Introductory address delivered by Professor John F. Cryan for Professor John O'Keeffe
PROFESSOR JOHN F.CRYAN in 深夜亚洲福利久久 College Cork, on 15 December 2014, on the occasion of the conferring of the Degree of Doctor of Science, honoris causa, on JOHN O鈥橩EEFE
A Sheansail茅ir agus a mhuintir uilig na hOllscoile, Chancellor of the NUI, Registrar of the NUI, President of UCC, Distinguished Guests, Ladies and Gentlemen.
Finding your place in the world - isn鈥檛 that鈥檚 all any of us are searching for鈥�.
Discovering where our memories are stored has been one of humankind鈥� s greatest challenges beguiling philosophers and scientists for millennia. The Ancient Egyptians thought little of the brain often removing it prior to mummification and believed that the heart was the centre of mental life. It wasn鈥檛 until the time of Hippocrates that a focus was placed on the brain. Also great philosophers like Plato began to see the brain as the seat of the mind. However, it was the Greek physician Galen of Pergamon who claimed that the brain was the supreme organ. His revolutionary idea needed more than a thousand years before being finally accepted. Even today we still say that we 鈥榣earn by heart鈥�, not learning by brain鈥�
Last week Professor John O鈥橩eefe along with Norwegian Scientists May-Britt & Edvard Moser received the most prestigious scientific price, the Nobel Prize "for their discoveries of cells that constitute a positioning system in the brain". Thus by trying to figure out how we all have our place in the world Prof O鈥橩eefe鈥檚 place is indelible. His influence on a whole generation of scientists has been immense and this well-deserved and long overdue Nobel is just the pinnacle of an amazing and inspiring career.
His lifework has been focused on understanding how the brain deals with space and place within it.
I鈥檓 reminded of the quote from the American Southern writer Flannery O鈥機onnor鈥檚 novel 鈥�Wise Blood鈥�:&苍产蝉辫;
鈥淲here you come from is gone, where you thought you were going to was never there, and where you are is no good unless you can get away from it. Where is there a place for you to be? No place... Nothing outside you can give you any place... In yourself right now is all the place you've got.鈥�
The place where John O鈥橩eefe was born is South Harlem in New York, and he grew up in the nearby Bronx. His father, Mikey, was from Newmarket in North Cork, having followed his three siblings to make a better life in the US in the late 1920s. His mother, was also Irish, Bridget Bourke, from Breaffy, outside Castlebar in Mayo. John, the oldest of three children, won a scholarship to the prestigious Jesuit Regis High School, which steered him away from the traditional roles of Irish-Americans of his generation (Firemen, car mechanics, bus drivers, builders & barmen) onto a voyage through philosophy and education instead. Having worked on a film set and having even driven a New York yellow cab, he switched to engineering, It was the era of Sputnik and there was a great sense of innovation and discovery. He studied aeronautical engineering at New York 深夜亚洲福利久久 (NYU) in the evening while working full-time at Grumman Aircraft factory on Long Island, making airplanes and preparing for a glamorous career in the aerospace industry. It was not to be.
At NYU, he was introduced to philosophy courses 鈥� in particular, those focused on the philosophy of the mind and he began to consider how studying the brain might help to explain some of the classical problems of philosophy, such as the mind鈥揵ody problem, consciousness and how we represent the external world. Its important to remember that neuroscience as a discipline did not exist per se at this stage and the fields of philosophy, psychology and physiology were still very disparate and divided.
Thus in 1960, he gave up his job and enrolled full-time at City College of New York. There, he came across Donald Hebb's 1949 classic 'Organisation of Behaviour', which is perhaps the most important text ever in Neuroscience, explaining how neurons that fire together wire together and in doing so, Hebb started to break down the boundary between psychology and physiology. Although like Ulysses and other great books, it is also perhaps the most unread book in Neuroscience.
Not for the young O鈥橩eefe who really got excited about the possibilities of understanding the mind and behaviour in terms of brain function. He proceeded to get a graduate place in Hebb's Psychology Department at McGill 深夜亚洲福利久久 in Montreal, one of the most important centres for what was then called 'physiological psychology'. For his Ph.D. work on the amygdala and subsequent postdoctoral work at UCL, O鈥橩eefe developed techniques for recording single units in behaving animals.
