Personal Genomes and Ethical Issues How to Analyze Your Own Genome

Personal Genomes and Ethical Issues 02-­‐223  How  to  Analyze  Your  Own  Genome  

Declining Cost of Genome Sequencing •  The  genome  sequencing  is  expected  to  happen  rouAnely  in   the  near  future    

Schadt,  MSB,  2012  

The  era  of  big  data:  the  genome  data  are  already  being  collected  in  a   large  scale  and  being  mined  for  scienAfic  discovery  to  drive  more   accurate  descripAve  and  predicAve  models  that  inform  decision   making  for  the  best  diagnosis  and  treatment  choice  for  a  given  paAent.    

Would  you  post  your  genome  on  the  web?  

Genomes and Privacy •  DNA  sequence  data  contain  informaAon  that  can  be  used  to   uniquely  idenAfy  an  individual  (i.e.,  genome  sequences  are   like  fingerprints)   •  Balancing  the  need  for  scienAfic  study  and  privacy  

Genomes and Privacy •  Privacy  concerns   –  Genome  sequence  data  and  other  related  types  of  data  (gene   expressions,  clinical  records,  epigeneAc  data,  etc.)  are  collected  for  a   large  number  of  paAents  for  medical  research   –  Most  types  of  data  are  freely  available  through  internet  except  for   genotype  data     •  NCBI  GEO  database  for  gene  expression  data   •  The  cancer  genome  atlas  data  portals   –  Genotype  data  are  available  to  scienAsts  through  restricted  access   –  ProtecAng  parAcipants’  privacy  through  informed  consent      

The Cancer Genome Atlas (TCGA) Data

hWps://tcga-­‐data.nci.nih.gov/tcga/tcgaHome2.jsp  

The Cancer Genome Atlas (TCGA) Data

hWps://tcga-­‐data.nci.nih.gov/tcga/tcgaCancerDetails.jsp? diseaseType=LAML&diseaseName=Acute%20Myeloid%20Leukemia  

Access Control for TCGA Data •  Open  access  data  Aer   –  –  –  –  – 

De-­‐idenAfied  clinical  and  demographic  data   Gene  expression  data   Copy-­‐number  alteraAons  in  regions  of  the  genome   EpigeneAc  data   Summaries  of  data,  such  as  genotype  frequencies,  compiled  across   individuals  

•  Controlled-­‐access  data  Aer   –  Individual  germline  variant  data   –  DNA  sequence  data   –  One  should  apply  for  an  access  to  the  data  through  NIH  (database  of   genotypes  and  phenotypes)  

Informed Consent for Scientific Research •  Standard  pracAce  for  enrolling  human  subjects  in  a  research   study     –  fully  informing  potenAal  parAcipants  on  all  aspects  of  a  study  including   the  aims  of  the  study,  risks,  benefits,  costs,  and  protecAon  of  personal   privacy   –  The  origins  of  modern  day  informed  consent  for  medical  research  can   be  traced  to  the  Nuremberg  Code  in  1947  in  an  effort  to  protect   parAcipants  in  research  studies  (Homan,  1991).    

Nuremberg Code •  Research  ethics  principles  for  human  experimentaAon     •  Established  ader  the  Nuremberg  Trials  at  the  end  of  the   Second  World  War  

hWp://www.hhs.gov/ohrp/archive/nurcode.html  

Nuremberg Code •  On  August  19,  1947,  the  judges  of  the  American  military  tribunal  in  the  case  of  the   USA  vs.  Karl  Brandt  et.  al.  delivered  their  verdict.  Before  announcing  the  guilt  or   innocence  of  each  defendant,  they  confronted  the  difficult  quesAon  of  medical   experimentaAon  on  human  beings.  Several  German  doctors  had  argued  in  their   own  defense  that  their  experiments  differed  liWle  from  previous  American  or   German  ones.  Furthermore  they  showed  that  no  internaAonal  law  or  informal   statement  differenAated  between  legal  and  illegal  human  experimentaAon.  This   argument  worried  Drs.  Andrew  Ivy  and  Leo  Alexander,  American  doctors  who  had   worked  with  the  prosecuAon  during  the  trial.  On  April  17,  1947,  Dr.  Alexander   submiWed  a  memorandum  to  the  United  States  Counsel  for  War  Crimes  which   outlined  six  points  defining  legiAmate  research.  The  verdict  of  August  19  reiterated   almost  all  of  these  points  in  a  secAon  enAtled  "Permissible  Medical  Experiments"   and  revised  the  original  six  points  into  ten.  Subsequently,  the  ten  points  became   known  as  the  "Nuremberg  Code."  Although  the  code  addressed  the  defense   arguments  in  general,  remarkably  none  of  the  specific  findings  against  Brandt  and   his  codefendants  menAoned  the  code.  Thus  the  legal  force  of  the  document  was   not  well  established.  The  uncertain  use  of  the  code  conAnued  in  the  half  century   following  the  trial  when  it  informed  numerous  internaAonal  ethics  statements  but   failed  to  find  a  place  in  either  the  American  or  German  naAonal  law  codes.   Nevertheless,  it  remains  a  landmark  document  on  medical  ethics  and  one  of  the   most  lasAng  products  of  the  "Doctors  Trial."   hWp://www.ushmm.org/informaAon/exhibiAons/online-­‐features/special-­‐focus/doctors-­‐trial/ nuremberg-­‐code  

Institutional Review Board (IRB) •  A  commiWee  that  has  been  formally  designated  to  approve,   monitor,  and  review  biomedical  and  behavioral  research   involving  humans   •  Title  45  Code  of  Federal  RegulaAons  Part  46   –  hWp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html  

Current Generation Informed Consents •  Single  study  focused   •  Top-­‐down  unidirecAonal  researcher-­‐parAcipant  (research  subject)   relaAonship.       •  ProtecAng  the  parAcipant  is  considered  among  the  chief  aims   •  Data  generaAon  on  study  parAcipants  usually  an  integral  part  of  the   consent   •  Data  ownership  and  terms  of  use  driven  by  the  invesAgator  and/or  hosAng   insAtuAon   •  Study  parAcipants  are  counseled  to  ensure  they  understand  all  aspects  of   the  study,  although  no  evidence  of  understanding  is  sought  or  required   •  In  most  cases,  anonymity,  privacy,  and  confidenAality  are  guaranteed  as  a   key  condiAon  for  a  parAcipant’s  consent   •  Big  data,  more  open  data  sharing  mentality  demand  a  new  genera