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The latter half of a charming video by Kurzgesagt[0] talks about the tension between anti-bacterial resistance and bacteriophage defenses - we might be able to see-saw treatments based on what local microbes have adapted to. I only mention it as a tangent, and because your comment makes me think you'd be interested.

[0]https://www.youtube.com/watch?v=YI3tsmFsrOg

The whole concept of phage therapy is somehow based on this: Bacteriophages inject DNA into specific bacteria that makes them copy the phage inside them until they burst open.

Basically use viruses against bacteria.

https://www.youtube.com/watch?v=YI3tsmFsrOg

⬐ searine

The issue with phage therapy is that it has to be targeted.

With antibiotics, they are very broad spectrum so you can throw augmentin at routine infections and it'll usually work.

With phages, you have to be much more specific. Phage X for bacteria Y. It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work.

⬐ nitrogen

It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work.

There are companies out there developing more rapid test panels that will give an answer within minutes or hours, and they charge in the $200 range to test for dozens of pathogens at once.

Someone I know works for such a company, and a lot of the "doctor ran 20 tests for $x000 when they should have just run one" stories in the news are actually about those types of all-in-one rapid tests, and the insurance/hospital doesn't know how to bill it reasonably.

⬐ Supermancho

Notably Kaiser Permanente does this

⬐ jjoonathan

> doesn't know how to bill it reasonably

That's a very charitable interpretation.

⬐ RcouF1uZ4gsC

> It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work.

Also you may not have time. If the person has meningitis for example, if you wait to try to figure out what bacteria they have before treating, they will be dead.

Broad spectrum antibiotics are great for this kind of thing in that you can start treatment immediately, and once you figure out the bacteria, narrow the treatment to that type of bacteria.

⬐ rdedev

Not just this, but our immune system recognizes phages and removes them from the blood stream quickly. So you would need a lot of phages to see some value

⬐ virtue3

The other side of this is that people get long term side effects from drugs like augmentin.

Muscle tightness can lead to injuries, depression, anxiety, etc. Not to mention it takes a very very long time to restore gut flora to pre-treatment conditions.

With enough money I'm sure they could make very very quick tests for each bacteria type that are commonly targeted.

⬐ Fomite

Time is a huge deal. There's a conflict right now between sepsis guidelines and antibiotic stewardship guidelines on when you should start treating, and having to wait for both the diagnostic and the phage prep is sort of a problem.

⬐ suifbwish

This is also why bacteria can develop resistance to antibiotics. You can’t develop resistance against something that is 99.999% effective through design

⬐ dnautics

it's not like bacteria haven't developed resistance to phages. what do you think CRISPR is?

⬐ Fomite

Interestingly, in several phage-treated patients, the bacteria then had increased susceptibility to antibiotics. Combination therapy is a remarkable thing.

⬐ GuB-42

It is not that bacteria can't become resistant to phages. It is that it is comparatively easy to make new phages to the resistant bacteria. Being viruses, they will evolve with the bacteria they target.

The problem with antibiotic resistance is not the resistance itself, but that we don't seem to find new antibiotics anymore. As a result, once bacteria are resistant to all what we have, it is the end.

⬐ FooBarWidget

But isn't that just a market problem? Once resistance is widespread, won't companies be incentivized to find new antibiotics?

⬐ galangalalgol

There are presumably a finite number of chemicals that are of the right molecular size to get where they need to go, kill a reasonbly broad range of bacteria, and don't harm humans. We may have found them all already.

⬐ suifbwish

We aren’t finding new antibiotics anymore because there are only so many human-safe systemic vulnerabilities to take apart/stop bacteria metabolism biochemically without moving into the genetic arena for further variation. What we are really exhausting are the biochemical differences between our cells and the bacteria cells by wiping out things that make the bacteria unique. This is really bad because it drives additional compatability with the human body while eliminating ways for our immune system to tell them apart as well. We have been driving the evolution of bacteria toward this since we discovered penicillin. What we need is to introduce new genes blocks into wild bacteria that make them susceptible to artificial compounds we create while also conferring a survival and even reproduction advantage to them over bacteria that lack the implanted gene blocks. This would balance out the evolutionary force of the artificial compound vulnerability. I’m fully expecting the Jurassic Park chaos mettling with nature speech but we have precious few options when completely resistant strains of new lethal bacteria inevitably emerge.

