Phages: The powerful new bio-ammo in superbug war

They're the most abundant form of life on Earth – they have astonishing properties – and we know bugger-all about them. Bacteriophages were only discovered in 1912, and the Red Army and the Wehrmacht both carried phage water as a bacterial treatment. Then antibiotics came along and science ignored bacteriophages for a very …

[Anonymous Coward]

Soviet research and use

The article rather downplays the amount of research, production and actual treatment that was carried out in the USSR, communist bloc, and now the post-Soviet countries

[Toastan Buttar]

I remember that

I remember watching a documentary yeeeeeears ago about phage research in the former USSR. It seemed like an incredibly promising technology, especially in the light of increasingly antibiotic-resitant organisms. There seemed to be barriers to exporting the technology to the West, but can't recall which side was making it difficult.

[Anonymous Coward]

@FatsBrannigan

"The article rather downplays the amount of research, production and actual treatment that was carried out in the USSR, communist bloc, and now the post-Soviet countries".

Well, what do you know... even The Reg is part of the establishment media system which believes (among other strange things) that Progress comes from only one place: the USA.

[JC_]

"supermarket science tabloid Nature"

New Scientist?

http://www.newscientist.com/article/dn21350-totally-drugresistant-tb-at-large-in-india.html

[Joe Harrison]

We're saved

Startup the lab, genetically-engineer a few bizarro versions of barely-understood nano creatures, then cross fingers and release into environment. What could possibly go wrong!

[Ru]

Hell yeah

Creating genetically engineered killers to dispose of inconvenient accidents is a tried and tested sci-fi plot. I'm sure it worked almost every time.

Anyway, you asked what could possibly go wrong. Well. Have you ever heard of Necrotising Fasciitis? If not, you should go look it up, its awesome. Normally, the causative agent is fairly innocuous, until attack by a particular bacteriophage upgrades it to its improved, lethal flesh-eating form. Good times!

[Charlie van Becelaere]

No worries

A good dose of sea water will generally end these threats.

[CaptainHook]

I remember seeing a Panorama (or something similar) report in the late 80s/early 90's about Phages use as an anti-biotic in the USSR. I honestly thought they would have been in use for decades by now.

Not exactly 'New' bio-ammo.

[J P]

I recall the same programme - I believe they were worried that they'd lose all their research & samples because the power kept going out in the meltdown of Communism, and the fridges went off. And I remember thinking that once a big enough pharma company heard about them they'd go the same way as the eternal lightbulb and the never-ending spark plug, bought out & hidden away in the vaults. I wonder if that ever happened..?

[Dixie Nourmous]

I seem to remember it was Horizon

[Yet Another Commentard]

Life, don't talk to me about life...

Interesting isn't it! Crystals self-organise and essentially self replicate. Alive?

Likewise, prions (as another mentions) are they alive?

The DNA thing is also interesting, a phage (or a virus come to that) can't replicate its own DNA, it cannot synthesise the bases nor does it have the machinery (transcriptase enzymes and ribosomes) to translate it into proteins (DNA -> RNA -> Protien. Enzymes, little biological machines, are proteins).

If DNA = life, would the strand of DNA in a test tube be alive? A corpse is full of DNA, is it alive?

HIV has RNA, not DNA, would that be "lifeless" with a "living" phage?

If an alien race arrived with a different non-DNA replication based evolution would they be alive?

I don't know the answer to what constitutes life, especially "at the borders" like this but I do like the thinking around it. In a similar manner, thinking back many millions of years, at what point did "chemistry" become "life"?

[Olafthemighty]

RE: At what point did "chemistry" become "life"?

About 2.30 in the afternoon. I think it was on a Thursday.

[Yet Another Commentard]

Life - what exactly is it?

“They're the most abundant form of life on Earth – they have astonishing properties – and we know bugger-all about them.”

That’s not quite right on a few counts. First of all, they are not “technically” alive. They do not respire or reproduce without another thing’s cellular machinery, leading to a debate over what constitutes “alive”.

Secondly, we know some stuff about them. Even in the 80’s when I was a mere undergraduate the entire genome of phage lambda (E Coli phage) had been mapped, and its entire process at the molecular level well understood. We knew how it bound to the target, how it put its DNA in it, and then how each gene was expressed in sequence and what it did to hijack the bacterium and pump out more phages. There’s more to that than it sounds, it had to get one of its genes transcribed to to make an enzyme which would transcribe the next gene. Some genes ran “backwards” across others, and we knew how those worked too.

