Diagnostic Applications of biotechnology


(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


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-


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


This article discusses the latest advances in diagnostics

and looks at where applications of biotechnology are headed.



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


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

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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.



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.

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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.


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.


MONOCLONAL ANTIBODIES. As discussed earlier,

monoclonal antibodies are highly specific. They are cloned,

or duplicated, from a single white blood cell that produces

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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


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.



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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.


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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


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.

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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


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







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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.




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.

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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.