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OCR for page 67
4
Analysis and Conclusions
about Three Approaches for
Providing US Infrastructure to
Counter Foreign Animal Disease
and Zoonotic Disease Threats
As part of its statement of task, the committee was asked to analyze three
options for achieving the infrastructure needed to address threats posed by for-
eign animal diseases (FADs) and zoonotic diseases. Those options are building
the National Bio- and Agro-Defense Facility (NBAF) as currently designed,
building a version of the NBAF of reduced size and scope to be described by the
committee, and maintaining the Plum Island Animal Disease Center (PIADC) in
conjunction with obtaining biosafety level 4 (BSL-4) livestock capacity through
partnerships with foreign laboratories. The committee analyzed the options with
regard to how they might achieve an overall integrated US system that incorpo-
rates the critical core functions of disease surveillance, diagnostics, outbreak
response and recovery, research and development, and workforce training de-
scribed earlier in this report, as well as expected future needs (see Chapter 3).
Successful implementation of those critical systemwide functions requires prac-
tical infrastructure and laboratory capacity. This chapter provides a brief history
of previous long-term planning efforts, which demonstrates that many of the
same issues have plagued the US system for addressing FAD and zoonotic dis-
ease threats for many years. The history provides context for the committee’s
current analysis. This is followed by the committee’s assessment of what the
needed research and diagnostic laboratory infrastructure would include, regard-
less of the option considered for the central laboratory facility. In subsequent
sections, the committee discusses the three options and assesses how they ad-
dress capacity needs, such factors as relative costs, and other considerations.
67
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68 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
PREVIOUS LONG-TERM PLANNING EFFORTS
In 1983, the National Research Council released the report Long-Term
Planning for Research and Diagnosis to Protect U.S. Agriculture from Foreign
Animal Diseases and Ectoparasites (NRC, 1983). The study was requested in
1982 by the US Department of Agriculture (USDA) to “assess the current state
of the USDA effort on FAD&E [foreign animal diseases and ectoparasites] di-
agnosis and research; assess, for three 10-year increments, current and projected
technology of biological containment; and assist USDA in planning, in three 10-
year increments, for research on and diagnosis of all FAD&E of livestock and
poultry” (NRC, 1983).
The deliberations and recommendations in the 1983 report have a strong
resonance with the questions posed to the current National Research Council
committee 30 years later. Main themes of the 1983 report were that the facilities
at PIADC for conducting FAD and ectoparasite research and diagnostics were
obsolete and that the United States needed to contemplate several options to
maintain strong protection of our animal industries and economy in the face of a
threat of FADs and ectoparasites. In addition to recommendations that addressed
the need for long-term research planning and coordination, the 1983 NRC report
said that
“USDA should increase coordination [of FAD&E activities] with other
federal agencies and foreign institutions” (NRC, 1983).
“USDA should establish a system of laboratories and university-based
collaborative research centers for investigation, research, and diagnosis of do-
mestic and foreign animal diseases and ectoparasites” (NRC, 1983).
“As soon as possible, USDA should proceed with construction of a new,
highly secure mainland laboratory to succeed PIADC as USDA’s principal cen-
ter for research on exotic airborne and fomites-transmitted non-avian animal
diseases” (NRC, 1983).
The report further suggested the need for BSL-4 capabilities and proximity
to a major airport and a major university campus to ensure ready access and a
supportive scientific environment. It also suggested that PIADC be maintained
for large-animal challenge and vaccine studies in view of the legal restrictions
on working with foot-and-mouth disease virus (FMDv) on the mainland.
Eleven years later, in 1994, USDA appointed a Task Force on Biocontain-
ment Facilities for Foreign Animal Disease Research and Diagnostic Activities
(USDA, 1994) to consider two issues: the progress made in the preceding dec-
ade in new technology development and use for handling FAD agents since the
publication of the 1983 National Research Council report, and the current status
of and physical requirements for large-animal biocontainment facilities for con-
ducting FAD research and diagnostic activities in the near term and the long-
range future.
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 69
Regarding progress on research and diagnostic technologies, the 1994 task
force indicated that in vitro modern technologies were available for studying
FAD pathogens but that the use of in vivo studies was still needed for
The isolation of etiological agents to activate federal programs for dis-
ease control and eradication, particularly in the case of new emerging pathogens
that could not be isolated in vitro.
Conducting pathogenesis studies and proving Koch’s postulates.
Continuing to train state and federal veterinarians in the recognition of
FADs by using live-animal reproduction of key FADs.
Those justifications of a facility with the capability for live-animal studies
under strict biocontainment remain highly relevant today and were previously
discussed in Chapters 2 and 3 of this report.
