A scientist of great stature, with an extraordinary memory, a fondness for cigarettes - and an occasionally intimidating interview technique.
Those were some of the impressions we received from our alumni when we asked them for their memories of Lord (Alexander) Todd, former Professor of Organic Chemistry here, who won the Nobel Prize for Chemistry in 1957.
Feats of memory
"Of course, he was Sir Alexander Todd when I first encountered him in 1953, the year that I matriculated at Pembroke and the year of Crick and Watson’s publication in Nature of the structure of DNA..." So begins Dr David Cohen's reminiscence. "My immediate first impression was of his memory when he delivered his lectures on the Nucleic Acids entirely without notes. To my delight, he accepted me as a research student in 1956 with the aim of synthesising oligonucleotides - and showed further feats of memory when he visited me in the lab, as he did daily when he was around. If, say, he wanted me to use a reagent such as dibenzylphosphorochloridate, he could provide from memory the reference to the Beilstein edition, the volume and the page to synthesise it."
Dr Cohen, Emeritus Registrar, University of Keele, adds: "In those days, I used to smoke. Alex would invariably ask me if I had a cigarette and would take the pack and leave it next to him during our discussion..."
Interview technique
Other alumni remember Todd for different reasons, including his somewhat intimidating interview technique. David Rand, Honorary Research Fellow at the Commonwealth Scientific and Industrial Research Organisation, recalls going to see him in the early 1960s to discuss conducting postgraduate research on nucleotides and finding it an unnerving experience. He says, "I entered a room that was surely more befitting a stately home than a chemistry laboratory. Lord Todd, a tall man, was reclining so far back in his chair that I was obliged to converse throughout with the soles of a pair of shoes which rested atop his highly polished desk."
And Professor Mark Bretscher, an alumnus who went on to spend almost his entire research career at the MRC Laboratory for Molecular Biology, also recalls an interview with Todd that didn't go quite as anticipated.
He says: "I was at Cambridge, studying Natural Sciences with lots of chemistry, a subject I really enjoyed. In my third year (early 1961), I applied to do a PhD in the chemistry department and had a meeting with Todd in his vast office. He ushered me to sit in a small chair in front of his huge desk and said he understood I wanted to do a PhD in his department: did I have any idea with whom? I said I had chosen Malcolm Clark (who was my Director of Studies at Caius). But Todd told me many students wanted to work with Clark and, were I accepted, I might have to work with someone else.
"I was unhappy with this; I was leaning towards biochemistry when someone suggested I look at Perutz's group in the Cavendish. I had never heard of them, but went along and discovered Francis Crick, who accepted me. When I went back to tell Todd of my move, he became pretty angry. If I went to Crick, he said, I would be "throwing away my career". He suggested that I get a PhD in a "well-founded" subject like organic chemistry and then I could "flirt" with molecular biology. I went to the Cavendish."
Others had different experiences. Sir John Sulston, who became the founding director of the Sanger Institute, from where he led UK research in the Human Genome Project, was taken on as a PhD student by Lord Todd after his original plans - to do voluntary service overseas - fell through. "I came, hat in hand, to the department and was interviewed by Alexander Todd," he says. "He was austere but amazingly accepting of this 'refugee' with his 2.1."
And David Cohen tells us that he enjoyed working for Lord Todd. "In those days, we had to prepare our own supplies of deoxyribonucleosides from herring sperm DNA but the biosynthetic method (published by Alex Todd and two Scandinavian co-authors) had not been able to produce the desired result for some time. My first task was to make it work!
Trial and error
"After a number of failures, I solved the problem serendipitously by the intervention of an American postdoc, Dr. Martin Stempien, who persuaded me to come to lunch in the neighbouring pub just as I had put another batch of DNA onto a waterbath. Returning late, I decided to check the solution by paper chromatography and found the sample totally degraded. This led me to take samples at intervals of 5, 10 and 30 minutes and finally of the starting material. I found that lab’s entire supply of DNA (several kilos) was apurinic acid - I presumed from the effect of CO2 and moist air. With a fresh supply of DNA, the process worked perfectly."
Dr Cohen recalls that in his second year of research, "Sir Alexander was awarded the Nobel Prize and there was a great celebration. I was asked to help organise the official party and put in charge of a special bottle of malt whisky which was only to be offered to designated guests. My final research year was marked by two memorable events; firstly, I had the pleasure of supervising Ian Fleming preparing for Part II and, secondly I was invited to go to Yale University initially as a post-doctoral student and subsequently as an instructor. This latter event came about remarkably when a distinguished Yale Professor, Werner Bergmann, wrote to Sir Alexander enclosing a sample of an unusual nucleoside. Werner had been looking into theories of the origin of “life” and argued that there must have been an evolution of DNA and RNA. He had been extracting material from primitive life forms and found these samples in a sponge (Cryptotethia Crypta). One resembling uridine, which he called “sponge-uridine”, was the sample he had sent. Quite by chance, Dan Brown had been attempting, without success, by chemical methods to covert ribosides to deoxyribosides and on one occasion instead of removing the oxygen on the C2 of the ribose ring, he had inverted the hydroxyl group creating uracil arabinoside. This proved to be identical with “sponge-uridine”.
"Werner was delighted to get such a rapid response and asked if Sir Alexander could recommend one of his doctoral students to come to Yale to work with him. I was very pleased to accept!"