The Demon in the Freezer

by Richard Preston

  The pox bricks had a crinkly, knobby surface, rather like a hand grenade—some experts call this feature the mulberry of pox. (A mulberry is a small fruit, the size of a thumbnail, which looks like a blackberry.) There are many species and families of poxviruses; smallpox is an orthopox, a poxvirus of animals. Poxviruses are among the largest and most complicated viruses in nature. A pox particle itself either makes or consists of around two hundred different kinds of protein, and many of the proteins are locked together into the particle like a Chinese puzzle. Pox scientists are slowly picking apart the structure of the mulberry of pox, but so far nobody has figured out the full design. Experts in pox find the pox virion mathematical in its structure and almost breathtakingly beautiful. At the center of the mulberry there is an odd shape that looks like a dumbbell, which scientists call the dumbbell core or the dogbone of pox. Inside the dumbbell, or dogbone, there is a clump of DNA, which is the long, twisted, ladderlike molecule that contains the genome of smallpox—the complete blueprint and operating software for variola. The steps of the ladder of DNA are the letters of the genetic code. The genome of smallpox has about 187,000 letters, which is one of the longest genomes of any virus. Smallpox uses a lot of this code to defeat the immune system of its human host. It has about two hundred genes (which make the virus’s two hundred proteins). By contrast, the AIDS virus, HIV, has only ten genes. In terms of the natural design of a virus, HIV has a simple design that works well. HIV is a bicycle, while smallpox is a Cadillac loaded with tail fins and every option in the book.

  Poxviruses are one of the few kinds of viruses that are just large enough to be seen in the best optical microscopes (in which they look like fine grains of pepper). The infinitesimal palaces of biology extend far into the unseen. It is hard for the mind to grasp just how small is small in the microscopic universe of nature, but one way is to imagine a scale of nature built on the scale of the Woodstock music festival, which took place in a natural amphitheater at Max Yasgur’s farm in Bethel, New York. It held up to a half-million people. Seen from low orbit above the earth, the crowd of people at Yasgur’s farm would have looked something like this:

  If a cell from the human body, in its natural size, were placed on this representation of the Woodstock festival, the cell would be an object about the size of a Volkswagen bus parked at the real festival. Bacterial cells are smaller than the cells of animals. If a single cell of E. coli (the main type of bacteria that lives in the human gut) were placed on the Woodstock on this page, it would be an object the size of a smallish watermelon, perhaps sitting on the grass beside the Volkswagen bus. A spore of anthrax would be an orange. On that same scale, a particle of smallpox would be a mulberry. (The particles of the common cold are the smallest virus particles found in nature; a cold virus would be a marijuana seed under the seat of the Volkswagen bus parked at Woodstock.) Three to five mulberries of smallpox floating into the air out of the Woodstock dot on the page would be invisible to the eye and senses, yet they could start a global pandemic of smallpox.

  AS DR. RICHTER pondered the view in the microscope, he was not unprepared for the national emergency it implied. Three years earlier, he had laid out a plan for what would be done if smallpox broke out on his watch. Now it was happening. He lined up an older pox expert, Dr. Josef Posch, and they were joined by another colleague, Professor Helmut Ippen. They organized a quarantine at the hospital, they got vaccine ready, and they gathered biohazard equipment, which Richter had previously stockpiled. He also made a telephone call to the offices of the Smallpox Eradication Program at the World Health Organization (WHO) in Geneva, Switzerland, asking for help.

  The WHO occupies a building constructed in the nineteen fifties on a hill above Geneva. It is surrounded by the flags of the world’s nations. In 1970, the Smallpox Eradication Program (SEP) was a relatively new effort at the WHO—it was inaugurated in 1966. The smallpox program operated out of a cluster of tiny cubicles on the sixth floor—the cubicles were exactly four feet wide, but they had a magnificent view southward across Lake Geneva toward Mont Blanc. Although the cubicles of the smallpox program were tiny and jammed together, the unit had a deserted feel, because at any given time more than half of the staff members were away, dealing with smallpox in various parts of the earth.

