Resistance to antibiotics has been a concern of scientists almost since their widespread use began. In a 1945 interview with the New York Times, Alexander Fleming himself warned that the misuse of penicillin could lead to selection of resistant forms of bacteria, and indeed, he'd already derived such strains in the lab by varying doses of penicillin the bacteria were subjected to. A short 5 years later, several hospitals had reported that a majority of their
Staph isolates were, as predicted, resistant to penicillin. This decline in effectiveness has led to a search for new sources and kinds of antimicrobial agents. One strategy involves going back to a decades-old approach researched by Soviet scientists: phage therapy. Here, they pit one microbe directly against another, using viruses called bacteriophage to infect, and kill, pathogenic bacteria.
Vincent Fischetti at Rockefeller University has used this successfully to kill anthrax,
Streptococcus pyogenes, and others. Another novel source of antibiotics has come from our own
innate immune system, one of our initial defenses against microbial invaders.
An enormous variety of organisms produce compounds called cationic antimicrobial peptides. A component of our own innate immune system, these are fairly short strings of amino acids (less than 100 a.a.'s) that have a net positive charge. It is thought that these peptides work primarily by disrupting the integrity of the bacterial cell wall, essentially poking holes in the wall, causing death of the cell. Since the peptides are targeted at the bacterial cell wall structure, it was thought that resistance would require a fundamental change in membrane structure, making it an exceedingly rare event. Therefore, these antimicrobial peptides might make an excellent weapon in the fight against multiply drug-resistant bacteria. Additionally, the remarkable diversity of these peptides, combined with the presence of multiple types of peptides with different mechanisms of action present at the infection site, rendered unlikely the evolution of resistance to these molecules (or so the common thinking went). However, evolutionary biologists have pointed out that therapeutic use of these peptides would differ from natural exposure: concentration would be significantly higher, and a larger number of microbes would be exposed. Additionally, resistance to these peptides has been detailed in a few instances. For example, resistance to antimicrobial peptides has been shown to be essential for virulence in
Staphylococcus aureus and
Salmonella species, but we didn't *witness* that resistance develop--therefore, it might simply be that those species have physiological properties that render them naturally resistant to many of these peptides, and were never susceptible in the first place.
Antimicrobial resistance is always a problem---it can render antibiotics much less useful, and make deadly infections almost untreatable. But resistance to these peptides could make us all vulnerable. The peptides of our innate immune system are one of our first lines of defense against an immense variety of pathogens, and we don't know what the outcome may be if we compromise this essential level of protection. But realistically, could such resistance evolve within the bacterial population?
Dr. Michael Zasloff of Georgetown University was originally a doubter. In
this 2002 Nature article, he states in conclusion:
Studies both in the laboratory and in the clinic confirm that emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics, and provides the impetus to develop antimicrobial peptides, both natural and laboratory conceived, into therapeutically useful agents.
Certainly in the short term, resistance was unlikely to evolve for the reasons I mentioned above. However, if these peptides are used over an extended period of time, could the mutations necessary to confer resistance accumulate? This was the question asked in a new study by Dr. Zasloff along with colleagues Gabriel Perron and Graham Bell. Following publication of his 2002 paper where he called evolution of resistance to these peptides "improbable," Bell challenged Zasloff to test this theory. Zasloff took him up on the offer, and they've published their results
in Proceedings of the Royal Society.
They tested this using strains of
E. coli and
Pseudomonas fluorescens. They started out growing these bacteria with low concentrations of a peptide antibiotic called
pexiganan, a derivative of a peptide originally isolated from a frog. (Carl Zimmer has an excellent post on this same topic
here). The experimental design was quite simple. They grew the bacteria, took a portion of the growth, and added that to a new tube with fresh media. Gradually, they increased the concentration of pexiganan in the growth medium. In all, they did 100 serial transfers of the bacteria (correlating to ~500-600 generations of bacteria), and the end result were--voilà !--bacterial populations that were resistant to the peptides.
