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1 Introduction 1.1 BACKGROUND In fall 2001, shortly after the September 11 attacks in New York City and Washington, D.C., U.S. citizens experienced a second set of attacks, this time involving the bacterium Bacillus anthracis (B. anthracis, or more simply, anthrax) placed in at least four and possibly five letters and sent through the mail. From October 4 to November 20, 2001, 22 cases of anthrax were identified—11 inhalational and 11 cutaneous. Five of the inhalational cases were fatal (Jernigan et al., 2002). Twenty infected individuals contracted anthrax as mail handlers or at worksites where contaminated mail was processed or received. Two victims who died from the infection had no known contact with any of the worksites in question. An additional 31 people tested positive for exposure to B. anthracis spores; approximately 32,000 individuals initiated antibiotic prophylaxis (Centers for Disease Control and Prevention [CDC], 2001a; Jernigan et al., 2002). Over the course of its investigation, known by the case name “Amerithrax,” the Federal Bureau of Investigation (FBI) devoted 600,000 investigator work hours to the case and assigned 17 Special Agents to a Task Force, along with 10 U.S. Postal Inspectors. The investigation spanned six continents; involved over 10,000 witness interviews, 80 searches, 26,000 email reviews, and analyses of 4 million megabytes of computer memory; and resulted in the issuance of 5,750 grand jury subpoenas (U.S. Department of Justice [DOJ], 2010, p. 4). Additionally, 29 government, university, and commercial laboratories assisted in conducting the scientific analyses that were a central aspect of the investigation (U.S. Department of Justice [USDOJ], 2010, p. 4). The investigation also accelerated the development of a nascent scientific field, called microbial forensics, involving a series of laboratory tests to pin - point the genetic identity of a microbial agent used for nefarious purposes. This field grew out of the multidisciplinary areas of genomics, microbiology, and forensics, among others. The development and application of microbial forensics became an essential part of the scientific investigation in the hands of 25

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26 SCIENTIFIC APPROACHES USED TO INVESTIGATE THE ANTHRAX LETTERS FBI investigators, who combined it with physicochemical analyses to narrow their search for the source of the anthrax used in the attacks. 1 In 2008, seven years into the Amerithrax investigation, the FBI asked the National Research Council of the National Academy of Sciences (NAS) to conduct an independent review of the scientific approaches used during the investigation of the 2001 B. anthracis mailings (see Box 1-1). During the course of the NRC committee’s deliberations, the DOJ announced on February 19, 2010, that it was closing the case based on its con - clusion that Dr. Bruce Ivins, a scientist at the U.S. Army Medical Research Insti - tute of Infectious Diseases (USAMRIID), had alone perpetrated the anthrax attacks. Dr. Ivins died on July 29, 2008 after taking an overdose of over-the- counter medications. The committee carried out its work mindful of the need to identify lessons that could be learned for future investigations in which science might play an important role. 1.2 CHRONOLOGY OF EVENTS OF FALL 2001 Public health officials in Florida announced on October 4, 2001, that Robert Stevens, a photo editor at American Media, Inc. (AMI) in Boca Raton, had inhalational anthrax. This was the first reported case of inhalational anthrax in the United States in almost 25 years. After one of Stevens’s coworkers, Ernesto Blanco, also fell ill and was diagnosed as having contracted anthrax, environmental assessments were made of the AMI facility. These assessments revealed B. anthracis contamination and postexposure prophylactic treatment was administered to AMI employees. No contaminated letter was ever found; it is thought to have been discarded after being opened (CDC, 2001a). A timeline of this and subsequent events is presented in Table 1-1. Less than two weeks later, additional cases of apparent anthrax exposure began to appear in New York City. These cases indicated the possible source of the exposure as most of those infected had come into contact with letters containing a powder. The New York letters addressed to Tom Brokaw of NBC News and the New York Post had a Trenton, New Jersey, postmark dated Sep- tember 18, 2001. Sampling of U.S. Postal Service drop boxes in the Trenton area found anthrax spores in only one mailbox, on Nassau Street in Princeton (see Chapter 3). A second wave of mailings caused additional cases of anthrax. Two more anthrax letters bearing the same Trenton postmark, but dated October 9, 2001, were addressed to Democratic U.S. Senators Tom Daschle of South Dakota and 1 In 2008 the National Bioforensic Analysis Center was established in the Department of Home - land Security’s National Biodefense Analysis and Countermeasure Center to assist in microbial forensics investigations.

