Yeah, there is something that is regularly overlooked about developing antibiotics: new ones end up on a shelf as the new last resort. If you've got a timeframe (imposed by patent lifetimes) in which you have to recoup your investment, that is a shitty situation for a pharma company to put itself in. "It's for the public good" is not the kind of due dilligence many shareholders like...

You can consider this problem in two ways. Either you see the need for increasing the patent lifetime - at least for certain drugs - or you consider this a weakness of a privatized pharmaceutical industry, and take it as an argument in favor of placing the government in charge of pharmaceutical developments.

I believe it shows the general insanity of the whole health and food-production systems.

As I understand the situation, antibiotic resistance isn't a generally useful adaptation - bacteria tend to lose it "in the wild". So prevalence of antibiotic resistant bacteria, in non human-to-human born diseases like Staph infections, is a somewhat direct result of maintaining a long term, antibiotic filled environment.

Yes and no. We do overuse (and mis-use) antibiotics, but as long as we use them at all, bacteria will have an evolutionary pressure to adapt to their presence. So while we can mitigate antibiotic resistance by reducing use, we'll only slow down the problem.

Antibiotics have changed the way we live, but the price of that change is that we have to invest in the arms race. We invest in all the other arms races, so why not this one?

"We do overuse (and mis-use) antibiotics, but as long as we use them at all, bacteria will have an evolutionary pressure to adapt to their presence."

Not necessarily a decisive pressure however. For bacteria which primarily "prey" on human beings this would be true. For bacteria which are primarily endemic to the environment, the loss of fitness involved in antibiotic vulnerability is something of a drop in the bucket. Remember this resistance has a cost in physiological adaptation too. These bacteria, like Staph, that might be "happy" to subside to resisting the common chemicals in a barnyard - unless we human produce an environment where tolerating antibiotic gives the organism a natural bridge to spread through - gigantic hospitals with filled with humans pumped with antibiotics or huge feed lots filled with similarly pumped animals "come to mind".

When very bad outbreaks start to occur because antibiotics' effectiveness starts dropping precipitously, I think there will be progress. It will take a few years to get ramped up, but given modern technology I think there will be some interesting partial solutions fairly soon after that.

The Russians were particularly interested in this sort of thing during the latter part of the Cold War, as I'm sure the West was, and still is. They were looking at enhancing the immune system as an alternative to antibiotics or vaccines for agents that could not necessarily be fought with antibiotics or vaccines (i.e. biological terrorism). They also looked at using immune response as a bioterror target (e.g. something like the reaction to TGN1412 but using a transmissible bioagent instead of a non-biological agent.) They were keenly aware that the two problems were linked.

Obviously, immune response is bad at all times when there's no active threatening infection to fight, but needs to be maximized at least along certain paths when there's a threatening infection. That was a difficult problem with 1980's technology. I'm optimistic that it's not quite so intractable a problem, at least in cases of common bacterial infections typically treated with antibiotics today. More narrowly targeted immune system boosting seems plausible now that there's a somewhat better understanding of immune system interactions...

"enhancing the immune system"

Note that one possible flip side of this is auto-immune diseases.

"immune response is bad at all times when there's no active threatening infection to fight"

I don't think that's at all true. Our immune systems tend to work wonderfully most of the time given that we're constantly bathed in potentially pathogenic bacteria. In this discussion scythe says of "the ESKAPE pathogens, which are the primary superbugs" that "in every case except S aureus, infection is basically unheard of when an individual has a functioning immune system; they are all opportunistic pathogens". I take that to mean that for a lot people, temporary immune system dysfunction, e.g. due to other insults to the body, are a big factor.

I noticed on Wikipedia that one of the ESKAPE bacteria, Acinetobacter baumannii (http://en.wikipedia.org/wiki/Acinetobacter_baumannii), "Colloquially, A. baumannii is referred to as 'Iraqibacter' due to its seemingly sudden emergence in military treatment facilities during the Iraq War. It has continued to be an issue for veterans and soldiers who serve in Iraq and Afghanistan. Multidrug resistant (MDR) A. baumannii has spread to civilian hospitals in part due to the transport of infected soldiers through multiple medical facilities."

That I assume is largely due to gross trauma (and lots more soldiers surviving because of much better body armor (even helps in non-comat accidents I've read) and ever better treatment) ... and e.g. car crashes in the US tell us we're not soon going to be rid of that problem....

I realize that auto-immune disease is a consequence of overactive immune system, and I thought I alluded to that in the last paragraph. I guess I don't believe that the only way to enhance the immune system is to make it more active in general or in ways that would necessarily lead to increased instances of autoimmune disease.

I should have said wherever rather than at all times when. I don't try to discuss this a lot so I guess I'm not as precise at organizing my thoughts as I'd like to be. Thanks. Yeah, "superbugs" are disproportionately at hospitals, and garden variety bacterial species; they cause problems because patients tend to have wounds or compromised immune systems, and because the frequency of antibiotic use at hospitals encourages thriving populations of resistant strains.

