Phage comes up a lot here - it seems to be on of HN's favorite biology topics.
I have a deep and abiding fondness for phage, but they're not quite as awesome as they seem at first glance. From the perspective of an infectious disease epidemiologist who has been super-interested in phage for my whole career (literally tried to get a job out of undergrad with a phage therapeutics startup):
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 (after being abandoned for some very real, very serious safety concerns back in the day), 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 tenured 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, especially when trying to treat at scale.
> it seems to be on of HN's favorite biology topics
Yeah, it seems HN knows more about phages than physicians, which is pretty bloody damning. Why TF don't physicians know about this?
"First, Strathdee found an obscure treatment that offered a glimmer of hope -- fighting superbugs with phages, viruses created by nature to eat bacteria."
According to TFA, Strathdee is also an infectious disease epidemiologist, and she didn't find out about phages until her husband had almost karked it, after several months of fighting an antibiotic-resistant infection.
There was a similar story on HN three years ago about a teenager in the UK with cystic fibrosis and an antibiotic-resistant infection after a lung transplant. The physicians treating her didn't know about phages, and her mother had to suggest it.
[https://news.ycombinator.com/item?id=19863445]
So that's at least two cases of people dying slowly from antibiotic-resistant infection until someone suggested phages, which were then successfully used to save their lives. Are the treating physicians incompetent?
It's not a standard therapy - she had to go to extremely specific specialists, including USAMRID. I've seen her talk multiple times, and am a great admirer of hers, but phage as they are are very much last ditch, bespoke treatments.
Specialist ID physicians know - there's whole sessions about it at major infectious disease conferences. But there's a huge gap between "Knowing" and "Have the capability to use this in practice".
Also, because I had a sneaking suspicion - Strathdee was an HIV researcher. In fairness, most of infectious disease epidemiology is HIV research.
It's entirely reasonable she wouldn't have necessarily heard of a fairly niche therapy in another area - phage is basically a non-starter for global health (where her work was), and hospital epidemiology is a very niche field.
Of course we learn about bacteriophages in medical school and university. I’m a radiologist and even I know about it. It’s just not FDA approved treatment. You’re talking about inoculating someone with a virus intentionally
Thanks for your insights here — is there any innovation going currently wrt phages either in academia or the startup world that looks significant from a practical point of view? I've also seen people claim that phages were never researched as much in the West because they were popular with the Soviets and therefore had a kind of tainted PR image, is there any truth to this or was their lack of prevalence primarily due to more serious issues?
Phages were used in the west prior to the advent of antibiotics. They had a repetitional issue then, because our purification methods weren't always great, so phage preparations had both phage and potentially bits of the cell wall of the bacteria they had killed. Bacterial cell walls contain endotoxins, which are potentially quite dangerous.
They were largely abandoned in the West because with the advent of antibiotics, a wildly more effective solution to bacterial infections was present. The Cold War meant the Soviet Union had less access, and so needed to continue working on phage research more intensively.
There's a lot of work on phages going on in academia - I don't know about the startup world, TBH. I think some of the most promising leads are in combination therapy. It appears that treating with phage can push bacteria back into susceptibility (basically, two selective pressures at the same time), which is a cool idea. But the gap phage has to jump from "Interesting bespoke one-time treatments" to a generalizable treatment is a pretty big one. My expectation at least in the medium term is they'll be supplemental treatments for a few well known conditions where you can maintain phage libraries for them.
A library is potentially quite large - essentially, you need a phage that's for that particular organism. Potentially a large number of each species, given that phage and bacteria are in an evolutionary arms race.
The trickier part is you have to keep them active and functional over long periods. That's not something most hospital labs are equipped to deal with.
Thanks for sharing. Multiresistant bacteria are high on my list of slow-mo crashes happening before our eyes that no one seems to be talking about (compared to eg climate change, which is also a slow-mo catastrophe, but at least one that people are talking about). And it's always puzzled me how little I hear about work being done on phages, which pose an interesting approach to tackle the problem (compared to eg quantum computing, where commercialization potential seems to be a lot further out).
At least in France, a series of antibiotics are not allowed to be used/sold outside of hospitals. This is to ensure that hospitals have some last resort antibiotics in hard cases. But even with that, they have issues.
In Germany, where I live at the moment, the risks and issues are well known and talked about. I have seen a large reduction of the prescription of antibiotics. The younger the MD, the less antibiotics are given.
But 80% (maybe even more) of the antibiotics are used by animal farming...
> But 80% (maybe even more) of the antibiotics are used by animal farming...
