She blinded me with science

Jenny is putting the finishing touches to a revised manuscript. I’m reading about a very interesting paper in my old field—and telling her about it.

Joshua is doomed, isn’t he?

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I fought the law

Jury service
Nobody commit any crimes any time soon, mkay?

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My iron lung (redux)

The is a modified version of a couple of posts that originally appeared in December 2006 on ‘Life of a lab rat’, my blog at the University of Sydney. Which is now sadly defunct.

It’s not what you know, it is who you know, especially when it comes to medical matters. And if you know someone who can prescribe antibiotics and get you into A&E’s X-ray unit on a Sunday morning then you must be doing pretty well. The good news is that it does not appear to be a fractured rib.

The bad news is that even if it was, you wouldn’t be able to see it because of the consolidated pneumonia and pulmonary effusion (“50% of hemithorax”). My specialist’s comment was “People with chest X-rays like that are usually already in hospital”. Oh, and “It’s getting better, but you’re taking a week off”.

So I went to the quack’s a week later, and fortunately did not get to see the muppet who managed to miss the pneumal party when I crawled into his office the previous 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 β-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?

The other thing that’s really nice about this drug, compared with the β-lactamase family (penicillin, etc.) and derivatives (cephalosporins) is that it just stops the bugs from growing. The β-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.

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Alice’s Restaurant Massacree

In other news, Australia’s ongoing experiment with biological warfare doesn’t appear to be having any more success than it did with cane toads.

Killing dingoes has side effects” (and presumably not just for the dingoes) screams the Nature Research Highlights headline.

If you poison dingoes, according to a paper in Proc Roy Soc B, you allow kangaroos to flourish, which leads to less vegetation, with less room for small critters to hide. In other words, “multiple cascade pathways induced by lethal control of an apex predator, the dingo, drive unintended shifts in forest ecosystem structure”.

Yeah. You’d think they’d have learned lessons like that a long time ago. Just shoot the bloody roos—there’s good eating on them.

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Downbound Train

A funny thing happened on the way to Borough this evening. The train was delayed as we pulled into Old Street. The driver said there was a faulty train ahead being taken out of service. He warned us that lots of passengers—who’d had to get off the faulty train—would want to get onto our train, and he wished us good luck.

Sure enough, it was a bit crowded, and, as we approached Moorgate, we had to wait to allow the faulty train to clear the station.

Then things started to get weird.

As we approached Bank, the automated PA said “The next station is closed. This train will not stop at the next station.”

And we didn’t. No matter, we collectively thought, silently. We’ll be able to get off at London Bridge. But the same thing happened. The driver came over the PA, and told us he wasn’t quite sure why this had happened.

When the same thing happened at Borough, he said he had asked the controller what was going on—and was waiting to hear back.

My fellow commuters appeared to be slightly worried, but were taking all this in good humour. There were a few sighs. Myself, I was wondering what would happen if we had a bomb on board, and had to keep going all the way to Morden. As you know, one does not simply walk into Morden.

As it happens, the train did stop at the next station—Elephant and Castle. Those of us who had been trapped on the train since Bank or London Bridge got up to leave.

But the doors remained closed.

The driver again announced over the PA that the train automated driving system was playing up and was not opening the doors. Finally however, and much to our collective relief, the doors did open. The driver said that there were obviously problems with the newly installed automated system.

“It’s Bob Crow‘s revenge,” I said, deadpan.

The entire car’s passengers creased up, and went upon their way, somewhat happier, I hope, than they may otherwise have done.

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Caption competition

IMG_7282

Go on. You know you want to.

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Guns + ammunition

Just after I started shooting I was listening to a couple of the old(er) timers bitching about their recent poor performance. One of them blamed the ammunition they were using. The other pointed out that while shooters often blame the grade or particular batch of ammunition, nobody ever credits their ammo when they shoot a particularly good card.

