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History, Scandals and Tragedies:Beecher, Tuskegee,Willowbrook and the RestSusan E. Lederer, Ph.D.September 25, 2019
DisclosureI have norelationships todisclose, and Iwill not discussoff label orinvestigationaluse products inmypresentation.Email: susan.Lederer@wisc.edu
Why do we have therules for research thatwe have?U.S. health policy asresponse to scandal andtragedy
The Patent Medicine Evil in the Early 20th century
Questionable safety of thefood supply
Food and Drug Act 1906
Elixir of Sulfanilamidetragedy 1937107 deaths
Diet and cosmetic dangersc. 1930sdinitrophenol
Food, Drug and CosmeticAct of 1938 Drugs or cosmetics must betested for toxicity beforemarketing Adequate directions for useneed to be on package Some drugs are designated“by prescription only”
Thalidomide1960-196183 children were bornwith unusual birthdefects, not linked tothalidomide use.a German scientistmakes connectionsbetween thalidomideuse and thousands ofbabies born with birthdefects.
Kefauver-HarrisAmendments to FDADrug makers mustestablish theeffectiveness of drugproducts before they goon the market, andafterwards report anyserious side effects.Requires clinicalstudiesconducted byqualified experts.Requires informedconsent by studysubjects
Animal WelfareAct, 1966
LIFE MAGAZINE1966
National ResearchAct, 1974
Both the history of humanexperimentation andhistory of controversy overhuman experimentationmuch older
United States Congress, 1900considers Senate bill 3424,a lawto require investigators to disclosein advance the purpose andprocedures of any nontherapeutic experiment involvinghuman beings.
Senate bill 3424calls for explicit ban onexperiments using those personsdeemed unable to consent,includinginfants,children under the age of 21,and pregnant women.
The U.S. Army Yellow FeverBoard in Cuba, 1900
Reed and his colleagues introducewritten permission formsavailable in bothEnglish and Spanish
The undersignedunderstands perfectly well that in case of the development ofyellow fever in him, that he endangers his life to acertain extent but it being entirely impossible for him toavoid the infection during his stay in this island, heprefers to take the chance of contracting itintentionally in the belief that he will receive from thesaid Commission the greatest care and the most skillfulmedical service.
Subjects receive 100 in gold, 200 if death occurs
“A written consent wasobtained from each one, sothat our moral responsibility wasto a certain extent lessened.Of course, only the healthiestspecimens were experimentedupon . . .”Aristides Agramonte
World War IIexperimentation President FranklinDelano Rooseveltestablishes theOffice for ScientificResearch andDevelopment Committee on Medical Research Unprecedented federal funding formedical research
Research related to wareffort gets greenlighthypothermiaeffects of high altitudede-salination studiesburns/woundsblood substitutesPrevention and treatment of infectious diseasesmalariagonorrheahepatitis
De-salting sea water
Malaria research
Nazi war-time medical researchagendahypothermiaeffects of high altitudede-salination studiesburns/woundsblood substitutesvaccines and treatmentmalariagonorrheahepatitis
Nazi researchers useconcentration campinmates as subjects
Dachau Concentration Camp—effectsof hypothermia
Dachau Concentration Campeffects of high altitude
Sea water studies A Roma victim ofNazi medicalexperiments tomake seawaterpotable.
Seawater experiments,Dachau 194444 camp inmatesages 16-49)German, Czech,and Polish Roma.“recruited” fromBuchenwald andAuschwitz for a“clean up workdetail” Group 1 no water at all Group 2 fresh water Group 3 ordinary sea water Group 4 chemically filteredsea water, Group 5 sea water with atomato extract to mask taste(but leaving high saltconcentration).
Rudi Taubmann’s testimonyat the Nuremberg ER?Christian faith?anesthesia?experience withhuman subjectsresearch?
Beecher concernedabout youngresearchers who failto understand theirresponsibilities
Who weretheresearchsubjects inBeecher’s22examples?“mentally defective” childrenmentally retarded and delinquentchildrenthe very elderlysoldiers in the armed forcescharity patientsthe terminally illalcoholicschildren and newbornspatients at the NIH Clinical Center
Example 16
Willowbrook studiesNewly admittedchildren (whoseparents giveconsent) are givenintramuscularinjections ofhepatitis or“milkshakes” withhepatitis
Dr. Saul Krugmanet al begin studiesto acquireinformation aboutthe natural historyof hepatitis andwork towardvaccine
Krugman continued to defendthe studies butissues persist about informedconsent, coercion, and studydesign (withholding gammaglobulin)
Example 17JewishChronicDiseaseHospitalcaseFunded by USPHS and AmericanCancer SocietyInjections of live cancer cells intoelderly patients withoutconsent"did not wish to stir up anyunnecessary anxieties in thepatients" who had "phobia andignorance" about cancer.
ChesterSoutham, M.D.Science, 1964
Revelation of the Tuskegee SyphilisStudyJuly 25, 1972
Study begins in 1932
Public Health Service SurgeonGeneral Thomas Parran,Shadow on theLandHead of PHS, 19361948
From treatment to “a study in nature”Dr. Raymond Vonderlehr offersNegro men “last chance forspecial free treatment” for their“bad blood”
Lumbar puncture(to obtain spinalfluid for diagnosis)
World War II PHS asks Tuskegee draftboard to exempt the menin the study from the draft They serve in another war
Nurse Eunice Rivers
Nurse Riversobtains permissionfor autopsyeasier when aburial stipend of 50 is providedonly one refusal in140 requests
1954for the first time, men in the studyidentified as “volunteers with socialincentives””
One dollarfor eachyear themen are inthe Study
--CDC convenes a blueribbon panel to determinewhether Tuskegee studyshould continue1969--the only physician notfamiliar with the Study arguesthat the experiment shouldend and the men receivetreatment--the Study continues until1972
Study Revealed July 25, 1972
Senator TedKennedy holdshearings on humanexperimentationincluding the TSS Legislation passed1974 National ResearchAct
1974 National ResearchActcreation of a NationalCommission to study the moralissues posed by humanexperimentationnew federal regulations for IRBsand written informed consent
Persistent stories about thedeliberate infection of themen in Tuskegee with syphilis
Presidential apology 1995
White House Apology for the Syphilis Study,
Revelations ofscandal and tragedycontinue
2010 President Obama andSecretary of State HillaryRodham Clinton apologize topeople of Guatemala forstudies conducted in 1946-1948
John Cutler, STD studies Using prostitutesinfected with syphilisand gonorrhea todeliberately infectGuatemalansoldiers andprisoners Infecting prisonersmanually with STDS
Guatemala, 1946-48 Infectinginmates ofmentalhospital withSTDS
experiments in Guatemala thateventually expose 1,308prisoners, soldiers and patientsat a psychiatric hospital toSTDs. The US team also takes bloodfrom 1,384 orphans and otherchildren to assess STDdiagnostic tests.
Ongoing challengeto protect humansubjects andadvance medicalknowledge
off label or investigational use products in my presentation. Email: susan.Lederer@wisc.edu. . marketing Adequate directions for use need to be on package . White House Apology for the Syphilis Study, Revelations of scandal and tragedy continue . 2010
