Listed Priority Pathogens as Triggers for Declarations:

ESTIMATED NUMBER OF US SITES CONTAINING/WORKING WITH AGENTS LISTED IN THE ROLLING TEXT

(Purely diagnostic or therapeutic facilities excluded)

Federation of American Scientists Working Group on BW Verification

August 1997

The US government controls nearly all the listed pathogens, and their locations are on record under:

1. US Department of Agriculture, Animal and Plant Health Inspection Service:

a) All the listed animal pathogens are restricted to a small number of sites, which must obtain permits.

b) Permits are required for all the listed plant pathogens.

c) Veterinary biologics producers must be licensed for interstate commerce.

2. US Food and Drug Administration (FDA): Producers of biologics for human use must be licensed, for interstate commerce.

3. US Centers for Disease Control (CDC): Requires registration of all sites transferring or receiving listed human agents.

4. US Department of Defense, Chemical and Biological Defense Program: all its primary sites and its many contractors, and their projects, are accessible for compilation by government.

There are a number of other readily accessible sources for information on commercial and research activities with listed pathogens. These include Federal research funding agencies such as NIH, NSF, USDA, etc.

1. Participants in the (Medical) Biological Defense Research Program

(Source: Environmental Impact Statement, BDRP, April 1989*)

3 Primary (government) sites; those using agents: 3

80 contractors; those US sites using agents: 52

(9 government, 5 commercial, 38 non-profit)

*Later detailed information is not publicly available. However, the number of sites has probably not increased significantly, if at all, since the year reported (1988), for which total obligations were $ 61,760,000, compared to the total medical BDRP budget for 1995: $ 50,213,000.

2. Participants in the Non-Medical BDRP

(Sources: US Annual BWC CBM report, April, 1995; DARPA)

Total: 79 sites, plus secondary contractors; those using listed agents: <15

(Numbers of sites not given); those using agents: est. <5

3. Non-BDRP US Government Sites

DOD, FDA, CDC, NIH, USDA, etc. (some have several sites): Total with >50 l, est. 20

4. Licensed Biologics Producers

(Sources: FDA: "Establishments and Products Licensed Under Section 351 of the Public Health Service Act, 1 March 1991;" Center for Veterinary Biologics, APHIS, USDA: "Veterinary Biological Products, Licensees and Permittees, February 1997;" K. Johnston, Bayer Agriculture Division)

Licensed US producers using listed agents for human use: <10

(Agents used: anthrax, botulinum, cholera, diptheria, plague, rabies, tetanus, yellow fever. Some probably use avirulent or attenuated strains or cloned antigens, which are exempt)

There are < 43 licensed US producers using listed agents for veterinary biologics; some of these no doubt use only attenuated or avirulent organisms. Twenty companies produce products for further manufacture; many of the others probably buy and re- formulate, using only killed, attenuated or avirulent organisms. Those handling live, virulent listed agents, <40

There are also some very small unlicensed intrastate companies, but few are likely to handle listed agents. Those that do, est. <10

5. Other Commercial Sites

(Sources: Institute for Biotechnology Information (IBI): "Pharmaceutical Industry Guide, 1997," "Biotechnology Industry Guide, 1996," and telephone consultation; Stanford Research Institute: "SRI Directory of US Chemical Producers, 1989;" expert consultation)

IBI lists <15 pharmaceutical companies that could possibly use listed agents;

IBI lists 1330 biotech companies (excluding pharmaceuticals and including many very small start-up companies, often without marketed products); 318 of these work in areas that might involve pathogens of any kind; est/ <<50 use listed agents;

There are fewer than 100 companies working on antimicrobials, of which <15 may use listed agents for testing products;

SRI and experts: 200-250 companies use fermentation for producing chemicals of any kind (including pharmaceutical and biotech companies but not biologicals producers); of these, <<50 are estimated to use listed agents.

Other (non-biologicals) commercial sites using listed agents: Total, est. <50

(Subtotal: sites (excluding non-BDRP research sites) with listed agents: <205)

6. Non-BDRP Research Sites

ANALYSIS BASED ON INDIVIDUAL AGENTS

These are mainly academic research institutions. There is some overlap with BDRP contractors; a few government laboratories are also included. Thus, there is some double-counting in adding these data to the above categories.

Human pathogens (43 listed; see page 10)

(Sources: expert opinions and Medline literature search)

a) Viruses (17 listed)

The following agents require BL4 containment:

1. Crimean-Congo hemorrhagic fever virus

4. Ebola virus

5. Hantavirus (Hantaan)

7. Junin virus

8. Lassa fever virus

9. Machupo virus

10. Marburg virus

12. Tick-borne encephalitis (Russian spring-summer) virus

17. Kyasanur Forest fever virus

There are 9 BL4 labs in the US, plus 3 or 4 that may work with BL4 agents in enhanced BL3 facilities.