Creationists/ID advocates (such as
chemist Phil Skell) often claim that "evolutionary theory contributes little to experimental biology," or that
"evolution has little to do with almost all research in biology and biotechnology", etc. etc. And sure, the theory of evolution didn't *directly* result in the discovery of peptide antibiotics. But advances in biotechnology do not exist in a vacuum, and we have seen what can occur from the misapplication of these types of technologies, unguided by an understanding of underlying evolutionary principles. Peptide antibiotics have not yet been used clinically to treat human infections, but imagine if they had gone into widespread use without a thought given to the evolution of resistance to these peptides. Imagine if they had gone into widespread use prior to an investigation of the relatedness of various peptides to those produced by humans. Imagine if, as a result of not considering these implications, we had lost an ancient protection against bacteria----which *evolved* over millions of years of host-pathogen interaction--due to a mere advancement in biotechnology. While I enjoy proving the evolution-doubters wrong, I hope it never comes down to that kind of situation in order to do so, and I hope this example is instructive to those who claim that evolution isn't useful.
96 Comments
k.e. · 15 November 2005
Strangely this example of evolution and the applied use of it is the one thing that will resonate louder in the minds of parents than any other belief, survival is natures greatest motor.
Presented with the choice between a man in a white coat with a cure and a pulpit thumper the ranks of the blind sheep would thin very quickly.
Somehow this message needs to be distilled and injected.
Tara Smith · 15 November 2005
jim · 15 November 2005
Hey,
Would retiring an anti-biotic for a period of time (say 10-30 years), give enough time for bacteria to lose their immunity to the drug? I would think that the mechanisms (I've heard they're selective pumps) to grant anti-biotic immunity would be an evolutionary disadvantage if none of that drug were present.
By giving evolution some time to select against the resistent strains we might be able to begin a program of cycling through antibiotics in a given order using a defined period of use to ensure that we never run out of them.
Rich · 15 November 2005
Blog problems.
Normally its the technicalterms or challenging concepts that make it hard for me to fully understand an article. But Tara has a hot picture on the top right of her blog that lowers my IQ to room temperature. Thanks Tara.
*twiddles pen, awkwardly*
Christopher Letzelter · 15 November 2005
Tara wrote, "Not to drag my own thread off-topic, but you might be surprised. Many people have been told so often that scientists are such evil "atheistic" materialists that they inherently distrust them, and value the word of their pastors over experts in the field. This has already happened with vaccination---while some parents are worried about thimerosal, others have objections on religious grounds, as fetal tissue has been used in the production of some vaccines."
And this is happening in Amish communities in the Midwest, where children have contracted polio:
http://www.nytimes.com/2005/11/08/national/08polio.html
Oddly enough, polio is never reported in societies where vaccinations are mandated; but in the Amish communities, where modern medicine is suspect and innoculation is rejected, these "dead" diseases reappear.
Maybe the Amish are feeling god's wrath? : )
Miguelito · 15 November 2005
I'm a geologist and not a biologist, so my grasp on biology literature is very poor.
Would anybody be able to recommend some references that show:
1) somebody mapping the genome of some bacteria
2) letting populations of that bacteria grow for many generations
3) remapping the genome of that bacteria to see where mutations in the DNA occurred
4) even better, said mutations enhance the survivability of the bacteria in certain environments
I am familiar with Richard Lenk's E. Coli experiments, but would like some more documentation to peruse if there is any.
Tara Smith · 15 November 2005
theonomo · 15 November 2005
The fact that bacteria evolve resistance to antibiotics just shows how marvelously well-designed they are. In fact, designing a system that is capable of evolving requires more intelligence and sophistication than designing a static system. It cracks me up how you fundies think it is such a big deal that bacteria evolve. ("Evolve" is a strong word for it -- they do, after all, remain not only bacteria, but practically the same kind of bacteria.)
