It's not just regulation. They're also not very good - there's a reason antibiotics won (we used to use phage in the West too - they developed a dangerous reputation because we weren't good at purification). Russia used them because antibiotic availability was constrained.
A post on this from a day or so ago, my usual take on phage, from the standpoint of someone who works in healthcare epidemiology and has always been fond of phage therapy:
1) Even with resistance on the rise, we still have antibiotics that work. Phage therapy is a "someday we're going to need this...we think" type treatment.
2) There's no such thing as a "broad spectrum" phage. They're organism specific, and that means not only would you need to keep a phage library on hand, but you'd have to do a lot of diagnostic tests. That's going to be both expensive and tricky.
3) Phages are living things. Not only is that a weird regulatory framework to be in for a drug, but it also means that you need to be able to keep phage alive. In contrast, antibiotics are inert.
4) Phage therapy is also relatively new in the West, which means there's just less of a R&D infrastructure behind it.
There have been people working on commercializing phage therapy since I was in undergrad (I'm now a tenure-track professor). The problem is it's hard, and antibiotics are so much better as a treatment that there's kind of a ceiling on the excitement that they can generate.
> 1) Even with resistance on the rise, we still have antibiotics that work. Phage therapy is a "someday we're going to need this...we think" type treatment.
We have antibiotics that work for most infections. For people with antibiotic-resistant infections (especially hospital-borne ones) they are already not an option. A childhood acquaintance of mine with CF recently died of an antibiotic-resistant infection in her newly-transplanted lungs. Lack of awareness and research into phage therapy was fatal in her case, as it meant they started the process late and it took longer than it needed to.
Said process is: take samples of the infectious agent, culture them, and send the cultured bacteria to "phage banks" so they can test their existing phages against it. There's a lead time both because of the initial setup required per-patient, and because of the scarcity of comprehensive phage banks and the lack of good coordination between them.
I'm not aware of any phage treatments suitable for lung infections - mostly, it's been skin and soft tissue sites, but I'd be happy to know if there is one.
And yes, highly resistant infections are a problem - and one I work on - but from a "market forces" perspective they're still relatively rare. Even for most highly resistant infections we still have some antibiotics that work - not well, and not without side effects, etc.
Not any current standard phage mixtures, but especially for lung disease they're an active area of research. Delivery mechanisms seem to be a pretty solved/relatively-trivial problem. See e.g. https://www.sciencedirect.com/science/article/pii/S156919931...
In this particular case, they found a phage for the particular infection, but at too late of a stage - most of the development I've heard of has been less about basic research and more about building institutional processes for quickly finding existing predators of a given bacterium. (Which, I agree, is a lot more expensive and risky than an antibiotic if you can find one that works.)
Re 1) It is useful to keep exploring other means of treatment because at some point you won't have antibiotics left. You want a secondary method that can be deployed instantly once the primary fails. Currently cryptographs are developing Quantum-Computer-resistant cryptographic algorithms not because there is a quantum computer that can crack RSA but because a quantum computer that can is in the not to distant future and if it exists then we need immediate replacement.
Re 2) I don't think that would be a problem considering together with 1 there will simply be a need to develop a quick but reliable method to test for which collection of phages work, probably even develop cocktails of phages for a more broad application. Reducing the amount of antibiotics used would also help reduce the risk of the broad spectrum antibiotic failing because of resistant bacteria.
3) Phages are living things depending on who you ask. Phages are rather simple and will to my knowledge remain viable for a good and long time. Antibiotics may be inert but also have an expiration date, you can't just use an 60yo antibiotic and hope that works. At some point the contents of the antibiotic will have broken down and oxidized.
4)Fair but apparently people have been using it in the Eastern Block for a while with some success. There are some shoulders to stand on and continue R&D.
On 1) I agree, but it's a hard ask in the face of antibiotics being markedly superior as treatments. Because it's not really "a secondary method if the primary fails" (that would be a 2nd class of antibiotics) it's an entirely different paradigm, and one that works less well on the ground.
2) "There will simply be a need to develop a quick but reliable method to test..." is a really big ask. We don't have quick but reliable tests for some common human pathogens. You can't simply posit that a great test will work. You're right about antibiotic stewardship, which is something I work on, but that's orthogonal to how good phage are as a clinical treatment.
3) While yes, in some particularly strict senses they're not alive, the actual point of that is there's currently no phage preparation technique that is not extremely lab intensive at the site of treatment.
4) Agreed - and the Russians and Georgians have some really cool work, but even there, it's for what are, clinically, extremely difficult edge cases, rather than the kinds of things antibiotics are routinely used for.
