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It's a new phage in medicine
April 4, 2008 10:42 PM   Subscribe

Bacteriophages ("phages" for short) were the only effective treatment against infectious diseases until antibiotics came along during WWII.

Phages are the most ubiquitous organism on Earth. They are naturally occurring viruses that infect bacteria and bacteria only. We live in a sea of phages. Our bodies are more phage than human. There approximately 10 to the 32 power of them around us. That's 10 with 32 zeros behind it.

Antibiotics cannot keep up with evolving infections, while phages naturally co-evolve with the bacteria.

Currently we are in a growing antibiotic crisis and phage therapy is getting a serious look again. Here's a fascinating discussion from National Public Radio.
posted by wsg (37 comments total) 20 users marked this as a favorite

 
Ok, so, since you haven't linked anything I've read lately, it isn't that we both chanced on the same material... which means you've got a camera stashed above my workspace monitoring my daily self-taught "mini-science" courses and you know that I went all gaga over bateriophages earlier this week.

That's it, right? You're not just fricking with me here.
posted by Durn Bronzefist at 10:52 PM on April 4, 2008


Nice post. Science Friday is great.
posted by chrisamiller at 11:32 PM on April 4, 2008


Our bodies are more phage than human.

What does that mean, exactly?
posted by CitrusFreak12 at 12:04 AM on April 5, 2008 [3 favorites]


Cool.

As a nitpicky qualifier, sulfa drugs predate WWII by a few years, and antibiotics in the form of mold poultices are over 2500 years old. I guess "effective" is the key word though.
posted by BrotherCaine at 12:35 AM on April 5, 2008


Our bodies are more phage than human.

What does that mean, exactly?


It's a somewhat misleading way to state the fact that there are a higher number of phages in your body (including your gut) than there are cells in your body. The same is true for microbes. By mass and volume, your human cells still dominate.
posted by chrisamiller at 1:12 AM on April 5, 2008


Much of the scientific research going on in Phage Biology outside of Tbilisi goes on in a lab at my school, and a lot of the work is done by undergraduates working closely with faculty.
posted by blasdelf at 1:45 AM on April 5, 2008


Aren't Phages what Jedi's have in abundance?
posted by michswiss at 2:16 AM on April 5, 2008


By mass and volume, your human cells still dominate

Even after your lungs are teleported out of your body?
posted by DreamerFi at 2:23 AM on April 5, 2008


Our bodies are more phage than human.

Oh mine is for sure! But instead of bacteria, it eats bacon.
posted by louche mustachio at 3:23 AM on April 5, 2008 [2 favorites]


I'd heard about phage therapy, but I'd always understood it to be kind of, well, bad.

It's interesting the hear that they've begun proper trials.
posted by kisch mokusch at 4:03 AM on April 5, 2008


Sadly, Felix d'Hererelle, one of the innovators in phage therapy died forgotten after the introduction of penicillin, despite having one of the greatest mustaches known to man.

Our bodies are more phage than human.

What does that mean, exactly?


Our genome has more retroviral DNA, transposons, and other junk elements than genes coding for our own proteins. I've never heard that phrase be used in the way chrisamiller describes, but I suppose he's right too.
posted by fermezporte at 5:50 AM on April 5, 2008


Where are the papers on this? This smells like hokey alternative medicine to me. You need to target the bacteriophage to the bacteria - it seems to work similarly to a cancer drug in that it would kill ALL the bacteria it was exposed to - not just the pathogenic bacteria .
posted by kldickson at 6:21 AM on April 5, 2008


This smells like hokey alternative medicine to me.

Um, no. This is more than just rubbing twigs and moss on your body while gargling with garlic extract.

Working with phages is incredibly difficult, because you have to get a bulls-eye for each bacteria or virus you want to eliminate. It's said that working with phages is more difficult and costly than developing a new pharmaceutical treatment (developing a new drug can cost a billion dollars).

This is real science on the bleeding edge. However, not enough resources are being thrown at working with phages.
posted by KokuRyu at 7:51 AM on April 5, 2008


Where are the papers on this?

Surprisingly easy to find if you bother to look! The wikipedia article on phage therapy, which is the top google hit for the phrase, has a sizeable list of references, including articles in big-name peer-reviewed journals like Lancet. The Evergreen lab, linked to upthread, would have led you to more references.

