Developments 1996 to
2001
From 1996 there was increasing concern in Washington about
weapons of mass destruction in the aftermath of the Gulf War and disclosures by
Saddam Hussein’s son-in-law and with better understanding of the scope of the
former Soviet Union’s offensive biological weapons programs. The threat of
further proliferation of weapons, technologies and skilled personnel from the
former Soviet Union was a particular worry.
To this point, Agriculture
and the food supply system had been omitted from what national planning had
taken place to protect critical U.S. infrastructures against deliberate
attack. The general perception in USDA was that there was no difference
between a natural outbreak of a disease like FMD, for example, and one caused
deliberately. And since USDA had apparently been prepared for over 100
years to respond to FMD, the Department felt that it did not need to do anything
new to prepare for deliberate attack – or encourage other agencies, such as the
FBI, to encroach on USDA turf. In fact, President Clinton, in a series of
Presidential Policy Directives, had already declared that deliberate attacks
were different – they were either crimes or acts of war – and that other
agencies would then take the lead, specifically the FBI at home and the State
Department overseas. Other entities, such as the Defense Department and
the Intelligence Community, were also given key roles. But USDA as a whole
was not a participant in counter-terrorism programs or planning.
Because ARS had been involved from the very beginnings of modern
biological weapons concerns in the late 1980s, we were the most knowledgeable
agency in USDA on these issues. Therefore, from 1996, ARS stimulated
internal USDA discussion and provided position papers and information about the
broader field of unconventional weapons threats. This effort culminated in
Secretary Glickman establishing a formal USDA Biosecurity Committee (chaired by
Floyd Horn) in 1999. Our efforts to educate other government agencies
about threats to agriculture and food also persuaded the National Security
Council (NSC) that agriculture and the food supply system were critical
infrastructures that should become part of core counter-terrorism planning and
preparedness – a NSC subcommittee was formed for this purpose in 1999.
Formal Intelligence Community assessments of foreign biological weapons programs
targeting agriculture were also made available.
In 1998, ARS sponsored
the first U.S. conference on food and agricultural security. The
proceedings of this conference were later published (1). Subsequently, ARS
sponsored an October 2000 conference on Agricultural Bioterrorism at the Banbury
Center, Cold Spring Harbor NY and initiated a 2001 National Academies of Science
study of biological weapons threats to agriculture and the food supply.
The products of these are well worth studying – if only to appreciate how little
has been done to protect agriculture and the food supply system over the past 6
years.
Of course, ARS and other USDA agencies requested funds from the
Congress to address the terrorism threat. After considerable advocacy,
these were regularly included in the President’s budget proposals but were not
supported by Congress, except for a $500,000 addition in FY 2001. However,
some resources – such as a skilled scientific cadre and specialized biological
safety level 3 and 4 (BSL 3 and 4) facilities – cannot be quickly provided in an
emergency, even if funds are immediately available. ARS devoted
considerable discretionary resources to establish state-of-the-art genomics and
functional genomics capabilities for foreign animal diseases and their livestock
hosts so as to maximize productivity and resources of the scientists we already
employed. In addition, vigorous efforts were made to replace the BSL 3
facilities at Plum Island NY, Athens GA, and Ames, IA, and to provide the first
BSL 4 facilities for livestock at Plum Island. We came very close – but
suffice it to say that after 6 years of effort there are no modern BSL 3
facilities for agriculture and the nation still has no BSL 4 facility in which
to prepare for such dangerous livestock infections as Hendra and Nipah viruses
and their cousins yet unknown. The recent investment of over $1 billion in
a national system of BSL 4 labs for human disease threats does not provide any
capability to study these infections in livestock species. Thanks in large
part to the action and leadership of USAHA, there is to be a new BSL 3 facility
at Ames, but it will be decades before agriculture has all the specialized
facilities it needs.
