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.
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.
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.
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.
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.
And this video is rly interesting
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.
But do these guys know what they're talking about?
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 . 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.
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)
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.
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.
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.
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
Yeah, no. Quite the opposite in fact.
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.
> However, in bacteria grown in anaerobic conditions, levels of reactive oxygen species were much lower and antibiotic resistance developed much more slowly. [ ... ]
> But in healthy humans, E. coli is found mainly in the large intestine, where conditions are anaerobic, meaning that the process described in the paper might not occur at the same rate in people, says Maier.
So the study shows that antidepressants help bacteria resist antibiotics if you test in oxygen-rich conditions. But that doesn't match conditions in the human body, so this may not even be relevant to humans.
Their next step is to study it in mice, which makes sense, but to me it seems like you can't conclude much right now.
Every person in the comments across the internet saying the rise in all of these disorders was just about self-reporting have been unknowingly shilling for big food.
Being anti conspiracy and overly trusting of certain (cough cough) fields of science denotes an inability to rationalize.
This may be true in specific cases... But surely isn't true in general.
It's the role of science and government to find out which anti-biotics, which hormones, and which pesticides case increased rates of which cancers.
As soon as there is evidence suggesting a specific pesticide has downsides that outweigh the advantages, it's time for the government to promptly ban it.
So far, I think the main failure in that process is that governments don't put enough money into science to find said evidence. Simply having a tax on biotech of say 1% to pay for independent scientists to do research would easily be enough to give us good evidence of the upsides/downsides of everything widely deployed.
Not if you subscribe to the precautionary principle
"The principle is often used by policy makers in situations where there is the possibility of harm from making a certain decision (e.g. taking a particular course of action) and conclusive evidence is not yet available. For example, a government may decide to limit or restrict the widespread release of a medicine or new technology until it has been thoroughly tested. The principle acknowledges that while the progress of science and technology has often brought great benefit to humanity, it has also contributed to the creation of new threats and risks. It implies that there is a social responsibility to protect the public from exposure to such harm, when scientific investigation has found a plausible risk. These protections should be relaxed only if further scientific findings emerge that provide sound evidence that no harm will result."
Just one of many brilliant decisions that the primarily white men who have ran this country throughout history made on behalf of all of us. Without our consent, of course.
Good luck proving your dad's colon cancer was caused by industrial solvents in our water supply. Call your congressman! It's a democracy!
The 'white Russians' that fought against the 'red' communists carried the association of whiteness with traditional monarchy forwards into the 20th century and this revanchist monarchism continues to shape radical politics and factional identities in the present, although the symbolism is so diluted as to be unrecognizable to most: https://en.wikipedia.org/wiki/White_movement
If we only look at 'white identities' in terms of racial coding, we fall into the trap of inadvertently criticizing people for a fact about themselves they didn't choose and can't change, and whose structural social privileges (vs those of non-European origin) are so unevenly distributed that the resulting intra-ethnic discontent has to be micromanaged through an elaborate ideological apparatus.
One of several roles of government is to overcome coordination problems that would otherwise inhibit the production of public goods, such as new antibiotics and other better treatments for bacterial infections.
Another role of government is to regulate markets by creating incentives in the form of laws and legal regulations. In this case, government could estimate the societal cost of agricultural antibiotic use, and then impose taxes on agricultural antibiotic use equal to the amount of that cost. if those costs turn out to be punitive, then tough shit, they'll need to figure it out. The proceeds from tax is levied could then be redirected to basic research as needed.
Of course, this doesn't tend to work so well in practice due to any number of corruption and regulatory capture channels, so it tends to be easier to just ban harmful practices outright, which of course governments also have the power to do.
Why not? Wealth-making attracts two kinds of people: those who are interested in mutually beneficial exchanges, and those who see trade as a zero- or negative-sum game. Research suggests these groups exist in a roughly 60:40 proportion to each other in human populations: https://www.science.org/doi/10.1126/sciadv.1600451
I do think your disagreement is sincere, since you propose allocating a tax on technological deployment to fund research and backing that up with strong regulation. But you overlook the phenomenon of regulatory capture by industry and bad-faith politicking. Just recently we saw how a regulator's observations about the surprisingly high negative externalities of gas stoves was quickly turned into a political football, pre-empting any meaningful policy discussion.
