Skeptophilia (skep-to-fil-i-a) (n.) - the love of logical thought, skepticism, and thinking critically. Being an exploration of the applications of skeptical thinking to the world at large, with periodic excursions into linguistics, music, politics, cryptozoology, and why people keep seeing the face of Jesus on grilled cheese sandwiches.

Saturday, December 15, 2018

Viral assassins

In yesterday's post, we looked at viral remnants in our own DNA and their possible role in long-term memory formation.  Today, we'll consider the possibility of using viruses in a different way -- to fight bacterial infections.

As I mentioned yesterday, labeling a virus as "alive" is highly debatable.  They certainly don't seem to respond, at least not in the way a living thing ordinarily does -- moving toward or away from a stimulus.  They're so un-life-like that they can actually be crystallized in a test tube, which makes them more like strange, self-replicating chemicals than they are like organisms.

Which is what makes the research that was published in Cell this week even more astonishing.  In "A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision," by Justin E. Silpe and Bonnie L. Bassler, we learn about a type of bacteriophage (bacteria-killing virus) that seems to be able to sense its prey, and launch an attack when the colony is at its most vulnerable.

Model of a typical bacteriophage [Image is licensed under the Creative Commons Adenosine, PhageExterior, CC BY-SA 3.0]

The prey bacteria is Vibrio cholerae, and it's certainly a deserving target.  It causes cholera, which makes water reabsorption in the intestine run backwards -- the host begins to dump water and blood solutes into the intestine, resulting in diarrhea so severe that an adult can dehydrate and die within twelve hours.  With quick treatment, the survival rate is quite good; without it, over half of infected people die, usually within two days of the onset of symptoms.

The virus that Silpe and Bassler were studying, VP882, can wipe out entire colonies of Vibrio cholerae by detecting a set of molecules responsible for quorum sensing, which is how colonial bacteria are able to respond to their environment differently depending of how many are nearby.  When the number of quorum-sensing molecules is low, the virus and the bacteria coexist peacefully.  When it reaches a certain threshold -- meaning there are lots of bacteria there -- the virus suddenly becomes virulent, attacks the bacteria, and wipes out the entire colony.

Other microbiologists have been quick to see the implications.  If VP882 is capable of killing a colony of cholera bacteria swiftly and efficiently, it could potentially be useful as a therapy.  And if it works for killing Vibrio cholerae, why couldn't it work for attacking other kinds of bacteria?  "If you have a lung infection, you might not be able to diagnose what bacteria [are] responsible in time and choose the right phage," said Mark Mimee of the Massachusetts Institute of Technology.  "To get around that, people use cocktails of different phages.  But manufacturing cocktails and adhering to drug regulations is too expensive...  [But] a single recombinant phage—yeah, that would be really interesting."

In other words, create a single viral assassin that could take out any sort of bacteria you wanted.  Silpe and Bassler were able to get VP882 to respond to signals from other bacterial species, including E. coli and Salmonella, but it remains to be seen if you could engineer one kind of phage that could take on any species of bacteria.

It remains to be seen if this would be a good idea.  In a normal, healthy human body, there are right around the same number of human cells and bacterial cells -- on the order of thirty trillion.  Having a normal intestinal and skin "flora" is critical for good health.  It's been shown that in order to treat intractable cases of ulcerative colitis and infection with Clostridium difficile (another bad guy of the bacterial world), there is a good chance that a fecal transplant will help.

Yes, that's exactly what it sounds like.  I'll leave the details of the procedure to your imagination out of respect for my more delicate readers, but suffice it to say that it results in replacing the sick person's intestinal flora with that of a healthy person -- and has a remarkably high cure rate.

So my question is -- apropos of the viral research by Silpe and Bassler -- if you are given a dose of phage intended to treat (for example) strep throat, what's to stop the phage from wiping out all the other bacteria they come into contact with?  I know the chemical signals differ -- that's how they modulated the kill switch for the virus with the three species of bacteria they worked with -- but it seems like there's a huge possibility for this to go very, very badly.  Yes, the therapy would have to be tested exhaustively and approved by the FDA, but the whole thing is a little worrisome, whatever its promise.

In any case, this highlights how little we understand the unseen microscopic world we're immersed in.  Viruses may not be the unresponsive little blobs we thought they were.  And as for VP882 -- it will be fascinating to see where this goes, and if we might have another weapon in our medical arsenal -- a virus that attacks bacteria.


One of the best books I've read recently is Alan Weisman's The World Without Us.  I wouldn't say it's cheerful, however.  But what Weisman does is to look at what would happen if the human race was to disappear -- how long it would take for our creations to break down, for nature to reassert itself, for the damage we've done to be healed.

The book is full of eye-openers.  First, his prediction is that within 24 hours of the power going out, the New York Subways would fill with water -- once the pumps go out, they'd become underwater caves.  Not long thereafter, the water would eat away at the underpinnings of the roads, and roads would start caving in, before long returning Manhattan to what it was before the Europeans arrived, a swampy island crisscrossed by rivers.  Farms, including the huge industrial farms of the Midwest, would be equally quick; cultivated varieties of wheat and corn would, Weisman says, last only three or four years before being replaced by hardier species, and the land would gradually return to nature (albeit changed by the introduction of highly competitive exotic species that were introduced by us, accidentally or deliberately).

Other places, however, would not rebound quickly.  Or ever.  Nuclear reactor sites would become uninhabitable for enough time that they might as well be considered a permanent loss.  Sites contaminated by heavy metals and non-biodegradable poisons (like dioxins) also would be, although with these there's the possibility of organisms evolving to tolerate, or even break down, the toxins.  (No such hope with radioactivity, unfortunately.)

But despite the dark parts it's a good read, and puts into perspective the effect we've had on the Earth -- and makes even more urgent the case that we need to put the brakes on environmental damage before something really does take our species out for good.

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