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Teaching Research Ethics to Bioscience Students, May 2011


 “You don't want to do it like that”:
            some (in)famous examples of
               research misconduct

                                      Dr Chris Willmott
                                  Dept of Biochemistry,
                                  University of Leicester
                                         cjrw2@le.ac.uk
                                               University of
                                               Leicester
http://tinyurl.com/ydwtdilt2011
Classification of misconduct (1)
Misconduct that distorts scientific knowledge
   • Fabrication – reporting of non-existent data
   • Falsification – selective reporting of data

Misconduct that misleads the scientific community
   • Authorship: Plagiarism, „Guest‟ authors,
     „Ghost‟ authors
   • Duplicate publication
   • Abuse of the peer-review process

“FFP” = Fabrication, Falsification, Plagiarism
Classification of misconduct (2)
Misconduct relating to human subjects
  • Consent issues
  • Exploitation issues (inc. financial)

Other issues
  • Conflicts of Interest
  • Poor record-keeping
  • Failure to obtain necessary ethical approval
  • Incidental findings?
Selection of cases for discussion
• Sadly there are plenty more cases than can be
  discussed in time available
• Omitted alleged cases before 1900
• Omitted cases where there is significant minority
  dissent re guilt
• Omitted cases from outside biology and biomedicine
• Have tried to balance UK, USA and other countries
• Have looked for combination of classic, curious
  and contemporary cases reflecting range of different
  types of misconduct
        i.e. cases likely to be useful in teaching
Piltdown Man (1912)




                                                                         http://tinyurl.com/dawsonhinton
• Report of hominid remains found
  in Sussex
• “Missing link”?
• Later shown to be skull of modern
  man and jawbone of orang-utan
• Fraud certain, but identity of
  culprit still uncertain
      - Charles Dawson?
      - Martin Hinton?



 Fabrication                         http://tinyurl.com/piltdownskull
Tuskegee Syphilis Study (1932-72)
                                • Poor African-Americans with
                                  advanced syphilis recruited to
                                  trial to study their “bad blood”
                                • Deliberately untreated to see
                                  long-term effects of infection,
http://tinyurl.com/tuskegee11
                                  even when treatments became
                                  available (e.g. Penicillin)
                                • Over 400 men (plus families)
                                  involved
   Consent                     • Breach of human rights
   Exploitation
   (Racism)
Nazi doctors (1940s)
• Medical experiments conducted on prisoners
     - sterilisation
     - modelling of battlefield wounds and infection
     - physiological response to extreme conditions
     - bizarre transplantation and twin studies
• Doctors included “Angel of Death” Joseph Mengele
  (escaped), plus several put on trial and hanged
• Led to Nuremberg Code of conduct for research
  involving human subjects (1947)

 Consent
 Exploitation
Porton Down (1940s-60s)
• Series of experiments conducted at Porton Down,
  UK Government and military research centre
• Participants thought they were volunteering for
  trials to find things such as cure for common cold
• Actually exposed to LSD,
  sarin, mustard gas, etc
• 2008, MOD agreed to £3M
  payout to surviving veterans


 Consent
 Exploitation
                                           http://tinyurl.com/portondown
William Summerlin (1974)
• Researching ways to overcome
  tissue rejection at Sloan-Kettering
  Institute in New York
• Included transplanting fur from
  black mouse onto white mouse
• “Transplanted” patches actually
  drawn on with black marker pen
  (removable with alcohol)




 Fabrication
Vijay Soman & Philip Felig (1978)
                                                               • NEJM sent Felig paper for review
http://tinyurl.com/soman11




                                  http://tinyurl.com/felig11   • Felig passed paper to junior
                                                                 colleague Soman
                                        • They rejected paper
                    • Few months later, Am J Medicine sent original author
                      paper by Soman to review
                    • Sections clearly copied from hers, plus additional
                      material later shown to be made up

                     Plagiarism
                     Fabrication
                     Violation of peer-review process
Dick van Velzen (1988-95)
• Senior pathologist at Alder Hey Children‟s Hospital
• Expert in cot death, was found to have organs from
  about 850 children without appropriate permission
• Struck off by GMC
• Along with scandal at
  Bristol Royal Infirmary
  led to Human Tissue
  Act (2004)