Therefore, about 13 sites might use these agents. Those using listed human viruses requiring BL4 containment, 13

No. 11, Rift Valley Fever, is restricted by USDA to 2 or 3 sites: 3

No. 13, Smallpox, is restricted by WHO to 1 site: 1

Nos. 14 (Venezuelan encephalitis virus) and 16 (Yellow fever) are usually studied in attenuated form or as incomplete genomes; Those using whole virulent agents, based on 3-yr. literature search: no. 14: 6 no. 16: 5

Nos. 2 (Chikungunya) and 6 (Japan. encephalitis) require BL3 or enhanced; Those using no. 2, expert est. 6 Those using no. 6, expert est. 6

Nos. 3 (Eastern encephalitis virus) and 15 (Western encephalitis virus) are indigenous to the US. Based on 3-yr literature search, Those using no. 3, 10 Those using no. 15, 6

b) Bacteria (8 listed, all endemic in parts of the US)

No. 1, Bacillus anthracis: exp. est. <<50 sites; est. based on 3-yr lit. search, 9

No. 2, Brucella: exp. est. <<50 sites; est. based on literature search, 13

No. 3, Chlamydia psittaci: expert est. <10

No. 4, Clostridium botulinum: expert est. <20

No. 5, Francisella tularensis: expert est. <10

No. 6, Pseudomonas mallei: expert est. <10

No. 7, Pseudomonas pseudomallei: expert est. <10

No. 8, Yersinia pestis: exp. est. <20 sites; based on 3-yr literature search, 9

c) Rickettsiae (3 listed)

No. 1, Coxiella burnetti: expert est. <<10 sites

No. 2, Rickettsia prowazekii: expert est. <<10 sites

No. 3, Rickettsia rickettsii: expert est. <<10 sites T

otal number of sites for all three (considerable overlap expected): <10

d) Fungi (1 listed)

Histoplasma capsulatum: exp. est. <60 sites; based on literature search, about 20

e) Toxins (14 listed)

Only toxin-producing organisms and significant toxin stocks considered here. (Source: Dr. Jack Melling, Director, Salk Institute Biologicals Development Center)

Toxins are widely used in research, but in very small quantities, which are almost always bought from a few suppliers. There are very few companies in the toxin- producing business, including those making products for medical use. Botulin and ricin are the most commonly used. Botulin: only two or three companies make botulin (of which it is estimated that several tens of thousands of vials, containing of the order of 10-20 ng, are sold each year in the US). Thus, even a low threshold would eliminate almost all users. Ricin: for medical purposes, only the A chain (incomplete toxin) is used; for production, the A chain is probably cloned in an otherwise harmless bacterium.

Total number of sites with organisms that can produce listed toxins, and/or with significant toxin stocks: est. <20

(Subtotal: non-BDRP research sites with listed human agents: <197 )

(There is tremendous overlap here. Many laboratories study a variety of pathogens.)

Animal pathogens (18 listed: see page 11)

(Sources: Animal and Plant Health Inspection Service (APHIS), US Dept. of Agriculture; Dr. L. King, Dean, Michigan State U. School of Veterinary Medicine, former Director of APHIS)

No. 9, Herpes B (monkey) is a primate virus requiring BL4 for propagation. Number of sites, est. <5

All other listed animal pathogens are restricted by APHIS (USDA) to a few sites:

No. 3, Bluetongue virus 30

No. 11, Newcastle disease virus 24

No. 18, Vesicular stomatitis virus 126

All others, total 15

(Subtotal: Non-BDRP research sites with listed animal agents: <200)

(Considerable overlap here)

Plant Pathogens (19 listed; see page11)

(Sources: Plant Protection Quarantine, APHIS, USDA: Web site and telephone consultation)

For more than 20 years, USDA has required permits for all the agents on the list. The permits are valid for two years and must be renewed unless the agent is de- stroyed. The permits specify no further distribution. In 1996 there were 147 permits issued for plant pathogens that are exotic or not widely distributed in the US; about 51 of these were for listed pathogens. Thus, about 102 such permits are issued in two years, and this is equivalent to the approximate number of currently valid permits for listed agents. Many of these permits were issued to the same person or institution; thus, there is considerable overlap.

Total number of sites with listed plant pathogens (corrected for overlap) about 75

(Subtotal: Non-BDRP research sites with listed plant agents: 75)

_________________________________________

Grand Total:

BDRP, government and commercial sites <205

Non-BDRP research sites with listed human agents <197

Non-BDRP research sites with listed animal agents <200

Non-BDRP research sites with listed plant agents 75

Approximate Maximum Number of US Sites with Listed Agents, TOTAL <677 (This number is the sum of high individual estimates with significant overlap)

PROBABLE TOTAL No. OF US SITES WITH LISTED AGENTS, about 550

Appendix

LIST OF AGENTS AND TOXINS

from Rolling Text, 1 August 1997

Human Pathogens