Fundamentalist Darwinian: "What?! You don't believe that the bat and the whale are close cousins and that this grizzly bear's many-greats-grandpappy was a fish? Well, I'll prove it to you: bacteria have been known to evolve resistance to antibiotics. So there."
Give me a break.
Tara Smith · 15 November 2005
I see you missed the entire point of my post, but thank you for your comments.
Ben · 15 November 2005
Tara Smith · 15 November 2005
theonomo · 15 November 2005
Thanks, but I'll take medicines that are well grounded in science.
CJ O'Brien · 15 November 2005
Wislu Plethora · 15 November 2005
Arden Chatfield · 15 November 2005
theonomo · 15 November 2005
Arden Chatfield · 15 November 2005
theonomo · 15 November 2005
Sir_Toejam · 15 November 2005
Katarina · 15 November 2005
Theonomo,
The reason scientists so often cite bacteria is that bacteria go through so many generations in so short a time, that evolution can be easily observed with them. However, this isn't the only observation of evolution and speciation, the observation has been made for higher organisms as well. Have you browsed through the TalkOrigins website?
The communication problem seems to stem from a conceptual problem. People who reject evolution cannot imagine why microevolution would lead to macroevolution, and macroevolution is the only way they define evolution. The only remedy to that is to do some work and read about what the theory of evolution says. If it still doesn't make sense, ask more questions and read more.
People at PT will usually make fun of you, unless you are asking a sincere question. Be specific in your question. Just by coming up with a specific question, you're halfway to understanding.
CJ O'Brien · 15 November 2005
Ask "how many," get told "many."
Realize you're probably talking to a creationist.
Maybe you should heighten your awareness of these matters.
Should I start with Genesis? Because I'm pretty sure there's no mention of bacteria.
Or do you have a more authoritative source on bacterial "kinds" in mind?
Miguelito · 15 November 2005
theonomo · 15 November 2005
Sir_Toejam · 15 November 2005
lol. right... so now explain how it works in the terms you use it in.
like several have already asked you.
why be a troll?
did you ignore what Katarina posted?
theonomo · 15 November 2005
Rich · 15 November 2005
"I see you missed the entire point of my post, but thank you for your comments."
You've been playing with creationists too long. Absence of evidence of understanding does not imply missunderstanding. I got the point, but you get drawn to the topright hand corner of your blog.
*shrug*
Tara Smith · 15 November 2005
Heh. Rich, that wasn't directed at you. And I'm sure if it's ever so distracting, a post-it note would cover up the pic just fine. :)
theonomo, I'd be very happy to address any concerns/questions you have about evolution, and I'm sure others would do the same. I much prefer to have real discussion rather than sniping.
theonomo · 15 November 2005
I am well aware that as soon as anyone on this board expresses an opinion that does not fall in line with the Official Story that is handed down by the Darwinian Priesthood they will be ridiculed. No big deal. I just like to express my thoughts on these matters once in a while.
By the way, the debating techniques used on here are typical of Darwinian fundamentalists: mention that you don't think that the fact that bacteria evolve resistance to antibiotics is good evidence for macro-evolution and next thing you know you are being asked to deliniate all the different kinds of bacteria that have ever existed. It's the "quick -- swamp him with requests for irrelevant details that will take him hours to figure out" defense.
Tara Smith · 15 November 2005
But you haven't expressed any "thoughts;" you've called names and started with the ridicule yourself. How about we start over and you post your valid criticisms, and we'll forget all the "kinds" stuff.
Rilke's Granddaughter · 15 November 2005
Rich · 15 November 2005
"typical of Darwinian fundamentalists"
Do shallow minds make broad-brush comments? More after the weather..
Surely the delimitation of "macro" and "micro" evolution is arbitrary, and VERY timescale dependent?
theonomo · 15 November 2005
roger tang · 15 November 2005
I am well aware that as soon as anyone on this board expresses an opinion that does not fall in line with the Official Story that is handed down by the Darwinian Priesthood they will be ridiculed.
