A virus helped a woman survive a dangerous antibiotic-resistant infection | Hacker News Reader

A virus helped a woman survive a dangerous antibiotic-resistant infection

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And old technology best-developed in the former USSR, now Georgia [0] [1].

[0]: https://en.wikipedia.org/wiki/George_Eliava_Institute

[1]: https://www.youtube.com/watch?v=Ee4EvVFTxIM

It's wild that there is a completely alternate tech tree that just never found popularity in the west.

Often gets down to profit sadly and if a company is unable to copyright or patent such technology due to prior art, then the incentives as a company are not there.

Sad I know, but the whole drug industry is primarily based around making money first. Which however coldhearted that sounds, is how business works.

This is all something touched upon recently here: https://news.ycombinator.com/item?id=30007863

It’s more efficient and cheaper mass produce antibiotics that work on most infections than customize a phage for each patient.

This has been a blessing and a curse, hence their overuse. Which has seen a diminished effect, leading us towards a stage that we are running out of antibiotics that work. Hence an increase in bacteria that has (due to excessive exposure), become antibiotic-resistant.

Whilst this has been known for a long time, its an area of concern.

[EDIT typo]

I think this is less about profit, and more about the fact that it just really wasn't that interesting from the invention of antibiotics until antibiotic resistance showed up.

By and large, there isn't that much profit in antibiotics these days; almost everything used in significant quantities is well out of patent.

Too true, unfortunately. Also, sick patients are more profitable than cured ones. Preventative medicine is less profitable than treating a developed disease, etc etc etc.

The profit incentives in health care are perverse and misaligned, and in many cases delaying healing is more profitable than healing. This is why we need more world-wide government funding of research in curing and preventing diseases.

If hypothetically a mixture of apple juice and turpentine were to cure COVID, we may never discover that, because 1) such a mixture would be extremely cheap and easy to make at home, and not really patentable, and therefore unprofitable, and 2) there may never be enough government medical research funding to discover it.

The thing is, phages require a lot more effort than antibiotics at all stages from production over stockkeeping and selection (unlike antibiotics, phages are highly specific to bacterial strains) to administration.

In the West, we simply used antibiotics which were good enough until a decade or two ago, so we didn't need to invest in phages.

We didn't use antibiotics, we abused them! For example, often doctors, instead of testing, and then prescribing a targeted antibiotic, give you on, two, three until you have an improvement without getting culture and prescribing the right antibiotic! Also, often, antibiotics are prescribed preventively for viral infection (like pneumonia), and not given ONLY when you have a proven bacterial infection, so, being lazy and cutting costs pretty much erase a whole arsenal of drugs!

Yeah, and add to that the abuse of reserve (!) antibiotics in farming to improve yield.

To be fair, lab testing can take a day or more, if you need to include an antibiotics screen, even more. Sometimes an infection can get very severe in this time span, so sometimes antibiotics are given prophylactically without waiting for the results to come back.

I hope the massive advances of sequencing will reach the clinics soon, it should be possible to get the genome of the infectious bacteria/virus in a couple of hours with today's tech. You can even infer the antibiotic resistance from this info, so you'd know how to treat the infection in a very targeted fashion.

>I hope the massive advances of sequencing will reach the clinics soon

What are the obstacles to this? I have been seeing articles lately about sequencing your own DNA at home in a few hours for about a thousand bucks. I guess the medical grade equipment has to be a lot more robust, so a lot more expensive? (And there might be an insufficient supply of biology interns to operate the equipment.)

We still abuse them HEAVILY.

My boyfriend got a whole stock of different antibiotics for his acne (that isn't even that bad). Women mention an itch in their private parts to doctors and, you guessed it, immediately get prescribed, often random, antibiotics.

I had a (not yet, but moving towards "life threatening") abscess. In the phase where we were still seeing if it could heal out by draining without antibiotics, no culture was done. When it quickly got worse, I got prescribed a set of three distinct antibiotics at once. That lead to me developing persistent gram negative folliculitis on the beard that another doctor wanted to treat with Ciprofloxacin, which is known to cause permanent tendon, cartilage, eye damage or death in a significant amount of patients. At my urging I got prescribed a different one. Which didn't help. I got rid of my folliculitis myself with an extreme regime of topical salicylic acid, tee trea oil and BPO.

Doctors pretty much roll the dice on which antibiotics they prescribe.

