FDA approves first US phage therapy trial (2019) | Hacker News Reader

FDA approves first US phage therapy trial (2019)

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I was laughed out of my uni's microbiology department for even mentioning this 15 years ago. While my feelings were somewhat hurt, it wound up working out great for me. That experience led me to neuroscience and a wonderful graduate program, but I couldn't help but chortle a little bit with satisfaction reading this this morning.

It's a shame that progressive thoughts get laughed at in the field of academia.

Not sure why you're getting down voted. I completely agree.

really don't understand your down votes. How many breakthroughs were treated with contempt and laughter when they were first presented.

Relativity? Immunotherapy? many others I'm sure

And that was before peer review!

Now it's much harder for disruptive ideas to make it past the "peer wall".

Phage therapy was researched by Félix d'Hérelle, a french-canadian scientist who was awarded the Leeuwenhoek Medal. Eli Lilly and Company were working on commercializing it in the U.S.

The problem was phage therapy couldn't stand up to a disruptive idea: the large scale production of penicillin in the mid-40's.

Didn't know that.

But I can see how it seemed that penicillin had solved that problem forever back then.

Indeed. While Flemming himself was concerned about resistance, penicillin is:

1) Much broader spectrum than phage preparations 2) Easier to manufacture in large quantities 3) Safer, because you don't need to filter the prep to remove endotoxins

It's basically a silver bullet - if you don't look too far in the future. It was incredibly disruptive.

Because it was a pointless blanket statement? Anecdote - One classmate went on to study phage therapy in Europe, another went to work for Intralytix a phage therapy biotech in the US, both PhDs. They were not laughed at by their advisor or their contemporaries for their decisions.

While true, phage therapy was dismissed as propagandized pseudoscience from the Soviet Union since they were the pioneers in the initial research (and the research did appear dodgy TBH). The landscape has changed, but really recently that was not the case and many microbiologists viewed anything phage related as utter nonsense. I am happy to see more research happening.

Note that phage therapy was used and understood in the west well before the Soviet Union came into existence. It fell out of use because of the dangers from poorly purified phage preps, and because antibiotics showed up at about the same time those issues could have been fixed, and are a far more useful general purpose tool.

Do you have some sources for this? Because the Wikipedia article on phage therapy appears to directly contradict you.

Directly after the paragraph about its discovery by an Englishman and a Frenchman:

> A Georgian, George Eliava, was making similar discoveries. He travelled to the Pasteur Institute in Paris where he met d'Hérelle, and in 1923 he founded the Eliava Institute in Tbilisi, Georgia, devoted to the development of phage therapy.

Georgia was part of the USSR at the time. It appears to be the first reference to any actual therapy.

In any case it's a pretty tight schedule from the discovery of bacterophages in 1915/1917 to the formation of the USSR in 1922.

https://en.wikipedia.org/wiki/Phage_therapy

Edit:

Found something here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442826/

> From its first field trials as a prophylactic against avian typhosis (Salmonella gallinarum) in rural France in 1919 [...]

I'm gonna file that under kinda, but not really.

Something more in Félix d'Herelle's biography: https://en.wikipedia.org/wiki/F%C3%A9lix_d%27Herelle

> The first patient was healed of dysentery using phage therapy in August 1919. Many more followed. At the time, none, not even d'Hérelle, knew exactly what a phage was.

Source: Infectious disease epidemiologist who has been interested in phage research for two decades ;)

But you will find on that same Wikipedia page an entry for d'Herelle, and if you follow that...as you note yourself, you get an animal trial in 1919 as well as a human trial. D'Herelle then heads to Indochina to work on Cholera, and he's awarded an honorary doctorate two years after the USSR is founded - along with one of the field's most prestigious medals.

---

Is that a tight timeline? Yes. But the idea that "The West" ignored phages because it was some sort of Soviet pseudoscience is contrary to the historical record.

The west abandoned phage therapy because unfiltered endotoxins made phage therapy dangerous, and until the modern era, antibiotics are pretty superior in nearly every respect.

Took me a while to dig up an online source of his 1921 monograph on the subject. For the curious:

https://archive.org/details/lebactriophages00hrgoog/page/n9/...

(PDF etc. downloads are at the bottom right)

If you're interested, Flemming's Nobel Prize speech transcript is here: https://www.nobelprize.org/uploads/2018/06/fleming-lecture.p...

