Novel antibiotic family - so many implications, what will the unintended results be?

Ok. I don't recall if I've ever posted a new thread on ATS. There are a number of reasons - one, a lot of this stuff just doesn't seem new to me so it doesn't dawn on me that you guys would be interested. Another is, the really good stuff I just am generally close-mouthed on.

So, I was following up the news on this to see where it was, and I realized I just hadn't seen a lot about it anywhere, and I don't believe I've ever seen it HERE. Thus, my first original post (I think).

This isn't classified, and I never worked on it in any form, so it seems safe to toss out. What baffles me is why you haven't really seen much on it in the MSM. I've been following it for a few years now.

This could go in so MANY topic headers. Military, Government, Medical Issues, you name it. But I picked S&T, maybe they'll move it. Who can say? They say that fairy tales start off "Once upon a time", and Army stories start off "This ain't no s--t", and this starts off as an Army story. This ain't no s--t....

The Army was interested in an antibiotic. Not just any antibiotic, but a NEW antibiotic, one that was safe in any reasonable dose so that anyone could administer it without immediate fears of rotting out someone's kidneys or inner ears. It should work on just about anything - gram positive, negative, mycobacteria, fungi, protozoans, whatever. And said target organisms should not be able to mount a defense against it. Ever.

You'd think that wouldn't be possible. However, it looks like it's about to happen. An UMass polymer science team headed by Dr Gregory Tew started looking into the more generic methods of immune self-defense used by animals, and became interested in defensins - small proteins that attack classes of bacteria without the complexity of phagocytes or the complement system. And they designed a class of artificial defensins that work on the same principles but without using a protein to do the job. The new defensins seek out any cell membrane that doesn't incorporate cholesterol, and perforate it, killing the cell.

All animal cells have membranes with cholesterol. The artificial defensin won't "fit" animal cell membranes - the cholesterol molecules prevent them from locking on, and the neutral surface charge doesn't attract it. Pretty much anything else gets it. The new defensin doesn't have to be absorbed by the target cell, so defense mechanisms like antibiotic "pumps" won't work. If the bacteria exposes a membrane, it gets perforated. Even bacteria that wrap themselves in wax like the bacteria that causes tuberculosis are susceptible.

There are some variations in the defensin design that optimize for organisms that use membranes with ergosterol, like fungi. But in general, two or three designs of artificial defensins given at the same time will kill pretty much any fungi, bacteria or protist, either given topically (spray or cream) or by IV. You don't have to worry about doing gram stains to determine what sort of bacteria it is - it'll kill positive or negative. And the bacteria don't develop resistance against it - they'd have to redesign their entire cell membrane configuration. Tew's group has been TRYING to breed resistance to it. So far, hundreds of generations of bacteria exposed to it in serial sub-lethal doses die just as quickly as the first generation.

Needless to say, the gubmint's been chunking cash at it left and right. The Army started off, but DARPA, DTRA, Navy et al are all hosing the bucks in. It's passed phase I and II trials - it doesn't kill people or other critters at any reasonable dose - the LD50 for this stuff is basically going to drown them - and with people the only side effect is momentarily numb lips when given at about 10x the necessary rate.

Phase III effectiveness tests in people are now underway. It works in cell cultures and in animals. I don't see it failing in people, although you never know. Preliminary info is that it's working as predicted.

So, why the lack of news? I don't really know.

Next, what are the ramifications? If you have a new antibiotic that you can get one good sized dose of IV, and that's it for bacterial and fungal infections, and they can't mount a defense against it, then we're down to viruses as the only cause of infection. Now, the Army wanted something a medic could give in the field without needing labs or C&S studies. What does that do to society, though? At first glance, it seems like a godsend. But will it cause a worse population explosion in third world countries?

Bang, instant TB cure. Bang, instant VD cure. No more cholera. No more plague. No more amoebic dysentery. No more malaria. VRSA, MRSA, MDR tuberculosis, all one with yesterday's snows. You'd still have viruses to contend with, at least for a while - defensins can be tooled up for viral infections too - but are there any drawbacks to curing people of pretty much any bacterial or fungal disease? Maybe it's just me wondering where the lions are.


Behold.

I would predict that such a "miracle" drug will never reach the masses. Why should it? If the government created it, then I suspect it will be used by the government only. Just another tool to keep folks in line.

