U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Institute of Medicine (US) Committee on a Strategy for Minimizing the Impact of Naturally Occurring Infectious Diseases of Military Importance: Vaccine Issues in the U.S. Military; Lemon SM, Thaul S, Fisseha S, et al., editors. Protecting Our Forces: Improving Vaccine Acquisition and Availability in the U.S. Military. Washington (DC): National Academies Press (US); 2002.

Cover of Protecting Our Forces

Protecting Our Forces: Improving Vaccine Acquisition and Availability in the U.S. Military.

Show details

3Current Status of Vaccines for Military Personnel

The Department of Defense (DoD) administers 17 different vaccines, as outlined in the Joint Instruction on Immunizations and Chemoprophylaxis (Secretaries of the Air Force, Army, Navy, and Transportation, 1995), for the prevention of infectious diseases among military personnel, where appropriate. The vaccines are administered to military personnel on the basis of military occupation, the location of the deployment, and mission requirements. In this chapter, the committee reviews information on the current availability of vaccines to DoD and describes key projects in DoD's vaccine development pipeline.


Table 3-1 provides an overview of the major infectious disease threats to U.S. military personnel and displays whether the appropriate vaccine product is available for military use, is licensed in the United States by the Food and Drug Administration (FDA), is an investigational new drug (IND), or is in development. It is an incomplete list of potential threats and does not include a number of infectious diseases or infectious disease agents for which a vaccine is neither available nor in development, but against which the military might have a need for a vaccine, such as Crimean-Congo hemorrhagic fever, West Nile encephalitis, Nipah virus, Norwalk virus, Lassa fever, and other common infections or infectious disease agents, such as gonorrhea, chlamydia, and tuberculosis. The information presented in the tables that follow are based on material provided by the U.S. Army Medical Research and Materiel Command (USAMRMC), FDA, and the Pharmaceutical Research and Manufacturers of America (PhRMA) websites, as well as presentations made to the committee.

TABLE 3-1. Status of Vaccines for Specific Infectious Disease Threats to the U.S. Military.


Status of Vaccines for Specific Infectious Disease Threats to the U.S. Military.

The committee is not aware of a standard definition of the term “vaccine availability” or of any threshold for determining whether a vaccine should be considered available. Some vaccines are available only through difficult and unusual processes or circumstances. For example, special operations troops may be at risk for smallpox, and in such cases arrangements must be made to transfer the smallpox vaccine from the Centers for Disease Control and Prevention (CDC) to DoD.1 Some vaccines are manufactured in small pilot lots and are available as INDs through DoD's Special Immunizations Program (SIP) to “individuals who have a high occupational risk—laboratory workers, facilities inspectors, vaccine manufacturers and certain military response teams” (Boudreau and Kortepeter, 2002). The precision displayed in Tables 3-1 to 3-5 by the use of dichotomies such as “limited availability” or “unavailable,” although helpful as an overview, belies a fluid and complex actuality. At a minimum, the names of the manufacturers keep changing as corporate entities merge, grow, or realign themselves. International coordination is required for some vaccines that are manufactured outside of the United States but licensed in the United States by FDA. Others are manufactured and licensed outside the United States, presenting different and usually more complex acquisition problems.

TABLE 3-5. Vaccines Administered as INDs That Are No Longer Being Produced and That Are of Limited Availability.


Vaccines Administered as INDs That Are No Longer Being Produced and That Are of Limited Availability.

Nonetheless, the 51 infectious disease threats listed in Tables 3-2 through 3-5 are classified according to the availability of related, specific vaccine products or other biological countermeasures. Specifically, Table 3-2 lists vaccines that are licensed and generally available for use by DoD personnel. It also lists the number of manufacturers involved. Table 3-2 demonstrates that most of these vaccines are manufactured by single suppliers and thereby suggests the fragility of the vaccine supply essential to military readiness. Table 3-3 lists vaccines that were previously licensed by FDA but that are no longer available to DoD. This list includes vaccines against smallpox and plague, further illustrating the armed forces' vulnerability to potential biological warfare agents. Tables 3-4 and 3-5 list vaccines that, although never licensed by FDA, have at times been available for DoD use as products with IND status. Table 3-4 lists those vaccines that are available only under the restrictive regulations governing the use of products with IND status, whereas Table 3-5 lists the subset of products that are no longer produced but that are available to a limited number of military personnel as INDs through DoD's SIP.

