Recombinant DNA Advisory Committee - 09/14-15/92 
Dr. Walters noted that Dr. Neel had published the first scientific article in the American 
Journal of Human Genetics, published in 1949, and thanked Dr. Neel for addressing the 
RAC. Dr. Walters asked Dr. Neel to address Muller's "load of mutations" theory, and 
whether these mutations could ever be reversed through technology or if humans must 
learn to cope with this inevitable condition. Dr. Neel answered that Mueller envisioned 
the human species as precariously balanced between an increase in the mutation rate 
and biological collapse. Dr. Neel stated that the prospects for the human condition are 
significantly better than those proposed by Mueller. 
Dr. Neel stated that he is not opposed to the approval of somatic cell gene therapy 
experiments for the treatment of disparate diseases of the type that the RAC has already 
approved. However, for protocols such as ADA, these children must be evaluated 
indefinitely. Sometimes the short-range gain is offset by long-term loss. An example of 
this scenario is the children who were cured of leukemia by intensive radiation and 
chemotherapy. Twenty years later, 20% of these individuals have induced secondary 
tumors. Dr. Murray thanked Dr. Neel. 
VII. PROPOSED ADDITIONS TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING THREE HUMAN GENE TRANSFER PROTOCOLS ENTITLED: (1) 
PHASE I/II STUDY OF THE USE OF RECOMBINANT HUMAN INTERLEUKIN 3 
STIMULATED PERIPHERAL BLOOD PROGENITOR CELL SUPPLEMENTATION 
IN AUTOLOGOUS BONE MARROW TRANSPLANTATION (ABMT) INPATIENTS 
WITH BREAST CARCINOMA OR HODGKINS DISEASE , (2) EVALUATION OF THE 
USE OF RECOMBINANT HUMAN GRANULOCYTE COLONY STIMULATING 
FACTOR (G-CSF) STIMULATED PERIPHERAL BLOOD PROGENITOR CELL 
SUPPLEMENTATION IN AUTOLOGOUS BONE MARROW TRANSPLANTATION IN 
PATIENTS WITH LYMPHOID MALIGNANCIES , AND (3) A TRIAL OF G-CSF 
STIMULATED PERIPHERAL BLOOD STEM CELLS FOR ENGRAFTMENT IN 
IDENTICAL TWINS /DR. SCHUENING 
Review-Dr. Geiduschek 
Dr. Murray called on Dr. Geiduschek to present his primary review of the three gene 
transfer protocols submitted by Dr. Friederich Schuening of the Fred Hutchinson Cancer 
Research Center, Seattle, Washington. Dr. Geiduschek provided a brief overview of 
these three protocols involving ABMT of CD34( + ) subpopulations of cells that have 
been transduced with a marker gene encoding for neo R . The investigators have 
presented a large amount of data derived from large animal models. These in vivo data 
suggest that there are wide fluctuations in the frequencies of clonal populations. Dr. 
Geiduschek stated that with the original review of these protocols, he had a number of 
concerns; however, Dr. Schuening responded to all of these questions satisfactorily. The 
one issue that remains to be resolved is that of safety testing and what constitutes a 
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