Putting Teeth in the Biological Weapons Ban Source: Technology Review Jonathan Tucker directs the chemical and biological
weapons nonproliferation project of the Center for Nonproliferation
Studies at the Monterey Institute of International Studies in
Monterey, Calif. In 1995 he served as an inspector on a UN Special
Commission team investigating biological weapons activity in Iraq,
including the suspected Al Hakam facility near Baghdad.
Pound for pound, disease-causing microbes such as
anthrax rival
nuclear weapons in their ability to inflict mass casualties. But the
intrusive inspection procedures needed to strengthen the treaty
banning biological weapons must not compromise the biotech industry's
valuable trade secrets. Links related to this article It took 20
years, but in April a treaty finally went into effect banning chemical
weapons. While the Chemical Weapons Convention is an important step
toward a safer world, it may have the undesired effect of encouraging
some countries to redouble their efforts to acquire biological
weapons -- disease-causing microbes and natural poisons such as
anthrax, pneumonic plague, and botulinum toxin. Biological weapons are
not only more potent than chemical weapons but they are easier to
produce in small, clandestine facilities.
A biological attack could create an almost unimaginable
catastrophe. According to an estimate by the U.S. Congress's former
Office of Technology Assessment, 100 kilograms of anthrax, released
from a low-flying aircraft over a large city on a clear, calm night,
could kill 13 million people. This figure is comparable to the
casualties from a one-megaton hydrogen bomb. When disseminated as an
aerosol, anthrax spores (analogous to microscopic seeds) are inhaled
deep into the victim's lungs and travel to the lymph nodes, where they
germinate and multiply. The bacteria then secrete potent toxins,
giving rise in about three days to a devastating illness. For the
victims to have any chance at all of surviving, antibiotics must be
administered intravenously before the onset of acute symptoms.
Because biological weapons are so potent yet much
cheaper and easier to produce than nuclear weapons, they have been
called "the poor man's atomic bomb." In addition to their potential
use as strategic weapons of mass destruction, biological agents are
well-suited for covert operations such as sabotage, terrorism,
counter-insurgency warfare, and assassinations.
The threat of biological warfare is not just an academic
concern. In October, the United Nations Special Commission (UNSCOM)
monitoring the elimination of Iraq's weapons of mass destruction
concluded that Iraq was still trying to conceal the full scale and
scope of its biological weapons program. Iraq acknowledged in 1995
that prior to the Gulf War,
it had produced large quantities of anthrax spores, botulinum toxin,
and a fungal poison called aflatoxin, filled them into at least 166
aerial bombs and Scud missile warheads, and stockpiled them ready for
use. Although Iraq claimed to have destroyed its biological arsenal
after the war, U.N. inspectors suspect that Iraq may still be hiding a
cache of anthrax spores and germ-filled warheads.
In November, Iraq barred U.S. experts from participating
in UNSCOM weapons inspection teams, apparently because the Americans
were hot on the trail of banned weapons activities. While the on-site
inspections were on hold, the Iraqis moved equipment and tampered with
surveillance cameras at ostensibly civilian facilities, such as
vaccine plants, that could potentially be used for producing
biological warfare agents as well. In a letter to the U.N. Security
Council, UNSCOM Executive Chairman Richard Butler warned that without
effective monitoring, the Iraqis could easily adapt laboratory or
industrial equipment in "a matter of hours" to produce stocks of
biological warfare agents.
Iraq is only the best-known example of several
countries -- among them China, Egypt, Iran, Iraq, Libya, North Korea,
Sudan, Syria, and Taiwan -- known or suspected to be pursuing a
biological warfare capability. The U.S. government also believes that
rogue elements within the Russian military may be continuing Soviet
programs to develop biological weapons, despite President Boris
Yeltsin's 1992 order that such activities cease.