No, that's wrong. You're just self fulfilling your prophecy, offering up deliberately inane comments specifically designed to attract attacks, in order to pile up persecution points.
That's...practically...all your repertoire.
You MIGHT get a difference response if you tried to grapple with the issues honestly (it's occurred on other occasions). And, to be honest, you're going to have to learn the lingo and defend your thesis as scientists do--otherwise, you're just conceding the battle and saying that you CAN'T play with the big boys.
Or do you feel you're not up to the task?
theonomo · 15 November 2005
Well, I am sure that most of you will be pleased to learn that I have to leave now due to the fact that I have 12,000 words of a novel to write before Thursday and need to stop procrastinating. You may interpret it as me running away from a fight if you wish -- there is nothing I can do to stop you.
Tara Smith · 15 November 2005
Sir_Toejam · 15 November 2005
that's right, run away ;)
roger tang · 15 November 2005
I did express my thought.
Yes, and you did it on a very gross level, without much of the detail that's necessary on a scientific level. "Practically the same kind", for example, is a qualitative statement; it doesn't get you anywhere when you try to do research. It ignores all the detail work where science is done.
And, of course, your smartass comment about defining practically is not helpful.
Are you willing to get down into the nitty gritty detail and deal with science on the same level? or are you going to concede the battle?
Ron Zeno · 15 November 2005
Sir_Toejam · 15 November 2005
Tara:
there is no meat, and he asked no questions.
he came, he saw, he preached, he left.
eos
Rilke's Granddaughter · 15 November 2005
Rich · 15 November 2005
In all seriousness, good luck with the Novel. The discussion will be waiting for you when you return.
Jim Harrison · 15 November 2005
People sometimes talk about antibiotic resistance as if it had an essence. But the term refers to a very heterogenous collection of mechanisms. The point isn't just nitpicking. It is often assumed that resistance to antibiotics would automatically diminish if we stopped using the antibiotics because antibiotic resistance has a cost to the bacterium. But the costs of resistance vary from considerable to nothing depending on the mechanism.
Consider the case of human resistance to malaria. The sickle cell allelle confers resistance to malaria but is fatal when it is homozygous. If malaria disappeared, natural selection would eliminate the sickle cell gene. But there are probably other mutations that increase resistance to the parasite by altering coat proteins. They may not have any metabolic cost at all and would presumably tend to persist even in areas without malaria. By this logic, some of the mutations that increase the resistance of bacteria to antibiotics may persist even in the absence of further use of the drugs.
RBH · 15 November 2005
Arden Chatfield · 15 November 2005
Ed Darrell · 15 November 2005
Theonomo,
Why not try expressing an opinion contrary to the general flow in a fashion that demonstrates genuine curiosity about life, rather than in an insulting, faux-superiority voice that drips with wish-to-denigrate-if-I-only-knew-what-I-was-talking-about ferocity?
You might get corrected if you get off base, but you won't get ridiculed until you put on that "kick me, please" tone of voice and content.
Rich · 15 November 2005
FAO Rilke's Granddaughter.
I can prove it, but I'd like to believe we live in a world where anything can be designed. To say otherwise would cap human potential. Its just a matter of time and smarts. Point (b) for me is the salient one.
roger tang · 15 November 2005
People sometimes talk about antibiotic resistance as if it had an essence. But the term refers to a very heterogenous collection of mechanisms. The point isn't just nitpicking. It is often assumed that resistance to antibiotics would automatically diminish if we stopped using the antibiotics because antibiotic resistance has a cost to the bacterium. But the costs of resistance vary from considerable to nothing depending on the mechanism.
Now, here's an example of dealing with the details, and examining the mechanisms. It's talks about the fine, not the gross; it makes predictions based ib the fine details of the mechanism.
Is theonomo going to answer in kind? Or will that worthy concede the battle?
RBH · 15 November 2005
Sorry -- I see Miquelito seems to be aware of Lenski's work. (Read the whole post, RBH!)
