Forty Signs of Rain

  By now it was evening. A sultry summer evening, sunset near, the air itself going yellow. He topped out and sat on the rim, feeling the sweat on his face fail to evaporate.

  There was a kayaker, below in the river. A woman, he thought, though she wore a helmet and was broad-shouldered and flat-chested—he would have been hard-pressed to say exactly how he knew, and yet he was sure. This was another savannah competency, and indeed some anthropologists postulated that this kind of rapid identification of reproductive possibility was what the enlarged neocortex had grown to do. The brain growing with such evolutionary speed, specifically to get along with the other sex. A depressing thought given the results so far.

  This woman was paddling smoothly upstream, into the hissing water that only around her seemed to be re-collecting itself as a liquid. Upstream it was a steep rapids, leading to the white smash at the bottom of the falls proper.

  The kayaker pushed up into this wilder section, paddling harder upstream, then held her position against the flow while she studied the falls ahead. Then she took off hard, attacking a white smooth flow in the lowest section, a kind of ramp through the smash, up to a terrace in the whitewater. When she reached the little flat she could rest again, in another slightly more strenuous maintenance paddle, gathering her strength for the next salmonlike climb.

  Abruptly leaving the strange refuge of that flat spot, she attacked another ramp that led up to a bigger plateau of flat black water, a pool that had an eddy in it, apparently, rolling backward and allowing her to rest in place. There was no room there to gain any speed for another leap up, so that she appeared to be stuck; but maybe she was only studying her way, or waiting for a moment of reduced flow, because all of a sudden she attacked the water with a fierce flurry of paddle strokes, and seemingly willed her craft up the next pouring ramp. Five or seven desperate seconds later she leveled out again, on a tiny little bench of a refuge that did not have a pushback eddy, judging by the intensity of her maintenance paddling there. After only a few seconds she had to try a ramp to her right or get pushed back off her perch, and so she took off and fought upstream, fists moving fast as a boxer’s, the kayak at an impossible angle, looking like a miracle—until all of a sudden it was swept back down, and she had to make a quick turn and then take a wild ride, bouncing down the falls by a different and steeper route than the one she had ascended, losing in a few swift seconds the height that she had taken a minute or two’s hard labor to gain.

  “Wow,” Frank said, smitten.

  She was already almost down to the hissing tapestry of flat river right below him, and he felt an urge to wave to her, or stand and applaud. He restrained himself, not wanting to impose upon another athlete obviously deep in her own space. But he did whip out his cell phone and try out a GPS-oriented directory search, figuring that if she had a cell phone with a transponder in the kayak, it had to be very close to his own phone’s position. He checked his position, entered thirty meters north of that; got nothing. Same with the position twenty meters farther east.

  “Ah well,” he said, and stood to go. It was sunset now, and the smooth stretches of the river had turned a pale orange. Time to go home and try to fall asleep.

  “In search of kayaker gal, seen going upstream at Great Falls. Great ride, I love you, please respond.”

  He would not send that in to the free papers, but only spoke it as a kind of prayer to the sunset. Down below the kayaker was turning to start upstream again.

  IT COULD be said that science is boring, or even that science wants to be boring, in that it wants to be beyond all dispute. It wants to understand the phenomena of the world in ways that everyone can agree on and share; it wants to make assertions from a position that is not any particular subject’s position, assertions that if tested for accuracy by any sentient being would cause that being to agree with the assertion. Complete agreement; the world put under a description—stated that way, it begins to sound interesting.

  And indeed it is. Nothing human is boring. Nevertheless, the minute details of the everyday grind involved in any particular bit of scientific practice can be tedious even to the practitioners. A lot of it, as with most work in this world, involves wasted time, false leads, dead ends, faulty equipment, dubious techniques, bad data, and a huge amount of detail work. Only when it is written up in a paper does it tell a tale of things going right, step-by-step, in meticulous and replicable detail, like a proof in Euclid. That stage is a highly artificial result of a long process of grinding.