  Dr. Richter ended up talking with an American doctor on the staff named Paul F. Wehrle, who spoke a little German. Dr. Wehrle (his name sounds like whirly) was a tall, thin, courtly epidemiologist with brown hair and green eyes who had a habit of wearing a jacket and tie with a white shirt when he went into the field, because he felt that a well-dressed doctor would inspire confidence in the midst of the shit terror of a smallpox outbreak. Wehrle now lives in quiet retirement with his wife in Pasadena. “I have unfortunately turned eighty,” he remarked to me, “but fortunately I have all of my hair, most of my teeth, and at least some of my brain.”

  A single smallpox virus particle (virion) from a pustule in human skin. Negative contrast electron microscopy, magnified about 150,000 times, showing the “mulberry” structure of the proteins on the surface of the particle. The photograph was made in 1966 by Frederick A. Murphy, who could be described as the Ansel Adams of electron microscopy.

  Diagram of a smallpox virus particle showing its surface and internal structure.Its dumbbell core (the dogbone) is visible; the dumbbell holds the genome of the virus, which consists of about 187,000 letters, or nucleotides, of DNA. (Both images courtesy of Frederick A. Murphy, School of Veterinary Medicine, University of California at Davis.)

  When Dr. Richter told him what was going on in Meschede, Dr. Wehrle understood the picture only too well. The WHO rule was to keep smallpox patients out of hospitals, because they could spread the virus all too easily—hospitals are amplifiers of variola. Smallpox could essentially sack a hospital, infecting doctors and nurses and patients, and from there the virus would continue out into the community and beyond. The WHO recommended keeping smallpox patients at home under the care of vaccinated relatives. Since there was nothing a doctor could do for a patient with smallpox, it was just as well to keep the patient away from doctors.

  Wehrle went down the hall to a double cubicle that was occupied by a tall, assertive medical doctor named Donald Ainslie Henderson. Everyone called Henderson “D.A.,” including his wife and children. D. A. Henderson was the head of the Smallpox Eradication Program. He was six feet two inches tall, with a seamed, rugged, blocky face, thick, straight, brown hair brushed on a side part, wide shoulders, big-knuckled hands, and a gravelly voice. Wehrle and Henderson discussed strategy, and Henderson made some telephone calls. The young man in the hospital at Meschede could start an outbreak across Europe. Henderson told Wehrle to go to Germany. Wehrle got a taxi to the airport, and that afternoon he was on a flight to Düsseldorf. Meanwhile, Henderson made arrangements to have one hundred thousand doses of smallpox vaccine shipped from Geneva to Germany immediately.

  WHILE PAUL WEHRLE was en route to Meschede, Dr. Richter and the German health authorities got Peter Los out of the St. Walberga Hospital—fast. The police closed off the hospital, and a squad of attendants dressed in plastic biohazard suits and with masks over their faces ran inside the building and wrapped Los in a plastic biocontainment bag that had breathing holes in it. He lay in agony inside the bag. The evac team rushed him out of the building on a gurney and loaded the bag into a biosafety ambulance, and with siren wailing and lights flashing, it took him thirty miles along winding roads to the Mary’s Heart Hospital in the small town of Wimbern. This hospital had a newly built isolation unit that was designed to handle extremely contagious patients. The Wimbern biocontainment unit was a one-story building with a flat roof, sitting in the middle of the woods. They placed Los on a silky-smooth plastic mat designed for burn victims, and he hovered on the edge of death. Construction crews began putting up a chain-link fence around the building.

  That same day, Dr. Richter and Dr. Posch organized vaccinations for everyone at St. Walberga, patients and sta
ff alike. They were given a special German vaccine that was scraped into their upper arms with a metal device called a rotary lancet, and then the doctors and their colleagues conducted interviews, trying to find out who had come into contact with Peter Los. Anyone who had seen Los’s face was assumed to have breathed smallpox particles. Twenty-two people were taken to the Wimbern hospital and put into quarantine. Everyone who had been in the south wing of St. Walberga but had not seen Los’s face was placed under quarantine inside the hospital, and they were ordered to remain there for eighteen days. Folding cots were brought in and set up in the bathrooms, where the medical staff slept. There wasn’t enough room to hold everyone, so the authorities took over a nearby youth hostel and several small hotels in the mountains and put people there, too. After a hospital worker escaped from quarantine and went home to his family, the authorities boarded up the doors of St. Walberga and nailed them shut, and stationed a police cordon around the hospital.

