5 ms·

Engineered phages help teenager with antibiotic-resistant infection

85 points by spking 7y ago

perilunar 7y ago
Amazing story, but the fact that the patient’s mother had to suggest phage therapy, and that the specialists didn't know much about it is pretty damning.
- sterlind 7y ago
  Phage therapy is a blind spot for Western medicine. It's a new category of drug, which means lots of work to get it through FDA or UK trials, and it's not a single molecule - it's a process. There's little point to taking a single combination of phages, packing them into a pill and ramming it through the clinical trials process - it'll be way too specific to be worth it. Instead, the entire pipeline - keeping a library of bacteriophages, testing them for efficacy against samples, modifying them for increased virulence, screening for safety - needs to be approved, and run for each patient. That's too experimental for the FDA, and the FDA is too rigid to allow approval for such pipelines (except in rare cases, like CAR-T immunotherapy.) Plus the UK has that anti-gene therapy law because of a disastrous adenovirus trial that killed six healthy volunteers. The West is too risk-averse and conservative to make the big bureaucratic changes to allow this. Russia had no such hangups, which is why phage therapy flourished there.
  - ummonk 7y ago
    >Plus the UK has that anti-gene therapy law because of a disastrous adenovirus trial that killed six healthy volunteers. Wait, what? Have a link for the uninformed?
    - Spare_account 7y ago
      As far as I can tell from a quick search, there is neither an anti-gene therapy law, nor has any trial resulted in any deaths in the UK. The closest I can get in the UK is the Parexel incident in 2006 where six men experienced a cytokine storm unexpectedly and were hospitalised as a result. https://www.bbc.com/news/health-22556736 https://www.bbc.com/news/health-22556736
  - roywiggins 7y ago
    The West was lucky enough to invent penicillin which rather limited the appeal of phage research- you don't need phages if you haven't discovered antibiotic resistance, and once you've committed to using broad-spectrum antibiotics you'll just do what we did, which is switch between them. It sounds like the USSR was just not very good at producing its own antibiotics, so phage therapy remained popular there, as it wasn't any less effective than their poor quality antibiotics, which ended up causing resistance there before they did in the West. If you've managed to spur resistance, and you have persistent supply problems with your antibiotics, pushing forward with phage research makes a lot of sense. http://discovermagazine.com/2017/oct/the-cold-wars--modern-resistance http://discovermagazine.com/2017/oct/the-cold-wars--modern-r...
    - adrianN 7y ago
      You don't have to discover antibiotic resistance, it's obvious to anybody working with bacteria. In fact the inventor of Penicillin warned against it already in 1945, only a few years after mass-production became possible.
  - perilunar 7y ago
    > It's a new category of drug Well that's the thing — it's not new. It dates back to the 1920s. I heard about it years ago, so for physicians in late 2017 to watch for months as a patient with antibiotic-resistant infections declines and then to "send her home with palliative care" — that is just appallingly negligent.
    - jlg23 7y ago
      We might have read the same articles "years ago", because I too remember to have read about that in pseudo-scientific publications (could have been about the Eliava Institute[1], that rings a bell with me). As probably did the mother of the patient who "suggested" phage therapy. Instead of blaming doctors (see below), we should praise the internet for allowing even these niche-topics to reach the masses. Wikipedia gives a nice summary of the political aspects of why lots of doctors educated in the west never learned about it[2]. According to the same article, it became accessible to the average practitioner in the west only 4 years ago: In June 2015 the European Medicines Agency hosted a one-day workshop [...] and in July 2015 the National Institutes of Health (USA) hosted a two-day workshop [...] And that just means that the tickle-down of knowledge within the medical community started at that point. Given that patients and their relatives are notorious for consulting google first and only then their doctors[3][4], I personally applaud the doctors for being so open minded to dig into the alternative treatment. [1] https://en.wikipedia.org/wiki/Phage_therapy#History https://en.wikipedia.org/wiki/Phage_therapy#History [2] https://en.wikipedia.org/wiki/George_Eliava_Institute https://en.wikipedia.org/wiki/George_Eliava_Institute [3] Like the sales person turned manager who skimmed Wikipedia for programming related topics and then gives you detailed, nonsensical advice and questions your expertise when you roll your eyes, frantically searching for a nice way of saying "STFU, my BS-dector maxed out" ..... [4] https://twitter.com/DrPascalMeier/status/699202717030490112 https://twitter.com/DrPascalMeier/status/699202717030490112
      - perilunar 7y ago
        If this was just a case of a random patient and their GP, I'd agree with you. But this was a double lung transplant, at the Great Ormond Street Hospital, one of the world's best children's hospitals. After 9 months of decline: "It was at this point that the patient’s mother brought up the idea of phage therapy. Spencer didn’t know much about it, but there was a hospital microbiologist, Dr. James Soothill, who’d worked on the viruses and agreed to help." So they had a microbiologist on staff who knew about phage therapy. They had a patient with a life threatening antibiotic resistant infection. It took them 9 months to connect the two, and it only happened because the patient's mother suggested it? Sorry, but that is just completely messed up.
  - altfredd 7y ago