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27 INTRODUCTION BOX 1-1 Charge to the Committee The NRC was asked by the FBI to conduct an independent review of the scientific approaches used during the investigation. The official charge to the committee stated: An ad hoc committee with relevant expertise will evaluate the scientific founda- tion for the specific techniques used by the FBI to determine whether these techniques met appropriate standards for scientific reliability and for use in forensic validation, and whether the FBI reached appropriate scientific con- clusions from its use of these techniques. In instances where novel scientific methods were developed for purposes of the FBI investigation itself, the com- mittee will pay particular attention to whether these methods were appropriately validated. The committee will review and assess scientific evidence (studies, results, analyses, reports) considered in connection with the 2001 Bacillus anthracis mailings. In assessing this body of information, the committee will limit its inquiry to the scientific approaches, methodologies, and analytical techniques used during the investigation of the 2001 B. anthracis mailings. The areas of scientific evidence to be studied by the committee include, but may not be limited to: 1. genetic studies that led to the identification of potential sources of B. anthracis recovered from the letters; 2. analyses of four genetic mutations that were found in evidence and that are unique to a subset of Ames strain cultures collected during the investigation; 3. chemical and dating studies that examined how, where, and when the spores may have been grown and what, if any, additional treatments they were subjected to; 4. studies of the recovery of spores and bacterial DNA from samples col- lected and tested during the investigation; and 5. the role that cross contamination might have played in the evidence picture. The committee will necessarily consider the facts and data surrounding the investigation of the 2001 Bacillus anthracis mailings, the reliability of the prin- ciples and methods used by the FBI, and whether the principles and methods were applied appropriately to the facts. The committee will not, however, under- take an assessment of the probative value of the scientific evidence in any specific component of the investigation, prosecution, or civil litigation and will offer no view on the guilt or innocence of any person(s) in connection with the 2001 B. anthracis mailings, or any other B. anthracis incidents.

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28 SCIENTIFIC APPROACHES USED TO INVESTIGATE THE ANTHRAX LETTERS TABLE 1-1 Timeline of Key Events in the Anthrax Mailings Case September: Letters containing anthrax spores are mailed to news organizations 2001 in New York (ABC, CBS, NBC, and the New York Post) and Florida (American Media, Inc.). While only two letters are actually recovered (one addressed to the New York Post and the other to Tom Brokaw at NBC), the existence of other letters is inferred from the pattern of infection (Piggee, 2008; Ember, 2006). September 18: Postmark date on the Post and Brokaw anthrax letters. The postmark indicates that the letters were mailed from Trenton, New Jersey (Cole, 2009, p. 89). October: Letters containing anthrax spores are mailed to U.S. Senators Thomas A. Daschle and Patrick Leahy in Washington, D.C. The FBI begins an investigation— code-named Amerithrax—into the mailings (Piggee, 2008). October 4: Robert Stevens, a photo editor working for American Media, Inc., in Boca Raton, Florida, is diagnosed with inhalational anthrax, believed to have been contracted as a result of contamination of his workplace by an anthrax mailing. The diagnosis, initially made by a physician-microbiologist at the hospital where Stevens received care, was then confirmed at the Florida State Laboratory in Jacksonville and the U.S. Centers for Disease Control and Prevention (Traeger, 2002). October 5: Robert Stevens dies from inhalational anthrax. He is the first of five persons to die of the illness. In total, 11 individuals are believed to have contracted inhalational anthrax as a result of the mailings (Ember, 2006; Cole, 2009, p. 197). October 9: Postmark date on the Daschle and Leahy anthrax letters. The postmark also indicates that the letters were also mailed from Trenton, New Jersey (USDOJ, 2010). October 12: The FBI recovers the Brokaw letter (USDOJ, 2010, p. 4). A case of cutane- ous anthrax is confirmed in Erin O’Connor, an assistant to Tom Brokaw. She is the first of 11 persons believed to have contracted cutaneous anthrax as a result of the anthrax mailings (Cole, 2009, p. 54). October 15: The Daschle letter is opened in the Senator’s office in the Hart Senate Office Building (Cole, 2009, p. 89). October 16, 17: The Hart Senate Office Building and other U.S. Senate and House office buildings are closed (Ember, 2006). October 18: The U.S. Postal Service’s Trenton Processing and Distribution Center in Hamilton Township, New Jersey, is closed for anthrax testing (Cole, 2009, p. 92). On the same day, in a joint announcement with Postmaster General Jack Potter, FBI Director Robert Mueller offers a $1 million reward for “information leading to the arrest and conviction for terrorist acts of mailing anthrax” (FoxNews, 2001). October 19: The New York Post letter is discovered and recovered (USDOJ, 2010, p. 4). October 21: Thomas L. Morris, Jr., a postal worker at the Washington, D.C., Brentwood Mail Processing and Distribution Center, which serviced Capitol Hill, is the second person to die from inhalational anthrax believed to have been contracted as a result of the anthrax mailings.(Cole, 2009, p. 65). The Brentwood Mail Processing and Distribution Center is closed the same day (Cole, 2009, p. 75). October 22: Joseph P. Curseen, Jr., a postal worker at the Washington, D.C., Brentwood Mail Processing and Distribution Center, is the third person to die from inhalational anthrax believed to have been contracted as a result of the anthrax mailings (Cole, 2009, p. 65).

