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IBM Research produces staph-killing polymers that leave healthy cells alone (ibm.com)
113 points by suchitpuri on Nov 28, 2013 | hide | past | web | favorite | 60 comments

In addition to the potential use for systemic delivery of drugs, scientists suggest that additional applications for these polymers could include adding them to every day personal and cleaning solutions.

Oh, good idea! Let's also put it in the drinking water and feed it to livestock! Nothing like that has ever caused resistance problems in the past!

True, caution is warranted.

But I think you missed a key point in the article. Unlike antibiotics, these polymers disintegrate. The article isn't clear on the mechanism–is it part of destroying a bacterium, decay over time or what?-but the implication is that they can be targeted to kill specific bacteria, without then escaping in to the wild to apply selection pressure on bacteria that aren't threatening somebody's life.

It's not like these researchers are unaware of drug-resistant bacteria. The whole point of the statement you quote is that adding them to cleaning agents won't breed resistant bacteria. They may be wrong, but they're not stupid.

"They try to mimic what the immune system does: the polymer attaches to the bacteria's membrane and then facilitates destabilization of the membrane. It falls apart, everything falls out and there's little opportunity for it to develop resistance to these polymers."

But yeah, caution might be a good idea.

Developing resistance is not individual bacteria "going to the gym" and training to be stronger.

To develop resistance, all that is needed is a random genetic mutation that makes a few of the bacteria cells less susceptible to the polymer. The polymer kills all other cells, and the resistant strain grows in numbers and takes their place.

Then it quits working (unlikely if the polymer attaches to vital cell membrane mechanisms but anyway). So what? Make a new polymer. That's the point; this can attack whatever. Its no longer a terrible problem if disease cells change or new ones appear.

And what's the alternative? Don't attack the cells? Let people get sick and die now, because in the future this mechanism which we aren't using might be obsolete? What's the logic there?

So what? Make a new polymer.

ORLY? Sorry to sound condescending but your glib comment shows an utter lack of awareness about discovering or designing novel drugs. It is never as simple as changing a line of code to get a new molecule that will kill the now resistant bugs and have no new adverse effects on the host.

Drug resistance is a huge problem today and threatens to grow bigger, where pathogens become resistant to drugs (known to be generally safe) and the arsenal of medicines is empty or has investigational drugs of unknown safety.

And what's the alternative? Don't attack the cells?

No. The alternative, in the short term, is to avoid indiscriminate use of drugs that still work, by testing the infecting bugs for pre-existing resistance markers and then using drugs that are orthogonal to co-evolving resistance mutations.

In the longer term, discovering wholly new classes of drugs, like this polymer, but testing for safety and adverse side-effects, is going to be our best hope. Again, the caveat against indiscriminate use applies.

This is absolutely not 'a new drug'. This wasn't made through the tedious try-1000-things-and-see-what-sticks.

This was a DESIGNED polymer, made explicitely through chemistry to attack a particular animicule.

The old antibiotics are done; the CDC calls the age of antibiotics 'over'. There is no longer any use in stonewalling or holding back on chemistry through some fear that it will ruin the status quo. The status quo is 'nothing works'.

This is a game-changer. The old arguments, the old ways of thinking, are probably obsolete. \ So cut out the 'glib' stale arguments and read the article again; come up with a cogent point.

You do know what an Eco-system is, don't you? Where things are linked in non-obvious ways, and changes almost certainly initiate other changes. This silver bullet mentality is prone to disaster. The bacteria may evolve, starting an arms race, leading to stronger bacteria, or possible fragmentation that makes management or synthesis time-consuming, difficult or may strengthen other nasties. Do you really know what the impacts are likely to be? I'm sure you don't, which is why caution is essential. Flippant "silver bullet" speculation not-withstanding.

Getting pretty esoteric there. So, you're about to be run over by a bus - do you just stand there contemplating your position in the universe, what good could be caused by your death, and let yourself be killed?

