MEMORANDUM 
TO 
FROM 
SUBJECT 
DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE 
PUBLIC HEALTH SERVICE 
NATIONAL INSTITUTES Or HEALTH 
Director, NIH date: December 9, 1977 
Director, Office of Recombinant DNA Activities, NIGMS 
: Comments of Dr. David Botstein on Proposed Revised Guidelines 
On October 31, 1977, Dr. David Botstein of the Massachusetts Institute 
of Technology briefly addressed the Recombinant DNA Molecule Program 
Advisory Committee with comments on the proposed revised Guidelines 
for Research Involving Recombinant DNA Molecules. 
Dr. Botstein emphasized that the language in the Guidelines needs to 
be precise. He was particularly concerned that the proposed revised 
definition of recombinant DNA is ambiguous with regard to "self-cloning" 
experiments. He proposed a specific modification in the sentence in 
the Introduction (Federal Register p. 49596) which deals with the pre- 
paration of a list of those combinations of DNAs which are not considered 
novel. The sentence now reads: 
"Ihe Director of NIH with the advice of the Recombinant DNA 
Molecule Program Advisory Committee shall prepare the list 
of those combinations of DNAs (viral, extrachromosomal or 
chromosomal) which are not considered novel for this purpose 
and are, therefore, not covered by these Guidelines." 
Dr. Botstein proposed that this sentence should be redrafted as follows: 
"The Director of NIH with the advice of the Recombinant ENA 
Molecule Program Advisory Committee shall prepare the list 
of those combinations of DNAs (viral, extrachromosomal or 
chromosomal) which are not considered novel for this purpose 
and are, therefore, not considered to represent any special 
hazard simply because they were made iji vitro . Ordinary 
precautions now used in comparable in vivo experiments are 
sufficient. For example, since Escherichia coli and many 
other enteric gram-negative species (Salmonella, Shigella, 
Klebsiella, Serratia, Proteus) recombine in vivo , any and 
all in vitro crosses among them will not be subject to 
regulations under these Guidelines." 
[Appendix A — 104] 
