Genetic Engineering

Also known as: biotechnology, gene splicing, recombinant DNA technology

Anatomy or system affected: All

Specialties and related fields: Alternative medicine, biochemistry,

biotechnology, dermatology, embryology, ethics, forensic medicine, genetics,
pharmacology, preventive medicine

Definition: Genetic engineering, recombinant DNA technology and

biotechnology – the buzz words you may have heard often on radio or TV, or
read about in featured articles in newspapers or popular magazines. It is a
set of techniques that are used to achieve one or more of three goals: to
reveal the complex processes of how genes are inherited and expressed, to
provide better understanding and effective treatment for various
diseases, (particularly genetic disorders) and to generate economic benefits
which include improved plants and animals for agriculture, and efficient
production of valuable biopharmaceuticals. The characteristics of genetic
engineering possess both vast promise and potential threat to human kind.
It is an understatement to say that genetic engineering will revolutionize the
medicine and agriculture in the 21st future. As this technology unleashes its
power to impact our daily life, it will also bring challenges to our ethical
system and religious beliefs.

Key terms:
GENETIC ENGINEERING: the collection of a wide array of techniques that
alter the genetic constitution of cells or individuals by selective removal,
insertion, or modification of individual genes or gene sets
GENE CLONING: the development of a line of genetically identical organisms
which contain identical copies of the same gene or DNA fragments
GENE THERAPY: the insertion of a functional gene or genes into a
cell/tissue/organ to correct a genetic abnormality
PCR: abbreviated from polymerase chain reaction, an in vitro process by
which specific parts of a DNA molecule or a gene can be rapidly made into
millions or billions of copies within a short time
RECOMBINANT DNA: a hybrid DNA molecule created in the test tube by
joining a DNA fragment of interest with a carrier DNA
SOUTHERN BLOT: a procedure that is used to transfer DNA from a gel to a
nylon membrane, which in turn allows the finding of genes that are
complementary to particular DNA sequences called probes

Genetic Engineering and Human Health

Soon after the publication of the short essay by Crick and Watson on DNA
structure (1953), research began to uncover the way by which DNA
molecules can be cut and
“spliced” back together. With the discovery of the first restriction
endonuclease by Hamilton Smith et al. (1970), the real story of genetic
engineering began to unfold. The creation of the first engineered DNA
molecule through splicing DNA fragments of two

unrelated species together was made public in 1972. Soon followed were a
whole array of recombinant DNA molecules, genetically modified bacteria,
viruses, fungi, plants and animals. The debate over the issues of “tinkering
with God” heated up and public outcry over genetic engineering was wide-
spread. The birth of “Dolly”, the first mammal ever cloned from an adult
body cell, has elevated the debate over the impact of biological research to a
new level. Furthermore, a number of genetically modified organisms (GMOs)
have been commercially released since 1996. Today, it is estimated that
over 70% of US foods contain some ingredients from GMOs.

Obviously, genetic engineering holds tremendous promise for medicine and

human well-being. Medical applications of genetic engineering include
diagnosis for genetic and other diseases; treatment for genetic disorders;
regenerative medicine using pluripotent (stem) cells; production of safer and
more effective vaccines, and pharmaceuticals; the prospect of curing genetic
disorders through gene therapy; the list goes on... Owing to its potential to
give humanity unprecedented power over life itself, the research and
application of genetic engineering has generated much debate
and controversy. Many human diseases, such as cystic fibrosis, Downs
syndrome, fragile X syndrome, Huntington’s disease, muscular dystrophy,
sickle-cell anemia, Tay-Sachs disease, etc. are inherited. There are usually
no conventional treatments for these disorders because they don’t respond
to antibiotics or other conventional drugs. Another area is the commercial
production of vaccines and pharmaceuticals through genetic engineering,
which has emerged as a rapidly developing field. The potential of embryonic
stem cells to become any cell/tissue/organ under adequate conditions
holds enormous promise for regenerative medicine.

