60084 
NOTICES 
(erred to another host by known phys- 
iologic means'] will exempt the follow- 
ing types of experiments: 
"Ah E. coh strain Is constructed In 
which a chromosomal gene of E. colt 
has been enzymatically Joined to plas- 
mid DNA; this plasmid is then trans- 
ferred by conjugation into another 
bacterial host that is not on the Direc- 
tor's List of bacteria that exchange 
with E. Colt 
“It seems logical that this experi- 
ment should be exempt, because It In- 
volves natural genetic exchange be- 
tween two organisms both of which 
are exempt. The E. Colt donor Is 
exempt because It represents a gene 
combination that could easily arise by 
natural means. As the transfer can 
also occur naturally, the same state- 
ment applies also to the second host 
carrying the plasmid. 
“If unidirectional plasmid transfer 
had been accepted as an adequate cri- 
terion for Inclusion on the Director's 
List, the strain would be automatically 
exempt. The reason for not accepting 
this criterion was that some doubts 
had been expressed as to whether uni- 
directional plasmid transfer automati- 
cally Implied bidirectional transfer of 
chromosomal genes. However. In the 
present case, the ability to construct 
the desired recombinant Is de facto 
evidence that it could arise by natural 
means. 
“A specific proposal was submitted 
to RAC • • • to splice an E. Colt sup- 
pressor Into an £- Colt transposon. 
then move the resulting combination 
Into Myxococcus by PI transduction. 
This strategy will allow the Isolation 
of suppresslble mutants of myxococ- 
cus and Its phages, which will greatly 
expedite genetic studies of develop- 
ment and motility In that organism." 
The change as proposed by the com- 
mentator is warranted In my view, and 
has been made, with minor rewording 
for clarity. 
There were many comments con- 
cerning the list of exchangers In Ap- 
pendix A to be exempt from the 
Ouldellnes under exemption I-E-4. 
Many commentators urged more ex- 
plicit standard for Inclusion on the 
list. As discussed In detail In the sec- 
tion of this document dealing with Ap- 
pendix A. the criteria for Inclusion on 
the list have been tightened and made 
more explicit, reducing the list consid- 
erably and thus exempting fewer ex- 
periments from the Guidellnea 
IT. CowTArHMnrr 
The object of the containment provi- 
sions of the proposed revised Guide- 
lines is to ensure that experimental 
DNA recombination will have no 111 ef- 
fects on the researchers, the general 
public, or the environment. Public 
comments on part II of the Guidelines 
and on the Laboratory Safety Mono- 
graph were generally supportive. How- 
ever. a number of pertinent Issues re- 
lating to physical and biological con- 
tainment were raised In correspond- 
ence and at the public hearing held on 
September 15. 1978. They deserve con- 
sideration and are addressed below. 
PHYSICAL CONTAIWMENT 
Effectiveness of Physical Containment 
One commentator observed that lab- 
oratories cannot provide foolproof 
containment of dangerous organisms 
and that a biohazard outbreak can 
rapidly spread to virtually any neigh- 
borhood on earth. He died the recent 
laboratory accident In England attrib- 
uted to the escape of a smallpox virus 
through a faulty filter. NIH agrees 
that when known hazardous agents 
are dealt with, the risk of a labora- 
tory-acquired infection cannot be to- 
tally eliminated. I believe, however, 
that adherence to the Guidelines pro- 
vides ample protection for laboratory 
personnel, the public, and the environ- 
ment. Even If an organism should 
escape from the laboratory, the muta- 
tional changes underlying “biological 
containment" would greatly decrease 
the probability that It would survive In 
the environment. The recent Incident 
In England Involves an extraordinarily 
hardy, resistant, and virulent orga- 
nism to which man Is very suscepti- 
ble— one that is hardly comparable to 
weakened strains of E. coll generally 
used tn recombinant DNA research or 
to the new host- vector (HV) systems 
now under consideration. 
Laboratory Practices 
A correspondent noted that persons 
on antibiotics or Immunosuppressive 
drugs, or those with open lacerations 
or chronic digestive abnormalities, are 
not prohibited from entering the labo- 
ratory under any of the physical con- 
tainment levels. In response. It should 
be pointed out that the Laboratory 
Safety Monograph (L8M), page 204. 
provides that "laboratory workers who 
are undergoing treatment with ster- 
oids. Immunosuppressive drugs or anti- 
biotics, or are suffering from colitis. 
Ileitis, active chronic diarThea, or 
other gastrointestinal disorders, 
should have a medical evaluation to 
determine whether they should be en- 
gaged In research with potentially haz- 
ardous organisms during the time of 
their Illness." Reference to this now 
appears In Section IV-D-l-h. which 
also mandates that, the Institution 
shall provide health surveillance of 
laboratory personnel. 
Several commentators noted that ab- 
sence of specific guidance for the 
rodent and Insect control programs re- 
quired In Section U-B-l-a-<9). II-B-2- 
a-<12), II-B-3-a-<12). II-B~4-a-<16). 
The large variety of situations and 
animal Involved makes precise specifi- 
cations impractical. It is the intent of 
the Guidelines, however, that ade- 
quate attention be paid to this prob- 
lem, and further guidance will be pro- 
vided In the next edition of the LSM. 
Emergency Procedures 
One commentator urged that the 
Guidelines include specifications for 
cleanup procedures to be followed In 
the event of a spill or accidental re- 
lease of organisms into the environ- 
ment. A witness recommends that for 
prompt and adequate response to 
emergencies, a team of experts from 
NIH and CDC be formed, and that 
their names and telephone numbers 
be published for easy access. Emergen- 
cy procedures are currently detailed in 
the LSM. pp. 194-195. These will be 
expanded In the next edition of the 
monograph to provide for an NIH- 
CDC emergency consultation and re- 
sponse program to assist institutions 
In managing serious accidents. 
Twenty-four-hour telephone coverage 
will afford an immediate reponse capa- 
bility. 
One correspondent recommended 
that all bacteria used in recombinant 
DNA experiments be tagged so that 
their spread, in the event of an acci- 
dent. could be detected In the environ- 
ment A general requirement to this 
effect is not now practicable. It should 
be noted, however, that In many cases 
bacteria are tagged to permit Identifi- 
cation. 
A correspondent raised the prospect 
that P2 and P3 containment facilities 
could be compromised by an earth- 
quake. Most Institutions have emer- 
gency plans for dealing with natural 
disasters. Selected references are cited 
In the LSM. If necessary, NIH and 
CDC are available to provide direct as- 
sistance In the management of specific 
emergency situations. Moreover, insti- 
tutions in areas subject to natural dis- 
asters such as earthquake must gener- 
ally conform to building code require- 
ments that are designed to minimize 
the effects of such disasters. 
Issues Related to Specific Contain- 
ment Levels 
A number of additional comments 
were received from public commenta- 
tors relating to the proposed actions at 
specific levels of physical containment. 
One correspondent said that the new 
PI and P2 containment conditions are 
not significantly different, and that 
the difference between PI and P2 
should be approximately the same as 
that between HV1 and HV2. He object- 
ed strongly to the escalation of the PI 
and P2 containment rules. 
NTH believes that the differences be- 
tween the two levels of containment 
are significant. For example, P2 re- 
quires use of biological safety cabinets 
to contain aerosol-producing equip- 
ment, use of the universal biohazard 
FCOECAL REGISTER, VOL 43, NO. 247— fRIDAY. DECEMBER 22. 1971 
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