Federal Register / Vol. 44, No. 232 / Friday, November 30, 1979 / Notices 
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would be the case without them. In the 
end unrealistic restriction will frustrate 
the general maintenance of necessary 
and reasonable precautions. 
NIH is committed to continuing risk 
assessment using both special 
experiments and continuing synthesis of 
all the accumulated data. Some studies 
are specifically designed to answer 
questions about containment, survival, 
and behavior of "recombinant" 
organisms. Data are also supplied by 
careful analysis of the Bteady stream of 
information emerging from other 
recombinant DNA experiments, as well 
as new knowledge in the areas of 
microbiology, infectious disease, cell 
biology, and genetics. Preceding sections 
of this document describe old and new 
information and analyses bearing 
directly on the "E. coli K-12/P1 
Recommendation." None of the specific 
risk-assessment studies now being 
carried out by NIH contractors is 
designed to yield information that will 
bear unequivocally on this decision. See 
further discussion on this point in 
Section III— D below. 
Data Are Not Sufficient to Justify 
Exemption 
Some commentators gave specific 
reasons for not exempting E. coli K-12 
experiments from the Guidelines at this 
time. Some noted that there are 
conflicting interpretations of the 
significance of the Rowe-Martin 
polyoma risk-assessment experiments. 
Some cited specific additional risk- 
assessment experiments which they feel 
should first be completed. One 
commentator noted that much risk 
assessment data has been obtained 
using EK2 systems and said that these 
data should not be extrapolated to EKl 
systems. In addition, he noted that 
certain data were used previously to 
justify the containment levels set in the 
December 1978 Guidelines and said, 
"One can thus ask what is the basis for 
the current committee's 
recommendation to use these same data 
to justify an additional lowering of 
containment?” 
In response to the last point. I note 
that various new data, available first in 
1979, were considered by the RAC along 
with "old" data. It is a continuous 
charge to the RAC to examine new data, 
but also to reexamine old data in coming 
to their recommendations. 
In regard to the Rowe-Martin 
experiments, the results are published, 
the data available to all to analyze. A 
number of letters on this issue are 
included in the book “Background 
Documents on E. coli K-12/P1 
Recommendation." At each of the last 
two RAC meetings, conflicting 
interpretations on the experiments were 
openly discussed. Also discussed by the 
RAC was extrapolation of data obtained 
with EK2 systems to EKl systems, and 
the perceived need for certain additional 
risk-assessment experiments to be 
completed. These are questions on 
which people will have different 
opinions. Indeed, in my analysis of the 
RAC discussion on this issue, I find 
these to be the major points which 
seemed to lead to the split vote by the 
RAC. That is it appears that the four 
RAC members who voted against the 
“ E . coli K-12/P1 Recommendation" felt 
that certain additional risk-assessment 
experiments should be done first, 
including some experiments previously 
done with EK2 systems which they 
would like repeated with EKl. On the 
other hand, the 10 RAC members who 
voted in favor of the proposal judged 
that the data in hand were sufficient to 
justify the proposal. 
Strong Directive to IBCs 
One RAC member wrote: 
I still have reservations about the 
exemptions and feel that if the proposal is 
accepted by Dr. Fredrickson, then a fairly 
strong directive to the IBC's is a minimum 
necessity * * * to the effect that they are 
expected to review the registration-MUA's at 
their earliest convenience, paying special 
attention to two questions: (1) is the 
experiment actually exempt and (2) does it 
involve the cloning of genes determining 
potentially hazardous polypeptides or other 
products. In the latter case, it might be 
suggested that a test of this possibility be 
performed. In the event of an irreconcilable 
difference of opinion involving the IBC and 
an investigator, ORDA should be consulted. 
I agree with the recommendation for a 
strong directive, and have taken steps to 
ensure, .when the final decision is made 
on the "E. coli K-12/P1 
Recommendation," that not only 
Institutional Biosafety Committees but 
also institutional leaders will be 
informed of their special responsibilities 
with regard to these experiments. 
Don 't Exempt 
A number of commentators urged that 
the experiments falling under the "E. 
coli K-12/P1 Recommendation” not be 
exempted from the Guidelines. — "I feel 
it is premature to exempt the vast 
majority of recombinant DNA 
experiments with E. coli K-12.” — "I 
oppose the proposed exemptions of the 
Recombinant DNA Advisory 
Committee." — “The purpose of this 
letter is to urge against the approval of 
the proposed complete exemption of 
cloning E, coli K-12 hosts from the NIH 
recombinant DNA guidelines and to 
encourage a more moderate relaxation 
of existing constraints as an alternate 
action." 
As I discuss in Section III— E below, 
my proposed decision is not to approve 
an exemption for these experiments: 
they would be retained under the 
control of the Guidelines, including the 
requirement for Pi and EKl 
containment. 
III-D. Alternatives 
In Section III-E of this announcement 
I provide a full exposition of my 
proposed decision on the " E . coli K-12/ 
PI Recommendation.” A summary of 
this proposed decision was provided at 
the beginning of Section III. Before 
coming to this proposed decision, I 
considered a number of alternative 
actions which are discussed below. 
Make No Change In The Guidelines 
Until Many More Risk-Assessment 
Experiments Are Completed 
Some argued that no changes should 
be made in the Guidelines until many 
more risk-assessment experiments are 
completed. 
I have discussed this in Section III-C 
above. NIH is firmly committeed to an 
ongoing program of risk-assessment 
studies. It is responsible, however, for 
husbanding the resources for what are 
often very expensive and time- 
consuming studies. The experiments 
that are undertaken should seek to s^'ve 
critical and, if possible, generic 
questions. We must be convinced that 
no significant risk to the worker or the 
public is inherent in the permissible 
work. Extraplation from specific risk- 
assessment experiments to generic 
conclusions is always limited. Results in 
the mouse may not hold in man, or in all 
men: observations with one plasmid 
cannot be extended to all plasmids. The 
almost limitless permutations of 
possible transplanted genetic material, 
vectors and hosts, and of experimental 
conditions, means that few absolute 
answers can ever be obtained. Thus we 
cannot by any finite number of risk- 
assessment experiments, assign precise 
numerical probabilities to those risks 
judged extremely unlikely; and we can 
never consider the low probabilities to 
be zero under every conceivable 
condition. Nature has, by far, the longest 
string of risk-assessment experiments 
and her record must be carefully 
considered as well. NIH and the public 
must remain committed to continuous 
reevaluation of the NIH Guidelines as 
more and more is learned. I believe this 
action I am proposing is fully supported 
by the new information as well as the 
reassessment of prior information as 
described earlier in this decision. 
[ 22 9 ] 