Regarding the status of facilities to conduct FAD research and diagnostic
activities, the 1994 task force found that despite the recommendations of the
1983 National Research Council report, the PIADC facilities remained badly in
need of upgrading to achieve world-class designation. In 1994, an estimated
$80-100 million was needed for repairs and upgrades. There have been periodic
upgrades and renovations of PIADC since the 1994 report, but the general state
of PIADC in 2012 has not changed. The task force also pointed out that several
existing or planned facilities on university campuses may be capable of FAD
research and diagnostic activities but that many of them may have obsolete
technologies, may be underused, or have not been adequately maintained. As
previously discussed in Chapter 3, however, the status of university and federal
facilities in 2012 is substantially different from that in 1994. Finally, the 1994
task force offered nine potential options regarding the future of PIADC, catego-
rized into three groups as listed below. The reader is referred to that report for
additional information on options that are not presented in detail below.
Group One—Retain Plum Island Operations
Options 1-4: Several possibilities for achieving this recommendation were
presented, but they are not central to this report.
Group Two—Relocate Plum Island Operations to a Mainland Site
Option 5: Construct new mainland FAD facilities. “Request an upfront,
lump-sum appropriation, and construct new FAD facilities at a mainland site.
Continue to use existing FAD facilities on Plum Island until construction is
completed on the mainland. Continue to conduct domestic disease and selected
FAD work in separate mainland facilities” (USDA, 1994).
Option 6: Construct new mainland facilities; consolidate domestic and FAD
work. “Request an upfront, lump-sum appropriation, and construct new FAD
facilities at a mainland site (for both domestic and FAD work). Continue to use
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70 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
the existing island and mainland facilities until construction is completed on the
mainland. Consolidate both foreign and domestic animal disease work at the
new mainland facilities” (USDA, 1994). (The completion of the National Cen-
ters for Animal Health in Ames, Iowa, now supersedes the consideration of con-
solidation of domestic and FAD facilities in a single facility.)
Option 7: Upgrade Plum Island for foot-and-mouth disease work only;
move other work to the mainland. “Request partial appropriations each year as
required to upgrade/repair the Plum Island facilities, but [in view of the legal
restrictions on working with foot-and-mouth disease virus on the mainland] only
to the extent needed to conduct live-animal FMD challenge work. Relocate all
other FAD activities to existing mainland sites” (USDA, 1994), such as the Na-
tional Animal Disease Center, the National Veterinary Services Laboratories,
the Southeast Poultry Research Laboratory, and the Arthropod-Borne Animal
Diseases Research Laboratory.
Group Three—Unacceptable Options
Option 8: Upgrade Plum Island for foot-and-mouth disease work; contract
other FAD work. “[Maintain] a small Plum Island unit for FMD studies and
[contract] all other FAD activities with universities on the mainland. This option
was discarded because it would have afforded insufficient control and oversight
to ARS and APHIS [the USDA Agricultural Research Service (ARS) and Ani-
mal and Plant Health Inspection Service (APHIS)], required large expenses for
renovated or new university containment facilities, and continued expenditures
at Plum Island” (USDA, 1994). (But with the construction of multiple new bio-
containment facilities throughout the United States since the 1994 report was
issued, the present committee views that this option should no longer be consid-
ered unacceptable, as discussed further below.)
Option 9: Have ARS and APHIS seek independent decision-making and
funding. “Option 9 would have isolated ARS and APHIS, setting each agency
off on its own to seek independent answers, decision making, and funding. This
option was discarded because it would have meant less control and oversight of
FAD work by ARS and APHIS, and it would have led to higher overall costs”
(USDA, 1994).
Additional USDA, Department of Homeland Security (DHS), and National
Research Council reports echoed many of those issues, including concerns that
the PIADC facilities were at the end of their lifespan and needed modernization
and other upgrades and that a facility with BSL-4 large-animal capabilities was
needed (USDA, 1999; NRC, 2005; DHS, 2007a,b, 2008a; CRS, 2008; 74 Fed-
eral Register, 2009).
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 71
Previous National Research Council reports provide a historical perspective
for consideration of the three options specified in the present committee’s state-
ment of task. However, the committee’s deliberations were conducted independ-
ently of previous report recommendations to ensure that the current context of
disease threats, the ideal infrastructure to counter the threats, the technology of
“today and tomorrow”, and the current US and global assets available for coun-
tering disease threats informed the current study. Nevertheless, previous rec-
ommendations remain, in part, as relevant today as they were in 1983, 1994, and
later. The following sections discuss the three options the committee was asked
to address with respect to capacity and capabilities, advantages and liabilities,
relative costs, and other considerations.
THE LABORATORY INFRASTRUCTURE NEEDED
FOR A FOREIGN ANIMAL DISEASE AND ZOONOTIC
DISEASE RESEARCH AND DIAGNOSTIC FACILITY,
REGARDLESS OF LOCATION AND SIZE
A US system to address the potential threats posed by FADs and zoonotic
diseases effectively must include the ability to conduct research and diagnostic
procedures, provide training to support a competent and prepared workforce,
and include specialized facilities for handling particular pathogens and for con-
ducting experiments in large animals. The facility and program components of
the ideal system are depicted in Figure 3-1, and a more detailed description of
the laboratory infrastructure that would be required to meet those objectives is
described below. The numbers beside the headings below correspond to the
numbers in Figure 4-1.
