Human Experimentation

Human ExperimentationHistorical Perspective of Breaches of Ethicsin US Health Care

Elizabeth J. Layman, PhD, RHIA, CCS, FAHIMA

Health care supervisors and managers may participate in ethical discussions and serve on ethicscommittees in their health care organizations. To aid them in their participation and service, thisarticle expands upon the knowledge of ethics that they obtained in their academic training. Thearticle provides readers with a common language based on frequently cited cases and keydocuments. The article traces a brief history of human experimentation, describes ethical breachesin the United States, and summarizes key documents guiding current thought on informed andvoluntary consent. The article concludes with 3 common misconceptions that health caresupervisors and managers will want to avoid in ethical discussions and ethical decision making.Health care supervisors and managers will be prepared to meaningfully contribute to thediscussion of ethical issues and to the resolution of ethical problems in their health careorganizations. Key words: codes of ethics, ethics, history, informed consent, research subjects

THIS ARTICLE PREPARES health care su-pervisors and managers to contribute to

discussions of ethics in their health care or-ganizations. Representing a variety of back-grounds, these health care supervisors andmanagers will be able to participate in theprocesses of their organizational ethics com-mittees. Unfortunately, history demonstratesthat ethical behavior cannot be assumed.Moreover, technology is advancing faster thanour philosophical understanding of its impli-cations. Thus, in academic curricula, the his-tory of ethical breaches may be abbreviated todiscuss current topics with the intention ofpreventing future breaches. The breadth anddepth of historical discussions may be onlythe origins of informed consent, such as theNuremberg Code1 and the US Public Health

Service Syphilis Study, more commonly knownas the Tuskegee Syphilis Study.2 To emphasizethe need for continued attention to the studyof ethics and ethical codes, this article ex-pands upon health care personnel’s academicpreparation in ethics.

The study of ethics is an element in thehealth disciplines’ academic curricula. Thisstudy is often mandated by the accreditingstandards for academic programs (Figure 1).These accrediting standards use terms andphrases, such as ethics, professionalism, pro-fessional standards, professional ethics, ethi-cal practice, and professional values.

The health disciplines have ethical codes.The establishment of these codes has evolvedover time, with the Hippocratic Oath ofmedicine being the first. The ethical codes ofnursing and allied health have emerged withthe professionalization of these disciplines.The health disciplines’ professional associa-tions maintain and apply these codes ofethics (Figure 2). These codes of ethics mayalso be known as codes of conduct or state-ments of ethics and professional conduct.

In the health disciplines’ academic curric-ula, the underlying principles of ethics andethical codes are studied, such as justice,fidelity, honesty, and autonomy. Then, the in-dividual standards of the codes are discussed

Author Affiliations: Department of Health

Services and Information Management, East

Carolina University, College of Allied Health Sciences,

Greenville, North Carolina.

Corresponding author: Elizabeth J. Layman,

PhD, RHIA, CCS, FAHIMA, Department of Health

Services and Information Management, East Carolina

University, College of Allied Health Sciences, Health

Sciences Bldg 4340D, 600 Moye Blvd, Greenville,

NC 27834 ([email protected]).

The Health Care ManagerVolume 28, Number 4, pp. 354–374Copyright # 2009 Wolters Kluwer Health |Lippincott Williams & Wilkins

354

9Copyright @ 200 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

with examples of modern-day behaviors, bothappropriate and inappropriate. Common top-ics include obtaining informed consent, main-taining confidentiality, and applying modelsof ethical decision making. Finally, the studyconcludes with discussion of suitable coursesof action for breaches of ethics within thestructure of the professional organization.

Expanding this study and preparation, thisarticle first traces a brief history of humanexperimentation. Throughout history, research-ers have used human subjects to assess therapiesand to advance medical knowledge.3 How-ever, human experimentation, improperly con-ducted, is an ethical breach. Specifically, ethicsare breached when researchers experiment

Figure 1. Representative examples of curricular standards on ethics.

Historical Perspective of Breaches of Ethics 355


on humans without their knowledge orinformed consent. Second, the article througha review of the literature provides informa-tion about human experimentation in theUnited States. Frequently cited cases of ethi-cal breaches in the use of human subjects aresummarized. Many of researchers who con-ducted unethical experiments on humanswere physicians. Third, the key documentsin the evolution of protections for US hu-man subjects are described. Finally, the article

addresses common misconceptions of whichhealth care supervisors and managers shouldbe aware during discussions of ethical issuesin health care organizations.

