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Wednesday, November 26, 2014

Jodorowski: Why Not?

I was recently privileged to watch the documentary Jodorowski's Dune, which has been showing on cable TV in the U.S. If you haven't seen it, seek it out as soon as you can. It may have the same remarkable effect on you that it has had on me.

It has changed how I think of what I do as a writer. And that's pretty profound, in and of itself.
Alejandro Jodorowski

Until I saw the documentary, I'd had no idea, frankly, who Jodorowski was (I now think of him as the sole legitimate living heir of Fellini) or that he had been among the first to obtain film rights (circa 1973) to Frank Herbert's great space epic. (The very first person to option Dune was Arthur P. Jacobs, who died of a heart attack soon after taking the project on.) The story of Jodorowski's involvement with Dune is quite literally fantastic, in every sense. Jodorowski's vision of Dune was and is breathtaking. He aproached Tangerine Dream, Pink Floyd, and Magma to do the music. For acting talent, he enlisted Salvador Dali, Orson Welles, David Carradine, Mick Jagger, and others. He signed artists H. R. Giger, Chris Foss, and Jean Giraud for set and character design. He wooed (and signed) Dan O'Bannon for special effects. The storyboards quickly grew to 3,000+ lovingly crafted images.

By the time Jodorowski went to Hollywood to look for a studio with whom to partner on production and distribution, much of the $9 million budget had already been spent in pre-production and the script had ballooned to the point where a 14-hour movie was inevitable. Predictably, the major Hollywood studios (although impressed with Jodorowski's pre-production work, and his roster of signed names) didn't know what to do with a 14-hour Shakespearean space drama. No one would touch it.

And so, the great tragedy of Jodorowski's Dune is that it never got made.

And yet the great triumph is, it did get made, in other ways. Dan O'Bannon went on to write Alien; H. R. Giger designed the monster for Alien. George Lucas, directly or indirectly, used various Herbert tropes and motifs in Star Wars; we see echoes of Jodorowski's vision in the Terminator movies, in Contact, Prometheus, Blade Runner. Plus, Jodorowski's storyboards for Dune spawned a series of groundbreaking science fiction comic books, most notably The Incal (which has been described as having a claim to be "the best comic book ever written") and also Technopriests and Metabarons.

Jodorowski's reaction to Hollywood's objections to the film is instructive. Studios told him: "But the movie will be fourteen hours long!" To which Jodorowski replied: "So what? So, what?"

Jodorowski's attitude was that film is cheap, and anyway, film isn't just film. Properly conceived, it's art. And art, properly so-called, is whatever it needs to be. If it needs to be 397 minutes of improvisational piano meditations packaged as ten vinyl records in a boxed set (Keith Jarrett's Sun Bear Concerts), let it be that. If it needs to be a 13-volume, 1.2 million-word novel (Proust, À la recherche du temps perdu), let it be that.

If it needs to be a 14-hour film that takes seven nightly trips to the theatre to see in its entirety—then why not? Let it be the first such! Someone has to be the first to do it, yes?

Jodorowski wanted Salvador Dali to play a certain part in Dune. He tracked the elusive artist down. Dali asked: "Can I have a helicopter?" Jodorowski: "Yes, you can have a helicopter." Dali: "Can I have a burning giraffe?" Jodorowski: "You can have a burning giraffe." Dali said he would have to think about it, but added that for him to do the film, he would have to emerge as the highest paid actor in motion picture history. Jodorowski calculated the onscreen time of the character. It was something like six minutes, total. Jodorowski's reply: "You'll be paid $100,000 per onscreen minute." Dali was delighted. He agreed to do the film.

This was Jodorowski's approach: Think big. Go all the way. No limits. Do whatever it takes. Let the work be whatever it needs to be.

How many of us work that way?

Do you work that way? Or are you contrained by "industry rules," genre "requirements," someone else's preconceived notion of what art is. The status quo. Orthodoxy. Best practices. Fucking recipes.

Your own ideas. Are they your own? Or are you force-fitting what you do into someone else's pre-measured box? "A first novel shouldn't be more than 100,000 words." "A good story shouldn't have more than a dozen characters." "A story shouldn't be heavy with description."

Why, not?

This is a new era for publishing. I was talking with my wife about this. She mentioned Marcel Duchamp, our favorite artist. She had only to mention his name. I knew at once what she was thinking. (If you haven't yet read Calvin Tomkin's biography of Duchamp, run, don't walk, to your nearest library or bookstore and obtain a copy at once.) And I thought to myself: Publishing is at a crossroads, now, similar to that faced by visual artists in the years just after World War I. It's possible, now, for publishing (no longer encumbered by the old rules of ink and pulp, circa 1999; no longer laboring under the heavy-handed hegemonic control of a few all-powerful Big Publishers) to go in entirely new directions. If a book needs to be words on paper, it can be; but if it needs to be more than that (whatever "more" means), it can be that, instead.

