Council of war. On the eighth day after Carlos and Monique’s arrival in Colorado, they met with their top people at the Fort Collins CDC installation, purposely trying to keep the meeting small and elite enough that data could be digested swiftly and firm operative plans agreed on without delay. Monique was there with all of her crew except the two who were on duty then and there in the lab. Carlos brought two of his top Shoeleather lieutenants, representatives of the Denver and Colorado Springs city/county health departments’ epidemiological staffs, a Parke-Davis official who had flown west to try to unsnarl the supply problem with the chloramphenicol, a couple of others. Frank Barrington’s presence was a little anomalous, but then his position had been a little anomalous right from the start, and he had proven himself far too useful not to have him around. Carlos had taken one look at Frank and Monique talking quietly and intensely, heads together over coffee in the conference room, and thought whatever thoughts that single look had led him to think, and raised his eyebrows to himself, and kept his mouth shut. Roger Salmon, the project coordinator at Fort Collins, was on the phone to Atlanta a little overlong, but as soon as he joined the group, Carlos nodded and stood up. “Okay, I have the Canon City figures up to last night. Do you want the figures first, or do you want Monique’s report first?”
“Let’s hear Monique first,” the coordinator said. “She may help us make more sense out of the figures.” There was a murmur of assent around the room.
“Okay, my dear, you have the floor.”
Monique looked exhausted, her face pale, her hair done back carelessly in a bun. “Well, I have good news and bad news,” she said. “The good news is that the whole state of Colorado isn’t infected yet. The bad news is that it has to be some sort of miracle that it isn’t.”
“Better enlarge on that,” Roger Salmon said.
“Of course. First of all, just to dispel any lingering doubts, the organism we are dealing with is definitely Yersinia pestis, and the infection is plague. There simply isn’t any question about that. We have some twenty-three separate biochemical and genetic markers we can use to identify the genus Yersinia and an additional eleven markers to put the cross hairs on the species pestis. Granted, you never hit all of these markers with any given strain. We’ll accept fourteen or fifteen markers as proof of Yersinia, for example; this strain exhibits nineteen. Seven or more pestis markers are pretty definite proof of species; here we have eight, so we’re dealing with a strain of pestis. The problem is that we also have half a dozen additional and totally bizarre species markers that don’t match anything we’ve ever encountered before.”
“Which means what?” Carlos asked.
“Which means we are dealing with a wild mutant,” Monique said. “A strain of plague organism that has undergone a natural genetic change, and almost certainly a very major change.”
“So we need to know what change, precisely, and in what directions,” Carlos said.
“Yes. Well, I have some answers there, and you’re not going to like them.” Monique took a piece of chalk to the blackboard. “It’s not exactly news anymore that practically any microorganism can undergo mutation or genetic change under certain circumstances. There are a million different mechanisms. A piece of DNA can break off and not get repaired, or get stuck back on incorrectly. Genes can be obliterated or replicated and stuck on in triplicate or just about anything you can imagine. Whole pieces of chromosome can get stuck back on the wrong base, or get teamed up into threesomes. Well over ninety-nine percent of all such mutational changes are going to be dead ends — they’re strictly nonsurvival, either leaving the organism fatally vulnerable to its environment or preventing reproduction in some way so the mutation hits a brick wall and dies.”
Monique went back to her chair. “Some organisms do this sort of thing more than others. Certain viruses mutate like mad, but they’re simple to figure out. Bacteria are more complex. Some, like the tuberculosis bacilli, don’t mutate much at all. The red-bugs killing Alaskan Eskimos today are virtually identical genetically to the ones that killed Mimi in La Bohème ninety years ago.” Monique paused. “Unfortunately, most of the Yersinia group, including the pestis or plague organism, tend to mutate constantly. That’s why no one strain exhibits all the identifying markers — some have lost some markers, while others have gained new ones we haven’t identified yet. The point is, they change.”
“Why them and not others?” one of the public-health men asked.
