Secret Universe
March 24, 2013 3:48 PM   Subscribe

The Hidden Life Of the Cell (57:24) There is a battle playing out inside your body right now. It started billions of years ago and it is still being fought in every one of us every minute of every day. It is the story of a viral infection - the battle for the cell. This film reveals the exquisite machinery of the human cell system from within the inner world of the cell itself - from the frenetic membrane surface that acts as a security system for everything passing in and out of the cell, the dynamic highways that transport cargo across the cell and the remarkable turbines that power the whole cellular world to the amazing nucleus housing DNA and the construction of thousands of different proteins all with unique tasks. The virus intends to commandeer this system to one selfish end: to make more viruses. And they will stop at nothing to achieve their goal. Exploring the very latest ideas about the evolution of life on earth and the bio-chemical processes at the heart of every one of us, and revealing a world smaller than it is possible to comprehend, in a story large enough to fill the biggest imaginations.
You may be familiar with molecular movies from my two previous megaposts collecting them, but this extended documentary uses original animation that is collected into a coherent educational narrative and is just so fucking gorgeous. Enjoy.

Seriously, this shit is so fucking beautiful I can even forgive the Eukaryotic chauvinism it sometimes displays.
posted by Blasdelb (20 comments total) 130 users marked this as a favorite

These are incidentally the same types of viruses being used in this post for Telomerase gene therapy that has extended mice lifetimes and improved health and age related diseases.
posted by Blasdelb at 4:08 PM on March 24, 2013

I just love your enthusiasm about the topic, Blasdelb. Gonna check if there's a high quality release available.
posted by Foci for Analysis at 4:21 PM on March 24, 2013 [1 favorite]

Something that is central to the narrative but only really sporadically explained is how our adaptive immune systems work. It is really cool in a way that should, in theory, protect us from an infinite number of potential pathogens but has a few significant drawbacks. As the white blood cells (shown in the video) that mediate the adaptive immune response get made, they each are born with a completely new antibody through a very randomized process that has a very specific and very random shape on the business end that could, in theory, bind to anything. These antibodies are how our bodies recognize foreign invaders that have some means of evading our innate immune systems (not really shown in the video but very important), and in theory there are enough white blood cells running around our bodies that one of them will have an antibody that will be effective against just about anything. Some of these white blood cells, B Cells, use their antiodies by excreting massive amounts of them to fly around the body so that the back end signals for more attention when the business end finds something bad, as was shown, while T Cells will stick their antibodies onto the outside of their cells so that the back end signals the cell itself when the business end finds something. One white blood cell of either kind though is not enough to meaningfully fight off an infection, and so whenever a mature T Cell cell encounters something that triggers its antibody it immediately races back to a lymph node and starts dividing like crazy to make enough cells to eliminate the infection. Then, once the infection is cleared, almost all of the new clones of the cells with the effective antibody will trigger themselves for death to make room for new white blood cells. One of the big draw backs to the fantastically complex process that is the adaptive immune system is how long it takes to get going, so a significant portion of them will change in such a way as to protect themselves from degredation and remain as a resevoir of memory cells waiting in case the infection ever comes back such that the process has a big head start the second time. This is the biggest reason why when people get sick with infections they then get better as well as why people don't tend to get sick from the same thing twice.

One of the big problems with that strategy that defines how sensitively it can be made though is what happens when the fundamentally randomly shaped antibody recognizes something that is actually us or for what ever reason actually belongs in us and shouldn't be attacked. Our bodies deal with this by immediately killing all of the white blood cells that are born with an antibody that recognizes a target within the first few weeks of being created, the idea is that if it sees something that quickly its probably something that should be there. During these couple of weeks, white blood cells go through an extensive process of 'education' where the the antigens present in the body that actually belong are paraded in front them to see if any bind. Auto-immune disorders are what happens when this system fails for a variety of reasons and our immune cells start attacking things that are us. The simplest and most common reason this fails is the violation of 'immune privileged' regions, places in the body that for a variety of reasons the immune system gets shut out of. The classic example of this is Type I diabetes; where the beta cells in the pancreas that regulate blood glucose are naturally hidden away from the immune system but if extraordinarily high fever, mechanical injury, and/or genetic predisposition causes it to be presented to the immune system all at once then there will be white blood cells that recognize these new patterns but haven't been selected against that will see them and mount a catastrophic response.