Around this time, the studies of Brenda Milner, who was also at McGill, on HM (who on his death 6 years ago we learned was Henry Molaison) were emerging. These studies focused on an area of the brain deep within the temporal lobe, which is named because of its seahorse shape, the hippo-campus. As an aside - to me it is more like a sausage but that would not be as beautiful in Latin. Molaison, was one of the more famous patients in medicine 鈥� he had a large part of his temporal lobe removed due to intractable epilepsy and lost the ability to make new memories - showed that the hippocampus had an important function in memory formation and storage. HM had lost what has later been named episodic memory, our ability to remember self-experienced events. Milner鈥檚 observations are a crucial discovery in modern neuroscience and turned the focus to the role of the hippocampus.
After moving to UCL, O鈥橩eefe thus turned his attention to the hippocampus. We all know that there are different forms of memory: remembering how to ride a bike, for example, is different from knowing how we can go from UCC to the train station, or knowing that Dublin is the capital of Ireland, although some would contest that this is really Cork- but that involves a different part of the brain that I won鈥檛 go into!
To be able to sense place and to navigate within it are some of the most fundamental brain functions and this has entranced philosophers and scientists for millennia. During the 18th century, the German philosopher Immanuel Kant argued that some mental abilities exist independent of experience. He considered perception of place as one of these innate abilities through which the external world had to be organized and perceived, that there was a priori representations of time & space in the mind.
O鈥橩eefe鈥檚 landmark discovery of what he termed 鈥榩lace cells鈥� in 1971 set about defining the neurobiology of place. These cells are specific neurons within the hippocampus that become activated when the animal enters a particular place in the environment, with neighbouring neurons firing at different locations, such that the entire environment can be represented by the activity of these cells throughout the hippocampus. In effect, he found a neuronal correlate of this cognitive map within the hippocampus, which was, and this was perhaps the most controversial at the time, far away from sensory inputs and motor outputs. In the 1940s, the American psychologist Edward Tolman had already proposed the concept of a cognitive map but lacked the tools to test them. It is worth noting that like many great discoveries in science, O鈥橩eefe鈥檚 proposition that the hippocampus was involved in spatial navigation was met with some scepticism. However, it was later appreciated that the proposal was seminal.
The idea of the cognitive map, its location in the hippocampal formation and the effects of damage to it on the animal's behaviour were subsequently spelt out in the now classic book 鈥淭he Hippocampus as a Cognitive Map", along with Lynn Nadel, published in 1978 by Oxford 深夜亚洲福利久久 Press. This book is a tour de force integrating philosophical, geographical and psychological theories with anatomy and physiology and a must read even 35 years later for all interested in cognitive neuroscience.
We now appreciate that place cells can encode not only for the current spatial location, but also where the animal has just been and where it is going next. Thus the past and present may also be overlapping in time in place cells which might allow the brain to remember temporally ordered representations of events, like in the episodic memory.
Subsequently, other important cells that guide navigation have been found in areas closely connected to the hippocampus - head direction cells have been found in the presubiculum, while entorhinal grid cells are thought to be signalling distance travelled in a particular direction, have been described by the Mosers some 30 years after O鈥橩eefe鈥檚 discovery and which led to them sharing in the Nobel Prize.
Through O鈥橩eefe鈥檚 discoveries, the cognitive map theory had found its representation in the brain, the 鈥渋nner GPS鈥� 鈥� the brain鈥檚 positioning system.
In the following decades, O鈥橩eefe showed that the place cells might have memory functions where a memory of an environment can be stored as specific combinations of place cells and this is among the most intriguing implications of the findings.
Determining how our thoughts and behaviours can arise from single cells is one of the ultimate goals of neuroscience. For certain domains such as motor function, this has been relatively easily worked out. However, when it comes to recalling the past or planning a route through space, it鈥檚 a huge challenge, and that鈥檚 where O鈥橩eefe鈥檚 place cells and the Moser鈥檚 grid cells come in. They represent a complete paradigm shift in our understanding of how groups of specialized cells work together to execute higher cognitive functions.