TABLE 3-2. FDA-Licensed Vaccines and Related Biologics Available to U.S. Military Personnel.


FDA-Licensed Vaccines and Related Biologics Available to U.S. Military Personnel.

TABLE 3-3. Selected Vaccines Previously Licensed by FDA but Not Available.


Selected Vaccines Previously Licensed by FDA but Not Available.

TABLE 3-4. Vaccines Available to U.S. Military Personnel as IND Products.


Vaccines Available to U.S. Military Personnel as IND Products.

Many of the special-use vaccines that were once licensed or used by the military as products with IND status are no longer available. This situation arises as a result of any of a variety of obstacles. For most vaccines that are products with IND status, there was simply insufficient funding for advanced development. For other products, it was deemed difficult, if not impossible, to demonstrate their effectiveness and safety in humans, thus preventing the possibility of their licensure. Market factors, such as inadequate sustained demand, are obstacles as are a lack of interest or monetary incentive for industry to participate in the development or scale-up of the production process, the lack of an adequate physical infrastructure to meet the regulatory requirements for manufacture of the vaccine, or the inability of manufacturers to meet other regulatory requirements. The last three factors also illustrate the importance of the transition from the production of pilot lots of a vaccine to scale-up of production to a level for clinical use of the vaccine by larger numbers of people. This transition requires that a manufacturer (1) have the technical ability to produce the vaccine, the physical infrastructure to produce the vaccine, and the personnel to divert toward production of the vaccine; (2) possess experience with the regulatory and clinical research affairs needed to successfully license a vaccine; and (3) have the financial motive to engage in the long, arduous, and expensive licensing process in the face of uncertain profits in the end. Time and again, these factors have limited the engagement of the most experienced vaccine manufacturers in the production and licensure of new vaccines, particularly special-use vaccines for use by the military.


Table 3-6 provides an overview of USAMRMC's infectious disease research program, showing the Joint Technology Coordinating Group-2 (JTCG-2)2 priority ranking and the funding available to each research activity. Brief descriptions of the current status of the select vaccine research programs supported by the Military Infectious Diseases Research Program (MIDRP)3 appear in the following paragraphs.

TABLE 3-6. USAMRMC Fiscal Year (FY) 2001 Program Priorities, in Decreasing JTCG-2–Assigned Rank, and FY 2000 Investment in Exploratory Research.


USAMRMC Fiscal Year (FY) 2001 Program Priorities, in Decreasing JTCG-2–Assigned Rank, and FY 2000 Investment in Exploratory Research.

Malaria Vaccine

Growing resistance to antimalarial drugs has increased the urgency of the malaria vaccine effort. A candidate Plasmodium falciparum vaccine— RTS,S4 —has been in development for more than a decade by SmithKline Beecham Biologicals (now part of GlaxoSmithKline [GSK]) and DoD. RTS,S combines the hepatitis B virus surface antigen with a circumsporozoite recombinant protein as a virus-like particle formulated with the proprietary adjuvant system AS02. In clinical trials, this vaccine was demonstrated to protect U.S. volunteers against P. falciparum malaria and protected 70 percent of semi-immune adults in a field trial conducted in The Gambia, albeit for only 2 months (Bojang et al., 2001; Stoute et al., 1997). The joint efforts of DoD and GSK are enhanced by a partnership with the Malaria Vaccine Initiative at the Program for Appropriate Technology in Health5 that is enabling evaluation of the vaccine for use in children. A Phase I6 trial is being conducted in The Gambia, and a Phase II trial is planned for Mozambique in 2002 (GSK, 2001; MVI, 2001). In 1998, a parallel navy program reported the safety of a candidate DNA-based vaccine and its capacity to elicit killer T cells with specificity for malaria peptides. The navy and its partners with which it has Cooperative Research and Development Agreements (CRADAs), Vical and Aventis, are now constructing and testing more complex vaccines. In November 2001, Vical and the U.S. Naval Medical Research Center announced the results of Phase II clinical trials. The trials indicated that the candidate vaccine was safe and well tolerated.

