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{\author Michele Rose Woodruff}{\operator Chad and Sarah Ludington}{\creatim\yr2004\mo6\dy22\hr12\min15}{\revtim\yr2004\mo6\dy22\hr12\min15}{\printim\yr2004\mo5\dy24\hr8\min11}{\version2}{\edmins1}{\nofpages14}{\nofwords12395}{\nofchars70656}
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Gene Therapy: Cure or Poison?
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The Proper Role of the FDA in the Bubble Boy Disease Question
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\par }\pard \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\i\fs36 \hich\af0\dbch\af17\loch\f0 Michele Rose Woodruff
\par }\pard \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\i\fs36 \hich\af0\dbch\af17\loch\f0 Class of 2004
\par \hich\af0\dbch\af17\loch\f0 Submitted May 24, 2004
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\par }\pard \s2\qc \li0\ri0\sl480\slmult1\keepn\widctlpar\aspalpha\aspnum\faauto\outlinelevel1\adjustright\rin0\lin0\itap0 {\fs18 \hich\af0\dbch\af17\loch\f0 this paper is submitted to satisfy the course requirement and the written requirem
\hich\af0\dbch\af17\loch\f0 ent.
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\hich\af0\dbch\af17\loch\f0 ...........................................................................................3}{
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The Disease..............................................................................14
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\hich\af0\dbch\af17\loch\f0  Regulator}{\fs32 \hich\af0\dbch\af17\loch\f0 ...................................................................33}{
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The FDA and The NIH............................................................33
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{\pntxta .}}\aspalpha\aspnum\faauto\ls3\outlinelevel7\adjustright\rin0\lin1215\itap0 {\fs32 \hich\af0\dbch\af17\loch\f0 The Trials.................................................................................38
\par }\pard\plain \qj \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\par }{\scaps\fs44 \hich\af0\dbch\af17\loch\f0 IV. The Society}{\fs32 \hich\af0\dbch\af17\loch\f0 ...........................................................................47}{\scaps\fs44 
\par {\pntext\pard\plain\s8 \fs32\cf1\lang1033\langfe2052\dbch\af17\langfenp2052 \hich\af0\dbch\af17\loch\f0 A.\tab}}\pard\plain \s8\qj \fi-495\li1215\ri0\keepn\widctlpar\jclisttab\tx1215{\*\pn \pnlvlbody\ilvl0\ls4\pnrnot0
\pnucltr\pnstart1\pnindent360\pnsp120\pnhang{\pntxta .}}\aspalpha\aspnum\faauto\ls4\outlinelevel7\adjustright\rin0\lin1215\itap0 \fs44\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\fs32 \hich\af0\dbch\af17\loch\f0 
The Rights................................................................................47
\par {\pntext\pard\plain\s8 \fs32\cf1\lang1033\langfe2052\dbch\af17\langfenp2052 \hich\af0\dbch\af17\loch\f0 B.\tab}}\pard \s8\qj \fi-495\li1215\ri0\keepn\widctlpar\jclisttab\tx1215{\*\pn \pnlvlbody\ilvl0\ls4\pnrnot0\pnucltr\pnstart1\pnindent360\pnsp120\pnhang
{\pntxta .}}\aspalpha\aspnum\faauto\ls4\outlinelevel7\adjustright\rin0\lin1215\itap0 {\fs32 \hich\af0\dbch\af17\loch\f0 The Lives............................................................\hich\af0\dbch\af17\loch\f0 .....................53
\par }\pard\plain \qj \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\par }\pard\plain \s25\qj \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \scaps\fs44\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 V. Conclusion}{\fs32 
\hich\af0\dbch\af17\loch\f0 .............................................................................55}{
\par }\pard\plain \qj \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\par }\pard\plain \s25\qj \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \scaps\fs44\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 Bibliography}{\fs32 
\hich\af0\dbch\af17\loch\f0 ...............................................................................56}{
\par }\pard\plain \qj \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\par }\pard\plain \s2\qj \li0\ri0\sl480\slmult1\keepn\widctlpar\aspalpha\aspnum\faauto\outlinelevel1\adjustright\rin0\lin0\itap0 \scaps\fs44\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 Acronyms
}{\fs32 \hich\af0\dbch\af17\loch\f0 ..................................\hich\af0\dbch\af17\loch\f0 .....................................................60}{\b\fs52 
\par }\pard\plain \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\par }\pard\plain \s2\qc \li0\ri0\sl480\slmult1\keepn\widctlpar\aspalpha\aspnum\faauto\outlinelevel1\adjustright\rin0\lin0\itap0 \scaps\fs44\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\fs52 \page 
\hich\af0\dbch\af17\loch\f0 Abstract
\par }\pard\plain \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 \hich\f0 
On January 14, 2003, the Food and Drug Administration \'93\loch\f0 suspended 27 gene therapy trials involving several hundred patients after learning that a second child treated in France had developed\hich\af0\dbch\af17\loch\f0 \hich\f0 
 a condition resembling leukemia.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  Andrew Pollack, \'93\loch\f0 \hich\f0 Gene Therapy Trials Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The New York Times}{\hich\af0\dbch\af17\loch\f0 , Jan
\hich\af0\dbch\af17\loch\f0 uary 15, 2003 at Health and at http://www.newyorktimes.com/2003/01/15/health/15GENE.html.}}}{\hich\af0\dbch\af17\loch\f0 
  Gene therapy treats diseases caused by defective genes by introducing healthy genes into the body.  For patients who are battling life-threatening diseases, the only chance of survival may be the hope of gene therapy, p\hich\af0\dbch\af17\loch\f0 
\hich\f0 erhaps because there is no known cure, no available matched transplant donor, or no cures without even worse side effects.  \'93\loch\f0 \hich\f0 Some of the trials being halted are intended to treat AIDS and cancer.\'94}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 Id.}}}{
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 The \'93\loch\f0 \hich\f0 second child treated in France,\'94\loch\f0  who caused the alarm\hich\af0\dbch\af17\loch\f0 \hich\f0 
, had received gene therapy treatment not for AIDS or cancer, but for the less common ailment \'93\loch\f0 \hich\f0 bubble boy disease,\'94\loch\f0 
 a severe and fatal immunodeficiency disorder.  Bubble boy disease attacks newborn boys, who while in the womb, relied on their mother\hich\f0 \rquote \loch\f0 s imm\hich\af0\dbch\af17\loch\f0 u\hich\af0\dbch\af17\loch\f0 
nity but, once born, are left helpless in fighting other diseases that attack their infant bodies.  With the trials halted, parents are left helpless to seek gene therapy for their children.  Is it right to eliminate alternate, but risky remedies? 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs16 \page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 I.  In\hich\af0\dbch\af17\loch\f0 troduction}{\fs52\ul 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 What is \'93\loch\f0 \hich\f0 bubble boy disease?\'94\loch\f0 
  Bubble boy disease is the popular term for a condition that leaves a male child without a working immune system.  The child can rely on the immunity transferred to him from his mother while in the womb, but once bo\hich\af0\dbch\af17\loch\f0 \hich\f0 
rn, the immunity promptly wears off, leaving the child helpless against disease.  Although other immunodeficiency disorders as acquired immunodeficiency syndrome (\'93\loch\f0 \hich\f0 AIDS\'94\loch\f0 )}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 This paper uses numerous acronyms.  Although these acronyms are defined repeatedly throughout the paper, a list of acronyms used is attached at the end of thi\hich\af0\dbch\af17\loch\f0 s paper.}}}{\hich\af0\dbch\af17\loch\f0 
 may be more notorious, bubble boys are fighting the same deadly handicap.  Since the\hich\af0\dbch\af17\loch\f0 \hich\f0 
 child cannot depend on a normal, healthy immune system to fight off diseases, a common cold can quickly worsen into pneumonia and be deadly.  \'93\loch\f0 
Without an immune system, a patient is completely vulnerable to infection a pathogen that would be harmless to \hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 \hich\f0  person with normal immunity would destroy a SCID patient.\'94}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0 
 \'93\loch\f0 Early Marrow Transplant May be Key to \hich\f0 \lquote \loch\f0 Bubble Boy\hich\f0 \rquote \loch\f0 \hich\f0  Disease Cure,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Doctor\hich\f0 \rquote \loch\f0 s Guide, }{
\hich\af0\dbch\af17\loch\f0 May 5, 1997 at http://www.pslgroup.com/dg/25666.htm.}}}{\hich\af0\dbch\af17\loch\f0  Unfortunately, unlike AIDS, there is no way to prevent this genetic disease, and left untreated, death is certain within two years.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 FDA Places Temporary Halt on Gene Therapy Trials Using Retroviral Vectors in Blood Stem Cells,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 FDA Talk P\hich\af0\dbch\af17\loch\f0 aper, }{
\hich\af0\dbch\af17\loch\f0 \hich\f0 January 14, 2003 at http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html (\'93\loch\f0 
Infants with X-SCID have a gene defect that leads to a complete lack of white blood cells that can fight infection.  Without treatment, they die from complications of infe\hich\af0\dbch\af17\loch\f0 \hich\f0 ctious diseases during the first year of life.
\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   Thus, it was the custom to isolate bubble boy patients in a p\hich\af0\dbch\af17\loch\f0 lastic bubble to keep out germs.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Who are these bubble boys?  Bubble boy disease is extremely rare, affecting only 0.001 percent of children at birth.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Homo Sapiens Diseases Immunity,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Molecular Immunology }{\hich\af0\dbch\af17\loch\f0 \hich\f0 
at http://xoomer.virgilio.it/medicine/pathohomotissueimmunity.html (\'93\loch\f0 severe combined immunodeficiency (SCID) / Swiss type agammaglobulinemia / \hich\f0 \lquote \loch\f0 bubbl\hich\af0\dbch\af17\loch\f0 e boy disease / syndrome\hich\f0 \rquote 
\loch\f0 \hich\f0  Epidemiology :  1 in 75,000 live births (1 in 100,000 live male births).\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 New Cure For Bubble Boy Disease,\'94
\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 CBS News, }{\hich\af0\dbch\af17\loch\f0 \hich\f0 April 17, 2002 at http://www.cbsnews.com/stories/2002/04/17/tech/main506451.shtml  (\'93\loch\f0 The five Frenc\hich\af0\dbch\af17\loch\f0 \hich\f0 
h boys were born with severe combined immunodeficiency, or SCID, an inherited disease that occurs in about 1 in 75,000 births.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  Yet it is a death sentence without explanation.  The only available treatment for these boys is bone mar\hich\af0\dbch\af17\loch\f0 row transplants.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 
FDA Places Temporary Halt on Gene Therapy Trials Using Retroviral Vectors in Blood Stem Cells,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 FDA Talk Paper, }{\hich\af0\dbch\af17\loch\f0 January 14,\hich\af0\dbch\af17\loch\f0 \hich\f0 
 2003 at http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html (\'93\loch\f0 \hich\f0 The only treatment for this condition is a bone marrow transplant.\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  
\'93\loch\f0 \hich\f0 Inherited (Congenital) Immune System Disorders,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0  at http://www.marrow.org\hich\af0\dbch\af17\loch\f0 \hich\f0 
/MEDICAL/immune_sys_disorders.html (\'93\loch\f0 \hich\f0 For almost all congenital immune system disorders, however, the treatment of choice is a blood stem cell transplant.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  Transplants require finding a matched and willing donor.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Inherited (Congenital) Immune System Disorders,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0  at http://www\hich\af0\dbch\af17\loch\f0 \hich\f0 .marrow.org/MEDICAL/immune_sys_disorders.html  (\'93\loch\f0 
The main obstacle to a blood stem cell transplant is lack of a matching donor.  Doctors first look for donors in a patient\hich\f0 \rquote \loch\f0 \hich\f0 s family, but only about one in four patients find a match in their own family.\'94\loch\f0 ). 
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 But see}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Early Marrow Transplant May be Key to \hich\f0 \lquote \loch\f0 Bubble Boy\hich\f0 \rquote \loch\f0 \hich\f0  Disease Cure,\'94
\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Doctor\hich\f0 \rquote \loch\f0 s Guide, }{\hich\af0\dbch\af17\loch\f0 \hich\f0 May 5, 1997 at http://www.pslgroup.com/dg/25666.htm (\'93\loch\f0 
They also have learned that these children need not have a perfectly matched donor, but can use a parent\hich\f0 \rquote \loch\f0 s \hich\f0 \lquote \loch\f0 hal\hich\af0\dbch\af17\loch\f0 f-matched\hich\f0 \rquote \loch\f0  marrow. . . .  \hich\f0 
\lquote \loch\f0 Until 1982, SCID was invariably fatal unless the patient had a brother or sister who was an exact match to donate bone marrow,\hich\f0 \rquote \loch\f0  [Rebecca] Buckley [chief of Duke\hich\f0 \rquote \loch\f0 
s division of pediatric allergy and immunology] explained.  \hich\f0 \lquote \loch\f0 What w\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0  see now is that a sibling match isn\hich\f0 \rquote \loch\f0 
t necessary; haploidentical parental marrow will work, too.\hich\f0 \rquote \loch\f0 \hich\f0   A haploid match is a half match.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   Transplants have the dangers associated with any surgical procedure.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  However, bubble boys no longer endure difficult pre-transplant treatments to prepare the body for the transplant, inclu\hich\af0\dbch\af17\loch\f0 ding radiation and chemotherapy. }{\i \hich\af0\dbch\af17\loch\f0  Compare }{
\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Early Marrow Transplant May be Key to \hich\f0 \lquote \loch\f0 Bubble Boy\hich\f0 \rquote \loch\f0 \hich\f0  Disease Cure,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Doctor\hich\f0 \rquote \loch\f0 
s Guide, }{\hich\af0\dbch\af17\loch\f0 \hich\f0 May 5, 1997 at http://www.pslgroup.com/dg/25666.htm (\'93\loch\f0 Furthermore, the babies do not need toxic pre-transplant chemotherapy, as is \hich\af0\dbch\af17\loch\f0 
often thought and currently practiced. . . .  [Rebecca] Buckley [chief of Duke\hich\f0 \rquote \loch\f0 
s division of pediatric allergy and immunology] also found that transplants can be done without exposing the infant to toxic chemotherapy, which can have life-long repercussion\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 
.  Many doctors give chemotherapy to all bone marrow transplant patients because they are following standard cancer treatment protocol, Buckley said.  But chemotherapy is not necessary in children with SCID because they have no T-cells to attack and destr
\hich\af0\dbch\af17\loch\f0 o\hich\af0\dbch\af17\loch\f0 y the foreign donor marrow, as is the case with cancer patients.  \hich\f0 \lquote \loch\f0 
Patients with SCID have no immune systems to reject the transplants.  Our approach avoids toxic agents and their possible complications,\hich\f0 \rquote \loch\f0 \hich\f0  she said.\'94\loch\f0 ) }{\i \hich\af0\dbch\af17\loch\f0 with}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Inherited (Congenital) Immune Sys\hich\af0\dbch\af17\loch\f0 \hich\f0 tem Disorders,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0 
\hich\f0  at http://www.marrow.org/MEDICAL/immune_sys_disorders.html (\'93\loch\f0 To prepare for a stem cell transplant, patients receive high doses of chemotherapy and/or radiation therapy to destroy their immune systems. . . 
\hich\af0\dbch\af17\loch\f0 .  The pre-transplant treatment can be very hard on a patient\hich\f0 \rquote \loch\f0 \hich\f0 s body, and there is a risk of organ damage, including permanent sterility.\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0 
\hich\f0   Transplants come with the deadly risk of incurring another fatal disease, graft versus host disease (\'93\loch\f0 \hich\f0 GVHD\'94\hich\af0\dbch\af17\loch\f0 ), a condition caused if the body reacts negatively to the new transplant.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Inherited (Congenital) Immune System Disorders,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0  at http://www.marrow.org/MED
\hich\af0\dbch\af17\loch\f0 \hich\f0 ICAL/immune_sys_disorders.html (\'93\loch\f0 In addition, the donated stem cells might attack the patient\hich\f0 \rquote \loch\f0 
s body.  This is called graft-versus-host disease (GVHD).  If GVHD develops, doctors can treat it with drugs, but GVHD still sometimes causes death after a stem \hich\af0\dbch\af17\loch\f0 c\hich\af0\dbch\af17\loch\f0 \hich\f0 ell transplant.\'94\loch\f0 
).  }{\i \hich\af0\dbch\af17\loch\f0 But see }{\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Early Marrow Transplant May be Key to \hich\f0 \lquote \loch\f0 Bubble Boy\hich\f0 \rquote \loch\f0 \hich\f0  Disease Cure,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 Doctor\hich\f0 \rquote \loch\f0 s Guide, }{\hich\af0\dbch\af17\loch\f0 \hich\f0 May 5, 1997 at http://www.pslgroup.com/dg/25666.htm (\'93\loch\f0 Moreover, [Rebecca] Buckley [chief of Duke\hich\f0 \rquote \loch\f0 
s division of pediatric allergy and immunology] \hich\af0\dbch\af17\loch\f0 has found a way to reduce a potentially fatal complication of transplants called graft-versus-host disease (GVHD).  By removing the donor\hich\f0 \rquote \loch\f0 
s T-cells before the transplant, the donor\hich\f0 \rquote \loch\f0 s marrow cannot rise up and attack the patient\hich\f0 \rquote \loch\f0 s vital organs -- a common \hich\af0\dbch\af17\loch\f0 c\hich\af0\dbch\af17\loch\f0 
omplication with bone marrow transplants.  And, by removing these cells before the transplant, the infant avoids the toxic drugs normally given to suppress the donor\hich\f0 \rquote \loch\f0 \hich\f0 s T-cells.\'94\loch\f0 ).}}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 While bone marrow transplants are the only }{\i \hich\af0\dbch\af17\loch\f0 available }{\hich\af0\dbch\af17\loch\f0 
treatments, they are not the only }{\i \hich\af0\dbch\af17\loch\f0 known}{\hich\af0\dbch\af17\loch\f0  treatments.  In 2000, a miraculous new treatment using gene therapy, which is a method \hich\af0\dbch\af17\loch\f0 
of treating genetic diseases by introducing healthy genes into the body, cured bubble boy disease for the first time.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy Cures 
\hich\f0 \lquote \loch\f0 Bubble Boy,\hich\f0 \rquote \'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 , April 3, 2002 at htt\hich\af0\dbch\af17\loch\f0 \hich\f0 
p://www.newscientist.com/news/news.jsp?id=ns99992124 (\'93\loch\f0 Alain Fischer\hich\f0 \rquote \loch\f0 \hich\f0 s team at the Necker Hospital in Paris reported the first-ever treatment in 2000.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  Gene therapy treatments of bubble boy disease promised almost perfect success rates, did not require any donor, and did not come with th\hich\af0\dbch\af17\loch\f0 e threat of a negative reaction to the treatment.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{
\hich\af0\dbch\af17\loch\f0  at\hich\af0\dbch\af17\loch\f0 \hich\f0  http://www.wrclarkbooks.com/downloads/healers_chapter.doc (\'93\loch\f0 There will be no more \hich\f0 \lquote \loch\f0 bubble boys.\hich\f0 \rquote \'94\loch\f0 ).}}}{
\hich\af0\dbch\af17\loch\f0   
\par \hich\af0\dbch\af17\loch\f0 However, there is a one in a hundred-thousand chance that any one transferred gene will integrate in the gene that causes leukemia.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  Andrew Pollack, \'93\loch\f0 
\hich\f0 2nd Cancer is Attributed to Gene Used in French Test,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The New York Times}{\hich\af0\dbch\af17\loch\f0 , January 17, 2003 at Health and at http://www.newyorktimes.com\hich\af0\dbch\af17\loch\f0 
\hich\f0 /2003/01/17/health/17GENE.html (\'93\loch\f0 Dr. [Christof] von Kalle [a doctor at the Cincinnati Children\hich\f0 \rquote \loch\f0 \hich\f0 
s Hospital Medical Center and a collaborator with the French researchers] said the chance of a virus landing on LMO-2 was about 1 in 100,0000.\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0 
  Moreover, for gene therapy to have a high chance of successfully inte\hich\af0\dbch\af17\loch\f0 grating in the right gene, doctors introduce one million genes into the body.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 But si\hich\af0\dbch\af17\loch\f0 \hich\f0 
nce each child was given about one million cells, the probability is very high that a child received at least one cell in which the virus landed on the gene [that causes leukemia].\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
 Although it usually takes multiple genetic changes to cause leukemia, the number of genes introduced genes made leukemia a possibility.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 But Dr. von Kalle said scientists believed that turning on just \hich\af0\dbch\af17\loch\f0 \hich\f0 
one oncogene [a cancer-promoting gene] would not be a problem because it usually requires multiple genetic changes to turn a cell cancerous.\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0   This concern was only hypothetical unti
\hich\af0\dbch\af17\loch\f0 l two children developed leukemia-like symptoms after undergoing gene therapy treatment for bubble boy disease.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 In both cases, the gene inserted into the boys\hich\f0 \rquote \loch\f0  blood-forming stem cells landed on or near an oncogene,\hich\af0\dbch\af17\loch\f0 \hich\f0 
 or cancer-promoting gene, called LMO-2, which can spur childhood leukemia.  In the first case the gene landed inside LMO-2 and the second landed near enough to turn on the gene, Dr. von Kalle said.\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 
See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  Joshua J. Loomis, \'93\loch\f0 X-SCID Gene Therapy in Fr\hich\af0\dbch\af17\loch\f0 ance \hich\f0 \endash \loch\f0 \hich\f0  An Undesirable Integration Event,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 Viral Vectors as Mediators of Gene Therapy}{\hich\af0\dbch\af17\loch\f0  at http://narnia.n.ml.org/skier/writings/doc/microm%20496.doc (noting that the LMO-2 gene on chromosome 11 has been linked to leukemia).}}}{
\hich\af0\dbch\af17\loch\f0   The French, English, and American governments responded to this occurrence and quickly halted the trials.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  Andrew Pollack, \'93\loch\f0 
Gene Therapy Tr\hich\af0\dbch\af17\loch\f0 \hich\f0 ials Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The New York Times}{\hich\af0\dbch\af17\loch\f0 
, January 15, 2003 at Health and at http://www.newyorktimes.com/2003/01/15/health/15GENE.html.}}}{\hich\af0\dbch\af17\loch\f0   Still, fifteen patients \hich\f0 \endash \loch\f0  eleven b\hich\af0\dbch\af17\loch\f0 oys in Paris and four boys in London 
\hich\f0 \endash \loch\f0  were cured of bubble boy disease from gene therapy before the trials were halted.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 
  Now, other patients, who were waiting to receive gene therapy treatments, face certain death, because this option is no longer availa\hich\af0\dbch\af17\loch\f0 
ble.  The fate of these patients spurs endless questions of public policy, constitutional rights, and ethical dilemmas.  This paper uncovers these questions and attempts to answer them in light of the controversial January 14, 2003 decision of the Food an
\hich\af0\dbch\af17\loch\f0 d\hich\af0\dbch\af17\loch\f0 \hich\f0  Drug Administration (\'93\loch\f0 \hich\f0 FDA\'94\loch\f0 \hich\f0 ) to suspend twenty-seven \'93\loch\f0 \hich\f0 gene therapy trials involving several hundred patients.\'94}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0  
\par }\pard\plain \s27\qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 
The FDA decision to halt the trials clearly prevents more patients from contracting leukemia or another life-threatening ailment through gene t\hich\af0\dbch\af17\loch\f0 
herapy treatments.  Yet it simultaneously prevents these patients from receiving a cure of different fatal diseases, including bubble boy disease.  The governmental decision to halt the trials clearly protects an unaware public from undergoing a dangerous
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 
procedure.  Yet it simultaneously blocks well-informed parents from choosing the uncertain risks of gene therapy over the certain risks of bubble boy disease for their beloved children.  The governmental decree rescues parents from making very difficult d
\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 cisions.  Yet it robs them of their right, perhaps a constitutional right, to make those decisions.  
