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must be conducted at the required level of physical containment of the just 
then issued Guidelines, and all new experiments must use the required level 
of biological containment specified by the Guidelines. In addition, the 
requirement for a so-called Memorandum of Understanding and Agreement, or 
MUA, was introduced at that time. 
Now, the MUA is a document which includes the following statements. The 
first is an assurance that the investigator is familiar with the Guidelines 
which were issued by the NIH and agrees to abide by their provisions. The 
second point is a description of the experiments being conducted which involve 
recombinant DNA molecules, and this is a description which is independent of 
a more detailed description which is contained within the grant application 
itself. Thirdly, there is a requirement for an assessment of the levels of 
physical and biological containment required for the experiments by the 
Guidelines. Fourth, a statement of the facilities and procedures which will 
be used to provide the required levels of containment. Fifth is certification 
by an institutional official that the facilities and procedures and training 
of the personnel have been reviewed by the institutional biohazards committee 
and found to be adequate and consistent with the requirements of the Guide- 
lines. Sixth is an agreement that the institutional biohazards committee 
will monitor the facilities and procedures and the training of the personnel 
throughout the duration of the project. And finally, there was a statement 
that recombinant DNA molecules being used will not be transferred to other 
investigators or institutions unless the recipient institution has the 
facilities and techniques which are adequate, and has a MUA on file with 
the granting agency. 
The requirement that this document, the MUA, be submitted, the date for 
submission of that was November 15, 1976. 
In addition, that directive of August 26, 1976, also brought to the 
fore the requirement for prior approval, and prior approval was required 
for introduction of recombinant DNA technology into any project which had 
not been reviewed and approved for the use of recombinant DNA, and prior 
approval by the NIH was also required for any significant alteration of an 
approved protocol. 
In September 1976 a directive was sent to NIH staff stating these 
requirements, and in addition, at that time — September 1976 — a requirement 
was added that on or after December 1, 1976, applications proposing to 
conduct recombinant DNA research must be accompanied by the Memorandum of 
Understanding and Agreement at the time of submission of the application to 
the NIH. 
Furthermore, a requirement was introduced that the initial review 
groups, which in general are the study sections here at the NIH, in addition 
to reviewing the scientific merit of the proposals, are responsible for an 
independent assessment of the levels of physical and biological containment 
required by the NIH Guidelines, and an assessment of the adequacy of the 
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