The future of antibiotics

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The future of antibiotics

Postby Lazar » Thu Aug 12, 2010 2:54 pm UTC

I'm not greatly knowledgeable in any relevant field, but this question has been bugging me for some time: will antibiotics eventually become obsolete and/or turn everything into superbugs? Will we have to turn to bacteriophages or nanites? What will be the long-term future of infection-fighting?
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Re: The future of antibiotics

Postby big boss » Thu Aug 12, 2010 5:38 pm UTC

Eventually bacteria and viruses will develop resistance to drugs that are currently in use now due to spontaneous mutations and transformation. But evolution works both ways. Since we get many of our drugs from plants and fungi (such as penicillin) these plants will need to evolve new ways to defend against these new pathogens. Then when they do we can use them to make new drugs. Only problem with this is that bacteria and viruses usually mutation and evolve at a much faster rate than plants and animals because it is "easier" for them and they propagate much faster, now whether plants can keep up I don't know.

Aside from drugs another possibility to fight infections can come from genomics and targeting the proteins in our bodies that bacteria and viruses use to identify potential cells to invade or that the bacteria and viruses use in their replication process. Or some kind of nanotechnology that is like antibodies or something similar to that might be invented in the future.
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Re: The future of antibiotics

Postby Coffee » Thu Aug 12, 2010 7:50 pm UTC

Bonnie Bassler had some interesting things to say about that.

http://www.ted.com/talks/bonnie_bassler ... icate.html
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Re: The future of antibiotics

Postby bigglesworth » Thu Aug 12, 2010 10:42 pm UTC

Lazar wrote:I'm not greatly knowledgeable in any relevant field, but this question has been bugging me for some time: will antibiotics eventually become obsolete and/or turn everything into superbugs? Will we have to turn to bacteriophages or nanites? What will be the long-term future of infection-fighting?
Individual antibiotics will become obsolete. But more will be created. We are moving from an age of discovered antibiotics (and minor alterations to those) to an age of rational drug design. We will look at bacterial proteins not found in humans, and develop accurate drugs that attack that specific protein. Bacteriophages are not a good way of killing bacteria (otherwise the bacteriophages would die out). Nanites are science fiction, emphasis on the 'fiction' part.
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Re: The future of antibiotics

Postby TaintedDeity » Thu Aug 12, 2010 10:44 pm UTC

Funny you mention that: This was recently on New Scientist
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Re: The future of antibiotics

Postby Josephine » Fri Aug 13, 2010 6:35 am UTC

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Re: The future of antibiotics

Postby big boss » Fri Aug 13, 2010 5:30 pm UTC

bigglesworth wrote:
Lazar wrote:I'm not greatly knowledgeable in any relevant field, but this question has been bugging me for some time: will antibiotics eventually become obsolete and/or turn everything into superbugs? Will we have to turn to bacteriophages or nanites? What will be the long-term future of infection-fighting?
Individual antibiotics will become obsolete. But more will be created. We are moving from an age of discovered antibiotics (and minor alterations to those) to an age of rational drug design. We will look at bacterial proteins not found in humans, and develop accurate drugs that attack that specific protein. Bacteriophages are not a good way of killing bacteria (otherwise the bacteriophages would die out). Nanites are science fiction, emphasis on the 'fiction' part.


What gives you the authority to say that Nanites are science fiction? History has shown us time and time again that humanity's current beliefs about what is possible and what is not is always lower than what can really be achieved and that time and time again humanity has been able to exceed its own expectations and redefine what is science and science fiction.
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Re: The future of antibiotics

Postby Izawwlgood » Fri Aug 13, 2010 5:48 pm UTC

Carl Zimmer wrote about the increase of antibiotic resistance in various parasites as being sort of a sliding scale, where if you scale in a bunch of immunities, you sacrifice, say, longevity, or virilunce. I'm not sure if this applies broadly to what you meant, but a number of our antibiotics are simply functional groups that contain a nearly infinite combination of variable subgroups.

