Dr. Joan Bushwell's Chimpanzee Refuge

Doc Bushwell here, pharmaceutical bogeyperson of the fast food-pharma-medical establishments’ collusion against the fundamentalist fat activists (FFAs). Yes, that’s right. We bench monkey pharma researchers lie awake at night, tossing, turning and vigorously scratching our nether regions, while we plot new ways of wresting money and adipose tissue from these hapless souls.

Truth be told, many large pharmaceutical companies have major obesity research programs which have fed, and intend to feed, the pipeline with compounds as clinical candidate hopefuls in the war against obesity. Some, like Sanofi-Aventis’ rimonabant/Accomplia, the CB-1 receptor antagonist, have moved far into the clinic in the hopes of replacing nastier entities like fen-phen. The purveyors of the newer meds hope to claim a sizeable chunk of this sizeable market.

Although we bench monkeys would like to think that good science drives target selection in discovery research, and in fact this is not an uncommon event, the pecuniary creatures in market analysis have increasingly worked their wiles into the earlier stages in the drug discovery process. Good science, although of paramount importance to us discovery types…


… is not always first and foremost in marketing’s mindset. Consequently, many pharma companies have research efforts directed toward obesity. Other than the niche-directed biotech boutiques, to remain competitive, obesity targets seemingly must be on the research docket of a large pharmaceutical company.

In terms of pure science, I have to admit there’s a certain degree of “Ah ha!” coolness surrounding some of the targets related to obesity. The “Ah ha!” factor is an especially seductive influence in science. Are there little spurts of dopamine released at those moments, tickling the reward centers of the brain druing the moment of discovery, and thereby making the process addictive? Enzymes involved with various parts of fatty acid metabolism and certain G-protein coupled receptors like the CB-1 receptor mentioned above and the ghrelin receptor represent interesting potential targets, and well, I can’t tell you about the others. But as enticing and challenging as those targets might be for the cell biologist, the med chemist and the biochemist, those of us grizzled old veterans of the pharma biz know the potential pitfalls of bringing forward drugs for chronic indications, and certainly obesity falls into the latter category.

For drugs which treat disease states afflicting patients over the span of decades, for example, high blood pressure or arthritis, the long term safety of the meds is of great concern. The patient takes these drugs daily for months, and more likely years, so adverse side effects are not particularly tolerable. This contrasts with 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 more refined and targetted approaches may allow cancer to be treated as a chronic condition. The estimated costs to bring a drug to market from its discovery vary from $800 million to $1.2 billion, and the proper trials to determine efficacy and long term safety of a potential obesity drug would factor significantly in this cost. All in the name of what? A 10-20% weight loss versus placebo?

To be fair, even if weight loss is rather modest, rimonabant appears to have a beneficial effect on blood glucose levels and circulating in patients with Type 2 daibetes according to the results of the RIO-DIABETESclinical trial. The findings were reported on June 12 at the American Diabetes Association conference in San Diego. The beneficial effects on blood glucose and triglycerides appeared to extend beyond what was expected from weight loss alone. Still, the FDA issued the good news- bad news “approvable” letter earlier this year and indicated that Sanofi-Aventis needed to address undisclosed issues with the drug. In other trials, it appears that there was a 2.7-fold increase in psychiatric disorders in patients dosed with the drug over those taking placebo. Given the emerging knowledge of the endocannabinoid system’s role in anxiety and depression, this shouldn’t be entirely unexpected. The Vioxx-buggered FDA is skittish, so it remains to be seen if “approvable” translates to “approved.”

So maybe obesity is a viable therapeutic area. I’m not so sure, and I freely admit that my bio-papal blessings on the targets which are brought into my shop are sprinkled with bias. One Friday evening while snarfing down pizza and quaffing beer at the local watering hole, a group of us discovery shlubs lamented the significant research efforts directed toward obesity One of the senior medicinal chemists working on an obesity target 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 to twenty 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 f*ckup of 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 variants which predispose them to the condition, and indeed, maybe a pill could be of benefit. Maybe. However, each pizza devouring, beer sloshing investigator believe that diet and exercise are first line treatments for most garden-variety forms of obesity.

