BIOTECHNOLOGY
1

On November 22, 1983, the sleepy
English village of Narborough awoke to
news of a horrific crime: A 15-year-oldgirl named Lynda Mann had been raped
and murdered on a country lane near her
home. The killer left behind few clues,
except for semen on the victim’s body and
clothes. Despite extensive investigation,
the trail of evidence ran cold and the
crime went unsolved.
2

Three years later, the horror resurfaced when
another 15-year old girl, Dawn Ashworth, was
also raped and murdered less than a mile away
from the first crime scene. When tests indicated
that the 1983 and 1986 semen samples could be
from the same man, police began to search for a
double murderer. After another extensive
investigation, a maintenance worker from a
nearby hospital was arrested and charged with
both crimes. Under considerable pressure from
police, the worker confessed to the second
murder, but denied committing the first.
3
DNA Technology

In an attempt to pin both murders on the suspect, investigators
turned to Alec Jeffreys, a professor at nearby Leicester University,
who had recently developed the first DNA fingerprint identification
system. Because the DNA sequence of every person unique
(except for identical twins), DNA fingerprinting can be used to
determine with near certainty whether two samples of genetic
material are from the same individual. Jeffreys compared DNA
from the 1983 and 1986 semen samples. As the police suspected,
the DNA analysis proved that the same person had committed
both crimes. However, when Jeffreys analyzed the suspect’s DNA,
it did not match either crime scene sample, proving that the
suspect must be innocent. The police quickly released the
suspect, making him the first person in legal history to be
exonerated by DNA evidence.
5

The detectives were back at square one. In an attempt to
collect more evidence, they asked every young male from
the surrounding area to donate blood for DNA testing.
Although 5,000 men were sampled, none had DNA that
matched the evidence from the crime scenes. The police
were once again stymied. The case finally broke when a
pub-goer described how a man named Cohn Pitchfork had
bullied him into submitting blood on Pitchfork’s behalf. The
police promptly arrested Pitchfork and took a sample of his
blood. Indeed, his DNA matched the samples from the two
crime scenes. Cohn Pitchfork pleaded guilty to both crimes,
closing the first murder case ever to be solved by DNA
evidence.
6

The Narborough murders were the first of many criminal investigations that have relied on DNA evidence. DNA
technology— methods for studying and manipulating genetic
material—have rapidly revolutionized the field of forensics, the
scientific analysis of evidence for legal investigations. Since its
introduction, DNA fingerprinting has become a standard law
enforcement tool and has provided crucial evidence (of both
innocence and guilt) in many famous cases, including the O.J.
Simpson murder trial and the impeachment of President Bill
Clinton. As we will see, DNA technology has applications in many
other fields, from cancer research to agriculture and even history.
Perhaps the most exciting use of DNA technology in basic
research is the Human Genome Project, whose goal was to map
the entire human DNA down to the level of its nucleotide
sequences. This project is expected to help us better understand
and treat many diseases.
7

There are several significant roles that
DNA technology has assumed in society,
including gene cloning to produce useful
products, DNA fingerprinting and forensic
science, human gene therapy for the
treatment of disease, comparisons of
genomes from different organisms, and
the agricultural production of genetically
modified organisms. There are also some
of the social, legal, and ethical issues that
are raised by these new technologies.
8





The use of technology to alter the genomes of
viruses, bacteria, and other cells for medical or
industrial purposes is called genetic engineering.
These days, bacteria, plants, and animals are genetically
engineered to produce biotechnology products.
Organisms that have had a foreign gene inserted
into them are called transgenic organisms.
(TRANSferred GENE = TRANS GENIC).
DNA technology is changing the pharmaceutical
industry and medicine
DNA technology, and gene cloning in particular, is widely
used to produce medicines and to diagnose diseases.
Biotechnology Products
9
DNA technology is changing the
pharmaceutical industry and
medicine
Therapeutic Hormones Consider human insulin
and human growth hormone (HGH).
 In the United States alone, about 2 million people
with diabetes depend on insulin treatment.
 Before 1982, the main sources of this hormone
were pig and cattle tissues obtained from
slaughterhouses.
 Insulin extracted from these animals is
chemically similar, but not identical, to human
insulin, and it causes harmful side effects in
some people.

DNA technology is changing the
pharmaceutical industry and
medicine



Genetic engineering has largely solved this
problem by developing bacteria that synthesize
and secrete actual human insulin.
In 1982, because growth hormones from other
animals are not effective in humans, HGH was
urgently needed. In 1985, molecular biologists
were able to produce HGH in bacteria.
Before this genetically engineered hormone
became available, children with a HGH deficiency
had to rely on scarce supplies from human
cadavers or else face dwarfism.
Human insulin produced by bacteria
◦ In 1982, Humulin became the first
recombinant drug approved by the Food and
Drug Administration
Figure 12.7A
Recombinant DNA technology means to
recombine the DNA of an organism to
make it more useful to humans.
 It is used to produce bacteria that
reproduce in large vats to get them to
make a large amount of a particular
protein, such as insulin, growth hormone, clotting proteins for hemophiliacs,
and hepatitis B vaccine.

From Bacteria
14
Hepatitis B Vaccine
DNA technology is also helping medical
researchers develop vaccines.
 A vaccine is a harmless variant or derivative of a
pathogen (usually a bacterium or virus) that is
used to prevent an infectious disease.
 When a person is inoculated, the vaccine
stimulates the immune system to develop lasting
defenses against the pathogen.
 For the many viral diseases for which there is no
effective drug treatment, prevention by
vaccination is virtually the only medical way to
prevent illness.

Vaccines
One DNA technology vaccine is for the
hepatitis B virus.
 Hepatitis is a disabling and sometimes
fatal liver disease, and the hepatitis B
virus may also cause liver cancer.