My guess is there'll be a time when we can't use, say, penicillin to fight off certain diseases, but the term antibiotic, when applied to any agent that murderfies some organism, isn't going anywhere to describe how we protect ourselves.
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Re: The future of antibiotics

Postby bigglesworth » Fri Aug 13, 2010 7:19 pm UTC

big boss wrote:What gives you the authority to say that Nanites are science fiction? History has shown us time and time again that humanity's current beliefs about what is possible and what is not is always lower than what can really be achieved and that time and time again humanity has been able to exceed its own expectations and redefine what is science and science fiction.
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Time and time again, trends have gone away from what is predicted, what sounds good. The radio telescope is a much better way at looking for extraterrestrial life than going out in spaceships. And in the same way, I don't see nanites producing much useful stuff in the foreseeable future.
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Re: The future of antibiotics

Postby big boss » Fri Aug 13, 2010 7:44 pm UTC

bigglesworth wrote:
big boss wrote:What gives you the authority to say that Nanites are science fiction? History has shown us time and time again that humanity's current beliefs about what is possible and what is not is always lower than what can really be achieved and that time and time again humanity has been able to exceed its own expectations and redefine what is science and science fiction.
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Time and time again, trends have gone away from what is predicted, what sounds good. The radio telescope is a much better way at looking for extraterrestrial life than going out in spaceships. And in the same way, I don't see nanites producing much useful stuff in the foreseeable future.


You didn't answer the other part of my question: What gives you the authority to claim its fiction, and I'm not claiming to have the authority or expertise to make such a claim either, just that its not impossible. Companies and individuals are designing flying cars/ miniplanes that are road legal. Japan has plans plans to build a lunar robot base, one step closer to a human occupied one. These types of things just don't happen overnight they take much time and many experiments to perfect. Yes many things that humans have dreamed of have been impossible, but many have also become reality, and man's ability to predict which ones are possible and which ideas are impossible is as reliable as flipping a coin.

edit: I agree with you that nanites don't have much viability in the next 20 or 50 years, but in 100 or 200 hundreds who knows where we will be, new technologies tend to increase at an exponential rate.

Even experts in science have predicted the future wrong and advocated beliefs that are know known to be wrong. Einstein didn't believe in the correctness of quantum mechanics, many geologists until fairly recently didn't in history didn't believe in the theory of plate tectonics. Now can we stopped playing this game because for every example you come up with of well this didn't happen I could come up with another example of well this did happen.
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Re: The future of antibiotics

Postby bigglesworth » Fri Aug 13, 2010 9:37 pm UTC

Note that I said "foreseeable future". I thought the most useful answer for Lazar would be the one that applied during that period of time.

Eventually, we might be holographic beings in computronium, and thus not need antibiotics, but that wouldn't be a very useful answer to the question either.
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Re: The future of antibiotics

Postby big boss » Sat Aug 14, 2010 12:15 am UTC

bigglesworth wrote:Note that I said "foreseeable future". I thought the most useful answer for Lazar would be the one that applied during that period of time.

Eventually, we might be holographic beings in computronium, and thus not need antibiotics, but that wouldn't be a very useful answer to the question either.


Guess so, but nanotechnology seems like a good possibility in the next 100 years or so, so while it may not be revelant to us, it might be relevant to the next generation.
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Re: The future of antibiotics

Postby bigglesworth » Sat Aug 14, 2010 8:52 am UTC

Well, in many ways organic chemistry already is nanotechnology. You're using chemical processes to manipulate molecules on an atomic level, adding a methyl group here, taking away an amino there... And that's what rational drug design is.
It's just nanites that make me go :|
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Re: The future of antibiotics

Postby Soralin » Sat Aug 14, 2010 1:55 pm UTC

It depends also what you call nanotechnology and nanites, like you say. Conventional looking universal machines might be out on infeasibility, but there is stuff like this, and further complexity that you could expand on based on them.:

http://www.sciencedaily.com/releases/20 ... 094621.htm
Scientists from UCLA's California NanoSystems Institute and Korea's Yonsei University have developed an innovative method that enables nanomachines to release drugs inside living cancer cells when activated remotely by an oscillating magnetic field.

and http://www.newscientist.com/article/dn1 ... actoe.html
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I saw another article on that somewhere, talking about using that effect to make smart drugs, that could say go into a bunch of cells, but only release a substance in the cells where there are conditions (A and B and not C), or some other simple set of logic. So ideally, you could have something like a chemotherapy substance that only releases it's payload inside cancerous cells.

