NOTICES 
60091 
concur with the recommendation and 
have made the change. 
On the other hand, I do not agree 
with the opinion of the correspondent 
who questioned the relevance of PI or 
P2 containment conditions to experi- 
ments in which recombinant DNA is 
cloned in higher plants. The corre- 
spondent believes that higher plants 
containing nonviral recombinant DNA 
should not require any containment. 
The proposed revised Guidelines 
(pages 33082 and 33084 in the Federal 
Register July 28, 1978) specifically 
define special PI and P2 conditions for 
work with plants. I do not believe that 
recombinant DNA work with higher 
plants should now be done with no 
containment at all. 
Finally, I have considered the re- 
quest of two correspondents discussing 
employment of the tumor insertion 
plasmid (Ti) of Agrobacterium tumefa- 
ciens as a cloning vector. They suggest 
adding the following sentence to Sec- 
tion III-C-4: “Inoculation of hosts 
with HV1 approved Agrobacterium 
containing the DNA recombinants re- 
quires P2 physical containment.” I do 
not believe inclusion of the sentence is 
warranted at this time. Data on the 
system can be submitted to the RAC 
for approval as an HV1 system. If ap- 
proval is granted, the RAC at that 
time can recommend the appropriate 
containment level. 
Section III-D. Complementary DNAs 
Two correspondents were concerned 
over the possibility of eukaryotic DNA 
being expressed in prokaryotic cells. 
They noted that genes cloned via a 
shotgun experiment will probably not 
be expressed because they retain their 
intervening sequences and the result- 
ing RNA is not likely to be processed. 
On the other hand, complementary 
DNA prepared from messenger RNA 
could serve in turn as a template for 
synthesis of the same RNA within the 
prokaryotic cell They suggest that a 
"distinction should be made between 
eukaryote DNA- and cDNA forpied 
from mRNA” 
In responding, I must note that con- 
tainment levels for eukaryotic DNA 
were developed on the assumption 
that such DNA, no matter what the 
source, could be expressed. The pro- 
posed Guidelines set the same contain- 
ment levels for eukaryotic DNA and 
cDNA formed from functional eukar- 
yotic mRNA. For cloning of viral DNA 
into E. coli K-12, however, there are 
differences in the containment levels 
depending on whether one is using the 
viral DNA itself of cDNA from viral 
mRNA (see Table III). The probable 
future uses of cDNA copies of func- 
tional mRNAs are discussed in the In- 
troduction and Overview of the Direc- 
tor’s Decision (Federal Register, July 
28, 1978, pp. 33044 and 33047). 
Section III-E. Synthetic DNA 
A correspondent argued that the dis- 
cussion of appropriate containment 
levels for synthetic DNA that codes 
for harmless polypeptide products 
“makes no sense.” He asks, “Why is 
any containment required for a harm- 
less product?” and recommends the 
following alternative language for this 
section: “If the synthetic DNA se- 
quence codes for a harmless product 
or if the synthetic DNA is not ex- 
pressed in vivo, the organisms con- 
taining the recombinant DNA are 
exempt (4) from the Guidelines.” 
In reply, the term “harmless prod- 
uct” refers to the normal toxicity or 
pathogenicity of the protein and not 
necessarily to the remote possibility of 
its otherwise disrupting the physio- 
logical balance of the organism in 
which it might inadvertently be intro- 
duced. I believe that the language of 
the NIH-proposed revision should 
remain as published, since the three 
paragraphs describing containment for 
synthetic DNA clearly describe three 
distinct concepts. The provisions of 
Section III-E are consistent with those 
of III-A-3 dealing with containment 
levels for purified or characterized 
DNA 
IV. Roles and Responsibilities 
responsibilities of the institution 
(GENERAL) 
Institution 
The general responsibilities of the 
institution are to ensure appropriate 
review and implementation procedures 
for all of the institution’s recombinant 
DNA activity that is covered by the 
Guidelines. Below are a- number of 
general institutional responsibilities 
that were addressed in correspondence 
and by witnesses at the DHEW public 
hearing. 
Exercising Institutional Authority. 
Both groups of commentators stated 
that the Guidelines should permit the 
institution to set new requirements 
beyond those of NIH. In the Guide- 
lines, the institution has this authori- 
ty, and a provision has been added spe- 
cifically stating that the institution 
may establish requirements and proce- 
dures for the general implementation 
of the Guidelines, including additional 
precautionary steps if deemed appro- 
priate. it should be noted, however, 
that these Guidelines and the stand- 
ards they embody are conservative and 
in no way constitute a minimum set of 
requirements. 
Establishing an Institutional Biosa- 
fety Committee. Requirements for 
membership on the Institutional Bio- 
safety Committee (IBC) drew substan- 
tial attention in the letters and at the 
public hearing. Much of the comment 
was directed to mandating various rep- 
resentation. Some commentators sug- 
gested that a local public health offi- 
cial and a nondoctoral person from a 
laboratory technical staff serve on the 
committee. Others recommended man- 
dating community leaders who are “in 
touch with grass roots attitudes,” in- 
cluding "environmentalists.” Others 
suggested that the membership reflect 
the demographic distribution of the 
community in which the institution is 
located. Requirements for membership 
distribution by age, sex, income level, 
professional background, and other 
variables were mentioned. It was sug-. 
gested that at least two members be 
custodial or janitorial workers. Others 
recommended that there be at a mini- 
mum one physician trained in infec- 
tious diseases, one epidemiologist, and 
one environmental scientist. 
Other commentators and witnesses 
suggested various ratios of scientists 
and nonscientists serving on the com- 
mittee. Some urged that one third of 
the membership represent “the inter- 
est of the community” and another 
third “scientific disciplines related to 
risk assessment.” It was also suggested 
that nominating procedures be speci- 
fied for selecting community repre- 
sentatives. 
On the other hand, some commenta- 
tors believed that the proposed revi- 
sion was presumptuous in mandating 
lay representation on- this committee, 
especially when the university may al- 
ready have several lay committees for 
oversight. 
Others suggested that the minimum 
membership for an IBC be raised from 
five to seven. The minimum of five 
members is recommended to take into 
account small universities with few 
projects. In these and many other 
cases, five is sufficient, and it remains 
as the minimum. Membership recom- 
mendations in the revised Guidelines 
attempt to balance professional exper- 
tise with members who represent the 
interest of the surrounding communi- 
ty. As pointed out by one correspon- 
dent, however, the IBC, in contrast to 
human-subject committees where 
broad concepts of social and ethical 
values are considered, is in large part 
an expert committee whose essential 
function is to evaluate research proto- 
cols in respect to containment levels, 
using the explicit instructions of the 
Guidelines. Rigid quotas are not neces- 
sary. Indeed, many small academic in- 
stitutions would have considerable dif- 
ficulty meeting specified demographic 
requirements. The IBC criteria are 
flexible to permit the institution to 
select a committee capable of fulfilling 
its responsibilities. 
The DHEW Committee carefully re- 
viewed all the comments and consid- 
ered at great length membership re- 
quirements for the IBCs. On balance, 
it was decided that the interest of the 
surrounding coummunity could be 
FEDERAL REGISTER, VOL. 43, NO. 247— FRIDAY, DECEMBER .22, 1978 
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