33058 
NOTICES 
haven, X T, March IS": and the 
ITortrfop o* Studies for Auexrr-.raf of 
Pc Initial Risk Au«i a ird flh P.ecsir.- 
t>-.nant DMA £-rpm w. rn.ta.tion, Fai 
mouth. Mass.. Jujw 1J77 r. 
3. Results from experiments specifi- 
cs’ Ij designed to test 'at the rzrrivabi- 
L;y and cokmi^sf ibCi'.T of £. colt K- 
13 and EK2 hos’-vector sys terns. (b) 
the trarsm-ssib lity of plasmids and 
pbsge vectors. <e> the potential of F 
coli K-13 for pathogenicity. and (d) 
the t>e*.erlial of genetc exchange be- 
tween diverse bacteria and between 
euUr>MX and prokaryotic c reams .-ns 
Each caicfonr of expcrimectj in 
part III of the ordinal guide lines was 
then extensively examined, applying 
the following criteria to the new ir.for- 
matloir 
• Tb e decree to which the DNA seg- 
ment has been purified away from 
other teres and shown to be free of 
harmful characteristics: 
• The potert.ai fc.chaxard associat- 
ed with the DNA of the cell or rrucro- 
ortuiism that serves as the DNA 
source <e*.. genes for toxin prod uc- 
• The potential biohazard 
ed w.th the vector that serves to trans- 
mit the source DNA to a recipient host 
cell: 
• The ability of the vector to sur- 
vive to natural environments or habi- 
tats: 
• The kinds and number of differ- 
ent organisms that are susceptible to 
infection by the vector or recipient: 
• The potential biohazard of the re- 
cipient host cell that serves to repli- 
cate the recombinant DNA molecule: 
o The ability of the recipient cell to 
survive to natural environments of 
habitats; 
a The ability of the recipient cell to 
trinsmit the recombinant DNA mole- 
cule to other cells capable of surviving 
in natural environments or habitats: 
• The potential of the recipient cell 
to obtain the source DNA by natural 
means, and 
o The evolutionary relatedness of 
the DNA source to humans. Tne po- 
tential dangers are considered to in- 
crease as the organism prov>d_ng the 
source DNA approaches humans phy- 
togenetically. Thus, source DNA from 
pnmate cells h considered to have 
greater potential danger than source 
DNA from prokaryotes. 
To present more dearly the changes 
in containment levels proposed by the 
PRG-RAC. a table was prepared for 
use at the December 1977 mecbng of 
the Advisory Committee to the Direc- 
tor. which compared the containment 
levels in the PRG-RAC with those of 
the 1976 guidelines. This table has 
now been expanded w.th a third 
column to show the containment 
levels of the proposed revised guide- 
lines which are row be to* proposed by 
NIH cabled PRG-NIH . Tne tab.e ap- 
pears as appendix A to the accompa- 
nying Environmental Impact Assess- 
ment. 
The rematoder of this section sum- 
marizes a number of the proposed 
changes comparing the 1976 gli de lines 
wits the PPG -RAC. (Not all the 
changes are discussed here: certain 
items in which the PRG-NIH tollers 
s^mficaaiiy from the PRG-RAC are 
considered below to the section enti- 
tled Review of Comments and NTH 
Proposed Guide lines.') The r.urr-bers 
in parentheses indicated the Lne num- 
bers on the table to which the pro- 
posed revision applies. 
Tne principal changes reflected to 
the table ere as follows: 
• Several categories of experiments 
< pr-.rr.xnly those involving prokaryotes 
that are exchangers of genetic Infor- 
mation with t cull to nature) are no 
longer subject to the provisions of the 
PKG-RAC due to the changes to the 
(Winner See Lnes 30. 21. 27. 46. and 
47 ) 
• Shotgun experiments involving 
b rds and mammals other than pri- 
mates sere the subject of lowering of 
containment from P3 - EK2 to 
P3-EK2 This action reflects the In- 
creased confidence of the RAC in the 
EK2 host-rector systems (See lines 4 
and S.) 
