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

(half-men/half-apes) “super-warriors”

• Drs. Karl Clausberg and Viktor Brack: X-irradiation/sterilization


• 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


• 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)

Nuremberg Doctors’ Trial

• Rascher died before trial

• Mengele fled for Argentina (remains verified 1985)

• Hallevorden committed suicide before trial

• Otto Ambros (chemist) – invented sarin (nerve gas), convicted of mass murder at Nuremberg Trials, later freed and worked with US chemical industry on thalidomide

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

• German Medical Association unanimously issues blunt, straightforward apology for its role in the Holocaust (2012)

Post-WW II Human Subject Experimentation

• James Ketchum (psychiatrist), L Wilson Green (scientist), Van Murray Sim – psychochemical warfare studies for US Army– Ketchum later joined faculty of University of

Texas Medical School


• 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)

Studies on Native Americans

• Sterilizations

• Radioactive iodine to study adaptation of thyroid gland to extreme cold

• Forced removal of children to English language, religious schools (c.f., Australia)

• Distrust and reluctance of minorities to participate in medical research

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


• 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


• 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%


• 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


• 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)


• 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


• Guatemala STD study (1946-8)– After Guatemala, Cutler oversaw the Tuskegee

Syphilis Study– Was acting dean at University of Pittsburgh in

1960s


• University of Minnesota malaria study (1940s)

• Drs. Thomas Francis, Jr. and Jonas Salk infect psychiatric hospital residents with influenza (?if consent adequate?)


• Atlanta prison gonorrhea study (1950s)

• Patuxent prison Asian flu experiment (1957)

• U.S. govt.-sponsored radiation, LSD (MK Ultra) experiments


• 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; radioactive cadmium over St. Louis


• 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


• Willowbrook Hepatitis Experiments (1960s)

• Pre-WW1: Joseph Goldberger’s pellagra experiments on Mississippi prisoners

• Henry Beecher, NEJM (1966)


• Ongoing sterilization programs– Buck v. Bell (USSC, 1927) – 60,000

Americans sterilized– WI, NJ, CA, IN, NC, 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


• 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)

• Monster Study (Wendell Johnson, 1939, University of Iowa) – deliberate induction of stuttering in orphan children

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


• 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)


• 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”


• Nerve-sparing clitoroplasty as substitute for female genital cutting– AAP reversal of position (2010)

• Kennedy Krieger Institute (Johns Hopkins) lead paint abatement study (1992)


• 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


• 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)


• 2003: Ban on industry experiments testing safety of pesticides/other potentially toxic chemicals in humans lifted by NAS and EPA– 2013 – EPA adds safeguards, issues regulations

prohibiting studies on pregnant women and children

• Monsanto’s Roundup purchased by US government for aerial spraying in Colombia as part of “War on Drugs”


• 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


• 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 kinase-associated 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.


• 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.


• 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.


• 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.


• 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.


• 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


• 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


• 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

• 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

Physician Criminals

• Violent crimes, including rapes of patients

• Performance of unnecessary, dangerous procedures

• Medicare fraud, kickback scams

• Ethical violations through participation in executions

War on Terror

• Doctors involved in torture, extraordinary renditions

• Investigations, outcry, but no real consequences

• Capture of Osama bin Laden involved (unsuccessful) sham CIA hepatitis B vaccination project to collect DNA (violation of public trust)

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– patients– society– institutions– families– government– world


• 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”


• 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…”


• 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

• 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):643-50)

• 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]

http://www.phsj.org/

mailto:[email protected]

human subject experimentation

Documents