A human comparison would be Hox genes in embryology.

Feel free to look it up on wiki. Oh, wait...

[Steve the Cynic]

According to wiki...

In order to look stuff up on wiki today, disable JavaScript... Or use your smartphone.

[ToddRundgren]

They are living

I would say life is DNA replication rather than burning glucose

[Chris 244]

Living =?

Prions replicate without using DNA. Alive?

[John Smith 19]

@Chris 244

Prions replicate without using DNA. Alive?

No. These little f**kers are basically a molecular catalyst that catalyses copies of *itself*.

That is *completely* useless to the human body but does stuff its brain cells with more of itself.

"Killing" it is more like some compound that binds *irreversibly* to the binding sites and stuff it completely, like cyanide with hemoglobin rather than an antibiotic.

[Yet Another Commentard]

@ John Smith

Pedant alert -

Cyanide knackers the electron transport chain in mitochondria. It stops repsiration, or at least the useful bit in the Krebbs cycle. Same effect ultimately, a very dead organism.

I think you are thinking of carbon monoxide that irreversably binds to haemoglobin, it also has a greater affinity for it than either oxygen or carbon dioxide.

[Michael H.F. Wilkinson]

This is different from Russian use

I did some mathematical modelling of the use of phages and predatory bacteria (such as the wonderfully named Bdellovibrio bacteriovorus) as antibiotic, in particular in the gut. All research I know of is aimed at viruses or bacteria killing the pathogenic bacteria.

There are many problems with this approach (one of which I modelled), and one is the build up of resistance to phages (e.g. by mutating the surface feature the phages use to gain access to the cell, or by restriction enzymes, which cut the viral DNA to pieces).

The proposed method tries to sneak new DNA into the cell, negating the resistance not to the phage, but to an antibiotic. I am not sure the same resistance mechanism as mentioned above could not cause problems.

Still, very interesting research.

[Ian McNee]

Correct me if I'm wrong...

...but my impression (admittedly from a rather old TV programme about Soviet phage research and use - Horizon from the late 90s?) was that the major advantage of phage therapy with reference to bacteriological resistance was that the phages, being DNA-based organisms themselves, were also capable of adapting by random genetic mutation to changes in their potential host bacteria.

It would seem to me that the approach of the Israeli lab would be one that the drug corporations would be happy with ("Don't worry, we can genetically modify a new phage for that and charge you an arm and a leg for it!") whereas the Soviet approach was much more low-tech and capable of being reproduced in local medical facility labs: the cataloguing and storage of collections of evolving phages used to treat infections prominent in that locality.

However good this "endless supply of ammunition" is, it is the way in which it is used that will determine if it benefits the rich few who are already over-treated or the large majority of humanity who are genuinely at risk from infections like TB or simple infected wounds.

As I said I'm not a medical professional in any way, I'd appreciate some enlightenment on this. And Wikipedia is down protesting SOPA! Panic!!!

[Frederic Bloggs]

The big difference between the Israeli model and the Georgian one is that, if the Georgians did not have a suitable phage in stock, they went down to the sewage outfall, collected a largish sample, and had a (usually successful) hunt around in that. The Israeli approach uses GM instead.

There are acceptance as well cost implications for both approaches ...

[Anonymous Coward]

Sounds like...

A Shitty Research Project for another Tory Intern...

[Mermite]

Bioavailability

If you try to reproduce it in a living animal by treating MRSA infections with a bacteriophage found effective in a bacterial culture, I suppose you are in for an unpleasant surprise.

Every 10 years or so some bright guy rediscovers bacteriophages, and then the interest fades.

(Tissue penetration. Nonspecific binding. Antibodies. Phagocytosis.) Solving the practical problems associated with clinical use requires a lot more than rediscovering textbook microbiology.

[Pat 11]

Presumably the same selection pressure operates...blocking the page will still mean survival.

[Hnk0]

As far as I'm aware Nature published no such thing, and I should know, I have the copy on my desk. There is however something about about tails, velociraptors and robots that could interest El Reg's readership: http://www.nature.com/nature/journal/v481/n7380/full/nature10797.html

I thought the official name was "uber-boffinry glamour mag Nature"?