BACKGROUND

Human experimentation is anything doneto individuals to learn how it will affectthem.4 The main objective of human ex-perimentation ‘‘is the acquisition of new

Figure 1. (continued)

356 THE HEALTH CARE MANAGER/OCTOBER–DECEMBER 2009


scientific knowledge rather than therapy.’’4(p164)

Human experimentation is also differentiatedfrom therapy because human experimenta-tion may be conducted on healthy individ-uals, sometimes actually inducing disease.4

A form of human experimentation is self-experimentation or autoexperimentation.Self-experimentation is when researchers usethemselves or their family members, col-leagues, or students, as subjects.5

Human experimentation has a long history.4

To provide a general frame of reference, a

few examples of human experimentationfrom history will be discussed. In Alexandria,in approximately 300 BCE, Herophilus bothdissected and vivisected (dissections of liv-ing beings) humans to learn and teach anat-omy.6-8 Theophanes, writing between 810and 814 CE, described a human’s vivisec-tion.9 According to Theophanes, physiciansin Constantinople had vivisected a prisonerfrom pubis to chest to understand anatomyand thus to improve treatment.9 In the early1800s, Hamilton, a Scottish physician in the




British Army Medical Department, describedan experiment on bloodletting. The subjectsof the 1809 experiment were 366 soldiersfighting in the Peninsular War in Portugal. Inthe experiment, Hamilton and another phy-sician did not use bloodletting, whereas athird physician did.10

HUMAN EXPERIMENTATION IN THEUNITED STATES

Human experimentation occurred in theUnited States, similar to its history in Europeand the Middle East. In the early and mid-1800s, few individuals expressed concern for

Figure 2. Representative list of ethical codes.



the subjects of human experimentation. Atthe time, the emphasis was the glory of sci-ence and the ‘‘march of knowledge.’’11(p119)

Concerns, though, about the ethics of humanexperimentation existed in the United Statesbefore World War II. For example, in 1916, theAmerican Medical Association consideredamending its ethical code to include a standardabout human experimentation, such as re-quiring consent.5 However, this amendmentwas not adopted.5 In addition, court cases inthe 1930s established the principle of in-formed consent, although the principle wasnot widely applied.12,13 Finally, some research-ers believed that 2 conditions made human ex-perimentation acceptable: prior experimentson animals and self-experimentation.5,14 How-ever, many research studies in the UnitedStates did not conform to these conditions.5

Thus, prior to World War II, few formalguidelines existed for researchers conductingexperiments on humans.5

The research on yellow fever has long beenthe ideal model for research on human sub-jects in the United States. Walter Reed and his3 colleagues, Jesse Lazear, James Carroll, andAristides Agramonte, conducted research onyellow fever in 1900 through 1901. In late1900 and early 1901, the team investigatedwhether yellow fever was transmitted bymosquitoes. The team conducted a series ofexperiments on humans because earlier ex-

periments on animals had been unsuccessful.In previous research, inoculating animals toinfect them had failed many times.15 In August1900, at Columbia Barracks, a US military basenear Havana Cuba, Carroll and Lazear allowedmosquitoes to bite them.16 From this autoex-perimentation, both developed yellow fever,Lazear’s case being fatal on September 25,1900.16 Agramonte was a Cuban scientist whohad worked in Reed’s research laboratory inthe United States.16 He had acquired immu-nity to yellow fever as a child.15,16 Beginningin November 1900, Reed conducted a struc-tured series of experiments at Camp Lazear, aquarantined research station on the ColumbiaBarracks.16 The 22 volunteer subjects con-sisted of 12 US Army personnel, 1 non–USArmy personnel, and 9 recent Spanish immi-grants to Cuba.15,16 Of the 22 volunteers, the4 immune subjects were the control groupand the remaining 18 nonimmune subjectswere the experimental group. There were 4series of experiments in which inoculationsand mosquitoes were tested as means oftransmission of yellow fever. The 4 series ofexperiments resulted in 14 cases of yellowfever; all the subjects recovered. In the UnitedStates, the yellow fever research is the idealmodel for research on human subjects for2 reasons. Animal experimentation precededhuman experimentation, and contributing tothe renown of the yellow fever research,




some members of the team subjected them-selves to autoexperimentation. Contrary tomyth, Walter Reed did not subject himself toautoexperimentation.17 Reed did not inocu-late himself because George Miller Sternberg,surgeon general of the Army, either orderedor strongly advised Reed not to experiment onhimself because of his age of 49 years.15,16

Second, notably, Walter Reed obtained signedinformed consent for the potential subjects.The subjects (or their designee in case ofdeath) were paid $100 in American gold andan additional $100 in American gold shouldthey contract yellow fever.15 Thus, since theearly 1900s, the yellow fever research hasbeen set forth as the standard in human ex-perimentation. Finally, until the mid-to-late1960s, the moral rectitude exhibited bythe yellow fever researchers justified self-regulation of biomedical research and de-terred its regulation.17

