Naive question here: Why can't new antibiotics be developed by just spraying fields of mushrooms or petri dishes full of fungi with antibiotic resistant bacteria and seeing which ones come up with novel ways to fight them?
Can't answer this particular question. But I remember hearing that developing new antibiotics is not very profitable - To minimize resistance building against new antibiotics, old antibiotics will be used until they are no longer working. So new antibiotics just won't sell that much for now.
About 1/8 of global deaths are due to some sort of bacterial infection, pretty close behind cancer ( 1/6 ).
However for children the number that die of infection in the UK is double that of cancer deaths - ( ~15% versus ~7% ) - and that's in an advanced economy.
Infection is a big problem.
In terms of barriers to making treatments - yes in part there is a problem with the right financial incentives - but it's not the only problem - finding molecules that simultaneously kill bacteria, won't be rapidly evolved around, and are safe to take isn't that easy. Then you have the problem of selectivity between bacteria - how many different sorts will it work with - 'good' verus 'bad' bacteria etc. Then you have the problem of being able to make the molecule at scale etc.
The good news is there is a constant bacteria on bacteria, fungus on bacteria chemical war going on - hence the paper.
> ( ~15% versus ~7% ) - and that's in an advanced economy.
There were 1,507 infection related child deaths between 1 April 2019 and 31 March 2022 (3 years); an overall rate of 4.20 deaths per 100,000 children per year. This was the equivalent of 15% of all child deaths in this period.
Overall, in 90% of the infection related deaths the child had an underlying health condition, including 68% who had a life-limiting condition (e.g., cerebral palsy), and 22% who had another underlying health condition (including prematurity). 10% had no underlying health condition.
In children where infection provided a complete and sufficient explanation of death, nearly a quarter (24%) had no underlying health condition.
We could definitely do more - one of the challenges here is that some bacteria are quite picky about where they grow - ie there a lots that don't grow on a petri dish. So not always so easy to grow side by side.
Note from the paper - they stored the soil samples for a year on growth media before testing ( to allow any compunds to build up presumably ). That doesn't sound like a fast process.
Our knowledge of what's out there is quite biased by what grows well in the lab - probably less than 1% of all bacteria will grow on an agar plate.
It’s because antibiotic resistance is a misunderstood issue. If one antibiotic doesn’t work, you move on to the next. Maintaining antibiotic resistance is energetically costly to the bacteria. If you aren’t actively selecting with that antibiotic, its resistance will be lost before long as mutants with deficient antibiotic resistance are now more fit and outcompete those with functional antibiotic resistance.
I read a fascinating paper around a decade ago that proposed, roughly speaking, to cycle through the limited set of different antibiotics that we have available in some careful order, so that as far as possible, only 1-2 are in use at any one time, ideally around the world. As soon as resistance against the incumbent antibiotic grows past a certain level, it is "benched" and replaced with the next in the sequence, with the goal being that, by the time that all other antibiotics in the sequence have been used and it's time to revisit the original one, the stresses placed on the bacterial population by the other antibiotics in the meantime have been sufficient to completely eliminate resistance to the original. This would mean that resistance to the original antibiotic the second time around would have to develop "the hard way", i.e., via novel mutations (rather than reactivation of alleles still present in the population), thus maximising the period for which it will remain effective.
Massive practical coordination problems, but I find the idea of consciously exploiting this "time dimension" really interesting.
Same goes for chemo therapy. There are many chemo therapies from 60s still being used due to the fact their patent is still owned by certain oligarchy.
> their patent is still owned by certain oligarchy.
I don’t know that it’s helpful to have such a blunt and un-nuanced take.
Theres no “certain oligarchy” that holds a single patent on "chemotherapy" as a broad concept, as it encompasses various chemical treatments for cancer. specific chemotherapy drugs and methods are patented by pharmaceutical companies and research institutions, for example:
- NanOlogy LLC: holds a patent for a method involving injecting large surface area microparticle taxanes directly into the tumor, combined with systemic delivery of immunotherapeutic agents.
- Johns Hopkins University: assigned patent rights for a method related to cancer treatment to Becton-Dickinson & Company, which then sublicensed them to Baxter.
- University of Cincinnati Clermont College: has a patent for breakthrough chemotherapy technology involving nanocarriers.
- Northeastern University: reports a patented molecule, WYC-209, that eliminates cancer cells.
It's like the claim that pharma had tripled the price of a 100 year old drug(insulin) that the inventors had sold for only $1 and were now charging $450 a month for it.
Then you dig into the claims and you find out that, the original insulin is still available, it's new formulations that have the higher cost.
>Until now, the only so-called “Walmart insulin” you could get for a lower price (roughly $25 to $35 per vial) was the older, human versions of insulin — R (or Regular) insulin, N (which is Novolin, aka NPH insulin); and a 70/30 mix of the two other types. Those formulations have been around since the early 1980s, but they work much differently and are seen as much less reliable than the analog insulins that first started appearing in the later 1990s.
https://www.healthline.com/diabetesmine/walmart-relion-novol...