Without new funds, it was impossible to establish
unconventional weapons defense programs of the necessary size and scope, but
existing investments were sharpened and additional funds obtained from external
sources. For example, we partnered with the State Department on very
important activities to prevent further spread of dangerous weapons technologies
from the former Soviet Union and with other government agencies on pathogen
detection to prepare for attack at home.
Since 1998, ARS has conducted
beneficial civilian agricultural research in cooperation with scientists and
institutes once engaged in biological weapons research and development in the
former Soviet Union. Work is underway in Russia, Kazakhstan and Uzbekistan
and is supported by some $6 million/year from the State Department.
Establishing strong open institutions in the newly-independent states prevents
scientists, materials and weapons-related knowledge leaking to other countries
and brings these scientists into the world community where they can make useful
contributions in both the national and international arenas. One
cooperative venture – between PIADC and the former weapons laboratory and test
site at Otar, Kazakhstan - has been exceptionally valuable in international
understanding of human and livestock pox viral diseases.
Pathogen Detection
Bacillus anthracis
was studied as an offensive biological weapon by several countries because the
natural properties of the organism make it highly-suitable for such use.
The organism forms a spore that is highly-resistant to degradation by heat and
the forces of an explosive delivery, the spore is optimally sized to penetrate
into the human lung, and the growing bacterium produces a series of toxins that
produce irreversible lung injury by the time illness first becomes
apparent. Pulmonary anthrax as the disease we have known is terrible
enough: fortunately, it is rarely seen naturally because humans are very
infrequently exposed to aerosols of spores.
Under the terms of the 1975
Biological Weapons and Toxins Convention, offensive biological weapons programs
are illegal. Defensive programs – development of vaccines, diagnostics and
other countermeasures - are fully acceptable. Scientists of the Former
Soviet Union, and perhaps other countries, were engaged in offensive activities,
such as studies of how to prepare fine powders of microorganisms that could be
dispersed over wide areas by missiles or artillery shells and how to modify the
properties of the microorganisms to defeat defensive countermeasures – to
overcome vaccination, confuse diagnosis, or create novel patterns of
injury. An advanced biological weapon is one whose biological properties
have been modified by genetic engineering or other means to defeat
countermeasures. As an example, Soviet scientists added a novel toxin gene
(from another microorganism) to Bacillus anthracis in an attempt to defeat the
U.S. vaccine. There are thus two challenges for detection of biological
weapons: 1. to detect the known pathogen, and 2. to detect an advanced pathogen
that has been modified genetically (and to understand the nature of the
modification for Biodefense). We seek to defend ourselves against known
disease agents and to anticipate and defend against technological surprise
through advanced biological weapons with unexpected properties.
Four of
the 10 pathogens listed in Table 1 are zoonotic: VEE, RVF, Newcastle disease and
avian influenza. VEE was developed as an advanced biological weapon to
target military personnel by the Soviet Union – for delivery as an aerosol with
a disease pathogenesis quite different from that of VEE as a mosquito-borne
infection. Newcastle disease – primarily a poultry disease of no
clinical significance for public health - produces conjunctivitis in humans –
not a fatal disease but certainly a force-incapacitating infection for the
pilots of an aircraft carrier. There were thus commonalities between ARS
and agencies charged with human health protection in detection of basic and
advanced biological weapons agents. ARS thus cooperated with other U.S.
government agencies to develop standardized means to detect potential biological
weapons agents, including advanced biological weapons based on the organisms in
Table 1. Initially, detection focused on samples of soil, water and air
because the goal was a standard platform and assay system for military force
protection on the battlefield. Later, this goal expanded to samples from
humans and animals under circumstances that might lead to a clinical
intervention.