“This we don’t know. We can do things in the laboratory to make them change, but that’s not what we’re talking about. Some changes come about as a result of natural selection in the face of a hostile environment — that’s why so few staph strains can be touched by penicillin anymore, and why we have so many penicillin-resistant gonococci around today. Maybe the Yersinia are extraordinarily sensitive to natural radiation. Maybe they have certain genes that direct mutation in a random fashion. It hasn’t been studied enough to know. We just know they do change, sort of constantly.”
“Then why aren’t we constantly having bizarre new strains turning up in epidemics?”
“Probably because most of the changes aren’t that big. How can I put it? We could say that Yersinia mutations fall into two classes: minor and major. A minor mutation, most common by far, may cause no detectable change in the organism’s behavior at all, or at least no change that makes any difference. Say there’s a minor DNA rearrangement, involving just one tiny bit of a strand, and all it does is alter the nature of some minor enzyme system, so the organism only makes two-thirds as much of that enzyme as formerly. So maybe all we would notice would be that that strain of organism, inoculated into a variety of sugar solutions, only seems to ferment two-thirds as much galactose as it used to. Same fermentation as before in all the other sugars, but the galactose consistently less. All right, this is a new marker; it tells us there’s been a mutation that affects the amount of galactose-fermenting enzyme — but so what? It doesn’t change the behavior of the organism in any way that matters to us. We can’t even tell for sure if it’s a survival or nonsurvival change for the organism.”
“We’d worry, though, if the mutation altered an enzyme system in a way that makes the organism more resistant to chloramphenicol, wouldn’t we?” Carlos said.
“Right. We’d call that a major mutation, because it would bother us as epidemiologists. A mutation that helps a plague organism survive and resist an antibiotic — that’s a major mutation, as far as we’re concerned. It could just be an enzyme change, or a co-enzyme change, or a vitamin change, or a dozen other things, but it could mean trouble. Another mutation might alter the biochemical toughness of the organism, enable it to survive and reproduce better in a marginal environment, so it’s harder to kill. Still another kind might affect virulence — the ability to cause disease, the seriousness of the disease, the incubation period it needs once it’s invaded a host. With Yersinia pestis, any such change could be exceedingly dangerous.”
“So what do we have down in Canon City?” Carlos asked.
Monique took a deep breath. “We’ve got an organism that’s jumped the fence,” she said. “From what we can see, there are two or three major changes back to back — changes involving a whole sequence of genes. This bug is still plague, but it’s different from any plague bug we’ve ever dealt with before. It’s incredibly virulent — it gets in under body defenses so fast that there’s already a raging septicemia before normal defense mechanisms even get the word that there’s been an invasion. I know it’s ridiculous to talk about an incubation period of only twelve hours before the infection is entrenched, but that’s what we’re looking at. There is some toxin produced that breaks down cell walls directly and converts normal intracellular protoplasm into a fantastic growth medium for this organism. You know what a staph organism can do to a bowlful of unrefrigerated chicken salad in about six hours. It can turn it into a bowlful of poison — except that the staph bug and its poison just give you a few hours of diarrhea. This plague bug invades soft tissues, invades the blood, invades the lymph and lymph glands, and starts ruining capillaries all over the body, all in a matter of hours. Worse yet, it thromboses capillaries in the lungs very early, jams them up tight, and then begins suppurating, eating right through the lung tissue itself and creating a fast-moving pneumonia. Ordinary plague only takes this pneumonic form in about fifteen percent or less of cases. This bug goes pneumonic in over eighty-five percent of our test animals, and I think Carlos will confirm that it’s doing that in humans too. It also follows the classical pattern of spread: infected rodent to flea to uninfected rodent — or to man, if the flea gets to him first — but once the man is infected, the course of disease is still likely to go to pneumonic infection, which means direct respiratory spread, person-to-person. That’s what hit that Comstock crowd so fast, and that’s what’s hitting everybody else.”