System Components
1 2 3 4 5 6
Option 1
Option 3
NBAF
PIADC
1
2 Option 2 NAHLN, RBL/NBL,
1 2 Private Sector
Streamlined 3
3
6 NBAF
1
3 3
5 6
4 2 54
3 Academe Academe
1 5
5
1
6
4 Academe,
6
NAHLN, RBL/NBL, NAHLN 4
5 Private Sector, RBL/NBL,
Private Sector
Academe
National BSL-4 Labs,
Academe, NAHLN
4 International BSL-4 Labs
6
National BSL-4 Labs,
International BSL-4 Labs
Private Sector, RBL/NBL,
Academe
FIGURE 4-1 Comparison of the three options analyzed by the committee with the com-
ponents of an ideal laboratory infrastructure. The examples given are for illustration only
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72 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
and are not meant to be inclusive. See Table 4-1 for more detail. NOTE: 1 = diagnostics,
2 = research on foot-and-mouth disease, 3 = research on non- foot-and-mouth disease
FADs and zoonotic diseases in BSL-3Ag facilities, 4 = special pathogen activities in
ABSL-4 and BSL-4 facilities, 5 = teaching and training, 6 = vaccine development.
NAHLN = National Animal Health Laboratory Network; RBL/NBL = Regional Biocon-
tainment Laboratories and National Biocontainment Laboratories.
Diagnostics (1)
Laboratory infrastructure for the isolation, identification, and diagnosis of
FADs and zoonotic diseases is needed at several levels of biocontainment. In
vitro diagnostic work with inactivated pathogens or pathogen components may
be conducted with BSL-2 containment. Such work would include identification
of an agent with nucleic acid-based methods, such as the polymerase chain reac-
tion (PCR); detection of antigens with antibody-based methods, such as the en-
zyme-linked immunosorbent assay (ELISA); or characterization of host immune
responses to key agent antigens. In addition, reference reagent preparation
(when working with inactivated pathogen material), proficiency-testing panels,
and other activities related to support for state-based testing laboratories can be
conducted with BSL-2 containment. In vitro diagnostic work and the isolation of
live pathogens may generally be conducted in space at BSL-2, BSL-3, or BSL-4
levels. BSL-3Ag space is generally not required for working in vitro.1
Research on Foot-and-Mouth Disease (2)
Ease of transmission and the potential for large economic effects of an out-
break of foot-and-mouth disease make it a disease of special consideration. Ac-
tive research is ongoing to develop diagnostics for and vaccines against foot-
and-mouth disease virus (FMDv) strains. Currently, foot-and-mouth disease
research can be conducted in only one US facility: PIADC, off the US mainland.
Because of the special circumstances and restrictions surrounding foot-and-
mouth disease research, the committee considers it separately. In vitro work on
foot-and-mouth disease is conducted at BSL-3E level, and in vivo experiments
with FMDv are conducted at the BSL-3Ag level.
1
The 5th edition of Biosafety in Microbiological and Biomedical Laboratories sup-
ports conducting in vitro work with animal pathogens at the BSL-3 level, restricting the
use of BSL-3Ag to only situations in which particular FAD agents are used in infectivity
studies and when animals are loose in an isolation room (in which the walls of the room
itself form the primary containment barrier). Those agents are African swine fever virus,
lumpy skin disease virus, highly pathogenic avian influenza virus, Mycoplasma mycoides
subsp. mycoides (small colony type), Mycoplasma capricolum, Newcastle disease virus
(velogenic strains), Peste des petits ruminants virus (plague of small ruminants), Rift
Valley fever virus, rinderpest virus, classical swine fever virus, and foot-and-mouth dis-
ease virus (CDC, 2009).
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 73
Research on Foreign Animal Diseases and Zoonotic
Diseases in BSL-3Ag Facilities (3)
The necessary laboratory infrastructure for in vivo experiments on many
FADs and zoonotic diseases includes animal holding facilities for microbiologi-
cal, immunological, and pathogenesis studies at BSL-3Ag and ABSL-3E level
containment. Experiments at ABSL-3E can occur where animals are housed in
cages. BSL-3Ag containment is required for in vivo experiments on large ani-
mals that must be housed directly in an isolation room. In addition, the capabil-
ity to conduct in vivo studies of some pathogens associated with arthropod vec-
tors requires BSL-3Ag facilities. A separate set of guidelines, known as
Arthropod Containment Levels, is used to define the biocontainment needed for
safe manipulation of live arthropods (ASTMH, 2003).
