High-Containment Biosafety Laboratories: Preliminary Observations
on the Oversight of the Proliferation of BSL-3 and BSL-4	 
Laboratories in the United States (04-OCT-07, GAO-08-108T).	 
                                                                 
In response to the global spread of emerging infectious diseases 
and the threat of bioterrorism, high-containment biosafety	 
laboratories (BSL)--specifically biosafety level (BSL)-3 and	 
BSL-4--have been proliferating in the United States. These	 
labs--classified by the type of agents used and the risk posed to
personnel, the environment, and the community--often contain the 
most dangerous infectious disease agents, such as Ebola,	 
smallpox, and avian influenza. This testimony addresses (1) the  
extent to which there has been a proliferation of BSL-3 and BSL-4
labs, (2) federal agencies' responsibility for tracking this	 
proliferation and determining the associated risks, and (3) the  
lessons that can be learned from recent incidents at three	 
high-containment biosafety labs. To address these objectives, GAO
asked 12 federal agencies involved with high-containment labs	 
about their missions and whether they tracked the number of labs 
overall. GAO also reviewed documents from these agencies, such as
pertinent legislation, regulation, and guidance. Finally, GAO	 
interviewed academic experts in microbiological research.	 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-08-108T					        
    ACCNO:   A77052						        
  TITLE:     High-Containment Biosafety Laboratories: Preliminary     
Observations on the Oversight of the Proliferation of BSL-3 and  
BSL-4 Laboratories in the United States 			 
     DATE:   10/04/2007 
  SUBJECT:   Accidents						 
	     Biocontainment laboratories			 
	     Biological research				 
	     Bioterrorism					 
	     Disease control					 
	     Emerging infectious diseases			 
	     Facility security					 
	     Federal agencies					 
	     Infectious diseases				 
	     Laboratories					 
	     Public health					 
	     Reporting requirements				 
	     Risk management					 
	     Safety regulation					 
	     Terrorism						 
	     CDC-USDA Select Agent Program			 

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GAO-08-108T

   

     * [1]Background

          * [2]BSL-3 and BSL-4 Labs
          * [3]Federal Agencies and BSL-3 and BSL-4 Labs
          * [4]Pertinent Laws and Guidance

               * [5]Pertinent Laws
               * [6]Pertinent Guidance

                    * [7]NIH and CDC BMBL Guidance
                    * [8]NIH Guidelines for Research Involving Recombinant
                      DNA Molecu

          * [9]The Select Agent Program

     * [10]Results in Brief
     * [11]Expansion of BSL-3 and BSL-4 Labs Is Taking Place across Man

          * [12]An Expansion of BSL-3 and BSL-4 Labs Is Taking Place in All

               * [13]The Expansion of BSL-3 and BSL-4 Labs Is Taking Place
                 Genera

     * [14]No Federal Agency Has the Mission to Track High-Containment
     * [15]Lessons Learned from Three Recent Incidents Highlight the Ri

          * [16]Identifying and Overcoming Barriers to Reporting
          * [17]Training Lab Staff in General Biosafety, as well as in Speci
          * [18]Developing Mechanisms for Informing Medical Providers about
          * [19]Addressing Confusion over the Definition of Exposure
          * [20]Ensuring that BSL-4 Labs' Safety and Security Measures Are C
          * [21]Maintenance of High-Containment Labs

     * [22]Concluding Observations
     * [23]Contacts and Acknowledgments
     * [24]GAO's Mission
     * [25]Obtaining Copies of GAO Reports and Testimony

          * [26]Order by Mail or Phone

     * [27]To Report Fraud, Waste, and Abuse in Federal Programs
     * [28]Congressional Relations
     * [29]Public Affairs

Testimony

Before the Subcommittee on Oversight and Investigations, Committee on
Energy and Commerce, House of Representatives

United States Government Accountability Office

GAO

For Release on Delivery
Expected at 10:00 a.m. EDT
Thursday, October 4, 2007

HIGH-CONTAINMENT BIOSAFETY LABORATORIES

Preliminary Observations on the Oversight of the Proliferation of BSL-3
and BSL-4 Laboratories in the United States

Statement of Keith Rhodes, Chief Technologist
Center for Technology and Engineering

Applied Research and Methods

GAO-08-108T

Mr. Chairman and Members of the Subcommittee:

We are pleased to be here today to discuss our preliminary findings on the
oversight of the expansion of high-containment biosafety level (BSL)-3 and
BSL-4 laboratories (labs) in the United States. This expansion is, in
part, a response to the global spread of emerging infectious diseases and
the threat of bioterrorism.

BSL-3 and BSL-4 labs often contain the most dangerous infectious disease
agents (for example, Ebola, smallpox, avian influenza, and severe acute
respiratory syndrome [SARS]), including those for which effective vaccines
or treatment may not be available. Although high-containment labs are
designed to promote the safety of researchers and the public, accidents
and security breaches have occurred in the past. In addition, these labs
can be used by terrorists or people with malicious intent to acquire or
develop harmful biological agents,^1 posing a severe national security and
public health threat.

The intentional dissemination of an agent--anthrax--in the U.S. mail
demonstrated the devastating effect such agents can have in the wrong
hands. As a result of exposure to anthrax-tainted mail in the fall of
2001, 22 individuals contracted anthrax disease in four
states--Connecticut, Florida, New Jersey, and New York--as well as in
Washington, D.C. Of these 22 individuals, 5 died.

These anthrax incidents highlighted major gaps in our civilian capacity to
respond to a biological attack; most noted among them, according to the
National Institute of Allergy and Infectious Diseases (NIAID), was the
shortage of high-containment lab capacity available to conduct research
leading to the development of medical countermeasures.^2 To address this
concern, the Administration and Congress responded by providing increased
funding for biodefense research and for additional BSL-3 and BSL-4 labs in
the private sector, especially in university settings.

^1Biological agent means any microorganism (including, but not limited to,
bacteria, viruses, fungi, rickettsiae, or protozoa) or infectious
substance or any naturally occurring, bioengineered, or synthesized
component of any such microorganism or infectious substance, capable of
causing death, disease, or other biological malfunction in a human, an
animal, a plant, or another living organism; deterioration of food, water,
equipment, supplies, or material of any kind; or deleterious alteration of
the environment.

^2National Institute of Allergy and Infectious Diseases, Survey for
Determining the Location, Capacity, and Status of Existing and Operating
BSL-3 Laboratories within the United States (Washington, D.C., June 2,
2005).

However, concerns have been raised about the oversight of these labs
because the deliberate or accidental release of biological agents can have
disastrous consequences, such as exposing workers and the public. In
addition, as the number of BSL-3 and BSL-4 labs has been increasing,
concerns have also been raised about their safety, as well as operations.
Finally, there are security concerns about the potential theft of the
material itself. Accordingly, you asked us to address the following three
questions:

           1. To what extent, and in what areas, has there been an expansion
           in the number of high-containment labs in the United States?
           2. Which federal agency is responsible for tracking the expansion
           of high-containment labs and determining the associated aggregate
           risks?
           3. What lessons can be learned from recent incidents at three
           high-containment labs?

To answer these questions, we interviewed officials from several federal
agencies, as well as experts; reviewed literature; conducted site visits;
and surveyed 12 federal agencies. We conducted our work from August 2006
through September 2007 in accordance with generally accepted government
auditing standards (see appendix I for our scope and methodology).

Background

Since September 11, 2001, there has been an increase in the funding for
research in biomedicine. This increase is intended to develop effective
medical countermeasures, against emerging infectious diseases and
biological agents, which can only be performed safely in BSL-3 and BSL-4
labs. A large part of this funding has been used to construct additional
high-containment BSL-3 and BSL-4 labs.

BSL-3 and BSL-4 Labs

The BSL labs are classified by the type of agents used and the risk posed
to personnel, the environment, and the community by those agents. The
Department of Health and Human Services's (HHS) Biosafety in
Microbiological and Biomedical Laboratories (BMBL) guidelines specify four
biosafety levels,^3 with BSL-4 being the highest. The levels include
combinations of laboratory practices and techniques, safety equipment, and
facilities that are recommended for labs that conduct research on
potentially dangerous agents and toxins. These labs are to be designed,
constructed, and operated in a manner to (1) prevent accidental release of
infectious or hazardous agents within the laboratory and (2) protect lab
workers and the environment external to the lab, including the community,
from exposure to the agents.

