Professor Jeffrey C Watkins, FRS, FMedSci
Wednesday 11 February 2015 - Orator: Professor David Lodge
Madam Chancellor, it is my privilege to commend to you Emeritus Professor Jeffrey Clifton Watkins to be an Honorary Fellow of this University. An Honorary Fellowship is the highest honour the University can bestow and one that is bestowed infrequently. In Jeff’s case, the Fellowship recognises particular distinction in his academic field. Regrettably, Jeff, now in his 80s, is not well enough to join us at this ceremony, but he is proud and touched that the University has chosen to honour him in this way, albeit in his absence.
It is a daunting task for me to do justice to Jeff’s tremendous achievements. These have changed the direction of basic and clinical neurosciences. Jeff’s discoveries have led to new treatments for neurological and psychiatric diseases.
Jeff was born in 1929 in Perth, Australia, and gained a scholarship to Perth Modern School, where he showed a natural aptitude for chemistry. So much so that Jeff’s parents presented him with a Boy’s Own Chemistry Set. He immediately set about making Glauber’s salt, a well-known laxative, by mixing caustic soda and sulphuric acid. To Jeff’s great alarm, his grandfather ingested a large quantity – no need to say that Jeff’s first compound tested in man was an explosive success!
After first class honours and MSc degrees in Organic Chemistry from the University of Western Australia, and a PhD from Cambridge University. Jeff undertook postdocs on the chemical structure of nucleic acids of sponges and of pigments in aphids! Jeff, however, realised that the chemistry of the brain was where the biggest challenges lay; challenges he wanted to tackle.
He was invited to a Research Fellowship at the Australian National University with Jack Eccles, a Nobel Laureate. The task was to identify the chemical messengers that transmitted signals between nerve cells in the brain. He chose sodium glutamate, an acidic amino acid, as one of the first compounds to try, and the rest, as they say, is history! But what a history!
Working in 1958 with David Curtis, Jeff showed that glutamate excited most nerve cells in the brain and spinal cord. This was a breakthrough discovery but also very perplexing. The ubiquitous effect of glutamate, its established role in cell metabolism and similar excitatory effects of non-natural amino acids such as N-methyl-D-aspartate, NMDA, all made it difficult for many to accept glutamate as a neurotransmitter. There was a lot of skepticism among scientists! This resulted in what Jeff describes as the ‘dark ages’ of glutamate research.
For the next 15 years, in Canberra, Babraham and Carshalton, Jeff synthesised large numbers of glutamate analogues and tested theories as to how these amino acids interacted with nerve cell membranes. He proposed a three point interaction model which has stood the test of time – remember this was the time well before the advent of molecular biology and crystallography.
Then in 1973, he came to Bristol, to the physiology and pharmacology departments, a move engineered by Professors Biscoe, Buller and Mitchell. Now the ‘dark ages’ were expunged and Jeff brought enlightenment. He designed and synthesised molecules that would selectively block the actions of NMDA. Most importantly, Jeff with Dick Evans and others showed that NMDA antagonists blocked the transmission of signals between nerve cells. This was Jeff’s Eureka moment; proof that glutamate was indeed a major excitatory transmitter in the mammalian brain.
Jeff and his group here in Bristol, using compounds they synthesised and tested, went on to classify several subtypes of glutamate receptor. Some are coupled to ion channels and others to intracellular messengers, the so-called metabotropic receptors.
Although Jeff is a quiet and humble man, faced with enquiring students, he was always eager to share with them the excitement of new discoveries, even before they were published in scientific journals! This enthusiasm for understanding extended well beyond his own laboratory. Jeff was very generous with compounds that had taken long hours of bench and fume cupboard work. Sought by scientists throughout the world, Jeff readily gave out these precious compounds and helped design experiments which resulted in astonishing discoveries.
For example, both development of the early nervous system and learning and memory throughout life are now known to depend on NMDA receptors. Jeff’s NMDA antagonists were needed to establish this. As a result, memantine, a drug which modulates NMDA receptors, is now in the clinic for memory loss in Alzheimer’s Disease.
Over-activation of the NMDA receptors leads to convulsions and to neurodegeneration, Jeff’s NMDA antagonists were needed to characterise and elucidate these effects. Indeed one of Jeff’s compounds and some close analogues, have been used by pharmaceutical companies for the treatment of brain damage, convulsions and pain. A drug, perampanel, acting at one of the other receptors that Jeff discovered, is now used in the treatment of epilepsy.
Other compounds, developed directly from Jeff’s, have had successful trials in schizophrenia, stopping the hallucinations of this psychiatric disease and in trials for anxiety and panic disorder.
I could go on. As a result of Jeff’s work, most pharmaceutical companies have glutamate programmes and his insightful discoveries are now being mined for the benefit of neurological and psychiatric patients.
The scientific community has recognised Jeff’s achievements with fellowships of the Royal Society, Academy of Medical Sciences, the Pharmacological Society et cetera and with numerous awards and prizes, including several from the United States. He also co-founded a highly successful company to distribute his chemical tools worldwide for glutamate receptor researchers. His company, Tocris was awarded the Queen’s Award for Enterprise in International Trade.
From the Australian schoolboy and his chemistry kit to internationally renowned scientist with a mission to understand the chemistry of synaptic transmission in the brain, this is the Jeff I know.
Madam Chancellor, I commend to you Jeffrey Clifton Watkins to receive the distinction of Honorary Fellowship of the University of Bristol.