Vaccines
Smallpox was once a dreaded human
disease, but it was eradicated worldwide
in the 1970s by widespread vaccination
with a harmless variant of the smallpox
virus.
 In fact, the harmless virus could be
engineered to carry the genes needed to
vaccinate against several diseases
simultaneously.
 In the future, one inoculation may prevent
a dozen diseases.

Vaccines
The new Reverse Vaccine utilizes modified DNA
to shut down specific sections of the immune
system.
 The vaccine has shown promising results in
combatting Type 1 diabetes.
 Most vaccines aim to boost a patient’s immune
response to a virus by injecting a genetically
modified version of the disease into the
body. The Stanford vaccine does the opposite,
intentionally turning off select portions of the
immune response that are malfunctioning.

‘Reverse' vaccine may help
combat Type 1 diabetes
19
Biotechnology Products From
Bacteria

Transgenic bacteria
can also help
plants. For
example, bacteria
that live in plants
have genes spliced
in that let them
resist insect
toxins; this
protects the roots
of the plants, too.

Bacteria can be
genetically engineered
to degrade a
particular substance,
for instance,
transgenic bacteria
have been produced
which have the
ability to eat oil
after an oil spill.
Biotechnology
Products From
Bacteria
Industry has found that bacteria can be used as
filters to prevent airborne chemicals from being
vented into the air.
 They can also remove sulfur from coal before it is
burned and help clean up toxic dumps.
 Furthermore, these bacteria were given
“suicide” genes that cause them to selfdestruct when the job is accomplished.

From Bacteria
22
Biotechnology Products From
Bacteria
Many major mining
companies already
use bacteria to obtain
various metals.
 Genetic engineering
may enhance ability
of bacteria to extract
copper, uranium, and
gold.

Biotechnology Products From
Plants

Plants can also be
genetically
engineered to
make cotton, corn,
soybeans, and
potatoes resistant
to pests because
their cells now
produce an insect
toxin.
Biotechnology Products From
Plants


Plants are also being
engineered to produce
human hormones,
clotting factors, and
antibodies, in their seeds.
One type of antibody made
by corn can deliver a
substance that kills tumor
cells, and another made by
soybeans can be used as
treatment for genital
herpes.
Genetically modified organisms
are transforming agriculture
Scientists concerned with feeding the
growing human population are using DNA
technology to make genetically modified
(GM) organisms for use in agriculture.
 A GM organism (Or GMO) is one that has
acquired one or more genes by artificial
means rather than by traditional breeding
methods. (The new gene may or may not
be from another species.)

Genetically modified organisms
are transforming agriculture
To make genetically modified plants,
researchers can manipulate the DNA of a
single cell and then grow a plant with a
new trait from the engineered cell.
 Already in commercial use are a number
of crop plants carrying new genes for
desirable traits, such as delayed ripening
and resistance to spoilage and disease.

Genetically modified organisms
are transforming agriculture




The most common vector used to introduce new genes into
plant cells is a piece of DNA from a soil bacterium.
With the help of a special enzyme, the gene for the desired
trait is inserted into a plant cell, where it is integrated into
a plant chromosome.
Finally, the recombinant cell is cultured and grows into a
whole plant.
If the newly acquired gene is from another species, the
recombinant organism is called a transgenic organism.
Genetically modified organisms
are transforming agriculture
Genetic engineering is rapidly replacing
traditional plant-breeding programs.
 For example, the majority of the American
soybean and cotton crops are genetically
modified.
 Many of these GM plants have received bacterial
genes that make the plants resistant to
herbicides or pests.
 Farmers can more easily grow these crops with
far less tillage and reduced use of chemical
insecticides.

Genetically modified organisms
are transforming agriculture



Genetic engineering also has great potential for
improving the nutritional value of crop plants.
“Golden rice,” a transgenic variety with a few
daffodil genes, produces grains containing betacarotene, which our body uses to make vitamin
A.
This rice could help prevent vitamin A
deficiency—and resulting blindness—among the
half of the world’s people who depend on rice as
their staple food.

Agricultural researchers are also making
transgenic animals. To do this, scientists first
remove egg cells from a female and fertilize
them in vitro. They then inject a previously
cloned gene directly into the nuclei of the
fertilized eggs. Some of the cells integrate the
foreign DNA into their genomes. The engineered
embryos are then surgically implanted in a
surrogate mother. If an embryo develops
successfully, the result is a transgenic animal,
containing a gene from a third “parent” that may
even be of another species.
Biotechnology Products From
Animals
Techniques have been developed to insert
genes into the eggs of animals.
 The procedure has been used to produce
larger fish, cows, pigs, rabbits, and sheep.
 Genetically engineered fishes are now
being kept in ponds that offer no escape
to the wild because there is much concern
that they will upset or destroy natural
ecosystems.

From Animals
33
Transgenic Pig

The goals of creating a transgenic animal
are often the same as the goals of
traditional breeding—for instance, to
make a sheep with better quality wool or
a cow that will mature in a shorter time.
Scientists might, for example, identify and
clone a gene that causes the development
of larger muscles (muscles make up most
of the meat we eat) in one variety of
cattle and transfer it to other cattle or
even to sheep.
Biotechnology Products From
Animals

Transgenic animals also have been
engineered to be pharmaceutical
“factories” that produce otherwise rare
biological substances for medical use.
Recently, researchers have engineered
transgenic chickens that express large
amounts of the foreign product in their
eggs. This success suggests that
transgenic chickens may emerge as
relatively inexpensive pharmaceutical
factories in the near future.
Biotechnology Products From
Animals
Gene pharming is the use of
transgenic farm animals to produce
therapeutic drugs in the animal’s
milk.
 There are plans to produce drugs for the
treatment of cystic fibrosis, cancer, blood
diseases, and other disorders.
 An anti-clotting medicine is currently
being produced by a herd of goats.

From Animals
37
Pharm Animals
Animals have been engineered to produce
growth hormone in their urine instead of
in milk.
 Urine is preferable to milk because only
females produce milk, and not until
maturity, but all animals produce urine
from birth.