Work in BSL-3 labs involves agents that may cause serious and potentially
lethal infection. In some cases, there are vaccines or effective
treatments available. Types of agents that are typically handled in BSL-3
labs include, for example, anthrax, West Nile Virus, Q fever, tularemia,
and avian flu. Work in BSL-4 labs involves the most dangerous agents for
which there are no effective vaccines or treatments available. Types of
agents that are typically handled in BSL-4 labs include, for example,
Ebola, hemorrhagic fevers, and smallpox.^4

Federal Agencies and BSL-3 and BSL-4 Labs

Many different federal agencies have some connection with BSL-3 and BSL-4
labs in the United States. These agencies are involved with these labs in
various capacities, including as users, owners, regulators, and funding
sources. For example, the Centers for Disease Control and Prevention (CDC)
has its own high-containment labs and regulates that portion of labs
working with select agents and toxins that represent a risk to human
health and safety. Similarly, the U.S. Department of Agriculture (USDA)
has its own labs and regulates labs working with select agents and toxins
posing a risk to animal and plant health. The NIAID has its own labs and
is a major funding source for construction and research involving
high-containment labs. The National Institutes of Health (NIH) both funds
research requiring high containment and provides guidance that is widely
used to govern many of the activities in high-containment labs. The Food
and Drug Administration (FDA) has its own labs and regulates manufacturing
of biological products, some of which require high-containment labs. The
Department of Commerce (DOC) regulates the export of agents and equipment
that have both military and civilian uses, which are often found in
high-containment labs. The Department of Defense (DOD) has its own labs
and funds research requiring high-containment labs. The Department of
Labor's (DOL) Occupational Safety and Health Administration (OSHA)
regulates some activities within high-containment labs, as well as general
safety in most high-containment labs. The Department of State (DOS)
regulates the export of agents and equipment that are specifically
designed for military use from defense-related high-containment labs and
maintains a listing of some high-containment labs, as part of the U.S.
commitments under the Biological and Toxin Weapons Convention (BWC). The
Department of Justice's (DOJ) Federal Bureau of Investigation (FBI) uses
high-containment labs when their forensic work involves dangerous
biological agents. The Department of Homeland Security (DHS) has its own
labs and funds a variety of research requiring high-containment labs. The
Department of Energy (DOE) has several BSL-3 labs doing research to
develop detection and response systems to improve preparedness for
biological attack. The Department of Interior (DOI) has its own BSL-3 labs
for work with infectious animal diseases. The Department of Veterans
Affairs (VA) has research and clinical BSL-3 labs for its work with
veterans. The Environmental Protection Agency (EPA) has its own labs and
also coordinates use of various academic, state, and commercial
high-containment labs nationwide, as part of its emergency response
mission.

^3 Department of Health and Human Services, Biosafety in Microbiological
and Biomedical Laboratories, 5^th ed. (Washington, DC., 2007).

^4 Smallpox is only handled at the CDC labs in Atlanta.

Pertinent Laws and Guidance

The pertinent laws and guidance include the following (see appendix II for
pertinent regulations):

  Pertinent Laws

The Antiterrorism and Effective Death Penalty Act of 1996 includes
provisions to regulate the transfer, between laboratories, of certain
biological agents and toxins and requires the Secretary of HHS to
implement these provisions. As part of the implementation of this act, the
first list of regulated biological agents was created. This became known
as the select agent list.

The Public Health Security and Bioterrorism Preparedness and Response Act
of 2002 revised and expanded the Select Agent Program. Among other
requirements, the new law (1) revised the list of agents deemed "select
agents," which possess the "potential to pose a severe threat" to public
health and safety, to animal or plant health, or to animal or plant
products; (2) directed the Secretaries of HHS and Agriculture to
biennially review and publish the select agent list, making revisions as
appropriate to protect the public; (3) required all facilities possessing
select agents to register with the Secretary of HHS, Agriculture, or both,
not just those facilities sending or receiving select agents; (4)
restricted access to biological agents and toxins by persons who do not
have a legitimate need and who are considered a risk by federal law
enforcement and intelligence officials; (5) required transfer
registrations to include information regarding the characterization of
agents and toxins to facilitate their identification, including their
source; (6) required the creation of a national database with information
on all facilities and persons possessing, using, or transferring select
agents; and (7) required the Secretaries of HHS and Agriculture to impose
more detailed and different levels of security for different select
agents, based on their assessed level of threat to the public.

  Pertinent Guidance

Pertinent guidance includes NIH and CDC BMBL guidance, as well as NIH
guidelines.

    NIH and CDC BMBL Guidance

The NIH and CDC prepared the BMBL as a guidance document for working with
particular select agents. According to the BMBL guidelines, (1) BSL-1
laboratories house agents and toxins that do not consistently cause
disease in healthy adult humans; (2) BSL-2 laboratories are capable of
housing agents and toxins that are spread through puncture, absorption
through mucous membranes, or ingestion of infectious materials; (3) BSL-3
laboratories are capable of housing agents and toxins that have a
potential for aerosol transmission and that may cause serious and
potentially lethal infection; (4) BSL-4 laboratories are capable of
housing agents and toxins that pose a high individual risk of
life-threatening disease, which may be aerosol transmitted and for which
there is no available vaccine or therapy.

The BMBL states that (1) biosafety procedures must be incorporated into
the laboratory's standard operating procedures or biosafety manual; (2)
personnel must be advised of special hazards and are required to read and
follow instructions on practices and procedures; and (3) personnel must
receive training on the potential hazards associated with the work
involved and the necessary precautions to prevent exposure. Further, the
BMBL contains guidelines for laboratory security and emergency response,
such as controlling access to areas where select agents are used or
stored. The BMBL also states that a plan must be in place for informing
police, fire, and other emergency responders as to the type of biological
materials in use in the laboratory areas.

    NIH Guidelines for Research Involving Recombinant DNA Molecules

Much of the work in BSL-3 and BSL-4 labs in the United States involves
recombinant DNA (rDNA), and the NIH Guidelines for Research Involving
Recombinant DNA Molecules (NIH rDNA Guidelines) set the standards and
procedures for research involving rDNA. Institutions must follow these
guidelines when they receive NIH funding for this type of research. The
guidelines include the requirement to establish an institutional biosafety
committee (IBC). The IBC is responsible for (1) reviewing rDNA research
conducted at or sponsored by the institution for compliance with the NIH
rDNA Guidelines and (2) approving those research projects that are found
to conform with the NIH rDNA Guidelines. IBCs also periodically review
ongoing rDNA research to ensure continued compliance with the NIH rDNA
Guidelines.

The Select Agent Program

The CDC is responsible for the registration and oversight of laboratories
that possess, use, or transfer select agents and toxins that could pose a
threat to human health. USDA is responsible for the registration and
oversight of laboratories that possess, use, or transfer select agents and
toxins that could pose a threat to animal or plant health or animal or
plant products. Some select agents, such as anthrax, pose a threat to both
human and animal health and are regulated by both agencies (see appendix
III for the list of select agents and toxins).

The select agent regulations require registration for U.S.-based research
institutions, government agencies, universities, manufacturers, and other
entities that possess, use, or transfer select agents. Registration is for
3 years. As part of the registration process, facilities must demonstrate
in their applications that they meet the recommendations delineated in the
BMBL for working with particular select agents. Such requirements include
having proper laboratory and personal protective equipment, precautionary
signage, and ventilation; controlled access; and biosafety operations
manuals. Facilities must also describe the laboratory procedures that will
be used, provide a laboratory floor plan showing where the select agent
will be handled and stored, and describe how access will be limited to
authorized personnel.

In addition, facilities must describe the objectives of the work that
requires the select agent. Each facility must identify a responsible
facility official who is authorized to transfer and receive select agents
on behalf of the facility. Individuals making false, fictitious, or
fraudulent statements on registration forms may be punished, under the
False Statements Act, by a fine of up to $250,000, imprisonment up to 5
years, or both. Violations by organizations are punishable by a fine of up
to $500,000 per violation. To ensure compliance with these requirements,
the program established a goal of inspecting these facilities once during
the 3-year registration period. Facilities may be inspected before and
after registration, but there is no requirement that inspections be
performed.

