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Limiting Antibiotics in Animals (nytimes.com)
105 points by ColinWright on May 1, 2013 | hide | past | favorite | 52 comments



> I am astonished by the letter from Bernadette Dunham, the director of the Food and Drug Administration’s Center for Veterinary Medicine, especially since she told a House committee on April 9 that she was unsure how antibiotic resistance develops.

I've posted this before, but some people may have missed it.

"Defeating the superbugs" (http://www.bbc.co.uk/programmes/b01ms5c6) has a segment showing bacteria developing resistance to antibiotics.

(http://v6.tinypic.com/player.swf?file=24goih4&s=6) (Sorry about the lousy host; YouTube's content sniffing detects this as BBC property and blocks it.)

They have a slab of jelly. The jelly has sections of differing strength of antibiotic. There's a section with no antibiotic, then 10x, then 100x then 1000x. (They cannot dissolve any more antibiotic into the jelly at that point.)

A time lapse camera shows the bacteria growing, and developing resistance to each section.

It's an excellent bit of video.


Excellent video. What would be even more powerful is if they repeated the experiment, but with the 1000x agar right next to the antibiotic-free medium to illustrate what happens when antibiotics are used properly.


I would like to see that as well, but I would want them to let it sit for a long time - months, maybe. Because eventually, you may still get a mutation that can withstand the jump from 0 to 1000x.


Quite possible, especially because there's a safe haven of antibiotic-free medium just across the border, and the likelihood of a beneficial mutation is correlated with the number of individuals present.

In a properly-applied therapeutic situation, there is no such safe haven, and one hopes that the subject's immune system would be able to exterminate the much smaller load once the antibiotic's done its job, instead of leaving any stragglers behind to develop resistance.


Without iterative improvement, the chance of a complex adaption occurring by random chance are much much smaller. I don't know how complex an adaption to become resistant to this substance is, so it's possible it could occur by random chance. But even if so, it would likely still take much longer.


I can't speak about what the adaptation is, so I don't know if the adaptations at the difference levels of concentration are different in kind or degree. If degree, it is more feasible. Certainly the environment is only different in degree. Keep in mind the adaptation to go from 0 to 10x did not happen iteratively - and I may be remembering wrong, but I think that the bacteria stopped at the 10x boundary longer than the others. That may indicate that the subsequent mutations were of degree, not kind. Anyway, I think it would be worth doing this experiment.


I wonder if this can be used to develop useful traits in bacteria.

For example, develop bacteria that can digest some pollutants.


Depends. In many cases of antibiotic resistance, the actual "resistance" is a matter of degrees. For example, Penicillin interrupts the cell walls of bacteria, so in Gram negative bacteria it is only active in the periplasm. Some forms of Penicillin resistance work by metabolizing the Penicillin before it can do its thing. Other forms work by simply pumping the Penicillin out of the periplasm. The former mechanism requires a specific enzymatic activity. The later usually just requires tuning the pre-existing pumps that maintain the environment of the periplasm to be more specific to Penicillin or pump faster over all. In fact, most "multidrug resistance" genes are simply pumps that can exclude drugs from the insides of bacteria in general.

But really, this is just the shortest of short answers. If you want to know more about how these things can evolve, you should read about Richard Lenski's long-term experiments: http://en.wikipedia.org/wiki/E._coli_long-term_evolution_exp...


Something similar to this is done with bacteria and other life forms for all kinds of reasons. It's called directed evolution, where you take a strain of bacteria with a certain property (say aerobic nitrogen fixation at 65 Centigrade) and try to force that property to evolve (say force the aforementioned aerobic fixation to work at STP).

It's a very understood method but it's really difficult to develop proper methodology since almost every experiment will be different. The success percentage is also relatively low and is like playing the lottery (literally, you never know if the evolution is even physically possible or it might be so statistically rare that you'd need millions of parallel cultures).


It would depend on what sort of pollutant you are talking about. Many antibiotics act in subtle and complex ways because they need to be able to damage bacteria without damaging the human. Effective, evolving resistance is just a small "fix" for the bacteria.

