Chapter 4 
The Pharmaceutical Industry 
Background 
The domestic sales of prescription drugs by 
L’.S. pharmaceutical companies exceeded S7.5 
billion in 1979. Of these, approximately 20 per- 
cent were products for which fermentation 
processes played a significant role. They in- 
cluded anti-infective agents, vitamins, and bio- 
logicals, such as \ accines and hormones, (ienet- 
ics is expected to he particularly useful in the 
production of these pharmaceuticals and bio- 
logicals, which can only be obtained by extrac- 
tion from human or animal tissues and fluids. 
.Although the pharmaceutical industry was 
the last to adopt traditional fermentation tech- 
nologies, it has been the first industry to make 
widespread use of such advanced genetic tech- 
nologies as recombinant DN'A (rDN’A) and cell 
fusion. Two major factors triggered the use of 
genetics in the pharmaceutical industry: 
• The biological sources of many pharmaco- 
logically active products are micro-orga- 
nisms, which are readily amenable to ge- 
netic engineering. 
• The major advances in molecular genetic 
engineering have been made under an in- 
stitutional structure that allocates funds 
largely to biomedical research. Hence, the 
Federal support system has tended to fos- 
ter studies that hav^e as their ostensible goal 
the improvement of health. 
Two factors, however, have tended to dis- 
courage the application of genetics in the chem- 
ical and food industries. In the former, econom- 
ic considerations have not allowed biological 
production systems to be competitive with the 
existing forms of chemical conv'ersion, with 
rare exceptions. And in the latter, social and in- 
stitutional considerations hav'e not fav'ored the 
development of foods to which genetic engi- 
neering might make a contribution. 
Past uses of genetics 
Genetic manipulation of biological systems 
for the production of pharmaceuticals has two 
general goals: 
1. to increase the lev el or efficiency of the 
production of pharmaceuticals with prov- 
en or potential value; and 
2. to produce totally new pharmaceuticals 
and compounds not found in nature. 
The first goal has had the strongest influence 
on the industry. It has been almost axiomatic 
that if a naturally occurring organism can pro- 
duce a pharmacologically valuable substance, 
genetic manipulation can increase the output. 
The following are three classic examples. 
• The genetic improvement of penicillin pro- 
duction is an example of the elaborate long- 
term efforts that can lead to dramatic 
increases. The original strains of Penicilli- 
um chrysogenum, NRRL-1951, were treated 
w'ith chemicals and irradiation through 
successive stages, as shown in figure 20, 
until the strain E-15.1 was developed. This 
strain had a 55-fold improvement in pro- 
ductivity over the fungus in which penicil- 
lin was originally recognized— the Fleming 
strain. 
• Chemically induced mutations improved a 
strain of Escherichia coli to the point where 
it produced over 100 times more L-asparag- 
inase (which is used to fight leukemia) than 
the original strain. This increase made the 
task of isolating and purifying the pharma- 
ceutical much easier, and resulted in low- 
ering the cost of a course of therapy from 
nearly $15,000 to approximately $300. 
• Genetic manipulation sufficiently improved 
the production of the antibiotic, gentami- 
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