From Animals
39
40
Scientists have begun the process of genetically
engineering animals to serve as organ
donors for humans who need a transplant.
 We now have the ability to transplant kidneys,
heart, liver, pancreas, lung, and other organs.
 Unfortunately, however, there are not enough
human donors to go round.

Fifty thousand Americans need
transplants a year, but only
20,000 patients get them.
As many as 4,000 die each year
while waiting for an organ.
Xenotransplantation
41
You might think that apes, such as the
chimpanzee or the baboon might be a
scientifically suitable species for this purpose.
 But apes are slow breeders and many people
object to using apes for this purpose.
 In contrast, pigs have been an acceptable meat
source, and a female pig can become pregnant
at six months and can have two litters a year,
each averaging about ten offspring.
 Ordinarily, the human body rejects transplanted
pig organs. Genetic engineering, however, can
make pig organs good for transplantation at
less of a rejection risk.

Xenotransplantation
42
Imagine that an animal has been
genetically altered to serve as an organ
donor. What would be the best possible
way to get identical copies of this animal?
 If cloning of the animal was possible, you
could get many exact copies of this
animal.
 Cloning is a form of asexual reproduction (without sex) because it
requires only the genes of that one
animal.

Cloning of Animals
43
Cloning
In 1997, scientists at the Raslin institute
in Scotland announced that they produced
a cloned sheep called Dolly. In 1998,
genetically altered calves were cloned in
the United States using the same method.
 CLONING VIDEO

Cloning of Animals
45
Clones
Clones
Clone?
As soon as scientists realized the power of
DNA technology, they began to worry
about potential dangers.
 Early concerns focused on the possibility
that recombinant DNA technology might
create new pathogens.
 What might happen, for instance, if
cancer cell genes were transferred into
bacteria or viruses?

Could GM organisms harm human
health or the environment?




To guard against such rogue microbes, scientists developed
a set of guidelines that were adopted as formal government
regulations in the United States and some other countries.
One safety measure is a set of strict laboratory procedures
designed to protect researchers from infection by
engineered microbes and to prevent the microbes from
accidentally leaving the laboratory.
In addition, strains of microorganisms to be used in
recombinant DNA experiments are genetically crippled to
ensure that they cannot survive outside the laboratory.
Finally, certain obviously dangerous experiments have been
banned.
Could GM organisms harm human
health or the environment?
Today, most public concern about possible
hazards centers not on recombinant
microbes but on genetically modified (GM)
crop plants.
 Advocates of a cautious approach fear
that some crops carrying genes from
other species might cause allergies in
humans or create super-weeds that are
hazardous to the environment.

Could GM organisms harm human
health or the environment?



Today, governments and regulatory agencies
throughout the world are grappling with how to
facilitate the use of biotechnology in agriculture,
industry, and medicine while ensuring that new
products and procedures are safe.
In the United States, all projects are evaluated
for potential risks by regulatory agencies such as
the Food and Drug Administration, Environmental
Protection Agency, National Institutes of Health,
and Department of Agriculture.
These agencies are under increasing pressure
from some consumer groups.
Could GM organisms harm human
health or the environment?



The Human Genome Project was a massive
effort to figure out what the sequence is of
all of the genes in human chromosomes.
This was just finished in 2003.
Project goals were to identify all the 25,000
genes in human DNA and determine the
sequences of the 3 billion nucleic acids that make
up human DNA.
This allows scientists to detect some defective
genes and tailor a treatment plan to the
individual.
The Human Genome Project
53
The Human Genome Project
Gene therapy gives a patient a
normal gene to make up for a faulty
gene.
 For example, there is a genetic disease of
the liver that causes it to malfunction and
leads to high levels of blood cholesterol,
which makes the patient subject to fatal
heart attacks at a young age.
 The person is injected with a virus that
contains the normal gene.

Gene Therapy
55
Another example is when fat enzymes are
coated with the missing gene to cure
cystic fibrosis and then sprayed into
patients’ nostrils.
 Anti-cancer genes can also be injected
directly into cancerous tumors.
 Perhaps it will be possible also to use
gene therapy to cure hemophilia,
diabetes, Parkinson disease, or AIDS.

Gene Therapy
56
DNA technology is being used increasingly
in disease diagnosis.
 It is used to determine which genes are
associated with genetic diseases.
 An individual’s gene expression profile
may someday allow physicians to tailor
treatments for many different disorders.

Diagnosis and Treatment of
Disease

Recombinant DNA technology
◦ Intentionally modifying genomes of organisms
for practical purposes
◦ Three goals
 Eliminate undesirable phenotypic traits
 Combine beneficial traits of two or more
organisms
 Create organisms that synthesize products
humans need
The Role of Recombinant DNA
technology in Biotechnology
58
Overview of
recombinant DNA
technology
59
Figure 8.1

Mutagens
◦ Physical and chemical agents that produce
mutations
◦ Scientists utilize mutagens to
◦ Create changes in microbes’ genomes to change
phenotypes
◦ Select for and culture cells with beneficial characteristics
◦ Mutated genes alone can be isolated
The Tools of Recombinant DNA
Technology
60
Natural Mutation in Fruit Fly

The Use of Reverse Transcriptase to
Synthesize cDNA
◦ Isolated from retroviruses
◦ Uses RNA template to transcribe molecule of
DNA
◦ Easier to isolate mRNA molecule for desired
protein first
 Allows cloning in prokaryotic cells
The Tools of Recombinant DNA
Technology
62

Synthetic Nucleic Acids
◦ Molecules of DNA and RNA produced in cell-free
solutions
◦ Uses of synthetic nucleic acids
 Elucidating the genetic code
 Creating genes for specific proteins
 Synthesizing DNA and RNA probes to locate
specific sequences of nucleotides
 Synthesizing antisense nucleic acid molecules
The Tools of Recombinant DNA
Technology
63

