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FEATURE STORY 49
Peptides, such as beta-endorphins, are the constituent
parts of proteins and are no longer than 50 amino acids.
Nature exploits their compactness in contexts where cell
signaling takes place often and rapidly---for instance, in the
central ner vous system, where peptides serve as neurotrans-
mitters. With 10 to 20 times fewer amino acids than an
average protein, peptides are produced by correspondingly
smaller DNA sequences, which made them good candidates
for synthesis using Biopreparat s limited means. Popov set
a research team to splicing synthetic endorphin-expressing
genes into various viruses, then infecting test animals.
Yet the animals were una ected. "We had huge pressure
to produce these more lethal weapons," Popov said. "I was
in charge of new projects. Often, it was my responsibility
to develop the project, and if I couldn t, that would be my
problem. I couldn t say, No, I won t do it. Because, then, what
about your children? What about your family?" To appease
their military bosses, Popov and his researchers shifted to
peptides other than beta-endorphins and discovered that,
indeed, microbes bearing genes that expressed myelin pro-
tein could provoke animals immune systems to attack their
own ner vous systems. While the Vector team used this tech-
nique to increase the vir ulence of vaccinia, with the ultimate
goal of applying it to smallpox, Popov was sent to Obolensk
to develop the same approach with bacteria. Still, he told me,
"We now know that if we d continued the original approach
with beta-endorphins, we would have seen their e ect."
This vision of subtle bioweapons that modi ed behav-
ior by targeting the ner vous system---inducing e ects like
temporary schizophrenia, memory loss, heightened aggres-
sion, immobilizing depression, or fear---was ir resistibly
attractive to Biopreparat s senior military scientists. After
Popov s defection, the research continued. In 1993 and
1994, two papers, copublished in Russian science jour-
nals by Ashmarin and some of Popov s former colleagues,
described experiments in which vaccines of recombinant
tularemia successfully produced beta-endorphins in test
animals and thereby increased their thresholds of pain sen-
sitivity. These apparently small claims amount to a proof of
concept: bioweapons can be created that target the central
ner vous system, changing perception and behavior.
I asked Popov whether bioweaponeers could design
pathogens that induced the type of e ects usually associ-
ated with psychopharmaceuticals.
"Essentially, a pathogen is only a vehicle," Popov replied.
"Those vehicles are available---a huge number of pathogens
you could use for di erent jobs. If the drug is a peptide like
endorphin, that s simple. If you re talking about triggering the
release of serotonin and dopamine---absolutely possible. To
cause amnesia, schizophrenia---yes, it s theoretically possible
with pathogens. If you talk about paci cation of a subject popu-
lation---yes, it s possible. The beta-endorphin was proposed as
potentially a paci cation agent. For more complex chemicals,
you d need the whole biological pathways that produce them.
Constr ucting those would be enormously di cult. But any
drug stimulates speci c receptors, and that is doable in dif-
ferent ways. So instead of producing the dr ug, you induce the
consequences. Pathogens could do that, in principle."
Psychotropic recombinant pathogens may sound science
ctional, but sober biologists support Popov s analysis. Har-
vard University professor of molecular biology Matthew
Meselson is, with Frank Stahl, responsible for the historic
Meselson-Stahl experiment of 1957, which proved that DNA
replicated semiconservatively, as Watson and Crick had
proposed. Meselson has devoted much e ort to preventing
biological and chemical weapons. In 2001, warning that
biotechnology s advance was transforming the possibilities
of bioweaponeering, he wrote in the New York Review of
Books, "As our ability to modify life processes continues its
rapid advance, we will not only be able to devise additional
ways to destroy life but will also become able to manipulate
it---including the fundamental biological processes of cogni-
tion, development, reproduction, and inheritance."
I asked Meselson if he still stood by this. "Yes," he said.
After telling him of Popov s accounts of Russian e orts to
engineer neuromodulating pathogens, I said I was dubious
that biological weapons could achieve such speci c e ects.
"Why?" Meselson bluntly asked. He didn t believe such
agents had been created yet---but they were possible.
No one knows when such hypothetical weapons will
be real. But since Popov left Russia, the range and power
of biotechnological tools for manipulating genetic control
circuits have grown. A burgeoning revolution in "targeting
speci city" (targeting is the process of engineering molecules
to recognize and bind to particular types of cells) is creating
new opportunities in pharmaceuticals; simultaneously, it is
advancing the prospects for chemical and biological weap-
ons. Current research is investigating agents that target the
distinct biochemical pathways in the central nervous system
and that could render people sedate, calm, or other wise
incapacitated. All that targeting speci city could, in princi-
ple, also be applied to biological weapons.
The disturbing scope of the resulting possibilities was
alluded to by George Poste, for mer chief scientist at Smith-
Kline Beecham and the sometime chairman of a task force on
bioterrorism at the U.S. Defense Department, in a speech he
gave to the National Academies and the Center for Strategic
and International Studies in Washington, DC, in January
2003. According to the transcript of the speech, Poste recalled
that at a recent biotech conference he had attended a presen-
tation on agents that augment memory: "A series of aged rats
were paraded with augmented memory functions.... And
some very elegant structural chemistry was placed onto the
board.... Then with the most casual wave of the hand the
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