“But what’s wrong with the antibiotics?” the Denver public-health man burst out. “Chloramphenicol and streptomycin should stop plague, by my book, once you pin it down, but they’re not working here. Are you saying it’s just the timing? The bug is moving too fast?”
“I wish that were all,” Monique said, “but it’s not just the timing. This bug shows only about twenty-eight percent sensitivity to streptomycin, seventeen percent to chloramphenicol and none whatever to tetracycline — our three major antibiotics against plague. Those figures have to represent mutation; they’re far, far lower than anything in our previous plague experience. In plain language, those drugs are not going to help very much, even if we could get them into patients early enough. With pneumonic disease spreading from person to person, and with modern air-travel patterns, an unsuspecting contact could be across the country — or across the ocean — before he begins to get symptoms, and have nothing to help him when he does.” Monique pushed a wisp of hair away from her face and looked around. “It’s not a pretty picture. And if you ask me how a mutated organism like this can turn up in Washington State and almost simultaneously in wild rodents in central Colorado, I can’t tell you how, but it’s done so. The earliest samples from up in Washington State show precisely the same mutation pattern as fresh samples from wild rodents down here in Colorado. Well, when you’ve eliminated the impossible, whatever is left has to be true. It just defies belief that identical, highly complex mutations of this sort could have occurred simultaneously, without any connection, in two such widely separated areas. Scientifically, it just couldn’t happen. It had to spread by way of rodents and fleas. The only possible answer is that it’s been spreading like wildfire through the sylvan rodent population, incredibly fast, for some unknown period of time and just never surfaced in a human case until Pamela Tate came along.”
“But if it’s spreading that fast in wild rodents,” one of the EIS girls said, “what’s it going to do when it hits city rats?”
“Maybe they won’t be susceptible,” somebody else said.
“They’re susceptible,” Monique said. “We’ve already run tests.” She looked around at the group, most of whom were staring at her glumly. “Carlos will brief you later and individually on rat control and where that fits in. I’ve got just a little more here on the microbiology. So far I’ve been telling you all the bad things I could think of, because we’re dealing with something quite malignantly different from classical plague, something that could get totally out of control very fast if we don’t slam it hard right now. But we do have a couple of bright spots in the picture. For one thing, our existing plague vaccine, which is a simple killed-bacteria vaccine, seems to give reasonably effective protection against this bug. It’s only about sixty percent effective ten days after the first inoculation, but it’s better than nothing, and we’ve pulled in enough from western state stockpiles to cover anyone with any contact with patients. So if you aren’t covered yet, check with Carlos and get covered. The other thing is antibiotics. Streptomycin and chloramphenicol are at least somewhat effective, and people can eat them like popcorn if need be, for prophylaxis. We’ll have some nerve deafness from the streptomycin, and there’s a certain statistical risk of bone-marrow depression in those who take the chloramphenicol — but they’re all we’ve got right now. Maybe not for long, though. Ted Bettendorf has shipped us samples of a dozen new antibiotics still under development by various drug companies, and we’ve already started sensitivities. One of them, from Sealey Labs, looks very good on preliminaries. That’s Sealey 3147 — Ted said it’s a close cousin to tetracycline, and on our first sensitivity plates, this mutant bug is extremely vulnerable to it, and it looks like it may stop it cold in test animals. There’s a Mr. Mancini from Sealey Labs on his way here now to check our preliminaries; he’ll be checking with you, Carlos, to expedite a clinical supply if preliminaries hold up and toxicity is low. That drug may save the day for us. Now that’s about all I’ve got to report.”
A buzz of conversation, then, when Monique had finished. A flurry of questions, mostly for background and detail. A pro forma request for dissenting opinions from the others on her team, with none forthcoming. Finally Carlos stood up. “Well, my friends, now it’s our turn. I’m going to start by briefing you on how it is out in the real world in Canon City, Colorado, and about a dozen other brush-fire sites in four states. Then we’re going to sit down and brainstorm exactly what we’re going to do to break this thing in half wherever it’s turned up.”
With Carlos at the head of the table, they turned to the disease at hand.