So the vector experiments fell to Burton.
They were reasonably simple and straightforward, designed to answer the question of how the disease was transmitted. Burton began with a series of cages, lined up in a row. Each had a separate air supply; the air supplies could be interconnected in a variety of ways.
Burton placed the corpse of the dead Norway rat, which was contained in an airtight cage, alongside another cage containing a living rat. He punched buttons; air was allowed to pass freely from one cage to the other.
The living rat flopped over and died.
Interesting, he thought. Airborne transmission. He hooked up a second cage with a live rat, but inserted a Millipore filter between the living and dead rat cages. This filter had perforations 100 angstroms in diameter– the size of a small virus.
He opened the passage between the two cages. The rat remained alive.
He watched for several moments, until he was satisfied. Whatever it was that transmitted the disease, it was larger than a virus. He changed the filter, replacing it with a larger one, and then another still larger. He continued in this way until the rat died.
The filter had allowed the agent to pass. He checked it: two microns in diameter, roughly the size of a small cell. He thought to himself that he had just learned something very valuable indeed: the size of the infectious agent.
This was important, for in a single simple experiment he had ruled out the possibility that a protein or a chemical molecule of some kind was doing the damage. At Piedmont, he and Stone had been concerned about a gas, perhaps a gas released as waste from the living organism.
Yet, clearly, no gas was responsible. The disease was transmitted by something the size of a cell that was very much bigger than a molecule, or gas droplet.
The next step was equally simple– to determine whether dead animals were potentially infectious.
He took one of the dead rats and pumped the air out of its cage. He waited until the air was fully evacuated. In the pressure fall, the rat ruptured, bursting open. Burton ignored this.
When he was sure all air was removed, he replaced the air with fresh, clean, filtered air. Then he connected the cage to the cage of a living animal.
Nothing happened.
Interesting, he thought. Using a remotely controlled scalpel, he sliced open the dead animal further, to make sure any organisms contained inside the carcass would be released into the atmosphere.
Nothing happened. The live rat scampered about its cage happily.
The results were quite clear: dead animals were not infectious. That was why, he thought, the buzzards could chew at the Piedmont victims and not die. Corpses could not transmit the disease; only the bugs themselves, carried in the air, could do so.
Bugs in the air were deadly.
Bugs in the corpse were harmless.
In a sense, this was predictable. It had to do with theories of accommodation and mutual adaptation between bacteria and man. Burton had long been interested in this problem, and had lectured on it at the Baylor Medical School.
Most people, when they thought of bacteria, thought of diseases. Yet the fact was that only 3 percent of them produced human disease; the rest were either harmless or beneficial. In the human gut, for instance, there were a variety of bacteria that were helpful to the digestive process. Man needed them, and relied upon them.
In fact, man lived in a sea of bacteria. They were everywhere– on his skin, in his ears and mouth, down his lungs, in his stomach. Everything he owned, anything he touched, every breath he breathed, was drenched in bacteria. Bacteria were ubiquitous. Most of the time you weren’t aware of it.
And there was a reason. Both man and bacteria had gotten used to each other, had developed a kind of mutual immunity. Each adapted to the other.
And this, in turn, for a very good reason. It was a principle of biology that evolution was directed toward increased reproductive potential. A man easily killed by bacteria was poorly adapted; he didn’t live long enough to reproduce.
A bacteria that killed its host was also poorly adapted. Because any parasite that kills its host is a failure. It must die when the host dies. The successful parasites were those that could live off the host without killing him.
And the most successful hosts were those that could tolerate the parasite, or even turn it to advantage, to make it work for the host.
“The best adapted bacteria,” Burton used to say, “are the ones that cause minor diseases, or none at all. You may carry the same single cell of Strep. viridians on your body for sixty or seventy years. During that time, you are growing and reproducing happily; so is the Strep. You can carry Staph. aureus around, and pay only the price of some acne and pimples. You can carry tuberculosis for many decades; you can carry syphilis for a lifetime. These last are not minor diseases, but they are much less severe than they once were, because both man and organism have adapted.”
It was known, for instance, that syphilis had been a virulent disease four hundred years before, producing huge festering sores all over the body, often killing in weeks. But over the centuries, man and the spirochete had learned to tolerate each other.
Such considerations were not so abstract and academic as they seemed at first. In the early planning of Wildfire, Stone had observed that 40 per cent of all human disease was caused by microorganisms. Burton had countered by noting that only 3 per cent of all microorganisms caused disease. Obviously, while much human misery was attributable to bacteria, the chances of any particular bacteria being dangerous to man were very small. This was because the process of adaptation– of fitting man to bacteria– was complex.
“Most bacteria,” Burton observed, “simply can’t live within a man long enough to harm him. Conditions are, one way or another, unfavorable. The body is too hot or too cold, too acid or too alkaline, there is too much oxygen or not enough. Man’s body is as hostile as Antarctica to most bacteria.”
This meant that the chances of an organism from outer space being suited to harm man were very slim. Everyone recognized this, but felt that Wildfire had to be constructed in any event. Burton certainly agreed, but felt in an odd way that his prophecy had come true.