Restriction Enzymes
◦ Bacterial enzymes that cut DNA molecules only
at restriction sites
◦ One enzyme might only cleave T-T apart;
another enzyme only cleaves A-T apart, etc.
◦ We use one enzyme, and see how many pieces
result. Then we use the next enzyme, etc. That
shows us the sequence of DNA in a sample.
◦ Restriction Enzymes video
The Tools of Recombinant DNA
Technology
64
Actions of
restriction
enzymes
65
Figure 8.2

Vectors
◦ Nucleic acid molecules that deliver a gene into
a cell
◦ Useful properties
 Small enough to manipulate in a lab
 Survive inside cells
 Contain recognizable genetic marker
 Ensure genetic expression of gene
◦ Include viral genomes, transposons, and
plasmids
The Tools of Recombinant DNA
Technology
67

Gene Libraries
◦ A collection of bacterial or phage clones
 Each clone in library often contains one gene of an
organism’s genome
◦ Library may contain all genes of a single
chromosome
◦ Library may contain set of DNA complementary
to mRNA
The Tools of Recombinant DNA
Technology
68
Multiplying DNA in vitro: The
Polymerase Chain Reaction (PCR)
 VIDEO CLIP

◦ Large number of identical molecules of DNA
produced in vitro
◦ Critical to amplify DNA in variety of situations
 Epidemiologists use to amplify genome of
unknown pathogen
 Amplified DNA from Bacillus anthracis spores in
2001 to identify source of spores
Techniques of Recombinant DNA
Technology
69

Multiplying DNA in vitro: The
Polymerase Chain Reaction (PCR)
◦ Repetitive process consisting of three steps
 Denaturation
 Priming
 Extension
◦ Can be automated using a thermocycler
Techniques of Recombinant DNA
Technology
70
Polymerase
chain
reaction
(PCR)
71
Figure 8.5a
Polymerase
chain
reaction
(PCR)
72
Figure 8.5b
Techniques of Recombinant DNA
Technology
73

Separating DNA Molecules: Gel
Electrophoresis and the Southern Blot
◦ Gel electrophoresis
 Separates molecules based on electrical charge,
size, and shape
 Allows scientists to isolate DNA of interest
 Negatively charged DNA drawn toward positive
electrode
 Agarose makes up gel; acts as molecular sieve
 Smaller fragments migrate faster and farther than
larger ones
 Determine size by comparing distance migrated to
standards
Techniques of Recombinant DNA
Technology
74
Gel electrophoresis
75
Figure 8.6

GEL ELECTROPHORESIS VIDEO
Video of our lab’s gel electrophoresis
 Electrophoresis Results video

76

Separating DNA Molecules: Gel
Electrophoresis and the Southern Blot
◦ Southern blot
 DNA transferred from gel to nitrocellulose
membrane
 Probes used to localize DNA sequence of interest
 Northern blot – used to detect RNA
◦ Uses of Southern blots
 Genetic “fingerprinting”
 Diagnosis of infectious disease
 Demonstrate incidence and prevalence of
organisms that cannot be cultured
Techniques of Recombinant DNA
Technology
77
The Southern
blot
technique
78
Figure 8.7

DNA Microarrays
◦ MICROARRAY VIDEO
◦ Consist of molecules of immobilized singlestranded DNA
◦ Fluorescently labeled DNA washed over array
will adhere only at locations where there are
complementary DNA sequences
◦ Variety of scientific uses of DNA microarrays
 Monitoring gene expression
 Diagnosis of infection
 Identification of organisms in an environmental
sample
Techniques of Recombinant DNA
Technology
79
DNA microarray
80
Figure 8.8

Inserting DNA into Cells
◦ Goal of DNA technology is insertion of DNA into
cell
◦ Natural methods
 Transformation
 Transduction
 Conjugation
◦ Artificial methods
 Electroporation
 Protoplast fusion
 Injection – gene gun and microinjection
Techniques of Recombinant DNA
Technology
81

Transformation is the genetic alteration of
a cell resulting from the direct uptake,
incorporation and expression of
exogenous DNA from its surroundings.
Transformation occurs naturally in some
species of bacteria, but it can also be
caused artificially.
Transformation
82
Transduction is when DNA is transferred
from one bacterium to another by a virus
 The virus is called a bacteriophage.


Conjugation is when a bacterium uses its
sex pilus to transfer some of its DNA to
another bacterium.
Transduction
83
Artificial methods of inserting DNA into
cells
84
Figure 8.9a/b
Artificial methods of inserting DNA into
cells
85
Figure 8.9c/d

Genetic Mapping
◦ Locating genes on a nucleic acid molecule
◦ Provides useful facts concerning metabolism,
growth characteristics, and relatedness to
others

Locating Genes
◦ Until 1970, genes identified by labor-intensive
methods
◦ Simpler and universal methods now available
◦ Restriction fragmentation
◦ Fluorescent in situ hybridization (FISH)
Applications of Recombinant DNA
Technology
86
Fluorescent in situ hybridization
Used to detect and
localize the
presence or
absence of specific
DNA sequences on
chromosomes.
Also allows for
more precise DNA
karyotyping.
87
Figure 8.10
Automated DNA sequencing
88
Figure 8.11

Environmental Studies
◦ Most microorganisms have never been grown in
a laboratory
◦ Scientists know them only by their DNA
fingerprints
 Allowed identification of over 500 species of
bacteria from human mouths
 Determined that methane-producing archaea are
a problem in rice agriculture
Applications of Recombinant DNA
Technology
89

Pharmaceutical and Therapeutic
Applications
◦ Protein synthesis
 Creation of synthetic peptides for cloning
◦ Vaccines
 Production of safer vaccines
 Introduce genes of pathogens into common fruits
and vegetables
 Injecting humans with plasmid carrying gene
from pathogen
◦ Humans synthesize pathogen’s proteins
Applications of Recombinant DNA
Technology
90