Adenovirus in the wild generally works largely by outrunning the adaptive immune system, which as I mentioned it takes a while to get going to mount an effective response. So even though the Adenovirus is reasonably immunogenic (stimulates the immune system), replicates really fast which is really stimulating, and has targets it can't get rid of that are very sensitive to antibody development, it doesn't just die out because by the time your immune system gets going it will have already caused you to infect an average of at least one person who will then need to go through the same process.
posted by Blasdelb at 4:41 PM on March 24, 2013 [8 favorites]

Thanks! Just started playing this and darted back to share that Bonnie freakin' Bassler makes an appearance, and some Whovians may be lured in if they were to know that David Tennant is the narrator.

Plus, the BBC has an interactive web site set up to enhance the show.
posted by maudlin at 4:45 PM on March 24, 2013 [1 favorite]

Dynamin, the protein that the adenovirus key fits into allowing entry into the cell, is also just about the coolest shit ever.
posted by Blasdelb at 4:46 PM on March 24, 2013 [1 favorite]

Eukaryotic chauvinism

Totally honest question: Can you explain what you mean by this? Because it sounds like a great term but I don't understand it.
posted by Sokka shot first at 4:47 PM on March 24, 2013 [2 favorites]

Blasdelb: "Eukaryotic chauvinism

Sokka shot first: Totally honest question: Can you explain what you mean by this? Because it sounds like a great term but I don't understand it.
At 23:45 Tennet, presumably under the instructions of Dr. Nick Lane who shortly doubles down hard on this, draws a distinction between Eukaryotes as 'complex life' and bacteria as 'simple life.' Never mind that this completely ignores Archaea and the life's work of Carl Woese, to call bacteria simpler is to ignore the incredible subtlety of their design that allows them to totally dominate their planet that we inhabit in favor of the cruft and comparatively inelegant mess that is us.
posted by Blasdelb at 5:01 PM on March 24, 2013 [5 favorites]

Something else that is really deep and touched on in the film is the debate as to just how living viruses are. If you go to an academic conference full of people who study viruses and ask around you will be likely to find at least as many answers to the questions of whether viruses are ‘alive’, whether they are ‘organisms’, how they should be made to fit into the tree of life, and if they should be made to fit into the tree of life at all as you’ll find researchers willing to humor you. The academic debate on this topic is currently more or less framed by a provocative paper published by two researchers working on a type of virus that could be said to blur the lines between viruses and life as we’ve always roughly defined it, a response to it suggesting a more conservative position, and a response to the response.
Redefining viruses: lessons from Mimivirus (PDF)
Viruses are the most abundant living entities and probably had a major role in the evolution of life, but are still defined using negative criteria. Here, we propose to divide biological entities into two groups of organisms: ribosome-encoding organisms, which include eukaryotic, archaeal and bacterial organisms, and capsid-encoding organisms, which include viruses. Other replicons (for example, plasmids and viroids) can be termed ‘orphan replicons’. Based on this suggested classification system, we propose a new definition for a virus — a capsid-encoding organism that is composed of proteins and nucleic acids, self-assembles in a nucleocapsid and uses a ribosome-encoding organism for the completion of its life cycle.

What makes a virus a virus? (PDF)
In a recent review, Raoult and Forterre (Redefining viruses: lessons from mimivirus. Nature Rev. Microbiol. 6, 315–319 (2008)1) proposed a dichotomy of the biological world, dividing it into ‘organisms’, those entities that encode a functional translational machinery, and viruses, those entities that have capsid shells instead. The implied definition of viruses, although highly relevant, does not rely on the most fundamental aspect of what makes a virus a virus: it breaks up and loses its bodily integrity, with its progeny becoming reconstituted after replication from newly synthesized parts. We propose that the defining attribute of all viruses is their disintegration and reconstitution, from the tiny geminiviruses (15–20 nm diameter; 2.5 kb DNA genome) to the colossal Mimivirus (400 nm diameter; 800 kb DNA genome). Importantly, disintegration and reconstitution are totally independent of time, with reconstitution occurring minutes, days, years or centuries after disintegration.