[Gavin McMenemy]

Is it suddenly 15 years ago?

Or even longer.

I studied this stuff at Uni.

[carlos_c]

Documentry on Horizon

I remember seeing a documentry on Horizon a few years ago which looked at phages and their use/development in the USSR and how the west ignored them as they were "communist" technology. An article on it is here http://twistedbacteria.blogspot.com/2008/02/virus-that-cures.html

good to see that there is progress

[carlos_c]

linky to Horizon

here is that Horizon documentry

http://twistedbacteria.blogspot.com/2008/02/virus-that-cures.html

[Caff]

cuba

I seem to recall reading a few years ago that cuban bacteriophage research was quite advanced due to trade restrictions.

[0laf]

Phage = virus

A phage is just a virus that infects a bacterial cell. We know lots about viruses. We even have whole "virology" departments dedicated to the study of them.

And they're not technically alive.

[Buzzby]

It's the Money

Big Pharma needs the money. Using phages for an antibiotic is not a new idea. They do however tend to be rather specific. So there has to be a twist about using phages to enable patents to be obtained and therefore the money.

[John Smith 19]

A few notes

Phage is an old name for virus and May&Baker marketed "Phage" products in the 1930s.

The article rather amusingly neglects to mention the Georgia in question is the *Republic* of Georgia in the FSU. The institute was founded by a French Virologist whose politics were left of centre.

But you could not patent living organisms then (IIRC you can now) so the drug companies (which is their *core* business. Stuff this "pharmaceutical" or "healthcare" b***cks) were never very keen on them. As people had not seen viruses they tried to sell them for treating virus as well as bacterial infections.

In contrast anti-biotics were *molecules* you could patent, synthesize (mostly using bacteria, but they could be tweaked to make *your* version of an antibiotic, or it could be "post processed" in various ways) and reverse engineer them. Much more like a *product* you could sell.

And they were great growth promoters in poultry. Too bad bacteria can exchange genetic data in "plasmids" and the drug companies shut down research on new antibiotics (It's all been done, and it's *really* expensive and time consuming. We can always tweak one we've got already).

Leading to one case in Guatemala in 1967 when a strain of dysentery acquired immunity to 7 antibiotics simultaneously, killing 12000 people.

We've kept on dosing the chickens and the bacteria have kept on evolving strategies to shut down, circumvent or just plain expel the antibiotics (and those pesky plasmids mean if one *harmless* strain learns the trick others can acquire it)

The tricky bit was culturing the virus *without* needing an equally large amount of the lethally dangerous bacteria you wanted them to kill.

BTW I don't think anyone has tried the "suicide" plasmid strategy. I suspect that it would be just a little too easy to create something that once transcribed inside the bacteria said "make this poison, metabolize it and while you're dying make more copies of me and rupture yourself."

This will kill bacteria.

All bacteria. Everywhere.

You might think a germ free world is a brilliant idea. I promise you it won't be.

[Ru]

"All bacteria. Everywhere"

Oh for crying out loud.

You are wrong in so many different ways I simply don't have the time to enumerate them. You should perhaps be writing science articles for the BBC or the Guardian, such is the depth of your fear-spreading ignorance.

[Anonymous Coward]

Well...

I call your bluff, please find the time to refute the OP's claims.

[Lord Elpuss]

Me too

+1 on calling your bluff; I found the OP's post quite original.

Don't just call bollocks, if you have evidence to refute, feel free to reference it.

[taxman]

Hang on

I thought these things caused all sorts of problems according to the Voyager programme

[John 62]

It caused lots of problems for the Vidiians

But didn't George Costanza's Syndicate (or whatever it was called that wanted to keep Jeri Ryan (understandable)) cure it?

[100113.1537]

Unknown?

Get a grip, it was experiments using bacteriophage which proved DNA was genetic material (Google "Hershey-Chase") and every molecular biology lab class has used lambda-phage in experiments. A whole group of genetic libraries are based on phage and it is one of the standard workhorses in research.

[Anonymous Coward]

"virus-that-cures.html" !!?

http://twistedbacteria.blogspot.com/2008/02/virus-that-cures.html

Let's hope Adobe don't get to hear about this ...

