UCL 2013 Prize Lecture in Clinical Science with Professor Gary Rukvun

Written by Lucy Bell, UCL MBPhD student

The UCL Prize Lecture in Clinical Science, held this year on 30 October,  is one of the university’s most exciting events – the annual invitation of one of the world’s most distinguished scientists to receive an award and speak about their career and research to a UCL audience.

This year’s recipient was Professor Gary Rukvun of Harvard Medical School, whose pioneering work in the discovery of microRNAs – small RNA species with potent regulatory effects – has arguably changed the accepted paradigm of cellular function over the past 20 years, showing that the functional products of genes are not always proteins.

It has also paved the way for a brave new world in genetic research, in which the functions of genes can be rapidly deleted and reconstituted; a level of manipulation unprecedented in molecular biology.

After an undergraduate degree in physics at the University of Berkeley, California, and several years of travelling and tree-planting across the Americas, Professor Rukvun embarked on doctoral training in genetics at Harvard that would eventually bring him to his research into the tiny roundworm Caenorhabditis elegans.

This was to be the model organism in which he and his long-term collaborator Victor Ambros identified and characterised the first microRNAs, lin-4 and let-7.

His work has since extended and expanded from this key observation, identifying many further microRNAs and describing the mechanisms by which they work, as well as investigating insulin signalling pathways in C. elegans, which have informed our fundamental understanding of ageing, longevity and human diseases such as diabetes.

Before his lecture, eight UCL MB PhD students, including myself, were lucky enough to have the opportunity to spend an hour with Professor Rukvun over tea and scones.

Despite having landed in the UK only the previous afternoon (and having braved the storm of the century in order to do so), he was engaging, witty and lively, and regaled us with tales of his experiences of science over the past 30 years.

Topics covered ranged from his experiences of scientific scepticism in the early days of microRNAs, to the importance of investigating your unexpected findings and the serendipitous consequences of doing so.

We were heartened to hear that you are never too successful to feel frustrated by yet another set of journal reviewers’ comments, or to feel intimidated by eagle-eyed questioners at the end of a seminar!

His remarks about considering evolutionary conservation from worms to mammals and from mice to men would ring true again later in his lecture, and his incredulity that we finish our British PhDs in less than four years, compared to the sometimes ten-year marathons across the Atlantic, highlighted the global variation that exists in scientific training.

He began the 2013 Prize Lecture in Clinical Science by telling us about C. elegans, the simplest complex organism studied by life scientists.

What followed was a whirlwind tour through an elegant series of observations made by his lab. Using microRNA technology, they have shown that deleting central components of cell function can counterintuitively increase the lifespan of these tiny worms.

Bizarrely, this was also associated with the worms becoming averse to food – almost as though they felt sick and couldn’t stomach the sight of a meal; at which point, Professor Rukvun digressed to point out the temptations of anthropomorphising your model organism too much!

Further investigation revealed that this wormy version of nausea was due to an anti-toxin, innate immune response: when the critical parts of their cells were malfunctioning, the worms were protecting themselves against ingesting any more of the toxins that might have caused their discomfort.

The endocrine response causing the worms to stop feeding turned out to involve bile acids, a part of biology that Professor Rukvun admitted he had never contemplated becoming interested in.

However, he is now a self-confessed bile acid enthusiast and concluded his lecture by drawing out some crucial consequences that this research could have for understanding human disease, from anorexia nervosa to depression and drug toxicity.

It was a striking description of a mechanism that gives insights into both human disease and fundamental cell biology; illuminating the link from basic cellular dysfunction to systemic hormonal cascades and sickness.

The audience was enthralled, and our new Provost, Professor Michael Arthur, expressed everyone’s appreciation as he wrapped up proceedings with a closing address and the presentation of the Clinical Prize Medal.

It was a fascinating afternoon and Professor Rukvun revealed himself to be not only one of the most pre-eminent and creative scientists of his generation, but also an engaging speaker with gallons of style and substance.

The group of young scientists privileged to speak with him personally found his advice inspiring and memorable, and were left with a lasting impression of how scientific success can go hand-in-hand with approachability and honesty.

It was doubtlessly another stellar year for the UCL Clinical Prize Lecture, which goes from strength to strength, providing the UCL community with a unique opportunity to hear from the world’s leading thinkers – long may it continue.