mirror of
https://github.com/opsxcq/mirror-textfiles.com.git
synced 2025-08-31 04:00:09 +02:00
595 lines
27 KiB
Plaintext
595 lines
27 KiB
Plaintext
|
|
|
|
|
|
|
|
(word processor parameters LM=8, RM=78, TM=2, BM=2)
|
|
Taken from KeelyNet BBS (214) 324-3501
|
|
Sponsored by Vangard Sciences
|
|
PO BOX 1031
|
|
Mesquite, TX 75150
|
|
|
|
August 25, 1990
|
|
courtesy of Double Helix at 212 865-7043
|
|
|
|
|
|
DIAGNOSTICS
|
|
|
|
(From "Biotechnology at Work" by Industrial Biotechnology
|
|
Association, Washington, DC 20006, Tel. 202/857-0244)
|
|
|
|
After five days of suffering a miserable sore throat, you
|
|
find yourself in your doctor's office. Your doctor thinks
|
|
you may have strep throat, a serious bacterial infection
|
|
that, if left untreated. can lead to kidney and heart
|
|
disease.
|
|
|
|
The doctor swabs your throat, sends the specimen to a labo-
|
|
ratory for analysis, and three days later you know if you
|
|
have strep throat. Meanwhile, the doctor is unsure whether
|
|
or not to prescribe an antibiotic to fight the infection.
|
|
But if the doctor could detect strep throat while you are
|
|
still in the office, appropriate treatment could begin imme-
|
|
diately.
|
|
|
|
Now, because of the diagnostic applications of biotechnolo-
|
|
gy, doctors can identify strep throat, right in their of-
|
|
fices, in a matter of minutes.
|
|
|
|
The first step in treating or curing any disease or infec-
|
|
tion is diagnosis, and the diagnostic applications of
|
|
biotechnology extend far beyond strep throat. Heart
|
|
disease, cancer, AIDS, cystic fibrosis, kidney disease and
|
|
sickle-cell anemia are just some of the areas for which the
|
|
biotechnology industry has been developing new diagnostic
|
|
tools.
|
|
|
|
This article discusses the latest advances in diagnostics
|
|
and looks at where applications of biotechnology are headed.
|
|
|
|
|
|
DISCOVERY OF DNA AND CELL FUSION TECHNOLOGIES
|
|
|
|
The origin of DNA technology can be traced to the mid-1800s
|
|
and the work of Gregor Mendel, an Austrian monk and
|
|
botanist. His work with pea plants uncovered the first
|
|
evidence that genetic traits were passed from generation to
|
|
generation.
|
|
|
|
In the early 1900s, biologists discovered that humans obeyed
|
|
the same basic laws of heredity expressed in Mendel's work.
|
|
THey found that conditions such as hemophilia, color
|
|
blindness and baldness were passed from parent to child
|
|
through chromosomes, the components of every living cell
|
|
|
|
Page 1
|
|
|
|
|
|
|
|
|
|
|
|
that contain genetic information.
|
|
|
|
By the early 1950s, scientists developed an understanding of
|
|
the workings of DNA, or deoxyribonucleic acid, the molecule
|
|
that carries the genetic information for all living systems.
|
|
|
|
In the early 1970s, genetic engineering entered a new
|
|
frontier. Scientists created new genetic instructions by
|
|
combining segments of DNA from different organisms. This
|
|
process is called gene splicing, or recombinant DNA.
|
|
|
|
At the same time, other scientists focused their attention
|
|
on monoclonal antibodies. Antibodies are produced in the
|
|
body by white blood cells. They locate (and assist the body
|
|
in attacking) bacteria, viruses, cancer cells and other
|
|
foreign substances. Monoclonals are highly specific
|
|
versions of the antibodies.
|
|
|
|
But it wasn't until the mid-1970s, when two scientists
|
|
discovered how to mass produce monoclonals, that their use
|
|
as diagnostic (and also therapeutic) tools began to take
|
|
shape. By fusing, in a laboratory petri dish, an antibody-
|
|
producing white blood cell with a cancer cell that produces
|
|
unlimited generations of cells, the scientists developed a
|
|
method to produce increased and consistent quantities of a
|
|
particular monoclonal antibody. This manipulation is called
|
|
hybridoma technology.