 Consent
 Fabrication
                                           http://tinyurl.com/vanveltzen05
Eric Poehlman (1992-2002)
                              • Research into ageing, menopause
                                and Hormone Replacement Therapy,
                                working primarily at Uni of Vermont
                              • Misconduct exposed by former lab
                                technician Walter DeNino
                              • Pleaded guilty to falsifying 17 grant
http://tinyurl.com/poehlman
                                applications and fabricating data in
                                10 research papers
                              • 2006, first scientist jailed for fraud
                                (also fined $200K)
 Fabrication
 Falsification
Malcolm Pearce (1994-95)
                              • Obstetrician at St George‟s, London
                              • Reported transplant of ectopic
                                pregnancy to uterus and live birth
                              • Colleagues at same hospital said no
                                knowledge of case
                              • Pearce tried to hack computer to
                                alter notes
                              • Also found to have invented patients
                                in study on polycystic ovary syndrome
http://tinyurl.com/pearce11   • Struck off by GMC
  Fabrication
Geoffrey Chamberlain (1995)
• Linked to Malcolm Pearce case
• World reknowned ultrasound expert
• Chamberlain was Pearce‟s Head of Dept, and Editor
  of British Journal of Obstetrics and Gynaecology
  where both fraudulent papers were published
• Accepted “gift authorship” for
  ectopic pregnancy paper
• Reprimanded by GMC
• “A considerable error of
  judgement” (Wells, 2008)
 Gift authorship
                                       http://tinyurl.com/chamberlain11
Andrew Wakefield (1998)
• Author on infamous Lancet paper linking autism with
  MMR vaccine
• Investigation for >2 years (ended May 2010) decided
  he was guilty of conflict of interest, both as recipient
  of money from lawyer looking for link to vaccine, and
  regarding company he set up looking to market test
• Highly selective reporting of data
• Unethical dealings with children




                                                         http://tinyurl.com/wakefield11
   Consent
   Exploitation
   Conduct of clinical trial
   Conflict of Interest (financial)
James Wilson (1999)
                               • Conducted clinical trial using gene
                                 therapy to combat OTC deficiency at
                                 U of Pennsylvania in which Jesse
                                 Gelsinger died
                               • President and major shareholder
                                 (30%) in Genova, company
http://tinyurl.com/jwilson11
                                 developing product under test
                               • Failed to report extent of adverse
                                 reactions during animal testing
 Consent
 Conduct of clinical trial
 Conflict of Interest (financial)
Raj Persaud (2003 & 2005)
• Celebrity psychologist appearing regularly on TV and
  radio (including own show All In The Mind on R4)
• 2003 book From the Edge of the Couch and various
  other writings including article on scientology
• Admitted plagiarism but claimed it was accidental
  due to pressure of work
• Suspended for 3 months




 Plagiarism
                                           http://tinyurl.com/persaud11
Hwang Woo-Suk (2004-05)
                             • 2 landmark papers in Science reporting
                               production of human embryonic stem
                               cells via Somatic Cell Nuclear Transfer
                             • Data fabricated and falsified
                             • Also obtained human eggs for research
http://tinyurl.com/hwang11     by unethical means, including requiring
                               female team members to superovulate
             • Suspended prison sentence for
 Fabrication embezzlement
 Falsification
 Exploitation
 Embezzlement
Gerald Schatten (2005)
• Corresponding author and




                                       http://tinyurl.com/schatten11
  senior scientist on 2nd Hwang
  paper
• U of Pittsburgh investigation
  found him innocent of fraud
  but said he “shirked” his
  responsibility to validate results
• Guilty of “research misbehaviour”
  not “research misconduct”



 Irresponsible authorship
Jon Sudbo (1993-2005)
• Research into prevention of oral cancer at Norwegian
  Radium Hospital, Oslo
• 2005 paper in Lancet raised almost instant accusation
  of fabrication as it included 900 patients from
  database that didn‟t exist at time cited
• Also found that second image in a 2001 NEJM paper
  just enlargement of first
• Eventually 15 papers (plus
  PhD) retracted

 Fabrication
 Falsification                            http://tinyurl.com/sudbo11
Vipul Bhrigu (2010)
                                           • U Michigan PhD student Heather Ames
http://tinyurl.com/amesbhrigu11




                                             struggled to get expts to work in her
                                             own lab, but worked fine in boyfriend‟s
                                             lab
                                           • Suspected PostDoc Vipul Bhrigu (inset)
                                             was sabotaging expts
                                           • Set up concealed camera and caught
                                             Bhrigu adding ethanol to cell culture




                                                                                     http://tinyurl.com/bhriguvideo
                                           • April 2011 pleaded
                                             guilty to destruction