Particularly alarming is the possibility that domestic
or international terrorist groups could acquire biological weapons and
use them against civilian targets. The Japanese cult Aum Shinrikyo,
which in 1995 carried out a deadly attack with a chemical nerve agent
on the Tokyo subway, was found to have an advanced microbiological
facility to produce anthrax and botulinum toxin. In 1993, cult members
repeatedly released anthrax spores from the roof of a high-rise
building in Tokyo in an attempt to inflict mass casualties.
Fortunately, technical problems with the delivery system rendered
these attacks ineffective.
In principle, production of biological weapons is
already banned by the Biological Weapons Convention (BWC), a treaty
that has been in force since 1975. But the BWC was born with a
crippling defect: it lacks a formal mechanism for investigating
alleged violations, and thus has come to be regarded as little more
than a gentleman's agreement. At the time the treaty was negotiated in
the early 1970s, verification procedures were considered unnecessary
because biological
weapons were believed to have little military value. Shortly after the
BWC took effect, however, the advent of recombinant-DNA technology
raised the specter of engineering new pathogens that might be more
controllable, lethal, or persistent, leading some defense analysts to
reassess their utility as warfare agents.
The coming year will provide an opportunity for progress
toward crafting an inspection regime to strengthen the BWC. A group of
member-countries, known as the Ad Hoc Group, will meet in Geneva for a
few weeks in January and then for three more negotiating sessions
later in the year. Their goal: to develop monitoring mechanisms to
check that member-countries are obeying the treaty's prohibitions.
This legally binding "compliance protocol" will specify how
international inspectors from a future BWC monitoring organization
will be allowed to enter and examine facilities suspected -- or merely
capable -- of producing biological warfare agents.
Possible elements of a compliance protocol include:
* requiring countries to declare the existence of all
relevant biological facilities.
* routine on-site visits to check the accuracy of such
declarations.
* occasional "challenge" inspections to pursue suspected
treaty violations at declared or undeclared facilities.
* field investigations to pursue allegations of
biological-weapons use and suspicious outbreaks of disease.
Whatever monitoring measures are agreed to will be
equally binding in all participating states. Operating under a kind of
"golden rule" for treaty negotiations, members of the Ad Hoc Group
must be prepared to accept the same types of intrusive monitoring they
wish to apply to others. Each nation must therefore find the right
balance between a regime that is intrusive enough to ensure that other
countries are following the rules and one that allows them to
safeguard sensitive industrial and national-security information. U.S.
pharmaceutical and biotechnology companies, for instance, have
expressed concern that intrusive inspections could open the door to
industrial espionage. Companies routinely invest millions of dollars
to develop and test new medications, production microorganisms, and
manufacturing processes. Any negotiated protocol must therefore
specify compliance measures that safeguard proprietary information.
While most of the countries in the Ad Hoc Group agree
that the compliance protocol should provide for short-notice
inspections of suspect facilities, they have been unable to reach
consensus on a mechanism for triggering them. Last summer, however,
the group took an important step forward by deciding to prepare a
draft treaty -- a "rolling text," in diplomatic parlance -- in which
non-agreed language is set off in brackets. Right now, the draft is
still full of brackets.
Contending with Ambiguity
The negotiators have their work cut out for them. The
equipment and facilities used to cultivate biological-warfare agents
are essentially the same as those used for the commercial production
of vaccines, antibiotics, vitamins, biopesticides, feed supplements --
even beer and yogurt. The spread of these "dual-capable" technologies
for industrial microbiology has given rise to a burgeoning global
potential for biological warfare, since countries can easily cloak
their acquisition of illicit agents under the guise of legitimate
research and production. Moreover, it takes only an extremely small
quantity of a microbial pathogen -- on the order of a few kilograms --
to produce a militarily effective weapon. A deadly arsenal could
therefore be made over a period of weeks, eliminating the need for
long-term stockpiling.