Couldn't agree more. The evidence of how ineffective the American scientific regulatory community is all around us.
An easy example is how fast rising yeast impacts gluten intolerance, or how high fructose corn syrup impacts insulin resistance or glucose response. Highly negative correlations here, even from the advent, but the potential revenue has outweighed the desire to protect Americans.
The truth is that American business sees citizens as two ways, suckers for making bad choices (while forcing those same choices down their throat), or simply unlucky. The rich avoid the obviously harmful aspects of America, while accepting the odds on the things they can't avoid.
Personally if I were very wealthy I would spend very little time in the United States.
and until they find the answer these farms should be shut down
Can someone translate dogwhistle to english here please?
But there are a myriad of illnesses that have been linked to environmental pollutants and a very high number of people will get offended if you point it out. Because the science isn't settled yet. I'll let you fill in the blanks there.
I am disabled. I cannot walk very well without an assistive device. I've noticed that, when you're disabled, the average person's level of caring about your disability extends right up until the point where you're even a mild inconvenience to them. And it's for any number of reasons: "you're faking it" "you're too young to have those issues" "it's bothersome to install a ramp for people in wheelchairs" "people's assistive devices (canes, walkers, ...) take up too much space" "you're too slow getting in/out of transportation" and the list goes on. I imagine it may at least in part be the bystander effect, but that doesn't explain people who can be actively malicious -- and that happens more often than you may think.
The point of this anecdote is that I think something similar applies here. IMO people _do_ genuinely care about what's in their food / how it's produced... but then _they_ would have to change for the situation to improve. Suddenly it's an inconvenience to them. If the relative suffering of a disabled person isn't enough to convince someone that an inconvenience is worth it, then caring about a bunch of animals in a factory farm is just an abstract concern that they don't care about too much, but changing it is something they care about because it affects them.
That's not to say that people are _selfish_, per se, or anything like that. There's only so much time in the day, life is busy for many people, social media demands attention, food costs and inflation and housing costs and ..., and many more are all issues that are a lot more immediate to people. It's hard to care about things that are mostly just abstract concepts you aren't exposed to, when you have much more meaningful day-to-day concerns.
I feel like 2 out of these 3 are not like the other (i.e. pesticides are by definition usually pretty toxic and hormones can mess up living things in all sorts of ways). And even then you need to get more specific than the broad groups to say anything intelligent about them.
> Being anti conspiracy and overly trusting of certain (cough cough) fields of science denotes an inability to rationalize.
First step to being rationale is to be able to talk about it. You wont even say which field of science you don't like. Is it biology in general?
I am a pro conspiracy theory person. But to be clear, there was a ton of disinformation around COVID, and this thread has nothing to do with COVID. I believe COVID is real, and that the vaccines were a good idea.
Empirical evidence and data can be used to selectively deceive. Companies can run hundreds of trials and only select ones that showed favorable results.
Somebody got a Nobel for that, the situation supposedly has improved since, but a lot of assumptions (and substances approved) are still based on research which was using these mice.
One person's agenda might be to make as much money as possible irrespective of consequences. Another person's agenda might be to decrease asthma rates. The fact that both people have some kind of agenda is basically irrelevant.
This is the same hole as in the classic "both sides" political attitude.
The lesser of two evils is still evil.
Was Occupy class-based? They were intersectional progressive/anarchist/professional activists, so essentially they were in favor of everything ever and habitually unable to prioritize. That combined with their official policy of not deciding what their demands were destroyed themselves pretty effectively. (They also had "progressive stacking", which was like an early form of DEI liberalism.)
Class-based leftism wasn't really popular till Bernie though.
That's some word salad right there.
Ashwagandha basically restored my gut health in 3 months, in combination with psyllium husk capsules, kefir, and large plain lettuce salads with a vinegar-based dressing. My theory is that my cortisol levels got so high after decades of stress and negative reinforcement that I had symptoms like Cushing's syndrome. So ashwagandha mopped that up, which raises testosterone/estrogen and probably fixes a whole host of issues. But I never tested those levels, so take that with a grain of salt.
I've experienced the connection between gut health and mood, now I do everything I can to stay in good shape. But I've noticed a resistance to this line of thinking, especially in older people who just want a pill from their doctor.