Special Pathogen Activities in ABSL-4 and BSL-4 Facilities (4)
Research with some pathogens can be conducted only at BSL-4 or ABSL-4
containment. Those pathogens currently include hemorrhagic fever viruses (such
as Crimean-Congo hemorrhagic fever virus) and the new genus of Henipavirus
in the Paramyxoviridae family (Nipah and Hendra viruses).2 BSL-4 laboratory
capabilities are also needed more generally as part of an effective US system to
counter FAD and zoonotic disease threats because of the possible emergence of
new highly contagious zoonotic pathogens. In particular, BSL-4 and ABSL-4
will be required for initial work on newly emerging or unknown diseases in or-
der to provide protection to researchers from unknown biological hazards until
these can be more fully characterized. The required laboratory capacity includes
the ability to undertake in vitro microbiological research, such as propagation
2
The primary reservoir for Henipaviruses is bats of the Pteropus family, whose range
includes the eastern coastal areas of Australia, Southeast Asia, and South Asia. Hendra
virus was first recognized in 1994, and outbreaks have occurred only in Australia; Nipah
virus was first recognized in 1998, and outbreaks have occurred in Malaysia, Bangladesh,
and India. The probability of a natural introduction and establishment of either Nipah
virus or Hendra virus in the United States is small, and an outbreak in animals or people
is unlikely to lead to establishment of either one of these two viruses in the Western
Hemisphere, because of the absence of the primary vector or reservoir bat species. How-
ever, capabilities to work with viruses that require BSL-4 and ABSL-4 conditions, such
as Hendra virus and Nipah virus, are desirable for counter-bioterrorism and for potential
vaccine development, primarily for human or animal use in endemic areas. Active re-
search on Nipah and Hendra viruses is under way at BSL-4 facilities in the United States
(in vitro and in vivo) and in Australia and Canada (in vitro and in livestock animal mod-
els), and active research on vaccines with cloned proteins is going on at several BSL-
2/BSL-3 laboratories in the United States and abroad.
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74 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
and basic characterization of pathogens, at the BSL-4 level.3 Facilities for in
vivo experimentation in animal systems are also required at the BSL-4 level, as
is a necropsy room for postmortem examinations on both small and large ani-
mals. ABSL-4 facilities are required for in vivo experiments.
Teaching and Training (5)
The facilities necessary to train a prepared workforce include teaching
classrooms outside primary containment and laboratory facilities at several con-
tainment levels. Animal holding facilities for the in vivo demonstration of clini-
cal and pathological manifestations of selected diseases in small animals housed
with primary containment cages require ABSL-3E or ABSL-3.4 Animal holding
facilities for in vivo demonstration in larger animals requires BSL-3Ag. A ne-
cropsy room for training and demonstration purposes is required at the BSL-3Ag
level.
Vaccine Development (6)
Laboratory experiments as part of vaccine or other product development for
FADs and zoonotic diseases (except for special pathogens) will require BSL-3
and BSL-3E facilities. In vivo pathogen challenge and vaccine efficacy experi-
ments in large animals will require BSL-3Ag.
Examination of the Three Options
With those requirements providing a framework, the committee turned to a
fuller discussion of the three options presented in the statement of task. The op-
tions are depicted in Figure 4-1, with demonstration of one example of several
possible configurations for Options 2 and 3, and presented in greater detail with
multiple examples in Table 4-1.
3
As noted earlier, BSL-4 containment is not required for basic diagnostic work with
inactivated pathogens and non-replicating methodologies, such as PCR and other nucleic
acid detection procedures.
4
For example, work with avian influenza in chickens housed in ventilated cages at the
ABSL-3 level.
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TABLE 4-1 Possible Location of Key Laboratory-Based Components of the Ideal System for Countering Foreign Animal
Disease and Zoonotic Disease Threats
RBL/NBL Private National International
NBAF as NBAF- BSL-3Ag
BSL-3 Sector BSL-4 BSL-4
Components Designed Streamlined NAHLN Laboratories Academe Laboratories Laboratories Laboratories
Diagnostics
In vitro— X X X
nonviable/performance
In vitro— X O X X X
nonviable/development
In vitro—viable X X
agents/performance
In vitro—viable X O X X
agents/development
In vivo diagnostics X X O O
(animal inoculations)
National reference function X X
Foot-and-mouth
disease virus research
In vitro activities X X
In vivo activities X X
(including training)
FAD research
(non- foot-and-mouth disease)
In vitro BSL-3/BSL-3E X X O O
In vivo BSL-3Ag X X O
(Continued)
75
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76
TABLE 4-1 Continued
RBL/NBL Private National International
NBAF as NBAF- BSL-3 BSL-3Ag Sector BSL-4 BSL-4
Designed Streamlined Laboratories Academe Laboratories Laboratories Laboratories
Components NAHLN
Zoonotic disease research
BSL-3/BSL-3E X O X X
BSL-4 X X X X
Training using animals
FADs except X O O X
foot-and-mouth disease
Vaccine development
Development of principle X O O O O
Proof of principle X O O O O
Scale-up development X X
Animal efficacy studies X X O
NOTE: X = principal location, O = optional location.
