Biotechnology and Health

The science of genetics is revolutionizing the way that doctors treat diseases. Although
many older treatment methods are still more effective, a large number of hereditary
diseases have now been identified and can be treated because of genetic studies.
Some treatments involve a specific diet. For example, phenylketonuria (PKU) is
a hereditary disease that causes a buildup of the amino acid phenylalanine in the
body. If PKU is not treated, phenylalanine accumulates and can damage the brain
tissue. This results in developmental defects, intellectual disabilities, and seizures.
Fortunately, PKU is easily diagnosed in a newborn baby, using a blood sample
obtained by pricking the babys heel (Figure 1). Children with PKU are kept on a
strictly controlled diet during childhood and adolescence. Although adults have
lesser symptoms of PKU, they still remain on a diet low in phenylalanine. Another
disease, familial hypercholesterolemia, is linked to high levels of bad, low-density
lipoprotein (LDL) cholesterol and early heart disease. It is controlled by dietary
modifications and the administration of a class of drugs called statins. WEB LINK
Some inherited diseases are treated by directly providing the proteins that are missing
due to defective genes. Clotting proteins are injected to treat hemophilia, and digestive
enzymes are taken orally to treat digestive disorders and cystic fibrosis (CF). CF results
in the accumulation of thick mucus in the lungs, digestive tract, and pancreatic ducts.
The mucus prevents pancreatic enzymes from reaching the intestines. Pancreatic enzyme
replacement can be administrated to aid with digestion and the absorption of food.
Surgical solutions to hereditary disorders might include repairing a defective organ
or replacing it with a transplant. For example, Alpha-1 antitrypsin deficiency (AATD)
can cause liver deficiency. It is the most common reason for liver transplants in children.
New gene therapies offer many innovative ways to address genetic diseases.
Rather than allowing a disease to affect the body and then trying to fix the symptoms, gene therapy gets to the source of the diseasethe mutated DNA sequence
itselfby replacing, removing, or altering the defective gene before the symptoms
are expressed.

8.4

Figure 1 All newborn babies in Canada

are tested for PKU.

gene therapy the insertion, removal, or

replacement of genes (to correct defective
genes) within an organisms cells to treat
a disease

Gene Therapy: Correcting Genetic Disorders

Gene therapy began with experiments using mice. In 1982, Richard Palmiter of the
University of Washington, Ralph Brinster of the University of Pennsylvania, and their
colleagues injected a growth hormone gene from rats into fertilized mouse eggs and
then implanted the eggs into a surrogate mother (Figure 2, next page). The mother
gave birth to normal-sized mouse pups, but some grew faster than normal, to about
twice the size of their littermates. These giant mice attracted extensive media attention from around the world.
Palmiter and Brinster next attempted to cure a genetic growth hormone deficiency
by gene therapy. They introduced a normal copy of the growth hormone gene into
fertilized eggs taken from mutant dwarf mice and then implanted the eggs into surrogate mothers. The transgenic mouse pups grew to slightly larger than normal,
demonstrating that the genetic defect in these mice had been corrected.
This type of experiment, in which a gene is introduced into the germ-line
cells (sperm cells or eggs) of an animal to correct a genetic disorder, is called
germ-line gene therapy. The changes made by germ-line gene therapy may be passed
on to future generations. For ethical reasons, germ-line gene therapy is not permitted with humans. Instead, humans are treated with somatic gene therapy, in which
genes are introduced into somatic cells (any body cells but germ cells). Any modifications and effects of somatic gene therapy will be restricted to the individual and
will not be inherited by offspring.
The first successful use of somatic gene therapy with a human subject was carried
out in the 1990s by W. French Anderson and his colleagues at the National Institutes

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germ-line gene therapy a process in

which germ cells (sperm cells or eggs) are
modified by integrating functional genes
into their genomes
somatic gene therapy a process in
which therapeutic genes are transferred
into somatic cells to treat a genetic
disease

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transgene
germ-line cells derived
from mouse embryo

cell with
transgene

1 Introduce the desired gene into

germ-line cells from an embryo
by injection or electroporation.

pure population of
transgenic cells

2 Clone the cell that has the incorporated transgene to produce

a pure culture of transgenic cells.

mice have transgenic cells in

body regions including germ line
4 Implant embryos into
surrogate mothers.

5 Allow embryos to grow

to maturity and be born.

3 Inject transgenic cells into

early-stage embryos (called
a blastocyst).

genetically engineered
offspringall cells transgenic
6 Interbreed the progeny mice.

Figure 2 The introduction of genes into mouse embryos using embryonic germ-line cells

