The Honorable Patricia Roberts Harris 
December 30, 1979 
Page Four 
a) In the use of the Brenner scheme, the burden of proof 
falls on the investigator to show that an experiment poses minimal 
hazard. In contrast, in the "EK1/P1" proposal, a very broad range 
of experiments with E.coli is assumed to be of minimal hazard. 
b) The Brenner assessment considers only risks to exposed 
individuals , not those to populations . This is a conservative 
approach because bacteria capable of affecting individuals may not 
be sufficiently virulent or produced in sufficiently large numbers 
to survive and spread from person to person. 
These differences are reflected in the substantive outcomes 
of the "EK1/P1" proposal and of application of the Brenner scheme. 
To give just one example, the cloning of the gene for a human 
hormone is classified as a Category IV or III experiment in Britain, 
if an EK1 host-vector system is used? Under the "EK1/P1" proposal, 
containment would be PI. 
In summary, the arguments developed in section III-B of the 
decision document do not support the contention that the probability 
of a harmful outcome of work with E.coli K-12 host-vector systems 
is always very low. Much of the evidence cited was used to justify 
revision of the guidelines in 1978. The new evidence that has come 
to light since that time does not justify the sweeping changes 
contemplated in this proposal. In addition, no empirical data are 
available on the hazards of organisms that are engineered to pro- 
duce proteins ( an area of great industrial importance) . Neither 
the immediate physiological effects or autoimmune effects of such 
bacteria in human and animal hosts have been studied. 
Given the weakness of the arguments supporting the "EK1/P1" 
proposal and the uncertainties and lack of empirical data still 
associated with the risks, particularly of industrially important 
processes, the most prudent course would be to continue to use 
the present NIH guidelines and to modify them on a case-by-case 
basis as the relevant risk assessment experiments are carried out 
and consensus regarding their implications is reached. The "EK1/P1" 
proposal calls for particular caution because it represents a 
major reversal of the policy of prevention and anticipation of 
hazard that originally informed the move to develop guidelines for 
the recombinant DNA field. If this change in policy is accepted, 
a most important means for monitoring developments in the recom- 
binant DNA field will be lost. At the same time, NIH will lose 
its moral influence on the policies adopted in other countries. 
Certainly, a precipitous rush to dismantle controls which coincides 
far more obviously with mounting industrial momentum in this field 
than with any breakthrough in understanding of its potential impact 
is bound to be regarded with skepticism. 
' > ' c See pp. 12-13 of Annex B of the Brenner report, section 11 of 
the "Background Documents." 
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