MILITARY MEDICINE. 170. 3:183, 2005

An Assessment of Health Status among Medical ResearchVolunteers Who Served in the Project Whitecoat Program at Fort

Detrick, Maryland

Guarantor; COL Phillip R. Pittman. MC USAContributors: COL Phillip R. Pittman, MCKellv T. McKee, Jr., MD

USA*; Sarah L Norris, MPH+: Kevin M. Coonan, MD'

Between 1954 and 1973. more than 2.000 men entering mili-tary service as conscientious objectors participated in ProjectWhitecoat as medical research volunteers for the Army's bio-logical warfare defense program. An assessment of self-re-ported, current health status among 358 "exposed" individu-als and 164 unexposed control subjects found no conclusiveevidence that receipt of investigational agents was related toadverse health outcomes. No differences in current overallhealth, current exercise levels, self-reported symptoms, andself-reported medical conditions were seen hetween the studygroups. Possible associations were seen between exposure toantibiotics or other biological agents and self-reported asthma(13.0% vs. 2.4%, relative risk [RR| = 6.00, 95% confidenceinterval [Cl] - 1.03-34.90, p = 0.050). as well as betweenreceipt of tularemia vaccine(s) and self-reported asthma (13.3%vs. 2.4%. RR - 6.15. 95% Cl = 1.03-36.70, p - 0.049} andincreased frequency/severity of headaches (35.6% vs. 18.3%,RR - 2.46, 95% Cl - 0.99-6.15. p = 0.074). However, the sizeof the population under study was insufficient to assert withconfidence that these statistical associations are real.

Introduction

U nited States govemment efforts to counter the threat ofbiological weapons have their genesis in the War Bureau of

Consultation, a commission of the National Academy of Sci-ences that was formed at Ihe request of Secretary of War HaroldStimson in 1941." This group recommended the urgent cre-ation ofa program of research to address the problem of biolog-ical warfare and. in 1942. President Roosevelt authorized Mr.Stimson to establish the War Research Sendee as a unit of theFederal Security Agency for this purpose. The War ResearchService, headed by George Merck (president of Merck Pharma-ceuticals), immediately undertook a program of study of hiolog-ical agents, conducted v^th "utmost secrecy."''

With increasing appreciation of the scope and complexity of alarge-scale program of research and development in this area,the War Research Service requested that the U.S. Army Chem-

•USAMRIID. Fort Detrlrk. MD 21702-5011,tScience Applications ltitemational Corp./USAMRIID, Fort Detrick, MD 21702-

5011,tCamber Corp./USAMRIID, Fort Detrick, MD 21702-5011.gCurrenl address: Department of Medical Infonnatics, University of Utah School ot

Medicine. Salt Lake City. IJT,The opinions expres.sed are those of the authors and should not he construed to

represent those of Camber Corp,. Science Applications Intemational Corp,, the De-partment of the Army, or the Department of Defense,

Reprints: COL Phillip R, Pittman, II,S, Army Medical Research Instituteof Infectious Diseases. 1425 Porter St.. Fort Detrick. MD 21702-5011: e-mail:phlllip ,pittmani®amedd,army .mil,

This manuscript was received for review in February 2004 and was accepted forpubllcaUon in March 2004.

ical Warfare Service assume responsibility. The initial site se-lected for the program was Edgewood Arsenal, near Aberdeen.Maryland. In 1943. a small National Guard airfield (DetrickField) just outside Frederick. Maryland, was purchased by theWar Department, and the hub ofthe operation was moved to therenamed Camp Detrtck.

The Office of the Army Surgeon General was involved in thebiological warfare research and development program from thetime of its inception in 1941. hut it was not directly responsiblefor any activities until 1956. when the U.S. Army Medical Unit atCamp Detrick was activated with a mission to evaluate thethreat of biological warfare and to develop approprtate counter-measures.-' During the same year. Camp Detrick became FortDetrick. From that time to the present. Fort Detrtck has been thehome of the nation's biological warfare defense program. TheArmy Medical Unit was redesignated the U.S. Army MedicalResearch Institute of Infectious Diseases (USAMRIID) in 1969.The contrtbutions of USAMRIID and its predecessor to militarymedical research and national securtty are legion, and theplanned integration of USAMRIID with National Institutes ofHealth and Department of Homeland Securtty programsthrough the formation of a national biodefense campus at FortDetrtck"' ensures its future leadership role in this area.