In February 2000, a joint workshop was held between ARS,
the FBI and the Department of Health and Human Services (HHS) in Beltsville
MD. Over 30 universities and companies demonstrated detection technologies
at this workshop. An expert inter-agency group assessed these and
determined that two portable devices for real time PCR analysis were immediately
deployable. Other government agencies had come to the same conclusion
after independent assessments, so ARS implemented a program to develop real time
PCR tests to be deployed on these devices for the most important foreign animal
and plant disease threats as part of a systematic government activity. ARS
deliberately chose to use devices and test technologies common to other federal
agencies involved in national security, law enforcement and public health so
that agriculture and the food supply system could take full advantage of tests
developed by these other agencies and vice versa.
As explained above,
several government agencies were interested customers for this new technology –
they needed it for comprehensive detection of biological weapons agents in soil,
water and air, and for investigation of potential crime scenes at home and
abroad. But only APHIS (or HHS) might need this technology to detect
pathogens in order to diagnose the cause of a disease state in animals, plants
(or humans). The APHIS Administrator’s office – the contact point for
biological weapons defense issues – encouraged the ARS detection
initiative. However, APHIS Veterinary Services did not support development
of new technologies - the policy was that the first diagnosis of a foreign
animal disease would be made by growth and identification of the organism
responsible by traditional means at Plum Island under BSL 3 conditions and then
subsequent diagnoses would be based on clinical signs or proximity to a known
infected herd or flock. APHIS Veterinary Services opposed transfer
of new rapid detection technology to the states. ARS had no position on
APHIS use or non-use of the new technologies, which were primarily directed at
other federal customers.
In 2000, ARS scientists developed
state-of-the-art PCR tests to detect FMD, classical swine fever, African swine
fever, Rinderpest, avian influenza, and Newcastle disease (to complement tests
for other pathogens in Table I prepared by other federal agencies). By
state-of-the-art we mean that the PCR target for the assay is based on extensive
knowledge of genomic variation to be expected in the pathogen; that the PCR
assay distinguishes the pathogen from its near and distant relatives (whether
pathogenic or not); and that the test can definably find the pathogen in
clinical samples from experimentally infected animals of various target host
species at various times before and after clinical disease is apparent.
These tests have not yet been validated or deployed by APHIS. None of the
tests deployed by the Department of Defense or the Department of Health and
Human Services have yet been validated by either Department to meet Food and
Drug Administration requirements for human clinical use – nevertheless they have
been deployed nationally and internationally for years to protect the war
fighter and public while validation is being pursued.
These PCR assays
were designed to be performed as real time assays outside BSL 3 containment
either in a laboratory or on portable devices taken to the site of the
problem. For the latter purpose, there are three machines now available:
the RAPID and RAZOR from Idaho Technology Inc. and the Smartcycler from Cepheid
Inc. In time, there will be other devices that are cheaper, faster and
more robust. But all will share the same characteristics. Assays
will be performed by persons of limited training (soldiers, technicians); assays
will be performed using quality-controlled standardized reagents and protocols
that are internationally consistent; results will be obtained in an hour or
less; assays will be reviewed over the Internet as they take place by technical
experts located at distant sites; and detection results will flow into an
Internet-based Command and Control system that will translate vast amounts of
information from the field into current insight for those federal, state and
local officials charged with responding to the event. To permit this, the
detectors are connected by wireless to the Internet and contain a global
positioning device to allow geographic information systems to be overlaid.
With the ARS test, about 10 particles of FMD virus can be found in a
saliva swab from an infected cow within about 90 minutes of arriving at the
farm: about 1000 particles are needed to establish an infection in cell culture
because not all particles are infectious. The ARS test is more sensitive
than the so-called “gold standard” of cell culture and more accurate in that it
detects all FMD virus serotypes and subtypes, including those that may have
unusual host cell tropisms (such as Type O1 Taiwan). The latter is an
important characteristic in advanced biological weapons defense. Most
importantly, the ARS test is a pre-clinical test in that it detects infected
cattle, swine and small ruminants before clinical signs of disease are
apparent. (The ARS classical swine fever PCR test is also a pre-clinical
test.)