|
|
|
|
Using monoclonals in diagnostic tests requires scientists to
|
|
produce the purest quality of these specific antibodies
|
|
possible. At the same time, scientists also need mass
|
|
quantities of the monoclonals. Hybridoma technology meets
|
|
both of these needs.
|
|
|
|
The 1970s gave us yet another major contribution from the
|
|
scientific world: DNA probes. Scientists developed the
|
|
ability to extract single, small strands of DNA that could
|
|
be used to seek their complementary matching strand.
|
|
|
|
These DNA probes can locate specific genetic material,
|
|
information that is useful for both the detection and the
|
|
treatment of various diseases.
|
|
|
|
|
|
IMPACT OF ADVANCES IN DIAGNOSTICS
|
|
|
|
The primary targets of research in the diagnostics field
|
|
have been genetic and infectious diseases. Genetic diseases
|
|
are those in which heredity plays either an exclusive or
|
|
significant role. Infectious diseases are spread from
|
|
person to person through exposure to a virus or bacterium.
|
|
|
|
Many Americans suffer from these conditions: Adult
|
|
polycystic kidney disease - 300,000 to 400,000; Sickle-cell
|
|
anemia - 50,000; Cystic fibrosis - 30,000; Huntington's
|
|
disease - 25,000; Duchenne muscular dystrophy - 20,000 to
|
|
30,000; Hemophilia - 20,000; Alzheimer's disease - 2 to 4
|
|
million; and Manic depression 1 to 2 million. These data
|
|
are reflective of the number of lives that are touched by
|
|
inherited diseases.
|
|
Page 2
|
|
|
|
|
|
|
|
|
|
|
|
To a large extent, the discovery of the genetic basis for
|
|
these diseases has occurred in the last decade. Currently,
|
|
there are more than 3,000 known genetic diseases. The
|
|
development of biotechnology-based diagnostics will allow
|
|
physicians to identify many of these illnesses more
|
|
accurately and quickly.
|
|
|
|
Meanwhile, infectious diseases are among the most prevalent
|
|
and dangerous threats to the health of the American public.
|
|
Federal officials estimate that more than 1.5 million people
|
|
have already been exposed to human immunodeficiency virus
|
|
(HIV), which can lead to the acquired immune deficiency
|
|
syndrome (AIDS). AIDS had already claimed the lives of more
|
|
than 30,000 Americans by early 1988.
|
|
|
|
Other infectious diseases do not share the headlines with
|
|
AIDS, but their dangers persist. For example, hepatitis B
|
|
is diagnosed in 300,000 patients every year. Influenza
|
|
causes up to 50,000 death per year.
|
|
|
|
Advances in biotechnology-based diagnostics will afford
|
|
improved and earlier detection of infectious and genetic
|
|
diseases. Currently, some diseases are extraordinarily
|
|
difficult to diagnose properly. What will these new
|
|
advances mean for the patient? Early diagnosis of diseases
|
|
can have a significant impact in three areas:
|
|
|
|
HIGHER SURVIVAL RATE. Breast cancer is one of the
|
|
leading causes of death in women, and most Americans are
|
|
aware of the value of monthly breast self-examinations.
|
|
Finding a lump in a breast before it spreads to other parts
|
|
of the body can save a woman's life. The theory is the same
|
|
for biotechnology-based diagnostics. In fact, some of these
|
|
diagnostics will be able to identify illnesses (cancer,
|
|
alcoholism and others) before the appearance of any
|
|
symptoms. Although early detection is not a guarantee of
|
|
survival against all diseases, many patients will live
|
|
longer if appropriate therapy begins as soon as possible.
|
|
|
|
IMPROVED QUALITY OF LIFE FOR THE PATIENT. By
|
|
identifying a disease at its earliest stages, doctors can
|
|
often prescribe treatments with the fewest side effects.
|
|
For heart disease, it may mean a change in diet and
|
|
increased exercise instead of surgery. For cancer, early
|
|
diagnosis may mean surgical alternatives to chemotherapy are
|
|
more feasible.
