by Jim Shepard
“Right,” Jeannine said, waiting. She looked at the slug with the moronic expression on her notepad.
“So what hit us was an analogy involving retroviruses.”
“Us?” Jeannine said.
“I’ve been going over everything with Graff and Jimenez and that woman at Detrick—Bonner,” Danice said.
“And you haven’t kept me in the loop?” Jeannine wanted to know.
“And I had this idea I ran by them,” Danice said. “And they’ve been working it and they’re excited about it too.”
“You ran it by them and not me?” Jeannine asked.
“Remember when it was discovered that retroviruses could deliver genes that caused cancer, and what freaked everyone out was the news that the genes they were delivering were human genes?” Danice told her.
“Yeah,” Jeannine said.
Danice shifted to her I’m-going-to-go-slow voice. “The idea was that there was a cellular oncogene that was causing cancer whose normal role was to regulate a particular type of cell, and determine when that cell type would divide. But the thing brought in by the retrovirus was a viral form of that gene that looked pretty much the same except it wasn’t. So that the normal form had its on/off switch but maybe in the viral form the on/off switch was mutated so it was always on.”
“Yeah, I’m following so far,” Jeannine said.
“So what about the possibility of something, maybe even a gene, having been picked up by the pathogen and then being returned to the host by the pathogen?” Danice said.
“Oh my God,” Jeannine said.
“Right?” Danice said excitedly.
“In the case of a viral pathogen it’d be obvious that was happening,” Jeannine said. “But no one would expect a bacterial pathogen to deliver DNA into human cells.”
“Exactly,” Danice said. Jeannine could just see her pacing around and waving one hand the way she did when something stirred her up.
“There was that story a few years ago about someone’s lab finding bacteria DNA in a sweet potato genome,” Jeannine remembered. “And everybody realizing that Aunt Syl’s annual Thanksgiving contribution was naturally transgenic.”
“And what if that bacterial DNA that got delivered was actually similar in some way to a human gene that controls some process in human cells?” Danice asked.
“Oh my God,” Jeannine said again. There was a buzzing on the line while they both worked that through. “I guess then you and I would be on the cover of Nature,” she added. “Maybe with Graff and Jimenez and what’s-her-name. But how come we can’t find this bacteria by PCR?”
“Suppose the symptoms were showing up after the infection had cleared?” Danice said. “If you’re talking about DNA getting inserted, the immune system could have cleared the bacterial infection, and it wouldn’t matter. In Guillain-Barré syndrome people develop neurological symptoms many weeks after infection.”
“Yeah, okay, but that’s due to antigenic mimicry,” Jeannine said. “So in this case the bacterium would be presenting a lot like the victim’s own nerve cells. And the victim’s immune response would clear the bacterium but then the antibodies would still be around and would start attacking the nerve cells.”
“I think it works. I think it’s possible,” Danice said when Jeannine didn’t say anything further.
“I’m thinking; I’m thinking,” Jeannine said. “It is the kind of thing my old microbiology prof used to call ‘totally novel.’ But why hasn’t anybody else thought of this?”
“That’s what we were thinking!” Danice said. “And then we thought: Why hadn’t we? Maybe partly because no one would imagine it could happen that fast? Or that there’d be a high enough infectivity to create something like an epidemic?”
“Fuck,” Jeannine said. “That is a problem with this idea. How does it spread?”
“Yeah, Jimenez is worried about the same thing,” Danice said. “That’s partly why I called you.”
“Let me think about it,” Jeannine told her. “Stay near the phone. Or should we do this by email?”
“You don’t want to talk to me?” Danice said.
“Hey, you’re the one who froze me out on this,” Jeannine reminded her.
“Nobody froze you out,” Danice told her.
“All right, I’ll get back to you,” Jeannine said. “If Jimenez doesn’t solve the problem first.”
She spent two hours working the problem from various angles. She even got some input from her old microbiology professor, who liked the idea but also said, “But how does it spread?” once she’d gotten that far with what they had.
Spores, spores, spores: she kept drawing little spores on a scratch pad to help her think. She called Danice back without even checking the time.
“So we’re talking about something that sporulates,” she said as soon as Danice picked up. “If once it got into the body it transferred DNA to the host cells and then sporulated really quickly, you could be spewing out spores while the immune system was getting rid of the bacteria. So you’d have high infectivity before any real symptoms. But usually bacteria sporulate under adverse conditions. Like with anthrax, the sporulating starts once the animal’s dead and the bacteria are losing their nutritional source. The spores allow the bacteria to hang out in the dead tissue until something else comes along to suck them up. But why would it sporulate in a living person?”
“Exactly. Fuck,” Danice agreed, and Jeannine hung up.
She walked out into the hall and over to a window, and just looking out for twenty minutes gave her another idea. She called back. “Bacteria move from site to site in people,” she said. “Like TB is inhaled first and then moves to the bloodstream. But you can be infected with TB but be asymptomatic for years. What about some kind of latency?”