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Re: The future of antibiotics

Postby Josephine » Sat Aug 14, 2010 5:30 pm UTC

by the way, the word 'nanite' is usually reserved for science fiction. nanotechnology or nanorobot(ic)s are better terms.
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Re: The future of antibiotics

Postby Telchar » Sat Aug 14, 2010 6:31 pm UTC

Neuroimmunology has already received a lot of research in the last 10 years and shows no signs of slowing soon. Making your body more efficient at fighting infections without intervention, or using the intervention not on the bacteria itself, would seem the best course of action in order to avoid "superbugs".

There's also something to be said about how medicine will deal with autoimmune diseases. Possibly exacerbated by previous advancements in antibiotics, the 1st world is now plagued by a growing number of auoimmune disorders.
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Re: The future of antibiotics

Postby Eebster the Great » Sun Aug 15, 2010 5:18 am UTC

bigglesworth wrote:We are moving from an age of discovered antibiotics (and minor alterations to those) to an age of rational drug design. We will look at bacterial proteins not found in humans, and develop accurate drugs that attack that specific protein.

This is an interesting point. I think we are on the cusp of that transition. Currently, nearly all big pharmaceutical companies find new drugs by trial and error, but that is just starting to change. Unfortunately, computer models are still of limited utility, but they are of course improving.

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Re: The future of antibiotics

Postby bigglesworth » Sun Aug 15, 2010 9:31 am UTC

Uh, that's about... five years out of date? Not very many of the drugs in the very earliest stages of development are the result of random finds, to the best of my knowledge. Now, plenty of the drugs released onto the market for the next five years will be, but that's because of the long time it takes to get a drug onto the market.

And yes, computer modelling on its own is of very limited utility, but it is perfectly adequate when combined with X-ray crystallography, or more recently NMR, plus gene-sequencing of the protein target.
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Re: The future of antibiotics

Postby Bruenor » Sun Aug 15, 2010 11:09 am UTC

Antibiotic resistance is a compromise. When you treat a large enough population of bacteria with antibiotics, a minority of that population will survive, as they have a random mutation allowing them to deactivate the antibiotic/actively pump it out/deny its entrance/affect its binding by changing the receptor/etc. However, this change makes the bacteria less "fit" than the wild type. It only survives because the antibiotic kills all the competition. If we were to stop using the antibiotic in question for a long enough period, the wild type would out-compete the resistant type, and that antibiotic would become effective again. Antibiotic rotation is required throughout the world.

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Re: The future of antibiotics

Postby seanchen » Sun Aug 15, 2010 1:47 pm UTC

Instead of using antibiotics, i prefer to put more efforts on developing the vaccine. Antibiotic can only work for a short time. For long term effect, vaccine is more useful.

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Re: The future of antibiotics

Postby gmalivuk » Sun Aug 15, 2010 2:51 pm UTC

Vaccines are for viruses, while antibiotics are for bacterial infections. You cannot possibly replace one with the other.
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Re: The future of antibiotics

Postby Charlie! » Sun Aug 15, 2010 8:02 pm UTC

gmalivuk wrote:Vaccines are for viruses, while antibiotics are for bacterial infections. You cannot possibly replace one with the other.

Well... you can't replace one with the other, but you can have vaccines for bacteria. They just sensitize the immune system to a bacterium instead of a virus.
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Re: The future of antibiotics

Postby Eebster the Great » Mon Aug 16, 2010 4:57 am UTC

bigglesworth wrote:Uh, that's about... five years out of date? Not very many of the drugs in the very earliest stages of development are the result of random finds, to the best of my knowledge. Now, plenty of the drugs released onto the market for the next five years will be, but that's because of the long time it takes to get a drug onto the market.


That's not the case for proteins and other large organic drugs, only for some smaller drugs. For protein analogs, the shotgun approach is still common, with often hundreds of substitutions being tested for stability and dozens for activity. Of course, substitutions are not chosen randomly, there is some justification behind the choices, but this is far away from the theoretical rationalization you describe.

Obviously this is not always the case, and it is becoming less the case just in the last couple years.