    > Phage therapy is a blind spot for Western medicine. It's a new category of drug It is a branch of traditional medicine, approximately 100000 years old and counting. "Western medicine" ignores phage therapy, because growing a bunch of mud in a bowl does not bring anyone 10000% cuts. Cultivating phages still requires labor and equipment, and can be quite profitable, just not 10000% profitable, — because pretty much anyone can do it.
    - Mvandenbergh 7y ago
      >It is a branch of traditional medicine, approximately 100000 years old and counting. No it isn't.
    - jdietrich 7y ago
      Antibiotics aren't commercially valuable, which is a critical problem - drug companies have no interest in developing new antibiotics, because they won't see a return on their investment. This is one area of medicine where the problem isn't drug company profiteering, but the lack of profit. https://www.idsociety.org/10x20/ https://www.idsociety.org/10x20/
      - Whack-kneed 7y ago
        Perhaps not, but the market for industrial antibiotics in everything from cattle-feed to shredded-cheese is huge and begs if not deservesdeserves to be taxed to make page therapy economically feasible. Unless you have another approach to fighting antibiotic resistant infections.
- wetpaws 7y ago
  US is pretty arrogant when it comes to everything outside of their worldview
- perlgeek 7y ago
  I know of several cases where patients heard from friends or relatives about experimental or new treatments that were a perfect fit for their situation, but that specialists had never heard of. It's worth the time and effort to research conditions that affect you (or your family) and actively seek non-standard treatments that your doctors don't know about. Don't blindly trust their expertise.
phront 7y ago
Realy great result but may it be a major step towards z apocalypse if something goes wrong?
_bxg1 7y ago
Playing the part of the optimist, I think we'll always be able to outsmart our ailments in the long run. It's startling to see an arms race start with antibiotics, because we've been winning in that arena with very little effort for over a century, but having to get creative again and being totally helpless against a coming apocalypse are two different things.
- iso1337 7y ago
  Able to? Yes. Willing to? Not as much. Just consider the following: 1) it’s been so long since people have first hand witness of the horrors of smallpox, polio, etc. So long that anti-vax is alive and well in affluent, educated enclaves. 2) antibiotics are not profitable. Achaogen tried but the business case just wasn’t there. https://www.bloomberg.com/news/articles/2019-05-03/antibiotics-aren-t-profitable-enough-for-big-pharma-to-make-more https://www.bloomberg.com/news/articles/2019-05-03/antibioti... So I agree with your last statement that we at not totally helpless, but I do think (as with global climate change or deferred maintenance on levees) there has to be an immediate and pressing need for people to put their money and actions in the right place.
- adrianN 7y ago
  It's not that hard actually. We just have to cycle through the various antibiotic components with a sufficiently long cycle time (so that any resistances have time to disappear from the gene pool) and stop overusing antibiotics, especially for livestock.
yegle 7y ago
A short video on Phage from Motherboard: https://youtu.be/aVTOr7Nq2SM https://youtu.be/aVTOr7Nq2SM
dang 7y ago
Also https://www.bbc.co.uk/news/health-48199915 https://www.bbc.co.uk/news/health-48199915, via https://news.ycombinator.com/item?id=19867303 https://news.ycombinator.com/item?id=19867303.
Insanity 7y ago
They wrote "helped prolong the patients life" in some paragraphs. That kept making me think that in the end the patient did die because of the infection but it just took longer. However, it appears that the patient is still alive today. That's quite the achievement and opens up interesting ways of beating antibiotic resistance. Interestingly and semi-related, one of my friends is resistant to antibiotics. Apperantly in her country of origin you can get them pretty much like normal medicine in the pharmacy. People use antibiotics for almost everything, and she did not know about the possibility of developing resistance against it. It was not even 'discovered' until she moved here (Western Europe). Hopefully more countries will raise awareness around this issue. Because of my bubble I thought everyone would be pretty much aware of it, but as with many things, that was just my bubble :)
- jdietrich 7y ago
  >They wrote "helped prolong the patients life" in some paragraphs. That kept making me think that in the end the patient did die because of the infection but it just took longer. The patient is alive and well, but her underlying illness (cystic fibrosis) is life-limiting; most CF patients die before the age of fifty and this treatment won't significantly change that life expectancy.
  - Insanity 7y ago
    Ah that explains :) Thanks!
  - DiseasedBadger 7y ago
    Are you sure you didn't mean "Ah that explains :(" ?
    - Insanity 7y ago
      Pretty sure that was a reply to me instead of the current parent. Yes, :( would have been more appropriate. I did not really think that much about the smiley, and did not use it as a reflection of the fact but more as a reflection on finding out the gap in my thinking.
sena 7y ago
Also a nice informative video on bacteriophage from Kurzgesagt: https://www.youtube.com/watch?v=YI3tsmFsrOg https://www.youtube.com/watch?v=YI3tsmFsrOg
Amygaz 7y ago
And then the endogenous CRISPR system will take care of making bacteria resistant to the engineered phages, because that’s what it naturally does, and we will be in another arm race. Eventually, mentalities around antibiotic used will have to changes: we have to use antibiotics only when necessary; we need to stop trusting that people will take their antibiotics properly and completely; we need to start using so-called “last-resort” antibiotics a lot sooner in the process.
m463 7y ago
I've wondered if phages would ever come into the spotlight ever since I read this article about 15 years ago: "How Ravenous Soviet Viruses Will Save the World" https://www.wired.com/2003/10/phages https://www.wired.com/2003/10/phages