I don't have a dog in this fight. I'm not even a scientist — just a curious guy with a few minutes to kill before breakfast. My point is, if you really wanted to know more about this, the resources are there. But hey, I guess it's easier to snark mindlessly about whatever's unfamiliar.
posted by nebulawindphone at 7:56 AM on April 5, 2008 [2 favorites]


The USSR, and particularly Georgia, have been researching and using phages for over 70 years now. Western Europe and the US started around the same time as well but dropped the research when antibiotics came around, while the USSR countries stuck with phages.
posted by jwells at 8:01 AM on April 5, 2008


Antibiotic resistance has always (rationally or not) scared me much more than nuclear war, terrorism, global warming, Y2K, peak oil, the Yellowstone volcano, or any of the other doomsday scenarios I'm supposed to worry about. So listening to this conversation on Science Friday seemed like the best news I've heard in a long time.

Harnessing the natural arms race between phages and bacteria? Wow. I really hope this can be made to work.

Go Science, Go!
posted by straight at 9:36 AM on April 5, 2008


Thanks chrisamiller and fermezporte!
posted by CitrusFreak12 at 9:43 AM on April 5, 2008


there are 50 million phages in 1 milliliter of seawater. remember that the next time you swallow a mouthful of ocean when you go to the beach.

phage therapy is real and one of the nice parts (for our government in the US) is that phage engineering wouldn't be too different from drug research or GM crop engineering. However, phage therapy could also eventually speed up lateral gene transfer between drug-resistant and non-resistant bacterial groups...

I'm convinced phage therapy will work but only if we accept the different risks associated with it...which can be minimized by substantial investment in phage biology research...which hasn't dominated biomedical research in decades.
posted by wantwit at 10:30 AM on April 5, 2008


Phages are also responsible for transferring genetic material to bacteria. For example, Viberio cholera can't make the toxin to cause disease (cholera) unless it is infected with a specific phage. Neat! Think of them as flying syringes of genetic material.
posted by Peter Petridish at 11:08 AM on April 5, 2008


Aaaagh! Stop saying "phages." That's just a suffix. It means "eaters." They're called bacteriophages because they eat bacteria. If you need something shorter, try "viruses."
posted by Sys Rq at 11:40 AM on April 5, 2008


Traditionally, researchers who study animal/plant viruses call what they study viruses. Researchers who study bacteriophages call what they study phages. It has to do with the fact that the two disciplines don't really talk to each other that much (which actually makes sense, as the two organisms are completely different). I'm in year five in grad school studying the evolution of T7 bacteriophage which infects E. coli. And everyone here calls them phages in casual conversation...
posted by Peter Petridish at 11:48 AM on April 5, 2008 [1 favorite]


Phages are great at killing bacteria. Just ask anyone in my lab, where we were unable to grow bacteria for nearly a month due to a T7 phage contamination, causing many of us to consider joining Peter Petridish on the dark side of the moon.
posted by StrangerInAStrainedLand at 12:03 PM on April 5, 2008


Phages are all kinds of awesome. Many thanks for posting this.

For those who are snarking about this being crankery, your woo-fu is weak.
posted by [expletive deleted] at 1:25 PM on April 5, 2008


Aaaagh! Stop saying "phages."

They're called phages. Sorry.
posted by rxrfrx at 2:58 PM on April 5, 2008


it seems to work similarly to a cancer drug in that it would kill ALL the bacteria it was exposed to - not just the pathogenic bacteria

You think antibiotics aren't broad-acting as well? There are a few potential problems with phage therapy (the horizontal gene-transfer that wantwit and Peter Petridish referred to being one of the biggest), but the concurrent death of commensal bacteria isn't going to prevent me (or you, I suspect) from wanting something to get rid of my vancomycin-resistant infection. (If, you know, I had a vancomycin-resistant infection)


This is real science on the bleeding edge. However, not enough resources are being thrown at working with phages.

Oh, I wouldn't say that. Seems like there's a bit of a race going on in the BioTech world regarding this. Good review of the topic here in Nature Biotechnology (found in the reference list nebulawindphone linked to). If it actually works (as evaluated by the Western system - the jury really is still out, by the looks of it), then I'm sure a lot of funds will be directed into further research.
posted by kisch mokusch at 4:03 PM on April 5, 2008


Hey, retroviruses are not phages.
posted by pullayup at 6:06 PM on April 5, 2008


If it actually works (as evaluated by the Western system - the jury really is still out, by the looks of it)

The Russians have been researching phage therapy for decades. It's not that it doesn't work, it's not that it isn't safe, but the technology as it is cannot be patented, so it's not an attractive investment to biotech firms and venture capitalists.
posted by Blazecock Pileon at 6:21 PM on April 5, 2008


It's not that it doesn't work, it's not that it isn't safe.

