Medical Research

This chapter describes ethical problems of medical research on vulnerable humans,
starting with an historical review of medical experimentation by Nazi physicians and
secret American medical research. Its major topics are the Tuskegee Study of untreated
syphilis in Alabama and later studies in Africa to prevent mother-to-child transmission of HIV. The chapter also discusses financial conflicts in research, especially with
research sponsored by pharmaceutical companies. It also discusses medical research
in vulnerable populations in developing countries, including a controversial experiment in neuroscience on Romanian orphans, the Bucharest Early Intervention Project. It also discusses the Krieger Lead Paint Study and the Jesse Gelsinger case.
INFAMOUS MEDICAL EXPERIMENTS
William Beaumont
In 1822, physician William Beaumont, the father of gastric physiology, treated
patient St. Martin for a bullet wound in the stomach; St. Martin survived, but the
wound healed strangely, leaving a hole. Beaumont then employed St. Martin as a
servant and proved the previously unknown fact that stomach juices digest food.
St. Martin ran away and Beaumont had him caught to continue to exhibit him.
Hospitals today in Texas and Michigan bear Beaumont’s name.
Nazi Medical Research
Besides participating in the Holocaust, physicians during the Nazi regime conducted
heinous experiments. They reasoned that if victims in concentration camps were
going to die anyway, why not use them to benefit medical science?
From 1943 to 1945, gay men, convicted criminals, Russian officers, Polish dissidents, Jews, and gypsies on Ward 46 at Buchenwald in Germany got experimental
CHAPTER 9
Medical Research on Vulnerable
Populations
Tuskegee, Krieger lead-paint, HIV Vertical Transmission
in Africa, Bucharest Early Intervention Studies
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vaccines against typhus. Physicians injected blood infected with typhus into 40 involuntary subjects, who served as a treatment group. Overall, they infected 1,000 prisoners, 158 of whom died.
In experiments at Buchenwald, physicians tried to cure gay men of being homosexual with hormone shots, had inmates shot to study gunshot wounds, starved inmates
to study the physiology of nutrition, and amputated women’s bones and limbs to study
regeneration. To study malaria, physicians used Anopheles mosquitoes to infect subjects.
Physician Ernst Grawitz infected legs of women with staphylococci, gas, and tetanus
bacilli. In testing sulfa drugs, he rubbed into wounds particles of glass and stone.
In experiments at Ravensbrück, physician Sigmund Rascher devised his “sky
ride wagon” to simulate rapid changes in altitude. Victims were locked inside an
enclosed box on wheels with monitoring equipment inside.1
Rascher froze 100 nude
Jewish and Russian prisoners in icy waters to study techniques to revive downed
pilots in similar waters. He also forced nude Jewish women to revive the subjects
sexually, degrading the subjects and women for the amusement of the guards.
Josef Mengele
Josef Mengele, known as the Angel of Death, participated in the deaths of 400,000
victims in concentration camps. Ambitious, young Mengele sought fame and studied medical anthropology and genetics between 1930 and 1936, when eugenics
movements swept Germany and America.
Contrary to some accounts, German medical schools did not resist, but led,
Nazi eugenics and the killing of undesirables. To advance, Mengele joined the
Brownshirts, a fanatical Nazi movement that promoted Aryan racial purity.
Mengele needed groundbreaking research to become a full professor. In 1943
at the Auschwitz concentration camp, he experimented to overcome the effects of
genetics by modifying environments. He wanted to produce blue eyes, blonde hair,
and healthy bodies free of genetic disease.
As subjects, he needed identical twins, natural controls. So he examined incoming trains of boxcars filled with Jews, looking for twins and other usable subjects,
signaling his choices with a flick of his wrist.
He injected blue dye into children’s eyes to see if he could create blue eyes. To
see if twins could be produced, he forced female twins to engage in coitus with
male twins. He interchanged blood of identical twins to observe results; he interchanged blood between pairs of twins.
One pair of fraternal twins consisted of a hunchback and a normal child;
Mengele surgically grafted the hunchback to the normal child’s back, creating the
effect of conjoined twins. He accentuated this effect by sewing their wrists back to
back. A witness reported that when these conjoined children returned to the barracks, “there was a terrible smell of gangrene. The cuts were dirty and the children
cried every night.”2
Mengele obtained between 150 and 200 twins, most of whom died. Mengele also
tested endurance by subjecting 75 prisoners to electric shock; 25 of them died immediately. He subjected Polish nuns to high dosages of radiation to produce sterility.
He once found a hunchback and the hunchback’s son; he had both of them
killed, their bodies boiled, their flesh stripped, and their skeletons dipped in
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gasoline for preservation for his anthropological studies of body types. Coming
upon seven dwarfs from a circus family, he exhibited them to visiting physicians.
When 300 Jewish children escaped a gas chamber, Mengele—cool, impersonal,
and detached—had them recaptured, lit a gasoline fire set in a large pit, and had
the children thrown in.
When the Russian army approached Auschwitz in 1945, Mengele escaped to
Paraguay. He lived there for 40 years, eluding Israelis who tried to capture him as a
war criminal. In later conversations with his grown son Rolf, he expressed no regret
for his actions: It was not his fault that Jews had to die at Auschwitz, he said, so why
not use them to advance medical knowledge and his own chances for a professorship?
Never captured or tried as a war criminal, Mengele died in Brazil in 1985.3
The Nuremberg Code
After World War II, at the Nuremberg trials in 1946, German physicians defended
themselves against charges of war crimes by saying that they had merely been following orders, that their experiments had been properly related to solving medical
problems of war, and that what they had done did not differ from similar research
done on captives by American physicians.
The judges at Nuremberg lacked a code of ethics for experimentation on captive
populations, so they created 10 principles for ethical experimentation, known as the
Nuremberg Code. Its most important principle was that people, even prisoners or
inmates of institutions, should freely consent to participation in any experiment.
Questionable American Research
In 1941, American researchers experimented on orphans at the Ohio Soldiers and
Sailors Orphan’s Home, on inmates at New Jersey State Colony for the Feeble-Minded, and on patients at a mental institution in Dixon, Illinois.4
To develop
a vaccine against shigella, they injected deadened forms of the bacteria into subjects.
None died, but many got sick.
Some questionable research used military personnel as subjects. Cornelius
Rhoads, Director of Memorial Sloan Kettering Cancer Hospital in New York City,
led the military’s secret chemical warfare service. He exposed thousands of American troops to mustard gas, accidentally learning that the gas killed white blood
cells and cancerous cells. After the war, he experimented with mustard gas as an
anticancer drug.5
About 4,000 to 5,000 subjects inhaled mustard gas in gas chambers. Altogether, in research conducted by the armed forces on poisonous agents,
60,000 subjects did not know what they were undergoing.6
During World War II, Franklin Roosevelt established the Committee on Medical
Research, which approached its work with a wartime mentality that carried over
after the war: Disease was the enemy, researchers battled it, and victory could be
won—with enough resources and enough will. As bioethicist David Rothman wrote,
during the war, ethical concerns about experiments carried little weight:
A wartime environment also undercut the protection of human subjects, because
of the power of the example of the draft. Every day thousands of men were compelled to risk death, however limited their understanding of the aims of the war or
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the immediate campaign might be. By extension, researchers doing laboratory work
were also engaged in a military activity, and they did not need to seek the permission of their subjects any more than the selective service or field commanders did
of draftees. … In a society mobilized for war, these arguments carried great weight.
Some people were ordered to face bullets and storm a hill; others were told to take
an injection and test a vaccine. In philosophical terms, wartime inevitably promoted
utilitarian over absolutistic positions.7
When subjects of secret chemical research later applied for treatment at veterans’
hospitals, the Veterans Administration (VA) denied that they had been exposed to
these agents. This scenario recurred after the war in Vietnam and after Operation
Desert Storm.
During the 1940s, radiation enthralled some physicians. Joseph Hamilton of the
University of California at Berkeley injected plutonium into 18 unsuspecting patients
diagnosed with cancer. According to Kenneth Scott, a scientist who later investigated these abuses, two patients were mistakenly diagnosed with cancer but nevertheless given “many times the lethal dose of plutonium.”8
Physicians also studied radioactive isotopes used in diagnosis and research. In
the late 1940s at Vanderbilt University, physicians injected 819 pregnant women
with radioactive iron in a nutritional study. A study in 1960 found that three of
their children died of rare forms of cancer.9
In 1945, Eda Charlton entered Strong
Memorial Hospital in Rochester, New York, with a mild case of hepatitis and was
secretly injected with plutonium-239 to study how her body eliminated radiation.
Physicians then secretly followed her for years to observe the effects (she died of a
heart attack in 1983).
From World War II to the mid-1970s, physician-researchers subjected over 16,000
American patients to radiation experiments.10 The Department of Energy or its predecessors conducted at least 435 experiments in 21 states. From the 1940s to the 1960s,
physicians exposed 1,500 military aviators and submarine crewmen to encapsulated
radium on the end of wires inserted high into their nostrils for several minutes.11
In another experiment, physician-researchers paid 130 male prisoners $200 to
undergo X-ray radiation of their testicles; afterward, these men got vasectomies. In
another, physicians injected plutonium into an indigent 36-year-old Texan’s injured
leg, which surgeons then amputated. In 1995, the President’s Committee on Human
Radiation Experiments investigated these experiments and concluded that the government should apologize to involuntary subjects and should compensate people
who had been injured.12
In 1966, Harvard medical professor Henry Beecher criticized 22 specific medical
experiments published in medical journals that had not obtained consent of subjects; he pointed out that this was the norm and criticized this fact.13 About the
same time, physician Henry Pappworth similarly criticized 500 medical experiments.14 That year, the U.S. Public Health Service began to require informed consent of subjects, an important fact in judging the Tuskegee Study.
In 1991 in Operation Desert Storm, officers forced soldiers to take experimental
vaccines against biological agents. Federal law stated that, under operational conditions, soldiers could not refuse such vaccinations. Subsequently, many soldiers
became sick. For years afterward, the Pentagon and Department of Defense denied
that their sickness was service-related. Yet the military’s own records showed many
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causes of such sickness, especially acting in combination, with sand storms, biological weapons, oil fires, contaminated water, rare microorganisms, the vaccines discussed earlier, chemical vapors from bombed Iraqi storage areas, unspent rocket
fuel, and high levels of stress.15
THE TUSKEGEE STUDY (OR “STUDY”)
Nature and History of Syphilis
Past victims of untreated syphilis included Cleopatra, King Herod of Judea, Charlemagne, Henry VIII, Napoleon Bonaparte, Frederick the Great, Catherine the
Great, Christopher Columbus, Paul Gauguin, Franz Schubert, Albrecht Dürer,
Johann Wolfgang von Goethe, Friedrich Nietzsche, John Keats, and James Joyce.16
Between 1900 and 1948, and especially during the two world wars, American
reformers mounted the Syphilophobia Campaign. Reformers emphasized that prostitutes spread syphilis and that it rapidly killed. As an alternative for men to visiting
prostitutes, they advocated clean, active sports, or “Muscular Christianity.”
Anti-syphilis crusaders split twice over methods to prevent spread of syphilis:
once during World War I over giving out condoms and again during World War II
over giving out penicillin. In each conflict, reformers who wanted to reduce the
harm of syphilis battled those who wanted to reduce illicit behavior.17
This conflict repeated over the next century in battles about venereal diseases,
prostitution, alcoholism, drug addiction, gambling, and sex education. The Harm
Reduction Movement (HRM) focuses on reducing the associated harms of these
behaviors, not on moral censure or eliminating the behaviors. Moralists who oppose
HRM attack the illicit behavior and view HRM as enabling it, for example, by
teaching men how to use condoms.
During the world wars, the armed services adopted HRM. Commanders who
needed healthy troops ordered the release of condoms in the first war and penicillin
in the second. After the wars, returning troops continued to use both, normalizing
these practices.
Physicians today treat syphilis with penicillin. Such treatment has been possible
only since 1948, when penicillin became available to everyone.
Schaudinn discovered in 1906 the spirochete that causes syphilis. It is a chronic,
contagious bacterial disease, often venereal and sometimes congenital. It has three
stages. In the first stage, primary syphilis, spirochetes mass and produce a primary
lesion, a chancre (pronounced “SHANK-er”). During this stage, syphilis is highly
infectious. After the chancre subsides, the disease spreads silently for a time, but
then produces an outbreak of secondary symptoms such as fever, rash, and swollen
lymph glands.
In the second stage of latent syphilis, spirochetes disseminate from the primary
lesion throughout the body, producing systemic and widespread lesions, usually in
internal organs. Syphilis may then spread silently from 1 to 30 years. During this
stage, symptoms vary so widely that syphilis was once known as the Great
Pretender.
In the last stage of tertiary syphilis, chronic destructive lesions damage the cardiac and neurological systems. Syphilis then may produce paresis (slight or
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incomplete paralysis), gummas (gummy or rubbery tumors), altered gait, blindness,
or lethal narrowing of the aorta.
Beginning in the sixteenth century, to treat syphilis physicians applied the
heavy metal mercury as a paste on the back. During the nineteenth century, they
similarly administered another heavy metal, bismuth. Neither mercury nor bismuth
killed the spirochetes, though they ameliorated symptoms.
In 1909, after the spirochete causing syphilis had been identified, two researchers—a
German, Paul Erlich, and a Japanese, S. Hata—tried 605 forms of arsenic and discovered
a “magic bullet” against it in combination of 606 heavy metals (which included arsenic).
Erlich humbly called this Salvarsan (implying salvation from syphilis); its generic name
is arsphenamine.18 After finding that it cured syphilis in rabbits, Erlich injected it intramuscularly into men with syphilis.
At first, Salvarsan seemed to work wonders, and during 1910, physicians greeted
Erlich with standing ovations. Later, syphilis recurred in some patients treated with
Salvarsan, and some died, either from syphilis or from Salvarsan. Erlich maintained
that the drug had been given incorrectly, but he still developed a less toxic form,
Neosalvarsan.
Physicians injected Neosalvarsan intramuscularly in 20 to 40 dosages over a year,
charging patients a dollar per visit. For full treatment, patients needed both time and
money. Neosalvarsan was no one-time treatment for syphilis, as penicillin later was.
Between 1890 and 1910, Norwegian Caesar Boeck studied the natural course of
untreated syphilis in 1,978 subjects. He correctly believed that heavy metals removed
only the symptoms of syphilis. Because they killed some syphilitics, he studied
whether subjects might fare better if left untreated.
In 1929, Boeck’s successor, J. E. Bruusgaard, selected 473 of Boeck’s subjects
for further evaluation.19 Bruusgaard learned that of subjects who had had syphilis
for more than 20 years, 73 percent were asymptomatic. Because this discovery dramatically contradicted the Syphilophobia Campaign, the leaders of this movement
resisted the fact that syphilis did not universally kill, much less did not do so rapidly
(foreshadowing similar battles later about AIDS). Even more disturbing to the Syphilophobia Campaign, Bruusgaard confirmed that some latent syphilitics might never
develop symptoms at all.
So when the Tuskegee Study began in 1932, Boeck’s and Bruusgaard’s studies
had caused physicians to question the received views about the natural course and
treatment of syphilis.
