Authors: David Hoffman
Yet the restless Sandakhchiev pushed him hard to synthesize enough genetic material to make artificial viruses. “From the beginning it seemed like a crazy idea,” Popov said, “but Sandakhchiev was a master of ambitious projects who set high goals. While we were struggling with making DNA fragments of 15 to 20 units long, he dreamed about thousands. We understood that in order to really speed things up we had to do the synthesis automatically. Sandakhchiev came up with the idea to build a huge warehouse or factory with automatic robots assembling DNA of different viruses. One virus a month, that would be an ideal productivity. And you could assemble biological weapons one after another.”
The World Health Organization campaign against smallpox had taken more than a decade to complete. Now Sandakhchiev was proposing to create a new virus every month.
“There was a green light given to Sandakhchiev’s idea,” Popov recalled. “What if the Soviet Union would be able to produce disease agents one after another? Agents with unbelievable efficacy, and without a means of protection against them? That was his brilliant idea.” Popov was told to study how to construct a “synthesizer,” an assembly line—what would it take? Sandakhchiev was interested in making SV40, a virus that causes cancer in monkeys, since the genetic sequence was the only one already known. It was more than five thousand nucleotides long. Popov told him it would require two or three years. Sandakhchiev was disappointed; he still wanted a new virus every month. “To me it
sounded like extreme stupidity,” Popov said, but “Sandakhchiev clearly understood the rules of the game with the Soviet military lobby. He stunned the generals with crazy, crazy, crazy ideas, well ahead of others.”
In the early 1980s, Popov and others at Vector, in conjunction with another institute in Moscow, genetically engineered an agent to create artificial interferon, an antiviral substance produced in the body.
5
Popov was decorated with a high state award for his work on interferon. Interferon was a valuable civilian invention, and part of Vector’s cover story. Meanwhile, behind the curtain, Vector began to study smallpox, hoping to give it new life as a biological weapon.
The smallpox virus is called
Variola
. The most severe and common is
Variola major
. Over the course of human history,
Variola major
claimed hundreds of millions of lives, and caused the most feared of deadly scourges. Historically,
Variola major
had an overall fatality rate of about 30 percent.
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Those who contracted smallpox suffered terribly. Jonathan Tucker, who has written extensively on smallpox, described it this way: “After a two-week incubation period, smallpox racked the body with high fever, headache, backache, and nausea, and then peppered the face, trunk, limbs, mouth and throat with hideous, pus-filled boils. Patients with the infection were in agony—their skin felt as if it was being consumed by fire, and although they were tormented by thirst, lesions in the mouth and throat made it excruciating to swallow.” For those who survived, the disease ran its course in two or three weeks. But it was highly transmissible, spread in the air by talking or sneezing, and remained contagious in clothing and bed linens. As recently as 1967, the disease sickened between 10 and 15 million people each year in forty-three countries and caused an estimated 2 million deaths.
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A long campaign to eradicate smallpox ended with the World Health Organization (WHO) declaration of success May 8, 1980. The WHO recommended the end of vaccinations worldwide. “The conquest of smallpox,” Tucker said, “the first—and so far, only—infectious disease to have been eradicated from nature by human effort, was among the greatest medical achievements of the twentieth century.”
Now, at Vector, Popov urged Sandakhchiev to consider smallpox for
reengineering in Project Factor, instead of re-creating SV40 or making artificial viruses. Why not invent something new out of smallpox? Smallpox was simple to grow, easily aerosolized, caused a disease with a high mortality and was stable in storage.
Popov did not at this point work directly on the dangerous smallpox virus, but used models with related viruses, such as
vaccinia
or
ectromelia
, mousepox. The models acted like a stand-in for the real thing. Popov recalled the institute was also coming under pressure from Moscow to produce results. It had been established almost ten years earlier and Sandakhchiev was being criticized for not producing more dramatic breakthroughs. “We were pushed very hard by the Central Committee to accelerate,” Popov recalled. “There were promises and big investments in the program, but no output. And that’s when Factor became a focus of my research.”
