38
Bioprocess Engineering
process that is carried out in discrete cycles
of ampliFcation, each cycle doubling the
amount of available DNA. Thus, minute
quantities of a rare target sequence can be
ampliFed to produce adequate quantities
with excellent faithfulness. PCR is used
to amplify DNA for protein products as
well as for detection of trace quantities of
contaminants. SpeciFc sequences of DNA
can also be chemically synthesized using
solid-phase procedures.
A
second
important
technology
is
the production of monoclonal antibod-
ies. Sensitized antibody-producing spleen
cells
are
hybridized
with
stable
can-
cer
cell
lines;
the
so-formed
hybrid
has the longevity of typical cancer cells
in
tissue
culture
and
the
speciFcity
of the original splenocyte. The repro-
ducible
character
of
the
monoclonal
antibodies has permitted the develop-
ment of new diagnostic procedures of
exquisite speciFcity, new protein sepa-
ration speciFcity, and new therapeutics
such as Herceptin, an antibody used
to block the overexpressed Her2 recep-
tor in breast cancer patients. While re-
combinant proteins can be expressed
in all types of host cells like bacteria
and yeast, the production of hybridoma
cells requires more stringent and far
more expensive mammalian tissue culture
procedures.
A third major branch of biotechnology
is the direct chemical synthesis of pep-
tides using the solid phase methodology
Frst developed by Bruce MerriFeld, a No-
bel laureate. The Frst amino acid of a
desired peptide sequence is coupled to
a latex particle, and subsequent amino
acids are coupled to it, step by step, in
highly automated instruments. The di-
rect synthesis yields an easier approach
for the synthesis of families of peptides
differing in only a single amino acid, a
point mutation. If the future holds more
personalized pharmaceuticals through the
Feld
of
pharmacogenomics
(study
of
polymorphisms in drug-metabolizing en-
zymes and the resulting differences in
drug effects), then the direct synthesis
method may be the production method
of choice.
A fourth major branch of biotechnol-
ogy is genomics. Now that the human
genome is sequenced, a huge amount of
controversy surrounds the use of the in-
formation. Genes for diseases are rapidly
being discovered, and medicines and ther-
apies are based on knowledge that is more
complete compared to the trial and error
methods of the past. The genome sequence
in combination with new techniques in
combinatorial chemistry, a greater under-
standing of receptors, and improved data
management tools using the fastest com-
puters is opening up an entirely new type
of bioprocessing industry. However, there
is a huge amount of resistance from a
variety of religious organizations fearing
the loss of human individuality, and many
other government agencies and individu-
als worldwide that are scared of transgenic
plants and animals after a couple of in-
cidents. Laws were passed or are under
consideration in many countries to limit
the use of genetics to protect human tissue
use and track genetically modiFed plants
from farm to consumer.
Detailed descriptions of all these and
other current processes are beyond the
scope of this brief review. Other ar-
ticles within this encyclopedia discuss
some in detail. Therefore, the key fea-
t
u
r
e
so
fo
n
l
yF
v
ea
s
p
e
c
t
so
fb
i
o
p
r
o
-
cessing are presented: enzyme engineer-
ing, whole-cell reactors, transgenic plants
and animals, transport and adhesion of
cells, and bioseparations or downstream
processing.
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