You might not think that your choice of ammunition would make such a difference. Pretty much like pipette tips, you might say, within limits a bullet is a bullet. I mean, yes, you’ve got your tips that come in bags so that you have to contaminate them yourself when you rack and autoclave them and you’ve got your ordinary racked tips and your plugged RNAse-free tips and tips that were packed by the lily-white fingers of virgins brought up on a diet of organic fava beans on a Pacific island, but essentially a pipette tip is a pipette tip. Except for the ones that stay on the Gilson just long enough for you to suck up 37.5 µl of incredibly rare primary antibody only to fall off halfway between one Eppendorf tube and the next, sending 5 years’ work down the drain but hey, never mind we get cheap tips because the lab tech is shagging the sales rep.

I mean, you’ve even got different calibres. 10 µl, 200 μl, 1 ml, 5 ml: that could almost be .22, .308, .38 Special and 50 cal.

Anyway, there are differences in quality of ammunition (or so the manufacturer claims) and as ever, you get what you pay for.

Before Joshua was born I was routinely shooting cards in the low- to mid-90s. Not brilliant, but getting better; and I entered into a winter competition. Handicapped of course; my team mate and I are up against people who have a similar average. Of course, then the man cub was born and I became chronically sleep-deprived and my averages dropped off to 90, 88 on a bad day. Not to worry—I figured that the man child will soon start sleeping through the night and then I won’t be so tired and I’ll be able to straighten up and shoot right again.

Laughing baby
Recent acquisition

Except… last week I was talking to one of the old(er) hands and I noticed that he was using some rather sexy looking black ammo, rather than the brass-cased entry level stuff I was using. So I asked him about it and he said that Eley were re-branding everything and that what he was using was anodized so that (he said) the round was more likely to leave the casing smoothly, without sticking at any point and therefore tumbling; resulting (he said) in more consistent shot-to-shot shooting.

He also said it’s good to use the same sort of ammo in a gun and as my recent acquisition was likely to have been using something a bit more than the entry-level stuff I might as well get used to it. And so even though I hadn’t yet collected said acquisition I thought that for an extra tuppence a round I might as well try out the sexy black stuff.

Components
Man cub

So I went to the range officer and bought 50 rounds of the sexy black stuff; put up a card for the competition; and promptly shot a 96. That’s better than anything I’ve put down the range since summer, and only 2 off my best score ever. Now, I’m not claiming that the ammunition made the difference, but it was the only thing that has changed.

Tomorrow night I’ll be going down the range with my own rifle for the first time, and it’ll be very interesting to see (if I manage to adjust all the adjustable bits and get comfortable with her in time) to see if I can get a score that high again, using the sexy black ammo of course. What I should do in addition is the experiment: club rifle, new ammo; my rifle, old ammo—but frankly that sounds too much like hard work. Science has its limits, eh?


Wondering about the title? Try this…

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Yakety sax

I made this a couple of years ago, but seeing as it’s almost Christmas I thought I should bring it out for another airing. Those of you who remember ‘Benny Hill’ should get a chuckle out of it; the rest of you, enjoy the amazingness of the big angry macrophage!

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On the River

Back in July I went, for one reason or another, on a meandering bike ride. I ended up here:

Thames Barrier, in calm conditions
My bike. And the Thames Barrier

The Thames Barrier is apparently the world’s second largest movable flood barrier (I believe the Dutch have the largest immovable such barrier: most of Holland is actually a giant dyke). I’ve never seen in it action; not even Thursday night when we were skirting Stormageddon and flying back into my favourite aerodrome—as the Barrier is west of the runway you only tend to get views of it on takeoff.

But it does spring into action, and yesterday the Environment Agency reported it closed against the highest tide since it was completed in 1984. What would have happened if the Barrier wasn’t there, or if it hadn’t closed?

Flooded River
What London might have looked like, today

Take another look at that—the red rectangle is the approximate location of my (ground floor) flat.

6Dec13
Wet

Yeah.

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