In 1966, in a pioneering article, Beecher18

questioned this moral rectitude. With the ‘‘enor-mous and continuing increase,’’ 624-fold, infederal funding between 1945 and 1965, thenumber of experiments using human subjectsincreased after World War II.18(p1355) Beecher18

raised awareness that subjects were not in-formed of the risks and that many subjectswere not even informed of their status as ex-perimental subjects.18 Beecher’s18 articlecited 22 instances of ethically questionablehuman experiments, many at leading univer-sities19. Beecher compiled his list of ethicallyquestionable human experiments from pub-lished research. His original list had 50 in-stances, but for reasons of space, he reducedthe list to 22 examples (Figure 3). The fol-lowing chronology of selected human ex-perimentation shows how researchers neithermet the conditions of acceptability nor con-formed to the ideal model set by the yellowfever research.

1800s to 1920

Experiments on human subjects were con-ducted in the United States from its earlyhistory. Often, these experiments were con-ducted on persons of lower socioeconomic

classes.11 Given society’s acceptance of socialclasses in the 19th century, there was littlecriticism.11

Beaumont conducted several experimentson gastric and digestive physiology between1823 and 1833.11 His subject was St Martin, aFrench-Canadian voyageur working in theUnited States. St Martin had been shot acrossthe abdominal wall with a resulting chronicgastric fistula.11 Beaumont used the fistula toadminister and insert various solutions andobjects.11 He then observed physiologicalprocesses, such as digestion times.11 Express-ing his dislike for his role, St Martin peri-odically disappeared.11 In 1832, to securehis experimental subject, Beaumont signedSt Martin to a 1-year contract. Per the con-tract, St Martin was to ‘‘obey, suffer and com-ply with all reasonable and proper orders orexperiments’’ for $150 and room, board, andclothing.11(p117) In 1833, St Martin wenthome to Canada, never to return to Beau-mont’s care.11 The difference in social statusand wealth makes Beaumont’s use of StMartin ethically questionable.

Between 1842 and 1846, Long, a physician,and Morton, a dentist, conducted experi-ments on humans. Working independently,they were each experimenting with potentialanesthetic agents.20,21 In March 1842, Longremoved a tumor from a patient’s neck, suc-cessfully anesthetizing the patient withether.20 Long did not publicize his experi-ment until December 1849, after reading sev-eral other writers’ accounts of ether’s use.20

In a letter to editor of the Medical Examiner,he explained that his ‘‘very laborious coun-try practice’’ prevented him from publishinghis findings earlier. In 1845, demonstratingat Harvard Medical School, Morton was un-successful in controlling a patient’s pain whileextracting a tooth.21 However, in 1846, atBoston’s Massachusetts General Hospital, Mor-ton successfully eliminated a patient’s painduring neck surgery using sulfuric ether.21

J. Marion Sims is known as the father ofgynecology.22 He invented a treatment forvesicovaginal fistula, a common condition inthe 1800s.22 Vesicovaginal fistula is an ab-normal tract between the bladder and the



Figure 3. Beecher’s list of unethical or questionably ethical experiments reported in the literature.



vagina caused by an obstructed obstetricaldelivery. The abnormal tract allows urine tocontinuously flow into the vagina. From 1845to 1849, Sims experimented on black slavesto develop his surgical treatment.23,24 The

first surgeries were performed without anes-thesia as the use of ether was still little knownand controversial.24 One slave with both avesicovaginal fistula and a rectovaginal fistulaunderwent 30 surgeries to repair the holes













among the bladder, rectum, and vagina.24 Inthe 1850s and 1860s, Sims performed surger-ies on poor, female Irish immigrants.22 Thelack of autonomy of vulnerable populations,such as slaves and impoverished people, castsdoubt on the voluntariness of their consent.22

In 1911 and 1912 at the Rockefeller Insti-tute in New York City, Noguchi was workingto develop a syphilis skin test similar to thetuberculin skin test.25 The subjects were re-cruited from clinics and hospitals in NewYork.26,27 In the experiment, Noguchi in-jected an extract of syphilis under the sub-jects’ upper arm skin.25 Skin reactions variedamong healthy subjects and syphilis patientsby the disease’s stage and its treatment.25-27

Of the 571 subjects, 315 had syphilis.26 Theremaining subjects were ‘‘controls’’ who didnot have syphilis and were orphans or hos-pital patients.25-27 The hospital patients hadnonsyphilitic diseases, such as malaria, lepro-sy, tuberculosis, and pneumonia.25,26 Finally,of the controls, 46 were normal individuals,mostly children between the ages of 2 and18 years.25,26 Critics at the time noted thatNoguchi violated the rights of orphans andhospital patients.25