The Racial Environment
In the 1930s, American-medicine was racist. Most physicians held stereotypes about
African-American patients, as in this example from a 1914 Journal of the American
Medical Association:
The negro springs from a southern race, and as such his sexual appetite is strong;
all of his environments stimulate this appetite, and as a general rule his emotional
type of religion certainly does not decrease it.20
Physicians saw African-Americans as dirty, shiftless, promiscuous, and incapable of personal hygiene. In 1900, a Georgia physician wrote, “Virtue in the negro
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race is like ‘angels’ visits’—few and far between. In a practice of 16 years in the
South, I have never examined a virgin over 14 years of age.”21 In 1919, a medical
professor in Chicago wrote that African-American men were like bulls in furor sexualis, unable to resist copulation around females.22
Given such racism, white physicians around 1929 saw syphilis as a natural
consequence of low character in African-Americans, described by one white physician as a “notoriously syphilis-soaked race.”23 Such physicians also assumed that
African-American men would not seek treatment for venereal disease.
Development of the Tuskegee Study
A Study in Nature Begins. Physiologist Claude Bernard in 1865 distinguished studies in nature from normal experiments: In the former, someone merely observes what
would have happened without any interventions; in the latter, scientists manipulate
a variable. The Tuskegee Study was a study in nature.
The great physician William Osler once said, “Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”24 Yet as
of 1932, syphilis’s natural history had not been documented, and because of Boeck/
Bruussgaard’s results, physicians doubted the inexorability of its course.
This explains why the U.S. Public Health Service (USPHS) believed it needed
a study in nature. Around 1929, six counties in America had high rates of syphilis—above 20 percent—and a charity, the Julius Rosenwald Foundation of Philadelphia, treated all syphilitics in those counties with Neosalvarsan. In 1930, this
foundation surveyed African-American men in Macon County, Alabama, where
Tuskegee is the chief town. Its citizens were 82 percent black, and its rate of syphilis
was then the highest in the nation, 36 percent. The foundation treated or partially
treated some of these 3,694 syphilitics with Neosalvarsan.
Then something unforeseen happened: In 1929 the Great Depression began.
Soon, funds for charity plummeted, and the Rosenwald Foundation left, hoping that
USPHS would continue its program. Funds for public health also plummeted, and
in 1935, the USPHS budget fell from $1 million to less than $60,000.
In 1931, USPHS repeated the Rosenwald Foundation’s survey of syphilis in
Macon County, testing 4,400 African-American residents, and found that 22 percent
of men had syphilis, as well as a dangerous 62 percent rate of congenital syphilis.
Of great importance for the Tuskegee Study, this survey identified 399 AfricanAmerican men who had had syphilis of several years’ duration, but who had never
been treated.
The Surgeon General himself, Raymond Vonderlehr, wrote in 1936 in the Journal
of the American Medical Association that the Tuskegee Study was “an unusual opportunity to study the untreated syphilitic patient from the beginning of the disease to
the death of the infected person.”25 His decision began the Tuskegee Study.
Three points deserve emphasis. First, the 399 subjects had latent syphilis, not
infectious syphilis. During this stage, syphilis is largely noninfectious during sexual
intercourse. Second, researchers did not divide the 399 subjects into the typical
experimental and control groups: They were all simply observed. There was, however, another group of natural controls, 200 age-matched African-American men
living in Macon County who had never had syphilis.
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Third, the 399 men with syphilis and the 200 men without it were perfect for a
study in nature because they were so vulnerable: They were poor, illiterate, and tied
to the land as tenant farmers. As such, unlike other people with syphilis over the
next four decades, they were unlikely to ever leave Macon County. Partly because of
this vulnerability, Vonderlehr implied, they presented an “unusual opportunity.”
Vonderlehr had no sense that it might be wrong to use such vulnerable subjects
in a lifelong experiment. Like many of his time, he may have assumed that people
with syphilis got what they deserved and that these poor black men would never
have had the means, will, or opportunity to get treatment, even though the Public
Health Service could have one day provided it.
The Middle Phase: Poor Design. No one physician oversaw this study. It lacked
written protocols, and later investigators often mixed up the subjects in the no-treatment group of 399 syphilitics with the 200 “controls” without syphilis. Nurse Eunice
Rivers, an African-American nurse assigned to stay in Tuskegee and keep track of
the study, kept poor records, lost them, and because many of the men had the same
last names, later researchers often confused one patient for another.
Researchers assumed that controls would remain uninfected, but in a county
where one in three people had syphilis, many controls eventually contracted syphilis. Unfortunately, when they happened, some were switched to the no-treatment
group of syphilitics.
The study had gaps. Federal doctors visited in 1939 and then not until 1948;
seven years passed between visits in 1963 and 1970. Only Nurse Rivers held the
shaky study together.
During the course of the research, many of the 399 syphilitic subjects, who were
supposed to remain untreated, obtained Neosalvarsan or penicillin outside Macon
County. James Lucas, a CDC physician, said, “Effective and undocumented treatment had been given to the vast majority of patients in the syphilitic group.”26 So
researchers would never know whether any observed subject really represented the
consequences of untreated syphilis or when the subject had contracted it.
Ultimately, the study proved nothing. Before it began, physicians knew that
syphilitics had greater morbidity and mortality than nonsyphilitics, and from Bruusgaard’s discovery, that not all men in the latent phase died of syphilis. The Tuskegee
Study added nothing new.
Spinal Taps and Deception. When physicians returned, they wanted to know, first,
if they had a subject in the study group, and second, if so, how far his syphilis had
progressed. To determine progression, they did spinal punctures on 271 of the 399
syphilitic subjects.
In doing spinal taps, they inserted a 10-inch needle between two vertebrae into
the cerebrospinal fluid to withdraw a small amount of fluid. Because this is a delicate and uncomfortable process, physicians warned subjects to stay still, lest the
needle swerve and puncture their spinal cord or spinal nerves, causing infection
and possible paralysis.
Some physicians then and now regard spinal taps as insignificant, justified to
prove a diagnosis. On the other hand, professionals who describe spinal taps this
way may be thinking more about administering one rather than receiving one.
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Unlike taking blood, a spinal tap is not a minor procedure. Some patients
experience effects such as being unable to stand for a week without a severe headache. One person in 1 million will become paralyzed or permanently comatose.27
Tapping someone involuntarily, without obtaining informed consent, is legally
a form of battery. Researchers who need healthy volunteers for spinal taps offer
subjects as much as $1,000.
To induce subjects to travel to town and undergo these painful taps, physicians
in this study offered a series of incentives: free transportation, free hot lunches, free
medicine for any disease other than syphilis, and free burials.
But these freebies and the persuasion of Nurse Rivers failed to get all men to
come to town for the “round-ups,” so researchers resorted to deception. Infamously,
they told the black men that they had “bad blood” and that the spinal taps were treatment
for their bad blood. Researchers sent the subjects the following letter, under the
imposing letterhead “Macon County Health Department,” with the subheading
“Alabama State Board of Health and U.S. Public Health Service Cooperating with
Tuskegee Institute”:
Dear Sir:
Some time ago you were given a thorough examination and since that time we hope
you have gotten a great deal of treatment for bad blood. You will now be given your
last chance to get a second examination. This examination is a very special one and
after it is finished you will be given a special treatment if it is believed you are in
a condition to stand it.28
The “special treatment” mentioned was the spinal tap to culture for neurosyphilis. The subjects were instructed to meet Nurse Rivers for transportation to “Tuskegee Institute Hospital for this free treatment.” The letter closed, in capitals:
REMEMBER THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT.
BE SURE TO MEET THE NURSE.
To repeat, the researchers never treated the subjects for syphilis. Although penicillin was developed around 1941–1943 and was widely available by 1948, the subjects
in the Tuskegee Study never received it, even during the 1960s or up to 1972. During
World War II, researchers contacted the local draft board, which prevented eligible
subjects from being drafted, and hence from being treated for syphilis with penicillin by the armed services.
Revelation of the Study to the World. In 1966, USPHS venereal disease investigator Peter Buxtun learned about the study. By this time, supervision of the study
(and Buxtun) had moved to the newly created Centers for Disease Control (CDC)
in Atlanta. When Buxtun asked about the study, the CDC threatened to fire him.
By 1969, Buxtun’s protests led to a meeting of a small group of physicians at
CDC to consider stopping the Tuskegee Study or revealing it. Ultimately, they voted
to continue the study and to keep it secret.
In 1970, the American Public Health Association published a monograph on
syphilis. It stated that treatment for late benign syphilis should consist of “6.0 to
9.0 million units of benzathine penicillin G given 3.0 million units at sessions seven
days apart.”29 The first author was William J. Brown, head of CDC’s Tuskegee
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section from 1957 to 1971. Brown, on the CDC committee in 1969, had argued for
continuing the study and not giving penicillin to any subjects.
Buxtun eventually contacted Jean Heller, who worked for the Associated Press.
On July 26, 1972, her story appeared on front pages of newspapers nationwide.30
She described a study run by the federal government in Tuskegee, Alabama, where
poor, uneducated African-American men had been used as guinea pigs. After noting
the terrible effects of tertiary syphilis, she stated that in 1969, a CDC study of 276
of the untreated subjects had proved that at least seven subjects died “as a direct
result of syphilis.”
Heller’s story stunned congressmen. Senator William Proxmire called it a
“moral and ethical nightmare.” In reply, J. D. Millar, chief of Venereal Disease Control at CDC, said that the study “was never clandestine,” correctly pointing to 15
published articles in medical journals over 30 years.
After Heller’s story appeared, the Secretary of Health, Education, and Welfare
terminated the study. The CDC estimated that 28 syphilitics had died of syphilis
during the study; it then gave penicillin to the remaining subjects.
In 1973, on behalf of the Tuskegee subjects, lawyer Fred Gray filed a class-action
suit against the federal government. In 1974, the U.S. government settled out of
court. According to the settlement, living syphilitics received $37,500 each; heirs of
deceased syphilitics, $15,000 (since children might have had congenital syphilis);
heirs of living controls, $16,000; heirs of deceased controls, $5,000. Controls and
their descendants received compensation, because they and their families had been
deprived of antibiotics during the decades of the study. The government provided
free lifetime medical care for the subjects, their wives, and their children.
In 1972, as a direct revelation of the study, the federal government required all
institutions that conduct human medical experimentation and receive federal funds
to have Institutional Review Boards (IRBs). Today, IRBs must scrutinize written
proposals and defend against abuses in medical research.
In 1988, 21 of the original 399 syphilitic subjects were still alive, each of whom
had had syphilis for at least 62 years.31 In addition, 41 wives and 19 children had
evidence of syphilis and had received free medical care.
In 1997, President Clinton met four of the eight living survivors to apologize
for the Tuskegee Study, “What the United States did was shameful, and I am sorry.”32
The youngest survivor then was 87, the oldest between 100 and 109.33 By then, the
government had paid $10 million to the study’s original 600 members or to their
families or heirs, who numbered more than 6,000. Because of lack of treatment for
syphilis of men in the study, any of these other people might have contracted
syphilis.34
Perhaps the worst effect of revelation of the study was distrust by African-Americans
of medical experiments, a legacy that researchers today must overcome.
ETHICAL ISSUES IN THE TUSKEGEE STUDY
Informed Consent and Deception
In the Tuskegee Study, the subjects did not know they were part of a government
study lasting throughout their lives, did not even know what syphilis was, and did
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not know that they weren’t being treated with available drugs. In other words,
they had no informed consent, which many critics considered to be ethically
outrageous.
R. H. Kampmeier, an emeritus professor of medicine at Vanderbilt Medical
School, worked as a syphilologist during the decades of the study.35 He argued that
a study undertaken in the 1930s could not be faulted for lack of informed consent,
which began only after 1966. Would it make sense, he argued, to judge Pasteur
unethical because he, too, did not get consent?
Kampmeier cited another landmark study by USPHS in 1943 that studied giving
penicillin to 35,000 syphilitics; it did not get consent from subjects. Medical historian and physician Thomas Benedek dismissed informed consent in the Tuskegee
Study as “anachronistic,” emphasizing that USPHS did not require informed consent until 1966.36
While it is true that informed consent in medical experiments was not mandated
by court decisions until 1966, the presumption had always been that physicians
would “First, do no harm” to their patients. Not obtaining consent for procedures
that might benefit subjects differs from procedures that might harm subjects.
Finally, and granted that telling patients the truth was not legally required
before 1966, was it ethical for the Tuskegee researchers to lie to their subjects for
all those decades? Isn’t the truth what one person owes another, especially as doctor
and patient?
Racism
The Tuskegee Study took place in Alabama and all its subjects were African-American.
Under such circumstances, was it only a coincidence that no subjects were white?
Would white subjects have been deceived and left untreated the same way?
In his classic work, Bad Blood, medical historian James Jones saw the Tuskegee
Study as a result of pervasive racism in American medicine during the 1930s.
It is true that some physicians then believed that syphilis ran a different course
in different races, and this implied the need for a parallel study of untreated white
syphilitics. That the USPHS did no parallel study of white subjects shows that it
saw black subjects as expendable but not white subjects.
Media Coverage
In defending the Tuskegee Study, Kampmeier objected to the “great hue and cry”
in the media in 1972 and to journalists’ claims that “treatment was purposefully
withheld to evaluate the course of untreated disease.” He said about Time and
American Medical News, “In complete disregard of their abysmal ignorance, members
of the fourth estate bang out anything on their typewriters that will make
headlines.”37
With regard to the first objection, Kampmeier exaggerated the “hue and cry”
of the media. Indeed, the media botched the story. Coverage shrank within days,
and the story moved to the back pages, where only short paragraphs followed it.
To begin with the second objection, Kampmeier attacked the media for reporting the damaging aspects of the study, such as the withholding of treatment. In
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defense of the media, researchers did intend to withhold treatment. That was precisely the intention of the study.
The Tuskegee Study deserved far more attention. True, it had complex issues
that involved racism at a time when racial turmoil upset Americans, but today such
a story would receive weeks of nationwide scrutiny and probably get a congressional
hearing on television.
The relation then between medicine and the media can also be questioned.
Before Heller’s story broke, the Tuskegee Study had been reported repeatedly in at
least 17 articles in medical journals between 1936 and 1972. Researchers did not
conceal the study within medicine. Despite this, no professional publication, physician, or editor alerted the nation to the story.
Between 1966 and 1971, one African-American professional at the CDC mailed
boxes of documents about the study to several national newspapers and magazines.38 Nothing happened. Why is that?
The answer is important to understanding many issues in medical ethics and
to whistleblowing about corruption. Print and television reporters need an expert
to help them understand such complex stories and, equally important, to take
responsibility for claims about wrongdoing. Virtually no reporters then or now have
the medical background to understand such complicated stories and, without that,
cannot risk charging physicians with possible crimes.
A natural tendency also exists to want someone else to be the whistleblower and
to bear the brunt of retaliation. As a result, merely mailing information or passing
it along conversationally is not enough for reporters to publicize wrongdoing.
Harm to Subjects
Kampmeier argued that if the Tuskegee Study had never occurred, its subjects would
have received no treatment and would have been no worse off. Such a claim can
never be proved. If the Tuskegee Study had not occurred, many things might have
happened. Another charity might have provided Neosalvarsan. A writer like John
Steinbeck might have soon written a novel about syphilis in Macon County, arousing
national concern and getting penicillin to people there infected with syphilis.
So what harm, if any, resulted to subjects with syphilis from nontreatment? This
question might seem even absurd: If subjects were left untreated, of course they
must have been harmed! However, the issue is not that simple.