It can be.

Think about it.

What does your work need to be? What does it demand to be? What does it cry out to be?

Let it be that.

"But you can't—"

Oh really?

Why, not?

Tuesday, November 18, 2014

Why We Need to Study Comets

News wires are full of stories today about the detection of organic molecules by the comet lander Philae. The more exciting news, arguably, is that Rosetta scientists are "very confident" Philae will wake up again as the comet gets closer to the sun. It should be noted that in October, Rosetta had already detected formaldehyde (an organic compound), sulfur dioxide, and hydrogen sulfide (which is nasty-smelling stuff, and quite chemically reactive), plus carbon monoxide and carbon dioixide, in the comet's vicinity.

How excited should we be about finding organic molecules on comet 67P/Churyumov-Gerasimenko? It's hard to know, actually, until the identities and abundances of the organic molecules are determined in greater detail, but we should bear in mind that the finding of organic molecules in space rocks is nothing new. That's not to say it's not exciting, though. It always is, IMHO.

Hydrocarbons are actually surprisingly abundant in space. The majority of stars in the Milky Way (and possibly elsewhere) are red and brown stars, including many brown dwarfs that are so cool (think room temperature) you wonder why they qualify as stars. Many of the brown dwarfs, in turn, are super-rich in methane (the simplest of hydrocarbons).

Carbon chemistry is amazingly complex in meteors. (For a great overview, I recommend the 2002 paper by Mark A. Sephton.) Only about 5% of meteorites are iron meteorites (and that percentage is probably greatly inflated by discovery error). Most of the rest are carbonaceous chondrites.

The Murchison meteorite is among the best-studied meteorites and shows monocarboxylic acids at 332 parts per million; amino acids at a concentration of about 60 ppm; sugar-related compounds at 60 ppm; urea at 25 ppm; alcohols, aldehydes, and ketones at 11 to 16 ppm each; purines at 1.2 ppm; pyrimidines (uracil and thymine) at 0.06 ppm; and a zoo of other minority constituents. The fact that many of the amino acids discovered in meteorites do not occur in proteins has been taken as evidence of an abiotic source chemistry. Also, the fact that the meteors' chiral amino acids tend to occur in racemic mixtures (with no enantiomeric excess of L- over D-forms) has been taken as evidence of abiotic chemistry, although this view should be tempered by the finding that on earth, D-enantiomers in natural sediments tend to increase in concentration with the age of the sediment. (In other words, as sediments age, natural racemization tends to even out the ratios of D- and L- amino acids.) Also, it should be noted that enantiomeric excess has, in fact, been observed for some meteorite amino acids. The presence of enantiomeric excesses of various kinds in various amino acids from various meteorites, and the possible reasons for those excesses, are still a matter of contentious debate. (See Sephton's paper for details.)

What's perhaps just as interesting (or more interesting) than the finding of amino acids in meteorites is the fact that much of the organic matter in carbonaceous chondrites is tied up in high-molecular-weight insolubles. Thus, the controversy over amino acids and their stereochemistry is somewhat like trying to understand the architecture of a house by analyzing the mortar holding together the bricks.

Aromatic compounds detected in Cold Bokkeveld and Murchison meteorites
using thermal degradation plus gas chromatography and mass spectrometry.
We know relatively little about the higher-molecular-weight components of carbonaceous meteorites. Sephton notes, however: "The majority of the carbon in meteoritic macromolecular materials is present within aromatic ring systems." Indeed, many species of aromatics have been recovered from meteorites using thermal degradation (pyroloysis).

Where do all these compounds come from? We know that interstellar clouds contain methane, formaldehyde, water, molecular nitrogen, and ammonia. These molecules are known to condense around dust grains (and comets), but there's also a lot of UV light, ionizing radiation, and heat in environments like the early solar system; and these could have led to a lot of chemistry. Studying comet 67P/Churyumov-Gerasimenko should tell us more about all this, which in turn could help us understand how life arose on earth. We know that every day, something like a million kilograms of extraterrestrial material rains down on earth. The fall-rate was probably much higher, early in earth's history. It's not inconceivable that 10% or more of the biomass on earth got its carbon from "somewhere else." (See the final paragraph of Sephton's paper.) Arrival of complex hydrocarbons from meteors, asteroids, and comets may well have jumpstarted life on earth. This isn't the only reason to study comets, but for me, it's one of the most compelling.

Saturday, November 01, 2014

A Virus Where It Shouldn't Be

Words like "bizarre" and "unexpected" hardly suffice when describing the results published this week in PNAS (one of the most respected journals in all of science) by Robert H. Yolken and 17 coworkers from Johns Hopkins, University of Nebraska, and Baltimore's Sheppard Pratt Health System, who wrote about finding a peculiar virus in the noses of a number of individuals. The virus they found (through DNA metagenome analysis) was something called ATCV-1, a large DNA virus normally associated with the freshwater alga Chlorella.