Vaccines Against Diarrheal Diseases

Current research activities directed at protecting military personnel and travelers against the most common types of diarrheal diseases by use of vaccines target some of the bacterial agents of those diseases, in particular, Campylobacter, enterotoxigenic Escherichia coli (ETEC), and Shigella. Several candidate vaccines are in development, although these efforts face many challenges, including the large number of serologically distinct types of these organisms causing diarrhea and the difficulty of inducing a mucosal immune response capable of blocking infection with enteric pathogens. A candidate Shigella flexneri vaccine developed at the Institut Pasteur and manufactured at Walter Reed Army Institute of Research (WRAIR) pilot lot production facility was first tested in healthy volunteers at the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) in 1996. A larger trial with 100 or more U.S. volunteers is planned for later in 2002. A Phase II clinical trial involving 200 to 300 Bangladeshi children to test the vaccine's efficacy in an environment where the disease is endemic is also planned (USAMMDA, 2001b). Vaccines against other species of the genus Shigella—Shigella sonnei and Shigella dysenteriae—are also being evaluated.

A vaccine designed to protect against ETEC is under evaluation in Egypt, and new vaccines based on microencapsulated ETEC antigens are under development. A Campylobacter vaccine is in advanced development, but it is likely that new approaches will be required to make the vaccine more effective. Industry partnerships supporting the research include a DoD Dual-Use Science & Technology program contract with Acambis, Inc. to develop Campylobacter and ETEC vaccines (Acambis, Inc., 2001), a CRADA with Antex Biologics, Inc. to develop Campylobacter vaccines (USAMMDA, 2001c), and a Small Business Innovation Research program grant from the National Institute of Allergy and Infectious Diseases to develop oral microbead vaccines against diarrhea. Antex Biologics, Inc. is also researching the possibility of a multivalent vaccine to prevent diarrhea caused by S. flexneri, S. sonnei, Campylobacter jejuni, and ETEC (Antex Biologics, Inc., 2001).

Dengue Vaccine

DoD scientists have a long history of experience with dengue vaccines and the development of diagnostic tests for dengue (Innis et al., 1988; Kanesa-thasan et al., 2001; Vaughn et al., 1996). WRAIR and GSK have worked to develop a tetravalent vaccine that is being evaluated in a Phase II clinical trial in Thailand (Innis, 2001; WHO, 2002).

Hepatitis E Vaccine

Epidemiological studies by CDC, the army, the navy, and scientists in Russia, Pakistan, Nepal, and other countries have shown that the hepatitis E virus (HEV) is the most common cause of hepatitis in adults in many developing countries (Clayson et al., 1998). Genelabs, Inc., in collaboration with CDC, isolated and cloned HEV (Genelabs Technologies, 2001). Investigators at the National Institutes of Health (NIH) developed a baculovirus-expressed recombinant protein candidate HEV vaccine in the late 1990s; that vaccine, developed at NIH, is licensed to GSK. Two Phase I clinical trials—one in the United States and one in Nepal—have been conducted through a joint effort of NIH, DoD, Genelabs Technologies, and GSK. A Phase II clinical trial of the vaccine with 2,000 adult volunteers is under way in Nepal (Genelabs Technologies, 2001).

Meningococcal Group B Vaccine

The efforts of investigators at WRAIR led to the development of a quadrivalent polysaccharide meningococcal vaccine that has been recommended for use by selected civilian populations, such as college students (AAP, 2000; CDC, 2000b). Efforts to develop a meningococcal group B vaccine continue, but such a vaccine has proved more difficult to develop (Brundage and Zollinger, 1987; Jódar et al., 2002). Although several promising candidate vaccines based on outer membrane protein processes of the group B meningococcus have proceeded to large-scale field trials, no licensed product is yet available in the United States.