“That’s what our group was thinking,” Danice said. “But how would it work?”
“If the infection was somehow reactivated, it could move back to the lungs and you could cough out the bacteria,” Jeannine said.
She drew a bouncing line from one spore to another on her pad. Her old microbiology professor was emailing with the subject line “AND WHAT ABOUT—???”
“I gotta find something to eat,” Danice said.
“I’ll call if I come up with something else,” Jeannine told her, clicking on her old professor’s email.
An hour later she called Danice back. She could hear her friend chewing. “You’re still eating?” she asked. “What’d you find?”
“I don’t know,” Danice said. “Some kind of protein bar.”
“So I remember reading somewhere a paper about TB in fish,” Jeannine said. “I just looked it up. Did you ever see that paper?”
Danice said she hadn’t.
Jeannine told her that the paper had established that TB in fish had become not antibiotic resistant, but antibiotic tolerant. In other words, the bacteria had survived antibiotics not because they were metabolically inactive but because they had acquired the ability to persist in the presence of antibiotics. That had made the whole question of dormancy—could something be alive but not culturable, because it was in some kind of dormant form?—a big open question.
“Okay, so we don’t call it ‘dormancy.’ But somehow, this thing thinks it’s in trouble in the host so it wants to go into some kind of dormant stage in the victim, and it starts giving off spores,” Danice said.
“Exactly,” Jeannine said.
“I love it when every so often I say something and you say, ‘Exactly,’ ” Danice said.
“So if the infection cleared quickly enough, there might not be enough evidence that there’d been one. And it’s just a matter of whether the DNA would have been transferred into the host cells by then,” Jeannine responded.
“But God, it has to sporul
ate so quickly. And get into cells so quickly,” Danice told her.
They took another break. Jeannine trooped down to the coffee machine and back. She took her second sip and Danice called back.
“The nose,” Danice was saying. “The nose!”
“Lower your voice,” Jeannine told her. “What about it?”
“There aren’t as many nutrients in the nose,” Danice told her. “What if you inhaled it, and the immune system started clearing it immediately, but it was still sporulating that fast? A lot of what we inhale comes in through the mouth and goes right into the lungs. But what if this came in primarily through the nose and there weren’t enough nutrients there? It would sporulate there and then, while meanwhile some of the bacteria could have made it down into the lungs long enough to transfer the DNA.”
Jeannine asked why it would come in primarily through the nose, and Danice answered that it might be like the flu, where some viruses stuck to the sugars on the surfaces of the nasal passages but others didn’t, because the surface sugars preferred by the viruses were a little different. H5N1, for example, was lethal but not that infectious because it adhered deep in the lungs but not in the upper respiratory tract, so it didn’t get coughed or sneezed out.
“That’s right,” Jeannine said.
Bacteria had all these amazing ways to stick to cells and hang on, Danice reminded her, and this one might have picked up the ability to stick to cells in the nose.
“But don’t we have a problem then with why it’s so lethal?” Jeannine asked. “Given how quickly in this scenario the bacteria’s being cleared? What did Jimenez say about that?”
They were up the rest of the night thinking about it. It wasn’t until Jeannine could see a hint of red over the hills from the coming dawn out the front windows that Danice called back. By then Jeannine had relocated to the atrium to try to think more clearly away from her computer screen. The entire building seemed empty, which was pretty rare, and completely quiet.
“So maybe the lethality comes from the DNA itself,” Danice suggested. “Especially if it’s host DNA to begin with: any sort of gene could have been picked up. Like apoptosis. Supposing it picked up a gene for promoting programmed cell death and that gene then lost its regulatory sequences? How would that present?”
“Like a whole lot of cell death,” Jeannine told her, after a silence.
“The one thing we’ve seen everywhere,” Danice told her.
The quiet on the line extended until it sounded to each of them like something other than quiet.
“We got a lot of people to call,” Jeannine told her. “You should start with your pals.”
“Jesus fucking Christ,” Danice said.
Archimedes Naked
The story Jeannine had always heard about Archimedes was that he’d come to his revelation about the buoyancy of an object in water being equal to the weight of the water displaced while in a public bath, and that he’d run down the streets naked exclaiming, “Heureka!,” Greek for “I have found it!” Before she’d gotten off the phone with Danice she’d repeated two or three times, “You did it!” And each time Danice had responded, “We all did it,” and even though in Jeannine’s mind it technically really was Danice’s Eureka!, Jeannine took her own victory laps anyway, jogging through the dark empty building from the atrium to the top floors and back. That took five minutes, and then she climbed back into her office chair, sweaty and exclaiming triumphant and incoherent things to herself every so often, and started sending text after text to everyone relevant back at the CDC.