However, some kinds of things like strong detergents, high temperatures, and so on qould require too much change to protect against so the bacteria can't evolve resistance to it. (sure, there are bacteria out there that might better resist these extreme conditions but you won't easily be able to evolve any bacteria you want to do the same)


Sure it could probably evolve resistance, it would just take much more time, and in an environment that constantly maintains a reasonable amount of selection pressure, increasing it as they evolve. Humans could assist the process by "island hopping". Like trying to select for ones that produce a certain chemical, then another chemical that requires that, step by step. As opposed to hoping they get a mutation that lets them produce a complex chemical by random chance.

It would still take a while, but bacteria have very short generations and can support huge populations, so it's far, far easier for them to evolve than anything else.


What you are suggesting seems awefully hard to do though. Its pobably easier to just get a ready-made gene from some other bacteria and insert it into the bacteria you care about.


That only works if such a gene exists already though.


This is definitely being studied. Here's one such grant by the EPA:

http://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/dis...


That's the principle behind selective breeding.

It and genetic engineering are pretty much exactly how such traits are developed.


That was easily one of the best bits of video I've seen in a long time. That explains a lot of science really well. Thank you!


Where I live, fruits and vegetables are ridiculously cheap, and meat is rather expensive. For example, apricots (which are just now in season) are $2.50 per pound. When the height of apricot season kicks in, the price will come down to around 50¢ per pound. But if I want a steak I can expect to pay at least $12 per pound.

I take a certain comfort in the notion that this price difference reflects the true cost of producing meat. Likewise, everything is locally sourced because there isn't really any other option, so everything taste fresh. Produce is only available when its in season, but this adds a fun sense of anticipation as the seasons change.

That's one point of view. The other point of view is that feeding antibiotics to cattle improves yield. Transporting produce long distances ensures that it can be grown where conditions are best, and flying fruits in from Chile means that supermarket customers can find what they crave even in the middle of winter.

The US has a long tradition of asking "can we?" not "should we?" Sometimes, as with the Apolo mission, this is a very good thing. Other times, as with the issue addressed here, it can be rather bad.

Edit: Also, as I always do when this topic comes up, I'll point to this extremely useful list on Wikipedia: http://en.wikipedia.org/wiki/Timeline_of_antibiotics . This battle is occurring on two fronts: the bugs are becoming more resistant, and we're having an increasingly hard time finding new weapons to fight them off.


A pound of steak does not have the same level of water content or nutritional value of a pound of apricot, so that comparison is not meaningful. Cost per pound of each nutrient is a relevant comparison.

Dried apricots cost $5-$10/lb. Does that make them overpriced compared to fresh apricots?


It was not my goal to compare apricots to steak, but rather the price of apricots here to the price in the US contrasted with the price of meat here to the price in the US. The US has optimized the production of meat such that the price is artificially low, but at what total cost?


I don't understand, how people, who supposedly must be well educated in biology, allow antibiotics to loose efficiency by feeding them to animals.


Self - interest and short-term orientation. Improving your own animals' health increases your profits and cash flow now. The downsides are long-term and shared by many others.

For regulators, the incentives might be skewed by lobbying and perhaps corruption.


Unfortunately, this is the way in which "market forces" fail us. When all motivations ultimately spring forth from ever-higher profits and market dominance, how can "doing the right thing" for society as a whole win out on a consistent basis?

On the other hand, relying on regulators seems to be fundamentally flawed. Some of the domains that these people are regulating are highly specific, niche, and complex. Where is the government going to get people who are well-versed and experienced in these domains if not the industries being regulated? And, once you are a regulator, from where do you source alternative job opportunities if not the companies you are regulating?


  | Unfortunately, this is the way in which
  | "market forces" fail us. When all motivations
  | ultimately spring forth from ever-higher profits
  | and market dominance, how can "doing the right
  | thing" for society as a whole win out on a
  | consistent basis?
Theory (aka fantasy):

- The people running the company will be selfish and want to minimize the future risks to their offspring/descendents.

- If the company uses a practice that is bad, all of their customers will just boycott / switch to a competitor.

Reality:

- The people running the company may not have any offspring and therefore not much riding on the future.

- Most of these companies all use the same practices, so it makes boycotting hard. Switching to competitors that don't use these practices are more expensive (i.e. organic), and food is something that people need.

- The detriments of certain practices may not be known right away, and stopping them later could lead to lower short-term profits (and maybe not even increased long-term profits, just betterment of society), and Wall Street doesn't like this because all Wall Street is concerned about is numbers going up or down (all other considerations are not considered).