HIV Vaccine

The goal of the U.S. Military HIV Research Program7 is to develop a vaccine that provides protection against all known subtypes of HIV type 1 (HIV-1) circulating throughout the world. Efforts to date have focused on (1) surveillance for determination of the HIV subtypes infecting U.S. forces; (2) characterization of prevalent subtypes of HIV-1 around the world, including genetic recombinants; (3) collaborative efforts with industrial partners to design vaccine constructs based on a broad array of subtypes, including both those prevalent in the United States and those prevalent in other regions of the world; (4) preparation of field sites in Thailand and Uganda for testing of a vaccine; and (5) conduct of early clinical safety and immunogenicity studies in Thailand, Uganda, and the United States. The program has candidate vaccines—including those that use naked DNA, vectored DNA, and recombinant proteins from HIV subtypes E, A, D, and C—in various stages of development and testing. A Phase III clinical trial, in collaboration with the Ministry of Public Health of Thailand, is scheduled to begin in fall 2002 for evaluation of a vaccine consisting of a canarypox virus vector. The clinical trial will be conducted in Thailand and is expected to last 5 years. In October 2002, DoD will transfer management of the HIV vaccine trial and research effort to NIH to comply with direction from the Office of Management and Budget (NIAID, 2002a).


As mentioned above, DoD maintains a Special Immunizations Program (SIP) within USAMRIID whose mission is to “offer FDA licensed vaccines and investigational new drug (IND) vaccines under informed consent to laboratory workers at USAMRIID, and to other, military, government, or contractor personnel who may be at occupational risk of exposure to highly hazardous pathogenic microorganisms or toxins” (Boudreau and Kortepeter, 2002). SIP administers five FDA-licensed vaccines and nine vaccines with IND status; these are listed in Tables 3-7 and 3-8, respectively. Table 3-9 lists the two vaccines for which CDC is the IND sponsor but which SIP administers to the military.

TABLE 3-7. FDA-Licensed Vaccines Used by SIP as of March 2002.


FDA-Licensed Vaccines Used by SIP as of March 2002.

TABLE 3-8. Vaccines with IND Status Used by SIP as of March 2002.


Vaccines with IND Status Used by SIP as of March 2002.

TABLE 3-9. Vaccines with CDC-Sponsored IND Status Administered by SIP.


Vaccines with CDC-Sponsored IND Status Administered by SIP.

A number of vaccines that DoD has developed over the years, including the vaccines listed in Table 3-8, have remained at the pilot level of production, with no commercial manufacturers identified. Incentives to pursue full-scale production have been limited primarily because of the geographically limited nature of the diseases that the vaccines were designed to prevent and the limited commercial potential of these products. DoD faces obstacles in keeping these products available to military personnel when the vaccines are needed. Some of the obstacles encountered include the challenges of meeting FDA regulatory requirements, difficulties associated with administering products with IND status, and the increased cost of vaccine development. Significantly, as described in the note to Table 3-8, live, attenuated vaccines against chikungunya virus, Junin virus, and Rift Valley fever virus that were previously available as INDs through SIP no longer have active IND status and thus are not available even for very specialized uses within DoD.

FDA regulations require that a biological product be evaluated for its immunogenicity, safety, and efficacy before licensure. Under current rules, FDA cannot grant a license to a vaccine that has not been shown to be efficacious and safe in clinical trials with humans or for which there is no robust laboratory evidence that indicates that the vaccine offers the same protective immunity demonstrated in earlier studies with another vaccine (FDA, 1998). Most of the vaccines that SIP manages are designed to prevent rare infections, natural occurrences of which are unpredictable in everyday settings. To a large extent, that may preclude the possibility of completing conventional clinical efficacy trials with these vaccines. The ability to conduct experimental challenge tests is severely limited or absolutely prohibited by well-accepted ethical rules guiding human experimentation. Therefore, it would be very difficult to meet the current FDA requirements for licensure for these vaccines.

Two FDA rules address the difficulty of providing sufficient evidence of efficacy for these vaccines. A rule finalized as the committee completes this report allows the use of data from animal studies as surrogates for human-study data when it is not feasible to conduct tests with humans. The rule concerns the constraints on the testing of the efficacy of a vaccine and does not address the requirement to demonstrate the safety of the product in large numbers of humans (FDA, 2002c). A second rule—subpart H: Accelerated approval of new drugs for serious or life-threatening illnesses8 —permits accelerated approval of new drugs for serious or life-threatening illnesses. It states that “FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials establishing that drug product has an effect on a surrogate endpoint.”

To detect relatively low frequency adverse events related to vaccine administration, tests need to be conducted with substantial numbers of subjects, making the demonstration of safety and efficacy not only difficult but also costly. Several published estimates from the pharmaceutical industry and others indicate that approximately 60 to 75 percent of vaccine development costs occur in the late stage of product development (Greco, 2001; Monath, 2000). These and related issues are discussed further along with the recommendations in Chapter 4.