RBH
Miguelito · 15 November 2005
Arden Chatfield · 15 November 2005
CJ O'Brien · 15 November 2005
qetzal · 15 November 2005
Re jim's questions on retiring antibiotics (#57641):
Another problem is that bacteria can be quite proficient at acquiring genes from other microbes. Say there's an antibiotic that rarely works any more (e.g. penicillin G), because most target bacteria have acquired a resistance gene (e.g. beta-lactamase). If we retired penicillin G for long enough, we might well find that bacteria lacking beta-lactamase became predominant again.
However, there would still be a reservoir of resistance genes around somewhere. Once we began using penicillin G again, these would be readily re-acquired and resistance would be re-established almost immediately.
I recall a fascinating study that I learned about in grad school. A famous bacteriologist (whose name escapes me) had a large collection of enteric bacteria stored in agar stabs. These were collected at various times going back to the early 1900s (IIRC). That meant that many of them were collected before antibiotics were widely used to treat human disease.
He recovered bacteria from a bunch of these stored samples and tested them for antibiotic resistance. He found that samples collected before widespread antibiotic use were almost never resistant. Resistance began to appear quite soon after clinical antibiotic use began. Pretty soon, most samples were resistant to one or more common antibiotics.
In most cases, resistance was due to the presence of specific resistance genes. Interestingly, these genes showed features consistent with acquisition from another microbe. They were usually found on mobile plasmids (small pieces of DNA, kind of like mini-chromosomes, that can often be passed between different "kinds" of bacteria). They were often flanked by sequences characterisitic of certain DNA elements that can actually hop in and out of chromosomes (transposons, insertion sequences, etc.).
Further investigation showed that the sensitive bacteria collected before antibiotic use often contained essentially the same mobile plasmids, but without the "hopping" (transposable) resistance genes.
The conclusion was that these resistance genes already existed somewhere in nature. That makes sense, since most of the early antibiotics were derived from compounds that fungi made to inhibit bacterial growth. The resistance genes likely evolved as a response.
Enteric bacteria were able to pass the mobile plasmids back and forth with lots of other bacteria. Occasionally, these mobile plasmids would pick up extra genes from one host and carry them to another. Those extra genes would sometimes include antibiotic resistance genes.
Before clinical antibiotic use, enteric bacteria presumably gained no advantage from resistance genes, and probably incurred a modest energetic cost. Thus, the genes weren't maintained.
Once we began using penicillin et al., enterics that happened to have acquired beta-lactamase from some other bacterium were much more likely to survive. They could grow while sensitive bacteria were killed. Moreover, they could share their resistance genes with other bacteria via the plasmids. Those factors combined to allow an amazingly rapid spread of antibiotic resistance in the bacterial population.
This is all from memory, so some details may be in error, but I hope I've gotten the gist of it correct. This is the kind of thing that I find fascinating and awesome (in the literal sense) about science. I imagine it's akin to the awe creationists feel in the face of what seems to them to be evidence of God's ineffable design.
ag · 15 November 2005
Guys, hasn't theonomo indicated that his main interest is in his novel? All those comments of his must be just parts of his novel - they display unmistakable features of fiction. Alas, they portend a novel which will be boring.
AR · 15 November 2005
If, as theonomo believes, bacteria are marvelously designed in a way enabling them to successfully resist antibiotics, what does this say about the designer's attitude to humans who suffer from bacteria? He (she, it, they?) must have hated humans but have an inordinate fondness for bacteria. Or perhaps there were many designers, some designing humans, others designing bacteria, etc. who (which?) were fighting each other? Indeed a good stuff for theonomo's novel.
KiwiInOz · 15 November 2005
OT
I'm with Rich with regards to the photo, Tara. Don't ever take it down.
