No antibiotics worked, so this woman turned to phage scientists
edition.cnn.com
edition.cnn.com
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.
And you're making an inconsistent comparison: it's not about being an expert, not even about having read a wikipedia article on the topic, it's merely about having heard of that thing existing. A Python dev who has never even heard of Rust or can't even guess what HPC might stand for would be strange indeed. And the same goes for medical professionals who haven't even heard about a whole class of treatment options for a serious global disease problem (and, as a corollary, cannot recommend consulting a specialist).
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 ban was a few years ago.
https://www.cidrap.umn.edu/news-perspective/2018/12/fda-repo...
1ml of sea water will contain billions of phages, but its pot luck if you get the right strain.
Another thing not mentioned with antibiotics is man y are penicillin based that when metabolised become penicillamine which is used to treat copper toxicity or Wilson's disease, ie it makes the liver dump copper out of the body. Copper is needed to produce Interleukin-2, a naturally occurring chemo drug, most effective when injected into tumours, but having naturally high levels circulating can be helpful as a prevention measure.
Creatine when metabolised becomes creatinine which in sufficient qty can kill gram positive and gram negative bacteria. If you get 3rd degree burns, the muscles catabolise to release creatine and then the creatinine helps to keep bacteria at bay with the wounds.
It probably also explains why the US military are reportedly the only one's to use copper sulphate to debride battlefield wounds. Even the WHO dont recommend using it! Copper sulphate will dissolve skin though.
Vitamin D also increases creatinine, and because creatinine is used for estimated glomular filtration rate kidney tests, high levels of creatinine can make you appear to have various stages of kidney disease. Medical lab tests (human and veterinary) can not tell if you are supplementing so dont get an inaccurate diagnosis.
https://www.fda.gov/animal-veterinary/safety-health/antimicr...
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.
So my wife uses the drops for several days and gets worse. What's the solution? Mix half distilled white vinegar (5% concentration) and half 91% isopropyl alcohol (or 190 proof ethanol). This is a cheap solution which is generally effective for both fungal and bacterial outer ear infections. She was better in less than week.
There has also been several (4 that I can find myself) studies done on using acidic drops as the only treatment for ear infections, all which has shown them non-effective to clear an infection. Alcohol can also irritate the skin further, increasing inflammation.
Ear infections are however complex since most of the studies are either done on children, commercial or military divers. The military protocol in the Netherlands is to start with an acidic solution and then if the inflammation get worse introduce steroids. If that doesn't clear it, then add a combination of antibiotics and steroids. Steroids has the problem of increasing risk to bacterial infection, but the combination of using antibiotics with the steroids reduces that risk. It is this combination that doctors use in post surgery.
The Dutch protocol seems like the optimal treatment protocol for now, but it assumes you got a doctor to monitor it. My guess is that regular doctors jumps to the last step with the assumption that it is bacterial infection in order to minimize the need for further visits. One study I read also mentioned that adherence to correct application of the drops was one of the most significant factor in outcomes, which might imply an other reason to go for the strongest treatment first.
One thing that favors alcohol however is that keeping the ear dry is extremely important in addressing outer ear infection and preventing bacteria from growing. The theory behind vinegar and alcohol does thus seem quite sound from a theory perspective, stopping the bacterial infection before it get a chance to grow.
It's interesting that the studies show that solution as ineffective. It cured my wife. Then someone at work had an outer ear infection that recurred after two treatments with antibiotic drops. This solution also solved their problem.
As a side note, my wife was on steroids when she contracted the infection. So I think that contributed to her catching it.
I don't know why the studies shows them to be ineffective. Since they include acid drops in the studies it seems to be a well known home remedy, and given that it used prophylactically by the military in several countries there seems to be some reason for it. I could make a guess that doctors in the military/pediatric care are already keeping the ear of the patient dry so that alcohol don't provide any additional benefits, and they remove vax/debri in case those prevent the ear from drying.
If you've never had one of these - you do not want to get one. They can be extremely painful.
I remember from high school organic chemistry that an acid combined with a base yields a water and a salt, but and acid combined with an alcohol yields a water and an ester.
https://en.m.wikipedia.org/wiki/Ester
"Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product."
Which debilitating, non-bacterial chronic illnesses are treated with antibiotics as a stopgap measure?
