J3048 
nonces 
Mtta. The removal at thte prabibitloo *u 
pmpn— I hi the l e p crt tt the Wortkit 
Oraup ob Vlnae* wh*rt met on Apr. W, 
in*. Hid ih n ed hr the RAC at iu Apr 
n-m t*m. m«Vr» The re— n tog behind 
pHcea at theae Hr— dcaed In A cadi 
K-12 pom no — rhh. end artaaiij ipcMi 
u> p— e etaariy tan na*. than wort with the 
whole InJerUou* vtraa HeeU. Since NCI rec- 
that wort with theae whale *lr 
wee not he prohibited hwt rather be pa*- 
farmed an her mcnwnmml ocothimae ataaj- 
lar to P*. there la no scientific reaaoa to pro- 
UWt rinneMiletnl DMA wart with theae vlr- 
— The -fUxibgKy clause refer* to 
power at the DWector. KIR. to waive peakl- 
MJena when the public lotereat may be 
served br auch action. 
(if) The Ouldellaea aaj at the beglanlar 
of PL m. Otven below are eowtaln— ewt 
(uldeU—e tat penal— hie experiment*. 
Oa— e In theae levele far — cdflc expert- 
aeou (or the a— nmmt at lev eh to expert 
menu not explicitly considered In this sec- 
tion) may be crprraalj approved bjr the Di- 
rector. KIR on the reoommcTVtaUon el the 
Recombinant DMA Advisory Cc ea—Uea* 
Inaertlon at such language into the (Ulde- 
Unee waa recommended by the RAC at IU 
Apr. r it 1978. meeUivt. It recognises that 
the of rxperimenU liven In 
PL HI wfD neeeaaarQy be Imperfect, aa In- 
vestigators tn the future devise new *ray» to 
conduct recombinant DNA experiments not 
currently fart— an and therefore not explic- 
itly considered In the gukieUnea. Alse. new 
data may become available showing that 
certain particular experiments currently as- 
signed a particular containment level are. 
Indeed, dearly more (or lem) safe than envi- 
sioned at this time. 
(if) See App C to Che ruldeRnea and Part 
IY at this Decision Document.’ 
(tT) In May 19TI. a resident of Frederick. 
Md.. brought suR In the UiJ DWtrVt Court 
for the District of Columbia to enjoin a pro- 
posed risk- amassment exper i ment sMrh 
was about to be ondertaAea la a maximum 
containment facility (PI) located at the 
Frederick Cancer Research Center. (Mack r. 
Caif/haa Civil Action No. 77 0 * 14 ). On Feb- 
ruary 9. 1911 the court issued a decision 
refusing to tra nt the toJucOon. In so doing, 
the court observed that the environmental 
Impact statement on the original guidelines 
constituted a "hard look" at recombinant 
DNA research performed In accordance 
with the (uidellnea The court further 
noted that compliance with tin guidelines. 
It appeared, would Insure that no recombin- 
ant DNA molecules would escape from the 
carefully con trolled laboratory to the envi- 
ronment. and that the guidelines "rep r es ent 
aa effort by many scientists to evaluate the 
hasarrto and provide safe methods for their 
control." 
The plaintiff appealed (Appeal No. 78- 
1188). and on Mar 8. 1978. the Court of Ap- 
peals for the District of Columbia upheld 
the district court decision. 
I. 8cor* or nt* Outd*unx» 
uvntw or aac-protosei guido. utxa 
It waa the determination of the Re- 
combinant Advisory Committee that 
advances In knowledge pertaining to 
recombinant DNA activities In past 
years warranted significant revisions 
in the ' purpose.'* 'definition.** and 
prohibition" sections ot the NIH 
guide tinea A comparison ot the pur- 
pose* language at the two seta af 
guidelines’ reweals that the standards 
in the PRO-RAC we r e meant to per- 
tain to r ec o mbinant DNA molecules In 
organisms. The analogues language tn 
the 1978 guidelines addresses recom- 
binant DNA molecules whether or not 
they are contained within a oeU or 
virus. Tbe rationale for ihM change Is 
that DNA by Itself (commonly re- 
ferred to as "naked** DNA) Is extreme- 
ly on likely to be hazardous under ex- 
perimental conditions, as ft Is rapidly 
Inactivated In nature. 
The definition in the PRG-RAC 
consisted of two parts: (1) an oper- 
ational dr (In) Lion of recombinant DNA 
and (3) a Qualification that the guide- 
lines would pertain only to "nowei" re- 
combinant DNA**. The operational 
definition does not differ significantly 
from that In the original guidelines. 