Cultivation of disease-causing microbes cannot be banned
outright because the same organisms that can kill thousands of people
also have legitimate medical and industrial uses. Pharmaceutical
companies, in particular, routinely grow large quantities of dangerous
pathogens for the production of vaccines. Similarly, potent toxins
such as ricin and botulinum play an increasingly important role in the
treatment of cancer and neurological diseases.
Recognizing these peaceful applications, the BWC
specifically prohibits the development and production of biological
and toxin agents only "in types and quantities that have no
justification for prophylactic, protective, or other peaceful
purposes." As a practical matter, however, it is difficult to
distinguish between offensive activities and benign ones. Merely
looking at a fermentation tank reveals little about its contents. Only
the analysis of an actual sample can tell which microbes are present,
and that will require on-site inspections of dual-capable facilities
such as vaccine plants.
Inspectors of a suspicious facility might take samples from various
steps in the production process, ranging from seed cultures to
finished products. Samples might also be swabbed from the surface of
production equipment, benches, walls, or floors, or collected from
soil, water, air, plants, and animals outside the buildings. These
samples would then be analyzed, using some combination of techniques
now common in the biotechnology industry and medical diagnostics.
Three sophisticated analytical methods are routinely
employed to identify disease-causing bacteria and viruses. In
classical bioassay, scientists cultivate a sample to grow live
microorganisms; these microbes can then be identified using a variety
of chemical or physiological tests. Immunoassay techniques employ
specific antibodies to detect unique molecular markers on the surface
of target microorganisms, as well as protein toxins. Genetic analysis
involves the use of "gene probes" -- short strands of synthetic DNA
that bind to complementary DNA sequences unique to each microbial
species.
Gene probes are often employed in conjunction with a
powerful technique called the polymerase chain reaction (PCR), which
multiplies a given DNA sequence more than a million-fold. With the aid
of PCR, scientists can identify a species of bacteria even if only a
few dozen cells are present in the sample -- avoiding the need to
culture them into large colonies over a period of days or weeks.
In some cases, sampling and analysis can yield
compelling evidence of illicit activities. When Japanese police raided
the Aum Shinrikyo cult's headquarters near Mount Fuji, they found an
advanced microbiology lab producing anthrax bacteria and botulinum
toxin, apparently intended for terror attacks.
Generally, however, the results of sampling and analysis
are less clear. Analytical techniques occasionally produce "false
positives" by appearing to recognize a biological-warfare agent that
isn't actually present. This problem may arise when the target DNA
sequence or molecular marker is present in both a pathogenic agent and
a harmless microorganism. To avoid false positives, inspectors should
confirm a positive result obtained by one analytical technique with
another method based on different scientific principles.
Samples may also be contaminated with pathogenic
microbes naturally present in the environment. Anthrax spores, for
example, are often found in sheep and cattle grazing areas in
concentrations of 100 to 500 spores per 100 grams of soil. These
levels, though well below the 10,000 or so spores that must be inhaled
to cause infection, are easily detectable with PCR. The pharmaceutical
industry therefore worries that anthrax spores naturally present in
the environment might be tracked into a vaccine plant on the bottom of
workers' shoes and detected by international inspectors -- raising
suspicion of a BWC violation where none is warranted and damaging a
firm's hard-won reputation. "The release of erroneous information
implying serious wrongdoing could cause irreparable harm to a
company's relationship with its shareholders and the general public,"
observes William Muth, a scientist at Lilly Research Laboratories in
Indianapolis
Thus in the absence of a "smoking gun," such as a rack
of bombs or warheads filled with biological agents, sampling and
analysis would not provide unequivocal proof of a treaty violation.
Detecting anthrax would not necessarily be incriminating, for example,
if the facility in question were culturing the agent for a legitimate
purpose, such as the production of a protective vaccine, or if anthrax
were endemic to
the surrounding region. Moreover, highly sensitive detection
technologies such as PCR could find minute traces of anthrax DNA,
while revealing little about the total amount of agent produced at the
site.
