n. 
PART II. SPECIFIC PROPOSALS 
A. Experiments with the E. col i -host vector system 
Vie have above stated two points: 
1. The committee can specify one "EK2" strain and one "EIC2" vector 
of each type and set up a lab-office which distributes them to 
all investigators doing cloning in JE. col l. 
2. ho new NIH grant support for inter-species recombinant DMA studies 
in E. coli should be administered from January, 1978 on. 
* 
Specific proposals for current E_. col i host-vector studies: 
(a) SHOTGUN EXPERIMENTS (non-puri Tied DNAs): 
( i ) EUKAR YOTIC DMA RECOMBINANTS 
It can be taken as a 'given' that recombinant DMA 
experiments with eukaryotic DMA are the most dangerous and 
speculative of all recombinant DMA molecule experiments. And, 
that 'shotgun' experiments, where large numbers of undefined 
genes are manipulated in a totally 'blind' situation, are 
potentially the most dangerous of all. Because of this, when 
they are to be done, such experiments -should only be performed 
under P4 containment. 
Mamma 1 s - for the following reasons we feel that such 
experiments should be deferred for an indefinite period: 
1) the extent of containment possible with any of the 
suggested host-vector systems remains to be studied and 
demonstrated ; 
2) A high probability of contamination in these experiments 
exists with either unknown or undetected 'cryptic genes' or 
other genes known to exist and code for products responsible • 
for cell transformation . 
In addition, there are genes coding for polypeptide hormones and 
enzymes converting bacterial metabolites into physiologically or pharma- 
cologically active substances, any of which might be produced and leaked 
out at an uncontrolled rate from the bacterium. The risk involved in such 
studies is inherently so high that it far outweighs any potential benefit. 
Cold-b l ooded a nimal s and all other e u karyotes 
The actual risks here are close to those in higher eukaryotes, 
though slightly lower perhaps in that C-type virus genomes and polypeptide 
hormones directly active in humans may not exist. Nonetheless invertebrates 
such as Anu_ra_ L the common frog, are afflicted with oncogenic viruses and 
the potential for conversions of prokaryotic metabolism do exist. 
Drosophi 1 a , for instance, is known to have several pigmentation loci, which 
involve conversion of amino acids to pigments. First products in such 
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