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July 13, 2009

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This is important stuff. Let's see if it gets as much play as Sarah Palin and so forth.

"There are lots of ways of promoting animals' growth that do not put people's lives at risk."

There are, but I'm curious about the myriad of ways that would promote the level of growth being aimed for here.

BTW, interesting organization there. Are all the other scientists "unconcerned?"

Every time I get disgusted with Obama's moral weakness, he astonishes me by bringing into the mainstream ideas that obviously make sense but nobody has dared mention for decades.

I suspect he raised it primarily as a bargaining chip, but we'll see.

Another advantage to this rule is that cutting down crowding in factory farms may also reduce their environmental impact.


Every time I get disgusted with Obama's moral weakness, he astonishes me by bringing into the mainstream ideas that obviously make sense but nobody has dared mention for decades.

JFK without the affairs and the possibility of war with the Soviet Union. Obama strikes me as bringing to the table a similar combination of boldness and timidity, crafty calculation and moral cowardice (sometimes hard to disentangle from each other), and a set of opponents who for the most part are barking mad. US politics today makes a lot more sense when you realise that we are presently at about mid-1961. I'm really, really hoping to skip over November 1963 entirely, BTW.

"Obama strikes me as bringing to the table a similar combination of boldness and timidity, crafty calculation and moral cowardice (sometimes hard to disentangle from each other), and a set of opponents who for the most part are barking mad."

I've made this point in the past, too. I forget whether you agreed with me, or I agreed with you. :-)

And it highlights the need for public campaigns to push the president to do what needs to be done, on most fronts, so the support is there, and so the president's hand is forced, rather than instead having the president's eye focused elsewhere. JFK on civil rights being the most obvious example here.

The other fear, of course, being Afghanistan turning into Vietnam.

"JFK without the affairs and the possibility of war with the Soviet Union."

One hopes.

Allow me to chime in and add my agreement to Gary's.

"There are lots of ways of promoting animals' growth that do not put people's lives at risk."

That is correct. Plus, some animals just aren't supposed to be as big as we force them to be.

Meat production in this country is f**ked up, plain and simple. Most other food production is as well, for that matter.

I'm delighted that Obama is jumping on this. The article is right, it probably won't pass without a fight, but just putting it on the calendar raises the issue.

Right on.

As long as it doesn't interfere with my ability to consume BACON!!!

That said, I've always thought that this use of antibiotics was one of the worst cases of how a free market can fail a society.

I'm under the impression that another reason new antibiotics aren't being developed very fast is that /we've hit all the easy targets already/. Simply the R&D is much harder than it used to be. If a building cements over its windows, building a better ladder to climb in through them simply doesn't do any good. Which makes it all the more critical that we use the antibiotics we have responsibly, lest ALL bacteria block up their windows.

Like we've only known this was a serious issue for what forty or fifty years, but somehow never got around to actually doing anything about it. That very omission, is probably a bad omen, the political and economic forces against sane antibiotic policy are probably pretty formidible. It's not just the ag-industry, but the pharma-industry, which makes good profits selling the stuff in the first place. So when it gets framed as short-term economic efficiency, versus some "theoretical" longterm concern, I think the going may get tough.

Do not, I repeat DO NOT put that into the healthcare bill. It will be difficult enough to fight the congressional lackeys of the insurance companies and to get away with a not totally horrible reform. Bringing the agro mafia and their shills in on the side of the enemy would make it impossible.
This is important enough to justify a bill of its own and should be easy enough for even the common moron..eh..citizen to understand.
Apart from that: mixed bills are a cancer! What cannot stand on its own should be either better supported or not brought up in the first place but not attached to another bill.

Implications for better livestock practices: not only would the decrease in antibiotics demand better sanitation but more humans to care for the stock. With "preventive antibiotics," you don't worry about scanning each pig and chicken daily or weekly to catch diseases. Without them, you need to watch and identify signs of illness.
An increase in the ratio of humans to animals suggests more jobs (even poorly paid agricultural jobs), perhaps better care, and increased costs. Do increased costs, passed to consumers, mean less intake of animal products ( & better diet?).

While we're at it, can we do something about restoring proper sterile procedure in hospitals? Misuse of antibiotics in the wider world might generate resistant strains, but cross-infection in hospitals is a major generator of multiply resistant strains, the real threat.

Antibiotics have made the medical comunity rather lazy about sterile procedure: Visit a hospital some time: Ever stop to ask how you sterilize carpeting and wall paper? Wondered where the UV lights have gone? Winced at people wandering the halls coughing?

It's easy for doctors to blame the agricultural industry, and fair enough, but they've got some serious issues of their own to take care of.

Fully agreed on that Brett and my impression is that it is not just lazyness or carelessness but that the very knowledge of those things is not necessarily present anymore. I think I remember studies showing that a lot of medical personnel these days(from nurse over assistant to doctor) can't do the procedures properly, i.e. they believe that they got the treated area germ free but made mistakes that reduced or nullified their efforts.