Pharmaceutical and Therapeutic
Applications
◦ Genetic screening
 DNA microarrays used to screen individuals for
inherited disease caused by mutations
 Can also identify pathogen’s DNA in blood or
tissues
◦ DNA fingerprinting
 Identifying individuals or organisms by their
unique DNA sequence
Applications of Recombinant DNA
Technology
91

Pharmaceutical and Therapeutic
Applications
◦ Gene therapy
 Missing or defective genes replaced with normal
copies
 Some patients’ immune systems react negatively
◦ Medical diagnosis
 Patient specimens can be examined for presence
of gene sequences unique to certain pathogens
◦ Xenotransplants
 Animal cells, tissues, or organs introduced into
human body
Applications of Recombinant DNA
Technology
92
DNA FINGERPRINT
VIDEO
DNA
fingerprinting
93
Figure 8.12

DNA technology plays an important role in forensic
science, the scientific analysis of evidence for crime scene
and other legal investigations. In violent crimes, body
fluids or small pieces of tissue may be left at the crime
scene or on the clothes of the victim or assailant; if rape
has occurred, semen may be recovered from the victim’s
body. With enough tissue or semen, forensic scientists can
determine the blood type or tissue type using older
methods that test for proteins. However, such tests require
fresh samples in relative large amounts. Also, because
many people have the same blood or tissue type, this
approach can only exclude a suspect; it cannot provide
strong evidence of guilt.
DNA technology is used in courts
of law
94



DNA testing, on the other hand, can identify the guilty
individual with a high degree of certainty because the DNA
sequence of every person is unique (except for identical
twins).
DNA testing requires only about 1,000 cells. In a murder
case, for example, such analysis can be used to compare
DNA samples from the suspect, the victim, and bloodstains
on the suspect’s clothes.
They provide a DNA fingerprint, or specific pattern of
bands.
DNA technology is used in courts
of law
95



DNA fingerprinting can also be used to establish family
relationships.
A comparison of the DNA of a mother, her child, and the
purported father can conclusively settle a question of
paternity.
Sometimes paternity is of historical interest: DNA
fingerprinting provided strong evidence that Thomas Jefferson or one of his close male relatives fathered at least one
child with his slave Sally Hemings.
DNA technology is used in courts
of law
96




Just how reliable is DNA fingerprinting? In most legal
cases, the probability of two people having identical DNA
fingerprints is between one chance in 100,000 and one in a
billion.
For this reason, DNA fingerprints are now accepted as
compelling evidence by legal experts and scientists alike.
In fact, DNA analysis on stored forensic samples has
provided the evidence needed to solve many “cold cases”
in recent years.
DNA fingerprinting has also exonerated many wrongly
convicted people, some of whom were on death row.
DNA technology is used in courts
of law
97

Traditional fingerprinting has been used
for years to identify criminals and to
exonerate those wrongly accused of
crimes. The opportunity now arises to
use DNA fingerprinting in the same way.
DNA fingerprinting requires only a small
DNA sample. This sample can come from
blood left at the scene of a crime, semen
from a rape case, even a single hair root!
DNA Fingerprinting and the
Criminal Justice System
98

The DNA is amplified, cut with restriction
enzymes, and separated by gel
electrophoresis to produce a unique DNA
fragment pattern. The same procedure is
done several times with restriction
enzymes, making it nearly impossible for
anyone else in the world would have the
same set of patterns. Advocates of DNA
fingerprinting claim that identification is
beyond a reasonable doubt.
DNA Fingerprinting and the
Criminal Justice System
99

Opponents of this technology, however, point out that it is
not without its problems. Police or laboratory negligence
can invalidate the evidence. For example, during the O.J.
Simpson trial, the defense claimed that the DNA evidence
was inadmissible because it could not be proven that the
police had not planted O. J's blood at the crime scene.
There have also been reported problems with sloppy
laboratory procedures and the credibility of forensic
experts. In addition to identifying criminals, DNA
fingerprinting can be used to establish paternity and
maternity, determine nationality for immigration purposes,
and identify victims of a national disaster, such as the
terrorist attack of September 11, 2001.
DNA Fingerprinting and the
Criminal Justice System
100
Considering the usefulness of DNA fingerprints, perhaps everyone
should be required to contribute blood to create a national DNA
fingerprint data bank. Some say however this would constitute
an unreasonable search, which is unconstitutional.
 Would you be willing to provide your DNA for a national DNA data
bank? What types of privacy restrictions would you want on your
DNA?
 If not everyone, do you think that convicted felons at least should
be required to provide DNA for a databank?
 Should all defendants have access to DNA fingerprinting (at
government expense) to prove that they did not do a crime?
Should this include those already convicted of crimes who want to
reopen their cases using new DNA evidence?

DNA Fingerprinting and the
Criminal Justice System
101
DNA Fingerprinting and the
Criminal Justice System
Defendant’s
blood
Blood from
defendant’s clothes
Figure 12.12A
Victim’s
blood
Figure 12.12B

Agricultural Applications
◦ Production of transgenic organisms
 Recombinant plants and animals altered by addition
of genes from other organisms
Applications of Recombinant DNA
Technology
103

Agricultural Applications
◦ Herbicide resistance
 Gene from Salmonella conveys resistance to
glyphosate (Roundup)
◦ Farmers can kill weeds without killing crops
◦ Salt tolerance
 Scientists have removed gene for salt tolerance
and inserted into tomato and canola plants
 Transgenic plants survive, produce fruit, and
remove salt from soil
Applications of Recombinant DNA
Technology
104

Agricultural Applications
◦ Freeze resistance
 Crops sprayed with genetically modified bacteria
can tolerate mild freezes
◦ Pest resistance
 Bt toxin
◦ Naturally occurring toxin only harmful to insects
◦ Organic farmers use it to reduce insect damage to crops
 Gene for Bt toxin inserted into various crop plants
 Genes for Phytophthora resistance inserted into
potato crops
Applications of Recombinant DNA
Technology
105

