History of Health Research Ethics

Learning Objectives

• Learn about the Nuremburg war crimes

• Learn about Nazi doctors’ atrocities on humans

• Learn about rise of first code of ethics in health research

• Learn about other unethical studies and international guidelines

© 2017 USP
 The Nuremberg War Crimes

• Conducted

 Among civilians and Allied forces during World War II

 Under the custody of the German Reich
 Without participants’ consent

• Committed murders, brutalities, cruelties, tortures, atrocities and other

inhuman acts

© 2017 USP
Unethical and Inhuman Experiments Conducted on Humans by
Nazi Doctors During World War II

© 2017 USP
 High Altitude Experiments
• Legitimate concerns of the
German Air force were:
➢Survival of pilots at extremely
high altitudes
➢Determining maximum safe
altitude for jumping from
damaged aircraft

• Conducted in low pressure

chambers that approximated
pressure at extremely high
altitudes.

• 40% died due to anoxia and

lung rupture
 Freezing Experiments

• Another concern was survival

time after parachuting into the
cold water of the North Atlantic

• Participants remained in ice

tanks for 3 hours, severely
chilled and re-warmed

• 30% died
 Other Unethical Nazi Experiments

• Malaria experiment
 Infected healthy humans with infected mosquitoes

• Sulfanilamide experiment
 Polish women were shot and slashed on legs
 Wounds were stuffed with glass, dirt and various bacteria cultures; then
sewn shut
 Treated with IP (sulfanilamide)

© 2017 USP
 Other Unethical Nazi Experiments

• Burn (bomb) experiment

 Mixture of phosphorus (from bombs) and rubber applied to skin of victims
and ignited
 Fire extinguished after burning for 2 minutes
 Burns were then “treated” with various chemicals and ointments

• Amputation experiment
 Upper and lower limbs amputated
 Attempted to treat with transplanted bone/muscle/nerve
 Neither victims nor tissue “donors” did well in these studies
 About half of the amputation victims died
 Remaining were disabled for life
9

© 2017 USP
 Other Unethical Nazi Experiments

• Gas Experiment
 Wounds inflicted on participants were infected with poison gas

• Epidemic jaundice experiment

 Participants infected with jaundice

• Sterilization of subjects by means of x-ray, surgery, and drugs

10

© 2017 USP
 Other Unethical Nazi Experiments

• Poison experiment
 Participants fedfood mixed with various poisons or shot with poison bullets
to investigate effects of the poisons

• Spotted fever experiment

 Healthy participants infected with typhus germs to develop vaccine

• Sea water experiment

 Subjects deprived of food and given chemically treated water

11

© 2017 USP
 The Nuremburg Code

• Twenty-three physicians and administrators were indicted for their willing

participation in atrocities.

• Despite their arguments, the tribunal condemned these experiments as

“crimes against humanity”
• 16 were imprisoned and 7 sentenced to death

• Judges included a section called "Permissible Medical Experiments” in

their verdict

• This section became known as “The Nuremberg Code” and has formed the
basis for international codes of ethics 12

© 2017 USP
 The Nuremburg Code (cont.)

• Promulgated by Allied nations in 1947 following World War II

• Basic principles include:

 Need for voluntary consent of human participant

 Need for research proposal to be essential and meaningful
 Need for prior animal experimentation
 Avoidance of all unnecessary physical and mental suffering and injury

13

© 2017 USP
 The Nuremburg Code (cont.)

• Drawbacks

 Did not provide how to apply the principles

 No guidance on applicability in developing countries

• Following dissemination of The Nuremburg Code, the medical

community developed another ethical guideline in a meeting at
Helsinki.

14

© 2017 USP
 Helsinki Declaration

• Adopted in 1964; modified in 1975, 1983, 1989, 1996, 2000, 2002, 2004
and 2008 by the World Medical Association

• The declaration includes:

 Need for review of protocols by independent committees

 Consideration of participation in research of less than fully autonomous
participants
 Assessment of risk/benefit ratio, i.e., concern for interests of participant must
always prevail over interests of science and society
 Duty of physician to protect life, privacy and dignity of human participant

15

© 2017 USP
 Helsinki Declaration (cont.)

• Provision that full information must be disclosed to participants prior

to their giving consent.

• Importance of written consent and consent of minors and others.

• Disclosure of conflicts of interest.

• Avoidance of coercion.

• Inclusion of sanctions for investigators who violate Declaration.

• E.g., rejecting manuscript for publication.

16

© 2017 USP
 Helsinki Declaration (cont.)

