Center for Health Sciences 
University of Wisconsin-Madison 
University Hospital and Clinics 
Attachment IV - Page 3 
600 Highland Avenue 
Madison, Wisconsin 53792 
February 21, 1985 
Leroy Walters 
Director 
Kennedy Institute of Ethics 
Georgetown University 
Washington, D.C. 
Dear Mr. Walters: 
I am pediatric immunologist at the University of Wisconsin. 
I am writing to you about "Points to consider in the design and 
submission of somatic-cell gene therapy protocols" that was 
published in the January 22, 1985 Federal Register. 
I will restrict my comments to gene therapy for adenosine 
deaminase (ADA) deficiency. I have personally cared for six 
children with ADA deficiency. Currently available therapies for 
ADA deficiency include: 1) enzyme replacement therapy (red blood 
cell transfusions); 2) thymic factor and/or thymic transplant; 
3) bone marrow transplant. Although the first two therapies are 
usually ineffective, bone marrow transplantation may cure ADA 
deficiency . 
I am now taking care of a 6 1/2 year old child with ADA 
deficiency and severe combined immune deficiency who I feel should 
receive gene therapy as soon as possible. Enzyme replacement 
therapy, thymic factor and thymic transplant have been tried in 
this child without success. A bone marrow transplant could be 
tried in this girl. However, since there is no sibling who is 
identical, it would be a mismatched transplant. In this child, a 
mismatched bone marrow transplant would be very difficult since 
the minimal immunity she has would have to be "wiped out" with 
chemotherapy and radiotherapy prior to transplantation. Also, 
her chronic lung disease could be significantly worsened by the 
chemotherapy and radiotherapy. I think it is very likely that the 
transplant attempt would kill her. Both the parents and I feel 
that the known risks of bone marrow transplantaton in this child 
(infection, graft versus host disease, lung toxicity, cancer) are 
greater than the potential risks of gene therapy. Her lung 
disease may become too severe if we continue to wait - I feel we 
have approximately 12 months to do something. 
I believe that the risk of the viral vector (retrovirus) 
combining with viruses in the patient to form a new infectious 
agent is remote. I would urge your committee to recommend 
initiating clinical trials of gene therapy in patients with 
life-threatening illnesses such as ADA deficiency as soon as 
possible. I feel that clinical trials should not wait for the 
results of non-human primate studies. 
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