- Most people have issues with long-term thinking. Things that happen slowly over long time-spans don't seem to register.


Awesome points.

> Switching to competitors that don't use these practices are more expensive (i.e. organic), and food is something that people need.

I do agree that people see this as an impediment. However, people use this excuse way too often - as a crutch, in my opinion. We (Americans, in my case) spend a pitifully small percentage of our incomes on food: http://www.motherjones.com/blue-marble/2012/01/america-food-...


I'd focus more on what the breakdown is for people below the median income. Obviously at a certain level, people can afford the more expensive, but the people in the lower echelons of society are the ones that are funnelled towards "what's cheap" when it comes to food choices.

That's not even getting into whom the largest consumers are. I'll bet that there is a lot of interfacing between companies like McDonald's/KFC/etc where other corporate interests are attempting to push down prices. Then you end up with multiple layers of corporate interests that end up insulating the consumer.

All of this can also be side-stepped (at least in this case) by moving to a vegetarian or vegan diet, but that's a large leap for some people and there are stigmas attached to it by some in society (i.e. 'dirty hippies,' etc).



Small daily doses of antibiotics act as a growth stimulant for animals. Bigger animals = more money, and there aren't any incentives in place to prevent farmers from killing the effectiveness of antibiotics.


I've heard that the vast majority of antibiotics that animals are fed are not of a type that has ever been approved for humans.


While true, it is also irrelevant. All known antibiotics belong to a very small number of classes by their mode of action. Resistance genes often confers resistance to not just one antibiotic, but an entire class, for example mecA in MRSA. Therefore it is possible for a bacterium to develop resistance to all therapeutic antibiotics without ever having encountered the exact types.

What's more alarming is that bacteria frequently exchange genetic material between species. Just because the resistance genes have not been discovered in a pathogen does not mean that the gene cannot be easily and instantly transferred from another species, and the chance of that happening is greatly increased if the environment is flooded with resistance genes due to selection by human use of antibiotics.


Just because it hasn't happened yet is not a reason not to do something. A tornado hasn't wiped out my house yet, should I move because it might happen some day? Of course there is a risk associated with their use, but the estimated risk is miniscule. It's not even measurable yet. Let's worry about problems we can identify and solve rather than wasting time fretting about what may be.


If by "risk" you meant the horizontal transfer of resistance, then I point you at genomic studies of horizontal gene transfer across bacteria. It happens with such regularity that the concept of a species cannot be naively applied to bacteria.

https://scholar.google.com/scholar?q=horizontal+gene+transfe...


You're correct, feed grade antibiotics aren't used for humans. The use of antibiotics that are used in human therapy for feed grade antibiotics is already outlawed by the FDA.


While it would be great if the FDA did something about this, there are probably global dimensions to this problem also. Presumably antibiotics are used globally against strains of disease that spread quite merrily from country to country.

I'd assume epidemiology is not domestically constrained: the antibiotic/agricultural practices of one nation impact all others.

I have no idea what is standard practice for domestic agriculture in my own country. Things I think I "know" about agriculture are distorted through the prism of American cultural influence - documentaries like Food Inc., are writ large in the imagination even where these are only concerned with domestic affairs.

What resources exist that document antibiotic use on a global basis?


Feeding the animals antibiotics constantly also 'increases yield' because the animals grow larger. You think that the head of any agriculture company is going to sign off on something that decreases yield? We've got quarterly profits to think of! Think of the profits that we would lose! </sarcasm>


What an unfortunate name to have in this field!

________________________

And for Pete's sake, I do note that I agree with her wholeheartedly on the substance. It's just the name that struck me out of left field ;-)


Animal research/experimentation is a misleading, conglomerate driven force that makes us all believe it is the only/best way to do biological and medical research for the benefit of humans. The reason it is conglomerate/pharmaceutical driven is because these organizations must rely on animal experimentation to get funding.

What affects an animal has for the most part no relationship to how it affects a human

Yes, there are relatively few instances where how something affects humans is the same as how it affects an animal, but leaving that up to chance as we do research is absolutely not the way to do this!

PCP, which has a violence inducing affect on humans is sometimes used as a horse tranquilizer.

Not only are humans biologically, physiologically different than animals, but each animal is biological/physiologically different from one another.