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29 INTRODUCTION TABLE 1-1 Continued October 31: Kathy T. Nguyen, a hospital worker at the Manhattan Eye, Ear, and Throat Hospital, is the fourth person to die from inhalational anthrax believed to have been contracted as a result of the anthrax mailings (Cole, 2009, p. 5). November 16: In a joint operation, the FBI, U.S. Environmental Protection Agency, and U.S. Postal Inspection Service discover the Leahy letter in a bag of unopened mail (Piggee, 2008). November 21: Ottilie Lundgren, an elderly woman in Oxford,Connecticut dies from inhalational anthrax. She is the last person to die from inhalational anthrax believed to have been contracted as a result of the mailings (Cole, 2009, p. 108). December: The Leahy letter is opened and examined at the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) at Fort Detrick in Frederick, Maryland (Cole, 2009, p. 90). December 31: The Dirksen Senate Office Building, which is connected to the Hart Senate Office Building by underground corridors, is reopened (New York Times, 2002). 2002 January 23: The Hart Senate Office Building is reopened. On the same day, the FBI increases the reward for help in solving the case to $2.5 million (Gallucci-White, 2008, p. 8). June: Officials say the FBI is “scrutinizing 20 to 30 scientists who might have had the knowledge and opportunity to send the anthrax letters” (Gallucci-White, 2008, p. 8). August 6: Attorney General John Ashcroft publicly names Steven J. Hatfill, a former USAMRIID scientist and biodefense expert, as a “person of interest” in the Amerithrax investigation. Hatfill would be cleared in 2008 (Freed, 2010). 2003 March: Anthrax decontamination begins at the American Media, Inc., building in Boca Raton, Florida, where Robert Stevens worked (BioOne, 2005). June: Searching for evidence related to the anthrax mailings, the FBI drains a pond in Frederick, Maryland. Nothing suspicious is found (Cole, 2009, p. 195). August: Steven Hatfill sues Attorney General John Ashcroft and other government officials, accusing them of using him as a scapegoat and demanding that his name be cleared (Washington Post, 2008, p. 11). December 22: The U.S. Postal Service’s Brentwood Mail Processing and Distribution Center is reopened (USDOJ, 2010, p. 3). 2005 March 14: The U.S. Postal Service’s Trenton Processing and Distribution Center in Hamilton Township, New Jersey, is reopened (USDOJ, 2010, p. 3). 2007 February 8: Federal environmental experts determine that the former American Media, Inc., building in Boca Raton, Florida, has been cleared of anthrax spores (Sarmiento, 2007). 2008 June: The federal government awards Steven Hatfill $5.82 million to settle his violation of privacy lawsuit against the Department of Justice (DOJ) (Freed, 2010; Washington Post, 2008). continued

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30 SCIENTIFIC APPROACHES USED TO INVESTIGATE THE ANTHRAX LETTERS TABLE 1-1 Continued July 29: USAMRIID microbiologist Bruce E. Ivins commits suicide as the FBI is about to file criminal charges against him for his role in the anthrax mailings (CBS News, 2008). August 8: DOJ officially clears Steven Hatfill of involvement in the anthrax mailings (Washington Post, 2008). August 18: The FBI holds two press briefings, one for scientific media and one for general media, to describe “the body of powerful evidence” that allowed the FBI to conclude that it had “identified the origin and perpetrator of the 2001 Bacillus anthracis mailing” (FBI, 2008). September 17: FBI Director Robert Mueller testifies before the Senate Judiciary Committee at a hearing entitled “Oversight of the Federal Bureau of Investigation.” At the hearing, Mueller states that the FBI was seeking an independent review of the scientific evidence in the anthrax mailings case. “Because of the importance of the science to this particular case and perhaps cases in the future,” he says, “we have initiated discussions with the National Academy of Sciences” to “undertake a review of the scientific approach used during the investigation” (Temple-Raston, 2008). 