72 • Impacts of Applied Genetics— Micro-Organisms, Plants, and Animals 
Over the past 20 years, large segments of the 
diagnostic and clinical laboratory industries 
have sprung up to detect and quantify particu- 
lar substances in specimens. Because monoclon- 
al antibodies are so specific, hybridomas seem 
certain to replace animals as the source of anti- 
bodies for virtually all diagnosis and monitor- 
ing. Tbeir use will not only improve tbe accu- 
racy of tests and decrease development costs, 
but should result in a more uniform product. 
Today, such assays are used to: 
• determine hormone levels in order to 
assess the proper functioning of an endo- 
crine gland or the inappropriate produc- 
tion of a hormone by a tumor; 
• detect certain proteins, tbe presence of 
which has been found to correlate with a 
tumor or with a specific prenatal condition; 
• detect the presence of illicit drugs in a per- 
son’s blood, or monitor the blood or tissue 
level of a drug to ensure tbat the dosage 
achieves a therapeutic level without ex- 
ceeding the limits that could cause toxic ef- 
fects; and 
• identify microbial pathogens. 
The extent of the use of antibodies and the 
biochemical properties that they can identify is 
suggested by table 6. No one assay constitutes a 
major market, and short product lifetime has 
been characteristic of this business. 
Other applications of monoclonal antibodies 
include: 
• the improvement of the acceptance of kid- 
ney (and other organ) transplants by injec- 
tion of tbe recipient with antibodies against 
certain antigens; 
• passive immunization against an antigen in- 
volved in reproduction, as a reversible im- 
munological approach to contraception. 
• localizing tumors with tumor-specific anti- 
bodies (see Tecb. Note 13, p. 81); and 
• targeting cancer cells with antibodies tbat 
bave anticancer chemicals attached to 
them. 
Enzymes and other proteins 
ENZYMES 
Enzymes are involved in virtually every bio- 
logical process and are well-understood. Ne\'er- 
theless, despite tbeir potency, versatility, and 
diversity, they play a small role in the practice 
of medicine today. Therapeutic enzymes ac- 
counted for American sales of about $70 million 
(wholesale) in 1978, but one-balf of those sales 
involved the blood-plasma-derived coagulation 
factors used to treat hemophilia. Although the 
figure is difficult to estimate, the total numher 
of patients receiving any type of enzyme ther- 
apy in 1980 probably does not exceetl v50,000. 
Enzymes cannot be synthesized by con\en- 
tional chemistry. Almost all those present 1\' 
employed in medicine are extracted from 
human blood, urine, or organs, or are produced 
by micro-organisms. Already the possibility of 
using rDNA clones as the source of enzymes— 
primarily to reduce the cost of i)roduction— is 
being explored. 
However, problems associated with the use of 
nonhuman enzymes (such as immune and feb- 
rile responses) and the scarcity of human en- 
zymes, have hindered research, de\('lopment, 
and clinical exploitation of enzyiiuvs foi- thei’- 
apeutic purposes. Today, the ex|)(>rimental ge- 
netic technologies of rDNA and somatic ('('ll fu- 
sion and culture open the only ('oncei\ able 
routes to relatively inexpensi\(' [H'odiu'tion of 
compatible human enzynies. 
The genetic engineering of enzymes is |)roh- 
ably tbe best example of a dilemma that ham- 
pers the exploitation of rDNA: Without a clinical 
need large enough to justify the iincstmenl, 
there is no incenti\ e to produce a |)roduct: yet 
without adequate supplies, th(! th('rapeutic pos- 
sibilities cannot be in\ estigated, I he substances 
that break this cycle will probably he those that 
are already produced in (|uantity from tiatural 
tissue. 
The only enzymes administered today .ire 
given to hemophiliacs— and tlu'v ai-e .iclu.ill\ 