As he began trying to manipulate some microbes, Popov faced a serious difficulty. It was hard to get organisms to increase the amount of toxin they discharged. They could emit a small amount, but if he tried to make them more productive, there was an unexpected side effect: the microbe became less poisonous. The virulence of the organism would decline, instead of increasing. “If we made them good producers,” he said, “we often ended up with poor killers.” Through years of work, Popov searched for a solution.
His work eventually took him in a slightly different direction. Working with others, he found a way to set off a biological trigger, or switch, to deceive the body’s immune system. Normally, when there’s a disease, the body attacks it. But in this new concept, if the microbe is made to appear similar to the human body, the immune system would be triggered not only against the invader, but to attack the healthy person, to turn on itself. This made the genetically engineered organism a powerful killer—without having to produce more of the poison.
“The idea was to subvert the natural regulation of the human body and direct it against itself,” Popov explained to me. “All this would require only a biological switch, or signal, which the body is expected to follow.”
The body’s immune system could be fooled to attack the body itself.
There were different possible targets considered in the research, Popov said, but a decision was made to have the immune system turn
against the body’s nervous system. Thus, if developed into a real weapon, it would cause victims to suffer in two waves. The first might be smallpox. But then, perhaps after a period of recovery, the body would turn on its own nervous system, and the victims would be paralyzed and die. The second wave would be unexpected; no vaccine could stop the process. “As a weapon, the thing would be absolutely untreatable,” he said. “Absolutely untreatable, because first of all it may come as a surprise after the initial disease has gone away, the person may recover completely. And then the new wave of disease would be the death response …”
In 1985, Popov built what is known as the “construct” of his idea, a piece of DNA that would be inserted somewhere into a genome. It was only the start, but it was significant enough that Sandakhchiev no longer needed the earlier proposal to manufacture large quantities of artificial DNA. They could make the deadly agents with just small bits of genetic material. And it became clear that a whole new generation of agents for potential use in weapons was beckoning.
At Koltsovo, scientists like Popov broke through barriers of knowledge, but building actual weapons was the job of the military, which maintained its own separate laboratories. Vector was a research facility. The “customer” was the 15th Main Directorate of the Ministry of Defense. Periodically, the customer came to visit Vector, to check on progress. And there was finally something to tell them.
Secluded in the forests outside of Moscow, another scientist was fighting his own battle. While Vector sought to alter viruses, Igor Domaradsky attempted to reengineer the genetic makeup of bacteria into an unstoppable warrior. Domaradsky walked with a slight limp; he had suffered polio as a child, and tuberculosis and malaria as an adult. He had a reputation for being irritable, hard to contain, and he later called himself a troublemaker, an inconvenient man. He was always restless. He yearned for the rewards of scientific discovery but worked in service of weapons of death.
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In 1984, he was fifty-nine years old. During the week, he lived alone in Protvino, a small town one hundred miles south of Moscow. He drove through the mixed forests of birch and bogs each day to start work at a
secret laboratory. The location was called Obolensk, after ancient princes who once ruled the forests. He was fond of the drive, and often, in winter, came face-to-face with roaming elk. He remembered when Obolensk was carved out of the woods. At first, there were temporary “huts,” long, crude one-story barracks for researchers. By the early 1980s, the modern Korpus No. 1 rose out of the forest. Outwardly, it appeared to be another eight-story, boxy Soviet office building. But inside it was 400,417 square feet dedicated to the study and manipulation of dangerous pathogens. The third floor was devoted to especially hazardous materials. Massive airlocks and seals guarded against leaks.
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Obolensk itself was dark and marshy, and Domaradsky considered it a privilege to have his apartment ten miles to the south in Protvino, in the fresh air near the banks of the Oka River.
The laboratory at Obolensk was known as Post Office Box V-8724, one of dozens of closed Soviet cities and laboratories devoted to Cold War military work.