"This is in part because spending money to develop new antibiotics doesn't make sense for pharmaceutical companies.


For one thing, antibiotics are used for short periods of time; the real money is in drugs for chronic conditions that have to be taken indefinitely."

I'm with you on the antibiotics/livestock thing, but you aren't right about the 'why we don't have more antibiotics' issue.

Any of the major pharmacuetical companies would LOVE to have a new major antibiotic. Whatever we want to say about where the real money is, a new broad spectrum antibiotic would be worth billions over the life of the patent. No company would turn that down if they thought they had a good lead. There have been a number that were in the pipeline, but that failed in trials in the past 5-10 years. The simple fact is that our current avenue of research in antibiotics has proven to be much to toxic. And we haven't identified the next one yet.

"Any of the major pharmacuetical companies would LOVE to have a new major antibiotic. Whatever we want to say about where the real money is, a new broad spectrum antibiotic would be worth billions over the life of the patent."

Not only that, but (assuming that the new antibiotic had a novel chemistry), derivatization of the antibiotic and reformulation with existing antibiotics would yield even more patentable therapeutic formulations and $$$.

Reading Derek Lowe on the pipeline blog, it seems as though existing medicinal chemistry has hit a brick wall in terms of targets and drug candidates. Prospecting in marine environments is yielding some new chemistries [too bad the coral reefs are dying off, so fewer species to prospect from].

I'd hope that synthetic biology might generate new families of chemical compounds not easily generated with existing synthetic chemistry methods, but that might be a misplaced hope in the same way combinatorial chemistry turned out to be a disappointment.

Oh, also, could Obama please please please please outlaw similar use of antivirals, and ask the Chinese to do the same?

70% of avian influenza strains circulating in chicken flocks in Southern China are already immune to M2 inhibitors. And we're already seeing oseltamivir (sp?) resistance appearing in some strains. We have even fewer antivirals than antibiotics, and it'd be awful if a short time after they're developed they become useless from indiscriminate agricultural overuse.

I'm with you on the antibiotics/livestock thing, but you aren't right about the 'why we don't have more antibiotics' issue.

Any of the major pharmacuetical companies would LOVE to have a new major antibiotic.

Sure, they just haven't wanted to pay for it. The last time the "innovation gap" in antibiotic classes was brought up, I vainly pointed out some of the literature noting that industrial antimicrobial R & D was languishing. To save some re-typing, this time I'll go with antimicrobial researcher Christopher T. Walsh:

Although the history of antibiotic development demonstrates the remarkably successful mining of NATURAL PRODUCT SCAFFOLDS by generations of medicinal chemists to meet the challenges of resistance development, it also emphasizes the ongoing, cyclical need for innovation. Indeed, it raises the question of whether progressive tinkering with antibiotic scaffolds has been hiding an innovation gap, as a dramatic gap existed between the introduction of quinolones in 1962 and the next new structural class of antibiotic, the oxazolidinone linezolid (Zyvox), which was approved almost 40 years later.

Does the innovation gap still exist? Inspection of the antibacterial drug candidates that are being advanced through clinical trials indicates that it does. Many of the agents that are in development at present continue to be minor modifications of the three structural scaffolds described above. These second- and third-generation molecules can be extremely important for achieving improvements in efficacy and pharmacokinetics, but they do not have new molecular structures. There are also variants of other approved classes of antibacterial drugs, such as the tetracyclines and glycopeptides of the vancomycin and teicoplanin family, that have been modified to regain efficacy against the pathogenic bacteria that, at present, cause the most common infectious diseases. The lipopeptide antibiotic daptomycin, at present in new drug approval review, acts by a mechanism that is distinct from the lipoglycopeptide teicoplanin and could fill a niche against the vancomycin-resistant enterococci (VRE), in addition to other pathogens. The second indicator that the clinical pipeline for antibiotics is empty is the fact that few large pharmaceutical firms are active in the antibacterial infectious disease arena. The exit and/or significant de-emphasis of many pharmaceutical companies (for example, Roche, GlaxoSmithKline, Bristol-Myers Squibb and Lilly) from this therapeutic area in the past 15 years reflects not only a mix of economic and market projections, but also a partial to complete failure of research programmes that have been built on existing models to find new leads that are robust enough to become clinical candidates.


--Nature Reviews Microbiology 1, 65-70 (October 2003). [Emphasis added]

But yes, yes, the market will take care of itself. Eventually. And hey, there's actually two other oxazolidinone antimicrobial candidate advancing through the industrial pipeline, though neither is from Big Pharma. Meanwhile, those drug ads aren't going to televise themselves.

You're taking a very disagreeable tone while quoting things that agree with me:

"but also a partial to complete failure of research programmes that have been built on existing models to find new leads that are robust enough to become clinical candidates."

We need new models and we haven't found them yet.

You take "few large pharmaceutical firms are active in the antibacterial infectious disease arena" as some sort of nefarious sign, when it is merely a reflection of the fact that you can't force through the pipeline drug candidates that don't exist.

