76 • Impacts of Applied Genetics — Micro-Organisms, Plants, and Animals 
p. 82.) The value of protoplast fusion, therefore, 
lies in potentially broadening the gene pool. 
Protoplast fusion is genetic recombination on 
a large scale. Instead of one or a few genes be- 
ing transferred across genus and species bar- 
riers, entire sets of genes can be moved. Success 
is not assured, however; a weakness today is the 
inherited instability of the “fused” clones. The 
preservation of traits and long-range stability 
has yet to be resolved. Furthermore, it seems 
that one of the most daunting problems is 
screening— determining what to look for and 
how to recognize it. (See Tech. Note 17, p. 82.) 
Recombinant DNA techniques are also being 
examined for their ability to improve strains. 
Many potentially useful antibiotics do not reach 
their commercial potential because the micro- 
organisms cannot be induced to produce suffi- 
cient quantities by traditional methods. The syn- 
thesis of certain antibiotics is controlled by 
plasmids, and it is believed that some plasmids 
may nonspecifically enhance antibiotic produc- 
tion and excretion. 
It may also be possible to transfer as a group, 
all the genes needed to produce an antibiotic 
into a new host. However, increasing the num- 
ber of copies of critical genes by phage or plas- 
mid transfer has yet to be achieved in antibiotic- 
producing organisms because little is known of 
the potential vectors. The genetic systems of 
commercial strains will have to be understood 
before the newer genetic engineering ap- 
proaches can be used. Genetic maps have been 
published for only 3 of the 24 or more indus- 
trially useful bacteria. 
Since 2,000 of the 2,400 known antibiotics are 
produced by Streptomyces, that is the genus of 
greatest interest to the pharmaceutical indus- 
try. Probably every company conducting re- 
search on Streptomyces is developing vectors, 
but little of the industrial work has been re- 
vealed to date. 
Nonprotein pharmaceuticals 
In both sales and quantity, over 80 percent of 
the pharmaceuticals produced today are not 
made of protein. Instead, they consist of a varie- 
ty of organic chemical entities. These drugs, ex- 
cept for antibiotics, are either extracted from 
some natural plant or animal source or are syn- 
thesized chemically. 
Some of the raw materials for pharmaceuti- 
cals are also obtained from plants; micro-orga- 
nisms are then used to convert the material to 
useful drugs in one or two enzymatic steps. 
Such conversions are common for steroid hor- 
mones. 
In 1949, when cortisone was found to he a 
useful agent in the treatment of arthritis, the 
demand for the drug could not be met since no 
practical method for large-scale production ex- 
isted. The chemical synthesis was complicated 
and very expensive. In the early and micl-195()'s, 
many investigators reported the microbial 
transformation of several intermediates to com- 
pounds that corresponded to the chemical syn- 
thetic scheme. By saving many chemical steps 
and achieving higher yields, manufactui'crs 
managed to reduce the price of stei'oids to a 
level where they were a marketable commodi- 
ty. A conversion of progesterone, for e.\ampU>, 
dropped the price of cortisone from $200 to 
$6/g in 1949. Through fui'thei’ impro\'(Mnents, 
the price dropped to less than $l/g. The 1980 
price is $0.46/g. 
Developments based on genetic; te('hni(|ucs to 
increase the production and secrcUioii of kc\ en- 
zymes could substantially improxc; the econom- 
ics of some presently inefficient pi’ocesses. Cur- 
rently, assessments are being ('ariied out by 
various companies to determine' which of the 
many nonprotein phai’macxnitieals c'an hc' man- 
ufactured more readily oi' more ('conomieally 
by biological means. 
Approximately 90 perccMit of the* pharmaceu- 
ticals used in the treatiimnt of hypei ten.sion ai'c 
obtained from plants, as well as are miscel- 
laneous cardio\asculai’ drugs. Morphine .md 
important \asodilators are obtained from tlie 
opium poj)py, Papaver sotttniferiim. All these 
chemical substances arc; produec'd by a series nl 
enzymes that ai’e codcnl h\' con-esponding ^;enes 
in the whole plant. The' long-term possihilitv 
(over 10 years) of using fermentation methods 
will depend on idcMitifving the important ^enes 
