Ch.4 — The Pharmaceutical Industry • 71 
rhe interferons are presently recei\ ing atten- 
tion largely because studies in Sweden and the 
L'nited States stimulated the appropriation of 
$5.4 million hy the American Cancer Society 
(.AC'S) for e.xpanded clinical trials in the treat- 
ment of cancer. That commitment hy the non- 
profit AC'S— the greatest hy far in its history— 
was followed hy a boost in NIH funding for in- 
terferon research from $7.7 million to $19.9 
million for fiscal year 1980. Much of the cost of 
interferon reseai'ch is allotted to procuring the 
glycopeptide. Initially, the ACS bought 40 billion 
units of leukocyte interferon from the Finnish 
Red Ca'oss for $50 per million units. In March 
1980, Warner-Lambert was awarded a contract 
to supph’ the National C'ancer Institute (N'Cl) 
with 50 billion units of leukocyte interferon 
within the ne.xt 2 years at an a\erage price of 
$18 per million units. \'C4 is also planning to 
purchase 50 billion units each of fibroblast and 
lymphohlastoid interferons. 
The bulk of the \IH funding is included in 
NCI’s new Biological Response Modifier (BRM) 
program— interferon accounts for $13.9 million 
of the $34.1 million allocated for BRM work in 
fiscal year 1980. (NCI expenditures on inter- 
feron in 1979 were $2.6 million, 19 percent of 
the amount budgeted for 1980.) Other impor- 
tant elements of that BRM program concern 
immunoproteins known as lymphokines and 
thymic hormones, for which molecular genetics 
has major implications. The program is aimed at 
identifying and testing molecules that control 
the acth’ities of different cell types. 
LYMPHOKINES AND CYTOKINES 
Lymphokines and cytokines are regulatory 
molecules that have begun to emerge from the 
obscure fringes of immunology in the past 10 
years. (Interferon is generally considered a lym- 
phokine that has been characterized sufficiently 
to deserve independent status.) 
Lymphokines are biologically active soluble 
factors produced by w hite blood cells. Studied 
in depth only within the last 15 years, they are 
being implicated at virtually ev'ery stage in the 
complex series of events that make up the im- 
mune response. They now' include about 100 
different compounds. Cytokines, w'hich have ef- 
fects similar to lymphokines, include several 
compounds associated with the thymus gland, 
referred to as thymic hormones.'* 
In 1979, the BRM subcommittee concluded 
that se\ eral of these agents probably have great 
potential for cancer treatment. Nevertheless, 
adeciuate quantities for laboratory and clinical 
testing of many of them will probably not he 
a\ ailahle until the problems of producing glyco- 
proteins by molecular cloning are overcome. No 
system is currently a\ailahle for the industrial 
production of glycoproteins, although yeasts 
may [)ro\e to he the most useful micro-orga- 
nisms. 
ANTIBODIES 
Antibodies are the best known and most ex- 
ploited protein components of the immune sys- 
tem. I’ntil recently, all antibodies were obtained 
from the blood of humans or animals; and they 
were often impure. Within the past 5 years, 
however, it has become possible to produce an- 
tibodies from cells in culture, and to achieve 
levels of purity previously unattainable. As with 
prex’ious adxances in antibody technology, re- 
searchers are examining ways to put this new 
le\el of purity to use. There have been hun- 
dreds, if not thousands, of examples of new 
diagnostic and research methods, new methods 
of purification, and new therapies published 
within the first 3 years that the technique has 
been available. (See Tech. Note 11, p. 81.) 
This high level of purity was attained by the 
development of monoclonal antibodies. These 
antibodies that recognize only one kind of anti- 
gen were the unanticipated fruit of fundamen- 
tal immunological research conducted by Drs. 
Caesar Milstein and Georges Kohler at the Med- 
ical Research Council in England in 1975. They 
fused two types of cells— myeloma and plasma- 
spleen cells— to form hybridomas that produce 
the monoclonal antibodies. (See Tech. Note 12, 
p. 81.) Not only are the antibodies specific, but 
because the hybridomas can be grown in mass 
culture, a virtually limitless supply is available. 
The most immediate medical application for 
monoclonal antibodies lies in diagnostic testing. 
■'For 40 of the best characterized cytokines, see footnote 1, p. 
69. 