                         Fabrication (sabotage)
Conclusions
Why tell students about misconduct?
  • It happens, we need to be realistic
  • Serves as warning: demonstrates points where
    acceptable action has been breached
Would you tell so many stories back-to-back?
  • Probably not, purpose today was to share a
    catalogue from which suitable cases can be picked
  • I use several in introductory lecture (van Velzen,
    Schön, Sudbø, Wakefield, Hwang, Persaud)
  • Others at relevant point (e.g. Wilson, Hwang)
Thank you
E-mail:    cjrw2@le.ac.uk
Twitter:   cjrw
Slideshare: cjrw2
Delicious: chriswillmott
Blogs:     www.bioethicsbytes.wordpress.com
           www.biosciencecareers.wordpress.com
           www.lefthandedbiochemist.wordpress.com

                                       University of
                                       Leicester

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(In)famous cases of research misconduct

  • 1. Teaching Research Ethics to Bioscience Students, May 2011 “You don't want to do it like that”: some (in)famous examples of research misconduct Dr Chris Willmott Dept of Biochemistry, University of Leicester cjrw2@le.ac.uk University of Leicester http://tinyurl.com/ydwtdilt2011
  • 2. Classification of misconduct (1) Misconduct that distorts scientific knowledge • Fabrication – reporting of non-existent data • Falsification – selective reporting of data Misconduct that misleads the scientific community • Authorship: Plagiarism, „Guest‟ authors, „Ghost‟ authors • Duplicate publication • Abuse of the peer-review process “FFP” = Fabrication, Falsification, Plagiarism
  • 3. Classification of misconduct (2) Misconduct relating to human subjects • Consent issues • Exploitation issues (inc. financial) Other issues • Conflicts of Interest • Poor record-keeping • Failure to obtain necessary ethical approval • Incidental findings?
  • 4. Selection of cases for discussion • Sadly there are plenty more cases than can be discussed in time available • Omitted alleged cases before 1900 • Omitted cases where there is significant minority dissent re guilt • Omitted cases from outside biology and biomedicine • Have tried to balance UK, USA and other countries • Have looked for combination of classic, curious and contemporary cases reflecting range of different types of misconduct i.e. cases likely to be useful in teaching
  • 5. Piltdown Man (1912) http://tinyurl.com/dawsonhinton • Report of hominid remains found in Sussex • “Missing link”? • Later shown to be skull of modern man and jawbone of orang-utan • Fraud certain, but identity of culprit still uncertain - Charles Dawson? - Martin Hinton?  Fabrication http://tinyurl.com/piltdownskull
  • 6. Tuskegee Syphilis Study (1932-72) • Poor African-Americans with advanced syphilis recruited to trial to study their “bad blood” • Deliberately untreated to see long-term effects of infection, http://tinyurl.com/tuskegee11 even when treatments became available (e.g. Penicillin) • Over 400 men (plus families) involved  Consent • Breach of human rights  Exploitation  (Racism)
  • 7. Nazi doctors (1940s) • Medical experiments conducted on prisoners - sterilisation - modelling of battlefield wounds and infection - physiological response to extreme conditions - bizarre transplantation and twin studies • Doctors included “Angel of Death” Joseph Mengele (escaped), plus several put on trial and hanged • Led to Nuremberg Code of conduct for research involving human subjects (1947)  Consent  Exploitation
  • 8. Porton Down (1940s-60s) • Series of experiments conducted at Porton Down, UK Government and military research centre • Participants thought they were volunteering for trials to find things such as cure for common cold • Actually exposed to LSD, sarin, mustard gas, etc • 2008, MOD agreed to £3M payout to surviving veterans  Consent  Exploitation http://tinyurl.com/portondown
  • 9. William Summerlin (1974) • Researching ways to overcome tissue rejection at Sloan-Kettering Institute in New York • Included transplanting fur from black mouse onto white mouse • “Transplanted” patches actually drawn on with black marker pen (removable with alcohol)  Fabrication
  • 10. Vijay Soman & Philip Felig (1978) • NEJM sent Felig paper for review http://tinyurl.com/soman11 http://tinyurl.com/felig11 • Felig passed paper to junior colleague Soman • They rejected paper • Few months later, Am J Medicine sent original author paper by Soman to review • Sections clearly copied from hers, plus additional material later shown to be made up  Plagiarism  Fabrication  Violation of peer-review process
  • 11. Dick van Velzen (1988-95) • Senior pathologist at Alder Hey Children‟s Hospital • Expert in cot death, was found to have organs from about 850 children without appropriate permission • Struck off by GMC • Along with scandal at Bristol Royal Infirmary led to Human Tissue Act (2004)  Consent  Fabrication http://tinyurl.com/vanveltzen05