On the other side of the coin, since it is not possible
to sample everywhere, inspectors may fail to detect actual violations
of the BWC. Thus the inability to find an illicit biological-warfare
agent at a suspected facility does not necessarily mean that the plant
is treaty-compliant. A covert proliferator might exploit a series of
negative findings to claim a clean bill of health. Because of the
possibility of false positives or false negatives, evidence of BWC
violations obtained by sampling and analysis must be interpreted in
the light of other types of information.
Protecting Trade Secrets
The pharmaceutical industry worries that sampling and
analysis used during on-site inspections could jeopardize industrial
trade secrets. The chemical industry initially had similar
reservations about the intrusive inspections allowed by the Chemical
Weapons Convention. For example, inspection of a chemical plant might
reveal a proprietary manufacturing process that provides a small but
significant competitive edge, such as lowering production costs of a
commodity chemical by a few cents per ton. In the pharmaceutical and
biotech fields, however, the financial stakes are much higher. Because
drug development is so research-intensive, it costs a large
pharmaceutical house between $350 million and $500 million to bring a
new product to
market. According to the Pharmaceutical Research and Manufacturers of
America, an industry trade association based in Washington, U.S.
pharmaceutical manufacturers spend 19.4 percent of sales on R&D,
compared to an average across all industries of 3.8 percent. U.S. drug
companies also lead the world in innovation, accounting for 36 percent
of global pharmaceutical research and development.
Biotechnology-based medicines represent a major growth
sector for the U.S. pharmaceutical industry. In 1995, U.S. firms and
organizations were responsible for about 80 percent of patents for
genetically engineered health-care and pharmaceutical products issued
by the U.S. Patent Office. From 1989 to 1996, the number of
biopharmaceuticals being developed by U.S. companies to treat diseases
ranging from the common cold to cancer soared from 80 to 284. Over the
same period, the number of U.S. companies developing new-generation
biotechnology drugs more than doubled, from 45 to 113.
Biotech companies fear that foreign inspectors visiting
their plants could gain insight into their production techniques or
even obtain a covert sample of a genetically engineered microorganism,
whose proprietary DNA sequences could then be determined. Such
information can be worth vast sums. For example, the genetically
engineered bacterium that produces human insulin is valued at more
than $1 billion, according to Lilly's Muth. With such huge investments
at stake, the U.S. pharmaceutical industry is determined to protect
its confidential proprietary information.
Most pharmaceutical industry representatives endorse the
concept of "managed access," an approach developed for on-site
inspections under the Chemical Weapons Convention. In this procedure,
the inspection team and the host country negotiate the amount of
access to be provided to sensitive areas of the inspected site. For
example, facility managers might turn off computers, lock up
documents, place cloth shrouds over items of production equipment
considered proprietary, and specify where and when samples may be
taken. In return for such limits on access, the inspected party must
make "every reasonable effort" to provide alternative means of
addressing the inspectors' compliance concerns. For example, the
inspectors might ask the facility representative to lift the shroud
covering a piece of equipment high enough to confirm that illegal
materials are not hidden underneath, or to review the plant's
production records. Failure to cooperate with such requests might lead
the inspectors to suspect the facility of concealing illicit
activities.
Some arms-control analysts doubt that managed access
will be effective in catching BWC violators because it assumes a large
degree of good faith and cooperation on the part of the inspected
party. "Managed-access negotiations could create delays that, unless
overcome by technology or diplomacy, might allow proliferators to
dispose of incriminating evidence," contends Michael Moodie, president
of the Chemical and Biological Arms Control Institute in Alexandria,
Va. For example, a violator might use the managed-access negotiation
as a
pretext to stall the inspection long enough to eliminate most if not
all traces of illicit biological agent production. Auditing of
production records, critics say, would not resolve compliance concerns
because such records can be falsified.