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 77
Figure 4-1 and Table 4-1 focus on potential US partnerships to address key
laboratory components of an ideal system to address FAD and zoonotic disease
threats, with the exception of international BSL-4 laboratory capacity, since this
was included in the committee’s task as part of option 3. However, the commit-
tee also notes that international collaborations can be developed to contribute to
laboratory infrastructure at other biosafety levels, such as BSL-3Ag.
ANALYSIS OF OPTION 1: THE PROPOSED NATIONAL BIO-
AND AGRO-DEFENSE FACILITY AS CURRENTLY DESIGNED
The Capacity and Capabilities of the Proposed
National Bio- and Agro-Defense Facility
The NBAF is envisioned as a modern laboratory resource for consolidating
the research, diagnostic, and training missions of DHS and USDA (specifically,
APHIS and ARS) in a single facility. Activities that would be conducted in the
proposed NBAF include studies of high-consequence FADs and zoonotic dis-
eases that pose a threat to the US animal industry—such as foot-and-mouth dis-
ease, African swine fever (ASF), and classical swine fever (CSF)—and studies
of emerging zoonotic and high-threat exotic agents that affect livestock and re-
quire high containment at the ABSL-4 level. According to DHS’s Updated Site-
Specific Biosafety and Biosecurity Mitigation Risk Assessment (DHS, 2012a),
the NBAF, once operational, would support or provide
Basic and applied research on transboundary (foreign), emerging, and
zoonotic diseases.
Enhanced ability to perform laboratory diagnostic detection of and re-
spond to FADs and zoonotic diseases.
Expanded and dedicated space for development of vaccines and other
countermeasures.
Training facilities for animal health specialists to improve US capabil-
ity of detecting and responding to FADs of high consequence.
The proposed NBAF campus, with an area of 715,000 gross ft2, would pro-
vide infrastructure needed by DHS and USDA to meet their program require-
ments and would provide supporting facilities (DHS, 2012b). In addition to cur-
rent mission needs, DHS, APHIS, and ARS propose to expand their relevant
research and development activities and have designed NBAF with that in mind.
ARS proposes to expand its programs on emerging and zoonotic pathogens be-
yond FMDv, CSF virus, and ASF virus and to expand its research program on
vector-borne diseases. APHIS anticipates expanding its activities related to di-
agnostic services and reference materials for emerging and zoonotic diseases
and to enhance FAD diagnostics and training. DHS anticipates expanding its
research programs on the development of new foot-and-mouth disease vaccines
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94 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
Changes the approach to addressing animal diseases by drawing on sci-
entific and research expertise in other federal and non-federal laboratories, pro-
viding both intellectual benefits and possible cost savings through increased
efficiencies by avoiding duplication or relocation of scientists at the NBAF and
fostering collaboration.
Provides more flexibility for periodically re-evaluating infrastructure
needs in light of new and emerging disease priorities and technologies.
Liabilities
Not all components of the ideal system are housed in a single integrated
facility.
May require movement of specimens or materials to other facilities.
Requires interagency cooperation in developing agreements in the use
of laboratory space.
Requires creation of agreements with partner facilities.
Requires funding commitments to partner facilities for collaborative
work and establishment of grant-management capacity to oversee collabora-
tions.
Would have policy implications that would need to be explored further.
Might require DHS and USDA to make priority-setting decisions.
ANALYSIS OF OPTION 3: MAINTAINING CURRENT
CAPABILITIES AT PLUM ISLAND ANIMAL DISEASE
CENTER WHILE LEVERAGING ABSL-4 LARGE-ANIMAL
CAPACITY THROUGH FOREIGN LABORATORIES
The third option in the statement of task to be considered by the committee
was to maintain the current capacity of PIADC and to use BSL-4 and ABSL-4
large-animal facilities that are currently available at foreign laboratories. PIADC
does not contain infrastructure for conducting research at BSL-4 and ABSL-4.
The committee was informed by DHS that BSL-4/ABSL-4 laboratory facilities
could not be constructed at PIADC; the committee therefore did not further con-
sider the possibility of building BSL-4/ABSL-4 space at PIADC.
Current Situation of Plum Island Animal Disease
Center Capacity and Capabilities
PIADC has a long history of serving the nation as the sole high-
biocontainment laboratory for performing research and diagnostic investigations
on foot-and-mouth disease and other FADs. A historical perspective of the role
of PIADC in FAD work is presented in Appendix C. PIADC remains the only
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 95
laboratory in the United States that has the capability and capacity to address the
threat of foot-and-mouth disease. The committee notes that foot-and-mouth dis-
ease is appropriately still considered the highest-priority disease threat to US
agriculture because of its highly contagious nature, as demonstrated by the con-
tinued occurrence of foot-and-mouth disease outbreaks in many areas of the
world (such as South Korea), the movement of hundreds of people and countless
goods to the United States daily, the continuous movement of FMDv strains
around the world (such as the appearance of SAT-2 in areas of north Africa)7,
and the threat of bioterrorism with FMDv as a means of disrupting the economic
and social infrastructure of the United States. It is imperative that the nation
maintain an infrastructure to address countermeasures against a FMDv outbreak,
whether naturally occurring or intentional.