Results in Brief

A major expansion of high-containment biosafety labs (BSL-3 and BSL-4) is
taking place in the United States, according to the literature, federal
agency officials, and experts. Concerning BSL-4 labs, which handle the
most dangerous agents, the number of these labs has increased from
5--before the terrorist attacks of 2001--to 15, including at least 1 in
the planning stage. The expansion is taking place across many
sectors--federal, state, academic, and private^5--and across most of the
United States. Information on expansion is available about
high-containment labs that are (1) registered with the CDC-USDA Select
Agent Program and (2) federally funded. However, much less is known about
the expansion of labs outside the Select Agent Program as well as the
nonfederally funded labs, including location, activities, and ownership.

No single federal agency has the mission and, therefore, is accountable
for tracking the number of all BSL-3 and BSL-4 labs within the United
States. Moreover, although several agencies have a need to know the number
and location of these labs to support their missions, no agency knows how
many such labs there are in the United States or their locations,
according to agencies' responses to our survey. Therefore, no agency is
responsible for determining the aggregate risks associated with the
expansion of these labs. According to the experts, there is a baseline
risk associated with any high-containment lab, attributable to human
errors. With this expansion, the risk will increase. However, the
associated safety and security risks will be greater for new labs with
less experience.

We identified six lessons from three recent incidents: failure to report
to CDC exposures to select agents by Texas A&M University (TAMU); power
outage at CDC's new BSL-4 lab in Atlanta, Georgia; and a release of
foot-and-mouth disease virus at Pirbright in the United Kingdom (U.K.).
These lessons highlight the importance of (1) identifying and overcoming
barriers to reporting in order to enhance biosafety through shared
learning from mistakes and to assure the public that accidents are
examined and contained; (2) training lab staff in general biosafety, as
well as in specific agents being used in the labs to ensure maximum
protection; (3) developing mechanisms for informing medical providers
about all the agents that lab staff work with to ensure quick diagnosis
and effective treatment; (4) addressing confusion over the definition of
exposure to aid in the consistency of reporting; (5) ensuring that BSL-4
labs' safety and security measures are commensurate with the level of risk
these labs present; and (6) maintenance of high-containment labs to ensure
integrity of physical infrastructure over time.

^5Private sector labs include commercial labs.

Expansion of BSL-3 and BSL-4 Labs Is Taking Place across Many Sectors and All
over the United States

An expansion in the number of BSL-3 and BSL-4 labs is taking place across
most of the United States,^6 according to the literature, federal agency
officials, and experts. Most federal officials and experts believe that
the number of BSL-4 labs in the United States is generally known. But the
number of BSL-3 labs is unknown. Information on expansion is available
about high-containment labs that are (1) registered with the CDC-USDA's
Select Agent Program, and (2) federally funded. However, much less is
known about the expansion of labs outside the Select Agent Program and the
nonfederally funded labs, including location, activities, and ownership.
For both BLS-3 and BSL-4, the expansion is taking place across many
sectors--federal, state, academic, and private--and all over the United
States.

^6There are a number of methodological issues associated with determining
the overall number of BSL-3 and BSL-4 labs. In our discussion with federal
agency officials, experts, and review of the literature, we found that the
total number depended upon how you ask the question. Most often data were
available on the number of facilities or sites that contained a BSL-3 or
BSL-4 lab. The precise number of independent rooms within those facilities
qualifying as BSL-3 or BSL-4 is not generally specified. Some facilities
contain more than one actual lab. For example, while CDC has two
facilities with BSL-4 capacity, one of the facilities actually contains
within it two separate BSL-4 labs, while the other has four separate BSL-4
labs. These officials and experts also told us that counting the number of
labs is problematic because the definition of the term "lab" varies. A
more meaningful measure is determining the net square footage of working
BSL-4 space. However, this information is often not available.

An Expansion of BSL-3 and BSL-4 Labs Is Taking Place in All Sectors in the
United States

For most of the last 50 years, there were only two sites with BSL-4 labs
in the United States. These were federal labs at the U.S. Army's Research
Institute for Infectious Diseases (USAMRIID) in Fort Detrick, Maryland,
and at the CDC in Atlanta, Georgia. Between 1990 and 2000, three new BSL-4
labs were built: a BSL-4 lab at Georgia State University in Atlanta--the
first BSL-4 lab in a university setting; a small BSL-4 lab on the NIH
campus in Bethesda, Maryland;^7 and a privately funded BSL-4 lab in San
Antonio, Texas. Since the terror attacks of 2001, nine new facilities and
one major remodeling effort containing BSL-4 space will either be
operational, in construction, or in planning by this year's end. The
number of BSL-4 laboratories has increased from 5, before 2001, to 15,
including at least 1 in planning.

Moreover, expansion is taking place across all sectors. Before 1990, all
BSL-4 labs were federal labs--either at USAMRIID or at the CDC. Today,
while expansion is taking place within the federal sector as well--there
are seven new federal facilities recently built, currently under
construction, or planned, which have one or more BSL-4 labs--there are
also BSL-4 labs at universities, as part of state response, and in the
private sector. (See table 1 for expansion in BSL-4 labs by sector.)

Table 1: Summary of Known BSL-4 Labs in the United States, by Sector

Sector             Before 1990 1990-2000 2001-Present Total 
Federal government           2         1            6     9 
Academic                     0         1            3     4 
State                        0         0            1     1 
Private                      0         1            0     1 
Total                        2         3           10    15 

Source: GAO analysis based on open source information.

Note: These numbers represent the lower bound of the number of BSL-4 labs.
Within each of these facilities, there may be several independent rooms
designated as work areas, each at BSL-4 level.

While the number is difficult to quantify, many more BSL-3 labs are
thought to exist compared with BSL-4 labs. Many lab owners--when building
new labs or upgrading existing ones--are building to meet BSL-3 level
containment, often anticipating future work, even though they intend for
some time to operate at the BSL-2 level with BSL-2 recommended agents. In
addition, much biodefense work, for example, involves aerosolization of
agents for challenge studies, and most of this type of activity is often
recommended for containment at the BSL-3 level.

^7This is lab was built as a BSL-4 but currently operates as an enhanced
BSL-3.

The expansion of BSL-3 labs is in all sectors. However, the only
definitive data available are on labs registered with the CDC-USDA Select
Agent Program. Within that program, two-thirds of registered BSL-3 labs
are outside the federal sector (see table 2).

Table 2: BSL-3 Labs Registered with the CDC and USDA Select Agent Program,
by Sector

Sector   CDC-registered labs USDA- registered labs  Total 
                         Number                Number Number 
Federal                  291                   167    458 
Academic                 429                    58    487 
State                    248                    20    268 
Private                   74                    69    143 
Total                   1042                   314   1356 

Source: GAO's analysis of CDC-USDA data.

Within the academic sector, for example, NIAID has provided funding for 13
Regional Biocontainment Laboratories (RBL) to provide regional BSL-3
capability for academic research requiring such containment. Expansion at
the state level is also taking place (see table 3). According to a survey
conducted by the Association of Public Health Laboratories (APHL) in
August 2004, since 2001 state public health labs have used public health
preparedness funding to build, expand, and enhance BSL-3 labs.^8 In 1998,
for example, APHL found that 12 of 38 responding states reported having a
state public health laboratory at the BSL-3 level. Today, at least 46
states have at least one state public health BSL-3 lab.

^8Association of Public Health Laboratories, Public Health Laboratory
Issues in Brief: Bioterrorisn Capacity (Washington D.C., April 2005).

Table 3: BSL-3 Labs in the State Public Health System

Calendar year State public health BSL-3 labs 
2001                                      69 
2002                                      71 
2003                                     139 

Source: Association of Public Health Laboratories, 2005.

  The Expansion of BSL-3 and BSL-4 Labs Is Taking Place Generally across the
  United States

Expansion of BSL-3 and BSL-4 labs is starting to take place geographically
as well as by sector. For example, before 1990, BSL-4 labs were clustered
at either USAMRIID at Fort Detrick or at CDC. Today, there are BSL-4 labs
built, under construction, or in planning in four states other than
Maryland and Georgia.