So to the FFAs who believe that the pharma industry wants you to be obese, well, to an extent you are right since your excess white adipose tissue shines like a golden goose egg (more like 1.0 * 10^9 goose eggs) 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 diseases, immune disorders, neurological diseases, and other such trivial pursuits.

And now we return to Mr. Beck’s Heavy Hitters program…

Comments

  1. #1 Buddha-Belly
    June 14, 2006

    Doc, are you pinch-hitting for Beck? How many FFAs are you addressing here, vs how much money is being made by pharma? Who has more influence? FFAs, BFB and NAAFA or wall street and pharma PR? Is there seriously a comparison being made that fat acceptance is a stronger social force than fat aversion? Have the FFAs taken to producing pro-obesity commercials that will be aired during the nightly newscasts? (I love the question mark most of all punctuation and would use it instead of commas, semicolons and quotes, but it would get confusing pronto.)

    Beck quoted a population of 11,000 FFAs in one group and an indeterminate number at BFB (not that large although disproportionately loud). So I guess the contention is that these people (the FFAs) are in some way more influential to the obesity “crisis” than the various social detriments that I enumerated in a flurry of questions. The FFAs seem to be the target of various rage because, well, they’re such big targets, and not very fast moving either. Besides, they must be stupid to be fat, else they wouldn’t be…

    Folks, do you see any similarity here in the way that some people trot out NAMBLA whenever they assail the ACLU? NAMBLA has as much to do with what the ACLU does as the FFAs and the BFBs have to do with the obesity “epidemic” in America but it’s the face of the bogeyman. I’ve never had these angry fat activists get in my face, but I see a lot of my friendly neighbors getting bigger by the day, and I see a lot of money being made off the hapless lot. Hoodia you say? Sure, let me get 60 pills for $25.

    So, those moth*#$%^ 15,000 FFAs have turned this ex-glorious country into what we are now, and our major issue is that the FFAs and the BFBs are to blame for the “commonplace acceptance” of girth growth. That these people are leading us all down the path of accepting 600 lb shut-ins as new beauty standard. Is that it? As a percentage, what is 15,000 slow, lethargic, wheezing, cheeto encrusted, mouse pushers out of 300 million cream o’ the crop, self motivated, disciplined Americans? Don’t like my number of 15,000 FFAs? Give me another. In the spirit of civil rights, should we count each one as five thirds?

    Shoot, there’s fewer of these keyboard activist shut-ins in America than there’s Al-Qaeda in Iraq. You’d think they’d be easier to neutralize if they were this big threat to our social consciousness.

  2. #2 Doc Bushwell
    June 15, 2006

    Oh, c’mon now, JKB. My blustery references to FFAs not withstanding, this is not so much about this vociferous and relatively small population than it is about shifting resources toward discovery of drugs intended solely for weight loss. K. Beck just gave me an opening. Upon closer reading, you might see that I agree with the FFAs in the sense that the 800 pound gorillas (gotta work a primate reference in here) of pharma marketing indeed view the obese as a patient population ripe for the picking. The pharma industry hasn’t concocted the increasing incidence of obesity among our population as a whole, but they are certainly ready to take advantage of it.

    As a researcher who knows how difficult it is to get a compound into the clinic (and I have done this), I am circumspect about expending resources on obesity. It’s one thing to come up with new pharmacological approaches to treat diabetes, high triglycerides, and hypertension, all of which may be aggravated by excessive weight (don’t I know it). These meds are ideally used in conjunction with diet and exercise. But a drug to help shed 20 pounds? Why not treat the metabolic consequences I just mentioned, and encourage to patient to lose 20 pounds by a safe and time honored method? I just don’t know. I have to confess that when our neurosciences and oncology divisions approached me for resourcing novel targets aimed at schizophrenia, depression and cancer, I was eager to get involved. Same thing for our metabolic diseases group when they requested help with a novel target for diabetes. I haven’t kept obesity targets out of our shop (we’re supporting one), but in proportion, the entire effort at the company is small compared to the biggies of cancer, metabolic disease, inflammation, etc. My dark overlords maintain an obesity program, but I expect it is a smaller effort than that found in other companies.

    I could stand to lose 20 pounds. Would I take a drug to do so? No f’ing way.

