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Federal Register / Vol. 58, No. 175 / Monday, September 13; 1993 / Notices 
National Institutes of Health 
Recombinant DNA Research: Action 
Under the Guidelines 
AGENCY: National Institutes of Health, 
PHS, DHHS. 
ACTION: Notice of Action Under the NIH 
Guidelines for Research Involving 
Recombinant DNA Molecules. 
SUMMARY: This notice sets forth an 
action to be taken by the Director, 
National Institutes of Health (NIH), 
under the May 7, 1986, NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules (51 FR 16958). 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. Nelson A. Wivel, Director, 
Office of Recombinant DNA Activities 
(ORDA), Office of Science Policy and 
Technology Transfer, National Institutes 
of Health. Building 31, room 4B11, 
Bethesda, Maryland 20892, (301) 496- 
9838. 
SUPPLEMENTARY INFORMATION: Today, 
one action is being promulgated under 
the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
This proposed action was published for 
comment in the Federal Register of 
November 2, 1992 (57 FR 48584), and 
reviewed and recommended for 
approval by the NIH Recombinant DNA 
Advisory Committee (RAC) at its 
meeting on December 3—4, 1992. 
I. Background Information and 
Decisions on Action Under the NIH 
Guidelines 
A. Addition of Appendix D-XLVJ to the 
NIH Guidelines 
In a letter dated October 8, 1992, Dr. 
James M. Wilson, University of 
Michigan Medical Center, Ann Arbor, 
Michigan, submitted a human gene 
therapy protocol to the Recombinant 
DNA Advisory Committee for formal 
review and approval. The title of this 
protocol is: Gene Therapy of Cystic 
Fibrosis Lung Diseases Using El Deleted 
Adenoviruses: A Phase I Trail. This 
request was published for comment in 
the Federal Register of November 2, 
1992 (57 FR 49584). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of December 3—4, 1992, by 
a vote of 16 in favor, 0 opposed, and no 
abstentions. Approval of the protocol 
was contingent on the following 
stipulations: (l) The patient eligibility 
criterion in the Informed Consent 
document requiring that patients are 
documented to be sterile will be 
replaced with a statement suggesting 
that all patients should exercise 
appropriate birth control methods; (2) 
the expected benefits of the procedure 
should be clearly stated in the first 
section of the document; (3) submission 
of a revised Informed Consent document 
incorporating minor changes suggested 
by committee members; and (4) the 
demonstration that there is less than one 
replication-competent adenovirus 
particle per 20 milliliters of vector 
supernatant. 
On June 24, 1993, Dr. Wilson 
submitted sequencing information on 
the recombinant adenovirus vector, 
Ad.CF-CFTR, that will be used in the 
protocol. On August 2, 13, and 16, Dr. 
Wilson submitted materials to satisfy 
the rest of the stipulations. These 
materials were reviewed by primary 
reviewers of the protocol, and it was 
determined that the stipulations of the 
RAC were met. The following section 
may be added to Appendix D: 
"Appendix D-XLVI 
"Dr. James M. Wilson of the 
University of Pennsylvania Medical 
Center, Philadelphia, Pennsylvania, may 
conduct" experiments on 20 adult 
patients with advanced cystic fibrosis 
lung disease. An isolated segment of the 
patients' lung will be transduced with 
the El deleted, replication-incompetent 
adenovirus vector, Ad.CB-CFTR using a 
bronchoscope for gene delivery. Ad.CB- 
CFTR contains the human gene 
encoding the cystic fibrosis 
transmembrane conductance regulator 
(CFTR) protein. Pulmonary biopsies will 
be obtained by bronchoscopy at 4 days, 
6 weeks, and 3 months following 
treatment. Patients will be monitored for 
evidence of CFTR gene transfer and 
expression, immunological responses to 
CFTR or adenovirus proteins, and 
toxicity." 
I accept this recommendation, and 
Appendix D— XLVI of the NIH 
Guidelines will be added accordingly. 
II. Summary of Actions 
A. Addition of Appendix D-XLVI to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
"Dr. James M. Wilson of the 
University of Pennsylvania Medical 
Center, Philadelphia, Pennsylvania, may 
conduct experiments on 20 adult 
patients with advanced cystic fibrosis 
lung disease. An isolated segment of the 
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Recombinant DNA Research, Volume 18 
