place in the world.
We would also like to express our warmest thanks to Dr. Bernardo Milani Alvares, who brought the Bugle in contact with Professor O’Keefe and made this interview possible.
This interview is presented in the Bedford Bugle with the permission of Professor John O’Keefe. Its content may not be reproduced or used outside the context of the official Psychology Society blog and for any other purposes without the permission of the Bugle and of Professor John O’Keefe.