History of Research Ethics

1
History of Research Ethics

• Examples that have
• lead to current standards

2
Early American History

• (1721-23) Rev. Cotton Mather and Dr. Zabdiel
  Boyleston vs. Dr. William Douglass
• Mid-1800s) African Americans in Antebellum period
• Slave corpses procured for research and
  dissection
• The cure for Vesico-Vaginal fistula Dr. Sims
  performed experimental surgical procedures on
  African American female slaves.

3
The inconsistency of research on African Americans

• Physicians of this period gave supposed medical
  evidence of African Americans physiological and
  mental inferiority based on the idea of inherent
  biological differences
• Yet research and teaching was done on African
  Americans as subjects and models with no
  attention to supposed differences that would call
  into question the applicability of the results to
  caucasians.

4
Nuremburg exposes Nazi experiments

• Malaria prisoners infected with malaria and
  given supposedly anti-malarial drugs. Many died
  from the drugs.
• Mustard gas prisoners intentionally wounded and
  wounds infected with mustard gas, or forced to
  inhale mustard gas.
• Sulfanilamide prisoners infected with bacterial
  culture , gangrene culture wood shavings or glass
  shards. Then treated with sulfanilamide for
  wound infection. Control group not given
  sulfanilamide.

5
Nuremburg

• Typhus prisoners injected with anti-typhus
  vaccine, then infected with typhus. Control
  group infected , but not to given the treatment.
  Others infected with typhus, to ensure the virus
  remained active in the prison camps.
• Poisons various poisons to prisoners in their
  food. Most died immediately, and those who did
  not die were killed for autopsy.
• Incendiary bombs prisoners burned with
  phosphorus material from English incendiary bombs
  so doctors could examine the wounds.

6
Nuremburg

• Sterilization because sterilization by surgical
  means was too costly and time-consuming prisoners
  were subjected to chemical sterilization and
  x-ray sterilization experiments
• Hypothermia
• Twins studies

7
Thalidomide

• In the late 1950s, thalidomide was approved as a
  sedative in Europe it was not approved in the
  United States by the FDA.
• drug during pregnancy caused severe deformities
  in the fetus
• Many patients did not know they were taking a
  drug that was not approved for use by the FDA,
  nor did they give informed consent.
• 12,000 babies born with severe deformities.

8
Beecher published these cases in 1964

• Melanoma transplanted from daughter to healthy
  volunteering mother in hope that the tumor
  antibodies might help the patient (who died on
  the day of the transplant.)
• Live cancer cells inserted into patients in
  Jewish Chronic disease hospital without informed
  consent
• Beechers examples and others demonstrate that
  leaving ethical analysis up to individual
  investigators has not adequately protected
  subjects

9
Tuskeegee (1932-1972)

• Prior to penicillin, experiment to follow the
  natural history of syphilis in African American
  males near Tuskeegee AL (1932)
• Unnecessary because a study on the natural
  history had already been completed in Oslo
• After proven that penicillin cured syphilis, the
  experiment was continued without offering the
  subjects the cure and in fact preventing them
  from treatment by local physicians (1948)

10
Belmont Report (1972-74)

• Respect for persons
• Beneficence
• Justice

• Informed consent
• Risk benefit ratio
• Selection of subjects

11
Respect for persons

• Always treat persons as ends in themselves, never
  merely as means to an end

• Research subjects must participate only after
  informed consent
• Subjects who begin a study may change their minds
  and withdraw at any time, regardless of whether
  study completed.

12
Informed consent

• Must entail mental capacity to understand
• Lack of coercive or undue influences
  (voluntariness)
• Comprehension

• Known risks and possibility of unknown risks
• Whether any potential for direct benefit
• Whether placebo arms or randomization
• No penalty or loss of care from refusal

13
Beneficence

• (i) Inhumane treatment of human subjects never
  morally justified.
• (ii) Risks reduced to those necessary to achieve
  the research objective, often by alternative
  procedures.
• (iii) When risk of serious impairment, review
  committees must insist on the justification of
  the risk (likelihood of benefit to the subject --
  or, in rare cases, to the manifest voluntariness
  of the participation).

14
Justice

• Selection of subjects must not
• Impose risks and burdens of research on
  vulnerable or disadvantaged subject groups
  unfairly (such as the Tuskeegee experiment)
• Distribute benefits of research participation and
  applicability of results unfairly to Favored or
  advantaged groups (such as the framingham heart
  study of white males)

15
Asilomar (1975)

• Conference on the unknown risks of re-combinant
  DNA research
• Fear that replication of such vectors as e. coli
  , if recombined with DNA from tumors or herpes
  would replicate and spread
• Beginning of the NIH Recombinant DNA Advisory
  Committee (RAC)
• Rules for lab standards for containment and
  bio-safety committee review

16
Human Genome Initiative (HGI) 1988-present

• Letter from 83 clergy representing wide array of
  religious groups concerned about moral
  implications of HGI to President Reagan
• James Watson creates Ethical Legal and Social
  Implications Division of HGI to address ethical
  concerns
• Research on anticipated ethical and social
  problems in order to minimize the risks and
  unintended consequences of HGI before the results
  were available and applied.

17
Issues in research with women, children and
minorities

• Reactions to Thalidomide, Tuskeegee, Willowbrook,
  etc protected vulnerable populations from
  research
• Invisibility of women also left them out of
  research, such as Framingham study.
• 1990s corrective action was implemented
• NIH requires when feasible inclusion of women
  children and minorities

18
Issues in international research

• HIV-AZT study
• After demonstration of effectiveness in US and
  France, trials of other protocols were done vs.
  placebo instead of equivalency studies
• Fair benefits
• Collaboration
• Transparency

19
Stem cell research and human cloning

• US. Ban on new cell lines for embryonic stem
  cells in federally funded research (2001)
• British policy allowing use up to 14 days old
• Proposals to ban even private embryonic stem cell
  research
• Ban on reproductive cloning in humans (1998)

20
Therapeutic misconception

• Patients who come to high powered medical centers
  for treatment are not sufficiently aware that
  research protocols are experimental
• Inherent conflict of interest
• Difficult to correct

21
Issues in reporting of data

• Data torturing
• Underreporting data
• Authorship
• Ownership of data
• Commercialization and conflicts of interest

22
Scientific misconduct

• Elias Alsabti who apparently plagiarized as many
  as 60 scientific papers during the late 1970s
• John Darsee whose scientific career in
  cardiovascular research appears to have included
  a series of fabricated experiments
• William Summerlin whose work in immunology in the
  early 1970s was challenged when skin grafts on
  mice were found to have been drawn with a black
  marking pen

23
Scientific Misconduct

• Robert Gallo's claims to priority in the
  isolation and identification of the AIDS virus
• David Baltimore's involvement in an immunological
  experiment that still cannot be replicated by
  other researchers