Something else to consider; this would take germ warfare to a new level. Find a Typhoid Mary and expose the enemy, while our troops pop a miracle pill and stay safe.

Very interesting thread.

S&F

I read your thread and the linked source.

This is amazing, but what do they do to replace the beneficial bacteria? If I read this correctly it will have a long-lasting effect and not exclusive. Major digestive alteration. But no more gas?

Guess we'll find out at the end of Phase II.

Originally posted by lakesidepark
I read your thread and the linked source.

This is amazing, but what do they do to replace the beneficial bacteria? If I read this correctly it will have a long-lasting effect and not exclusive. Major digestive alteration. But no more gas?

Guess we'll find out at the end of Phase II.

edit on 18-2-2012 by lakesidepark because: (no reason given)

If it crosses into the gut, I imagine you'll get one heck of a case of the trots. But then again, They® say that Crohn's disease is a bacterial infection of the gut. Maybe one slurp of polymedix instacure and you're done with appendicitis and Crohn's, C-diff and ulcers. The temporary squirts would be a small price to pay.

Woah. Now that's something. Literally beating bacteria to death seems like a much more elegant solution than poisoning them. And I have to agree, a couple days of digestive issues seems a small price to pay for a guaranteed 'cure' for a nasty bacterial infection.

You always post some of the most informative things about such a wide range of topics Bedlam, but this is a little more concrete and more immediately amazing than most.

reply to post by framedragged


Yeah, I had just done some checking on their status since I remembered they were going to phase III this month or thereabouts, and it struck me that I hadn't heard jacksquat about it, even yet, and with their trials still going really well. And I'd heard from a DARPA hack that is indirectly connected to the project that it was working pretty damn well in vivo with animals.

It's going to be a big hairy deal, unless it turns out it gives you mutant superpowers or something.

Wow thanks for this, truly amazing. Do you know how long it persists in the human body?

Go Darpa. You'd think there would be way more press surrounding this simply to silence those who complain about defense spending going to nothing worthwhile (though, I'm personally quite happy with that incredibly asymmetrical safety net of ours). I mean, you have constantly have folks frothing at the mouth over money going into more accurate bombs but the moment they were exposed to this their entire line of reasoning goes out the window.

Did the darpa guy have an explanation about the numb lips you mentioned?

reply to post by framedragged


They say it's similar to the feeling you get when you've had your teeth numbed for dental work and it's starting to wear off, and it passes within a few hours. Why it happens at all is mysterious - why not generalized numbness? What's specific about that set of nerves?

Anyway, maybe your grandkids won't grow up knowing about dental work - a bit of this in the toothpaste and no more tooth decay.

Originally posted by framedragged
Go Darpa. You'd think there would be way more press surrounding this...

That's one of the reasons I started the thread. Why isn't there? I mean, it's not like you can't find basic info on it online, and they've done some press releases I think.

It wasn't a dud, at least not so far. I've seen other medical stuff hyped earlier in its cycle than this, too.

I haven't found a medical professional who's seen anything on this. And it's not so geeky/niche-y that no one would be interested, like, say, a big DARPA project on improving submarine INS accuracy/size by using whispering gallery plasmon delay rings.

Don't get me wrong - if you read down a list of non-classified (!) gubmint projects, some of them ought to light up Noah Shachtman's warning indicators but understanding WHY they should is the problem. If you see the gubmint spending a WAD on investigating Fermi gases, it's probably not to further random general knowledge in the area of condensed matter physics for the good of mankind.

What's fun is when you know what the 'meta project' is that the studies are for, and you see the research grants being let here and there in little non-obvious innocent looking chunks. I've often wondered who is in charge of turning big classified project research efforts into little non-classified misleading research efforts.

reply to post by Bedlam


Well said Bedlam, it's a shame that more people don't see the importance of this, even if it is only entering Phase 3 for topical application.

Your job is way too cool Bedlam. Or is at least more interesting than most. I know you're more of an engineer/designer guy, but would you have any clue as to how to get involved in general defense contract work (or whatever it would be) from the physics/science side? Get an internship with Northrup? Submit an interesting research proposal? I'm not talking about highly sensitive stuff, just general contractor work. I'm a physics/math double major and it seems like very little interesting work (for me at least) goes on in any commercial or pure university field. On the other hand it seems like a lot of very interesting work goes on from the government funded side, especially when it comes to plasma physics/high energy. I hope this isn't too up front. Any input at all is appreciated.

