80 • Impacts of Applied Genetics — Micro-Organisms, Plants, and Animals 
Clearly, there is no simple formula to identify 
all the impacts of applied genetics on the phar- 
maceutical industry. Even projections of eco- 
nomic impacts must remain crude estimates. 
Nevertheless, the degree to which genetic engi- 
neering and fermentation technologies might 
potentially account for drug production in spe- 
cific categories is projected in appendix I-B. 
Given the assumptions described, the inimedi- 
ate direct economic impact of using genetic ma- 
nipulation in the industry, measured as sales, 
can be estimated in the billions of dollars, with 
the indirect impacts (sales for suppliers, savings 
due to decreased sick days, etc.) reaching 
several times that value. 
Technical notes 
1. Many hormones are simply chains of amino acids (poly- 
peptides); some are polypeptides that have been mod- 
ified by the attachment of carbohydrates (glycopep- 
tides). Hormones usually trigger events in cells remote 
from the cells that produced them. Some act over 
relatively short distances— between segments in the 
brain, or in glands closely linked to the brain, others 
act on distant sites in tissues throughout the body. 
2. For peptides about 30 AA in length, the cost may ap- 
proach $1 per mg as the volume approaches the kilo- 
gram level— a level of demand rarely existing today but 
likely to be generated by work in progress. Today, the 
cost of the 32 AA polypeptide, calcitonin, which is syn- 
thesized chemically and marketed as a pharmaceutical 
product by Armour, is probably in the range of $20 per 
mg, since the wholesale price in vials containing ap- 
proximately 0.15 mg is about $85/mg. (That price is an 
educated guess, since such costs are closely guarded 
secrets and since the price of a pharmaceutical in- 
cludes so many variables that the cost of the agent 
itself is a small consideration.) 
3. In addition to those helped by the National Pituitary 
Agency, another 100 to 400 patients are treated with 
hGH from commercial sources. The commercial price 
is approximately $15 per unit (roughly $30/mg). The 
production cost at the National Pituitary Agency is 
about $0. 75/unit ($1. 50/mg). The National Pituitary 
Agency produces 650,000 international units (lU) 
(about 325 g) of hGH, along with the thyroid-stimulat- 
ing hormone, prolactin, and other hormones, from 
about 60,000 human pituitaries collected each year. 
That is enough hGH both for the current demand and 
for perhaps another 100 hypopituitary patients. 
4. Workers at the Howard Hughes Medical Institute of 
the University of California, San Francisco, isolated 
messenger RNA from a human pituitary tumor and 
converted it into a DNA-sequence that could be put into 
E. coli. The sequence, however, was a mixture of hGH 
and non-hGH material. It has been reported that Eli Lil- 
ly &, Co., which has provided some grant money to the 
Institute, has obtained a license to the patents relating 
to this work. Grants from the National Institutes of 
Health and the National Science Foundation were also 
acknowledged in the publication. 
At practically the same time, researchers at Genen- 
tech, in conjunction with their associates at City of 
Hope National Medical Center disclosed the production 
of an hGH analog. This was the first time that a human 
polypeptide was directly expressed in E. coli in func- 
tional form. The work was supported by Kabi Gen .AB, 
and Kabi has the marketing rights. 
The level of hGH production reported in the scientif- 
ic account of the Genentech work was on the same 
order as that reported for the insulin fragments— 
approximately 186,000 hGH moUu'ules per c(’ll— a k‘\ ('l 
that might be competitiv e even lud'orc* efforts are made 
to increase yield. Genentech stresses llu? point that de- 
sign, rather than classical mutation and selection, is the 
logical way to improve the system, since the hormotie's 
"blueprint" is incorporatcKl in a plasmid that can he 
moved between strains of E. coli, betwc'en s|)ecies, oi' 
even from simple bacteria into more complex orga- 
nisms, such as yeast. 
5. Since erythropoietin is a glyco|)rot(!in. it may not be 
feasible to synthesize the; active; hor-mone w ith |)resent- 
ly available rDNA techtii(|U(;s. 
6. Antigens are surface compoiuMits o( pathogenic oiga- 
nisms, toxins, or other proteins se'ci'cted by |)alhogenic 
micro-organisms. I'Ikw are; also the specific counter- 
parts of antibodies: antibodie^s ar<‘ formed by the 
body’s immune .system in respotise* to their presence 
Antibodies are synthesizeul by u bite blood cells and are 
created in such a way that they ai-e uni(|uely struc- 
tured to bind to s|)ccific antigens. 
7. Many of the most d(;vastating infectious diseases in- 
volve complex parasit(!s that I'efuse to grow under lab- 
oratory conditions, rlu; first cultivation of the most 
malignant of the s|)(;ci(;s of jiiotozoa that causes ma- 
laria, using human ixul blood cells, was described in 
1976 by a Rockelell(;r Univei sity jiarasitologist. W ilium 
Rager, Expm'iiiHintal immunogens were prepared and 
showed [jromise in monkews, but concern about the ex- 
istence of the r(;d blood ci>ll remnants— w Inch could 
give rise to autoimmune I'cactioiis— curtailed the pros 
pect for making practical vaccines by that route Sever 
al biotechnology' firms are currentlv Irving to svnihe 
size malai'ia antigi'iis by molecular cloning I his ellort 
may product; tt;chnic;il solutions to such si oiirges as 
