108 
is indigenous to human beings and all warm-blooded 
animals, is carried by many other organisms such as 
insects and fish, and can be found throughout the bio- 
sphere in soil and water. This microbe can normally 
exchange genetic information with 40 other species of 
micro-organisms, and though the likelihood of ex- 
change from the genetically enfeebled strain has been 
markedly reduced, it still may occur. The vast sea of 
micro-organisms in the environment makes events 
whose probability is the reciprocal of Avogadro's 
number (i.e., 1/1 0 23 ) not impossible.* 
Many experiments being carried out employ “shot- 
gun’' technics where complete chromosomes of unde- 
fined gene sequence are split into manv segments fol- 
lowed by insertion of these unknown genes into Esch. 
coli with potentially unpredictable results. Every im- 
planted eene becomes a new hypothesis, and there 
w ill be tens of thousands of such new hypotheses in- 
serted. This is the “Catch-22” dilemma associated 
with the technology. Could we inadvertently, via un- 
expected transfer of genetic information from the en- 
feebled host strain to one of the estimated 10 13 to 10 M 
healthy Esch. cnli organisms in the human bowel, cre- 
ate a novel self-replicating pathogen? Do we know for 
certain the effect in human beings or any other crea- 
ture of the biosphere, of a novel micro-organism pro- 
ducing a powerful insulin-like hormonal activity? 
Cloning of the insulin gene is but one of many experi- 
ments now in progress, any of which could have po- 
tential toxic or autoimmune effects. What effect might 
such a micro-organism have on other varieties of en- 
feebled hosts — the human patients who are on an- 
tibiotics therapy, who are immunosuppressed or who 
are otherwise debilitated by disease. In some cases 
these patients reside in hospitals that also include re- 
combinant DNA research laboratories. We do not as 
yet know the answers to the above questions. These 
questions should be addressed, and their answers and 
solutions fiamed in a new and badly needed public- 
health policy. 
That the NJH is providing millions of dollars for 
construction of containment facilities for some of this 
research is to its credit. Yet the “Fort Detrick Experi- 
ence’ 3 and the records of the Center for Disease Con- 
trol make it painfully clear that absolute containment 
of micro-organisms is impossible — even in laborato- 
ries where workers are exceedingly well trained and 
experienced in working with pathogenic organisms. 
Human frailty will guarantee mistakes. What, then, 
can be expected from numerous new laboratories re- 
cently involved in recombinant DNA research whose 
personnel have at best had a three-day course on con- 
tainment procedures? Here, we have the potential for 
a unique form of pollution, biologic pollution, and it 
will be distinguished by its irreversibility. In contrast 
to nuclear-power plants, which can be closed down, 
micro-organisms will reproduce and perpetuate them- 
selves. They cannot be recalled. Unlike the defined 
pathogens studied at Fort Detrick, their escape can- 
not be monitored for. 
The great deal of time and effort put into self-regu- 
lation, and the development of biologic and physical 
containment systems by the proponents of the tech- 
nology, is unprecedented. They have set an example 
of genuine concern for human well-being and the bio- 
sphere. But they have not faced containment of their 
ow n exponentially expanding activities, which may be 
an equally irreversible route to ecologic disaster at the 
rate at which the research activities are expanding. In 
reality, we have all become experimental subjects for 
recombinant DNA experiments. Yet none of us have 
signed an informed-consent statement. 
A risk-assessment panel has recently been con- 
vened by the NIH to determine the risks involved and 
where information is lacking to propose experiments 
to obtain the information. This is a proper and im- 
portant step in terms of public-health considerations. 
The burden of proof or lack of hazards should rest nei- 
ther on the opponents nor on the proponents of the re- 
search. Their role should simply be to distill and de- 
fine the issues for the remainder of the biomedical 
community and the public at large. The go-ahead sig- 
nal should be the result of a public-health decision- 
making process, developed by decision-making bodies 
democratically appointed and representative of a rich 
diversity of ethical and scientific points of view. 
And in the interim? I believe that the research 
should proceed, but on a more limited basis, perhaps 
only at regional facilities of high containment staffed 
by experienced and well trained personnel. A host 
bacterium less ubiquitous than Esch. coli also seems a 
wiser choice. Such a temporary slowdown would have 
no effect on freedom of inquiry. Rather, it would ef- 
fect freedom of manufacture — the manufacture of 
novel self-replicating micro-organisms. A miscalcula- 
tion on our part as scientists would have far more 
damaging effects than a temporary slowdown on sci- 
ence as we know it in terms of public outrage and mis- 
trust. 
The societal benefits that may well arise from gene 
transplantation studies will be valuable whether they 
come in 20 years versus 25, or 50 years versus 55. 
These benefits and the sheer excitement and beauty of 
•C urn, k Potential biohazards of recombinjnl [)X X r.ulecules tunpuh- 
'hed memor jndum lo Paul Bcrp cl al ) August 6. Ix"4 
