Morality and Medicine: A Historical Perspective

1. MORALITY AND MEDICINEAN HISTORICAL PERSPECTIVE GBI July 26, 2018 Cheryl L. Kunis, M.D. M.S. Clinical Professor of Medicine Columbia University

2. Morality & Ethical Behavior • These are the principles that guide our lives • A subject that philosophers have pondered for years • Morality stems from childhood experiences • Determined by society • A group decision • Monitored by the government/legal system

3. Morality & Ethical Behavior • One can do good accidentally, but one can not be moral accidentally • To be human means to use reason/to be rational in overcoming one’s more aggressive instincts, to have sympathy, empathy, to understand the concept & advantage of cooperation • A new role in medicine and research with the biotechnology revolution

4. “Morals and Conduct”in “Human Nature and Conduct” by John Dewey • Morals is the most humane of all subjects. It is that which is closest to human nature.…Since it directly concerns human nature, everything that can be known of the human mind and body in physiology, medicine, anthropology and psychology is pertinent to moral inquiry….Moral science is not something with a separate province. It is physical, biological and historic knowledge placed in a human context where it will illuminate and guide the activities of man….The path of truth is narrow…. It is only too easy to wander beyond the course….

6. The Egyptian Book of the Dead This was the 1st historical reference that one’s moral character could influence one’s fate after death. There was a hall within the Netherworld where the dead underwent judgment by the gods. The deceased had to answer questions to convince the gods that he/she had lived according to the principles of Maat, the Egyptian concept of order, right and truth. This determined whether one was able to enter the after-life.

7. The Oath of Hippocrates (5th Century BCE) “I will apply dietic measures for the benefit of the sick according to my ability and judgment; I will keep them from harm and injustice. I will neither give a deadly drug to anybody if asked for it, nor will I make a suggestion to this effect. Similarly I will not give to a woman an abortive remedy. In purity and holiness I will guard my life and my art. I will not use the knife, not even on sufferers from stone, but will withdraw in favor of such men as are engaged in this work. Whatever houses I may visit, I will come for the benefit of the sick, remaining free of all intentional injustice, of all mischief and in particular of sexual relations with both female and male persons, be they free or slaves.

8. THE DOCTOR (Fildes, Tate Britain) I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon's knife or the chemist's drug (Hippocrates)

10. Professor Claude Bernard(1813-1878)

11. Professor Claude Bernard(1813-1878) • “The principle of medical and surgical morality consists in never performing on man an experiment which might be harmful to him to any extent, even though the result might be highly advantageous to science, i.e. the health of others”. (1865) • Ardent proponent of vivisection: “The physiologist is no ordinary man…possessed and absorbed by a scientific idea…he does not hear the animals’ cries of pain…he is blind to the blood that flows…..he sees nothing but his idea”……

12. The Eugenics MovementSir Francis Galton(1822-1911)

13. The Holocaust: Auschwitz

14. Nazi Doctor Experimentation

15. The Nuremberg Code • Informed consent is absolutely essential. • Qualified researchers use appropriate research designs. • Favorable risk/benefit ratio. • Participants must be free to stop at any time. • The code does not address clinical research in patients with illness.

16. Dr. T. Clark Nurse Rivers THE TUSKEGEE SYPHILIS TRIAL USPHS (1932-1972)

17. SPECIAL ARTICLE Ethics and Clinical ResearchHenry K. Beecher, M.D.†N ENGL J MED 1966; 274:1354-1360June 16, 1966

18. National Research Act1974 • Response to the Tuskegee Syphilis Study. • Created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. • To identify basic ethical principles for conduct of human research • To develop just and ethical guidelines

19. The New Medical Ethics of the 20th Century Ethical conduct becomes a crucial issue in medicine (1) Inhumane treatment had become public knowledge (2) The 1960’s: Unique period of social and political change (3) Technology led to new medical dilemmas The Birth of Bioethics

20. The 4 Principles of Bioethics • Autonomy**** • Respect for persons, informed consent, the incompetent patient must be protected • Beneficence • Non-maleficence • Justice • Autonomy replaces paternalism**** • The President’s Commission on Bioethics

21. Informed Consent • The “cornerstone” of autonomy • The patient must be fully informed to understand the purpose, the procedures, and the benefit/risk ratio in order to make an “informed decision” • Are the concepts ones that the patient/study participant can truly understand? • If not, is informed consent truly informed? • Is informed consent solely for the well being of the patient?

22. Informed Consent • Consent forms are too long, complicated and burdensome for medical legal reasons • Protects the institution more than the patient • Final Conclusion: Informed Consent is worthwhile so that the physician/medical researcher respects the subject as a person, and not just as a patient.

23. The Kolff Rotating Drum(1943)

24. Ingredients used to build the theKolff dialysis machine

25. “There is a growing awareness that something new has been added to Claude Bernard” (1813-1878)

26. “Now Homeostasis applies not only to the organism but to artificial organs and to the peculiar relationship that must develop when man and machine, when a person and a thing, are coupled for survival” George Schreiner, 1959

27. Clyde Shields(Dialysis:1960-1971)The Northwest Kidney Center, Seattle

29. There was nothing more precious than this boy’s contribution to how medical research is conductedAN UNSUNG HERO ON THE BATTLEFIELD JESSE GELSINGER

30. Protecting Research Subjects The Johns Hopkins Crisis (2001) Death of a healthy 24 year old laboratory employee enrolled as a control subject in one of her lab’s research projects Multiple violations of research had taken place and the medical center was ordered to immediately shut down all research