• Pitfalls

 Permits investigators to ask for waiver of consent

 No guidance provided on applicability in developing countries

17

© 2017 USP
 Tuskegee Syphilis Experiment

• US Public Health Service study on natural history of syphilis from

1932-1972

• Studied 399 illiterate black farmers from Alabama

• Informed they were being treated with “bad blood” and were given
token doses of medicine

• Data taken from participants’ autopsies

18

© 2017 USP
 Tuskegee Syphilis Experiment (cont.)

• No informed consent.

• Study was stopped in 1973 and participants were given treatment.

• Treatment extended to wives and children born with congenital syphilis by

1975.

• In 1974, the US National Research Act became law, creating the National
Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research.

• Deliberations by the Commission that began at the Smithsonian Institution's

Belmont Conference Center in Washington, DC, resulted in “The Belmont
19
Report”. © 2017 USP
 The Belmont Report

• The “Ethical Principles and Guidelines for the Protection of Human

Subjects of Research” address three bioethics principles.
➢Respect forpersons
➢Beneficence
➢Justice

• Pitfall
• Overemphasis on individual rights.

20

© 2017 USP
 Willowbrook Hepatitis Study

• Study was designed to determine the period of infectivity for hepatitis

• In 1964, newly admitted mentally disabled children were inoculated with

infectious hepatitis

• Parents were not informed of the risks

• Benefit of study for participants: Better hospital facilities and care for the
children

21

© 2017 USP
 The Jewish Chronic Disease Hospital Study

• In 1963, elderly patients were injected with live cancer cells in a study of
rejection responses.

• Participants were not informed that the injected material contained live
cancer cells.

• No approval by a review committee was sought

• Physicians responsible for patients' care had not been consulted

• Researchers were found guilty of fraud, deceit, and unprofessional conduct

22

© 2017 USP
 Int’l Ethical Guidelines for Biomedical
Research

• Following emergence of ethical breach on health research, guidelines

continued to be developed.

• Council for International Organizations of Medical Sciences (CIOMS)

in 1982 promulgated additional guideline, in collaboration with WHO,
revised in1993.

• This produced “International Ethical Guidelines for Biomedical

Research involving Human Subjects”

23

© 2017 USP
 Int’l Ethical Guidelines for Biomedical
Research

• The CIOMS Guidelines:

 Address problem of research in developing countries sponsored by external

agencies.

 Recognize the primacy of local concerns when evaluating research protocol

objectives.

 Provide specificrecommendations with respect to medical care for

participants and compensation in case of injury.

24

© 2017 USP
 Int’l Ethical Guidelines for Biomedical
Research

• Address information to be given, opportunity to ask questions, issues of

deception, undue influence, intimidation, documentation and continuing
consent as far as informed consent is concerned.

• Recognize possibility of not obtaining direct free informed consent always:

– E.g., use proxy consent for children, mentally disabled, and underprivileged
communities by parents, guardians or community leaders.

25

© 2017 USP
 Int’l Ethical Guidelines for Biomedical
Research

• Acknowledge inadequacy of informed consent alone to protect research

participants from abuse.

• Emphasis on need for an independent review.

26

© 2017 USP
 Int’l Ethical Guidelines for Biomedical
Research (cont.)

• Recognize limitation of international guidelines to be strictly uniform due

to cultural and legal variability:

– For example, different countries have different cultures and laws pertaining to
research directed toward termination of pregnancy and research involving
prisoners.

• Pitfall
 Do not suggest resolution for ethical dilemma in some areas though appreciates the
problem.
 This suggested the need for operational guidelines for ethic review committees

27

© 2017 USP
 Operational Guidelines for Ethics
Committees

• Operational Guidelines for Ethics Committees that Review Biomedical

Research were formulated by WHO/TDR in 2000 and cover:

 Role of ethics review committee

 Establishment of ethics review system
 Constitution of ethics committee
 Application and submission for ethics review
 Review process
 Decision-making and communicating
 Follow-up
 Documentation

28

© 2017 USP
Operational Guidelines for Ethics Committees

• Pitfall

 Cannot address specific problems EC can face, hence, the need for
national ethics review committee.

29

© 2017 USP
 Summary

• Many atrocities were committed in the name of research by the Nazi

government.

• These gave rise to development of ethical codes and guidelines for

biomedical research.

• The first was The Nuremburg Code.

• A number of different international ethical guidelines soon followed.

• Today, there are a variety of ethical guidelines.

30

© 2017 USP
 Acknowledgements

• Forum for Ethical Review

Committees in Asia and the
Western Pacific

31

© 2017 USP