a. Prevention of Genetic Disorders

Although prevention may be achieved by avoiding these environmental
factors that cause the abnormality, the most effective prevention, when
possible, is to reduce the frequency of or eliminate entirely the harmful
genes (mutations) from the general population. As more precise tools and
procedures for manipulating individual genes are optimized, this will
eventually become a reality. The prevention of genetic disorders at present
is usually achieved by ascertaining those individuals in the population who
are at risk of passing a serious genetic disorder to their offspring, offering
them genetic counseling and prenatal screening followed with the selective
abortion of affected fetuses.
Genetic counseling is the process of communicating information gained
through classic genetic studies and contemporary research to those
individuals who are themselves at risk or have a high likelihood of passing
defects to their offspring. During counseling, information about the disease
itself - its severity and prognosis, whether or not there are effective
therapies, and the risks of recurrence is generally presented. For those
couples who find the risks unacceptably high, counseling may also include
discussions of contraceptive methods, adoption, prenatal diagnosis, possible
abortion and artificial insemination by a donor, etc. Even though the final
decision must still rest with the couple themselves, the significant increase in
the accuracy of risk assessment made possible with genetic technology
makes it easier for parents to make well-informed decisions.
To these couples who find the burden of having an affected child
unbearable, prenatal diagnosis may solve their dilemma. Prenatal screening
could be performed for a variety of genetic disorders. It requires samples of
fetal cells or chemicals produced by the fetus through either amniocentesis
or chorionic villus sampling. After sampling, several analyses could be
performed. First, biochemical analysis is used to determine
the concentration of chemicals in the sample and therefore diagnose
whether a particular fetus is deficient or low in enzymes that facilitate
specific biological reactions. Next, analysis of the chromosomes of the fetal
cells can show if all the chromosomes are present, and whether or not there
are any structural abnormalities in any of them. Finally, the most effective
means is to detect the defective genes through recombinant
DNA techniques. This has become possible with the rapid increase of DNA
copies through a technique called PCR, which can produce virtually unlimited
copies of a specific gene or DNA fragment, starting with as little as a single
copy. Routine prenatal diagnosis is being performed to screen fetus for
Down syndrome, Huntington’s disease, sickle-cell anemia and Tay-Sachs
disease. Procedures are being developed for prenatal diagnosis of more and
more severe genetic disorders. Thus, an effective roadblock to the passing
of defective genes from one generation to another in the population is
possible.

b. Treatment of Diseases and Genetic Disorders

Genetic engineering may be used for direct treatments of diseases or
genetic disorders through various means, including the production of
possible vaccines for AIDS, treatment for various cancers, synthesis of
biopharmaceuticals for a variety of metabolic, growth and development
diseases, etc. In general, biosynthesis is a process where gene coding for a
particular product is isolated, cloned into another organism (mostly
bacteria), and later expressed in that organism (host). By cultivating host
organism, large quantities of the gene products can be harvested and
purified. A few examples will illustrate the useful features of biosynthesis.
Insulin is essential for the treatment of insulin-dependent diabetes, the most
severe form of diabetes. Historically, insulin was obtained from a beef or pig
pancreas. Two problems exist for the traditional supply of insulin. First,
large quantities of the pancreas are needed to extract enough insulin for
continuous treatment of one patient. Second, insulin so obtained is not
chemically identical to human insulin, hence some patients may produce
antibodies which can seriously interfere with the treatment. Human insulin
produced through genetic engineering is quite effective yet without any side-
effects. It has been produced commercially and made available to patients
since 1982.

Another successful story in biosynthesis is the production of human growth

hormone (HGH), which is used in the treatment of children with growth
retardation called pituitary dwarfism. The successful biosynthesis of HGH is
important due to several reasons. The conventional source of HGH was
human pituitary glands removed at autopsy, which only exist in brain and
liver. Each child afflicted with pituitary dwarfism needs twice-a-
week injections until the age of 20. Such a treatment regime requires over a
thousand pituitaries. It’s obvious that autopsy supply could hardly keep up
with the demand. Furthermore, due to a small amount of virus
contamination in the extracted HGH, many children receiving treatment
developed virus related diseases. Other biopharmaceuticals under
development or in pre-clinical or clinical trials through genetic engineering
include anti-cancer drugs, anti-aging agents and a possible vaccine for AIDS,
malaria, etc. Broadly speaking, three types of gene therapy exist, germ line
therapy, enhancement gene therapy and somatic gene therapy. All gene
therapy trials currently underway or in the pipeline are restricted to the
somatic cells as targets for gene transfer. The germ line therapy involves
the introduction of novel genes into germ cells such as egg/early embryo.
Although it has the potential for correcting defective genes once for all,
germ line gene therapy is highly controversial and currently banned by many
countries. The enhancement gene therapy, through which human potential
might be enhanced for some desired traits, raises an even greater ethical
dilemma. Both germ line and enhancement gene therapy have been banned
based on the unresolved ethical issues surrounding them. Somatic gene
therapy is designed to introduce functional gene(s) to body cells,
which enable the body to perform normal functions thus providing temporary
correction for genetic abnormalities. The cloned human gene is first
transferred into a viral vector, which is used to infect white blood cells
removed from the patient. The transferred (normal) gene is then inserted
into a chromosome and becomes active. After growth to enhance their
numbers under sterile conditions, the cells are re-implanted into the
patient, where they produce a gene product that is missing in the untreated
patient, allowing the individual to function normally. Several disorders are
currently being treated with this technique, including severe combined
immunodeficiency (SCID). Individuals with SCID have no functional immune
system and usually die from infections that would be minor in normal people.
Gene therapy is also being used or tested as a treatment for cystic fibrosis,
skin cancer, breast cancer, brain cancer, and AIDS. However, most of these
treatments are only partially successful, yet prohibitively expensive. Over a
10year period (1990-2000), more than 4000 people were treated through
gene therapy. Unfortunately, most of these trials were failures that led to a
loss of confidence in gene therapy. The major reasons for these failures
have been attributed to inefficient vectors. In the future, as more efficient
vectors are engineered, gene therapy is expected to be a common method
for treating a large number of genetic disorders.