62 • Impacts of Applied Genetics— Micro-Organisms, Plants, and Animals 
—have become competitive with those derived 
from current biological sources. Since frag- 
ments of peptide hormones often express activ- 
ities comparable or sometimes superior to the 
intact hormone, a significant advantage of 
chemical synthesis for research purposes is that 
analogs having slight pharmacological differ- 
ences from natural hormones can be prepared 
by incorporating different amino acids into 
their structures. In principle however, geneti- 
cally engineered biosynthetic schemes can be 
devised for most desirable peptide hormones 
and their analogs, although the practicality of 
doing so must be assessed on a case-by-case 
basis. Ultimately, tbe principal factors bearing 
on the practicality of the competing alternatives 
are: 
• The cost of raw materials. For genetically 
engineered biosynthesis, this includes the 
cost of the nutrient broth plus some amor- 
tization of the cost of developing the syn- 
thetic organism. In the case of chemical 
synthesis, it includes the cost of the pure 
amino acid subunits plus the chemicals 
used as activating, protecting, coupling, lib- 
erating, and supporting agents in the proc- 
ess. 
• The different costs of separating the de- 
sired product from the cellular debris and 
tbe culture medium in biological produc- 
tion, and from tbe supporting resin, by- 
products, and excess reagents in chemical 
synthesis. 
• The cost of purification and freedom from 
toxic contaminants. The process is more 
expensive for biologically produced materi- 
al than for materials produced by conven- 
tional chemistry, although hormones from 
any source can be contaminated. 
• Differences in the costs of labor and equip- 
ment. Chemical synthesis involves a se- 
quence of similar (but different) operations 
during a time period roughly proportional 
to the length of the amino acid chain (three 
AA per day) in an apparatus large enough 
to produce 100 grams (g) to 1 kilogram (kg) 
per batch; biological fermentations use vats 
—with capacities of several thousand gal- 
lons— for a few days, regardless of the 
length of the amino acid chain. 
• The cost and suitability of comparable 
materials gathered from organs or fluids 
obtained from animals or people. 
In the past decade, some simpler hormones 
have been chemically synthesized and a few are 
being marketed. However, synthesizing glyco- 
proteins— proteins bound to carbohydrates— is 
still beyond the capabilities of chemists. Data 
obtained from companies directly inxolved in 
the production of peptides by chemical synthe- 
sis indicate that the cost of chemically preparing 
polypeptides of up to 50 AA in length is ex- 
tremely sensitive to volume (see Tech. Note 2, p. 
80.); although the costs are high, the production 
of large quantities by chemical synthesis offers 
a competitive production method. 
Nevertheless, rDNA production, also known 
as molecular cloning, has already been used to 
produce low-molecular weight polypeptides. In 
1977, researchers at Genentech, Inc., a small 
biotechnology company in California, inserted a 
totally synthetic DNA sequence into an E. coli 
plasmid and demonstrated that it led to the pro- 
duction of the 14 AA polypeptide seciuence cor- 
responding to somatostatin, a hoi'inone found in 
the brain. The knowledge of somatostatin’s 
amino acid sequence made the experiment pt)s- 
sible, and the existence of sensiti\e assays al- 
lowed the hormone’s expression to be detect('d. 
Although the primary motive foi’ using this par- 
ticular hormone for the first demonstration was 
simply to show that it could he cIoik?, (ien(Mit('ch 
has announced that it plans to mark(>t its 
genetically engineered molecule foi’ r(\s(^ar('h 
purposes. (See figure 21.) 
Somatostatin is one of about 20 i'ecogniz('d 
small human polypeptides that can he made 
without difficulty hy chemical synthesis. (Se(* 
table 4.) Unless a sizable market is found foi" one 
of them, it is unlikely that fei inentation meth- 
ods will be developed in tbe foreseeable luture. 
Some small peptides that may justify tlie dewl- 
opment of a biosynthetic process of production 
are: 
• The seven AA seciuenci* known as MSN 
ACTH 4-10, w'hich is reputed to influence 
memory, concentration, and other p.sycho- 
logical-hehavioral ('fleets: should such 