But the new stuff works better, is faster acting and allows a freer lifestyle.
I agree that there is a problem with the pharma industry but lying about the problem to try and get change is not going to help the cause.
Outright "communist" states like Cuba and Venezuela no longer have sponsors, and are sanctioned by the US, so they're exempt from having to prove that their economies could conceivably generate any innovation.
Right-wing "post-democratic" states like Russia and Hungary are, by some definition, capitalist, but you see no innovation there either. Presumably someone if not you could blame America for them being unable to innovate. One could equally say that their markets aren't free, because they're fully captured and manipulated by their respective mafia/oligarchies.
Ahem. Just like the so-called communist countries are.
Then of course there's China. Where capitalism is also a plaything of the governing power. Similarly, no major drug developments have come out of there. Although we did have a fantastic example recently of how not to manage a biolab doing gain of function research.
Pray tell, which countries without free markets do anything at all? I'm not holding my breath for North Korea to cure cancer, no matter how much of their GDP is spent trying to keep their Dear Leader alive.
Blaming difficulty of problems on capitalism alone is disingenuous. There are huge scientific projects that are not profitable and still done because there is a somehow clearer path forward (ex: UKBioBank, CERN, ITER).
When I hear "{x} is not very profitable" I think people mean "we are not sure if we succeed doing {x} and it requires us to divert lots of resources from other things that we think would be more useful".
Pharma companies invest already huge amounts in drugs and many fail anyhow. Quote: "It takes 10 to 15 years and around US$1 billion to develop one successful drug. Despite these significant investments in time and money, 90% of drug candidates in clinical trials fail." (https://www.asbmb.org/asbmb-today/opinions/031222/90-of-drug...)
That quote itself seems to be disingenuous, conflating "one successful drug" which costs $1B with "drug candidates in clinical trials." Even more so when taken from context, as the next sentence in the article is
> Whether because they don’t adequately treat the condition they’re meant to target or the side effects are too strong, many drug candidates never advance to the approval stage.
And that doesn't sound "successful" at all. How much money is sunk into R&D at the point of failure is the much more relevant statistic to consider. If the pharmaceutical industry wasn't wildly profitable, they'd be investing those billions elsewhere, leaving drugs to a slow-cooking niche.
There is no claim that each drug costs 1$ billion. If you stop after 1-2 years of development you might have wasted some millions, if you stop after 3-4 years you wasted tens of millions and so on. The 10% success is still very low, because you can still fail after 10 years (potentially investing a lot)
If you are interested in the topic, for example for oncology: https://jamanetwork.com/journals/jamanetworkopen/fullarticle... , to quote "Failed drug development in oncology incurs substantial expense. At an industry level, an estimated $50 billion to $60 billion is spent annually on failed oncology trials."
There is no "oracle" that says invest 50 million (or 100 million or 1 billion) in X or Y and it will succeed (in pharma or other domains). And this is not exclusively because of capitalism, it is because doing some things is hard.
Bacteriophages suck. What some people never tell you is that the body treats phages as invaders and can very effectively get rid of them, they are not adapted to the human environment. These are only good for local treatments, sometimes...
Well, you actually want the body to clear things. That’s not a problem, it’s a feature. If the phage is able to target the bacteria before it is fully cleared, that’s all you need. Humans have been injected with phages and it has been shown to work. The Soviets actually did a lot of research on it, IIRC. The practical issue that is really challenging for broad phage therapy adoption is that phages are very specific to the bacteria they target. So, you can’t just get injected with any old phage and expect it to work. Instead, you need to catalog all the phages you find in a database and search for one that can target the specific bacteria the patient has been infected with. Phages are simply viruses that target bacteria. You’re awash in them all the time.
>you need to catalog all the phages you find in a database and search for one that can target the specific bacteria the patient has been infected with.
Most of the time the doctor doesn't know the exact pathogen you are infected with. He'll suspect a bacterian infection of some kind and prescribe a wide range antibiotic.
Doing what you suggest will require changing the way we do medicine. Which might not be a bad thing but requires some determination.
This is correct, it's called empiric treatment. If a patient comes in with altered mental status and neck rigidity, you don't have time to take a lumbar puncture and culture bacteria. I don't know anything about phage treatment, but from what the other commenter said, it seems like then you'd have to do some sort of PCR test as well. You simply don't have time for any of that -- your only choice is to blast them with vancomycin + ceftriaxone.
If you come into ED with GGP's symptom's, you might only have an hour to live. Hopefully for you it's bacterial and didn't pick up resistance from horizontal transference from a strep throat treatment that's trivial to culture and, while unpleasant, can wait a few hours to start treatment while the correct bacteriophage is readied.
Feels like it might be more practical to simply distribute phage therapy to a whole population targeting a known pathogen, like this year’s cold strain. Especially of the goal is just to reduce the use of antibiotics, not eliminate.