Current regulations preclude the use of products with IND status without adherence to extant regulations applicable to clinical research with experimental products.9 This includes the submission to FDA of certain information pertaining to the product and the proposed clinical studies, prior approval by an independent institutional review board, the collection of informed consent, and detailed recordkeeping.10 The myriad procedures and documentation steps can be difficult—if not impossible—to adhere to during military operations.

In 1990, at the request of DoD, FDA published an interim rule addressing DoD's concerns about the use of products with IND status in combat situations. The interim rule allowed the FDA commissioner to waive the informed consent requirement when such a waiver was requested by the Assistant Secretary of Defense for Health Affairs. Application of the rule was restricted to the “use of an investigational drug (including an antibiotic or biological product) in a specific protocol under an investigational new drug application” and was “limited to a specific military operation involving combat or the immediate threat of combat.”11 The rule was applied during the Gulf War, allowing the use of pyridostigmine bromide and a botulinum toxoid vaccine to protect against the potential use of weaponized biological or chemical agents (Rettig, 1999).

When service members returned from the Gulf War deployment and reported medically unexplained symptoms, many questioned the safety and efficacy of the vaccine and drug products used during the war and the wisdom of DoD's use of the interim rule. These perceptions, which may have been different had there been credible evidence of the actual use of chemical or biological weapons by forces opposing U.S. and allied personnel, sparked changes in the government's policy regarding the IND waiver. In part because of concerns that grew out of the use of the interim rule during the Gulf War, the U.S. Congress passed an amendment to the Defense Authorization Act for FY 199912 that vests solely with the president the authority to waive the informed consent requirement. Accordingly, FDA revoked the 1990 interim rule and established a new interim final rule outlining the limited circumstances in which the president could waive the informed consent requirement: “if the President finds obtaining informed consent (1) not feasible; (2) contrary to the best interests of the members; or (3)not in the best interests of national security” (FDA, 1999, p. 54181).

DoD was again criticized for administering a product with IND status without close adherence to the FDA guidelines when it used the tick-borne encephalitis (TBE) vaccine in the Bosnian conflict. For many years, the military had administered the TBE vaccine to U.S. personnel who inspected military sites in the Soviet Union, where TBE is endemic. The vaccine, developed by scientists from Austria and the United Kingdom, had been widely used in Europe but had not been licensed for use in the United States. In 1993, the Armed Forces Epidemiological Board (AFEB) was asked to evaluate and make a recommendation regarding the use of the TBE vaccine (for which the Army held an IND application). AFEB recommended that the vaccine against TBE be used “under IND protocol with informed consent” to protect military personnel with significant potential for exposure to TBE (AFEB, 1993). In 1996, the Assistant Secretary of Defense for Health Affairs outlined, based on input provided by USAMRMC and the surgeons general, DoD policy regarding the use of a vaccine against TBE. The policy instructed that the TBE vaccine should be offered to “personnel at very high risk of tick exposure” and that it should not be used to routinely immunize all DoD personnel (ASD[HA], 1996). DoD offered the TBE vaccine to soldiers deployed to areas in Bosnia known to be affected by tick-borne encephalitis. To receive the vaccine, however, individuals had to volunteer to participate in a study of the IND product and, accordingly, to provide written informed consent.

An investigation by the General Accounting Office into the Army's recordkeeping practices during the Bosnian conflict (GAO, 1997) found that nearly one-fourth of the immunizations against TBE in Bosnia were not properly documented. FDA, also, found “significant deviation” from the guidelines related to the use of a product with IND status in DoD's use of the TBE vaccine in Bosnia (FDA, 1997b). Although DoD officials “acknowledged faulty recordkeeping,” they maintained that IND guidelines were followed (Gillert, 1998). The TBE vaccine is no longer available to U.S. military personnel as a product with FDA IND status.

The sequence of events outlined above highlights the difficulties inherent in complying with FDA rules related to an IND product and conducting well-documented clinical trials of investigational vaccines among military personnel engaged in combat or participating in peacekeeping duties under hazardous conditions. They also point out the difficulties that commanders face when they must confront the rules and regulatory practices that are in place when they are deploying forces into situations that are likely to expose those forces to infectious disease threats for which licensed vaccines may not be available.