[david 12]

Virus that cures HTML ?

The web is a disease?

[stuart Thompson]

I remember reading years ago about how phages were being investigated for use in nano-technology, if i remember correctly they were planning to use phages alter bacteria to create the basic building blocks for nano machines.

I'm fairly sure people have been genetically engineering these things for about 10 years now

[Anonymous Coward]

So if you catch the rotting plague.....

Your party would rather have a level 9 phage instead of a cleric??

I'll be leaving since we don't have a WoW or Dungeons and Dragons icon. Let me get my cloak and tunic off the hook over there.

[John Smith 19]

@Marketing Hack

"Your party would rather have a level 9 phage instead of a cleric??"

Indeed.

Much better to have a phage than a mage.

[Arfur Smiff]

If I was an alien

I'd like to look like that....

[ChrisMcD]

For surface treatment only

As I remember phages do not work well inside bodies.

So, great for washing out wounds for the Wehrmacht and Red Army - and now presumably the Israeli Defence Force - but not for the systemic diseases that require antibiotics.

Which is probably why bacteriophages have been the next great thing every ten years or so for the last 60 years.

And while we are going down memory lane, didn't the Cubans have a great white hope from phages as well?

[Local Group]

Blogophages

They guard against trolls.

I have to go now.

[CJO]

They have also been used in video game story arcs -

in Mass Effect - a popular Xbox360/PC game from the middle of the last decade one of the back stories about a space faring race (spoiler from here) is about something called the genophage, which was used in the genocide of unborn children and hence crippling said race - geno(cide)phage?!

Thats my nerdy side served for the day!

[John Smith 19]

let me add a few references.

My memory was a Dysentery outbreak starting in 1967 in Guatemala but I don't have the original reference (although somehow the phrase "The men who s**t themselves to death" kind of stuck in my head).

However "Alcamo's fundamentals of microbiology" Jeffrey C. Pommerville, I. Edward Alcamo states it *started* there, ran for 3 years and killed 12 000. However the strain involved only 4 antibiotics (chroamphenicol, tetracycline, streptomycin and sulphanilamide. Farrar (J.Infectious Diseases (Vol 152, #6, Dec 85) confirms the antibiotics list but ups the infected count to 500 000. All resistances were listed as being carried on a plasmid type O(B).

A briefing papers from the Food Marketing Institute ( www.fmi.org ) "Low-Level Uses of Antibiotics in Livestock and Poultry" states the FDA licensed antibiotics for use in feed at "subtheraputic" levels to help animals "grow faster, produce more meat and avoid illness" about 50 years ago. Note banning antibiotics *now* will not magically eliminate drug resistance from the bacteria (first seen in the late 1940s). There is no *negative* evolutionary pressure to disadvantage a bacteria with the immunity over strains that do not. Long term *may* be a different matter and it's a start.

Inheritance is a beautiful thing, is it not?

As for my *speculation* about crafting a plasmid that causes the cell to copy the plasmid (or perhaps more accurately incorporate the plasmid into the bacterial DNA then copy that, in the process triggering plasmid production and a cellular poison to kill the bacteria itself) what I have read of "plasmid incompatibility groups" (at least 30, with no apparent upper limit) still does not seem to violate the idea, or its consequences.

RE: Antibiotic research. http://www.inpharm.com/news/169966/industry-supports-bid-revitalise-antibiotic-research states Innovative Medicines Initiative is Europes *biggest* PPI (c2Bn Euros)

http://www.investorplace.com/2011/07/antibiotics-pharmaceuticals/ reports only GlaxoSmithKline and AstraZeneca have active antibiotic R&D programs (presumably only in the US, but it's doubtful the position would be different elsewhere), down from 20 in 1990, according to the Infectious Diseases Society of America.

Why. Investorplace.com says

"Because antibiotics aren’t as profitable as medications for cancer, heart disease and high-blood pressure."

Which rather confirms my characterization of drug companies of both their R&D activity and their priorities. They are businesses and no one should be surprised. I just despise PR that pretends they're anything else.

Keep in mind on this planet the biology is like a computer environment with 1 processor architecture.

I've corrected the areas I'm aware of and provided background to others.

What other points would you like to address?