|
|
|
|
REDUCED HEALTH CARE COSTS. Again, by diagnosing a
|
|
disease at its earliest stages, patients can often avoid
|
|
surgery and hospitalization by undergoing less expensive
|
|
treatments. Not only does this benefit the patient
|
|
afflicted with the disease, but it can have an impact on
|
|
health care and insurance costs throughout society.
|
|
|
|
APPLICATIONS OF BIOTECHNOLOGY-BASED DIAGNOSTICS
|
|
|
|
MONOCLONAL ANTIBODIES. As discussed earlier,
|
|
monoclonal antibodies are highly specific. They are cloned,
|
|
or duplicated, from a single white blood cell that produces
|
|
|
|
Page 3
|
|
|
|
|
|
|
|
|
|
|
|
a specific type of antibody. Because of their specificity,
|
|
monoclonals can be used to diagnose infectious diseases and
|
|
other conditions.
|
|
|
|
In order for a monoclonal antibody to be used in health care
|
|
application, it must be linked to some sort of substance,
|
|
such as a drug or an imaging agent. The monoclonal acts as
|
|
a guided missile programmed to reach an exact location. When
|
|
it hits its target, an imaging agent, such as a tiny
|
|
radioactive particle, transmits information back to the
|
|
doctor.
|
|
|
|
Many people are already using monoclonal technology in their
|
|
homes to detect blood in the stool (an early warning sign of
|
|
rectal cancer and other illnesses), to identify the time of
|
|
ovulation, or to test for pregnancy. Diagnostic uses of
|
|
monoclonal antibodies in laboratories include testing for
|
|
sexually transmitted diseases (syphilis, gonorrhea,
|
|
chlamydia), hepatitis B and cystic fibrosis.
|
|
|
|
Monoclonals are also used in the battle against AIDS.
|
|
Current technology allows doctors to identify the existence
|
|
of antibodies produced by the body when it is exposed to
|
|
HIV. But scientists are trying to develop a monoclonal
|
|
antibody-based diagnostic that will confirm when a patient
|
|
has actually been infected with AIDS. They are also trying
|
|
to find a way to treat AIDS using monoclonal antibodies.
|
|
|
|
Although not yet available for widespread use, clinical
|
|
testing of monoclonal antibody-based technology for heart
|
|
disease is underway. It is hoped these tests will locate
|
|
dangerous blood clots, determine the severity of
|
|
atherosclerosis (the hardening or narrowing of arteries,
|
|
which is the underlying cause of most deaths from
|
|
cardiovascular disease), and the extent of damage to a
|
|
patient's heart following a heart attack.
|
|
|
|
Other diagnostic applications of monoclonal antibodies focus
|
|
on cancer. One currently available diagnostic test
|
|
identifies the continued presence of ovarian cancer in women
|
|
who have already undergone initial treatment. This test
|
|
helps doctors determine the necessity of follow-up
|
|
exploratory surgery, and assists them in deciding to alter
|
|
or discontinue therapy following this second look. Some
|
|
12,000 women die from ovarian cancer each year.
|
|
|
|
Clinical trials are underway for another monoclonal-based
|
|
diagnostic, designed to help diagnose six cancer types
|
|
(lung, colorectal, breast, pancreatic, stomach and ovarian).
|
|
Together these cancers account for over 60 percent of the
|
|
annual cancer deaths in the United States.
|
|
|
|
In this procedure, a radioactive substance is linked to a
|
|
monoclonal antibody that can identify the presence of any
|
|
one of these six types of cancer. The monoclonal transports
|
|
the radioisotope to tumor sites, making their location
|
|
visible through the use of an X-ray machine.
|
|
|
|
|
|
|
|
Page 4
|
|
|
|
|
|
|
|
|
|
|
|
The test also confirms the malignancy of the tumors, and
|
|
helps physicians determine which tumors can be successfully
|
|
removed before surgery ever takes place. These distinctions
|
|
were not possible with previous diagnostic methods.