The human body has many defenses and mechanics to keep bacteria in balance. I would point particularly towards the gut/intestant, the skin, ears, anus, bladder and genitalia for places where bacteria need to be constatly kept at the correct balance. Some things are treatable. Some things are possible to cut off. Some things are less known/fixable, in which case symptoms is the only thing possible to addressed at this time.
When livestock get sick, they are “culled,” not treated.
Which makes the use of antibiotics (“growth promoting anti-microbials”) all that more outrageous.
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.
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.
So if he had received the phage treatment sooner, would that have lessened these effects? Or are they sure that these effects were not caused by the phages themselves? Obviously it's better to be alive, even with these effects, but if doctors were choosing between several options for a future patient, they'd presumably want to know the causal chain.
Phages are also highly adapted to attack bacteria and often specific bacteria. It’s highly unlikely to affect humans. That’s easy to show since dirt is loaded with bacterial phages.
Additionally there was significant research in Soviet bloc on the safety and efficacy of phage treatment.
I’m hoping phage treatment becomes more common and better. The rise of bacterial superbugs is one of the greatest threats to modern life, as in we don’t expect ourselves or loved ones to die routinely from bacterial infections. However that’s very recent thing in human history. I’d readily wager that bacterial diseases have killed far more people than viral infections. They’re the literal plague.
In the beginning of her recovery, she survived life-threathening bacterial infections with phage therapy.
> Then she convinced phage scientists around the country to hunt and peck through molecular haystacks of sewage, bogs, ponds, the bilge of boats and other prime breeding grounds for bacteria and their viral opponents. The impossible goal: quickly find the few, exquisitely unique phages capable of fighting a specific strain of antibiotic-resistant bacteria literally eating her husband alive.
> Next, the US Food and Drug Administration had to greenlight this unproven cocktail of hope, and scientists had to purify the mixture so that it wouldn't be deadly.
> Yet just three weeks later, Strathdee watched doctors intravenously inject the mixture into her husband's body -- and save his life
The second is auto vaccines and Lysates which present dead bacteria to the body so it can create an appropriate immune response. They are used in Russia for things like Urinary tract Infections which in the West are often untreatable with antibiotics but they do seem to work. Get the immune system to recognise the baddy and work out how to kill it and then in the harder to reach places it can be effective. Works fairly well for Chronic infections but the issue is identifying the bacteria precisely to match and existing mix or collecting the bacteria and cultivating and killing it mechanically or with heat so it can be injected back into the patient safely in other places in the body.
Both techniques were outrun by antibiotics in the beginning, antibiotics are a lot easier to administer as you don't have to identify the pathogen precisely and its easy to make in bulk. But both these more natural solutions are a lot harder for bacteria to become immune to and have undergone the evolutionary process alongside us and them. I think both are worth serious efforts and development.
The virus evolves and adapts with the bacteria, modifying its receptors and modes of action as the host survivors mutate, which is beyond the capability of a chemical antibiotic.
This is why it is so important to pre-treat the phage in a concentrated solution of the target pathogen prior to injection into a patient, which allows the virus to maximize infectivity.
Manufacture a serum loaded with hundreds or thousands of phages known to target superbugs and let them decimate the bacteria. Choose the survivors. If you could automate the last step it could be something any old doctors office could do.
This tool can't be used like antibiotics. It requires expertise in classification.
I remember when Google was claiming they could track the Flu based on searches, it was going to revolutionize tracking pandemics.
For me, the most foreseeable application of ML to phage work is predictive models of antibiotic treatment failure.
It took me a year of doctor shopping to get an approved treatment for a common condition.
What keeps us from having a register/bank of highly effective phages to treat people with those boring old multi drug resistant bacteria bacteria?
Why do we keep saving and at the same time ruining peoples lifes with fluoroquinolones, gentamicin and other dangerous antibiotics instead of just giving them phages?
- Bacteria adapt to phage infections, just as they do to antibiotics
- Many phages are very host-specific, so a given cocktail might not even be able to target the pathogenic bacteria in question. There are phages with broader host spectra, but then they might be able to target the rest of your microbiome, which can lead to other health problems
- Since phages have protein shells, human antibodies will target them, and may prevent them from reaching the infected tissue. You might also only be able to use a particular phage once for this reason.