Ashwagandha is a nightshade, so you likely weren't allergic to nightshades if it helps.
Also, I'm not sure how you concluded that you have "low serotonin" due to gut issues. Serotonin in the gut doesn't migrate to the central nervous system. It serves different purposes throughout the body, but the synthesis in your brain remains local to the brain.
There are a lot of unrealistically specific claims in your post about cortisol and serotonin, but it's impossible to make such specific diagnoses. You might be reading too much into the alternative medicine world that misuses surface-level knowledge about hormones and neurotransmitters to provide false comfort. Real medical diagnoses aren't so specifically centered on singular chemicals.
To be blunt, 2019 was one of the worst years of my life. I found myself out of work with no insurance and worse, no executive function. I went from loving my job and hitting gym PRs to broke and barely able to get out of bed in the morning. 20 years of trying to win the internet lottery and failing had sapped my motivation. Then the pandemic hit and things went from bad to worse to even worse to past the point of believability. But thankfully that series of traumas led to my conscious awakening and so I am grateful for that experience. And am gainfully employed and having fun with my work again, which is priceless. And hitting gym PRs again, which is frankly a miracle.
I guess I keep OCD'ing on this because working in tech is so high-risk that mental health issues are all but inevitable IMHO. But there are basic preventative steps we can do that western medicine seems reluctant to advocate for whatever reason. I have to be honest - without publicly funded healthcare, our system is garbage because it's being ruled by the profit motive and a tiny elite who spend their ill-gotten gains on lobbying to get out of paying their taxes. Their greed preventing win-wins like preventative medicine is just another hurdle for people on the edge, effectively talking them out of getting the care they need. Maybe the breadcrumbs I leave might help someone struggling to get just well enough to schedule an appointment.
I should add that I finally did go to the doctor and got some treatment, but they had trouble isolating any specific cause. I feel that the everlywell.com (no affiliation) food sensitivity test I took and dietary changes were the main fix, YMMV.
I know my mood changes drastically down when I fail to eat properly for a period of time.
From a science angle it makes more sense to just collect this data from everybody all the time and let the studies be post hoc explorations of that giant dataset. But how do you get people to cooperate when they have reason to believe that the data will be used against them?
Either we accept the diminished value of isolated study-at-a-time datasets (as we're doing now), we figure out how to do this kind of research through a layer of homeomorphic encryption which the layman trusts (a tall order), or we wait for an era with more trustworthy institutions (potentially a long time).
For this reason, I think it'll be like fusion power: the perpetual "next big thing".
It won't be. We aren't able to culture most gut bacteria. Most die immediately in oxygen.
The best we can do at the moment is correlation.
"To conclude, this review provides evidence that continuing SSRIs for 1 year reduces risk of MDD and relapse."
And, even if they are better than just an active placebo, the mechanism is probably not the effects on serotonin levels. (Discussed previously here: https://news.ycombinator.com/item?id=32160703)
It's interesting they picked antidepressants to do so but the logic should apply to many substances people like to kill bugs
Like green tea and spices which hinder bacteria should also make them resistant to antibiotics.
It's like discovering that some plant derived psychiatric drugs are behavior modifiers for the plants too
The suggestion that mental process begins at the cellular level.
My layman understanding is that antibiotics gum up the mechanism to produce the cell wall.
Sure, bacteria may develop where the mechanism works a bit differently and is not affected by a certain chemical. But it seems like “disrupt cell wall production” is a huge target and we could probably disrupt it in many other ways. Humans lack a cell wall entirely, so we “just” need to avoid side effects in some other system.
Is the concern that studies to confirm lack of effects will take too long? Not that it’s a difficult engineering challenge? Couldn’t we be doing this research already, of finding other ways to disrupt the mechanism?
The antibiotic bottleneck centers around patients who show up to the hospital with very vague signs of infection (fever, sweats, rigors, lethargy, etc.) and are sick. Like on the verge of going to the ICU sick. Or already in the ICU sick. These people need an effective antibiotic and they need one fast. You don't have the luxury of sending a culture to the lab and waiting for the antibiotic susceptibility profile to come back because that can take multiple days. So you need a toolbelt of "broad spectrum" antibiotics that are highly effective against the dozen or so bacteria that are the most common culprits of serious infection - something that you can use in the critical first 48 hours, while you're still waiting for culture results.
