This article yet again reports on the lack of awareness about bacteriophages in the medical community. I just can’t understand why it is like that. I, an idiot, have heard about it. How do people, who seemingly work with superbugs all the time and understand the threat, not know this thing that is amongst the very first things one is exposed to when one takes a superficial glance at the available literature?
A shortlist of answers:
- Bacteriophages are evolutionarily close to viruses. Their proteins will resemble viral proteins, so the body will most likely initiate an immune response against it.
- Bacteriophages are really quite specific in what they'll infect. This makes them much less useful as an antibacterial. You'd spend a lot of time and money on making one that would infect your mrsa strain, and mrsa would probably just start the arms race, leaving you back at the start.
- Bacteriophages are (evolutionarily close to) viruses, and thus also have the immense mutation rate of those. Even if you were to make one that had all the properties you wanted, it'd probably get rid of most of them because they are evolutionarily disadvantages.
- Probably a few other fairly good reasons which my coffee-deprived brain can't think off right at this moment.
Actually developing resistance against bacteriophages requires such invasive changes that most bacteria that develop it lose resistance against anti-biotics. That is why an anti-biotic therapy is often used together with a phage therapy.
It requires some huge changes, sure. However, MRSA exists because Staph was able to adapt to be resistant to multiple antibiotics at the same time. There is no reason to assume that it could not adapt to become resistant to the phage used as well as some of the most used antibiotics.
However, none of them explain why medical professionals are not even aware that bacteriophages are a thing, in contrast with laypeople like the parent poster (or myself, and presumably many more on HN since there have been a few articles on this topic over the years).
A challenge for a startup?
Sounds questionable to me that this is even the cause, to be honest. However, assuming this is true, the main reason I could think for why would be the case if this: medicine is an extremely specialised field. Not only do you focus solely on the human body, but not even the body as a whole, but on what can go wrong with it. The only knowledge a medical professional needs about bacteria, viruses and other pathogens is what they require for them to be diagnozed, what kind of illnesses they convey and how they can be gotten rid of. And not even this is accurate, because within the field of medicine there's even further specialisation into even smaller sub-fields.
That there are also viruses which infect bacteria is of no (direct) importance on the medical field. In fact, it'd frankly be a waste of time for them during their study to learn about phages in any detail. The basic degree alone is already very long and full to the point of bursting. It'd be similar to expecting welders to understand the minutea of all states of matter, because TIG welding uses plasma to melt metal.
To give a somewhat comparable example, it’s more like someone saying asking why the average programmer doesn’t know anything about quantum computers as a solution for critical cryptographic problems.
My guess is because phage treatments are difficult or impossible to patent, and therefore unattractive to pharmaceutical companies. And pharmaceutical companies are incentivized to push their own treatments on doctors and hospitals.
Sadly of course like any complex behavior it was also hijacked for sumptuary purposes (grape shears, egg spoons, not finishing your plate in some cultures) but I hold out a hope (probably in vail) that those kinds of rules won't be revived.
When I was a kid growing up in the late 1950s, I thought we had this problem solved.
All the local restaurants kept a jar of mustard and a jar of mayonnaise on each table. (Yes, mayo sitting out all day, but let's ignore that for now.)
They didn't have separate utensils for these jars, you just used the table knife from your place setting. This led to a problem.
What if you had already cut your burger in half and then decided you want more mayo or mustard? You certainly wouldn't use a dirty table knife that would get bits of lettuce and tomato and bread and beef into the condiments.
Fortunately, my mom taught us basic sanitation: before you dip your table knife into the mustard or mayo jar, you must first lick it clean!
My recollection: we don't know how to treat silver poisoning.
its my understanding that silverware is very safe, and getting silver poisoning from eating off it is extremely unlikely. they'd have to be eating their silverware to notice any difference
Argyria it the result of ingested silver particles that are not able to pass through the body. Historically, this was caused by particles from silver eating utensils being swallowed along with food or silver being taken for medicinal purposes. Aristocrats were originally the ones who could afford medicine and who enjoyed the daily privilege of eating off of silver plates, drinking from silver vessels, and, as the saying goes, being born with “a silver spoon in their mouth.” Thus, Argyria was a condition that was more common among the upper class.
