[Blahah]

That's not the only reason no-one uses phage therapy - there's also a strong cultural resistance in the west. I've worked on phage targeting various Salmonella serovars, and while you do require cocktails for the most effective treatment, but phage evolve along with the pathogen. There's no inherent limit on the availability of phage like there is with our current suite of antibiotics.

With extensive sequencing-based environmental monitoring, as we're starting to see in many western countries, we can detect the evolution of new bacterial and phage strains in near real-time and isolate the phage to treat the pathogens. We can keep up with pathogen evolution. There's no equivalent system for generating new antibiotics. I reckon this kind of tech is only a few years away - all the pieces are coming into place.

[haldujai]

No but it's the main reason. If I had a nickel every time someone told me we can do real-time sequencing I'd be rich. You're greatly overestimating our technical capabilities and underestimating the costs and challenges that would be involved. Theoretically we can identify a new phage a week after resistance is detected, factor in all of the other costs and time involved and it's even worse. The major downside of phage therapy is that there is no readily available phage if resistance develops as there is with antibiotics (the manufacturing process for a new phage is not that short). If you find a methicillin resistant infection you can give a tetracycline or cephalosporins.

Additionally, don't forget that phages are not all lytic and not all are effective (i.e. look at C. difficile) and that phages won't affect intracellular pathogens (i.e. Salmonella, to my knowledges phages don't work but please share as you say you have experience with this).

So while phages can be useful (I never said they weren't) their use is limited and has it's own drawbacks.

[j_baker]

but phage evolve along with the pathogen.

How do you prevent the phage from evolving to target the human cells?

[haldujai]

(Bacterio)phages target bacteria only by nature, there are several mechanisms that prevent them from targeting human cells. They recognize bacterial membranes and not human, their replication mechanisms don't work in human cells and our cells have defenses against them. In short it would take a great amount of evolution to make them target human cells in the order of thousands of years at least due to the several existing barriers.

See: https://en.wikipedia.org/wiki/Bacteriophage

Edit: Just in case someone calls me out on this 'thousands of years' is an educated guess on my part from studying evolution not something I've actually read.

[tedunangst]

How long did bacteria and penicillin coexist? Thousands of years? Then practically overnight the bacteria decided they needed to evolve...

I don't think evolution always works according to the popular "and then the next giraffe's neck was 1mm longer than its parents'" gradual change model.

[lutusp]

> How long did bacteria and penicillin coexist?

In different places, not an issue. It's only when penicillin is directly applied to a bacterial colony is there any chance for bacterial evolution to take place.

> Then practically overnight the bacteria decided they needed to evolve

You mean, when humans applied penicillin to bacteria on a large scale for the first time? That changed the bacteria's environment, most died, except those naturally resistant. It's classic natural selection.

> I don't think evolution always works according to the popular "and then the next giraffe's neck was 1mm longer than its parents'" gradual change model.

But one can argue that evolution almost never works, on the ground that the vast majority of mutations aren't adaptive. But the argument misses the point that some tiny fraction of the mutations become the entire future species because of increased reproductive fitness.

Also, the "gradual change" you describe normally arises because of the odd beneficial mutation, which, apart from being very improbable, might require many thousands of years to manifest itself.

[j_baker]

Fair enough, but I suspect "thousands of years" of evolution may come very quickly if phages were to be used half as widely as antibiotics are.

Besides that, not all of the cells bacteriophages could harmfully target are human cells. What about the billions of gut bacteria in our digestive tract?

[coryrc]

You don't take phages back out of the person, so the source is not under evolutionary pressure to affect humans -- each batch is "seeing" humans for the first time.