Agricultural Applications
◦ Improvements in nutritional value and yield
 Tomatoes allowed to ripen on vine and shelf life
increased
◦ Gene for enzyme that breaks down pectin suppressed
 BGH allows cattle to gain weight more rapidly,
◦ Have meat with lower fat content and produce 10%
more milk
 Gene for β-carotene (vitamin A precursor)
inserted into rice
 Scientists considering transplanting genes coding
for entire metabolic pathways
Applications of Recombinant DNA
Technology
106
Supremacist view – humans are of greater value
than animals
 Long-term effects of transgenic manipulations are
unknown
 Unforeseen problems arise from every new
technology and procedure
 Natural genetic transfer could deliver genes from
transgenic plants and animals into other
organisms
 Transgenic organisms could trigger allergies or
cause harmless organisms to become pathogenic

The Ethics and Safety of Recombinant
DNA Technology
107
Studies have not shown any risks to
human health or environment
 Standards imposed on labs involved in
recombinant DNA technology
 Can create biological weapons using same
technology

The Ethics and Safety of Recombinant
DNA Technology
108

Ethical Issues
◦
◦
◦
◦
◦
◦
Routine screenings?
Who should pay?
Genetic privacy rights?
Profits from genetically altered organisms?
Required genetic screening?
Forced correction of “genetic abnormalities”?
The Ethics and Safety of Recombinant
DNA Technology
109
Are Genetically Engineered Foods
Safe?

A series of focus groups conducted by the
Food and Drug Administration in 2000
showed that although most participants
believed that genetically engineered foods
might offer benefits, they also feared
unknown long-term health consequences
that might be associated with the
technology. Some say that when it comes
to human and environmental safety, there
should be clear evidence of the absence of
risks.
Are Genetically Engineered Foods
Safe?
111




The discovery that a genetically engineered corn called
Star Link had inadvertently made it into the food supply
triggered the recall of chocolate shells, tortillas, and many
other corn-based foodstuffs from supermarkets.
Further, the makers of Star Link were forced to buy back
Star Link from farmers and to compensate food producers
at an estimated cost of several hundred million dollars.
Star Link is a type of corn that contains a foreign gene
taken from a common soil bacterium whose insecticidal
properties have long been known.
About a dozen varieties of this corn, as well as potatoes
and one variety of tomato, have now been approved for
human consumption.
Are Genetically Engineered Foods
Safe?
112

These strains contain a gene for an insecticidal protein.
The makers of Star Link decided to use a gene for a related
protein. They thought that using this molecule might slow
down the chances of pest resistance to the genetically
modified corn. In order to get FDA approval for use in
foods, the makers of Star Link performed the required
tasks. Like the other now approved strains, Star Link was
not poisonous to rodents, and its biochemical structure is
not similar to those of most food allergens. However, it
resisted digestion and longer than the other genetically
modified proteins when it was put in simulated stomach
acid and subjected to heat. Because most food allergens
are stable like this, Star Link was not approved for human
consumption.
Are Genetically Engineered Foods
Safe?
113

The scientific community is now trying to devise
more tests for allergens because it has not been
possible to determine conclusively whether or
not this second protein is an allergen. It is also
unclear how resistant to digestion a protein must
be in order to be an allergen, and it is also
unclear what degree of sequence similarity a
potential allergen must have two unknown
allergy and to raise concern. Therefore, it is not
understood yet where the thresholds are for
sensitization to food allergens and thresholds for
the visitation of a reaction with food allergens.
Are Genetically Engineered Foods
Safe?
114

Other scientists are concerned about the
following potential drawbacks to planting
this variety of genetically modified corn:
resistance among populations of the
target pest, exchange of genetic material
between the transgenic crop and related
plant species, and crops impact on nontarget species. They feel that many more
studies are needed before it can be said
for certain that genetically modified corn
has no ecological drawbacks.
Are Genetically Engineered Foods
Safe?
115

Despite controversies, the planting of genetically
engineered corn increased in 2001. The USDA
reports that US armors planted genetically
engineered corn on 26% of all corn acres, 1%
more than in 2000. In all, US farmers planted at
least 72 million acres with mostly genetically
engineered corn, soybeans, and cotton. The
public wants all of genetically engineered foods
to be labeled as such, but this may not be easy
to accomplish because most corn meal is derived
from both conventional and genetically
engineered corn. So far, there has been no
attempt to sort out one type of food product
from the other.
Are Genetically Engineered Foods
Safe?
116
Genetic Profiling

Now that the human genome has been sequenced,
researchers are using various means to discover which
sequencing differences among people might forecast the
possibility of a future disease. No doubt, there are benefits
to genetic profiling. For example, knowledge of your genes
might indicate your susceptibility to various types of
cancer. This information could be used to develop a
prevention program, including the avoidance of
environmental influences associated with the disease.
Also, you would be less inclined to smoke if you knew your
genes make it almost inevitable that smoking will give you
lung cancer. Are there any reasons not to be in favor of
genetic profiling?
Genetic Profiling
118

People, however, worry that insurance companies and
employers could use their genetic profile against them.
Perhaps employers will not higher, or insurance companies
will not ensure, those who have a propensity for particular
diseases. The federal government and about 25 states
have passed laws prohibiting genetic discrimination by
health insurers, and 11 have passed laws prohibiting
genetic discrimination by employers. The legislation states
that genetic information cannot be released to anyone
without the subject’s permission. Is that such legislation
enough to ally are fears of discrimination? Might an
employer not hire you or an insurance company not ensure
you simply because you will not grant permission to access
your genetic profile?
Genetic Profiling
119

Say that two women are being considered for the same
position, and each meets all the basic requirements for the
job. The first denies access to her genetic profile, while
the second one grants permission to look at her genetic
profile. Thinking that the first woman might have had
something to hide, employer hires a second one. The
possibility that sick days may be needed by the first
woman makes the second woman a more cost-effective
choice. People who have genetic profiles proving they are
likely to be healthy in the future might even use them in
order to have an advantage over those who have profile
showing that they are likely to develop serious illnesses in
the future. In this way, we might create a genetic
underclass.
Genetic Profiling
120