That really sounds nice.

Lets say it does work and it does take a while till the bacteria can get around it (They ALWAYS Do!) That would mean that anybody taking this antibiotic would not only carpetbomb their Gut/Skin/mouth/eye/ear/stomach microbiom they would rain Nuclear hellfire of Obliteration on it.

Killing all bacteria does NOT sound wise. Since we need the 99.99999999% of the bacteria in and on our body to live. They are in a symbiotic relationship with us. And i wont be suprised if it doesnt work as well on TB as advertised. M. Tubercolosis is a real smart fellow. It has loads of aces up its sleave there are loads of resistent strains out there.

Im since forever a Advocate of Phage therapy. Phage (a virus that infects and kills bacteria) a Highly specific and only kill the One bacteria you want to kill. Its cheap to produce and has NO sideeffects. (u can eat a spoon of phage and nothing happens) and i really really dont get why the FDA makes it so impossibly hard to make business with them. There is a company that produces phage for desinfection of meat (listeria) and they had to wait over 10 (YES TEN!!!) years to get approved. Since every disease requires a different Phage its practicly impossible to market it.

reply to post by smyleegrl


you know this theory on human culling
with viruses and the like well maybe
this is for the 500,000,0000 who will
be left TPTB or THE ELITE
who ever they are

Originally posted by framedragged
Your job is way too cool Bedlam. Or is at least more interesting than most.

You know, it used to be way more cool when I was in my early 30's, I say that because I got started late, did a stint in the Army first, got out in my late 20's and hit the books, got a physics/EE double, went on to a masters in EE and went to work. But now those six months stretches in sequestered engineering projects suck ass, even when the project's cool.

First thing I did was go to work at LANL. That's one thing I would check into if you like that sort of thing - a stint at a national lab. There are service related opportunities but it's a bear to get into those, like NRL. It's more straightforward to pick a national lab that's doing things you like, and go interview with the directors of the projects you are interested in. LANL is great, Sandia, Idaho, there's a wide assortment of opportunities, especially in high energy physics. If you get clearance, and get hooked into a happening project and you really apply some energy to it and get known as a dependable go-to guy, you will end up "in the community" so to speak, for good or aye.

Have you tried asking the profs where you went to school? Another thing you can do is call or email some major players in the fields you like and ASK who/where the action is. You'd be surprised how many people would be happy to hook you up. I've made some great relationships that way, just by looking in the school directory at MIT or whatnot and calling the Head Professor In Charge of my currenly favorite subject.

Not sure where you stopped with your educational career, but going for a doctorate under a guy that's doing research you like is another path, especially if said mentor is doing a lot of work for a national lab and thus has funding for his efforts.

There are a number of commercial ventures if you can get into them - Lockheed and Boeing do quite a bit of plasma and laser work on the black side of things. SAIC is actually the DIA in drag, and they have LOTS of engineering oriented projects, so it's less theory and more practice. Alliant TechSystems is another good bet for more engineering oriented stuff.

The problem with going to work for a special projects division of a big contractor is first getting in there, and then not falling through the cracks.

Another way to go is to go to work for a government agency front that's more blatant about it than SAIC. QinetiQ or In-Q-Tel have a lot of design work, QinetiQ is better to work for IMHO, and has little research shops all over the place, maybe even one close to you that you didn't know about. On top of which, if you're not averse to it, CIA hires LOTS of scientists and engineers directly, as does NSA.

The agency and NSA probably don't have a lot of high energy plasma type stuff, although there is some wild design stuff that goes on at CIA, I s--t you not. They do a LOT of plasma and laser at Kirtland - and I bet you'd get some real surprises there if you're a laser guy - that's mainly a Phillips Laboratory thing although the contractor scene out there changes constantly, you might see if the KAFB employment office can/will refer you to the contractors that are currently there.

You can also direct pitch to the government through the SBIR/STTR program. The issue there is that as an individual, you often don't have the money to do the real gravy parts of the project so you only get the phase I work. Also they usually want at least one guy on the team to have a doctorate. I have seen people get SBIR money without (polishes nails on tshirt) but you have to submit one hell of a proposal. Some of that stuff is way off the egghead scale.