Goldberger and Wheeler,28 in 1915, stud-ied pellagra to determine its cause. Unknownat the time, pellagra is a nutritional disordercaused by a deficiency of niacin (a B complexvitamin). Pellagra can involve multiple bodysystems, including skin, gastrointestinal, neu-rological, and psychological. Goldberger andWheeler28 believed that they could producepellagra in people by controlling their dietbecause previous related studies had shownhigher rates of disease in people with certaindiets. Therefore, with the assistance of theMississippi governor, Goldberger and Wheeler28

controlled the diet of 11 healthy prisoners. Inreturn for participating in Goldberger andWheeler’s study,28 Mississippi’s governor of-fered the prisoners a pardon. For 61/2 months,the prisoners were fed the experimental diet,consisting mostly of grains, such as whitewheat flour, corn meal, hominy grits, whiterice, sweet potatoes, cabbage, collards, turnips,and turnip greens. Of the 11 prisoners, 6 de-veloped pellagra rashes after 5 months. Thus,

Goldberger and Wheeler28showed the causeof pellagra to be diet. The ethical concern iswhether the participation of prisoners canever be truly voluntary.

1921 to 1974

The US Public Health Service Syphilis Study,more commonly known as the TuskegeeSyphilis Study, was conducted from 1932through 1972.2 The 399 African-Americanmale subjects had syphilis.29 The men camefrom poor, rural counties around Tuskegee,Alabama.2,5 The stated purpose of the studywas to obtain information about the course ofuntreated syphilis.5 Although initially shortterm, after 6 months the study was modifiedinto a ‘‘death as end-point study.’’5(p225) Themedical researchers did not tell the men thatthey had syphilis. Instead, the researchers ledthe men to believe that they were receivingspecial treatment from the US Public HealthService for their ‘‘bad blood.’’29 In fact, themen did not receive the period’s conventionaltreatments for syphilis; the men received onlyvitamins and aspirins to deceive them intothinking they were receiving treatments.2

Moreover, the medical researchers acted toprevent the men from receiving treatments bytracking them to other public health depart-ments, by intervening with local physicians,and by preventing them from being draftedinto military service (drafted soldiers beingroutinely treated).2,29 Also, the Public HealthService continued the study after the adventof penicillin in 1940s.29 Finally, many of themen’s wives were infected, and their childrenwere subsequently born with congenitalsyphilis. The Public Health Service SyphilisStudy ended only in 1972 after public outcryand congressional hearings.2

Prisoners are a vulnerable population be-cause the mere status of being incarceratedcasts doubt on the voluntary nature of theirconsent.30,31 Beecher31 explains that ordi-nary people do not willingly risk their health.Thus, subtle coercion may occur when peo-ple, such as patients and prisoners, consent toprocedures that will harm them.31 However,in the 1940s through the 1960s, prisoners



were often subjects in research studies.5 Forexample, in 1943, 241 federal male prisonersat Terre Haute Federal Penitentiary wereinjected with various strains of the gonococ-cus bacteria.5 In this federally sponsoredresearch, the prisoners received $100, a cer-tificate of merit, a letter of commendation fortheir parole boards, and a promise of treat-ment should they contract gonorrhea.5 Alsoduring World War II, more than 1,300 priso-ners at 4 US prisons had been part of researchstudies on malaria. These prisoners also re-ceived $100.5 Only in the 1970s did the UnitedStates discontinue wide-scale experiments onprisoners.5

Sponsored by several US federal agencies,researchers conducted radiation experimentson human subjects between 1944 and 1972.32

In total, there were approximately 4,000human radiation experiments.33 Represen-tative examples of these 4,000 experimentsare listed and described in a special reportto President Clinton.33 The report is orga-nized in chapters by type of human radia-tion experiment, such as research on sickpatients, children, prisoners, and atomic vet-erans.34 Authors of the report and otherwriters described several ethically question-able experiments.

