Tuesday, October 13, 2009

III: complications

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“You can’t even give me a hint? Something preliminary? A gut feeling?” Daisy asked the figure on the other side of the video chat. Today he was a black-and-white cat -- two, actually -- lying on a bed, disinterested. The Internet liked to pull his avatars from YouTube videos.

One cat looked at her, disapproving. “I told you, that’s not how I work. I’ve spawned off the analysis subroutine, and won’t hear back until it’s done.” He turned to the other cat. “We wouldn’t want to bias the results with our hypotheses, would we?”

Number two closed his eyes. “I’m not listening,” he said in a sing-song voice.

Daisy sighed. It was like working with a giant, omnipotent tweenager.

Unlike the Internet, she could not possibly keep still, not with the results this close. Four years’ worth of crazy, completely impossible collaboration with a secret superintelligence were about to come to a head. Daisy had been surprised at how easy it had been to float absolutely jaw-dropping amounts of money while keeping everything under wraps, but the Internet had apparently mastered the technique of convincing arrogant rich people that these things were their ideas. Hence her appointment as “special researcher” to the brand-new J. Craig Venter Institute of In-Situ Microbiology.

It didn’t hurt, she supposed, that they were actually fantastically good ideas. The Institute’s latest claim to fame, the In-Situ Microfluidics Microbiomic Analyzer, had already been the subject of several papers in the top journals, each with a mile-long list of authors. People were calling it the greatest stroke of collaborative science since the Manhattan Project, mostly because no one could quite remember whose idea the thing had been in the first place.

There was a mockup of one on her desk, which Daisy now set upon in a flurry of fidgeting. It was a nondescript little contraption, with a cheap-looking plastic shell that belied the complexity inside. The only things that visually distinguished the Analyzer from a malformed Rubbermaid were a couple sampling ports around the perimeter and an abundance of warning stickers in several languages.

The Analyzers were the video to what had been microbial science’s still photography, an attempt to capture dynamically the kinds of information that Daisy and the Internet could previously only catch in fleeting glimpses. Most research up to this point had been done on single microbial environments, with little coordination among studies -- a hot spring here, an oceanic survey there. That had been enough for the Internet to piece together the shape of something out there, like Daisy might intuit the presence of a person walking through the woods from half a footprint and a patch of fabric. Daisy’s samples, intentionally collected in a similar manner from a number of environments, had helped to outline the shape a bit. But you couldn’t tell if a person was sleeping or dead from a photograph; they still weren’t sure whether the patterns in the microbes were remnant of some ancient consciousness, or possibly pieces of something more.

To really understand what was going on, they needed to see how populations of microbes were changing and interacting simultaneously in thousands of locations across the world. The Analyzer had two tools to make this a reality: a gene sequencer and a mass spectrometer.

The sequencer was necessary to give them a detailed picture of what was present in each environment. Bacteria, like humans, have genomes which contain the various instructions that make up the organism; but in bacteria, there are many fewer genes, and the instructions are much easier to decipher. That makes decoding a bacterial genome a lot more tractable. But where you can get copies of the same DNA from thousands of cells for a particular human, each bacterial cell in a population might have a completely different genome.

To get around this problem, the Analyzer used an advanced microfluidics system to separate bacteria, cell by cell, and deliver them to the sequencer. Essentially microscopic plumbing -- the Internet insisted on calling it a series of tubes -- the microfluidics system was manufactured using the same lithographic techniques used to make microchips. If you considered its capabilities, the analogy ran deeper: the microfluidics chip could replicate, cheaper, faster, and much, much more compactly, the capabilities of an entire roomful of ten-year-old scientific equipment that tended to look a lot like the computer mainframes of yore.

Daisy impatiently poked the Analyzer’s sampling port with her fingernail, imagining bacteria getting slurped in, separated, and their DNA purified. The next step blew her mind, and was so new it wouldn’t even have been possible when they’d started this adventure: that bacterium’s single, circular genome was enzymatically copied, or amplified, dozens of times; the copies of long double-stranded DNA were unzipped and fragmented into smaller pieces; and then, one by one, stuck onto a transparent patch in the microtubes. Base by base, letter by letter, the complementary strand to each fragment was re-synthesized, with each addition marked by a barely detectable flash of fluorescent light. These flashes were recorded, added up, and reconstructed into genomes, at the rate of a billion per hour, or about 5,000 bacterial genomes per day.

