Transcript Human Subject Experimentation

Human Subject Experimentation
The Nazis
Lessons for Contemporary Research
The Role of the Physician in Society
Martin Donohoe
“When a doctor [goes] wrong, he is the first
of criminals. He has nerve and he has
knowledge.”
- Sherlock Holmes to Dr. Watson, Arthur
Conan Doyle
Nazi Medicine
• Guiding philosophy = Hegelian (rational
utility)
• Social Darwinism - parallels in American
and British Eugenics Movement
– medical journals relatively silent
• Ethics reduces morality to efficiency,
economics, and aesthetics
Nazi Medicine
• An arm of state policy
• Focus on racial purity
– from eugenic sterilization (370,000)
– to involuntary euthanasia (70,000)
– to large-scale genocide (over 6 million)
Nazi Medicine
• Individual worth stated in economic terms;
propaganda re obligations to the state
– “I Accuse”
– “Mathematics in the Service of Political
Education”
Nazi Medicine
• Doctoring the nation more important than
doctoring individuals - Nazism as “applied
biology” (Rudolph Hess)
• Focus on preventive medicine and public health:
anti-tobacco and anti-alcohol campaigns,
environmental toxins, organic farming
to improve Aryan stock
• Nazi soldiers given anabolic steroids to increase
aggresiveness
Nazi Physicians
• 52,000 physicians
• National Socialist Party Members
• Jews ostracized; replaced by young Aryans
– today 0.2% of German physicians are Jews, c/w
17% pre-Nazis
– 5% of non-Aryans committed suicide; 25%
murdered
Nazi Physicians
• Economic hard times, physicians salaries
rise, academic perks
• Blutkitt (“blood cement”)
• Rare resistance
– Catholics
– Marxists
– Dutch
Nazi “Physician-Researchers”
(Torturers)
• Dr. Sigmund Rascher - coagulation/amputation
studies; hypothermia experiments
• Dr. Karl Gebhart: heteroplastic transplantation
experiments
– c.f. Stalin’s attempts to create interspecies (halfmen/half-apes) “super-warriors”
• Drs. Karl Clausberg and Viktor Brack: Xirradiation/sterilization
Nazi “Physician-Researchers”
• Drs. Joachim Mrugowsky, Erwin Ding-Schuler,
and Waldemar Hoven: IV phenol and gasoline
executions
• Dr. Friedrich Wegener (“Wegener’s
Granulomatosis”): German pathologist, Nazi party
member, autopsied a prisoner with oxygen
injected into his bloodstream in an embolism
study; may have participated in experiments on
concentration camp inmates
Nazi “Physician-Researchers”
• Dr Hans Conrad Reiter (formerly “Reiter’s
Syndrome”, now “reactive arthritis”): senior
Nazi official
• Dr. Joseph Mengele: Septicemia/twin
vivisection studies
• Dr. Hans Eppinger - “father of modern
hepatology”
“Indirect Participants”
• Prof. J Hallevorden: “Look here now, boys,
if you are going to kill all these people at
least take the brains out so that the material
could be utilized … the more (brains) the
better….I accepted these brains of course.
Where they came from and how they came
to me was really none of my business.”
Doctors and Resistance
• German invasion of Poland (1939)
• Drs Eugene Lazowski and Stanislaw
Matulewicz created a fake typhus epidemic,
using a harmless bacterium to innoculate
non-Jews, knowing that infected Jews
would be summarily executed
• Germans fooled, quarantined area, many
Jews escaped death
Nuremberg Doctors’ Trial
• 23 German physicians tried
• 16 found guilty
– 7 hanged (incl. Gebhardt, Brack, Hoven, and
Mrugowsky)
• Rascher died before trial; Mengele fled for
Argentina (remains verified 1985);
Hallevorden committed suicide before trial
Nuremberg Code
• Voluntary consent is absolutely essential
• Avoidance of unnecessary physical and
mental suffering
• Option to quit/responsibility to terminate
• Other safeguards
Declaration of Geneva
• “I will not permit considerations of religion,
nationality, race, party politics or social standing
to intervene between my duty and my patient”
• “I will not use my medical knowledge contrary
to the laws of humanity.”
