74 • Impacts of Applied Genetics— Micro-Organisms, Plants, and Animals 
coupled to the production of the others. Hence, 
the industry would still have to orchestrate the 
production of the other proteins even if just one 
of them, such as Factor VIII, becomes a target 
for biological production. 
Another enzyme, urokinase, has been tar- 
geted for use in removing unwanted blood clots, 
which lead to strokes, myocardial infarctions, 
and pulmonary emboli. Currently, the drug is 
either isolated from urine or produced in tissue 
culture. (See Tech. Note 14, p. 81.) 
Urokinase is thus far the only commercial 
therapeutic product derived from mammalian 
cell culture. Nevertheless, some calculations 
suggest that production by E. coU fermentation 
would have economic advantages. The costs im- 
plicit in having to grow cells for 30 days on fetal 
calf serum (or its equivalent) or in having to col- 
lect and fractionate urine— as reflected in uroki- 
nase’s market price ($150/mg at the manufac- 
turer’s level)— should be enough incentive to en- 
courage research into its production. In fact, in 
April 1980, Abbott Laboratories disclosed that 
E. coli had been induced to produce urokinase 
through plasmid-borne DNA. 
The availability of urokinase might be guar- 
anteed by the new genetic technologies, but its 
use is not. For a variety of reasons, the Amer- 
ican medical community has not accepted the 
drug as readily as have the European and Japa- 
nese communities. Studies to establish the use 
of urokinase for deep vein thrombosis, for ex- 
ample, are now being conducted almost exclu- 
sively in Europe.® 
OTHER PROTEINS 
In addition to the proteins and polypeptides 
already mentioned, the structural proteins, 
such as the collagens (the most abundant pro- 
teins in the body), elastins and keratins (the 
compounds of extracellular structures like hair 
and connective tissue), albumins, globulins, and 
a wide variety of others, may also be susceptible 
to genetic engineering. Structural proteins are 
less likely to be suitable for molecular genetic 
manipulations: On the one hand, their size and 
®For additional information about how urokinase came to play a 
role in therapy, see footnote 1, p. 69. 
complexity exceed the synthetic and analytic 
capabilities that will be available in the next few 
years; on the other, either their use in medicine 
has yet to be established or material derived 
from animals appears adequate, as is the case 
with collagen, for which uses are emerging. 
Plasma, the fluid portion of the blood, con- 
tains about 10 percent solids, most of which are 
proteins. During World War II, a simple pro- 
cedure was developed to separate the various 
components. It is still used today. 
Serum albumin is the smallest of the main 
plasma proteins but it constitutes about half of 
plasma’s total mass. Its major therapeutic use is 
to reverse the effects of shock. ^ It is a reason- 
able candidate for molecular cloning, although 
its relatively high molecular weight complicates 
purification, and its commercial \alue is rela- 
tively low. The market value of normal serum 
albumin is approximately $3/g, hut the \’olume 
is such that domestic sales exceed $150 million. 
Including exports, annual production is in th(* 
range of 100,000 kg. 
Normal serum albumin for treating shock is 
already regarded as too expensive compared 
with alternative treatments, to expand its use 
would require a lower price. On the other hand, 
the Federal Government— and especially the De- 
partment of Defense— might disregai'd the im- 
mediate economic prospects and conclude' that 
having a source of human serum albumin tliat 
does not depend on payments to blood donors 
might be in the national intei'est. Since* many na- 
tions import serum albumin, proeku'ts ele*ri\e*el 
from molecular cloning e;e)ulel he expoi te*el. 
Serum albumin is presently the prineipal 
product of blood plasma fractie)nation, a e-hange 
in the way it is manufactureel we)ulel signifie'ant- 
ly affect that industry, lieeiau.sei a numhe*r eif 
other products (such as cle)tting fae'tors) are al.se) 
derived from fractie)natie)ii, a growth in the* 
need for plasma-elei’iveel albumin e’e)ulel ha\ c a 
significant impact e)ii the a\ailahility anel the* 
cost of these hypre)elucts. 
Tor a cietailc-d cli.snission ol (he cosIn and bcin-lils ol .ilbtj 
min and the striiclur(M)l iIh> indu.sirv. M'c loolnoic I p (i!i 