In 1931, penicillin was unavailable, so physicians withheld Neosalvarsan from
subjects. Because Neosalvarsan was expensive and cumbersome to administer, even
if this study had not occurred, subjects might not have received it. Boeck and
Bruusgaard had also undermined claims about the benefits of heavy metals, so harm
is difficult to prove. In a review of medical evidence available in 1940, medical
historian Benedek concluded that in 1937, untreated syphilitics actually lived longer
and better than those partially treated with heavy metals.39
Not everyone agrees. UAB professor of internal medicine Benjamin Friedman,
whose career spanned the decades of this study, countered:
In the 1940s it was known that patients receiving as few as 20 injections of arsenicals rarely developed symptomatic aortic disease. Since we could not determine in
advance which of the latent syphilitics would, after 20 or 30 years, develop
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symptomatic aortic disease, it was necessary to treat all of them. One cannot maintain that some small number of syphilitics deprived of treatment did not therefore
suffer injury.40
By 1934, the major professional organization of physicians treating syphilis in
America, the Cooperating Clinical Group, proved that use of heavy metals improved
Bruusgaard’s statistics and recommended that all syphilitics get Neosalvarsan, mercury, and bismuth.41 Even if many patients could not afford such therapy, they
should have been told about it.
Later during the study, penicillin became available. Although Alexander Fleming discovered penicillin in 1929, the world did not appreciate his discovery until
1941, and only around 1946, as a result of wartime production to treat soldiers, did
penicillin become available to most Americans. By 1948, anyone could get it.42
Kampmeier argued that withholding penicillin in 1946 did not harm subjects
with latent syphilis, which he said was a “chronic, granulomatous, self-limiting disease” and not fatal. He argued next that proof of penicillin’s effectiveness did not
come until 1948 and then only for primary syphilis. So the study’s subjects by 1948
could no longer have been helped by penicillin; the damage to them had already
been done.43
Benedek disagreed. He concluded that giving penicillin to latent syphilitics in
1948 “might have exerted a definitely beneficial effect on the prognosis of only
12.5 percent of the subjects.”44 Still, that would have helped 50 subjects.
Effects on Subjects’ Families
“Virtually all subjects were or had been married” and had an average of 5.2 children.45 Recall that Macon County had a rate of congenital syphilis of 62 percent.
When we consider the subjects’ families, wouldn’t the men in the study want
to know they had syphilis? Even in latency, wouldn’t they want to know they could
become infectious again? Did the researchers withhold the truth because they
thought these men couldn’t refrain from sex?
These researchers subjected women and children in Macon County to harm.
Either the researchers discounted this harm or thought it didn’t matter.
Kant and Motives of Researchers
When physicians at CDC and USPHS debated the Tuskegee Study in 1969, many
assumed that if no harm could be proved, nothing unethical had been done. This
is also Kampmeier’s unstated assumption.
Focusing on consequences, however, is only one way to judge morality. We can
also adopt, not a consequentialism or utilitarianism, but a Kantian ethics focused
on motives or a virtue ethics focused on the character of researchers.
Although we cannot prove that being left untreated harmed the study’s subjects, it may have been only good luck that the study caused no more harm than
it did. Why is that?
Historical evidence cuts both ways. We cannot use differing historical standards
at differing times to excuse lack of informed consent but not pay attention to what
else researchers believed at the time. Let us put ourselves in the minds of
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researchers in the late 1940s. The crucial fact is that when penicillin became available,
most physicians believed it would help latent syphilitics.
So they believed that subjects would be harmed by not getting penicillin. For
all anyone knew in 1948, penicillin could have helped patients with aortic heart
disease or at least would have ameliorated it.
For Kantian ethics, researchers deliberately willed harm on these subjects. They
used them as “mere means,” as guinea pigs, and could not universalize such behavior as a maxim for all physicians to act on. Not only did they lack what Kant calls
a “good will,” they had an ill will toward vulnerable subjects.
It is no good appealing to sophisticated knowledge that came later about how
the damage from syphilis had already occurred. Researchers then believed they
were depriving syphilitics of something likely to help them, or depriving them
of something that could help them not pass syphilis on to their female partners.
But out of a desire by researchers to prove the final ravages of syphilis, or lack
thereof, researchers deceived subjects and believed they were allowing them to
be harmed.
OTHER STUDIES LIKE THE TUSKEGEE STUDY
HIV Prevention in Africa: Another Tuskegee Study?
Unfortunately, research by physicians in wartime and the Tuskegee Study are not
the only examples in the history of modern medical ethics of questionable research
on vulnerable subjects. We now discuss a famous study in Africa that involved not
syphilis but AIDS, and readers can see how the issues of the Tuskegee Study frame
some of the criticisms of the African study.
In 1994, researchers had proved that giving the drug AZT (zidovudine) during
pregnancy cut by two-thirds transmission of HIV from mother to child in North
America.46 In 1995, CDC, NIH, and the World Health Organization (WHO) began
to study whether doing a similar study in Africa could prevent HIV in the 800
infected babies born there every day and started a randomized control trial (RCT).
One might well ask, “As the ability of AZT to block vertical HIV transmission
had already been proven, why conduct such a study at all in Africa?” One answer:
the strain of HIV in Africa differs from that common in North America. A second
answer: in Africa, researchers felt that they needed a quick proof that AZT could
block mother-to-child transmission of HIV.
In 1997, Marcia Angell, executive editor of the New England Journal of Medicine,
claimed that this research mimicked the Tuskegee Study because researchers gave
pregnant, HIV-infected black women placebos (harmless sugar pills), and thus
babies were born with preventable HIV infections.47 Because giving AZT to all HIV+
pregnant women was the American standard of care, not giving AZT in a placebo
group was unethical: “If it is unethical to do placebo-controlled trials in America,
it should also be unethical to do them in third-world countries.”48
This study had subjects who were highly vulnerable because they were (1) black,
(2) female, (3) poor, (4) illiterate, (5) victims of sexually transmitted diseases, and
(6) without other available treatment. Like the Tuskegee Study, magisterial but distant governmental agencies conducted the research. Like the Tuskegee Study,
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vulnerability and powerlessness characterized the subjects. Columnist Ellen Goodman noted that the Tuskegee Study had not ended but had been merely exported.49
Apologists passionately retorted that, had their research not been done, infected
mothers would not have gotten AZT and their babies would have been infected
anyway.
African officials replied that Angell and Goodman were ethical imperialists,
imposing American ethical standards on African countries.50 Such officials were
also black and had lost children to HIV unlike the white USPHS physicians of the
Tuskegee Study.51
They also replied that if they could prove—via a placebo-controlled trial—that a
shorter regimen of AZT could reduce HIV transmission by half, they could save
150,000 children a year. If skeptics such as Angell caused delays of proof, more
children would die.
Officials also claimed that a placebo-controlled trial of HIV-transmission could
be done faster and with fewer subjects than a AZT-controlled study, and that once
they had good results, African governments would give all pregnant, HIV+ women
the new, smaller dosage of AZT.
Researchers also argued procedurally that review committees in both countries
had approved the studies and that, unlike the Alabama men, the women themselves
had consented. Subsequent interviews by the New York Times cast doubt on how
much the women understood.
Angell argued that researchers didn’t need placebo-controlled studies; comparing dosages of AZT to other anti-HIV drugs could prove the same thing. Given the
poverty of such countries, she denied that a proven, reduced dosage would later be
given to all pregnant women because—even at $80—AZT costs 11 times more per
year than that normally spent on such African women.
Both sides invoked justice.52 One philosophical side invoked Bentham, utilitarianism, and public health ethics. The other hailed Kant, his axiom that people can
never be used as a “mere means,” and his belief that ethical principles are not local
but universal.
For researchers, the risk/benefit ratio had to be different for poor, illiterate
women in impoverished countries who otherwise would not have gotten treatment.
For critics, the same reasoning had led to the Tuskegee Study and to Nazi experiments: “They’re going to get die anyway, so we might as well study them to learn
something.”53 As Angell retorted, “People can’t be used as a means to a noble end.”54
In 1998, CDC proved that $80 worth of AZT in the last four weeks of pregnancy
cut transmission in half, and they suspended the study.55 At this early cessation,
both sides claimed victory.
The Krieger Lead Paint Study
In 2001, after Ellen Roche died in a study of a drug to prevent asthma, the federal
Office of Protection from Research Risks (OPRR) halted all federally funded research
at Johns Hopkins Medical School. When she volunteered for the study, Ellen was
healthy; soon, she was dead.
After its research stopped, a physician from Hopkins on television denounced
suspension of Hopkins’s research monies, claiming Hopkins had only killed one
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person in many decades of medical research and that lives would be lost from such
a suspension because of delayed cures.
The Krieger case was a study by a branch of Johns Hopkins Medical School
that studied mental handicaps in children from lead paint—which six of seven
judges on Maryland’s highest court likened it to the Tuskegee Study.56 The study,
conducted in the mid-1990s by Hopkins’s Kennedy Krieger Institute, recruited 108
poor, vulnerable, black families to live in East Baltimore in houses with lead paint.
Ingesting lead-based paint is a known cause of cognitive disability in small
children. According to the Krieger Institute, the study sought cheaper ways to
reduce lead contamination in houses so landlords in East Baltimore would not abandon them.
Did the parents understand the nature of the study? Did they understand the
risk to their children by living in these houses? “It can be argued that the researchers intended that the children be the canaries in the mines but never clearly told
the parents,” one critic said.57 Moreover:
Maryland Court of Appeals Judge Dale R. Cathell, who wrote last week’s scathing
opinion, said the board [had] instructed Kennedy Krieger researchers to write consent forms for study participants that skirted federal regulations requiring disclosure
about risks.
The Court of Appeals ruling ordered trials to be held in lawsuits filed against
Kennedy Krieger by two women, Viola Hughes and Catina Higgins, whose children
were involved in the study. Hughes’s daughter now suffers from learning disabilities
and cognitive impairments, both of which are often associated with lead poisoning.
… Higgins says researchers withheld tests results that showed high levels of lead
contamination from her. …
Kennedy Krieger is a major institution in the study of lead paint abatement.
Marc Farfel, who conducted the study, said today that it identified more effective
ways to remove lead hazards and prompted legislation forcing landlords to remove
those hazards.58
Amazingly, an investigation by OPRR revealed that the IRB at Johns Hopkins,
which supposedly had reviewed and discussed the ethics of the Krieger Study and
all other research at the medical school, had rarely met face-to-face.
The Krieger Study resembled the Tuskegee Study in that vulnerable, poor black
people were deliberately recruited to a study where physicians foresaw harm to
subjects. Researchers rationalized the harm by saying that if the study had not
occurred, the subjects would have lived in such housing anyway. Revelation of the
Krieger Study further damaged already bad relations between Baltimore’s AfricanAmericans and Hopkins.
1946–1948: The Guatemalan Syphilis Study
In 2011, Wellesley historian Susan Reverby, while researching the Tuskegee Study,
chanced upon documents at the National Archives revealing that the USPHS
between 1946 and 1948 paid syphilis-infected prostitutes in Guatemala to visit prisoners and inmates of mental institutions to study how easily syphilis could be transmitted and if penicillin could prevent transmission.59 When men failed to become
infected, researchers scraped penises and faces and injected infected pus, causing
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about 1,300 of the 5,500 enrolled men to catch syphilis or gonorrhea. Following this
revelation, Secretary of State Hillary Clinton apologized to the Guatemalan people
for the actions of the United States in this shameful episode of research on people
even more vulnerable than those in the Tuskegee Study.
Financial Conflicts and Twenty-First-Century Research
The Bayh-Dole Act of 1980 erased an ethical bright line between academic and
corporate medicine and allowed universities and their researchers to patent and
reap royalties together. Since then, scandals about money keep recurring in medical
research.
Thirty-five years later, pharmaceutical companies fund most research into drugs
and devices at universities. They do not fund independent peer review of their new
drugs and do not publicize bad results. By indirectly paying physicians to test new
drugs and by financially encouraging physicians to recruit patients for experiments,
drug companies cause physicians to choose their drug and not the best drug for
their patients.
In 1998, a study by the Department of Health and Human Services concluded
that IRBs could no longer handle the job of protecting subjects from abuses in
medical experimentation.60 It found that IRBs were underfunded and overworked
and that the volume of work expected of volunteers could not be accurately and
conscientiously performed. Another study in 2002 by the Institute of Medicine
reached similar conclusions.61 Since then, several medical research centers
improved their structures for reviewing research, although financial conflicts
continue.
In 1991, the federal government adopted the Common Rule, under which universities’ IRBs must review all protocols the same way, regardless of funding. This
rule subjects all protocols to the same standards as those required by NIH and the
U.S. Federal Drug Administration (FDA).
Several scandals erupted in the 1990s, wherein a few physicians appeared to
have taken millions of dollars from drug companies for dubious research.62 Some
doctors in Georgia allegedly made $4 million over seven years from aggressively
soliciting people with schizophrenia for drug trials; they made another $6 million
over the same period from testing other drugs.63
In 1996, Apotex Inc. tried to suppress adverse findings by Nancy Olivieri, a
Canadian hematologist.64 When using its experimental iron chelating drug
(deferiprone) on patients with thalassemia, a heritable blood disorder, in a clinical
trial paid for by Apotex, she discovered serious risks and attempted to publish them,
but Apotex threatened to sue her for doing so. Because of its financial ties to Apotex, her employer, the University of Toronto (UT), failed to support her. In 1998,
she published her findings and UT terminated her employment. The case exposed
the limits of academic freedom in Canadian medicine and the ties between medical
universities and drug companies. An investigation in 2001 by the Canadian Association of University Teachers vindicated Olivieri.65
Physicians who work for drug companies can make half-million dollars a year
flying around the country giving talks to physicians to promote a pharmaceutical
company’s new drug.
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Medical journals run expensive ads from drug companies, and almost all medical practices allow drug representatives to buy them and their staff expensive daily
lunches or dinners. Drug companies give these gifts because they work. Learning
to take free stuff from drug companies begins in medical school, when students
learn to expect free food at lunch paid for by drug companies. The organization No
Free Lunch tries to counter these gifts on medical students and physicians (look at
their website for more information).
Toward International Standards of Research Ethics
Over the last 50 years, Big Pharma has exported lots of research to people in developing countries, although less than 10 percent of that research is intended to benefit
such people.66 In North America and Europe, despite some famous exceptions,
consensus has developed about standards of ethical research.
During the past 50 years, many thousands of people in third-world countries
were subjects of studies, many of them placebo-controlled. One occurred in 1996
by Pfizer in Kano, Nigeria, during an epidemic there of deadly meningitis in children. Pfizer researchers flew there and gave half of 200 infected children either the
low dosage of the standard antibiotic ceftriaxone or Pfizer’s experimental drug Trovan. Pfizer had never tested this drug in oral form on children.67
Researchers commonly create conditions most favorable to proving efficacy of
their own drugs, such as giving low dosages of standard drugs or “washing out” all
traces of previous drugs in subjects, making them worse off.68 In this study, five
children died who took Trovan, six died who took the lower dose of ceftriaxone,
and “many others [were] blind, deaf, paralyzed, or brain-damaged.”
Work over the past decade in bioethics has focused on four questions about
such medical research in developing countries: (1) How can we prevent vulnerable
patients from being exploited by research? (2) How can such patients give informed
consent? (3) Is it right to apply standards of research of developed countries to
research in developing countries, or can there be a double standard? (4) Are there
special problems of context in doing research on poor, illiterate people in developing
countries?
The first problem, of exploitation, can be illustrated by the fact that the 10
biggest pharmaceutical companies in 2002 had more combined profits than the
combined profits of the other 490 companies on the Fortune 500 list.69 Given such
profits isn’t any drug testing by Big Pharma on vulnerable patients likely to exploit
them? The 2005 film The Constant Gardener chronicles one such case in Africa. Is
there any way to adequately compensate poor Africans for being the guinea pigs
for new drugs that will mainly benefit children in North America?