• “It is unethical for physicians to employ
scientific knowledge to imperil health or destroy
life.”
Declaration of Helsinki
• Patients’ rights to respect, self
determination, informed decision-making
• Investigators’ duties: primacy of subjects’
welfare, ethical considerations take
precedence over laws and regulation
• Allows for surrogate consent
Post-WW II
• Over 700 Nazi rocket scientists and their
families brought to the U.S. (including
Werner von Braun) to help build nuclear
missile program
– Operation Paperclip
• Japanese scientists brought to Fort Detrick,
MD, to help establish U.S.
biological/chemical weapons program
Post-WW II Human Subject
Experimentation
• Tuskegee Syphilis Study
– “The men’s status did not warrant ethical
debate. They were subjects, not patients;
clinical material, not sick people.”
• Dr John Heller, Director of Venereal
Diseases at PHS between 1943 and
1948 (interviewed in 1976)
Research on Prisoners
• 1905: cholera experiments on “volunteers”
• 1915: Joseph Goldberger – pellagra studies
– Parole in exchange for participation
– 1941: Physician William Black infects
children with herpes virus, paper
published by J Peds
Post-WW II Human Subject
Experimentation
• Pharmaceutical and government sponsored
studies on prisoners
– 1940s and 1950s esp.
– Halted in mid-1970s after drug company
executives admitted prisoners were cheaper to
use than chimpanzees
• WW II: gonorrhea, gas gangrene, dengue
fever, malaria
Post-WW II Human Subject
Experimentation
• Guatemala STD study (1946-8)
– U.S. researchers deliberately infected 1,500
prisoners, military conscripts, prostitutes,
orphans (provided by Sisters of Charity), and
mental health patients with gonorrhea and
syphilis
– Scientists treated 87% of those infected (10%
later required re-treatment), lost track of 13%
Post-WW II Human Subject
Experimentation
• Guatemala STD study (1946-8)
– Wives, children, and grandchildren treated, but
sexual contacts not traced
– Study approved by Guatemalan government
• Received material for resource-starved institutions
in return
– Subjects received cigarettes for participating
Post-WW II Human Subject
Experimentation
• Guatemala STD study (1946-8)
– U.S. apologized (2010), has pledged $1 million
to study research ethics, $775,000 to fight
STDs in Guatemala
– Class action lawsuit against U.S. government
filed on behalf of 700 victims/relatives (2011)
Post-WW II Human Subject
Experimentation
• Guatemala STD study (1946-8)
– Dr. John Cutler (research coordinator): “Unless
the law winks occasionally, you have no
progress in medicine”
– In 1943, Cutler infected volunteer federal
prisoners in Indiana with gonorrhea in
exchange for cash
Post-WW II Human Subject
Experimentation
• Guatemala STD study (1946-8)
– After Guatemala, Cutler oversaw the Tuskegee
Syphilis Study
– Was acting dean at University of Pittsburgh in
1960s
Post-WW II Human Subject
Experimentation
• University of Minnesota malaria study
(1940s)
• Drs. Thomas Francis, Jr. and Jonas Salk
infect psychiatric hospital residents with
influenza (?if consent adequate?)
Post-WW II Human Subject
Experimentation
• Atlanta prison gonorrhea study (1950s)
• Patuxent prison Asian flu experiment
(1957)
• U.S. govt.-sponsored radiation, LSD (MK
Ultra) experiments
Post-WW II Human Subject
Experimentation
• Pentagon/CIA experiments on soldiers and
civilians
– Edgewood Arsenal Experiments (involving
more than 7,000 soldiers who were exposed to
at least 250 biological and chemical agents)
• Including sarin, VX, LSD, ritalin
• Caused long-term health effects
– Deliberate release of Serratia over San
Francisco Bay
Post-WW II Human Subject
Experimentation
• 1963: Dr. Chester Southam injects tumor
cells into extremely infirm patients at
Jewish Hospital for Chronic Disease in NY
without informing them that the shots
contain cancer cells
– Southam later elected President of American
Association for Cancer Research
Post-WW II Human Subject
Experimentation
• Willowbrook Hepatitis Experiments (1960s)
• Pre-WW1: Joseph Goldberger’s pellagra
experiments on Mississippi prisoners
• Henry Beecher, NEJM (1966)
Post-WW II Human Subject
Experimentation
• Ongoing sterilization programs
– Buck v. Bell (USSC, 1927) – 60,000
Americans sterilized
– WI, NJ, CA, IN, OR, others
– Alabama’s Governor Graves vetoed law in
1930s law citing “hazard to personal rights”
– Oregon governor Kitzhaber apologized in 2002
for the over 2500 state-forced sterilizations that
occurred between 1917 and 1983
– 2012 – NC to compensate victims
Post-WW II Human Subject
Experimentation
• Iowa elementary school race experiment
(1968; good or bad?)
