Page Two 
September 13, 1978 
I . Scope of the Guidelines 
I note that the new section I . contains considerably 
more substance than the 1976 Guidelines. While this is 
appropriate, the pending House legislation, if it should 
ever come to pass, will need to be amended to include 
I - D on prohibitions and perhaps parts of I - E on exemptions, 
in addition to Sections II and III as parts of the Guidelines 
which will be universially applicable. 
The definition of recombinant DNA need not distinguish 
between natural and synthetic DNA's, since the general 
definition of DNA would include both. However, it doesn't 
hurt anything to make the distinction. There is a potential 
problem with requiring that DNA segments be joined "to DNA 
molecules that can replicate in a living cell". Technically, 
this definition excludes cases where only the recombinant 
molecule may have the capacity to replicate in a living 
cell, but where the DNA molecule(s) to which DNA segments 
are joined may not be able to replicate alone. This is 
at least a theoretical possibility which would be covered 
by adopting the definition of recombinant DNA in H.R. 11192. 
Under I - D Prohibitions , the reference to "potent toxins" 
needs to be clarified somewhat. While discussions in subse- 
quent parts of the Guidelines distinguish between polypeptide 
toxins, and those requiring an entire biosynthetic pathway 
requiring many genes, the range of species which these 
toxins effect is not made clear anywhere. Clearly, if all 
lifeforms are included, DNA from fungi which produce 
antibiotics would be covered. Or does this only refer to 
human toxins? At the Congressional briefing, Dr. Rowe said 
it was intended to cover all vertebrate toxins. If so, this 
should be so stated in the Guidelines. 
Under I -D-5, I would delete the clause, "that are 
not known to acquire it naturally," from the prohibition 
concerning drug resistance genes. The "natural" acquisition 
of drug resistance by pathogens, in part, no doubt, a result 
of the indiscriminant use of antibiotics in medicine and 
agriculture, has created a number of serious public health 
problems. The primary purpose of the Guidelines is, after 
all, public safety. The second part of this sentence 
clearly limits this prohibition to cases where the control 
of disease agents could be compromised, which should be 
the sole criterion upon which this prohibition is based, 
[A-129] 