Critics of managed access have suggested alternatives
that would protect corporate proprietary information while also
increasing the likelihood of detecting illicit production. The
inspected facility might, for example, provide escorts for the
inspectors to keep them from touching equipment and taking covert
samples. In addition, inspectors could be required to remove their
street clothes and don
disposable coveralls, booties, head coverings, and surgical masks, all
of which would be destroyed after use. The inspectors would also
shower after each inspection to make sure they do not remove
proprietary microorganisms on their skin. Finally, the inspected
facility would have the right to demand the removal of any inspector
caught taking unauthorized samples.
As a further means of safeguarding proprietary
production microorganisms, the Federation of American Scientists
Working Group on Biological and Toxin Weapons Verification has
proposed that personnel at an inspected facility could inactivate
sampled microbes by heating them, and then partially digest the
microbial genes with a special "restriction enzyme" to disrupt any
confidential DNA sequences. Only then would the inspectors be allowed
to verify the identity of the microbe or to screen for a list of
biological-warfare agents with gene
probes and immunoassays. In principle, the restriction enzyme would
destroy proprietary information but leave enough characteristic DNA
sequences to verify the identity of an illicit agent. This approach
will need to be validated, however, both in the laboratory and in the
field.
A number of government and commercial organizations are
developing chip-based sensors containing an array of gene probes for
detecting microbial pathogens and toxins of biological-warfare
concern. Such devices might eventually be cheap enough to discard
after use, like a disposable pregnancy-test kit. This approach would
reassure the
pharmaceutical industry, which fears that reusable analytical
instruments accompanying an inspection team could, deliberately or
inadvertently, remove samples containing proprietary microorganisms
In crafting a set of on-site measures for monitoring BWC
compliance, the Ad Hoc Group will need to balance costs and benefits.
While technical and political constraints may circumscribe the use of
sampling and analysis during on-site inspections, the mere possibility
of sampling could deter potential violators by making illicit
production more risky and expensive and by necessitating aggressive
cleanup measures that would themselves arouse suspicion. At the same
time, devising approaches to sampling and analysis that can safeguard
legitimate industrial or national-security secrets remains a major
challenge. Over the next few years, however, the development of
accurate but inexpensive biosensors for the identification of
microbial and toxin agents may make it easier for the Ad Hoc Group to
find an acceptable tradeoff between these competing objectives.
The biotech and pharmaceutical industries have a huge
stake in the outcome. So far, companies have mainly played the
spoiler, complaining that proposed verification methods would intrude
on their proprietary rights. They need to become more constructively
involved. The biological weapons threat to international security has
made it imperative to institute verification measures that will
fortify the BWC, converting it from a gentleman's agreement into
enforceable international law. Companies that have the most to gain
from biotech innovation -- and the most to lose from unwanted
disclosure of their trade secrets -- need to help find suitable ways
to allow international inspections of their production facilities
without
compromising the economic health of a leading U.S. industry.
SIDEBAR:
How Countries Might Cheat
Determined violators of the BWC may seek to evade any
monitoring regime that is put in place. A violator might, for example,
attempt to modify DNA sequences or protein structures, disguising
germ-warfare agents as benign organisms. Alternatively, plant
operators could attempt to clean up a biological-warfare agent
production facility after receiving notice of an on-site inspection.
The first evasion technique -- using genetic engineering
to disguise germ-warfare agents -- is unlikely to work. Such efforts
would demand a great deal of expertise and effort, and might interfere
with the microbial agent's viability or ability to cause disease.
Inspectors could also foil such evasive maneuvers with fairly simple
countermeasures, such as devising batteries of assays directed at
multiple DNA sequences or molecular markers characteristic of a given
pathogen. Even though inspectors would employ only a few of these
tests at a given facility, the potential violator would be unaware of
which tests would be chosen and hence would have to counter all of
them to ensure successful evasion -- a daunting task.
The cleanup route has a better chance of success. With
sufficient notice, the plant operators could disassemble biological
production equipment, clean it with bleach, and then grow a new
culture of non-forbidden microorganisms in the same equipment.