The second problem, of informed consent, has been contested by people who
say it upholds an individualistic model of autonomous, educated patients not
applicable to members of illiterate tribes in South America and Africa. In the
vertical-HIV-transmission trial, consent of tribal leaders was the best that could
be achieved.
Perhaps that is so, but it also resembles excuses of the USPHS in not telling
the men of the Tuskegee Study about “bringing them to autopsy” because the men
were too ignorant to understand.
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The third problem, a double standard, vexes many people. In America, IRBs and
the FDA monitor research, but nothing like these institutions exist in most developing
countries. Who then monitors, say, Merck Pharmaceutical’s research in Guatemala?
A problem here is where placebos can be used in developing countries. In
developed countries, a new drug or device is generally tested against the traditional
drug or device, not a placebo. Even where researchers did not originally do placebocontrolled studies, new drugs are usually only tested against currently used drugs,
not placebos. Yet the vertical-HIV-transmission study on vulnerable African mothers
did use a placebo before it was stopped.
One solution is to have domestic IRBs of researchers monitor overseas research
and apply the same standards. In that case, the vertical-HIV-transmission research
could not have been done because, as said, giving AZT to all HIV+ babies was the
standard of care at the time.
The final dilemma concerns contextual problems of doing research overseas in
poor countries. In America but not in the middle of the savannah or jungle, should
a problem arise in a Phase I study of a drug, emergency rooms, EMT personnel,
and local hospitals are available to treat allergic reactions. Does that mean such
research can never be done in the wild?
The Collaborative Model
One widely discussed solution to most of these problems is for the institution sponsoring the research and the area of the developing country to develop a long-term
partnership. Rather than an international company swooping down for a one-time
research trial, both sides should think of an arrangement lasting for decades. In this
way, both sides can potentially benefit.
First, research on vulnerable populations should not be done if such people
cannot benefit from the research at all. Second, if the research is successful, the
people on whom it has been tested should receive adequate supplies of the drugs
as partial recompense for their participation.
Third, it might be necessary to help a developing country build infrastructure
to facilitate a long-term partnership in research. When UAB built an AIDS hospital
in Zambia, it was necessary to fund small refrigerators running on small generators
to keep medicine cool in remote areas.70 Similarly, it might be necessary to train
and fund medical technicians, midwives, or local physicians to draw blood over a
decade in order to study the long-term effectiveness of interventions. More radically,
traditional tests for diseases depend on high-tech, faraway, diagnostic labs not available in developing countries. Lack of such labs and their results may affect the
health of many people in poor countries. To overcome this gap, point-of-care testing
with wireless transmission back-and-forth via satellites may be necessary to help
indigent populations.71
The reverse of this seems obvious: If no partnership exists, researchers will be
perceived as exploitive and countries will refuse to grant rights to investigate, to
take samples, or to apply for patents. If something like Severe acute respiratory
syndrome or SARS breaks out, this could be dangerous for the world.
Such collaboration is called the Fair Benefits Model and emphasizes sharing the
benefits of successful medical research.72 One good start is the third edition in 2002
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of the International Ethical Guidelines for Biomedical Research Involving Human Subjects
by the Council for International Organizations of Medical Sciences (CIOMS).73
These are good guidelines for researchers in North American countries funded by
multinational pharmaceutical companies, using vulnerable subjects in low-resource
countries for the subjects, and include guidelines for compensating such subjects
who are injured in research.
The Death of Jesse Gelsinger
The death of teenager Jesse Gelsinger from gene therapy changed American medical
research. In 1999 in Tucson, Arizona, 17-year-old Jesse worked as a clerk and rode
a motorcycle on weekends. He volunteered for experimental gene therapy at the
University of Pennsylvania for his inherited disorder, ornithine transcarbamylase
(OTC) deficiency.
In OTC, the liver doesn’t properly cleanse blood of ammonia, produced in
normal metabolism, resulting in toxic levels. Many OTC newborns die around birth;
half don’t live to age 5. A new regimen of drugs and diet enabled Jesse to live to
be a teenager, but without a cure, he would eventually die.
Jesse entered the study as a healthy research volunteer. A friend said he “wanted
to prove he was a man.”74 Penn researchers claim they told Jesse that the experiment
wouldn’t help him, but that it might help OTC babies. Jesse wanted “to help save
lives,” his father said.
Penn researcher James Wilson injected an adenovirus into Jesse that contained
copies of the gene lacking in OTC patients. Four days later, Jesse’s liver had been
destroyed, his blood thickened to jelly, and all his organs shut down.75
A subsequent wrongful death lawsuit claimed that Wilson both knew that the
virus had injured other OTC adults and that he failed to explain this to the Gelsingers. Penn bioethicist Arthur Caplan claimed Wilson’s study was never even possibly
therapeutic for Jesse, merely a Phase I safety-toxicity study, going so far as to say, “If
you cured anybody, you’d publish it in a religious journal. It would be a miracle. All
you’re doing is you’re saying, I’ve got this vector. I want to see if it can deliver the
gene where I want it to go without killing or hurting or having any side effects.”76
Wilson also had a financial conflict of interest. His company, Genovo, owned
patents on the adenovirus, and Biogen, Inc. had already paid Genovo $37 million
for rights to genetic therapies developed by Wilson and Genovo. Wilson denied that
money influenced his decisions, claiming that he was only motivated to be the first
to cure a genetic disease.77
Yet Wilson reported to the FDA only 39 of 700 problems about the virus,
although the law required reporting all 700. In 2000, researchers concluded that
adenoviruses should be used only as a last resort, not on healthy volunteers, and
NIH halted gene therapy.
The Gelsinger family settled out of court with Penn for undisclosed monies.
After an investigation of Wilson’s research, the NIH in 2000 suspended medical
research at Penn. After a congressional hearing into Jesse’s death, the NIH vowed
to better monitor medical research. As a result, it suspended medical research at
the University of Colorado Medical Center, at the University of North Carolina, at
Johns Hopkins Hospitals, and at the University of Alabama at Birmingham.
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THE BUCHAREST EARLY INTERVENTION PROJECT (BEIP)
Nicolae Ceaușescu ruled Romania as a dictator as part of the Union of Soviet Socialist Republics from 1967 until he was killed in 1989. Desiring to increase his population, he made use of contraception and abortions a crime, resulting in many
unwanted children, whose parents often dumped them in state-run orphanages. In
1990, over 170,000 children resided in Romanian orphanages.
In 2001, researchers Charles Nelson of Harvard Medical School, Charles
H. Zeanah of Tulane Medical School, and psychologist Nathan Fox of the University
of Maryland saw a study in nature, hence an opportunity to follow these children
to study how neglect damaged the developing brain. They screened 187 orphans
under the age of 31 months and divided them into two groups: a control group of
33 boys and 35 girls to remain in orphanages and an intervention group of 34 boys
and 34 girls, who were placed in foster homes.
The study continued until 2013, when the authors published their Romania’s
Abandoned Children, which became a landmark study in neuroscience proving that
lack of stimulation severely damages the brain.78 Hearing about BEIP, bioethicist
Joseph Fins likened it to the Tuskegee Study because a control group existed that
could have been helped by intervention.79
Nelson, Fox, and Zeanah replied that Romanian officials suspected agents of
foster care with selling babies and also saw nothing wrong with their orphanages.
These officials needed hard proof that life in their orphanages harmed children.
The researchers also replied that no children were worse-off because of BEIP, that
IRBs at their three institutions approved the study, that the hard evidence proved
by BEIP helped millions of orphans worldwide to leave institutions, and that after
the study finished, Romania banned institutionalization of children under age 2.
Nevertheless, parallels with the Tuskegee Study were striking: Both studies had
a non-treatment group over many years for a comparison, both used vulnerable,
poor subjects who could not leave; both were run by prestigious organizations, and
both were not secret. Moreover, in both studies, researchers claimed the subjects
would not have gotten treatment anyway and that local officials cooperated with
them. Finally, visiting evaluators in BEIP were ordered not to touch the subjects
and, if they started crying, to leave the room, so as to not influence the children.
Critics claimed that in 2001 when BEIP began, substantial evidence already
existed that extreme deprivation harmed the developing human brain. Also, was it
really necessary to leave children in the control group for 12 years? Shouldn’t a stop
rule have been invoked, once it became obvious that deprivation was harming kids
who were controlled? Were children in the control group, in Kant’s terms, treated
as a mere means to scientific knowledge?
Even if it is true that without BEIP, no orphans might have been adopted, once
the researchers included the orphans in their research, didn’t they have any obligations to them? Did Romania get enough benefits from the research? Did Harvard,
and the MacArthur Foundation (which helped fund BEIP), have any obligations to
use their vast endowments to help children in the control group?
Fins believes that some of the greatest abuses occur because no one speaks
truth to power. Is this one of those cases?
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Chapter 9 Medical Research on Vulnerable Populations 217
FURTHER READING
Thomas Benedek, “The ‘Tuskegee Study’ of Untreated Syphilis: Analysis of Moral Aspects
versus Methodological Aspects,” Journal of Chronic Diseases, vol. 31, 1978, pp. 35–50.
James Jones, Bad Blood, New York: Free Press, 1981.
Charles Nelson, Nathan Fox, and Charles Zeanah, Romania’s Abandoned Children: Deprivation,
Brain Development, and the Struggle for Recovery, Cambridge, Mass: Harvard University
Press, 2014.
DISCUSSION QUESTIONS
1. Even if subjects can’t be proven to have been harmed by not getting penicillin
in the 1940s, explain how Kant would say the research was still wrong.
2. Were the studies to prevent vertical transmission of HIV in Africa really like
the Tuskegee Study? What was the same and what differed?
3. Why did the controls of the Tuskegee Study without syphilis also get compensation?
4. Knowledge of the Tuskegee Study has prevented many black patients from
participating in medical research. Is it time now to get over that? If blacks don’t
participate in medical research, will studies be done to help them?
5. Wasn’t Mengele a sadist? Can you do such things just because of ambition?
6. Was the Krieger lead paint study like the Tuskegee Study?
7. What does the model of collaborative research with developing countries imply
about licensing genetic versions of patented drugs for poor areas with HIV,
malaria, and tuberculosis?
NOTES
1. Eugene Kogon, The Theory and Practice of Hell, Berkley Trade, New York, 1998.
2. Vera Alexander, The Search for Mengele, HBO movie, October 1985; interviewed by Central Television (London) and quoted in Gerald Posner and John Hare, The Complete Story, Cooper Square
Press, New York, 2000, p. 37.
3. William Curran, “The Forensic Investigation of the Death of Joseph Mengele,” New England Journal
of Medicine 315, no. 17 (October 23, 1985), pp. 1071–1073.
4. David Rothman, “Ethics and Human Experimentation,” New England Journal of Medicine 317, no. 19
(November 5, 1987), p. 1198.
5. Robert Bazell, “Growth Industry,” New Republic, March 15, 1993, p. 14.
6. Constance Pechura, “From the Institute of Medicine,” Journal of the American Medical Association
269, no. 4 (January 27, 1993), p. 453.
7. Rothman, “Ethics and Human Experimentation.”
8. Dan Stober, Knight-Ridder Newspapers, “Dr. Hamilton Was Enthusiastic Experimenter in Radiation,”
Birmingham News, February 20, 1994, p. 10A; “America’s Nuclear Secrets,” Newsweek, December 27,
1993, p. 15.
9. Keith Schneider, “Scientists Are Sharing the Anguish over Nuclear Experiments on People,” New
York Times, March 2, 1994, p. A9.
10. Robert Burns, “Radiation Experiments Were Far-Reaching,” Associated Press, Birmingham PostHerald, August 18, 1995, p. E6.
11. Dennis Domerzalski, “Radiation ‘Guinea Pigs’ Tell Stories,” Scripps-Howard News Service, Birmingham
Post-Herald, February 3, 1994, p. A8.
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218 Chapter 9 Medical Research on Vulnerable Populations
12. Philip J. Hilts, “U.S. Is Urged to Repay Some in Radiation Tests,” New York Times, July 17, 1995,
p. A9. See also Final Report, Advisory Committee on Human Radiation Experiments, U.S. Government Printing Office, Washington, D.C.
13. H. Beecher, “Ethics and Clinical Research,” New England Journal of Medicine 274 (1966), pp. 1354–1360.
14. H. Pappworth, Human Guinea Pigs, Beacon, Boston, MA, 1968.
15. Arthur Caplan, “Rethinking the Cost of War,” Due Consideration, Wiley, New York, 1998, pp. 123–124.
16. Molly Selvin, “Changing Medical and Societal Attitudes toward Sexually Transmitted Diseases:
A Historical Overview,” in King K. Holmes et al., eds., Sexually Transmitted Diseases, McGraw-Hill,
New York, 1984, pp. 3–19.
17. Alan Brandt, “Racism and Research: The Case of the Tuskegee Syphilis Study,” Hastings Center
Report 8, no. 6 (December 1978), pp. 21–29.
18. Paul de Kruif, The Microbe Hunters, Harcourt Brace, New York, 1926, p. 323.
19. J. E. Bruusgaard, “Öber das Schicksal der nichtspezifischbehandeltenLuetiker” (“Fate of Syphilitics
Who Are Not Given Specific Treatment”), Archives of Dermatology of Syphilis 157 (April 1929),
pp. 309–332.
20. H. H. Hazen, “Syphilis in the American Negro,” Journal of the American Medical Association 63
(August 8), 1914, p. 463.
21. James Jones, Bad Blood, Free Press, New York, 1981, p. 74.
22. Ibid.
23. Ibid.
24. Quoted in E. Ramont, “Syphilis in the AIDS Era,” New England Journal of Medicine 316, no. 25
(June 18, 1987), pp. 600–601.
25. R. A. Vonderlehr, T. Clark, and J. R. Heller, “Untreated Syphilis in the Male Negro,” Journal of the
American Medical Association 107, no. 11 (September 12, 1936), pp. 856–860.
26. Jean Heller, “Syphilis Victims in U.S. Study Went Untreated for 40 Years,” New York Times, July 26,
1972, p. 1, 8.
27. Or worse: in 1988, a malpractice suit brought against a hospital in Vermont was settled out of court
for $2.7 million on behalf of a 28-year-old woman who had gone into a coma after being incompetently tapped by a resident. “Malpractice Suit Settled for $2.7 Million,” Burlington Free Press
(Alabama), December 21, 1988.
28. Archives of National Library of Medicine; quoted in Jones, Bad Blood, p. 127.
29. W. J. Brown et al., Syphilis and Other Venereal Diseases, Harvard University Press, Cambridge, MA,
1970, p. 34.
30. Heller, “Syphilis Victims in U.S. Study.”
31. Ibid.
32. Allison Mitchell, “Survivors of Tuskegee Study Get Apology from Clinton,” New York Times, May
17, 1997, p. A1.
33. Carol Yoon, “Families Emerge as Silent Victims of Tuskegee Syphilis Experiments,” New York Times,
May 9, 1998, p. A1.
34. Marcia Angell, “The Ethics of Clinical Research in the Third World,” New England Journal of Medicine
337, no. 12 (September 18, 1997), pp. 847–849.
35. R. H. Kampmeier, “The Tuskegee Study of Untreated Syphilis” (editorial), Southern Medical Journal
65, no. 10 (October 1972), pp. 1247–1251.
36. Thomas Benedek, “The ‘Tuskegee Study’ of Untreated Syphilis: Analysis of Moral Aspects versus
Methodological Aspects,” Journal of Chronic Diseases 31 (1978), pp. 35–50. I have drawn considerably
on this excellent article.