|
|
|
|
DNA PROBES. In the 1970s, scientists found ways to cut
|
|
DNA into fragments at predictable points, using a kind of
|
|
chemical scissors called restriction enzymes. After
|
|
studying large groups of family members and their genetic
|
|
makeup, they identified variations in the size of the DNA
|
|
segments, called polymorphisms, that appeared along with
|
|
certain diseases.
|
|
|
|
Using this knowledge, scientists devised DNA probes, short
|
|
portions of DNA that are able to attach themselves to the
|
|
polymorphism associated with a specific disease. The probes
|
|
are labeled with a radioactive substance. They can be
|
|
easily visualized by exposure on film.
|
|
|
|
DNA probes are used to diagnose a variety of genetic
|
|
diseases, including Huntington's disease, Duchenne muscular
|
|
dystrophy, and cystic fibrosis. Because they can often
|
|
detect and identify diseases and infections in a matter of
|
|
hours, DNA probe-based tests could replace current tests
|
|
that take days to complete.
|
|
|
|
Dentists are also using DNA probes to diagnose periodontal
|
|
(gum) disease, perhaps the most prevalent of all infectious
|
|
diseases other than the common cold. According to the
|
|
National Institute of Dental Research, more than 90 million
|
|
Americans have periodontal disease. At least 23 million of
|
|
them have severe cases. Gum disease accounts for 70 percent
|
|
of all adult tooth loss.
|
|
|
|
Although this infection can be extremely painful, it often
|
|
begins and progresses unnoticed. A test using DNA probe
|
|
technology can now detect the various bacteria that cause
|
|
the disease. This test establishes progression of the
|
|
condition, helps dentists select appropriate therapy, and
|
|
monitors treatment results.
|
|
|
|
Another important application of DNA probes is found in the
|
|
food industry. DNA probe-based diagnostic tests can rapidly
|
|
detect disease-causing microorganisms such as Salmonella, a
|
|
bacterium that is a common cause of food poisoning.
|
|
|
|
The standard culture method for the detection of Salmonella
|
|
in food requires a minimum of four days to identify negative
|
|
samples. If the culture is positive, indicating the
|
|
presence of the bacteria, an additional two to three days
|
|
are required for confirmation,
|
|
|
|
This slow process causes a considerable expense to food
|
|
processors, whose food must remain in quarantine during
|
|
these diagnostic tests. Rapid detection of Salmonella in
|
|
food products benefits the food industry by reducing
|
|
inventory costs and response time in the event of a
|
|
contamination problem.
|
|
|
|
|
|
Page 5
|
|
|
|
|
|
|
|
|
|
|
|
A new DNA probe-based assay provides much quicker diagnosis
|
|
of Salmonella contamination. When the probe is labeled with
|
|
an identifiable "tag," it can determine the presence or
|
|
absence of the bacteria. Nearly 100 samples can be analyzed
|
|
in four to five hours following the growth of a culture in
|
|
the laboratory. The test also provides confirmation of
|
|
positive samples.
|
|
|
|
GENE MAPPING. Human genetics is in the midst of a
|
|
revolution. In the mid-1970s, about all that could be done
|
|
was study inherited diseases and track their frequency. Not
|
|
it is possible to locate and identify those genes that cause
|
|
hereditary diseases. As scientists learn more about
|
|
defective genes, the role they play in disease, and their
|
|
locations relative to each other, they are able to create a
|
|
type of map. This process is called gene mapping.
|
|
|
|
Just as the explorers Lewis and Clark pieced together
|
|
information into maps that guided settlers of the new
|
|
American frontier, scientists are creating maps that will
|
|
help lead medical researchers into the 21st century, and
|
|
beyond.
|
|
|
|
Genetic mapping allows for the development of tests to
|
|
diagnose diseases. Further study of the gene may provide
|
|
new directions for treatment.
|
|
|
|
The complete genetic code of a human being is contained in
|
|
50,000 to 100,000 genes comprised of DNA. As discussed
|
|
earlier, these genes are located in the 23 pairs of
|
|
chromosomes that each of us possess.
|
|
|
|
Scientists are able to break the chromosomes into pieces
|
|
called RFLPs, or restriction fragment length polymorphisms.