\par }\pard \s27\qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The government\hich\f0 \rquote \loch\f0 
s growing paternal virtues may be a direct result of the American people hastily reacting in anger, disappointment, and shock whenever a ra\hich\af0\dbch\af17\loch\f0 
re but highly publicized failure, especially one that results in death, hits the news stands.  The result for the American public is often the sought-after higher standards of safety, but those higher standards mean fewer available choices.  Less choice i
\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 
 sometimes better; the public does not always have the resources to make risk-benefit decisions for everyday incidents.  Perhaps, this cycle is useful in the majority of the FDA decisions covering everyday resolutions on food labeling, nonprescription dru
\hich\af0\dbch\af17\loch\f0 g\hich\af0\dbch\af17\loch\f0 s, and truthful advertising.   
\par }\pard\plain \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 
However, bubble boy disease is far from an everyday incident, and the FDA decision is hardly an everyday resolution.  This paper analyzes whether the proper role of the FDA should be different in rare life-threatening situat\hich\af0\dbch\af17\loch\f0 
ions than in everyday situations.  In cases of uncommon fatal diseases, this paper determines that the FDA should adopt less rigid regulations, allow for more personal autonomy, and grant alternative treatment options despite a higher risk level involved.
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 
 A governmental tolerance for high-risk treatments in cases of rare fatal diseases actually makes legal, financial, and ethical sense.  Legally, this paper asserts that the United States Constitution gives a dying person the right to choose a risky treatm
\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 
nt that offers the only chance at survival.  Financially, a person suffering from a rare disease is more likely to dedicate proportionally more resources to the disease than the public.  Ethically, the individual who will die if left untreated deserves th
\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0  opportunity of treatment, despite its risks, though the public would decide against the risk.  This paper discusses each of these reasons in detail below.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The United States Constitution limits the authority of the federal government in favor of individual
\hich\af0\dbch\af17\loch\f0  power on issues of privacy, self-dignity, and personal autonomy.  For example, the famous case of }{\i \hich\af0\dbch\af17\loch\f0 Roe v. Wade}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 , 410 U.S. 113 (1973).}}}{\hich\af0\dbch\af17\loch\f0  stands for upholding rights to autonomy and privacy in making decisions over one\hich\f0 \rquote \loch\f0 s body, following the paths carved from }{\i 
\hich\af0\dbch\af17\loch\f0 Griswold v. Connecticut}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Griswold v. Connecticut}{\hich\af0\dbch\af17\loch\f0 , 381 U.S. 479 (1965).}}}{
\hich\af0\dbch\af17\loch\f0  and }{\i \hich\af0\dbch\af17\loch\f0 Eisenstadt v. Baird}{\hich\af0\dbch\af17\loch\f0 .}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Eisenstadt v. Baird}{\hich\af0\dbch\af17\loch\f0 , 405 U.S. 4
\hich\af0\dbch\af17\loch\f0 38 (1972).}}}{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0  }{\hich\af0\dbch\af17\loch\f0 The well-known case of }{\i \hich\af0\dbch\af17\loch\f0 Cruzan v. Director, Missouri Dep\hich\f0 \rquote \loch\f0 
t of Health}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Cruzan v. Director, Missouri Dep\hich\f0 \rquote \loch\f0 t of Health}{\hich\af0\dbch\af17\loch\f0 , 497 U.S. 261 (1990).}}}{\hich\af0\dbch\af17\loch\f0 
 held that every person has constitutional rights to life and dignity in death.  Finally, }{\i \hich\af0\dbch\af17\loch\f0 Maher v. Roe}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
Maher v. Roe}{\hich\af0\dbch\af17\loch\f0 , 432 U.S. 464 (1977).}}}{\hich\af0\dbch\af17\loch\f0  represents a case where the United States Supreme Court\hich\af0\dbch\af17\loch\f0 
 found a right to medical treatment.  These significant constitutional cases represent individual rights, religious and philosophical rights, and medical rights that state personhood, self-dignity, and life are critical considerations under the U.S. Const
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 tution.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 Similar discussions surface in cases against the FDA specifically dealing with rare fatal diseases.  For example, during the AIDS revolution, AIDS patients fought for investigational new drugs (\'93\loch\f0 \hich\f0 
IND\'94\loch\f0 ), which are usually limited to clinical studies,\hich\af0\dbch\af17\loch\f0  to be available to non-clinical participants as treatment under certain conditions.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  42 U.S.C. \'a7\loch\f0 
 300cc-12 (requiring the FDA to encourage sponsors of clinical trials to make AIDS drugs available for treatment purposes if t\hich\af0\dbch\af17\loch\f0 here is preliminary evidence that the drug prevents or treats AIDS).  }{\i 
\hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  Peter B. Hutt and Richard A. Merrill, \'93\loch\f0 \hich\f0 The AIDS Revolution,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Food and Drug Law: Cases and Materials}{
\hich\af0\dbch\af17\loch\f0 \hich\f0 , Westbury, NY: The Foundation Press Inc (1991) at 552 (discussing the \'93\loch\f0 revolu\hich\af0\dbch\af17\loch\f0 \hich\f0 
tion in the availability of investigational drugs to treat life-threatening diseases, in the early approval of new drugs for these diseases\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0 
  Cancer patients also fought these fights, arguing that their constitutional rights of privacy protected their right to use available, albeit not approved, drugs to treat\hich\af0\dbch\af17\loch\f0  their disease.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 438 F. Supp. 1287 (W.D. Okl. 1977).  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  On appeal, the Tenth Circuit agreed and acknowledged the special case of these patients.  The Tenth Circuit asked, \'93\loch\f0 [W]hat can \hich\f0 \lquote \loch\f0 generally recognized\hich\f0 \rquote \loch\f0  as \hich\f0 \lquote \loch\f0 
safe and effective\hich\f0 \rquote \loch\f0  mean as to such persons who are so fatally stricken with a disea\hich\af0\dbch\af17\loch\f0 \hich\f0 se for which there is no known cure?\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 582 F.2d 123\hich\af0\dbch\af17\loch\f0 4, 1237 (10th Cir. 1978).  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  Admittedly, the law does not always side with this view, and the Supreme Court unanimously reversed this decision by the Tenth Circuit, finding that there is \'93\loch\f0 no special provision for drugs used to treat terminally i
\hich\af0\dbch\af17\loch\f0 \hich\f0 ll patients.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 442 U.S. 544 (1979).  }}
}{\hich\af0\dbch\af17\loch\f0 
  Nonetheless, the continuing AIDS and cancer fights maintain that constitutional rights of privacy, self-dignity, and autonomy should allow patients of rare, fatal diseases to choose more dangerous, and less certain treatments.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 Even the FDA recognized that it must make its decision in light of the fatal results of the disease.  }{\i \hich\af0\dbch\af17\loch\f0 See }{\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 FDA Places Temporary Halt on Gene Therapy Trials Using Retroviral
\hich\af0\dbch\af17\loch\f0 \hich\f0  Vectors in Blood Stem Cells,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 FDA Talk Paper, }{\hich\af0\dbch\af17\loch\f0 \hich\f0 January 14, 2003 at http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html (\'93
\loch\f0 FDA\hich\f0 \rquote \loch\f0 s continuing review of adverse event reports from all U.S. studies involving retroviral vectors has to date found no evidence \hich\af0\dbch\af17\loch\f0 
of leukemia caused by the gene therapy.  Moreover, the agency has to consider the potential risks of any experimental therapy within the context of the disease it may treat \hich\f0 \endash \loch\f0 \hich\f0 
 in this case a devastating disease in children.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   This paper \hich\af0\dbch\af17\loch\f0 argues that these same rights extend to riskier gene therapy treatments, as well.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 When the FDA placed the halt\hich\af0\dbch\af17\loch\f0  on gene therapy treatments, it made a similar statement, although it has failed to follow through on its promise.  }{\i \hich\af0\dbch\af17\loch\f0 See }{\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 
\hich\f0 FDA Places Temporary Halt on Gene Therapy Trials Using Retroviral Vectors in Blood Stem Cells,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 FDA Talk Paper, }{\hich\af0\dbch\af17\loch\f0 January 14, 2003 at htt\hich\af0\dbch\af17\loch\f0 
\hich\f0 p://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html (\'93\loch\f0 \hich\f0 FDA will consider and evaluate specific requests for clinical indications for fatal or life-threatening disorders for which there are no viable alternative treatments.
\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   If there is not an available transplant-donor match, a child inflicted with bubble boy disease will die.  In that case, the United States Constitution and common law guaran\hich\af0\dbch\af17\loch\f0 
tees that boy an autonomous right to make his personal and private decision among all known treatments, regardless of risk, to best maintain his dignity and treasure his life.
\par \hich\af0\dbch\af17\loch\f0 Second, there is the practical consideration of limited resources.  With everyda\hich\af0\dbch\af17\loch\f0 
y products, the public consumption is widespread, and thus the FDA will concentrate its efforts on those issues.  Correspondingly, the individual will devote few resources to learning more about each of these numerous trivial products.  Conversely, for ra
\hich\af0\dbch\af17\loch\f0 r\hich\af0\dbch\af17\loch\f0 
e diseases, the FDA will devote fewer resources, because it affects a small percentage of the public, but the inflicted individual will concentrate a great amount of resources on the singular and relatively significant disease.  Therefore, limited resourc
\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 s dictate that the FDA or another public establishment is probably the best conductor of a risk-benefit analysis in cases of everyday products.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See }
{\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Risk-Benefit Analysis,\loch\af0\dbch\af17\hich\f0 \'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 WUSTL}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
, October 12, 1994 at http://capita.wustl.edu/ME567_Informatics/concepts/riskben.html (\'93\loch\f0 
When individuals are exposed to involuntary risk, risk which they have no control, they make risk aversion their primary goal.  Under these circumstances individ\hich\af0\dbch\af17\loch\f0 \hich\f0 
uals require the probability of risk to be as much as one thousand times smaller then for the same situation under their perceived control.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  Yet the individual is probably the best conductor of risk-benefit analysis in cases of rare fatal diseases.  T\hich\af0\dbch\af17\loch\f0 
he FDA will proportionally devote fewer resources to bubble boy disease as compared to diseases that affect more children, while the parents of an inflicted child will devote almost a hundred percent of their resources to understanding this disease.  In l
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 
ght of this disparity of dedicated resources, the individual in the rare fatal case of bubble boy disease should make the risk-benefit decision regarding gene therapy.  Although the risks of gene therapy are high, allowing the individual to make this deci
\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 ion is the most sound approach, with respect to both finances and time, design.
\par \hich\af0\dbch\af17\loch\f0 Finally, there is the unduly risk-averse characteristic of public organizations.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id. }{\hich\af0\dbch\af17\loch\f0 \hich\f0 (\'93\loch\f0 
Real future risk as disclosed by the fully matured future circumstances when they develop.  Statistic\hich\af0\dbch\af17\loch\f0 
al risk, as determined by currently available data, as measured actuarially for insurance premiums.  Projected risk, as analytically based on system models structured from historical studies.  Perceived risk, as intuitively seen by individuals.  Air trans
\hich\af0\dbch\af17\loch\f0 p\hich\af0\dbch\af17\loch\f0 ortation as an example: Flight insurance company - statistical risk.  Passenger - perceived risk.  Federal Aviation Administration (FAA) \hich\f0 \endash \loch\f0 \hich\f0  projected risks.\'94
\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   News media have limited resources of space, time, and money to inquire about current happenin\hich\af0\dbch\af17\loch\f0 
gs.  Consequently, mass media reports failures, catastrophes, and errors more often than consistent performances, expected successes, and unencumbered results.  Thus, the public perceives the risk of activities to be greater than in actuality, such as the
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 risks of a plane crashing, beef carrying mad cow disease, and earthquakes striking California.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 Real future risk as disclosed by the fully matured future circumstances when they dev\hich\af0\dbch\af17\loch\f0 
elop.  Statistical risk, as determined by currently available data, as measured actuarially for insurance premiums.  Projected risk, as analytically based on system models structured from historical studies.  Perceived risk, as intuitively seen by individ
\hich\af0\dbch\af17\loch\f0 u\hich\af0\dbch\af17\loch\f0 als.  Air transportation as an example: Flight insurance company - statistical risk.  Passenger - perceived risk.  Federal Aviation Administration (FAA) \hich\f0 \endash \loch\f0 \hich\f0 
 projected risks.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   Consequently, the public seeks greater insurance against these risks than suitable.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 Although many people feel that flying is more risky than driving, sta\hich\af0\dbch\af17\loch\f0 \hich\f0 
tistics show otherwise.  Perception of control is a very important factor that explains why voluntary activities have risks of 100 to 1000 times greater than involuntary activities.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  As public servants, Congressional representatives vying for reelection re\hich\af0\dbch\af17\loch\f0 
spond to these demands by directing administrative regulators, like the FDA, to set higher than necessary standards to avoid these risks.  The resultant, unduly risk-averse nature of the FDA is desirable in an everyday setting, where the majority of indiv
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 duals has risk-adverse preferences and does not want to ascertain the risk for numerous trivial everyday purchases.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 
The Theory of Risk Aversion,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New School}{\hich\af0\dbch\af17\loch\f0  at http://cepa.newschool.ed\hich\af0\dbch\af17\loch\f0 \hich\f0 u/het/essays/uncert/aversion.htm (\'93\loch\f0 
We first turn to the concept of univariate \hich\f0 \lquote \loch\f0 risk aversion\hich\f0 \rquote \loch\f0 
 which, intuitively, implies that when facing choices with comparable returns, agents tend chose the less-risky alternative, a construction we owe largely to Milt\hich\af0\dbch\af17\loch\f0 o\hich\af0\dbch\af17\loch\f0 \hich\f0 
n Friedman and Leonard J. Savage (1948).\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   However, this resultant unduly risk-adverse nature is undesirable in rare fatal situations, where there is a higher chance that the indivi\hich\af0\dbch\af17\loch\f0 
\hich\f0 dual will prefer high-risk options, especially when those options offer the only chance for survival.  \'93\loch\f0 \hich\f0 Doctors at Great Ormond Street say two UK patients have died in 2002, because they did not start gene therapy in time.
\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\lquote \loch\f0 Miracle\hich\f0 \rquote \loch\f0 \hich\f0  Gene Therapy Trial Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
New Scientist}{\hich\af0\dbch\af17\loch\f0 , October 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992878.}}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 This paper tells the full sad s\hich\af0\dbch\af17\loch\f0 
tory of children suffering from bubble boy disease, the medical developments of gene therapy, the promising trials that the FDA abruptly halted, and the standard FDA procedures that threaten lives.  The first section of the paper introduces the medical de
\hich\af0\dbch\af17\loch\f0 v\hich\af0\dbch\af17\loch\f0 
elopments of bubble boy disease, exposing why the traditional treatment of bone marrow transplants is often impossible, inadequate, or unusually lethal in itself for bubble boy patients.  The paper then introduces the history of gene therapy, illustrating
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 
the science of gene therapy treatments that use retroviruses, like in the bubble boy treatments, to show why they have a higher risk.  It then shares the complete history of the halted trials, from the early successful results to the nervous apprehension 
\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 fter the first boy contracted leukemia to the immediate decision to suspend trials after the second child contracted leukemia.  
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
After giving a vivid picture of the disease, the treatment options, and the FDA decision, the paper then discusses the role of \hich\af0\dbch\af17\loch\f0 \hich\f0 
the FDA.  The paper introduces the standard procedure of the FDA, and the manner in which the FDA regulates gene therapy.  The paper delves into the structure of the FDA, including its relationship with the National Institutes of Health (\'93\loch\f0 
\hich\f0 NIH\'94\loch\f0 ) in regulat\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 ng bubble boy disease, gene therapy, and clinical trials.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
With a complete picture of the disease, the science, the treatment, and the regulator, the paper discusses the legal and social consequences of the FDA decision to halt the gene therapy trials that \hich\af0\dbch\af17\loch\f0 
promised to cure bubble boy disease.  On one hand, the FDA has a duty to protect the American people, and faces certain liability for failure to live up to its duty.  The American people demand that the FDA use its power to avoid putting the American peop
\hich\af0\dbch\af17\loch\f0 l\hich\af0\dbch\af17\loch\f0 
e in risk of peril.  On the other hand, the Constitution upholds privacy, autonomy, and self-dignity.  Children suffering from bubble boy disease are facing imminent death unless treated, and gene therapy is sometimes the only chance for life.  The parent
\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 
 of these children are willing to devote proportionally more resources to determine the individual risk-benefit analysis for their child.  Furthermore, they are in the best position to understand if the risk is not a risk at all, because it has become the
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 r last hope.  This final section of the paper discusses a way of achieving a proper balance between the two competing and conflicting interests.