Of course, Daisy was really excited about the tiny mass spectrometer. The Analyzer’s mass spec extracted chemicals from the bacterial environment, separated them in a tiny chromatography column, blasted them with a laser, and then sent the fragments flying through an electromagnetic maze towards a detector. By modulating the EM frequencies, the Analyzer could ‘tune’ the spec to different types of molecular fragments. After referencing these fragments against a database of possibilities -- in this case, the set of genomic ‘instructions’ from the same environment -- they could reconstruct which chemicals the bacteria were producing, and in what quantities.

If the sequencer showed them the shapes of what they were looking for, the mass spec would show them the motion.

Assuming the analysis ever finished. It must be some sort of law: no matter now powerful the processor, you would always gather enough data to take an annoyingly long time to process.

Suddenly, one of the virtual felines jumped. “Someone’s coming. Act like a cat!”

Daisy, engrossed, hadn’t noticed the administrative assistant walk up behind her. A stack of mail flopped onto the desk in front of her. “You know, dearie, the mail only works if you read it,” he said, reprovingly. “This lot’s practically growing cobwebs!”

She grimaced. It was ridiculous, but she’d been ignoring the office mailbox since she’d seen her ex’s return address on an envelope a few weeks ago. “Sorry, Pete. Thanks for bringing it by. I’ve been, er--” she glanced at the faux YouTube page splashed prominently across her screen -- “busy?”

The cat said, “Uh, Meow?”

Pete snorted. “Right,” he said, walking out. “Funny, I haven’t been able to load YouTube all day. The Internet’s been dreadfully slow.”

She stifled a giggle. “Thanks again!” she called after him.

Daisy flipped through the mail. Nothing really important -- confusing and stomach churning, she thought, staring briefly at the letter in question; but not strictly important -- and she sighed, shoving the pile wholesale into the recycling bin.

The Internet meowed sympathetically.

“I’m alright.” She wiped at something that was most definitely not a tear.

“You sure? I know of a website with HOT SINGLES FROM YOUR AREA.”

She rolled her eyes. “How about finishing up the analysis so Mr. McGuinnes can look at his YouTubes?”

“Actually...” The cat grinned, and was replaced on the screen by an array of graphs, tables, and maps. “Ta-da!”

Daisy felt her heart thump in her chest. On her screen, a rotating image of the Earth appeared, the thousands of Ana

lyzer locations highlighted as nodes in a growing web of nerve-like connections. Next to it, a flickering series of mass spectrometer traces were resolving one by one into chemical diagrams.

“Daisy -- this is it. This is her!” The Internet’s voice, though still vaguely mechanical, was quivering with excitement.

Stunned, she stared at the map. Connections between bacterial types layered and layered in complexity, until the whole Earth became a fractal ball of color. The mass spectrometer had identified thousands of small molecule messengers, like neurotransmitters, connecting the myriad microbial threads into something immense and cohesive. It was beyond her wildest imaginings: microbes, that ubiquitous and invisible majority, formed the structure of something immense; a sort of global brain, an organic World Wide Web.

“Gaia!” she breathed. For a moment she just stared, captured with the Internet in awestruck silence.

But there was something more, something niggling at the edge of her consciousness. Something about one of the charts...

“Internet!” she snapped, brows furrowing. “Map the density of Type IV secretion pathways, and overlay with known and predicted antibiotic resistance genes.” Bacterial secretion pathways, also called ‘pathogenicity islands,’ were mobile pieces of genome that encoded for the kinds of things a bug needed to infect animal hosts; they were like virulence toolboxes that could be swapped between different bacteria, changing an innocuous commensal into a killer.

Antibiotic resistance genes, of course, made such things difficult to deal with.

On the map, red and yellow dots started peppering the globe. As they filled in, Daisy felt her stomach clenching. Most areas of the planet -- oceans, the poles, deserts -- were hardly touched.

But here and there, the dots were merging into dense, angry, seething orange splotches. Those places had names; names like Chicago, New York, Moscow, Beijing. They were the places with people -- lots of people.

“Oh.” The Internet had assumed a new avatar, this time of a lemur. The lemur’s eyes were very wide, and he was, for once, speechless.

They had found God. And she was in the mood for smiting.

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