This is what needs to be talked about more. Like guns in the US, or telecom oligopolies in Canada, it seems animal based agriculture gets the “thoughts and prayers” treatment rather than any substantive discussion about what harm it is causing the planet, human health, and biological safety via antibiotic resistance.
It kind of worries me when people talk about reduction in prescription of antibiotics. If we are talking about primarily about false diagnoses and prescription of antibiotics when there exist equal or better treatment plans, then a reduction in antibiotics is good. The day when people got antibiotics in order to treat a cold is hopefully over.
The cases that worries me most is however debilitating chronic illnesses (where antibiotics is used as a stop gap until medical science find a cure), and illnesses which if let untreated might turn into a debilitating chronic problem. I hope they are keeping a close watch on the outcomes from those younger MDs.
Antibiotics in animal farming is obviously terrible. Animals should not be allowed to be kept unless it is in an environment that is safe and healthy for them. Antibiotics is a tool used to fix how poor some large scale farmers treat their animals.
I have a collection of antibiotic prescriptions that were routinely given to my kids at the public clinic (South American country here) at the smallest sign of a sore throat or some other infection. I didn't give them the antibiotics and my kids got well after a few days (they did take antibiotics whenever it was more serious). At the other end of the aisle, I have friends who will switch doctors if they don't prescribe their kids an antibiotic whenever there's a simple sore throat. A lot of doctors here will prescribe them right and left, just to be safe from any later criticism of not giving their patients enough medication. Oh, and I never had a doctor here ask for a test to see wether a throat infection was viral or bacterial.
These measures that disallow use of antibiotics by humans are inhumane.
For example, a chart in the article below shows huge growth in number of admissions after 2002 guidelines to replace full antibiotic therapy for acute UTI with 3-day antibiotic treatment.
There are plenty of people/companies working on phage therapies, and there are clinical trials happening now [1]. In some eastern European countries you can buy phage solutions over the counter. It just doesn't get much press - though I'd speculate that's because phage therapy clinical trials have been pretty lackluster so far.
Really I feel like this has been a hot topic for at least 15 years.. for example 5 years ago this https://youtu.be/plVk4NVIUh8 was on hacker news and got a lot of discussion as I recall…
Ok maybe you are right my search yielded few posts that got any traction - so maybe it was just me sharing with people I know!
What an amazing story, one which should give hope to the many people that are battling superbugs as we speak. Her (Strathdee's) Wikipedia page gives some more background, out of which this stood out to me:
"Although phage therapy had been used for one hundred years in Eastern Europe, it was not licensed for clinical use in the United States or most of Western Europe" [0]
Which indicates (if not proves) that healthcare is one one of the casualties of our polarized world.
Eastern Europe had to continue with phage therapies because they didn't have great access to antibiotics, which have many superior properties. Phage was used in the Western world, but early versions had serious purification issues, where people were getting killed by bacterial endotoxins present in the solutions.
It's not really "lost" as much as a readily obvious alternative was present in one setting and not the other.
> Eastern Europe had to continue with phage therapies because they didn't have great access to antibiotics […]
This is a very bubble centric view of the history. Eastern bloc countries, notably East Germany, Hungary and Yugoslavia, had very active and thriving drug research and manufacturing sectors. The Soviet Union, whilst having the drug research and manufacturing of their own, was purchasing swaths of drugs from the three aforementioned countries.
Azithromycin, one of the most widely prescribed macrolide antibiotics in the US today, was, in fact, discovered in Yugoslavia and licenced to Pfizer in 1980s.
Phage therapy was considered a novel area of research in a few of the Eastern bloc countries, but it never became neither widespread nor a substitute for antibiotics. It was just as fringe in those countries as it was elsewhere.
it's really terrible how the caring for one's health aspect of the medicine industry has taken a secondary role, the really important thing is corporate profit, patients are getting treated, but not healed
this is not to say the treatments are not effective, but I think it's telling to consider that the reason treatments remain effective is to avoid defrauding customers (err. patients), not becuase the intention is healing people.
Research in the field of phage therapy has traditionally been strong in the Soviet Union since the 1920s and in other Eastern Bloc countries such as the GDR after WW2. In recent years, the area has gained renewed attention in Germany. There exists currently an extensive programme of basic research on phages funded by the German Research Foundation (DFG). The project Web-site is located at: https://spp2330.de/
Broad Spectrum Antibiotics were superior to Phage Therapy when they were first introduced, as they didn't necessitate time intensive cultivation of the pathogen prior to administration. The high selectivity of Bacteriophages was their main disadvantage. Today, with all the knowledge about the importance of a healty gut Biome, the potential risk to "good bacteria" has to be weighed before administration of antibiotics is considered. Fast diagnostic tests, like the use of PCR to detect Covid-19, turn Phage Therapies greatest Drawback, its selectivity, into its greatest advantage.
