1. Historical backgrounds of WHY U.S. regulations cover biomedical and social behavior Melody Lin, Ph.D. Deputy Director, Office for Human Research Protections Director, International Activities Department of Health and Human Services Melody.Lin@hhs.gov Dec. 12, 2012

2. Objectives Historical cases of unethical research Historical cases of unethical research National Research Act National Research Act National Commission National Commission Biomedical Biomedical Behavioral Behavioral

3. Nuremberg 23 German doctors were charged with crimes against humanity 23 German doctors were charged with crimes against humanity experiments without subject consent experiments without subject consent

4. The Nuremberg Code (1947) Rules for "Permissible Medical Experiments" voluntary consent voluntary consent benefits outweigh risks benefits outweigh risks withdraw from participation withdraw from participation

5. Nuremberg Code Informed consent without coercion Informed consent without coercion Prior animal experimentation Prior animal experimentation Justify by anticipated scientific results Justify by anticipated scientific results Qualified scientists Qualified scientists Avoid physical and mental suffering Avoid physical and mental suffering No expectation of death or disabling injury No expectation of death or disabling injury

6. Did the Nuremberg Code Impact the behavior of American scientists who did research on humans? No

7. But, in America Willowbrook (1950s) Willowbrook (1950s) Mentally retarded children were deliberately injected with hepatitis virus to study its effects Jewish Chronic Disease Hospital (1960s) Live cancer cells were injected into 22 senile patients. Jewish Chronic Disease Hospital (1960s) Live cancer cells were injected into 22 senile patients. … with no benefit to patients, and no consent of kin.

8. The 18th World Medical Assembly (1964), in the Declaration of Helsinki Set forth additional recommendations to guide medical doctors in biomedical research involving human subjects Set forth additional recommendations to guide medical doctors in biomedical research involving human subjects

9. Beecher Article “Ethics and Clinical Research” Henry K. Beecher New Engl J Med 274 (1966):1354-60 22 published medical studies presenting risk to subjects without their knowledge or approval 22 published medical studies presenting risk to subjects without their knowledge or approval Published in some of the most prestigious journals and conducted at some of the most prestigious institutions Published in some of the most prestigious journals and conducted at some of the most prestigious institutions

10. Tuskegee Syphilis Study PHS conducted 1932-1972 PHS conducted 1932-1972 400 Black American Men 400 Black American Men Natural course of untreated syphilis Natural course of untreated syphilis Unknowing participants Unknowing participants No treatment when drugs were available No treatment when drugs were available

11. National Action 1973 - Kennedy Hearings. Tuskegee, etc., and ta search for ethical issues in social/behavioral research: 1973 - Kennedy Hearings. Tuskegee, etc., and ta search for ethical issues in social/behavioral research: Stanley Milgram’s Obedience Study Stanley Milgram’s Obedience Study Laud Humphreys’ Study of “tearoom trade” Laud Humphreys’ Study of “tearoom trade” 1974 - National Research Act established the National Commission for Protection of Human Subjects of Biomedical & Behavioral Research Required IRBs at institutions receiving HEW support for human subjects research.

12. The Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research Respect for persons BeneficenceJustice National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979

13. The Milgram Study 1961 Psychologist, Yale Univ.

14. The Milgram Study Experiment on obedience to authority figures Experiment on obedience to authority figures Study on the conflict between obedience toward authority and ones personal conscious Study on the conflict between obedience toward authority and ones personal conscious

15. E – Experimenter T – Teacher (Subject) L – Learner (Actor) (E) orders (T) to give what the subject believes are painful electric shocks to (L). The subjects (T) believed that for each wrong answer, the (L) was receiving actual shocks, but in reality there were no shocks. (L) set up a tape recorder integrated with the electro- shock generator, which played pre-recorded sounds for each shock level.

