chapter 10 
The Question of Risk 
Introduction 
The perception that the genetic manipulation 
of micro-organisms might gi\e rise to unfore- 
seen risks is not new . The originators of chem- 
ical mutagenesis in the 1940's were warned that 
harmful uncontrolled mutations might he in- 
duced hv their techni(|ues. In a letter to the 
Recombinant D\.\ Ad\ isorv Committee (RAC) of 
the National Institutes of Health (N'lH) in Decem- 
ber of 1979, a pioneer in genetic transformation 
at the Rockefeller l'ni\ ersity, w rote: . I did 
in 1950, after some deliberation, perform the 
first drug resistance DN'A transformations, and 
in 1964 and 1965 took part in early warnings 
against indiscriminate transformations’ that 
were then being imagined.”’ 
‘Kollin I). Hotrhkis.s. Hectimhinant l)\A Hesearch, vol. o, .MM pul)- 
lic-iition .\o. 80-2131). March 1980. p 484 
The initial fear of harm 
For the purposes of this discussion, harm (or 
injury) is defined as any undesirable conse- 
quence of an act. Such a broad definition is w ar- 
ranted by the broad targets for hypothetical 
harm that genetic manipulation presents: injury 
to an indix idual’s health, to animals, to the en- 
vironment. 
The inital concern inx oh ed injury to human 
health. Specifically, it was feared that combin- 
ing the Di\A of simian \ irus 40, or S\'40, with an 
Escherichia coli plasmid would establish a new 
route for the dissemination of the virus. Al- 
though the S\'40 is harmless to the monkeys 
from which it is obtained, it can cause cancer 
w'ben injected into mice and hamsters. And 
while it has not been shown to cause cancer in 
humans, it does cause human cells to behave 
like cancer cells u'hen they are grown in tissue 
culture. W'hat effect such viruses might have if 
they were inserted into E. coli, a normal in- 
habitant of the human intestine, w'as unknown. 
This uncertainty, combined with an intuitwe 
\'et none of this earlier public concern led to 
as great a controversy as has research with re- 
combinant DNA (I'DNA). No doubt it was en- 
couraged because scientists themselves raised 
questions of potential hazard. The subsequent 
open debates among the scientists strengthened 
the public’s perception that there w^as legitimate 
cause for concern. This has led to a continuing 
attempt to define the potential hazards and the 
chances that they might occur. 
judgment, led to a concern that something 
might go wrong. The dangerous scenario went 
as follows: 
• SV40 causes cells in tissue culture to be- 
have like cancer cells, 
• S\'40-carrying E. coli might be injected ac- 
cidently into humans, 
• humans would be exposed to SV40 in their 
intestines, and 
• an epidemic of cancer would result. 
This chain of connections, while loose, was 
strong enough to raise questions in at least some 
people’s minds. 
The virus SV'40 has never actually been 
shown to cause cancer in humans; but the po- 
tential hazards led the Committee on Recombi- 
nant DNA Molecules of the National Academy of 
Sciences (NAS) to call in 1974 for a deferment of 
any experiments that attempted to join the DNA 
of a cancer-causing or other animal virus to vec- 
tor DNA. At the same time, other experiments. 
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