Project Whitecoat was the title given to an Army researchprogram "to use human volunteers in medical studies to evalu-ate the effect of certain biological pathogens upon humans in aneffort to detemiine the vailnerahility to attack with biologicalagents" (W.S. Augerson, 1976, cited in Ref. 4. p 20). The objec-tives of the studies involved were to develop medical defensesagainst biological warfare and included techniques for rapiddiagnosis, improved therapeutic and prophylactic agents, anddevelopment of vaccines against biological weapons and en-demic disease threats. The program evolved after a sertes ofmeetings in 1954-1955 hetween representatives of the ArmySurgeon General and the Seventh Day Adventist Church. Withthe background of the Church s philosophy and practice ofmedical service and encouragement of noncombatancy and itslongstanding cooperation with the military in health and medicalpractice. Project Whitecoat became an accepted and respected\'ehicle by which conscientious objectors could serve the nation."'From its inception in 1954 to its termination in 1973, approxi-mately 2.300 individuals participated in this program, more than90% of whom were Seventh Day Adventists. Tbe group partici-pated in more than 135 clinical research studies involving expo-sure to live agents, receipt of investigational vaccines, and studiesof metabolic and psychologicaJ effects of environmental- and infec-tion-induced stress.-"^ Most volunteers participated in at least oneproject, whereas some participated in several. The current study

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4. TITLE AND SUBTITLE An assessment of health status among medical research volunteers whoserved in Project Whitecoat program at Fort Detrick, Maryland, MilitaryMedicine 170:183 - 187

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6. AUTHOR(S) Pittman, PR Norris, SL Coonan, KM MeKee, KT Jr

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7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) United States Army Medical Research Institute of Infectious Diseases,Fort Detrick, MD

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14. ABSTRACT Between 1954 and 1973, more than 2000 men entering military service as conscientious objectorsparticipated in Project Whitecoat as medical research volunteers for the Army’s biological warfare defenseprogram. An assessment of self-reported, current health status among 358 "exposed" individuals and 164unexposed control subjects found no conclusive evidence that receipt of investigational agents was relatedto adverse health outcomes. No differences in current overall health, current exercise levels, self-reportedsymptoms, and self-reported medical conditions were seen between the study groups. Possible associationswere seen between exposure to antibiotics or other biological agents and self-reported asthma (13.0% vs.2.4%, relative risk [RR] = 6.00, 95% confidence interval [CI] = 1.03-34.90, p = 0.050), as well as betweenreceipt of tularemia vaccine(s) and self-reported asthma (13.3% vs. 2.4%, RR = 6.15, 95% CI = 1.03-36.70,p = 0.049) and increased frequency/severity of headaches (35.6% vs. 18.3%, RR = 2.46, 95% CI =0.99-6.15, p = 0.074). However, the size of the population under study was insufficient to assert withconfidence that these statistical associations are real.

15. SUBJECT TERMS Whitecoat Project, health status, volunteers, human

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184 Health Status among Project Whitecoat Volunteers

was designed to assess the long-terai effects on the health of thesemen resulting from their involvement in this vital program.

Methods

Study Design

This was a controlled, unblinded, retrospective, cohort studyto assess the health status of indi\'iduals who volunteered toparticipate in Project Whitecoat at Fort Detrtck, Maryland, dur-ing 1955-1973.

Study Population

Approximately 2.300 men who entered military service andwere classified as conscientious objectors participated in ProjectWhitecoat. Most were assigned to Fort Detrick. Maryland, andindividuals there were assigned a vartety of duties in support ofthe medical research efforts at the facility. Some worked astechnicians in research laboratories, some worked as hospitalcorpsmen. and others were assigned predominantly administra-tive duties and responsibilities, Pertodically. the group member-ship was approached regarding interest in participating as vol-unteers for clinical research studies. Most studies were relatedto exposure to infectious diseases, for which volunteers wouldreceive proven therapies and occasionally investigational pro-phylactic agents (e.g., vaccines).