37. Kampmeier, “The Tuskegee Study of Untreated Syphilis.”
38. “The Deadly Deception” (with George Strait), Nova, January 28, 1992.
39. Benedek, “The ‘Tuskegee Study’ of Untreated Syphilis,” p. 44.
40. Personal correspondence, April 25, 1985. Benjamin Friedman is professor emeritus of medicine,
UAB.
pen07945_ch09_196-220.indd 218 9/8/16 9:51 AM
Chapter 9 Medical Research on Vulnerable Populations 219
41. Benedek, “The ‘Tuskegee Study’ of Untreated Syphilis.”
42. G. W. Hayes et al., “The Golden Anniversary of the Silver Bullet,” Journal of the American Medical
Association 270, no. 13 (October 6, 1993), p. 1610.
43. R. H. Kampmeier, “Final Report of the ‘Tuskegee Study’ of Syphilis,” Southern Medical Journal 67,
no. 11 (1974), pp. 1349–1353. Kampmeier advances a fourth argument that is somewhat more
technical. Penicillin achieves seroreversal in latent syphilis, but Kampmeier insists that such seroreversal has never been proved to be associated with decreased morbidity or mortality. A related
point is possible uncertainty over diagnosis and thus over therapeutic effects. (S. Edberg and
S. Berger, Antibiotics and Infection, Churchill Livingstone, New York, 1983, pp. 141–142; K. Holmes
et al., Sexually Transmitted Diseases, McGraw-Hill, New York, 1984, p. 1352; John Hotson, “Modern
Neurosyphilis: A Partially Treated Chronic Meningitis, Western Journal of Medicine 135 [September
1981], pp. 191–200; Sarah Polt, Professor of Pathology, UAB, personal correspondence.)
44. Benedek, “The ‘Tuskegee Study’ of Untreated Syphilis.”
45. Ibid.
46. Sheryl Gay Stolberg, “U.S. Ends Overseas HIV Studies Involving Placebos,” New York Times,
February 19, 1998.
47. Marcia Angell, “Tuskegee Revisited,” Wall Street Journal, October 28, 1997.
48. Ruth Macklin, “Ethics and International Collaborative Research, Part I,” American Society for Bioethics and Humanities Exchange 1, no. 2, p.1. Reprinted in Ruth Macklin, Ethics in Global Health,
Oxford University Press, 2012.
49. Ellen Goodman, 2006. “Is Tuskegee Study OK Abroad?” The Boston Globe, September 25, 1997.
50. Ibid.
51. D. Bagenda and P. Musoke-Mudido, “We’re Trying to Help Our Sickest People, Not Exploit Them,”
Washington Post, September 28, 1997, p. C3.
52. Macklin, “Ethics and International Collaborative Research.”
53. Marcia Angell, “Tuskegee Revisited,” Wall Street Journal, October 28, 1997.
54. Goodman, “Is Tuskegee Study OK Abroad?”
55. Stolberg, “U.S. Ends Overseas HIV Studies.”
56. Manuel Roig-Franzia, “Probe Opens on Study Tied to Johns Hopkins,” Washington Post, August 23,
2001, p. B1.
57. Tamar Lewin, “U.S. Investigating Johns Hopkins Study of Lead Paint Hazard,” New York Times,
August 24, 2001.
58. Grimes v. Kennedy-Krieger Institute, 782 F2d 807 (Ct App Md 2001). (Maryland Court of Appeals,
2001, no. 128, September Term, 2000.)
59. Ronald McNeil, “Panel Hears Grim Details of V.D. Test on Inmates,” New York Times, August 31,
2011, p. A21; A Study Guide to “Ethically Impossible” STD Research in Guatemala from 1946 to 1948,
Presidential Commission for the Study of Biomedical Issues, November 2012, http://www.bioethics
.gov.
60. Rick Weiss, “Research Volunteers Unwittingly at Risk,” Washington Post, August 1, 1998, p. A1. See
also this article from the online journal Target Health: Target Health, June 14, 1998, http://www.
targethealth.com/.
61. Institute of Medicine, Responsible Research: A Systems Approach to Protecting Research Participants,
National Academy Press, Washington, D.C., 2002.
62. For psychiatrists who abused patients in psychiatric research on schizophrenic patients, see Robert
Whitaker, “Lure of Riches Fuels Testing,” Boston Globe, November 17, 1998, p. A1; for another story
about abuse of subjects and fraud in medical research, see Douglas M. Birch and Gary Cohn, “How
a Cancer Drug Trial Ended in Betrayal,” Baltimore Sun, June 24, 2001.
63. Steve Stecklow and Laura Johannes, “Drug Maker’s Relied on Clinical Researchers Who Now Await
Trial,” Wall Street Journal, August 15, 1997, p. A1.
64. The Olivieri Report: The Complete Text of the Report of the Independent Inquiry Commissioned, Canadian
Association of University Teachers, Lorimer, 2001; Miriam Shuchman, The Drug Trial: Nancy Olivieri
and the Science Scandal that Rocked the Hospital for Sick Children, Random House, New York, 2005.
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220 Chapter 9 Medical Research on Vulnerable Populations
65. The Olivieri Report.
66. Harold Shapiro and Eric Meslin, “Ethical Issues in the Design and Conduct of Clinical Trials in
Developing Countries,” New England Journal of Medicine 345 (July 12, 2001), pp. 139–142.
67. George Annas, “Global Clinical Trials and Informed Consent,” New England Journal of Medicine 360,
no. 20 (May 14, 2009), pp. 2050–2053.
68. See author’s Elements of Bioethics, Chapter 8.
69. Carl Elliot, White Coat, Black Hat, Beacon Press, Boston, MA, 2010, p. 60.
70. Personal communication to author from Michael Saag, MD, head of UAB AIDS research unit.
71. Ilesh Jani and Treveror Peter, “How Point of Care Testing Could Drive Innovation in Global Health,”
New England Journal of Medicine 368, no. 24 (June 13, 2013), pp. 2319–2324.
72. A conference in 2002 first described this model: files/4314/3472/9176/me-10-fair-benefits-forresearch.pdf.
73. http://www.recerca.uab.es/ceeah/docs/CIOMS.pdf.
74. Richard Jerome, “Death by Research,” People, February 21, 2000, p. 123.
75. Deborah Nelson and Rick Weiss, “Hasty Decisions in the Race to a Cure? Gene Therapy Proceeded
Despite Safety, Ethics Concerns,” Washington Post, November 21, 1999, p. A1.
76. Arthur Caplan is quoted extensively in Complaint for Civil Action filed by John Gelsinger for estate
of Jesse Gelsinger against Trustees of University of Pennsylvania et al., www.sskrplaw.com/links/
healthcare2.html.
77. Nelson and Weiss, “Hasty Decisions.”
78. Charles Nelson, Nathan Fox, and Charles Zeanah, Romania’s Abandoned Children: Deprivation, Brain
Development, and the Struggle for Recovery, Harvard University Press, Cambridge, MA, 2014.
79. Joseph Fins, “Romanian Orphans: A Reconsideration of the Ethics of the Bucharest Early Intervention
Project,” Bioethics Forum, October 10, 2013.
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HHS.gov U.S. Department of Health & Human Services
The Belmont Report
Office of the Secretary
Ethical Principles and Guidelines for the Protection of Human
Subjects of Research
The National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research
April 18, 1979
AGENCY: Department of Health, Education, and Welfare.
ACTION: Notice of Report for Public Comment.
SUMMARY: On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law,
there-by creating the National Commission for the Protection of Human Subjects of Biomedical
and Behavioral Research. One of the charges to the Commission was to identify the basic ethical
principles that should underlie the conduct of biomedical and behavioral research involving human
subjects and to develop guidelines which should be followed to assure that such research is
conducted in accordance with those principles. In carrying out the above, the Commission was
directed to consider: (i) the boundaries between biomedical and behavioral research and the
accepted and routine practice of medicine, (ii) the role of assessment of risk-benefit criteria in
the determination of the appropriateness of research involving human subjects, (iii) appropriate
guidelines for the selection of human subjects for participation in such research and (iv) the
nature and definition of informed consent in various research settings.
The Belmont Report attempts to summarize the basic ethical principles identified by the
Commission in the course of its deliberations. It is the outgrowth of an intensive four-day period
of discussions that were held in February 1976 at the Smithsonian Institution’s Belmont
Conference Center supplemented by the monthly deliberations of the Commission that were held
over a period of nearly four years. It is a statement of basic ethical principles and guidelines that
should assist in resolving the ethical problems that surround the conduct of research with human
subjects. By publishing the Report in the Federal Register, and providing reprints upon request,
the Secretary intends that it may be made readily available to scientists, members of Institutional
Review Boards, and Federal employees. The two-volume Appendix, containing the lengthy reports
of experts and specialists who assisted the Commission in fulfilling this part of its charge, is
available as DHEW Publication No. (OS) 78-0013 and No. (OS) 78-0014, for sale by the
Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.
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Unlike most other reports of the Commission, the Belmont Report does not make specific
recommendations for administrative action by the Secretary of Health, Education, and Welfare.
Rather, the Commission recommended that the Belmont Report be adopted in its entirety, as a
statement of the Department’s policy. The Department requests public comment on this
recommendation.
National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research
Members of the Commission
Kenneth John Ryan, M.D., Chairman, Chief of Staff, Boston Hospital for Women.
Joseph V. Brady, Ph.D., Professor of Behavioral Biology, Johns Hopkins University.
Robert E. Cooke, M.D., President, Medical College of Pennsylvania.
Dorothy I. Height, President, National Council of Negro Women, Inc.
Albert R. Jonsen, Ph.D., Associate Professor of Bioethics, University of California at San
Francisco.
Patricia King, J.D., Associate Professor of Law, Georgetown University Law Center.
Karen Lebacqz, Ph.D., Associate Professor of Christian Ethics, Pacific School of Religion.
*** David W. Louisell, J.D., Professor of Law, University of California at Berkeley.
Donald W. Seldin, M.D., Professor and Chairman, Department of Internal Medicine,
University of Texas at Dallas.
***Eliot Stellar, Ph.D., Provost of the University and Professor of Physiological Psychology,
University of Pennsylvania.
*** Robert H. Turtle, LL.B., Attorney, VomBaur, Coburn, Simmons & Turtle, Washington,
D.C.
***Deceased.
Table of Contents
Ethical Principles and Guidelines for Research Involving Human Subjects
A. Boundaries Between Practice and Research
B. Basic Ethical Principles
1. Respect for Persons
2. Beneficence
3. Justice
C. Applications
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1. Informed Consent
2. Assessment of Risk and Benefits
3. Selection of Subjects
Ethical Principles & Guidelines for Research Involving Human Subjects
Scientific research has produced substantial social benefits. It has also posed some troubling
ethical questions. Public attention was drawn to these questions by reported abuses of human
subjects in biomedical experiments, especially during the Second World War. During the
Nuremberg War Crime Trials, the Nuremberg code was drafted as a set of standards for judging
physicians and scientists who had conducted biomedical experiments on concentration camp
prisoners. This code became the prototype of many later codes(1) intended to assure that
research involving human subjects would be carried out in an ethical manner.
The codes consist of rules, some general, others specific, that guide the investigators or the
reviewers of research in their work. Such rules often are inadequate to cover complex situations;
at times they come into conflict, and they are frequently difficult to interpret or apply. Broader
ethical principles will provide a basis on which specific rules may be formulated, criticized and
interpreted.
Three principles, or general prescriptive judgments, that are relevant to research involving human
subjects are identified in this statement. Other principles may also be relevant. These three are
comprehensive, however, and are stated at a level of generalization that should assist scientists,
subjects, reviewers and interested citizens to understand the ethical issues inherent in research
involving human subjects. These principles cannot always be applied so as to resolve beyond
dispute particular ethical problems. The objective is to provide an analytical framework that will
guide the resolution of ethical problems arising from research involving human subjects.
This statement consists of a distinction between research and practice, a discussion of the three
basic ethical principles, and remarks about the application of these principles.
[RETURN TO TABLE OF CONTENTS]
Part A: Boundaries Between Practice & Research
A. Boundaries Between Practice and Research
It is important to distinguish between biomedical and behavioral research, on the one hand, and
the practice of accepted therapy on the other, in order to know what activities ought to undergo
review for the protection of human subjects of research. The distinction between research and
practice is blurred partly because both often occur together (as in research designed to evaluate a
therapy) and partly because notable departures from standard practice are often called
“experimental” when the terms “experimental” and “research” are not carefully defined.
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For the most part, the term “practice” refers to interventions that are designed solely to enhance
the well-being of an individual patient or client and that have a reasonable expectation of success.
The purpose of medical or behavioral practice is to provide diagnosis, preventive treatment or
therapy to particular individuals.(2) By contrast, the term “research’ designates an activity
designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or
contribute to generalizable knowledge (expressed, for example, in theories, principles, and
statements of relationships). Research is usually described in a formal protocol that sets forth an
objective and a set of procedures designed to reach that objective.
When a clinician departs in a significant way from standard or accepted practice, the innovation
does not, in and of itself, constitute research. The fact that a procedure is “experimental,” in the
sense of new, untested or different, does not automatically place it in the category of research.
Radically new procedures of this description should, however, be made the object of formal
research at an early stage in order to determine whether they are safe and effective. Thus, it is
the responsibility of medical practice committees, for example, to insist that a major innovation
be incorporated into a formal research project.(3)
Research and practice may be carried on together when research is designed to evaluate the
safety and efficacy of a therapy. This need not cause any confusion regarding whether or not the
activity requires review; the general rule is that if there is any element of research in an activity,
that activity should undergo review for the protection of human subjects.
Part B: Basic Ethical Principles
B. Basic Ethical Principles
The expression “basic ethical principles” refers to those general judgments that serve as a basic
justification for the many particular ethical prescriptions and evaluations of human actions. Three
basic principles, among those generally accepted in our cultural tradition, are particularly relevant
to the ethics of research involving human subjects: the principles of respect of persons,
beneficence and justice.
1. Respect for Persons. — Respect for persons incorporates at least two ethical convictions:
first, that individuals should be treated as autonomous agents, and second, that persons with
diminished autonomy are entitled to protection. The principle of respect for persons thus divides
into two separate moral requirements: the requirement to acknowledge autonomy and the
requirement to protect those with diminished autonomy.
An autonomous person is an individual capable of deliberation about personal goals and of acting
under the direction of such deliberation. To respect autonomy is to give weight to autonomous
persons’ considered opinions and choices while refraining from obstructing their actions unless
they are clearly detrimental to others. To show lack of respect for an autonomous agent is to
repudiate that person’s considered judgments, to deny an individual the freedom to act on those
considered judgments, or to withhold information necessary to make a considered judgment,
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when there are no compelling reasons to do so.
However, not every human being is capable of self-determination. The capacity for
self-determination matures during an individual’s life, and some individuals lose this capacity
wholly or in part because of illness, mental disability, or circumstances that severely restrict
liberty. Respect for the immature and the incapacitated may require protecting them as they
mature or while they are incapacitated.
Some persons are in need of extensive protection, even to the point of excluding them from
activities which may harm them; other persons require little protection beyond making sure they
undertake activities freely and with awareness of possible adverse consequence. The extent of
protection afforded should depend upon the risk of harm and the likelihood of benefit. The
judgment that any individual lacks autonomy should be periodically reevaluated and will vary in
different situations.
