I did something really weird today. As I was sitting at my computer, staring at a jumble of numbers and genetic symbols, I started semi-subconsciously rooting through my desk drawer. I was looking for a cigarette.
What's odd is that I haven't smoked for more than a year. OK, it's been one year, seven months, nine days, 17 hours, and 43 minutes, to be more precise. But old habits die hard. Part of the reason for that is that my genes, which are most likely of the smoking variety, haven't changed since I was choking down two packs a day.
What type of gene could possibly make a person want to smoke dried plant leaves? That's what I was trying to figure out on the computer, which was running one of the many statistical software packages we use to analyze genetic data. Our hypothesis is that different people have slightly different forms of the nicotine receptor, the molecule that senses the presence of the drug in the brain. Perhaps some people have a receptor that makes nicotine feel good whereas others have a receptor that makes it feel bad.
Six months ago, we discovered one tiny change in one particular nicotine receptor gene that was associated with an increased likelihood of becoming hooked on cigarettes. At least that was the case in the first 350 or so research subjects we looked at. But to be sure, we decided to check the result in a new population of some 750 independently collected research subjects.
It didn't look good. Now the DNA variant we discovered seemed to be associated with a somewhat lower probability of nicotine addiction. When I averaged the data across studies, it was a wash. Zilch. Nada. This sort of nonreplication is the rule rather than the exception in behavior genetics; there are so many different genes and other factors involved in complex traits like cigarette smoking that it's easy to be misled by looking at only one study population. I'm just grateful that we didn't rush into print with the initial finding.
Lunch was tuna salad on a bagel accompanied by our fiscal year 2001 laboratory budget. They were both low-fat. I was proud that we'd been able to reduce our expenditures for DNA analysis by developing a new method that uses cheaper equipment. Of course, it will be offset by looking at more samples, but still, that's sort of a savings, right?
My afternoon task was to help set up our brand-new DNA analyzer, which was being installed in the DNA core facility. It's an awesome machine, the Cadillac of sequencers, with 16 capillaries instead of one like on our present device. This baby is really going to speed up our genotyping.
There was only one problem: the plug. The new device requires a special type of outlet that needs to be installed by a contract electrician, which means writing a work order, which means a long wait. Something tells me they don't have this problem at private genome companies like Celera.
Finally came the fun part of the day—talking with my colleagues inside the laboratory and out about what they're up to and what they hope to do next. A research fellow from Russia had a clever new scheme for improving DNA amplification, while a Belgian graduate student was getting mixed results recruiting subjects through the Web. The scientist who discovered the nicotine receptor variant was disappointed by the failure to replicate the association to nicotine addiction but had some good ideas for alternative strategies. Meanwhile, a professor at Princeton, whom I've known since we were postdocs together, agreed to help us with an experiment that can be done only on mice.
It was a good day (except for the plug fiasco), and for a rare change I was finished up by 6 p.m. There were no excuses left. I headed off for the gym to give my basketball gene its long-overdue exercise.