Interestingly, this is allegedly the area where the NIH has an advantage. Government programs do basic research, pharmaceutical companies do better applied research. The problem is that at the moment, basic research hasn't come up with any promising new leads in the area that aren't insanely toxic. Which is a bummer. But not an evil plot fueled by naughty profit.

Hmm, let me see if I can rearrange and reemphasize the entire sentence to make cause-and-effect a little clearer:

Not only a mix of economic and market projections, but also the partial to complete failure of research programs that have been built on existing models to find new leads that are robust enough to become clinical candidates has led to the exit and/or significant de-emphasis of many pharmaceutical companies (for example, Roche, GlaxoSmithKline, Bristol-Myers Squibb and Lilly) from this therapeutic area in the past 15 years.

Again, the failure of existing approaches has led to abandonment or de-emphasis of antimicrobial research by most big pharmaceutical companies for economic reasons, not by gearing up the quest for new classes.

So if your point was that much of big pharma has decided that it's unprofitable to pursue new classes of antimicrobial agents when their standard approaches no longer panned out, then yes, Professor Walsh agrees with you. It just seemed like you were trying to argue the opposite of his position, which is critical of big pharma's priorities in this area. My apologies.

And interestingly, this is the area where the NIH does have an advantage. And not just with elucidating new classes; e.g., further work in vancomycin and oxazolidinone mechanisms and refinements is occurring in NIH-sponsored research right now. But academic labs frequently lack a clinical trial division, and only a couple of small startups have bothered with new oxazolidinone trials on the industrial side. Still, the stimulus money has helped keep some antibiotic projects going locally that otherwise would have been cut back. Perhaps we should start running expensive primetime commercials urging people to ask their doctors about NIH-funded basic research.

It seems implausible that drug companies would not try to duplicate the incredible profit of, say, penicillin. Say what you will about Botox, but EVERYONE IN THE WORLD needs antibacterials. You really do make it up in volume.

It's especially odd, when Big Pharma is already researching and developing new antibacterials. IANAChemist, but I know that a big chunk of R&D cost is clinical trials and the other costs of getting a mostly-developed drug approved by the FDA. If they're already putting that much money into R&D of non-innovative variations, why not also make a reasonable try at innovation?

In fact, it sounds like Big Pharma already does put some money into pre-trials R&D of antibacterials. Why would they give that less then the necessary budget? That's just pure waste (like the proverbial second-best army in Europe). If they do not want to put enough money into that kind of research to make results likely, why put in any at all?

Being as how this ain't my field, I'm speculating in a vaccuum here (or insert colorful phrase of choice). Could one of the SMEs please describe in layman's terms what the difference is between the sort of program Big Pharma does, and the sort you think they should do, including a ballpark figure for the percentage difference in cost of antibacterial R&D as a whole? Without that, I can't begin to guess whether the accusation makes sense.

I assume you include academic grants funded by Merck & SGK as part of their R&D efforts?

"Again, the failure of existing approaches has led to abandonment or de-emphasis of antimicrobial research by most big pharmaceutical companies for economic reasons, not by gearing up the quest for new classes."

That isn't what it says, and it isn't what it shows. The evidence shows de-emphasis because of lack of avenues. The companies have been trying and failing. It isn't obvious that they should keep throwing money at failing avenues. If that is what you mean by "economic reasons" I guess you are right, but you don't have much of a point. You stop hitting your head against the wall when it hurts right?

"So if your point was that much of big pharma has decided that it's unprofitable to pursue new classes of antimicrobial agents when their standard approaches no longer panned out, then yes, Professor Walsh agrees with you. It just seemed like you were trying to argue the opposite of his position, which is critical of big pharma's priorities in this area."

This is incoherent. There aren't a lot of people investigating anti-gravity either, even though it could be REALLY USEFUL. They don't because there isn't a good theoretical underpinning leading to it. So scattershot approaches would be really expensive and unlikely to be fruitful. Unless you are arguing for straight up wasteful spending I don't see your point. You haven't demonstrated that throwing more money at the problem would be fruitful.

They are doing current research in the areas they think are likely to be fruitful. They aren't doing research in the areas they don't think are liely to be fruitful. Unless you are asking them to spend more money in areas they don't think are likely to be fruitful, I don't understand your point.

Do you think that merely spending more money will automatically lead to more antimicrobials?

Some interesting points here. I've been googling a bit to find out what is the current state of the research and there seem to be a lot of interesting avenues (such as antibiotics as signalling agents, antibiotics attacking bacteria communication systems), but I have no idea if these are commercially viable or not. I also found this SFChronicle article about the state of development of antibiotics and it seems that that genome sequencing has captured the imagination of people and companies, but that is not helpful for creating good antibiotics, which suggests that it is not avenues so much as ways of looking at the problem. However, googling 'antibiotics pipeline' gets a range of links either trumpeting improvement or predicting doom. I'm curious what sources everyone is looking at and seeing where everyone is getting their info. Thanks.

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