Research Ethics Controversies,
Then and Now
Jeffrey P. Baker MD PhD
Trent Center for Bioethics, Humanities,
and History of Medicine
Duke University
Objectives
• Briefly review the history of research ethics
in the United States
• Examine several controversies in more
detail
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Fernald School radiation studies
Sloan Kettering cancer cell infusion studies
Willowbrook hepatitis studies
Tuskegee and the Guatemala syphilis studies
Edward Jenner and Smallpox
Vaccine
• Observations re:
cowpox
• Inoculated 1 yo son
• Then inoculated 8 yo
James Phipps
Jenner’s Experiment
• “The more accurately to observe the
progress of the infection, I selected a
healthy boy, about 8 years old, for the
purpose of inoculation for the cow-pox.
The matter was inserted into the arm of the
boy by the means of two incisions.”
What were the ethical norms for
human subject research in 1796?
Hippocratic Oath
“I will use my power to help the sick to the
best of my ability and judgment; I will
abstain from harming or wronging any man
by it”
Does not directly address human
experimentation… but might permit it so
long as risks minimal and outweighed by
potential benefit
Rise of Laboratory Medicine
• Rise of germ theory
and laboratory science
introduces many new
potential therapies by
late 1800s
• At some point had to
be tested in humans
Research Ethics:
Claude Bernard (1865)
“Among the experiments that may be tried on
man, those that can only harm are
forbidden, those that are innocent are
permissible, and those that may do good are
obligatory”
William Osler (1907)
• Hopkins faculty
• Perhaps most famous physician in America
• Once animal experiments established safety,
physicians who obtained “full consent” could
introduce new therapies
“We have no right to use patients entrusted to our
care for the purpose of experimentation unless
direct benefit to the individual is likely to follow”
Consent: Another View
• “In practical work in medical wards, the
patients do virtually give their consent to
what is done to them, and if they raise any
objection, the procedure is not carried out”
--Francis Peabody, Harvard physician
--Letter to Walter Cannon, 1916
U.S. Research Ethics before WWII:
Summary
• Focus on “lesser harms” reasoning rather than
consent: intervention justified only if risk it
entails are lower than risks of natural disease it is
intended to prevent or treat
• Patient safety depended upon professional norms,
not legal regulation
Nuremberg: The Doctors Trial
(1946)
The Defense: Ethical Relativism
Malaria Experiments
• Human trials in
Illinois penitentiary
• Prisoners inoculated
with malarial
mosquitoes
• Praised in Life
Magazine as heroes..
The Verdicts
• Trial completed
August 20, 1947
• 15 of 23 defendants
found guilty
• 7 sentenced to
hanging, 5 to life
imprisonment
The Nuremberg Code (1946)
• 10 basic principles that must be observed in
order for human experimentation to be
ethical
• First principle:
The voluntary consent of the human subject
is absolutely essential.
Henry Beecher, “Ethics in
Clinical Research,” NEJM 1966
• Summarized 22 studies from prestigious
medical journals in which researchers
provided no indication of having explained
risks to patients
• Included: invasive procedures, adults
infused with cancer cells, institutionalized
children deliberately exposed to hepatitis
Tuskegee Syphilis Study:
1932-1972
• 40 year study of
“untreated syphilis
in the male Negro”
• Exposed in 1972
• Public outcry and
government
commission
The Belmont Report (1974):
Central Bioethical Principles
• Respect for Autonomy: protect patient’s
right to informed consent
• Beneficence/Nonmaleficence: physician’s
duty to help and not harm the patient
• Justice: Burden of risks and benefits should
not fall disproportionately on those most
vulnerable
The Common Rule 1981
• Codified principles of Belmont Report into
law
• Revised, but remains the central body of
regulations protecting human subjects
• Reliance on informed consent and review
by institutional review boards (IRBs)
History of Research Ethics:
Summary
• Before WWII: Subject to professional
norms and practices (emphasizing lesser
harms over consent)
• Nuremberg Code articulates informed
consent: 1946
• Tuskegee scandal triggers public outcry and
regulation: 1972-81
Cases
Deceptions
The Fernald School
The Fernald School Radioisotope
Studies
• Researchers by MIT working with school
staff carried out nontherapeutic experiments
in nutrition from 1946 though 1953
• Involved low dose radiation
• Parents not informed
The Science Club
Students from the Fernald School, 1954
Letter to parents, May 1953
• “We have asked for volunteers to give a
sample of blood once a month for three
months, and your son has agreed to
volunteer because the boys who belong to
the Science Club have many additional
privileges.”
What are the ethical problems?
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•
•
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Harm? Exposure was very low
Deception
Using humans as a means to an end
Taking advantage of a vulnerable
population
Betrayal of Trust
Brooklyn, New York 1963
Jewish Chronic Disease Hospital
• Lawsuit: 22
terminally ill
patients had been
given infusions of
cancer cells without
their knowledge
Sloan Kettering Cancer Study
(Dr Chester Southam, 1954-63)
• Purpose: Determine if cancer patients
lacked immune response to cancer cells
• Inoculated cancer cells in cancer patients
and healthy controls (prisoners); found that
the latter cleared the cancer faster
• Did this reflect cancer or poor health?
