You can take the rat out of the lab…
… but you can’t complete translation without a ribosome.
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?
It was always trying, visiting Mary’s mother. Most Saturdays Slater would rise early and sit in the box room he liked to call his study with a pile of academic papers, perhaps a lab notebook or two or a student’s thesis, and catch up with everything he hadn’t been able to do during the week. He’d emerge briefly around 11 for fresh coffee, then take a late lunch. Towards late afternoon, if Mary wasn’t visiting friends they’d go for a walk out towards Fulbourn or over the Gogs, afterwards often heading into town for dinner. They never booked ahead, but rather looked around until they found somewhere not too busy, hang the cost.
Was the spontaneity of their Saturday evenings was an attempt to recover some lost romanticism? Or maybe one or other of them was trying to apologize for something—or even simply reminding themselves that perhaps not having children was not without its benefits. All his friends had grown up, had children, and although they seemed to work as hard as he did he could occasionally feel their envy, disguised though it was as pity.
Whatever the reason, he looked forward to Saturdays—except when once a month when they’d make the tedious drive to Leicester, to the drab Fifties vision that was the Eyres Monsell estate, to the semi smelling of stale cigarettes, Camp coffee and cat piss.
In another life, perhaps, he could have got on with Mary’s mother. She had been, by all accounts, quite a looker in her youth. But while some women age gracefully, maintaining an air of elegance, even desirability, well into their greying years, she had fared no better than her council estate environment. Neither was she immune to the more medical slings and arrows of age: the signs of creeping dementia and incipient angina were clear.
She’d also taken an immediate and deep-seated dislike to her only son-in-law. When they arrived at her door, Mary had to tell her Tom’s name repeatedly. When at last she did appear to remember him, she would ask why he’d dropped out of med school, or what kind of career was journalism for the husband of her daughter. He had almost convinced himself that the old bat wasn’t at all senile, but rather was deliberately needling him.
As usual, they had driven home in silence. Slater let Mary through the door first, then threw his keys with slightly more force than intended onto the table. Mary frowned without saying anything, and Slater hated himself just a little bit more.
The decanter was rattling on the edge of the whisky tumbler when the doorbell rang.
That was the single thought that occupied his mind. The blue lights reflecting off the windows in the quiet Cherry Hinton street, the two uniformed officers hammering on the door, the shrillness of Mary’s voice, audible even out here in the allotments.
When, two hours after they’d arrived, the police went back to their car and drove off, Michel wasn’t totally surprised that Tom wasn’t with them. Even the Cambridge police must have realized there wasn’t a shred of evidence. No; what was surprising was that they had got involved at all at this stage. There was but one hypothesis that fit his observations, but he couldn’t yet be sure he was right. He needed the fox to come out of its hole.
He’d waited all afternoon; a little longer wouldn’t hurt.
And there it was. The white Ford with the Sheffield licence plates turning into the cul-de-sac, reaching the end, and reversing into the Slaters’ driveway. And the platinum blonde—and someone else he didn’t recognize—crunching up to the front door and ringing the bell.
When the door opened, he pinched out the joint and walked slowly up to the house.
When the police had gone, Slater stood with his forehead pressed against the wood of the front door, the tumbler still in his hand but the whisky untouched. Behind him there was silence, but it was the silence before an earthquake.
I will be calm, he thought. Whatever happens, I will be calm.
A chair creaked; footsteps across the hall to the kitchen. A clink of glassware and the sound of running water.
The footsteps returned, and he heard Mary gulp down the water.
“What,” she said, just a hint of a quiver in her voice , “was that all about?”
Slater moved his head away from the door and looked up at the architrave. Hmm. Mould. That’s going to be have to seen to this summer.
He turned around to face her, dispassionately noting the water dripping from the corner of her mouth; the wide, unblinking eyes; her hand, still holding a glass, hanging limply at her side.
“There’s some mould up there above the door. We should get the wood treated,” he said.
He barely flinched as the glass exploded against the doorframe, inches from his face.
I am so fucking calm, he observed, a bomb could go off and I wouldn’t notice it.
He looked down, and poked a piece of broken glass with the toe of his shoe. “For some reason,” he said, “the Cambridgeshire Constabulary think I had something to do with the death of Charlotte Stowell. They’re not the sharpest tools in the shed, as you know.” He looked up, and smiled brightly. “Good job that was one of the cheap Tesco glasses and not your mother’s crystal.”
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.
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.
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.
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.
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.
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…
It must be really tense in mission control during an ISS spacewalk on Christmas Eve. What better time to eat a burrito?
From http://www.nasa.gov/multimedia/nasatv/index.html#.Urm5rEDhyPG 2013-12-24 16.44.25 Zulu