In the late 1940s through early 1950s, atthe residential Fernald School, 32 mentallyretarded children were fed radioisotopes inthe milk for their breakfast oatmeal.13,32 Thepurpose was to study the effect of oat ce-reals on the absorption of the milk’s cal-cium.13 Researchers, with the collusion of theschool’s administrator, had essentially trickedthe children’s parents into giving consent bydescribing the activity as participation in a‘‘science club.’’32 Also, at the school, another17 mentally retarded children were fed ra-dioactive iron to learn about iron absorp-tion in the body.13 Occurring between 1945and 1971, other examples include (1) inject-ing 18 terminally ill patients with high dosesof plutonium to learn whether the humanbody absorbed it, (2) injecting 6 hospital pa-tients with uranium salts to determine thedose required to produce renal injury, and(3) exposing the testicles of 131 prisoners to

x-rays to study the effects of radiation on theproduction of sperm.13

In the 1950s, Gardner and Dukes35 experi-mented on female patients at a volunteerclinic.36 Fifteen infection-free patients wereinoculated with bacterium from the vaginaldischarge of infected patients. Of the 15, 11developed Haemophilus vaginalis vaginitis.According to the researchers, ‘‘Some of thesepatients were allowed to go untreated for aslong as 4 months, none showed spontaneouscure or alteration in the clinical picture.’’35(p968)

In the published article describing the ex-periment, no mention is made of informedconsent.36

In the mid-1950s, there were about 6,000residents at Willowbrook State School in NewYork.37 Of the residents, 77% were severelyor profoundly mentally retarded, 64% couldnot feed themselves, 60% were not toilettrained, 39% were nonambulatory, and 30%had seizures.37 Hepatitis was endemic at theinstitution, with an annual attack rate of 25per 1,000 for children and 40 per 1,000 foradults.37 Beginning in 1956 and for the next20 years, researchers conducted an experi-ment at the school to learn more about thenatural course of hepatitis and its preven-tion.37 The experiment exposed newly ad-mitted children to the Willowbrook strain ofthe hepatitis virus.37 Consent to the experi-ment was obtained from the children’s pa-rents prior to their admission, at first throughindividual meetings and then through groupmeetings.37 However, the consent was de-ceptive because it was worded to read asthough the children were receiving a vaccineagainst the virus rather than being infectedwith the virus.38 Using manipulation anddeceit disregards the rights of subjects and isethically problematic.

In 1963, at Jewish Chronic Disease Hospi-tal, 3 physicians experimented on 22 chron-ically ill and weakened patients.29,39 Thephysicians injected live cancer cells beneaththe patients’ skin to measure the patients’ability to reject foreign cells.29,39 The patientswere told that the injections were a test oftheir resistance to disease.39 They were nottold that the injection was a part of a research



study.39 Nor were the patients told that theinjection was unrelated to any treatments forthem.39 In terms of ethical breaches, thephysicians did not clearly and simply informany of the patients that the injections wereunrelated to their treatment and were part ofan experiment.29,39

1975 to Present

From 1988 through 2000, drugs for thetreatment of AIDS were tested on children infoster care. An investigation conducted byAssociated Press found that foster childrenin at least 7 states were involved in morethan 48 government-funded studies of variousAIDS drugs. The children had HIV, and thestudies allowed the children to receive AIDSdrugs not yet on the market. Often, the re-searchers did not adhere to federally man-dated protections for vulnerable populations,such as advocates for foster children. In termsof representative numbers, 465 foster chil-dren in New York City and 200 foster chil-dren in Illinois were in the pediatric AIDSdrug studies.40,41

In 1996 at the University of Rochester Medi-cal Center, a healthy volunteer died undergo-ing bronchoscopy as part of an experiment.The volunteer was a 19-year-old nursing stu-dent at the university. The experiment inves-tigated the relationship between airbornechemicals and lung cancer.42 Researchersdid not follow approved protocols, and amaximum dose of the topical anesthesia fora healthy subject, lidocaine, was not estab-lished. Lidocaine toxicity was the cause ofthe student’s death.

Gelsinger was 18 years old with a geneticdisorder that affected his ability to metabolizenitrogen.43 ‘‘Relatively fit,’’ Gelsinger’s disor-der could be managed through diet anddrugs.43,44(p2244) In September 1999, as partof a gene therapy trial, a viral vector carryingthe gene was infused directly into Gelsinger’sliver through a catheter.43,45 Gelsinger re-ceived a ‘‘massive dose’’ of the vector; thehighest dose of the 18-subject trial.44(p2244)

Four days after the infusion, Gelsinger died ofmultisystem organ failure.46 Of note, in the

consent, the researchers omitted informationthat monkeys had previously died of toxicityfrom the treatment.43 The researchers alsodid not adequately evaluate Gelsinger prior tothe trial; pre-erythroblast cells in his bonemarrow were depressed, possibly caused byanother genetic disorder or a viral infec-tion.43,44 Moreover, the researchers deviatedfrom their protocol as approved by the Foodand Drug Administration.43,44 Gelsinger’s am-monia levels were 30% to 60% higher than theprotocol’s criterion of eligibility.43,44 Thus, inthis case, information necessary for informedconsent was withheld, and the potential riskexceeded the potential benefit.

