The Nobel Prize week began with some very happy, almost unreal coincidences for me.
For one, not even a month back I met all three of the Physiology/Medicine Nobel Laureates for 2014 – John O’Keefe, May-Britt Moser and Edvard Moser – together, awed by their path-breaking work and wondering why they had not got the Nobel yet. What’s more, upon the invitation of the lovable, super-fit Moser couple, I visited their laboratory in Trondheim, the mecca of sciences in Norway, and came back wondering again – really, they haven’t got it yet?
The announcement of the Nobel Prize for Physiology or Medicine yesterday, therefore, felt like déjà vu – as if my attending the Kavli Prize ceremony in Oslo and visiting the Mosers’ lab in Trondheim was a sort of ‘meet the future Nobel winners’ event, star-studded with brilliance in neuroscience, nanoscience and astrophysics. Small wonder that O’Keefe, recipient of the Kavli Prize in Neuroscience, 2014 (along with Brenda Milner and Marcus E. Raichle) mentored the Mosers during their postdocs and beyond. “These two make me very proud”, he had said biting into a venison fillet at the Kavli banquet in Trondheim. “They are doing some exceptional work.”
Earlier in the day, O’Keefe, a professor of cognitive neuroscience at the University College London, was explaining the workings of our brain – the organ which contains ten times more nerve cells than there are people on this planet. How do these cells interact and perform all the complicated operations? O’Keefe’s work on the hippocampus (the region of the brain that gets its name from its resemblance to a seahorse – ‘hippos’ is horse and ‘kampos’ a sea monster in Greek) got him both the Kavli and the Nobel. In 1971, this affable man with a neat white Lincoln-style chin curtain beard, along with John Dostrovsky discovered that the hippocampus contains special nerve cells that determine an animal’s specific location. He called them ‘place cells’.
The suggestion that the hippocampus holds some kind of ‘cognitive map’ that helps us move – both physically and mentally – from one location to another, was initially controversial. As we know now, the theory has been ultimately pretty influential. “I continue to work on how this cognitive map theory can be expanded to explain the episodic memory deficit in patients whose hippocampus is damaged,” he says. In Alzheimer’s Disease, the first symptoms are usually detected when patients start getting lost in their own familiar neighbourhoods. Getting to know this memory function will help us understand what exactly changes for those with Alzheimer’s, he contends.
It’s a beautiful evening in Trondheim and the chirpy May-Britt Moser is taking us around the labs at the Kavli Institute of Systems Neuroscience at NTNU, the Norwegian University of Science and Technology. “That one is called Happy,” she says, pointing to a rat running around inside an open top rectangular box – the rat’s brains are being monitored on a computer through electrode implants in its head. “We call him ‘Happy’ because he is always so agile,” she explains.
May-Britt and her PhD students know most of the rats in the labs by their names. “Look at this one with a crown, below which we conceal his implant – he looks like a King, doesn’t he?” she says laughing out her characteristic infectious laugh. Accompanying us is Brenda Milner, Kavli Prize awardee in Neuroscience for 2014, who loves the rats and takes one of them out of the cage to stroke it gently and whispers sweet nothings.
Edvard Moser, who shares his life and passions with wife May-Britt ever since they were undergraduate students (and famously got engaged atop Mount Kilimanjaro for their love of volcanoes), explains their research work: “After O’Keefe’s discovery of the place cells, and over the subsequent 30 years a lot was learnt about these cells. But one question that was not addressed at all was where do these’ place’ signals come from, since it is in the middle of the brain far away from the sensory functions. That is what our lab started out to answer around the year 2000.”
One of the first things the Mosers did was to disconnect the area of the hippocampus, where most people thought the place cells were, from the rest of the hippocampus. “The idea was that if we break that intrinsic circuit of the hippocampus, we would know the area of the place cells signal. But it did not happen – we still found place signals,” he says. This led to the idea that there was a different connection – and there was one connection left, another brain area called the entorhinal cortex.
That is when they found the ‘grid cells’. When rats and other mammals move around, these grid cells in the brain send electrical signals at specific points which combine to form a Chinese-checkers-like grid. “The grid cells answer a lot of neural codes for cognitive functions,” he says.
The couple, working in their lab far away from the world’s cutting-edge research hubs, has been churning out some ground breaking work over the years. It has fetched them many international awards and finally the first Nobel for Norway.
As we come out of NTNU, Edvard Moser leaves us with the thought that since the grid pattern is formed inside the brain and not generated from outside, we are just about scratching the surface in our understanding of space and memory. “There will be lot of surprises, and I am not telling you since I don’t know them yet,” he says laughing a hearty laugh.
The Nobel for O’Keefe and the Mosers has certainly not been one of those surprises.
Updated on 8 October, 2014:
Stefan W. Hell, winner of Kavli Prize 2014 in the nanoscience category got the Nobel Prize in Chemistry today along with Eric Betzig and William E. Moerner “for the development of super-resolved fluorescence microscopy”. He accompanied us on the tour to the Mosers lab and I am starting to secretly believe there was some ‘Nobel dust’ in the lab air that day!