60086 
NOTICES 
ecological and biological Issues that 
must be carefully and thoughtfully ad- 
dressed. As one correspondent cau- 
tions. "We must be very careful when, 
bolstered by our confidence in E. coli 
K-12 systems, we try to extrapolate to 
B. subtilis. yeast, etc." Two Working 
Groups of the RAC have recently met 
to consider alternate systems and to 
develop more precise and objective cri- 
teria for certification.* Many prob- 
lems. however, persist for setting gen- 
eral standards that could be applied to 
all organisms. I believe that the proc- 
ess of review and approval described in 
the Guidelines will allow for full and 
deliberate examination on a case-by- 
case basis of putative HV systems and 
of pertinent ecological and biological 
Issues. This process will, of course, 
comply fully with NEPA. 
In response to one correspondent’s 
suggestion, text has been added to 
Section II-D-2-a further clarifying the 
roles of the NIH Director and ORDA 
in the process of certification. 
Data Required for Certification 
One correspondent suggested an ex- 
pansion of Section II-D-2-b-(l), relat- 
ing to data to be submitted for certifi- 
cation of HV1 systems other than E. 
coli K-12. Specifically, he would re- 
quire a thorough discussion of the 
physiological properties of the orga- 
nism. particularly those related to its 
reproduction and survival and the 
mechanisms by which It exchanges ge- 
netic Information— not simply the 
range of organisms with which It ex- 
changes. I believe these characteristics 
to be especially crucial In approval of 
new systems: accordingly. Section II- 
D-2-tMl) has been amended to incor- 
porate this suggestion. 
EK1 Systems 
One correspondent noted that most 
host components of EK 1 systems used 
In recombinant DNA research have 
mutations in addition to those ac- 
quired during K-12's laboratory evolu- 
tion that confer special nutritional re- 
quirements. cause recombinants to be 
defective, or otherwise diminish sur- 
vival or reduce the likelihood for 
transmission of recombinant DNA. It 
has been suggested that use of such 
mutations should be encouraged. In 
my view, much of the value of the 
EK 1 host Is its flexibility, and it does 
not seem necessary to explicitly rec- 
ommend certain strains of E. coli K-12 
as EK1 strains. The investigator will 
generally choose the more readily 
transformable E. coli K-12 strains, 
and many of the characteristics that 
enhance transformabllity decrease 
survival. In addition, by suggesting the 
•The Working Group on Prokaryotic 
Host-Vectors Other Than E. Coli met on 
September 12. 1976: and the Working Oroup 
on Lower Eukaryote Host-Vector Systems 
met on September 19. 1978. 
use of certain mutations, we may shut 
off research on others which might 
prove even more useful and safe. 
FLEXIBILITY IK CHOOSING PHYSICAL AND 
BIOLOGICAL CONTAINMENT LEVELS 
One witness and one correspondent 
questioned the rationale for allowing 
alternate levels of physical and bio- 
logical containment. The concept of 
"flexibility" is discussed at some 
length in the Decision document. Fed- 
eral Register. July 28. 1978. pp. 
33052-33053. and in the accompanying 
Environmental Impact Assessment, p. 
33113. Moreover, the flexibility al- 
lowed in alternate P and HV levels is 
carefully explained in the text of the 
Guidelines, and the investigator must 
follow the explicit requirements set 
forth in part III, of the Guidelines and 
Tables I and II. 
III. Containment Guidelines tor 
Covered Experiments 
GENERAL CONSIDERATIONS 
Many of the commentators support- 
ed the levels of containment recom- 
mended for covered experiments. 
They concurred with the scientific ar- 
guments presented in the Decision 
document and Environment Impact 
Assessment (Issued July 28. 1978) as a 
rationale for lowering containment 
levels. Some cited the reports of the 
Falmouth and Ascot risk-assessment 
meetings as confirmatory evidence, 
and reiterated that E. coli K-12 
cannot be converted into an epidemic 
pathogen even by the introduction of 
additional genes from knpwn patho- 
genic strains. 
Many commented favorably on spe- 
cific sections of the Guidelines, such 
as the lowered containment levels for 
viral DNA. Others supported the pro- 
posed containment levels for the clon- 
ing of primate DNA. One further 
stated that relaxation would permit 
major studies to be made In locating 
and mapping human genes. Another 
noted that the proposed revisions 
would permit the conduct of research 
with plants and plant-associated mi- 
croorganisms and endorsed the 
changes based on the Workshop on 
Risk Assessment of Agricultural Path- 
ogens. 
A number of commentators, while 
generally supportive of the changes 
proposed, believed the Guidelines to 
be still too restrictive. Some urged 
that they either be dispensed with en- 
tirely or. in the opinion of one com- 
mentator. be replaced with the follow- 
ing sentence: "It would seem prudent 
to conduct work with organisms con- 
taining recombinant DNA under labo- 
ratory conditions appropriate to the 
degree of pathogenicity of the donor 
organisms." 
I appreciate the thoughtfulness and 
care that have gone into the many let- 
ters. I also acknowledge a belief that 
the proposed revised Guidelines repre- 
sent a conservative lowering of con- 
tainment based on data and analysis 
discussed in detail In the Decision doc- 
ument and Environmental Impact As- 
sessment of July 28. 1978. 
On the other hand, there were com- 
mentators and witnesses who believed 
the lowering of containment levels in 
the proposed revised Guidelines was 
not justified. While there was a differ- 
ence of emphasis in many of the com- 
ments. there appeared to be several 
major concerns. I shall consider each 
of these in turn. 
• Commentators state that "much 
of the evidence tthat NIH cites as a 
basis for lowering containmant] has 
never been published or is available 
only In summary form.” Also that "A 
great deal of weight has been placed 
on semi-authorized reports of discus- 
sions held at closed scientific meet- 
ings. attended by a small number of 
selected participants." They express 
concern that such action by NIH has 
prevented the wider scientific commu- 
nity from critical appraisal of the 
data. Various of these commentators 
state that the results of the Falmouth 
conference were published only two 
months before the proposed revision 
of the Guidelines was Issued, that the 
proceedings of the Ascot conference 
have not been Issued, and that the re- 
sults of the Rowe-Martin risk-assess- 
ment experiments have not yet been 
published. 
The extensive proceedings of the 
Falmouth meeting, held In June 1977. 
were published In the Journal of Infec- 
tious Diseases In May 1978. Publica- 
tion In Journal form usually Involves a 
considerable delay, even after the 
edited manuscript, in this case con- 
structed of transcripts of papers and 
discussions edited by participants, has 
been completed. The moderator of the 
Falmouth meeting. Dr. Sherwood Gor- 
bach. Professor of Medicine and Mi- 
crobiology. Tufts University School of 
Medicine, summarized the outcome of 
the meeting in a letter to me on July 
17. 1977. (This letter was published as 
Appendix M to the October 1977 Envi- 
ronmental Impact Statement, and was 
also published along with letters from 
other participants in the Recombinant 
DNA Technical Bulletin, Volume 1, 
No. 1. Fall 1977.) 
The report of the Ascot meeting was 
published as Appendix E to the Envi- 
ronmental Impact Assessment (EIA) 
in the Federal Register on July 28, 
1978. pp. 33159-33167, and previously 
in the Federal Register on March 31, 
1978. pp. 13748-13755: Its introduction 
says. "A draft of this report was sent 
to the members for comment and reVl- 
FEDERAL REGISTER. VOL 43. NO. 247 — ERIOAV, DECEMBER Tt 1978 