of Health (NIH) in Bethesda, Maryland. The subject was a young girl with a genetic
disorder called adenosine deaminase deficiency (ADA). Without the adenosine
deaminase enzyme, white blood cells cannot mature. As a result, the bodys immune
response is so poor that most children with ADA die of infections before reaching
puberty. The researchers successfully introduced a functional ADA gene into mature
white blood cells that had been isolated from the girl. These cells were then reintroduced into the girl, and expression of the ADA gene provided a temporary cure for
her ADA deficiency. The cure was not permanent because mature white blood cells,
produced by the differentiation of stem cells in the bone marrow, are non-dividing
cells with a finite lifetime. Therefore, the somatic gene therapy procedure has to be
repeated every few months. The subject in this example still receives periodic gene
therapy to maintain the necessary levels of the ADA enzyme in her blood. In addition, she receives direct doses of the normal enzyme. CAREER LINK
Successful somatic gene therapy has also been achieved for sickle-cell disease. In
December 1998, the bone marrow cells (the source of blood cells) of a 13-year-old
boy were replaced with stem cells from the umbilical cord of an unrelated infant. The
hope was that the stem cells would produce healthy bone marrow cells. The procedure worked, and the patient was declared cured of the disease.
Despite enormous efforts, human somatic gene therapy has not been the panacea
that people expected. Relatively little progress has been made since the first gene
therapy clinical trial for ADA deficiency, described above. In fact, there have been
major setbacks. In 1999, for example, a teenage patient in a somatic gene therapy trial
died as a result of a severe immune response to the viral vector being used to introduce a normal gene to correct his genetic deficiency. Furthermore, some children
in gene therapy trials that use retrovirus vectors to introduce genes into blood stem
cells have developed a leukemia-like condition. Thus, somatic gene therapy is not yet
an effective treatment for most human genetic diseases. It has occasionally been successful, however, for correcting models of human genetic disorders in experimental
mammals. Although no commercial human gene therapy product has been approved
for use, research and clinical trials continue as scientists try to combat genetic diseases. Some diseases, such as muscular dystrophy and cystic fibrosis, are debilitating;
others may cause intelligence deficiencies, such as learning disorders; but a few, such
as diabetes, are treatable.
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Genetic Screening
Some genetic mutations are known to be associated with specific genetic disorders.
Genetic screening uses biochemical and molecular tests to detect these mutations. In
some cases, early genetic screening means that treatment or therapy can be started
before the disease fully takes hold in the body. For example, Huntingtons chorea is a
neurodegenerative disorder that usually does not affect people until after they have
had children. People who know that this disease exists in their family can choose to
have a genetic screening test to help them decide if they want to have children of their
own or if they want to adopt instead. However, since Huntingtons chorea is such a
severe disease, knowing that you have it could be emotionally damaging. Do you
really want to know, or do you not? Should you know?
Doctors may recommend that some pregnant women, especially older ones, whose
risk of mutations in the germ cell DNA is higher, have amniocentesis. Amniocentesis
is a prenatal test that detects whether a baby carries chromosomal abnormalities such
as trisomy 21 (which can indicate Down syndrome), trisomy 18 (which can indicate
Edwards syndrome), or monosomy X (which can indicate Turner syndrome). With
this knowledge, parents can better prepare for the arrival of a child with developmental challenges. Tests are also available for phenylketonuria, cystic fibrosis, and
Duchennes muscular dystrophy.

genetic screening biochemical or

molecular tests that are used to identify
inherited disorders in parents, potential
parents, embryos, or children after they
are born

amniocentesis a genetic sampling

method for testing in utero

Research This
Evaluating the implications of Gene Therapy
Skills: Researching, Evaluating, Communicating, Defining the Issue,
Identifying Alternatives, Defending a Decision

skills
handbook

A4.1, A4.2

Gene therapy is a technology in its infancy. Although gene therapy has had some
promising results, it has also had some devastating setbacks, such as the death of test
subjects. In the future, society will have to make choices about the use of gene therapy to
treat disorders or diseases. What risks are we willing to take? Under what circumstances
or conditions should gene therapy be used?
1. Using the Internet and other sources, research and distinguish between the three
types of gene therapy: gene insertion, gene modification, and gene surgery.
A. Answer the following questions. T/I
Describe how each type of gene therapy works.
In your opinion, what are some of the arguments for and against gene therapy?
Describe some ways in which genes can be inserted into a genome to correct a
defective gene.
Differentiate between somatic gene therapy and germ-line gene therapy.
What are some challenges that scientists have faced with gene therapy research?
B. Propose a set of guidelines to direct the future of gene therapy research. Consider
the following criteria when developing your guidelines:
what the risk is to the population
who has access
what constitutes a disease
which type of gene therapy is worth the most research money

T/I

C. In your opinion, do the risks of gene therapy outweigh the benefits? Comment
using your guidelines and other research as supporting evidence. Summarize your
argument in one page. Make sure that you account for ethical considerations in your
argument. T/I C
WEB LINK

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8.4

Review

Summary
Genetic therapy involves replacing, removing, inserting, or repairing defective
genes with genes that function properly.
Somatic gene therapy improves the functioning of an individuals body cells,
but the changes are not passed on to any offspring.
Germ-line gene therapy involves sperm cells and eggs, so changes in an
individuals DNA are passed on to the offspring.
Genetic screening consists of biochemical or molecular tests to identify
inherited disorders in people.

Questions
1. In your own words, define gene therapy. K/U
2. Create a graphic organizer to compare and contrast
somatic gene therapy and germ-line gene therapy.
K/U

3. Does genetic screening help people? Consider both

the pros and cons of genetic screening in your
answer. K/U T/I
4. Explain how changing the diet of someone with
phenylketonuria helps, and what change is made. K/U
5. What is amniocentesis? Why is it more likely to be
recommended for older parents? K/U
6. What are other possible ways to treat genetic
defects, besides gene therapy? K/U
7. Palmiter and Brinster devised germ-line gene
therapy. Without checking Internet sources, develop
a procedure that could possibly be used in germ-line
gene therapy. K/U T/I

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8. Describe how somatic gene therapy has been

successful in combatting sickle-cell disease but has
failed in other applications. K/U T/I
9. How are patients with the following diseases treated?
K/U

(a) ADA defect

(b) sickle-cell disease
10. As shown by the example of insulin in this chapter,
genetic engineering has many advantages. Gene
therapy has saved innumerable lives. Research
some other illnesses that gene therapy may provide
T/I
solutions for in the future.
11. Using the Internet and other sources, research one
of the latest advances in gene therapy. Present your
T/I
C
findings as a report or a poster.
WEB LINK

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