• Another category which the RAC 
decided was to need of revision was 
that pertaining to the cloning of DNA 
from orgarusms producing a toxic 
product. This aas clarified to the 
PRG-RAC by specifying whether or 
not polypeptide toxins are produced, 
and setting containment lev f j accord- 
ingly. Polypeptide toxins are specified, 
since they might be encoded by a 
single gene or cluster of gen**- Tcxins 
of other chemical structure would not 
result from a single gene or cluster of 
genes. <See Lines 8 9. 10. 11. 12. 16. 17. 
and 19.) 
• For several categories of experi- 
ments. it is proposed that the investi- 
gator have the option of working at 
P2-EK1 or PI - EK2 rather than the 
P2-EK1 levels previously specified. 
This agan reflects confidence m the 
EK2 systems. See lines 7. 14. and IS.) 
• The toweling of containment for 
experiments with rigorously charac- 
terized clones free of harmful genes 
was revised to provide more fexibuity. 
Under the PRG-RAC. institutional 
biosafety committees IBCs* would be 
able to lower coctairunect by a single 
level. The IB J should consider the 
purity, extent of characterization. and 
harmlessness of the done before al- 
lowing such lowering. Reduction of 
containment by more than one level 
would require approval by NTH. Under 
the 1976 guidetoies. NTH had the 
option of towering containment down 
to ceri.i specified levels or not lover- 
tog it at aLL The PRG-RAC wc^ld 
al’-cv NTH to consider all available 
data for the done and to tower con- 
Uuaaent according’ y. 
In add:* ton. the sect, an now applies 
to Vigorously characterized clones 
from any perm-ss-ble experiment in F 
coil K 12 Under the ongjial r— de- 
lutes. cootajiment for F coil K-13 
clones coot Lahunc characterized and 
harmless port. or. of viruses and plas- 
mids could not be towered. 
The rationale for these proposed 
changes is explained in f urther oetah 
to the Envu-ocir-eniai Impact Assess- 
ment . 
trurw or cc iocrvrs » vr xie reoposm 
error rxrs c tv Emu. ) 
Reftoaole 
Part m of the guidel-nes received 
the most extensive comment of any 
section touring the dsreiopenent of the 
original gu - del: ties in early 1976 WhOe 
there aas also much d-sc*. tssjon of this 
pan to the PRG-RAC. the issues 
raised did not primarily address the 
proposed changes in the containment 
levels but more general topics such as 
the need for a ranona’-e for each of 
the changes. 
A number of cccamialors asked 
that the rationale for the classifica- 
tion of percuss. z> experiments be 
dearly spelled out. It was pointed oat 
that (1) the part on permissible ex- 
periments b especially -ilficult for a 
lay person to understand. (2) the 
whole categorization is dependent 
upon invest igator-al confidence rather 
than documented fact, and (3) the 
Quantification of conta.’rmer.t levels, 
the means by which the levels were 
decided, and the rationale for racing 
and lowering these levels are not clear. 
In general the classification may 
appear somewhat arbitrary, because it 
depends in large part on the soectifie 
judgment of the RAC rather than on 
demonstrable risk since there b actu- 
ally no scientific evidence of hazard to 
any recombinant DNA expermer.t. 
The rationale for classifying differ- 
ent recombinant DNA experiments at 
different containment levels was ex- 
plained to the ' Decision of the Direc- 
tor. Nat;;nai Institutes of Health. To 
Release Guidelines for Research on 
Recombinant DNA Molecules." which 
was published along with the current 
r--de Lines to the Fspes.u. Rxgiste* on 
July 7. 1976. as follows: 
The gj ndffn es theeas levels of 
m a -wryrri tor expenmedi a vtucij DNA 
from ddferec: sc _-res is to x a-lrotoiced 
su> ir. £ coil K-12 boss-vector itsol The 
nraua s taxed cc boot f tens azto issrn- 
(n& There are tome pn tm ices bacteria 
which ecnstar.dj firtiap DNA vr-.h £ 
coh. Here r. h assumed lhal e xp er -t n-e-c.Ul 
ccxxamoQS b eyooa those :ou_-yc a rarefuL 
rauuw Kicroeucwocy laboratories are sper 
ffbfXAl tEO'STE# VOL <3 MO l«4 — £« OAT JUST » 1*7* 
[ 19 ] 