Sir_Toejam · 15 November 2005
Steve S · 15 November 2005
Sir_Toejam · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
snaxalotl · 15 November 2005
you guys don't know how to quit while you're ahead. when you have a creationista enthusing about how god created evolution as a mechanism to accomplish his ends, you need to step back and consider just how much the fundies' views have been forced to adjust to scientific fact over the last few years.
Paul Flocken · 15 November 2005
theonomo--The fact that bacteria evolve resistance to antibiotics just shows how marvelously well-designed they are. In fact, designing a system that is capable of evolving requires more intelligence and sophistication than designing a static system.
Evolution is a consequence of two things: 1) Replication is always imperfect, in some way, when life reproduces, ensuring that progeny are different from parents and siblings (sexual reproduction guarantees this); 2) There are only limited resources available in a constantly changing environment, therefore life must compete for reproductive privilege.
How is it necessary that either one of these be intelligently designed? They exist quite naturally(nothing is perfect and the earth does not have infinite resources) I should think that a static system would actually be harder to design since it would require perfect replication to maintain its static nature and an unchanging earth to support it. And we all know that change is the only constant in the universe. Please explain why evolution would have to be intelligently designed.
Sincerely, Paul
Hrun · 15 November 2005
Just a tiny bit of nitpicking: Vince Fischetti works at the Rockefeller University not the Rockefeller Institute. Rockefeller University was originally founded in 1901 as the Rockefeller Institute, but it was granted the right to confer degrees in 1955 and thus became a University. ;)
Tiax · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
Sir_Toejam · 15 November 2005
I'm collecting ideas for t-shirts.
so far i have:
Recovering Fundamentalist
Doctor of the Dark Side
any other suggestions?
Sir_Toejam · 15 November 2005
oh, and of course Mummert's famous quote.
Tiax · 15 November 2005
Sir_Toejam · 15 November 2005
'Rev Dr' Lenny Flank · 15 November 2005
Ben · 16 November 2005
Wayne Francis · 16 November 2005
jim · 16 November 2005
T-Shirt slogans:
Evolution Happens
jim · 16 November 2005
T-Shirt slogans:
Procreation
Arden Chatfield · 16 November 2005
CJ O'Brien · 16 November 2005
Sir_Toejam · 16 November 2005
Dembski's whole street theatre fiasco reminds me of that Saturday Night Live skit that John Lovitz used to do where they would do something absolutely ridiculous, then excuse it all by sayting "ACTING!".
I can just imagine Dembski playing the part of Lovitz in a skit of his entire life.
Sir_Toejam · 16 November 2005
t-shirt slogans so far:
Recovering Fundamentalist
Doctor of the Dark Side
Evolution Happens
Life evolves. Get used to it.
"We've been attacked by the intelligent, educated segment of the culture." - Ray Mummert
steve s · 16 November 2005
qetzal · 16 November 2005
CJ O'Brien · 16 November 2005
Tiax · 16 November 2005
Steve S · 16 November 2005
KiwiInOz · 16 November 2005
OK, enough of being shallow (#57839). Tara, your writing brings microbiology to life in a way that my undergrad lecturers never did.
Cheers
Brian Spitzer · 16 November 2005
Renier · 17 November 2005
jim · 17 November 2005
Don't know if this would fit on a T-Shirt and isn't a "pro-evolution" saying, but it IS funny :) :
Thou shalt not covet thy neighbor's wife,
his lamb thou shalt not slaughter,
thank Heavens there is no Commandment,
about coveting thy neighbor's daughter!
Tara Smith · 17 November 2005
Wislu Plethora · 17 November 2005
Renier · 18 November 2005
Well, it's a good thing that they seem clear on the scientific method, therefore clearly state that lots of testing still needs to be done. Just think, if ID people did this it would be "Something designed the peptides to be used by humans, and since the designer is intelligent we can ASSUME it is safe. Bring the needle!" :-)
Question. What are the odds that we will start finding bacteria strains that learns (evolves) to resist the peptides?
Tim Hague · 18 November 2005
Tara Smith · 18 November 2005