• Milgram’s obedience studies (1963);
Milgram redux (2008)
• Soviet psychiatry
• US military/pharmaceutical vaccine and
medication trials in the developing world
GM foods, biopharmaceuticals
• Largest uncontrolled trial in history of
humanity
• E.g., Chinese children with vitamin A
deficiency used for feeding trials of Golden
Rice by Tufts University investigators
– Without preceding animal studies
– ? Nature of informed consent
– May violate Nuremberg Code
Research on Prisoners
• >90% of pharmaceutical industry research
in early 1970s
• Rapidly curtailed by state/federal laws and
new university regulations
• 2006: IOM approves with safeguards
– 2009: 44% of jurisdictions allow compensation
Self-Experimentation
• Albert Hoffman (LSD)
• Werner Forssmann (right heart
catheterization)
• Barry Marshall (Helicobacter pylori)
• Others
Disturbing Experiments
• Inter-species breeding (ape-man, Ilya
Ivanovich Ivanov, Guinea, 1927)
• Two-headed dog (Vladimir Petrovich
Demikhov, 1950s, Russia)
Contemporary Issues and Ethical Dilemmas
• 90% of research dollars spent on diseases
affecting 10% of the world’s population
– Neglected tropical diseases
• Research on special populations (cultural
minorities, prisoners, developing world, etc.)
• Ghostwriters
• Contract Research Organizations
• Role of institutional and for-profit IRBs
Contemporary Issues and Ethical Dilemmas
• Use of placebo controls
– Various drug trials
– Anti-HIV medications and maternal-fetal
transmission(sub-Saharan Africa)
– Surfactant for neonatal RDS (Brazil, Bolivia)
– Hep A vaccine (Thailand)
– Trovan/meningitis/Nigeria (control =
inadequate ceftriaxone dose)
Contemporary Issues and Ethical Dilemmas
• 1/3 of phase 3 US drug company trials are
conducted solely outside the US
• Majority of phase 3 US drug company trial
sites outside US, many in developing
countries
– Majority of developing nation trial sites without
institutional review boards
– Victims may seek redress under “Alien Torts
Statute”
Contemporary Issues and Ethical Dilemmas
• Nerve-sparing clitoroplasty as substitute for
female genital cutting
– AAP reversal of position (2010)
• Kennedy Krieger Institute (Johns Hopkins)
lead paint abatement study (1992)
Contemporary Issues and Ethical
Dilemmas
• Uninsured become research subjects to
receive needed care
• Human guinea pigs (professional lab rats)
• Parent investigators
• Neonatal analgesia
• Under-representation of women and
minorities in clinical trials
Contemporary Issues and Ethical
Dilemmas
• Informed consent for treatment –
physician/patient negotiation vs. unilateral
decision-making when treatment options
limited
• Relaxation of international research
standards by eliminating Declaration of
Helsinki standards (FDA, 2008)
Contemporary Issues and Ethical Dilemmas
• 2003: Ban on industry experiments testing
safety of pesticides/other potentially toxic
chemicals in humans lifted by NAS and
EPA
• Monsanto’s Roundup purchased by US
government for aerial spraying in Colombia
as part of “War on Drugs”
Contemporary Issues and Ethical
Dilemmas
• 2008: Former director of UCLA School of
Medicine’s donated body program pleads guilty to
5 year scheme to sell donated body parts to
medical, drug, and research companies, netting
more than $1 million
• Clinical Trials Registry
– Drug company noncompliance
Contemporary Issues and Ethical Dilemmas
• Physician participation in “War on Terror,”
Abu Ghraib, Guantanamo, Black Ops sites
– “Basic Science Consultation Teams”
– Co-optation of anthropologists in Iraq,
Afghanistan
– Nurses injecting psychotropic drugs to forcibly
sedate deportees
– AMA, AAP, APA oppose physician
involvement in interrogation/torture
What to do with data acquired via
unethical means?