In most cases of research involving human subjects, respect for persons demands that subjects
enter into the research voluntarily and with adequate information. In some situations, however,
application of the principle is not obvious. The involvement of prisoners as subjects of research
provides an instructive example. On the one hand, it would seem that the principle of respect for
persons requires that prisoners not be deprived of the opportunity to volunteer for research. On
the other hand, under prison conditions they may be subtly coerced or unduly influenced to
engage in research activities for which they would not otherwise volunteer. Respect for persons
would then dictate that prisoners be protected. Whether to allow prisoners to “volunteer” or to
“protect” them presents a dilemma. Respecting persons, in most hard cases, is often a matter of
balancing competing claims urged by the principle of respect itself.
2. Beneficence. — Persons are treated in an ethical manner not only by respecting their
decisions and protecting them from harm, but also by making efforts to secure their well-being.
Such treatment falls under the principle of beneficence. The term “beneficence” is often
understood to cover acts of kindness or charity that go beyond strict obligation. In this document,
beneficence is understood in a stronger sense, as an obligation. Two general rules have been
formulated as complementary expressions of beneficent actions in this sense: (1) do not harm
and (2) maximize possible benefits and minimize possible harms.
The Hippocratic maxim “do no harm” has long been a fundamental principle of medical ethics.
Claude Bernard extended it to the realm of research, saying that one should not injure one person
regardless of the benefits that might come to others. However, even avoiding harm requires
learning what is harmful; and, in the process of obtaining this information, persons may be
exposed to risk of harm. Further, the Hippocratic Oath requires physicians to benefit their patients
“according to their best judgment.” Learning what will in fact benefit may require exposing
persons to risk. The problem posed by these imperatives is to decide when it is justifiable to seek
certain benefits despite the risks involved, and when the benefits should be foregone because of
the risks.
The obligations of beneficence affect both individual investigators and society at large, because
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they extend both to particular research projects and to the entire enterprise of research. In the
case of particular projects, investigators and members of their institutions are obliged to give
forethought to the maximization of benefits and the reduction of risk that might occur from the
research investigation. In the case of scientific research in general, members of the larger society
are obliged to recognize the longer term benefits and risks that may result from the improvement
of knowledge and from the development of novel medical, psychotherapeutic, and social
procedures.
The principle of beneficence often occupies a well-defined justifying role in many areas of
research involving human subjects. An example is found in research involving children. Effective
ways of treating childhood diseases and fostering healthy development are benefits that serve to
justify research involving children — even when individual research subjects are not direct
beneficiaries. Research also makes it possible to avoid the harm that may result from the
application of previously accepted routine practices that on closer investigation turn out to be
dangerous. But the role of the principle of beneficence is not always so unambiguous. A difficult
ethical problem remains, for example, about research that presents more than minimal risk
without immediate prospect of direct benefit to the children involved. Some have argued that
such research is inadmissible, while others have pointed out that this limit would rule out much
research promising great benefit to children in the future. Here again, as with all hard cases, the
different claims covered by the principle of beneficence may come into conflict and force difficult
choices.
3. Justice. — Who ought to receive the benefits of research and bear its burdens? This is a
question of justice, in the sense of “fairness in distribution” or “what is deserved.” An injustice
occurs when some benefit to which a person is entitled is denied without good reason or when
some burden is imposed unduly. Another way of conceiving the principle of justice is that equals
ought to be treated equally. However, this statement requires explication. Who is equal and who
is unequal? What considerations justify departure from equal distribution? Almost all
commentators allow that distinctions based on experience, age, deprivation, competence, merit
and position do sometimes constitute criteria justifying differential treatment for certain purposes.
It is necessary, then, to explain in what respects people should be treated equally. There are
several widely accepted formulations of just ways to distribute burdens and benefits. Each
formulation mentions some relevant property on the basis of which burdens and benefits should
be distributed. These formulations are (1) to each person an equal share, (2) to each person
according to individual need, (3) to each person according to individual effort, (4) to each person
according to societal contribution, and (5) to each person according to merit.
Questions of justice have long been associated with social practices such as punishment, taxation
and political representation. Until recently these questions have not generally been associated
with scientific research. However, they are foreshadowed even in the earliest reflections on the
ethics of research involving human subjects. For example, during the 19th and early 20th
centuries the burdens of serving as research subjects fell largely upon poor ward patients, while
the benefits of improved medical care flowed primarily to private patients. Subsequently, the
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exploitation of unwilling prisoners as research subjects in Nazi concentration camps was
condemned as a particularly flagrant injustice. In this country, in the 1940’s, the Tuskegee
syphilis study used disadvantaged, rural black men to study the untreated course of a disease
that is by no means confined to that population. These subjects were deprived of demonstrably
effective treatment in order not to interrupt the project, long after such treatment became
generally available.
Against this historical background, it can be seen how conceptions of justice are relevant to
research involving human subjects. For example, the selection of research subjects needs to be
scrutinized in order to determine whether some classes (e.g., welfare patients, particular racial
and ethnic minorities, or persons confined to institutions) are being systematically selected simply
because of their easy availability, their compromised position, or their manipulability, rather than
for reasons directly related to the problem being studied. Finally, whenever research supported by
public funds leads to the development of therapeutic devices and procedures, justice demands
both that these not provide advantages only to those who can afford them and that such research
should not unduly involve persons from groups unlikely to be among the beneficiaries of
subsequent applications of the research.
Part C: Applications
C. Applications
Applications of the general principles to the conduct of research leads to consideration of the
following requirements: informed consent, risk/benefit assessment, and the selection of subjects
of research.
1. Informed Consent. — Respect for persons requires that subjects, to the degree that they are
capable, be given the opportunity to choose what shall or shall not happen to them. This
opportunity is provided when adequate standards for informed consent are satisfied.
While the importance of informed consent is unquestioned, controversy prevails over the nature
and possibility of an informed consent. Nonetheless, there is widespread agreement that the
consent process can be analyzed as containing three elements: information, comprehension and
voluntariness.
Information. Most codes of research establish specific items for disclosure intended to assure
that subjects are given sufficient information. These items generally include: the research
procedure, their purposes, risks and anticipated benefits, alternative procedures (where therapy is
involved), and a statement offering the subject the opportunity to ask questions and to withdraw
at any time from the research. Additional items have been proposed, including how subjects are
selected, the person responsible for the research, etc.
However, a simple listing of items does not answer the question of what the standard should be
for judging how much and what sort of information should be provided. One standard frequently
invoked in medical practice, namely the information commonly provided by practitioners in the
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field or in the locale, is inadequate since research takes place precisely when a common
understanding does not exist. Another standard, currently popular in malpractice law, requires the
practitioner to reveal the information that reasonable persons would wish to know in order to
make a decision regarding their care. This, too, seems insufficient since the research subject,
being in essence a volunteer, may wish to know considerably more about risks gratuitously
undertaken than do patients who deliver themselves into the hand of a clinician for needed care.
It may be that a standard of “the reasonable volunteer” should be proposed: the extent and
nature of information should be such that persons, knowing that the procedure is neither
necessary for their care nor perhaps fully understood, can decide whether they wish to participate
in the furthering of knowledge. Even when some direct benefit to them is anticipated, the subjects
should understand clearly the range of risk and the voluntary nature of participation.
A special problem of consent arises where informing subjects of some pertinent aspect of the
research is likely to impair the validity of the research. In many cases, it is sufficient to indicate to
subjects that they are being invited to participate in research of which some features will not be
revealed until the research is concluded. In all cases of research involving incomplete disclosure,
such research is justified only if it is clear that (1) incomplete disclosure is truly necessary to
accomplish the goals of the research, (2) there are no undisclosed risks to subjects that are more
than minimal, and (3) there is an adequate plan for debriefing subjects, when appropriate, and
for dissemination of research results to them. Information about risks should never be withheld
for the purpose of eliciting the cooperation of subjects, and truthful answers should always be
given to direct questions about the research. Care should be taken to distinguish cases in which
disclosure would destroy or invalidate the research from cases in which disclosure would simply
inconvenience the investigator.
Comprehension. The manner and context in which information is conveyed is as important as
the information itself. For example, presenting information in a disorganized and rapid fashion,
allowing too little time for consideration or curtailing opportunities for questioning, all may
adversely affect a subject’s ability to make an informed choice.
Because the subject’s ability to understand is a function of intelligence, rationality, maturity and
language, it is necessary to adapt the presentation of the information to the subject’s capacities.
Investigators are responsible for ascertaining that the subject has comprehended the information.
While there is always an obligation to ascertain that the information about risk to subjects is
complete and adequately comprehended, when the risks are more serious, that obligation
increases. On occasion, it may be suitable to give some oral or written tests of comprehension.
Special provision may need to be made when comprehension is severely limited — for example,
by conditions of immaturity or mental disability. Each class of subjects that one might consider as
incompetent (e.g., infants and young children, mentally disable patients, the terminally ill and the
comatose) should be considered on its own terms. Even for these persons, however, respect
requires giving them the opportunity to choose to the extent they are able, whether or not to
participate in research. The objections of these subjects to involvement should be honored, unless
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the research entails providing them a therapy unavailable elsewhere. Respect for persons also
requires seeking the permission of other parties in order to protect the subjects from harm. Such
persons are thus respected both by acknowledging their own wishes and by the use of third
parties to protect them from harm.
The third parties chosen should be those who are most likely to understand the incompetent
subject’s situation and to act in that person’s best interest. The person authorized to act on behalf
of the subject should be given an opportunity to observe the research as it proceeds in order to
be able to withdraw the subject from the research, if such action appears in the subject’s best
interest.
Voluntariness. An agreement to participate in research constitutes a valid consent only if
voluntarily given. This element of informed consent requires conditions free of coercion and undue
influence. Coercion occurs when an overt threat of harm is intentionally presented by one person
to another in order to obtain compliance. Undue influence, by contrast, occurs through an offer of
an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain
compliance. Also, inducements that would ordinarily be acceptable may become undue influences
if the subject is especially vulnerable.
Unjustifiable pressures usually occur when persons in positions of authority or commanding
influence — especially where possible sanctions are involved — urge a course of action for a
subject. A continuum of such influencing factors exists, however, and it is impossible to state
precisely where justifiable persuasion ends and undue influence begins. But undue influence
would include actions such as manipulating a person’s choice through the controlling influence of
a close relative and threatening to withdraw health services to which an individual would
otherwise be entitle.
2. Assessment of Risks and Benefits. — The assessment of risks and benefits requires a
careful arrayal of relevant data, including, in some cases, alternative ways of obtaining the
benefits sought in the research. Thus, the assessment presents both an opportunity and a
responsibility to gather systematic and comprehensive information about proposed research. For
the investigator, it is a means to examine whether the proposed research is properly designed.
For a review committee, it is a method for determining whether the risks that will be presented to
subjects are justified. For prospective subjects, the assessment will assist the determination
whether or not to participate.
The Nature and Scope of Risks and Benefits. The requirement that research be justified on
the basis of a favorable risk/benefit assessment bears a close relation to the principle of
beneficence, just as the moral requirement that informed consent be obtained is derived primarily
from the principle of respect for persons. The term “risk” refers to a possibility that harm may
occur. However, when expressions such as “small risk” or “high risk” are used, they usually refer
(often ambiguously) both to the chance (probability) of experiencing a harm and the severity
(magnitude) of the envisioned harm.
The term “benefit” is used in the research context to refer to something of positive value related
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to health or welfare. Unlike, “risk,” “benefit” is not a term that expresses probabilities. Risk is
properly contrasted to probability of benefits, and benefits are properly contrasted with harms
rather than risks of harm. Accordingly, so-called risk/benefit assessments are concerned with the
probabilities and magnitudes of possible harm and anticipated benefits. Many kinds of possible
harms and benefits need to be taken into account. There are, for example, risks of psychological
harm, physical harm, legal harm, social harm and economic harm and the corresponding benefits.
While the most likely types of harms to research subjects are those of psychological or physical
pain or injury, other possible kinds should not be overlooked.
Risks and benefits of research may affect the individual subjects, the families of the individual
subjects, and society at large (or special groups of subjects in society). Previous codes and
Federal regulations have required that risks to subjects be outweighed by the sum of both the
anticipated benefit to the subject, if any, and the anticipated benefit to society in the form of
knowledge to be gained from the research. In balancing these different elements, the risks and
benefits affecting the immediate research subject will normally carry special weight. On the other
hand, interests other than those of the subject may on some occasions be sufficient by
themselves to justify the risks involved in the research, so long as the subjects’ rights have been
protected. Beneficence thus requires that we protect against risk of harm to subjects and also
that we be concerned about the loss of the substantial benefits that might be gained from
research.
The Systematic Assessment of Risks and Benefits. It is commonly said that benefits and
risks must be “balanced” and shown to be “in a favorable ratio.” The metaphorical character of
these terms draws attention to the difficulty of making precise judgments. Only on rare occasions
will quantitative techniques be available for the scrutiny of research protocols. However, the idea
of systematic, nonarbitrary analysis of risks and benefits should be emulated insofar as possible.
This ideal requires those making decisions about the justifiability of research to be thorough in the
accumulation and assessment of information about all aspects of the research, and to consider
alternatives systematically. This procedure renders the assessment of research more rigorous and
precise, while making communication between review board members and investigators less
subject to misinterpretation, misinformation and conflicting judgments. Thus, there should first be
a determination of the validity of the presuppositions of the research; then the nature, probability
and magnitude of risk should be distinguished with as much clarity as possible. The method of
ascertaining risks should be explicit, especially where there is no alternative to the use of such
vague categories as small or slight risk. It should also be determined whether an investigator’s
estimates of the probability of harm or benefits are reasonable, as judged by known facts or other
available studies.
Finally, assessment of the justifiability of research should reflect at least the following
considerations: (i) Brutal or inhumane treatment of human subjects is never morally justified.
(ii) Risks should be reduced to those necessary to achieve the research objective. It should be
determined whether it is in fact necessary to use human subjects at all. Risk can perhaps never
be entirely eliminated, but it can often be reduced by careful attention to alternative procedures.
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(iii) When research involves significant risk of serious impairment, review committees should be
extraordinarily insistent on the justification of the risk (looking usually to the likelihood of benefit
to the subject — or, in some rare cases, to the manifest voluntariness of the participation). (iv)
When vulnerable populations are involved in research, the appropriateness of involving them
should itself be demonstrated. A number of variables go into such judgments, including the
nature and degree of risk, the condition of the particular population involved, and the nature and
level of the anticipated benefits. (v) Relevant risks and benefits must be thoroughly arrayed in
documents and procedures used in the informed consent process.
3. Selection of Subjects. — Just as the principle of respect for persons finds expression in the
requirements for consent, and the principle of beneficence in risk/benefit assessment, the
principle of justice gives rise to moral requirements that there be fair procedures and outcomes in
the selection of research subjects.
Justice is relevant to the selection of subjects of research at two levels: the social and the
individual. Individual justice in the selection of subjects would require that researchers exhibit
fairness: thus, they should not offer potentially beneficial research only to some patients who are
in their favor or select only “undesirable” persons for risky research. Social justice requires that
distinction be drawn between classes of subjects that ought, and ought not, to participate in any
particular kind of research, based on the ability of members of that class to bear burdens and on
the appropriateness of placing further burdens on already burdened persons. Thus, it can be
considered a matter of social justice that there is an order of preference in the selection of classes
of subjects (e.g., adults before children) and that some classes of potential subjects (e.g., the
institutionalized mentally infirm or prisoners) may be involved as research subjects, if at all, only
on certain conditions.
Injustice may appear in the selection of subjects, even if individual subjects are selected fairly by
investigators and treated fairly in the course of research. Thus injustice arises from social, racial,
sexual and cultural biases institutionalized in society. Thus, even if individual researchers are
treating their research subjects fairly, and even if IRBs are taking care to assure that subjects are
selected fairly within a particular institution, unjust social patterns may nevertheless appear in the
overall distribution of the burdens and benefits of research. Although individual institutions or
investigators may not be able to resolve a problem that is pervasive in their social setting, they
can consider distributive justice in selecting research subjects.
