UNIVERSITY COLLEGE DUBLIN
HONORARY CONFERRING
Friday, 14 June 2019 at 3 pm
TEXT OF THE INTRODUCTORY ADDRESS DELIVERED BY PROFESSOR STEPHEN GORDON, School of Veterinary Medicine on 14 June 2019, on the occasion of the conferring of the Degree of Doctor of Science, honoris causa on PATRICK JOSEPH BRENNAN.
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President, Honoured Guests, Ladies and Gentlemen
The control of infectious disease is a major challenge in veterinary and human medicine. This challenge is encompassed within the ‘One Health’ concept that highlights how the health of animals, humans and the environment are intimately linked. Vaccines and antibiotics are the cornerstones of modern veterinary and human healthcare, but with the spectre of newly emerging infectious diseases and the increased prevalence of antimicrobial resistance there is an urgent need to use our existing antibiotics prudently, and to develop new antibiotics, vaccines and diagnostics to address these challenges in both veterinary and human contexts.
Developing new ways to combat infectious disease is the challenge that Prof Patrick Brennan has risen to over his fifty-year career in studying the bacterial pathogens that cause tuberculosis and leprosy.
Prof Patrick Brennan, Pat to his many colleagues, is a Distinguished Professor in the College of Veterinary Medicine and Biomedical Sciences in Colorado State University, USA. His research career has focused on the study of mycobacteria, a diverse group of bacteria that include some of the most important disease-causing bacteria of humans and animals globally. For example:
- Mycobacterium bovis is the causative agent of bovine tuberculosis but can also cause TB in wildlife and be spread to humans through contaminated food.
- Mycobacterium tuberculosis causes TB in humans, a disease which is still one of the most important infectious diseases globally, with someone in the world dying of TB every 25 seconds.
- Mycobacterium leprae causes leprosy, a disease that many people think of as long eradicated, but globally has over 200,000 new cases every year. Indeed, we see the historic scars of leprosy here in Ireland; Leopardstown, just down the road, is not referring to a town of ‘leopards’ in any veterinary sense, but rather is a semantic change over time of ‘town of the lepers’, referring to when Leopardstown was the site of a medieval leprosy colony.
Pat Brennan’s research on the mycobacteria has opened up new understanding of how these bacteria function at the molecular level, information that has catalysed the development of new drugs, diagnostics and tools for the control of mycobacterial diseases.
Patrick Brennan was born in Boyle, County Roscommon in 1938, and after completing his secondary school education in nearby Blackrock College he went to University College Cork where he received BSc and MSc degrees in Biochemistry. He then returned to Dublin in 1962 to study for a PhD with Prof Frank Winder in Trinity College Dublin exploring how isoniazid, one of the key drugs for the treatment of TB in humans, acted to kill the bacteria. Pat’s studies focussed on the action of the drug on the mycobacterial cell wall, a remarkably complex structure that possesses an array of unusual proteins, lipids, and carbohydrates that are unique amongst the microbial world. Understanding how the intricate biochemical structure of the mycobacterial cell wall is woven together, and how we can use this knowledge to create the new drugs, diagnostics and vaccines that are so desperately needed, would become the overriding goal of Pat Brennan’s research career over the subsequent decades.
After completing his PhD in 1965 he undertook a postdoctoral fellowship in the University of California at Berkeley where he continued his studies into the mechanisms of bacterial cell wall biosynthesis. He returned to Trinity in 1967 as a research lecturer, and in 1968 married Carol Blair who was a postdoctoral researcher in Trinity at the time. In 1971 Pat joined the UCD Department of Biochemistry, then based in Merville House across campus, as a College Lecturer. Pat recalls his time here in UCD with fond memories, building up his own independent research group, while outside of work starting his family with Carol who had obtained a faculty position in Trinity College. But life takes many unexpected turns, and when Carol was appointed to the faculty of Colorado State University in 1975, Pat followed her the following year to the USA, leaving UCD for a position at the National Jewish Hospital in Colorado. From there he moved to the University of Colorado and finally also joined the faculty of Colorado State University in 1980.