In recent years, much has been written about the need for rapid
tests. But very few have asked the question: What could one do differently
with a rapid test that one can’t do now by taking samples from the site of the
problem to a diagnostic laboratory? ARS developed this generation of tests
primarily for other government agencies charged with countering terrorism and
biological weapons. These agencies have long deployed these portable
devices on the battlefield, around military assets, or at high-value targets to
acquire real time analytical results to protect military personnel or political
leaders. In such circumstances, a positive test causes personnel in the
area to don protective clothing and respiratory devices immediately and to
remain protected until the pathogen has been inactivated or they have left the
area. The act of detection is immediately followed by a time-sensitive
action to protect those at risk and to minimize or frustrate the impact of the
attack. There is no time to take samples from the site of collection to a
state or federal laboratory – time is the precious commodity if catastrophe is
to be avoided.
Thus far, agricultural agencies in the U.S. and abroad
have not deployed rapid detection – or indeed any other modern technologies – to
counter foreign animal disease outbreaks. Other than use of the telephone,
control measures still closely follow those introduced by Cardinal Lancisi
almost 300 years ago. Provided with a portable state-of-the-art device
that can detect FMD and other viruses on farm within minutes, USDA has
reluctantly deployed a handful of machines to fixed sites in a dozen state
diagnostic laboratories. Given the size of the U.S., this does not add
significant new capability. To put this deployment in perspective, the
distance between the state diagnostic laboratory in Pullman WA and the dairy
industry in Puget Sound is about 300 miles – the same distance as between London
and Paris. Putting a fixed FMD detection machine in Pullman is like
providing Great Britain with rapid detection capability by placing a machine in
Paris, France.
On-site detectors should transform disease
surveillance and control, not echo history over smaller geographies. In
our view, a federal or state official equipped with an Internet-linked detection
device should be on the site of any suspected foreign animal disease outbreak in
the U.S. within 4 hours or less of notification so that vigorous informed
control measures backed by positive diagnosis can be implemented nationally
within 6 hours. Once the presence of FMD is confirmed, as part of an
Internet-based Command and Control system, continuous real-time surveillance
must be employed to define the extent of the problem around the initial
detection and to predict and track the progress of infection through the
national agricultural commerce streams. And to prevent natural
introduction, real time surveillance must also be extended to all commercial
flows entering the U.S. This cannot be achieved by taking samples to a
central laboratory.
Invention of portable, real time PCR machines
fundamentally changed who can make a state-of-the-art detection, where that
detection takes place, and who controls the information subsequently.
These are the reasons why general field deployment has been delayed. Until
now, detection of foreign animal disease pathogens involved growing live agents
in highly-specialized biocontainment laboratories that are exclusively
controlled by governments around the world. Detection could not be
de-centralized for biological safety reasons. Detection thus became a
cottage industry employing a handful of specialists in each country. All
this has changed. Everyday, scores of U.S. soldiers all over the world
conduct routine PCR tests for a wide range of highly-dangerous biological
weapons agents according to standard methodologies, on uniform devices and with
quality-controlled standardized reagents. In the U.S., the Centers for
Disease Control and Prevention have established a nationwide network of hundreds
of labs following common protocols for detection of human biological weapons
agents. We look forward to the day when the foreign animal disease threats
are detected in the U.S., the rest of North America and overseas using standard
methodologies and devices and the same quality-controlled reagents. In the
U.S., this will involve as many personnel as are needed to be on-site in 4 hours
or less.
Events of 2001 and
2002
Foot and mouth disease In February 2001, FMD was discovered
in Great Britain and quickly spread to become a nationwide epidemic that reached
other countries of the European Union. There was great concern that
infection might be brought to the U.S. ARS immediately demonstrated its
real time PCR tests: over the Internet, USDA officials in Washington DC followed
real time assays (on samples containing live viruses) in progress at PIADC (for
FMD) and Athens GA (for Newcastle disease): they were able to speak directly to
the scientists conducting the tests and to ask questions about the results as
these were acquired. Officials also watched tests underway in USDA
headquarters.