In practice, however, cleaning is not always complete,
particularly if the process is rushed. The shorter the notification
period for an on-site challenge inspection, the greater the
probability that a violator will make a mistake and leave behind
traces of illicit production. Indeed, molecules of microbial DNA are
robust and may survive autoclaving (prolonged heating with pressurized
steam, the standard method for sterilizing equipment). Thus while the
incriminating microbes themselves would be destroyed, telltale DNA
fragments would be left behind.
Experience with Iraq provides some confidence that
sampling and analysis can uncover germ-warfare activity even if a
country is determined to hide its activities. In the wake of the Gulf
War, the UN Special Commission (UNSCOM) learned of a large
fermentation plant called Al Hakam, situated at a barren desert
location some 80 kilometers southwest of Baghdad. Iraq claimed that
the facility was engaged in the legitimate production of two
commercial products: single-cell protein as a supplement for animal
feed, and a microbial insecticide known as Bacillus thuringiensis
(BT).
BT bacteria normally contain tiny crystals of a protein
toxin that kills insects. Yet when UNSCOM weapons inspectors took
samples of BT at the facility in December 1994 and examined them under
an electron microscope, the crystals were absent, indicating that the
bacteria lacked insecticidal activity. Moreover, the BT product that
emerged from the production line was a dry powder that was too fine
for agricultural use but was in the ideal form for dispersing a
biological warfare agent. These findings suggested that Iraq's
cultivation of BT may have been intended as a clandestine training
exercise for the production of anthrax bacteria, which grow under
similar culture conditions and can be induced to form rugged spores.
On the basis of this and other evidence, UNSCOM razed the Al Hakam
facility in June 1996.
In recent years, UNSCOM weapons inspection teams have
used medical swabs to collect material from equipment and other
surfaces for laboratory analysis. Since Iraq is well aware of the
power of these techniques, it is possible that one reason Baghdad
moved in November to bar U.S. inspectors from UNSCOM inspection teams
was a growing concern over the effectiveness of sampling and analysis.
According to journalist Richard Preston, author of The Hot Zone, a
biological weapons inspector told him that the Iraqi "minders," or
escorts, "clump up in a group and get real agitated whenever we whip
out our swabs."
by Jonathan B. Tucker
http://www.techreview.com/articles/jf98/tucker.html
Disease
Biological-
Warfare Agent
Incubation Period
Main Symptoms
Fatality Rate (untreated)
Contagiousness
Previous Use as Weapon
Anthrax
(pulmonary)Bacillus anthracis (bacterial
spore)
High fever, labored breathing, rapid
pulse, shock
Possible covert use during the Rhodesian
civil war (1978-80)
Botulism
Botulinum toxin, produced by
Clostridium botulinum (bacterium)
Fatigue, nausea, headache, cramps,
giddiness, respiratory paralysis
Before the 1991 Gulf War, Iraq filled
botulinum toxin into bombs
and warheads
Encephalitis, Venezualan equine
VEE virus
Infection of central nervous system
None known
Plague,
pneumonicYersinia pestis (bacterium)
Infection of lungs, fever, headache,
pneumonia, hemorrhages, heart
failure
During World War II, Japan dropped bombs
containing plague-infested
fleas on Chinese towns
Ricin
intoxicationToxin extracted from the seeds of the
castor bean plant, Ricinus communis
Ingestion causes nausea, vomiting, bloody
diarrhea, stupor, convulsions,
shock, and liver and kidney damage
In 1978, the Bulgarian Secret Service used
ricin to assassinate
a dissident living in London
Smallpox
Variola virus (eradicated except for
laboratory specimens in U.S.
and Russia)
Headache, chills, fever, lesions of skin
and mucous membranes
In 1763, British forces at Fort Pitt (Pa.)
gave contaminated blankets
to rebellious Indians