I need to give you the pseudonym of a gene to use in this story. I’m pretty sure the gene in question was not c-fos, c-jun or NGFI-A, only M-dawg knows. Let’s call M-dawg’s pet gene Dict-Factor 5, like it’s some German industrial punk band at the turn of the millennia. That’s too long so we’ll use DF5 which is too much like def con 5. “Dict” is for Addiction because that’s where this is all going. Colloquially, one might say, “Ugh, look at that poor guy, he’s so dict.” or “Don’t shoot that! You’ll get totally dict.”

Twang, oh Clio, of the brilliance of deadheads turned molecular biologists, of the advanced degrees, of the data and the publishing, and of the painstaking cell-line cultivation. Tell, oh muse, how the VA, beleaguered scapegoat, stopped re-filling the liquid nitrogen in the cryogenic canister which stored the life’s work of M-dawg and changed the course of history.

I felt REALLY bad because my concern for the mechanism by which the doomed canister was filled amounted to nothing. It was an intractable problem involving multiple grants and grant granting organizations with a confusing array of services and an even more confusing array of answers to the question: is there any money left in that grant? Who, exactly, fills the canister? The VA just comes along and fills it?!? For free?!? Really? Wow. No they don’t. And when their contract or whatever runs out they sure as hell don’t let you know, “Hey! person in the lab, we are only filling this one more time” or “this is the last time we fill this bitch” or “pay us so we can continue to keep your cell-lines alive.” What happens is you casually point to the canister one day and say “So when was the last time they filled that?” And you all look and find it is at room temperature and the beings within that magical microcosmic fairy land have been lost, FOREVER. Yeah, I felt horrid and angry at myself for not untangling the convoluted mess of funding mechanisms. I felt terrible for my friend, inspiration and post-doc hero M-dawg.

It was not long after this tragic episode that, very much in the mood to science the shit out of something, M-dawg struck intellectual gold which differs from real gold only in its financial value and insofar as intellectual gold is more dazzling. He was an avid reader who annually read Mary Shelly’s famous book every halloween to keep things in perspective. In his work he practiced rigorous intellectually honesty. He had recently completed William S. Burroughs’ “Naked Lunch” for fun and came to me with the proposal for a special experiment. Specifically the inspiration for the following experiments was found in the Appendix to Naked Lunch where Burroughs writes,

“A few points, it seems to me, have received insufficient attention: the metabolic incompatibility between morphine and alcohol has been observed, but no one, so far as I know, has advanced an explanation. If a morphine addict drinks alcohol he experiences no agreeable or euphoric sensations. There is a feeling of slowly mounting discomfort… If an alcoholic becomes addicted to morphine, morphine invariably and completely displaces alcohol. I have known several alcoholics who began using morphine. They were able to tolerate large doses of morphine immediately (1 grain to a shot) without ill effects, and in a matter of days stopped taking alcohol. The reverse never occurs. The morphine addict can not tolerate alcohol when he is using morphine or suffering morphine withdrawal. The ability to tolerate alcohol is a sure sign of disintoxication. In consequence alcohol can never be substituted for morphine directly. Of course a disintoxicated addict may start drinking and become an alcoholic.”

M-dawg put it succinctly as: “A morphine addict is never an alcoholic and an alcoholic is never a morphine addict”. We should have created the AMAINAAAAAINAMA support group then and there but neuroscience was afoot. Burroughs had been looking at the phenomena systemically and suspected metabolism and the liver as the locus of the dis-preference but we went looking in the brain. M-dawg designed the experiment to use the expression of the DF5 gene in the amygdala as the indicator for addiction, or more specifically a possible indicator of “agreeable or euphoric sensations”. This might seem like a stretch because how do you know when a rat is feeling agreeable or euphoric and how does DF5 expression in the amygdala play a role in addiction? The former part of the question is easier to answer and more visceral or confirmed through behavioral observations. The answer to the later part of the question is beyond me. M-dawg suspected the signal of the expression of DF5 in the amygdala would confirm Burroughs’ observation and bring to light some of the gene expression and neuroscience involved in addiction. There were four groups: Morphine (MG), Alcohol (AG), Morphine & Alcohol (MAG), and the control group. Each group had a ridiculous but affordable ‘n’ of 2 male rats. Day one was almost typical. The drug was injected intraperitoneally (I.P.) and normal .9% saline solution for control. I considered myself, by this point, pretty competent with the animals (rats, mice, gerbils) and rats were especially easy to work with due to their size and temperament. But when I went to give the I.P. injections they put up quite a fuss. Normally, I could just hold the rat in my left, heavily gloved, hand and give the injection with my right, a skill that took several months to master. Not on Day one of this trial though, they were feisty. I managed to not get bit and only to resorted to the plastic conical restraint a few times. The MG group, which was injected first were squirmy and deeply upset with me before and after the injection similar to the other groups. The nth rat is always the most difficult, the first the easiest, when the animals can observe their group mates being injected. I noticed this with turkey slaughtering once. The last turkey is always the hardest to catch so we can safely say animals are conscious of their own mortality in some way.

Day two was a horrifying epiphany. The rats are kept in their own room, their cages fill movable walls much like a library with moveable shelving units. As I walked in the door, the way the units were arranged allowed me to clearly see all four groups. There was nothing in the control or the MAG to indicate they had even been given anything, they looked bored as usual. The AG looked sluggish but nothing too extraordinary. The MG, however, had pressed their faces up against the transparent plastic cage and had been desperately following me with their eyes from the moment I set foot in the room, they stared fixedly at me, their bodies rigid, tense with expectation. As I administered the day’s injections only the behavor of the MG stood out. When I opened their cage they seemed to relax and moved toward my gloved hand. I petted them a little as was my habit and they seemed relaxed. When I picked one up he leaned his head back and spread open his fore and hind legs, relaxing on his back and completely exposing his furry belly. This had never happened to me before and I was astounded and shocked. I immediately resolved never to get addicted to morphine. I gave all the injections. It went on for at least 7 days. Close to that. After they were sacrificed and their brains sectioned we did the immunohistochemistry. It was the first time I had ever seen an experiment so elegant and simple in design go perfectly according to the hypothesis. The MAG showed no signal indicating DF5 expression while both MG and AG groups showed the amygdala was ablaze with DF5 expression! Somehow Alcohol and Morphine canceled out the expression of the gene. But what this means exactly is still quite open. Does DF5 indicate cell structure changes during addiction, or is it just a very good marker for addiction. Or is it connected more closely with drug induced feelings of agreeableness and euphoria? We got a strong signal, data never seems that clean, but there it was.