In practice (at least in the US), your selection of broad spectrum antibiotics is limited to vancomycin plus either cefepime or combination piperacillin/tazobactam. That's it. There really aren't very many other antibiotics that are effective against a sufficiently wide range of bacteria. We do have "back up" antibiotics to use if those fail, but these are powerful agents that come with some really nasty side effects, like seizures (for carbapenems) or widespread muscle breakdown (for daptomycin). And they are pretty limited in number too.
If vancomycin, cefepime, or piperacillin/tazobactam resistance starts to become a lot more common before the next generation of antibiotics comes in, we're screwed. And antibiotic development has been stuck in a rut for decades.
Literally 4D chess and we don't even know what the board looks like (okay it isn't chess but it is 4D).
Basically, there's plenty of antibiotics that are effective against, say, 25% of the critical bacterial species, but very few that cover 90%+. So emerging resistance to any one of those few would be a very, very big problem.
I suppose there may still be some common sub mechanism that we could target? But we don’t understand the mechanism well enough to do that intentionally. It’s really tragic how little of biology we can simulate today.
Thanks for the informative responses!
It's scary because if you can't kill the bacteria, the bacteria kills you.
> My layman understanding is that antibiotics gum up the mechanism to produce the cell wall.
This layman's idea is incorrect. Not all antibiotics work on cell walls. Not all bacteria have defined cell walls. Look up Mycoplasma.
> Is the concern that studies to confirm lack of effects will take too long? Not that it’s a difficult engineering challenge? Couldn’t we be doing this research already, of finding other ways to disrupt the mechanism?
Most of the antibiotics we have were either found by accident, or computed derivatives of something that was found by accident. We've exhausted the low hanging fruit. More complex antibiotics often have bad side effects (ciprofloxacin) or are effective enough that we use them in the most guarded fashion to keep them in the chamber when needed (carbapenem derivations).
There's a metric crap ton of money going into the research of new antibiotics, it's just not straight forward.
It's getting more attention, but its been faltering for a long time.
> Venture capitalists are investing far less funds to develop new antibiotics than they are for oncology drugs, according to a new report that highlights the need for more financial incentives to fight off the growing threat of drug-resistant bacteria.
> The report, published Monday by the Biotechnology Innovation Organization, found that investors are increasingly shying away from antibiotic research due in part to large companies exiting the space. That’s left small companies, that typically rely on investment capital, struggling to carry out new clinical trials.
> Newer antibiotics are more important than ever as the Covid-19 pandemic has forced people into hospitals for longer periods of time, increasing the chances for the spread of antibiotic-resistant germs, the biotech trade group said.
> But in the past 10 years, venture capital funding for U.S. antibiotic development amounted to $1.6 billion, compared to $26.5 billion for oncology, according to Monday’s report. The group noted that there are currently 64 new antibacterial therapeutics in the clinical trial pipeline, 80% of which originated from small companies.
The report mentioned is The State of Innovation in Antibacterial Therapeutics - https://www.bio.org/sites/default/files/2022-04/BIO-Antibact...
Because it can makes otherwise simple to treat bacterial infections into an ICU stay. ICUs don't have a lot of spare capacity, and it's difficult to add more.
> In bacteria grown in well-oxygenated laboratory conditions, the antidepressants caused the cells to generate reactive oxygen species: toxic molecules that activated the microbe’s defence mechanisms. Most prominently, this activated the bacteria’s efflux pump systems, a general expulsion system that many bacteria use to eliminate various molecules, including antibiotics. This probably explains how the bacteria could withstand the antibiotics without having specific resistance genes.
So the study was:
* Done in a petri dish
* Done in an environment dissimilar to the human body
* Showed an adaptation to the environment unrelated to antibiotic resistance
Showing adaptation "efflux pumps" for oxygen removal and claiming it's applicable to antibiotics seems like claiming yoga mats are made from jet fuel because they both contain water.
It would be really interesting if they tested a null here which I don't see noted anywhere. If the adaptation happened in the oxygen rich environment without the antibiotic it would indicate that antibiotics are not causal.