85 points by spking 7y ago

Amazing story, but the fact that the patient’s mother had to suggest phage therapy, and that the specialists didn't know much about it is pretty damning.

sterlind 7y ago
Phage therapy is a blind spot for Western medicine. It's a new category of drug, which means lots of work to get it through FDA or UK trials, and it's not a single molecule - it's a process. There's little point to taking a single combination of phages, packing them into a pill and ramming it through the clinical trials process - it'll be way too specific to be worth it. Instead, the entire pipeline - keeping a library of bacteriophages, testing them for efficacy against samples, modifying them for increased virulence, screening for safety - needs to be approved, and run for each patient. That's too experimental for the FDA, and the FDA is too rigid to allow approval for such pipelines (except in rare cases, like CAR-T immunotherapy.) Plus the UK has that anti-gene therapy law because of a disastrous adenovirus trial that killed six healthy volunteers. The West is too risk-averse and conservative to make the big bureaucratic changes to allow this. Russia had no such hangups, which is why phage therapy flourished there.
- ummonk 7y ago
  >Plus the UK has that anti-gene therapy law because of a disastrous adenovirus trial that killed six healthy volunteers. Wait, what? Have a link for the uninformed?
  - Spare_account 7y ago
    As far as I can tell from a quick search, there is neither an anti-gene therapy law, nor has any trial resulted in any deaths in the UK. The closest I can get in the UK is the Parexel incident in 2006 where six men experienced a cytokine storm unexpectedly and were hospitalised as a result. https://www.bbc.com/news/health-22556736 https://www.bbc.com/news/health-22556736
- roywiggins 7y ago
  The West was lucky enough to invent penicillin which rather limited the appeal of phage research- you don't need phages if you haven't discovered antibiotic resistance, and once you've committed to using broad-spectrum antibiotics you'll just do what we did, which is switch between them. It sounds like the USSR was just not very good at producing its own antibiotics, so phage therapy remained popular there, as it wasn't any less effective than their poor quality antibiotics, which ended up causing resistance there before they did in the West. If you've managed to spur resistance, and you have persistent supply problems with your antibiotics, pushing forward with phage research makes a lot of sense. http://discovermagazine.com/2017/oct/the-cold-wars--modern-resistance http://discovermagazine.com/2017/oct/the-cold-wars--modern-r...
  - adrianN 7y ago
    You don't have to discover antibiotic resistance, it's obvious to anybody working with bacteria. In fact the inventor of Penicillin warned against it already in 1945, only a few years after mass-production became possible.
- perilunar 7y ago
  > It's a new category of drug Well that's the thing — it's not new. It dates back to the 1920s. I heard about it years ago, so for physicians in late 2017 to watch for months as a patient with antibiotic-resistant infections declines and then to "send her home with palliative care" — that is just appallingly negligent.
  - jlg23 7y ago