2010 February 19: DOJ, the FBI, and the U.S. Postal Inspection Service formally conclude the investigation into the 2001 anthrax attacks and the Department of Justice issues an Amerithrax Investigative Summary. In the summary, DOJ concludes that “Evidence developed from [the] investigation established that Dr. [Bruce] Ivins, alone, mailed the anthrax letters” (USDOJ, 2010, p. 1). Patrick Leahy of Vermont. The letter addressed to Senator Daschle was opened by a member of the Senator’s staff on October 15. After discovering the Daschle letter, the House and Senate Office Buildings were closed for environmental assessment and decontamination. The U.S. Postal Service suspended mail ser- vice to the U.S. Capitol and closed the Hamilton, New Jersey, postal center where the four recovered letters had been processed. Postal officials subsequently determined that two contaminated envelopes were processed at the U.S. Postal Service Processing and Distribution Center in Washington, D.C. (the Brentwood facility) on October 12. Exposure to spores from the unopened envelopes at the postal facilities went undetected until after the implicated envelope was opened at the Hart Senate Office Building. On October 21, officials closed the Brentwood facility after a postal worker was diagnosed with an anthrax infection. Several workers at the postal facility that processed the letter fell ill with inhalational anthrax, and two eventually died. On November 16, 2001 FBI officials, U.S. Postal investigators, and U.S. Environmental Protection Agency hazardous material personnel found an unopened letter addressed to Senator Leahy that appeared to contain anthrax. The letter, with an October 9, 2001, Trenton, New Jersey postmark, was located in one of more than 230 drums—containing 642 bags of unopened mail sent

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31 INTRODUCTION to Capitol Hill—that had been sequestered since the discovery of the anthrax letter mailed to Senator Daschle (Beecher, 2006). The letter had a Greendale School return address, block handwriting, and other characteristics similar to the Daschle letter. A misread zip code caused the Leahy letter to be misdirected to the State Department mail annex in Sterling, Virginia, where a postal worker contracted inhalational anthrax. The anthrax in the Senate letters was a highly refined dry powder consist - ing of about one gram of nearly pure spores, as determined in subsequent laboratory analyses (see Chapter 4). The preparation was thus more potent than the material in the first (New York) set of mailings. By the beginning of December 2001, it appeared that the mailings had ended, as no additional letters had been discovered and no further cases were identified. But it was clear that more was required than a public health response by CDC. The attacks warranted a major law enforcement investigation led by the FBI, in which science would play a leading role. Identifying the source of the letter materials could lead to the person or persons responsible for the attacks. Key questions focused on the contents of the letters, how, where, and when the materials in the letters might have been produced, whether the material in all the evidence collected was identical, whether the material had been produced in such a manner as to be more easily dispersible, whether it had any distinguishing physical or chemical properties of value in determining the source, and whether its biological characteristics could provide leads to its origins. 1.3 BRIEF SUMMARY OF THE FBI’S SCIENTIFIC INVESTIGATION During its investigation of the anthrax mailings, the FBI worked with other federal agencies to coordinate and conduct scientific analyses of the spore powders recovered from the letters, environmental samples, clinical samples, and samples collected from laboratories that might have been the source of the letter-associated spores. The agency relied on external experts, including some who had previously developed tests to differentiate among strains of B. anthracis. Early in the investigation the spores in the letters, as well as environmen - tal and clinical isolates, were identified as the “Ames strain” of anthrax. This strain was originally isolated from a dead cow in Texas in 1981 and shipped to USAMRIID in Frederick, Maryland. Over time it was shared with research and development laboratories around the world. Thus, the identification of the strain of B. anthracis used in the mailings was insufficient to identify its source, although it narrowed the possibilities considerably. The evidence had to be examined for additional unique and distinguishing features that could then be compared to samples obtained from laboratories holding the Ames strain as a means to narrow the search for the possible source material, and perpetrator(s).