In 2001, 24-year-old Ellen Roche, a healthyvolunteer, died as a result of an experiment.47

The experiment’s purpose was to study air-way hyperresponsiveness in asthma by ex-perimenting on the normal airways of healthyvolunteers. In the research protocol, the healthyvolunteers inhaled hexamethonium bromide, aneurotransmission blocker. Roche was the thirdsubject in the experiment. The first subjectdeveloped shortness of breath and a dry cough.Five days after inhaling the hexamethoniumbromide, Roche was hospitalized. Approxi-mately 1 month later, Roche died of progressivehypotension and multiorgan failure; autopsyshowed diffuse alveolar damage.47 At questionis the consent form, which described hexame-thonium bromide as a medication. In fact, theFood and Drug Administration removed hexa-methonium bromide from the US market in1972 after it was shown ineffective in the treat-ment of hypertension.47 The hexamethoniumbromide used in the study was specifically la-beled, ‘‘For laboratory use only, not for drug,household, or other uses.’’47(p717) Thus, thestatement in the consent, that hexametho-nium bromide was a medication, was false. Ahealthy volunteer was put at risk for a non-therapeutic experiment, and her safety wasnot protected.

EVOLUTION OF PROTECTIONS FORHUMAN SUBJECTS

Contemporary beliefs that human beingsneed protection during experiments evolved



over time. In the 1700s and 1800s, the UnitedStates had a class system that allowed in-dentured servants and slaves. Lower classeswere considered socially inferior and notworthy of the same ethical considerations asother citizens.11 As Numbers11 noted, ‘‘In anation that still tolerated involuntary servi-tude and even slavery, it is hardly surprisingthat [the use of humans] for scientific pur-poses elicited little criticism.’’11(pp133,134) Inaddition, the doctor-patient relationship wasinsufficient to protect humans from researchtransgressions.48 Finally, though, beginningin the early 1900s and extending through thesecond half of the 20th century, eventschanged opinions. Key documents that ad-vanced protections for human subjects arelisted in Table 1.

Nuremberg Code

In the United States, current thinking aboutsafeguarding the rights of human subjectsbegan with the Nuremberg Code.19,49 Thetrials at Nuremberg began in 1945 with aninternational military tribunal for the cap-tured Nazi leaders. Extending through 1949,subsequent trials were conducted by individ-ual countries, such as the US Military Tribu-nals (also called American Military Tribunals).Tried at the 12 US Military Tribunals wereNazis from various industries, such as law,finance, manufacturing, and medicine.49 Atthe US Military Tribunal-Doctors’ Trial, 23scientists, 20 of whom were physicians, werecharged with committing war crimes in theconduct of their medical experiments.49

These medical experiments included subject-ing civilian prisoners to hypothermia, castra-tion by x-rays and intrauterine injections,high-altitude conditions by decompressionchambers, injection of typhus and malaria,bone transplantation, and introduction ofbacteria into wounds.12 The NuremburgCode was the set of principles used to judgethe 23 Nazi scientists.19,50 Thus, the NurembergCode evolved from the trial documents of theUS Military Tribunal-Doctors’ Trial. The Codecomprised 10 basic requirements for con-ducting human experimentation.19 Included

within the 10 principles are the concepts of(1) voluntary consent, (2) the subject’s rightto end participation, and (3) the anticipatedhuman benefit to exceed the potential degreeof risk.19 The code became an internationalstatement that human participation researchmust be voluntary and with informed consent.

Declaration of Helsinki

The Declaration of Helsinki is a guide tophysicians conducting biomedical research.The Declaration of Helsinki emerged fromstatements generated by the World MedicalAssociation. The World Medical Associationwas established in 1947. At its second as-sembly at Geneva in 1948, the organizationissued a contemporary restatement of theHippocratic Oath.12 At its assembly in Romein 1954, the organization promulgated ‘‘Prin-ciples for Those in Research and Experimen-tation.’’ The principles included many of thesame concepts as the Nuremberg Code.Beginning in 1961, the ethical committee ofthe World Medical Association drafted con-clusions from its study of human experimen-tation.12 In 1964, the final version of theseconclusions was accepted by the assemblyat Helsinki. Known as the Declaration ofHelsinki, the formal name of the declarationis the Code of Ethics on Human Experimen-tation of the World Medical Association.12 TheDeclaration made 2 important distinctions re-garding human experimentation; it differen-tiated (1) ethical and legal requirements and(2) therapeutic and nontherapeutic experi-ments.51 As a document issued by a physicians’organization, the Declaration of Helsinki in-fluenced the development of similar codesworldwide.51 In the United States, severalmedical associations, including the AmericanMedical Association endorsed it.4