• Recruited 22 terminally ill controls
(JCDH)—without consent!
Questions: Ethical and
Psychological
• Again raises the same issues as the Fernald
school: deception, exploitation
• This case is interesting as a case study in
moral psychology: how did a respected
physician get to this point?
Dr. Southam, Interview, 1964
•• “The reason we did
not tell them was for
their sake, not ours.
The cancer patients at
Memorial Hospital
seem to develop a
bizarre, defensive
reaction against the
knowledge they have
cancer…”
•
An Irony
• Between the Nuremberg Code (1946) and
the exposure of Tuskegee (1972), medical
investigators were more likely to obtain
consent from prisoners than patients
• The Nuremberg code was seen as applying
to healthy volunteers, not patients
“One of the real ludicrous aspects of
talking about a prisoner being a captive,
and therefore needing more protection
than others, is that there’s nobody more
captive than a sick person”
From oral history interview, Dr
Thomas Chalmers
Recent Parallels:
Jesse Gelsinger
• 18 yo who died in
1999 gene therapy
experiment
• ?whether consent
was adequate
• Allegations of
conflict of interest
for Univ of Penn
researchers
Experiments in Nature
The Willowbrook Hepatitis Studies
Staten Island, New Jersey, 1955-1972
Dr Saul Krugman
Context
• Extreme
overcrowding
• Krugman found
that infection with
hepatitis was
virtually
inevitable…yet
mild in children
The Studies
• Decided to deliberately expose some
children in order to learn more of natural
history of hepatitis and thereby control it
• Researchers believed that the strain was
very benign in children, and might protect
against others
• The studied did in fact lead to important
knowledge (and first hepatitis B vaccine)
Exposure and Lawsuits:
1968-72
Geraldo Rivera
Patients
Were parents fully informed?
• Lawsuit launched in early 1970s claimed
children entered into study without consent
• In fact, there was an elaborate process of
consent involving group meetings and
written consent for all participants
• Controversy reflected the context of the
times (1968-72)
Was the study justifiable as a
“study of nature”?
• Krugman argued that children were going to
be infected either way; his study was
justified morally as a way to help control
the infection
• Critics charged that the researchers should
never have collaborated with an institution
under such conditions
• The question was further charged by the
exposure of the Tuskegee study…
A Recent Parallel:
Baltimore Lead Abatement Study
• Hopkins researchers
studied whether less
expensive forms of lead
abatement were as
effective
• Researchers worked with
landlords to recruit
families with children
• ?consent
Syphilis Studies:
Tuskegeee and Guatemala
Tuskegee
• President Clinton’s
apology
• Most famous of all
research scandals in
US history
• Remembered.. But
how accurately?
The Lessons of Tuskegee
• Violated all three of the basic principles of
ethical research:
– Decepttion and failure to obtain consent
– Posing harm to the patient (at least potentially)
– Research in a vulnerable populatoin
• Also raises issues of race and gender
Tuskegee’s Legacy
• Far more than the other examples, the
memory of Tuskegee has persisted– in the
African-American community
• Often cited as reasons to distrust researchers
• And an example of memory becoming
mythology: widespread belief that subjects
were deliberately infected with syphilis
Headlines: 8 June 2011
Guatemala Victims of US Syphilis Study
still haunted by the ‘devil’s experiment”
The Guardian
“
Dr John Cutler
• Died in 2003
• Former Assist
Surgeon General
and Deputy
Director of Pan
American Sanitary
Bureau
• And a Tuskegee
doctor
Cutler in Alabama, 1960s
Cutler in Guatemala: 1946-48
• PHS had long
history of int’l
work, especially via
Pan American
Sanitary Bureau
• Close cooperation
with Guatemala
Context: The Soldiers Return–
with STDs?
• Was immediate
penicillin
sufficient?
• Could there be a
better chemical
prophylactic?
• 2 years of studies
Prison Studies
• Prostitutes with syphilis were allowed to
provide services to inmates at Guatemala
City’s Central Penitentiary, paid for by
PHS funds
• Different chemical prophylaxis techniques
applied
• If subject developed syphilis, was given
penicillin
Orphanage Studies
• Researcher recruited 438 children in
national orphanage to study value of
different blood tests
• Not inoculated with syphilis
Asylum for Mentally Ill
• The PHS cooperated with the institution,
not the subjects or families
• Introduced syphilis via infected prostitutes
• But also through deliberate inoculation via
abrasion
• Anyone infected was given penicillin
Was anyone harmed?
• Records reviewed so far suggest 696
subjects were exposed to syphilis
• Preliminary recent analysis suggests 14% of
those with syphilis may not have received
adequate treatment
Response and Apology
Reasons to study this history
• Lessons for formulating policy
• Understanding motivations: why physicians
did actions we consider unethical
• And to grapple the question of whether we
can judge the past.
Can we judge the past?
Objections
• Cultural Ethical Relativism: we can only
make moral judgments with respect to
cultural context
• Culturally Induced Ignorance: we cannot
condemn individuals for not escaping
ignorance of relevant knowledge (ie, risks)
or shared enculturated beliefs (ie, no one
condemned the practice)