And yes, computer modelling on its own is of very limited utility, but it is perfectly adequate when combined with X-ray crystallography, or more recently NMR, plus gene-sequencing of the protein target.

The relevant question is whether computer models are accurate enough to find new treatments faster than trial-and-error NMR. It takes a long time to set up molecular dynamics runs (and in the absence of a supercomputer, a very long time to run them) and the chance for error is high. NMR and crystallography can be done with only marginally greater expense (if the facilities are already in place, which they are) and with a more reliable result.

I can tell you from personal experience that molecular dynamics suites like GROMACS and CHARMM have serious limitations and are also not easy to use. Obtaining accurate results often depends on carefully choosing a wide variety of parameters which may not be obvious until the correct value is already known. I am currently having difficulty even matching known data, so finding new data that can be trusted is certainly a significant challenge.

What computer models are good at is rationalizing previously discovered results. If you know that a given protein analog is superstable but are not sure why, a computer model of that analog can provide insight into the source of that stability and in doing so suggest further improvements.

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Re: The future of antibiotics

Postby ImagingGeek » Mon Aug 16, 2010 10:39 pm UTC

gmalivuk wrote:Vaccines are for viruses, while antibiotics are for bacterial infections. You cannot possibly replace one with the other.


Sorry, but that is plain wrong. Vaccines simply expose the immune system to a pathogen's antigens in a safe manner. That includes viral, bacterial, protozoans, helminths and other types of pathogens. Examples of existing vaccines against bacteria include:
  • Haemophilus Influenzae (HiB vaccine)
  • Pertussis
  • Diptheria
  • Tetanus
  • Tuberculosis
  • Meningococcus (bacterial meningitis vaccine)
  • Pneumococcus (bacterial pneumona vaccine)
  • Typhoid (Salmonella typhi bacterium)
  • Typhus (Rickettsiae typhi bacterium)
  • Anthrax
  • Cholera
  • Plague (Yersinia pestis bacterium)

As for the OP, it is generally thought that antibiotics have a limited future. The discovery of new antibiotics - either natural ones or synthetic - has slowed over the past few decades. The major issue we face is that most "new" antibiotics are variants of old ones, and thus existing antibody resistance genes are either already active against the new agent, or can quickly evolve to break down new agents. There is some hope in the small molecule field, which conceivably could identify novel compounds. Unfortunate, antibiotics are not high-profit drugs, so pharma does not put a lot of $$$ into their development (limp willies, on the other hand, is a multi-billion dollar area of research - how f*cked up is that?).

Of course, we could just use antibiotics in a proper manner, instead of doing what we do today - prescribing them willy-nilly, putting them in animal feed, etc. Resistance can be managed, with no/minimal need for new drugs, if we have the will.

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Re: The future of antibiotics

Postby bigglesworth » Tue Aug 17, 2010 2:09 pm UTC

Eebster the Great wrote:That's not the case for proteins and other large organic drugs, only for some smaller drugs. For protein analogs, the shotgun approach is still common, with often hundreds of substitutions being tested for stability and dozens for activity. Of course, substitutions are not chosen randomly, there is some justification behind the choices, but this is far away from the theoretical rationalization you describe.

Obviously this is not always the case, and it is becoming less the case just in the last couple years.
Ah, yes, didn't think about protein analogues; good point.
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Re: The future of antibiotics

Postby wiserd911 » Mon Aug 23, 2010 7:35 am UTC

I agree that phage will be used more prominently in the future. The claim by Bigglesworth that phage would die out if they were effective is inaccurate. Therapeutic phage are selected to be lytic only (without a lysogenic phage.) The lysozymes that phage use may also be useful by themselves since they can be 'evolved' fairly easily to outpace bacterial resistance. Cocktails of phage will probably be used in combination with antibiotics, and other chemicals will be used to augment the antibiotics (such as augmentin, which can destroy beta lactamase, thus undoing one effective method of resistance to penicillan)

Phage have so far only been used externally and in the GI tract. Intralytics was working on long-cycling injectible (patentable) phages but I don't know if they ever brought anything to market.

Some more expensive methods of antibiotic resistance (chemical pumps) will still cost bacteria energy and slow their production.