One British king had portraits delivered to him of a potential mate and was disappointed when she showed up and wasn't as attractive as her portrait. One source mocked him for it, saying he should have realized it was probably idealized, after all, it was his own portrait artist he sent, a guy who had been making him look good for years.
Colloidal silver still sometimes causes blue skin:
"Born with a silver spoon in their mouth" is not usually a nice thing to say. It usually means they are basically overprivileged assholes.
In chelation groups, metal poisoning is generally viewed as having a negative impact on the personality. Perhaps people who routinely dealt with "blue bloods" had enough first-hand experience to notice that visible signs of silver poisoning correlated to asshole behavior.
Anyway, I don't actually think the questions being put to me are in good faith from people sincerely curious about my knowledge or my opinions. I think the pattern of downvotes and questions suggests everyone here thinks I'm a clueless idiot and they are trying to politely let me know how stupid I am because civility is demanded by the rules of the forum.
So continuing to try to answer questions in good faith is likely making me look stubborn, pigheaded, difficult and so much of a nutjob that there is no hope of reaching me.
It's not a dance I care to engage in further.
The concept of "overpriviledge" is modern.
The Moors occupied territory in parts of what is now Spain and Portugal for nearly a thousand years.
If you want antimicrobial metal kitchenware, copper makes more sense than silver, though it should still not be overused.
Additionally, copper surfaces in hospitals have a proven track record of helping to kill infection and reduce the transmission of hospital acquired infections.
If you can afford it (as it isn't cheap) and want to Prep for a post antibiotic world, copper fixtures of various sorts in your home would not be a bad idea.
Now, if it was silver and arsenic, or some other toxic compound, that'd be a very bad time, but elemental silver shouldn't be any worse than mildly annoying.
Great book if you’re in to near-future dystopia.
What actually is the risk of inter person bacterial infection like this? Is there not more risk of getting ecoli from the shared salad, than the shared salad spoon?
(For the record, a better way to handle it is to sneeze into the inside of your elbow or immediately wash your hands after.)
I was guessing he had dry skin and had trouble picking up a fork unless he moistened his fingers first?
In any case I quietly went to a different container to get my own fork.
Fussy? Aren’t these just common sense? I wouldn’t consider them to even be “table manners”.
Well yes, I agree they are sensible but it seems in the USA they are not only typically unknown but seen as pretentious.
E.g. rather than have a butter knife for transferring butter to your plate and then using a regular or smaller but regular style knife for spreading it on your bread, each person (in a typical semi-fancy US restaurant) is issued a butter knife which is used both to retrieve butter and to spread it on your (potentially bitten) bread.
And they are learned matters.
I have more than enough karma to take a hit once in a while. No need to apologize :)
> it seems in the USA they are not only typically unknown but seen as pretentious
I live in the US, so I'm finding it surprising that you think these are not the norm. Perhaps I'm self-selecting the people I'm around, or don't pay attention to the people who do these things…
this isn't really scary at all. i'm not scared. are you scared? why be scared?
The FDA granted Fast Track designation for their antibiotic, only later refuse to approve it for use in bloodstream infections due to quibbling over study size (which was admittedly smaller than it could have been, largely in part due to the Fast Track designation). The antibiotic has been relegated to on-label use for complicated UTIs. Though it can still be used off-label, this isn't enough to attract further investment or keep sales strong enough to sustain ongoing operations. Achaogen was forced to lay off nearly all staff, and is now entering bankruptcy.
Unfortunately, this sort of thing is hardly unique among early stage pharma companies focusing on antibiotics, and it's steering investors away from such companies. It's also driving pharma professionals away.
Bacteriophages as a solution to our antibiotic resistance crisis have been largely ignored in the West due to unpatentability, research mainly performed in Eastern Europe, etc — but her story is that a bacteriophage cocktail saved her husband’s life where antibiotics failed...and the only reason they even were able to go that route was because she’s an epidemiologist who pulled some strings, pulled research teams together, got approvals, and managed the project herself.
