Historical Cases of Unethical Research

We’ve Come a Long Way,But Not Quite Far Enough

Tuskegee Syphilis Study• In 1932, the Tuskegee Syphilis Study was a 40-year

project administered by the US Public Health Service in Macon County, Alabama.

• The American Government promised 400 men free treatment for bad blood which had become an epidemic in the county. The treatment was never given to the men and was in fact withheld.

• The study sample was made up of poor African American men who were told that they had "bad blood".

• These men did not receive standard treatment for syphilis even when penicillin was available later during the study.

• The men in the study were not informed of the research design and it's risks to them.

Tuskegee Syphilis Study

• Symbolized the medical misconduct and blatant disregard for human rights that takes place in the name of science.

• The investigators were government physicians, respected men of science, who published their reports of the study in medical journals.

• The burden of medical experimentation has historically been borne by those least able to protect themselves.

Tuskegee Syphilis Study

Tuskegee Syphilis Study• The government doctors who participated in this

study failed to obtain informed consent from the subjects.

• The study's unethical features did not come to light until 1972 when Jean Heller broke the story.

• By this time, over one hundred of the infected men died and others suffered from serious syphilis related conditions. Wives and children had been infected.

Tuskegee Syphilis Study

• When a class action civil suit of $1.8 billion was filed against those who were involved in the study.

• The case never came to trial. • Each participant only received $37,500 in

damages, and the heirs of the deceased received $15,000.

Research abuse by Nazi doctors during World War II

• 23 German physicians practiced unethical medical experiments on Jews, gypsies, and political prisoners

• Most of the subjects of these experiments died or were permanently crippled as a result.

Nazi Experimentation• Experiments aimed at facilitating the

survival of Axis military personnel–Used a low-pressure chamber to determine the

maximum altitude from which crews of damaged aircraft could parachute to safety. – Freezing experiments using prisoners to find an

effective treatment for hypothermia. – Testing of various methods of making seawater

potable

Nazi Experimentation• Developing and testing pharmaceuticals and

treatment methods for injuries and illnesses– Testing vaccines and sera for the prevention and

treatment of contagious diseases, including malaria, typhus, tuberculosis, typhoid fever, yellow fever, and infectious hepatitis. –Bone-grafting experiments– Subjected prisoners to phosgene and mustard

gas in order to test possible antidotes.

Nazi Experimentation• Experiments to advance the racial and

ideological tenets of the Nazi worldview–Medical experiments on twins. – Studies to determine how different "races"

withstood various contagious diseases. –Research to establish "Jewish racial inferiority." –Mass sterilization experiments.

Nazi Experimentation

• In 1947, Nuremberg Code and other international codes of ethics written to protect research participants. –Under this code, the physicians were convicted

for crimes against humanity. – This also led to standards in research requiring

that subjects participate voluntarily and are informed of the risks of the research.

Willowbrook Hepatitis Study• From 1963 to 1966, the Willowbrook Study

involved a group of children diagnosed with mental retardation, who lived at the Willowbrook State Hospital in Staten Island, New York.

• These innocent children were deliberately infected with the hepatitis virus

• The study's purpose was to study the history of the disease when left untreated and later to assess the effects of gamma globulin as a therapeutic intervention.

• This study involved the deliberate infection of the children and the attempts to convince the parents to enroll them in the study in exchange for admission to the hospital (which was deliberately short of space).

Willowbrook Hepatitis Study

• New York Senator Robert Kennedy and a television crew visit Willowbrook State school in Staten Island NY. • He stated that the residents of these

institutions were “denied access to education and are deprived of their civil liberties.”

• Later that same year, he addressed a joint session of the NYS Legislature on the “dehumanizing conditions” of the State’s institutions

Project Shipboard Hazard and Defense (SHAD)1963 to 1969

• The U.S. Army performed tests which involved spraying several U.S. ships with various biological and chemical warfare agents, while thousands of U.S. military personnel were aboard the ships. • The personnel were not notified of the tests, and

were not given any protective clothing. • Chemicals tested on the U.S. military personnel

included the nerve gases VX and Sarin, toxic chemicals, and a variety of biological agents.

In 1979, the federal government developed regulations of ethical principals and standards that are contained in the Belmont Report.