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs40 \page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 II.  The Science}{\fs52\ul 
\par }\pard \qj \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs40 \hich\af0\dbch\af17\loch\f0 A.  The Disease}{\b\fs40 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 X-linked severe combined immunodeficiency (\'93\loch\f0 \hich\f0 X-SCID\'94\loch\f0 )}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  There are many different forms of Severe Combined Immunodeficiency (\'93\loch\f0 SCID\loch\af0\dbch\af17\hich\f0 \'94\loch\f0 \hich\f0 ).  This paper focuses on X-linked SCID (\'93\loch\f0 \hich\f0 X-SCID\'94\loch\f0 \hich\f0 
), the most common form of SCID, known also as bubble boy disease, because it affects only male children.  However, ADA-SCID, which is SCID caused by the absence of the enzyme adenosine deaminase (\'93\loch\f0 \hich\f0 ADA\'94\loch\f0 ), 
\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 
nother known form of SCID, affects both male and female children.  In fact, ADA-SCID, although less famous, was identified much sooner, and was understood almost immediately to be single-gene defect, which is easier to treat.  Thus, treatments were availa
\hich\af0\dbch\af17\loch\f0 b\hich\af0\dbch\af17\loch\f0 \hich\f0 le for ADA-SCID before the causes of X-SCID were known.  Indeed, at that time, X-SCID had not even been identified.  This paper uses the terms \'93\loch\f0 \hich\f0 X-SCID\'94\loch\f0 
\hich\f0  and \'93\loch\f0 \hich\f0 bubble boy disease\'94\loch\f0 \hich\f0  interchangeably.  This paper uses the term \'93\loch\f0 \hich\f0 SCID\'94\loch\f0  to include all forms of SCID\hich\af0\dbch\af17\loch\f0 .\hich\af0\dbch\af17\loch\f0 \hich\f0 
  When referring to other forms of SCID, this paper identifies it with a different prefix, such as \'93\loch\f0 \hich\f0 ADA-SCID.\'94}}}{\hich\af0\dbch\af17\loch\f0  is the proper medical t\hich\af0\dbch\af17\loch\f0 \hich\f0 erm, but \'93\loch\f0 
\hich\f0 bubble boy disease\'94\loch\f0 
 evokes a remarkably accurate image of the condition afflicting only male children with such severe immune system impairments at birth that they live in a bubble.  During pregnancy, SCID infants carry the immunity transferred \hich\af0\dbch\af17\loch\f0 t
\hich\af0\dbch\af17\loch\f0 \hich\f0 o them from their mother, but once born, they gradually lose their defense against infection.  Without medical intervention, every single child plagued with SCID has an early death sentence.  \'93\loch\f0 
Most infants with severe combined immunodeficiency disease dev\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 \hich\f0 lop pneumonia, thrush, and diarrhea, usually by age 3 months.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 
Severe Combined Immunodeficiency Disease,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{\hich\af0\dbch\af17\loch\f0  at http://www.merck.com/mrkshared/mmanual_home2/sec16/ch184/
\hich\af0\dbch\af17\loch\f0 ch184i.jsp.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   With a malfunctioning immune system, these serious infections progress into conditions that are even more serious.  \'93\loch\f0 \hich\f0 
If not treated, these children usually die before age 2.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Severe Combined Immunodeficiency Disease,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{\hich\af0\dbch\af17\loch\f0  at http://www.merck.com/mrkshared/mmanual_home2/sec16/ch184/ch184i.jsp.}}}{\hich\af0\dbch\af17\loch\f0  
\par \hich\af0\dbch\af17\loch\f0 Although it af\hich\af0\dbch\af17\loch\f0 fects only one child in about 75,000 births, SCID appalls parents and doctors alike.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 
Homo Sapiens Diseases Immunity,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Molecular Immunology }{\hich\af0\dbch\af17\loch\f0 at http://xoomer.virgilio.it/m\hich\af0\dbch\af17\loch\f0 \hich\f0 edicine/pathohomotissueimmunity.html (\'93\loch\f0 
\hich\f0 severe combined immunodeficiency (SCID) / Swiss type agammaglobulinemia / \'93\loch\f0 \hich\f0 bubble boy disease / syndrome\'94\loch\f0 \hich\f0  Epidemiology : 1 in 75,000 live births (1 in 100,000 live male births)\'94\loch\f0 ).  }{\i 
\hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 New Cure For Bubble Boy Di\hich\af0\dbch\af17\loch\f0 \hich\f0 sease,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 CBS News, }{\hich\af0\dbch\af17\loch\f0 
\hich\f0 April 17, 2002 at http://www.cbsnews.com/stories/2002/04/17/tech/main506451.shtml (\'93\loch\f0 \hich\f0 The five French boys were born with severe combined immunodeficiency, or SCID, an inherited disease that occurs in about 1 in 75,000 births.
\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   \'93\loch\f0 Severe combined immunodeficiency disease is the most serious immunodeficiency disorder.  It can be caused by several different genetic defects, most of which are heredi
\hich\af0\dbch\af17\loch\f0 \hich\f0 tary.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Severe \hich\af0\dbch\af17\loch\f0 \hich\f0 Combined Immunodeficiency Disease,\'94\loch\f0  }{
\scaps \hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{\hich\af0\dbch\af17\loch\f0  at http://www.merck.com/mrkshared/mmanual_home2/sec16/ch184/ch184i.jsp.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  Unfortunately, while scientists understand some of the diverse genetic origins of SCID well, other causes of SCID remain inexplicable.  \'93\loch\f0 
The most common type is linked to the X chromosome, making this form affect only males.  Other forms of SCID u\hich\af0\dbch\af17\loch\f0 
sually follow an autosomal recessive inheritance pattern or are the result of spontaneous mutations.  One of these other forms is linked to a deficiency of the enzyme adenosine deaminase (ADA).  Other cases of SCID are caused by a variety of other defects
\hich\af0\dbch\af17\loch\f0 .\loch\af0\dbch\af17\hich\f0 \'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Severe Combined Immunodeficiency,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
The SCID Homepage}{\hich\af0\dbch\af17\loch\f0  at http://www.scid.net/. }}}{\hich\af0\dbch\af17\loch\f0   
\par \hich\af0\dbch\af17\loch\f0 X-SCID or bubble boy disease is the most common form of SCID, but scientists identified ADA-SCID in the 1970s, much earlier than X-SCID.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy: The Fi\hich\af0\dbch\af17\loch\f0 \hich\f0 rst Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{
\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0   ADA-SCID was recognized as a single-gene defect immediately.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Long before cloning and sequencing the gene, clin\hich\af0\dbch\af17\loch\f0 ical studies showed that different mutations in a single common gene caused all the different severity levels in ADA-SCID cases.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Single-gene defects as opposed to multi-gene defects are much easier to isolate and treat.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Consequently, treatments for ADA\hich\af0\dbch\af17\loch\f0 -SCID were developed much earlier than for X-SCID, despite X-SCID being the more prevalent form.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Indeed, gene therapy for ADA-SCID was one of the first gene-therapy treatments available and led the way for the gene therapy treatments for X-SCID discussed\hich\af0\dbch\af17\loch\f0  in this paper.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Today, scientists have identified X-SCID as another single gene defect, and have similarly isolated the X-SCID gene.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Despite not understanding all the causes of bubble boy disease, the tragic significance of the disease is exceedingly cl
\hich\af0\dbch\af17\loch\f0 ear.  The children affected with SCID possess immune systems that noticeably lack a distressing amount of essential T cell and B cell functions, which are types of white blood cells and essential to the immune system.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy Cures \hich\f0 \lquote \loch\f0 Bubble Boy,\hich\f0 \rquote \'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist
}{\hich\af0\dbch\af17\loch\f0 , April \hich\af0\dbch\af17\loch\f0 \hich\f0 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992124 (\'93\loch\f0 \hich\f0 The faulty gene stops the development of T cells, a key part of the immune system.\'94
\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Severe Combined Immunodeficiency,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The SCID Homepage}{\hich\af0\dbch\af17\loch\f0 
\hich\f0  at http://www.scid.net/ (\'93\loch\f0 The definin\hich\af0\dbch\af17\loch\f0 \hich\f0 g characteristic is usually a severe defect in both the T- & B-lymphocyte systems.\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See also}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Inherited (Congenital) Immune System Disorders,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
 at http://www.marrow.org/MEDICAL/immune_sys_disorders.html (\'93\loch\f0 SCID patients e\hich\af0\dbch\af17\loch\f0 \hich\f0 
ither have no B cells and T cells, or those cells have severe defects.  Several genetic defects can cause SCID, including not having enough of an enzyme called ADA (adenosine deaminase) and having a defect in the gene that helps shape T cells.\'94
\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   \'93\loch\f0 This usually results in the onset o\hich\af0\dbch\af17\loch\f0 \hich\f0 
f one or more serious infections within the first few months of life.  These infections are usually serious, and may even be life threatening, they may include pneumonia, meningitis or bloodstream infections.\'94}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 
Severe\hich\af0\dbch\af17\loch\f0 \hich\f0  Combined Immunodeficiency,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The SCID Homepage}{\hich\af0\dbch\af17\loch\f0  at http://www.scid.net/.}}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 When a normal, healthy immune system detects \hich\af0\dbch\af17\loch\f0 
foreign adverse cells, it reacts in different ways to defend the body depending on the type of invasion.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Inherited (Congenital) Immune System Disorders,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0  at http://www.marrow.org/MEDICAL/immune_sys_disorders.html. }}}{\hich\af0\dbch\af17\loch\f0 
  One critical way, the way that affects bubble boys, involves white blood cells that identify and destroy invaders.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 
White blood cells called \hich\af0\dbch\af17\loch\f0 \hich\f0 lymphocytes identify and destroy invaders.\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0   One type of these white blood ce\hich\af0\dbch\af17\loch\f0 
lls, B cells, make antibodies to mark foreign cells that other cells will attack.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 \hich\f0 
One type of lymphocyte, a B cell, makes antibodies to mark foreign cells to be attacked.\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0   Meanwhile, another type of these white blood cells, T cells, make strong chemicals to kill foreign cells.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 \hich\f0 Another type of lymphocyte, a T cell, makes strong chemicals to kill foreign cells.\'94\loch\f0 ). }}}{
\hich\af0\dbch\af17\loch\f0   Thus, these B cells and T cells work together to determine which\hich\af0\dbch\af17\loch\f0 
 cells are the bad cells, and then to attack and destroy them.  Although there are other ways for the immune system to defend the body, the low number and malfunction of T cells in SCID patients is morbid to the body.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Ogden Bruton achieved the first breakt\hich\af0\dbch\af17\loch\f0 
hrough in 1952 for the heart-breaking condition of these children, when he discovered that there was an absence of certain proteins, critical to the immune system, in the blood.  Through this discovery, Bruton finally found an explanation for immunodefici
\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 
ncy, at least a general, basic explanation.  Since then, scientists have now identified over fifty forms of genetically determined immunodeficiency diseases, including SCID, which is the most severe of them all.  At first, the only way known to guard thes
\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 \hich\f0  children without normal immune systems to protect them, predominantly due to X-SCID, was to make sure they were never exposed to any germs, so they never got any illnesses.  \'93\loch\f0 
In the past, children with this disorder were kept in strict isolation, sometim\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 s in a plastic tent, leading to the disorder being called \hich\f0 \lquote \loch\f0 bubble boy syndrome.\hich\f0 
\rquote \'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 S\hich\af0\dbch\af17\loch\f0 \hich\f0 evere Combined Immunodeficiency Disease,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{
\hich\af0\dbch\af17\loch\f0  at http://www.merck.com/mrkshared/mmanual_home2/sec16/ch184/ch184i.jsp.}}}{\hich\af0\dbch\af17\loch\f0 
  This plastic-tent life was hardly ideal, could not completely prevent the children from getting sick, and did not protect the children from being doomed to an early death, \hich\af0\dbch\af17\loch\f0 but it postponed the inevitable for a brief while.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy Cures \hich\f0 \lquote \loch\f0 Bubble Boy,\hich\f0 \rquote \'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist
}{\hich\af0\dbch\af17\loch\f0 , April 3, 2002 at http://www.newscientist.com/ne\hich\af0\dbch\af17\loch\f0 \hich\f0 ws/news.jsp?id=ns99992124 (\'93\loch\f0 \hich\f0 
Children must be kept in isolation to protect hem from catching infections and usually die young.\'94\loch\f0 ). }}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Then, in 1968, shortly after the discovery of a method to check for matches in transplants,}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 The discovery of HLA-antigens, certain proteins on cell surfaces that are important in identifying cross matches for transpl\hich\af0\dbch\af17\loch\f0 \hich\f0 antation procedures, allowed for researchers to \'93\loch\f0 \hich\f0 match\'94\loch\f0 
 transplant donors and recipients.}}}{\hich\af0\dbch\af17\loch\f0  some success with bone marrow transplantation occurred in two patients with otherwise fatal immunodeficiency di\hich\af0\dbch\af17\loch\f0 seases.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 
\hich\f0 Severe Combined Immunodeficiency Disease,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{\hich\af0\dbch\af17\loch\f0 
 at http://www.merck.com/mrkshared/mmanual_home2/sec16/ch184/ch184i.jsp.}}}{\hich\af0\dbch\af17\loch\f0 
  This critical discovery played a significant role later in developing treatments for bubble boy disease, whose causes remained unclear at this time.  The two patients received transplants of matched}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  By \'93\loch\f0 mat
\hich\af0\dbch\af17\loch\f0 \hich\f0 ched,\'94\loch\f0 \hich\f0  the bone marrow cells had identical HLA-antigens.  These \'93\loch\f0 \hich\f0 HLA-identical\'94\loch\f0  bone marrow cells allowed transplants to become a reality, instead of just a theory.
}}}{\hich\af0\dbch\af17\loch\f0  bone marrow cells from a matched donor, becaus\hich\af0\dbch\af17\loch\f0 
e bone marrow is a primary source of immune cells.  Transplanting bone marrow cells thus offered the patients a new source of immunity.  This milestone in SCID research demonstrated that the defect in this immunodeficiency disease was not due to the failu
\hich\af0\dbch\af17\loch\f0 r\hich\af0\dbch\af17\loch\f0 
e of the marrow to support cell growth, but instead to dysfunction in development of blood cell lines.  Unfortunately, early marrow transplants were marked with disappointments.  Researchers learned that SCID patients were unusually, and extremely suscept
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 \hich\f0 ble to graft versus host disease (\'93\loch\f0 \hich\f0 GVHD\'94\loch\f0 
), a condition caused by the transplanted bone marrow T cells reacting against the patient.  Hence, on top of the difficulty of finding a matched donor for a bone marrow transplant to become even a possibility, ther\hich\af0\dbch\af17\loch\f0 e
\hich\af0\dbch\af17\loch\f0  is the prone danger of SCID children facing an even sooner end by contracting GVHD. 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Amidst all these new medical understandings and developments, in 1971, David Vetter was born.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See }{\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Severe Combined Immunodeficiency,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The SCID Homepage}{\hich\af0\dbch\af17\loch\f0  at http://www.scid.net/. }}}{
\hich\af0\dbch\af17\loch\f0   David is probably the most famous SCID case.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See\hich\af0\dbch\af17\loch\f0  id.}{\hich\af0\dbch\af17\loch\f0  }}}{
\hich\af0\dbch\af17\loch\f0   He was the first X-SCID pat\hich\af0\dbch\af17\loch\f0 \hich\f0 ient given the name \'93\loch\f0 \hich\f0 bubble boy,\'94\loch\f0 
 who lived in isolation in a sterile plastic bubble with filtered air for almost thirteen years, from his birth in 1971 to his death in 1984.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0   From his birth in Texas, David suffered from a genetic mutation leading to SCID\hich\af0\dbch\af17\loch\f0 .}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0   He experienced human touch only once.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0 
  Sadly, the attempt at treating David with a bone marrow transplant from his older sister failed, because her tissue carried a virus that causes mononucleosis.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0   After the failed operation, David\hich\f0 \rquote \loch\f0 s likelihood of s\hich\af0\dbch\af17\loch\f0 
urvival disappeared, and David lived the remaining two weeks of his life outside the bubble, dying before he was even a teenager.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   
\'93\loch\f0 SCID is often called \hich\f0 \lquote \loch\f0 bubble boy disease.\hich\f0 \rquote \loch\f0   SCID became widely known during the 1970\hich\f0 \rquote \loch\f0 s and 80\hich\f0 \rquote \loch\f0 s, when the world learned of 
\hich\af0\dbch\af17\loch\f0 \hich\f0 David Vetter, a boy with X-linked SCID, who lived for 12 years in a plastic, germ-free bubble.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{
\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0   It was the later Disney film rendition of David\hich\f0 \rquote \loch\f0 \hich\f0 s life that ensured the notoriety of David, the \'93\loch\f0 \hich\f0 bubble boy,\'94\loch\f0 
 and increased public awareness of bubble boy dis\hich\af0\dbch\af17\loch\f0 ease.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0  }}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
Although the cause of immunodeficiency was discovered in 1952, a treatment using bone marrow transplants for immunodeficiency was discovered in 1968, and David made the disease famous from his birth in 1971, the disease was nameless until 1975.  In 
\hich\af0\dbch\af17\loch\f0 
1975, John Soothill, M.D. suggested at the World Health Organization Conference in Geneva that this syndrome should be called severe combined immunodeficiency, and it soon acquired the acronym, SCID.  Yet even then, the X-SCID gene remained unidentified, 
\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 nd far from being isolated.  Then, in 1990, before the X-SCID gene was identified, the gene therapy treatments for other forms of SCID and for other diseases had already begun.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  W. French Anderson, \'93\loch\f0 \hich\f0 Human Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 392 Nature 25, 25-30 (1998), }{\hich\af0\dbch\af17\loch\f0 
also at http://www.frenchanderson.org/docarticles/pdf/humangenetherapy_0498.PDF.}}}{
\par }\pard\plain \s27\qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 
Thus, gene therapy was never an option for David, because the gene, which when\hich\af0\dbch\af17\loch\f0  mutated causes X-SCID, the form of SCID that affected David, had not been identified even by 1990, let alone during David\hich\f0 \rquote \loch\f0 
s lifetime.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy\hich\af0\dbch\af17\loch\f0 \hich\f0 : The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
The Journey Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0 
  Indeed, the biochemical nature of the defect causing X-SCID was not even known.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Furthermore, there was no known prote
\hich\af0\dbch\af17\loch\f0 in that would have allowed working backward to isolate the gene.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  As previously mentioned, X-SCID is genetically distinct from ADA-SCID which, at the time, was a better understood form of SCID, and the ADA-SCID gene had been identified and isolated.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Eve\hich\af0\dbch\af17\loch\f0 n as late as 1990, when gene therapy treatments were available for other diseases,}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  W. French Anderson, \'93\loch\f0 \hich\f0 Human Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 392 Nature 25, 25-30 (1998), }{\hich\af0\dbch\af17\loch\f0 also a\hich\af0\dbch\af17\loch\f0 
t http://www.frenchanderson.org/docarticles/pdf/humangenetherapy_0498.PDF.}}}{\hich\af0\dbch\af17\loch\f0  including ADA-SCID, identification of the X-SCID gene seemed unattainable in the near future.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0 
 at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{
\par }\pard\plain \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 
The isolation and cloning of the X-SCID gene occurred sooner than expected, t\hich\af0\dbch\af17\loch\f0 wo years later.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  Then, Japanese researchers in a completely unrelated project published their results in \'93\loch\f0 Science\hich\f0 \rquote \loch\f0  after finding, isolating, and sequencing the protein that would allow working backward to isolate the X-SCID gene.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Just two years earlier,\hich\af0\dbch\af17\loch\f0  such a discovery seemed impossible, but this unconnected research hastened the discovery.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   
\par \hich\af0\dbch\af17\loch\f0 In early research, scientists searched for the chromosomal location of the X-SCID gene by studying how the gene segregates families affected with X-SCID.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Obviou\hich\af0\dbch\af17\loch\f0 sly, the researchers noticed immediately that X-SCID only affected males, and from this observation, deducted that the general chromosomal association was the X chromosome.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy Cures \hich\f0 \lquote \loch\f0 Bubble Boy,\hich\f0 \rquote \'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist
}{\hich\af0\dbch\af17\loch\f0 \hich\f0 , April 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992124 (\'93\loch\f0 \hich\f0 The disease affects boys because they only have one X chromosome.\'94\loch\f0 ). }}}{\hich\af0\dbch\af17\loch\f0 
  Any further understanding of the X-SCID gene location on the X chromosome emerged\hich\af0\dbch\af17\loch\f0  very slowly, because the rarity of X-SCID meant there were very few families available for study of X-SCID carriers.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy: The First Hal\hich\af0\dbch\af17\loch\f0 \hich\f0 ting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
The Journey Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0 
  Furthermore, sadly, X-SCID infected boys did not survive long enough for an inclusive research.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Finally, comparison of the inheritance
\hich\af0\dbch\af17\loch\f0  pattern of the X-SCID gene with better known X chromosomal functions narrowed its location to a smaller region of DNA, but still one that was too large to isolate, clone, or sequence.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 Meanwhile, though, Japanese researchers, in an unrelated project havin\hich\af0\dbch\af17\loch\f0 g nothing to do with X-SCID, were studying the structure of a molecule found on the surface of T cells.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   T cells make and release a small hormone-like molecule which other cells consume to help them respond to an infection.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Remarkably and surprisingly, \hich\af0\dbch\af17\loch\f0 T cells themselves consume the same molecule that they produce.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   During a response to a particular immune challenge, T cells release this molecule into their immediate vicinity, and then consume some of the molecule they had just released to produce more 
\hich\af0\dbch\af17\loch\f0 of their own kind to fight the infection.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The T cell receptor, allowing them to grab this hormone-like molecule, initially was thought to consist of two different protein chains.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Yet certain aspects of the receptor\hich\f0 \rquote \loch\f0 s function seemed inconsistent with t\hich\af0\dbch\af17\loch\f0 his two-protein model.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The researchers were studying the T cell to explain the disparity in the theory.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  From their research, they found that there was indeed a third protein chain.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The Japanese researchers then isolated and sequenced the protein, and\hich\af0\dbch\af17\loch\f0  promptly published their discovery.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 This description and characterization of the receptor\hich\f0 \rquote \loch\f0 s newly discovered third protein chain explained many of the puzzles relating to the molecule\hich\f0 \rquote \loch\f0 s function.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Using this information, a research team at the National \hich\af0\dbch\af17\loch\f0 \hich\f0 Institutes of Health (\'93\loch\f0 \hich\f0 NIH\'94\loch\f0 
) made the connection of this protein with X-SCID.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id\hich\af0\dbch\af17\loch\f0 .}}}{\hich\af0\dbch\af17\loch\f0 
  The NIH researchers showed that the protein bound only to the X chromosome, specifically to one location.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The NIH researchers further showed that the DNA from every X-SCID pa\hich\af0\dbch\af17\loch\f0 tient sampled had mutation in a gene of the third protein.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   There were no mutations in any of the normal individuals sampled.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Thus, it became clear that the gene of the third protein was the gene that, in mutant form, causes X-SCID.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   \'93\loch\f0 Boys with X-SCID 
\hich\af0\dbch\af17\loch\f0 \hich\f0 (severe combined immunodeficiency) have a faulty copy of a gene on their X chromosome that makes an immune protein called interleukin-2.  As a result, they have no resistance to infection and die unless treated.\'94}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\lquote \loch\f0 Miracle\hich\f0 \rquote \loch\f0 \hich\f0  Gene Therapy Trial Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
New Scientist}{\hich\af0\dbch\af17\loch\f0 , October 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992878.}}}{
\par \hich\af0\dbch\af17\loch\f0 From this information, in late 1992, scien\hich\af0\dbch\af17\loch\f0 tists isolated the X-SCID gene, and through the known characteristics of the third protein, understood the exact cause of X-SCID.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinica\hich\af0\dbch\af17\loch\f0 
l Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0 
  Children inflicted with X-SCID have the hormone-like molecule to fight off disease, but the malfunctioning third protein pre\hich\af0\dbch\af17\loch\f0 
vents them from being able to grab the molecule and properly function.  Consequently, the T cells do not perform correctly, and X-SCID children are left with virtually no immune protection.  However, clinical experiments with a perfect third-protein gene 
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 
nserted into a retroviral vector showed that this gene can be delivered to bone marrow cells and B cells.  These gene therapy treatments promised that there would never be another bubble boy.  At this point, the science behind the disease begins to merge 
\hich\af0\dbch\af17\loch\f0 w\hich\af0\dbch\af17\loch\f0 ith the science behind the treatments, especially gene therapy.