Ah, yes, I can see that now, "[m]ore narrowly targeted immune system boosting" is definitely an option. Although ... do we want everyone in the country/world taking the same "ImmuneBoost(TM)"...? (Not a particularly useful criticism, but still something to also think about.)

Especially if we can find ways sufficiently weighted towards bacteria. The major thing that saves us with them is that their significant low level differences from eukaryotic cells, e.g. those smaller and different ribosomes that provide a handy target for various antibiotic families (they're the organelles that synthesize proteins). Or their plant style cell walls.

(I stopped paying attention to the details of immune system in the late '70s when I noted how fast we were learning about it, i.e. for me it's something to learn/review "on demand", so I can't make any really specific suggestions as to what to do or judge the feasibility.)

I'm a fan of distributed separately-evolving defenses, and identical ImmuneBoost(TM) given to everyone, that has the same effects in everyone, could I suppose create susceptibility to some HIV-style pathogen that triggers and/or hijacks the specific boosted aspects of the immune system. HIV is very careful (i.e. has evolved) to stay dormant for a long time... it probably didn't start out that way, and suffered as a result. Any sort of pathogen that targets the immune system has to be similarly careful; otherwise it suffers the same fate of all extremely lethal pathogens: killing the host population faster than it can spread.

Another promising research avenue is bacteriophages. I don't know why it's being pursued more in the former Soviet Union than it is in the West. I suppose even with targeted bacteriophages there's some risk that they could mutate and start targeting beneficial bacteria, which would be a problem.

A cute CS-inspired theoretical approach would be to throw variable layers at the problem. With genetic engineering, create bacteria that function as a supplemental immune system, but in a very narrow way; the bacteria would, possibly in collaboration with the host immune system, generate specific bacteriophages for any pathogenic bacteria they come into contact with. Obviously it wouldn't work against pathogenic viruses, but other than the (perhaps impossible) difficulty of having a cell able to generate novel bacteriophages, it doesn't seem so outlandish. If we get to the point where we can write code for a wide variety of biological activity and get it translated into DNA, then such a bacteriophage-generating bacterium might be possible.

I realize there are pathologies imaginable with any possible solution. The question is how likely is it that natural or engineered pathogens will target whatever new targets are available. Bacteriophage-generating bacteria could be hijacked by viruses, mutated by gene transfer with harmful bacteria to do bad things, or even give their bacteriophage-generating properties to pathological bacteria which might then gain mutations to generate human-targeting viruses... wouldn't that be fun.

> When very bad outbreaks start to occur because antibiotics' effectiveness starts dropping precipitously, I think there will be progress.

Hospital acquired infection is a significant cause of death.

> In the United States, the Centers for Disease Control and Prevention estimated roughly 1.7 million hospital-associated infections, from all types of microorganisms, including bacteria, combined, cause or contribute to 99,000 deaths each year.

> In Europe, where hospital surveys have been conducted, the category of Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year.

(http://en.wikipedia.org/wiki/Hospital-acquired_infection)

These are just nosocomial (hospital acquired) and not necessarily antibiotic resistant.

Resistant infections in hospitals must not yet be a significant enough problem to get lots of smart people working on the problem. Or, rather, they're working on trying to contain infections and reduce transmissions rather than on how to treat the infections, right? The other shoe has to drop before other half of the problem gets serious attention.

Interesting. I had a bacterial infection (chronic) lately and was thinking of doing biochemistry as there was no cure in the market for my infection. Surprisingly, honey did a lot more than any class of antibiotics that I tried.

Can I reach you by email?

I use honey along with something called the specific-carbohydrate diet to control (but not eradicate) an infection in my gut.

Certain honeys -- and not particularly the more expensive ones -- are much more antibacterial in this regard than others.

I also thought of natural antibiotics like honey or garlic as substitutions, but I also thought that they would only help with gut infections (e.g. no use for infected hip joint after transplant) - is that not so?

I'm using it with my eyes and it's helping my blepharitis more than steroid and antibiotics did. I don't have deep biochemistry knowledge, but I guess they already tried to find out the antibiotics properties of honey/garlic and it didn't help much in real scenarios.

> I guess they already tried to find out the antibiotics properties of honey/garlic and it didn't help much in real scenarios.

Speaking more generally, there is limited interest from big pharma in the use of natural or herbal products because they will have to spend a ton of money on clinical trials to prove effectiveness, but they won't get the patent protection necessary to recoup the cost of R&D, like they would with synthetic drugs.

I've dreamed about doing an app for crowd-sourced clinical trials. Obviously something like this wouldn't have the level of control as having participants under direct supervision, but it could be close to free if done right.

They just change one atom in the big ole organic molecule that doesn't change the effectiveness, and boom: new and patentable drug.

Presumably you'd then have many more possible patentable, innocuously "different" molecule patterns, ruining the competitive edge.

Just follow the money. There are plenty of research dollars for cures for diseases that afflict rich people. Just claim that you're targeting cancer in some way and cash the checks.

(At least that's the way it was when I was still in the field.)

Allow me to assure you that saying " I just program websites " is selling yourself short.

At the VERY least I urge you to design novel experiments and post them publicly.