  Paul Wehrle arrived in Meschede on the evening of January 16th, having traveled by train from Düsseldorf. He was met at the station by Richter and Posch. (Richter did the driving, since Posch had lost an arm in the Second World War.) They took Wehrle to a hotel, and they stayed up most of the night, planning a quarantine and vaccination campaign. The Germans wanted to vaccinate people with the special German vaccine, but Wehrle did not trust it. It was a killed vaccine that the German government had been using for many years, but the WHO doctors believed it didn’t give people much immunity. “The German vaccine had one small problem. It didn’t work,” Wehrle claims. “It was as close to worthless as a vaccine can be, only I couldn’t say that to the Germans and live, because they tended to be a bit protective of their vaccine.” He liked and respected the German experts and didn’t want to offend them, but he gently urged them to give everyone at the hospital a second vaccination with the WHO vaccine. It couldn’t hurt to have two vaccinations and might help, he said, and they agreed. He also persuaded them to use the WHO vaccine for the larger vaccination in Meschede.

  The WHO maintained a stockpile of millions of doses of smallpox vaccine in freezers in a building in downtown Geneva they called the Gare Frigorifique—the Refrigeration Station. Much of the vaccine in the freezers had been donated to the Smallpox Eradication Program by the Soviet Union. The traditional vaccine for smallpox is a live virus called vaccinia, which is a poxvirus that is closely related to smallpox. Live vaccinia infects people, but it does not make most people very sick, though some have bad reactions to it, and a tiny fraction of them can become extremely sick and can die.

  A staff member from the Gare Frigorifique drove a couple of cardboard boxes full of glass ampules of the Russian vaccine to the Geneva airport—one hundred thousand doses took up almost no space. The vaccine did not need to be kept frozen, because after it was thawed it would remain potent for weeks. Thousands of smallpox-vaccination needles were also shipped to Germany. They were a special type of forked needle called a bifurcated needle, which has twin prongs.

  As quickly as possible, the German health authorities organized a mass vaccination for smallpox all around the Meschede area. This was known as a ring-vaccination containment. The smallpox doctors intended to encircle Peter Los and his contacts with a firewall of immunized people, so that the tiny blaze of variola at the center would not find any more human tinder and would not roar to life in its host species.

  Meschede came to a halt. People left their jobs and homes, and lined up at schools to be vaccinated, bringing their children with them. A fear of pox—a Pocken-angst—spread across Germany faster than the virus. People who drove in cars with license plates from Meschede found that gas stations wouldn’t serve them, nor would restaurants. Meschede had become a city of pox.

  Nurses and doctors gave out the vaccine. A person who was working as a vaccinator would stand by the line of people, holding a glass ampule of the vaccine and a small plastic holder full of bifurcated needles. The vaccinator would break the neck of the ampule and shake a needle out of the holder. She would dip the needle into the vaccine and then jab it into a person’s upper arm about fifteen times, making bloody pricks. You could have blood running down your arm if the vaccination was done correctly, for the bifurcated needle had to break the skin thoroughly. Each glass ampule was good for at least twenty vaccinations. As people passed in the line, a vaccinator could do hundreds of vaccinations in an hour. Each needle was put into a container after it had been used on one person. At the end of the day, all the needles were boiled and sterilized to be used again the next day.