National Research Act, PublicLaw 93-348

Congress passed the National Research Actin 1974. Origins of the Act can be traced backto the early 1950s. In 1953, the Medical Boardof the Clinical Center of the National Institutes



of Health mandated that clinical researchcommittees review clinical projects involv-ing unusual hazards.52,53 In 1966, the PublicHealth Service required that researchers’ ‘‘in-stitutional associates’’ review their clinical re-search.53 The National Research Act of 1974has 2 important aspects. First, the act re-quired that a local oversight committee withlay members review research on human sub-jects. Second, as a response to the reports ofcontemporary ethical transgressions, such asthe Tuskegee Study, the act also created aNational Commission for the Protection ofHuman Subjects of Biomedical and BehavioralResearch.48 The charge of the commission

was ‘‘to identify the basic ethical principlesthat should underlie research on human sub-jects, develop guidelines for such research,and make recommendations to the Secretary ofHealth, Education and Welfare’’ (now knownas Health and Human Services).54(p14) Thus,with the National Research Act, all federallyfunded research required oversight from insti-tutional review boards (IRBs).

Belmont Report

The National Commission for the Protec-tion of Human Subjects of Biomedical and Be-havioral Research issued 5 reports concerning

Table 1. Key documents underpinning ethical treatment of human subjects

Document Source Year Purpose

NurembergCode

US MilitaryTribunal-Doctors’Trial

1947 International statement that humanparticipation research must be voluntaryand with informed consent

Declarationof Helsinki

World MedicalAssociation

1964, Amended1975, 1983,1989, 1996

Guide to physicians conducting biomedicalresearch

NationalResearchAct (PublicLaw 93-348)

US Congress July 12, 1974 Regulation that created the NationalCommission for the Protection of HumanSubjects of Biomedical and BehavioralResearch. The Commission was chargedto identify the basic ethical principlesthat should underlie the conduct ofbiomedical and behavioral researchinvolving human subjects and to developguidelines that should be followed toensure that such research is conductedin accordance with those principles

BelmontReport

US Department of Health,Education, and Welfare;National Commission forthe Protection of HumanSubjects of Biomedicaland Behavioral Research

1979 Fundamental statement of basic ethicalprinciples and guidelines that shouldassist in resolving the ethical problemsthat surround the conduct of researchwith human subjects

Code of FederalRegulations(CFR), Title 45Part 46(45 CFR 46)

Department of Health andHuman Services

1981, Amended2005

Basic federal policy for the protection of humanresearch subjects with subparts on additionalprotections for pregnant women, fetuses,and neonates; for prisoners; and for children.In 1991 adopted by most federal agenciesand is known as the ‘‘Common Rule’’

CFR, Title 21,Parts 50and 56

Food and DrugAdministration

1981 Codification by the Food and DrugAdministration of protections for humansubjects in biomedical and behavioralresearch involving food, colorings, drugs,medical devices, and biological andelectronic products

CFR, Title 38,Part 16

Veterans Administration 1991 Codification by the Veterans Administrationof protections for human subjects inbiomedical and behavioral research



safeguards for human subjects. The first4 reports addressed safeguards for specialgroups, human fetuses, prisoners, mental pa-tients, and children.53 The final report wasthe Belmont Report in which the commis-sion summarized the basic ethical principlesunderlying research on human subjects.These underlying principles are respect forpersons, beneficence, and justice.55 Fromthese underlying principles come the re-quirements for informed consent, anticipat-ed benefit greater than potential risk, and fairselection of subjects.55 As a set of guidingbeliefs underpinned by ethical principles,the Belmont Report greatly influenced thedevelopment of bioethics in the UnitedStates.56

MISCONCEPTIONS TO AVOID

Health care supervisors and managers shouldbe aware of misconceptions in ethical decisionmaking. Awareness may assist health person-nel to avoid these fallacies when making ethi-cal decisions. Three common misconceptionsare ethical relativism, overreliance on the pro-tections accorded by IRBs or human subjectscommittees, and dependence on truisms.

Ethical Relativism

Ethical relativism is the belief that moralvalues depend upon social, cultural, histori-cal, or personal contexts. In ethical relativism,there are no objective standards or universaltruths for moral behavior. In ethical relativ-ism, excuses are made, such as ‘‘It was adifferent world then’’ or ‘‘We can’t judge thepast by contemporary standards.’’32(p26) Forexample, some writers used ethical relativ-ism to justify Sims’ use of female slaves forsurgical experimentation.22,24 Thus, in thisflawed perspective, ethics becomes based oncontext. Buchanan,32 though, explains thatthis perspective denies the existence of hu-man rights also known as the ethical principleof sanctity. Our sanctity is based on just beinghuman. Therefore, how we are treated as hu-mans is independent of context; our sanctity

is not dependent on the time or place inwhich we live.32 Individuals deserve to betreated well and with respect just becausethey are humans, not because they live in aparticular time or place.

