Big Fat Golden Goose Eggs (also to be found on Cognitive Emesis)

Several thunderstorms of Midwestern caliber recently passed through the Land o' Ten Thousand Superfund sites, a.k.a. The Gaaah-dun State, which assured that the Saturday morning air, though laden with dripping moisture, was a darned site more bearable than the cloacal conditions in benighted regions of South Florida, at least as described by the Chief Cognitive Emetic. I hauled my jiggling ass out for an early perambulation with the extra motivation of having obtained a good glimpse of my posterior, ballooning toward barnlike proportions, in the expansive mirrors of a friend's bathroom during a recent visit post-vino.

I know what I need to do to reverse the trend toward buttocks of agricultural outbuilding size. An EFD (Every Fucking Day) plan of lurching bipedal locomotion, and just saying "no" to gorfy junk scattered about at departmental meetings as well as too copious amounts of good food, seem to be the ticket toward decreased adiposity, but only with consistency of these practices over a goodly amount of time. The requirement for this endeavor got me to thinking about the Fattists, oft the brunt of flowery and simultaneously scatological verbosity on this very site, and their rampant braying that the obesity epidemic is a false alarm created by collusion of the medical community and greedy Big Pharma. These ruminations, as inspired by the Campos camp, causes me to come clean and confess the reality of my situation:

I am not the amorphously shaped, menopausal drudge as described above. In truth, I am a reprehensibly wealthy research minion of the pharmaceutical industry. I giggle with glee, digging deep with the heels of my Manolo Blahniks, as I tread up the backs of blue-haired Medicare ladies whilst clambering to my late model Porsche Carrera. There, I rip open my tidy white lab coat, revealing my bosom straining the weft of a snug Juicy T-shirt, legs akimbo beneath my little Prada skirt. I then pull my mane of hair loose from its sensible ponytail. My mouth forms a little pout as I run over various patients and Canadian-bound consumers in search of the bargain basement prescription, on my route to my pied-a-terre in Tribeca. This makes for an ever so bumpy ride after all. I yearn to upgrade my other residence, an all too modest 6 bedroom cottage tucked away in the Hamptons, but that will only come if I, in league with my sinister colleagues, bring forth multiple medications for the obese or even barely overweight. Thus, I am motivated, no, make that hungry to discover the Magic Fat pill which will do a damn slight bit of good, cause multitudes of side effects, but will put reams and reams of dead Presidents in my Gucci pocketbook.

Well, perhaps I have slightly exaggerated my appearance and my financial situation. "Dowdy matron" suits me just fine, and as for my salary, I can't complain but in this affluent neck of the woods, I ain't among the rich. But unfortunately, I know all too well that the industry is pursuing drugs for obesity, but not for the reasons that the Fattists claim. Big Pharma has not concocted the obesity epidemic with their partners in crime, the medical establishment, but rather, in its typical voracious fashion, seized upon the trend toward decreased physical activity and burgeoning gullets as a large (pun intended) market opportunity.

Although we bench monkeys would like to think that good science drives discovery research, and in fact this is not an uncommon event, the pecuniary creatures in market analysis have in the past decade or more, increasingly worked their wiles earlier and earlier in the stages in the drug discovery process. "Good science" is not always first and foremost in marketing's greedy mindset. Consequently, many pharma companies have research efforts directed toward obesity. Woe to those who do not. Other than the niche-directed biotech boutiques, to remain "competitive," obesity targets must be on the research docket {Aside: "targets" meaning discreet biochemical entities such as enzymes and receptors which have potential to be affected pharmacologically.} Now, in terms of pure science, I have to admit there's a certain degree of "Ah ha!" coolness to some of the targets related to obesity. The "Ah ha!" factor is an especially seductive influence in a scientist's work. Hours of tedium are whittled away in experiments for that moment of discovery. I suspect that little spurts of dopamine are released at those moments, tickling the reward centers of the brain, and thereby making the process addictive. For example, interesting enzymes involved with fatty acid metabolism and certain GPCRs, which appear to regulate satiety, represent potential, and challenging, targets. {Second aside: GPCRs = G-protein coupled receptors; remember this, my comrades in emesis, since I may very well use this term again in subsequent verbal vomitus.} But those of us grizzled old veterans, as tempted by the "Ah ha!" factor as we might be, know the pitfalls of bringing forward drugs for chronic indications, and certainly obesity falls into the latter category.

For drugs that treat chronic conditions, for example, high blood pressure or arthritis, the safety of the meds is of great concern. The patient takes these drugs daily for months or years, more likely, so adverse side effects are not particularly tolerable, in contrast to a cancer patient who bears the brunt of cytotoxic chemicals coursing through his or her system in the effort to drive back tumor growth although a thought-trend in oncology is to approach cancer as a chronic state. Unfortunately, with the rush to market certain cox-2 inhibitors, safety and proper direction of the drug toward its intended patient group, went out the window. The Vioxx debacle, in my opinion, was a wake-up call to both the pharma industry and the FDA, but that's the subject for another screed. Drugs cost a fucktacular amount of money to bring to market, and the proper trials to determine efficacy and long term safety of a potential obesity drug (let's not forget Fen-phen; I'm sure Wyeth would like to forget it) will add significantly to this cost. All in the name of what? A 10-20% weight loss versus placebo?

One Friday evening at the local watering hole, a group of us shlub scientists were lamenting the research efforts directed toward obesity. One of the sr. chemists working on an obesity target, himself a moderately portly fellow who was scarfing down pizza and drinking beer like the rest of us, opined that his intellectual blood, sweat and tears were being spilled on a hypothetical pill which a 300 pound person would swallow, only to lose a walloping ten pounds as a result, then sue the manufacturer when his or her stools take on the ballistic strength of an AK-47 or when once pliant skin becomes an infected, arid wasteland due to some pharmacologically induced fuckup in fat metabolism. All of us gathered around that pub table recognized that yes, there exists a population of the morbidly obese who quite likely have some genetic variant predisposing them to the condition, but this population of folks does not exactly represent a billion dollar market. To a person, we investigators each believed that diet and exercise are first line treatments for most garden-variety obesity.

So to the Fattists who believe that the pharma industry wants you to be fat, well, to an extent you are right since your obesity shines like a golden egg to the devils in pharma marketing. However, let me assure you, many of us who actually try to discover drugs wish you'd just walk, bike, swim or run more, and eat less, so we can direct our attention and our "Ah ha!" cravings toward drugs to treat cancer, infectious disease, immune disorders, neurological disease, and such.