I literally have a standard "Why phage are a problem", from the perspective of an infectious disease epidemiologist whose been super-interested in phage for like...a decade.
1) 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. There are treatment guidelines for things like sepsis right now that are basically un-doable with phage therapy because of the time it takes to tune a phage library.
2) 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.
3) 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.
Also, I would like to note that phage therapy wasn't only ignored due to unpatentability. A couple other reasons:
1) Antibiotics were superior in basically every respect. It's hard to justify decades of sustaining research into the fussy, expensive, edge-case alternative to something that works amazingly well.
2) Phage therapy was used in the West. Due to the technology at the time, it had a tendency to, well, kill people, due to contamination with bacterial endotoxins.
3) It's not clear phage can be turned into anything other than a pretty bespoke, custom tailored product. Even in the East it's not doable "at scale" in the way we talk about antibiotics.
1) Broad spectrum phages don't exist in nature but gene-editing techniques can be applied and this technology now exists. Several biotechs are now working in this space.
2) Phages are not hard to keep 'alive'. They need to be refrigerated and kept away from sunlight.
3) True that phage therapy is relatively new in the West but the field is exploding. There are very few pharmas still developing antibiotics and very few in the pipeline, esp for gram-negatives, so there is an imperative to have alternatives to antibiotics.
With an ever-expanding phage library of well characterized phages, it is possible to generate personalized phage cocktails in days. An antibiotic takes a decade to develop, at around a billion $, and has collateral damage on the microbiome. For more on the story, check out ThePerfectPredator.com
To touch on a few of your points:
1) I'm hopeful about these, and have been sort of idly following them, but I think they're a long way from anywhere close to the utility the average HackerNews reader is hoping to get out of them.
2) When compared to "There's an inert, shelf-and-temperature stable blister pack of these living at the bottom of a bag" they're hard to keep alive.
While not relevant in your husband's case, the vast burden of AMR is going to end up falling on the global poor, and in those cases, solutions that require a cold chain aren't reliable solutions.
3) It is exploding, but I've been following phage research for 15 years now, and it's one of those technologies that has lived in the "any day now" space that whole time. So I tend to try to temper the expectation of folks because I fear that it's going to end up, at best, as a supplemental solution to a very complex problem, rather than the "a new technology will get us out of this" path the popular media sometimes portrays it as.
Maybe 100 other equally qualified spouses tried equally ambitious programs to save someone, they all died, and we never heard about it...
Right now, antibiotics are a point-and-shoot, frontline treatment for things, and phage therapy is a sort of "treatment of last resort" bespoke therapy.
Are phage super-useful for cases like the one in the article, where you have something super-resistant like Acinetobacter? Yes.
Is there much hope, near term, that they'll work as a drop-in replacement for the antibiotics we're losing? No.
Alternatives to antibiotics are desperately needed.
She's not pushing phage research per se, just research into alternatives generally.
It closes on
"The possibility of living in a post-antibiotic era where simple surgeries or scrapes could lead to an infection that requires limb amputation or results in death means we need to improve AMR surveillance, diagnosis and treatment. This includes antibiotics, but should also include phage therapy. We can’t afford to bury a promising alternative to antibiotics for another hundred years."
She is absolutely pushing phage research. Not exclusive to any alternatives, but that is basically the point of the article.
Yes, sterile technique is used to minimize the occurrence of surgical site infections. Sterile technique, when performed 100% correctly, isn't perfect and prophylactic antibiotics are standard to help mitigate any remaining risk.
Keep in mind at the same time this is happening we also have to deal with climate change and not blowing ourselves up in all out Nuclear War. And even if we avoid all that you could still step outside and be shot or stabbed by a ruffian who leaves you dead all the same.
Also, can anybody explain why the CDC doesn’t mandate reporting?
There are several Einstein quotes along the lines of "A problem cannot be solved using the same thinking that created it."