Great story and glad about the positive outcome. But also highlights the benefits of being well connected. Doubtful a couple in a similar situation that were not a professor and associate dean at a well known university could've obtained the same outcome.
Yes, I had the same reaction. Altogether it's inspiring and I'm happy to see novel treatments like it when antibacterial therapies are desperately needed. At the same time seeing these inequities in the system was disturbing to me.
It's not only the special privileges the couple enjoyed -- how they received the treatment and another did not -- it's also how generating some sort of enthusiasm about a research area can require this kind of private string pulling. If one of those researchers had submitted a research grant on phage therapy would it have been approved?
I liked the article and am not meaning this as a criticism of it, the couple, the people involved, or the therapy. It's just revealing of structural problems in academics, health care, and society.
> Legal staff at Texas A&M expressed concern about future lawsuits. "I remember the lawyer saying to me, 'Let me see if I get this straight. You want to send unapproved viruses from this lab to be injected into a person who will probably die.' And I said, "Yeah, that's about it,'" Young said.
>"But Stephanie literally had speed dial numbers for the chancellor and all the people involved in human experimentation at UC San Diego. After she calls them, they basically called their counterparts at A&M, and suddenly they all began to work together," Young added.
>"It was like the parting of the Red Sea -- all the paperwork and hesitation disappeared."
You might notice something very peculiar about this story. Here are the pieces:
> What she accomplished next could easily be called miraculous [bullshit]
> Buoyed by her newfound knowledge, Strathdee began reaching out to scientists who worked with phages: "I wrote cold emails to total strangers, begging them for help," she said at Life Itself.
> she convinced phage scientists around the country to hunt and peck through molecular haystacks
> One stranger who quickly answered was Texas A&M University biochemist Ryland Young. He's been working with phages for nearly 45 years. Young, a professor of biochemistry and biophysics who runs the lab at the university's Center for Phage Technology. "We just dropped everything. No exaggeration, people were literally working 24/7" ... [that's what happens when I need help, university departments drop what they're doing to assist]
> Next, the US Food and Drug Administration had to greenlight this unproven cocktail of hope [in a week]
> But the woman who answered the phone at the FDA said, " 'No problem.' ... " [like magic]
> And then she tells me she has friends in the Navy [who doesn't]
> Yet just three weeks later, Strathdee watched doctors intravenously inject the mixture into her husband's body
> Legal staff at Texas A&M expressed concern about future lawsuits ... But Stephanie literally had speed dial numbers for the chancellor and all the people involved in human experimentation at UC San Diego. After she calls them, they basically called their counterparts at A&M, and suddenly they all began to work together [suddenly it happened, a miracle]
Ready for it?
> Strathdee was the associate dean of global health sciences at the University of California, San Diego
It wasn't a miracle. It was extreme privilege. She had elite access and got extraordinarily special treatment and response at every step. The phage aspect is very interesting, I've been reading about phages on HN for over a decade probably (and in that time there has seemingly been relatively little progress in their usage in the West). The rest of the story is rather disgusting in how it's portrayed in the article vs what's actually going on (connections, status, privileged treatment). Oh but it was like a miracle - no, no it wasn't.
It has little to do with her having "extreme privilege" or "elite access" and a lot to do with her being an infectious disease specialist and knowing who to reach out to for help. This is literally what people on HN do all the time. But apparently when someone outside of "tech" takes advantage of their industry connections, it's "extreme privilege" rather than just being smart.
It's so hypocritical to see these kinds of comments about "privilege" being posted to a forum where so many people don't grasp the kind of privilege they have that so casually lets them judge others. (Or do you make comments like this when HNers offer to help other HNers with their job hunts, or when complaints about Google, etc., reach the front page and something actually happens to get the situation resolved?)
I hope your point is that access to this shouldn't be restricted to such privileged people. The legal and regulatory barriers could be lifted, and if that happened then companies could be started to provide the therapy.
I got this from the article too. This couple was incredibly connected.
But.. they lived and worked in a field for 40 odd years, why the hell couldn't they take advantage of it? This isn't like Dad getting his frat bro son a job at Goldman.
People with wealth and connections can get worse medical care for exactly the same reason.
John F. Kennedy and Adolph Hitler ended their lives addicted to injections of opiates and amphetamines. Michael Jackson died from lack of sleep because he had “connections.”
I could make a much longer list of people whose “connections” got them killed.
https://en.wikipedia.org/wiki/Halicin - a recently (2019) discovered ATB with "an unusual mechanism of action" has been found to be effective against Acinetobacter Baumanii in mice. Found using deep-learning.