An indirect way to do things, too, and it won't work if the project's going black, but you can see what SBIRs have been let that you really LIKE, and then find out who won it, and apply to them to work on that project. Use the SBIR system as a cool job search system as it were.

edit to add: It often works better to call and speak to someone ON a project and see if they are willing to forward your CV into the system for that project or group of projects rather than go through the generic application bot on the website.

Also to add, you might check out civilian employ at a place that does testing on the sorts of things you like, Redstone and a number of other military offices in Huntsville come to mind. They do a LOT of high energy testing out on the Arsenal when no one's looking. THEL was a hot item at one time there when it was sort of secret still. Heh. You do need egghead types to do the math on that sort of thing to explain why it did/didn't work after the fact.

last ps: Phillips is AFRL and PTI now, everyone still calls it Phillips. You can get jobs directly with AFRL or PTI, they also have several other programs where you work there while you're doing your thesis with their toys etc. Also, as a fun waste of time, peruse fbo.gov to see if there's any work going on you're interested in. It might not be directly applicable, but you can sometimes follow the thing to the bidding agency and find job opportunities in the same project.

Originally posted by Inesophet
That really sounds nice.

Lets say it does work and it does take a while till the bacteria can get around it (They ALWAYS Do!)

So far, they've been encouraging them to get around it - and they've not managed it yet. Also, the natural defensin system's been around for several million years and the bacteria haven't gotten around IT yet, although in its natural state, it's not anywhere near as effective as this is.

Let's see...

It's not good for pharmaceutical companies who specialize in antibiotics.
It's not good for anyone in the medical community who abuses the medicare system to earn a living by treating only symptoms or treating people with the wrong antibiotics.
It's not good for insurance companies who earn high premiums because of a crooked medical community, so it would hurt some money making portion of Obamacare.

So really, it's mainly going to hurt the crooks.

So it it never makes it out to the general public, you know who's looking out for the criminals once and for all.

My cynical guess:

it will be held up forever in interminable FDA burrocracy. The only legal application will be feeding it in mass doses to caged farm animals swimming in infected feces, as now they could pack even more in with the filth.

There will be big-time cloning of the real and fake drug in China.

Really interesting OP, thanks. Actually this sounds like a really cool technology.

The new defensins seek out any cell membrane that doesn't incorporate cholesterol, and perforate it, killing the cell. All animal cells have membranes with cholesterol. The artificial defensin won't "fit" animal cell membranes - the cholesterol molecules prevent them from locking on, and the neutral surface charge doesn't attract it. Pretty much anything else gets it.

There is some indication in research I skim that the massive quantity of bad fats in our common food intake, and lack of decent phospholipids (not helped by the MSM urge to avoid eggs and eat canola oil...) results in many composite cell membranes which, due to lack of having all the ideal building materials, incorporate the "less ideal lipid structures." The body's way of hacking it with duct tape when it's gotta be done. There is some indication that this may cause a variety of issues related to what can't get into a cell (nutrients), out of a cell (waste), and the environment they are within as a result (resulting in inflammation and all that comes with it). That is to say, that while some of the cell membrane may be created with cholesterol or whatever the normal materials are (I think there's more than one really) that perhaps, to hugely simplify this, let's say that the left-half of some cell uses other, less ideal lipids.

Does this kill any cell with a less than perfect membrane? In theory that sounds fine, but in practice it seems scary.

reply to post by Bedlam


Thanks Bedlam, that is bloody interesting to say the least.

Of course, being a glass half empty kinda guy, my mind immediately started thinking...if only we could engineer these artificial defensins to REMAIN in the body...permanently!

Like antibodies, but with artificial defensins instead, poised to strike a bacterium or fungi the moment they infect us.

These could be given to recruits as part of their normal round of jabs when joining up, they'd stick around in the body until needed.

But will it cause a worse population explosion in third world countries?

No, i don't think it would do.

The reason the 3rd world has a high brithrate, is due ironically to their relatively high death rate.

More offspring = A higher chance at least one of them will survive to pass along their genes (among other economic reasons).

If the death rate dropped and dropped dramatically, the birth rate would plummet in a short time IMO.