THE JOHNS HOPKINS UNIVERSITY 
SCHOOL OF MEDICINE 
DEPARTMENT OF MICROBIOLOGY 
72.5 N. WOLFE STREET 
BALTIMORE, MARYLAND 21205 
December 16, 1977 
Dr. Donald S. Fredrickson 
Director, National Institutes of- Health 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Dr. Fredrickson: 
Bernard Talbot asked me to submit a suggested definition of 
recombinant DNA that would include synthetic genes. I suggest 
addition of a footnote to the definition given in the Introduction 
of the draft of revised guidelines dated 6/23/77, as follows: 
"Synthetic genes, i.e., polydeoxynucleotides coding for natural 
polypeptides (or analogs thereof) that are synthesized chemically or 
enzymatically without use of a natural template, are included under 
the term "segments of DNA". Such synthetic DNA will be considered 
as derived from the species of organism that contains the analagous 
gene. " 
Two additional comnents: 
1) Synthetic polydeoxynucleotides that code for non- translated 
RNA (e.g., tRNA's), or for regulatory signals, or for no known natural 
product were intentionally excluded from designation as "synthetic genes". 
2) For later parts of the guidelines, synthetic genes should be 
considered equivalent to cloned DNA segments in terms of purity. 
Sincerely 
Daniel Nathans 
DN/lc 
[Appendix A— 135] 