It was at Colorado State University that Pat’s world leading reputation was established, founding the Mycobacterial Research Laboratories and nurturing a multidisciplinary team of scientists to study mycobacterial pathogens and the host response to infection. The discoveries made by Pat and his colleagues are too numerous to mention in detail today, with Pat having published over 350 research articles and having been in receipt of decades of continuous research funding. His seminal discoveries include: deciphering the biosynthesis of the mycobacterial cell wall; revealing novel enzymes involved in mycobacterial metabolism that are targets for the next generation of antibiotics; identifying antigens that form the basis for improved immune diagnostics and vaccines; and shedding light on the evolution of the mycobacteria from ancient environmental bacteria to modern day pathogens.
However, from the One Health angle of links across veterinary and human medicine, one aspect deserves particular attention. Pat identified and described the chemical structure of a unique lipid in Mycobacterium leprae, a phenolic glycolipid, that was also antigenic and was used to develop a new serological diagnostic for leprosy in humans. It had previously been shown that Mycobacterium bovis produced a similar phenolic glycolipid. In the same way that the M. leprae phenolic glycolipid formed the basis of a serological test, could the bovine immune response to this Mycobacterium bovis glycolipid antigen provide a new test for bovine TB? To explore this, a research project was developed between Pat and Prof Dan Collins, the Professor of Farm Animal Clinical Studies in the UCD School of Veterinary Medicine who had a lifelong research focus on bovine TB. Aidan Kelly, well known in a different guise to our final year students, went to Pat Brennan’s laboratory in 1989 to perform the research that would investigate the potential of this new Mycobacterium bovis antigen. Aidan’s work at CSU revealed that the serological response to this new antigen was, however, too insensitive for it to be used as a diagnostic reagent for bovine TB. Nevertheless, this research project speaks again to the One Health concept, where cross fertilisation of ideas can catalyse the development of new tools to control infectious disease in humans and animals. And indeed this project served as the first of a number of research exchanges between UCD School of Veterinary Medicine and Colorado State University.
Pat Brennan’s outstanding international reputation has seen him invited to Chair numerous national and international committees, including the World Health Organisation Program for Tropical Disease Research and the U.S.-Japan Cooperative Medical Sciences Program. Pat has also provided advice to our own national bovine TB eradication program. When Liam Downey became the head of the Irish bovine TB eradication program in 1988 one of his key goals was to ensure disease control policy was formulated on sound science. Towards this goal, he undertook a study tour in 1989 of leading bovine TB researchers, and along with Prof Dan Collins from UCD and Michael Sheridan from the Department of Agriculture, visited Australia, New Zealand and of course Pat’s research group in Colorado. This study tour led to the development of a research roadmap for the Irish bovine TB eradication programme that would include the implementation of the new bovine gamma interferon assay and a badger vaccine programme. These areas are currently led by Prof Eamonn Gormley in the School of Veterinary Medicine and have seen Ireland roll out vaccination of badgers in 2018 as an integral part of the bovine TB eradication programme. In another One Health link, the badger vaccination programme uses the same BCG vaccine that is used to protect humans.
Pat has maintained his input and intertest in bovine TB research over the years, and attended the first International Mycobacterium bovis meeting that was held here in UCD in 1990. This meeting has been held every five years in various countries around the world, and Pat returned to Dublin again for the 2005 meeting. The meeting returns again to Ireland in 2020 when the Seventh such meeting will be held in Galway, and Pat, we hope to see you there.
Pat Brennan’s persistence and resilience in tackling the mycobacteria is paralleled in his athletic pursuits, being an avid runner who won the annual Belfast to Dublin walk twice in the mid 1960s, in a record time I might add, before graduating to the more manageable distance of marathon running in subsequent years.
Pat Brennan’s career is a shining example of how the pursuit of scientific excellence and translation of that research into new control tools can produce benefits across both human and veterinary medicine. Today as you embark on your own careers as new graduates, I hope Pat’s career will serve as an example to you all.
Praehonorabilis Praeses, 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.