|
|
RFLPs are also called genetic markers because they mark the
|
|
location of a defective gene. Imagine you are looking for
|
|
the public library, and someone tells you that it is next to
|
|
a certain landmark, such as city hall. Now every time you
|
|
try to find the library, you may look for the landmark and
|
|
know that you will find it.
|
|
|
|
An RFLP is like city hall, a marker that helps scientists
|
|
find the approximate location of a defective gene.
|
|
Currently, genetic markers are useful for diagnosis in
|
|
families in which specific inherited diseases are prevalent,
|
|
such as cystic fibrosis.
|
|
|
|
Scientists have pinpointed the gene that causes cystic
|
|
fibrosis, a disease that affects the digestive and
|
|
respiratory systems so severely that, if not diagnosed
|
|
early, premature death is often the result. With the
|
|
discovery of the defective gene, the fetus of a woman who
|
|
already has one child afflicted with cystic fibrosis can now
|
|
be screened and diagnosed early in her pregnancy with 99
|
|
percent accuracy.
|
|
|
|
While there is no known cure for cystic fibrosis, early
|
|
diagnosis can lead to therapy that can improve both the
|
|
quality of life and the life expectancy of the patient.
|
|
|
|
Page 6
|
|
|
|
|
|
|
|
|
|
|
|
Defective genes have been linked to other diseases as well,
|
|
including Duchenne muscular dystrophy, adult polycystic
|
|
kidney disease, a familial form Alzheimer's disease, a
|
|
familial form of colon cancer, and a form of manic
|
|
depression found among the Pennsylvania Amish.
|
|
|
|
USES IN AGRICULTURE. Have you ever noticed a house
|
|
plant that has sagging leaves? Or maybe they have turned
|
|
yellow, or have fallen off their stems. When it comes to
|
|
their health, plants are a little like people. Infectious
|
|
diseases can make them sick. The same is true with farm
|
|
animals. That's why biotechnology-based diagnostics will
|
|
play an important role in agriculture.
|
|
|
|
Some of the most promising aspects of new diagnostics are
|
|
their potential to reduce the use of certain chemicals, and
|
|
to better target the application of some necessary chemicals
|
|
in the fields. By quickly identifying a crop disease, a
|
|
farmer can use a more specific type of herbicide or
|
|
fungicide in a smaller dose. This can help a farmer
|
|
increase the yield and reduce the cost of raising crops. To
|
|
the consumer, it might mean lower food prices. It can also
|
|
mean a cleaner environment, including fewer chemicals in
|
|
groundwater.
|
|
|
|
Diagnostics for conditions that cause rotting in stored
|
|
vegetables can also prevent tremendous losses, as can tests
|
|
for diseases common among expensive fruit trees.
|
|
|
|
Monoclonal antibody-based diagnostics can identify fungal
|
|
diseases affecting many plants. An example of a test
|
|
already in use involves turf grass. It is being marketed to
|
|
golf courses and will soon be available to home gardeners.
|
|
|
|
The turf grass diagnostic kit detects three highly
|
|
destructive fungal diseases (pythium blight, dollar spot and
|
|
brown patch) before visible symptoms appear. As with early
|
|
diagnosis of diseases in humans, early identification of
|
|
turf grass problems means appropriate treatment can begin at
|
|
a time when it can be the most beneficial.
|
|
|
|
The disease can be diagnosed by using a dipstick. A plastic
|
|
stick is coated with the diagnostic material. The stick is
|
|
dipped into the soil, and if a disease is present, the tip
|
|
of the dipstick is turns purple. The severity of the
|
|
disease is determined by the depth of the color.
|
|
|
|
Monoclonals will also provide quick and definitive diagnoses
|
|
of animal diseases. Now, when an animal gets sick, the
|
|
farmer or veterinarian often can only treat the symptoms.