Subjects for this study were recniited from among the mem-bership of the Project Whitecoat alumni group. A total of 358men who were exposed to an infectious agent or vaccine (studygroup) and 164 men who participated in research studies asunexposed eontrol subjects (control group) agreed, after signinga wrttten infoniied consent agreement, to complete a self-ad-ministered questionnaire that inquired about health status, on-going clinical symptoms and signs, reproductive outcomes, anddiseases or conditions diagnosed by competent medical author-ities. The study was renewed and approved by the institutionalreview board at USAMRIID. as well as by the Human SubjectsResearch Review Board ofthe U.S, Army Surgeon General.

Exposure Histories

Records for participation in clinical protocols, including re-ceipt of vaccines and disease-causing agents, were obtained byreviewing archives at USAMRIID, The name and type of study inwhich each volunteer participated were extracted from th'eserecords and entered into an automated database for analysis. Atotal of 197 volunteers received investigational vaccines. Theavailable data did not allow distinction between live vaccinesand killed/toxoid products, nor did they allow enumeration ofthe numbers of different vaccine candidates involved in testing.Two hundred eleven indi\iduals were exposed to disease-caus-ing agents (some of which might have involved exposure todifferent strains of a given pathogen), and 46 received antibiot-ics or other therapeutic agents (in physiological or other studiesseparate from treatment for exposures in other protocols),

Statistical Analyses

The x^ and Fisher exact tests were used to compcire propor-tions and the ( test was used to compare mean differencesbetween the exposed (study) and control groups. Rate differ-ences between groups were compared with Fisher exact tests

adjusted for multiple compartsons using a resampling bootstrapapproach (SAS MULTTEST) for sets of related vartahles (e.g.,symptoms, diseases and conditions, and reproductive out-comes). To examine the effect of multiple exposures in the ex-posed (study) group by itself, logistic regression analysis of thenumber of studies in which subjects were enrolled was used. Toexamine the possibility that confounder vartables could explaingroup differences, further analysis was done using logistic re-gression analysis of demographic vartables. Subgroup analysiswas conducted based on class of exposure (vaccine, pathogen,or therapeutic agent). Effects of individual agents were as-sessed; however, sample sizes were insufficient for conclusiveresults, All analyses used SAS version 8.2 (SAS Institute. Cary.North Carolina),

The statistical power of this study to detect rate differencesbetween groups was assessed using a power analysis program.^With the sample sizes of 358 control subjects and 164 studysubjects, with testing at the 5% level of significance (one-tailedj.a minimal difference in relative rtsk (RR) of twofold could bedetected with at least 80% probability' for rates of health relatedoutcomes, over a range of background health condiUon rates forthe control subjects.

Results

Study Population Charactertstics

Study subjects were male and predominantly (91,0%) Cauca-sian, The median duration of assignment at Fort Detrtck was 2.0years (range. 0-8 years). The mean age of the population at thetime that the survey was performed was 58.4 years (range.46-79 years); the majority of study subjects were highly edu-cated (58.2% possessed college or graduate degrees). Although12.8% of those completing surveys were retired at the time ofthestudy, less than one-half (47.9%) were fully employed. No de-mographic differences were found between subjects who hadbeen exposed to test agents- in the course of participation inclinical research studies and those who had served as controlsubjects for the same studies (Table I).

Eighty-seven percent ofthe study participants reported theircurrent state of health as good or excellent, and 72.6% claimedto engage in at least some exercise every week. Exposed andcontrol subjects did not differ with regard to current overallhealth status or current exercise level (Table II),

A relatively small proportion of individuals reported tobaccoand/or alcohol use. Only 14.9% of survey respondents admittedto having ever smoked cigarettes. 7,7% to having ever smokedcigars. 7,9% to having ever smoked a pipe, and 1,1% to havingever used chewing tobacco or snuff. Aside from a slightly higherpercentage of subjects who had been exposed to test agentsclaiming to have quit smoking cigarettes, no differences betweenthe exposed and control groups with regard to tobacco andalcohol consumption were evident (Table II).

