Dennis Slamon
UNIVERSITY COLLEGE DUBLIN
HONORARY CONFERRING
Thursday, 26 September 2024
TEXT OF THE INTRODUCTORY ADDRESS DELIVERED BY PROFESSOR JOHN CROWN, School of Medicine on 26 September 2024, on the occasion of the presentation of the Ulysses Medal on DENNIS SLAMON.
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A Uachtarán, a mhuintir na hOllscoile agus a dhaoine uaisle (President, members of the University, and Distinguished guests)
It is strange that only extraordinary men make the discoveries, which later appear so easy and simple. - Georg C. Lichtenberg
The impact that Dr Dennis Slamon‘s work has had on the field of cancer research is immense, and extends very substantially beyond that of his now famous and ground-breaking discoveries concerning the Her- 2 oncogene.
No, his influence extends substantially beyond his own multiple areas of investigation, into the very way that clinicians, scientists, the biopharma industries and academic research groups approach the cancer problem.
His inspiring life story begins in the town of New Castle in Pennsylvania, where his father, a former coal-miner and the son of a Syrian immigrant moved after surviving a mining cave-in. Dennis was a bright child who went to Washington and Jefferson college and then onto the MD/PhD and medical residency programs of the University of Chicago.
He undertook fellowship training in haematology and oncology at UCLA, where he subsequently joined the faculty.
His early research focussed on retrovirally induced malignancy and if his subsequent career didn’t provide the rest of us with enough grounds for feelings of inadequacy, it should be noted that before he embarked on the HER-2 journey he already had four first author publications in Science.
While a young faculty member, and in between looking after patients, starting a beautiful family with his wife Donna, running a lab and writing first author papers for Science, he began collecting and freezing breast cancer samples.
Some years later he attended a lecture by another great American cancer researcher, Robert Weinberg, concerning the neu oncogene, now known as HER-2/neu or more colloquially HER-2, which coded a unique protein.
In one of those inexplicable moments where the fate of millions of women and some men, many yet unborn, would be decided, Dr Slamon decided to study his frozen breast tissues for HER-2. He found that approximately 20% of breast cancers had alterations in this gene. He subsequently checked the medical records of these patients, and found that their cancer had a substantially more aggressive behaviour and was tragically much more frequently fatal.
Over the next years he and his team confirmed the result, again-published in Science, proved the importance of the HER-2 alteration by transfecting HER-2 normal breast cancer cells with HER-2 and observing the same increase in aggressiveness found in nature and began the process of persuading the biotechnology firm Genentech to develop an anti-HER2 therapeutic antibody.
He now had to call on another crucial personal and professional attribute, in addition to his research brilliance.
It was dogged determination in the face of extreme scepticism by most of the established breast cancer thought leaders, and reluctance by the leadership of Genentech to make the necessary investment to develop a HER-2 based treatment.
These were trying times for Dr Slamon. It is often said that the discovery of the importance of HER-2 was inevitable, and would have been made by others with time. Dr Slamon himself is generous to a fault in acknowledging the importance of the work of other investigators in this field, but a cold-eyed analysis of where the rest of breast cancer research was going and continued to go for the next decade and a half, suggests that the unique combination of inspiration, perspiration, brilliance and perseverance which he brought to this endeavour made it happen a generation earlier than would have been possible if we had had to wait for multi-omics revolution.
But he did win out, Genentech with his help and collaboration developed trastuzumab. Dr Slamon developed, led and conducted the international trials which demonstrated that trastuzumab treatment was so effective in HER-2 altered breast cancer that it now had a better and possibly the best prognosis of the different types of breast cancer.
Second and third generations of anti-HER2 drugs emerged, drugs which complemented the effects of trastuzumab, and may in some cases improve on them. He has collaborated in many of these developments, but all of them are ultimately derivative from his original work
Every morning when he looks at himself in the shaving mirror, Dennis Slamon has the quiet satisfaction of knowing that in the previous 24 hours alone, hundreds of women have had their lives extended, improved and very often saved directly as a result of his work.
He subsequently turned his focus on the most common type of breast malignancy, ie endocrine dependent breast cancer. He and his laboratory colleagues identified the activity of a group of cell cycle active drugs called the CDK4/6 inhibitors, and again designed and led the international trials which led to two of these drugs being approved and now widely used for the benefit of breast cancer patients around the world.
More recently he has brought the same laboratory and clinical skills to the new area of antibody drug conjugates, and at the most recent European Society of Medical Oncology, his research team presented very promising data in ovarian cancer.
Impressive as these discoveries are, the aggregate influence of his thankfully ongoing life’s work is greater than the sum of these awesome parts. He was the first to demonstrate that a molecularly targeted cancer treatment had efficacy in the treatment of solid tumours.
On behalf of our patients - thank you Dennis
Dr Slamon’s specific influence on Irish oncology, Irish research science and most importantly on the health and lives of Irish cancer sufferers has also been very substantial. We will hopefully discuss this in our fireside chat.
Dennis has already been awarded multiple national and international awards, including the Lasker Award, the Sjoberg Award and the Karnofsky Medal. I know that he is particularly proud of his President of Ireland Award and his Fellowship of the Royal College of Physicians of Ireland.
We are honoured that he will make space on his mantelpiece for the UCD Ulysses award.
Dennis, old friend, you have a very special place in many Irish hearts. So when I say, welcome to UCD, the welcome comes from the hearts of your many Irish friends, and most importantly from the thousands of Irish hearts which are still beating because of your work.
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Praehonorabilis Praeses, totaque Universitas,
Praesento vobis hunc meum filium, quem scio tam moribus quam doctrina habilem et idoneum esse qui recipiatur insigne ulixis; idque tibi fide mea testor ac spondeo, totique Academiae.