The talk of ecosystems is overused. In 'nature' its 'every organism for itself'. That means we get to try to outrun the bugs any way we can.

This was a DESIGNED polymer, made explicitely through chemistry to attack a particular animicule.

So are HIV protease inhibitors. Go read the facts on those, at CDC, FDA and elsewhere.

Modern drugs are designed, just like this polymer.

And your 'glib' comments are still glib.

To be fair, I didn't see anybody suggest that. This conversation tributary was about using the polymer as broadly as antibiotics are used now, in agriculture etc.

No issue with resistance. Its this kind of unthinking FUD that muddies the conversation. Can we talk about what this polymer actually does?

Life evolves to improved fitness.

The polymer works by destabilizing the cell membrane. A mutation which reduces the efficacy of that mechanism would, in fact, promote resistance to the method. Whether or not the polymer design could be modified to adapt to that change (and what the costs of this might be) are an open (and very interesting) question.

However: it's virtually certain that widespread and indiscriminate use would promote resistance to the existing design and method.

This is true, except the polymers in question work not on a cell activity principle but on a chemical disassembly potential [1].

This would be analagous to humans evolving to the point where you could not kill one by shooting it in the head with a bullet. It could happen, people with their central nervous system in some part of the body other than the brain would survive a bullet to the head, and there are bullet to the head survivors, for whom brain structure may play a role, but it isn't a huge risk associated with shooting people in the head.

[1] "They try to mimic what the immune system does: the polymer attaches to the bacteria's membrane and then facilitates destabilization of the membrane. It falls apart, everything falls out and there's little opportunity for it to develop resistance to these polymers."

the polymers in question work not on a cell activity principle

That's not a necessary condition of evolutionary adaptation. Though I'll freely admit to being outside my bounds of expertise here.

Others have mentioned the lack of bacteria which have adapted to bleach (I haven't confirmed this myself through literature). My general sense is that there's a potential space in which possible solutions exist, and some solution are on the edges of that space, making them harder to reach and/or harder for multiple adaptations to simultaneously exist. There are extremophiles which survive in what would generally be considered extremely hostile environments (ice, high elevations, undersea steam vents, highly acidic geothermal pools, abiotic environments, etc.). Few of these thrive in more generally hospitable environments, presumably because the adaptations which allow them to survive the extreme environments also pose a comparative disadvantage to life forms which don't need to carry the evolutionary baggage / armor / support systems required to survive such environments.

Carl Zimmer wrote a few months ago about a simulation of evolution in which there wasn't a penalty for complexity, his musing on that aspect of the simulation are interesting:


In this experiment there was no cost to extra complexity–something that may not be true in the real world. The human brain makes huge demands of energy–twenty times more the same weight of muscle would. There’s lots of evidence that efficiency has a strong influence on the anatomy of our brains. Perhaps we might have more complex brains if we did. And if the animats had to pay a cost for extra complexity, they would evolve only the bare minimum. That’s an experiment I’d like to see.

> humans evolving to the point where you could not kill one by shooting it in the head with a bullet.

If there were billions of bullets flying around, and humans reproduced by the billions in a matter of hours with a generation-to-generation gap of minutes, this would happen in short order.

What has evolved a resistance to bleach? It seems for as long as we've been using it, something should be able to withstand it now.

I think of the analogy that antibiotics work like a machine gun while bleach works like napalm.

Is there an actual difference at that level?

Could you please explain, for the layman, why resistance isn't an issue?

You are asking a layman for a layman's explanation.

Has anything developed resistance to regular household bleach?

Resistance, maybe:


"The researchers found that hypochlorous acid, the active ingredient in bleach, causes the unfolding of proteins in bacteria in much the same was that heat stress or fever does. Those denatured proteins then clump together irreversibly into a mass in living cells, similar to what happens to proteins when you boil an egg, according to the researchers.

