Ch. 4— The Pharmaceutical Industry • 61 
Potential uses of molecular genetic technologies 
l\)lypeptities— proteins— are the tirst abun- 
dant end prodiiets of genes. Thev inelude pep- 
tide hormones, enzymes, antibodies, and cer- 
tain \aeeines. Producing tliem is the goal of 
most current efforts to harness genetically 
directed processes. Houe\er, it is just a matter 
of time and the exolution of technolog\' before 
complex non[)roteins like antibiotics can also he 
manufactured through rI)>J,\ techni(|ues. 
Hormones 
The most ad\anced apf)lications of genetics 
today, in terms of technological sophistication 
and commercial de\ elopment, are in the field of 
hormones, the potent messenger molecules that 
help the body cooi dinate the actions of \ arious 
tissues. (See Tech. Note 1, p. 80.) The capacity to 
synthesize proteins through genetic engineer- 
ing has stemmed in large part from attempts to 
prepare human peptide hormones (like insulin 
and growth hormone). The diseases caused by 
their deficiencies are presently treated with ex- 
tracts made from animal or human glands. 
The merits of engineering other peptide hor- 
mones depend on understanding their actions 
and those of their deri\ati\es and analogs. 
E\idence that they might be used to improxe 
the treatment of diabetes, to promote wound 
healing, or to stimulate the regrowth of nerv'es 
will stimulate new scientific investigations. 
Other relati\ely small polypeptides that influ- 
ence the sensation of pain, appetite suppression, 
and cognition and memory enhancement are 
also being tested. If they prove useful, they will 
unquestionably be evaluated for production via 
fermentation. 
VV'hile certain hormones have already at- 
tained a place in pharmacology, their testing 
and use has been hindered to some extent by 
tbeir scarcity and high cost. Until recently, 
animal glands, human-cadaver glands, and 
urine were the only sources from which they 
could be drawn. Their use is also limited 
because polypeptide hormones must be ad- 
ministered bv injection. Thev are digested if 
they are taken orally, a [)rocess that curtails 
their usefulness and causes side-effects. 
Thei'e are four technologies for producing 
[)oly peptide hormones and polypeptides: 
• extraction from human or animal organs, 
sei'um, or urine; 
• chemical synthesis; 
• |)i'oduction by cells in tissue culture; and 
• production by microbial fermentation after 
genetic engineering. 
One major factor in deciding which technol- 
ogy is best for which hormone is the length of 
the hormone’s amino acid chains. (See table 3.) 
Modern methods of chemical synthesis have 
made the preparation of low-molecular weight 
polypeptides a fairly straightforward task, and 
chemically synthesized hormones up to at least 
32 amino acids (AA) in length— like calcitonin 
Table 3.— Large Human Polypeptides Potentially 
Attractive for Biosynthesis 
Amino acid 
residues 
Molecular 
weight 
Prolactin 
. . . 198 
Placental lactogen 
. . . 192 
'Growth hormone 
. .. 191 
22,005 
Nerve growth factor 
... 118 
13,000 
Parathyroid hormone (PTH) . . . 
. . . 84 
9,562 bovine 
Proinsulin 
. . . 82 
Insulin-like growth factors 
(IGF-I &IGF-2) 
. . . 70, 67 
7,649, 7471 
Epidermal growth factor 
6,100 
'Insulin 
. . . 51 
5,734 
Thymopoietin 
. . . 49 
Gastric inhibitory polypeptide 
(GIP) 
. . . 43 
5,104 porcine 
'Corticotropin (ACTH) 
. . . 39 
4,567 porcine 
Cholecystokinin (CCK-39) . . . . 
. . . 39 
Big gastrin (BG) 
. . . 34 
Active fragment of PTH 
. . . 34 
4,109 bovine 
Cholecystokinin (CCK-33) . . . . 
. . . 33 
3,918 porcine 
'Calcitonin 
. . . 32 
3,421 human 
Endorphins 
. . . 31 
3,435 salmon 
3,465 
'Glucagon 
. . . 29 
3,483 porcine 
Thymosin-<yt 
. . . 28 
3,108 
Vasoactive intestinal peptide (VIP) 28 
3,326 porcine 
'Secretin 
. . . 27 
'Active fragment of ACTH .... 
. . . 24 
Motilin 
. . . 22 
2,698 
'Currently used in medical practice. 
SOURCE: Office of Technology Assessment. 