31. Dr. Edward D. Miller, Dean at Johns Hopkins • There is an inherent trade-off between the potential importance of the information that may be gained and the potential risk to the patient. • At a certain point some patient is going to die in clinical trials, there is no question about it • The challenge is to do everything possible to ensure the safety of research subjects and to make the risk as small as possible • The alternative is not to do any clinical investigation, the status quo, and still have children on ventilators after polio

32. Dr. Edward D. Miller, Dean at Johns Hopkins • We find it difficult to understand why a relatively new agency would take these draconian measures in an institution that has cared for thousands of people in clinical trials for over one hundred years • We have only had one death in all of these years in a healthy human volunteer

33. Research Violations at Johns Hopkins • Consent form led participants to believe that the drug was safe and FDA approved • The drug was not manufactured for patient use and was being given by an unorthodox route • An IND from the FDA was not obtained • The researcher was ill informed of drug toxicity • “Illegitimate Control” (Coercion: participant was an employee in the lab: acts that undermine voluntariness invalidate consent) • The researcher did not report an adverse event for patient # 1

34. Research Violations at Johns Hopkins • Patient # 2 should not have received the medication until patient # 1’s symptoms had completely resolved &/or the etiology of the symptoms was determined • The PI did not take full responsibility for his errors in judgment and for not following an ethical protocol • The Dean of the University publicly made arrogant excuses for the errors made • The IRB was inadequate and not doing their job

35. Research Misconduct makes News Dr. Hwang Woo-suk Korean researcher who falsely claimed that he had created human embryonic stem cells via cloning (2006)

36. Protecting the Integrity of Science The meaning of data • The purpose of science is to generate new knowledge from new data • New data needs interpretation, sorting (eliminate “outliers”) • Scientists are aware that they can “slant the data” • When do uncorrected errors in data actually become falsifications?

37. Data Torturing • If you torture your data long enough, it will tell you what you want • i.e. if data is manipulated in enough different ways, it can prove whatever the investigator desires • When this manipulation goes beyond a reasonable interpretation of the facts, it is “DATA TORTURING” • Data torturing may disseminate incorrect information to the scientific community, to patients and to the public

38. Data Torturing • (1) Opportunistic Data Torturing: The researcher desperately tries to find an association within his data and then devises a biologically acceptable hypothesis to fit the association • (2) Procrustean Data Torturing: the researcher makes the data fit a predetermined hypothesis • How to Lie with Statistics, 1954

39. PROCRUSTES “He who stretches” ONE SIZE FITS ALL

40. Privacy • An important aspect of patient care & research • “To be left alone” • A “human right” • Despite de-identification of data in studies, many believe that privacy can not be maintained in the digital age • The media is tracking all of our decisions and companies are marketing this data • The public is nervous about this loss of privacy

41. You have zero privacy anyway………Get over it

42. The Havasupai Diabetes Study • A small tribe of Native Americans living at the base of the Grand Canyon • High incidence of diabetes and severe vascular complications at a young age • Tribal leaders approached Arizona State University in an attempt to better understand and prevent diabetes and its complications • Blood samples were taken and stored

43. The Havasupai Indian Study • The consent form: “to study the causes of behavioral/medical disorders” • The Havasupai were under the impression that their biological samples would only be used for diabetes research • Their blood was used for a number of studies other than for diabetes • They were particularly offended by the anthropological study which claimed that they had migrated across the Bering Strait

44. Indian Tribe Wins Fight to Limit Research of Its DNA (The New York Times, April 21, 2010)

45. What does the Havasupai Study teach us? • Consent form must be precise • The 1st study to demonstrate that ethical behavior is important for epidemiologic &/or genetic research which was previously not thought to produce harm • Research can not be done on subjects or their stored biological specimens without their specific consent • Respect for one’s culture is mandatory • Privacy must be respected • Inconvenient Truths may be discovered • Indigent or uneducated populations need to be protected in research • 1st lawsuit which involved genetic biobanking & set a legal precedent for use of stored biological specimens

46. Research using Biobanked Specimens New ethical dilemmas have arisen What kind of consent is needed to use biobanked specimens? What if the patient has died? Inconvenient Truths? How much do we want to know or not know?

47. New Ethical Questions Raised by Big Data • Participant Selection • availability of online data is a tempting target for research • demographic characteristics vary • Invasiveness • Big Data often contain more information than necessary • this may compromise anonymity • Informed Consent (cornerstone of research ethics) • often proceeds without consent • Privacy/Anonymity • Big Data is less likely to disappear • What is anonymous today may become personally identifiable tomorrow

48. Experimental evidence of massive-scale emotional contagion through social networksJuly 17, 2014

49. Religion in Medical Ethics • Religion played little role in medical ethics until the Bioethics Revolution • The principles of bioethics requires that religious beliefs be respected, even if it results in the untimely death of the patient • The IOM, citing theologians: death is part of the human condition and prolonging life with advanced technology may result in “grotesque and fragmented existences” with no potential for human interaction Clinical Practice Guidelines: Directions for a New Program, Institute of Medicine, 1990

50. Religion and the PVS • Does the public perceive differences in the sanctity of life by the type of altered state of cognition? • Does religion play a role in the perception of altered states of consciousness? • Recent experiments involving people with diverse backgrounds demonstrated that lay people considered PVS “more dead than dead” • The more religious, the greater the belief that early death was better than remaining in a PVS Gray, etal. More dead than dead: Perceptions of persons in the persistent vegetative state. Cognition 121:275-280, 2011