Overreliance on Protections Accordedby Institutional Review Boards

Institutional review boards also known ashuman subjects committee are bodies thatprovide oversight for research studies con-ducted within institutions. Over the last30 years, they have been very successful inensuring that researchers conduct well-designed research studies and that theyobtain informed consent.57 However, as localbodies, they have limitations. First, patient-consumers’ demand for new experimentaltreatments has overridden the protectionsof informed consent. Patient-consumers, nolonger suspicious of the risk of experimentaltreatments, want to obtain these experimen-tal treatments, believing that these treatmentsmay be the most advanced and therapeutic.Patients with AIDS were the first to demandexperimental drugs; now, other patients withother conditions, such as Alzheimer diseaseand Parkinson disease, are making similardemands.57,58 Second, members of IRBs as-sess the quality of the scientific protocol; theydo not assess the research’s potential implica-tions for policy or society.57 Thus, an IRB ap-proved a research protocol for experimentsthat underpinned human cloning.57 The mem-bers of the IRB had not assessed the moraland societal ramifications of this medical tech-nology.57 Finally, the procedures of IRBs donot make publicly visible the development ofparadigm-shifting technologies. Thus, thesenew technologies, which have implicationsfor public policy and law, are not submittedto public scrutiny and debate about theirdesirability.57

Dependence on Truisms

In dependence upon truisms, persons putexcessive faith in the truth of common say-ings, such as ‘‘for the public good,’’ ‘‘in thegeneral interest,’’ or ‘‘society cannot afford it.’’



Although these sayings often contain a germ oftruth, ethical issues are too complex to resortto simple axioms. For example, persons areoften asked to relinquish individual rights forthe public good. People with infectious dis-eases are quarantined; they have relinquishedthe right of free movement. However, asJonas59 states, ‘‘I cannot be required to die forthe public good.’’59(p225) Furthermore, societycan afford deaths at a normal rate of incidence,and in fact, deaths are necessary to avoidoverpopulation.59 What society cannot affordare pandemics, such as the Black Death in theMiddle Ages or excessively high or low birthrates. These instances do imperil the future ofthe society. Only in these cases can extraor-dinary measures be sought. Thus, rather thandepending on truisms, health care supervisorsand managers must critically weigh opposingethical principles, striving to achieve a delicatebalance between individual rights and societalrights.

While participating in ethical discussions intheir health care organizations or serving onan ethics committee, health care supervisorsand managers can contribute to the quality ofthe ethical decision making by avoiding thesecommon mistakes. Moreover, they can assistother health personnel in avoiding thesemisconceptions as well.

CONCLUSION

The article armed health care supervisorsand managers with tools to address ethicalissues in their health care organizations. Intoday’s health disciplines’ academic curricu-la, attention to current ethical problems oftentakes precedence over reflecting on the past.This article provides health care personnelwith information on allusions and referencescommonly used during discussions of ethics.

Armed with this knowledge, health care su-pervisors and managers can meaningfully con-tribute to the deliberations of ethical issuesand to the resolution of ethical problems intheir health care organizations.

Human experimentation advances knowl-edge of medicine and science. The medicaland scientific bodies of knowledge would bemuch smaller without the knowledge gainedfrom experiments on human subjects. Hu-man experimentation involves investigationsof therapies for patients with the disease,experiments on healthy volunteers, and re-searchers’ autoexperimentation. Human ex-perimentation is often necessary becauseanimal research cannot answer all questionsabout human responses. However, it isparamount that, for all people, the ethicalprinciples of autonomy, sanctity, and justiceare preserved and protected. Thus, informedconsent and genuine voluntary consent, freeof deception and subtle coercion, are critical.

Ethical errors have occurred in the UnitedStates. Through a review of the literature onethical breaches in the United States, thisarticle exposed health care supervisors andmanagers to a focused history of sentinelevents in bioethics in the United States.Described in the article are several cases ofethical errors chronicled in the literature. Thearticle also provided a basic list of key docu-ments on ethics. These documents advancedthe thought about the ethical underpinningsof the protection of human subjects.

Ethicists and other health personnel fre-quently cite these cases and documents intheir discussions of ethical problems. Aware-ness of this lexicon of cases and key sourcesincreases the ability of health care supervi-sors and managers to effectively participatein ethics and oversight committees of theirhealth care organizations.

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Preface to Ethical Aspects of Experimentation With

Human Subjects.



Documents

Human Experimentation