With regard to the core laboratory needs identified above and used as a
framework for considering Options 1 and 2, PIADC currently provides capabil-
ity and capacity for
In vitro diagnosis—maintains full range of diagnostics for confirmatory
diagnosis of index cases of foot-and-mouth disease, CSF, ASF, and other FADs
(it should be noted that confirmatory testing for a number of other FADs is also
performed at NVSL, Ames); presumptive-level testing in outbreak investiga-
tions other than priority 1 is now allowed and performed in NAHLN laborato-
ries;8 some BSL-2 work is done at NVSL, Ames and at PIADC, including
preparation of reference reagents and proficiency-testing support.
FAD work (in vitro and in vivo); it should be noted that work with
some pathogens or species is done at NVSL, Ames and SEPRL.
Special-pathogens work, but no capacity for BSL-4/ABSL-4.
Vaccine development—some in vitro and selected challenge work; two
new challenge-study rooms are being commissioned and will increase capacity.
Foot-and-mouth disease work—all done at PIADC in accordance with
current laws.
Training—nearly all FAD training with animal demonstrations; some
laboratory training is done at CVB in Ames, IA.
The laboratory space currently available at PIADC is summarized and com-
pared to the equivalent biocontainment level space in the proposed NBAF in
Table 4-5. The total space available in the main buildings at PIADC is 142,700
net ft2 and 245,940 gross ft2, compared to 176,000 net ft2 and 580,200 gross ft2
available in the main building of the proposed NBAF (Johnson and Barrett,
7
SAT-2 foot-and-mouth disease virus is one of three major virus serotypes designated
as South African Territories (SAT) 1-3. SAT-2 is the most common type causing foot-
and-mouth disease in sub-Saharan Africa and West Africa (Bastos et al., 2003).
8
The procedures for conducting investigations of potential foreign animal diseases are
outlined in Veterinary Services Memorandum 580.4 (USDA, 2010).
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96 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
2012). The committee notes that the condition and functionality of the space are
also important considerations beyond a direct comparison of square footage.
TABLE 4-5 Comparison of Space Available at PIADC and the Proposed NBAF
Space available at Space available at proposed
PIADC (net square feet) NBAF (net square feet)
BSL-4 laboratories 0 13,400
81,100a
BSL-3Ag and BSL-3E 72,400
laboratories
BSL-2 laboratories 5,300 9,700
BSL-2 Biotechnology 0 8,300
Development Module
Office and support space 65,000 63,500
SOURCE: Johnson and Barrett, 2012.
The proposed NBAF includes 37,460 net ft2 of BSL-3E and 53,925 net ft2 of BSL-3Ag
a
laboratory space (including animal support), which totals 91,385 net ft2 (DHS, 2012b).
The approximately 10,285 net ft2 difference between this total and the 81,100 net ft2
listed above presumably represents the animal support component.
Land, buildings, and other facilities of PIADC were transferred to DHS in
June 2003. Since then, the DHS Science and Technology Directorate has been
responsible for operating and maintaining the Plum Island site. Operational ser-
vices—including security, building and site maintenance, and operation of ma-
rine vessels and transportation—are contracted out to an independent private
organization. DHS provides the director of PIADC. ARS and APHIS have es-
tablished agreements with DHS for their continued operations at PIADC, and
each provides a director for its research and diagnostic programs. Each USDA
agency is responsible for providing its own scientific and technical support staff
and for paying for its own scientific operations (cost of diagnostic operations or
cost of bench and animal research activities).
Analysis of Option 3: Laboratory Capacity
PIADC has been able to provide the basic facilities for research, diagnosis,
and training needed for the protection of the United States against FADs for
more than 50 years, but there are several important limitations in its laboratory
capacity. Some remodeling of the main biocontainment building, Building 101
(now approaching 60 years old), was done in 1994, and the building of two new
animal holding rooms and the remodeling of one necropsy room have provided
needed additional space for current work. However, the basic building structure,
the size of the animal rooms, and other ancillary infrastructures are seriously
deficient for state-of-the-art research and diagnostic work at high biocontain-
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 97
ment. The building does not meet current standards for BSL-3Ag and does not
have capabilities for BSL-4 and ABSL-4. All physical support for the building—
such as high-efficiency particulate air filters, heating, ventilation, and air-
conditioning—is within the biocontainment envelope, where maintenance and
repairs are more difficult, expensive, and time-consuming. PIADC requires con-
tinuing high annual operating costs and will continue to need renovations. Fi-
nally, as noted above, the committee was advised that adding BSL-4/ABLS-4
containment to PIADC was not possible, given the need for political and local
acceptance to conduct such work on Plum Island. If this is correct, the building
cannot meet all the components of an ideal system as identified by the commit-
tee. The need for replacement facilities and the decommissioning of existing
buildings were noted in the previous studies of the facility and in the recent 2006
DHS decision to build the NBAF on the US mainland (NRC, 1983; USDA,
1994, 1999; DHS, 2008b; 74 Federal Register, 2009).
