Tragic and stupid beyond belief if this is true. Equivalent to using one's own kitchen sink as a toilet bowl.
No, there isnt. It’s theoretical.
What’s most concerning isn’t antibiotic use by farms but how wide a range of antibiotics are used. If we limited the industry to only use a specific set of antibiotics that would be one thing, but they keep having access to newer drugs.
Phages also have their own caveats but I don't remember what it is. The TLDR is that in the worst case scenario we still have phages and as far as I understand no bacteria can adapt to phages. But we need to figure out a way to make it commercially viable as you put it.
I’m sure this is dumb because if it wasn’t somebody would have done it by now, though.
There's an arms race between bacteria and humans: bacteria infect humans → humans develop antibiotics to kill bacteria → bacteria evolves resistance against antibiotics → humans develop new antibiotics to kill resistant bacteria → bacteria evolves resistance to new antibiotics → ...
Developing more and more new antibiotics for resistant bacteria is slow and expensive. Bacteriophages (viruses that infect bacteria) on the other hand would naturally evolve with the bacteria, like how COVID evolved new strains in response to our vaccines.
They are among the most abundant "forms of life" in the whole world, as google details:
> There are up to ten times more phages in the oceans than there are bacteria, reaching levels of 250 million bacteriophages per millilitre of seawater.
If we were able to quickly find the right phage for bacteria that causes infection, that bacteria would have no chance. And we do know that for every bacteria there would be infinite phage variants they just can not defend themselves against by design. From what we know bacteria, all life in general will always stay vulnerable to viruses.
The problem is that our science on finding, producing and using bacteriophages is extremely limited for technical and financial reasons.
Yeah, no. Quite the opposite in fact.
It's just... really hard, takes weeks to months (if you're engineering, and then it's GMO, which is another can of regulatory worms).
It's not even expensive; we just use regular lab equipment. But people are doing lot of things by hand today. But we're finding ways to scale up and insert robots like OpenTrons and Singer!
> extremely limited for technical and financial reasons
The severance packages of each tech layoffs is more than what our entire field gets every year in funding.
And not even viruses are safe from viruses: https://en.m.wikipedia.org/wiki/Virophage
First they're difficult to make and store (antibiotics are mostly shelf stable... phages aren't). Second, they are not broad spectrum. Third, (at least in the US) phage therapy hasn't taken off because the initial forays into phages showed that they can cause reactions. Lastly, not all bacteria have phage counterparts.
So if you even could use phages, you're looking at weeks of testing to determine what bacteria to target, before production. You could keep a library of phages for known bacteria, but that library would be highly specific.
There's also the pre-treatment testing that would be necessary to determine what to target. There's also the shipment of a bacterial specimen that would be used to create a phage (which is something we don't do currently... we'll ship a specimen to a testing center, best case). Those are two different bacterial specimens needed. Then you have to ship the phages back. Alive. Then store and administer then properly. People fail to take their antibiotics properly. They're going to royally screw up phages.
What about bacteria that you can't culture (treponema pallidum, aka syphilis)?
All of this is in contrast to antibiotics. Is it gram positive or gram negative? Treat. Did it work? Yes, good. No, treat again. Did it work? Yes, good. No, test for resistance. Move to a stronger antibiotic and repeat.
You really don't even need to know what the exact bacteria is that you're targeting with antibiotics.
https://www.dsmz.de/press/press-releases/singleview/zertifiz...
And this video is rly interesting https://m.youtube.com/watch?v=YI3tsmFsrOg
They're not without their problems, but there are also problems with antibiotics (bacterial resistance, penicillin allergy). So why not use them whenever use of antibiotics is problematic? They're cheap, and reproduce at a phenomenal rate. They were used successfully in the Soviet Union, and are still being used in Georgia.
There are still challenges though.
For bacteria with high resistance (which is what we have the biggest issue with), we've typically done a workup of the bacterium to target. In the worst case, these are what land people in the hospital. Hospital settings would be the best administration point for these therapies. The problem would still be the creation of the specific phages in a reasonable fashion. This would only really be available at major hospitals in major cities. And so... limited in usage.
