![\"\"](\"http:\/\/www.postech.ac.kr\/chem\/labbi\/lab\/DNA_CHIP\/2-europe\/2-europe-07.jpg\")
<\/p>\nThe principle behind the AutoCrap(TM) 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.<\/p>\n
\n<\/p>\n
\nThe 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<\/em>. When I had finished the AutoCrap(TM) could justifiably be called the AutoQuitereasonablereally(TM).<\/p>\n \nIn 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. <\/p>\n \nAnd 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.<\/p>\n \nI 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<\/em> one up.<\/p>\n \nWhile 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.<\/p>\n \nThis was called ‘gNAPS’, for ‘genomic Nucleic Acid Purification System’. We, naturally, took to calling it ‘guh naps<\/em>‘, much to the chagrin of Management. ‘Gee naps,’ they said, to little avail.<\/p>\n \nAs 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?”<\/p>\n \n“Never you mind,” they retorted. “What the customer wants the customer gets. Make it so.” <\/p>\n \nI 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’.<\/p>\n \nIt 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.<\/p>\n \nA 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).<\/p>\n \nPeter, 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<\/em>.<\/p>\n \nYou 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. <\/p>\n \nOne 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.<\/p>\n \nAnd then Peter disappeared.<\/p>\n \nWell, 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.”<\/p>\n \nThat evening I called him at home. “Peter,” I said, “what’s happening?”<\/p>\n \n“Richard, they’ve fired me.”<\/p>\n \n(to be continued…)<\/p>\n","protected":false},"excerpt":{"rendered":" The principle behind the AutoCrap(TM) 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 … Continue reading