Human Subject Experimentation

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Human Subject Experimentation

• The Nazis
• Lessons for Contemporary Research
• The Role of the Physician in Society
• Martin Donohoe

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• 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

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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

4
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)

5
Nazi Medicine

• Individual worth stated in economic terms
  propaganda re obligations to the state
• I Accuse
• Mathematics in the Service of Political
  Education

6
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

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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

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Nazi Physicians

• Economic hard times, physicians salaries rise,
  academic perks
• Blutkitt (blood cement)
• Rare resistance
• Catholics
• Marxists
• Dutch

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Nazi Physician-Researchers(Torturers)

• Dr. Sigmund Rascher - coagulation/amputation
  studies hypothermia experiments
• Dr. Karl Gebhart heteroplastic transplantation
  experiments
• c.f. Stalins attempts to create interspecies
  (half-men/half-apes) super-warriors
• Drs. Karl Clausberg and Viktor Brack
  X-irradiation/sterilization

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Nazi Physician-Researchers

• Drs. Joachim Mrugowsky, Erwin Ding-Schuler, and
  Waldemar Hoven IV phenol and gasoline executions
• Dr. Friedrich Wegener (Wegeners
  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

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Nazi Physician-Researchers

• Dr Hans Conrad Reiter (formerly Reiters
  Syndrome, now reactive arthritis) senior Nazi
  official
• Dr. Joseph Mengele Septicemia/twin vivisection
  studies
• Dr. Hans Eppinger - father of modern hepatology

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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.

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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

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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

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Nuremberg Code

• Voluntary consent is absolutely essential
• Avoidance of unnecessary physical and mental
  suffering
• Option to quit/responsibility to terminate
• Other safeguards

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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.

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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

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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

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Post-WW II Human Subject Experimentation

• Tuskegee Syphilis Study
• The mens 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)

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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

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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

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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

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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

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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)

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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

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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

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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?)

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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

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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

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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

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Post-WW II Human Subject Experimentation

• Willowbrook Hepatitis Experiments (1960s)
• Pre-WW1 Joseph Goldbergers pellagra experiments
  on Mississippi prisoners
• Henry Beecher, NEJM (1966)

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Post-WW II Human Subject Experimentation

• Ongoing sterilization programs
• Buck v. Bell (USSC, 1927) 60,000 Americans
  sterilized
• WI, NJ, CA, IN, OR, others
• Alabamas 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

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Post-WW II Human Subject Experimentation

• Iowa elementary school race experiment (1968
  good or bad?)
• Milgrams obedience studies (1963) Milgram redux
  (2008)
• Soviet psychiatry
• US military/pharmaceutical vaccine and medication
  trials in the developing world

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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

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Research on Prisoners

• gt90 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

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Self-Experimentation

• Albert Hoffman (LSD)
• Werner Forssmann (right heart catheterization)
• Barry Marshall (Helicobacter pylori)
• Others

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Disturbing Experiments

• Inter-species breeding (ape-man, Ilya Ivanovich
  Ivanov, Guinea, 1927)
• Two-headed dog (Vladimir Petrovich Demikhov,
  1950s, Russia)

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Contemporary Issues and Ethical Dilemmas

• 90 of research dollars spent on diseases
  affecting 10 of the worlds 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

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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)

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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

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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)

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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

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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)

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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
• Monsantos Roundup purchased by US government for
  aerial spraying in Colombia as part of War on
  Drugs

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Contemporary Issues and Ethical Dilemmas

• 2008 Former director of UCLA School of
  Medicines 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

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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

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What to do with data acquired via unethical means?

• Eduard Pernkopfs Atlas Dachau Hypothermia
  Experiments Phosgene gas experiments biological
  weapons data (offensive vs. defensive)
• Japans Unit 731 and biological warfare
  experiments

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What to do with data acquired via unethical means?

• Move to rename Hallevordan-Spatz syndrome
  pantothenate kinase-associated degeneration or
  neurodegeneration with brain iron accumulation
• Breast cancer cure scenario

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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.

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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.

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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.

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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.

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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.

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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.

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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

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Scientists and War Research

• Archimedes, da Vinci, Galileo, Haber, Fieser
• Farraday
• Nobel, Einstein, Szilard

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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

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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

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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

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Doctors as Murderers

• Dr. H. H. Holmes, - "the torture doctor,"
• Linda Burfield Hazzard - "the starvation doctor"
• Dr. Marcel Petiot
• GP Harold Shipman worlds most notorious serial
  killer (up to 400 victims)
• Ophthalmologist John Taunton anti-immigrant,
  white supremacist

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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 countrys
  black population)
• Aquited of 67 criminal charges in 2002
• Still practicing, Health Professions Council of
  SA considering revocation of medical license
• Others

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War on Terror

• Doctors involved in torture, extraordinary
  renditions
• Investigations, outcry, but no real consequences

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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)

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The role of the doctor in society

• Public health versus individual health
• Roles, responsibilities, and obligations
• patients
• society
• institutions
• families
• government
• world

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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

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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

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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.

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Ethical Issues Relating to Mixed Agency of
Military Physicians

• Triage and return to combat
• Confidentiality
• Communication
• Loyalties/Command
• Experimentation
• The Sea and Poison

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Medical Education Lacking

• 2007 survey 5,000 medical students at 8 medical
  schools, 35 response rate (Int J Hlth Serv
  200737(4)643-50)
• 94 received lt 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

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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)

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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

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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

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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

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Contact Information

• Public Health and Social Justice Website
• http//www.phsj.org
• martindonohoe_at_phsj.org