I could see major hospitals keeping a large amount of gonococcal phages on hand though.
Edit::
One more thing. As far as antibiotic allergies (you mentioned beta lactams) we typically have antibiotic alternatives. Doxycycline is pretty much well tolerated by everyone. And it's available in pill form.
I think you are overlooking some of the major technical problems with phages. In no particular order:
1. The immune system develops antibodies for many phages.
2. Microbes develop resistance to phages.
3. Phage multiplication using host cell is a primary step for phage production, and this causes many (serious) adverse effects.
4. Only obligate lytic phages that lyse the bacterial cell directly instead of integrating its genome in bacterial DNA (temperate) are usable for phage therapy. Temperate phages play a major role in the exchange of genetic material between different bacterial strains and often contribute to the pathogenicity.
Drug resistant bacteria are here. Hasn't push already come to shove?
Phages are interesting, but given that there are substantial challenges on the road to making and administering them (and you can be in a race against the clock as someone's infection progresses), shouldn't we also be trying to use existing antibiotics far more strategically?
Phages do work, and we've treated a small bunch of people at Phage Australia for our clinical trial.
There's a few things about using phages for treatments I think everyone should be aware of:
(1) phages work!! The physicians we work with (and ourselves) are surprised every time they work. It's just really labor and time-intensive.
(2) if antibiotics are "bite sized snacks" then phages are like "getting a personalized chef - a course of phages should be highly personalized to the pathogens causing trouble, and sometimes the antibiotics. Too generic and it won't work. Too personalized and it's too expensive. Tricky balance. We're collecting data and trying to figure out what that balance is. Every patient is very different though and it's hard to draw conclusions and see patterns.
(3) at Phage Australia we're not doing the cocktail approach — we're (trying to) assembling a library of phages that should be able to cover lots of common pathogens and local outbreaks. We work with antibiotic resistance reference labs and hopefully eventually get enough coverage, by building a library of phages that we can mix and match before we get an inquiry. The TGA is onboard with this. (The FDA is looking into this tentatively; look up Adaptive Phage Therapeutics). The kind of phage therapy we're looking at is closer to CAR T-cell therapy, FMT and other kinds of individual / personalized therapies.
tl;dr: Phages work, but getting them and getting/paying for them is more like a service and less like a pill. It's also very expensive and hard to do today. We to work with regulators to push more personalized therapies. The age of generic pills in a bottle is slowly fading away.
(Source: I'm the "computer person" aka research software engineer on the Phage Australia clinical trial)
The original patent for insulin was given away by it's discoverers because they wanted everyone to be able to have access to inexpensive insulin. That hasn't stopped pharma companies from coming up with patents around formulations, manufacturing methods, delivery methods, etc. and making tons of money off of insulin.
Sibling comments have pointed out the real reasons it's not commonly used despite the promise. I just wanted to point out not being able to patent something is almost never a barrier for pharmaceutical companies if they think they can come up with a profitable therapeutic.
[1] https://patents.google.com/patent/US10357522B2/en?q=phage+th...
But do these guys know what they're talking about?
https://phage.directory/capsid/phage-patentability
You may have heard through the grapevine that “phages can’t be patented”, and yet, several phage patents exist, and biotech and pharma are starting to invest in phage-based therapeutics. What’s the deal? [...] However, the patentability of phage therapies has been called into question. Several patents in the same category as phages have actually failed to hold up in court. This suggests that even if companies can find ways to successfully file phage patents, these patents may end up being worthless.
So phages may need protection in other ways.
Here is some info from a leading IP firm on the challenges around phage patents and how to address them when filing [1]. As they pretty clearly point out there are some challenges, but creating defensible patents in this area can be and is done. These companies can pretty much always find a way to create a defensible patent if they want to.
[1] https://www.nixonpeabody.com/insights/alerts/2021/03/03/pate...