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Domaradsky worked in the laboratory during the week, living in his Protvino apartment, and drove two hours back to Moscow to see his family on weekends, sometimes lingering in the city on Monday. His wife, Svetlana Skvortsova, was a talented actress and teacher who thrived in Moscow’s rich cultural life. Domaradsky worked in lonesome isolation.
The enforced solitude caused him to ponder all that he had done. In the apartment, he began collecting papers and hiding notes of his life’s work, making illicit photocopies so the evidence of his achievements would not be destroyed by the secret services that watched over him.
On weekday mornings, Domaradsky switched on the radio in his apartment to listen to Radio Free Europe, the BBC and Deutsche Welle, the German broadcaster, which were easier to receive in the countryside than in the big cities. “Nobody bothered me, and I luxuriated in my freedom to listen to foreign radio, learning a great deal of news about the USSR and the world that was not available in Moscow.” He would then put on a record of his favorite music. Sometimes he went skiing, in the mornings or evenings after work, through a park and forest. Food shortages were common, but Domaradsky was permitted to shop at the small elite “Ryabinka” grocery store for directors of a nearby physics institute. While Soviet citizens were in lines for the basics, the store carried such rare commodities as instant coffee and caviar, delivering them to his door
and taking his order for the next delivery. He felt well off, but his science was difficult, and its goals, he knew, were dreadful.
Tularemia, commonly known as “rabbit fever,” is caused by a bacterium that is highly infectious. It is formally known as
Francisella tularensis
and is found in animals, especially rodents, rabbits and hares. In the early 1980s, the microbe became the object of Domaradsky’s research. He yearned to work on several other pathogens at the same time, but the Soviet bosses wanted results from tularemia. He was searching for a way to make tularemia into an agent that would infect people while resisting both antibiotics and vaccines. He was searching for an unstoppable supergerm.
In general, the Soviet military preferred to use contagious pathogens like the smallpox virus and plague because they could cause epidemics. The military would simply light the spark, and the disease would spread like wildfire on its own. Tularemia is not contagious, and thus cannot be passed from human to human. Yet the military retained interest in tularemia because it required as few as ten microorganisms inhaled or ingested to infect someone.
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Tularemia is also stable and easy to aerosolize; the microorganism can survive for weeks at low temperatures.
Unlike viruses, which are nothing more than a few genes and protein, with perhaps a membrane, bacteria live inside rigid outer walls. The wall is critical to the cell’s survival, giving it structure and support. Without it, the cell dies. In the 1930s and 1940s, antibiotics were developed that could attack bacteria; the first was penicillin. These drugs could slow or even kill the bacteria in several ways: weaken the cell wall, inhibit its growth or stop its replication. Antibiotics helped defeat infections that have threatened man through the centuries. Diseases such as rheumatic fever, syphilis and bacterial pneumonia became easily treatable. These miracle medicines held promise that some diseases could be wiped out. By the 1940s, there were dozens of antibiotics, but then came another twist: bacteria acquired resistance to them. Within a few years, many of the powerful wonder drugs were losing their efficacy. The remaining bacteria were no longer vulnerable to antibiotics, as a result of natural selection—those which were genetically able to resist the drugs had survived. Over time only the resistant bacteria remained, and the drugs lost their effectiveness.
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The goal of Domaradsky’s research was to build a new microbe that
would be resistant to many antibiotics. As an instrument of war, it would slice through helpless populations or armies like a scythe. According to Ken Alibek, who rose to become deputy director of the Soviet bioweapons program in the late 1980s, Domaradsky had once proposed to develop a strain of tularemia that would stand up against a whole spectrum of antibiotics, overcome vaccines and at the same time not lose its virulence. “The Soviet army wasn’t satisfied with weapons resistant to one type of antibiotic,” Alibek said. “The only worthwhile genetically altered weapon, for military strategists, was one that could resist all possible treatments.”
13
The generals wanted a strain that could resist up to ten different antibiotics at once, Alibek recalled. The proposal was audacious, complex and difficult to fulfill.