⬐ ghgdynb1

That's true, but I have a thesis for why this might be good for the biotech ecosystem.

A lot of people will dismiss phage therapy on economic grounds, suggesting that you'd need to essentially design a new phage therapy for each individual infection you wanted to treat. But, with the advances we're seeing in microfluidics, diagnostics, gene sequencing, computational biology, laboratory automation, and the theory of precision medicine, that host specificity can turn from a disadvantage to an advantage. We know there are a lot of human-dwelling bacteria we wouldn't want to knock but can't save from a broad-spectrum treatment. With a personalized phage therapy, this isn't as much of a concern, and with the above advances, custom therapeutic design can scale economically.

But here's the most important implication of phage-host specificity for biotech business models. When a biotech company gets approved to roll out custom therapies for each individual patient, that opens the door to solving two important roadblocks to biotech innovation. First, firms could get around the problem where they're subject to regulatory scrutiny based on a naive interpretation of the difference between their manufacturing costs and their sale prices. Second, such a paradigm of treatment could permit biotechs to offer gradations of service and charge based on how finely-tuned your therapy is. This would enable them to much more closely fit the demand curve of patients. They could bring the latest technology to the masses cheaply and relatively quickly, while charging a premium for the cutting edge.

Bacteriophages (viruses that infect bacteria) are particularly interesting, because we might be able to use them as targeted antibiotics: https://www.youtube.com/watch?v=YI3tsmFsrOg

Also a nice informative video on bacteriophage from Kurzgesagt: https://www.youtube.com/watch?v=YI3tsmFsrOg

A very insightful and concise video on bacteriophages by Kurzgesagt: https://www.youtube.com/watch?v=YI3tsmFsrOg

⬐ war1025

That video was awesome. I really liked the animation style they used.

⬐ lugg

Maybe not so animated but I really got excited by this ted talk about phages.

https://www.ted.com/talks/alexander_belcredi_how_a_long_forg...

Kurzgesagt has a great short video on phages: https://youtu.be/YI3tsmFsrOg

Relevant Kurzgesagt video explaining _everything_ about bacteriophage[1]. I posted this a while ago, but since it's a video it didn't get much attention.

[1]: https://www.youtube.com/watch?v=YI3tsmFsrOg

⬐ ArtWomb

Actual movies of phage infection will soon be visualized using Cryo-EM resolution techniques ;)

Counterpoint: A recent Kurzgesagt video suggests that we may be able to deploy bacteriophages (bacteria-attacking viruses) to combat superbugs. https://www.youtube.com/watch?v=YI3tsmFsrOg

Note: I'm not a doctor/biologist/etc., so I cannot comment on the details of this claim (e.g. how far away we are from a widely deployed phage-based treatment).

⬐ acjohnson55

Reading the Wikipedia article, it sounds like we're nowhere close to being able to deploy phage therapy on a large scale, due to practical, economic, and regulatory challenges.

https://en.wikipedia.org/wiki/Phage_therapy

⬐ DonaldFisk

They were deployed on a large scale in the Soviet Union. They're not patentable, so it's difficult for private companies to make money out of them. Phage therapy could still be developed by a government-owned and run health service.

⬐ ceejayoz

Why wouldn't phage therapy be patentable? A quick Google reveals a number of them.

⬐ DonaldFisk

Because they're natural organisms. You can't patent them any more than you could patent a breed of dog.

You might be able to patent genetically engineered ones, or a novel process involving them.

⬐ WalterSear

Constant evolution.

⬐ tim333

The phages are found in nature so you cant really patent them. Using them to treat patients has been done for a century or so so it's hard to patent that.

The FDA could help by letting anyone provide phage therapy without further testing given it's been proven over the decades and is pretty harmless to humans. At the moment I think you'd be blocked by regulations, unnecessary ones in my opinion.

⬐ acjohnson55

It's unclear to me whether this is something a normal person would have access to, in the same way as antibiotics. Maybe it is, but I'm just not assuming this to be the case.

⬐ searine

Phage therapy is as effective as antibiotics but it is not as convenient as chemotherapy.

One of the problems with phage therapy is precision. You have to know roughly what kind of bacteria is causing the infection. To know that it takes tests, and time, which cost money. Antibiotics on the other hand are broadspectrum and can be deployed without much prior knowledge (which is cheap, but also a problem that causes resistance).