In the US (and Australia tends to follow the US in these things), treatments require FDA approval, which phage therapy currently doesn't have (apart from some clinical trials). It needs to past the test(s) that any other treatment does. It's not just IP, the bar is set much higher nowadays (there are plenty of drugs/treatments/vaccines that we use today that wouldn't past muster if they had to go through FDA approval process today).

Perhaps I should've said "if it works better than the other treatments, either as a stand alone or in conjunction with other therapies, then I'm sure a lot of funds will be directed into further research."

You have no idea whether it's truly safe. It might provide great treatment for the patient, but greatly promote the spread or drug resistance factors to other species of bacteria, thereby making the "antibiotic crisis" even worse. In such a case, phage therapy would be a terrible treatment for the community as a whole.
posted by kisch mokusch at 7:07 PM on April 5, 2008


I thought this sounded familiar.
posted by acro at 7:30 PM on April 5, 2008


Perhaps I should've said "if it works better than the other treatments, either as a stand alone or in conjunction with other therapies, then I'm sure a lot of funds will be directed into further research."

If the fruits of research cannot be patented, the resulting therapy won't get developed, period. There might be some government-funded basic research, but that's about it. There has to be an IP payoff somewhere, something investors can make or license for a period of time.

It might provide great treatment for the patient, but greatly promote the spread or drug resistance factors to other species of bacteria, thereby making the "antibiotic crisis" even worse.

The FDA doesn't care if a drug makes the target more drug-resistant; this doesn't rate in criteria used in clinical trials. It only cares about the alternative hypothesis, that the new drug is better than the old drug without deleterious clinical side effects, for some period of time x. Drug-resistance only enters into the conversation years after the fact, once a population gets treated. By that time, the profits are made.

It's difficult to imagine a private concern paying for three stages of clinical trials without some way to make money down the road.
posted by Blazecock Pileon at 7:38 PM on April 5, 2008


I never said IP wasn't an issue. Of course it is. But the treatment does have to be better than what's currently available, and that hasn't been formally tested yet.

As for the safety thing, you're conjoining two separate lines of argument. My "spread-of-resistance" comment was in response to your "it's safe" statement, not related to the FDA (I agree with you, it's out of the scope of a clinical trial to assess the effects of a treatment on the community). My mention of the FDA was is response to your "it works" statement.
posted by kisch mokusch at 7:53 PM on April 5, 2008


You think antibiotics aren't broad-acting as well? There are a few potential problems with phage therapy (the horizontal gene-transfer that wantwit and Peter Petridish referred to being one of the biggest), but the concurrent death of commensal bacteria isn't going to prevent me (or you, I suspect) from wanting something to get rid of my vancomycin-resistant infection.

Antibiotics are broad-acting, mind, but they're somewhat more controllable than bacteriophages by virtue of the fact that they're molecules, not self-replicating viruses.
posted by kldickson at 8:41 AM on April 6, 2008


Anybody know where I can find a transcript of the NPR show?
posted by Afroblanco at 11:06 AM on April 6, 2008


Phages are big science and have been for years, not because they might replace antibiotics, but because they provide an easy way to get at the DNA of bacteria. The first DNA engineering experiments in E. coli were performed with phage lambda; I continue to recommend Mark Ptashne's spectacular monograph about the history of this, called "A Genetic Switch," for anyone with an interest and a college-level grasp of basic biology.

Phages, which is a word synonymous with bacteriophages in usage*, have nothing to do with human retroviruses, transposons, or so-called junk DNA.

* "Those who would combat usage with grammar make fools of themselves." - Montaigne
posted by ikkyu2 at 1:18 PM on April 6, 2008


There [are] approximately 10 to the 32 power of them around us. That's 10 with 32 zeros behind it.

Actually, it's only 1 followed by 32 zeroes, so if it helps, there are only 10% as many of them as you were worried about. I know I feel safer.
posted by A-Train at 2:41 PM on April 6, 2008


If the fruits of research cannot be patented, the resulting therapy won't get developed, period. There might be some government-funded basic research, but that's about it. There has to be an IP payoff somewhere, something investors can make or license for a period of time.

Having sat through a meeting where someone explained our IP strategy on a drug candidate I can say that I'm sure someone could find about a million things to claim IP rights to in the development of such technology. Just so long as I don't have to sit through a meeting where they explain it to me as it's as it's as painfully dull as you might imagine.
posted by Kid Charlemagne at 9:18 PM on April 6, 2008


"...I can say that I'm sure someone could find about a million things to claim IP rights to in the development of such technology."

Kid Charlemagne, I'm glad to know that and I hope it's the case. Maybe the big drug companies will get behind it, then.
posted by wsg at 11:56 PM on April 8, 2008


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