ATCV-1 virions attached to a Chlorella cell.
Just to bring you up-to-date quickly: The scientists in question stumbled onto the fact that DNA from the ATCV-1 virus appears to exist in the noses and throats of a surprising fraction (43%) of randomly chosen individuals. The study population of 92 people is not large, however, and we should not be too quick to jump to conclusions. Nevertheless, the mere finding of this virus's DNA in that many people's noses is shocking, because this is a virus that, until now, was thought to occur only in algae, not higher life forms (and certainly not in humans).

To understand how shocking this is, you have to realize that viruses are generally extremely highly adapted to specific hosts. A virus that attacks tobacco plants only attacks tobacco plants. A virus that infects bacteria only infects bacteria, and generally only a specific species of bacterium. Viruses coevolve very closely with their hosts, developing extremely intricate, fine-tuned adaptations to a specific organism. For a virus to cross species lines (let alone Kingdoms) is unusual, to say the least. And thank goodness! Otherwise, you might come down with pox from an insect bite, or get any number of deadly diseases from eating ordinary foods.

As it turns out, ATCV-1 (Acanthocystis turfacea Chlorella virus) has appeared in this blog once before, back in March, in a post I did called "A Virus, a Worm, and a Louse Walk into a Bar." The point of that post (ironically) was to show that while most virus genes tend to have a great deal of DNA homology with their host counterparts, the genes of certain algae viruses actually appear to have greater homology with genes in the human body louse. Which perhaps should have been a tipoff, of sorts, to the Yolken et al. findings. Certainly, it adds more color to the story, knowing (as we do) that phycodnavirus DNA may have have crossed species lines before. ("Phycodnavirus" is the name scientists have given to the family of large DNA viruses that infect algae.)

What do we know about ATCV-1? It's fairly large, as viruses go, with a genome of 288,047 base pairs, encompasssing as many as 860 genes. The fact that the genome has been fully sequenced doesn't mean we know how it works, though. In fact, we don't know what most of the 860 genes do. Some of the genes are (as in many king-size viruses) devoted to DNA-synthesis functions of a type commonly associated with nuclear-expressed genes in the host, meaning that the virus appears well adapted to take over the nucleus of a cell. This is not always the case; some viruses are adapted to thrive in the cytoplasm, away from the nucleus.

Intriguingly, the Yolken group conducted tests of cognitive function among enrollees in its study and found that there was a statistically significant reduction in cognitive ability (on the particular measures tested) in the group of people that tested positive for ATCV-1. To determine if this was just a fluke, researchers evaluated the effects of the virus on mice. As it happens, inoculated rodents showed deficits in recognition memory and attention while navigating mazes. In other words, exposure to the virus is associated with cognitive deficits in both humans and an animal model.

This is remarkable, since (if true) it would suggest that the virus traveled through the blood (of humans and mice), crossed the blood-brain barrier, gained entry to brain cells, and expressed its DNA inside brain cells (a type of cell the virus would presumably never encounter in its normal habitat of freshwater marshes and lakes). It all sounds (and is) very unlikely. But there you are: PNAS is one of the most esteemed science journals in the world. They published the result. It's as real as can be.

Of course, the work needs to be replicated and extended. And I'm sure it will be.

And I think what we'll find is that phycodnaviruses have been crossing species boundaries for some time. If you go back to my original blog about this, you'll see an example of a particular gene, encoding a ribonucleoside reductase, in another Chlorella virus (called PBCV-1), which shows greater homology to the ribonucleoside reductase of the human body louse than to the same gene in the virus's "normal" host, Chlorella. (The homology between PBCV-1 and louse reductases is 53%, versus 48% for virus and Chlorella. These are protein-sequence homology numbers.)

If we check the ATCV-1 reductase for homology with reductases in other organisms, we find that the highest scoring non-viral match (53%) occurs not with Chlorella (the virus's host), but with Lichtheimia corymbifera, a fungus found in soil and decaying plant matter. Interestingly, this fungus is known to cause pulmonary, CNS, and rhinocerebral infection in animals and humans. (But there is no known association whatsoever between ATCV-1 and the fungus.) One wonders whether the fungus has learned a few tricks from marine viruses; or perhaps vice versa?

If you're wondering how the people in the Yolken et al. study could have come in contact with ATCV-1, maybe the answer is as simple as taking a drink of water from a mountain stream, or drinking unfiltered water from a well, or swimming in a lake, or perhaps just walking in a marsh.

Suffice it to say, a good deal more remains to be learned regarding the ecology and life cycles of the phycodnaviruses, and cross-species infection/transfection generally. I feel certain the recent results of Yolken et al. will stimulate a great amount of much-needed followup research.

In the meantime, would you grab me a bottled water?

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