The second part, however, called for 
the creation of a list of organisms that 
exchange genetic information In 
nature, mrwnvnniy referred to as "non- 
novel exchangers." Recombinant DNA 
formed with DNA from such organ 
Isms would be exeaapted from tbe pro- 
visions of the PRO-RAC. with the ra- 
tionale that there Is no Justification 
for requtrtng containment procedures 
for the handling of recombinations 
that occur regularly In nature and are 
not known to be associated with any 
special hazard* 
The provision of an open-ended list- 
ing was recommended rather than Is- 
suance or a blanket exemption, be- 
cause this would allow the RAC and 
NTH to consider evidence that (1) the 
putative gene transfers do take place 
naturally and (2) their exemption 
from the guidelines Is Justifiable (see 
footnote 1 of the PRG-RAC). 
Although the PRG-RAC deals with 
prohibited experiments under Part IIL 
this decision document, for purposes 
that become apparent below, win con- 
sider the definition, exemptions, and 
prohibitions together under section L 
The “prohibitions" section was 
called section III- A. "Experiments 
That Are Not To Be Performed. - ' in 
both the 1976 guidelines and PRG- 
RAC. Changes from the 1978 guide- 
lines. proposed tn the PRG-RAC. in- 
cluded minor wording changes In 
Items (HI). (!v). and (vl). 
The ability to grant exemptions for 
certain experiments from tbe ‘'prohi- 
bitions'' was limited in the 1978 guide- 
lines to only the sixth prohibition 
(large-scale experiments with recom- 
binant DNA’s known to make harmful 
products). In the PRG-RAC the Dlrec- 
1 The current guidelines u published In 
the Pro dial Racism. July 7. 1978 (41 FR 
27902). and the RAC « proposed revisions 
(PRO-RAC) as published in the Fkdxxai 
Racism. Sept. 27. 1977 ( 42 FR 49598). 
Mu. NIH. Is gives the authority to 
grant exceptions from any ot tbe ate 
prohibitions. Such a determinaban 
must be based upon the recommenda- 
tion of the RAC, and w e igh t most be 
given In the decision making “both to 
scientific and societal benefits and to 
potential risks." The rationale lor this 
proposed change waa the desire of the 
RAC not to preclude the possibility of 
conduction such experiments fer some 
compelling social or scientific rea- 
sons— for example, risk -assessment ex- 
periments. 
The sections of the PRG-RAC deal- 
ing with purpose of (he guidelines, 
definition of recombinant DNA. ex- 
emptions. and prohibitions evoked a 
great deal of comment both before 
and after the December 1977 public 
h e aring . An anytsts of theae comments 
and my decision tn response to the 
issues raised are presented In the fol- 
lowing section. 
arvirw or comrorrs aim icththopostd 
GUIDELINES 
There was considerable discussion at 
the public hearing over the scope of 
the guidelines. Some felt that the 
guidelines were too narrow in their 
preoccupation with recombinant DNA. 
as there exist other forms of genetic 
re s e a rc h capable of producing organ- 
isms of unknown potential hazard. It 
was farther suggested that the title of 
the guidelines be modified to reflect 
the preoccupation with experiments 
Involving prokaryotes and cells in cul- 
ture. and that a companion document 
be released dealing with higher eukar- 
yote*. On the other hand. It was also 
argued that genetic research has now- 
received attention far beyond Its doe. 
and that other matters of experimen- 
tation await their turn. 
While It is true that other tech- 
niques In genetic research, such as cell 
fusion and chromosome transfer, may 
result tn formation of recombinant 
molecules. I do not believe at this time 
that we should mandate or extend the 
guidelines to these research areas. 
There are Inherent in these tech- 
niques a range of natural barriers to 
tbe formal Ion of hazardous organisms 
which apparently afford adequate con- 
tainment. making unnecessary the Is- 
suance of Fe dera l standards. I base 
this conclusion on the fact that such 
techniques have been used In the labo- 
ratory for decades with no known 
harmful effects on either tbe public 
health or the environment. I should 
also emphasise that the entire area of 
laboratory safety Ls of primary con- 
cern to NTH and is the subject of con- 
stant review and attention. A descrip- 
tion of NTH activities tn these areas ls 
presented In the environmental Impact 
assessment. 
A commentator suggested that the 
language be deleted stating that “• • * 
FEDCLAl LEGIST! 8. VOL 43. MO. 146— FtlOAY, JULY 28. 1978 
( 9 ] 
