Life of a Lab Rat

Question: If you can ask if you're delirious, does that automatically mean you're not?

It's all right, I've cut the analgesic dosage (mmm codeine) so I should be reasonably coherent now.

Went to the quack's on Friday, and fortunately did not get to see the muppet who managed to miss the pneumal party when I crawled into his office last Thursday, barely able to breathe and unable to stand. Instead I saw a nice lady doctor who continued my roxithromycin prescription and also prescribed a cephalosporin. That is because I said I did not want a penicillin, as we use beta-lactamases in the lab all the time and I did not want to take the risk that anything pathological in me had managed to acquire resistance. Unlikely I know, but always a worry.

I don't actually think she knew what I was talking about, but tried her best. She had never prescribed cephalosporins before, and knew nothing about them, but spent a good few minutes looking in various books before deciding what to do. She didn't even know who Ed Abraham was, which is a shame, because I did my DPhil in The Sir William Dunn School of Pathology, where the whole antibiotic story took off.

Roxithromycin is a bit of a wonder drug, really. lt works by binding to the large ribosomal subunit and prevents nascent peptide from translocating (look, just STFW, OK?). This means that the bacterium stops growing because it can not make any protein, and becomes a sitting duck for any big, angry macrophages that are in the area. Interestingly, roxithromycin concentrates in phagocytes, which are of course recruited to sites of infection. So if you're a streptococcus in my pleural tissue, this big, angry macrophage bearing down on you is not just going to eat you up, it's going to lay down an artillery barrage of antibiotic that will keep your mates busy until it can get around to them. Pretty clever, huh?

(Okay, I admit it. This post is an excuse to use the phrase "big angry macrophage" again. Number one on Google. Go me.)

The other thing that's really nice about this drug, compared with the beta-lactamase family (penicillin, etc.) and derivatives (cephalosporins) is that it just stops the bugs from growing. The beta-lactamase family kill growing bacteria: They are incorporated into the growing cell wall of the bacterium, weakening it. Normally, the bug's cell wall maintains the cell's shape and size. But if that cell wall is weakened, the bug will eventually go POP! and spew all that icky bacterial goo everywhere. So there's a bit of a mess to clean up. With roxithromycin and other macrolides, the bug just waits to be disposed of tidily.

The cephalosporins are still pretty remarkable. You know about Howard Florey and Ernst Chain, but it was Edward Abraham who proposed the correct structure for penicillin. He then went on to develop the cephalosporins, and was allowed to patent them which was a major boon for British science, especially in Oxford. I did my Part II project in a lab opposite his office, and finished my DPhil on the same floor, and used to bump into him quite a bit. If I'd known then what I know now, perhaps I could have asked him why cefuroxime tastes of bacon-flavour crisps. On the way down and on the way up (i.e. when coughing five hours later), if you see what I mean.

Another forgotten character in the antibiotic story is Norman Heatley. I met Norman a few times while at the SWDSOP - I remember a gentle, kindly man who always carried a penknife. This was a veritable sonic screwdriver that he used to fix any recalcitrant equipment around the place. He also seemed to be the only person who knew how to operate the School's flagpole.

Finally, one of my close college friends and the Queen's bridesmaids was the great-niece of Lady Margaret Florey. Margaret Jennings was on Florey's original team, looking at the effect of penicillin on animals. His wife at the time, Ethel, organized and carried out the clinical trials. By all accounts, it was not a happy marriage, but they stayed together until her death. After a suitably brief period of mourning, Howard married Margaret (after a 27 year affair), and they were happy for a tragically brief time, Howard dying suddenly eight months later.

I saw Lady Florey just the once, in the lecture theatre at the SWDSOP. Old age had sadly affected her by then and she died soon after. I was fortunate enough to be able to go to her memorial service. I seem to remember it being a lovely sunny day in summer at the Marston parish church, but the WWW seems not to think her important enough to give me any clues as to the date. Somewhere, in a box of old papers and memorabilia, I might have a service card.