The expansion of BSL-3 labs is widespread across most states. Because of
the need for individual state response to bioterrorist threats, most
states now have some level of BSL-3 capacity--at least for diagnostic and
analytical services--in support of emergency response. In addition, within
the academic research community, the RBLs being constructed by the NIAID
are intended to provide regional BSL-3 laboratory capacity to support
NIAID's Regional Centers of Excellence for Biodefense and Emerging
Infectious Diseases Research (RCE). Hence, the RBLs are distributed
regionally around the country. Operational, under construction, or
currently planned BSL-4 labs and some of the major BSL-3 facilities in the
United States are shown in figure 1.

Figure 1: Known BSL-4 Labs and Some of the Major BSL-3 Labs in the United
States

No Federal Agency Has the Mission to Track High-Containment Labs in the United
States

No single federal agency has the mission to track and determine the risk
associated with the expansion of BSL-3 and BSL-4 labs in the United
States, and no single federal agency knows how many such labs there are in
the United States. Consequently, no one is responsible for determining the
aggregate risks associated with the expansion of these high-containment
labs.

None of the federal agencies that responded to our survey indicated that
they have the mission to track and know the number of BSL-3 and BSL-4 labs
within the United States (see table 4).

Table 4: Federal Agencies' Mission to Track and Know the Number of All
BSL-3 and BSL-4 Labs within the United States

Agency                                  Mission to track Know the number 
Department of Commerce                  No               No              
Department of Defense                   No               No              
Department of Energy                    No               No              
Department of Health and Human Services No               No              
Department of Homeland Security         No               No              
Department of Interior                  No               No              
Department of Justice                   No               No              
Department of Labor                     No               No              
Department of State                     No               No              
Department of Veterans Affairs          No               No              
Environmental Protection Agency         No               No              
U.S. Department of Agriculture          No               No              

Source: GAO Survey of Federal Agencies Involved with BSL-3 and BSL-4 Labs,
2007.

Some federal agencies do have a narrow mission to track a subset of BSL-3
and BSL-4 labs, and they do know the number of those labs. For example,
the CDC and USDA together know the number of high-containment labs working
with select agents because, by federal regulation, such labs are required
to register with them. But these regulations only require that the
entities registering with the Select Agent Program do a risk assessment of
their individual labs. No agency, therefore, has the mission to determine
the aggregate risks associated with the expansion of high-containment labs
that work with select agents. According to the federal agency officials,
the oversight of these labs is fragmented and relies on self-policing.

While the number and location of all BSL-3 and BSL-4 labs is not known,
several federal agencies indicated that they have a need to know this
information in support of their agency missions. Some intelligence
agencies, for example, indicated that they need to know a subset of the
number and location of high-containment labs within the United States
because these labs represent a capability that can be misused by
terrorists or people with malicious intent.^9 Without knowledge of the
number and location of the BSL-3 and BSL-4 labs, some agencies' work is
made more difficult. For example, the FBI has a need to know the number
and location of BSL-3 and BSL-4 labs for forensic purposes. Without this
information, the FBI's work is made more difficult.

According to the experts, there is a baseline risk associated with any
high-containment. With expansion, the aggregate risks will increase.
However, the associated safety and security risks will be greater for new
labs with less experience. In addition, high-containment labs have health
risks for individual lab workers as well as the surrounding community.
According to a CDC official, the risks due to accidental exposure or
release can never be completely eliminated, and even labs within
sophisticated biological research programs--including those most
extensively regulated--have had and will continue to have safety failures.
In addition, while some of the most dangerous agents are regulated under
the CDC-USDA's Select Agent Program, many high-containment labs work with
agents not covered under this program. Labs outside the Select Agent
Program also pose risks, given that many unregulated agents can cause
severe illness or even death (see appendix IV for a list of some agents,
but not select agents, recommended to be worked on in high-containment
labs). These labs also have associated risks because of their potential as
targets for terrorism or theft from either external or internal sources.
Even labs outside the Select Agent Program can pose security risks in that
such labs represent a capability that can be paired with the necessary
agents to become a threat. While the United States has regulations
governing select agents, many nations do not have any regulations
governing the transfer or possession of dangerous biological agents.

^9Some intelligence agencies have a mission to track and a need to know
the number of all BSL-3 and BSL-4 labs or equivalent abroad. However, they
do not know the total number of those labs.

Lessons Learned from Three Recent Incidents Highlight the Risks Inherent in the
Expansion of High-Containment Labs

We identified six lessons from three recent incidents: failure to report
to CDC exposures to select agents, in 2006, by TAMU (see appendix V);
power outage at CDC's new BSL-4 lab, in 2007; and the release of
foot-and-mouth disease virus, in 2007, at Pirbright, the U.K. These
lessons highlight the importance of (1) identifying and overcoming
barriers to reporting in order to enhance biosafety through shared
learning from mistakes and to assure the public that accidents are
examined and contained; (2) training lab staff in general biosafety as
well as in specific agents being used in the labs to ensure maximum
protection; (3) developing mechanisms for informing medical providers
about all the agents that lab staff work with to ensure quick diagnosis
and effective treatment; (4) addressing confusion over the definition of
exposure to aid in the consistency of reporting; (5) ensuring that BSL-4
labs' safety and security measures are commensurate with the level of risk
these labs present; and (6) maintenance of high-containment labs to ensure
integrity of physical infrastructure over time.

Identifying and Overcoming Barriers to Reporting

While the Select Agent Program and the rDNA Guidelines have reporting
requirements, institutions sometimes fail to report incidents. According
to CDC, there were three specific types of incidents that TAMU officials
failed to report to CDC: (1) multiple incidents of exposure, including
illness; (2) specific types of experiments being conducted by researchers;
and (3) missing vials and animals.

In addition, in November 2006, during our first visit to TAMU--a meeting
in which all key officials who knew about these incidents were present--we
asked if there had been any incident in which a lab worker was exposed to
a select agent. TAMU officials did not disclose any of these incidents.
Moreover, in August 2007, during our second visit, the biosafety officer
said that he had conducted an investigation of the incident, in which the
lab worker was exposed to Brucella, and wrote a report. However, the
report that was provided to us was dated June 17, 2006, but discussed
other incidents that had occurred in 2007, a discrepancy that TAMU failed
to explain to us.^10

^10The biosafety officer at TAMU told us the following: He had no training
in biosafety but was an industrial hygienist by education and experience.
He was asked to take on the additional duty of biosafety officer when the
previous biosafety officer retired. He was also designated as an alternate
responsible officer (RO) but did not know what duties he had to perform as
an alternate RO.

According to the literature and discussion with federal officials and
experts, accidents in labs are expected, mostly as a result of human error
due to carelessness, inadequate training, or poor judgment. In the case of
theft, loss, occupational exposure, or release of the select agent, the
lab must immediately report certain information to CDC or USDA. However,
there is a paucity of information on barriers to reporting by
institutions. It has been suggested that there is a disincentive to report
acquired infections and other mishaps at research institutions because of
(1) negative publicity for the institution or (2) the scrutiny from a
granting agency, which might result in the suspension of research or an
adverse effect on future funding.^11 Further, it is generally believed
that when a worker acquires an infection in the lab, it is almost always
his or her fault, and neither the worker nor the lab is interested in
negative publicity.

In order to enhance reporting, barriers need to be identified and targeted
strategies need to be applied to remove those barriers. It is also
important that these incidents be analyzed so (1) biosafety can be
enhanced through shared learning from mistakes and (2) the public may be
reassured that accidents are thoroughly examined and contained. One
possible mechanism for analysis, discussed in the literature, is the
reporting system used for aviation incidents, administered by the National
Transportation Safety Board and the Federal Aviation Administration.^12
When mistakes are made, they are analyzed and learned from without being
attributed to any one individual. Experts have agreed that some form of
personal anonymity would encourage reporting.

Training Lab Staff in General Biosafety, as well as in Specific Agents Being
Used in the Labs

Training is a key requisite for safe and secure work with dangerous
agents. Moreover, it is important that this training is specific to the
agent to be worked with and activities to be performed.

The lab worker at TAMU who was exposed was not authorized to work with
Brucella but was, we were told, being escorted in the lab only to help out
with the operating of the aerosolization chamber.^13 According to the
select agent regulations, all staff are required to be trained in the
specifics of any agent before they work with it. However, the worker did
not receive training in the specifics of Brucella, including its
characteristics, safe handling procedures, and potential health effects.
While the worker was experienced in general BSL-3 procedures, her normal
work regimen involved working with Mycobacterium tuberculosis, and her
supervisor surmised that the differential potential for infection from
Brucella was partially to blame for the exposure.^14

^11High-Containment Biodefense Research Laboratories, Meeting Report and
Center Recommendations, Biosecurity and Bioterrorism, vol. 5, 1 (New
Rochelle, N.Y.: March 2007).