\par }\pard \qj \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs40 \page \hich\af0\dbch\af17\loch\f0 B.  The Treatment}{\scaps\fs40 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
Despite the endless discussions marveling at the breakthrough of gene therapy, the FDA has not approved a single gene therapy for general use.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Cellular and Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Center for Biologics Evaluation and Research}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
 at http://www.fda.gov/cber/gene.htm (\'93\loch\f0 FDA has not yet approved any human gene therapy produc\hich\af0\dbch\af17\loch\f0 \hich\f0 t for sale.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   Thus, not one human gene-the
\hich\af0\dbch\af17\loch\f0 rapy product is for sale.  The possibilities of gene therapy began its promise of miracles for fatally ill patients as early as the 1960s.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  W. French Anderson, \'93\loch\f0 \hich\f0 Human Gene Therapy:  The Initial Concepts,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Gene Therapy for Diseases of the Lung,}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
 Brigham, K.L., eds.: Marcel Dekker, Inc. (1997) at 3-16, also at http://www.frenchanderson.org/docarticles/pdf/hgt_initial.pdf (\'93\loch\f0 Ho\hich\af0\dbch\af17\loch\f0 wever,
\par }\pard \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 as early as 1963 Lederberg wrote in an article \hich\f0 \lquote \loch\f0 Biological Future of Man\hich\f0 \rquote \loch\f0 
: We might anticipate the in vitro culture of germ cells and such manipulations as the interchange of chromosomes and segments.  The ultimate application of molecular biology w\hich\af0\dbch\af17\loch\f0 \hich\f0 
ould be the direct control of nucleotide sequences in human chromosomes, coupled with recognition, selection and integration of the desired genes\'85\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93
\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0  at\hich\af0\dbch\af17\loch\f0 \hich\f0 
 http://www.wrclarkbooks.com/downloads/healers_chapter.doc (\'93\loch\f0 \hich\f0 The possibilities for applying the emerging techniques of molecular biology to human gene therapy were appreciated by a handful of people as early as the late 1960s.\'94
\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   Yet the FDA refuses to approve gene therapy treatments beyond an experimental phase where individual patients are g\hich\af0\dbch\af17\loch\f0 
iven a chance at life on a case by case basis.  Thus, many people die waiting for their chance at a miracle.  Since the halt of the twenty-seven gene therapy trials on January 14, 2003, even fewer patients have a chance at a miracle.  Admittedly, while ge
\hich\af0\dbch\af17\loch\f0 n\hich\af0\dbch\af17\loch\f0 
e therapy may suggest a non-intrusive remedy similar to psychological care, it is an imperfect, dangerous, and precise procedure with multifaceted consequences.  Gene therapy techniques can correct defective genes responsible for disease development, but 
\hich\af0\dbch\af17\loch\f0 c\hich\af0\dbch\af17\loch\f0 an also mutate healthy genes causing new and different diseases.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  These risks particularly\hich\af0\dbch\af17\loch\f0 
 emerge in retroviral gene therapy, which uses a type of virus, called a retrovirus, to infect the defective cell and introduce the properly functioning gene.  The retroviral can infect many types of cells, besides the defective cell, and can cause seriou
\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 
 complications, including death.  Thus, retroviral gene therapy, which is used to treat bubble boy disease, entails a much higher risk than other types of gene therapy, and all the gene therapy trials halted by the FDA on January 14, 2003 involved retrovi
\hich\af0\dbch\af17\loch\f0 r\hich\af0\dbch\af17\loch\f0 al gene therapy treatments.  Retroviruses, the retroviral gene therapy technique, and the risks associated with this technique are discussed in this paper.}}}{
\par }\pard\plain \s27\qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 \hich\f0 
For boys affected with bubble boy disease, gene therapy is sometimes the only treatment available.  \'93\loch\f0 Treatment with antibiotics and immune globulin is helpful.  The best treatment is transpl\hich\af0\dbch\af17\loch\f0 \hich\f0 
antation of stem cells from bone marrow or umbilical cord blood.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Severe Combined Immunodeficiency Disease,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{\hich\af0\dbch\af17\loch\f0  at http://www.m\hich\af0\dbch\af17\loch\f0 erck.com/mrkshared/mmanual_home2/sec16/ch184/ch184i.jsp.}}}{\hich\af0\dbch\af17\loch\f0 
  However, as discussed above, bone marrow transplants are not always an available or a safe option.  Even if transplants and antibiotics were an option for a high percentage, it remains tha\hich\af0\dbch\af17\loch\f0 \hich\f0 
t there are boys without this option.  \'93\loch\f0 
Gene therapy seems to be effective in some infants who have one form of severe combined immunodeficiency disease.  Gene therapy consists of removing some white blood cells from the infant, inserting a normal gene in\hich\af0\dbch\af17\loch\f0 t
\hich\af0\dbch\af17\loch\f0 \hich\f0 o the cells, and returning the cells to the infant.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{
\par \hich\af0\dbch\af17\loch\f0 There are many gene therapy approaches, using different methods to introduce healthy genes into the body, each with different types of risks.  In the most common gene-therapy procedure, researchers inse
\hich\af0\dbch\af17\loch\f0 
rt a normal gene into the body to replace a nonfunctional gene.  A second distinct method swaps an abnormal gene for a normal gene.  A third method repairs the abnormal gene through reverse-mutation to returns the gene to its normal function.  A fourth me
\hich\af0\dbch\af17\loch\f0 t\hich\af0\dbch\af17\loch\f0 hod alters the strength of the abnormal gene to prevent it from functioning at all. 
\par }\pard\plain \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 
The idea is simple but the actualization is much more complicated.  These methods require using viruses to invade the body, but with healthy genes instead of sickly genes.\hich\af0\dbch\af17\loch\f0 
  These viruses serve as viral vectors in the gene therapy treatment to direct the healthy genes to different locations in the body.  The danger of using viral vectors is that they create additional complications, including the risk of viral infection.  H
\hich\af0\dbch\af17\loch\f0 o\hich\af0\dbch\af17\loch\f0 wever, non-viral vectors, as an alternative to viral vectors, while presenting fewer complications, are thus far much less efficient at introducing the healthy genes into the body.
\par \hich\af0\dbch\af17\loch\f0 There are four classes of viruses used in gene therapy treatments.  One cla\hich\af0\dbch\af17\loch\f0 
ss of viruses, adenoviruses, have double-stranded DNA genomes that typically cause respiratory, intestinal, and eye infections in humans, like the virus that causes the common cold.  Adenoviral vectors target a wide range of cells, allowing for a high pro
\hich\af0\dbch\af17\loch\f0 b\hich\af0\dbch\af17\loch\f0 
ability of effectiveness.  Yet adenoviral vectors are non-integrating, which means they do not incorporate themselves into the body permanently, and must be reintroduced repeatedly to treat gene therapy patients.  Another class of virus used in gene thera
\hich\af0\dbch\af17\loch\f0 p\hich\af0\dbch\af17\loch\f0 
y treatments, adeno-associated viruses, are small, single-stranded DNA viruses that can insert their genetic material only at one fixed chromosomal location, making them nonrealistic options for many gene therapy patients.  A third class of viruses, herpe
\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 
-simplex viruses, like the virus that causes cold sores, are double-stranded DNA viruses that also can only infect a particular cell type, neurons, similarly making them less valuable in gene therapy treatments.  Unfortunately, none of these classes of vi
\hich\af0\dbch\af17\loch\f0 r\hich\af0\dbch\af17\loch\f0 uses can be used to treat bubble boy disease.
\par \hich\af0\dbch\af17\loch\f0 The class of viruses used in treating bubble boy disease is retroviruses, which create double-stranded DNA copies of their genomes that can be integrated into the chromosomes of host cells very effectively.  A 
\hich\af0\dbch\af17\loch\f0 \hich\f0 familiar retrovirus, namely the human immunodeficiency virus (\'93\loch\f0 \hich\f0 HIV\'94\loch\f0 ), more commonly referred to by its acronym, reveals the menacing characteristics of this virus.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  W. French Anderson, \'93\loch\f0 \hich\f0 Human Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 392 Nature 25, 25-30 (1998), }{\hich\af0\dbch\af17\loch\f0 
also at http://www.frenchanderson.org/docarticles/pdf/humangenetherapy_0498.PDF.}}}{\hich\af0\dbch\af17\loch\f0   The quality that allows HIV to incorporate itself quickly in the body, threatening fatal a\hich\af0\dbch\af17\loch\f0 
nd permanent damage to the immune system, makes retroviral vectors very good at integrating with the body to deliver healthy genes for long-term, ideally permanent, remedies.  Yet retroviruses, like adenoviruses, can integrate into a wide range of cells, 
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 \hich\f0 ncreasing their utility in gene therapy treatments, but also increasing the risk of infecting the wrong cell, since they randomly integrate, sometimes in regions where they should not.  
\'93\loch\f0 Gene therapy involved shuttling the gene into a patient\hich\f0 \rquote \loch\f0 s cells usin\hich\af0\dbch\af17\loch\f0 g\hich\af0\dbch\af17\loch\f0 \hich\f0 
 a harmless virus.  But transferred genes cannot be targeted to insert into a specific part of the chromosome.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\lquote \loch\f0 Miracle\hich\f0 
\rquote \loch\f0  Gene Therapy Trial\hich\af0\dbch\af17\loch\f0 \hich\f0  Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 , October 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992878.}}}
{\hich\af0\dbch\af17\loch\f0   This characteristic explains the reason the gene therapy treatment that cured the two children may have integrated into the gene that causes l\hich\af0\dbch\af17\loch\f0 
eukemia.  Furthermore, retroviruses, unlike adenoviruses, can integrate permanently, promising a permanent cure while threatening permanent damage.  Finally, retroviruses only infect rapidly dividing cells, which increases the chance that the treatment wi
\hich\af0\dbch\af17\loch\f0 l\hich\af0\dbch\af17\loch\f0 
l have quick results.  However, this characteristic also specifically increases the risk of leukemia, a disease where blood cells proliferate out of control, since the gene that causes leukemia is a rapidly dividing gene. 
\par \hich\af0\dbch\af17\loch\f0 Scientists began isolating and se\hich\af0\dbch\af17\loch\f0 
quencing proteins since the 1950s.  With the complete amino acid sequence of a protein and using the genetic code, it is possible to work backwards and predict the sequence of the corresponding gene.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  Peter B. Hutt and Richard A. Merrill, \'93\loch\f0 \hich\f0 Regulation of Biotechnology,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Food and Drug Law: Cases and Materials}{\hich\af0\dbch\af17\loch\f0 
, Westbury, NY: The Foundation Press Inc (\hich\af0\dbch\af17\loch\f0 
1991) at 964-985 (noting that the James Watson and Francis Crick discovery of 1953, the double-helix structure of DNA, opened the field of molecular biology and led to the possibility of gene therapy). }}}{\hich\af0\dbch\af17\loch\f0 
  However, individual genes could not yet be isolated, a\hich\af0\dbch\af17\loch\f0 
nd thus gene therapy remained only a theoretical possibility.  Yet the dream of gene therapy grew with the breakthrough of the 1960s, when physician and scientist Stanfield Rogers observed that viruses could deliver genes, one of the founding blocks to mo
\hich\af0\dbch\af17\loch\f0 d\hich\af0\dbch\af17\loch\f0 ern gene therapy.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 
Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Jo\hich\af0\dbch\af17\loch\f0 urney Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0 
 at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0  Rogers was using rabbits to study one of the genes carried by a common wart-causing virus.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   This gene encodes a certain enzyme that degrades excess amount of an amino acid, a building block of protein, as discussed above.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id}}}{\hich\af0\dbch\af17\loch\f0   In rabbits i\hich\af0\dbch\af17\loch\f0 nfected with this virus, the levels of this amino acid in the blood were unusually low.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id}}}{\hich\af0\dbch\af17\loch\f0   Then, upon removing blood samples from people in the laboratory, Rogers found that laboratory personnel handling the infected rabbits had become infected with the vir\hich\af0\dbch\af17\loch\f0 
us, not an uncommon occurrence in the laboratory.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id}}}{\hich\af0\dbch\af17\loch\f0 
  The critical finding, however, was that these people also had extremely low levels of this amino acid.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id}}}{\hich\af0\dbch\af17\loch\f0 
  This finding proved that genes carried as part of a viral genome could alter normal physiological p\hich\af0\dbch\af17\loch\f0 rocesses in a human being.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id}}}{\hich\af0\dbch\af17\loch\f0   Thus, viruses could theoretically deliver genes to different cells in the human body.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id}}}{\hich\af0\dbch\af17\loch\f0 
  Of course, at this point, human genes had never been isolated, and thus gene therapy remained only an idea, but the possibilities for apply\hich\af0\dbch\af17\loch\f0 
ing the emerging techniques of molecular biology to human gene therapy were born.  Subsequently, in 1967, Marshall Nirenberg, the Nobel Prize winner, wrote of programming cells with synthetic messages, making the subject of gene therapy into an ethical de
\hich\af0\dbch\af17\loch\f0 b\hich\af0\dbch\af17\loch\f0 ate.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  John C. Fletcher, \'93\loch\f0 \hich\f0 
Evolution of Ethical Debate About Gene Therapy,\'94\loch\f0  1 }{\scaps \hich\af0\dbch\af17\loch\f0 Human G\hich\af0\dbch\af17\loch\f0 enet Therapy}{\hich\af0\dbch\af17\loch\f0 
 55, 55-60 (Spring 1990) (tracing the development of gene therapy from the beginnings by Nobelist Marshall Nirenberg).}}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 In the 1970s, isolating individual genes became a possibility.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0 
 at http://www.wrclarkbook\hich\af0\dbch\af17\loch\f0 s.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0 
  Thus, the theoretical advances discussed above, from knowing the complete amino acid sequences of quite a few proteins, came together and made isolating genes a reality.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id}}}{\hich\af0\dbch\af17\loch\f0   In 1977, the \hich\af0\dbch\af17\loch\f0 first human gene, part of the oxygen-carrying molecule of red blood cells, was isolated and cloned.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  LeRoy Walters, \'93\loch\f0 \hich\f0 Ethical Issues in Human Gene Therapy,\'94\loch\f0  2 }{\scaps \hich\af0\dbch\af17\loch\f0 Journal of Clinical Ethics}{\hich\af0\dbch\af17\loch\f0 
 267, 267-274 (Winter 1991) (discussing the unauthorized experiment of Martin Cline after hemoglobin, the gene in red blo\hich\af0\dbch\af17\loch\f0 od cells responsible for carrying oxygen to the entire body was isolated).}}}{\hich\af0\dbch\af17\loch\f0 
  Defects in this gene can cause diseases like severe anemia,}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 This disease discussed here is thalassemia, which is a genetic blood disorder when the body can not make enough hemoglobin, a part of the red blood cells that carries oxygen to al\hich\af0\dbch\af17\loch\f0 
l of the body.  Thalassemia is one of the most serious forms of anemia, which is the more general disorder describing an absence of functioning red blood cells. }}}{\hich\af0\dbch\af17\loch\f0 
 which is the inability to make red blood cells and is life-threatening.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  LeRoy Walters, \'93\loch\f0 \hich\f0 
Ethical Issues in Human Gene Therapy,\'94\loch\f0  2 }{\scaps \hich\af0\dbch\af17\loch\f0 Journal of Clinical Ethics}{\hich\af0\dbch\af17\loch\f0  267,\hich\af0\dbch\af17\loch\f0 
 267-274 (Winter 1991) (discussing the unauthorized experiment of Martin Cline).}}}{\hich\af0\dbch\af17\loch\f0   Subsequently, a phy\hich\af0\dbch\af17\loch\f0 
sician at UCLA, Dr. Martin Cline, working with another UCLA scientist, tried introducing the gene into mouse bone marrow cells using a viral vector.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id}}}{\hich\af0\dbch\af17\loch\f0   The experiment worked.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id}}}{\hich\af0\dbch\af17\loch\f0 
  More importantly, when the altered bone marrow cells were put back into mice, th\hich\af0\dbch\af17\loch\f0 ere was evidence that they survived and that the added gene was functioning.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The researchers then applied to their university\hich\f0 \rquote \loch\f0 \hich\f0 s Human Subjects Protection Committee, an institutional review board (\'93\loch\f0 \hich\f0 IRB\'94\loch\f0 
), for permission to try the same thing in human pati\hich\af0\dbch\af17\loch\f0 ents with severe anemia.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Unable to get permission from UCLA, Cline recruited patients suffering from this condition in foreign institutions.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Several patients had samples of their bone marrow removed, exposed to the vector containing the healthy gene, a\hich\af0\dbch\af17\loch\f0 nd then infused back into their bloodstream.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The experiment failed to alter the course of their disease, but the patients appeared to suffer no harm from the procedure either.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   His institution, the federal government, and the international scientific co\hich\af0\dbch\af17\loch\f0 mmunity denounced Martin severely.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Thus, the first attempt at gene therapy using cloned DNA destroyed hopes with the poor results and the negative response from the community.  Nonetheless, the research continued.  