The problem of antibiotic resistance won't be solved with the same mindset that got us here.
One thing contributing to the rise of antibiotic resistance is poor santitation in developing countries. Another is poverty.
There is also research into how to break up biofilm and thereby reverse antibiotic resistance. It points to issues with body chemistry which can basically be tied to diet.
I think there are clearly avenues we can pursue, but most people are extremely dismissive of those avenues. So they simply aren't being pursued in earnest.
I assume this is why you were getting downvotes? I was going to too, but it does actually check out.
So if that line you quoted is getting me downvotes, then everyone downvoting me has failed basic reading comprehension.
I have read other things that state more directly that we breed antibiotic resistant infections in less developed countries, no reading between the lines required.
But I have also read up on research into stunting. It has pertinent findings about lack of sanitation fostering low grade chronic infections that basically cause failure to thrive that isn't readily resolvable because the problem isn't rooted in the individual. It is rooted in the lack of sanitation of a larger area.
The right gut microbes help infants grow
What causes stunting?
Beyond Malnutrition: The Role of Sanitation in Stunted Growth
Pertinent quotes from that last article:
In countries such as India, for instance, stunting occurs even among well-fed children, and that’s led investigators to consider other causes, especially poor sanitation and hygiene. Evidence shows that children who live without adequate sanitation, hygiene, and clean drinking water don’t grow as well as children who do.
In somewhat newer thinking, researchers are exploring the possibility that poor hygiene and a lack of sanitation induce a gut disorder called environmental enteropathy (EE) that diverts energy from growth toward an ongoing fight against subclinical infection.
Maybe they should have done their own research? I don't know. The sample size of one in the article by itself doesn't justify the sweeping statement you made.
Ultimately and unfortunately people will say unsubstantiated and unpleasant things and some reasonable comments get caught in people's 'spam filter'.
so I was confirming to others you aren't being racist or anything.
It worked for hormones (do you see much BST cow milk)?
The next thing is convincing India to stop handing out antibiotics like candy, but that's not something an individual can do.
Because a great deal of this is done at the state level. Working on these kind of problems, there's a very difficult balance of reporting requirements, agreed upon definitions (especially not just what you have but where you got it), various stakeholders, etc.
And the CDC collects a lot of data even if things are universally reportable. And there's a lot of ongoing improvement.
Read here for more info: https://www.bloomberg.com/news/articles/2019-05-03/antibioti...
Moreover, if you dig into soviet medicine, you may find several awesome things. At the moment there are _two_ widely available st.aureus vaccines in russia. For those who work with farm animals. These vaccines may be used for both prevention and treatment. I've used them for myself to treat multiple-antibiotic resistant st.aureus infection and got rid of it.
The other interesting thing is a synhetic analogue of thymopoietin - an incredible immune stimulant which may in multiple cases help you to deal with an infection without antibiotics.
Unfortunately, russian doctors are idiots and russian medicine is almost dead and noone is interested in any stuff from there.
I, personally, regret that we didn't hear any news about epimerox - that only substance would solve 80% of our problems with bacterias, including multi-resistent ones.
Disclaimer: consult your doctor first, it's just a random advice from internets, blah-blah.
You may just pick old soviet vaccines and resolve this particular problem (see my other post in this topic).
Also there are a lot of great antibiotics (see epimerox) which still aren't on the market because of many different reasons.
I would love to have a hotline my next of kin can call to begin treatment whether or not my doctors are aware of its availability.
The problem is it's not particularly clear they work, and they are very expensive, and often a pain to clean.
And expense. Of course.
> it is thought that B. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape 
> an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates 
Wouldn't it be nice if we had more eradication programs? Evolution is going to work around every vaccine eventually unless we eradicate the disease. Yes, this is a hard problem but I think long term its worth it. Eventually we might get good at it.
Polio almost is, the issues are social and political and have little to do with vaccine escape.
If it lives on in other species, it's a much harder problem.
Unfortunately, certain other efforts are compromising this.
Honestly, it's not one of the more promising eradication targets.