• Ethical principals upon which a research study is evaluated in the United States.

• Moral basis of the present US Federal regulations of human subject research conduct with Federal funds from the majority of Federal agencies

• Forerunner of Institutional Review Board.

Three Guiding Principles of Ethical Research

• Respect for Individuals• Beneficence• Justice

Respect for Individuals• Individuals act as autonomous agents• Individuals who are not capable of acting as

autonomous agents are entitled to special protections– Minors– Mentally incapacitated persons– Prisoners

Beneficence

• Guided by two basic principles:–Do no harm–Maximize benefits and minimize potential harms

• Risks should be in proportion to potential benefits

• Research design should ensure valid results

Justice

• Benefits and risks of human research should be fairly distributed• Social vs. individual justice

Current Regulations• Regulations to protect public welfare,

human subjects and establish the IRB. –1981–Department of Health and Human Services

(DHHS) and the Food and Drug Administration (FDA) issued regulations based on the Belmont Report.

Federal Policy for the Protection of Human Subjects, or "Common Rule." –1991–DHHS regulations were formally adopted by

more than a dozen other Departments and Agencies that conduct or fund research involving human subjects

Current Regulations

Main elements of the Common Rule

Requirements for: • assuring compliance by research institutions; • researchers obtaining and documenting informed

consent; • Institutional Review Board (IRB) membership,

function, operations, review of research, and record keeping.

• additional protections for certain vulnerable research subjects-- pregnant women, prisoners, and children

The role of the IRB is to protect the rights and welfare of individual research subjects.

The IRB assures that:1. risk to subjects are minimized2. risk to subjects are reasonable in relation to anticipated benefits,3. selection of subjects is equitable, i.e. fair4. informed consent is sought form each subject or his/her legally authorized representative,5. informed consent is appropriately documented,6. when appropriate, the research plan makes provisions for monitoring data collection,7. privacy and confidentiality of research subjects is appropriately protected, and8. when some or all of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards have been included.

In 1987 the US Supreme Court ruled in United States v. Stanley, 483 U.S. 669, that a U.S. serviceman who was given LSD without his consent, as part of military experiments, could not sue the U.S. Army for damages.

Dissenting the verdict in U.S. v. Stanley, Justice Sandra Day O'Connor stated:

No judicially crafted rule should insulate from liability the involuntary and unknowing human experimentation alleged to have occurred in this case. Indeed, as Justice Brennan observes, the United States played an instrumental role in the criminal prosecution of Nazi officials who experimented with human subjects during the Second World War, and the standards that the Nuremberg Military Tribunals developed to judge the behavior of the defendants stated that the 'voluntary consent of the human subject is absolutely essential ... to satisfy moral, ethical, and legal concepts.' If this principle is violated, the very least that society can do is to see that the victims are compensated, as best they can be, by the perpetrators.

Sandra Day O’Connor

So, now what?

From 1988 to 2008, the number of overseas clinical trials for drugs intended for American consumption increased by 2,000%, to approximately 6,500 trials.

These trials are often conducted in areas with large numbers of poor and illiterate people who grant their consent by signing an "X" or making a thumb print on a form.

On January 15, 1994, President Bill Clinton formed the Advisory Committee on Human Radiation Experiments (ACHRE).

Created to investigate and report the use of human beings as test subjects in experiments involving the effects of ionizing radiation in federally funded research.

So, it’s all better now, right?

In August 2010, the U.S. weapons manufacturer Raytheon announced that it had partnered with a jail in Castaic, California in order to use prisoners as test subjects for a new non-lethal weapon system that "fires an invisible heat beam capable of causing unbearable pain.”

What is Ethics in Research & Why is it Important?

• “Misconduct probably results from environmental and individual causes, i.e. when people who are morally weak, ignorant, or insensitive are placed in stressful or imperfect environments.” (Resnik, 2012, p8)

Considering the analogies discussed…

• And reflecting on the quote from the Ethics paper– Write a 1-2 page story about a researcher faced with an

ethical dilemma who chooses to behave in an unethical manner. • What did he/she do?• What happened as a result?• How did the researcher feel before, during, and after the

unethical act(s)?