It's a good thing, unless the body clears off the phage first, leading to both reduced effectiveness and the body wasting immune resources. It does work locally, and one can probably engineer it today to work even better. But it seems to be destined to be relegated to a secondary cure. We seem to be able to keep finding new antibiotics with benefits like 'massive safety testing' or 'we know exactly how they work', or 'very easy to administer'.
that seems like a good thing. they only infect bacteria, not humans
phages are found in large quantities in mucus, where they seemingly contribute to the barrier function of mucus by preying on any bacteria that try go cross
To expand on what you wrote, the challenge with phages is that they’re highly specific to certain bacteria, in the same way that some viruses target gorillas and some target humans. We have yet to find broad spectrum phages. While humans have been saved from bacteria by phages, it requires identifying the bacteria strain, looking up appropriate phage that can target that bacteria, cultivating a dose of the phage, etc. So, yea, phages are highly effective, but there are practical challenges. As you say, antibiotics are lazy.
Ok, another naive question: Not suggesting we just eat a bunch of bacteriophages, but why wouldn't studying phage mechanisms / proteins for killing bacteria be equally useful?
I'm sure people are studying them. But as GP said, antibiotic are lazy. A doctor would much rather prescribe an antibiotic than do the work to match the specific bacterial infection with the particular phage to deal with it.
And since antibiotics still work (for now), there's not all that much money in phage research. If we do get to the point where we "run out" of antibiotics due to bacterial resistance, I imagine phage research will become a lot more attractive as a destination for research funding.
They're viruses, so they work by infecting bacteria and making the bacteria create more of itself.
Antibiotics are found by isolating a compound some i.e. fungi naturally produces. We figure out how to produce the compound and don't fill people with fungi to produce it. Bacteriophages are already the analogy to the compound itself.
So we should be investing heavily in creating and distributing all variety of bacteriophage for all our common bacterial infections. 20k deaths/year from MRSA in the USA alone, 120k infections/year in USA and many of the survivors are left with life-long complications.
We need to implement it! Steffanie Strathdee could save her husband's life because she was the director of UC San Diego’s Global Health Institute. "Regular" people deserve to live too.
Hey @rscho
I saw a comment of yours from a few months ago on this site and I want to get a hold of you, I didn't know a better way than replying to your latest comment.
Can you message me on discord? username: tag_durden
If you have a better contact method let me know i just didnt wanna put my email out here.
It's a fantastic show, but I am not sure it touches on the commenter's point at all. The show is a take on what might happen if a panacea was actually found to exist. That's a bit different than a mere novel antibiotic. I even think the writers are pulling a lot of punch with how violent and insane Big Pharm, Governments and even independent groups would get about control over it.
Still, highly recommend people watch it. Great animation and art style, good writing and characterization, music is pretty rad and it's quite the trip at times.
I haven't watched the show, but your description just made me think about the "panacea". Virus-wise, I was obsessed with the idea of the DRACO antiviral concept for years.[0] It's really unclear why funding was pulled for it.
Then again, the idea behind "28 Days Later" was that everyone got a cancer vaccine and turned into zombies...
What makes you think there exists a way to fight that isn't harmful the host. Antibiotics work by stopping some biologicial pathway - there are only so many of those in bacteria, you can stop them at any point of course, but you have to stop it. However most of those pathways are also in other lifeforms and so stopping the pathway means you kill not only the bacteria but also human/mushroom.
We have been lucky that we have found a few pathways that are not in human (read mammals) that are in bacteria we worry about. However bacteria just finds a different pathway and odds are that is a pathway in humans and so we can't use it because it would kill humans as well.
Or try an evolutionary approach. Artificially enforce some dependency between an organisms' (fungi, bacteria) ability to kill a wide spectrum of targets, and their own continued survival. Let the organism spread on a large matrix in close contact with the targets and zap the areas where the targets are thriving; repeat until you have evolved strains that are effective in destroying the targets. Wonder if it's possible or even been tried.
Producing large quantities of drug resistant bacteria sounds at least BSL3. The principle might make sense, but one wouldn’t “spray the fields” of something like that.
I'm absolutely not educated in the world of antibiotics, but i can imagine it might be very difficult to monitor this kind of complex behaviour in a (hopefuly) very secured controlled environment.
It's much easier if you invest in observing the natural world that has had hundreds of millions of years to do the work, without the limitation of human intention.
The Amazon rainforest has evolved for at least 55 million years. It is
likely home to millions of compounds of potential medicinal value. In
just 50 years 100 million hectares, 390 billion individual trees
16,000 visible species and (estimated unknown) >100,000 types of
non-visible fungi, bacterium, microbes etc, have been destroyed. It's
why I found this wide-eyed statement in TFA particularly cringe:
The discovery shows that "there is terrifically interesting stuff
hiding in plain sight".