Exposures

Among the 358 exposed subjects. 303 participated in onestudy while assigned to Fort Detrtck, 75 participated in twostudies, 17 participated in three studies, and 1 participated infour studies. Vaccine exposures included Venezuelan equineencephalitis (73 persons), tularemia (45 persons), yellow fever

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Health Status among Project Whitecoat Volunteers 185

TABLE I

DEMOGRAPHIC DATA

Study(n = 358)

Control[n = 164)

Race(%)Caucasian 90.8 91,5 0.832African American 3.6 4.3Other 5.3 4.3

Male 100.0 100,0 NTMean age. years (range) 58.4 (47-74) 58.5 (46-79)0.822Mean time spent at Fort Detrtck. 1.5 (<l-8) 1.5 (<l-3) 0.635

years (range)100.0 100.0 NT55.9 63.4 0,126

Served in military (%)College degree or higher (%)Current employment statusRetiredEmployed full-timeEmployed part-timeNot working because of

disabllitv

11.751.131.0

5.6

t5,240.938.4

5,5

0.145

"Tests are two-tailed. NT. not tested.

TABLEn

HEALTH AND BEHAVIORAL CHARACTERISTICS

Studytn = 358)

Control(n = 164)

Current health status (%) 0.375Excellent 39.4 47.6Good 46.6 41.5Fair 10.6 9.1Poor 2.8 1.8

Current exercise level (%) 0.579None 25.4 20.1More than 5 times/week 10.9 10.4Up to 5 times/week 60.1 65.9Disabled 3.1 3.0

Tobacco historyEver smoked cigarettes (%) 14.8 15,2 0.896No. of packs/day (mean) 1.0 1.5 0.285No, of years smoked (mean) 10.0 11.8 0,500Quit (among those ever 96.2 80.0 0.031smoked) (%)

Years since quitting (mean) 23.0Ever smoked pipe (%) 7.5Ever smoked cigars (%) 7.8Ever dipped snuif/used chewing 1,4tobacco(%)

Alcohol use. ever drink (%) 15.1 19.5 0.206

16,58,57.30.6

0.0840.7261,0000,670

° Tests are two-tailed.

(31 persons). Eastern equine encephalitis (29 persons), Westemequine encephalitis (28 persons), plague (13 persons), Q fever(11 persons). Rift Valley fever (8 persons), anthrax (7 persons),chikungunya (six persons), and adenovirus (4 persons). Virulentagent exposures included Cordelia humetii (Q fever) (58 per-sons), sand fly fever (30 persons), staphylococcal enterotoxin B(20 persons). Franciseiia iuiarensis (tularemia) (11 persons).Venezuelan equine encephalitis (7 persons), and Pseudomonasendotoxin (2 persons). Antibiotic and other therapeutic agentexposures included tetracycline (25 persons), amino acids (15persons), chloramphenicol (4 persons), and tyrosine (4 persons).

Subjects who volunteered to participate in virulent bactertalagent exposure studies (e.g.. Q fever or tularemia) also receivedcurative antibiotics during, or at the conclusion of, each project.

OutcomesMost (87%) study participants reported having had children.

The proportions of exposed and control subjects with childrenwere similar (87.4% and 86.0%. respectively). A total of 1,052children were reported to have been sired hy the 522 studyparticipants. The vast majority (92,3%) of these children werereported as normal and healthy. No differences between exposedand control groups in the numbers of children per individual.children uith congenital abnormalities, or children with mentalretardation were seen (Table 111),

No differences between exposed subjects and control subjectswere seen with regard to self-reported clinical signs and symp-toms or diseases (or other medical conditions) (Tables IV and V],When symptoms and diseases among individuals who had re-ceived all vaccines and those who had received all virulentagents were examined separately, there remained no differencesbetween the groups. Asthma was reported more freqtientlyamong the group of subjects exposed to all antibiotics or othernonagents than among control subjects (13.0% vs, 2.4%, RR =6.00.95% confidence interval [CI] - 1.03-34.9, p = 0.050, afteradjustment for multiple compartsons).

