The Public Health Service Syphilis Study (1932-1972)

One of the seminal events in the development of the current regulatory environment was the Public Health Service (PHS) Syphilis Study (1932 - 1972), frequently referred to as the "Tuskeegee Syphilis Study" [see "Bad Blood: The Tuskegee Syphilis Experiment", Revised Edition by James H. Jones] . Initiated and funded by the PHS, this study was designed as a natural study of the course of syphilis in African-Americans. At the time the study began there was no known safe and effective treatment. Hundreds of men who did not know they had syphilis and hundreds of men without syphilis (serving as controls) were enrolled into the study. The men were recruited without their fully informed consent. They were deliberately misinformed about the need for some of the procedures. For example, spinal taps were described as necessary and special "free treatment" for "bad" blood.

More importantly, even after penicillin was found to be a safe and effective treatment for syphilis in the 1940s, the men with syphilis were denied antibiotics. In addition, the researchers continued to protect the status of the study as a "natural history." To prevent the subjects from being treated by the military or by local physicians, the investigators arranged with the local draft board to prevent the men from being drafted, arranged with local physicians to withhold treatment, and told the men that if they volunteered for the military, they would no longer receive financial compensation for taking part in the study. The study continued to track these men sporadically until 1972 when the first public accounts of the study appeared in the national press. Not providing penicillin once it was deemed safe and effective may have been responsible for 28 deaths, 100 cases of disability, and 19 cases of congenital syphilis. [Levine]

Ethical problems: lack of informed consent, deception, withholding information, withholding available treatment, putting men and their families at risk, exploitation of a vulnerable group of subjects who would not benefit from participation.

More Recent Events

Death of a Normal Volunteer

On March 31, 1996, a 19-year-old Asian -American student at the University of Rochester responded to an advertisement for study subjects to undergo bronchoscopy for the harvest of alveolar macrophages. The bronchoscopy was difficult and required numerous doses of topical lidocaine. The investigators repeatedly asked the subject if she wanted to continue and the subject nodded her head "yes." The study was completed, but the subject returned to the hospital in cardiac arrest from an overdose of lidocaine and died April 2, 1996. An investigation into this death revealed that the protocol did not specify the number of lidocaine doses, that the doses were not documented, that the subject was not observed after the bronchoscopy, and that the concentrations of lidocaine were increased without IRB approval.

Ethical problems:Exploitation of a vulnerable population (student volunteers), inadequate informed consent

Death on Gene Transfer Trial

In the fall of 1999, 18-year-old Jesse Gelsinger died as a result of his participation in a gene transfer trial. Jesse had a rare metabolic disorder that was being controlled by medication and a strict diet. Shortly after the gene transfer attempt Jesse experienced multiple organ failure and subsequently died. This case catapulted gene transfer research into the national news. Serious concerns related to conflict of interest, data safety monitoring, and informed consent made the Gelsinger case a contemporary illustration of continued doubts about the ethical integrity of research with human subjects.

Ethical problems:Institutional and researcher conflict of interest, inadequate informed consent

Wichita Jury Case (1953)

In this study researchers tape-recorded jurors' private deliberations in six courtroom trials to measure the influence that attorney comments have on subsequent jury decision making. The judge and attorneys knew the research was being conducted, but the jurors did not, so as not to bias their behavior. The tapes were played at a law conference and the study was reported in a local newspaper. The resulting concern that the possibility of future taping could have a repressive effect on future juror deliberations resulted in a 1956 federal law banning all recording of jury proceedings.

Ethical problems: Compromising the integrity of important social institutions, lack of informed consent, invasion of privacy.

Milgram's "Obedience to Authority Study" (1963)

The purpose of this study was to learn more about how humans respond when given instructions from people in positions of authority. The researchers informed study volunteers that the purpose of the research was to study learning and memory. Each subject was told to teach a "student" and to punish the students' errors by administering increasing levels of electric shock. The "students" were confederates of the researcher and were never actually harmed. The "students" pretended to be poor learners. They mimicked pain and even unconsciousness as the subjects increased the levels of electric shock. Sixty-three percent of the subjects administered what they thought were lethal shocks; some did so even after the "student" claimed to have heart disease. Some of the subjects, after being "debriefed" from the study, experienced serious emotional crises.

Ethical Problems: Deception, unanticipated psychological harms.

Allen's “Nazi Seizure of Power Study” (1965)

In his study “The Nazi Seizure of Power; the Experience of a Single German Town, 1922-1945,”,first published in 1965, William Sheridan Allen interviewed residents of a town in Germany about their lives during Hitler's rise to power. He made a commitment of confidentiality with regard to the names of his informants and of the town and used pseudonyms for the town and individuals when writing a book based on the interviews. After the book was subsequently translated into German, based on the information provided and additional investigative journalism, a German magazine was able to determine the real name of the town and the identities of many of Allen's narrators and published the information in an article.

Ethical Problems: Failure to maintain adequate confidentiality to protect against deductive disclosure of identity by others with additional information.

Humphreys' "Tea Room Trade" (1970)

In this study the researcher observed homosexual practices in public restrooms. The researcher went undercover as a homosexual and gained the confidence of the men by acting as a "look out." The researcher identified 100 active subjects by tracing their car license numbers. A year after he completed the observational portion of his study, the researcher disguised his appearance and in the communities where he knew the subjects lived interviewed some of the "tearoom regulars" in their own homes. He used a social health survey collecting data about their sexual orientation and marital status. Interviews were sometimes conducted in the presence of wives and children. At no time did he tell them anything about the relationship of the interview to the prior observational work.

Though the publication of the book based on the dissertation may have been helpful in dispelling some stereotypes, the report had sufficient detail that the identities of some of the participants were obvious to them and their families.

Ethical problems: Invasion of privacy, use of a vulnerable population, lack of informed consent, failure to protect against deductive disclosure of identity. [ Warwick]

Zimbardo "Simulated Prison" (1973)

This landmark psychological study of the human response to captivity and, in particular, prison life, involved assigning roles to normal male student volunteers to create groups of "prisoners" and "guards." The research became so intense, as physical and psychological abuse of "prisoners" by "guards" escalated, that several of the subjects experienced distress less than 36 hours after the study began. Dr. Philip Zimbardo, the researcher, did not stop the experiment/simulation until six days had passed. See Dr. Zimbardo's web site for more details on this study.

Ethical problems: Harm to subjects, lack of neutrality of researcher.

Restaurant Letter Study (2001)

It is important to note that not all the events that raise concerns about research ethics in both biomedical and social and behavioral research occurred before the 1974 congressional hearings. In 2001, a faculty member from the business school of a major university designed a study to see how restaurants would respond to complaints from putative customers. As part of the project, the researcher sent letters to restaurants falsely claiming that he and/or his wife had suffered food poisoning that ruined their anniversary celebration. The letters disclaimed any intention of contacting regulatory agencies and stated that the only intent was to convey to the owner what had occurred "in anticipation that you will respond accordingly." Restaurant owners were understandably upset and some employees lost their jobs before it was revealed that the letter was a hoax. The researcher later admitted the falsehood in a letter of apology to each restaurant. The study had not been submitted to an IRB for review. An investigation by the Federal Office for Human Research Protections (OHRP) followed. In addition, the restaurants filed a lawsuit against the university.

Ethical problems: Deception, lack of informed consent, infliction of emotional distress.