Prevention of the spread of plasmids containing antibiotic resistance is another route.
http://www.ncbi.nlm.nih.gov/pubmed/17630285

Targeting of animal populations which are disease reservoirs is another tactic. (improved methods of killing disease)
Improved sanitation (such as testing of blood banks) has been helpful, though I don't know if this method has been maxed out yet.

While vaccinations work against the worst diseases, the occasional side effects make vaccination for non-lethal non-common diseases prohibitive.
But as testing improves, it's possible to attach a protein to antigens for the flu to make it attack the new target. (this requires rapid identification of diseases, and doesn't allow for broad spectrum cures.)

And perhaps we'll have more antivirals like tamiflu which block particular ports or resveratrol which re-activate DNA repair enzymes (p53 in this case), thus acting as broad spectrum anti-virals.

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Re: The future of antibiotics

Postby Eternal Questionner » Mon Aug 23, 2010 11:59 am UTC

ImagingGeek wrote:
gmalivuk wrote:Vaccines are for viruses, while antibiotics are for bacterial infections. You cannot possibly replace one with the other.


Sorry, but that is plain wrong. Vaccines simply expose the immune system to a pathogen's antigens in a safe manner. That includes viral, bacterial, protozoans, helminths and other types of pathogens.


Not only that, drugs are beginning to be developed (although not on the market yet AFAIK) which act as broad-spectrum antivirals, to kill a large number of different viruses, just like antibiotics kill a large variety of different bacteria.

http://www.sciencedaily.com/releases/20 ... 113801.htm

Not to mention all the narrow-spectrum anti-virals that are used to treat things such as HIV. Sure, they're not technically antibiotics, but roughly the same principle applies.

http://en.wikipedia.org/wiki/Antivirals

Although it should be noted that antivirals tend to inhibit growth, while most antibiotics tend to kill the bacteria directly.

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Re: The future of antibiotics

Postby ImagingGeek » Mon Aug 23, 2010 6:38 pm UTC

wiserd911 wrote:I agree that phage will be used more prominently in the future. The claim by Bigglesworth that phage would die out if they were effective is inaccurate. Therapeutic phage are selected to be lytic only (without a lysogenic phage.)


I'm not entirely sure this is the case. Many years ago I worked in a department where there was a researcher trying to develop phage-based therapies. AFAIK, they never made it past animal testing, and were never successful in actually treating an infection, for three reasons:

1) Many bacteria already have resistance to phage, which limits the use of phage. There is also the obvious issue of these genes being transfered to susceptible bacteria, just as antibiotic resistance genes are.

2) Phage are recognized by our immune systems as being foreign. So even though they cannot infect us, they are eventually destroyed by our immune system. This means that a single phage is essentially a one-use tool - a week or so after it is administered you'll have some neutralizing antibodies against it. Within 2 weeks you'll have enough Ab's to opsonize (bind it up with antibody) and eliminate it before it has a chance to act.

3) The phage must gain access to the infected site. Since they lack mechanisms to leave the blood stream, you're limited to treated infections in injectable/aersolisable sites.

From an immunology standpoint (I'm an immunologist, BTW), lytic phage could be hugely dangerous as a therapeutic. Our bodies are remarkably sensitive to bacterial products, and small quantities in our blood can induce a lethal response termed "sepsis". Many of the antibiotics we currently use avoid this issue by not directly lysing the bacteria, but rather preventing their growth. This allows our immune cells to clear the bacteria in a way which prevents the mass release of bacterial products into the circulation. Lytic phage could potentially turn a modestly dangerous infection into a highly dangerous septicemia.

That said, there have been some minor successes in animal models, for example:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC104512/

At the end of the day, all new therapies, regardless of their mechanism of action, will face the same problems - our immune systems response against forign substances, and the incredible ability of bacteria to evolve.

