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Antibiotics and Nanotechnology
Evil Pete writes: "In an article at Nature Update there is what appears to me is the first use of nanotechnology in a significant way. A team from Scripps Research Institute has used molecular assemblages to destroy bacteria by puncturing their cell walls. The tests on mice cured staph a. infections by injecting a solution of the nanotubes into the mice."
I didn't see it explicitly mentioned, but it would be good if these new "antibiotics" could target specific types of bacteria. The author even goes so far as to call bacteria "bugs", however one must realize that not all bacteria are harmful (i.e. there are "good" bacteria such as Lactobacillus acidophilus and Lactobacillus bifidius). Traditional antibiotics when ingested orally, will attempt to destroy ALL bacteria in the gut, possibly leading to a condition called Candidiasis, characterized by the overgrowth of fungi in the intestines, which are known to emit some 70 or so types of toxins. Restoration of wellness is not possible when chronic candidiasis is present. Many people are diagnosed with CFS or some other bullshit condition because the popular notion in the medical community is that conditions like candidiasis don't exist (that's at least the experience I've had with it).
Generally, antibiotics have led to the conquering of many types of once deadly diseases have saved many lives, but not without a cost. They are prescribed much too often, which has ultimately led to these resistant strains of bacteria we hear about in the news today. Use of antibiotics reach further than just the medical field. First-world consumers demand that their cleaning products that "destroy 99.9% of germs", and chemical companies produce such projects, but neither hardly ever realizes the consequences of such a request. Antibiotics and growth hormones are given to farm animals, and passed along to humans in the food they eat. I have never had a doctor recommend that I supplement antibiotic use with bifidus and/or acidophilus, and with the amount of training in clinical nutrition/alternative treatments that most doctors get in medschool, I don't expect to have this happen for a long while. For these reasons I avoid antibiotics unless absolutely necessary, as they have caused me more harm than good in the past in situations where their use wasn't entirely justified.
The self-assembling aspect of these things is how it builds the tubes out of rings. The rings are picked beforehand to be attracted to the bacteria and not any human cells, so even if the tubes broke down and reassembled differently, they'd still be targetted at bacteria.
My question:
How long do the nanotubules last?
Because it seems to me that, once the mice shit the things out, the nanotubules are pretty much "released into the wild."
I'm not sure this is a desirable thing, particularly as the tubes were tuned to "prefer" bacteria -- which, to my reading, means that they'll happily go about puncturing other things as well.
It's best if these things have a reasonable half-life, perhaps a day or two. Inject 'em, let 'em savage the bacteria, let 'em get processed into mouse poop, and then have them decompose.
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What I find disturbing, is how the selection process works. Just dump a bunch of these things in the soup and see what they kill. Imagine if the tubes that kill staf bacteria also happen to chew into nerve cells? Or even more disturbing...what if these things were specifically selected to damage healthy host cells? They would make an excellent, and likely hard to detect, chemical weapon.
This technology is simply amazing IMO, but just like other treatments it is frightening as well. From what I understand the quote above is correct, the cyclic peptides were selected to bind specifically to bacteria. Bacterial cell walls are significantly different than the plasma membranes surrounding our cells, but how different is different enough? They mentioned testing the peptides against red blood cells, but in our bodies there are a multitude of different cell types. So herein lies a major obstacle. Until they can tell exactly how these peptides are binding to the bacteria (at the molecular level) and be sure that mammalian cells don't have any similar structures on their surfaces, I wouldn't volunteer for a phase I clinical trial. Imagine you get a the highest dose in the trial and for some unpredictable reason, the peptide binds to and punches holes in... let's say... blood vessels deep in your brain. Not fun.
Another issue is how selective are these peptides for pathogenic bacteria and how are they metabolized? The problem lies in the fact that we have a multitude of normal bacterial flora, much of which probably looks the same to a nano-peptide as pathogenic enterococcus (for example). If the peptides are really effective and have a short half-life, one could imagine a lot of normal flora being wiped out along with the bad guys.
One more thing, don't think that nature hasn't thought of this already. This is one of the same principals by which bacteria are already targeted by our own immune systems. Specifically, when your body generates Antibodies against a particular bacteria, the antibodies bind to the bacteria, then a specific cascade of events involving the Complement system occurs. The result of this cascade is called the Membrane Attack Complex which is a complex of proteins which pokes holes in whatever is covered (opsonized) by antibody.
Furthermore, when T-cells target infected cells for destruction, they release a protein called perforin which, once again, pokes holes in the cell slated for destruction.
Congratulations to the authors for taking such a biological prinicipal and engineering it to our advantage!
Prediction: SirCam turns into another "All Your Base" phenomenon, and while you're laughing now, in six weeks you, and half of Slashdot, will be hunting me down with intent to terminate with extreme prejudice. The last words I hear will be "Hi! How are you! I send you this bullet to get your advice on how to get the fad to stop!" ;-)
(Hmm, or maybe not. Maybe the last words the Iceman heard before he got frozen into the glacier were "Ook! Og send you this arrow...")
I send you this nanotube in order to have your advice!
The bacteria see how effective this weapon is and start to incorporate it to better infect our cells.