What makes a virus a virus: reply from Raoult and Forterre (PDF)
The correspondence on our Opinion article (Redefining viruses: lessons from mimivirus. Nature Rev. Microbiol. 6, 315–319 (2008)1) by Wolkowicz and Schaechter (What makes a virus a virus? Nature Rev. Microbiol. 16 July 2008 (doi:10.1038/nrmicro1858-c1)2) has allowed us to clarify some of the elements of our virus definition. The authors rightly insist that the phenomenon of disappearance and reappearance of a virus (eclipse phase) is a major characteristic of viruses. They then go a step further, however, to suggest that it is the most fundamental aspect of a virus and propose to use this feature, instead of the capsid, to define viruses. Although the eclipse phase is informative in terms of virus description and could be added to our virus definition, we think that such a feature cannot be solely used to define viruses, because it is a phenotypic trait that cannot readily be assigned to a particular gene or set of genes (unlike the capsid) in the viral genome. Consequently, a definition of viruses that is based only on such properties would have a pre-Darwinian flavour (similar to the prokaryote or eukaryote classification system).
posted by Blasdelb at 5:12 PM on March 24, 2013 [4 favorites]

My favourite bit was the overhead shot at 32:43 showing the proteosome spinning towards its target, looking every bit the TARDIS. With David Tennant narrating, I'm sure the Dr. Who reference is intentional.
posted by Popular Ethics at 5:33 PM on March 24, 2013 [1 favorite]

This was super-cool and riveting. Thanks.
posted by exlotuseater at 6:12 PM on March 24, 2013

Well I watched the whole video and it was amazing, made moreso by your commentary, Blasdelb. Thank you.
posted by Sokka shot first at 7:36 PM on March 24, 2013

Eukaryotic chauvinism

I'd wear the T-shirt!
posted by Twang at 10:01 PM on March 24, 2013 [1 favorite]

Gorgeous graphics, but somewhat racist -- evil black virus, virtuous white antibodies.
posted by fredludd at 2:03 AM on March 25, 2013

"Gorgeous graphics, but somewhat racist -- evil black virus, virtuous white antibodies."

Heh, if you were to make a super concentrated solution of adenovirus or antibodies they would look like a milky opalescent white along with most of the proteins displayed - think clean thumbnail.
posted by Blasdelb at 2:28 AM on March 25, 2013

is there a science fiction author that uses the metaphors or concepts of microbiology to inform the world-building?
posted by ohshenandoah at 12:34 PM on March 25, 2013

The best I can think of at the moment is super old school, here is a link to the book
posted by Blasdelb at 12:50 PM on March 25, 2013

That video was pretty amazing, but it showed things like virii bouncing along cell walls, but I suspect other forces stronger than gravity would be acting at this scale. Also, the narration repeatedly used the word 'designed' in relation to evolution, but evolution doesn't 'design' anything. Anyway, I'm not even a scientist, so I suppose I can't nitpick too much. I do think this is immensely educational and beautiful. Also, fredlud, your comment would be funnier if it didn't hit so close to the truth :(
posted by PigAlien at 2:17 PM on March 25, 2013

Yeah, you're absolutely right, the part with the viral particles flying towards the cell against the apparent flow of fluid from the movement of the antibodies didn't look at all like natural diffusion, particularly when they bounced against the cell like basketballs on a court.
posted by Blasdelb at 3:50 PM on March 25, 2013 [1 favorite]

There could be charged interactions going on? But IDK how ionic either the cell membrane or adenovirus particles are.

Blasdelb: you're my new Metafilter crush. The Whelk: move over.

I'm about to finish my biology degree from McGill, it looks like you're in Belgium? I have a burning desire to do my graduate degree in Europe, so I might memail you to pick your brain, if that's OK.
posted by Strass at 8:04 AM on March 27, 2013 [1 favorite]

"There could be charged interactions going on? But IDK how ionic either the cell membrane or adenovirus particles are."

Human cells tend to carry a net negative charge on the outside, though hunting through the literature really quick it seems that studied adenoviruses don't seem to tend to take advantage of this with a net positive charge. Adenovirus models specifically though are associated with a whole bunch of cell receptors like integrins that reduce viral entry when you fuck them up in mutants, and are likely at least partially involved in initial adhesion. Some integrins do use divalent cations in their binding sites, that the adenovirus is likely recognizing and that would make interactions reminiscent of the ionic bonding one learns about in Gen Chem but weirder, but the best answer is probably that it’s really just a mess of different kinds of interactions that make the adenovirus stick, some of which would also be involved in making it internalize.

I'd be happy to give advice, you might also benefit from the two askme questions I made. Also the beer here really is more amazing than you dare hope and everyone has a crush on The Whelk :)
posted by Blasdelb at 12:03 PM on March 27, 2013

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