Pursuing Option 3 would therefore require the United States to seek ABSL-
4 large-animal laboratory capacity through partners such as foreign laboratories.
BSL-4 capabilities for in vitro and small-animal work exist at current facilities
in the United States and abroad.9 The United States lacks ABSL-4 large-animal
capacity, and such capacity is extremely limited in the entire Western Hemi-
sphere (only the facility in Winnipeg, Canada has the capacity for ABSL-4 work
in livestock, and this facility is small). Option 3 would require the United States
to obtain this capacity, when it is needed, through partnerships with foreign
laboratories; Table 3-2 identifies some of the international facilities that have
ABSL-4 capabilities.
Despite the limitations noted above, the committee emphasizes here and
elsewhere in this report that the facilities available at PIADC must be main-
tained until a new US biocontainment facility is constructed and commissioned.
The committee also believes that, given the current lack of US ABSL-4 facilities
that could handle large animals, it is advisable for the United States to enter into
formal cooperative agreements now with foreign laboratories to conduct re-
search that may require ABSL-4 large-animal containment. Such agreements
could be established in the interim until a new US biocontainment facility with
ABSL-4 large-animal space is built and commissioned. As indicated in the his-
tory of PIADC (Appendix C), successful international research cooperative
agreements existed before the creation of PIADC to work with FMDv in several
European laboratories, and this model could be replicated for the emergency use
of ABSL-4 facilities until this critical capacity is available in the United States
or as an emergency supplement to future US ABSL-4 large-animal capacity.
9
As indicated above, the committee does not agree with USDA and DHS statements
that BSL-4 capabilities are required for unpacking diagnostic samples or for basic diag-
nostic procedures when nucleic acid detection technologies are used. Such work can be
and is performed safely in regular BSL-3 or BSL-3E facilities.
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98 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
Relative Costs
Annual PIADC operating costs in FY 2020 are estimated at $56 million
($50 million for operations and maintenance, $6 million for DHS salaries). That
does not include the salaries and operations of ARS and APHIS personnel and
programs at PIADC. However, the aging PIADC facilities are in need of sub-
stantial improvements. Initial rough estimates total $90 million for short-term
improvements (including improvements in the liquid-waste decontamination
facility, Plum Island and Orient Point Harbors, information technology up-
grades, utility and building upgrades, security hardening, detection and access
control, and marine-vessel replacement and lighthouse restoration), while long-
term improvements are estimated at $210 million if PIADC is required to main-
tain its existing mission and to continue operating for another 25 years.
Advantages and Liabilities of Option 3:
The Plum Island Animal Disease Center
PIADC is currently the only US facility that can provide several of the criti-
cal core functions of an integrated system to address FAD and zoonotic disease
threats and is the only laboratory in the United States that is authorized to con-
duct research, diagnostics, and training related to foot-and-mouth disease. It
represents an existing investment that would avoid the costs of construction of a
new biocontainment facility. If a full commitment were made to improving and
maintaining PIADC, the avoidance of constructing a new facility would also
obviate the need for a facility transition period with a potential temporary loss of
function. In addition, capital improvements and other investments are needed at
PIADC over the next 10 years, whether the facility is maintained only until a
new facility is constructed or continues to serve as the central laboratory for a
US system to address FADs and zoonotic diseases over a longer period. Thus,
pursuing Option 3 would continue to realize the benefit of those investments
over a longer period. It would also exclude the risk that necessary investments
are being forgone to save costs during the years just before PIADC cedes its
activities to a new NBAF. By relying on the ABSL-4 capacity of other existing
US laboratories (for in vitro and small-animal work) or foreign partners (for
ABSL-4 large-animal work), this option also saves the United States from in-
vesting in in-country BSL-4/ABSL-4 capacity. Cooperative agreements with
foreign partners in case of an ABSL-4 need also enhance international coopera-
tion in FAD and zoonotic disease research.
In contrast, continuing to maintain and operate PIADC even without reno-
vation entails substantial annual costs of about $60-90 million. The facilities at
PIADC are aging and do not meet current standards for high-biocontainment
laboratories, including the 2004 Homeland Security Presidential Directive 9
[HSPD-9 (2004)] mandate to build new biocontainment facilities. Under Option
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 99
3, the United States would not have a modern biocontainment facility for FAD
research, particularly research on foot-and-mouth disease, and would not have
ABSL-4 capacity. The need to rely on foreign partners for ABSL-4 large-animal
capacity might limit the availability of such capacity in a time of emergency if
US needs were considered secondary to the needs and priorities of the partner
country. Finally, the long-term maintenance of PIADC will continue to experi-
ence difficulties in hiring new high-level scientists to work there; this is a chal-
lenge because of the aging infrastructure and the remote location. The commit-
tee did not further consider this or other site-specific issues as site was
prohibited from consideration in the statement of task.