  In the case of Leo and his lab, and the matter of the new targeted nonviral delivery system from Maryland, several hundred hours of human labor and many more of computer time were devoted to an attempted repetition of an experiment described in the crucial paper, “In Vivo Insertion of cDNA 1568rr into CBA/H, BALB/c, and C57BL/6 Mice.”

  At the end of this process, Leo had confirmed the theory he had formulated the very moment he had read the paper describing the experiment.

  “It’s a goddamned artifact.”

  Marta and Brian sat there staring at the printouts. Marta had killed a couple hundred of the Jackson labs’ finest mice in the course of confirming this theory of Leo’s, and now she was looking more murderous than ever. You didn’t want to mess with Marta on the days when she had to sacrifice some mice, nor even talk to her.

  Brian sighed.

  Leo said, “It only works if you pump the mice full of the stuff til they just about explode. I mean look at them. They look like hamsters. Or guinea pigs. Their little eyes are about to pop out of their heads.”

  “No wonder,” Brian said. “There’s only two milliliters of blood in a mouse, and we’re injecting them with one.”

  Leo shook his head. “How the hell did they get away with that?”

  “The CBAs are kind of round and furry.”

  “What are you saying, they’re bred to hide artifacts?”

  “No.”

  “It’s an artifact!”

  “Well, it’s useless, anyway.”

  An artifact was what they called an experimental result that was specific to the methodology of the experiment, but not illustrating anything beyond that. A kind of accident or false result, and in a few celebrated cases, part of a deliberate hoax.

  So Brian was trying to be careful using the word. It was possible that it was no worse than a real result that happened to be generated in a way that made it useless for their particular purposes. Trying to turn things that people have learned about biological processes into medicines led to that sort of result. It happened all the time, and all those experimental results were not necessarily artifacts. They just weren’t useful facts.

  Not yet, anyway. That’s why there were so many experiments, and so many stages to the human trials that had to be so carefully conducted; so many double blind studies, held with as many patients as possible, to get good statistical data. Hundreds of Swedish nurses, all with the same habits, studied for half a century—but these kinds of powerful long-term studies were very rarely possible. Never, when the substances being tested were brand-new—literally, in the sense that they were still under patent and had brand names different from their scientific appellations.

  So all the little baby biotechs, and all the start-up pharmaceuticals, paid for the best stage-one studies they could afford. They scoured the literature, and ran experiments on computers and lab samples, and then on mice or other lab animals, hunting for data that could be put through a reliable analysis that would tell them something about how a potential new medicine worked in people. Then the human trials.

  It was usually a matter of two to ten years of work, costing anywhere up to five hundred million dollars, though naturally cheaper was better. Longer and more expensive than that, and the new drug or method would almost certainly be abandoned; the money would run out, and the scientists involved would by necessity move on to something else.

  In this case, however, where Leo was dealing with a method that Derek Gaspar had bought for fifty-one m
illion dollars, there could be no stage-one human trials. They would be impossible. “No one’s gonna let themselves be blown up like a balloon! Blown up like a goddamn bike tire! Your kidneys would get swamped or some kind of edema would kill you.”

  “We’re going to have to tell Derek the bad news.”

  “Derek is not going to like it.”

  “Not going to like it! Fifty-one million dollars? He’s going to hate it!”

  “Think about blowing that much money. What an idiot he is.”

  “Is it worse to have a scientist who is a bad businessman as your CEO, or a businessman who is a bad scientist?”

  “What about when they’re both?”

  They sat around the bench looking at the mice cages and the rolls of data sheets. A Dilbert cartoon mocked them as it peeled away from the end of the counter. It was a sign of something deep that this lab had Dilberts taped to the walls rather than Far Sides.

  “An in-person meeting for this particular communication is contraindicated,” said Brian.

  “No shit,” Leo said.

  Marta snorted. “You can’t get a meeting with him anyway.”