  3. #3 Kevin Beck
    June 15, 2006

    Just for fun, I’m going to reply to Buddha-Belly without reading what Joan wrote and see how closely our responses match up.

    “I guess the contention is that these people (the FFAs) are in some way more influential to the obesity “crisis” than the various social detriments that I enumerated in a flurry of questions.”

    It would be helpful to you as you read these installments to suspend your view of the world — be it right or wrong — as nothing but a series of warring and conniving factions battling for ultimate supremacy and everyone else’s riches.

    Neither I nor Dr. Joan has tried to pin the cause for America’s expanding waistlines on noisy fat people or, for that matter, on anything else. I understood quite well yesterday that in your comments you were agitating for me to admit that food marketers and manufacturers can claim the lion’s share of responsibility for America’s ongoing blotation; the reason I didn’t bother is because I’m not addressing the causes of obesity in the first place (although I’ll tap into some physiology and biochemistry tomorrow). It’s as if I’m writing about a controversy over how a certain cancer should be treated (chemo? Rays? Watch-and-wait?) while you’re screaming about the goddamned mutagens that chemical plants are churning out in ridiculous amounts right under the EPA’s nose. But if it eases your pain, go ahead and blame big corporations for sealing the behavioral and rhetorical fates of people inherently prone to both weight gain and denial, however many of them there are. I’m right there with you, all 21 of my digits pointed straight at Big Grease, Big Cola and Big Pastry.

    What I’m doing here is simple: looking at the medical data regarding obesity in the context of a growing number of people who want no part of it. Whether or not they ultimately pay attention to these data doesn’t concern me. Regarding your various hyperbolic droppings, I have emphasized that this isn’t about cosmetics, I don’t care to “neutralize” fat activists any more than you presumably want this domain shut down because you take issue with some of the content, and FFAs cause me no rage; they take nothing from me.

    Regarding Joan’s post, what she has done is explain that drug companies aren’t especially eager to develop weight-loss drugs, for one primary reason: Doing so is costly. So if anything, she’s agreeing with you — the marketing folk are not not humanitarian but simply greedheaded.

    I really can’t tell if you’re amused or enraged — maybe both, as you strike me as a cross between Jerry Fletcher and Dennis Leary — but in any case, I return you to your talk of NAMBLA-sponsored nutri-terrorist cells stocked with vociferous morons of size, and look forward to you comments on my final three installments in the same manner I look forward to being fellated by a starving mountain lion.

  4. #4 Jess
    June 15, 2006

    I started to comment here, and then I stopped, because you were so sarcastic (borderline nasty) to Buddha-belly right out of the gate. Then I started again because I’d decided to give you the benefit of the doubt; I’ve never known ScienceBlogs to be the kind of place where you get shot down for expressing polite and reasonable dissent, and I like that — sets the science bloggers apart from the Republicans. Then I stopped again because the comment got too damn long, and posted it over on my blog instead.

  5. #5 Buddha-belly
    June 15, 2006

    Just trying to lower the level of discourse to its natural level. Your comment sections were barren as the desert and I found it superficial to discuss obesity acceptance without social drivers, enablers and the ecosystem of the free-range wild shut-ins.

    Doc — that was way uncool to out me like that. It says on typepad that I needs to put an email address to post. I may use lots of names but I don’t sockpuppet. I’m Buddha-belly because in kitchy statues, he seems content of his rotundness in a non-threatening way.

    Beck, everyone deserves a troll. You aren’t loved unless people are trolling you and calling your ideas wrong-headed, misguided and disingenuous; not to worry — you’ll be quoted in NYT and TNR soon enough, and if not them, the quality of your work guarantees freelancing for advocacy PR firms. They’re always looking for scientists with a rage complex that isn’t askeered to scapegoat.

    Hell because of your trolling and linking I may have drawn some FRA psychos to my neighborhood, and now need to get to the range to make sure all the hardware still works right. Totally throws my weekend out of whack, but gives me a chance to rub elbows with other local rednecks.

    And Jerry Fletcher was right. They was out to get him. Or are you speaking of the business consultant?