Attempts to assess frequencies of clinical signs and symp-toms or diseases by individual vaccine, individual virulentagent, and individual antibiotic/other agent exposure yieldednumbers too small for meaningful analysis for all except recip-ients of Venezuelan equine encephalitis vaccine(s), tularemiavaccine(s). or virulent C. btimdit. Among these exposures, apossible association between asthma and receipt of tularemiavaceine(s) was observed (13,3%ofvaccineesvs. 2.4% of controlsubjects. RR - 6.15, 95% Cl = 1,03-36.70. p = 0.049. afteradjustment for multiple compartsons). In the same cohort, anassociation with an increased frequency of headaches (never orrarely a problem vs. occasionally or more frequently a problem)among tularemia vaccinees was suggested (35.6% vs. 18.3%),but the difference from control subjects did not reach statisticalsignificance (RR = 2.46, 95% CI = 0.99-6.15. p = 0.074, afteradjustment for multiple compartsons). There were no differ-ences in any outcome vartables (general health, exercise levels,reproductive outcomes, reported symptoms, or reported medicalconditions) between subjects participating in one study andthose participating in two or more studies (data not shown).

TABLEmREPRODUCTIVE OUTCOMES

No. of children, mean (range)Had anv childrenHad children with birth defects

or mental retardationNo. of children (,'V= 1.052)

"Normal/hcalthy-With birth/congenital defectsWith mental retardation

Study(n = 358)

2,0 (0-7)313(87,4%)

25 (7,0%)

Control(n = 164) ff

2.0 (0-6) 0.502141 (86.0%) 0.647

15(9.1%) 0.381

698 (95.6%) 306 (95.0%) 0.54024 (3,3%)

8(1.1%)14 (4,3%)2 (0,6%)

' Tests are two-tailed.

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186 Health Status among Project Whitecoat Volunteers

TABLE IV

SELF-REPORTED DISEASES AND CONDITIONS

TABLE V

SELF-REPORTED SYMPTOMS

Study

Condition No.

Controi

No. %Amylotdosi.s 0 0,0 0 0.0 1.000Anemia 6 1.7 2 1.2 1.000Anemia of rhronic disease 1 0.3 0 0.0 1.000Aplastic anemia 0 0,0 0 0,0 1,000Arthritis 55 15,4 25 15,2 1,000Asihma 25 7.0 4 2.4 0.165Atopic dermatitis 2 0.6 2 1.2 1.000Cancer 26 7.3 17 10.4 1.000Diabetes mellitus 25 7.0 17 10.4 1,000Eczema 13 3,6 5 3,0 1,000Erythema nodosum 1 0,3 0 0.0 1.000Freqiieni colds 20 5.6 8 4.9 0,998Glomerulonephritis 0 0.0 2 1.2 1.000Goodpasiure's syndrome 0 0.0 0 0.0 1.000Guillain-Barre syndrome 2 1,2 1 0.3 1,000Hay fever 55 15,4 26 15,9 1,000Hemolytic anemia 0 0,0 2 1.2 1.000Hod,̂ kin's disease 0 0.0 0 0.0 1.000I lyperiension 78 21.8 41 25.0 1.000Immune complex disease 1 0,3 1 0.6 1.000Iron deflfiency anemia 1 0,3 2 1,2 1,000Kidney disease 8 2.2 12 7,3 1.000leukemia 0 0.0 1 0.6 1.000lx>\v white blood cell count 9 2.5 2 1.2 0,964Lupus 0 0,0 0 0.0 1,000Multiple myeloma 0 0,0 0 0.0 1,000Multiple sclerosis 1 0.3 0 0.0 1.000Neuritis 2 0.6 0 0.0 1.000Parkinson's disease 3 0.8 1 0.6 1.000Platelet problems 3 0,8 3 1,8 1,000Pneumonia 43 12,0 24 14,6 1,000Pneumoniti.s ] 0.3 0 0.0 1.000Reiter's syndrome 1 0.3 1 0.6 1.000Rheumatoid arihritis 4 i.l 3 1.8 1.000Sarcoidosis 2 0,6 2 1.2 1,000Semm sickness 0 0,0 0 0,0 1,000Sjogren's syndrome 0 0.0 0 0,0 1.000Temporal arieritis I 0.3 1 0.6 1.000Thyroid disease 11 3.1 7 4,3 1.000Ulcers 23 6,4 7 4,3 0.938Uveitis 2 0,6 0 0,0 1,000VascullUs 0 0,0 2 1.2 1,000Vitamin B,̂ deficiency 2 0.6 I 0.6 1.000Wcgeners granulomatosis 0 0.0 0 0.0 1.000Total 427 222