"The bacteria aren't totally defenseless, however. Under those circumstances, a protein chaperone called heat shock protein Hsp33 springs to action, protecting proteins from the aggregation effect and increasing the bacteria's bleach resistance. Protein chaperones are generally defined as proteins whose function is to help other proteins."

No, apart from the inherent bleaching properties of sodium hypochlorite, the pH of bleach is extremely high - even extremeophiles can't tolerate pH 13-14. Unfortunately neither can human skin, and diluting bleach is a trade off between effectiveness and safety.

Drinking bleach won't cure your staph infection though.

Yes, this is kind of the point I'm making, poorly.

Some things like anti biotics are misused and that's caused resistance.

But handwashing with certain microbicides doesn't create colonies of resistant bacteria on our wrists (where the microbicide is diluted) because these microbicides have a different action.

Thus, putting this polymer in all sorts of places is less likely to lead to resistance problems.

Actually, it probably will.

It'll also cure you though.

Effective antibacterials / antimicrobials / antitumor treatments have differential effects. Preferably harsher on what you're trying to get rid of than on you. Though the description of chemotherapy as "killing you slightly less effectively than it kills the cancer" has a lot of truth to it.

Iodised Salt?

It possibly can be a good thing, yes we should be cautious, but I think it's rash to judge it negatively from the very start.

Great research from IBM here. Antibiotic resistance is a prevalent problem in our society today, with doctors prescribing antibiotics to everyone for everything (to no fault of their own - because of patient demand).

Nanotechnology combining with advanced materials will lead to a better understanding of pathogens and ultimately how to eradicate them. These are great steps towards solving many real and serious issues facing society today. It's certainly refreshing to see different disciplines coming together to move us forward.

These [polymers] are years away from clinical use, but this is a glimpse into the not too distant future.

doctors prescribing antibiotics to everyone for everything (to no fault of their own - because of patient demand)

This happened when resistance wasn't well understood. I don't think it happens nearly as much now. I've had doctors tell me "antibiotics won't help what you have, stay in bed and you should feel better in a few days"

"that move quickly to target infected cells in the body": does it make sense to write this when you talk about bacteria? It looks to me like the author confused them with how viruses work: With bacteria you don't target "infected cells", you target infectious agents, the bacteriums.

I always wondered if there would ever be a post antibiotic mechanism to kill bacteria/viruses, along the lines of nanobots perhaps. Nice to see progress is being made in this regard...the human race may be depending on it!

This sounds like an excellent material to make central lines out of, given the current rates (~5%) of infection by antibiotic resistant S. Aureus and friends.

We're already making central lines out of antimicrobial materials, like ionic silver.

What are central lines?

Very rudimentary understanding of Cancer so if someone from a field is here please do comment: can this technique also be used for destroying Cancerous cells?

Not a biologist (but used to work next to some for a few years). But...

This molecule can distinguish between normal cells membranes and bacteria membranes. That's quite easy. Most of the difference between cancer cells and normal cells is in the nucleus, not the membrane, and most anti-cancer drugs target the stage where the nucleus replicates. So, my tentative response is "No".

Having said that, the potential ingenuity of the human race is beyond what I can image right now.

The problem is bacteria have all kinds of targets on them that our cells don't.

Drugs to attack fungi, let alone cancer, are far more difficult because we're both eukaryotes and share many, many molecular targets. The really hard part is to kill a cell that looks like our cells, but not our cells.

Doubtful. That is the problem with cancer cells - they are indistinguishable from others. I think the current bleeding edge in cancer research are ways to disable the cell mechanism that turns off the immune system near the cells.

The relationship between the immune system and cancer is incredibly complicated. There is, however, some fascinating research dealing with using pathogens that somehow preferentially infect cancer areas of the patient, to stimulate the immune system in that area:

http://stm.sciencemag.org/content/2/44/44ra57.abstract is a paper that talks about it. It's pretty neat!

It's very easy to destroy cancerous cells.

The real art form is to find a mechanism that kills the cancer sufficiently faster than the patient.