Due to the fact that animal experimentation/research for the most part (relatively speaking) has not had positive results, researchers started to rely on more extreme methods, such as injecting human DNA into animals so that the animals become more human when they do their research. This causes bacteria/virii which normally would not have been able to penetrate a human, to learn through animals being used as a human DNA surrogate, and therefore becoming stronger and knowing how to attack human cells. Hence the topic of this article and antibiotics becoming less and less effective.

edit, references:

1. Lethal Medicine (Documentary)

Part 1: http://www.youtube.com/watch?v=9iYOTH_krTk

Part 2: http://www.youtube.com/watch?v=KF3yn4-9obw

Part 3: http://www.youtube.com/watch?v=v8Rp9xxW2yc

Part 4: http://www.youtube.com/watch?v=ld8F9yhUb4M

2. http://www.livescience.com/7962-human-dna-injected-animals.h...

http://www.nbcnews.com/id/7681252/ns/health-cloning_and_stem...

-In 2004, researchers looking to study viral infections injected human blood stem cells into pigs. The unexpected result: pig cells, human cells and some that combined bits of both developed in the pigs' blood.

-In 2005, researchers created a flock of sheep with bits of human organs growing inside of them, part of an effort (alson carried out in pigs) to eventually create human organ factories.

-Some lab monkeys pack a human form of the Huntington's gene which allow scientists to investigate the development of the disease.

-There are mice with human-like livers that allow studying the effects of drugs.


Everybody should know there is way more to animal research than what you talk about here. Your first sentence makes it sound like there is no independent animal research whatsoever and that everything is driven by money, which is blatantly false. Lots of neurophysiological research for instance has nothing to do with pharmaceutics at all, and is purely done to figure out how brains work. Moreover experiments done both with macaques and humans show there are relatively lots of brain areas that do the same task, which is exactly one of the reasons it actually makes sense using macaques for such research.

"PCP, which has a violence inducing affect on humans is sometimes used as a horse tranquilizer."

First of all, PCP _can_ have a violence inducing effect, you make it sound like it always does. Second, so what? This doesn't prove that animal research is misleading. If you give a human the same dosage per weight as you'd use to tranquilize a horse, the human would be tranquilized as well. Just like with ketamine which is used as an animal tranquillizer a lot and at the same time in lower doses has all kinds of effects on humans. And the other way around works as well btw: if you give animals less than the dosage needed to tranquillize them, you see similar effects like dizziness.


I'm an anti-vivisectionist, but I'm not sure how your comment is relevant to the article.

I do wish there was a scientifically-literate anti-vivisection group.


It's tangentially related because it's animal experimentation that has/could have led (at least in part) to bacteria being able to resist antibiotics.

Watch the documentary I linked, it includes a bunch of scientifically-literate people.


Do you have a reference for the "injecting human DNA into animals" claim you make? It would be extremely disturbing, if true.


Why is it extremely disturbing?

Researchers can take human cancerous (cells) and transplant them into an animal to study. So the animal has human cancerous cells growing on it.

The human DNA doesn't change the animal, it grows on top of it.

See: http://emice.nci.nih.gov/aam/mouse/transplantation-mouse-mod...



There is such a preponderance of FUD about how livestock are cared for that it boggles the mind. People that have never once talked to a farmer or rancher have these huge opinions about how food "should" be produced based on some bullshit they saw in an article or some agitprop documentary.

In this instance the inference is that livestock are just fed mountains of antibiotics indiscriminately. Are you kidding me? Why would anyone do that? While not as expensive as meds for humans, veterinary medications are not cheap and no operator is going to waste money treating a whole herd unless it is absolutely necessary.

Furthermore, take some time to read up on the FDA website about how livestock production is regulated. It is far from the free for all that is so frequently represented.

If you are interested in a very educated and thorough perspective on how livestock are cared for at a feedyard, check out this blog by a Dartmouth educated operator in Nebraska: http://feedyardfoodie.wordpress.com/

On a semi-related note, can you name the product that was responsible for the last three E. coli outbreaks here in the States?


Actually, a lot of those "people" are, at least in my social circle, actual veterinary doctors and agriculture technicians. As for large-scale farmers, this is a debate against their economic interest, boo-hoo. And there's economic reasons for feeding livestock antibiotics, and at least in legislations I know anything about it's only illegal for "organic" farming (though it does require veterinary supervision — but it doesn't have to be for health reasons unless it's "organic").

