Dr. Donald Fredrickson, Director 
-3- 
January 4, 1978 
important part of illness-high fever, and when the dose 
is large enough shock develops, with the bottom dropping 
out of the blood pressure, followed by coma and death. 
There are peculiar kinds of hemorrhagic reactions that 
occur in the skin and in a lot of internal organs, and it 
looks as though a lot of important physiological mechanisms 
had been unhinged by this toxin. But when you look at an 
endotoxin closely it 1 s difficult to find anything about it 
that is really toxic in the sense that it inflicts a primary 
kind of damage . It doesn't poison the cells if you put it 
in cell cultures. It_ looks more like a signal than like a 
toxin . (Dr. Thomas, in "The New Yorker", p. ^0; emphases 
added. ) 
I think that it must be admitted that the subtleties of why an 
innocuous organism becomes pathogenic under certain conditions are 
not well understood. When the possibilities are considered of 
bacteria causing misreading of eukaryotic control signals, and 
autoimmune reactions, after having incorporated fragments of 
eukaryotic genomes, it can be seen that the definition of "toxin" 
under the present Guidelines and the proposed revisions are inadequate. 
Given Dr. Thomas' examples it is apparent that virtually any highly 
conserved, physiologically active eukaryotic protein (collagen, 
histones, initiation factors) or fragment thereof could be highly 
toxic when introduced out of context by a bacterium which received 
the appropriate gene in a recombination experiment, or picked it up 
from another which did so. 
I therefore do not understand the confidence of those who claim 
that novel pathogens cannot be created in recombinant DNA experiments. 
I think that if the experiments are to proceed at all, we are entirely 
dependent on high containment to avoid populating the biosphere with a 
whole slew of critically modified microorganisms some of which will 
eventually cause grave difficulties to existing metazoans. While 
EK2-P^ conditions conceivably meet these safety requirements, most 
work is now going on at much lower levels of containment. Given the 
probabilities of human error and inevitable occasional contamination 
of bacterial host stocks under these conditions, it would seem that 
the present Guidelines should be strengthened rather than relaxed. 
I would appreciate your placing this letter in the public record 
as testimony regarding the proposed revisions. 
Sincerely 
Stuart A. Newman 
Assistant Professor of 
Biological Sciences 
SAN : 1ms 
[Appendix A — 185] 
