Ch. 4— The Pharmaceutical Industry • 81 
schistosDiiiiasis (hilliar/ia). tilariasis (oncln)ceiTiasis 
and elephantiasis), leshmaniasis. hookworm, amehie in- 
teetions, aiui lr\ panosomiasis (slt*eping sickness and 
Chagas disease). 
« .Another potential use of antigens is suggested hv the 
e.xperimental treatment ol stage I lung cancer patients 
with vaccines prepared Irom purified human lung 
cancer antigens, which apjjears to suhstantially pro- 
long survival. And the Salk Institute is expanding clin- 
ical trials in vv Inch a pi’ocine myelin protein prepared 
by Kli l.illv <St C'o. is injected into multiple scleiosis pa- 
tients to mop up the antimvelin antibodies that those 
patients are jn-oducing. Fifteen to forty-two g of myelin 
have htHMi injected w ithout adv erse effects, suggesting 
a new therapeutic approach to auto immune diseases, 
rhe protein appears to sup()ress the sv niptoms of ex- 
perimental allergic encephalomyelitis, an animal dis- 
ease resembling multiple sclerosis. Should this re- 
search succeed, the use of molecular clones to produce 
human protein antigens seems inev itahle. 
9. rhere are at least two distinct kinds of "classicar inter- 
ferons— leukocyte interferon and fibroblast interferon, 
so-called for the types of cells from which they are ob- 
tained. A third kind, called Iv iiijthohlastoid because it is 
produced from cells deriv ed from a Burkitt's Iv nipho- 
ma. appears to be a mixture of the other two inter- 
ferons. All produce the antiv iral state and are induced 
by viruses. A fourth kind, known as "immune" inter- 
feron, is produced by Ivmphocytes. Some ev idence in- 
dicates that it may he a more potent antitumor agent 
than the classical types. Currently, interferon is ob- 
tained chiefly from white blood cells (leukocytes) from 
the blood bank in Helsinki that serv es all of Finland, or 
from fibroblasts grown in cell culture. 
10. Recently, G. D. Searle & Co. announced that new tech- 
nologv" developed at its R&.D facility in England has in- 
creased the yield of fibroblast interferon by a factor of 
60. On tbe basis of this process, Searle expects to sup- 
ply material for the first large-scale clinical trial of 
fibroblast interferon. Abbott Laboratories also recently 
announced plans to resume production of limited 
quantities of fibroblast interferon for clinical studies it 
plans to sponsor. 
L'nlike leukocytes and specially treated fibroblasts, 
which can be used only once, lymphoblasts derived 
from the tumor Burkitt's lymphoma grow freely in 
suspension and produce the least costly interferon 
presently obtainable. However, they also produce a dis- 
advantageous mixture of both leukocyte and fibroblast 
interferons. The Burroughs-Wellcome Co. produces 
lymphoblastoid interferon in 1,000-1 fermenters and 
has begun clinical trials in England, but the U.S. FD,A 
has generally resisted efforts to make use of products 
derived from malignant cells. It is used extensively in 
research, and FDA is considering evidence from Bur- 
roughs-W'ellcome that may lead to a relaxation of the 
prohibition, under pressure from the National Cancer 
Institute. 
11. What may be a landmark patent has been issued to 
Hilary Koprowski and Carlos Croce of the Wistar Insti- 
tute (for work done under the then Department of 
Health, Education, and Welfare funding) on the pro- 
duction of monoclonal antibodies against tumor cells. 
In a number of examples, these reseaichers demon- 
strated that an animal can be immunized with tumor 
cells, and that hyhridomas derived from that animal 
will produce antihodies that demonstrate a specificity 
for the tumor. 
rhe final sentence of the patent text provides the ra- 
tionale for the use of antibodies in both cancer and in- 
fectious disease therapies: "If the (tumor) antigen is 
present, the patient can be given an injection of an anti- 
body as an aid to react with the antigen." (II. S. 
4,172,124.) 
12. .Myeloma cells grow v igorously in culture and have the 
uniciue chaiacteristic of producing large quantities of 
antihodi(!s. Each spleen cell of the immune type, on the 
other hand, produces an antibody that recognizes a 
single antigen, hut these do not grow well in culture. 
W hen normal immune spleen cells are fused with mye- 
loma cells, the resulting mixture of genetic capacities 
forms a cell, called a "hybridoma, " which displays the 
desired characteristics of the parent cells: 1) it secretes 
the antibody specified by the genes of the spleen cell; 
and 2) it disjjlays the v igorous grow th, production, and 
longev ity that is typical of the myeloma cell. 
13. rhe use of high-correlation antibody assays in cancer 
studies bas only just begun. Antibodies that have been 
treated so they can be seen with X-rays and that are 
specific for a tumor, can be used early to detect the oc- 
currence or spread of tumor cells in the body. Because 
some 785,000 new cancer cases will be detected in 
1980 with current diagnostic methods, because cancer 
will cause 405,000 deaths, and because early detection 
is the major key to improving survival, the implications 
are indeed enormous. 
14. In the late 1950’s, Lederle Laboratories marketed a 
preparation of 95-percent pure streptokinase (a bac- 
terially produced enzyme that dissolves blood clots) for 
intravenous administration. They withdrew the prod- 
uct from the market around 1960 because it caused 
allergic reactions, which dampened clinical enthusiasm 
for its therapeutic potential. 
The presence in human urine of urokinase, an en- 
zyme also capable of removing blood clots, was also dis- 
covered in the early 1950's. Urokinase was purified, 
crystallized, and brought into clinical use in the mid- 
1960’s. From the beginning it was apparent that “an in- 
tense thrombolytic state could be achieved with a 
much milder coagulation defect than occurred with 
streptokinase; no pyrogenic or allergic reactions were 
noted, and no antibodies resulted from its administra- 
tion . . , There did not appear to be as great variation in 
patient responsiveness.” In 1967-68 and 1970-73, the 
National Heart and Lung Institute organized clinical 
trials that compared urokinase with streptokinase and 
heparin, an anticoagulant, in the treatment of pul- 
monary embolism. The trials indicated that strep- 
tokinase and urokinase were equivalent and superior 
to heparin over the short term, although their long- 