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Re: The future of antibiotics

Postby Razi-Al-Amin » Tue Aug 31, 2010 3:43 am UTC

Antibiotics are used to destroy the bacteria.Bacteria have the ability to start mutation,and change their DNA pattern to protect themselves from the attack of antibiotics. When bacteria change their gene pattern, the antibiotics do not work against them. As a result, these bacteria become antibiotic resistant. The main reason of the antibiotic resistance is the indiscriminate use of antibiotics against bacteria. This indiscriminate use of antibiotics allows the bacteria to identify the mechanism of antibiotics, and bacteria change their gene pattern according to their identification. Lack self consciousness of the patients, not completing the required antibiotic course provided by the physician, self medication of the patients, and commercial thinking of the physician are some reasons behind the indiscriminate use of antibiotics. So, these deeds have to be stopped for securing the future of antibiotics.

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Re: The future of antibiotics

Postby BlackSails » Tue Aug 31, 2010 3:59 am UTC

ImagingGeek wrote:From an immunology standpoint (I'm an immunologist, BTW), lytic phage could be hugely dangerous as a therapeutic. Our bodies are remarkably sensitive to bacterial products, and small quantities in our blood can induce a lethal response termed "sepsis". Many of the antibiotics we currently use avoid this issue by not directly lysing the bacteria, but rather preventing their growth. This allows our immune cells to clear the bacteria in a way which prevents the mass release of bacterial products into the circulation. Lytic phage could potentially turn a modestly dangerous infection into a highly dangerous septicemia.


I thought the concern with lytic phages is the herxheimer reaction, not sepsis?

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Re: The future of antibiotics

Postby ++$_ » Tue Aug 31, 2010 4:28 am UTC

Eventually, shouldn't we be able to custom-build viruses that are bacteriostatic rather than lytic?

Just to clarify how this would work, they would be lytic only when given a certain chemical stimulus. You grow a bunch of them in a medium laced that chemical, and then inject them into the body, where the chemical is absent.

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Re: The future of antibiotics

Postby TheNorm05 » Tue Aug 31, 2010 7:54 am UTC

I'd just like to mention a cautionary when we start considering using bacteriophages to fight illness. Viruses can change at a pretty rapid pace, and once you start administering them en masse you open a whole can of worms. It's like Jurassic Park, or Resident Evil. Even when you think you've considered all the possible outcomes, you haven't.

Now I have a simple idea that may or may not be correct. Penicillin comes from mold, no? When we get these superbugs, why not simply let a battery of different fungi take a crack at whooping the bacteria around until we get one that does well? It sounds pretty strait forward, kinda like Thunderdome(2 men enter, 3 men leave!.. wait, what??). While it's prolly at least a bit more complex that that I find that the good solutions are often pretty simple.. If wood is too hard to nail, grab a bigger hammer. Since the lifespan of a mold is generally much faster than ours, it'd probably adapt to bacterial changes well before we do, so it at least seems somewhat logical to let fungi be first at bat.

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Re: The future of antibiotics

Postby BlackSails » Tue Aug 31, 2010 2:32 pm UTC

TheNorm05 wrote:I'd just like to mention a cautionary when we start considering using bacteriophages to fight illness. Viruses can change at a pretty rapid pace, and once you start administering them en masse you open a whole can of worms.


It would take staggeringly huge changes for bacteriophages to infect eukaryotes.

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Re: The future of antibiotics

Postby Turtlewing » Tue Aug 31, 2010 2:48 pm UTC

TheNorm05 wrote:Now I have a simple idea that may or may not be correct. Penicillin comes from mold, no? When we get these superbugs, why not simply let a battery of different fungi take a crack at whooping the bacteria around until we get one that does well? It sounds pretty strait forward, kinda like Thunderdome(2 men enter, 3 men leave!.. wait, what??). While it's prolly at least a bit more complex that that I find that the good solutions are often pretty simple.. If wood is too hard to nail, grab a bigger hammer. Since the lifespan of a mold is generally much faster than ours, it'd probably adapt to bacterial changes well before we do, so it at least seems somewhat logical to let fungi be first at bat.


I believe that is basicly how new plants/fungi/etc. with medicinal proporties are found. A bunch of grad students scoure the rainforest for samples, then exposes colonies of bacteria/cancer cells/virii (whatever they're looking for a cure for) to extracts from the collected samples under controled conditions. The ones that kill the colonys are then studied to see if the extracts can be made into a useful medacin.

Unless I'm wrong this sort of reaserch goes on all the time and is responcible for a sizable number of advances.


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