Readit News
I have a deep and abiding fondness for phage, but they're not quite as awesome as they seem at first glance. From the perspective of an infectious disease epidemiologist who has been super-interested in phage for my whole career (literally tried to get a job out of undergrad with a phage therapeutics startup):
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 (after being abandoned for some very real, very serious safety concerns back in the day), 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 tenured 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, especially when trying to treat at scale.
Yeah, it seems HN knows more about phages than physicians, which is pretty bloody damning. Why TF don't physicians know about this?
"First, Strathdee found an obscure treatment that offered a glimmer of hope -- fighting superbugs with phages, viruses created by nature to eat bacteria."
According to TFA, Strathdee is also an infectious disease epidemiologist, and she didn't find out about phages until her husband had almost karked it, after several months of fighting an antibiotic-resistant infection.
There was a similar story on HN three years ago about a teenager in the UK with cystic fibrosis and an antibiotic-resistant infection after a lung transplant. The physicians treating her didn't know about phages, and her mother had to suggest it. [https://news.ycombinator.com/item?id=19863445]
So that's at least two cases of people dying slowly from antibiotic-resistant infection until someone suggested phages, which were then successfully used to save their lives. Are the treating physicians incompetent?
Specialist ID physicians know - there's whole sessions about it at major infectious disease conferences. But there's a huge gap between "Knowing" and "Have the capability to use this in practice".
It's entirely reasonable she wouldn't have necessarily heard of a fairly niche therapy in another area - phage is basically a non-starter for global health (where her work was), and hospital epidemiology is a very niche field.
Phages were used in the west prior to the advent of antibiotics. They had a repetitional issue then, because our purification methods weren't always great, so phage preparations had both phage and potentially bits of the cell wall of the bacteria they had killed. Bacterial cell walls contain endotoxins, which are potentially quite dangerous.
They were largely abandoned in the West because with the advent of antibiotics, a wildly more effective solution to bacterial infections was present. The Cold War meant the Soviet Union had less access, and so needed to continue working on phage research more intensively.
There's a lot of work on phages going on in academia - I don't know about the startup world, TBH. I think some of the most promising leads are in combination therapy. It appears that treating with phage can push bacteria back into susceptibility (basically, two selective pressures at the same time), which is a cool idea. But the gap phage has to jump from "Interesting bespoke one-time treatments" to a generalizable treatment is a pretty big one. My expectation at least in the medium term is they'll be supplemental treatments for a few well known conditions where you can maintain phage libraries for them.
(I know nothing about this)
The trickier part is you have to keep them active and functional over long periods. That's not something most hospital labs are equipped to deal with.
In Germany, where I live at the moment, the risks and issues are well known and talked about. I have seen a large reduction of the prescription of antibiotics. The younger the MD, the less antibiotics are given.
But 80% (maybe even more) of the antibiotics are used by animal farming...
This is what needs to be talked about more. Like guns in the US, or telecom oligopolies in Canada, it seems animal based agriculture gets the “thoughts and prayers” treatment rather than any substantive discussion about what harm it is causing the planet, human health, and biological safety via antibiotic resistance.
The cases that worries me most is however debilitating chronic illnesses (where antibiotics is used as a stop gap until medical science find a cure), and illnesses which if let untreated might turn into a debilitating chronic problem. I hope they are keeping a close watch on the outcomes from those younger MDs.
Antibiotics in animal farming is obviously terrible. Animals should not be allowed to be kept unless it is in an environment that is safe and healthy for them. Antibiotics is a tool used to fix how poor some large scale farmers treat their animals.
For example, a chart in the article below shows huge growth in number of admissions after 2002 guidelines to replace full antibiotic therapy for acute UTI with 3-day antibiotic treatment.
https://bjgplife.com/confronting-the-urinalysis-tyrant/
Your last sentence is the most probable cause of superbugs.
1: https://clinicaltrials.gov/ct2/results?cond=&term=phage+ther...
Ok maybe you are right my search yielded few posts that got any traction - so maybe it was just me sharing with people I know!
I got tenure this year.
https://www.merck.com/stories/antimicrobial-resistance-an-em...
"Although phage therapy had been used for one hundred years in Eastern Europe, it was not licensed for clinical use in the United States or most of Western Europe" [0]
Which indicates (if not proves) that healthcare is one one of the casualties of our polarized world.
[0] https://en.wikipedia.org/wiki/Steffanie_A._Strathdee#Role_in...
Eastern Europe had to continue with phage therapies because they didn't have great access to antibiotics, which have many superior properties. Phage was used in the Western world, but early versions had serious purification issues, where people were getting killed by bacterial endotoxins present in the solutions.