And if you really want to speak about regulations in US, an appropriate page is one Google away: http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforc...

Notice the wording about "voluntary", and it's 2012. It was actually developed due to that "FUD" you're writing about. Note "Increase production by making the animal gain weight faster and by improving the animal’s ability to convert the food it eats (improved feed efficiency)."


You missed the part earlier in the article where it says that is not considered judicious use.

Also, you should understand what types of antibiotics are used in feed versus those that are used in treatment. The feed isn't some concoction of all antibiotics available on the market, and most food animal antibiotics aren't used in humans.


If you're going to start with a comment about FUD, could you enlighten us with the rest of the comment instead of rhetorical questions?

Cattle raised on corn (aka, most cattle raised for human consumption) require continuous use of antibiotics in their feed to prevent rumen diseases. The rumen was "designed" to digest grass and cellulose, not corn. But we feed cows corn because it's cheaper than grazing, and the cows are meaty enough for slaughter after just 18 months.

That link you provided is very feel-good-family, but can you provide some science?


Same goes for you. You're asking that we have some science to back up the claim that it isn't harmful, I haven't seen any evidence provided that it is harmful. No one has been able to show deleterious effects from the use of ionophores or tetracycline in feed, which I'm willing to take as a negative proof that their use is acceptable.


80% of antibiotics produced in the US are used in agriculture.

30 billion pounds just last year. That's half a billion cubic feet, or a pile about 800 feet high. And while the more or less official definition of "mountain" is 1,000 feet, I don't think it provides much solace that it takes 2 years instead of 1 for America's livestock to consume a literal mountain of antibiotics.


Important correction, checking fda's actual numbers it's only 30 million pounds, not billion. So that's only an 80 foot high pile per year, which is still quite a lot but not as crazy an amount.

Regardless, somewhere between 3/4 and 4/5 of antibiotics used in agriculture is used "sub-therapeutically", merely to increase the growth rate of animals and not to treat disease.


80% of the antibiotics used in the US are used in agriculture because they make up 80% of the mass. Dosage is based on weight, and it's purely a question of mass, not a choice between animals or people.

I also think your billion is wrong. According the Union of Concerned Scientists, the 30 billion was the cost of the antibiotics, not the weight. The antibiotics weighed 24 million pounds. Besides, what does the total mass have to do with prudent use? If I said we used 100 billion pounds to save people, would you consider that acceptable?

You also need to put that number in context. In 2010, American meat companies produced: 26.4 billion pounds of beef 22.5 billion pounds of pork 5.8 billion pounds of turkey 313 million pounds of veal, lamb and mutton 37.2 billion pounds of chicken

Finally, there is no clear evidence that the proper use of antibiotics in food animals has ever led to a disease resistant bacteria in humans. Don't you find it much more alarming that your GP will prescribe antibiotics to common visitors just to get them out the door? It's far more likely you're going to die purely because someone next to you won't leave the doctor until they get an antibiotic, regardless of their health status.


I realize I'm responding to an account created today, which has already posted multiple pro-antibiotic comments, so I understand that gwt561324 likely has a strong vested interest in this and is likely not a regular HN member.

But I would like to point out the final paragraph here is pure FUD rhetoric. "Don't you find it much more alarming", "It's far more likely" (with no evidence to support claim).

The problem here isn't how frequently antibiotics used in agriculture cause resistance, it's the scale of the problem once they do. Sub-prime mortgage derivatives were traded millions of times without a problem, but once the system broke things got very bad very fast. That's the best analogy I can think of for antibiotic resistance, there is a massive systemic risk, being ignored for short-term profits.


Interesting blog. In one article [1] she makes a point of only injecting 2-5% of her animals with antibiotics. In a second article [2], she talks about feeding ionophores and how they are not classified by the FDA as antibiotics. Of course they are antibiotics, they just aren't used as human drugs.

[1] http://feedyardfoodie.wordpress.com/category/antibiotics-hor...

[2] http://feedyardfoodie.wordpress.com/2011/12/13/the-misunders...

Edit: Here's an article discussing the enormous use of tetracycline in agriculture:

http://www.livablefutureblog.com/2010/12/new-fda-numbers-rev...

So the agricultural use of human useful antibiotics is at a similar or higher level than the use of ionophore feed additives.




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