Some populations, especially institutionalized ones, are already burdened in many ways by their
infirmities and environments. When research is proposed that involves risks and does not include
a therapeutic component, other less burdened classes of persons should be called upon first to
accept these risks of research, except where the research is directly related to the specific
conditions of the class involved. Also, even though public funds for research may often flow in the
same directions as public funds for health care, it seems unfair that populations dependent on
public health care constitute a pool of preferred research subjects if more advantaged populations
are likely to be the recipients of the benefits.
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One special instance of injustice results from the involvement of vulnerable subjects. Certain
groups, such as racial minorities, the economically disadvantaged, the very sick, and the
institutionalized may continually be sought as research subjects, owing to their ready availability
in settings where research is conducted. Given their dependent status and their frequently
compromised capacity for free consent, they should be protected against the danger of being
involved in research solely for administrative convenience, or because they are easy to
manipulate as a result of their illness or socioeconomic condition.
(1) Since 1945, various codes for the proper and responsible conduct of human experimentation
in medical research have been adopted by different organizations. The best known of these codes
are the Nuremberg Code of 1947, the Helsinki Declaration of 1964 (revised in 1975), and the
1971 Guidelines (codified into Federal Regulations in 1974) issued by the U.S. Department of
Health, Education, and Welfare Codes for the conduct of social and behavioral research have also
been adopted, the best known being that of the American Psychological Association, published in
1973.
(2) Although practice usually involves interventions designed solely to enhance the well-being of
a particular individual, interventions are sometimes applied to one individual for the enhancement
of the well-being of another (e.g., blood donation, skin grafts, organ transplants) or an
intervention may have the dual purpose of enhancing the well-being of a particular individual,
and, at the same time, providing some benefit to others (e.g., vaccination, which protects both
the person who is vaccinated and society generally). The fact that some forms of practice have
elements other than immediate benefit to the individual receiving an intervention, however,
should not confuse the general distinction between research and practice. Even when a procedure
applied in practice may benefit some other person, it remains an intervention designed to
enhance the well-being of a particular individual or groups of individuals; thus, it is practice and
need not be reviewed as research.
(3) Because the problems related to social experimentation may differ substantially from those of
biomedical and behavioral research, the Commission specifically declines to make any policy
determination regarding such research at this time. Rather, the Commission believes that the
problem ought to be addressed by one of its successor bodies.
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Research Ethics
2016, Vol. 12(1) 14–28
© The Author(s) 2015
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/1747016115599568
rea.sagepub.com
Informed consent and
the Facebook emotional
manipulation study
Dr Catherine Flick
De Montfort University, UK
Abstract
This article argues that the study conducted by Facebook in conjunction with Cornell University
did not have sufficient ethical oversight, and neglected in particular to obtain necessary informed
consent from the participants in the study. It establishes the importance of informed consent
in Internet research ethics and suggests that in Facebook’s case (and other, similar cases), a
reasonable shift could be made from traditional medical ethics ‘effective consent’ to a ‘waiver
of normative expectations’, although this would require much-needed change to the company’s
standard practice. Finally, it gives some practical recommendations for how to implement such
consent strategies, and how the ethical oversight gap between university-led research and
industry-led research can be bridged, potentially using emerging Responsible Research and
Innovation frameworks which are currently gathering momentum in Europe.
Keywords
computer ethics, Facebook, informed consent, research ethics, Responsible Research and
Innovation
Introduction
Informed consent is a concept that is traditionally associated with medical ethics.
However, over time it has come to be a vital part of research ethics in any research
involving human subjects, including research in the social sciences, medical
Corresponding author:
Dr Catherine Flick, Centre for Computing and Social Responsibility, Faculty of Technology,
Gateway House, The Gateway, De Montfort University, Leicester LE1 9BH, UK.
Email: cflick@dmu.ac.uk
599568 REA0010.1177/1747016115599568Research EthicsFlick
research-article2015
Article
Flick 15
sciences and computing sciences etc. Universities mostly self-govern research ethics
approval, with committees (such as research ethics committees [REC] in the UK or
institutional review boards [IRB] in the USA) that assess potential research projects
and their impact on the research subjects and greater society. Even simple questionnaires that appear to have little impact on their research subjects are highly regulated
within the scientific research arena, with informed consent requirements including
information sheets, signatures, and the ability for the research subject to withdraw
from the study. Failure to go through this process is considered an academic offence
or malpractice, and can be dealt with through penalties such as removal of funding,
cancellation of the research or the researcher being fired, amongst others, depending
on the severity of the offence. In the age of ‘big data’ social networking it is easy to
share information online, but it is not correspondingly easy for researchers to request
informed consent for that information, and it is not always obvious which parties are
responsible for obtaining that consent.
It is within this environment that the problems with the Facebook emotional
manipulation study (Kramer et al., 2014) begin to emerge. The study is used in this
article as a case study to draw conclusions about poor practices in mixedinstitutional big data research projects, and to subsequently explore alternatives.
In this article I argue for the requirement of informed consent in experiments such
as the titular, in order to protect the basic human rights that have been the focus of
informed consent development over the years. I then draw up some recommendations based on internet research ethics and a re-thought form of informed consent
that has been used to develop a better informed consent process for other situations
that require requests for consent en masse. Finally, I summarize these recommendations at various levels and briefly discuss them within the responsibility setting
that can potentially be addressed by the currently developing area of Responsible
Research and Innovation (RRI).
Informed consent, internet research ethics and
Facebook
In this section, I will give a brief overview of the Facebook emotional manipulation study, identify that there is a problem with lack of informed consent gathering
according to current internet research ethics procedures, and discuss informed
consent and information and communication technologies, focusing on the environment in which the Facebook study is situated.
The Facebook study
The Facebook study, entitled Experimental evidence of massive-scale emotional
contagion through social networks (Kramer et al., 2014), was a collaborative
16 Research Ethics 12(1)
endeavour between Facebook and Cornell University’s Departments of
Communication and Information Science. In it, Facebook researchers directly
manipulated Facebook users’ news feeds to display differing amounts of positive
and negative posts from the people they followed in order to determine whether
their subsequent posts were affected by the positivity or negativity of the set of
posts they were viewing. This effect, that more positive or negative posts read by
a user could change their own emotional state positively or negatively, is the ‘emotional contagion’ referenced in the article. Facebook allowed the scientists (both
internal and those from Cornell) access to the huge amount of data that was produced by manipulating what Facebook users saw according to computerized determination of positivity and negativity levels. The Facebook researchers performing
the data collection did not seek explicit informed consent from any participants,
and although an IRB was consulted at the university, the board deemed that the
researchers were ‘not directly engaged in human research and that no review […]
was required’ because the data collection was ‘conducted independently by
Facebook’ prior to the involvement of its researchers (Carberry, 2014). Facebook
does have an internal review process, but at the time it was not independent, and
subsequent improvements to this process have apparently been made since the
conclusion of the study (Meyer, 2014b; Schroepfer, 2014).
At face value, the study seems as though it would be a reasonable one to conduct, with potentially valuable outcomes for the understanding of the impact of
social media on society. However, there were significant questions about the conduct of the experiment, focusing on the data manipulation and analysis methods
used for identifying positive and negative posts (Grohol, 2014), the ethical conduct of the research, the burden of responsibility for this conduct, and the publication of the article by a peer-reviewed journal that requires IRB, REC or equivalent
approval of such research. Because this article is concerned with informed consent, I will focus on the latter points, as a wider critique of research methods is
outside the scope of this article.
‘Traditional’ informed consent
Informed consent has a long history in medical and bioethics, but only a relatively
recent history specifically in technology, where it is most notoriously displayed in
terms of service or end-user licence agreements. The seminal form of informed
consent that is appealed to in technology situations, effective consent, was described
by Faden and Beachamp (1986) within the context of medical research ethics, but
the theory has since moved beyond that field. Effective consent involves the
aspects of autonomy (of the consent decision action), competence (of the person
making the decision to consent), disclosure (of all of the risks, benefits, terms,
conditions and any other limitation), understanding (on the part of the consenter of
Flick 17
the former) and voluntariness (of the consenter to consent) (Faden and Beauchamp,
1986). Where traditional research ethics involving human subjects usually involves
face-to-face contact between researcher and subject, allowing for a conversation
to occur, technology removes that contact, which significantly dilutes the ability
for consent-seekers to determine autonomy, competence and understanding, and
for consenters to understand the ramifications of the disclosure – for example, in
Facebook’s case, providing thousands of words of difficult-to-read text1 (although
a face-to-face disclosure of this same information is neither a good nor practical
solution to this problem). It is common for consent-seekers in these kinds of situations to appeal to the effective consent model, but focus on disclosure as the main
aspect, disregarding the more important aspects of the requirements of informed
consent (Flick, 2013). This is insufficient for real informed consent, yet technology companies persist with it because, although legally dubious at best, it has
become the de facto standard. So even though Facebook had not included ‘research’
in its terms of service (Hern, 2014) at the time of conducting the research, if it had,
this would not be ethically sufficient for its users, even at a most basic effective
consent level.
I have previously discussed the fact that this sort of informed consent is wholly
unsuitable for information technology (Flick, 2013) and that the theory of waiver
of normative expectations (Manson and O’Neill, 2007) may be better suited.2 I
will return to this theory in a later section where I suggest a better approach for
technology-based informed consent procedures.
Internet research ethics
Internet research ethics is currently an area that is pushing boundaries and still
establishing best practices. The sorts of ethical research procedures that used to be
commonplace in traditional research have been somewhat shoehorned into the
online sphere, though many aspects are not directly translatable. The debate over
what constitutes public and private data, for example, is ongoing (British
Psychological Society, 2013). Despite this, there are extensive guidelines for
researchers available at various levels (universities [e.g. University of Brighton,
2014], professional organizations [e.g. British Psychological Society, 2013] and
independent bodies [e.g. The Association of Internet Researchers, 2012]) that outline the issues and provide suggestions to researchers on how to approach their
research. All of these guidelines include the requirement for informed consent
procedures in human research. Ignoring for the moment the discussion about
whether the Facebook study should have had official ethical oversight (through an
IRB or equivalent) – I will get to this later in the article – if the researchers involved
were adhering to good research ethics, and were acting as professional researchers, they should have followed these ethical guidelines and performed informed
18 Research Ethics 12(1)
consent procedures. The journal that published the article, the Proceedings of the
National Academy of Sciences of the United States of America (PNAS), also
requires any research with human participants to undergo ethical review. However,
in a correction to the original article by PNAS Editor-in-Chief IM Verma, owing
to the conclusion drawn by the Cornell University IRB the editors felt that it had
been adequately screened, and that ‘as a private company Facebook was under no
obligation to conform to the provisions of the Common Rule when it collected the
data used by the authors’ (Kramer et al., 2014). However, the correction continues,
‘it is nevertheless a matter of concern that the collection of the data by Facebook
may have involved practices that were not fully consistent with the principles of
obtaining informed consent and allowing participants to opt out’.
Such a situation is considered a ‘policy vacuum’ (Moor, 1985), where the existing policy does not adequately fit current technological challenges. In the Facebook
study situation, there is no explicit guidance of what to do, as noted by Harriman
and Patel (2014). Harriman and Patel looked at UK National Health Service (NHS)
ethics board procedures and found little in the way of explicit guidance for
Facebook-style experiments. However, there are general guidelines for internetbased research, such as those discussed above, but they are not generally checklist
or explicit guidance style approaches. The Association of Internet Researchers
(AoIR) argues that it is impossible to create ‘one-size-fits-all’ rules for this sort of
research, but that ‘ethical decision-making is best approached through the application of practical judgement attentive to specific context’ (AoIR, 2012: 4), and that
‘researchers should consult as many people and resources as possible’ (AoIR,
2012: 5) to assist in ethical deliberation prior to research being conducted. In internet research ethics, the following principle is of primary importance, according to
the AoIR: ‘Because all digital information at some point involves individual persons, consideration of principles related to research on human subjects may be
necessary even if it is not immediately apparent how and where persons are
involved in the research data.’ (AoIR, 2012: 4). Although there are no hard and fast
rules for this sort of research, in failing to carry out informed consent procedures
and restricting their ethical review to an internal process, Facebook did not follow
these principles.
The questions for researchers presented by the AoIR (along with similar guidelines posed by those institutions mentioned previously), as part of the suggested
ethical deliberation, focus particularly on the ethical issues that the Facebook
study encounters: ethical issues surrounding the participants of the study and the
object of study; data storage, management and presentation; data analysis; potential harms and risks; potential benefits; recognition of autonomy of others (informed
consent procedures); and issues to do with minors and vulnerable persons. It recognizes the potential differences between community and researcher expectations
of norms, asking whether the research definition of the context matches ‘the way
Flick 19
owners, users, or members might define it’, and asking researchers to define their
own position within the context and compare it with their participants (AoIR,
2012). This is important within the Facebook context because if the researchers
had done this there may not have been the same backlash against the study as was
demonstrated. For the issue of consent the discovery and establishment of normative expectations is, as we shall see, particularly important.
Informed consent as a waiver of normative expectations
A brief outline of the Manson and O’Neill (2007) theory of informed consent follows. Informed consent should be made up of a series of waivers of expected
behavioural and social norms. For any procedure or situation that may violate a
person’s normative expectation for behaviour, such as using a knife to cut into a
person’s body, the person needs to waive that particular behaviour (for surgery, for
example). If they do not waive the expected norm, then consent has not been given
(as would be expected in cases such as a stabbing). In order for people to make an
informed decision, they must be involved in an effective communication framework that allows for simple, easy to understand language, and epistemic responsibility on behalf of the consent-requester for the consenter’s level of understanding
in the consent transaction. In this theory, the focus shifts substantially from the
assessment of the consenting party (and their autonomy) to the assessment of the
quality of communication of the nature of the norms that are to be waived. This
theory is less ambiguous than the currently practised theories (especially the effective consent disclosure model discussed above), not simply providing a set of
minimum threshold requirements for assessing autonomy of a user’s actions but
placing specific and explicit responsibility for accurate communication of requests
for waivers of normative expectations on the consent-obtaining party.
The problem of disclosure, such as that encountered with overly lengthy and
incomprehensible terms of service such as those used by Facebook, can be
addressed more directly by the waiver-based approach. Facebook can, in fact,
improve their terms of service in such a way that the expected norms are included
as part of the base standard, but that expectations that need to be waived are communicated effectively and consented to (either negatively or positively) by the
user. The use of the theory of communication as a transaction can more easily
restrict the types of language used in a waiver disclosure, because successful
communication requires that it be written in a language that is intelligible, easy to
follow and relevant to its audiences, ‘rather than overwhelming them with a flood
of irrelevant or distracting – even if intelligible – information’ (Manson and
O’Neill, 2007: 85). Also, both parties should know some background about each
other – sites and companies employing such terms of service should know the
target markets for their services and adjust the language accordingly. However,
20 Research Ethics 12(1)
this is not all that a successful communication transaction requires: in addition,
the communication must not be dishonest, and needs to be accurate for the purpose. A company should state up front if they are going to be, for example, using
user data for purposes other than as communication between users, and, as accurately as possible, what sorts of outcomes this use may have. This theory requires
successful communicators to be responsible in the truth-claims they make in
order not to undermine the communication transaction and thus undermine the
informed consent procedure. In this way, sites that wish to violate normative
expectations of their users should communicate explicitly with their users about
these potential violations in ways that emphasize the truth-claims being made
rather than focusing on full disclosure saturation of information, as is often traditionally required. This can avoid the ‘numbness’ that is associated with getting
users to read, understand and accept the traditional terms of service and similar
documents across multiple sites.
