Recombinant DNA Advisory Committee - 01/14/93 
Dr. Royston's protocol is minimally invasive, involving the peripheral subcutaneous 
injection of gene-modified cells. 
On December 23, 1992, Dr. Liotta, Dr. Wivel, and Mr. Lanman (NIH's legal counsel) 
met with the staff of the Assistant Secretary for Health and representatives of the FDA. 
At that meeting, the FDA representatives announced that Dr. Royston's single patient 
IND for compassionate use of gene therapy would probably be granted. In light of this 
announcement, Mr. Lanman advised NIH that absent any mechanism for compassionate 
plea exemption in the NIH Guidelines, it is within the authority of the NIH Director to 
make a decision regarding this request, pending FDA approval. 
On December 28, 1992, the FDA advised NIH in writing that Dr. Royston's IND request 
had been approved with the use of Dr. Bernd Gansbacher's vector, NAPAD/IL2. Dr. 
Gansbacher had previously received NIH and FDA approval for the use of this vector in 
melanoma and renal cell carcinoma trials. The FDA viewed Dr. Royston's protocol as 
an extension of Dr. Gansbacher's protocol. Dr. Healy stated that based on FDA 
approval and concurrence from Dr. Liotta, Mr. Lanman, and several NIH institute and 
division directors, she approved Dr. Royston's compassionate plea request. 
Subsequently, this action was endorsed unanimously by the NIH institute and center 
directors. 
Dr. Healy stated that her decision was based on the grave condition of the patient, the 
failure of all other available therapies, and an estimated survival of less than two months. 
First and foremost, the decision was a compassionate response to the request of a dying 
patient. This action was taken only after the assurance that there was no significant risk 
to either the health of the patient or the public. 
Dr. Healy reminded the RAC that this meeting was not held for the purpose of 
critiquing this action. Rather, the RAC should consider with some urgency the 
development of a process for considering compassionate plea requests for gene therapy 
in the future. During the December 1992 meeting, one element was missing from the 
RAC's discussion; namely, the element of concern for an individual patient and their 
family. The evolution of genetic research now imposes this element upon us. Given the 
serious plight of Dr. Royston's patient, the following two alternatives offered by the RAC 
were unacceptable: (1) inclusion of the patient in Dr. Oldfield's protocol, and (2) 
continued deliberations at the March 1-2, 1993, RAC meeting. 
Dr. Healy stated that there are at least three deficiencies in the current system for 
dealing with this new frontier of human gene therapy. First, the specific issue of 
compassionate use exemption is not encompassed by the NIH Guidelines, which embrace 
only research involving the use of recombinant DNA. Therefore, the argument can be 
made that a non-research compassionate plea exemption for a single patient is outside 
[ 10 ] 
Recombinant DNA Research, Volume 17 