^12Department of Transportation, Federal Aviation Administration, FAA
Procedures for Handling National Transportation Safety Board
Recommendations (Washington, D.C.: Federal Aviation Administration, March
22, 1995). Also see Federal Aviation Administration, Accident and Incident
Data (Washington, D.C.: Federal Aviation Administration, Sept. 29, 2006).

In particular, the exposed lab worker was highly experienced in handling
M. tuberculosis, an infectious agent. A lab director of a BSL-2 lab for
the last 5 years, she had a PhD in medical sciences and was, by many
accounts, highly competent and reliable. She had applied the procedures
governing safe work with M. tuberculosis to the Brucella experiment.
However, her experience with M. tuberculosis might have provided a false
sense of security.

Had training been given in Brucella, the worker might have been more aware
when cleaning the aerosol chamber. Typical routes of infection differ
between M. tuberculosis and Brucella and normal procedures, including
gowning and respiratory equipment, vary between the two agents. For
example, the lab worker wore protective glasses, but they were not tight
fitting. This was adequate when working with M. tuberculosis, but not with
Brucella. The investigation concluded that the agent entered the lab
worker through the eyes.

According to one expert who has managed high-containment labs, there are
risks working alternately in BSL-2 and BSL-3 labs, with their different
levels of procedures and practices. The fear is that lab workers may
develop a routine with BSL-2 procedures that might be difficult to
consciously break when working with the more dangerous agents and
activities requiring BSL-3 containment.

^13According to the CDC, regardless of escort, since the lab worker was
not authorized to work with Brucella, having the lab worker help out with
the aerosolization chamber during the Brucella experiments constituted
unauthorized access to a select agent and violated the regulations.

^14Although a person typically has to breathe in M. tuberculosis bacteria
to get an infection, Brucella can enter the system through mucous
membranes such as those in the eyes. During the experiment, the lab worker
who got exposed had been wearing a respirator that filtered the air she
breathed as is recommended for work with M. tuberculosis.

Developing Mechanisms for Informing Medical Providers about All the Agents that
Lab Staff Work with

Severe consequences for the worker can result from delays in (1)
recognizing when an exposure has occurred or (2) medical providers'
accurately diagnosing any resulting infection. Further, if the worker
acquires a disease that is easily spread through contact, there can also
be severe consequences for the surrounding community.

In the Brucella incident at TAMU, at the time of the exposure on February
9, 2006, the lab worker did not know she was infected nor did anyone else
in the lab. In fact, the CDC conducted a routine inspection of TAMU on
February 22, 2006--13 days after the exposure--but had no way of knowing
that it had happened. According to the exposed worker, it was more than 6
weeks after the exposure that she first fell ill. Then, the first
consultation with her physician indicated that she had the flu; it was
only after the symptoms persisted that a consultation with an infectious
disease specialist confirmed that her blood contained an unknown
microorganism. It was at this point that she recalled her work with
Brucella weeks earlier. Confirmation of infection with brucellosis was
made on April 16, 2006, by the Texas State Public Health Lab--62 days
after the exposure. During much of this time, the worker had resumed her
normal activities, interacting with many people.

In fact, the exposed lab worker had become seriously ill and the delay in
recognizing her infection as brucellosis aggravated her condition. Such
misdiagnosis is not uncommon with infectious diseases, as the initial
symptoms often appear flu-like and brucellosis is not generally endemic in
the population. If the worker had not recalled the experiment with
Brucella and alerted her physician to this fact, according to the CDC, she
might have developed an even more severe infection, possibly affecting her
central nervous system or the lining of her heart.

In this incident, it was also fortunate that the disease was such that
transmission beyond the initial exposed individual was difficult and that
there were no risk of spread to the surrounding community. While
brucellosis is not easily transferred between humans, many agents cause
diseases that are easily transferred from human to human through coughing
or fluid transfer, including some agents that are not select agents, such
as SARS and tuberculosis.

According to BMBL, the causative incident for most laboratory-acquired
infections is often unknown. It can only be concluded that an exposure
took place after a worker reports illness--with symptoms suggestive of a
disease caused by the relevant agent--some time later. Since clinical
symptoms can take weeks to become apparent, during which time an infected
person may be contagious, it is important that exposure be identified as
soon as possible and proper diagnosis and prompt medical treatment
provided.

Addressing Confusion over the Definition of Exposure

In addition to the incident of exposure to Brucella, the CDC noted several
incidents of potential exposure to Coxiella burnetii that TAMU had failed
to report. While the Brucella exposure eventually became apparent because
of clinical symptoms in the lab worker, the C. burnetii incidents
illustrate situations where the determination of exposure can be more
problematic. In attempting to address the failure to report, questions
were raised about what constitutes sufficient evidence of an exposure that
the entity must report to the CDC.

One indication of exposure that can be used for C. burnetii and other
agents is to periodically measure the titer levels--antibody
levels--within the blood serum of lab workers working with those agents.
If a person has a raised level over his or her baseline level, then a
conclusion can be drawn that the person has been exposed to the agent.
However, there are issues with using titer levels as an indication of
exposure. For example, determining when the exposure took place is not
straightforward.

TAMU has a program of monitoring blood serum for workers with C.
burnetii--a select agent and the causative agent for Q fever in humans.
While humans are very susceptible to Q fever, only about one-half of all
people infected with C. burnetii show signs of clinical illness. During
the CDC inspection, triggered by the uncovering of the Brucella incident,
CDC came across clinical records that showed that several lab workers were
found to have elevated titers for C. burnetii. But no reports had been
sent to the CDC. The CDC noted this issue and, on April 24, 2007, TAMU
submitted the required Form 3 to report the possible exposure.

However, as a result of subsequent discussion with the individuals who had
the elevated titers, TAMU officials began to have doubts about whether or
not the elevated titers resulted from exposures that had occurred at TAMU.
In one case, TAMU said, one of the infected lab workers had only recently
been hired by TAMU but had worked in a clinical lab in China, where C.
burnetii was known to have been present. In another, the worker claimed to
have been exposed many years earlier and had always registered high,
although the actual levels varied. CDC officials disagree with this
interpretation and believe the high titers resulted from exposures at
TAMU.

TAMU initially responded to the uncovering of the elevated titer incidents
by reporting, to the CDC, any subsequent elevated titer level uncovered in
any of their lab workers. But TAMU is now unsure how to proceed. It has
notified the CDC that, in its opinion, an exposure suggested by an
elevated titer should be defined to have occurred only after clinical
symptoms appear in the individual. TAMU has, therefore, ceased reporting
incidents of merely elevated titers. In the absence of clarity over the
definition of exposure, TAMU officials have chosen to define it as they
see fit.

When we asked the CDC about the confusion over the definition of an
exposure, officials agreed that terms need to be clearly defined and are
drafting new guidance. CDC officials noted, however, that it is unwise to
wait until clinical symptoms appear before determining that an exposure
has taken place, as this could potentially endanger a worker's life and
potentially, in the case of a communicable disease, others.

Experts have told us that correctly interpreting the meaning of elevated
titers--whose characteristics can vary by agent, host, and testing lab--is
challenging since many serological testing methods have not been
validated. Gaps in the scientific understanding of infectious
diseases--such as the meaning of elevated titers--may become more
problematic as the expansion of labs continues. The development of
scientifically sound and standardized methods of identifying exposure is
critical, so that individual lab owners are not left to determine for
themselves what is and what is not reportable.

Ensuring that BSL-4 Labs' Safety and Security Measures Are Commensurate with the
Level of Risk These Labs Present

An hour-long power outage, in June 2007, at the CDC's newest BSL-4
facility raised questions about safety and security, as well as the backup
power system design. The incident showed that, even in the hands of
experienced owners and operators, safety and security of high-containment
labs can still be compromised. The incident also raises concerns about the
security of other similar labs being built around the nation.