This approach also, importantly, avoids allowing those who deliberately mislead their users or assume acceptance of activities, such as in the Facebook study,
to get away with such behaviour by making them just as responsible for the appropriate and accurate transaction of information as the user who signs up for the site
and agrees to the terms of service by doing so. It is too easy under the current
system for these parties to state that they adhered to the requirements of full disclosure, while failing to mention that in fully disclosing, the important information
was buried so deeply within the agreement so as to be virtually drowned out by
useless or inappropriate information. Currently the responsibility for understanding and isolating the relevant pieces of information is entirely that of the user, as,
arguably, the consent-requester can avoid accountability by pointing to their disclosure of the information which theoretically empowered the user to make an
autonomous decision. The waiver-based approach firmly states that this is not
acceptable, because the required standard of communication dismisses full disclosure as an appropriate way to inform the user. If full disclosure is used as a defence
but there is inadequate or unreliable communication (such as that brought about by
the ‘flood of irrelevant or distracting […] information’ [Manson and O’Neill,
2007: 85]), then the informed consent procedure has failed, and the consent given
by the user was not informed. Such is the case in Facebook’s study – any information about what a user’s data might be used for is deep within the terms of service
and data use policies, which are a long and complex read for most users (the terms
of service running at over ten pages worth of text that is not often drawn to the
attention of the user outside of initial sign-up, and which can be modified at any
time). Even if the user were to read (and re-read) these documents, the wording is
ambiguous; for example, in the Data Use Policy, research is only mentioned as
part of internal operations, and does not necessarily describe externally publishable research (such as that of the study).
Flick 21
It is important to recognize that the responsibility for successful informed consent events is shifting back to the consent requestor – there is a strong incentive for
Facebook’s users to accept the terms of service, because being on Facebook is
socially desirable, and a strong disincentive for Facebook to narrow the general
terms of service. If Facebook can keep their terms of service general (within legitimate normative expectations of users – these will be discussed later) and seek
explicit consent through successful informed consent procedures for potential
norm violations, this may make it easier for them to retain legitimacy and favour
with their users, and to cover themselves legally.
In this section I have described the Facebook emotional manipulation study, identified there to be a problem with the lack of informed consent in the study according
to research ethics, described the problems with obtaining informed consent in traditional forms in ICT situations, and offered a solution to this problem that in turn can
solve future informed consent gathering problems in social media (and similar) sites.
In the next section I will suggest some ways for companies such as Facebook to
identify normative expectations that they should request explicit consent for in the
method described above, and describe some suggestions as to how to present the
waiver for users to consent to the violation of these expectations.
Normative expectations
Similarly to internet research ethics, there is no ‘one-size-fits-all’ solution to the
determination of what normative expectations exist. However, researchers, if they
engage with the community prior to carrying out the research, can identify concerns users may have, what they would consider to be inappropriate or uncomfortable for them, etc. They should also consult with experts in research methods and
ethics to ensure that all aspects are covered, whether through an ethics committee
(such as an IRB or a REC) or independent consultants. In fact, unlike many traditional research projects, where potentially interacting with the community could
sway results, big-data projects such as Facebook can easily separate those participating in community engagement procedures and those to be involved in experimental research projects as subjects, if afraid of potential bias.
As an example of some normative expectations that Facebook and similar
organizations might want to consider, I have identified some themes that have run
through the reactions of users to the Facebook emotional manipulation study as
reported in the press and on blogs. This is not an exhaustive review in any way,
and ideally there would be direct engagement with the population to provide a
fuller list of expectations that might potentially be violated. I have focused on
consent-related issues specifically, though there are other issues that are highly
likely to be important to users of the system. These reactions were collected via a
search of Google News for terms related to the Facebook study, including the title
22 Research Ethics 12(1)
of the article, ‘Facebook emotional manipulation study’, ‘Facebook study’3 etc.,
which were then further filtered to ensure the applicability of the results to the
actual study (and not other studies). These articles were then read, and consentrelated problems described within them identified for further analysis. The
responses from lay stakeholders were separated from responses from academics,
which were used as a comparison mechanism. The limitations of this approach
include that they were post-hoc (as described before, ideally stakeholders are queried about potential issues before such activities are undertaken or included within
a terms of service document), they were not particularly representative of all perspectives of the study (although this does not impact the initial findings as we are
looking for potential consent-related problems, not positive aspects), and that it is
not an exhaustive review, but, as mentioned before, simply attempts to identify
some illustrative emergent aspects (violated normative expectations) that stakeholders had with the study, and that could be used within the waiver approach.
Some of the main problems, as identified by ‘users or members’, reported online
by the media (Hern, 2014; Hill, 2014; Meyer, 2014b; Waldman, 2014) and users in
blogs and online polls (a particularly well curated set of responses was written by
Deterding [2014a], and a poll conducted by The Guardian [Fishwick, 2014]), with
the consent in this particular study can be broken down into these main issues:
A. Users were not asked to participate in the experiment, and didn’t know they
were participating in research;
B. users did not know their news feeds were being manipulated by Facebook
(although they were not surprised upon finding out);
C. users were not made aware on signing up for the service that they could be
potentially involved in any experiments while using Facebook; and
D. Facebook did not see fit to seek ethical oversight despite ostensibly manipulating peoples’ emotions.
These match some of the issues with the Facebook study as found by academics
commenting on the study (boyd, 2014; Hunter, 2014; Klitzman and Appelbaum,
2014). B is a particularly interesting finding because there is an element of manipulation that Facebook conducts on the news feeds even when they are not carrying
out research. Even so, according to the literature mentioned above, users were still
unaware that their feeds were being manipulated at all, let alone for the study.
From these, I suggest the following normative expectations that explicit consent
ought to be sought for prior to violation of them:
1. Users expect their news feeds in Facebook to be published faithfully by the
people, communities, and organizations they follow and not manipulated.
(Resulting from issue B)
Flick 23
2. Users expect to be explicitly asked to participate in any experimental
research conducted by Facebook. (A, C)
3. Users expect Facebook to conduct human research under the auspices of
some sort of independent ethics committee. (A, C, D)
It is important to note that some of these extend outside research situations –
especially (1), so the issue of manipulation of news feeds could be dealt with at
sign-up and change of manipulation procedures. It is similarly important to note
that any explicit consent requests to waive these expectations cannot be done only
once at sign-up, but ought to be re-requested if situations are to change. For example, with (1), there could be an option for users to view their news feeds with no or
minimal manipulation (as there are currently the ‘Most recent’ and ‘Top stories’
options), and those for whom it is manipulated should be notified if algorithms to
do this change.
Practical implementation of this is not technically difficult. Modern web development techniques allow Facebook to pin a notification to the top of the news feed
or similar, or, as currently occurs when an unusual login is detected, offer a notification, until the user has acknowledged it in some way. It is important that this
particular notification is not simply a disclosure situation – a user has to be free to
consent or not consent to the changes. Subsequent design decisions will need to be
made carefully so that the option to not consent does not necessarily bar the user
from using the site (though, depending on the consent request that was denied,
perhaps puts them on a lower-scale bare bones version of the site). Obviously this
will need to be further investigated in specific examples as they arise, but could
also lead to better designed experiences for users too.
Responsible Research and Innovation
With suggestions for Facebook’s informed consent issues out of the way, it is
important to look at the responsibility for enforcing the practice of ethical human
research. The ‘Facebook loophole’ (Deterding, 2014b) that allowed the research to
be associated with Cornell University and published in PNAS shows a gap in the
approaches to human research between private companies and research groups
(such as universities) (boyd, 2014; Hunter, 2014).
It is important at this point to note that there has been a response from a group
of bioethicists stating that there was not any ‘egregious breach of ethics or law’
in the study (Meyer, 2014a) and that turning to regulation could drive such
research ‘underground’: ‘If critics think that the manipulation of emotional content in this research is sufficiently concerning to merit regulation or charges of
unethical behaviour, then the same concern must apply to Facebook’s standard
practice — and many similar practices by companies, non-profit organizations
24 Research Ethics 12(1)
and governments.’ As discussed earlier in this article, and as I have advocated
for end-user licence agreements and privacy policies previously (Flick, 2013), it
is absolutely the case that Facebook’s standard practice is also at issue, and that
problematic informed consent procedures in the realm of technology need to be
fixed in order to protect users and consumers of that technology. However, there
have also been significant issues brought to light in this study that show that
there are problems with human research within big data companies, exemplified
by the Facebook study, and particularly problems of informed consent, as discussed earlier in this article. The fact that the bioethicists involved in drafting
the Nature article could not agree on whether the manipulation of news feeds
was a normative expectation to begin with shows that there are significant problems with the understanding of the community and the normative expectations
involved, so to make a decision from an ethical perspective that these should be
automatically waived without consultation is professionally irresponsible at
best. In fact, these bioethicists suggesting that the status quo of allowing companies to operate outside of independent ethical oversight to continue is negligent
at best – allowing companies to acknowledge that their avoidance of human
research ethics has been condoned by a group of bioethicists – and at worst
undermines the hard work of the field of computer ethics, which attempts to
address these issues and fill Moor’s ‘policy vacuums’. Yes, rigorous science
should be conducted, but science conducted within a company should not be
treated any differently from an ethics perspective than science conducted within
a university. This does not shift that science ‘underground’; it gives it that desired
rigour.
This brings us to the question of how we can fill the wider gap between requirements for university-led research and that conducted within a company – the
‘Facebook loophole’ (Deterding, 2014b). The emerging discourse around RRI
might be able to provide pointers toward a framework for further discussion and
research into how this might be achievable. RRI aims to empower research and
innovation to be responsible – both in research institutions and in industry. RRI
is defined by Stahl (2013) as a ‘higher-level responsibility or meta-responsibility
that aims to shape, maintain, develop, coordinate and align existing and novel
research in innovation-related processes, actors and responsibilities with a view
to ensuring desirable and acceptable research outcomes’. There is a significant
movement coming from the European Union to move these principles into higher
level research policy as well as into industrial contexts, with projects funded like
Responsible-Industry (2014) looking at best practices to institute this metaresponsibility. The idea of bringing responsibility in at a meta-level allows us to
organize responsible innovation with existing frameworks, such as, in Facebook’s
case, integration with ethics review, codes of ethics, stakeholder consultations,
and other best practices, but requires the industry itself to get involved and
Flick 25
willingly accept such a meta-responsibility. To do so the incentives to drive that
acceptance must be found – this is one of the goals of the Responsible-Industry
project.
Indeed, so far the analysis of the applicability of RRI frameworks to industry has
raised familiar results. Once again, there is unlikely to be a ‘one-size-fits-all’
approach, but ‘the most promising route is to tailor [academic] frameworks for
specific industry sectors and for differently sized organisations’ (Søraker and Brey,
2014: 24). According to Søraker and Brey, corporate social responsibility (CSR) is
used as an example of integration of responsibility mechanisms within industry,
and could be used as part of the wider RRI frameworks. Standards and certifications could be used to further establish companies’ reputations and improve accountability to their users. However, these ideas need further research and implementation
– and for companies to buy into the idea of its worth – before we see any change in
this regard. Such an effort would not be without challenges, though, if the response
from Facebook is any indication, ‘bottom-up’ grassroots reactions such as these can
significantly incentivize change in processes within large industry players: Facebook
has recently responded officially to the uproar around the study, stating their commitment to doing research ‘in the most responsible way’ (Schroepfer, 2014) by
improving their guidelines for research and their review and training processes. For
other companies, however, it may not be so easy. Small companies (such as startups) with few resources may find such frameworks difficult to implement, or put
them at a lower priority. Large companies may wait for something ‘bad’ to happen
before implementing such a framework. The incentives, barriers and risks for this
sort of approach need to be further examined.
Companies that are involved in dealing with human data, and especially those
involved in peoples’ daily lives to the degree that social media like Facebook is,
need to remember that there are people at the end of the data rainbow. This means
treating them as people with different ages, genders, backgrounds, cultures,
desires, wishes, dreams, disabilities, strengths and vulnerabilities, and many other
aspects. Facebook and other social media companies have a responsibility to their
users to treat them with care and respect. It goes beyond the question of whether
the Facebook study is just ‘no more than usual’ (Meyer, 2014a) and into the dayto-day running of the company. If companies are acting ethically from the outset
(and performing their research and innovation responsibly), then the ‘Facebook
loophole’ would not exist. Until that day, however, it would be prudent to maintain
the ethical requirements and quality of human research science to reject research
studies from any organizations, whether research or industry, where the data collection is not performed with ethical oversight (and if not independent ethical
oversight, then at least procedures that would satisfy such oversight should it
exist). Ideally, however, all modern market research that involves humans should
come under such ethical scrutiny if we wish to close the research ethics gap.
26 Research Ethics 12(1)
Conclusions
The Facebook study was controversial for good reasons – it violated the normative expectations of the very users it was studying. The lack of informed consent
to waive these expectations directly resulted in the backlash that caused the editor of the journal to publish a correction (Meyer, 2014a), that caused one author
to make a statement apologizing for ‘the way the article described the research
and any anxiety it caused’ (Kramer, 2014). Additionally, the COO of Facebook,
Sheryl Sandberg, also apologized for the lack of communication (although she
did not agree that the study was problematic in itself) (Bailey, 2014). The fact
that these are considered communications issues by those involved further highlights the importance of engaging with the users in order to determine their
expectations and gaining informed consent from those users before proceeding
with such studies. If these studies, and associated daily practices, had been
brought into a broader framework that ensured engagement with stakeholders
over these sorts of issues, such controversy would have been more likely to
emerge well before the data collection had begun. Whether or not this higherlevel ‘meta-responsibility’ were to incorporate an independent ethics review
committee should be the focus of future research, as well as incentives to drive
uptake of such a framework, but for now it is plain to see that there is a gap
between university-led research and industry-led research when it comes to ethics, and this should be rectified in some way.
In this article I have argued that the study conducted by Facebook and Cornell
University researchers as described by Meyer (2014a) did not have adequate ethical oversight and did not perform informed consent procedures as required by
internet research ethics, and that even if Facebook’s terms of service had had that
users’ data could be used for research added to it, this would not have constituted
valid informed consent. I identified that there is a significant gap between university-driven human research and industry-driven research in terms of research ethics, and that this is a problem which needs to be rectified. I suggested a new
theoretical method for introducing informed consent into social media sites that
requires the company rather than the user to be responsible for the consent decision, and gave some practical suggestions of identification of normative expectations that such companies could use in informed consent procedures. Finally, I
pointed in the direction of RRI – a relatively new but quickly spreading movement
to incorporate responsibility into the innovation process – and looked at how larger
issues of differences between university-led research and industry-led research
need to be addressed.
Declaration of conflicting interests
The author declares that there is no conflict of interest.
Flick 27
Funding
This work received no specific grant from any funding agency, but the author is a member of
the Responsible-Industry consortium, which is funded under the European Commission’s 7th
Framework Programme, Grant Agreement #609817.
Notes
1. https://www.facebook.com/legal/terms.
2. Some of this material on the background to the Manson and O’Neill theory is adapted
from my previously unpublished PhD thesis (Flick, 2009) but has been updated and modified for the current situation.
3. Terms used were: ‘Facebook emotional manipulation study’, ‘Facebook study’, ‘Facebook
emotions study’ (this last phrase suggested by Google News) and ‘Facebook news feed
manipulation’.
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