  6. #6 Kevin Beck
    June 15, 2006

    “I started to comment here, and then I stopped, because you were so sarcastic (borderline nasty) to Buddha-belly right out of the gate.”

    Jess, not only is there nothing nasty in anything I’ve written to Buddha-Belly, he’d only enjoy it all the more if there were. That’s why he’s here; he’ll admit it’s a habit of his. Similarly, he knows I’m not really enraged when I write these things, although he often seems to wish I were. Read his responses to each of my “installments” and the borderline relevant mention of my name under this topic and decide for yourself who’s doing the bulk (ha ha) of the button-pushing.

    I read through your blog entry-cum-comment and will simply say the same thing to you as I did to Buddha during one of hus lucid moments of typing in which he appeared more interested in the topic than in mimicking fingernails on slate: The multiple causes of obesity are simply not at issue here. I’m not writing about how or why people become fat or holding them accountable for doing so. I’m writing about how they (some of them) respond once they’re there. As with abiogenesis and evolution, these issues are interrelated but distinct.

    I’m not going to make this kind of interjection again because I could not be more clear if I spray-painted the above declaration on the inside of everyone’s eyelids in hunter orange. (By the way, that wasn’t nastiness, it was a joke.) I am genuinely surprised that given your apparent agreement with most everything I have written (you seem to be taking issue only with what I haven’t) about where fat activists go astray that you seem so put off. Perhaps you assume — on what basis I do not know — that I am making moral or otherwise overly harsh judgments of overweight people as a group. I could say more, but it seems foolish to unnecessarily spread this across the comment fields of multiple blogs, so maybe when I wrap this up on Monday I’ll be interested in visiting your hive.

    I’ll remind you both that this is a five-part series, meaning that not all of the content appears at once. This may help explain any information or explanations you believe might be missing so far.

  7. #7 Doc Bushwell
    June 15, 2006

    Doc — that was way uncool to out me like that. It says on typepad that I needs to put an email address to post. I may use lots of names but I don’t sockpuppet. I’m Buddha-belly because in kitchy statues, he seems content of his rotundness in a non-threatening way.

    Oh, man…my apologies, Jack K. Bauer, er, I mean Buddha-belly. I wasn’t too observant on that and didn’t intend to take away your disguise. Now, might I rub your belly for good luck before you return to saving our great country from imminent disaster all within a day’s time?

    And keep up the commentary, B-b. KB can handle it, and well, it makes me nostalgic. My current place of employment has a polite culture. This is all well and good, but one of the upshots is that the well entrenched scientists are loath to criticize each other’s work. Criticism is essential for scientific progress, and sometimes, things can be rancorous. The modus operandi at my former milieu, an intensely competitive place, was screaming, shouting and stopping this close of calling each other dumbfucked morons. Oh, yeah. It was lively.

    Anyway, I just wanted to note that scientific discourse is not a tea party. So have at it, lads.

  8. #8 Jess
    June 15, 2006

    All right, if you have an established mutually antagonistic relationship. I thought his comments sounded basically reasonable and your responses sounded way out of kilter (and yes, borderline nasty, I’m sticking by that one), but — like many of your visitors, I imagine — I don’t have the benefit of history.

    I’m not sure you got my drift, though. My question to you was why you’re not addressing the causes of obesity, because I really don’t believe that you can purport to discuss the “obesity epidemic” as some kind of monolithic structure. I understand that you’re not addressing it, but my contention was that it’s as one-sided to discuss only the failings of the [F]FA community as it is to acknowledge (as they do) only the causes and health effects that fit the party line.

    Perhaps you assume — on what basis I do not know — that I am making moral or otherwise overly harsh judgments of overweight people as a group.

    Ah, but that’s the thing. You don’t need to. It’s a given. And this, I think, is why fat advocacy people get so easily bent out of shape. The attitude towards the obese in our society is such that if you don’t explicitly acknowledge that Fat does not necessarily equal Bad, then you’re implicitly saying that it does. That’s why NAAFA is so apparently allergic to the existence of a “healthy weight”; the diagnosis of obesity so often comes with a negative judgment, even from health professionals, that they feel their efforts would be better spent erasing the whole concept of “overweight.”