On June 8, 2007, the CDC campus in Atlanta experienced lightning strikes
in and around its new BSL-4 facility, and both primary and backup power to
that facility were unavailable. The facility was left with only battery
power--a condition that provides limited power for functions such as
emergency lighting to aid in evacuation. Among other things, the outage
shut down the negative air pressure system, one of the important
components in place to keep dangerous agents from escaping the containment
areas. In looking into the power outage, the CDC determined that, some
time earlier, a critical grounding cable buried in the ground outside the
building had been cut by construction workers digging at an adjacent site.
The cutting of the grounding cable, which had gone unnoticed by CDC
facility managers, compromised the electrical system of the facility that
housed the BSL-4 lab.^15

According to CDC officials, the new BSL-4 facility is still in preparation
to become fully operational and no live agents were inside the facility at
the time of the power outage. However, given that the cable was cut, it is
apparent that the construction was not supervised to ensure the integrity
of necessary safeguards that had been put in place.

Further, according to CDC officials, it was not standard procedure to
monitor the integrity of the electrical grounding of the new BSL-4
facility. However, CDC has now instituted annual testing of the electrical
grounding system.

Because of the power outage incident, questions about the design of the
backup power system for the new facility resurfaced. When the CDC designed
the backup power system for the new BSL-4 facility, it used backup
generators at a central utility plant which serve other facilities, as
well as functions such as chillers, on campus besides the new BSL-4
facility. According to internal documents provided to us, during design
phase for the facility, some CDC engineers had questioned the remotely
placed, integrated design rather than a simpler design using local backup
generators near the facility.

According to CDC facility officials, the full backup power capabilities
for the new BSL-4 facility are not in place yet, but are awaiting
completion of other construction projects on campus. Once these projects
are completed, these officials said, the new BSL-4 facility will have
multiple levels of backup power, including the ability to get power from a
second central utility plant on campus, if needed. But some CDC engineers
that we talked to questioned the degree of complexity in the design. They
are worried that an overly integrated backup might be more susceptible to
failure. As a result of this power outage incident, CDC officials said,
the CDC is doing a reliability assessment for the entire campus power
system, which will include the backup power design for the new BSL-4
facility.

^15A subsequent third-party investigation determined that the grounding of
another building housing CDC's older BSL-4 labs was also compromised in a
similar fashion.

Some experts have suggested that BSL-4 labs be similar in design to a
nuclear power plant, with a redundant backup-to-backup power system, along
with adequate oversight. Like such plants, BSL-4 labs are considered
targets for terrorists and people with malicious intent. Release of an
agent from any of these labs could have devastating consequences.
Therefore, appropriate design of labs and adequate oversight of any nearby
activities--such as adjacent construction with its potential to compromise
buried utilities--are essential.

Maintenance of High-Containment Labs

High-containment labs are highly sophisticated facilities, which require
specialized expertise to design, construct, operate, and maintain. Because
these facilities are intended to contain dangerous microorganisms, usually
in liquid or aerosol form, even minor structural defects--such as cracks
in the wall, leaky pipes, or improper sealing around doors--could have
severe consequences. Supporting infrastructure, such as drainage and waste
treatment systems, must also be secure.

In August 2007, contamination of foot-and-mouth disease was discovered at
several local farms near Pirbright in the U.K., the site of several
high-containment labs that work with live foot-and-mouth disease virus.
Foot-and-mouth disease is one of the most highly infectious livestock
diseases and can have devastating economic consequences. For example, a
2001 epidemic in the U.K. cost taxpayers over -L-3 billion, including some
-L-1.4 billion paid in compensation for culled animals.^16 Therefore, the
U.K. government officials worked quickly to contain and investigate this
recent incident.

The investigation of the physical infrastructure at the Pirbright site
found evidence of long-term damage and leakage of the drainage system
servicing the site, including cracked and leaky pipes, displaced joints,
debris buildup, and tree root ingress. While the definitive cause of the
release has not been determined, it is suspected that contaminated waste
water from Pirbright's labs leaked into the surrounding soil from the
deteriorated drainage pipes and that live virus was then carried offsite
by vehicles splashed with contaminated mud.

^16Department for Environment, Food, and Rural Affairs, Foot and Mouth
Disease: Applying the Lessons (London, U.K.: National Audit Office, Feb.
2, 2005).

The cracked and leaky pipes found at Pirbright are indicative of poor
maintenance practice at the site. The investigation found that (1)
monitoring and testing for the preventative maintenance of pipework for
the drainage system was not a regular practice on site and (2) the
investigation found that a contributing factor might have been a
difference of opinion over responsibilities for maintenance of a key pipe
within the drainage system.

High-containment labs are expensive to build and expensive to maintain.
Adequate funding for each stage needs to be addressed. Typically, in
large-scale construction projects, funding for initial construction comes
from one source. But funding for ongoing operations and maintenance comes
from somewhere else. For example, in the NIAID's recent funding of the 13
BSL-3 labs as RBLs and 2 BSL-4 labs as National Biocontainment Labs (NBL),
the NIAID contributed to the initial costs for planning, design,
construction, and commissioning. But the NIAID did not provide funding to
support the operation of these facilities. In this case, the universities
themselves are responsible for funding any maintenance costs after initial
construction.

The Pirbright incident shows that beyond initial design and construction,
ongoing maintenance plays a critical role in ensuring that
high-containment labs operate safely and securely over time. Because even
the smallest of defects can affect safety, ensuring the continuing
structural integrity of high-containment labs is an essential recurring
activity.

Concluding Observations

The expansion of BSL-3 and BSL-4 labs taking place in the United States is
proceeding in a decentralized fashion, without specific requirements as to
the number, location, activity, and ownership of such labs. While some
expansion may be justified to address deficiencies in lab capacity for the
development of medical countermeasures, unwarranted expansion without
adequate oversight is proliferation, not expansion. Since the full extent
of the expansion is not known, it is unclear how the federal government
can ensure that sufficient but not superfluous capacity--that brings with
it additional, unnecessary risk--is being created.

The limited federal oversight that does exist for high-containment labs is
fragmented among different federal agencies, and for the most part relies
on self-policing. The inherent weaknesses of an oversight system based on
self-policing are highlighted by the Texas A&M University case. While CDC
inspected the labs at Texas A&M in April 2006, as part of its routine
inspection, its inspectors failed to identify that (1) a worker became
exposed and ill; (2) unauthorized experiments were being conducted and
unauthorized individuals were entering the labs; and (3) agents and
infected animals were missing. It was not until a public advocacy group
found out about the Brucella incident and, according to this group,
applied pressure--by demanding records about the incident--that TAMU
reported this incident to the CDC. This report prompted the subsequent
in-depth investigations by the CDC.

However, this incident raises serious concerns about (1) how well the CDC
polices select agent research being conducted in over 400 high-containment
labs at various universities around the country, which are registered
under the Select Agent Program, and (2) whether the safety of the public
is compromised. Moreover, if similar safety breaches are occurring at
other labs, they are not being reported. And the CDC is not finding them
either. According to the experts, no one knows whether the Texas A&M
incidents are the tip of the iceberg or the iceberg.

Mr. Chairman, this concludes my prepared remarks. I would be happy to
respond to any questions that you or other members of the subcommittee may
have at this time.

Contacts and Acknowledgments

For further information regarding this statement, please contact Keith
Rhodes, at (202) 512-6412 or [email protected], or Sushil K. Sharma, Ph.D.,
Dr.PH, at (202) 512-3460 or [email protected]. Contact points for our
Offices of Congressional Relations and Public Affairs may be found on the
last page of this statement. William Carrigg, Jeff McDermott, Jean
McSween, Jack Melling, Laurel Rabin, Corey Scherrer, Rebecca Shea, and
Elaine Vaurio made key contributions to this statement.

Appendix I: Scope and Methodology

To determine the extent of expansion in the number of high-containment
facilities and the areas experiencing the growth, we interviewed agency
officials and experts, as well as reviewed documents provided by agencies
and the literature.