This is very much true in India too, where antibiotics are sometimes administered even for common cold, without any tests, on the doctors judgement. Healthcare policies has also changed the attitude of the people as they tend to consider any medical tests suspiciously as an unnecessary money making venture by the doctor and / or hospital. Moreover, most people also don't strictly follow the instructions to take the antibiotic doses for the requisite period and often stop in the middle, once they feel better.

>unlike antibiotics, phages are highly specific to bacterial strains

Considering the negative effects of antibiotics (disregulating the gut microbiome which leads to all kinds of problems, and exerting evolutionary pressure in the direction of antibiotic resistance), isn't selectivity actually a huge plus?

Indeed, the problem is that if the patient comes into the ER with a suspicion of acute sepsis due to bacterial infection, you don't have much other choice than to blast him with broad-spectrum antibiotics as it takes time for making blood cultures - time the patient may not have.

Could a large sample of phages be administered instead?

The article discusses "training" phases, where the stock phage is applied to a sample of the specific pathogen, and only the most successful daughter phages are retained, over several repetitions.

This process of encouraging adaptation appears to greatly increase successful outcomes.

That makes sense for resistant infections, but for general infections a pre-made stock should work, no?

For something that is already resistant to antibiotics, the training phase seems prudent. Exploiting evolution as part of the treatment leads to greater success.

The emergence of phage-resistant pathogens should not be encouraged, as we have encouraged antibiotic resistance.

I think it's a change in mindset, as well as a change in procedure.

The article states that the "six most dangerous antibiotic-resistant bacterial pathogens" are known as "ESKAPE."

The viral phages used to target this group are used in tandem with appropriate antibiotics, and the phages are "trained" in several rounds to optimize effectiveness prior to application.

It would seem reasonable to begin general distribution of this treatment for ESKAPE, and begin preparing similar treatments for what we might guess are the next few dozen that will join this group.

It's not what happened: it was actually invented and developed in France by Félix d'Hérelle[1] (who taught George Eliava, the Georgian scientist responsible for the Soviet developments of the field) and used to be quite popular here too before it was supplanted by the antibiotics, more convenient and easier to industrialize, during the 70s.

Having lost all that knowledge is really a pity, and it's quite fortunate that the Soviets then the Georgians kept it going.

On a side note, d'Hérelle was a fantastic adventurer and his life is fascinating (the French version of [1] has a nice summary), even moreso than Yersin's (the discoverer of the bacteria responsible for the Plague[2], and founder of the city of Đà Lạt[3] in Vietnam).

[1]: https://en.wikipedia.org/wiki/F%C3%A9lix_d%27H%C3%A9relle

[2]: https://en.wikipedia.org/wiki/Yersinia_pestis

[3]: https://en.wikipedia.org/wiki/Da_Lat

> On a side note, d'Hérelle was a fantastic adventurer and his life is fascinating (the French version of [1] has a nice summary), even moreso than Yersin's (the discoverer of the bacteria responsible for the Plague[2], and founder of the city of Đà Lạt[3] in Vietnam)

Did you mean Alexandre Yersin or was Félix d'Hérelle also in Việt Nam at the time?

I meant Yersin. His biography is pretty awesome, yet d'Hérelle is still even more badass:

France military deserter, he fled to Canada and founded an alcohol making business there, then in Mexico. Self taught biologist as a hobby (he dreamed of becoming the next Pasteur), he found a way to use a bacteria as a pest control against crickets before discovering the first known bactoriophage. He then developed a bacteriophage-based cure for dysentery, plague and cholera.

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

Yersin somehow looks here like taken straight from the streets of Brooklyn.

Da Lat is a fantastic part of Vietnam. It is kind of similar to the Tahoe region in California. Lots of pine trees and nature. Cooler temperatures too. Yersin and Pasteur are everywhere in Vietnam. Tons of major streets in many towns named after the both of them.

Solar phootovoltatic was an alternative tech tree that was discovered as early as 1839, basically during the industrial revolution.

Imagine an alternative timeline where it was a discovered in a nation whose theology involved lot of plants and trees. Powering civilization itself based on solar energy would be a dream from the getgo, so you would have a lot of academic attention and research early on.

Wouldn't they be outcompeted by others? Even 2022 solar tech is less convenient than 1900s fossil fuel engines that can just run day and night (ignoring lung damage like we've historically been doing).