    This is why it’s too complex an issue for you to expect people to sit quietly while you finish your series, even if you paint your objections on their eyelids. The principle that allows NAAFA to get so bent out of shape — that is, the principle that most people who discuss obesity are operating from a position of disgust and moral judgment — really is not that far off. And you can’t just ignore that simply because their understanding of the issue is so incomplete.

  9. #9 Jess
    June 15, 2006

    Also, I apologize for using the word “society,” which is a crutch I tell my students never to use. I should say 20th and 21st century American culture. And all I can really speak to is 20th and 21st century East Coast American culture.

  10. #10 Kevin Beck
    June 15, 2006

    This’ll be the last response I make here because there’s no reason this discussion should be going on under Joan’s post. Coments about what I have written should be entered under what I’ve written — not ’cause I’m anal about the look of the place, but because I should get a comment notification, not Joan, every time someone goes to put a boot in my ass.

    Alrighty then:

    “I’m not sure you got my drift, though. My question to you was why you’re not addressing the causes of obesity, because I really don’t believe that you can purport to discuss the ‘obesity epidemic’ as some kind of monolithic structure.”

    First of all, you’ve put words — and with them, pathos — in my mouth. I have not once mentioned the term “obesity epidemic,” which I don’t even like. Second, I believe I have explained that this is a multi-part series, meaning you can decide after reading the whole thing whether I have adequately addressed all appropriate aspects of fat acceptance (I’d love to print all 7,000 words at once, but decided against it over a week ago). Third, the fact that I am examining the interaction between clinicians and overweight people does not obligate me from a moral or epistemological perspective to speculate about the relative contribution of genetics, activity level, and environment (to include food, meds, and a zillion other things) to any individual’s propensity for gaining weight.

    Given that some fat activists, as you know, basically deny that food is a contributor to either size or disease and pin all of the blame for remaining heavy on genes and dieting, are you suggesting I either debunk or support this? Fair enough. Or are you simply asking for an explicit personal statement from me about how much more easily some gain weight than others, or a nod to the nastiness of the particular brand of shame heavy people face at the doctor’s office and elsewhere? Does the following passage look familiar?

    On its Web site, NAAFA claims — accurately, to be sure — that many fat people do not receive adequate preventative health care owing to “prejudicial medical treatment and harassment by health care professionals.”

    Did you even what I wrote tomorrow about set-point theory and leptin? Whoops — not your fault…must…slow…down.

    “Ah, but that’s the thing. You don’t need to. It’s a given. And this, I think, is why fat advocacy people get so easily bent out of shape. The attitude towards the obese in our society is such that if you don’t explicitly acknowledge that Fat does not necessarily equal Bad, then you’re implicitly saying that it does.”

    Are you telling me that I cannot convince you I am not making judgments about the character, “willpower,” intelligence, motivation, pride, etc. of fat people even if I flat-out say I’m not?

    I disagree with you when it comes to where the primary onus for disarmament lies. I’m sorry about what the laws of society does to the spirits of people who consider themselves outcasts for any reason, and it bothers me to think that if I happen to pass a very heavy person during a run, safely shielding my own frailties and insecurities, that such a person might instinctively reckon that I presume to be superior. But in the world I live in, I can’t be bothered to go out of my way to pre-emptively tell anyone that I don’t think ill of them. This would, among other things, take forever (although not in my case, since I do think ill of practically everybody … just seeing if you’re still awake).

    I understand that this attitude on the part of fat activists explains much of their contentiousness, but at a time when well over half of the country can be labeled overweight, it’s encroaching on paranoia to assume everyone else thinks you’re a slovenly ball of weakness until announced otherwise. So yes, it’s an issue, but on whose side is it the greater one?

    “This is why it’s too complex an issue for you to expect people to sit quietly while you finish your series…”

    Again, nowhere did I say I expect people to not comment, period (otherwise I’d just disable comments, and besides, I expected and welcome discussion on a topic I knew would resonate in various ways). And I did not mean to imply that Buddha-Belly is being 100 percent the gadfly, as it’s closer to 90-95 percent. What I wish people would not do is complain that I’m not being fair and balanced when only half the see-saw is built. (Well, bad analogy. I wrote the whole thing a while ago and split it into five roughly equal chunks once I found I’d be littering this place with verbal dross.)