16. The Milgram Study Only the "teacher" is an actual subject, i.e. unaware about the actual setup Only the "teacher" is an actual subject, i.e. unaware about the actual setup The subject and the learner were told by the experimenter that they would be participating in an experiment helping his study of memory and learning in different situations The subject and the learner were told by the experimenter that they would be participating in an experiment helping his study of memory and learning in different situations

17. The Milgram Study: Results In the first set of experiments, 65 percent of the subjects administered the experiment's final massive 450-volt shock In the first set of experiments, 65 percent of the subjects administered the experiment's final massive 450-volt shock many were very uncomfortable doing so; many were very uncomfortable doing so; some said they would refund the money they were paid for participating in the experiment some said they would refund the money they were paid for participating in the experiment

18. Ethical Issues Respect for Persons: Stanley Milgram deceived his study's subjects (failure to disclose important aspects of study to allow a voluntary decision to participate) Respect for Persons: Stanley Milgram deceived his study's subjects (failure to disclose important aspects of study to allow a voluntary decision to participate) Beneficence: Subjects (T) were placed under more pressure than many believe was necessary to test the study hypothesis Beneficence: Subjects (T) were placed under more pressure than many believe was necessary to test the study hypothesis Respect for Persons: Subjects were coerced into remaining in study against their will Respect for Persons: Subjects were coerced into remaining in study against their will

19. Humphreys: Tearoom Trade Ph.D. dissertation (sexual) Deviance Sociologist, Wash. U. Laud Humphreys studied homosexual encounters in “tearooms” – public restrooms Laud Humphreys studied homosexual encounters in “tearooms” – public restrooms Homosexuals who engage in sex in tearooms like to have a third person present, someone they call a “Watch queen” Homosexuals who engage in sex in tearooms like to have a third person present, someone they call a “Watch queen”

20. Humphreys (cont’d) As a “Watch Queen” Humphreys made observations in order to do research As a “Watch Queen” Humphreys made observations in order to do research He wrote down the license plate numbers of the men and traced their home addresses He wrote down the license plate numbers of the men and traced their home addresses A year later, he visited them at home, and conducted a follow-up survey A year later, he visited them at home, and conducted a follow-up survey

21. Humphreys (cont’d) 38% of men having tearoom sex were married 38% of men having tearoom sex were married Most identified themselves as heterosexual Most identified themselves as heterosexual It turns out, most of these men were frustrated their wives It turns out, most of these men were frustrated their wives

22. Ethical issues The researcher acted as a lookout, alerting participants engaged in an illegal activity The researcher acted as a lookout, alerting participants engaged in an illegal activity Unknown to the subjects, the researcher noted the license numbers of their cars Unknown to the subjects, the researcher noted the license numbers of their cars License numbers were traced to reveal the name and address of each car owner License numbers were traced to reveal the name and address of each car owner Traced subjects were interviewed as part of a larger public health survey (true purpose of their participation not revealed) Traced subjects were interviewed as part of a larger public health survey (true purpose of their participation not revealed)

23. Ethical Problems Aiding in crime Aiding in crime Since the Missouri law forbade homosexual activity Humphreys was assisting in a crime by acting as a lookout (i.e., the “watch queen”) Since the Missouri law forbade homosexual activity Humphreys was assisting in a crime by acting as a lookout (i.e., the “watch queen”)

24. Ethical Problems (cont’d) Informed consent Informed consent Did not seek informed consent Did not seek informed consent Likely they would have refused participation Likely they would have refused participation Endangering subjects Endangering subjects Took some care here: the names in safety deposit box in another state, refusing to tell police what he was doing Took some care here: the names in safety deposit box in another state, refusing to tell police what he was doing What if name had been released? What if name had been released? Would the publication lead to a “crack down”? Would the publication lead to a “crack down”?

25. Laud Humpheys’ Postscript Because of his study, the sociology department lost federal funding, many senior faculty left Because of his study, the sociology department lost federal funding, many senior faculty left Sociology program later eliminated Sociology program later eliminated Laud Humphreys (1930-1988) received his Ph.D. Career SUNY (Albany, NY) Laud Humphreys (1930-1988) received his Ph.D. Career SUNY (Albany, NY)

26. Summary National Research Act. 1974 National Research Act. 1974 Federal response to harm arising from biomedical and behavioral experimentations Federal response to harm arising from biomedical and behavioral experimentations National commission for the protection of human subjects of biomedical and behavioral research National commission for the protection of human subjects of biomedical and behavioral research National commission outlined ethical principals upon which the ethics of research study are evaluated in the U.S. National commission outlined ethical principals upon which the ethics of research study are evaluated in the U.S.