Probing Ethics in Human Research

February 1, 2005
Stephen O. Sodeke

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-02-01-2005,

Perhaps a way forward is to refocus our efforts on a "culture of conscience," since our conscience often guides our actions.

Ample evidence suggests that the ethical problems of involving humans in scientific experimentation have a long history. The earlier codes and oath, which included affirmations to abstain from intentional wrongdoing and harm, especially from abusing the bodies of humans, bound or free, had their dissenters. Cornelius Celsus, a 1st century Roman physician and noted writer in medicine and human experimentation, once characterized the mindset of that era this way: "It is not cruel to inflict on a few criminals sufferings which may benefit multitudes of innocent people through all centuries."1

Stephen O. Sodeke

With such a spirit, and the atmosphere of brutal utilitarianism that it fostered, early experimenters with humans operated in an era of little guidance, with the vulnerable, the disenfranchised, and the powerless. One could conscientiously opine that issues of concern might include perceptions of 1) what constitutes cruelty, 2) whether criminality or one's lower status in life makes one less human, 3) experimentation with those identified as less than human, 4) what justifies experimentation with humans, and 5) what is ignorance, arrogance or faulty reasoning.

In the 19th century, many medical abuses of those enslaved in the United States were documented. Attorney Vernellia Randall observed that the "bold, occasionally brilliant, clinical feats" performed by American physicians of the 1800s occurred on blacks and the poor.2

Such egregious acts would suggest similar issues of concern as those of earlier centuries.

Enduring mindset

Could it be that the mindset of earlier centuries endured during the 20th century, the era of regulations, and beyond? After the Declaration of Helsinki was published, and even in the wake of the Kefauver-Harris Amendment

3

of 1962, Dr. Henry K. Beecher reported in 1966 on 22 studies that showed ethical lapses in their designs and informed consent.

4

Several images continually haunt us, including those of the infamous Tuskegee Study of Untreated Syphilis in the Male Negro, Macon County, Alabama (1932-1972); Protocol 126, Fred Hutchinson Cancer Center, 1981-1993; and the gene therapy trial of Jesse Gelsinger in 1999. Equally troubling are the 21st century cases of ethical lapses in clinical research.

5

Again, one could almost hear the reverberation of the same issues of concern identified for the 1st century.

Lapses persist in clinical research

Today, ethical lapses in clinical research have involved informed consent, parental consent, and assent. Also of concern have been conflicts of interest, mostly financial; increased litigations, inappropriate study designs, placebo use, equipoise, therapeutic misconceptions, underreporting of adverse events, and the neglect of the duty to warn. We have tried to curb excesses and flagrant disregard for human dignity with regulations: the Belmont Report's respect for persons, beneficence, and justice as the hallmarks of ethical principles; IRB oversight; compliance; inclusiveness and equitable selection of research participants, particularly vulnerable populations.

To be fair, investigators do try to comply with regulations, and most people will admit that we have made some progress. However, I would argue that slavish adherence to procedures required in regulations misses the point of protecting the rights and interests of human research participants. Regulations are necessary, and we will see more of them, not less. But they are insufficient to make moral progress in assuring protection if the ethical violations continue in the world of clinical trials.

Photo: Phot Disc Illustration: Paul A. Belci

What has changed? What has remained the same? Is there a way to move forward?

Through the ages, changes have been made from a period of no guidance to periods of some guidance, to the current periods of regulations, ethical theories, and principles. However, issues of concern have remained the same; they can be traced to the same root. Compliance may be a watchword in the 21st century, but human nature, the human spirit, and human conscience have not changed. Perhaps a way forward then is to refocus our efforts on a "culture of conscience," since our conscience often guides our actions.

Identifying unethical behavior

In an effort to move forward and make moral progress, we must identify and highlight unacceptable, demeaning, unethical actions toward the vulnerable. But we must not single out people as evil. As the United Nations Secretary General Kofi Annan once reminded us, "Evil labels action, not people." We must also pay due attention to human nature and the nature of ethical lapses. Dr. Marcia Angell, former editor-in-chief of the

New England Journal of Medicine

, has also reminded us that "ethical lapses are almost never cases of bad people, doing bad things, for no good reason. More often they are good people, doing bad things, for good reasons." We must believe in the resilience of the human spirit. Social entrepreneur Bill Shore writes of a ray of hope in his recent revolutionary, charming, and effective two books,

The Cathedral Within

and

The Light of Conscience

. He reminds us that "the human spirit has not changed regardless of changes in our circumstances. There is transforming power in solitary acts of conscience."

6-7

Culture of compliance

Some definitions, characterization, and connection might help to specify and elaborate on what I am suggesting. Here are some operating definitions: Culture has been defined as "the totality of socially transmitted behavioral patterns, art, belief, institutions, and all other products of human work and thought."

8

Compliance has been defined as "the act of complying with the wish, request, or demand from others; a disposition or tendency to yield to the will of others."

8

Conscience has been defined as "the awareness of a moral or ethical aspects to one's conduct together with the urge to prefer right to wrong."

8

A culture of compliance is characterized by control. It is power-driven, regulation bounded, reality-centered, has a punishment focus, is litigation rich, might promote distrust, might truncate potential, and has done some good. But a culture of conscience would be characterized by partnership and power-sharing. It would go beyond regulation, would be possibility-driven, would have a forgiveness, grace, and kindness focus, would capitalize on lessons learned, would engender trust, might be of the greatest potential, and might portray and encourage the highest good.

In the linkage paradigm for ethics of experimentation with humans that I am proposing, we will be engaged in connected reflection in a cycle of two cultures: a culture of compliance and a culture of conscience. One culture will not be in and of itself complete without the other. Some of us may have already reflected on these issues and made the necessary changes. We should applaud this category of people. For the rest of us, the change may be gradual and cyclical. But when we do change, we will be making moral progress in the world of clinical trials, and in the protection of human research participants.

References

1. C. Celsus,

On Medicine

, I, Proem 23, 1935, translated by W. G. Spencer, (Loeb Classics Library, 1992).

2. V.L. Randall, "Slavery, Segregation and Racism: Trusting the Health Care System Ain't Always Easy! An African American Perspective on Bioethics,"St. Louis University Public Law Rev., 15, 191-235 (1996).

3. K. Getz and D. Borfitz, Informed Consent: A Guide to the Risks and Benefits of Volun-teering for Clinical Trials (Thomson CenterWatch, Boston, MA, 2003).

4. H. Beecher, "Ethics and Clinical Research," New England Journal of Medicine, 274, 1354-1360 (1966).

5. Alliance for Human Research Protection, "Human Experiments: A Chronology of Human Research," compiled by V. Hassner Sharav, 2004, http://www.researchprotection.org/history/chronology.html

6. B. Shore, The Cathedral Within (Random House, New York, 2001).

7. B. Shore, The Light Of Conscience (Random House, New York, 2004).

8. The American Heritage College Dictionary, 1997.

Acknowledgment

The author would like to thank Dr. Leo T. Upchurch and Dr. Isaac Mwase, both of Tuskegee University, for their insightful comments during the development of the ideas expressed in this commentary.

Stephen O. Sodeke, PhD, MT(ASCP) is associate director, Tuskegee University National Center for Bioethics in Research and Health Care, Tuskegee, AL, 36088, email: sodeke1180@yahoo.com.

Related Content:

FDA