    Enough out of me.

  11. #11 Kevin Beck
    June 15, 2006

    Jess — I really think we’ve just been talking around each other rather than really disagreeing (not that disagreeing is verboten). That’s to be expected when you consdier the very idea I’m proposing (that people’s different ideas and emotions and perspectives are at the root of the whole need for fat activism) and it would be naive for me to expect nothing but clarity here. I certainly don’t claim to have a handle on the whole matter – it’s an exploration.

    I promise just the things you bring up will be mentioned tomorrow right off the bat, and I also promise I’m not editing any of what I already wrote. I swear to Zeus! I just looked at tomorrow’s entry and it’s actually pretty funny to see what’s in there.

    KB

  12. #12 Jess
    June 15, 2006

    I really think we’ve just been talking around each other rather than really disagreeing (not that disagreeing is verboten).

    Yeah, that’s the sense I had from the beginning. And you’re right that you’re not under any obligation to write the definitive treatise — even when you have five parts to do it in. (I think it’s well established that five blog posts isn’t remotely sufficient to cover every aspect.)

    I didn’t mean to imply that I was quoting you when I said “obesity epidemic,” by the way — the bunny-quotes were just because I question its validity as a concept. Sorry about that.

    Are you telling me that I cannot convince you I am not making judgments about the character, “willpower,” intelligence, motivation, pride, etc. of fat people even if I flat-out say I’m not?

    No, my point was just that it’s what’s assumed, in the absence of… well, in the absence of strenuous assertions to the contrary, I guess. That’s not your fault; I just wanted to point it out as the platform from which NAAFA is making a lot of its assumptions, and one of the places where I don’t think they’re wrong. (“It” in the previous sentence is “the fact that judgment is usually presupposed when talking about weight.”)

    Anyway, I think you’re right that we’re talking around each other, and it’s pretty clear that we’re on the same side. And I’m glad you’re writing about the ways in which NAAFA (and other fat acceptance activism groups) fail as activists — I was just trying to get my mother to put that into her article, but I’m not sure there will be room. I was just concerned when your initial response to a question about causes was “I’m not talking about causes,” since the multiplicity of causes is such an inextricable part of the issue.

  13. #13 Buddha-belly
    June 16, 2006

    These meds are ideally used in conjunction with diet and exercise. But a drug to help shed 20 pounds? Why not treat the metabolic consequences I just mentioned, and encourage to patient to lose 20 pounds by a safe and time honored method? I just don’t know.

    Hmmm, why use a drug to shed 20 lbs when exercise will do?

    Hey Doc, in my quest to use question marks more often lemme ask you — Why don’t mom’s stay at home, cook, clean, and make real meals on a daily basis? Could it be that many of them are working (or busy self preening) and may not have the time? Could it be that socially things have changed and the moms set different examples than they did 50 years ago? Are there more things/gadgets to fill our day than there were 50 years ago and finding time to exercise may not be an option (but popping a pill may be an option, in the same sense that either eating out – get your mind out of the gutter there – or eating processed food is a time saver? Is our predisposition to take pills linked to the upswing of heavily processed food choices (buy it, not make it and save time).

    Do you remember back in the 60s where the meals of the future were represented as pills and tubes? Can I make it through this post with only questions?

  14. #14 Leo
    January 17, 2007

    The diabetes in America became an essential problem, struggle with which is priority problem American Diabetes Association WBR LeoP

  15. #15 Leo
    January 18, 2007

    The diabetes in America became an essential problem, struggle with which is priority problem American Diabetes Association WBR LeoP

  16. #16 Doc Bushwell
    January 18, 2007

    The diabetes in America became an essential problem, struggle with which is priority problem American Diabetes Association WBR LeoP

    Yep, agreed. Type II diabetes is increasingly prevalent. Again, it’s a disorder affected largely by lifestyle factors although genetic predisposition compounds this. I would assume that dietary modifications and increased exercise are first line treatments. There are a number of pharmacological treatments coming on line which address diabetes specifically, e.g., the dipeptidyl peptidase inhibitors, and not obesity.

The site is undergoing maintenance presently. Commenting has been disabled. Please check back later!