\par \hich\af0\dbch\af17\loch\f0 In 1983, three separate laboratories p\hich\af0\dbch\af17\loch\f0 ublished the gene sequence encoding ADA, one of the earlier human genes to be isolated and cloned for study, and the malfunction of which causes ADA-SCID.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
The Journey Begins: The Clinical Trials for ADA-SC\hich\af0\dbch\af17\loch\f0 ID}{\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  In the late summer of 1990, the NIH Recombinant DNA Research Advisory Committee (\'93\loch\f0 \hich\f0 RAC\'94\loch\f0 ), working wi\hich\af0\dbch\af17\loch\f0 
th the FDA, and the FDA finally were sufficiently convinced by the preliminary laboratory data to approve the first human gene therapy trial.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   Thus, in 1990, National Institutes of Health (\'93\loch\f0 \hich\f0 NIH\'94\loch\f0 ) doctors conducted the first clinical trial of gene therapy.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   It succeeded.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  A four-year-old girl named Ashanti DeSilva received genetically altered cells to fix a rare condition she had inherited at birth.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  That rare condition happened to be a form of SCID, although ADA-SCID, not X-SCID.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   DeSilva had been in a
\hich\af0\dbch\af17\loch\f0 dvanced stages of her disease, and standard therapies were not working.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 Before final FDA approval had been obtained for the entire gene therapy procedure, samples of T cells were collected from DeSilva\hich\f0 \rquote \loch\f0 s blood and infected with the ADA vector in vitro.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   \hich\af0\dbch\af17\loch\f0 The cells were first triggered to start dividing, in order to enhance penetration by the retroviral vector.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   After exposure to the virus, the cells were grown in an incubator for about a week to expand their total numbers.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Final FDA approval was receive\hich\af0\dbch\af17\loch\f0 d on the morning of September 14, 1990.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   In that afternoon, four-year-old DeSilva was infused with her own T cells containing the retroviral ADA vector, and became the first human being in history to undergo gene therapy for therapeutic purposes.}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   
\par \hich\af0\dbch\af17\loch\f0 The p\hich\af0\dbch\af17\loch\f0 rocedure went smoothly.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Her white blood cells received a gene that makes an immune system protein, the third protein of a T cell, that she lacked.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The genetically treated white blood cells perform for only a few months, because the T cells do not live \hich\af0\dbch\af17\loch\f0 very long unless stimulated from fighting off foreign cells.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Thus, the effect is only transient, because the gene therapy treatment for ADA-SCID transforms the T cells.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   However, stimulated T cells become long-lived \'93\loch\f0 \hich\f0 memory\'94\loch\f0  T cells, and these previousl\hich\af0\dbch\af17\loch\f0 
y generated memory cells normally handle most of an immune response.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Over time, a SCID patient in whom even a small proportion of T cells were kept alive long enough to be stimulated might build up a repertoire of T cells capable of responding to most ty\hich\af0\dbch\af17\loch\f0 pes of foreign cells.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   This situation describes the prognosis for DeSilva.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  For a while, she had to continue to receive gene therapy on a regular basis.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  After four infusions over a four-month period, DeSilva\hich\f0 \rquote \loch\f0 s T cell counts were climbing toward normal.\hich\af0\dbch\af17\loch\f0   Direct analysis of DeSilva\hich\f0 \rquote \loch\f0 
s T cells showed that nearly all of them expressed the newly inserted ADA gene.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Today, DeSilva is relatively healthy, lives a normal life, and no longer receives gene therapy treatments of infusions of gene-altered T cells.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 DeSilva is now 17 years old and is considered a success story for gene therapy.  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy Turns 10,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
Current Science}{\hich\af0\dbch\af17\loch\f0 , January 19, 2001 at http://www.findarticles.com/cf_dls/m0BFU/10_86/69527187/p1/article.jhtml.  }}}{\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0  DeSilva\hich\f0 \rquote \loch\f0 \hich\f0 
s daily existence illustrates the hope of gene therapy attained, and explains the ceaseless hope for those, like \'93\loch\f0 \hich\f0 bubble boys,\'94\loch\f0  to try this treatment as well.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 One of the conditions imposed by the Recombinant DNA Research Advisory Committee (\'93\loch\f0 \hich\f0 RAC\'94
\loch\f0 )\hich\af0\dbch\af17\loch\f0  was that DeSilva and subsequent patients receiving ADA-SCID gene therapy continue taking PEG-ADA.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Gene Therapy: T\hich\af0\dbch\af17\loch\f0 \hich\f0 he First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{
\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0 
  PEG-ADA is a drug, ADA protein, which had been approved by the FDA as a standard treatment for ADA-SCID in 1990, just shortly before the Recombinant DNA Re\hich\af0\dbch\af17\loch\f0 \hich\f0 search Advisory Committee (\'93\loch\f0 \hich\f0 RAC\'94
\loch\f0 ) approved ADA gene therapy.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  In many children, PEG-ADA causes a marked initial increase in the number of T cells, alleviating many of the complications of ADA-SCID.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   On the other hand, some children gain little or no sust\hich\af0\dbch\af17\loch\f0 
ainable benefit after a few administrations of the ADA drug, and it is enormously expensive, more than two hundred thousand dollars per year for the average patient.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   PEG-ADA does not correct the underlying defect, but simply alleviates its symptoms, and \hich\af0\dbch\af17\loch\f0 thus must be taken regularly for the life of the patient.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  DeSilva was being treated with PEG-ADA at the time she began gene therapy.  Although she did not seem to be responding to the drug, it was considered inappropriate to discontinue its use.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Hence,\hich\af0\dbch\af17\loch\f0 
 evaluation of gene therapy in its first and longest lasting trial is complicated by the continued administration of a drug with the same potential effect of gene therapy, an increase in viable T cells.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0  
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Some investigators feel that the PEG-ADA may actual\hich\af0\dbch\af17\loch\f0 
ly be working against the effectiveness of the underlying gene therapy treatment.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  PEG-ADA helps keep all T cells alive, whether or not they are malfunctioning.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   From a gene therapist\hich\f0 \rquote 
\loch\f0 \hich\f0 s point of view, PEG-ADA is helping \'93\loch\f0 \hich\f0 bad\'94\loch\f0 \hich\f0  as well as \'93\loch\f0 \hich\f0 good\'94\loch\f0  T cells to\hich\af0\dbch\af17\loch\f0  survive.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0 
  There is reason to believe that, in the absence of PEG-ADA, those T cells infected with a healthy ADA gene would have a selective advantage for survival, and would eventually outgrow and displace the malfunctioning T cells.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   However, they were\hich\af0\dbch\af17\loch\f0  unable to convince the RAC and FDA to allow them to wean DeSilva or other patients off the PEG-ADA in order to find out.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 In September 1999, gene therapy suffered a major setback with the first death from gene therapy, eighteen-year-old Jesse Gelsinger, a\hich\af0\dbch\af17\loch\f0 n otherwise relatively healthy patient.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 \hich\f0 Sally Lehrman, \'93\loch\f0 \hich\f0 Virus Treatment Questioned After Gene Therapy Death,\'94\loch\f0  401 }{\scaps \hich\af0\dbch\af17\loch\f0 Nature}{
\hich\af0\dbch\af17\loch\f0  517, 517-18 (October 7, 2001) and at http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v401/n6753/full/401517b0_fs.html  (discussing the setback of gene therapy \hich\af0\dbch\af17\loch\f0 after Gelsinger
\hich\f0 \rquote \loch\f0 s death).}}}{\hich\af0\dbch\af17\loch\f0   Gelsinger was participating in a gene therapy trial for a metabolic disorder.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  Joan Stephenson, \'93\loch\f0 \hich\f0 Studies Illuminate Cause of Fatal Reaction in Gene-Therapy Trial,\'94\loch\f0  285 }{\scaps \hich\af0\dbch\af17\loch\f0 JAMA: The Journal of the American Medical Association}{
\hich\af0\dbch\af17\loch\f0  2570 (May 23-30, 2001) and at http://jama.ama-assn.org/cgi/content/full/285/20/25\hich\af0\dbch\af17\loch\f0 70 (discussing the cause of Gelsinger\hich\f0 \rquote \loch\f0 s death eight months later).}}}{
\hich\af0\dbch\af17\loch\f0   A severe negative immune response to the high dose of an early-generation adenoviral vector caused multiple organ failures, including \hich\af0\dbch\af17\loch\f0 
failure of the liver, kidney, and lungs.  Four days after starting the treatment, Gelsinger passed away.  Following Gelsinger\hich\f0 \rquote \loch\f0 
s death, government officials investigated the treatment and found that gene therapy researchers were careless with patient safet\hich\af0\dbch\af17\loch\f0 y\hich\af0\dbch\af17\loch\f0 , and were even neglecting to report deaths.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  United States Congress, Senate, Committee on Health, Education, Labor and Pensions, Subcommittee on Public Health, \'93\loch\f0 
Gene Therapy: Is There Oversight for Patient Safety?: Public Hearin\hich\af0\dbch\af17\loch\f0 \hich\f0 g,\'94\loch\f0 
 Washington, D.C.: Unpublished testimonies and documents from the hearing, 69 pages (February 2, 2000) (featuring testimony from Gelsinger\hich\f0 \rquote \loch\f0 s father, gene therapy patients, and medical experts).}}}{\hich\af0\dbch\af17\loch\f0 
  Gelsinger\hich\f0 \rquote \loch\f0 s death resulted in decreased clinical participation, tighter regulations, and more obstacles for researchers.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
Id.  See also }{\hich\af0\dbch\af17\loch\f0 \hich\f0 Alfred J. Smuskiewicz, \'93\loch\f0 Genetic Medicine Up\hich\af0\dbch\af17\loch\f0 \hich\f0 date,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 World Book}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
, 2001 at http://home.earthlink.net/~ajjsart/genmedwb.html (\'93\loch\f0 Gelsinger\hich\f0 \rquote \loch\f0 
s death triggered action by federal health authorities to strengthen monitoring and regulation of gene therapy experiments in the United States.  In March 2000, the FDA\hich\af0\dbch\af17\loch\f0 
 and the U.S. National Institutes of Health (NIH) announced that they planned to conduct more unscheduled inspections of gene therapy facilities and maintain greater oversight of gene therapy experiments.  The agencies also said they would provide more in
\hich\af0\dbch\af17\loch\f0 f\hich\af0\dbch\af17\loch\f0 \hich\f0 ormation to scientists and the public.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0   Nonetheless, gene therapy persevered, albeit a bit more slowly.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  Trisha Gura, \'93\loch\f0 \hich\f0 After a Setback, Gene Therapy Progresses . . . Gingerly,\'94\loch\f0  291 }{\scaps \hich\af0\dbch\af17\loch\f0 Science}{\hich\af0\dbch\af17\loch\f0 
 1692, 1692-1697 (March 2, 2001) and at http://www.sciencemag.org/cgi/content/full/291/5509/1692 (discussing the slow progres\hich\af0\dbch\af17\loch\f0 sion of gene therapy treatment for hemophilia in light of Gelsinger\hich\f0 \rquote \loch\f0 s death).
}}}{
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0  
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\ul \page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 III.  The Regulato\hich\af0\dbch\af17\loch\f0 r}{\scaps\fs52\ul 
\par }\pard \qj \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs40 \hich\af0\dbch\af17\loch\f0 A.  The FDA and the NIH
\par }{\tab \hich\af0\dbch\af17\loch\f0 
The curt story of the science behind bubble boy disease is depressing at best.  Bubble boy disease destroys the immune system, insuring a very early death if left untreated.  The available treatments are limited mostly to bone ma
\hich\af0\dbch\af17\loch\f0 \hich\f0 rrow transplants, which require a matched donor and come with the high risk of graft versus host disease (\'93\loch\f0 \hich\f0 GVHD\'94\loch\f0 
), which is also fatal.  Gene therapy trials were extremely promising, curing every boy treated, but alas had different risks.  Furthermore, th\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 
 FDA has since halted all the trials after two of the fifteen boys treated developed leukemia-like symptoms.  
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
Thus, the dismal future of the bubble boys reduces to the connected and much more complicated story of the FDA, whose far-reaching, well establis\hich\af0\dbch\af17\loch\f0 
hed, and strong authoritative role began with a congressional mandate.  The FDA, a part of the Department of Health and Human Services since 1979, obtains its authority under the Federal Food, Drug, and Cosmetic Act of 1938.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0   }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  Peter B. Hutt and Richard A. Merrill, \'93\loch\f0 \hich\f0 The Federal Food, Drug, and Cosmetic Act of 1938,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
Food and Drug Law: Cases and Materials}{\hich\af0\dbch\af17\loch\f0 , Westbury, NY: The Foundation Press Inc (1\hich\af0\dbch\af17\loch\f0 991) at 6.  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 also
}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Frequently Asked Questions,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 U.S. Food and Drug Administration}{\hich\af0\dbch\af17\loch\f0 
 at http://www.fda.gov/opacom/faqs/faqs.html (noting the 1979 amendment to the 1938 Act in 93 Stat. 668, 695 (1979)). }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   \'93\loch\f0 Authorized by Congress to en\hich\af0\dbch\af17\loch\f0 \hich\f0 
force the Federal Food, Drug, and Cosmetic Act and several other public health laws, the agency monitors the manufacture, import, transport, storage, and sale of $1 trillion worth of goods annually, at a cost to taxpayers of about $3 a person.\'94}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0   }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Designation and Locations of FDA in Federal G\hich\af0\dbch\af17\loch\f0 \hich\f0 overnment,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 U.S. Food and Drug Administration}{\hich\af0\dbch\af17\loch\f0  at http://www.fda.gov/opacom/morechoices/designat.html. }}}{\hich\af0\dbch\af17\loch\f0   Congress,\hich\af0\dbch\af17\loch\f0 
 however, could not have known the questions the FDA faces today.  The FDA\hich\f0 \rquote \loch\f0 
s objectives, guidelines, and procedures determine the decisions that allow some treatments but not others, including those decisions that affect babies fighting for their lives ag\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 
inst bubble boy disease.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 In 1974, the National Institutes of Health (\'93\loch\f0 \hich\f0 NIH\'94\loch\f0 ) began regulating recombinant DNA research.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0 
 at http://www.wrclarkbooks.com/downloads/healers_chap\hich\af0\dbch\af17\loch\f0 ter.doc.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   The Recombinant DNA Research Advisory Committee (\'93\loch\f0 \hich\f0 RAC\'94\loch\f0 
) to the NIH Director was also created at this time.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The RAC approves all resea
\hich\af0\dbch\af17\loch\f0 rch projects involving recombinant DNA in laboratories in the United States, handles gene-marking research, and reviews all gene therapy trials with the FDA.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   In other words, the RAC oversees all federally funded research involving recombinant DNA.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The \hich\af0\dbch\af17\loch\f0 
intrusion of the RAC into clinical trials involving recombinant DNA grew out of a defining moment in the history of molecular biology.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Scientists began making recombinant DNA molecules almost as soon as it became possible in the 1970s.  The initial expe
\hich\af0\dbch\af17\loch\f0 riments figured out only }{\i \hich\af0\dbch\af17\loch\f0 the conditions}{\hich\af0\dbch\af17\loch\f0 
 necessary for cutting and stitching together pieces of DNA from various sources in test tubes.  Before long, scientists were eager to move on to more interesting and practical possibilities.  Thus, some scientists be\hich\af0\dbch\af17\loch\f0 
gan carrying out experiments involving intact genomes removed from bacteria and viruses.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
In 1973, Herb Boyer and Stanley Cohen created the first biologically functional recombinant DNA molecule.  They had placed a toad gene into bacteria.  The bacteria pro\hich\af0\dbch\af17\loch\f0 
mptly began making the corresponding toad protein.  Scientists closely followed the new, widely known experiments with recombinant DNA, and started to get nervous.  No one had ever before tampered with the genome of a living organism.  There was no eviden
\hich\af0\dbch\af17\loch\f0 c\hich\af0\dbch\af17\loch\f0 e that such experiments were in fact dangerous, but the suggestion was made that all the scientists involved should suspend further experimentation until the community had a discussion.