Genetic information is sometimes
misunderstood, particularly by laypeople.
In the past, for example, as an effort to
combat sickle cell disease, many people
were screened for it. Unfortunately, those
who were found to have the sickle trait,
and not the actual disease, experienced
discrimination at school, or from
employers and insurance carriers. It is
possible misunderstanding of the results
enough not to do genetic profiling, or do
the potential benefits outweigh the risks?
Genetic Profiling
121

On the other hand, employers may fear
that the government might use genetic
information one day to require them to
provide an environment specific to every
employee's need, in order to prevent
future illness. Would you approve of this,
or should individuals be required to leave
an area or job that exposes them to an
environmental influence that could be
detrimental to their health?
Genetic Profiling
122

Some people believe that free access to genetic profiling
data is absolutely essential to developing better
preventative care for all. If researchers can match genetic
profiles to the environmental conditions that bring on
illnesses, they could come up with better prevention
guidelines for the next generation. Should genetic profiles
and health records become public information under these
circumstances? It would particularly help in the study of
complex diseases, such as cardiovascular disorders, noninsulin-dependent diabetes, and juvenile rheumatoid
arthritis. Perhaps there would be some way to protect
privacy and still make the information known?
Genetic Profiling
123

If present legislation to protect privacy is
inadequate, what can be done to truly
keep such information private? Should
the information be coded in some way, so
that only the medical profession can read
it? Should people be responsible for
keeping the only copy of their profiles,
which would be coded so that even they
cannot read it? Or, do you believe that
anyone should have access to anyone's
profile, for whatever reason?
124



Should people be encouraged or even required to
have their DNA analyzed so that they can
develop programs to possibly prevent future
illness?
Should employers be encouraged or required to
provide an environment suitable to a person's
genetic profile? Or should the individual ovoid a
work environment that could bring on an illness?
How come we balance individual rights with the
public health benefits of matching genetic
profiles to detrimental environments?
125


Potent chemicals derived from exotic
animals are yielding a range of treatments.
One creature you don't want to stumble upon it
in a dark forest is a hungry vampire bat. The 3
inch long, pointy eared night stalker has an anticlotting substance and its saliva that allows it to
dine on an unending flow of its victim’s blood.
There is, however, one group of people that may
come to see the vampire bats as lifesavers.
They are stroke patients to desperately need
improved clot-busting drugs that prevent brain
damage and paralysis by restoring blood flow to
stroke ravaged tissues.
Medicine’s Wild Kingdom Time
Magazine
126

That's the idea behind a new drug that 15
US hospitals will soon begin testing. It's a
synthetic copy of an enzyme bats secrete
when they salivate over freshly bitten
gray. Stroke experts are already buzzing
because early studies in mice suggests
patients may be able to safely receive the
bat spit up to nine hours after they've had
a stroke. The only clot-busting drug now
on the market must be given within three
hours.
127
Medicine’s Wild Kingdom




Bats are not the only scary animals that may someday
contribute to the world's expanding medicine cabinet.
Scientists are studying everything from Gila monsters to
scorpions to copperhead snakes.
The toxins these creatures use to kill their prey or ward off
foes hold seemingly boundless potential to treat human
diseases ranging from diabetes to brain cancer.
Refined through millions of years of evolution, these
substances found in animal saliva, then um, and, in some
internal organs homed in on targets such as nerve cells
better than most chemical combination's scientists concoct.
And often, they circulate in the body for hours on end.
Medicine’s Wild Kingdom Time
Magazine
129




Still, turning Mother Nature’s toxins into life-saving drugs
can be harder than killing a Python with a pebble.
First, researchers must isolate, analyze, and synthesize
specific compounds in such a way that they can be
tolerated by humans and mass produced.
The risk of failure is so high that many pharmaceutical
companies shun poison derived experimental drugs until
they are well past the developmental stage.
That leaves scientists dependent upon scarce venture
capital and public funding.
Medicine’s Wild Kingdom Time
Magazine
131





Scientists are also racing against a biological clock.
Species identified to date may represent just 1/10 of the
biological diversity on earth.
And potentially therapeutic creatures are vanishing at
unprecedented rates.
Although the vampire bat is not endangered, 13 other bat
species are.
The natural world is the largest pharmaceutical factory we
have, and a lot of potential benefit is being lost.
Medicine’s Wild Kingdom Time
Magazine
132



Drugs like the synthesized bat spit can earn attractive
returns.
An anticoagulant derived from leach saliva pulled in an
estimated $38 million last year.
And a hypertension drug derived from the venom of the
South American viper drew more than $1 billion in annual
sales before the compounds became available in generic
form in the mid-1990s.
Medicine’s Wild Kingdom Time
Magazine
133





Many animal poisons have the ability to hit specific bull’seyes in the body.
One species of snail, for example, injects its prey with a
poison that paralyzes nerve cells.
The tiny Ecuadorian Poison Dart Frog secretes a skin toxin
that keeps predators at bay.
Both substances block pain signals to the brain and have
led to experimental pain medications that could be as
potent as morphine but with no risk of addiction.
The poison in puffer fish has also been found to ease the
pain of heroin withdrawal and cancer.
Medicine’s Wild Kingdom Time
Magazine
135



For sheer horror, nothing matches staining of the 8 inch
giant yellow Israel scorpion.
It packs neurotoxins that can cause excruciating pain.
Yet at least one of the hundreds of proteins involved in that
process also has the ability to seek out and find to a
receptor that is abnormally expressed on the surface of
brain tumor cells but not on normal selves.
Medicine’s Wild Kingdom Time
Magazine
138



Last year, to cancer centers began testing a copy of the
protein that was developed from this toxin.
The researchers compared the synthesized protein with a
radioactive isotope and injected it into the brains of clinical
trial patients suffering from a cancer called glioma.
In the brain, they believe, the drug travels straight to the
tumors and kills them without damaging nearby healthy
cells. It's like a guided missile.
Medicine’s Wild Kingdom Time
Magazine
140