• Eduard Pernkopf’s Atlas; Dachau
Hypothermia Experiments; Phosgene gas
experiments; biological weapons data
(offensive vs. defensive)
• Japan’s Unit 731 and biological warfare
experiments
What to do with data acquired via
unethical means?
• Move to rename “Hallevordan-Spatz
syndrome”: “pantothenate kinaseassociated degeneration” or
“neurodegeneration with brain iron
accumulation”
• Breast cancer cure scenario
What to do with data acquired via unethical
means – AMA Policy E-2.30 – Adopted 1998
• All proposed experiments using human subjects
should undergo proper ethical evaluation by a
human studies review board before being
undertaken.
• Responsibility for revealing that the data are from
unethical experiments lies in the hands of authors,
peer reviewers, and editors of medical texts that
publish results of experimental studies.
What to do with data acquired via unethical
means – AMA Policy E-2.30 – Adopted 1998
• Each publication should adopt a standard
regarding publication of data from unethical
experiments.
• If data from unethical experiments can be
replaced by existing ethically sound data
and achieve the same ends, then such must
be done.
What to do with data acquired via unethical
means – AMA Policy E-2.30 – Adopted 1998
• If ethically tainted data that have been validated by
rigorous scientific analysis are the only data of that nature
available, and such data are necessary in order to save
lives, then the utilization of such data by physicians and
editors may be appropriate.
• Should editors and/or authors decide to publish an
experiment or data from an experiment that does not reach
standards of contemporary ethical conduct, a disclaimer
should be included. Such disclosure would by no means
rectify unethical conduct or legitimize the methods of
collection of data gathered from unethical experimentation.
What to do with data acquired via unethical
means – AMA Policy E-2.30 – Adopted 1998
• This disclaimer should:
– (1) clearly describe the unethical nature of the origin of
any material being published
– (2) clearly state that publication of the data is needed in
order to save human lives
– (3) pay respect to the victims
– (4) avoid trivializing trauma suffered by the participants
– (5) acknowledge the unacceptable nature of the
experiments
– (6) endorse higher ethical standards.
What to do with data acquired via unethical
means – AMA Policy E-2.30 – Adopted 1998
• Based on both scientific and moral grounds, data obtained
from cruel and inhumane experiments, such as data
collected from the Nazi experiments and data collected
from the Tuskegee Study, should virtually never be
published or cited.
• In the extremely rare case when no other data exist and
human lives would certainly be lost without the knowledge
obtained from use of such data, publication or citation is
permissible.
• In such a case, the disclosure should cite the specific
reasons and clearly justify the necessity for citation.
What to do with data acquired via unethical
means – AMA Policy E-2.30 – Adopted 1998
• Certain generally accepted historical data
may be cited without a disclaimer, though a
disclosure of the ethical issues would be
valuable and desirable.