Belly Up to the Workbench
Necrosis and apoptosis were not the same things, but the similarity was in the way both created a situation in which everything was coming apart. Once the blood vessels started to disintegrate, the infected started to go into shock, and as the vessels hemorrhaged fluid, there was no longer enough blood pressure to get oxygen to the vital organs. The body was responding as if there was an invader and the invader was everywhere, and so it thought it was fighting its battle on every front, and ended up destroying itself. And in an autopsy, apoptosis might at first present like simple necrosis: like just your basic dead tissue.
And within a few hours, word started pouring in that double checking was proving them right: something had turned on apoptosis in the people infected. Their DNA was fragmenting. Her new supervisor at the CDC directed her to get more cells from Aleq’s lungs, to see if what the cells were undergoing could be blocked with apoptosis inhibitors. Jeannine wrote back that she’d already scheduled the procedure with the boy for later that morning. She asked in a follow-up text how her previous supervisor was doing, and her new supervisor didn’t respond.
The Test Case
Another question with the boy was whether he was a carrier or a convalescent, or whether in a case like this there was even much of a distinction. With cholera you could have people who were infected but not infectious, but cholera cycled, and the million-dollar question with cholera was always whether it was cycling—coming back—because of changing dynamics with phages or other elements that were destroying the bacteria in the water, or because it just had run out of suitable hosts and now there were more, or just because it came and went, for reasons no one had ever figured out.
Welcome to Danice World
The next time Danice called back, Jeannine launched into four or five hypotheticals that she found pretty compelling until she realized that Danice hadn’t said a word in response.
“You there?” Jeannine finally asked. “Did you hear what I said?”
“I’m sick,” Danice said.
Jeannine’s chest electrified with terror. “What?” she said.
It sounded like Danice might be crying. Jeannine, after she got her voice back, had to say What? again.
Danice told her that she’d sent out a thousand emails and had been on the internet with everybody all day. And around dinnertime she’d felt funny and had thought that maybe she just needed a break and had been gathering up her things and had felt how sweaty she was and then had known.
She said she’d just stood there at first, with her thoughts shorting out, and then she’d picked up the phone to call Jeannine but she’d been unable to. She said that at that point Dr. Hammekin had stuck his head in the room and had told her they needed to do a better job of finding and isolating earlier in the process medical staffers who were getting sick, and she’d dropped onto her desk everything she’d gathered together, and had told him, “Well, you can start with me.”
He’d hustled her into isolation and she’d gone into the bathroom and looked at herself in the mirror to prove there was nothing to worry about and then had cried out at her own expression. It had apparently sounded so awful it had made a couple of nurses come running.
And now it was the whole nine yards, she added. The fever, the chills, the trouble breathing.
“Oh, honey,” Jeannine said.
“Oh, God,” Danice answered quietly, and the sound made Jeannine hunch where she was standing, like someone had hit her.
“Look, we already know how many people have been hanging on in Ililussat,” she finally reminded Danice a little desperately.
“It’s like whenever something awful would happen when I was a kid, my mother would go, ‘Welcome to Danice World,’ ” Danice said.
“Oh, honey,” Jeannine repeated, aware that she was being less than articulate. “What’s your temperature?”
“One hundred and three. And the chest X-ray looks like a snowstorm,” Danice told her.
Jeannine could hear the wheezing.
“And just for the record,” Danice said, “I think there’s also some myalgia and photophobia.”
“What’re they doing for you?” Jeannine wanted to know.
She could hear Danice messing with something on her end and it took a minute before
she spoke. “Oh, you know. Something borrowed, something blue. Every therapeutic they can think of.”
“Did you tell them to try apoptosis inhibitors?” Jeannine asked.
“First thing,” Danice said. “They’re going to try a couple of versions. They had to be shipped from Nuuk.”
“You should’ve gone straight to Atlanta for that,” Jeannine told her.
“Jerry’s all over that,” Danice said. “He’s been dealing with them nonstop. He’s a little freaked out, as you might expect.”
“Is he okay?” Jeannine asked.
“Some back pain, some other muscle pain, that’s about it,” Danice said. “So yes, probably.”
“I’ll call Atlanta when I get off with you,” Jeannine said. “And I’ll find out if anyone has had any success with anything else that’s been slowing this down. There’s a list of apoptosis inhibitors as long as your arm. And I’ve been hearing about new anti-virulence strategies as well.”
Danice sniffed. “Come one, come all,” she said. “I’m ready for anything we got.”
“Fuck,” Jeannine said.
“Yeah,” Danice agreed. She hadn’t had time to let anyone else know, she said. She wanted to use the time she had to work on what they were working on.
“I don’t know who I’d call anyway,” she added.
“How about your mother?” Jeannine asked. “Your brother?”
“Yeah,” Danice agreed.
“Maybe we gotta get some other medical people there, too, besides Jerry,” Jeannine said. “Is this Hammekin guy any good at all?”
“He doesn’t seem to think much of me, but when things get hairy, I think he’s the kind of guy you want to have around,” Danice said. “And Jerry knows what he’s doing.”