1900s was a long time out. From 1812 to 1880 steamships required sail backups. Without a massive investment in the technology steam would have stayed unreliable and expensive.

Really what kickstarted the whole thing was pumping water from mines which didn’t need anything close to 24/7 operation and could thus handle the expensive, heavy, and unreliable nature of early steam engines.

And it was hard to make a steam engine with the technology of the time. A well sealing piston. Heavy reciprocating mass. Valves. Hot high pressure steam. And internal combustion is a few levels up from there then.

An electrical motor might have been a lot simpler.

Not necessarily. Academic research needs not be 'practical' or be ready for commercialization, much like research into fusion.

I hope you are aware of the term "solarpunk".

[1] this is sad that those people had to work in environment like that, what if they had access to modern, actually funded labs?

https://en.m.wikipedia.org/wiki/Bacteriophage

Astounding little things. I hope the west picks up the pace for research in this area.

I first saw this on a documentary about 20 years ago. Still hoping :)

I'm guessing it's this BBC Horizon documentary? https://archive.org/details/BBCHorizonS1997e13TheVirusThatCu...

If so, it's from 1997: 25 years =)

lol, yeah, I am ancient.

I thought it's strange that the article doesn't mention what kind of viruses it's talking about until halfway through. Of course, they wanted to keep the catchy "virus helps agains bacteria" headline, but they could have at least mentioned phages in the subheading. Strangely enough, the "title" attribute of the page is "Bacteriophage therapy: How a virus helped a woman survive [...]", but the first part seems to have vanished from the actual title of the article...

In this news sites they usually do kind of A/B testing for titles. The editor comes with a bunch of titles, and they rotate them to find the one bringing more hits from the front page or social sites.

"Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae"

https://www.nature.com/articles/s41467-021-27656-z

I'd highly recommend Vincent Racianello lecture(s) [0] for a introduction in virology (he talks phages obviously). Perhaps one of the most fascinating lecture i ever watched!

[0] https://youtu.be/jX3MhWWi6n4

Tangential: this reminds me of the intentional infection with disease / virus in one of the Takeshi Kovacs novels (Woken Furies, I think), in which one character deliberately maintains a level of infection due to the body's reaction to the infection being a net positive in regards to <something I can't remember>, and there being mention of the fact that they know it's unsustainable, but want to ride it as long as their body is able.

Something along the lines of increasing the body's core temperature in order to be able to deal better surfing in colder water.

Designer viruses to get a specifically desired symptom. Interesting concept.

If you're interested in phage therapy there's an episode covering them and other therapeutic viruses[0] in a series of online virology lectures given by a Columbia University virologist who first published the genome for the Poliovirus and now does a whole bunch of interesting podcasts about science with other experts in those fields(virology, microbiology, neuroscience, immune system, evolution).

0. https://www.youtube.com/watch?v=T6GGPtEC_KY

Research also suggests that biofilm can be broken up by reducing inflammation generally in the body. So we have some options here for combatting antibiotic resistant infections. We just need to start focusing more on those approaches and less on finding novel or stronger antibiotics as our only answer.

Infections aren't stupid. They adapt. If you only have one tool, well, that's relatively easy to adapt to. We need to focus more on these adjunct therapies for enhancing the effectiveness of existing antibiotics.

The nice thing about phages is that they also adapt.

'Part of the treatment’s success is due to the “training of the phages,” says Pirnay. This involves directing the evolution of these viruses by growing one generation after the other alongside the bacteria that is infecting the patient. In each generation, the virus that kills the most bacteria is selected and moves to the next round. The result is an elite force of phages specially adapted to fight a specific pathogen...

'“Phages are able to stop the bacteria from being resistant to antibiotics,” she says. “The bacteriophages attack the same molecular targets that bacterias use to avoid the effect of antibiotics. If you administer phages first, then antibiotics, you block their resistance and the infection subsides.”'

Fwiw, rarely can lab designed viruses i.e. made through splicing have features that are more "optimal" (or efficient) than those that are evolved. Directed evolution is truly marvelous when done properly (it won a Nobel!).

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

Sorry for the hi-jacking but somewhat related.

I read some years ago (maybe 10?) about a someone and their team doing research in "bacteria communication" and how they use signal/markers to coordinate. Their research, IRC, was about trying to find ways to disrupt this communication in order to prevent the disease from happening and getting rid of the infection. Does this ring a bell to anyone? If yes, is this something still going on or promising? In any case a link to a recent article about it would be highly appreciated!