It's not really "lost" as much as a readily obvious alternative was present in one setting and not the other.
This is a very bubble centric view of the history. Eastern bloc countries, notably East Germany, Hungary and Yugoslavia, had very active and thriving drug research and manufacturing sectors. The Soviet Union, whilst having the drug research and manufacturing of their own, was purchasing swaths of drugs from the three aforementioned countries.
Azithromycin, one of the most widely prescribed macrolide antibiotics in the US today, was, in fact, discovered in Yugoslavia and licenced to Pfizer in 1980s.
Phage therapy was considered a novel area of research in a few of the Eastern bloc countries, but it never became neither widespread nor a substitute for antibiotics. It was just as fringe in those countries as it was elsewhere.
this is not to say the treatments are not effective, but I think it's telling to consider that the reason treatments remain effective is to avoid defrauding customers (err. patients), not becuase the intention is healing people.
[1] https://eptc.ge/
It's not only the special privileges the couple enjoyed -- how they received the treatment and another did not -- it's also how generating some sort of enthusiasm about a research area can require this kind of private string pulling. If one of those researchers had submitted a research grant on phage therapy would it have been approved?
I liked the article and am not meaning this as a criticism of it, the couple, the people involved, or the therapy. It's just revealing of structural problems in academics, health care, and society.
>"But Stephanie literally had speed dial numbers for the chancellor and all the people involved in human experimentation at UC San Diego. After she calls them, they basically called their counterparts at A&M, and suddenly they all began to work together," Young added.
>"It was like the parting of the Red Sea -- all the paperwork and hesitation disappeared."
If you know who to call, things happen fast.
https://mybacteriophage.net/
Anyone with an aggressive bacteriological infection should be aware of and consider phage therapy when beginning treatment.
It is also important to pre-treat the selected phage in a concentrated solution of the pathogen to allow time for adaptation prior to injection.
> What she accomplished next could easily be called miraculous [bullshit]
> Buoyed by her newfound knowledge, Strathdee began reaching out to scientists who worked with phages: "I wrote cold emails to total strangers, begging them for help," she said at Life Itself.
> she convinced phage scientists around the country to hunt and peck through molecular haystacks
> One stranger who quickly answered was Texas A&M University biochemist Ryland Young. He's been working with phages for nearly 45 years. Young, a professor of biochemistry and biophysics who runs the lab at the university's Center for Phage Technology. "We just dropped everything. No exaggeration, people were literally working 24/7" ... [that's what happens when I need help, university departments drop what they're doing to assist]
> Next, the US Food and Drug Administration had to greenlight this unproven cocktail of hope [in a week]
> But the woman who answered the phone at the FDA said, " 'No problem.' ... " [like magic]
> And then she tells me she has friends in the Navy [who doesn't]
> Yet just three weeks later, Strathdee watched doctors intravenously inject the mixture into her husband's body
> Legal staff at Texas A&M expressed concern about future lawsuits ... But Stephanie literally had speed dial numbers for the chancellor and all the people involved in human experimentation at UC San Diego. After she calls them, they basically called their counterparts at A&M, and suddenly they all began to work together [suddenly it happened, a miracle]
Ready for it?
> Strathdee was the associate dean of global health sciences at the University of California, San Diego
It wasn't a miracle. It was extreme privilege. She had elite access and got extraordinarily special treatment and response at every step. The phage aspect is very interesting, I've been reading about phages on HN for over a decade probably (and in that time there has seemingly been relatively little progress in their usage in the West). The rest of the story is rather disgusting in how it's portrayed in the article vs what's actually going on (connections, status, privileged treatment). Oh but it was like a miracle - no, no it wasn't.
It has little to do with her having "extreme privilege" or "elite access" and a lot to do with her being an infectious disease specialist and knowing who to reach out to for help. This is literally what people on HN do all the time. But apparently when someone outside of "tech" takes advantage of their industry connections, it's "extreme privilege" rather than just being smart.
It's so hypocritical to see these kinds of comments about "privilege" being posted to a forum where so many people don't grasp the kind of privilege they have that so casually lets them judge others. (Or do you make comments like this when HNers offer to help other HNers with their job hunts, or when complaints about Google, etc., reach the front page and something actually happens to get the situation resolved?)
But.. they lived and worked in a field for 40 odd years, why the hell couldn't they take advantage of it? This isn't like Dad getting his frat bro son a job at Goldman.
John F. Kennedy and Adolph Hitler ended their lives addicted to injections of opiates and amphetamines. Michael Jackson died from lack of sleep because he had “connections.”
I could make a much longer list of people whose “connections” got them killed.