DynPort Vaccine Corporation, DoD's prime vendor contractor through the Joint Vaccine Acquisition Program, has linked with BioReliance to produce a smallpox vaccine. The vaccine is being evaluated at the University of Kentucky, and Phase I clinical trials began in April 2002 (Gay, 2002; Johnson-Winegar, 2001) .


A discussion of the role and function of the JTCG-2 group is provided in Chapter 2.


A discussion of the role and function of MIDRP is provided in Chapter 2.


RTS,S—“RTS,S is a fusion protein of the carboxyl-terminal half of the P. falciparum circumsporozoite protein, which includes part of the central repeating sequence ‘R' and major T cell epitopes ‘T', and which is fused with the entire surface antigen ‘S' of the hepatitis B virus” (Bojang et al., 2001, p. 1927).


The Malaria Vaccine Initiative was created through initial funding from the Bill and Melinda Gates Foundation.


Prelicensure vaccine trials are divided into three phases. Phase I clinical trials mark the first tests conducted with humans and test the candidate vaccine's safety and immunogenicity in a small number (~20 to 80) of healthy volunteers. Phase II clinical trials also test the vaccine's immunogenicity and safety, but at this phase dose-ranging tests (how much of the vaccine/drug is needed to produce the desired effect) are often initiated. About 100 to 300 subjects are often included in these tests. Phase III clinical trials measure the vaccine's safety, efficacy, and immunogenicity. This phase should generally include thousands of patients and should provide sufficient benefit to risk data to ensure licensure and “provide an adequate basis for product labeling” (FDA, 2001c). Although FDA provides guidelines to steer manufacturers toward licensure of a product (Current good manufacturing practice in manufacturing, processing, packing, or holding drugs; general. 21 C.F.R. § 210 [2001]; Current good manufacturing practice for finished pharmaceuticals. 21 C.F.R. § 211 [2001]; Investigational new drug application [IND]. 21 CFR § 312.20–312.21, subpart B [2001]; Biological products: General. 21 C.F.R. § 600 [2001]; FDA, 1998), the number of individuals included in prelicensure trials of vaccines varies broadly. However, the committee understands that recent FDA requests for prelicensure trials of vaccines to be used in civilian populations have often included 10,000 subjects and in one recent case 60,000 subjects. Efficacy and safety data require use of statistical evaluation to assist in determining the sizes of both types of studies. Safety studies may need to have larger sample sizes than efficacy studies.


HIV vaccine research is managed as a Congressional Special Interest extramural research program (USAMRMC, 2002a). The research program is a collaborative effort of the air force, army, and navy. The program is headed by WRAIR and research is conducted in collaboration with the Henry M. Jackson Foundation for the Advancement of Military Medicine (U.S. Military HIV Research Program, 2002).


Accelerated approval of new drugs for serious or life-threatening illnesses. 21 CFR § 314.500– 314.560, subpart H (2001).


Investigational new drug application (IND). 21 CFR § 312.20–312.21, subpart B (2001); Informed consent of human subjects. 21 CFR § 50, subpart B (2001).


From DoD Directive 6200.2: Use of Investigational New Drugs for Force Health Protection (DoD, 2000).

4.8.1. Notice Requirement for IND Use: When using an IND for force health protection, DoD Components shall provide prior notice to personnel receiving the drug or biological product of the following: That it is an IND (including specific information on whether it is approved by FDA and/or whether it is unapproved for its applied use). The reasons the IND is being used.


Informed consent of human subjects. 21 CFR § 50, subpart B (2001).


Strom Thurmond National Defense Authorization Act for Fiscal Year 1999. P.L. 105-261 (1998). Information regarding the possible side effects of the IND, including any known side effects possible as a result of interaction of the IND with other drugs or treatments being administered to such personnel. Other information as required to be disclosed by the FDA.

4.8.2. Information to Providers for IND Use: DoD Components shall ensure that healthcare providers who administer the IND or who are likely to treat members who receive the IND receive the information identified in sections and above.

4.8.3. Record Keeping on Use of IND and Notice Requirement. DoD Components shall ensure that medical records of personnel who receive an IND accurately document the receipt of the IND and the notice required by section 4.8.1 above.

Copyright 2002 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK220954


  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this title (4.1M)

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...