In memory of my mentor, colleague and friend, David Ish-Horowicz FRS

David Ish-Horowicz, who died on July 19th just two weeks short of his 76th birthday, pioneered the application of molecular biology to the analysis of Drosophila development in the UK. His laboratory at the Imperial Cancer Research Fund (ICRF) unit in Mill Hill performed ground-breaking studies that paved the way for the molecular revolution that has driven our subject over the last 40 years. He began by cloning and characterising the Drosophila gene hairy, identified as one of the pair-rule class by his friends and colleagues Christiane Nüsslein-Volhard and Eric Wieschaus, with whom he had worked in the laboratory of Walter Gehring in Basel. Later, in his lab at the legendary ICRF DBU (Developmental Biology Unit) in Oxford, he applied his skills to the identification and analysis of the Notch ligand, Delta, in vertebrates. His many accomplishments were recognized by the BSDB through the award of the Waddington Medal in 2007. He leaves an indelible mark on the field, both through his research and through the many PhD students and post-docs that he mentored.

 

I first met David exactly 44 years ago this month, at the 1980 EMBO Drosophila Workshop in Crete. This was a meeting reserved for principal investigators to which I had somehow gained admission, despite still being a mere PhD student. As I entered the reception on the first evening, I was feeling extremely nervous and intimidated by all the senior scientists gathered around chatting in groups and was desperately looking around the room for someone who might speak to me. And then I came across David, who, with his characteristic smile, engaged me in conversation about my research interests. He immediately put me at my ease and gave me the confidence to make the most of the meeting, something I will never forget.

Eighteen months later I saw an advertisement for a research fellowship in David’s lab and did not hesitate to apply. David invited me for interview at the ICRF labs in Mill Hill, an experience that for me was both exhilarating and life-changing. We talked all day about how fruit fly embryos develop and his plans to understand the function of the “hairy” gene that he had just succeeded in cloning – one of the first of the so-called segmentation genes to be isolated molecularly. The combination of David’s razor-sharp mind and child-like enthusiasm was irresistible and I did not think twice about accepting when he offered me the post. So began three of the most exciting years of my scientific career. David’s thirst for knowledge was infectious and I could not wait to get into the lab each day to see what new phenomena we would uncover.

The joy of making new discoveries – be they inside or outside the lab – is something David never lost. Indeed, only a few weeks ago when I last visited David and Ros, his wife, in their flat in London, he excitedly told me that he had discovered a new entrance to the Barbican Arts Centre! When he explained that this was located half-way down the ramp to the underground car park, I must admit that I did wonder if his illness (glioblastoma) might be playing tricks with his memory. But I happily agreed to go for a walk with him so that he could show me – and sure enough, as we descended the ramp into the carpark, there was the door that led us straight into the entrance foyer of the centre!

David’s satisfaction at having found the best route into the Barbican from his flat was palpable, a reflection of his constant quest to find the best way of doing everything. This trait was worth its weight in gold to those who worked in his lab – he consumed the scientific literature obsessively and could always tell you the latest and best ways of doing things, often prefaced by “what you should have done”! It was David who introduced me to SP6 polymerase, which revolutionized the synthesis of probes for in situ hybridization. The fact that this superseded the single stranded DNA probes, the synthesis of which David himself had perfected with his post doc, Julian Burke, was of no concern to him – he thrived on technological progress.

Outside the lab, David could always tell you the best places to ski, the best restaurants to eat at, the best wines to drink – the list was endless, informed by his voracious appetite for reading “Which”! There was only one occasion when he got things badly wrong: I had wanted to buy a HiFi so naturally sought his advice. He told me which turntable, amplifier and speakers to buy and which audio store to buy them from, in West Hampstead as it happened, which I duly visited one Saturday afternoon. The next Monday David asked excitedly if I had got everything – “yes” I replied “and I bought a CD player too!” David’s expression immediately changed and he shook his head: “no, no” he exclaimed, “CDs will be obsolete in a couple of years when Sony launch DAT (Digital Audio Tape)” That was in 1984!

Not only was David always happy to give advice, he was also incredibly generous with his time. I recall him staying late one evening to show me how to do colony lifts of a phage library that he had helped me construct in an effort to clone the trithorax gene, something he encouraged me to do in my “spare” time. We did this in his cramped and cluttered lab-cum-office whilst listening to the Archers on the radio! Many years later, after I had moved away from the DBU in Oxford – where we had been colleagues for nearly 10 years – and established what was to become an MRC Centre in Sheffield, I asked David if he would serve on its Scientific Advisory Board. He agreed without hesitation; and most recently it was David to whom I turned when I needed an external assessor on an appointments panel for the Living Systems Institute in Exeter, a role he fulfilled with his customary thoroughness, insight and good humor.

David began his scientific career sequencing a tRNA – he has left us enriched by the qualities denoted by the much shorter sequence of a well-known restriction site, CCGG: Caring, Compassionate, Generous, Genius.

Thank you for everything David – I will miss you.

Philip Ingham FRS

Raymond Schinazi and Family Chair of Life Sciences

University of Bath

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