Étude de cas / Case studyLe cas de M. Andrew Gobea, le premier enfant à recevoir une thérapie génique expérimentale pour le déficience immunitaire combinée sévère (DICS), et une réflexion sur les implications éthiques associées à la recherche en thérapie génique.The case of Andrew Gobea, the first child to receive experimental gene therapy for severe combined immunodeficiency (SCID), and a reflection on the associated ethical implications of gene therapy research

Williams-Jones, Bryn

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B Williams-Jones BioéthiqueOnline 2012, 1/4(http://bioethiqueonline.ca/1/4)Somatic Cell Therapy: A Genetic Rescue for a Tattered Immune System?ÉTUDE DE CAS / CASE STUDYBryn Williams-Jones1Reçu/Received: 25 Oct 2011 Publié/Published: 19 Mar 2012Éditeurs/Editors: Maude Laliberté & Renaud Boulanger© 2012 B Williams-Jones, Creative Commons Attribution 3.0 Unported LicenseRésumé SummaryLe cas de M. Andrew Gobea, le premier enfant à recevoir une  thérapie  génique  expérimentale  pour  le  déficience immunitaire combinée sévère (DICS), et une réflexion sur les  implications  éthiques  associées  à  la  recherche  en thérapie génique.The  case  of  Andrew  Gobea,  the  first  child  to  receive experimental  gene  therapy  for  severe  combined immunodeficiency  (SCID),  and  a  reflection  on  the associated ethical implications of gene therapy research.Mots clés Keywordscellules  somatiques,  la  thérapie  génique,  la  recherche expérimentale, les essais cliniquessomatic cell,  gene therapy, experimental research, clinical trialsAffiliations des auteurs / Author Affiliations1  Programmes de  bioéthique,  Département  de  médecine  sociale  et  préventive,  Faculté  de  médecine,  Université  de Montréal, Montréal, CanadaCorrespondance / CorrespondenceBryn Williams-Jones, bryn.williams-jones@umontreal.caRemerciements AcknowledgementsJe  tiens  à  remercier  les  éditeurs,  Maude  Laliberté  et Renaud Boulanger,  pour  leurs précieux commentaires et corrections.I  would  like  to  thank  the  editors,  Maude  Laliberté  and Renaud  Boulanger,  for  their  helpful  comments  and corrections.Conflit d'intérêts Conflicts of InterestBryn Williams-Jones est  l’éditeur  en chef de la  revue et directeur de thèse de Maude Laliberté.Bryn  Williams-Jones  is  the  Editor-in-chief  of  the  Journal, and PhD supervisor of Maude Laliberté.This  case  study,  which  is  based  on  the  PBS  story  "A Genetic  Rescue  for  a  Tattered  Immune  System?"[1],  was  initially  published  in  shorter  form  on  my  website,  Genethics.ca,  in  2002  (http://genethics.ca/somatictherapy.html).The Case Andrew Gobea was born in  1993 with  a rare,  normally  fatal  genetic  disease – severe combined immunodeficiency (SCID).[2] SCID – which can take various forms – destroys much of the immune system,  particularly  the  T  cells,  leaving  newborns  defenseless  against  infection.[3]  There  are  a number of causes for SCID, but, in Andrew’s case, he had two defective copies of the gene that codes for a critical enzyme, adenosine deaminase (ADA). Without the enzyme, the body fails to break down chemicals produced during normal metabolism that are toxic to T cells; and without T cells, there is no immunity, and with no immunity, death is inevitable.A bone marrow transplant from a tissue-matched donor, usually a sibling, is the most common and effective treatment for SCID. Unfortunately, it is relatively rare that a person such as Andrew would find a matched donor, even within their family; as a result, they must be put on a waiting list to obtain  a bone marrow transplant from an unrelated matched donor.[3] In 1993, however, a novel treatment – ISSN 1923-2799 1 / 3B Williams-Jones BioéthiqueOnline 2012, 1/4(http://bioethiqueonline.ca/1/4)experimental gene therapy – existed that offered the potential to keep Andrew alive. Working copies of the ADA gene would be inserted into the T cells, in cord blood stem cells, and then re-introduced into  Andrew’s system. But Andrew’s condition meant that his stem cells also lacked a functioning ADA gene, so a modified virus would be used to insert a working ADA gene into these cells. The hope was that the virus would infect and then deposit the genes into enough cells to give Andrew a working immune system.At only 4 days old, Andrew Gobea became the first baby to receive gene therapy using cord blood cells.