Tag: science

Categories
nostalgia science

Intimidated

I looked at my site stats for the first time ever. Intimidating! Not that there are that many site visits, but apart from the four or five people who comment here, I didn’t really believe anyone read my blog.

It’s better to imagine that no-one reads it except for a tiny few. Now I feel all intimidated and inhibited in what I might write!

I spent yesterday evening with my brother-in-law Paul. We ate Szechuan food and he talked to me about scary stuff; scary because of just how serious it is – his biotech company, the share price, investors, pitching to big-shot stock brokers, mergers and aquisitions, clinical trials.

And not for the first time recently it struck me how all my friends from my science days are now reaching quite elevated positions in their work, where the fortunes of quite a few people rest on their shoulders. Magda making full Professor at Monash University, my Spanish friend Ana considering a job as Country Manager for a clinical research organisation, Paul as Vice-President for Drug Discovery at his super-cool biotech outfit Phylogica.

Meanwhile I make up stories about conspiracy theories and actually get paid for it…

When I listen to Paul and Magda talk, I can’t help but wonder what I’d be doing now if I hadn’t left science. It’s not regret as such but curiosity because you know what…science is so, so, SO cool, especially biological science. It’s world-changing, awesome, totally mesmerizing.

Why would anyone study anything else?

Which I guess shows just how much I’ve been rehabilitated. Because when I left science I was tired and jaded, fed up of running gels and spending my weekends looking after tissue culture cells and worrying about funding.

Meanwhile Paul is as hilarious as ever. It was freezing as we walked to the restaurant, and Paul remarked that he wished global warming would properly kick in if it’s going to, cos all this cold was pretty rubbish. He’d just come back from Davos, Switzerland where they’ve had some nice deep, early snow. We talked about carbon footprints and people’s guilt over that. “The only people I’ve got time for,” he said, “the people with the tiniest footprint are people like my Dad. He consumes almost nothing, cycles everywhere and recycles as much as possible. And he doesn’t give a damn about the environment – he does it out of thrift! Good Scottish thrift. He’d reuse a nail! That’s why people shouldn’t waste stuff.”

I’m very fond of Ted (Paul’s Dad) too. When we go to Perth we stay in a flat built by Ted, on top of his own house. (He’s not a builder by trade, actually he was a Professor of Philosophy…but why hire builders, a real man should be able to do that himself!) It has terrific views towards a meadow and a pond which is almost dried out when we are there. Palm trees grow at the side of the house, which has a verandah all the way around the top. The trees are and nourished by waste water and the septic tank under the house. When a breeze blows the palm fronds rustle against the roof. Ted pre-stocks the fridge for us with a stack of Aussie beers, a huge slab of cheddar cheese, bread and industrial quantities of ice-cream. And because he knows I’m terrified of spiders he always does a special check for huntsmen and redbacks, scourge of Western Australia.

Best of all, the flat houses the collection of books with which my brother-in-law and his six siblings grew up. Including an entire collection of E.Nesbit books, which I settle down to re-read with enormous pleasure.

Categories
nostalgia science

Yay Smithies et al, the Nobel prize is yours…!

And the prize goes to…the gene targeting guys!

There’ll be a few more scientists I used to know gnashing their teeth this week as more of their friends win the Nobel prize and they don’t.

(I once heard of one guy who would get wildly depressed with jealousy every year that one of his friends and not him joined the Nobel prize-winners club. I wrote a short story about it…which shall remain unpublished or because I named actual real scientists I know, to make it funnier… This story is handwritten in a drawer and I show it to me special science friends once in a while, for a giggle. The coda to this tale is that the guy in question finally did win. Obviously I can’t name any names…)

This year the Nobel Prize for Medicine went to the Sir Martin Evans, Mario Capecchi and Oliver Smithies, the guys who developed the technologies for creating a mouse with a gene ‘knocked out’. This means that you could look at the effect, in theory, of a single gene in a mouse, by creating a mouse that was normal in every way except that it lacked, say, the haemoglobin gene.
The early days of any new technique are always fraught with difficulties. I came into the gene targeting game in 1993, early-ish, but quite a few mouse knockouts had already been done. It still wasn’t easy though. Nowadays I bet rich labs just order a knockout mouse via the Web…

I was put on a project to knockout a gene called the FGFR3 – fibroblast growth factor receptor 3. It’s an interesting gene because a single mutation – one tiny change in the DNA code – results in the condition known as achondroplasia – aka dwarfism.

