Through the Looking Glass:

Reflections of a Research Ethicistor

The Collapse of Science and Ethics?

Michael Goodyear

Department of Medicine,Queen Elizabeth II Health Sciences Centre,

Dalhousie University, Halifax,Nova Scotia, Canada

MSMR Waltham MA, June 2006

Alice was sitting curled up in a corner of the great arm-chair, half talking to herself and half asleep

Learning Objectives

• I: How Did We Get Here From There?

• II: Where are We Now?

• III: Lessons from TGN1412

• IV: Moving Forward

Summary

“The aim of science is not to open a door to infinite wisdom but to set a limit to infinite error”Brecht B. The Life of Galileo (Leben des Galilei) 1943

Bertolt Brecht (1898 –1956)

Part I

How Did We Get Here From There?

We All Know Where We Have Come From

Or Do We?

History

• Human experimentation since time immemorial– Generally more vulnerable populations

• Prisoners, slaves, patients

History

• Thomas Percival (1740-1804) Medical Ethics: a Code of Institutes and Precepts Adapted to the Professional Conduct of Physicians and SurgeonsRussell, London 1803

Adopted by AMA 1847, modified many times

History

• Claude Bernard (1813-1878)

– Must have potential benefit

– Prisoners not considered human

History

• William Osler (1849-1918)

– Consent

– Animal experimentation

• George Bernard Shaw (1856-1950)

– “Human Guinea Pigs” (1913)*

*Disclaimer: No Guinea Pigs were harmed in this production

History

• Germany– Prussian regulations 1900– Third Reich 1931

Nürnberg

Nuremberg CodeNuremberg Code 19471947

Trials of war criminals before the Nuremberg military tribunals under Control Council Law, No 10, Vol 2. Washington DC: US Government Printing Office, 1949: 181.

Nuremberg Code 1947

1. Voluntary Consent Essential2. Must Yield Valid Results3. Based on Animal Experiments4. Avoid Physical and Mental Suffering5. Avoid Injury6. Risk Proportional to Benefit7. Subjects Must be Protected8. Qualified Investigators9. Voluntary Withdrawal10. Must be Terminated if Necessary

Top Secret

Nuremberg Code 1947

3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the experiment.

(1)The voluntary consent of the person on whom the experiment is to be performed must be obtained

(2)The experiment must be performed under proper medical protection and management.

(3)(3)The danger of each experiment must be The danger of each experiment must be previously investigated by previously investigated by animal animal experimentationexperimentation

American Medical AssociationJudiciary Council

December 10th, 1946

David Rothman PhDDirector, Center for the Study of Society and MedicineColumbia College of Physicians and Surgeons

Strangers at the Bedside: A history of how law and bioethicstransformed medical decision makingNY Basic Books 1991

“Neither the horrors described at the Nuremberg trial nor the ethical principles that emerged from it had a significant impact on the American research establishment” because they did not seem “directly relevant to the American Scene”

Rothman p. 62

LF Ross

“To most Americans, however, Nuremberg addressed madness, not medicine”

Shapiro HT.Waggoner Lecture, U MichiganDec 5 2001Ethical Considerations in Research on Human Subjects:A Time for Change…Again

Nürnberg, Germany

Tuskegee, Alabama

Tuskegee, AlabamaTuskegee, Alabama(1932 – 1972)(1932 – 1972)

RIPRIP

“I don’t know what they used us for. I ain’t never understood the study”

1965

Are humans used as guinea pigs not told?

(1904-1976)

“What seem to be breaches of ethical conduct in experimentation are by no means rare, but are almost, one fears, universal”

“No physician is justified in placing science or the public welfare first and his obligation to the individual, who is his patient or subject, second”

“No doctor, however great his capacity or original his ideas, has the right to choose martyrs for science or for the general good” Maurice Pappworth

Pappworth M.H. Human Guinea Pigs Penguin 1967, p.27

L Swartz

The Dark Side

• Willowbrook Hepatitis Study• Jewish Hospital Cancer Study• Tearoom Trade Study• Wichita Jury Study• Milgram Obedience Study• San Antonio Contraceptive Study• Radiation Studies• etc…………..

…and the Light

Belmont Report1979

Ethical Principles and Guidelines for the Protection of Human Subjects of Research

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

April 18, 1979

So We Fixed it?

Right?

Advisory Committee on Human Radiation Experiments (1994-5)

Human Radiation ExperimentsAssociated with the

U.S. Department of Energyand Its Predecessors

(1944 – 1974)

X-Files?

Unfortunately, however, the government's conduct with respect to some research performed in the past has left a legacy of distrust

1.

We did find evidence of some serious problems in the conduct …of human research today

We realize, however, that regulations and policies are no guarantee of ethical conduct

2.

It is essential that the research community come to increasingly value the ethics of research involving human subjects as central to the scientific enterprise

The revision of regulations that govern human research (and) professional ethics are necessary, but are not sufficient, means to needed reform. Of at least equal import is the development of a more common understanding among the public of research involving human subjects

3.

Some of what is regrettable about the past happened… because we

as citizens let it happen

Let the lessons of history remind us all that the best safeguard for the future is an informed and active citizenry

4.