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OCR for page 42
..~:he first fruits..`
........
Technicians inspect the
control unit at the bottom of
a large-scale evaporator used
in the final steps of purifying
human insulin produced by
genetically engineered
bacteria.
~2
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............... ~,~,.,.,, :
4=ts
sms imnIar~ted
contributed handsomely to
human welfare in the few
short years since they
appeared.
· Insulin, needed by millions of diabet-
ics, has been produced commercially by
genetically engineered bacteria since 1982.
The product is identical to human insulin
and so does not cause the allergic reactions
sometimes produced by insulin derived from
animals. Nor is its supply subject to the ups
and downs of the livestock market.
· Human growth hormone (HGH),
needed for normal physical development,
has been available as a genetically engi-
neered product since 1985. Previously, many
of the more than 10,000 U.S. children low in
HGH could not get treatment with the
natural substance, which is extracted in tiny
amounts from the pituitary glands of
cadavers at autopsy. And in 1985, distribu-
lion of HGH from this source was stopped
after evidence suggested it might be contam-
inated with a virus causing a rare, fatal
disease. Today, however, there is plenty of
pure biosynthetic HGH.
· Tissue-plasrruinogen activator, or t-PA,
appeared as a genetically engineered product
E N G ~ N E E R ~ N G A N D T H E A D VA N C E M E ~
9~d
,.._,
Do
in late 1987. It quickly dissolves blood clots
that cause heart attack and prevents their
recurrence. It is already standard treatment
for heart attack victims at hundreds of U.S.
hospitals.
These and other genetically engineered
products now available are created through
the efforts of biologists and engineers. It is
biologists who "engineer" new organisms by
splicing a gene from one organism into
another. Traditional engineers provide an
indispensable bridge from biology lab to the
public. They design and build the mechani-
cal systems that allow the new organisms to
grow in large quantities and that process the
valuable substances the organisms produce.
In addition, they develop complex laboratory
instruments that simplify and speed the
work of genetic engineering.
A genetically engineered product begins
with biologists who find a gene that pro-
duces a valuable substance such as HGH.
Using enzymes that dissolve bonds to
neighboring genes, they cut the valuable
gene out of the DNA, the genetic material of
a cell. Then they insert this gene into another
organism such as the common bacterium
Escherichia cold that will multiply itself and
the foreign gene along with it.
! Once the genetically engineered "bug"
has been created, engineers design a system
in which its product can be produced and
processed in large quantities at a reasonable
cost. The production of human insulin, the
first commercial product of genetic engineer
ing, is a good example. It was developed in
the United States and appeared commercial
ly under the trade name Humulin, first in the
T O F ~ U M ~ N W E ~ FA ~ E
OCR for page 43
United Kingdom and later in the United
States.
The insulin molecule is composed of two
parts called A and B chains. The original
Humulin process used two versions of E. cold
t~ to produce the chains. One version contained
a gene producing A chains and the other
contained the B-chain gene. Each version
was grown, or fermented, in a large separate
tank. The chains they produced were
extracted from the bacteria and purified.
Afterward, A and B chains were combined in
a third vessel. The complete molecules were
then purified and crystallized into a usable
form of human insulin.
The Humulin process demanded special
engineering to handle the uncertainty
surrounding the first large-scale use of
genetically engineered microbes. Scientists in
the late 1970s did not know whether such
bugs might survive in nature and contami-
nate the environment. So the bacteria were
grown in closed stainless steel tanks with the
inflow of nutrients and oxygen carefully
! controlled by computer. Water vapor and
carbon dioxide that flowed out were decon-
taminated. A special double seal was
invented to prevent the escape of microbes
from around the shaft of the paddle-like
agitator that stirred the culture. And the
tanks were designed to function under
negative pressure the opposite of conven-
tional tanks to suck back any bacteria that
otherwise might escape. Engineers also
developed a new pasteurization system hot
enough to kill the bacteria as they were
withdrawn from the tanks, but cool enough
not to damage the A or B chains.
The big challenge In producing
Humulir~, however, was in scaling up
production from expensive 10-liter batches in
the laboratory to less expensive batches of
40,000 liters ire the factory. The scaleup was
particularly difficult because these bacteria
store the A or B chains within themselves,
unlike microbes that produce antibiotics and
secrete them. Engineers devised a way to
extract the chains by pressurizing the cells ire
a tank and then shooting them out into
no~.~al atmosphere, where the pressure
change caused the cells to explode like
balloons and release their contents. The
G E N E T ~ C ~ ~ LY E N G ~ N E E R E D P R O D ~ C T S ~
1
l
Ill
A spiraling chain of DNA,
the genetic blueprint of life,
shimmers in this computer-
generated molecular model.
Certain DNA segments malce
up the genes that produce
insulin, human growth
hormones and other important
so stances.