Although these studies were all conducted in rats, evidence from brain imaging techniques and from patients who have undergone neurosurgery has indicated that place and grid cells also exist in humans. In fascinating studies, O鈥橩eefe with Eleanor Maguire, an Irishwomen, Neil Burgess and colleagues used a virtual reality simulated town to show that the hippocampus is indeed recruited during complex spatial navigation in humans. Similar mechanisms may underlie the remarkable findings of Maguire and colleagues who demonstrated that the hippocampus of London taxi drivers, which undergoes extensive training to learn how to navigate between thousands of places in the city without a map, grew during the year-long training period and that the taxi drivers after this training had significantly larger hippocampal volume than control subjects. Hippocampal place cells allow us to move flexibly, to be able to deal with novelty and unexpected events. When a cab driver is trying to plan a route, this part of the brain lights up and stays active. When they have to follow a simple route, they don鈥檛 need this part of the brain. It is intriguing to wonder if John in his days of driving a cab in New York ever realised the impact of such experience on his own brain.
Brain disorders are the most common cause of disability and despite the major impact on people鈥檚 lives and on society in general, there is no effective way to prevent or cure most of these disorders. Advances in neuroscience are crucial to keep our ageing societies and our economy healthy. Brain-related disorders will affect at least one in every three of us during our life and treating these disorders costs already now some 800 billion Euro in Europe every year says the European Union. Deciphering how our brain works is good for our health, our society and our industrial competitiveness.
Episodic memory is affected in several brain disorders, including dementia and Alzheimer鈥檚 disease. A better understanding of neural mechanisms underlying spatial memory is therefore important, and the discoveries of place and grid cells have been a major leap forward to advance this endeavour. O鈥橩eefe and co-workers have showed in a mouse model of Alzheimer鈥檚 disease that the degradation of place fields correlated with the deterioration of the animal鈥檚 spatial memory. It is worth noting that the hippocampal formation is one of the first structures to be affected in Alzheimer鈥檚 disease and knowledge about the brain鈥檚 navigational system might help understand the cognitive decline seen in patients with this disease.
As we saw in the Symposium held earlier today, the hippocampus plays critical roles in many aspects of brain disorders and understanding what regulates hippocampal activity will be an important aspect for future endeavours. Studies of the navigation system have opened new avenues for studying how cognitive processes are computed in the brain.
Despite such amazing advances we are still in the early days of finding out how the brain works especially in the context of the neural basis of neurodegenerative and psychiatric brain diseases. However, this is an exciting time in Neuroscience; last year the European Union have invested 1billion Euro in the Human Brain Project which is focused on building a computerised model of brain function. In the USA, President Obama has launched the Brain initiative; with Brain standing for 鈥淏rain Research through Advancing Innovative Neurotechnologies鈥� and this has as its goal the ambitious aim of mapping the activity of every neuron in the human brain. O鈥橩eefe is very optimistic about such ventures.
O鈥橩eefe has been in UCL since the 1960鈥檚, becoming professor in 1987. Like myself, he is a Neuroscientist in an Anatomy Dept, again highlighting the close relationships between structure and understanding function. He is a Fellow of the Royal Society and of the U.K. Academy of Medical Sciences. In addition, he received the Feldberg Foundation Prize in 2001 and the Grawemeyer Award in psychology in 2006 (with Lynn Nadel). In 2007, he received the British Neuroscience Association Award for Outstanding Contribution to British Neuroscience and in 2008, he received the Federation of European Neuroscience Societies鈥� European Journal of Neuroscience Award. Later in 2008, O'Keefe was awarded the Gruber Prize in Neuroscience. In 2011, he was appointed as the inaugural director of the Sainsbury Wellcome Centre for Neural Circuits and Behavior which opened this year. In 2013, he received the Louisa Gross Horwitz Prize (with Edvard Moser and May-Britt Moser). In 2014, he was a co-recipient of the Kavli Prize awarded by the Norwegian Academy of Science and Letters which he co-shared with Brenda Milner, whose work inspired the entire field and with Marcus Raichle of Washington 深夜亚洲福利久久.
He continues to publish, having published in papers Science, Nature & PNAS in the past two years alone and is the consummate bench scientist.
In thinking of O鈥橩eefe and his Norwegian prot茅g茅es, the Mosers鈥� work on mapping the brain, I鈥檓 especially drawn to the final stanza of Elizabeth Bishop鈥檚 Poem 鈥楾he Map鈥�
Mapped waters are more quiet than the land is,
lending the land their waves' own conformation:
and Norway's hare runs south in agitation,
profiles investigate the sea, where land is.