The first thing I had to do was to ‘restriction map’ the DNA in the chromosome – i.e. make a map of all the sites where ‘restriction’ enzymes could specifically cut into the DNA. Since DNA is too tiny to cut with scissors, molecular biologists use these naturally occuring enzymes to snip DNA into pieces. It’s just a matter of knowing which enzymes cut where and then picking your tools; the enzymes which will cut you out a nice chunk of precisely tailored DNA.

The mouse FGFR3 gene was spread over quite a large region of DNA so I used this delish and elegant new method that I’d read about. It worked like you wouldn’t believe, first time too!

I’d just mapped the FGFR3 gene and got partway into making the ‘knockout construct’ – the DNA molecule that you use to inject into mouse embryonic stem (ES) cells – a first stage towards the knockout mouse (the stage that Smithies contributed to the whole process).

And then a Big Hot Lab in the USA published the FGFR3 knockout mouse in a Damn Hot Journal.

Bah. So that was several months of my work down the drain! I went to see my boss. Did he know that Big Hot Lab had a couple of postdocs and a techie or two on the same project as little me?Hmmm, he said and peered hard at his computer screen, as if something rather canny had just occurred to him. “I may have heard a rumour or two…”

And that’s why I didn’t develop the FGFR3 knockout mouse and get a Cell paper and why I ultimately gave up science and had to do other things. Yes, but for that I might never have written a single novel.

Meanwhile, Oliver Smithies. I heard him talk once. What a character! He’s a Brit – a Yorkshireman I think (I may have remembered that wrong). but lives in North Carolina now. He flew in to talk at the Dunn School of Pathology, Oxford when I was a grad student. I mean that quite literally – Smithies has a pilot’s license and like John Travolta, flies himself to all his engagements.

This is rare for a scientist.

Smithies gave a fascinating talk, one of the best I ever saw in my whole time as a scientist. It featured lots of photos of his lab and his makeshift equipment. This guy is one of those rare, rare things – a scientist who is also a natural engineer.


Check out Smithies’ homemade electroporator – known by scientists as a ‘zapper’ for hitting cells with an electric current so that DNA goes in.

Years before Perkin-Elmer had patented the Polymerase Chain Reaction (PCR) and made a machine which allowed people to amplify DNA molecules by basically just sticking some DNA and Taq polymerase enzyme in a test tube and putting it into a Perkin-Elmer thermal cycler, Smithies was doing early ground-breaking PCR using bits of washing machine timers to do the thermal cycling. He showed us photos of stuff that you wouldn’t believe could be used to do proper science, equipment literally cobbled together from bits and bobs and stuck together with sticky tape. He was an elderly man even then but brimming with enthusiasm. I remember being quite inspired.

I’m chuffed he’s won. Best Nobel Prize news since Paul Nurse won for the yeast cell cycle genes.

Categories
Joshua Files nostalgia raves science

Weekend in Cornwall

Prussia Cove, Porth-en-Alls

taken with my BlackBerry

Some dear friends of ours from my days in the Nuffield Department of Medicine were over from Melbourne. (That’s where the UK bioscience brain drain has been for the past ten years, or so it seems to me; if I count up all my best friends from doctorate and post-doc years about half have ended up in Oz. Okay, most of those were originally Australian, but hey…)

They’d always talked about taking us to their favourite haunt in Cornwall, where they’d rent a cottage almost every year when they lived in the UK. We hadn’t seen them for years, so this it was wonderful that this time, we could join them there.

I’ve been to Cornwall once before, North Cornwall, which is gorgeous but this place was even better! It has the Lizard on one side and Lands End on the other (both far in the distance); old smugglers caves, gorgeous little coves as well as wide, sandy beaches with all the stuff kids like (e.g. rock pools, pebbles, shells), amazing clifftop walks with views out to St Michael’s Mount.

So after a gorgeous weekend eating Cornish pasties (veggie and yummy!), visiting ice-cream parlours and eating cake, I’ve probably gained a pound or three, despite the exercise of walking.