The overall advantages and liabilities considered by the committee are
summarized in the lists of bulleted items below.
Advantages
Is an existing US facility that provides many of the laboratory infra-
structure components needed and would avoid the costs of constructing a new
replacement facility.
Is the only US facility that is authorized to conduct research, diagnos-
tics, and training in foot-and-mouth disease.
If there were a full commitment to PIADC, a transition period to a new
facility with a window of potential loss of function would not be needed.
Realizes the benefits of the capital renovations and improvements that
must be made for a longer period.
Does not require investment in BSL-4/ABSL-4 capabilities in the
United States.
Could function as part of an integrated national system that also in-
cludes distributed and collaborative partnerships
Enhances international cooperation for work on FADs and emerging
animal and zoonotic diseases.
Liabilities
Has a high cost to maintain and operate PIADC.
Does not provide the United States with a modern biocontainment fa-
cility for FAD and zoonotic disease research, particularly on foot-and-mouth
disease.
Does not provide the United States with BSL-4/ABSL-4 capability for
handling large animals.
Requires establishing agreements with foreign partners for access to
BSL-4 laboratories and presumably funding to support the collaborations.
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100 CRITICAL LABORATORY NEEDS FOR ANIMAL AGRICULTURE
May limit the availability of BSL-4 capabilities in times of need, de-
pending on priorities of other countries.
Continues to highly limit ABSL-4 large-animal capacity in the Ameri-
cas.
Maintaining PIADC long term will continue to compound the difficul-
ties in hiring new high-level scientists to work there due to the continued isola-
tion of the national laboratory site from academic and other research and devel-
opment centers.
CONCLUSIONS ABOUT THE THREE OPTIONS
As a result of its evaluation of the three options in its statement of task, the
committee finds
Option 1: The NBAF as currently designed includes all components of
the ideal laboratory infrastructure in a single location and has been designed to
meet the current and anticipated future mission needs of DHS, ARS, and
APHIS; but the proposed facility also has drawbacks (Conclusion 1).
Option 2: A partnership of a central national laboratory of reduced
scope and size and a distributed laboratory network can effectively protect the
United States from FADs and zoonotic diseases, potentially realize cost savings,
reduce redundancies while increasing efficiencies, and enhance the cohesiveness
of a national system of biocontainment laboratories. However, given the limited
and insufficient information provided by DHS, the cost implications of reducing
the scope and capacity of a central facility cannot be known without further in-
formation and study (Conclusion 2).
Option 3: Maintaining PIADC and drawing on the ABSL-4 large-animal
capacity of other partners would utilize an existing US facility that provides
some of the needed laboratory infrastructure components and would avoid the
costs of constructing a new replacement facility. However, the facilities at
PIADC are aging and do not meet current standards for high-biocontainment
laboratories, there are substantial costs associated with maintaining and operat-
ing it, it lacks BSL-4 and ABSL-4 large-animal capabilities, and the committee
was informed by DHS that such facilities could not be constructed at PIADC
(Conclusion 3).
OTHER OPTIONS
The committee recognizes that the three options it was asked to address in
the statement of task are not the only possible options for meeting the nation’s
laboratory infrastructure needs with regard to animal and public health. For ex-
ample, the possibility of constructing BSL-4/ABSL-4 space on Plum Island
could be revisited; the option of constructing an entirely new laboratory facility
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ANALYSIS AND CONCLUSIONS ABOUT THREE APPROACHES 101
on Plum Island, perhaps connected to the mainland by a bridge, could be con-
sidered; NBAF could be built only as a replacement for the existing facility on
Plum Island, with newly constructed ABSL-4 large-animal space co-located
with existing ABSL-4 laboratory space now used to study zoonotic diseases in
small animals and primates; or a variety of other options. As a result, the com-
mittee notes that there are numerous possibilities for creating an integrated na-
tional strategy and a network of collaborative partnerships to achieve the ideal
system for addressing FAD and zoonotic disease threats. However, evaluating
the full array of options and their relative advantages and disadvantages funda-
mentally draws not only on infrastructure needs but also on discussions of site
locations, risk assessments, political considerations, adaptability for the future,
and other elements explicitly outside of the committee’s statement of task, as-
pects of which have also been the subject of previous reports.
SUMMARY
In this chapter, the committee has described how an NBAF of reduced size
and scope might be envisioned and has discussed the advantages and liabilities
of the three options that it was asked to consider in its statement of task. On the
basis of the committee’s research and discussions, Chapter 5 provides the com-
mittee’s additional conclusions and recommendation on how the laboratory re-
search needed to enable the United States to address FADs and zoonotic dis-
eases might be effectively assembled.
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