9 
Dr. Clewell said his laboratory performed seme studies several years ago on 
the mobilization by conjugative plasmids of chromosomal genes in faecalis . 
Trans fer was seen at the frequency of 10“^ per donor. This study is the 
only published demonstration of mobilization of chromosomal markers in gram- 
positive bacteria. 
Dr. Pattee said his laboratory had investigated faecalis /S. aureus pairs 
and had only observed plasmid transfer. 
Dr. Dean said seme data on the chromosomal transfer of chromosomal ly- located 
streptomycin resistance genes between cereus and thuringiensis exist but 
these data have not been published. 
Dr. Friedman introduced to the working group Dr. Susan Gottesman of the NIH. 
He asked Dr. Gottesman, a member of the RAC, to describe the philosophical 
basis of Appendix A of the NIH Guidelines. 
Dr. Gottesman said under Section III-D-4 organisms vhich exchange DNA by known 
physiological processes have been exempted from the NIH Guidelines. The argument 
supporting this exemption is the following: if exchange of chromosomal genes 
can be shown to occur under natural conditions, no novel combinations would 
arise in the laboratory through use of recombinant DNA techniques. 
Dr. Gottesman said in 1978, RAC accepted evidence of chromosomal exchange be- 
tween organisms as an indication that no "novel" organism would be created 
through laboratory combination of the genes of these organisms? RAC also accepted 
data demonstrating plasmid mobilization of chromosomal genes as an indication 
no "novel" organisms would be created. Later, information in gram-negative 
bacteria demonstrating that chromosomal gene exchange occurred at some frequency 
with plasmid exchange accumulated. Eventually, for gram-negative bacteria 
RAC accepted that plasmid exchange could result in transfer of chromosomal 
genes . 
Dr. Cohen asked whether the working group would have to demonstrate that ex- 
changes occur in nature to support their r eccmne nda t ion . Was the effect of 
different ecological niches on the transfer frequency considered vhen the 
gram-negative bacteria were evaluated for inclusion in Appendix A? Dr. Gottesman 
replied that if exchange could be shown in the laboratory, RAC has accepted 
the argument that given enough time and space such genetic exchange could occur 
in nature. She said RAC did not consider the effect of different ecological 
niches on the probability of exchange. 
Dr. Baltz asked vhether RAC considered the effect of site-directed changes on 
organisms exempted from the NIH Guidelines. Site-directed mutagenesis speeds up 
the process of evolution and might generate an organism vhich had not arisen in 
nature. Dr. Gottesman said RAC has chosen to ignore the effect of site-directed 
nutagenesis on evolution. However, any testing in the environment of a modified 
organism must be reviewed by RAC and approved by NIH and the IBC even if laboratory 
manipulations involving the modified organism are exerrpt frem the NIH Guidelines. 
[540] 