It's an excellent read.

What did happen because of the USSR is the institute in Georgia not abandoning phage research because they continued to have much more limited access to penicillin thanks to the Cold War.

And how many ideas are touted and never pan out?

You can’t blame people for being skeptical.

I agree that arguments should stay academic and not resort to ridicule.

Skeptical and sober is fine. It's how science should work.

Laughing and ridiculing is not. It's how groupthink reinforces itself.

Yeah, isn't curiosity and discovery what science is all about?

In the 80s in order to prove that ulcers were caused by bacteria, a doctor infected himself with said ulcer-causing bacteria and treated himself with antibiotics.

https://www.discovermagazine.com/health/the-doctor-who-drank...

In the 19th century, in order to prove that "dirtyness" causes cholera, a man named Pettenkofer drank a vial of clear water contaminated with cholera. Fortunately he attempted to control the experiment by neutralizing his stomach acids beforehand, which prevented the cholera from becoming pathogenic. The colony passed through his digestive tract without incident.

He neutralised his stomach acids to keep the V. cholerae alive, actually.

They didn't pass through him without incident, every account of this story I can find notes that he did get sick. The modern perspective of the story seems to be that he had an immunity from previously having dealt with cholera.

The story I heard was that Cholera automatically stops reproducing if its population gets high enough, and that keeping the cholera alive prevented it from spreading.

they'd be surrounded by constant quackery otherwise. ideas are a dime a dozen. clinical test plans and execution are not.

One person's experience is not generalizable.

20 years ago, the potential for phage therapy was a suggested review paper for an upper level virology class I was taking.

There is a guy on YT who created and used a crispered phage at some canadian hackerspace biolab. He is no longer lactose intolerant. He can laugh at academia & .gov institutions and their archaic rules and regulations. Coincidentally we see similar trends in neuroscience as individuals playing with things such as TMS/TCS etc. can't be held back by institutions such as the FDA & academia thus rush beyond them. TL;DR Be proud to be at the forefront - it's worth so much more than a dinosaur opinion.

Surely there must be some potential risk here, right?

I'm pretty sure this is the video that describes the whole process, in case you want to hear more about it. (Haven't watched it myself but it's been on my to-watch list for while) Comes from a YouTube channel called Though Emporium: https://www.youtube.com/watch?v=J3FcbFqSoQY

I fully expect a follow-up to that video where he's developing a therapy to treat his obesity after years of eating pizza and ice cream.

Brings to mind this: https://www.youtube.com/watch?v=evx_Ps85yu8

Iirc the cure was temporary and he won't be doing it again, but yeah he proved it can work, and work easily.

Sounds like ThoughtEmporium, but I don't remember him using a phage to do this. Might have to rewatch this video soon.

https://www.youtube.com/watch?v=J3FcbFqSoQY

He used a virus if I remember correctly.

They were idiots when they laughed. The Soviet Union was actually leading in this for a long time (Georgia).

I don't know why this stuff didn't go anywhere.

I remember reading this article, from 2003:

https://www.wired.com/2003/10/phages/

There are very real challenges to the mass application of phage therapy. I love it, have for several decades, and am especially excited about the potential based on some new findings for it to work in combination with antibiotics, but from a practical perspective, it's difficult.

Opposite for me - We could pick a three month project in our undergraduate (about 11 years ago), and one of the listed projects aims was to manipulate yeast cells with phages. I did not even consider it at the time because it seemed so far fetched and strange, and the probability of success so small.

Good to see something came out of that line of research.

Great to see that useful results came

In the back of my mind, I knew that if I got an antibiotic resistant infection in the US - an infection that didn’t respond to a few rounds of different drugs - I’d fly ASAP to Tbilisi, Georgia to go to the Phage Therapy Center.

I’m beyond excited about this. Not only are phages useful as another option in fighting resistant infection, they’re targeted: the phages can be engineering to only kill specific bacteria, unlike traditional antibiotics. Your gut bacteria would be spared!

I recall a documentary of over 10 years ago mentioning phage therapy in USSR and how it was completely dismissed and ignored in the west (not invented here syndrome, I suppose). If my memory doesn't fail me, they showed nursed collecting sewage (?) water to isolate the needed phages.

It's great to see this whole field finally overcoming prejudice.

