The principle behind the AutoCrap™ was, actually, quite clever. There was a plastic sealed cylinder with a membrane separating top and bottom. You pipetted 1.5 ml bacterial culture into the top, sealed it, and pressed the start button. Everything was driven by hydraulics. Positive pressure forced the broth through the membrane leaving the bugs behind. Lysis reagents were squirted into the top and clever changes in pressure mixed them up. Then everything was filtered through into the lower chamber where the plasmid DNA stuck to a slight variation on the standard matrix. The normal washes, a drying step, and then the DNA was eluted in water into Eppendorf tubes.
The first thing I did was optimize the volumes of the lysis and wash reagents, and determine which of the various DNA-binding matrices we could find performed best (the best matrix for the manual kits did not perform so well in the columns). Then I went to the machine itself, taught myself TurboPascal and re-programmed the machine to take advantage of the improved chemistry. Then back to the chemistry for more tweaks, and a final round of protocol wrangling in TB. I took the new machine out to various labs in London (trying to absorb as much nonsense from the rep as possible) showing them how, this time, it actually worked. When I had finished the AutoCrap™ could justifiably be called the AutoQuitereasonablereally™.
In my spare time I fielded phone calls, sat in on marketing meetings, visited labs, showed Charlie (Venture Capitalists) around and wondered why the CEO was such a creep.
And all this time my line manager did little more than use his PC to check the football score and send emails to his girlfriend. Occasionally he’d claim he went to management meetings so that we could be spared the bullshit. The IT manager visually scanned web traffic logs for signs of wrong-doing (I stung him on this one. One day he went around telling everyone that someone had been downloading porn, he knew who it was, and they were for the high jump. An inveterate Mac-hater, he had no way of knowing that ‘G3’ and ‘hotnaked’ in the URL merely meant someone had stripped a G3 Mac and posted pictures of the internals of a computer on the web. Face, meet egg) and on Fridays (management meeting day) over half the company got locked into the meeting room.
I spent a while tinkering with the machine, making sure it was as good as it possibly could be, and wondering how Marketing were going to cock this one up.
While I had been working on this, the other ‘senior’ scientist in the company had been developing a rapid and high-throughput method for rapidly extracting genomic DNA from whole blood. The protocol was simple: add 1 ml blood to a column with a certain type of Whatman paper in it, heat for 2 minutes, wash, elute with water. Presto! PCR-ready genomic DNA.
This was called ‘gNAPS’, for ‘genomic Nucleic Acid Purification System’. We, naturally, took to calling it ‘guh naps’, much to the chagrin of Management. ‘Gee naps,’ they said, to little avail.
As I must have been looking a bit bored, Management spake unto me, saying ’Go thou, and make this work for large volumes of blood. Say ten to 25 ml." And I looked at the setup, dicked around for a week and saith unto Management, “Nay, for I canst not break the laws of Physiks. Furthermore, what wouldst anyone do with that much DNA?”
“Never you mind,” they retorted. “What the customer wants the customer gets. Make it so.”
I went off, muttering that if they needed to archive material they could just run two columns instead of one, and that any fool could see that you couldn’t get heat transfer into the middle of the paper fast enough for it to work. But I talked to the tame engineer and got him to mock up a heating block, and destroyed hundreds of 50 ml syringes and burned through gallons of expired human blood from Addenbrookes (the smell of hot plastic and cooked blood still haunts me) in a futile attempt to ‘make it work’.
It was then things started getting interesting. About the same time I was preparing my report to show that really, this was not going to work, ever, we had a business meeting to talk about future directions.
A few months after I’d started Peter (the CSO, inventor of the automated column system and founder of the company) asked me if I knew anyone who could set up and start running a genomic DNA extraction service. The plan was to get clients to give us clinical blood samples, we’d prep DNA, and sell it back to the client. I said that Kate was looking for a job, and so he hired her. Kate then almost single-handedly set up and ran the service (including doing the extractions!), which I believe became the first commercial DNA extraction service in the UK. (And then the CEO realized it was a success and hired a manager over her head to run it. Which was typical, really).
