January 5, 2015, by Editor

An awful shame

Here is the sixth blog from our Emeritus Professor, Malcolm Stevens, FRS: 

Nitrogen fixers  

In 1967 the work of my small team at the Pharmacy Department, Heriot-Watt University, focussed on three related structures: triazines, which are six-membered rings containing three nitrogen and three carbon atoms; triazenes, which contain an array of three contiguous nitrogen atoms substituted at each end; and azides, which superficially resemble triazenes but are substituted at only one end. Although all nitrogen-rich and unstable to a more or lesser degree, these chemical types differ markedly in their properties. They could be transformed in high yields to products with potential biological activity. In the late 1960s our group had no local biological inputs or outlets and compounds had to be sent to the National Cancer Institute in Washington for testing for putative anticancer activity. We published lots of papers in mainstream chemistry journals and presented our work, tentatively at first, but then with increasing confidence, to meetings of The Royal Society of Chemistry (RSC), usually in drizzly cities in the North of England. In August 1968 I spent a productive three months working in Münster, Westfalia with Prof Alfred Kreutsberger, himself a triazines man. With our expertise in 1,2,3- and 1,2,4-triazines and Kreutzberger’s interest in 1,3,5-triazines we had all triazine bases covered. My visit to Germany coincided with two historic events: students were revolting across Europe and the ‘Uprising’ almost toppled the French Government when workers came out in support of the students; the administrative block and library of Münster University was occupied by students throughout my stay. August of that year also marked the demise of the ‘Prague Spring’ when the tanks of the Warsaw Pact countries crushed the reformist regime of the popular Alexander Dubcek. NATO F-104 Starfighters patrolled overhead to reassure the locals that the tanks would not continue westward.

Sighs  

Rare visits to London at New Year to attend meetings of the Heterocyclic Group of the RSC at Queen Elizabeth College in Kensington were eye-popping – and not just for the chemistry. Kensington positively swung. One of the first boutiques opened in 1965 on Kensington Church St opposite a bus stop. Some time later I went with my wife to the large Biba store relocated on Kensington High St and she bought a large floppy-brimmed black hat of the style popularised by Jean Shrimpton, the original ‘super-model’. In 1966, courtesy of some biased refereeing, Alf Ramsey’s English ‘wingless wonders’ won the World Cup, which went down like a stone balloon in Scotland. Up north there were plenty of parties organised by the Watt pharmacy students who always invited the younger staff (and more dissolute older ones like my pal Basil) along to their revelries. Most of the time music was provided solely from the Beatles’ album ‘Sergeant Pepper’s Lonely Hearts Club Band’ which was released on 1^st June 1967. Because of the cold climate the ‘miniskirt’ tsunami took a couple of years to travel from Kensington and Chelsea to conservative Edinburgh. Its much anticipated debut in the Pharmacy Department was championed by a long-haired, leggy, ex-convent school girl who drove hemlines remorselessly skywards. Some armchair academics tentatively linked an outbreak of ‘hysteria’ amongst female pharmacy students to their wearing short skirts and the cold winds from the North Sea that constantly blew thereuppem. (For good reasons the side streets in Edinburgh are called ‘wynds’) Outbreaks were clustered around exam time and I recall my first experience of invigilating; ominously it had been a cold and stormy spring. The first sign of trouble was when an audible sighing started: then suddenly a student smote all the paraphernalia on her desk to the floor – exam papers, pencil case, cosmetics, polo mints, etc – and fled the room. Apparently this girl, as well as wearing very short skirts, had ‘form’ and the other students just carried on unperturbed. The candidate returned ten minutes later (having spoken with another invigilator) and calmly resumed answering the paper. Soft Stevens probably violated exam regulations by allowing her an extra ten minutes to finish. Well why not?

Distractions

I grew to love Edinburgh despite its dreichclimate and grey buildings and took to finishing work each Friday with a few jars in one of the Grassmarket’s pubs with assorted oddballs from The Watt. Socialising at the end of the week became a custom that I continued throughout my academic career, even frequenting the Johnson Arms in Dunkirk on Fridays after work well into the new millennium. If I am perceived to have reasonable ‘people skills’ it may be because of my accessibility which such beery interaction fosters. But of course it’s what pubs have been doing for centuries. My two children, Ewan and Angela were born in Edinburgh but I could never get them to support the Scots when engaged in sporting warfare with the ‘auld enemy’. During my Watt years I became one of the staff managers of the student’s football club.  Tiresomely, students are on vacation over the busiest times of the season when fixtures have to be fulfilled. As a result most Saturdays I either played, or was linesman or, in extremis, referee. The Watt first team played in the East of Scotland League, which included Edinburgh University and local outfits, Edinburgh City Police, and reserve teams from lesser Scottish League clubs. Usually it was rather ugly stuff, notably from the Police, who played a 1:10 formation with the 10 solely intent on kicking the c–p out of the students. But then all Scottish football teams have their quota of Billy Bremners who react with flailing boots and fists at the slightest provocation. I had the misfortune, when reluctantly thrust into goal, to come up against one Joe Baker. Remember him? Together with Denis Law he was one of the first footballing exports to Italy, both signing for Torino in 1961. Baker’s career back in Scotland was on the slide and he was returning from injury to face a weakened Watt eleven. I prefer to forget how many he scored that day and I was mortified to read in a newspaper the day after that..…“The University goalkeeper couldn’t reasonably be blamed for more than five of the six goals conceded”.