\par \hich\af0\dbch\af17\loch\f0 The meeting to discuss the implications and possible risks of recombin\hich\af0\dbch\af17\loch\f0 ing the DNA of living organisms took place at the Asilomar Conference Center near Monterey, California, in 1974.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   All of the major laboratories working with recombinant DNA attended, along with representatives of the federal agencies funding this research\hich\af0\dbch\af17\loch\f0 .}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Out of this meeting came a proposal to ask the prestigious National Academy of Sciences to establish a committee to review the current status of recombinant DNA technology.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   This committee would also advise the government whether and how to regulate s\hich\af0\dbch\af17\loch\f0 
uch research using this technology.  The committee ultimately recommended that the NIH permanently establish the RAC, which the NIH formed almost immediately.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Over the next two years, the RAC began formulating guidelines for carrying out recombinant DNA \hich\af0\dbch\af17\loch\f0 research funded by federal research grants.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   NIH published these guidelines in 1976.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Almost immediately, virtually all laboratories in the United States carrying out such research, however funded, adopted the guidelines.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Indeed, most governments throu\hich\af0\dbch\af17\loch\f0 ghout the world also eventually adopted the guidelines in one form or another.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0  
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The early workings of the RAC dealt almost exclusively with safety issues for laboratory research.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The major concern initially was that altered life forms would escape from \hich\af0\dbch\af17\loch\f0 laboratories and infect plants, animals, or people on the outside.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   RAC, in responding to this concern, disseminated guidelines for \'93\loch\f0 \hich\f0 containment\'94\loch\f0 
 procedures, handling and storage of recombinant DNA, and other practical issues, to research laboratories thr\hich\af0\dbch\af17\loch\f0 oughout the country.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   Institutions sponsoring such research were required to establish institutional review boards (\'93\loch\f0 \hich\f0 IRB\'94\loch\f0 
) to ensure implementation of the RAC guidelines, and to assure that all applications for government research funding submitted to NIH\hich\af0\dbch\af17\loch\f0  met RAC standards.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Mindful of the furor that had attended the earlier forays in the direction of human gene therapy, the RAC also established a permanent Human Gene Therapy Subcommittee.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   This subcommittee took on the task of carrying out initial revie\hich\af0\dbch\af17\loch\f0 ws of all research involving human genes, whether intended for therapeutic purposes or not.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The government later decided that any proposals to introduce DNA into human beings would also be subject to clinical trials as defined by the FDA.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Thus, for the\hich\af0\dbch\af17\loch\f0  time being, both the RAC and the FDA approved clinical trials for gene therapy.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   When gene therapy moved out of the laboratory and into humans, there was a move on the part of some biotechnology companies and a few academics to have the RAC abolished, an\hich\af0\dbch\af17\loch\f0 
d to transfer sole authority for approving clinical trials to the FDA.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  However, the unique role the RAC plays in assessing the quality and value of the basic science underlying and likely to emerge from clinical trials was a considerable value.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 In 1996,\hich\af0\dbch\af17\loch\f0 
 the review of individual gene-therapy protocols became the sole responsibility of the FDA.  However, the RAC continues to review protocols that involve new technologies, and to recommend regulatory changes based on evolving techniques.  The FDA oversees 
\hich\af0\dbch\af17\loch\f0 t\hich\af0\dbch\af17\loch\f0 \hich\f0 
he safety and efficacy of the genetically altered products, the safety of the manufacturing process, and control of the final product.  Within the FDA, the Center for Biologics Evaluation and Research (\'93\loch\f0 \hich\f0 CBER\'94\loch\f0 \hich\f0 
) regulates gene therapy.  \'93\loch\f0 CBER is the Center \hich\af0\dbch\af17\loch\f0 w\hich\af0\dbch\af17\loch\f0 
ithin the FDA responsible for ensuring the safety and efficacy of blood and blood products, vaccines, allergenics, and biological therapeutics.  CBER\hich\f0 \rquote \loch\f0 
s regulation of biological products has expanded in recent years to include a wide variety of new product\hich\af0\dbch\af17\loch\f0 s\hich\af0\dbch\af17\loch\f0 \hich\f0 
 such as biotechnology products, somatic cell therapy and gene therapy, and banked human tissues.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0   }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Frequently Asked Qu
\hich\af0\dbch\af17\loch\f0 \hich\f0 estions,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Center for Biologics Evaluation and Research}{\hich\af0\dbch\af17\loch\f0  at http://www.fda.gov/cber/faq.htm. }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  Gene therapy, as a biologic, is subject to the regulations under the Public Service Health Act, as well as the Federal Food, Drug, and Cosmetic Act.  \'93\loch\f0 Biol\hich\af0\dbch\af17\loch\f0 \hich\f0 
ogics have been predominantly regulated under the Public Health Service Act although they are also defined as drugs under the Food Drug and Cosmetic Act.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   Gene therapy thus endures an extraordinarily difficult review process.  \'93\loch\f0 Gene transfer clinical tri\hich\af0\dbch\af17\loch\f0 
als have a unique oversight process administered by the National Institutes of Health (NIH), through the Recombinant DNA Advisory Committee (RAC) and the NIH Guidelines for Research Involving Recombinant DNA molecules, and the Food and Drug Administration
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 \hich\f0 (FDA) through review and approval of gene therapy protocols and premarket approval requirements for gene therapy products.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Transfer,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Genetics and Public Policy Center}{\hich\af0\dbch\af17\loch\f0 
 at http://www.dnapolicy.org/genetics/transfer.jhmtl;$sessionid$4I4DCIQAACY4WCQBAT#RVQQ.}}}{\hich\af0\dbch\af17\loch\f0  
\par }\pard \qj \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\page }{\fs40 \hich\af0\dbch\af17\loch\f0 B.  The Trials
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 Before the FDA became involved a few decades ago in 1962, clinical trials were generally informally organized stud
\hich\af0\dbch\af17\loch\f0 ies carried out by physicians, usually in collaboration with drug companies, to test a new drug, medical device or clinical procedure.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{
\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 G\hich\af0\dbch\af17\loch\f0 \hich\f0 ene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{
\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0   These studies were often not standardized, lacked important controls, and did not pay attention to proper statistical a
\hich\af0\dbch\af17\loch\f0 nalysis of data.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Consequently, many clinical trials produced data of little real value.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Yet patients were put at risk during such trials, and patients subsequently treated by drugs or devices approved for general use as a result of faulty clinical tria\hich\af0\dbch\af17\loch\f0 
ls were unknowingly also at risk.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0  
\par \hich\af0\dbch\af17\loch\f0 Starting in the 1970s, the federal government began formulating specific sets of guidelines for clinical trials.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Today, all new drugs and invasive medical devices are subject to rigorously controlled clinical tests bef\hich\af0\dbch\af17\loch\f0 ore being available for general clinical use.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Clinical trials in the United States are overseen by the FDA, and the FDA has final authority for approving a new drug or invasive medical device for manufacture, marketing, and general use by the medical com\hich\af0\dbch\af17\loch\f0 munity at large.}
{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Clinical trials are most often carried out in university medical centers under the guidance of physicians who also have strong basic science backgrounds, or have basic science consultants as part of the overall clinical trial team.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   In \hich\af0\dbch\af17\loch\f0 
most cases, a potential manufacturer or marketer of a new drug or procedure will be an active partner in clinical trials, providing the drug itself and any other materials needed for the trials, and generally underwriting their costs.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0  
\par \hich\af0\dbch\af17\loch\f0 As discussed above,\hich\af0\dbch\af17\loch\f0 \hich\f0  one of the major RAC guidelines is that all institutions sponsoring clinical trials must have an internal institutional review board (\'93\loch\f0 \hich\f0 IRB\'94
\loch\f0 ) to review clinical trial proposals before they are even submitted for FDA approval.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The IRB, sometimes called th
\hich\af0\dbch\af17\loch\f0 e Human Subjects Protection Committee, carries out an initial assessment of the scientific soundness of the proposal, and makes certain that the data collection and analysis procedures are valid and meaningful.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Furthermore, the IRB determines that the pr\hich\af0\dbch\af17\loch\f0 
oposed patient population is appropriate for the aims of the trial, and that the proposal follows the proper patient informed consent procedures.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Similarly, all gene therapy treatments fall under these same clinical procedures.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 Before a clinical trial c\hich\af0\dbch\af17\loch\f0 an begin, the FDA must see compelling evidence from laboratory studies that a proposed new drug or procedure is safe in animal and in vitro studies.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   This preclinical phase of testing generally involves laboratory experiments with human cells grown outsid\hich\af0\dbch\af17\loch\f0 
e the body, to gain insight into potential toxicity and to be sure that the drug will be safe for humans.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The next step is to test the drug or procedure in animals.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  This work often begins with rats and mice, for reasons of economy and because of the la\hich\af0\dbch\af17\loch\f0 rge backlog of experience with these animals and knowledge of how their physiology compares with humans.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   A very useful animal model that finds increasing use in drug testing is the so-called nude mouse.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Nude mice have a genetic defect that prevents the\hich\af0\dbch\af17\loch\f0 m from immunologically rejecting human cells and tissues.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   A closely linked defect prevents them from developing fur, hence the \'93\loch\f0 \hich\f0 nude\'94\loch\f0  designation.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   It is thus possible to transplant into nude mice a small piece of the human tissue a new drug is supposed\hich\af0\dbch\af17\loch\f0  to affect, to inject that drug into the mice, and to monitor the drug\hich\f0 
\rquote \loch\f0 s effect on the human tissue.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  In some cases, it may be appropriate to test the drug further on a larger animal before testing in humans, but increasingly the nude mouse model has been\hich\af0\dbch\af17\loch\f0  able to satisfy federal regulators.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 Ultimately, of course, any new drug or procedure must be tested on human beings to be absolutely certain it is safe and has the effect intended by its developers.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The FDA has developed very strict guidelines for cond\hich\af0\dbch\af17\loch\f0 ucting human clinical trials.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The first principle of any clinical trial is fully informed consent of the human subjects who will participate in the trial.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Patients must clearly understand the experimental nature of the procedures they will undergo, the\hich\af0\dbch\af17\loch\f0  possible dangers they may face, and the uses of the gathered information.}{\cs18\super 
\chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Researchers cannot mislead patients about benefits to their underlying disease, or risks of the treatment.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Researchers must assure confidentiality of the patient information.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   \hich\af0\dbch\af17\loch\f0 
The FDA must review a copy of information provided to each patient as part of the overall approval process for any new clinical trial.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 Most clinical trials proceed in four phases.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The FDA reviews each phase while it proceeds, and each phase must be comp\hich\af0\dbch\af17\loch\f0 leted and approved before the next phase can begin.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Although the exact description of each phase may be slightly different for each new drug or procedure, the following general guidelines apply to the majority of trials conducted.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   In the first phase, i\hich\af0\dbch\af17\loch\f0 nvestigators look at how long the drug remains in the system.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The FDA observes whether its properties change once it is inside a human body, and whether it causes any measurable side effects, either as reported by the subject or as detected in laboratory
\hich\af0\dbch\af17\loch\f0  tests.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The first phase usually tests a range of dosages that are guided by earlier toxicity tests on animals.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Sometimes the first phase tests infected persons, and sometimes the first phase tests healthy volunteers.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   When first phase tests the drug o\hich\af0\dbch\af17\loch\f0 
n infected persons, the patients are usually battling advanced stages of the disease and have failed to respond to standard current therapies for the disease.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id\hich\af0\dbch\af17\loch\f0 .}}}{\hich\af0\dbch\af17\loch\f0   The number of patients involved in this first phase is particularly few, no more than the numbe\hich\af0\dbch\af17\loch\f0 r required to get preliminary data for the points under study.}
{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Thus, at this phase, typically less than ten individuals have a chance to receive the treatment.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 During the second phase, investigators focus on the effectiveness of the new treatment.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   Dos\hich\af0\dbch\af17\loch\f0 
age and toxicity limits derived from the first phase are used to design the larger-scale second phase trials to begin assessing the value of the new drug or treatment as compared to existing treatments.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   The second phase may test patients with less advanc\hich\af0\dbch\af17\loch\f0 ed stages of disease.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Investigators continue to monitor patients closely for toxicity and any side effects.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  In this second phase, a larger numbers of patients are usually involved, up to a few hundred individuals.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0  
\par \hich\af0\dbch\af17\loch\f0 At the third phase, larger numbers o\hich\af0\dbch\af17\loch\f0 
f patients, up to thousands of individuals, are tested in a variety of clinical settings, including community hospitals, university medical centers, and private facilities.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Additional data on the interaction of the new drug with existing drugs used to tr\hich\af0\dbch\af17\loch\f0 eat the disease are gathered.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Information gathered in the third phase will eventually be used to instruct physicians about use of the new drug.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{\hich\af0\dbch\af17\loch\f0   Toxicity is still closely monitored.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  The drug developer will usually apply for formal approval from the FD\hich\af0\dbch\af17\loch\f0 A to market the new drug after successful conclusion of the third phase of clinical trials.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 The fourth and final phase of clinical trials occurs after the drug is approved by the FDA, and is required to continue studying the effects of the drug after gene\hich\af0\dbch\af17\loch\f0 ral release.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  In this fourth phase, the drug may be extended to slightly different patient populations than those studied in earlier trials, or dosages may be altered, or the drug tested in combinations with other previously-approved drugs.}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   The drug may\hich\af0\dbch\af17\loch\f0  also be extended for use in related conditions not specified in the original trials.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
See id.}}}{
\par \hich\af0\dbch\af17\loch\f0 Clinical trials test new products before allowing them to be sold publicly.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Thus, these strict and time-consuming phases are often very important to produce sound, sci\hich\af0\dbch\af17\loch\f0 entifically meaningful information about proposed new drugs, devices, or procedures, and protect the patients involved in the trials.}
{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   They represent the transition phase between highly promising basic laboratory research on a new drug or treatment method\hich\af0\dbch\af17\loch\f0 
, and the general release of that drug or treatment to the larger medical community for use in standard therapy.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0 
  Thus, clinical trials represent a riskier choice rather than waiting for FDA approval.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}}}{\hich\af0\dbch\af17\loch\f0   
\par \hich\af0\dbch\af17\loch\f0 However, others view these phases as overly rigid a\hich\af0\dbch\af17\loch\f0 
nd risk-averse, especially in dealing with life-threatening diseases and patients who have no hope to still be alive when the treatments are finally approved.  For instance, scores after discovering the promise of gene therapy,}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begin\hich\af0\dbch\af17\loch\f0 
s: The Clinical Trials for ADA-SCID}{\hich\af0\dbch\af17\loch\f0 \hich\f0  at http://www.wrclarkbooks.com/downloads/healers_chapter.doc (\'93\loch\f0 
The possibilities for applying the emerging techniques of molecular biology to human gene therapy were appreciated by a handful of people as early as the lat\hich\af0\dbch\af17\loch\f0 \hich\f0 e 1960s.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
 decades after perfecting th\hich\af0\dbch\af17\loch\f0 e science,}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0  (\'93\loch\f0 \hich\f0 
 By 1987 Anderson had prepared an initial proposal for clinical trials using the cloned human ADA gene to treat patients with ADA-SCID.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0  and years after testing on nude mice,}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 Indeed, there were expectations that clinical trials for gene therapy of X-SCID would be un\hich\af0\dbch\af17\loch\f0 derway in the United States by 1997, but was delayed until at least three years and not in America, but instead in France.  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy: The First Halting Steps,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Journey Begins: The Clinical Trials for ADA-SCID}{
\hich\af0\dbch\af17\loch\f0  at http://www.wrclarkbooks.com/dow\hich\af0\dbch\af17\loch\f0 nloads/healers_chapter.doc.}}}{\hich\af0\dbch\af17\loch\f0  human gene therapy was finally ready }{\i \hich\af0\dbch\af17\loch\f0 just}{\hich\af0\dbch\af17\loch\f0 
 to begin the clinical trial process.  However, by this time, fifty years later, many bubble boys had died.  Furthermore, gene therapy introduced some new complicat\hich\af0\dbch\af17\loch\f0 
ions and concerns that scared the FDA into making the approval process even more difficult than it had been in the past.  Thus, clinical trials often represent the only chance at a cure, when waiting means certain death.
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 It was this later situation in the \hich\af0\dbch\af17\loch\f0 
trials that cured bubble boy disease for fifteen children, four in London and eleven in Paris.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\lquote \loch\f0 Miracle\hich\f0 
\rquote \loch\f0 \hich\f0  Gene Therapy Trial Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 \hich\f0 , October 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992878 (\'93\loch\f0 
A total of 15 patients, have been treated so far \hich\f0 \endash \loch\f0 \hich\f0  11 in Paris and four in London.\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See \hich\af0\dbch\af17\loch\f0 also}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 
\hich\f0 Gene Therapy Causes Cancer in Mice,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 \hich\f0 , April 18, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992186 (\'93\loch\f0 
So far, around 400 patients have received gene therapy in the UK alone, but only a few were treated with retroviruses.  Th\hich\af0\dbch\af17\loch\f0 ey include two \hich\f0 \lquote \loch\f0 bubble babies\hich\f0 \rquote \loch\f0 
 otherwise condemned to living forever in germ-free \hich\f0 \lquote \loch\f0 bubbles\hich\f0 \rquote \loch\f0 \hich\f0  because their immune systems do not work.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  The treatment had been permissible in France since 2000.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\lquote \loch\f0 Miracle\hich\f0 
\rquote \loch\f0 \hich\f0  Gene Therapy Trial Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 , October 3, 2002 at http://www.newscientist.com/news/news.js\hich\af0\dbch\af17\loch\f0 \hich\f0 
p?id=ns99992878 (\'93\loch\f0 \hich\f0 In 2000, a team lead by Alain Fisher at Necker Hospital, Paris, carried out the first gene therapy treatment, which replaced the faulty gene.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  The gene therapy treatment for bubble boy disease involves using retroviruses to insert the healthy \hich\af0\dbch\af17\loch\f0 
genes into blood stem cells to direct them to the T cells.  The known risk of this particular method was that the retrovirus would transfer the gene to other cells as well, resulting in a disease causing mutation.}{\cs18\super \chftn {\footnote 
\pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Transfer,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Genetics and Public Policy Center}{\hich\af0\dbch\af17\loch\f0 
 at http://www.dnapolicy.org/genetics\hich\af0\dbch\af17\loch\f0 \hich\f0 /transfer.jhmtl;$sessionid$4I4DCIQAACY4WCQBAT#RVQQ (\'93\loch\f0 
Thus, a significant concern with gene transfer is that the introduced gene will integrate in the genome and cause interruption or disruption of other gene functions, causing mutation and possibly diseas\hich\af0\dbch\af17\loch\f0 e
\hich\af0\dbch\af17\loch\f0 
.  This was considered a largely hypothetical concern until the recent occurrence of leukemia in a child who had gene transfer to treat a severe immune deficiency.  While the transferred gene appeared to function and alleviate the immune deficiency, the a
\hich\af0\dbch\af17\loch\f0 p\hich\af0\dbch\af17\loch\f0 \hich\f0 pearance of the leukemia may have been due to the insertion of the transferred gene in yet another gene resulting in a disease causing mutation.\'94\loch\f0 ).}}}{
\hich\af0\dbch\af17\loch\f0   Leukemia, the disease contracted by two \hich\af0\dbch\af17\loch\f0 
of the children treated with gene therapy for bubble boy disease, is where the blood cells, which naturally proliferate, proliferate out of control due to a mutation of the gene.  Nonetheless, the serious effects of leukemia should not overshadow the fact
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 
that both these boys were successfully cured of bubble boy disease, which would have killed them within a couple years if left untreated.  Furthermore, the other thirteen bubble boys treated with gene therapy benefited from the procedure without developin
\hich\af0\dbch\af17\loch\f0 g\hich\af0\dbch\af17\loch\f0  leukemia.
\par \hich\af0\dbch\af17\loch\f0 
In August 2002, it did not actually come as a surprise to the doctors, the government, or the parents when a child successfully treated for X-SCID with gene therapy developed leukemia.  However, in response, France promptly halted the trials the
\hich\af0\dbch\af17\loch\f0 re as the FDA allowed the trials to continue in the United States.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 
Miracle Gene Therapy Trial Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 , October 3, 2002 at http://www.newscientist.com/new\hich\af0\dbch\af17\loch\f0 \hich\f0 s/news.jsp?id=ns99992878 (\'93
\loch\f0 A \hich\f0 \lquote \loch\f0 miracle\hich\f0 \rquote \loch\f0  gene therapy treatment for children suffering from the fatal \hich\f0 \lquote \loch\f0 bubble boy\hich\f0 \rquote \loch\f0 \hich\f0 
 disease has been halted in France, after one of the patients developed leukemia as a direct consequence of the treatment.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0 
  Then, in January 2003, a second child treated in a French gene therapy trial developed a leukemia-like condition.  Again, however, researchers anticipated this unfortunate consequence as \hich\af0\dbch\af17\loch\f0 
a side effect from the science.  The FDA immediately halted all gene therapy trials using retroviral vectors in blood stem cells as a response.  At the time, there were two hundred gene-therapy trials under way, with sixty trials involving retroviruses, a
\hich\af0\dbch\af17\loch\f0 n\hich\af0\dbch\af17\loch\f0 
d twenty-seven trials using retroviruses to insert the genes into blood stem cells.  Thus, the halted trials only represented fifteen percent of the gene therapy trials at the time.  Yet, for the people affected by these fifteen percent of trials, the FDA
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 decision is deadly harsh, overly risk-averse, and unfairly dictatorial.
\par \hich\af0\dbch\af17\loch\f0 At the end of February 2003, the FDA\hich\f0 \rquote \loch\f0 \hich\f0 s Biological Response Modifiers Advisory Committee (\'93\loch\f0 \hich\f0 BRMAC\'94\loch\f0 
) met to discuss possible measures that could allow a number of retroviral gene therapy \hich\af0\dbch\af17\loch\f0 
trials for treatment of life-threatening diseases to proceed with appropriate safeguards.  The BRMAC recommended guidelines that would increase the benefit to risk ratio significantly.  For instance, the BRMAC would deny gene therapy to X-SCID patients wh
\hich\af0\dbch\af17\loch\f0 o\hich\af0\dbch\af17\loch\f0  had another treatment option, i.e., who had found matched}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  By \'93\loch\f0 \hich\f0 matched,\'94\loch\f0  th\hich\af0\dbch\af17\loch\f0 
e donor had HLA-identical bone marrow cells as the patient.  HLA-identical means that the cell surfaces had the same HLA-antigens. }}}{\hich\af0\dbch\af17\loch\f0 
 donors for marrow transplants.  The BRMAC would permit X-SCID patients to undergo gene therapy if they could not find a matched donor, if their matched transplantation failed, and if their circums\hich\af0\dbch\af17\loch\f0 
tances were otherwise so dire that gene therapy was the only remaining option.  These recommendations would make gene therapy available only as a last recourse.  However, today it is not available at all, because the FDA, over a year later, has not yet ac
\hich\af0\dbch\af17\loch\f0 t\hich\af0\dbch\af17\loch\f0 ed on the BRMAC recommendations from this meeting.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0   }{\i \hich\af0\dbch\af17\loch\f0 See}{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 \hich\f0 Gene Therapy,\'94
\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Human Genome Project Information}{\hich\af0\dbch\af17\loch\f0  at http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genet\hich\af0\dbch\af17\loch\f0 \hich\f0 
herapy.shtml (noting that as of December 9, 2003, the \'93\loch\f0 \hich\f0 FDA had not yet to make a decision based on the discussions and advice of the BRMAC meeting\'94\loch\f0 ).  }{\i \hich\af0\dbch\af17\loch\f0 See also}{\hich\af0\dbch\af17\loch\f0 
\hich\f0  \'93\loch\f0 \hich\f0 CBER Talkpapers,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Center for Biologics Evaluation and Research}{\hich\af0\dbch\af17\loch\f0  at http://www.fda.gov/cber/talkp\hich\af0\dbch\af17\loch\f0 
apers.htm (noting the FDA decision to halt the trials on January 14, 2003, and the BRMAC meeting on February 28, 2003, but without any update on the matter through March 26, 2004). }}}{\hich\af0\dbch\af17\loch\f0 
  The January 14, 2003 FDA decision to halt gene therapy trials, although affecting a very small percentage of the American population, calls the entire role of the FDA into question as overly risk-averse \hich\af0\dbch\af17\loch\f0 
and authoritarian.  Indeed, its own BRMAC recommended that the FDA allow gene therapy options in certain cases.  The FDA\hich\f0 \rquote \loch\f0 
s refusal to act upon these recommendations in one way or another, and thus take responsibility for its decision, instead of evading l\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 ability for the boys who die waiting for the FDA, is shameful. 

