SEPTEMBER 6-7 - MINUTES OF MEETING 
10 
neglected. With regard to the question of active polypeptides, Dr. Gottesman 
said that the level necessary to get a result is higher than one is 
likely to achieve in a recombinant DNA experiment. With regard to the 
hormone question. Dr. Walters said that the quantities of insulin that 
would be made would be small compared to the amounts used in attempts to 
develop oral insulin. He said that there is the question of the action 
of other hormones on normal and compromised individuals. Dr. Novick 
said that there are one or two unanswered questions, and that the RAC 
could restrict the proposed exemption until additional data are available. 
With regard to the question of antigenicity/ Dr. Paul Burnett of Eli 
Lilly and Company said that feeding experiments involving E. coli K-12 
carrying the insulin A and B chains had been carried out with germ-free 
and normal animals. He said that, although there was temporary colonization, 
no insulin binding activity or antibody formation was observed in the 
animals. Dr. Novick said that the RAC would like to knew whether antibodies 
would be elicited if the 0-galactosidase-insulin fused protein was injected 
directly. Dr. Ross of Genentech said that in preliminary experiments 
detectable antibody to 8-galactosidase or insulin was not raised in rabbits. 
Mr. Dach of EDF said that the RAC should issue requests for information 
from industry. In response, Dr. Johnson of Eli Lilly and Company said 
that all of the data will eventually be published. 
Dr. Walters asked if there was agreement that the antigenicity question 
is the one with the least data. Dr. Rcwe agreed that the least data are 
available on this question. He said that he had previously solicited 
comnents from immunologists on this question. He said that there was 
not much concern, but there were some possibilities that should be tested. 
In response to a question about autoantibodies. Dr. Krause stated that 
it is easy to make autoantibodies in certain animals, but that it has 
never been demonstrated that autoantibodies have anything to do with 
producing a disease in rabbits that mimics rheumatoid arthritis. Dr. Wright 
said that GMAG is using the scheme of Dr. Brenner to assess experiments, 
and that she understands that experiments involving expression are being 
placed in category III. 
Dr. Gottesman said that there are still questions at some levels. Dr. Novick 
asked whether the RAC considers that active polypeptides are a hazard. 
Dr. Walters asked what kind of standards the Committee has for data. He 
said that leading immunologists have stated in letters that there is no 
tJieoretical basis for concern. Dr. Ross of Genentech said that they 
were unable to test for antibody response to the fused protein because 
it is a denatured, insoluble molecule. Dr. Krause said that one would 
expect some antibody to injected insulin in the rabbit. Dr. Goldstein 
said that he felt that there was not a consensus on this issue. In 
response to a comment, Dr. Setlow noted that Dr. Brenner had been invited 
but was unable to attend the RAC meeting. 
[ 159 ] 