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32 SCIENTIFIC APPROACHES USED TO INVESTIGATE THE ANTHRAX LETTERS The FBI subpoenaed samples from laboratories known to have Ames strain B. anthracis and collected them in an FBI Repository (FBIR) that ultimately included 1,070 samples from 20 laboratories—17 domestic and 3 international (in Canada, Sweden, and the United Kingdom). In addition, the FBI and part- ners within the Intelligence Community collected environmental samples from an undisclosed overseas site at which they had reason to suspect activities by a terrorist group in producing anthrax. Although cultures of these samples did not produce B. anthracis, molecular analysis provided inconsistent evidence for the presence of B. anthracis Ames strain DNA in some samples (see section 3.4.3) Scientists from the Department of Defense examined the spore materials in the letters and identified several variants in the samples based on their colony morphology.2 With support from the National Institutes of Health, the National Science Foundation, and other government agencies, FBI scientists worked with the Institute for Genomic Research (TIGR) to identify several genetic mutations associated with the altered appearance of the cultured variants found in the letters (see Chapter 5 for an extensive discussion of this work). FBI investigators contracted the assistance of four laboratories to develop highly specific molecular-genetic assays to detect four specific mutations found in the evidence. These mutation detection assays were used in the examination of the samples in the FBIR, as described in Chapters 5 and 6. The analysis of samples in the FBIR led the FBI to focus attention on a par- ticular spore-containing flask at USAMRIID known as RMR-1029. The analysis of the repository samples and the bacteria in this flask is described in Chapter 6. In addition, analytical approaches such as scanning and transmission elec - tron microscopy, energy-dispersive X-ray analysis, carbon dating by accelerator mass spectrometry, and inductively coupled plasma-optical emission and mass spectrometry were used to determine the chemical and elemental profiles of the spore powders (see Chapter 4). These studies were done to determine when the anthrax preparation might have been made, whether there were contaminants or trace elements that would provide a clue to the production location or mate - rials used, and whether there was evidence of an effort to deliberately include additives to improve dispersal of the anthrax. 1.4 SUMMARY OF FBI AND DOJ SCIENTIFIC CONCLUSIONS The scientific analyses led the FBI and DOJ to draw a number of conclu- sions (see Table S-1 in the Summary). The committee found it challenging, how - ever, to identify the FBI’s definitive conclusions because those provided publicly by DOJ in its briefings and investigative summary and those provided by FBI officials in oral presentations to the committee varied. For the purposes of this 2 Morphological variants are observable physical or biochemical characteristics of an organism. These characteristics are determined by both genetic makeup and environmental influences.

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33 INTRODUCTION report, the committee’s analyses are based on the scientific conclusions pro- vided by the FBI to the committee on September 24, 2009 (left-most column of Table S-1), those issued publicly by DOJ on February 19, 2010, when it closed the case (USDOJ, 2010) (column second from the left in Table S-1), and those provided by Louis Grever, Edward Montooth, and Rachel Lieber on January 14, 2011 (FBI/USDOJ, 2011). 1.5 COMMITTEE PROCESS Under the terms of the NRC contract with the FBI, the FBI initially pro- vided two boxes containing approximately 9,000 pages of materials to the com- mittee, and then in December 2010, the FBI gave the committee an additional 641 pages related to the scientific investigations undertaken by the FBI and by various external experts working at the behest of the Bureau during the course of the anthrax investigation. Throughout the NRC study process these materials were covered by FOIA Exemption 7, “law enforcement sensitive,” and were not publicly available. Upon release of this report, as specified in the contract, these documents have been deposited in the NRC Public Access File. 3 Documents were initially delivered in two batches containing reports of the scientific analyses (see the Index of Documents Provided by the Federal Bureau of Investigation for a listing).4 The first batch included technical review panel reports, laboratory analytical test reports and results pertaining to Ames strain identification, carbon dating, stable isotope analysis, agar and heme analysis, and assay development, and published papers. Batch two included materials regarding genetic diversity and phylogenetic characterization of B. subtilis (another bacterial species); repository screening and molecular analy - sis of pathogen strains and isolates and genetics of the A1, A3, B, D, and E mutations found in the evidence; statistical analysis; cross contamination; and chemical and physical properties of the spore powders. The third batch of documents received in December 2010 contained reports of scientific review meetings and some additional information about sample collection, laboratory notebooks, and reports of investigations of individuals. Additional documents were provided by the FBI at the committee’s request throughout the study; these documents are listed in the Index of Documents Provided by the Federal Bureau of Investigation under the heading Supplemental Documents. No written explanatory materials were provided with these documents that would fully inform the committee as to why the analyses were done and how these 3 The public can gain access to these materials by contacting the NRC Public Access Records Office. 4 In this report, the principal documents received from the FBI are referenced according to the following convention: “FBI Documents, B*M*D*” where B = Batch, M = Module, D = Document, and * = Number. Thus “FBI Documents, B1M1D1” would refer to the first document in the first module of the first batch of materials received from the FBI.