When this happens, the current antibiotic-resistant 'superbugs' are going to look pretty tame in comparison.
I gots ta ding a ding dang my dang a long ling long
It's funny until you realize that Scripps received a $20m grant from the Gates Foundation in 1999...
Last night I was in a hurry and grabbed a "dinner" from the salad bar at my local Shopper's Food Warehouse. Within hours food poisoning had set in, and I was clutching my gut and moaning in pain.
That experience led me to realize a perfect use for these; create nanotubes that destroy bacteria that cause food poisoning, and put them onto the salad bars at crappy grocery stores, dirty restaurants, etc! If they can't be put on the food, they can be injected with those air pressure guns used to innoculate masses of children in poor areas! The perfect solution to spending Friday nights getting drunk at a club and not rolling around in bed clutching one's abdomen!
Since nanotechnology is a newly emerging field, there are many definitions in current use among researchers. None of these, as far as I know, is limited to "electronic circuits and devices." Lets look at some contemporary definitions:
The foresight institute's official definition of "molecular nanotechnology":
Thorough, inexpensive control of the structure of matter based on molecule-by-molecule control of products and byproducts of molecular manufacturing.
From the web page of the University of Washington Center for Nanotechnology (the first PhD. program in nanotechnology in the world, I believe):
Nanotechnology refers to the ability to manipulate individual atoms and molecules, making it possible to build machines using molecular building blocks or create materials and structures from the bottom up, designing properties by controlling structure.
From the sci.nanotech FAQ:
Nanotechnology is an anticipated manufacturing technology giving thorough, inexpensive control of the structure of matter. The term has sometimes been used to refer to any technique able to work at a submicron scale; Here on sci.nanotech we are interested in what is sometimes called molecular nanotechnology, which means basically "A place for every atom and every atom in its place."
The main reason, I believe, that this work can be considered nanotechnology is because it takes advantage of the concept of self-assembly. Self-assembly is the property of certain molecules to spontaneously assemble themselves into ordered super-molecular structures. Looking for ways to take advantage of self-assembly processes is a major focus of state-of-the-art nanotechnology.
Now whip some up that scour the crap off the walls of my arteries and we'll be in good shape!
I'm trying to teach myself to set people on fire with my mind... Is it hot in here?
Since bacterial cell membranes are completely different than a mamillian cell, making something that will only alter one is easy to think of. That is exactly how certian antibiotics, such as ampicillin, function. Those known as beta-lactamases clean the beta-1-4 linkages of peptidoglycan in the bacterial cell wall. This causes the cells to eventually become unstable and burst. Since our metazoan cells don't contain peptidoglycan in their cell walls, we are safe from such chemicals.
THe second point about it begin hard for bactera to evolve resistance mechanisms is a great point. Most antibiotics are isolated from bacteria themselves. So, in order for a bacteria to be able to produce antibiotics and still live... it has to be able to have a system to protect itself. The typical antibiotic/resistance genes evolve at the same time in an organism. With this new technology, the microbes will have to co-opt systems already in the cell to meet the new stresses of the nanotubules. This could in theory take longer to adapt than typical resistance mechanism.....BUT remember that by using any sort of system like this... where you are brut force killing organisms...you strongly select for individules who have the ability to survive, and pass the ability to flourish to their progeny.
Just my thoughts:)
Specificity and power are the keys here. First, design the nanites so they go after very specific species of bacteria rather than against bacteria in general. Second, make them overwhelmingly powerful so the "bad" bacteria don't have a chance to evolve resistance. If we get good enough at that sort of design, the bacteria will no more evolve into resistant strains than humans can evolve resistance to a sniper's bullet in the back of the head.
I have reasonable hopes that the day isn't too far off when we'll be able to custom-produce drugs which not only go after specific pathogens, but also work with patients' specific biochemistries. Pharmacies will no longer stock drugs; instead they'll be drug factories which, given the lab workup on a patient, can turn out exactly the right medicine for the patient _and_ the disease within a few hours. My guess is that disease-specific meds are five years off, disease-and-patient-specific meds are about fifteen years off.
The correlation between ignorance of statistics and using "correlation is not causation" as an argument is close to 1.
... Contract with biotech companies in 3rd world countries to, as the article says, "train" these nanotubes to attack healthy tissue and sell them to other third world countries.
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As the article points out, it would be difficult (though not yet proved impossible) for a pathogen to develop resistance to these things. Traditional antibiotics attack only one aspect of a cell's function: the synthesis of peptidoglycan (a substance used to reinforce the cell wall, without it the wall weakens and bursts) is a favourite, and these are relatively easy to work around through minor modification to the affected pathway. Not only that, but our antibioitics are derived from compounds already present in nature (e.g. penicillin), and tests on old bacterial samples show that the resistance genes predate our use of antibiotics. The bugs already had a defence ready to roll.
With these things, not only do they represent a "blanket attack" on pathogenic organisms, they are a completely novel form of attack for which bacteria are yet to even begin developing a defence. This should put the bugs on the backfoot in the pharmaceutical arms race for some time, if not forever.
I would love to say "Transform!" and then turn into a car and drive to work.