Clearly, the bug they had found could kill men. But it was not really adapted to men, because it killed and died within the organism. It could not be transmitted from corpse to corpse. It existed for a second or two in its host, and then died with it.
Satisfying intellectually, he thought.
But practically speaking they still had to isolate it, understand it, and find a cure.
***
Burton already knew something about transmission, and something about the mechanism of death: clotting of the blood. The question remained– How did the organisms get into the body?
Because transmission appeared to be airborne, contact with skin and lungs seemed likely. Possibly the organisms burrowed right through the skin surface. Or they might be inhaled. Or both.
How to determine it?
He considered putting protective suitings around an experimental animal to cover all but the mouth. That was possible, but it would take a long time. He sat and worried about the problem for an hour.
Then he hit upon a more likely approach.
He knew that the organism killed by clotting blood. Very likely it would initiate clotting at the point of entrance into the body. If skin, clotting would start near the surface. If lungs, it would begin in the chest, radiating outward.
This was something he could test. By using radioactively tagged blood proteins, and then following his animals with scintillometer scans, he could determine where in the body the blood first clotted.
He prepared a suitable animal, choosing a rhesus monkey because its anatomy was more human than a rat’s. He infused the radioactive tagging substance, a magnesium isotope, into the monkey and calibrated the scanner. After allowing equilibration, he tied the monkey down and positioned the scanner overhead.
He was now ready to begin.
The scanner would print out its results on a series of human block outlines. He set the computer printing program and then exposed the rhesus to air containing the lethal microorganism.
Immediately, the printout began to clatter out from the computer:
[graphic of disease spread in human body]
It was all over in three seconds. The graphic printout told him what he needed to know, that clotting began in the lungs and spread outward through the rest of the body.
But there was an additional piece of information gained. Burton later said, “I had been concerned that perhaps death and clotting did not coincide– or at least did not coincide exactly. It seemed impossible to me that death could occur in three seconds, but it seemed even more unlikely that the total blood volume of the body-five quarts-could solidify in so short a period. I was curious to know whether a single crucial clot might form, in the brain, perhaps, and the rest of the body clot at a slower pace.”
Burton was thinking of the brain even at this early stage of his investigation. In retrospect, it is frustrating that he did not follow this line of inquiry to its logical conclusion. He was prevented from doing this by the evidence of the scans, which told him that clotting began in the lungs and progressed up the carotid arteries to the brain one or two seconds later.
So Burton lost immediate interest in the brain. And his mistake was compounded by his next experiment.
***
It was a simple test, not part of the regular Wildfire Protocol. Burton knew that death coincided with blood clotting. If clotting could be prevented, could death be avoided?
He took several rats and injected them with heparin, an anticoagulating drug– preventing blood-clot formation. Heparin was a rapid-acting drug widely used in medicine; its actions were thoroughly understood. Burton injected the drug intravenously in varying amounts, ranging from a low-normal dose to a massively excessive dose.
Then he exposed the rats to air containing the lethal organism.
The first rat, with a low dose, died in five seconds. The others followed within a minute. A single rat with a massive dose lived nearly three minutes, but he also succumbed in the end.
Burton was depressed by the results. Although death was delayed, it was not prevented. The method of symptomatic treatment did not work.
He put the dead rats to one side, and then made his crucial mistake.
Burton did not autopsy the anticoagulated rats.
Instead, he turned his attention to the original autopsy specimens, the first black Norway rat and the first rhesus monkey to be exposed to the capsule. He performed a complete autopsy on these animals, but discarded the anticoagulated animals.
It would be forty-eight hours before he realized his error.
The autopsies he performed were careful and good; he did them slowly, reminding himself that he must overlook nothing. He removed the internal organs from the rat and monkey and examined each, removing samples for both the light and electron microscopes.
To gross inspection, the animals had died of total, intravascular coagulation. The arteries, the heart, lungs, kidneys, liver and spleen– all the blood-containing organs– were rock-hard, solid. This was what he had expected.
He carried his tissue slices across the room to prepare frozen sections for microscopic examination. As each section was completed by his technician, he slipped it under the microscope, examined it, and photographed it.
The tissues were normal. Except for the clotted blood, there was nothing unusual about them at all. He knew that these same pieces of tissue would now be sent to the microscopy lab, where another technician would prepare stained sections, using hematoxylin-eosin, periodic acid-Schiff, and Zenker-formalin stains. Sections of nerve would be stained with Nissl and Cajal gold preparations. This process would take an additional twelve to fifteen hours. He could hope, of course, that the stained sections would reveal something more, but he had no reason to believe they would.
Similarly, he was unenthusiastic about the prospects for electron microscopy. The electron microscope was a valuable tool, but occasionally it made things more difficult, not easier. The electron microscope could provide great magnification and clear detail-but only if you knew where to look. It was excellent for examining a single cell, or part of a cell. But first you had to know which cell to examine. And there were billions of cells in a human body.
At the end of ten hours of work, he sat back to consider what he had learned. He drew up a short list:
1. The lethal agent is approximately 1 micron in size. Therefore it is not a gas or molecule, or even a large protein or virus. It is the size of a cell, and may actually be a cell of some sort.
2. The lethal agent is transmitted by air. Dead organisms are not infectious.
3. The lethal agent is inspired by the victim, entering the lungs. There it presumably crosses over into the bloodstream and starts coagulation.
4. The lethal agent causes death through coagulation. This occurs within seconds, and coincides with total coagulation of the entire body vascular system.
5. Anticoagulant drugs do not prevent this process.
6. No other pathologic abnormalities are known to occur in the dying animal.
Burton looked at his list and shook his head. Anticoagulants might not work, but the fact was that something s the process. There was a way that it could be done. He knew that.
Because two people had survived.
17. Recovery
AT 1147 HOURS, MARK HALL WAS BENT OVER THE computer, staring at the console that showed the laboratory results from Peter Jackson and the infant. The computer was giving results as they were finished by the automated laboratory equipment; by now, nearly all results were in.
The infant, Hall observed, was normal. The computer did not mince words:
SUBJECT CODED– INFANT– SHOWS ALL LABORATORY VALUES WITHIN NORMAL LIMITS
However, Peter Jackson was another problem entirely. His results were abnormal in several respects.
SUBJECT CODED JACKSON, PETER
LABORATORY VALUES NOT WITHIN NORMAL LIMITS FOLLOW
TEST : NORMAL : VALUE
HEMATOC : 38-54 : 21 INITIAL
25 REPEAT
29 REPEAT
33 REPEAT
37 REPEAT
BUN : 10-20 : 50
COUNTS RETIC : 1 : 6
BLOOD SMEAR SHOWS MANY IMMATURE ERYTHROCYTE FORMS
TEST : NORMAL : VALUE
PRO TIME : L2 : 12
BLOOD PH : 7.40 : 7.31
SGOT : 40 : 75
SED RATE : 9 : 29
AMYLASE : 70-200 : 450
Some of the results were easy to understand, others were not. The hematocrit, for example, was rising because Jackson was receiving transfusions of whole blood and packed red cells. The BUN, or blood urea nitrogen, was a test of kidney function and was mildly elevated, probably because of decreased blood flow.
Other analyses were consistent with blood loss. The reticulocyte count was up from 1 to 6 per cent. Jackson had been anemic for some time. He showed immature red-cell forms, which meant that his body was struggling to replace lost blood, and so had to put young, immature red cells into circulation.
The prothrombin time indicated that while Jackson was bleeding from somewhere in his gastrointestinal tract, he had no primary bleeding problem: his blood clotted normally.
The sedimentation rate and SGOT were indices of tissue destruction. Somewhere in Jackson’s body, tissues were dying off.
But the pH of the blood was a bit of a puzzle. At 7.31, it was too acid, though not strikingly so. Hall was at a loss to explain this. So was the computer.
SUBJECT CODED JACKSON, PETER
DIAGNOSTIC PROBABILITIES
1. ACUTE AND CHRONIC BLOOD LOSS ETIOLOGY GASTROINTESTINAL .884 NO OTHER STATISTICALLY SIGNIFICANT SOURCES.
2. ACIDOSIS ETIOLOGY UNEXPLAINED FURTHER DATA REQUIRED SUGGEST HISTORY
Hall read the printout and shrugged. The computer might suggest he talk to the patient, but that was easier said than done. Jackson was comatose, and if he had ingested anything to make his blood acid, they would not find out until he revived.
On the other hand, perhaps he could test blood gases. He turned to the computer and punched in a request for blood gases.
The computer responded stubbornly.
PATIENT HISTORY PREFERABLE TO LABORATORY ANALYSES
Hall typed in: “Patient comatose.”
The computer seemed to consider this, and then flashed back:
PATIENT MONITORS NOT COMPATIBLE WITH COMA — EEG SHOWS ALPHA WAVES DIAGNOSTIC OF SLEEP
“I’ll be damned,” Hall said. He looked through the window and saw that Jackson was, indeed, stirring sleepily. He crawled down through the tunnel to his plastic suit and leaned over the patient.
“Mr. Jackson, wake up…”
Slowly, he opened his eyes and stared at Hall. He blinked, not believing.
“Don’t be frightened,” Hall said quietly. “You’re sick, and we have been taking care of you. Do you feel better?”
Jackson swallowed, and nodded. He seemed afraid to speak. But the pallor of his skin was gone; his cheeks had a slight pinkish tinge; his fingernails were no longer gray.
“How do you feel now?”
“Okay… Who are you?
“I am Dr. Hall. I have been taking care of you. You were bleeding very badly. We had to give you a transfusion.”
He nodded, accepting this quite calmly. Somehow, his manner rung a bell for Hall, who said, “Has this happened to you before?”
“Yes,” he said. “Twice.”
“How did it happen before?”
“I don’t know where I am,” he said, looking around the room. “Is this a hospital? Why are you wearing that thing?”
“No, this isn’t a hospital. It is a special laboratory in Nevada.”
“Nevada?” He closed his eyes and shook his head. “But I’m in Arizona…”
“Not now. We brought you here, so we could help you.”