To determine which federal agency has the mission to track and determine
the aggregate risks associated with the proliferation of BSL-3 and BSL-4
labs in the United States, we surveyed 12 federal agencies that are
involved with BSL-3 or BSL-4 labs in some capacity--for example, research,
oversight, or monitoring. The survey requested information on the agency's
involvement with high-containment labs--specifically, whether the agency
has a mission to track the number of high-containment labs, whether it has
a need to know, and whether it knows the number of operating BSL-3 and
BSL-4 labs. The agencies that received our survey include the U.S.
Department of Agriculture (USDA); the Department of Commerce; the
Department of Defense; the Department of Energy; the Environmental
Protection Agency; the Department of Health and Human Services (HHS),
including the Centers for Disease Control and Prevention (CDC); the
Department of Homeland Security; the Department of Interior; the
Department of Justice, including the Federal Bureau of Investigation
(FBI); the Department of Labor, including Occupational Safety and Health
Administration (OSHA); and the Department of States. In addition, we sent
our survey to intelligence agencies, including the Central Intelligence
Agency (CIA), the National Counter-Terrorism Center (NCTC); the Defense
Intelligence Agency (DIA); and the Office of Intelligence Analysis within
DHS. We also met with officials of the Select Agent Program at both the
CDC and the USDA to gain additional information about the expansion of
high-containment labs. Finally, we reviewed documents these agencies
provided, including pertinent legislation, regulation, and guidance, and
reviewed scientific literature on risks associated with high-containment
labs.

To develop lessons learned from recent incidents at three high-containment
labs, we interviewed academic experts in microbiological research
involving human, animal, and plant pathogens, and conducted site visits at
selected federal, civilian, military, academic, and commercial BSL-3 and
BSL-4 labs, including the sites involved in the recent incidents.
Specifically, we conducted site visits to the CDC and Texas A&M University
(TAMU); talked to the U.K. officials at Health Safety Executive and the
Department for Environment, Food, and Rural Affairs; and reviewed
documents and inspection reports.

To discuss the incidents at TAMU and the CDC, we conducted site visits and
interviewed the relevant officials. We also conducted a site visit to the
CDC and interviewed relevant officials, including the officials of CUH2A,
Inc.--the contractor who designed the backup power system for the new
BSL-4 lab in Atlanta--as well as the expert hired by this firm to conduct
the reliability study for the backup power system.

We conducted our work from August 2006 through September 2007 in
accordance with generally accepted government auditing standards

Appendix II: Pertinent Regulations

The regulations governing the Select Agent Program became effective on
April 15, 1997, and were revised in March 2005. The regulations include
six primary components: (1) a list of select agents that have the
potential to pose a severe threat to public health and safety; (2)
registration of facilities before the domestic transfer of select agents;
(3) a process to document successful transfer of agents; (4) audit,
quality control, and accountability mechanisms; (5) agent disposal
requirements; and (6) research and clinical exemptions.

For facilities registered with the CDC and the USDA that possess, use, or
transfer select agents, the select agent regulations require (1) an FBI
security risk assessment for a number of individuals, including each
person who is authorized to have access to select agents and toxins; (2)
written biosafety and incident response plans; (3) training of individuals
with access to select agents and of individuals who will work in or visit
areas where select agents or toxins are handled and stored; (4) a security
plan sufficient to safeguard the select agent or toxin against
unauthorized access, theft, loss, or release, and designed according to a
site-specific risk assessment that provides protection in accordance with
the risk of the agent or toxin; (5) possible inspection by the CDC or USDA
of the facility and its records before issuance of the certificate of
registration; (6) maintenance of records relating to the activities
covered by the select agent regulations; and (7) facility registration
with the CDC or the USDA that indicates (a) each select agent that the
entity intends to possess, use, or transfer; (b) the building where the
agent will be used and stored; (c) the laboratory safety level; (d) a list
of people authorized to have access to each select agent; (e) the
objectives of the work for each select agent, including a description of
the methodologies or laboratory procedures to be used; (f) a description
of the physical security and biosafety plans; and (g) assurance of
security and biosafety training for individuals who have access to areas
where select agents are handled and stored.

Appendix III: The Select Agents and Toxins List

HHS Select Agents and Toxins

Abrin
Cercopithecine herpesvirus 1 (Herpes B virus)
Coccidioides posadasii
Conotoxins
Crimean-Congo haemorrhagic fever virus
Diacetoxyscirpenol
Ebola virus
Lassa fever virus
Marburg virus 
Monkeypox virus
Reconstructed 1918
influenza virus^1
Ricin
Rickettsia prowazekii
Rickettsia rickettsii
Saxitoxin
Shiga-like ribosome inactivating proteins
South American Haemorrhagic Fever viruses
  Flexal
  Guanarito
  Junin
  Machupo
  Sabia
Tetrodotoxin
Tick-borne encephalitis complex (flavi) viruses
  Central European Tick-borne encephalitis
  Far Eastern Tick-borne encephalitis
  Kyasanur Forest disease
  Omsk Hemorrhagic Fever
  Russian Spring and Summer encephalitis
Variola major virus (Smallpox virus) and Variola minor virus (Alastrim)
Yersinia pestis

USDA Select Agents and Toxins
African horse sickness virus
African swine fever virus
Akabane virus
Avian influenza virus (highly pathogenic)
Bluetongue virus (Exotic)
Bovine spongiform encephalopathy agent
Camel pox virus
Classical swine fever virus
Cowdria ruminantium (Heartwater) 
Foot-and-mouth disease virus
Goat pox virus
Japanese encephalitis virus
Lumpy skin disease virus
Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1)
Menangle virus
Mycoplasma capricolum/ M.F38/M. mycoides Capri
  (contagious caprine pleuropneumonia)
Mycoplasma mycoides mycoides (contagious bovine pleuropneumonia)
Newcastle disease virus (velogenic)
Peste des petits ruminants virus
Rinderpest virus
Sheep pox virus
Swine vesicular disease virus
Vesicular stomatitis virus (exotic)

^1Reconstructed replication-competent forms of the 1918 pandemic influenza
virus containing any portion of the coding regions of all eight gene
segments.

Overlap Select Agents and Toxins
Bacillus anthracis
Botulinum neurotoxins
Botulinum neurotoxin producing species of Clostridium
Brucella abortus
Brucella melitensis
Brucella suis
Burkholderia mallei (formerly Pseudomonas mallei)
Burkholderia pseudomallei (formerly Pseudomonas pseudomallei)
Clostridium perfringens epsilon toxin
Coccidioides immitis
Coxiella burnetii
Eastern Equine Encephalitis virus
Francisella tularensis
Hendra virus
Nipah virus
Rift Valley fever virus
Shigatoxin
Staphylococcal enterotoxins
T-2 toxin
Venezuelan Equine Encephalitis virus

USDA Plant Protection and Quarantine (PPQ) Select Agents and Toxins
Candidatus Liberobacter africanus
Candidatus Liberobacter asiaticus
Peronosclerospora philippinensis
Ralstonia solanacearum race 3, biovar 2
Schlerophthora rayssiae var zeae
Synchytrium endobioticum
Xanthomonas oryzae pv. Oryzicola
Xylella fastidiosa (citrus variegated chlorosis strain)

Appendix IV: Biological Agents Recommended for BSL-3 or BSL-4 Containment
that Are Not Select Agents

There are a number of biological agents causing severe illness or death
that are not select agents. For example, there are five agents that are
recommended for containment at BSL-4 because of (1) their close antigenic
relationship with a known BSL-4 agent and (2) the fact that there is
insufficient experience working with them (see table 5).

Table 5: Nonselect Agents Recommended for BSL-4 Containment

Agent      Family     
Absettarov Flavivirus 
Alkhumra   Flavivirus 
Hanzalova  Flavivirus 
Hypr       Flavivirus 
Kumlinge   Flavivirus 

Source: GAO analysis of BMBL data, 5^th Edition

BMBL containment and safety recommendations for B. anthracis, the
causative agent for anthrax and a select agent, are to include the use of
BSL-2 practices, containment equipment, and facilities for clinical and
diagnostic quantities of infectious cultures. However, BSL-3 practices,
containment equipment, and facilities are recommended for (1) work
involving production quantities or high concentrations of cultures,
screening environmental samples especially with powders, and (2) for
activities with a high potential for aerosol production. Safety and
containment recommendations for some agents, which are not regulated under
the Select Agent Program, are as strict or stricter than the
recommendations for B. anthracis. Some nonselect agents, to which
containment recommendations at BSL-3 under certain conditions apply, are
listed in table 6.