I was a regular follower of concerts in the Usher Hall given by the Scottish National Orchestra. As I couldn’t afford tickets for big performances in the Edinburgh Festival I used to turn up at the end of the interval and sit on a radiator just before the music restarted. Timing was critical as the staff were not disposed to make a scene when the conductor had just taken to the rostrum. I recall a magical performance of Mahler’s 5^th Symphony, a work which became a favourite of mine. I used snatches of this symphony to accompany my professorial inaugural lecture several years later.

Being brilliant  

Back in the lab we had made significant progress in developing syntheses of bicyclic compounds comprising five- and six-membered rings with a ‘bridgehead’ nitrogen atom embedded between both rings. This feature could be used to control the ring-opening of the six-membered partner, a property which was exploited in the discovery of the antitumour imidazotetrazines a decade later. I also developed an interest in small, lipophilic analogues of methotrexate, a dihydrofolate reductase inhibitor, which was one of the pioneering examples of the antimetabolite class of antitumour agent developed after WW2. I also met for the first time the legendary Dr. Tom Connors, the ‘father’ of UK cancer chemotherapy. His inspirational example was to have a major influence on the careers of myself and my contemporaries. His stock slogan, often shouted over the hub-hub in a pub, was “Be Brilliant!” and was a reminder to all young scientists not to waste the opportunities that a job at the tax-payer’s expense gave them.

Grass is greener  

It was actually the climate that pushed me to think of England again. Edinburgh has only two seasons of the year, early winter and late winter; very occasionally they get a third – nuclear winter. As a keen gardener I was denied the opportunity to grow sweet corn, tomatoes, runner beans and other sensitive crops; even ground-hugging parsley had to be staked down to prevent it being blown away in the cold lashing gales which shredded plants in my exposed garden. Then in 1972 I was invited to apply for a Readership in the Pharmacy Department at The University of Aston in Birmingham. Aston was located on a roundabout in a grim area of run-down Birmingham. The city didn’t exactly present itself in an attractive guise in early 1972: there was a miner’s strike and a three-day week had been declared by Edward Heath, the Prime Minister. Power cuts were frequent. However, the Department had a relatively advanced research ethos for an ex-CAT and the Professoriate was adamant that they were going to create a dynamic teaching and research enterprise. I recall we discussed, over candlelight in the Midland Hotel on New St, the prospects of Aston Pharmacy Department becoming the MUFC of the pharmacy sector. As a loyal BWFC supporter myself (see Blog 1) I swallowed the indignity on this occasion and the top spot in the pharmacy premiership was indeed achieved in the 1980s. The avuncular Vice-Chancellor at the time, Joseph Pope, was an ex-Nottingham professor after whom the Pope Building at Nottingham was named. I was interviewed and offered the job. My Watt associates were mortified that I could even contemplate swapping the Athens of the North for Brummagen. One close colleague at my going-away do in a pub on the Royal Mile lamented that “it seems an awful shame”. It works better if you try it in a Scottish accent – choking back tears.

Postscript 1  

In July, 1981 the University Grants Committee (UGC), at the behest of our own Pharmaceutical Society, recommended a significant reduction in the numbers of funded pharmacy students. Even Nottingham, traditionally with a small, but high-quality, intake, was threatened by becoming too small to be economic. At the same time the UGC recommended that Heriot-Watt University Pharmacy Department should be “considered for closure” pointing out that two other Scottish Institutions provided sufficient places to meet demand in Scotland. The not-so-hidden agenda, however, was that their research activity was not deemed to be of university qualityto warrant continued funding.Despite a vigorous campaign in the Scottish press and Parliament the Department took its last entry in the 1984/5 academic year. I often wondered whether or not the decision would have been any different if I had stayed at The Watt and built up a vigorous research group there. Perversely, new pharmacy departments have been erupting like boils all over England in the last few years and, inevitably, another lancing of student numbers seems inevitable. Sadly, all those wonderful aspiring wannabe pharmacists from Edinburgh, the East of Scotland and the Borders have no local University to go to. Now that is “an awful shame”.

Postcript 2  

This will be the last Blog covering the earlier part of my pharmaceutical career. The productive Aston Years (1972-1992), which included the discovery of the ‘block-buster’ anti-cancer drug temozolomide, will be published from there.

                                                                   Malcolm Stevens, 11th Jan, 2015

• Share on Facebook
• Share on Twitter
• Share on Google+
• Share on LinkedIn