  “Ha ha.” But Leo was far enough out on the periphery of Torrey Pines Generique’s power structure that getting a meeting with Derek was indeed difficult.

  “It’s true,” Marta insisted. “You might as well be trying to schedule a doctor’s appointment.”

  “Which is stupid,” Brian pointed out. “The company is totally dependent on what happens in this lab.”

  “Not totally,” Leo said.

  “Yes it is! But that’s not what the business schools teach these guys. The lab is just another place of production. Management tells production what to produce, and the place of production produces it. Input from the agency of production would be wrong.”

  “Like the assembly line choosing what to make,” Marta said.

  “Right. Thus the idiocy of business management theory in our time.”

  “I’ll send him an e-mail,” Leo decided.

  So Leo sent Derek an e-mail concerning what Brian and Marta persisted in calling the exploding mice problem. Derek (according to reports they heard later) swelled up like one of their experimental subjects. It appeared he had been IVed with two quarts of genetically engineered righteous indignation.

  “It’s in the literature!” he was reported to have shouted at Dr. Sam Houston, his vice president in charge of research and development. “It was in The Journal of Immunology, there were two papers that were peer-reviewed, they got a patent for it! I went out there to Maryland and checked it all out myself! It worked there, damn it. So make it work here.”

  “ ‘Make it work’?” Marta said when she heard this story. “You see what I mean?”

  “Well, you know,” Leo said grimly. “That’s the tech in biotech, right?”

  “Hmmm,” Brian said, interested despite himself.

  After all, the manipulations of gene and cell that they made were hardly ever done “just to find things out,” though they did that too. They were done to accomplish certain things inside the cell, and hopefully later, inside a living body. Biotechnology, bio techno logos; the word on how to put the tool into the living organism. Genetic engineering meant designing and building something new inside a body’s DNA, to effect something in the metabolism.

  They had done the genetics; now it was time for the engineering.

  So Leo and Brian and Marta, and the rest of Leo’s lab, and some people from labs elsewhere in the building, began to work on this problem. Sometimes at the end of a day, when the sun was breaking sideways through gaps in the clouds out to sea, shining weakly in the tinted windows and illuminating their faces as they sat around two desks covered by reprints and offprints, they would talk over the issues involved, and compare their most recent results, and try to make sense of the problem. Sometimes one of them would stand up and use the whiteboard to sketch out some diagram illustrating his or her conception of what was going on, down there forever below the level of their physical senses. The rest would comment, and drink coffee, and think it over.

  For a while they considered assumptions the original experimenters had made:

  “Maybe the flushing dose doesn’t have to be that high.”

  “Maybe the solution could be stronger, they seem to have topped out kind of low.”

  “But that’s because of what happens to the …”

  “See, the group at UW found that out when they were working on …”

  “Yeah that’s right. Shit.”

  “The thing is, it does work, when you do everything they did. I mean the transference will happen in vitro, and in mice.”

  “What about drawing blood, treating it and then putting it back in?”

  “Or hepatocytes?”

  “Uptake is in blood.”

  “What we need is to package the inserts with a ligand that is really specific for the target cells. If we could find that specificity, out of all the possible proteins, without going through all the rigamarole of trial and error …”

  “Too bad we don’t still have Pierzinski here. He could run the array of possibilities through his operation set.”

  “Well, we could call him up and ask him to give it a try.”

  “Sure, but who’s got time for that kind of thing?”

  “He’s still working on a paper with Eleanor over on campus,” Marta said, meaning UCSD. “I’ll ask him when he comes down.”

  Brian said, almost as if joking, “Maybe you could try to make the insertion in a limb, away from the organs. Tourniquet a lower leg or a forearm, blow it up with the full dose, wait for it to permeate the endothelial cells lining the veins and arteries in the limb, then release the tourniquet. They’d pee off the extra water, and still have a certain number of altered cells. It wouldn’t be any worse than chugging a few beers, would it?”

  “Your hand would hurt.”