ARS immediately offered the real time PCR test to British
veterinary authorities and later demonstrated it directly in Britain. The
test was declined, although at the time and subsequently there were many pleas
by authorities in that country for a rapid, “pen-side” test.
British
authorities cited lack of a differential test as a critical reason why vaccine
could not be used. Such a test had been described by ARS and APHIS in 1994
and was available from a commercial source in the U.S. and had been since
1999.
Although the necessary tests were available in 2001,
authorities in Great Britain and the U.S. chose not to use them. What
should concern U.S. livestock owners (and perhaps British farmers) more is that
in 2004 these tests are still not deployed for their protection – while
government money is being wasted to duplicate discoveries already transferred to
the private sector.
Anthrax In September and October 2001, Washington DC
was paralyzed by postal anthrax attacks. Federal agencies and businesses
were plagued by reports of suspicious white powders. Mail room workers
were very worried about potential exposure to anthrax spores in their
workplaces. The sheer number of samples overwhelmed response
capacity.
To meet this challenge, ARS deployed a mobile laboratory
equipped with two real time PCR machines to central Washington DC. Because
we had chosen to develop detection platforms common to other federal agencies,
we were able to use commercially available anthrax test reagents developed by
the Department of Defense. Suspicious white powders could be examined
within minutes and accurate information provided to those who feared
exposure. At the end of each work day, technicians took dust swabs from
federal mail rooms all over the Capital and used a military air sampler to
capture air-borne dust. The next morning, before work started, mail room
employees were informed of the results of tests performed overnight on their
workplaces. They did not have to wait several days to a week to know if
they might have been exposed. The response to the anthrax attacks
demonstrated the value of real time, on-site testing and the value of time
gained compared to sending samples to a distant laboratory.
Newcastle
disease In fall 2002, Newcastle disease broke out in the Southwestern U.S.
USDA again chose not to deploy the real time PCR test developed and demonstrated
2 years earlier by ARS scientists in Athens, GA. The stated reason was
that this test had not been validated by APHIS – lack of APHIS validation had
also been cited as a reason not to deploy the FMD test in 2001. In fact,
in February 2001, APHIS had never validated any of the PCR tests it had long
employed for detection of foreign animal disease agents, had never licensed any
PCR test for any animal disease in the U.S., and had no protocols for how
validation should be conducted.
Some weeks after the State of California
developed and deployed its own real time PCR test for Newcastle disease, APHIS
allowed states to use the ARS test without validation. But much critical
time had been lost.
Conclusions
Rinderpest virus and the
disease it causes in cattle have probably changed very little since Cardinal
Lancisi set out his plan to stem the epidemic in Europe almost 300 years
ago. But commercial agriculture – especially in the U.S. – and public
opinion have changed enormously. And the costs of traditional epidemic
control measures are in fact the very factor that makes these diseases
attractive as weapons – if FMD did not have a multibillion dollar potential
economic impact it would not be a realistic threat. The control tactics of
the past are no longer appropriate and may even encourage attack. Over the
past 15 years, we have provided new tools and technologies to meet today’s
needs, including measures to counter deliberate attack. We believe it is
long past time for a radical overhaul of U.S. plans to combat foreign animal
disease introductions – accidental or deliberate. This must start with
recognition of the fact that it is not the choice of the U.S. as to whether
there is or is not an accidental or deliberate outbreak. That is not under
our control and never will be. What is under our control is what happens
before and after the outbreak is detected – and this depends in turn on our
degree of preparedness. In the long term, the U.S. will mobilize as many
thousands of people and spend as much as is necessary to control and eliminate
the infection. But to deter, prevent, minimize, thwart and frustrate
attack, what matters most is what we do in the short term – before attack and in
the first hours, days and even weeks after disease is detected. Time is
the critical element – the more time, the more options and the more likely that
these options will be attractive.
A coordinated national defense should
be built upon the following: