The two dead monkeys were both in the India group. There had never been an animal known to be killed by any strain of smallpox. This was the first time anyone had seen variola amplified fatally in any species other than humans.
Feeling somewhat overwhelmed but extremely eager to find out what the India strain had done to the monkeys, Martinez got a pole and gently touched the dead monkeys. He wanted to make certain they were dead. A not-quite-dead monkey that is hot with India smallpox and has canine teeth would be an exceedingly dangerous animal. The touch of the pole revealed that the monkeys were stone dead. One of them, a smaller male designated C171, was in rigor mortis.
Martinez was the team’s pathologist. He wanted to do posts on them fast—he wanted to see tissue. He examined the dead animals’ eyes. They were normal-looking; there was no sign of blood, as there is in humans with bloody smallpox. He decided to do a necropsy—a postmortem exam—of the heavier male, Monkey C115. He carried the monkey into the necropsy room, laid it on a metal table, and assembled his tools. He closed the door behind him. Animal-use laws prohibit any necropsy or surgical procedure on an animal within the sight of other animals of the same species.
LISA HENSLEY went straight to the necropsy room without stopping to see what was happening with any of the other monkeys. She wanted to get on the necropsy fast.
Martinez had already started by the time she arrived. The monkey was opened on the table; its abdominal cavity was wide, and it was puddled with free hemorrhages—the same thing that happens with human hemorrhagic smallpox. There were hemorrhagic spots all over the internal organs, especially the intestines.
Martinez lined up a row of plastic bins along the edge of the metal table, and he began filling them with samples of the monkey’s organs. He worked very fast.
Hensley’s heart was pounding. There was an emergency telephone hanging on the wall near the monkey cages. She called Jahrling, reaching him just as he arrived at his office at USAMRIID.
Jahrling started shouting over the phone at her. She could barely hear his voice through her earplugs and the roar of air in her suit. He wanted her to call him from the MCL and report whatever she and Martinez saw, all through the day. He sounded hyper.
The monkey’s stomach was bloody, wrecked by the smallpox. The lungs were bloody and speckled by hemorrhage. The liver was necrotic—mostly dead. The virus had gone everywhere inside the monkey.
She was face-to-face with variola major for the first time in her life. Until she had seen this hemorrhagic monkey, she had had no idea how powerful the virus was, how truly frightening. It was scarier than Ebola, much scarier, because it was a virus that was superbly adapted to humans, and it spread in the air. Ebola spread only by direct contact, and it was not well adapted to humans. Here, variola would be coming straight into the air out of the animal’s body cavity.
“Lisa!” Martinez shouted.
He handed her a plastic bin containing a half-dollar-sized lump of dark meat.
“What the heck’s that?” she asked.
“Spleen.”
The spleen was a mottled, cloudy, ultraswollen ball—and it was mostly dead. She picked up two scalpels, one in each hand, and bent over the sample in an awkward stance, holding her body back and away from the countertop, with her elbows out. This piece of spleen would contain several million human deaths’ worth of variola. She cut delicate bits, mincing the tissue. This spleen is a moosh, she thought.
She worked quickly, because Martinez was in a flurry of cutting, and the samples were piling up fast. She stood at a little counter opposite the necropsy table. Occasionally, she unhooked her air hose and carried samples of blood or tissue into her lab and processed them, spinning the blood in a centrifuge, looking at it under a microscope, doing red-cell counts and white-cell counts. She was hurrying back and forth, her hands full of amplified India blood.
The day dragged on, and the first necropsy took hours, because what they saw in the monkey was new to science. Around noon, they considered taking a break. They wanted to get something to eat and go to the bathroom, but they also wanted to get moving on the second dead monkey, which was still lying in its cage. They decided to just keep going.
Meanwhile, word had been traveling fast around the CDC that monkeys were down in the MCL—down with variola. The emergency telephone on the wall of the monkey room rang steadily. Hensley took the calls. People were calling from all over the CDC, and Jahrling and Huggins kept calling from Fort Detrick. Whatever their reservations might have been about Army people working with smallpox, the CDC people were getting excited, too. A CDC expert in Ebola named Pierre Rollin volunteered to help, and he arrived in MCL West with some compounds that could be used to prepare the tissues for viewing under an electron microscope.
In the cage on the upper left of the bank of cages in the monkey room, the inquisitive male with the light hair and unusual face, Monkey C099, was taking the scene in calmly. He seemed flushed. Maybe he was going to go down, too. Another infected monkey was looking very sick and was sitting down. Most nonhuman primates do not like to sit down in the presence of humans and will get to their feet if a person is near them. But if a monkey is ill, he will sit down in the presence of a person. The sick monkey hugs its knees and watches people, and it won’t eat. A monkey never lies down in front of a human if it can possibly help it. If a monkey is very sick, it will lie down when people turn their backs, but if anyone looks at the monkey, it will sit up again.
The sick monkey was huddling and holding its knees, and there were starlike speckles on its eyelids. When Hensley turned her back, the monkey lay down in its cage.
Martinez was standing next to Hensley. He shouted, “It’s going to kill all of them fast. I’ll bet we’ll be out of here in two weeks.”
“You wait and see,” she shouted back. “I’ll bet there will be one survivor. And we’re going to be here for a long time, Mark.”
They carried the second dead monkey into the necropsy room. Martinez was in good physical condition, but the strain of the necropsies was already starting to wear on him. He was a white-water kayaking instructor, yet doing pathology work in Level 4 with animals dying of hemorrhagic smallpox was pushing the envelope of his sense of physical control of his surroundings. The work was intense. Every move had to be right. You had to watch your hands, and you had to be superaware of who was around you and what they were doing.
Martinez found a chair, carried it into the necropsy room, and sat on it while he performed the second necropsy. He found that it helped him focus. Hensley had to keep running samples back into her lab, so she remained on her feet. Her back began to hurt, and she was freezing cold. It was the cutting posture that strained her back—bent over in that hunch, elbows out, body held back and away from the scalpel blades, while she took tiny slices of hot tissue. Something about the dry air inside the suit and the air-conditioning in the MCL was enough to practically give you hypothermia, even in summer in Atlanta. Her boots were thin rubber, and she could feel the concrete of the floor through her socks.
They finished the second necropsy at three o’clock in the afternoon.
“Let’s shower out after this,” Hensley said, and Martinez nodded.
But when they returned to the monkey room, they were shocked to find that the third monkey had already died. This monkey was the first to die of the Harper strain.
They forgot about taking a break and did the third necropsy. The work dragged on for hour after hour, and the sun began to set. There were no windows in the MCL to the outdoors, but a line of windows in the main room looked into a glassed atrium in Building 15. The light in the atrium went dark, as people went home from work. Martinez and Hensley had been in their space suits since eight o’clock that morning. They hadn’t eaten anything, and they hadn’t been able to make a pit stop in the rest room. The air in the suits was bone-dry, and they were dehydrated and thirsty.
At about eight o’clock at night, Martinez suddenly unhooked his air hose and signaled
to Hensley that he was going to exit. She thought he was having trouble with his air supply. He ran out of the room, hurrying for the air lock. The trouble was with his bladder.
He stood in the chemical shower in the air lock in agony. The shower cycle was automatic and took nine minutes, and he couldn’t get out until it had finished. Then he ran through the gray zone, tearing off his suit, on his way to the bathroom.
The team returned to the hotel that night and sat around the swimming pool, feeling a little stunned. Businesspeople passed by, talking about sales and deals; a man shot baskets on a little court near the pool; children yelled in the water. Life went on. The purpose of the work in the hot lab was to protect these people from variola, people who probably never thought about the disease and had little idea what it was.
Hensley went to her room and lay down flat on the floor and looked at the ceiling, trying to relieve the pain in her back. This was dramatic work that was going to get international attention. It might be published in some big journal like Science or Nature, and it was likely to upset the smallpox eradicators.
Harper
JUNE 4–20, 2001
TWO DAYS AFTER the three monkeys died, Monkey C099, the handsome monkey, had tiny pimples spreading across his thighs, although he didn’t seem very sick. They anesthetized him, laid him down on the necropsy table, and inspected him. They opened his mouth and found several small pustules on his palate and inside his lips. They used a swab to take a sample of saliva from the back of his throat. They wanted to find out if the virus moved into the air from the back of the monkey’s mouth, as it seems to do in humans. They returned him to his cage, and he woke up shortly afterward. He seemed perkier than the very sick ones.
In the next few days, C099 developed classical ordinary smallpox. It looked to Hensley and Martinez exactly like human smallpox, which meant that it could be a model of smallpox that the Food and Drug Administration might accept.
As the pustules enlarged and spread over the monkey’s face and hands and feet, the team saw that the pustules had dimples in them. This was a centrifugal smallpox rash, just like the ones humans get. Martinez brought an underwater camera into the lab, and he photographed the monkey. He had to use a waterproof camera because in order to take it out of Level 4 he had to submerge it in a dunk tank full of Lysol for half an hour.
The pustules clustered thickly around the animal’s extremities, just as they did in people with smallpox. The scientists began to feel sorry for him. They named him Harper, after the strain he had received.
Harper had one hundred and fifty pustules; they counted them while he was unconscious on the table. Hensley found the classic form of the disease more awful to look at than the bloody form, and this pale-faced monkey reminded her of a human child. She didn’t doubt that animal research was needed to save human lives—a prime example being research to find drugs that would be effective on HIV. The smallpox experiment had been reviewed and approved by the USAMRIID and CDC animal-use committees. Any animal that was clearly dying had to be sacrificed right away, and painlessly, so that its suffering would stop. But Harper was not dying. He was experiencing a form of agony that was the heritage of humanity, not of monkeys.
On the morning of June 7th, Harper was huddled in the back of his cage, visibly much sicker. The worst of it was his hands. The pustules of variola had erupted there.
The hand is a symbol of humanity, part of what makes us human—the hand that carved the Parthenon, painted the hands of God and Adam on the ceiling of the Sistine Chapel, and wrote King Lear was the only hand that had known smallpox. That same hand had now given the disease to a monkey.
The scientists were watching Jim Stockman, too. He was a serious man in his fifties who had worked with animals for his entire career and he was naturally gentle around animals. They felt that he might be having a difficult time watching Harper come down with smallpox. The monkey was getting dehydrated because he could hardly swallow. Stockman went to a drugstore and bought a bottle of grape-flavored Pedialyte—a fluid replacement that is often given to children who have diarrhea—hoping it would appeal to Harper. Hensley and Martinez prowled the breakfast bar at the hotel, picking over the fruit salad, taking red grapes, peaches, slices of mango and soft banana, tucking the fruit into foam coffee cups, and bringing it into MCL West to see if Harper would want any of it.
Stockman poured Pedialyte into a syringe that had a long plastic tube on it. The monkey took the liquid in his mouth. He seemed to trust the people in the space suits. Shamblin and Stockman pulped up bits of fruit and put them on a tongue depressor and offered them to Harper. He couldn’t chew, but he mouthed the mush and swallowed it. He had pustules on his haunches, and Mark Martinez got a soft pad and managed to slide it under the monkey, to help him sit more comfortably. They discovered that he liked the red grapes best of all, and Hensley would clean out all the grapes from the breakfast bar. Stockman bought bags of marshmallows, and Harper managed to chew and swallow them.
Harper had gone semiconfluent across the face. He began to reach the stage of early crust, the most dangerous stage of human smallpox, when the cytokine storm goes out of control. Around June 10th, when the monkey had crusted, Stockman offered him a whole red grape. He reached out, took the grape, and put it in his mouth.
Harper began to seem a little better, and he developed a passion for the grapes. If he noticed that someone had a cup of them, he would hold out both blistered hands and then stuff grapes into his cheek pouches until they bulged with grapes, saving them for later.
LISA HENSLEY had been phoning Peter Jahrling every day, and the team e-mailed pictures of Harper’s face to him. In late June, Jahrling brought some of the pictures to a meeting in Washington at the National Academy of Sciences, where he ran into D. A. Henderson. Members of the National Academy and leading experts on biological weapons were chatting and milling around a coffee machine. Jahrling and Henderson’s personal relationship had become tense and sour since Jahrling had begun to argue in favor of keeping smallpox.
Jahrling handed Henderson a color photograph of Harper. “Take a look at this, D.A.” The pustules were all over the monkey’s face, and they had dimples in them.
Henderson nodded and said something like, “Well, that looks just like smallpox.” His point seemed to be that Jahrling didn’t need to do experiments with smallpox when monkeypox looked so much like the real thing.
“Well, guess what, D.A.? It is smallpox.”
According to Jahrling, Henderson shoved the photograph into Jahrling’s stomach, turned on his heel, and walked away without a word. Henderson says that never happened.
JUNE TURNED INTO JULY, and Atlanta simmered with heat. Hensley was perpetually chilled in her space suit, and she welcomed the muggy weather when she walked out the doors of the MCL. She had no time for any kind of normal life. Go back to the hotel every evening. Heat up a Healthy Choice dinner. Lie down on the floor. Call Rob. She was making herself less available to him and knew she was doing it, but the experiment was in white water.
Harper had scabbed over, and his health had returned. They continued to feed him delicacies by hand, but they knew that he wouldn’t be permitted to live. The protocol of the experiment required the euthanasia of all animals, in order to gather more data on the effects of smallpox. And there was a biosafety rule that an animal infected with a Level 4 pathogen could not be taken out of Level 4 alive. Smallpox could leave the facility with the animal.
When the day came on which Harper had to be sacrificed, in late July, Jim Stockman announced that he had business to attend to in Maryland, and he would be flying home. Then it turned out that Josh Shamblin suddenly needed to fly home, too.
That night, each of the team members went into the monkey room, one by one, and paid visits to Harper. He had healed almost completely and had no scars. They left him heaps of marshmallows, peanuts, bunches of grapes, and a pear, more than he could eat. The next morning, Hensley and Martinez put Harper to sleep. They used an
anesthetic that would cause no pain. The monkey had been anesthetized before, and he would not have found anything unusual about it this time.
Martinez placed Harper, unconscious, on the table and watched him go. He had to note the death formally. Hensley turned her face away.
OF THE EIGHT MONKEYS that were given the Harper or India strains, seven died, six of hemorrhagic smallpox, one of classical pustular smallpox. Harper was the only survivor.
The team infected two more sets of monkeys. In round two, they infected six animals, five of which died. One of these monkeys got pustular smallpox and one of the others developed the brilliant red eyes of human black pox victims. In round three, the final round, they lowered the dose and infected nine monkeys, and none of them got sick at all.
Peter Jahrling felt that the experiements were successful. “We were able to put to rest the myth that smallpox infects no species but man,” he said. “We were able to create a disease in the monkeys that approximates the course of the human disease. This means it will be useful for validating antiviral drugs and vaccines for the FDA.” He said that the next step would be to challenge monkeys with smallpox and then try to cure them with the antiviral drug cidofovir.
I asked Jahrling about how he justified the suffering of the monkeys in the experiment. “My blood pressure would come down twenty points if we didn’t have to work with variola in monkeys,” he said. “It really bothers me. The thing is, you look into their eyes and you see they’re intelligent. You go into a monkey room at night and you hear them vocalizing, and it sounds like people talking. It really gets to me. But a critical countermeasure to smallpox is going to be antiviral drugs, and the FDA requires testing the drugs on the authentic smallpox virus in an animal. Frankly, I myself could accept and live with an antiviral drug that we’ve tested in human tissues in vitro”—in test tubes—“and in, say, genetically engineered mice that have been given a humanlike immune system. But testing smallpox on a mouse that has a human immune system isn’t going to be acceptable to the FDA anytime soon. Tens of monkeys are going to be sacrificed to this cause, but that is not the same thing as tens of millions of humans with smallpox, and I do believe that smallpox is a clear and present danger. But the truth is that I’ve been at the point where I really thought I couldn’t do this anymore.”