  “Big fucking deal.”

  “You might get phlebitis if it was your leg. Isn’t that how it happens?”

  “Well use the hand then.”

  “Interesting,” Leo said. “Heck, let’s try it at least. The other options look worse to me. Although we should probably try the mice on the various limits on volume and dosage in the original experiment, just to be sure.”

  So the meeting petered out, and they wandered off to go home, or back to their desks and benches, thinking over plans for more experiments. Getting the mice, getting the time on the machines, sequencing genes, sequencing schedules; when you were doing science the hours flew by, and the days, and the weeks. This was the main feeling: there was never enough time to do it all. Was this different from other kinds of work? Papers almost written were rewritten, checked, rewritten again—finally sent off. Papers with their problems papered over. Lots of times the lab was like some old-fashioned newspaper office with a deadline approaching, all the starving journalists churning out the next day’s fish-wrap. Except people would not wrap fish with these papers; they would save them, file them by category, test all their assertions, cite them—and report any errors to the authorities.

  Leo’s THINGS TO DO list grew and shrank, grew and shrank, grew and then refused to shrink. He spent much less time than he wanted to at home in Leucadia with Roxanne. Roxanne understood, but it bothered him, even if it didn’t bother her.

  He called the Jackson labs and ordered new and different strains of mice, each strain with its own number and bar code and genome. He got his lab’s machines scheduled, and assigned the techs to use them, moving some things to the front burner, others to the back, all to accommodate this project’s urgency.

  On certain days, he went into the lab where the mouse cages were kept, and opened a cage door. He took out a mouse, small and white, wriggling and sniffing the way they did, checking things out with its whiskers. Quickly he shifted it so that he was holding it at the neck with the forefingers and thumbs of both hands. A quick hard twist and the neck broke. Very soon after that the mouse
was dead.

  This was not unusual. During this round of experiments, he and Brian and Marta and the rest of them tourniqueted and injected about three hundred mice, drew their blood, then killed and rendered and analyzed them. That was an aspect of the process they didn’t talk about, not even Brian. Marta in particular went black with disgust; it was worse than when she was premenstrual, as Brian joked (once). Her headphones stayed on her head all day long, the music turned up so loud that even the other people in the lab could hear it. Terrible, ultraprofane hip-hop rap whatever. If she can’t hear she can’t feel, Brian joked right next to her, Marta oblivious and trembling with rage, or something like it.

  But it was no joke, even though the mice existed to be killed, even though they were killed mercifully, and usually only some few months before they would have died naturally. There was no real reason to have qualms, and yet still there was no joking about it. Maybe Brian would joke about Marta (if she couldn’t hear him), but he wouldn’t joke about that. In fact, he insisted on using the word “kill” rather than “sacrifice,” even in write-ups and papers, to keep it clear what they were doing. Usually they had to break their necks right behind the head; you couldn’t inject them to “put them to sleep,” because their tissue samples had to be clear of all contaminants. So it was a matter of breaking necks, as if they were tigers pouncing on prey. Marta was as blank as a mask as she did it, and very deftly too. If done properly it paralyzed them so that it was quick and painless—or at least quick. No feeling below the head, no breathing, immediate loss of mouse consciousness, one hoped. Leaving only the killers to think it over. The victims were dead, and their bodies had been donated to science for many generations on end. The lab had the pedigrees to prove it. The scientists involved went home and thought about other things, most of the time. Usually the mice deaths occurred in the mornings, so they could get to work on the samples. By the time the scientists got home the experience was somewhat forgotten, its effects muted. But people like Marta went home and dosed themselves with drugs on those days—she said she did—and played the most hostile music they could find, 110 decibels of forgetting. Or went out surfing. They didn’t talk about it to anyone, at least most of them didn’t—this was what made Marta so obvious, she would talk about it—but most of them didn’t, because it would sound both silly and vaguely shameful at the same time. If it bothered them so much, why did they keep doing it? Why did they stay in that line of business?