The other problem is production and regulation. Antibiotics are chemical, phages are biological. It is much harder to produce a consistent safe product with a biologic compared. We don't have the infrastructure (yet) to mass produce viral phages for consumers.

⬐ AstralStorm

Even if we did, the sampling itself would be onerous. Unless you could somehow guess the phage based on immune response or metabolic products as in blood sample. Which is extremely hard to pull off and still much harder than guessing the right antibiotic in most cases.

⬐ DonaldFisk

Bacteriophages were used instead of antibiotics in the Soviet Union, and are still used today in Georgia.

⬐ smaddox

My extremely limited understanding is that a given bacteriophage only attacks a very specific strain, and thus that you would need to constantly evolve them to fight new strains. While perhaps not useless, that doesn't sound like a replacement for antibiotics.

⬐ DonaldFisk

In the Soviet Union, they used cocktails of bacteriophage in much the same way as broad-spectrum antibiotics are used, whenever it was impractical to identify the bacterial strain.

Bacteriophage evolve of their own accord, so phage resistance is temporary. Often the bacteriophage strain you need already exists and you just have to find it. This is much less effort than developing a new antibiotic.

⬐ AstralStorm

The general problem is that bacteria co-evolve with phages making outdated stains as worthless as last year's flu vaccine most of the time.

⬐ JulianMorrison

Also bear in mind that as far as new strains in one patient go, unlike antibiotics they will evolve themselves to chase the new strain down, and that's useful.

⬐ AstralStorm

And sometimes not. Please provide serious efficacy numbers compared to antibiotics.

⬐ sdabdoub

You are correct, however with new sequencing technologies like the MinION[1] we have access to real-time sequencing in something roughly the size of a cell phone.

They are still in development and there are some technical hurdles, but before too long cheap, fast, and accurate strain typing should be ubiquitous. The next issue is then creating the specific phages, but the first stage is pretty close at hand.

[1] https://nanoporetech.com/products/minion

⬐ AstralStorm

And the final issue will be actually getting this in the field for non laboratory personnel. Where a GP can fashion a phage in their office and/or order one as easily as the right antibiotic.

Good luck trying to even get the bacterial sample to do it for quite a few kinds of infections. Lungs and other organs would need a good biopsy or at least really well done aspiration, handling of samples is very messy.

It is a good method to use in hospital settings perhaps where you want to sample anyway.

⬐ JulianMorrison

Possibly with CRISPR patching of their innards, you can tailor-and-deploy them automatically?

⬐ aaronblohowiak

The other parts of the process are still quite onerous

⬐ ManFromUranus

Well not an easy replacement anyway, but something that is always useful forever.

⬐ balls187

Given how medicine works in the US, that's not a problem, but an opportunity.

US Medicine is for profit, and the money is in reoccuring treatment, not cures. So a never ending battle of cat-and-mouse is the type of R&D phramas would love.

A potential future scenario:

Keep going to your doctor to get a Rx for the latest strain or pay a monthly fee to a Bacteriophage-As-A-Service SV tech company to get the latest delivered right to your door you use in conjunction with a smartphone app.

The latter of which would have operated illegally until sufficiently large enough to hire insider DC lobbyists to gut the FDA.

⬐ DonaldFisk

And yet phage therapy's been successfully used under communism but not capitalism. This is because it's cheap, low tech, and there are no economic barriers to market entry.

⬐ AstralStorm

You forgot to mention the scale. It does not easily scale as the required laboratory space to handle even a few hundred phage strains is enormous.

Please provide numbers of patients treated with phages, time to treat one and efficacy numbers.

A short animated introduction to Bacteriophage by Kurzgesagt: https://www.youtube.com/watch?v=YI3tsmFsrOg

Is this Kurzgesagt video relevant? https://youtube.com/watch?v=YI3tsmFsrOg

Kurzgesagt video on bacteriophages released a few days ago.

https://www.youtube.com/watch?v=YI3tsmFsrOg

Kurzgesagt goes through bacterophages in this video: https://www.youtube.com/watch?v=YI3tsmFsrOg

I think this is the case mentioned by Kurzgesagt in the video, although he doesn't use names, so I can't be sure. Super cool, anyways!