  • 12. Eric Poehlman (1992-2002) • Research into ageing, menopause and Hormone Replacement Therapy, working primarily at Uni of Vermont • Misconduct exposed by former lab technician Walter DeNino • Pleaded guilty to falsifying 17 grant http://tinyurl.com/poehlman applications and fabricating data in 10 research papers • 2006, first scientist jailed for fraud (also fined $200K)  Fabrication  Falsification
  • 13. Malcolm Pearce (1994-95) • Obstetrician at St George‟s, London • Reported transplant of ectopic pregnancy to uterus and live birth • Colleagues at same hospital said no knowledge of case • Pearce tried to hack computer to alter notes • Also found to have invented patients in study on polycystic ovary syndrome http://tinyurl.com/pearce11 • Struck off by GMC  Fabrication
  • 14. Geoffrey Chamberlain (1995) • Linked to Malcolm Pearce case • World reknowned ultrasound expert • Chamberlain was Pearce‟s Head of Dept, and Editor of British Journal of Obstetrics and Gynaecology where both fraudulent papers were published • Accepted “gift authorship” for ectopic pregnancy paper • Reprimanded by GMC • “A considerable error of judgement” (Wells, 2008)  Gift authorship http://tinyurl.com/chamberlain11
  • 15. Andrew Wakefield (1998) • Author on infamous Lancet paper linking autism with MMR vaccine • Investigation for >2 years (ended May 2010) decided he was guilty of conflict of interest, both as recipient of money from lawyer looking for link to vaccine, and regarding company he set up looking to market test • Highly selective reporting of data • Unethical dealings with children http://tinyurl.com/wakefield11  Consent  Exploitation  Conduct of clinical trial  Conflict of Interest (financial)
  • 16. James Wilson (1999) • Conducted clinical trial using gene therapy to combat OTC deficiency at U of Pennsylvania in which Jesse Gelsinger died • President and major shareholder (30%) in Genova, company http://tinyurl.com/jwilson11 developing product under test • Failed to report extent of adverse reactions during animal testing  Consent  Conduct of clinical trial  Conflict of Interest (financial)
  • 17. Raj Persaud (2003 & 2005) • Celebrity psychologist appearing regularly on TV and radio (including own show All In The Mind on R4) • 2003 book From the Edge of the Couch and various other writings including article on scientology • Admitted plagiarism but claimed it was accidental due to pressure of work • Suspended for 3 months  Plagiarism http://tinyurl.com/persaud11
  • 18. Hwang Woo-Suk (2004-05) • 2 landmark papers in Science reporting production of human embryonic stem cells via Somatic Cell Nuclear Transfer • Data fabricated and falsified • Also obtained human eggs for research http://tinyurl.com/hwang11 by unethical means, including requiring female team members to superovulate • Suspended prison sentence for  Fabrication embezzlement  Falsification  Exploitation  Embezzlement
  • 19. Gerald Schatten (2005) • Corresponding author and http://tinyurl.com/schatten11 senior scientist on 2nd Hwang paper • U of Pittsburgh investigation found him innocent of fraud but said he “shirked” his responsibility to validate results • Guilty of “research misbehaviour” not “research misconduct”  Irresponsible authorship
  • 20. Jon Sudbo (1993-2005) • Research into prevention of oral cancer at Norwegian Radium Hospital, Oslo • 2005 paper in Lancet raised almost instant accusation of fabrication as it included 900 patients from database that didn‟t exist at time cited • Also found that second image in a 2001 NEJM paper just enlargement of first • Eventually 15 papers (plus PhD) retracted  Fabrication  Falsification http://tinyurl.com/sudbo11
  • 21. Vipul Bhrigu (2010) • U Michigan PhD student Heather Ames http://tinyurl.com/amesbhrigu11 struggled to get expts to work in her own lab, but worked fine in boyfriend‟s lab • Suspected PostDoc Vipul Bhrigu (inset) was sabotaging expts • Set up concealed camera and caught Bhrigu adding ethanol to cell culture http://tinyurl.com/bhriguvideo • April 2011 pleaded guilty to destruction  Fabrication (sabotage)
  • 22. Conclusions Why tell students about misconduct? • It happens, we need to be realistic • Serves as warning: demonstrates points where acceptable action has been breached Would you tell so many stories back-to-back? • Probably not, purpose today was to share a catalogue from which suitable cases can be picked • I use several in introductory lecture (van Velzen, Schön, Sudbø, Wakefield, Hwang, Persaud) • Others at relevant point (e.g. Wilson, Hwang)
  • 23. Thank you E-mail: cjrw2@le.ac.uk Twitter: cjrw Slideshare: cjrw2 Delicious: chriswillmott Blogs: www.bioethicsbytes.wordpress.com www.biosciencecareers.wordpress.com www.lefthandedbiochemist.wordpress.com University of Leicester