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34 SCIENTIFIC APPROACHES USED TO INVESTIGATE THE ANTHRAX LETTERS documents contributed to the FBI investigations and conclusions. The mate- rial regarding analyses of the FBIR specimens was coded, often with different numbers for the same sample set. Consequently, the committee spent a consider- able amount of time sorting through and attempting to interpret the available materials before it could begin to evaluate the science and consider the scientific conclusions. In addition, much of the information provided to the committee was compartmentalized and sections of some documents were redacted. When the committee posed questions to the FBI for clarification, the agency was always responsive; however, responses to questions were sometimes minimal or terse, or were deflected as intruding into the criminal investigation and beyond the purview of the committee despite the committee’s explanation that the questions were of a scientific nature. Some of these responses may reflect tension between the scope of the scientific review expected by the FBI and the committee’s interpretation of its charge. In summary, the FBI provided some of the primary information related to the scientific analyses and was generally responsive to committee questions, but early on it was difficult for the committee to ascertain details of what was done in the course of some of the FBI scientific work, the identity of some of the samples analyzed, and the relationships among the samples in the repository. In addition to materials provided directly by the FBI to the committee, FBI officials also briefed the committee on several occasions. Some of these briefings were done in open session, while others were conducted in closed sessions covered by FOIA Exemption 7. In these closed sessions the committee heard from a number of DOJ/FBI personnel including: John Fraga, Christian Hassell, Louis Grever, Edward Montooth, and Rachel Leiber. FBI consultant Ranajit Chakraborty (University of Cincinnati and currently University of North Texas Health Sciences Center) and Daniel Martin (Dugway Proving Ground) also briefed the committee in closed session. In addition, the committee heard from a number of other experts: Bruce Budowle (formerly FBI; University of North Texas Health Sciences Center); Rita Colwell (University of Maryland and Johns Hopkins University); Claire Fraser-Liggett (The Institute for Genomic Research and University of Maryland School of Medicine); Hank Heine (for- merly USAMRIID); Congressman Rush Holt; Paul Keim (Northern Arizona University); Joseph Michael (Sandia National Laboratories); Steven Schutzer (University of Medicine and Dentistry of New Jersey); Jennifer Smith (formerly FBI; BIOFOR Consulting); Patricia Worsham (USAMRIID); and Peter Weber (Lawrence Livermore National Laboratory). In conducting its review, the committee focused on the biological, physical, and chemical sciences applied to evidentiary materials. The committee was not charged to consider or evaluate any of the traditional forensic science meth - ods and techniques used (e.g., hair, fiber, fingerprint, or handwriting analysis) (NRC, 2009a) nor did it consider any of the psychological or behavioral sci - ences, such as linguistics, used by the FBI in its investigation.