[4] Some of the cells did indeed take up the gene and began producing T cells with a functioning ADA gene. To insure Andrew’s survival, though, he had to be given weekly injections of the missing ADA enzyme, at the time at a cost of $2,200US per dose. These injections worked to clear the toxic metabolites out of his blood stream and allow the uncorrected T cells to survive. When Andrew was 18 months old, his doctor began tapering off the amount of enzyme in the injections, to see if the T cells that produce ADA could take over; and at four years old, he was cut off the enzyme altogether. For two months, things went well, but then Andrew caught a cold, which developed into a yeast infection of the mouth, something commonly found in immunocompromised patients. Andrew’s immune system was  crashing  and  it  was  necessary  to  resume  the  ADA treatment.  The  modified  genes  did  not succeed in getting integrated into a sufficient number of cells to maintain the effect, and thus Andrew continues to need regular enzyme doses. The challenge for future research would be to find ways to get more cells to take up their message and keep producing the enzymes or other proteins critical for a patient’s health.Gene therapy for SCID again made the news in 2000, when two children in a clinical trial showed the  development  of  functioning  immune systems.  But  the  clinical  trial  was stopped  when two of  the participants were found to have developed leukemia[5]. Ten years later – and 18 years since Andrew first  received his treatment – and the early hopes of gene therapy for SCID are starting to show promise; most of the children in two recent studies had functioning immune systems, re-igniting the hope that a cure for SCID is near.[6]Questions to consider:1. Is the time and money involved in gene therapy research worth the investment given the still  relatively  low  success  rate  of  clinical  trials?  Should  such  economic  issues  not  be  a consideration? How would one decide?2. Is experimental gene therapy ethically different from other novel treatments, in terms of how we should evaluate the balance of risks and benefits?3. Does the potential benefit of gene therapy for SCID (or for other rare disease) to provide a permanent  cure  (instead  of  regular  treatment)  justify  the  risks  that  patients  take  (e.g.,  of developing leukemia, other cancers)?4. What risks should Andrew, his family, and society at large consider with regards to the use of  modified viruses as vectors for gene therapy?5. Are families of children such as Andrew being given unreasonable hope that a cure is “around the corner” when they consent for their children to participate in clinical trials? List of References1. 1997. “Cracking the Code: A Genetic Rescue for a Tattered Immune System?” PBS Innovation Program, December 16.ISSN 1923-2799 2 / 3B Williams-Jones BioéthiqueOnline 2012, 1/4(http://bioethiqueonline.ca/1/4)2. Stolberg, S. 1993.“Baby 1st to Receive Gene Treatment : Medicine: Childrens Hospital team uses the therapy on a newborn in historic surgery. Doctors hope to cure his rare immune disorder before disease sets in.” Los Angeles Times, May 16. (http://articles.latimes.com/1993-05-16/news/mn-36196_1_gene-therapy/2)3. 2011. “Learning About Severe Combined Immunodeficiency (SCID)” National Human Genome Research Institute (http://www.genome.gov/13014325) Updated, Oct 3 2011.4. Stolberg, S. 1993. “4-Day-Old Trailblazer: Gene Therapy Used On Newborn For First Time” Los Angeles Times, May 17. (http://community.seattletimes.nwsource.com/archive/?date=19930517&slug=1701701) 5. Check, E. 2002. “Gene therapy: A tragic setback” Nature 420(6912): 116-118 (http://www.nature.com/nature/journal/v420/n6912/full/420116a.html)6. Check Hayden, E. 2011. “Gene-therapy successes spur hope for embattled field: Technique now being tested in a range of conditions.” Nature (http://www.nature.com/news/2011/110824/full/news.2011.500.html)ISSN 1923-2799 3 / 3

Somatic Cell Therapy: A Genetic Rescue for a Tattered Immune System?

The case of Andrew Gobea, the first child to receive experimental gene therapy for SCID, and a reflection on the associated ethical implications of gene therapy research

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Somatic Cell Therapy: A Genetic Rescue for a Tattered Immune System?

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