Not sure why you were down voted but yes, the Russians have been using phage therapy for years. The issue (for the USA at least) is how do you approve a drug or treatment that can evolve? We simply don't have a regulatory framework for this mechanism of treatment. Fun read here: https://www.nature.com/news/phage-therapy-gets-revitalized-1...

I don't know if its the same one but Vice/Motherboard made this mini doc in 2017 and researcher dude does this in connecticut: https://youtu.be/aVTOr7Nq2SM?t=462

It's not a matter of NIH syndrome.

There's very real obstacles to phage therapy. The west was using phage therapy...until it started killing people (bad phage preps are dangerous). Penicillin came along, and you have something that's just outright better.

Antibiotics are by and large less dangerous, more stable, broader spectrum, etc. It's also a difficult challenge from the regulatory perspective - as with fecal transplant, "bespoke set of microbes" is...weird...from a legal perspective. The reasons the USSR was leading phage research was they were behind on antibiotics.

We've come back around because we need a backstop against antibiotics failing.

Penicillin came along in late 19th century though. Well before anyone even knew what a "phage" was.

Flemming's work was in 1928, over a decade after folks were using phage therapy, and the mass production of penicillin was in the mid-40's.

Note that we were using phage therapy before we knew what phages were, because as it turns out, that's not really necessary. Except that if you don't know what they are, you also don't know that your preparation is full of endotoxins from ruptured bacteria, which are a threat to your patient. Which is one of the reasons it wasn't terribly popular.

I fail to understand why the broader scientific community failed to entertain the idea of phages for sometime. You apply the scientific method, and you seek truth. Maybe earlier indicators to the effectiveness weren't great, but you will only know for certain if you apply the scientific method.

The West used phage therapy for a long time. It developed a reputation for killing people, because poorly prepared phage preparations contain bacterial endotoxins that will kill your patient.

But it wasn't the scientific community "failing to entertain the idea of phages". It was very real logistical challenges to the use of phage therapy, which may or may not be overcome, but were definitely in a "The juice is not worth the squeeze" realm until recently.

But I've been working in infectious diseases for 20 years, and we've been discussing and evaluating the potential of phage or phage-derived compounds that entire time.

0. Is this significant because the FDA was institutionally-(/culturally-)against phage therapies because the Soviets went that way rather than antibiotics? Does anyone know how much of a hurdle that is still?

1. Isn't it the case that resistances to phages should be perhaps (an) order(s)-of-magnitude less likely for prokaryotes and fungi to evolve resistances compared to static compounds like antibotics/antimycotics because phages are probably the most abundant "almost life" parasitizing other microbes in the wild?

2. Are we any closer to computational molecular-level engineering of custom antigens against any particular pathogen?

3. Although probably tiny, is there a risk of horizontal gene transfer between phages and other pathogens?

Armata BioSciences and C3J Therapeutics merged in April.

https://investor.armatapharma.com/2019-05-09-C3J-Therapeutic...

Loosely related, from 2019: https://news.ycombinator.com/item?id=19863445

2018: https://news.ycombinator.com/item?id=17085827

2017: https://news.ycombinator.com/item?id=14226790

So will this be one specific phage that they can package up and send out? Or will it be unique to each patient?

Last I read about phage therapy they’d actually culture the infection and locate phage viruses already preying on those exact bacteria and then scale them up as the therapy.

It'll end up being specific to the species of bacteria causing the patient's infection, which means they'll first have to isolate the source of infection. Sometimes this will be an easy task, sometimes not. I suspect over the long term treatments that go to market will combine several (or many) natural or engineered phages into a single delivery protocol and those that don't find their natural targets will die out harmlessly.

This is a super interesting area of research that I think will ultimately complement treatments like biota transplants for chronic diseases and antibiotics for acute disease. As a therapeutic approach (at least in the US) its still young though, so I wouldn't expect to see dramatic changes for years yet.

I'd say that a "broad spectrum phage" is still well within the realm of science fiction.

Curious how you get the persons immune system not to attack the phages in order to keep it effective.

Probably direct application - like injection to wound plus overwhelming amount, so even if immune kills most, some will reach regions infected with target bacteria.

After target is eliminated, regular antibiotics are used to kill remainder of phage bacteria.

What is phage bacteria?Bacteriophages are a virus. If phage therapy is successful, there shouldnt be any target bacteria left to kill.

Oh, you’re right.

I somehow thought bacteriophages are another bacterias hunting for problematic ones.

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