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35 INTRODUCTION The committee met seven times in person in open and closed sessions and continued its deliberations by conference call. Closed sessions were reserved for review of law enforcement materials (FOIA Exemption 7) relevant to the FBI investigation, committee analyses, deliberations, and report drafting. Public sessions were convened to gather information from the scientific community about various aspects of the scientific investigation or areas of scientific research relevant to the matters at hand. DOJ closed its investigation of the anthrax mailings after the committee’s fourth meeting. In November 2010, the FBI contacted the National Academies and requested the opportunity to provide the committee with additional materials and another briefing. The committee subsequently received and reviewed the third batch of materials, an additional 641 pages of documents, and met for one final briefing with FBI and DOJ officials in mid-January 2011. 1.6 ISSUES FOR CONSIDERATION IN READING THIS REPORT The FBI’s anthrax investigation involved the development and use of mod- ern science in an attempt to solve a crime committed with a biological agent. The use of science in legal investigations is not new. Science is called on to answer questions, for example, about the safety of drugs, risks from exposure to environmental toxins, and identification of DNA from a rape or murder vic - tim. Yet science and the judicial system do not always have an easy relationship because of differences in culture and overall objectives. The scientific process takes time, raising questions and seeking answers, and challenging and revising accepted theories and notions until new hypotheses are generated. The judicial system, on the other hand, aims to settle disputes with the information available at a point in time. It typically does not have the opportunity to conduct another study and wait for complete information. Scientific investigation usually is a more open-ended endeavor than a legal or criminal investigation as scientists acknowledge appropriate degrees of uncertainty—both small and large—in their investigations and are inspired to do future work on the questions of interest, yielding more certainty and more information. In contrast, the justice system, to be effective, requires decisions to be made rather than deferred, and thus scientific uncertainty has to be weighed in light of all other evidence. Toler- ance for scientific uncertainty may or may not be tempered by the strength of other, nonscientific evidence. As demonstrated in this investigation, the FBI used science in two different ways: 1) to identify and analyze evidence using methods that are acceptable for presentation in the courtroom; and 2) to identify leads for a criminal investiga - tion. In the latter case, the science per se is not intended to be presented in the courtroom but it may provide leads to inform and direct the law enforcement investigation. In either case, the science must be conducted correctly and per- formed at a high level of scientific standards.

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36 SCIENTIFIC APPROACHES USED TO INVESTIGATE THE ANTHRAX LETTERS The committee recognized that forensic science is the application of scien - tific methods to matters of interest to the judicial system and must, therefore, consider the norms of both science and the law (NRC, 2009a, Chapter 3). The committee also recognized that sometimes pressing national interest or security concerns, such as those present during this investigation, demand that newly emerging methods be applied to the assessment of forensic evidence even before those methods have been widely adopted or validated by peer review in the forensic and scientific communities. It should be noted that future biologi - cal attacks will probably pose greater challenges than did this attack: the agent may be a member of a species with a more complex and poorly understood population structure, the agent may be genetically modified in a manner that further obscures its origin, or a sample of the attack material may not be readily available (as it was in this case). This last possibility may mean that environ- mental or clinical samples, with their inherent added challenges, will have greater importance in a future investigation. National security concerns and the pressures of an ongoing criminal investi- gation may require that the collection of samples and their evaluation be carried out under circumstances of secrecy that limit the capacity of outside observers to assess the validity of the forensic interpretations. Such circumstances pose special challenges in which the optimal application and evaluation of scientific methods may in some instances run counter to security interests. The commit - tee faced this tension between science and security in its deliberations. In the end, the committee considered the facts and data of the scientific investigation, the reliability of the principles and methods used by the FBI, whether the principles and methods were applied appropriately to the facts, and the conclusions related to these efforts. The committee does not, however, offer a view on the guilt or innocence of any person(s) in connection with the 2001 B. anthracis mailings or any other B. anthracis incidents. 1.7 ORGANIZATION OF THE REPORT Based on its review of the materials provided, the committee developed the findings presented in this report. The report is organized to provide back- ground on the scientific characteristics of B. anthracis (Chapter 2); describe and review the procedures used in the early stages of the investigation concerning the collection of evidence and its processing and preservation, as well as the creation of a repository of B. anthracis samples collected from around the world for comparative and investigative purposes (Chapter 3); review and assess the physicochemical analyses of the anthrax evidence (Chapter 4); review and assess the biological characteristics of the material in the letters (Chapter 5); and review and assess the analyses and results of the FBI’s comparison of the evidentiary material against the samples in the FBI Repository (Chapter 6). The committee’s findings, analysis, and recommendations can be found in Chapters 3 through 6.