From dictionary.com: nanotechnology (nn-tk-nl-j) n.
The science and technology of building electronic circuits and devices from single atoms and molecules
Labelling this as nanotechnology seems a bit inaccurate to say the least. This is really *very cool* molecular biology, but unless being nano and in a technical field = nanotechnology, this isn't it.
As a side note, I work at Scripps (across the hall from Ghadiri actually) and can tell you the amount of money received from the Gates Foundation is barely even pocket change.
-Ted
-=-=- Quantum physics - the dreams stuff are made of.
Iguess it's just a matter of time...
On a serious note, these asemblages were entirely static in nature (no nanobots yet...) but it doesn't really discuss how these injected nanutubes were exponged, and after how long. Presumably they were released as part of the mice fecal matter but how long does it take to exponge the tubules?
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You skimmed too fast. The nanotubes don't pop the infected cells, they pop the virus. Thusly the article title, "Bacterial back-stabbing -Antibiotic prototype punctures bugs. 26 July 2001"
The common flu and cold virus retain their internal code under a disposable outer coating. Once popped, they lose their transport mechanism and are 100% vulnerable to the human body's defenses.
A simple example would be having you go swimming in a wetsuit in the ocean, then I come along like a shark, tear away your wetsuit along with your arms and legs, then go looking for another snack.
I could go into detail about things like flagella or cilia. Flagella being a whiplike tail like on a sperm cell used for swimming. Cilia being hundreds of tiny oars on the cell body used for swimming. And I could mention that without these, the viruses are pretty much dead in the water without arms or legs to move them, but I already have. As for HIV, once popped, the virus is still just as deadly. Most other viruses cannot withstand the popping though.
"Face it, a nation that maintains a 72% approval rating on George W. Bush is a nation with a very loose grip on reality.
1)Time - a) most non-life-threatening bacterial infection will run their course in about a weeks time (except for chronic sinusitis, TB, chronic acne etc). Antibiotic use will still happen and be the best choice in these cases (instead of the nanotubes) because by the time you get one matched several days will have elapsed. Why? to target the nanotubes after a specific bacteria, you must first CULTURE IT! This takes minimum of a couple days culture and get enough of a sample to test your tubes on. By this time, with a 20 dollar prescription of amoxicillin, zithromycin, etc you could have knocked out most of the common infections
2)MONEY! - This will NEVER be less expensive than our generic / non-brand name antibiotics. If your child has Otitis media (ear infection), and they are wailing keeping you up at night would you rather wait for 2 days or more for that super nanotube that will kill them and pay a prohibitive price OR pay 20 bucks for an amoxicillin suspension that morning and get a good night's rest THAT night. 3)Location of infection - this sounds like this will really only be effective against sepsis/bacteremia (when the blood becomes colonized and bacteria start multipling in your own blood). One thing antibiotics are really good at is pervading the tissues not just the blood stream. If you have cellulitis (infection of skin that can rapidly progress) you need a antibiotic with good spectrum coverage and that will also be excreted/oozed out through the blood vessels into the surrounding tissues (say Augementin for example). They said nothing in this article about whether these nanotubes can migrate from the blood stream to the tissues. And what about an abcess for instance? Abcesses will have walled them selves of from the surrounding tissues with a cavity liner and it can be very difficult to get antibiotics to get there, i don't see how nanotubes would be any more effective.
Another issue that i can think about is people that are more likely to suffer from gout (buildup of urate crystals in the periphery and joints such as big toes, knees, and elbows. IF these nanotubes do leave the bloodstream to the tissue level, they may be comparable in size to urate crystals, so would they all buildup and cause a nano-gout reaction (instead of a urate-gout buildup)
Another example, Bactrim (aka TMP/SMZ (trimethoprim/sulfamethoxazole)) which wildly successful for bladder infections because it leaves the blood stream rapidly and concentrates in the bladder. Where are the nanotubes excreted at?
This work is a mix of various biological and chemical techniques. As far as I can tell, the field of nanotechnology contributed nothing significant to these developments.
They've figured it out. Now when you get aids or cancer, they'll just have you come in for periodic injections of these little nanoprobe things and you'll be A OK, for a little while, until it's time for another shot. So just like drug dealers, they'll have people coming back over and over again, rather than curing the disease so the people can just live happily.
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Virii introduce themselves into the host cell, splice their own RNA into the DNA of the cell, and then allow the cell to act like a little virus factory to crank out copies of the original virus. The cell fills up with these copies and pops when it surpasses critical containment volume, releasing all the copies to repeat the process with other host cells.
So there is no point in using a nanotube to pop the host cell, as this will simply do what is going to happen anyway.
To stop virii in general, it helps to inhibit the virus's ability to splice its RNA into the host cell's DNA. This approach is where the most promising and effective HIV treatments reside today. However, the only way to whack a virus is to get the body's own destroyer cells to eat them. This is difficult to do with HIV because the invader-signaller cells are the ones that HIV loves to use as factories. So the body loses its ability to know it's being attacked.
Net-net: This nanotube approach is great against living invaders (bacteria, and possibly even some types of cancer), but not useful against virii: HIV, or any other.
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