\par }\pard \qc \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\ul\cf0 \page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 IV.  The Society}{\scaps\fs52\ul 
\par }\pard \qj \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs40 \hich\af0\dbch\af17\loch\f0 A.  The Rights
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 The NIH established the Recombinant DNA Research Advisory Committee (\'93\loch\f0 \hich\f0 RAC\'94\loch\f0 \hich\f0 
), and the FDA established the Center for Biologics Evaluation and Research (\'93\loch\f0 \hich\f0 CBER\'94\loch\f0 ),\hich\af0\dbch\af17\loch\f0 
 both to regulate gene therapy.  Thus, gene therapy ended up being regulated twice, by two different federal organizations, and then within those two organizations, two separate committees that focused on gene therapy.  Evidently, gene therapy deserves tw
\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 
ce the scrutiny than any other treatment, despite the fact that gene therapy offers the only hope for many patients.  Hence, the sad truth of the science working against bubble boy patients only becomes worse by the rigid FDA regulations working against b
\hich\af0\dbch\af17\loch\f0 u\hich\af0\dbch\af17\loch\f0 bble boy treatments. 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
Gene therapy passed multiple FDA tests before it even reached the human clinical trials that the FDA halted on January 14, 2003.  As discussed earlier, leukemia was a known risk before the X-SCID gene therapy began trials.  Nonetheles
\hich\af0\dbch\af17\loch\f0 s, the two cases of boys }{\i \hich\af0\dbch\af17\loch\f0 cured}{\hich\af0\dbch\af17\loch\f0  of X-SCID who developed leukemia-like symptoms still caused the FDA to halt the treatments responsible for the }{\i 
\hich\af0\dbch\af17\loch\f0 cure}{\hich\af0\dbch\af17\loch\f0 .  The disease is deadly, but the FDA faces a duty to protect the American public.  These two realities work a\hich\af0\dbch\af17\loch\f0 
gainst each other.  Children are dying and parents are willing to do anything to save them.  Children suffering from bubble boy disease are facing imminent death unless treated, and gene therapy is sometimes the only chance for life.  Therapies are far fr
\hich\af0\dbch\af17\loch\f0 o\hich\af0\dbch\af17\loch\f0 
m well understood and the FDA avoids the risks of the unknown.  These conflicting interests are important, and yet at complete odds.  Amongst these life and death decisions when each decision risks death, and no decision guarantees life, where do the righ
\hich\af0\dbch\af17\loch\f0 t\hich\af0\dbch\af17\loch\f0 s of the parties involved lie?
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The United States Supreme Court has found that the Constitution guarantees a right to privacy.  In }{\i 
\hich\af0\dbch\af17\loch\f0 Griswold v. Connecticut}{\hich\af0\dbch\af17\loch\f0 ,}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Griswold v. Connecticut}{\hich\af0\dbch\af17\loch\f0 
, 381 U.S. 479 (1965) (finding that the right to \hich\af0\dbch\af17\loch\f0 privacy guarantees the right to contraception).  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0  the Supreme Court noted, \'93\loch\f0 
The association of people is not mentioned in the Constitution, nor in the\hich\af0\dbch\af17\loch\f0  Bill of Rights.  The right to educate a child in a school of the parents\hich\f0 \rquote \loch\f0  choice \hich\f0 \endash \loch\f0 
 whether public or private or parochial \hich\f0 \endash \loch\f0  is also not mentioned.  Nor is the right to study any particular subject or any foreign language.  Yet the First Amendment has bee\hich\af0\dbch\af17\loch\f0 n\hich\af0\dbch\af17\loch\f0 
\hich\f0  construed to include certain of those rights.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  The Supreme Court found that \'93\loch\f0 \hich\f0 the First Amendment has a penumbra where privacy is protected from governmental intrusion.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{
\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   In applying this penumbra to affirm the privacy of marriage, the Court stated, \'93\loch\f0 We\hich\af0\dbch\af17\loch\f0 \hich\f0  deal with a privacy older than the bill of rights.
\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0   This same statement applies to the privacy of life, self-preservation, and medical treatment, which is even older than the institution of marriage.  The }{
\i \hich\af0\dbch\af17\loch\f0 Griswold }{\hich\af0\dbch\af17\loch\f0 \hich\f0 Court stated, \'93\loch\f0 The foregoing cases sugg\hich\af0\dbch\af17\loch\f0 \hich\f0 
est that specific guarantees in the Bill of Rights have penumbras, formed by emanations from those guarantees that help give them life and substance.  Various guarantees create zones of privacy.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}{
\hich\af0\dbch\af17\loch\f0  }}}{\hich\af0\dbch\af17\loch\f0   No other right is more fundamental than the right to life.\hich\af0\dbch\af17\loch\f0 
  No other penumbra can give more life to this right than the right to medical treatment.  The zone of privacy this right creates is the privacy to choose the medical treatment of gene therapy when there are no other treatment options.  In }{\i 
\hich\af0\dbch\af17\loch\f0 Eisenstadt v. Ba\hich\af0\dbch\af17\loch\f0 ird}{\hich\af0\dbch\af17\loch\f0 ,}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Eisenstadt v. Baird}{\hich\af0\dbch\af17\loch\f0 , 405 U.S. 438 (1972).}}}{
\hich\af0\dbch\af17\loch\f0  the Court affirmed this right of privacy found in }{\i \hich\af0\dbch\af17\loch\f0 Griswold}{\hich\af0\dbch\af17\loch\f0 .  The }{\i \hich\af0\dbch\af17\loch\f0 Eisenstadt }{\hich\af0\dbch\af17\loch\f0 \hich\f0 Court stated, 
\'93\loch\f0 If the right of privacy means anything, it is the right of the }{\i \hich\af0\dbch\af17\loch\f0 individual}{\hich\af0\dbch\af17\loch\f0 , married or single, to be free from unwarranted governmental intrusion into matters s
\hich\af0\dbch\af17\loch\f0 \hich\f0 o fundamentally affecting a person as the decision whether to bear or beget a child.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 
  Similarly, the matter of gene therapy treatment, as a matter of life versus death, fundamentally affects an X-SCID patient. 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The Supreme Court reaffirmed this right to \hich\af0\dbch\af17\loch\f0 privacy in }{\i \hich\af0\dbch\af17\loch\f0 
Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 .}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {
\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 , 410 U.S. 113 (1973).}}}{\hich\af0\dbch\af17\loch\f0   The }{\i \hich\af0\dbch\af17\loch\f0 Roe}{\hich\af0\dbch\af17\loch\f0 
\hich\f0  Court stated, \'93\loch\f0 The Constitution does not explicitly mention any right of privacy.  [But] the Court has recognized that a right of personal privacy, or a guarantee of certain areas or zones of privacy, does exist under the 
\hich\af0\dbch\af17\loch\f0 \hich\f0 Constitution.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 
  The Court has held that this right to privacy allows one to control one\hich\f0 \rquote \loch\f0 s own body.  In }{\i \hich\af0\dbch\af17\loch\f0 Roe}{\hich\af0\dbch\af17\loch\f0 \hich\f0 , the Court found that this right extends to abortion, \'93
\loch\f0 because until the end of the first trimester mortality in abortion is less than mortality in\hich\af0\dbch\af17\loch\f0 \hich\f0  normal childbirth.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}
}{\hich\af0\dbch\af17\loch\f0 
  This analysis is particularly analogous to the gene therapy discussion, where the mortality of X-SCID patients is much higher without the right to this treatment than if this treatment were available.  Both abortion and gene therapy 
\hich\af0\dbch\af17\loch\f0 are procedures that protect one\hich\f0 \rquote \loch\f0 
s mortality, but one is a rightful, undeniable choice, and one is an unlawful unavailable choice.  Peculiarly, it is the choice that is unneeded by the availability of contraception that is legal, where the choice that is n\hich\af0\dbch\af17\loch\f0 e
\hich\af0\dbch\af17\loch\f0 eded by the inescapable nature of genetic disorders is illegal.  Peculiarly, the choice that, without, may come with a higher risk of mortality is legal, where the choice that, without, guarantees mortality, is illegal.  

\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 In deciding }{\i \hich\af0\dbch\af17\loch\f0 Roe}{\hich\af0\dbch\af17\loch\f0 , the Court noted, \loch\af0\dbch\af17\hich\f0 
\'93\loch\f0 This right of privacy, whether it be founded in the Fourteenth Amendment\hich\f0 \rquote \loch\f0 s concept of personal liberty [as] we feel it is, [or] in the [Ninth Amendment], is broad enough to encompass a woman\hich\f0 \rquote \loch\f0 
s decision whether or not to terminate her pregnancy.  The detr\hich\af0\dbch\af17\loch\f0 i\hich\af0\dbch\af17\loch\f0 \hich\f0 
ment that the State would impose upon the pregnant woman by denying this choice altogether is apparent.  Specific and direct harm medically diagnosable even in early pregnancy may be [involved].\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 , 410 U.S. 113 (1973).}}}{\hich\af0\dbch\af17\loch\f0   Again, this statement can easily include gene therapy, whe\hich\af0\dbch\af17\loch\f0 \hich\f0 
re the specific harm that the government imposes with the halted trials is undeniable: boys die.  The Court upheld \'93}{\i \hich\af0\dbch\af17\loch\f0 Roe}{\loch\af0\dbch\af17\hich\f0 \rquote \loch\f0 \hich\f0 s essential holding\'94}{\cs18\super \chftn 
{\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i 
\hich\af0\dbch\af17\loch\f0 Planned Parenthood of Southeastern Penn. v.\hich\af0\dbch\af17\loch\f0  Casey}{\hich\af0\dbch\af17\loch\f0 , 505 U.S. 838 (1992).}}}{\hich\af0\dbch\af17\loch\f0  in}{\i \hich\af0\dbch\af17\loch\f0 
 Planned Parenthood of Southeastern Penn. v. Casey}{\hich\af0\dbch\af17\loch\f0 .}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   The Court there stated, \'93\loch\f0 
[It] is tempting, as a means of c\hich\af0\dbch\af17\loch\f0 
urbing the discretion of federal judges, to suppose that liberty encompasses no more than those rights already guaranteed to the individual against federal interference by the express provisions of the first eight amendments to the Constitution.  But of c
\hich\af0\dbch\af17\loch\f0 o\hich\af0\dbch\af17\loch\f0 \hich\f0 urse this Court has never accepted that view.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   The Court noted, \'93\loch\f0 
\hich\f0 It is a promise of the Constitution that there is a realm of personal liberty which the government may not enter.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   The Court then resolved, \'93
\loch\f0 [It] is settled now, as it was when the Court \hich\af0\dbch\af17\loch\f0 heard arguments in }{\i \hich\af0\dbch\af17\loch\f0 Roe}{\hich\af0\dbch\af17\loch\f0 , that the Constitution places limits on a State\hich\f0 \rquote \loch\f0 
s right to interfere with a person\hich\f0 \rquote \loch\f0 \hich\f0 s most basic decisions about family and parenthood, as well as bodily integrity.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}
}{\i 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The Supreme Court has also found a right to liberty, similar to the\hich\af0\dbch\af17\loch\f0 
 right of privacy, which also allows one to control one\hich\f0 \rquote \loch\f0 s own body.  For instance, }{\i \hich\af0\dbch\af17\loch\f0 Cruzan v. Director, Missouri Dep\hich\f0 \rquote \loch\f0 t of Health}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 
Cruzan v. Director, Missouri Dep\hich\f0 \rquote \loch\f0 t of Health}{\hich\af0\dbch\af17\loch\f0 , 497 U.S. 261 (1990) (finding, }{\i \hich\af0\dbch\af17\loch\f0 inter alia}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
, that a person can refuse medical treatment eve if that refusal will cause death).  \'93\loch\f0 But when still a vibrant pers\hich\af0\dbch\af17\loch\f0 on Nancy had once remarked that she did not want to live \hich\f0 \lquote \loch\f0 as a vegetable.
\hich\f0 \rquote \'94\loch\f0   }{\i \hich\af0\dbch\af17\loch\f0 Id.}{\hich\af0\dbch\af17\loch\f0 \hich\f0   \'93\loch\f0 \hich\f0 
[The] principle that a competent person has a constitutionally protected liberty interest in refusing unwanted medical treatment may be inferred from our prior decisions.\'94\loch\f0   }{\i \hich\af0\dbch\af17\loch\f0 Id.  See also Vacco v. Quill}{
\hich\af0\dbch\af17\loch\f0 \hich\f0 , 521 U.S. 793 (1997) (noting that \'93}{\i \hich\af0\dbch\af17\loch\f0 [e]veryone}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
, regardless of physical condition, is entitled, if competent, to refuse unwanted lifesaving medical treatment\'94\loch\f0 ); }{\i \hich\af0\dbch\af17\loch\f0 Washington v. Glucksberg}{\hich\af0\dbch\af17\loch\f0 , 521 U.S. 702 (1997) (citing }{\i 
\hich\af0\dbch\af17\loch\f0 Cruzan}{\hich\af0\dbch\af17\loch\f0  as supp\hich\af0\dbch\af17\loch\f0 \hich\f0 ort that \'93\loch\f0 \hich\f0 the Due Process Clause protects the traditional right to refuse unwanted lifesaving medical treatment\'94\loch\f0 
).}}}{\hich\af0\dbch\af17\loch\f0  held the right to liberty guaranteed the right to refuse medical treatment, even if the treatment would be life-saving and to r\hich\af0\dbch\af17\loch\f0 efuse it would be life-threatening.  The Court has found }{\i 
\hich\af0\dbch\af17\loch\f0 Cruzan}{\hich\af0\dbch\af17\loch\f0 \hich\f0  to hold, \'93\loch\f0 The Due Process Clause guarantees more than fair process, and the \hich\f0 \lquote \loch\f0 liberty\hich\f0 \rquote \loch\f0 
 it protects includes more than the absence of physical restraint.  [The] Clause also provides heightened p\hich\af0\dbch\af17\loch\f0 \hich\f0 rotection against government interference with certain fundamental rights and liberty interests.\'94}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Washington v. Glucksberg}{\hich\af0\dbch\af17\loch\f0 , 521 U.S. 702 (1997).}}}{\hich\af0\dbch\af17\loch\f0   Along with }{\i \hich\af0\dbch\af17\loch\f0 Maher v. Roe}{
\hich\af0\dbch\af17\loch\f0 ,}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super 
\chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Maher v. Roe}{\hich\af0\dbch\af17\loch\f0 , 432 U.S. 464 (1977) (upholding, }{\i \hich\af0\dbch\af17\loch\f0 inter alia}{\hich\af0\dbch\af17\loch\f0 , Connecticut\hich\f0 \rquote 
\loch\f0 s use of Medicaid fu\hich\af0\dbch\af17\loch\f0 nds to reimburse women for the costs of medically necessary, including for reasons of mental health, abortions).}}}{\hich\af0\dbch\af17\loch\f0 
 where the Court found a right to medical treatment, the Court\hich\f0 \rquote \loch\f0 s finding of rights to privacy, autonomy, personhood, liberty, life,\hich\af0\dbch\af17\loch\f0 
 and dignity support a Constitutional right to gene therapy when there are no other options.  The }{\i \hich\af0\dbch\af17\loch\f0 Roe}{\hich\af0\dbch\af17\loch\f0 \hich\f0  Court held, \'93\loch\f0 [Where] certain \hich\f0 \lquote \loch\f0 
fundamental rights\hich\f0 \rquote \loch\f0  are involved, the Court has held that regulation limiting these rights may be justified only by a \hich\f0 \lquote \loch\f0 compe\hich\af0\dbch\af17\loch\f0 \hich\f0 lling state interest,\'94\loch\f0 \hich\f0 
 and that legislative enactments must be narrowly drawn to express only the legitimate state interests at stake.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 , 410 U.S. 113 (1973).}}}{
\hich\af0\dbch\af17\loch\f0   What is the compelling state interest in denying medical treatment, in denying control over one\hich\f0 \rquote \loch\f0 s own body, in denying\hich\af0\dbch\af17\loch\f0 \hich\f0 
 the right to privacy, in the FDA decision that denies the option of gene therapy?  Although overruled by the Supreme Court, the Tenth Circuit made a powerful argument, \'93\loch\f0 [W]hat can \hich\f0 \lquote \loch\f0 generally recognized\hich\f0 
\rquote \loch\f0  as \hich\f0 \lquote \loch\f0 safe and effective\hich\f0 \rquote \loch\f0  mean as to such persons who\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 \hich\f0 
are so fatally stricken with a disease for which there is no known cure?\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 
, 582 F.2d 1234, 1237 (10th Cir. 1978).  }}}{\hich\af0\dbch\af17\loch\f0 \hich\f0   The concern of the Supreme Court in overruling this decision was in finding that there is \'93\loch\f0 \hich\f0 
no special provision for drugs used to treat terminally ill patients.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 442 U
\hich\af0\dbch\af17\loch\f0 .S. 544 (1979).  }}}{\hich\af0\dbch\af17\loch\f0   However, these p\hich\af0\dbch\af17\loch\f0 
atients are not arguing for a special right for terminally ill patients any more than abortion gives a special right for pregnant women or the right to refuse medical treatment gives a special right for those in need of medical treatment.  Instead, the Su
\hich\af0\dbch\af17\loch\f0 p\hich\af0\dbch\af17\loch\f0 
reme Court should view it as a right for all to choose riskier treatments when death is imminent and there are no alternate treatments.  Furthermore, the Tenth Circuit decision articulates that the compelling state interest in protecting human life,}{
\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{
\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 See, e.g.}{\hich\af0\dbch\af17\loch\f0 , }{\i \hich\af0\dbch\af17\loch\f0 Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 \hich\f0 , 410 U.S. 113 (1973) (\'93\loch\f0 
We repeat, however, that the State does have an important and legitimate interest in preserving and protecting the health of the pregnant woman [and] that it has still }{\i \hich\af0\dbch\af17\loch\f0 another }{\hich\af0\dbch\af17\loch\f0 important and 
\hich\af0\dbch\af17\loch\f0 \hich\f0 legitimate interest in protecting the potentiality of human life.\'94\loch\f0 ).}}}{\hich\af0\dbch\af17\loch\f0  and i\hich\af0\dbch\af17\loch\f0 
n thus prohibiting life-threatening treatments, cannot be applied to a person whose only chance of survival is the life-threatening treatment.  
\par }\pard \qj \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\fs40 \page \hich\af0\dbch\af17\loch\f0 B.  The Lives
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 The FDA admittedly has a congressional mandate to regulate gene therapy and to protect the Ameri\hich\af0\dbch\af17\loch\f0 
can public.  However, the proper interpretation of this mandate must be different in cases involving rare life-threatening diseases.  Under the Supreme Court rulings above, the FDA should adopt less rigid regulations, allow for greater personal autonomy b
\hich\af0\dbch\af17\loch\f0 y\hich\af0\dbch\af17\loch\f0 
 permitting high-risk treatment options when there are no other options, and the disease is fatal.  A governmental tolerance for high-risk treatments in cases of X-SCID makes legal, financial, and ethical sense, since the United States Constitution guaran
\hich\af0\dbch\af17\loch\f0 t\hich\af0\dbch\af17\loch\f0 ees individual liberty, the resources of the FDA are limited, and the alternative for these children is only death.  
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
The FDA mandate should include a duty to protect American rights, as well as American lives.  Thus, in fatal diseases, especially where th\hich\af0\dbch\af17\loch\f0 
ere are no other options, the FDA regulations must be more flexible, to acknowledge that the compelling state interest of protecting life changes in those cases.  The FDA mandate should include a duty to inform and educate patients to help patients make t
\hich\af0\dbch\af17\loch\f0 h\hich\af0\dbch\af17\loch\f0 
eir constitutionally protected choice.  The FDA mandate would continue to include a duty to protect lives. For high-risk treatments of life-threatening diseases, the FDA could require that the patients sign a contract that binds patients and waives claims
\hich\af0\dbch\af17\loch\f0  \hich\af0\dbch\af17\loch\f0 for damages.}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  This option is not currently available under the Investigation New Drug (\'93\loch\f0 \hich\f0 IND\'94
\loch\f0 ) process for drugs that are currently in the clinical trial phase that treat fatal diseases.}}}{\hich\af0\dbch\af17\loch\f0 \hich\f0 
  In the case of X-SCID gene therapy treatments, the FDA could adopt the standards recommended by the Biological Response Modifiers Advisory Committee (\'93\loch\f0 \hich\f0 BRMAC\'94\loch\f0 
).  The FDA could limit potential gene therapy candidates to patients who do not hav\hich\af0\dbch\af17\loch\f0 \hich\f0 e a donor match for a bone marrow transplant, have a high likelihood of contracting graft versus host disease (\'93\loch\f0 \hich\f0 
GVHD\'94\loch\f0 ), or have had an unsuccessful transplant.  