|
|
But many diseases can produce similar symptoms, so without a
|
|
quick and accurate diagnosis, the farm animal -- or the
|
|
domestic companion animal -- may not receive proper
|
|
treatment.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page 7
|
|
|
|
|
|
|
|
|
|
|
|
ETHICAL CONSIDERATIONS
|
|
|
|
As the advances in diagnostics expand our knowledge of the
|
|
human genetic code, society must ensure that this
|
|
information is used properly. The biotechnology industry
|
|
must be careful to protect the rights and safety of people;
|
|
it does not take this responsibility lightly. This is one
|
|
of the roles of government regulation, and various federal
|
|
agencies are working with the scientific community to ensure
|
|
that our health and the environment are protected.
|
|
|
|
While biotechnology-based diagnostics may confirm the
|
|
presence of some diseases for which there are no life saving
|
|
treatments at this time, the ability to use the tests to
|
|
study these diseases enables scientists to develop new
|
|
approaches for prevention and cure.
|
|
|
|
|
|
|
|
THE FUTURE OF DIAGNOSTICS
|
|
|
|
Have you ever wondered why some people smoke two packs of
|
|
cigarettes a day and live to be 90 years old, while others
|
|
develop lung cancer at the age of 45? Or why an apparently
|
|
healthy person dies of a heart attack at 40, while someone
|
|
who is overweight and has bad eating habits seems to be
|
|
immune to heart disease?
|
|
|
|
The answer may lie in their genes. It appears some people
|
|
are more likely than others to develop high blood pressure,
|
|
heart disease, cancer, diabetes, arthritis, alcoholism and
|
|
other conditions. These people are said to have a genetic
|
|
predisposition to certain diseases.
|
|
|
|
Scientists hope that gene mapping will lead us into a new
|
|
era of diagnostics. Much of the scientific community is
|
|
concentrating its efforts on mapping the genome, the entire
|
|
genetic material of humans. The project, which is being
|
|
worked on by government and private scientists, is expected
|
|
to take years to complete. It will probably cost hundreds
|
|
of millions of dollars to pay for this research.
|
|
|
|
Through the mapping of defective genes and their markers,
|
|
many diseases could be diagnosed just a few weeks after
|
|
conception. In some instances, gene mapping may lead to
|
|
effective treatments where currently there is no cure.
|
|
|
|
In late 1987, several judges around the country allowed the
|
|
results of biotechnology-based tests to be used as evidence
|
|
in criminal cases. A Florida court convicted a man of rape
|
|
and assault on the basis of a DNA test.
|
|
|
|
Some scientists and law enforcement officials believe that
|
|
DNA probes and monoclonal antibody-based tests will be used
|
|
more extensively in the future. The tests, which can
|
|
analyze blood and other body fluids, may provide more
|
|
accurate identification of both suspects and victims. As
|
|
the use of these tests becomes more widespread, prosecutors
|
|
and defense attorneys may turn to biotechnology to support
|
|
their cases.
|
|
Page 8
|
|
|
|
|
|
|
|
|
|
|
|
Biotechnology-based diagnostics that have been approved by
|
|
federal regulatory agencies involve in vitro (in the
|
|
laboratory) techniques. But researchers are developing
|
|
diagnostics that are used in vivo, or in the body. In vivo
|
|
diagnostics will allow doctors to "see" diseases as they
|
|
appear within our bodies. This will provide doctors with
|
|
greater insight into diseases that have confounded us for
|
|
centuries, leading to improved treatment for all of us.
|
|
|
|
But the most promising potential result of advances in
|
|
diagnostics goes beyond merely treating the diseases that
|
|
affect our lives. The understanding that biotechnology-
|
|
based diagnostics will provide may help scientists find the
|
|
true causes of these diseases and provide them with the
|
|
information necessary to prevent and cure them.
|
|
|
|
--------------------------------------------------------------------
|
|
|
|
If you have comments or other information relating to such topics as
|
|
this paper covers, please upload to KeelyNet or send to the Vangard
|
|
Sciences address as listed on the first page. Thank you for your
|
|
consideration, interest and support.
|
|
|
|
Jerry W. Decker.........Ron Barker...........Chuck Henderson
|
|
Vangard Sciences/KeelyNet
|
|
--------------------------------------------------------------------
|
|
If we can be of service, you may contact
|
|
Jerry at (214) 324-8741 or Ron at (214) 484-3189
|
|
--------------------------------------------------------------------
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page 9
|
|
|
|
|