    We might have read the same articles "years ago", because I too remember to have read about that in pseudo-scientific publications (could have been about the Eliava Institute[1], that rings a bell with me). As probably did the mother of the patient who "suggested" phage therapy. Instead of blaming doctors (see below), we should praise the internet for allowing even these niche-topics to reach the masses. Wikipedia gives a nice summary of the political aspects of why lots of doctors educated in the west never learned about it[2]. According to the same article, it became accessible to the average practitioner in the west only 4 years ago: In June 2015 the European Medicines Agency hosted a one-day workshop [...] and in July 2015 the National Institutes of Health (USA) hosted a two-day workshop [...] And that just means that the tickle-down of knowledge within the medical community started at that point. Given that patients and their relatives are notorious for consulting google first and only then their doctors[3][4], I personally applaud the doctors for being so open minded to dig into the alternative treatment. [1] https://en.wikipedia.org/wiki/Phage_therapy#History https://en.wikipedia.org/wiki/Phage_therapy#History [2] https://en.wikipedia.org/wiki/George_Eliava_Institute https://en.wikipedia.org/wiki/George_Eliava_Institute [3] Like the sales person turned manager who skimmed Wikipedia for programming related topics and then gives you detailed, nonsensical advice and questions your expertise when you roll your eyes, frantically searching for a nice way of saying "STFU, my BS-dector maxed out" ..... [4] https://twitter.com/DrPascalMeier/status/699202717030490112 https://twitter.com/DrPascalMeier/status/699202717030490112
    - perilunar 7y ago
      If this was just a case of a random patient and their GP, I'd agree with you. But this was a double lung transplant, at the Great Ormond Street Hospital, one of the world's best children's hospitals. After 9 months of decline: "It was at this point that the patient’s mother brought up the idea of phage therapy. Spencer didn’t know much about it, but there was a hospital microbiologist, Dr. James Soothill, who’d worked on the viruses and agreed to help." So they had a microbiologist on staff who knew about phage therapy. They had a patient with a life threatening antibiotic resistant infection. It took them 9 months to connect the two, and it only happened because the patient's mother suggested it? Sorry, but that is just completely messed up.
- altfredd 7y ago
  > Phage therapy is a blind spot for Western medicine. It's a new category of drug It is a branch of traditional medicine, approximately 100000 years old and counting. "Western medicine" ignores phage therapy, because growing a bunch of mud in a bowl does not bring anyone 10000% cuts. Cultivating phages still requires labor and equipment, and can be quite profitable, just not 10000% profitable, — because pretty much anyone can do it.
  - Mvandenbergh 7y ago
    >It is a branch of traditional medicine, approximately 100000 years old and counting. No it isn't.
  - jdietrich 7y ago
    Antibiotics aren't commercially valuable, which is a critical problem - drug companies have no interest in developing new antibiotics, because they won't see a return on their investment. This is one area of medicine where the problem isn't drug company profiteering, but the lack of profit. https://www.idsociety.org/10x20/ https://www.idsociety.org/10x20/
    - Whack-kneed 7y ago
      Perhaps not, but the market for industrial antibiotics in everything from cattle-feed to shredded-cheese is huge and begs if not deservesdeserves to be taxed to make page therapy economically feasible. Unless you have another approach to fighting antibiotic resistant infections.
wetpaws 7y ago
US is pretty arrogant when it comes to everything outside of their worldview
perlgeek 7y ago
I know of several cases where patients heard from friends or relatives about experimental or new treatments that were a perfect fit for their situation, but that specialists had never heard of. It's worth the time and effort to research conditions that affect you (or your family) and actively seek non-standard treatments that your doctors don't know about. Don't blindly trust their expertise.

phront 7y ago

Realy great result but may it be a major step towards z apocalypse if something goes wrong?