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 Finally, the FDA could focus more, especially with bubble boy disease, on early diagnosis.  \'93\lquote 
\hich\af0\dbch\af17\loch\f0 This once-fatal disease should be now seen as a pediatric emergency, a condition that needs immediate diagnosis and treatment,\hich\f0 \rquote \loch\f0  says Dr. Rebecca Buckley, chief of Duke\hich\f0 \rquote \loch\f0 \hich\f0 
s division of pediatric allergy and immunology.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 \hich\f0  \'93\loch\f0 Early Marr\hich\af0\dbch\af17\loch\f0 ow Transplant May be Key to \hich\f0 \lquote \loch\f0 
Bubble Boy\hich\f0 \rquote \loch\f0 \hich\f0  Disease Cure,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Doctor\hich\f0 \rquote \loch\f0 s Guide, }{\hich\af0\dbch\af17\loch\f0 May 5, 1997 at http://www.pslgroup.com/dg/25666.htm.}}}{
\hich\af0\dbch\af17\loch\f0   SCID patients would have a higher cha\hich\af0\dbch\af17\loch\f0 \hich\f0 nce of survival with an early diagnosis, before the disease reached advanced stages. \'93\loch\f0 
The transplant needs to be done before the onset of opportunistic infection, she explained, and in the first few weeks of the baby\hich\f0 \rquote \loch\f0 s life, when the donor marrow takes ho\hich\af0\dbch\af17\loch\f0 l\hich\af0\dbch\af17\loch\f0 
\hich\f0 d quickest.  Waiting until after the first four weeks of life increases the risk of infection, as well as slowing the development of immunity from the donor transplant.\'94}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}
}{\hich\af0\dbch\af17\loch\f0   Indeed, researchers recommend testing newborn babies, because even a month-old baby \hich\af0\dbch\af17\loch\f0 \hich\f0 has an increased risk in the transplant than a newborn.  \'93\loch\f0 
Early diagnosis of SCID is rare because doctors do not routinely perform a test in newborns to count white blood cells.  Such a blood test could pick up children with SCID as well as those with oth\hich\af0\dbch\af17\loch\f0 e\hich\af0\dbch\af17\loch\f0 
\hich\f0 r serious immune deficiencies that would not be apparent until the child developed an infection.\'94}{\cs18\super \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\hich\af0\dbch\af17\loch\f0 
  Doctors argue for early diagnosis to give more time to find a matched transplant donor, to have a chance to do the transplant while the child is still healt\hich\af0\dbch\af17\loch\f0 \hich\f0 hy, and to allow for less costly procedures.  \'93\lquote 
\loch\f0 A simple blood test could allow us to treat, and most likely cure, SCID in an infant at a reasonable cost.  If found later, less effective treatment can run into the millions.\hich\f0 \rquote \loch\f0   Buckley states, \hich\f0 \lquote \loch\f0 
What we\hich\f0 \rquote \loch\f0 re s\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 ying is that essentially every baby with SCID could be cured if diagnosed early enough.  SCID should be considered a pediatric emergency.\hich\f0 \rquote \'94}{
\cs18\super \hich\af0\dbch\af17\loch\f0  \chftn {\footnote \pard\plain \s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super 
\chftn }{\hich\af0\dbch\af17\loch\f0  }{\i \hich\af0\dbch\af17\loch\f0 Id.}}}{\fs40 \hich\af0\dbch\af17\loch\f0  }{
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 V.  Conclusion}{\scaps\fs52\ul 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 In conclusion, the American public has a legal right to choose the best treatment for life-threat\hich\af0\dbch\af17\loch\f0 
ening diseases when there are no available risk-free treatments and there is a guarantee of an early death without any treatment.  In the case of rare fatal diseases, the individual patient is in the best position to research options, and make decisions b
\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 sed upon those options.  The overly risk-averse nature of the FDA may violate constitutional rights and American values. 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
The FDA can implement less rigid regulations for high-risk treatments involving life-threatening diseases without threatening its auth\hich\af0\dbch\af17\loch\f0 
ority in protecting the American public.  Although the FDA cannot be responsible for the risks of gene therapy when those risks are well understood, the FDA can bind patients who choose risky procedures.  These contracts could include clauses that waive t
\hich\af0\dbch\af17\loch\f0 h\hich\af0\dbch\af17\loch\f0 e patient\hich\f0 \rquote \loch\f0 s rights to file a claim later against the hospitals, doctors, and researchers for liability or damages.}{\cs18\super \chftn {\footnote \pard\plain 
\s17\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\cs18\super \chftn }{\hich\af0\dbch\af17\loch\f0 
 Under the Federal Tort and Claims Act, patients cannot sue the FDA, but this new waiver would similarly protect\hich\af0\dbch\af17\loch\f0  hospitals, doctors, and researchers of dangerous treatments for rare and fatal diseases, like X-SCID.}}}{
\hich\af0\dbch\af17\loch\f0   Furthermore, the FDA could limit potential gene-therapy candidates to patients who do not have a donor match for a bone marrow transplant, \hich\af0\dbch\af17\loch\f0 \hich\f0 
or have a high likelihood of contracting graft versus host disease (\'93\loch\f0 \hich\f0 GVHD\'94\loch\f0 ).
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\hich\af0\dbch\af17\loch\f0 
American values cherish individual freedoms of privacy, human dignity, and autonomy.  Thus, it is imperative for the FDA to change its standard procedures to fall in line with tho\hich\af0\dbch\af17\loch\f0 
se values.  In an effort to protect society from itself, the rolling wheels of the legal system too often enact paternal laws that conflict with these values.  Unfortunately, while American may possess a model system, it still fails to check and balance l
\hich\af0\dbch\af17\loch\f0 a\hich\af0\dbch\af17\loch\f0 ws as quickly as they can be passed.}{\fs32 
\par }\pard \qj \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 Bibliography
\par }\pard\plain \s4\ql \li0\ri0\sl480\slmult1\keepn\widctlpar\aspalpha\aspnum\faauto\outlinelevel3\adjustright\rin0\lin0\itap0 \fs28\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\scaps\fs40 \hich\af0\dbch\af17\loch\f0 
A.  Statutes
\par }\pard\plain \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 93 Stat. 668, 695 (1979).

\par \hich\af0\dbch\af17\loch\f0 \hich\f0 42 U.S.C. \'a7\loch\f0  300cc-12.
\par }\pard\plain \s5\ql \fi-720\li720\ri0\sl480\slmult1\keepn\widctlpar\aspalpha\aspnum\faauto\outlinelevel4\adjustright\rin0\lin720\itap0 \scaps\fs36\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\fs40 
\hich\af0\dbch\af17\loch\f0 B.  Cases
\par }\pard\plain \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\ul \hich\af0\dbch\af17\loch\f0 
Cruzan v. Director, Missouri Dep\hich\f0 \rquote \loch\f0 t of Health}{\hich\af0\dbch\af17\loch\f0 , 497 U.S. 261 (1990).}{\ul 
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\ul \hich\af0\dbch\af17\loch\f0 Eisenstadt v. Baird}{\hich\af0\dbch\af17\loch\f0 , 405 U.S. 438 (1972).
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\ul \hich\af0\dbch\af17\loch\f0 Griswold v. Connecticut}{\hich\af0\dbch\af17\loch\f0 ,\hich\af0\dbch\af17\loch\f0  381 U.S. 479 (1965).
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\ul \hich\af0\dbch\af17\loch\f0 Maher v. Roe}{\hich\af0\dbch\af17\loch\f0 , 432 U.S. 464 (1977).
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\ul \hich\af0\dbch\af17\loch\f0 Planned Parenthood of Southeastern Penn. v. Casey}{\hich\af0\dbch\af17\loch\f0 , 505 U.S. 838 (1992)}{\ul 
\par \hich\af0\dbch\af17\loch\f0 Roe v. Wade}{\hich\af0\dbch\af17\loch\f0 , 410 U.S. 113 (1973).
\par }{\ul \hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 438 F. Supp. 1287 (W.D. Okl. 1977).  
\par }{\ul \hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 582 F.2d 1234, 1237 (10th Cir. 1978).  
\par }{\ul \hich\af0\dbch\af17\loch\f0 Rutherford v. United States}{\hich\af0\dbch\af17\loch\f0 , 442 U.S. 544 (1979).  
\par }{\ul \hich\af0\dbch\af17\loch\f0 Vacco v. Quill}{\hich\af0\dbch\af17\loch\f0 , 521 U.S. 793 (1997).
\par }{\ul \hich\af0\dbch\af17\loch\f0 Washington v. Glucksberg}{\hich\af0\dbch\af17\loch\f0 , 521 U.S. 702 (1997).
\par }\pard\plain \s4\ql \li0\ri0\sl480\slmult1\keepn\widctlpar\aspalpha\aspnum\faauto\outlinelevel3\adjustright\rin0\lin0\itap0 \fs28\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\scaps\fs40 \hich\af0\dbch\af17\loch\f0 
D.  Publications
\par }\pard\plain \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 \fs24\cf1\lang1033\langfe2052\loch\af0\hich\af0\dbch\af17\cgrid\langnp1033\langfenp2052 {\hich\af0\dbch\af17\loch\f0 \hich\f0 
Anderson, W. French, \'93\loch\f0 \hich\f0 Human Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 392 Nature 25, 25-\hich\af0\dbch\af17\loch\f0 30 (1998), }{\hich\af0\dbch\af17\loch\f0 
also at http://www.frenchanderson.org/docarticles/pdf/humangenetherapy_0498.PDF.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 Anderson, W. French, \'93\loch\f0 \hich\f0 Human Gene Therapy: The Initial Concepts,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Gene Therapy for Diseases of the Lung,}{\hich\af0\dbch\af17\loch\f0 
 Brigham, K.L., eds.:  Marcel Dekker, Inc. (1997) at 3-16, al\hich\af0\dbch\af17\loch\f0 so at http://www.frenchanderson.org/docarticles/pdf/hgt_initial.pdf
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 CBER Talkpapers,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
Center for Biologics Evaluation and Research}{\hich\af0\dbch\af17\loch\f0  at http://www.fda.gov/cber/talkpapers.htm. 
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Cellular and Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
Center for Biologics Evaluation and Research}{\hich\af0\dbch\af17\loch\f0  at htt\hich\af0\dbch\af17\loch\f0 p://www.fda.gov/cber/gene.htm.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Designation and Locations of FDA in Federal Government,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 U.S. Food and Drug Administration}{\hich\af0\dbch\af17\loch\f0  at http://www.fda.gov/opacom/morechoices/designat.html. 
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Early Marrow Transplant May be Key to \hich\f0 \lquote \loch\f0 Bubble Boy\hich\f0 \rquote \loch\f0 
\hich\f0  Disease Cure,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Doctor\hich\f0 \rquote \loch\f0 s \hich\af0\dbch\af17\loch\f0 Guide, }{\hich\af0\dbch\af17\loch\f0 May 5, 1997 at http://www.pslgroup.com/dg/25666.htm.
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 FDA Places Temporary Halt on Gene Therapy Trials Using Retroviral Vectors in Blood Stem Cells,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 FDA Talk Paper, }{\hich\af0\dbch\af17\loch\f0 
January 14, 2003 at http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html.
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Freq\hich\af0\dbch\af17\loch\f0 \hich\f0 uently Asked Questions,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Center for Biologics Evaluation and Research}{\hich\af0\dbch\af17\loch\f0 
 at http://www.fda.gov/cber/faq.htm. 
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Frequently Asked Questions,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 U.S. Food and Drug Administration}{\hich\af0\dbch\af17\loch\f0  at http://www.fda.gov/opacom/faqs/faqs.html. 
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Gene Therapy,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Human Genome Project In\hich\af0\dbch\af17\loch\f0 formation}{\hich\af0\dbch\af17\loch\f0 
 at http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml.
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Gene Therapy Causes Cancer in Mice,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 , April 18, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992186.

\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Gene Therapy Cures \hich\f0 \lquote \loch\f0 Bubble Boy,\hich\f0 \rquote \'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 N\hich\af0\dbch\af17\loch\f0 ew Scientist}{\hich\af0\dbch\af17\loch\f0 
, April 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992124.
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Gene Therapy Turns 10,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Current Science}{\hich\af0\dbch\af17\loch\f0 
, January 19, 2001 at http://www.findarticles.com/cf_dls/m0BFU/10_86/69527187/p1/article.jhtml. 
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Gene Transfer,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Genetics and P\hich\af0\dbch\af17\loch\f0 ublic Policy Center}{\hich\af0\dbch\af17\loch\f0 
 at http://www.dnapolicy.org/genetics/transfer.jhmtl;$sessionid$4I4DCIQAACY4WCQBAT#RVQQ.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 Gura, Trisha, \'93\loch\f0 \hich\f0 After a Setback, Gene Therapy Progresses . . . Gingerly,\'94\loch\f0  291 }{\scaps \hich\af0\dbch\af17\loch\f0 Science}{\hich\af0\dbch\af17\loch\f0 
 1692, 1692-1697 (March 2, 2001) and at http://www.sciencemag.or\hich\af0\dbch\af17\loch\f0 g/cgi/content/full/291/5509/1692.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Homo Sapiens Diseases Immunity,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
Molecular Immunology }{\hich\af0\dbch\af17\loch\f0 at http://xoomer.virgilio.it/medicine/pathohomotissueimmunity.html.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 Hutt, Peter B. and Richard A. Merrill, \'93\loch\f0 \hich\f0 Regulation of Biotechnology,\'94\loch\f0  }{
\scaps \hich\af0\dbch\af17\loch\f0 Food and Drug Law: Cases and \hich\af0\dbch\af17\loch\f0 Materials}{\hich\af0\dbch\af17\loch\f0 , Westbury, NY:  The Foundation Press Inc (1991).
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Inherited (Congenital) Immune System Disorders,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
The National Marrow Donor Program}{\hich\af0\dbch\af17\loch\f0  at http://www.marrow.org/MEDICAL/immune_sys_disorders.html.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 Lehrman, Sally, \'93\loch\f0 Virus Treatment Questioned After Gen\hich\af0\dbch\af17\loch\f0 \hich\f0 
e Therapy Death,\'94\loch\f0  401 }{\scaps \hich\af0\dbch\af17\loch\f0 Nature}{\hich\af0\dbch\af17\loch\f0  517, 517-18 (October 7, 2001) and at http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v401/n6753/full/401517b0_fs.html.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 Loomis, Joshua, \'93\loch\f0 X-SCID Gene Therapy in France \hich\f0 \endash \loch\f0 \hich\f0  An Undesirable Integration Event,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 Viral Ve\hich\af0\dbch\af17\loch\f0 
ctors as Mediators of Gene Therapy}{\hich\af0\dbch\af17\loch\f0  at http://narnia.n.ml.org/skier/writings/doc/microm%20496.doc. 
\par \loch\af0\dbch\af17\hich\f0 \'93\lquote \loch\f0 Miracle\hich\f0 \rquote \loch\f0 \hich\f0  Gene Therapy Trial Halted,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 New Scientist}{\hich\af0\dbch\af17\loch\f0 
, October 3, 2002 at http://www.newscientist.com/news/news.jsp?id=ns99992878.
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 New Cure For Bubble Boy Di\hich\af0\dbch\af17\loch\f0 \hich\f0 sease,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 CBS News, }{\hich\af0\dbch\af17\loch\f0 
April 17, 2002 at http://www.cbsnews.com/stories/2002/04/17/tech/main506451.shtml.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 Pollack, Andrew, \'93\loch\f0 \hich\f0 2nd Cancer is Attributed to Gene Used in French Test,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The New York Times}{\hich\af0\dbch\af17\loch\f0 
, January 17, 2003 at Health and at http://www.newyorktimes.com/\hich\af0\dbch\af17\loch\f0 2003/01/17/health/17GENE.html.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 Pollack, Andrew, \'93\loch\f0 \hich\f0 Gene Therapy Trials Halted,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 The New York Times}{\hich\af0\dbch\af17\loch\f0 , January 15, 2003 at Health and at http://www.newyorktimes.com/2003/01/15/health/15GENE.html.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Risk-Benefit Analysis,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 WUSTL}{
\hich\af0\dbch\af17\loch\f0 , October 12, 1994 at http://capita\hich\af0\dbch\af17\loch\f0 .wustl.edu/ME567_Informatics/concepts/riskben.html
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\hich\af0\dbch\af17\loch\f0 \hich\f0 Smuskiewicz, Alfred J., \'93\loch\f0 \hich\f0 Genetic Medicine Update,\'94\loch\f0  }{\scaps 
\hich\af0\dbch\af17\loch\f0 World Book}{\hich\af0\dbch\af17\loch\f0 , 2001 at http://home.earthlink.net/~ajjsart/genmedwb.html.
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\loch\af0\dbch\af17\hich\f0 \'93\loch\f0 \hich\f0 Severe Combined Immunodeficiency,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 
The SCID Homepage}{\hich\af0\dbch\af17\loch\f0  at http://www.scid.net/. 
\par \loch\af0\dbch\af17\hich\f0 \'93\loch\f0 Sev\hich\af0\dbch\af17\loch\f0 \hich\f0 ere Combined Immunodeficiency Disease,\'94\loch\f0  }{\scaps \hich\af0\dbch\af17\loch\f0 The Merck Manual \hich\f0 \endash \loch\f0  Second Home Edition}{
\hich\af0\dbch\af17\loch\f0  at http://www.merck.com/mrkshared/mmanual_home2/sec16/ch184/ch184i.jsp.
\par \hich\af0\dbch\af17\loch\f0 \hich\f0 Stephenson, Joan, \'93\loch\f0 \hich\f0 Studies Illuminate Cause of Fatal Reaction in Gene-Therapy Trial,\'94\loch\f0  285 }{\scaps \hich\af0\dbch\af17\loch\f0 JAMA: The Journ\hich\af0\dbch\af17\loch\f0 
al of the American Medical Association}{\hich\af0\dbch\af17\loch\f0  2570 (May 23-30, 2001) and at http://jama.ama-assn.org/cgi/content/full/285/20/2570.
\par 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\page }{\scaps\fs52 \hich\af0\dbch\af17\loch\f0 Acronyms
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\hich\af0\dbch\af17\loch\f0 ADA-SCID = adenosine deaminase severe combined immunodeficiency
\par \hich\af0\dbch\af17\loch\f0 AIDS = acquired immunodeficiency syndrome
\par }\pard \ql \fi-720\li720\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0 {\hich\af0\dbch\af17\loch\f0 BRMAC = Biologi\hich\af0\dbch\af17\loch\f0 cal Response Modifiers Advisory Committee 
\par \hich\af0\dbch\af17\loch\f0 CBER = Center for Biologics Evaluation and Research
\par \hich\af0\dbch\af17\loch\f0 FDA = Food and Drug Administration
\par \hich\af0\dbch\af17\loch\f0 GVHD = graft versus host disease
\par \hich\af0\dbch\af17\loch\f0 HIV = human immunodeficiency virus
\par \hich\af0\dbch\af17\loch\f0 IND = investigational new drugs
\par \hich\af0\dbch\af17\loch\f0 IRB = institutional review\hich\af0\dbch\af17\loch\f0  board 
\par \hich\af0\dbch\af17\loch\f0 NIH = National Institutes of Health
\par \hich\af0\dbch\af17\loch\f0 RAC = Recombinant DNA Research Advisory Committee
\par \hich\af0\dbch\af17\loch\f0 SCID = severe combined immunodeficiency
\par }\pard\plain \s15\ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\cf1\lang1033\langfe2052\loch\af6\hich\af6\dbch\af17\cgrid\langnp1033\langfenp2052 {\f0 \hich\af0\dbch\af17\loch\f0 
X-SCID = X-linked severe combined immunodeficiency
\par }}