The FDA. The only freedom you have in the USA is to die.
Oh, sure, you are allowed to do it entirely yourself and with your own funds, but you can't share the burden with people. Yay freedom.
Fascinating article. Although the page spontaneously reloaded while I was in the middle of reading, twice! Very annoying to try to read something with so much ad code doing reflows, popups and reloads …
> Isolated from Western advances in antibiotic production in the 1940s, Russian scientists continued to develop already successful phage therapy to treat the wounds of soldiers in field hospitals. During World War II, the Soviet Union used bacteriophages to treat many soldiers infected with various bacterial diseases e.g. dysentery and gangrene.[28] Russian researchers continued to develop and to refine their treatments and to publish their research and results. However, due to the scientific barriers of the Cold War, this knowledge was not translated and did not proliferate across the world.
https://en.wikipedia.org/wiki/Phage_therapy
See also https://en.wikipedia.org/wiki/Marine_bacteriophage (for fun, or maybe horror? The oceans are grey goo.)
I would hazard a guess that the reasons are other than translation. Keen scientists learn enough of foreign languages to read papers in their area of interest - reading scientific language in a speciality area is much easier than learning a language generally (I personally know scientists that have self-taught themselves for Russian, German, French, etcetera).
“Many researchers agree that the development of phage therapy has stalled because of ‘concerns over intellectual property protection’ and ‘lack of a predefined regulatory pathway’ (Kingwell, 2015)” https://academic.oup.com/phe/article/13/1/82/5741402?login=f...
> across the world.
Is that an American centric worldview? It makes little sense. Maybe the USA and allies, but there is a lot more to the world than that, and phages haven’t been used. The reasons for that are very unlikely to be due to what appears to be a simplistic world view.
I have no idea how widespread phage therapy was in the Soviet bloc nations.
The Cold War distorted a lot of things.
We're just gearing up with a team distributed across Aus that tackles the clinical, biology and data/engineering side (this is my job).
This clinical trial is a bit different from trad drug discovery, since this clinical trial assesses the entire PROCESS of: (1) sourcing the phage (2) testing the phage's effectiveness against a patient's bacteria (3) manufacturing the phage to be safe for the patient/indication. We're not trialling a phage itself, like most active phage therapy clinical trials out there right now.
We're emphasizing the "therapy" aspect, of collecting data on the phage, bacteria, and measuring immune reaction in the patient to figure out what works, what doesn't work, and most importantly safety.
Phages are interesting because we can "train" them to work specifically for each patient's infection, and this is much more complex than just throwing antibiotics at a wall. In essence, effective and large scale phage therapy is a data problem — we need to figure out why a phage works (or doesn't work) for a specific bacteria and indication first. (How will a phage respond to pseudomonas in the lungs? How will it work in the gut? On the skin? etc.). We also need to know what phages will work in combination with antibiotics, because most doctors will want to keep using antibiotics.
But ideally, we want to be able to predict what phages will work in a patient, so we can just prep and manufacture those ahead of time, and have some amount of certainty that given our data this will work.
There are tons of phage therapy clinical trials going on, including from places like UCSD, Mayo Clinic in the US, in Portugal, Israel, Belgium. Most of these aren't trialling the process itself like Phage Australia though — they're trialling the phage itself, or a combination (a phage cocktail)... And there's more countries like Canada and the UK getting interested in it as well.
Some other places doing cool phage stuff right now: - https://www.biomx.com/our-pipeline/ - https://www.armatapharma.com/ - http://technophage.pt/2020/ - Felix: https://www.cff.org/news/2022-03/cf-foundation-awards-1-mill... - https://www.aphage.com/science/case-studies/ - http://www.yalephagecenter.com/ - https://medschool.ucsd.edu/som/medicine/divisions/idgph/rese... (Steffanie Strathdee's project) - Mayo Clinic: https://www.mayo.edu/research/clinical-trials/cls-20512857 - TAILOR at the Baylor College of Medicine: https://www.bcm.edu/research/research-centers/tailor#:~:text.... - Queen Astrid Military Hospital in Belgium: https://phage.directory/capsid/phage-futures-jean-paul-pirna... -