Exotic animals and their secretions don't necessarily have
to be lethal to help humans.
One pharmaceutical company hopes to obtain food and
drug administration approval for a diabetes drug derived
from a hormone that Gila monsters secrete while munching
on mice, bird eggs, and other favorite foods.
This substance mimics the human hormone that regulates
insulin, which in turn controls blood sugar.
But unlike the human molecule, which is quickly degraded
by enzymes in the body, the lizard version sticks around for
hours.
And it helps the body regenerate insulin making cells. This
can take us to new levels of blood sugar control.
Medicine’s Wild Kingdom Time
Magazine
141





Despite the promise of animal-based drugs, the path from
the rain forest to the FDA is rough with pitfalls.
For many companies, the biggest challenge has been
figuring out how to develop and produce chemical copies of
naturally occurring substances.
A professor at the University of Southern California School
of medicine in has been developing a cancer drug based on
the venom of the Southern copperhead snake.
With a shoestring budget from public grants, he managed
to coax mammalian cells to make copies of the venom
protein.
But it will be at least a year before a drug is ready for
human testing.
Medicine’s Wild Kingdom Time
Magazine
142




Emerging technologies should help speed the discovery and
development of exotic drugs.
Computerized screening systems, for example, allow
researchers to test experimental compounds against
thousands of potential disease targets simultaneously.
That's important because science has barely scratched the
surface of nature’s therapeutic potential.
There are 10 million organisms out there waging chemical
warfare against each other; the abundance of possible
drugs can not even be imagined.
Medicine’s Wild Kingdom Time
Magazine
143



The problem is that many of these potential remedies are
disappearing before they are even spotted.
Half of the world's plants and animals live in tropical
forests, and most of these species are still unknown.
At the current rate of forest destruction, two thirds of land
dwelling plant and animal species will be extinct by the end
of this century.
Medicine’s Wild Kingdom Time
Magazine
144

The urgency of preserving nature's bounty is not lost on
patients like Duane Rualo. The 24-year-old accounting
student at Cal State Long Beach was diagnosed with
glioma in late 2001 and told he probably would not live
long enough to make it to his fall 2003 graduation. After
surgery and several shots of scorpion venom, his latest
brain scan came up clear of cancer. His doctors can't say
yet how important the scorpion has been to his recovery.
But these days, Rualo pauses when he comes across a
scorpion exhibit at a zoo. “I stop and think:’ Wow, they
may have saved my life’”, he says. And who knows what
other life-saving drugs may be lurking beyond the
scorpions layer, the Gila monsters burrow, and the bats
caves?
Medicine’s Wild Kingdom Time
Magazine
145
New Cures on the Horizon

Now that we know the sequence of the
bases in the DNA of all the human
chromosomes, biologists all over the
world believe this knowledge will result in
rapid medical advances for ourselves and
our children.
New Cures on the Horizon
147


First prediction: Many new medicines tailored to the
individual will be available.
Most drugs are proteins or small chemicals that are able to
interact with proteins. Today's drugs were usually
discovered in a hit or miss fashion, but now researchers
will be able to take a more systematic approach to finding
effective medicines. In a recent search for a menace and
that makes wounds heal, researchers cultured skin cells
with 14 proteins that can cause skin cells to grow. Only
one of these proteins actually made skin cells grow and did
nothing else. They expect this protein to become an
effective drug for conditions such as venous ulcers, which
are skin lesions that affect many thousands of people in
the United States. Tests leading to effective medicines can
be carried out with many more proteins that scientists will
discover by examining the human genome.
New Cures on the Horizon
148
Many drugs potentially have unwanted
side effects. Why do some people and not
others have won or more of the side
effects?
 Most likely, this is because people have
different genetic profiles.
 It is expected that a physician will be able
to match patients to drugs that are safe
or them on the basis of their genetic
profiles.

New Cures on the Horizon
149
One study found that various
combinations of mutations can lead to the
development of asthma. A particular
medicine, called albuterol, is effective and
safe for patients with certain combinations
of mutations and not others.
 This example and others showed that
many diseases are multi-factorial and that
only a genetic profile is able to detect
mutations are causing an individual to
have a disease and how it should be
properly treated.

New Cures on the Horizon
150
Second prediction: A longer and healthier life will be yours.
 Pre-embryonic gene therapy may become routine once we
discovered the genes that contribute to a longer and healthier
lives. We know that the presence of three radicals causes cellular
molecules to become unstable and cells to die. Certain genes are
believed to code for antioxidant enzymes that detoxify free
radicals.
 It could be that human beings with particular forms of these
genes have more efficient antioxidant enzymes, and therefore
live longer. If so, researchers will no doubt be able to locate
these genes and also others that promote a longer, healthier life.
Perhaps certain genetic profiles allow some people to live far
beyond the normal lifespan.
 Researchers may be able to find which genes allow individuals to
live a long time and to make them available to the general public.
Then, many more people would live longer and healthier lives.

New Cures on the Horizon
151

Third prediction: You will be able to design
your children.

Genome sequence data will be used to identify many more
mutant genes that cause genetic disorders than are
presently known.
In the future, it may be possible to cure genetic disorders
before the child is born by adding a normal gene to any
egg that carries a mutant gene.
Or an artificial chromosome, constructed to carry a large
number of corrective genes, could automatically be placed
in eggs.
In vitro fertilization would have to be utilized in order to
take advantage of such measures for current genetic
disorders before conception.



New Cures on the Horizon
152
Genome sequence data can also be used
to identify genes for traits such as height,
intelligence, or behavioral characteristics.
 A couple could decide on their own which
genes may wish to use to enhance a
child's phenotype.
 In other words, the sequencing of the
human genome may bring about a
genetically just society, in which all types
of genes would be accessible to all
parents.

New Cures on the Horizon
153
155
Finished!
Congratulations!
156