" One-tailed(bootstrap).

Fisher exact test adjusted for multiple comparisons

Discussion

Men entertng military service between 1955 and 1973 whovolunteered to serve at Fort Detrtck in Project Whitecoat partic-ipated in a wide vartety of clinical research studies invohingexposure to investigational vaccines, pathogenic agents, otherbiologicals (such as antibiotics), and environmental stresses. Ibrthe purpose of prepartng our nation against the threat of bio-logical warfare. Most, but not all. Project Whitecoat participantswere members of the Seventh Day Adventist Church. Individu-

SymptomArthralgia

SevereModerateMild/none

FatigueSevereModerateMild/mine

MyalgiaSevereModerateMild/none

InsomniaSevereModerateMild/none

DepressionSevereModerateMild/none

Memory lossSevereModerateMild/none

Abdominal painSevereModerateMild/none

HeadacheSe\'ereModerateMild/none

MalaiseSevereModerateMild/none

TremorsSevereModerateMild/none

FeversSevereModerateMild/none

RashesSevereModerateMild/none

Study.No.

31126201

26100232

1080

268

2497

237

1353

292

951

298

446

308

671

281

1847

293

113

344

017

341

431

323

Control.No.

1549

100

739

118

737

i20

1240

112

818

138

523

136

214

148

129

134

6i8

140

18

155

06

158

211

151

Study.%

8.735,256,1

7.327.964,8

2,822.374.9

6,727,166,2

3.614,881,6

2.514,283,2

l.I12,886.0

1,719.878.5

5.013,181,8

0.33.6

96,1

0,04.7

95.3

1,18.7

90.2

Control.%

9,129,961.0

4.323,872,0

4.322.673.2

7,324,468.3

4.911.084,1

3,014.082.9

1.28.5

90.2

0,617,781,7

3.711.085,4

0.64.9

94,5

0,03.7

96.3

1,26.7

92.1

pfi

0.488

0.204

0.671

0,799

0.419

0.939

0.357

0.504

0,593

0.676

0,653''

0.746

" Comparisons by ̂ test exeepl as noted.''Two-tailed Fisher exact test,

als were recruited from the ranks of enlisted soldiers (predomi-nantly draftees) with a 1-A-O (conscientious objector) classifi-cation who were engaged in basic or advanced indiWdualtraining at the Medical Training Center, Fort Sam Houston.Texas. Upon arrtval at Fort Detrtck, personnel underwent acomplete sertes of medical evaluations (including detailed his-tory, physical examination, and laboratory studies) and thenwere assigned to a vartety of duties within the Medical Research

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Health Status among Project Whitecoat Volunteers 187

Unit/USAMRIID, such as laboratory technician, animal care-taker, medic, or supply clerk. All duties were noncombatant innature. All remained full-time soldiers, and most remained atFort Detrick for the duration of their service obligations. Nospecial consideration or prt\ileges were accorded Project White-coat participants.

