Federal Register / Vol. 52, No. 154 / Tuesday. August 11. 1987 / Notices 
29801 
III. Proposal to Mqdify and Amend the 
"Guidelines for Research Involving 
Recombinant DNA Molecules" to Refer 
Specifically to Research with Plants and 
Animals 
It has been recognized that the Nil! 
Guidelines for Research Involving 
Recombinant DNA Molecules do not 
include specific guidelines for 
containment of research involving whole 
plants and animals ever, though many 
scientific experiments involving 
recombinant DNA are now possible and 
often conducted with these whole 
organisms. 
On June 26, 1986, the U.S. Department 
of Agriculture (USDA) issued an 
"Advanced Notice of Proposed USDA 
Guidelines for Biotechnology Research 
(51 FR 23367). A notice in the December 
9, 1986, Federal Register (51 FR 44397) 
stated that USDA would be proposing 
new provisions relating to agricultural 
research for inclusion in the NIH 
Guidelines in lieu of the Advanced 
Notice of Proposed USDA Guidelines for 
Biotechnology Research published on 
June 26, 1986. USDA organized a 
workshop in Arlington. VA, on 
December 13-15, 1986, in part to develop 
proposed guidelines for plants and 
animals. Proposed changes to the NIH 
Guidelines developed by USDA were 
reviewed and revised by an NIH 
Working Group on Revision of the 
Guidelines w’hich met on June 22 and 
July 16. 1987. 
In this proposal, language has been 
developed to modify Sections II and III 
of the NIH Guidelines to refer 
specifically to containment for research 
with whole plants and animals. 
Containment is described in the 
proposed amendments Appendix P for 
plants and Appendix Q for animals. The 
suggested modifications and additions 
will provide guidance to the Institutional 
Biosafety Committees (IBC.s) and 
Principal Investigators (Pis) to assure 
safe conduct of such experiments. 
ORDA and NIH staff will make 
necessary editorial modifications to the 
proposed changes after review by the 
RAC and prior to incorporation into the 
NIH Guidelines. 
1. Section II of the NIH Guidelines 
2. It is proposed that the following 
language be added to Section II, 
Containment, before the final paragraph: 
3. "Physical containment conditions 
within laboratories, described in 
Appendix G. may not always be 
appropriate for all organisms because of 
their physical size, the number of 
organisms needed for an experiment, or 
the particular growth requirements of 
the organism. Likewise, biological 
containment for microorganisms 
described in Appendix I is not 
appropriate for all organisms and for 
higher eukaryotic organisms in 
particular. Considerable information 
exists, however, on the design of 
research facilities and experimental 
procedures applicable to higher 
organisms carrying recombinant DNA 
cither integrated into the genome or into 
microorganisms associated with the 
higher organism as a symbiont, 
pathogen, or other relationship. This 
information includes types of facilities 
for physical containment of organisms 
other than in traditional laboratories, 
and practices for limiting or excluding 
unwanted establishment, transfer of 
genetic information, and dissemination 
of organisms beyond an intended 
location based on both physical and 
biological containment principles. 
Research conducted in accordance with 
these conditions effectively confines the 
organism.” 
4. "For research involving plants, four 
biosafety levels (BL1-P to BL4-P) are 
described in Appendix P. Biosafety 
Level 1 for plantB (BLl-P) is designed to 
provide a moderate level of containment 
for specific recombinant DNA research 
involving plants and is recommended for 
experiments for which there is no 
recognizable and predictable risk to the 
environment in the event of accidental 
release or for which there is convincing 
biological evidence that precludes the 
possibility of survival, transfer, or 
dissemination of the recombinant DNA 
molecules into the environment. 
Biosafety Level 2 for plants (BL2-P) is 
designed to provide greater containment 
of plants and certain associated 
organisms and is recommended for 
experiments in which there is a 
recognized possibility of survival, 
transmission, or dissemination of the 
recombinant DNA-containing organisms 
but the consequence of such a release 
has a predictably minimal biological 
impact in the event of inadvertent 
release. Biosafety Level 3 (BL3-P) and 
Biosafety Level 4 (BL4-P) for plants 
describe additional containment 
conditions for research with plants and 
certain pathogens and other organisms 
that require special containment 
because of their recognized potential for 
significant detrimental impact on 
managed or natural ecosystems." 
5. "BLl-P relies upon accepted 
scientific practices for conducting 
research in most ordinary greenhouse or 
growth chamber facilities and 
incorporates accepted procedures for 
good pest control and cultural practices. 
Such facilities and procedures, through 
providing a modified and protected 
environment for propagation of plants 
and of microorganisms associated with 
the plants, also provide a degree of 
containment that adequately controls 
sexual and vegetative reproduction and 
minimizes the potential for release of 
biologically viable plants, plant parts, 
and microorganisms associated with 
them. BL2-P and BL3-P also rely upon 
accepted scientific practices for 
conducting research in greenhouses with 
organisms infecting or infesting plants in 
a manner that minimizes or prevents 
inadvertent contamination of plants 
within or surrounding the greenhouse. 
BL4-P describes facilities and practices 
known to provide containment of certain 
exotic plant pathogens. 
6. "For research with animals that are 
of a size or have growth requirements 
that preclude the use of conventional 
primary containment systems used for 
small laboratory animals, four biosafety 
levels (BLl-N to BL4-N) are described in 
Appendix Q." 
7. "Biosafety Level 1 for animals (BL1- 
N) describes containment which is used 
for animals in which the germ line has 
been modified through recombinant 
DNA techniques (transgenic animals) 
and is designed to eliminate the 
possibility of sexual transmission of the 
modified genome or transmission of 
recombinant-DNA-derived viruses 
known to be transmitted only vertically 
(i.e., transmitted from animal parent to 
offspring only by sexual reproduction). 
Procedures, practices, and facilities 
follow classical methods of avoiding 
genetic exchange between animals." 
8. "Biosafety Level 2 for animals (BL2- 
N) describes containment which is used 
for transgenic animals and animals 
associated with recombinant-DNA- 
derived organisms and is designed to 
eliminate the possiblity of vertical or 
horizontal transmission. Procedures, 
practices, and facilities follow classical 
methods of avoiding genetic exchange 
between animals or controlling 
arthropod transmission." 
9. "Biosafety Level 3 for animals (BL3- 
N) and Biosafety Level 4 for animals 
(BL4-N) describe higher levels of 
containment which are used for research 
with certain transgenic animals and 
with agents posing a recognized 
hazard." 
10. Section III of the NIH Guidelines. 
11. It is proposed that Section III— B, 
Experiments That Require IBC Approval 
Before Initiation, be changed as follow's: 
12. Proposed changes in Section JJI-B- 
1. Experiments Using Human or Animal 
Pathogens (Class 2. Class 3, Class 4. or 
Class 5 Agents [I]) as Host-Vector 
Systems: 
13. These changes specify in the NIH 
Guidelines the contaiments 
recommended for research with 
[ 22 ] 
Recombinant DNA Research, Volume 13 
