Page Six 
September 13, 1978 
one level below shotgun experiment containment. However, none 
of these terms are defined precisely enough to guarantee any 
uniformity among decisions rendered by different IBC's. This 
section should be expanded to include more specific guidance to 
IBC's including criteria for purity (other than simply "99$' ), what "free 
from"really means and how it is to be determined, and, pro- 
bably most important, a definition of "harmful gene". 
Footnote 3 clarifies these terms somewhat, but not enough, 
in my opinion, to really provide adequate guidance to IBC's. 
The interpretation of "harmful gene" may be a bit too narrow 
as it is used here, in that genes which might not be harmful 
when expressed in their original organism could indeed be 
"harmful" if expressed out of context in an unrelated organism. 
That is, the term should be interpreted more broadly than 
to be limited to toxins or purely pathogenic effects. It is 
also essential that possible harmful effects on organisms 
other than man or to specific ecosystems be taken into account 
in making such judgements. 
The assumption that risk somehow increases as the cloned 
DNA source is phy logenet ically closer to man has been made 
since the earliest versions of the Guidelines were written. 
I still am unconvinced that it is justified, except perhaps 
regarding the risk of the cloned DNA harboring viral sequences 
which may be able to enter and propogate in human cells. 
Even if the cloned DNA were highly homologous to human DNA, 
how is it envisioned that when carried in a bacterial host, 
it would somehow be more dangerous to man than non-homologous 
DNA? Clearly, genetic modifications which might render a 
bacterial host more pathogenic will have nothing to do with 
the degree of homology DNA inserts bear to human DNA. 
The argument that certain gene products might be more 
harmful to man if similar to human gene products might, in a 
few cases, have merit, but, in general, even this assumption 
is tenuous. Even if a bacterium produced an active human 
polypeptide hormone, it would somehow have to enter the blood 
stream to be effective. Possible risk due to the production 
of pharmacologically active agents will clearly not depend 
upon evolutionary similarity to man. In fact, such products 
are more likely to be specified by plant genes, or by genes 
from insects, lower animals or microorganisms. 
My other concern with the phylogenetic argument is that 
potential risks to life forms other than man need to be con- 
sidered as well. By being overly preoccupied with possible 
direct harm to humans, we may not give enough attention 
to potential hazards to plants, animals and microorganisms, 
[A-133] 