When volunteers were needed for specific research studies, abrtefmg to an assembly of Project Whitecoat personnel was pro-vided by the commanding officer, regarding the nature andpurpose ofthe project, the rtsks involved, and the requirementsfor each participant. Questions were then entertained. Thoseexpressing interest in participating were subsequently inter-viewed individually: details of the study were recounted, indi-viduals were allowed to ask questions, and. if the indi\1dualagain expressed interest in participating, signed consent wasobtained (USAMRIID 1969 Fact Sheet, cited in Ref, 8).

Durtng the course of the program. Project Whitecoat volun-teers participated in approximately 150 studies." Althoughsome of the projects remain classified, the vast majority ofthework was conducted openly and was reported in the scientificand medical literature. No fatalities directly attrtbutable to par-ticipation in these clinical trtals occurred. Although the trtalsmet and often exceeded the ethical standards of the day forresearch involving human subjects, the current clinical re-search climate would preclude repetition of many of these stud-ies today. The data obtained from research invohing ProjectWhitecoat volunteers therefore stand as unique and representthe only human data available in many areas.

To date, there has been no systematic attempt to assess thelong-term impact of these exposures on the health of ProjectWhitecoat volunteers. In 1991-1992, a questionnaire designedto capture reflections on their expertences, the reasons behindtheir interest in participating in the program, and demographicprofiles was completed by approximately 200 former partici-pants.^ One question in this survey addressed potential residualeffeets of program participation on health. At that time, only oneindiNidual in the program had been awarded a service-con-nected disability designation. A "few" other Project Whitecoatparticipants cited program participation as a cause of currentmedical problems: none was confirmed by medical review,^" Thecurrent study was an attempt to objectively assess the impact ofparticipation in clinical research studies by the Project White-eoat population by compartng questionnaire responses fromthose who were exposed to agents, biologicals, or other potentialstressors and those in the program who served as control sub-jects for the expertments.

Analyses of questionnaires completed by volunteers for thisstudy provided no evidence that exposures sustained by partic-ipants in Project Whitecoat were associated with adverse healthoutcomes. The exposed and control groups were comparable in

most demographic and liiestyle parameters. No differences werereported in overall health status between the two groups, andthere were no evident effects on reproductive outcomes. Asthmawas reported more frequently among subjects exposed to anti-biotics or other inert substances than among control subjects,and similar borderline higher frequencies were observed forreported asthma and headaches among subjects exposed totularemia vaccines. However, the size of the population understudy proved insitlficient to conclude that these statistical as-sociations were real.

This study has a number of shortcomings. Mortality ratescould not be assessed because ol" incomplete reporting for thetotal Project Whitecoat population. There are selection and otherbiases inherent in a volunteer study of this nature, which mighthave affected our findings. The sample sizes available were in-sufficient to detect rare health effects. Furthermore, no labora-tory studies were performed as part of the study, and no reviewof medical records was attempted. Tlierefore, health conse-quences from exposures expertenced by Project Whitecoat par-ticipants ntight have been missed. However, the dearth of evi-dence suggesting adverse health effects reported by thevolunteers who agreed to participate argues against such apossibility.

Project Whitecoat represents an important chapter in thehistory of medical defense against biological weapons and inhuman expertmentation. The men who volunteered to partici-pate in the seminal studies that pro\1ded proof of concept in somany crttical areas should be heralded for their contrtbutions toscience and medicine in both the military and civilian sectors. Itis gratifying that no adverse impact on the overall health ofProject Whitecoat volunteers could be conclusively attributed totheir participation in these important research studies.

References

1, Clenciemn iiM: St'ieiiif andTerhnoiogy at Fort Detrick 1943-1968. Washington.t)C, tJ.S, Army. 196«,

2, Smart JK; 1 listory of clipinical and biological warfare: an American perspective.In: Medical Aspeci.s of Cheniiciil and Biologic-al Warfare, pp 9-85- Edited by SideliVR. Takafiijl ET. Frann DR, Washington, Df, Uoriieri iiislitntc. Waiter Reed AmiyMedirat Center. 1997.

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Mmtarv Medicine, Vol. 170. March 2005

Approved for public release. Distribution is unlimited.

Approved for public release. Distribution is unlimited.