THE JOURNAL OF INFECTIOUS DISEASES . VOL. IJ7. NO. 5 . MAY 1978 
C 1978 b> I tie Uimcrmi o( Clmigo 18)22 1899/78' 370S 001 8500. 88 
Recombinant DNA: An Infectious Disease Perspective 
Sherwood L. Cor bach 
I lie title of this meeting implies areas of com- 
mon ground among the participants which 
formed the basis of our discussions. First, is that 
there are potential risks associated with recom- 
binant DNA experimentation. The level of risk 
and its application to specific experiments re- 
main highly controversial, but all prudent sci- 
entists would recognize that certain experiments 
cannot lie exonerated of unexpected, and even 
serious, misadventures. 'Flic second area of com- 
monality is that such risks can be assessed, mea- 
sured. quantitated, and subjected to the same sci- 
entific scrutiny that characterizes the nature of 
the research endeavor itself. 
The major focus of concern over recombin- 
ant DNA has been whether disease will lie pro- 
duces! in laboratory workers or innocent bystand- 
ers, particularly the public at large. This confer- 
ence lias lieeu an attempt, perhaps the first of its 
kind, to bring molecular biologists together with 
scientists interested in the pathogenesis of dis- 
ease. Diverse disciplines were represented: micro- 
biology. epidemiology, gastroenterology, and cn- 
tlucrinology. One of the avowed purposes of the 
meeting was to widen the scope of discussion to 
include researchers interested in mechanisms of 
disease. It is ironic that infectious disease ex- 
perts have, in general, remained at the sidelines 
during this great debate, not engaging in the dis- 
cussions of |>otcntial epidemics and unique viru- 
lence factors, areas aliout which they arc partic- 
ularly knowledgeable. 
.Another reason for convening the meeting 
was to develop, through interdisciplinary discus- 
sions, experimental protocols which could assess 
die risk of recombinant DNA research. A scries 
of cx|K'iiments were designed in model systems 
to produce data that would permit rational 
PU-aw- ad«ln-ss requests fur reprints lo Dr. Sherwood L. 
(•orliacli. Ilcpai imciil of Medicine. Tufls-Ncw England 
Medical Center Hospital. 171 HarTison Aycnuc. Boston, 
Massachusetts 021 1 1. 
From the Department of Medicine, Tufts-New England 
Medical Center Hospital, Tufts University School of 
Medicine, Boston, Massachusetts 
evolution of the guidelines for recombinant DNA 
research. Despite the political implications and 
external pressures, the meeting was a forum in 
which reason and science prevailed over philos- 
ophy and polemics. 
Defining the Risks 
Discussions of risk assessment are often con- 
founded by the onus to prove the absolute zero 
}x>ssibility of hazard, a task which in scientific 
terms is virtually impossible. It is equally impos- 
sible to deal with all conjectural risks, esjierial- 
ly those that have no foundation in scientific ob- 
servations. On the other hand, there remains a 
significant middle ground: legitimate areas of 
|xitcntial risk in recombinant DNA research 
which deserve to lie approached with the high- 
est degree of caution and restraint. These po- 
tential hazards can be grouped into three cate- 
gories. 
(/) An organism such as Escherichia colt K12 
may be converted, by the transfer of foreign 
DNA, into a pathogenic strain that resembles 
other pathogens already familiar to us. By in- 
creasing its virulence, the recipient strain could 
cause disease in a single |ierson or be propagated 
in the environment, thereby spreading to other 
individuals. This mechanism implies that the or- 
ganism has gained the ability to colonize the sus- 
ceptible host, to produce disease, and to sur- 
vive in nature. (2) The foreign DNA insert may 
be transferred from the recipient bacterium to 
other microorganisms or to somatic cells in high- 
er organisms. In the case of E. coli K12, even 
if the organism does not survive in the bowel, 
it may transfer its genes to other bacteria in the 
microflora. It has been |K>stulated, particularly 
with viral inserts, that the foreign DNA may pass 
the mucosal barrier to the somatic cells of the 
host. (?) The foreign DNA may encode for in- 
jurious products. Such products include toxins, 
hormones, or even proteins which could induce 
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