Everything able to replace, as a cheap and therefore widely used biocide, this guy: http://en.wikipedia.org/wiki/Isothiazolinone which is responsible for my allergy and awful dermatitis, it is a good thing.

What of the huge population and variety of bacteria that are symbiotic and in some cases necessary for good health such as gut bacteria? How would this technology target only bad bacteria? Is it so customizable that variants can be generated for specific pathogen species?

How long until we stop targeting bacterial cells and start targeting healthy human cells? I'm surprised no one's commented yet about the weaponization prospects for these polymers.

I'm baffled by how this is both high-tech and totally bonkers, being able to produce a polymer specifically targeting specific harmful bacteria is quite an achievement by itself but it is dwarfed by the ability of IBM to do away with the laws of physics, making matter just disappear is an incredible feat.

I wonder if this polymer just turns invisble or if it cease to exist without leaving any other compounds, residues or energy.

They claim that it's "biodegradable." I don't know the details, but I'm guessing the polymer breaks apart into smaller, benign pieces over time? I wonder if that means they have to make it right before using it, and what, exactly, triggers the breakdown.

> adding them to every day personal and cleaning solutions

... is the best way to breed resistance...

The polymer doesn't work in a way that resistance is likely or even possible. They spill the bacterias guts. Its like getting resistance to head-blowed-off - not going to happen.

To be fair... the mechanism of penicillin when described for the lay person is remarkably similar to the description that IBM provides.

"the polymer attaches to the bacteria's membrane and then facilitates destabilization of the membrane" vs "act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls".

And the resistance isn't to getting your head blown off. That's thinking too much in the box. It's more like being resistant to having a bullet shot at your head, either by somehow becoming invisible to your assailant's vision, wearing a sufficiently good helmet, or having your vital organs located somewhere else.

While I agree that it seems much harder for bacteria to overcome this new approach, it really isn't safe to say that it's not possible. We have no idea about the microbial world. We barely know a fraction of the microbes that swarm around us, we have no idea what defenses, mechanisms and quirks they have that might provide a method of resistace.

And since this is a passive process (just some polymer floating around) that somehow does not damage human cells, you can bet that there's someway to spoof that.

To be clear (from an undergraduate microbiologist), my thought process behind the claim that IBM's polymer is less likely to promote resistance: Faster-acting agents that cause immediate destruction are much harder to develop resistance to because normal minor variation from mutations is much less likely to produce anything that will save a cell from death. So even if a cell produces a minor variation in its membrane protein it will likely still be killed and the "resistance" gets no chance to develop.

For something like penicillin, the bacteria gets quite some time to die (it inhibits synthesis!) and there are many different places in the peptidoglycan synthesis pathway for the cell to develop a resistance.

Does that make sense?

Indeed it does! Thank you.

I would not be so sure of that until long term tests have been done to bacteria populations. All it would take is a random mutation which makes it harder for the polymer to attach to the bacteria.

Sure, given that, what does it matter? Don't kill the bacteria now because...what?

The old argument was, don't make our current antibiotics useless by breeding 'resistant' varieties. But now, IBM is making 'magic bullet' antibiotic polymers on their 3D polymer printer.

So what does it matter that new varieties mutate or whatever, if you can just print up a new polymer to handle it.

This is a game-changer. The old ways of thinking are probably obsolete.

Possible according to the article: "little opportunity for it to develop resistance to these polymers"

At the risk of sounding snarky, why does fluoride still work for oral hygiene?

Because it gets embedded into the tooth's enamel. Fluorid-enriched enamel is more resistant to acids produced by bacteria. (i.e. fluoride doesn't affect bacteria, it makes teeth more resistant to byproducts of bacteria's feeding on sugars.)

Fluoride is not used to kill pathogens, but because it is a substance that is good for your teeth, that a lot of people do not get in sufficient quantity otherwise.

Consider it the equivalent of putting vitamin pills in foods, not putting antibiotics in meat.

This is very very cool.

Nobel prize

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