_bxg1 7y ago

Playing the part of the optimist, I think we'll always be able to outsmart our ailments in the long run. It's startling to see an arms race start with antibiotics, because we've been winning in that arena with very little effort for over a century, but having to get creative again and being totally helpless against a coming apocalypse are two different things.

iso1337 7y ago
Able to? Yes. Willing to? Not as much. Just consider the following: 1) it’s been so long since people have first hand witness of the horrors of smallpox, polio, etc. So long that anti-vax is alive and well in affluent, educated enclaves. 2) antibiotics are not profitable. Achaogen tried but the business case just wasn’t there. https://www.bloomberg.com/news/articles/2019-05-03/antibiotics-aren-t-profitable-enough-for-big-pharma-to-make-more https://www.bloomberg.com/news/articles/2019-05-03/antibioti... So I agree with your last statement that we at not totally helpless, but I do think (as with global climate change or deferred maintenance on levees) there has to be an immediate and pressing need for people to put their money and actions in the right place.
adrianN 7y ago
It's not that hard actually. We just have to cycle through the various antibiotic components with a sufficiently long cycle time (so that any resistances have time to disappear from the gene pool) and stop overusing antibiotics, especially for livestock.

yegle 7y ago

A short video on Phage from Motherboard: https://youtu.be/aVTOr7Nq2SM https://youtu.be/aVTOr7Nq2SM

dang 7y ago

Also https://www.bbc.co.uk/news/health-48199915 https://www.bbc.co.uk/news/health-48199915, via https://news.ycombinator.com/item?id=19867303 https://news.ycombinator.com/item?id=19867303.

Insanity 7y ago

They wrote "helped prolong the patients life" in some paragraphs. That kept making me think that in the end the patient did die because of the infection but it just took longer. However, it appears that the patient is still alive today. That's quite the achievement and opens up interesting ways of beating antibiotic resistance. Interestingly and semi-related, one of my friends is resistant to antibiotics. Apperantly in her country of origin you can get them pretty much like normal medicine in the pharmacy. People use antibiotics for almost everything, and she did not know about the possibility of developing resistance against it. It was not even 'discovered' until she moved here (Western Europe). Hopefully more countries will raise awareness around this issue. Because of my bubble I thought everyone would be pretty much aware of it, but as with many things, that was just my bubble :)

jdietrich 7y ago
>They wrote "helped prolong the patients life" in some paragraphs. That kept making me think that in the end the patient did die because of the infection but it just took longer. The patient is alive and well, but her underlying illness (cystic fibrosis) is life-limiting; most CF patients die before the age of fifty and this treatment won't significantly change that life expectancy.
- Insanity 7y ago
  Ah that explains :) Thanks!
- DiseasedBadger 7y ago
  Are you sure you didn't mean "Ah that explains :(" ?
  - Insanity 7y ago
    Pretty sure that was a reply to me instead of the current parent. Yes, :( would have been more appropriate. I did not really think that much about the smiley, and did not use it as a reflection of the fact but more as a reflection on finding out the gap in my thinking.

sena 7y ago

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

Amygaz 7y ago

And then the endogenous CRISPR system will take care of making bacteria resistant to the engineered phages, because that’s what it naturally does, and we will be in another arm race. Eventually, mentalities around antibiotic used will have to changes: we have to use antibiotics only when necessary; we need to stop trusting that people will take their antibiotics properly and completely; we need to start using so-called “last-resort” antibiotics a lot sooner in the process.

m463 7y ago

I've wondered if phages would ever come into the spotlight ever since I read this article about 15 years ago: "How Ravenous Soviet Viruses Will Save the World" https://www.wired.com/2003/10/phages https://www.wired.com/2003/10/phages