This is very general and there are a ton of people working on things like that. I did my MSc on extracellular vesicles (eg.: exosomes and microvesicles), and even just that subtopic of intercellular communication has been booming in the last decade.

Research is VAST, very vast.

I'm absolutely not knowledgeable in the subject so I could not be more accurate. I'm always found of research that offers glimmers of hope for what seems to be a dark future. Happy to hear there is tone of research being done around it!

My memory (as a layman) was "quorum sensing."

Quick Google:

https://www.nature.com/articles/s41522-021-00211-w

https://asm.org/Articles/2020/June/How-Quorum-Sensing-Works

https://www.frontiersin.org/articles/10.3389/fmicb.2019.0247...

Thanks a lot for the links and clarification!

Cool when stuff like this works. Kinda like before they figured out you could cure syphilis with penicillin, they would infect the patient with malaria, which could be treated, which would then kill the syphilis.

This is what astounds me the most about the scientific world's response to COVID. We have a once-in-a-lifetime opportunity to study the positive health applications of a ubiquitous novel virus that most of us are going to get eventually and repeatedly, over and over, year after year, for the rest of all of our lives, and here we are trying to stamp it out as if nothing was at stake. Future generations will look back at our efforts to destroy COVID and will mourn a lost opportunity.

We're trying to stop millions of deaths in the process.

I'm not sure if this is sarcastic or not but rest assured, the sociopaths that hoard the IP behind the vaccines have all but guaranteed that there will be plenty of opportunities to study these alleged "positive health applications" at the back of the global south.

> the sociopaths that hoard the IP behind the vaccines

Uhh... what? The Oxford vaccine (better known as AZ) is available for licensing for everyone interested [1], which the Serum Institute of India has done.

The problem with vaccine equity is not the patents question (Moderna also has announced to not prosecute any IP violations during the pandemic fwiw), the problem is that many poor nations lack the prerequisites of manufacturing high-quality vaccines: a stable electricity grid, political stability (last thing you want is a bunch of warlords or drug cartels quarreling over a vaccine factory), competent people to staff the factories, in case of mRNA vaccines delivery chains that can keep up with handling the storage requirements of the components...

[1]: https://innovation.ox.ac.uk/technologies-available/technolog...

> the problem is that many poor nations lack the prerequisites of manufacturing high-quality vaccines

At least wrt Moderna (and I think Biontech as well), isn’t the issue also that part of the production process are not patented, but trade-secrets and thus simply not available?

I’ve read this multiple times, but so far I have to find a definitive answer (true or false) either way ;)

>>>Uhh... what? The Oxford vaccine (better known as AZ) is available for licensing for everyone interested.

Sure, sure but that is not the whole story[1] and kind of misleading.

[1]: https://khn.org/news/rather-than-give-away-its-covid-vaccine...

Ugh. Many global south countries have more vaccinated as a percentage of the population than the US. The reason some countries are having a very low percentage of vaccinated is not IP but lack of organizational will. As an example, dirt-poor Cuba has developed two vaccines in-house and 86% of the population is fully vaccinated.

Cuba has historically funded healthcare and medical research very well. It has a lot of the infrastructure and organisation in place already compared to other poor countries.

Arguably this is what those other countries should have been doing all along. However that level of coordination usually requires a degree of public activity that tends to reduce external private funding from countries like the US. They're in a tricky situation.

I think poor coupled with stability allows this.

Cuba, regardless of its regime, has been stable for a very long time. This enables projects, funding, etc.

But if a civil war, insurrection happens every decade... well, so much for public services.

It also helps being an island. Some dudes can't just walk in.

Cuba is a middle-income country. Vaccination rate in very poor countries is still mostly poor.

Cuba is only one example. Most of Latin America and East Asia is in the 65-80%. It's first in Africa you find very low numbers, down to 0.2% in the Congo.

What?

The article is about bacteriophages (virii that kill bacteria) and SARS-COV-2 is not one of those.

Covid isn't a bacteriophage, it's a human virus.

Did Covid write this?

" the positive health applications of a ubiquitous novel virus" what are those positive applications you are referring too?

also even if we successfully cured everyone of covid tomorrow its not like we don't have probably thousands of living samples in labs all over the world to refer to.

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