Table 6: Some Nonselect Agents Requiring BSL-3 Containment under Certain
Conditions

Agent                                      Disease                         
Bordetella pertussis                       pertussis (whooping cough)      
Chlamydia psittaci                         psittacosis                     
Mycobacterium tuberculosis complex         tuberculosis                    
Neisseria gonorrhoeae                      gonorrhea                       
Neisseria meningitidis                     meningitis, septicema           
Salmonella typhi                           typhoid fever                   
Hepatitis B, C, and D viruses              hepatitis B, hepatitis C        
Human herpes virus                         herpes simplex et al.           
Noncontemporary human influenza strains    influenza                       
(H2N2)                                                                     
Lymphocytic choriomeningitis virus         aseptic meningitis,             
                                              encephalitis                    
Lyssaviruses                               rabies                          
Retroviruses                               HIV                             
SARS coronavirus                           SARS                            

Source: GAO analysis of BMBL data, 5^th Edition

Appendix V: Description of Incidents at Texas A&M University

TAMU is registered with CDC's Select Agent Program and approved for work
on several select agents. TAMU has several BSL-3 laboratories and works
extensively on animal diseases, including those caused by the select
agents Brucella melitensis, Brucella abortus, and Brucella suis. Brucella
can cause brucellosis in humans, a disease causing flu-like symptoms such
as fever and fatigue. But in severe cases, it can cause infections of the
central nervous system. TAMU is also registered for use of Coxiella
burnetii, an animal agent that can cause Q fever in humans.

According to the CDC, in February 2006, a lab worker was helping out with
an experiment to aerosolize Brucella. The lab worker had no familiarity
with the specifics of working with Brucella, but did have experience
working with the aerosol chamber. It was determined that the lab worker
got exposed to the agent during cleaning of the chamber after the
experiment was run.

At the time of the exposure, neither the exposed worker nor anyone else
had any indication that an exposure had taken place. In fact, CDC
inspectors were on campus days after the Brucella exposure for a routine
inspection but uncovered nothing that alerted them to the fact that an
incident had taken place.^1 Symptoms did not start to appear in the
exposed worker until more than a month after the exposure, and then the
symptoms were flu-like. Confirmation of brucellosis was not made until
another month had passed and symptoms had worsened. However, once the
brucellosis determination had been made, the worker notified appropriate
authorities at TAMU. But no report was subsequently made to the CDC as
required by federal regulation and a year passed before--by chance--an
independent watchdog group reviewing unrelated documentation,^2 acquired
through the Freedom of Information Act (FOIA),^3 uncovered the lapse in
reporting and forced TAMU to notify the CDC.

The subsequent investigation by the CDC revealed a number of other
violations of the select agent regulations including (1) TAMU was not
authorized to aerosolize Brucella in the first place; (2) a number of lab
workers from another BSL-3 lab had tested positive for Coxiella antigens
in their blood serum, suggesting potential exposures had taken place for
that agent as well, but without reports going to CDC; (3) unauthorized
access to select agents and toxins; (4) missing vials and animals; (5) and
other protocol and procedural deficiencies.

^1The CDC inspected labs at TAMU on February 22, 2006, and documented 47
facility "departures," but did not note any of the violations later
uncovered.

^2The Sunshine Project, Mandate for Failure, The State of Institutional
Biosafety Committees in an Age of Biological Weapons Research (Austin,
Texas, Oct. 4, 2004).

^35 U.S.C. S 552.

On April 20, 2007, the CDC issued a cease-and-desist order for all work on
Brucella within the affected high-containment lab, as well as all
aerosolization work at TAMU involving select agent and toxins. That order
was subsequently expanded to include all work with select agents and
toxins at TAMU--the first time the CDC has ever issued such an order
entitywide under the select agent regulations. That order remains in
effect as of the date of this testimony.

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(460587)

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Highlights of [47]GAO-08-108T , a testimony before the Subcommittee on
Oversight and Investigation, Committee on Energy and Commerce, House of
Representatives

October 4, 2007

HIGH-CONTAINMENT BIOSAFETY LABORATORIES

Preliminary Observations on the Oversight of the Proliferation of BSL-3
and BSL-4 Laboratories in the United States

In response to the global spread of emerging infectious diseases and the
threat of bioterrorism, high-containment biosafety laboratories
(BSL)--specifically biosafety level (BSL)-3 and

BSL-4--have been proliferating in the United States. These
labs--classified by the type of agents used and the risk posed to
personnel, the environment, and the community--often contain the most
dangerous infectious disease agents, such as Ebola, smallpox, and avian
influenza. This testimony addresses (1) the extent to which there has been
a proliferation of BSL-3 and BSL-4 labs, (2) federal agencies'
responsibility for tracking this proliferation and determining the
associated risks, and (3) the lessons that can be learned from recent
incidents at three high-containment biosafety labs. To address these
objectives, GAO asked 12 federal agencies involved with high-containment
labs about their missions and whether they tracked the number of labs
overall. GAO also reviewed documents from these agencies, such as
pertinent legislation, regulation, and guidance. Finally, GAO interviewed
academic experts in microbiological research.

A major proliferation of high-containment BSL-3 and BSL-4 labs is taking
place in the United States, according to the literature, federal agency
officials, and experts. The expansion is taking place across many
sectors--federal, academic, state, and private--and all over the United
States. Concerning BSL-4 labs, which handle the most dangerous agents, the
number of these labs has increased from 5--before the terrorist attacks of
2001--to 15, including at least 1 in planning stage. Information on
expansion is available about high-containment labs that are registered
with the Centers for Disease Control and Prevention (CDC) and the U.S.
Department of Agriculture's (USDA) Select Agent Program, and that are
federally funded. However, much less is known about the expansion of labs
outside the Select Agent Program, as well as the nonfederally funded labs,
including location, activities, and ownership.

No single federal agency, according to 12 agencies' responses to our
survey, has the mission to track the overall number of BSL-3 and BSL-4
labs in the United States. Though several agencies have a need to know, no
one agency knows the number and location of these labs in the United
States. Consequently, no agency is responsible for determining the risks
associated with the proliferation of these labs.

We identified six lessons from three recent incidents: failure to report
to CDC exposures to select agents by Texas A&M University (TAMU); power
outage at the CDC's new BSL-4 lab in Atlanta, Georgia; and release of
foot-and-mouth disease virus at Pirbright in the United Kingdom. These
lessons highlight the importance of (1) identifying and overcoming
barriers to reporting in order to enhance biosafety through shared
learning from mistakes and to assure the public that accidents are
examined and contained; (2) training lab staff in general biosafety, as
well as in specific agents being used in the labs to ensure maximum
protection; (3) developing mechanisms for informing medical providers
about all the agents that lab staff work with to ensure quick diagnosis
and effective treatment; (4) addressing confusion over the definition of
exposure to aid in the consistency of reporting; (5) ensuring that BSL-4
labs' safety and security measures are commensurate with the level of risk
these labs present; and (6) maintenance of high-containment labs to ensure
integrity of physical infrastructure over time.

Summary of Known BSL-4 Labs in the United States by Sector

Sector             Before 1990 1990-2000 2001-Present Total 
Federal government           2         1            6     9 
Academic                     0         1            3     4 
State                        0         0            1     1 
Private                      0         1            0     1 
Total                        2         3           10    15 

Source: GAO analysis based on open source information.

References

Visible links
  30. http://www.gao.gov/cgi-bin/getrpt?GAO-07-1135T
  31. http://www.gao.gov/cgi-bin/getrpt?GAO-07-333R
  32. http://www.gao.gov/cgi-bin/getrpt?GAO-07-265
  33. http://www.gao.gov/cgi-bin/getrpt?GAO-07-70
  34. http://www.gao.gov/cgi-bin/getrpt?GAO-06-793
  35. http://www.gao.gov/cgi-bin/getrpt?GAO-06-644
  36. http://www.gao.gov/cgi-bin/getrpt?GAO-06-132
  37. http://www.gao.gov/cgi-bin/getrpt?GAO-05-214
  38. http://www.gao.gov/cgi-bin/getrpt?GAO-03-847
  39. http://www.gao.gov/cgi-bin/getrpt?GAO-03-315R
  40. http://www.gao.gov/
  41. http://www.gao.gov/
  42. http://www.gao.gov/fraudnet/fraudnet.htm
  43. mailto:[email protected]
  44. mailto:[email protected]
  45. mailto:[email protected]
  46. http://www.gao.gov/cgi-bin/getrpt?GAO-08-108T
  47. http://www.gao.gov/cgi-bin/getrpt?GAO-08-108T
*** End of document. ***