43
OCR for page 44
chains were separated from cell debris in
several steps ending with high-performance
liquid chromatography. This laboratory
technique is perfo~`ed by pouring a mixture
through a pencil-sized column of material
that sifts out certain molecules. But for large-
scale Humulin production, columns 10 feet
tall and 12 to 16 inches in diameter had to be
designed. Today, Humulin is produced by a
The first insulin produced by
bacteria implanted with
human insulin genes was
processed into crystals. The
insulin must be separated
from the bacteria and
purified in relatively large
quantities in order to be I
useful to many diabetics.
~11__
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_ . ,~
· , ....' A.` .':'.- _:..:.:.:.-''
i.
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fir
Potentially useful genes are
often identified by analyzing
the proteins they produce. A
protein sequencer is used to
determine the order of amino
acids making up ~ chainlike
protein molecule, thereby
uncovering the identity of the
gene that made it.
44
,>..~.~
. ~
similar, but more efficient process involving a
new type of genetically engineered bacteria
and only one fermentation tank.
Traditional engineers are not directly
involved in some other aspects of genetic
engineering, such as the genetic alteration of
plants and animals or the potential treatment
of humans with genetic disorders. They are,
however, becoming more involved with
processing the products that are produced by
genetically altered plants and microorgan-
isms. Biologists are modifying organisms to
produce everything from pha~raceuticals to
food processing agents to specialty chemi-
cals. In fact, the greatest use of genetic
engineering in the future may be in the
I production of products that are now created
by chemical processes, which often involve
high temperatures and pressures as well as
toxic by-products. Biological synthesis, on
the other hand, usually takes place at room
temperature under normal pressure and
produces biodegradable waste.
In the meantime, people have already
begun to investigate the use of genetically
altered microbes to clean up toxic waste,
degrade pesticides, or to turn organic waste t
material into useful products. They may one
day use genetically altered bacteria to loosen
underground oil so it can be pumped to the
surface or to leach precious minerals from
ore.
Perhaps the biggest contribution of
traditional engineering to this field has been
the development of instruments that speed
the process of genetic engineering and
expand its possibilities. Two devices the
protein sequencer and the DNA synthesizer-
have already had tremendous impact on the
detective work of genetic engineering. For
instance, one biologist working with a DNA
synthesizer can do the amount of work in
one afternoon that would have taken 25
biologists five years to complete in the early
1970s.
The discovery of a valuable gene often
begins with identifying the sequence of
amino acids in the protein it produces. There
are only 20 different amino acids. But the
chainlike protein molecules have hundreds
of amino acids linked in specific order. An
instrument that can decipher this sequence
appeared on the market in 1969. It is essen-
tially a computer-controlled plumbing device
that uses solvents to cut one amino acid at a
time from the end of a protein molecule.
Knowing the amino acid order, biologists can
identify the gene that made the protein.
Another device, which entered the
market in 1982, can actually build small
genes or gene fragments out of DNA the
genetic material found in cells. A DNA
synthesizer hooks together subunits, called
bases, in the proper order for a particular
gene or gene fragment. These synthetic genes
and fragments can then be used for several
purposes, including genetic engineering. For
example, the genes that produce Humulin
are really synthetic genes created by a DNA
synthesizer.
The dream machine of genetic engineer-
ing, though, is a device that can rapidly
sequence DNA, much as proteins are
sequenced. Human DNA contains more than
3 billion bases, and today's DNA sequencers
can analyze only about 9,000 bases per day.
The challenge for today's engineers is to
develop in the next four or five years
machines that are at least 10 times faster than
present sequencers.
The amount of genetic information
already being generated by DNA sequencers
is overwhelming. To check a new sequence
against the massive, growing data bank of
E N G I N E E R I N G Ji N D T H E A D VA N C E M E N T O F H U M A N W E L FA R E
OCR for page 45
known sequences will require faster comput-
er systems. One under development uses a
series of 500 or more microprocessors that
can each be programmed to recognize one of
the four types of DNA base. Essentially, the
series is programmed to reflect the order of
bases in the new DNA sequence. As known
sequences from the data bank flow past the
series, each microprocessor "lights up" when
its particular base passes by. When all light
up together, they signal the location of an
identical sequence in the data stream. Using
I this recognition system, the computer can
search the DNA data bank for similar
patterns thousands of times faster than
existing computers.
Work is under way to determine the
entire sequence of human DNA, called the
genome, and map the location of all 100,000
or so genes. This data would reveal more
about human biology and disease than has
been learned in the past 200 years. Scientists
and engineers would dearly love to map the
entire human genome. With the right tools,
they may soon do it. Completing the project
would be, some believe, the biological
equivalent of putting a man or woman on
the moon.
G E N E T I C a L LY E N G ~ N E E R E ~ P R O D U C ~ S
For nine years, a deficiency in
human growth hormone tHGH,
stunted the growth of this
California girl. But in her
tenth year, injections of HGH
produced by genetically
altered bacteria stimulated
a 5-inch burst of growth,
catching her nearly up to the
normal height of a girl her
age.
45
Representative terms from entire chapter:
genetic engineering