My friend Magda gave me a lovely scientist flashback moment when she went through the slides for a talk she gave last week at a conference in London; a fantastically effective new way to use nano-particles as part of a new vaccine for diseases like malaria. My very first research job was with a team developing one of the UK’s earliest candidates for an AIDS vaccine, so it was vaguely familiar territory. I’m so proud of Magda, of all my scientist friends she’s the first to be made a full Professor. Professor Magda!

In other news, someone is selling a bound proof of The Joshua Files: Invisible City on ebay. There are only a few hundred in circulation, I believe…

Only!

It should go for a very, very reasonable sum, i.e. cheap-as-chips, given that at this point in time i) almost no-one has heard of the title and ii) almost no-one has heard of the author…

Categories
getting published jaguar's realm Joshua Files nostalgia other books science writing

My New Editing Regime…and Memories of Subcloning


The publisher and I have agreed a deadline for Joshua bk 1 v3.0. I’m deep in the process of writing Jaguar though, and can’t let the momentum go. So I try to work on Jaguar in the morning at my desk, take a two-hour break to refresh and then it’s on with the editing, which seems to require a different skillset as far as I can tell.

Thank goodness for editors. I’ve said it before and I’ll say it again. Mine is probably going to save me from being a laughing stock, if nothing else – hopefully a lot else but you can’t predict these things.

I like to take my manuscript out for little walks. I can’t be bothered going all the way to the Bod this time around – I’m only spending 2 hours a day on it, what with the Jaguar writing taking up all my morning brain activity. So I’ve been going to Summertown.

The above photo is taken of my set-up at the Summertown Wine Cafe, a bijoux little joint on South Parade which makes the best coffee in Summertown (there are many Italian coffee machines in Summertown, but few baristas who have a clue how to use them). Sadly however, they charge a small fortune for savoury food – best to stick to cake, I’m trying to avoid blimpdom so that’s out.

Blah, blah, blah. Nothin of consequence in this entry sadly. I’m just writing something to have to test in a new way to do an RSS feed. If you read this, you’ve just participated in an experiment.

Do you feel used?

I kind of miss doing experiments. Somewhere in the back of my mind is the niggling feeling that a PROPER day’s work is what I used to pull off at the height of my keenness as a graduate student…a long day in the lab which ends with a successfully identified new DNA subclone to use in a lovely biological experiment.

‘Subcloning’ is a way of starting with a widgey little bit of DNA that is no use to anyone and two days later having bucketloads (as much as a milligram!) of the stuff that you can use to do biological experiments in tissue culture cells or even in unsuspecting fluffy creatures. (Some journals are so fussy that you can’t get published unless your results are in a live organism.)

You insert a piece of experimental DNA into a ‘vector’ of usually bacterial or yeast DNA which has the ability massively to replicate it. Then you can grow the ‘bugs’ in a 500ml culture overnight and in the morning extract enough DNA to ‘transfect’ cells which allow you to test the properties of your experimental DNA. The tricky bit is that when you try to stick your experimental DNA to the vector DNA, only a small fraction will combine to give you the subclone. The rest will just be vector DNA that sticks back to itself.

When I were a lass we used to pick at least 24 bacterial colonies in the hope that 2 or 3 would have the subclone. It could take up to a whole day, a day spent ‘doing minipreps’, as we used to call it. Sometimes you had to use radioactivity and horrible, ooky, gloopy, neurotoxic polyacrylamide gel to help identify the subclone.

(Any molecular biologists reading this, bright young things with your PCR, your DNA synthesisers and sequencing machines…it’s all very easy now, I’ll bet.)

But! Throughout most of career as a molecular biologist I noticed that although I was a good little scientist and picked my 24-48 colonies everytime I wanted to find a correctly subclone, more often than not, colony 1 (the first I picked with a sterile toothpick) actually had the subclone. i.e. I didn’t need colonies 2-24 and all the effort in ‘working them up’ was not actually essential.

Other people in my lab noticed this too. It turns out that in maths the number 1 is disproportionately represented (there’s some rule and it’s used as a way to detect fraud), well, in molecular biology this seems true too.

Don’t think we let that observation go to waste, either. Towards the end of my time in the lab, I would often just pick a colony right off, inoculate my 500ml flask and grow up the bugs without testing whether they had the subcloned DNA in them. It saved a whole day! Of course I tested a sample before I used it to transfect my tissue culture cells. Well, duh.

If you didn’t understand a thing I wrote in the last few paras, tell me. R1X did, so I have tried to rewrite it so that it makes sense.