1) It's a lot cheaper to have antibiotics properly regulated and conservatively prescribed. That's how Norway still manages to do just fine with Penicillin in majority of cases. Voila, no need for phages.
4) USSR jumped onto antibiotics as soon as they were available, and hasn't really looked back.
1) Can you get the industrialized farm lobbies on board with this? How about 3rd world rural clinics? How about 3rd world farmers using powerful antibiotics of last resort to make animals get a little bigger?
Successfully regulating antibiotics is a worldwide effort. I'm not confident we'll ever be more than moderately successful at that.
If that was easy that would obviously been done by now. Doesn't mean the alternatives (like phage libraries in "3rd world rural clinics") are more realistic.
Proper antibiotics circulation is a policy problem; phage therapy is scientific, technological and policy problem.
5) phages are viruses and our bodies are very efficient at not letting them in, so you can't just pop a pill, you need them injected into the bloodstream
6) you need a lot of phages (and/or a steady supply of them) because they don't replicate in our bodies (they don't infect us), but our immune system is very good at clearing them out so their blood concentration drops really fast
7) because phages are viruses and we need them injected into bloodstream in copious amounts, our own immune response to them may become a problem. Potentially-fatal-cytokine-storm kind of a problem.
Viruses are more like a delicate molecule than like a living thing, because they don't have a metabolism. Kept in the proper conditions they last indefinitely.
"more like" in this context. "Are viruses alive" is the most popular thread in bio-ontology, locked by the moderator after 12,493 pages of heated debate.
I chose "alive" because, well, HN is not always the best at biological nuance.
But there's a few major concerns:
1. Most preparations are bespoke. The FDA has made some headway with this because of fecal transplants, but it's still a problem.
2. Phages evolve. That's one of the benefits of them. Generally speaking, self-adaptive medications are not something we have a good regulatory context for.
3. They need culturing, isolation, identification, etc. and those are "wet lab" things.
I wonder about the unknown cost of antibiotics. Seems like there are a lot of health problems associated with destroying gut bacteria. As these costs become more clear over time I think the value of phages will increase.
bacteriocidal antibiotics tend to be cytotoxic with aminoglycosides causing hearing loss, fluoroquinolones causing heart problems tendon problems psychiatric problems and even more. Cdiff colitis is a deadly risk and also toxic epidermal necrolysis. These effects are noted to be happening more often than previously thought in clinical trials, in some cases because they can develop overtime rather than immediately.
No they're not. Virus particles are totally inert on their own. They incorporate themselves into and modify other living systems. But that's no different from drugs.
Viruses themselves don't actually multiply. They just force the host (in this case the bacteria) to produce more copies of the virus. Is there some kind of rule that a drug can't force the bacteria to produce more of the drug?
Every virologist I know considers viral replication to be a process of the virus. This argument is like saying "Humans themselves don't build porches, they just force their power drills to."
And while there's no rule that prevents that, I don't know of a single drug - or even the suggestion of a drug - that's capable of integrating with a bacterial host genome, producing the needed compounds, and then exporting them out of the cell.
It's not impossible, no, but it's not a thing presently happening.
How is that any different from probiotics or yeast? Those are also "living" but my understanding is that they are dormant and inactive until reactivated.
(Lots of good points raised in your comment, though.)
- Viruses aren't particularly stable. They're fussy little things - it's easy to deactivate them.
- How you get phage preparations is to find them where the bacteria you want to target are growing, then culture them, filter out the bacterial endotoxins (because that'll kill someone), and then use that purified preparation. That needs a lab, and one that's reasonably good at what it does, vs. a random pharmacist at Walmart.
A post on this from a day or so ago, my usual take on phage, from the standpoint of someone who works in healthcare epidemiology and has always been fond of phage therapy:
1) Even with resistance on the rise, we still have antibiotics that work. Phage therapy is a "someday we're going to need this...we think" type treatment.
2) There's no such thing as a "broad spectrum" phage. They're organism specific, and that means not only would you need to keep a phage library on hand, but you'd have to do a lot of diagnostic tests. That's going to be both expensive and tricky.
3) Phages are living things. Not only is that a weird regulatory framework to be in for a drug, but it also means that you need to be able to keep phage alive. In contrast, antibiotics are inert.
4) Phage therapy is also relatively new in the West, which means there's just less of a R&D infrastructure behind it.
There have been people working on commercializing phage therapy since I was in undergrad (I'm now a tenure-track professor). The problem is it's hard, and antibiotics are so much better as a treatment that there's kind of a ceiling on the excitement that they can generate.