Ethical Perspectives on Scientific
Research and War
• Denial of moral responsibility for consequences
• Recognition of moral responsibility but competing
obligations
• Recognition of moral responsibility and refusal to
participate
• Responsibility to inform or lead public opinion
• Publication of research on dangerous/novel
pathogens
Scientists and War Research
• Archimedes, da Vinci, Galileo, Haber,
Fieser
• Farraday
• Nobel, Einstein, Szilard
Doctors as Terrorists
• Pediatrician George Habash – founder of
Popular Front for the Liberation of Palestine
– Behind aircraft hijackings of Black September
• Dr. Fathi Shiqaqi – founder of Palestinian
Islamic Jihad
Doctors as Terrorists
• Ayman Al-Zawahiri – leader of Al Qaeda
• Ikuo Hayashi – chief of circulatory
medicine at a leading Japanese hospital
– Pleaded guilty to planting sarin gas on Tokyo
subway
• Radovan Karadzic (psychiatrist) – on trial
for war crimes against Bosnian Croats and
Muslims
Doctors as Terrorists
• Dr Bilal Abdullah convicted in bungled Heathrow
Airport car bombing (2007)
• Psychiatrist Major Nidal Hasan – awaiting trial for
Fort Hood shootings (2009)
• Humam Khalil Abu-Mulal al-Balawi: Jordanian
suicide bomber, killed 7 CIA agents in
Afghanistan (2009)
• Bashir Assad (Syrian President, ophthalmologist)
– 2011/12 civilian bombings
Doctors as Murderers
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Dr. H. H. Holmes, - "the torture doctor,"
Linda Burfield Hazzard - "the starvation doctor"
Dr. Marcel Petiot
GP Harold Shipman – world’s most notorious
serial killer (up to 400 victims)
• Ophthalmologist John Taunton – anti-immigrant,
white supremacist
Doctors as Murderers
• South African cardiologist Wouter Basson (aka “Dr.
Death”) – ran “Project Coast” in 1980s (clandestine
military program linked to chemical and germ warfare,
assassinations, poisonings, kidnapping, and plots to
sterilize the country’s black population)
– Aquited of 67 criminal charges in 2002
– Still practicing, Health Professions Council of SA
considering revocation of medical license
• Others
War on Terror
• Doctors involved in torture, extraordinary
renditions
• Investigations, outcry, but no real
consequences
Primo Levi
“A country is considered the more
civilized the more the wisdom and
efficiency of its laws hinder a weak
man from becoming too weak or a
powerful one too powerful.”
(U.S. – largest maldistribution of wealth of
any industrialized country)
The role of the doctor in society
• Public health versus individual health
• Roles, responsibilities, and obligations
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patients
society
institutions
families
government
world
The role of the doctor in society
• Theodore Billroth:
– “If the whole of Social Medicine needs to
be part of the curriculum of the medical
student, it must not take more than two
hours per semester … during the last two
semesters; otherwise, it will surely be
detrimental to his other studies”
The role of the doctor in society
• Rudolph Virchow:
– “Doctors are natural attorneys for the
poor … If medicine is to really
accomplish its great task, it must
intervene in political and social
life…”
The role of the doctor in society
• World Health Organization:
– “The role of the physician … in the
preservation and promotion of peace
is the most significant factor for the
attainment of health for all.”
Ethical Issues Relating to Mixed
Agency of Military Physicians
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Triage and return to combat
Confidentiality
Communication
Loyalties/Command
Experimentation
“The Sea and Poison”
Medical Education Lacking
• 2007 survey: 5,000 medical students at 8 medical
schools, 35% response rate (Int J Hlth Serv 2007;37(4):64350)
• 94% received < 1 hr. instruction on military
medical ethics
• 3.5% aware of legislation already passed making a
“doctors’ draft” possible
• 34% did not know Geneva Conventions require
physicians to treat the sickest first, regardless of
nationality
Medical Education Lacking
• 34% not aware Geneva Conventions
prohibit ever threatening or demeaning
prisoners or depriving them of food or water
• 34% could not state when they would be
required to disobey an unethical order
(answer = always)
The Death Penalty and Health
Professionals
• AMA, APHA, ANA, and ABA
(anesthesiologists) oppose participation
of health professionals in executions
• Only 7/35 death penalty states
incorporate AMA ethics policy,
including barring doctors from taking
an active role in the death chamber
The Death Penalty and Health
Professionals
• 2001:
– 3% of physicians aware of AMA
guidelines prohibiting physician
participation
– 41% would perform at least one
action in the process of lethal
injection disallowed by AMA
Ethical Issues Relating to Mixed
Agency of Civilian Physicians
• Physician participation in torture and
executions
– Most torturers never identified/held accountable
– 2008 study at University of Illinois at Chicago
• 35% of medical students said torture could be
condoned under some circumstances
• Pharmaceutical company provision of
agents used in lethal injection executions
Contact Information
Public Health and Social Justice
Website
http://www.phsj.org
[email protected]