Are they assigned, or can the countries pick their colors?
-What suits the character or the native waters best.
Topography displays no favorites;
North's as near as West.
More delicate than the historians' are the map-makers' colors.
O鈥橩eefe鈥檚 colours have been ones of innovation, persistence and curiosity.
Whilst our maps change as new countries or types of nerve cells emerge and boundaries shift, our understanding of the brain鈥檚 working will continue to increase.
The travel writer Robert Macfarlane鈥� has said that 鈥榗artographers have often tended also to be dreamers, seduced into their science by the beauty of maps and the flights of imagination that they prompt. Maps seek to mark the world and fix its flux, but in doing so they also loosen it from its moorings: as documents, they are at once fiercely empirical and faintly mystical鈥�.
As a cartographer of space within the brain John O鈥橩eefe is more than a dreamer; he is a philosopher.
What is particularly inspirational about Prof O鈥橩eefe is that he is a maverick in all senses, he has used his position to make important points about today鈥檚 society that also have a huge impact on our ability to do science.
- He has been critical of British immigration rules which make it difficult to bring in the world鈥檚 best scientists. As an immigrant in the UK and the son of immigrants, he is particularly well placed to make such points. There are no boundaries in the maps science.
- He used his Nobel Dinner address last week to comment on the pernicious rise of xenophobia.
- He has spoken actively how the use of animals in research is so important for understanding complex human states. Moreover, his focus on fundamental what we call today 鈥渂asic鈥� research is an important signal to funding agencies of its value.
- He has also been a strong advocate of encouraging young people in science and has been a very valuable mentor to some of today鈥檚 finest cognitive neuroscientists including his Nobel co-winners.
- Seeing as we are in a 深夜亚洲福利久久 environment, it is also worth noting that O鈥橩eefe has been extremely generous in acknowledging the support he has got from his own 深夜亚洲福利久久, UCL and also going back further the importance of the City College system in New York, in those days tuition-free, in giving him his start.
It is important to note that John left CCNY with more than a solid education. He met his wife, Eileen, who is part Irish, German and Polish, in a philosophy class there and they have this year celebrated their 50th wedding anniversary. Together they have two grown sons, Riley & Kieron and two grandchildren.
Navigation isn鈥檛 far from John鈥檚 pastimes where he is a keen hill walker and has spoken of his fondness for the ordinance survey map. Moreover, he still navigates the basketball court at least once a week with students and colleagues.
O鈥橩eefe鈥檚 journey has followed the road less travelled for the son of an Irish emigrant; although it is worth noting that there is another Irish American called O鈥橩eefe who was fascinated with space, albeit on a larger scale. The late NASA scientist John Aloysius O鈥橩eefe was credited with the discovery of the earth鈥檚 鈥減ear shape鈥� after studying satellite data from the 1950s. Together their work is a clear sign that Irish ingenuity continues to resonate all around the world and even in space, big and small.
It is also worth contemplating the what ifs, like John F. Kennedy in his famous New Ross speech where he said if his ancestors hadn鈥檛 left Ireland, he probably would have been working in the Albatross fertilizer factory; what if John鈥檚 dad hadn鈥檛 left Newmarket or had returned there like one of his brothers, would he be navigating the north Cork farmland or perhaps more likely be a Professor here in UCC? O鈥橩eefe and his US family have kept strong connections with Ireland and we are delighted to have many of his extended family from New York, Cork and Mayo here today including his sister Linda from New York and their many first cousins.
Understanding the brain is one of the great challenges for society and O鈥橩eefe鈥檚 work has not only revolutionised our understanding of this amazing puzzle, it has opened new avenues for understanding complex cognitive processes, such as memory, thinking and planning and given us insight into our own existence.
John O鈥橩eefe: neuroscientist, philosopher, innovator, and cartographer of the mind, it gives me great pleasure to invite you to receive the Degree of Doctor of Science, honoris causa.
Praehonorabilis cancellarie, totaque universitas!
Praesento vobis hunc meum filium, quem scio tam moribus quam doctrina habilem et idoneum esse qui admittatur, honoris causa, ad gradum Doctoratus Scientiae, idque tibi fide mea testor ac spondeo, totique Academiae.