  Each successfully vaccinated person became infected with vaccinia. They developed a single pustule on the upper arm at the site of the vaccination. The pustule was an ugly blister that leaked pus, and oozed and crusted, and many people felt woozy and a little feverish for a couple of days afterward, for vaccinia was replicating in their skin, and it is not a very nice virus. Meanwhile, their immune systems went into states of screaming alarm. Vaccinia and smallpox are so much alike that our immune systems have trouble telling them apart. Within days, a vaccinated person’s resistance to smallpox begins to rise. Today, many adults over age thirty have a scar on their upper arm, which is the pockmark left by the pustule of a smallpox vaccination that they received in childhood, and some adults can remember how much the pustule hurt. Unfortunately, the immune system’s “memory” of the vaccinia infection fades, and the vaccination begins to wear off after about five years. Today, almost everyone who was vaccinated against smallpox in childhood has lost much or all of their immunity to it.

  The traditional smallpox vaccine is thought to offer protective power up to four days after a person has inhaled the virus. It is like the rabies vaccine: if you are bitten by a mad dog, you can get the rabies vaccine, and you’ll probably be okay. Similarly, if someone near you gets smallpox and you can get the vaccine right away, you’ll have a better chance of escaping infection, or if you do catch smallpox, you’ll have a better chance of survival. But the vaccine is useless if given more than four to five days after exposure to the virus, because by then the virus will have amplified itself in the body past the point at which the immune system can kick in fast enough to stop it. The doctors had started vaccinating people at St. Walberga Hospital five and six days after Peter Los had been admitted. They were closing the barn door just after the horse had gone.

  The incubation period of smallpox virus is eleven to fourteen days, and it hardly varies much from person to person. Variola operates on a strict timetable as it amplifies itself inside a human being.

  The Student Nurse

  JANUARY 22, 1970

  ELEVEN DAYS AFTER Peter Los arrived at St. Walberga Hospital, a young woman who had been sleeping on a cot in one of the bathrooms woke up with a backache. She was a nursing student, seventeen years old, and I will call her Barbara Birke. She was small, slender, and dark haired, with pale skin and delicate features. She was a quiet person whom nobody knew much about, for she had been working at the hospital for only two weeks, and had been living in the nursing school dormitory while she received her training. The previous year, Barbara had been a kitchen helper in a Catholic hospital in Duisburg, where she had converted to the Catholic faith (her family was Protestant), and she had set her sights on becoming a nurse. She had spent Christmas with her family and had told her parents that she intended to become a nun, but she wanted to finish nursing school before she made up her mind. The Sisters of Mercy had reserved a place for her in the cloister.

  Barbara Birke had never seen Los’s face. She always worked on the third floor of the hospital, and she had been tending to a sick elderly man in Room 352, near the head of the stairwell that went down through the middle of the building. She had received both the German vaccine and the WHO vaccine a few days earlier.

  Birke told the doctors that she wasn’t feeling well, and they saw that she had a slight temperature. They immediately gave her an intravenous dose of blood serum taken from a person who was immune to smallpox
. Smallpox-immune serum is blood without red blood cells—a golden liquid—and it is full of antibodies that fight the virus. They put Birke inside a plastic bag, and she lay in the bag while an ambulance carried her on the winding road to Wimbern and through the fence to the isolation unit.

  Barbara Birke developed a worried, anxious look, while a reddening flush began to spread across her face, shoulders, and arms, and on her legs. Her fever went up, and her backache grew worse. Her skin remained smooth, and no pustules appeared, although the reddening deepened in color. When the doctors pressed their fingers on her skin, it turned white under the pressure, but when they released their fingertips the blood came rushing back in a moment, filling under the skin. The doctors recognized this sign, and it was very bad.

  I DON’T KNOW how much the doctors told Birke of what they understood was coming. The red flush across her face deepened until she looked as if she had a bad sunburn, and then it began to spread downward toward her torso. It was a centrifugal rash that had begun on the extremities. She developed a few smooth, scattered, red spots the size of freckles across her face and arms. More red spots began to appear closer to her middle, following the movement of the creeping flush. She was forbidden to have any visitors, and there were no telephones at Wimbern that the patients could use. She couldn’t speak with her family.

  The red spots began to enlarge, and there were more and more of them. They began to join together, like raindrops falling on a dry sidewalk, gradually darkening the pavement: she was starting to flood with hemorrhages beneath the skin.