Federal Renter / VoL 56. No. 138 / Thursday. July 18. 1991 / Notices . _ >^.^33177 
protocols to the Recombinant DNA 
Advisory Committee for consideration 
during the May 30-31, 1991. meeting. 
■ '^This request was published for 
comment in the Federal Register on 
April 29. 1991 (56 FR 197763- 
At the meeting of May 30-31, 1991, the 
Recombinant DNA Advisory Committee 
considered the recommendations of the 
Human Gene Therapy Subcommittee. 
Additional data was provided 
concerning the efficiency of transduction 
of bone marrow cells widi the gene 
coding for neomydn resistance. There 
were several changes made in the 
informed consent document It was 
suggested that the chemotherapy 
consent form be separated from the gene 
transfer consent form. 
The RAC, by a vote of 19 in favor, 
none opposed, and no abstentions, 
approved the two protocols. 
I accept this recommendation, and 
appendix D-XVin of the NIH Guidelines 
will be added accordingly. 
D. Addition to Appendix D of the "NIH 
Guidelines" Regarding a Human Gene 
Transfer Pwtocol/Dr. Deisserotb 
In a letter dated December 20, 1990, 
Dr. Albert B. Delsseroth of the MD 
Anderson Cancer Center of Houston. 
Texas, indicated his intention to submit 
a human gene transfer protocol to the 
'Human Gene Therapy Subcommittee 
and the Recombinant DNA Advisory 
Committee for former review and 
approval The tide of this protocol is; 
“Autologous Transplantation for 
Chronic Myelogenous Leukemia: 
Retroviral Marking to Discriminate 
Between Relapses Arising from Residual 
Systemic Disease vs. Residual 
Contamination of Autologous Marrow.*' 
This request was published for 
comment in the Federal Register on 
March 7. 1991 (56 FR 9707). 
The protocol was considered during 
the April 5, 1991, Human Gene 'Therapy 
Subcommittee meeting. The Hirnian 
Gene Therapy Subcommittee gave 
provisional approval with the 
stipulation that there be a major 
revision of the, consent form including 
text for differentiating the gene transfer 
part of the research from the other part 
of the research. Additional data needs 
to be provided about the level of 
neomycin resistance gene expression 
and BCR-Abl gene expression in 
colonies of cells isolated during blast 
crisi.i. ; 
The Human Gene 'Therapy 
Subcommittee forwarded this protocol 
to the Recombinant DNA Advisory 
Committee for consideration during the 
May .30-31. 1991 meeting. 
This request was published for 
comment in the Federal Register on 
April 29. 1991 (56 FR 19776). 
At the meeting of May 30-31. 1991. the 
Recombinant DNA Advisory Committee 
considered the recommendations of the 
Human Gene Therapy Subcommittee. 
Major changes were made in the 
consent form and there was a clear 
differentiation between the gene 
transfer portion of the protocol and the 
other cli^cal research studies. 
Additional data was presented 
regarding the efficiency of the gene 
transduction procedures, and the 
identification of colony-forming cells. 
It Was suggested that the investigator 
conduct one additional pre-clinical 
transduction experiment on a larger 
scale than previously shown. ‘This 
would provide important data about the 
efficiency of the transduction 
procedures under conditions more 
nearly related to the actual study of 
patients. 
*1110 RAC, by a vote of 19 in favor, 
none opposed, and no abstentations, 
approved the protocol 
I accept this recommendation, and 
appendix XIX of the NIH Guidelines will 
be added accordingly. 
EL Addition of Appendix D-XX to the 
"NIH Guidelines" Regarding a Human 
Gene Transfer Protocol/Drs. Ledley and 
Woo 
In a letter dated December 19. 1990, 
Drs. Fred D. Ledley end Savio L.G Woo 
of the Baylor College of Medicine of 
Houston, Texas, indicated their 
intention tc submit a human gene 
transfer protocol to the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee 
for formal review and approval. The title 
of this protocol is: 
“Hepatocellular Transplantation in 
Acute Hepatic Failure and Targeting 
Genetic Markers to Hepatic Cells.“ 
This request was published for 
comment in the Federal Re^ster on 
March 7, 1991 (56 FR 9707). 
This protocol was considered during 
the Apd 51, 1991, Human Gene Therapy 
Subcommittee meeting. ‘The Human 
Gene ‘Therapy Subcommittee gave 
provisional approval with the 
stipulation that more data be prorided 
about the transduction efficiency with 
the neomycin resistance gene in human 
hepatocytes. Additional changes were to 
be made in the consent form which 
would clarify the differences between 
the hepatocellular transplantation 
procedures and the use of the neomycin 
resistance gene as a marker. 
The Human Gene ‘Therapy 
Subcommittee forwarded this protocol 
'•to the Recombinant DNA Advisory 
Committea for consideration during the 
May 30-31, 1991, meeting. - 
The request was published for 
comment in the Federal Renter on 
April 29. 1991 (56 FR 19776). 
At the meeting of May 30-31, 1991. the 
RAC considered the recommendations 
of the Human Gene ‘Th^py . 
Subcommittee. In response to the 
H uman Gene Therapy Subcommittee 
request for additional data concerning 
the transduction efficiency .of the 
neomycin resistance gene, the ' • 
investigators presented data from 
different patients. ‘The preclinical data 
demonstrates that the transduction 
efficiency is in the range of 0.1 percent 
to 1 percent ‘The requested changes 
were made in the consent form. Du ring 
the course of discussion by the 
Recombinant DNA Advisory Committee, 
it became apparent that there are a 
number of fluorescent dye labeling 
techniques which are more efficient than 
genetic^y marking celb. One of these 
membrane dyes, DiL has been used in 
baboon hepatocytes without untow^ 
effects. Dll has been shown to be non- 
metabolized, non-diffimible, and stable 
in vivo for prolonged periods of time. 
Given this discussion about non-genetic 
marking of cells, the protocol was 
provisionally approved pending receipt 
of further information about the safety 
of this dye in human subjects. 
‘The RAG by a vote of 18 in favor, 
none opposed, and no abstentions, 
approved this protocoL Following the 
Recombinant DNA Adidsory Committee 
meeting, the principal Investigator 
contacted the manufacturer of Dil, 
Moleodar Probes, Inc., and ascertained 
that there is no data on the use of this 
dye in bumains. There is no plan to 
develop such a dye for human use. Tnus. 
this approach for labeling hmnan 
hepatoc}rtes is not feasible at this time. 
I accept this recommendation, and 
appendix D-XX of the NIH Guidelines 
be added accord'mgly. 
F. Amend the "Points to Consider in the 
Design and Submission of Protocols for 
the Transfer of Recombinant DNA Into 
the Genome of Human Subfects"/Dr. 
Mclvor 
In a letter dated March 4. 1991, Dr. R 
Scott Mclvor of the University of 
Minnesota proposed having more 
explicit directives for animal model 
systems and cell culture studies in 
Section I— B-2 of the Points to Consider. 
Section I-B-2 in the Points to 
Cons/c/er currently reads: . • 
"Z. Preclinical studies, including risk- 
assessment studies. - ; ' ' 
“Describe the experimental basis . 
(derived from tests in cultured cells an 
*! 
I 
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Recombinant DNA Research, Volume 14 