Peter, naturally, wanted to expand the company’s horizons. He suggested that we started offering SNP detection services, concentrating on P450 to start with. There was the market, and any number of primers—we also had a really rather hot sequencing machine and a competent monkey to run it. But in front of the entire company (all 20 of us) the Marketing Manager stood up and said that no, we couldn’t offer that, because it was too difficult.
You might imagine the feeling among R&D at this point, being told something was too hard for us. And my line manager? Not. A. Word.
One day, Peter dug out some notes from two years previously, and asked if I could do anything with them. What he had come up with was a one-tube method for making plasmid DNA. No matrix, no spin column: just one tube and certain organic reagents. He also showed me, in an old freezer at the back of the lab, certain enzymes that no one had worked on since they were discovered. Suddenly, I had new projects.
And then Peter disappeared.
Well, that is to say, he didn’t turn up to work for a week. At the end of that week, the CEO called us all together and said, “Peter is taking some leave to consider his future.”
That evening I called him at home. “Peter,” I said, “what’s happening?”
“Richard, they’ve fired me.”
(to be continued…)
Now, that is getting interesting!
I’m waiting for the film companies to approach me.
{Giggling}
It’s a bit like the sciency version of The Office right now.
I knew I’d seen the CEO before…
I still don’t know what a bodice is.
Well, I haven’t written part 3 yet so maybe I can work one in.
Be careful to define the term at its first use, Richard.
Henry: It is “the upper part of a woman’s dress” or a “corset” (archaic). You know, kind of like the things that women wear in all the fantasy movies when they mostly look like 15th century and forward :)
if you want pics (since I am at home now) you can find some decent ones here….:
number one
number two
number three
(I really left the indecent in the google part. ;) do not want to get banned )
Richard: I am starting to be happy that I am so young. Less time to be exploited and sad about crazy mangement ;) Still, it is kind of evil to cut it in half in the middle of the tension!!! What did you say to him (Peter) after hearing that? And what went through your mind? (leave leave leave??)
… and I am quite sure you knew what it was so I guess it is all a question about how innovative the description would be from Dr Grant?!
Careful what you assume about Dr Gee. He is a sensitive soul. And you’ll have to wait until part III to find out, Åsa!
Oh. Oh. Let me guess. Peter missed the drilling, warning-off glare that accompanied “too difficult”, and —
aaaaaaahh! I want to know!
I reckon he accidentally snuffed one of the marketeers during a mishap in demonstrating the AutoCrap — all that was left was a bit of DNA in a tube.
But Jenny, that would be the perfect murder (just make sure to dispose of the tube) – unless there were witnesses.
Um…except for the DNA evidence.
(taboom tish!)
Didn’t we get rid of that by disposing (properly) of the tube? Maybe I should have specified incinerating or autoclaving it.
We actually did some work for the Forensic Service. Turns out you can get a pretty good fingerprint from autoclaved DNA.
Richard: really? The autoclave does not destroy it?? (I’d better stop now so my lack of knowledge is showing too much :)
happy new years. at least today I don’t have to wait until next year to read the rest of it =)
*resists incoherent ranting about autoclaves and DNA
Your startup experience is SOOOO much more dramatic than mine was. Either that, or you just tell it well.
I would also like to acknowledge Jennifer’s very clever DNA joke (see above). Give me a week or two and I might even have thought of that. Or not.
But – vaguely back on topic – two things I would never have attempted: (1) try to set up a clinically-certified DNA prep lab for profit, and (2) develop P450 DNA tests (I confess I belong in the “too hard” camp, although it is also true that there was a company down the street already doing it successfully, and that we were being suckers for punishment for an equally confusing test for various rare blood group antigen polymorphisms, the story of which is far too tedious and boring to relate here).
Comments fully hijacked now, guess I’ll move on.
resists incoherent ranting about autoclaves and DNA
Competent cells?
We actually were well placed to do the SNP testing, and the DNA prep service was successful. In fact—
but no. Wait for part 3.
Wait for part 3
I’m on the edge of my seat.
Do you think you could get this reproduced in NatureJobs?
It is gripping!
Heh. I’m under a lot of pressure now, you realize!
You know, of course, that Jenny will be
buggeringbugging you to serialise a version of this for Lablit now, yeah?That’s not such a bad idea. Like I haven’t enough writing projects on…
Hey – I didn’t say anything!
You don’t have to…