CHAPTER 4
Molecular Biology in Medicine.
Readings Pages 100 - 130
Key points
• Enhance knowledge of molecular biology
• Understand a range of applications of
molecular biology in medicine, including –
designer drugs, diagnosis of genetic
conditions before and after birth,
production of hormones and plant
vaccines.
• Ethical implications
Molecular Biology in Medicine involves
• knowledge and manipulation of genetic material
• Design and development of drugs to prevent the specific action
of an infective micro-organism
• Design and development of drugs to inhibit the action of specific
chemicals in the body
• Manufacture of compounds for use by people deficient in a vital
chemical, such as a particular hormone
• Development and delivery methods for efficient drug use
Molecular Biology – the beginning
Reading page 101
• Discovery of the link between inheritance and the human
condition, Aklaptonuria (as an inherited disease) in 1902. Sir
Archibald E. Garrod related this condition to a lack of an enzyme
• Oswald Avery: “inherited material was DNA” in 1943
• Watson & Crick – DNA structure discovery 1953
• Today, the role of proteins, not just DNA is increasing in
emphasis
Molecular Biology – testing new borns
Reading pages102-104
Inherited Diseases
• also known as genetic disorders
• exist because of some kind of defect in the code or amount of DNA
Tesing New Borns
• begun in the 1960’s
• Blood from baby’s heel prick laboratory tested for four disorders, three
which are inherited:
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galactosaemia
cystic fibrosis
phenylketonuria
hypothyroidism (not genetic)
Galactosaemia
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Inherited disorder
1 in 40 000 babies
Lacks enzyme that metabolises galactose (product of lactose breakdown)
Build of of galactose fatal
Treatment: feed with formulae not containing galactose
Cystic Fibrosis CF
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Inherited disorder
1 in 2 500 babies
Sufferer produces abnormal secretions
Treatment:
Hypothyroidism
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not an inherited disorder
1 in 3 500 babies
Caused by small or improperly functioning thyroid gland
Untreated: baby brain damage and growth impaired
Early Treatment: normal development
Phenylketonuria – PKU
Reading pages 103-105; Biozone 39
• Is an inherited disease
• Prevelance 1 in 10 000
• Affected person fails to produce the enzyme phenylalanine
hydroxylase
• Prior to 1960: untreated affected person unable to metabolise
phenylalanine to tyrosine
• Build up of phenylalanine causes brain damage
• Testing: today – mass spectrometry
• Treatment: supply of diet free of phenylalanine – results in
normal development
Tasks
Read 105
Biozone 41-42
Quick Check 1-3
Medical Treatments: Gene Therapy
Reading pages 106-107; Biozone 235
Some genetic diseases can’t be treated by diet changes. Why not try to insert a
normal functional gene into cells that contain a defect. Such a procedure is
called gene therapy.
Defn: Gene Therapy
• A medical procedure that modifies the genetic material of living cells of
an individual so that the gentic effect is corrected
Two categories of Gene Therapy
1.
2.
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in vivo gene therapy given directly to a patient
Ex vivo gene therapy (cells manipulated outside the body then reinserted)
functional piece of DNA called a cloned gene
often inserted with use of a vector, such as a virus:
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Retroviruses
Adenoviruses
Tasks
Quick Check 4-7
Medical Diagnosis – prenatal testing
Reading pages 109-114
Genetic tests of unborns include:
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Ultrasound
Chorionic villus sampling (CVS)
Amniocentesis
electrphoresis
Genetic Tests after birth include:
– Presymptomatic testing for; breast cancer & Huntington’s disease
Medical Diagnosis – continued
Ultrasound:
– Technique using sound waves to form an image of internal structures,
including a fetus in its mothers uterus
Chorionic villus sampling (CVS)
– Prenatal process of obtaining a sample of chorion tissue that surrounds a
developing embryo or early fetus and includes cells of embryonic or fetal
origin
Amniocentesis
– Procedure in which a sample of amniotic fluid that surrounds a fetus in
uterus (containing fetal cells) is obtained
Electrophoresis
– Technique for sorting out lengths of DNA fragments through an electric field
Presymptomatic Tests
– DNA-based technique for distinguishing whether a person is ‘at risk’ but
who shows no clinical sign of a given genetic disease
Tasks: Quick Check 8 - 12
Ultrasound:
Technique using sound waves to form
an image of internal structures,
including a fetus in its mothers uterus
Amniocentesis
Procedure in which a sample of amniotic
fluid that surrounds a fetus in uterus
(containing fetal cells) is obtained
Chorionic villus sampling (CVS)
Prenatal process of obtaining a sample of chorion
tissue that surrounds a developing embryo or early
fetus and includes cells of embryonic or fetal origin
Electrophoresis
Technique for sorting out lengths of DNA fragments through an electric field
Presymptomatic Tests
DNA-based technique for distinguishing
whether a person is ‘at risk’ but who shows no
clinical sign of a given genetic disease
Drug Design
Reading page s 114-118
Rational Drug Design
•
essentially involves finding out how the infective agent works against a
cell and using that information to design a drug that prevents the
infective agent from being able to do what it does
Example: Relenza – anti influenza drug
• Neuraminidase, protein on surface of the virus, allows exit of new virus
particles from a cell
• Neuraminidase structure varies between virus strains
• Scientists found a common structural component, which was the active
site
• Computer modelling of the active site was completed
• A drug to bind with the active site was then designed
this technique, in which the active site of a molecule is determined and
a second molecule (the drug) is constructed to fit into the active site to
inhibit the activity of the first molecule, is called rational drug design
Read page 116
Developing Vaccines
Reading page s 117-122
DEFINITIONS
Vaccine
• Suspension of attenuated living or dead micro-organisms that, when
introduced into a person, stimulates the immune system to produce specific
antibodies
Antigens
• Markers on cells or parts of cells that are either self or non-self (which
initiate an immune response)
Antibodies
• Proteins produced by animals (B-Cells) in response to antigens which
react specifically with the antigen,
Pathogen
• Organism or agent able to cause disease
Tasks
Biozone 163-164
Quick Check 13-16
Manufacturing Biological Molecules
Reading pages 123-125
Insulin Production
• role of insulin: hormone that controls uptake of glucose
• DNA sequence coding for insulin (a protein) production well known
• Sequence of DNA can be constructed and inserted into a plasmid vector
• Plasmid inserted into bacteria where they replicate
• Bacteria become insulin factories, secreting insulin
• Insulin is isolated, purified and packaged into vials for diabetics
See figure 4.29 a&b
Growth Hormone Production
• role of growth hormone: growth
• Normally produced by pituitary gland
• Gene can be copied through genetic engineering
Factor VIII Production
• role of Factor VIII: involved in blood clotting (absence causes –haemophilia)
• Gene on X chromosome (much more common in males as it is recessive)
• Factor VIII produced by similar methods to insulin and growth hormone
Drug Delivery by plants
The delivery of vaccines in plant material, as food, is currently being
investigated. To develop such vaccines:
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the molecular structures of proteins in the infective agent that cause the
immune response are determined
•
the DNA that codes for some of these proteins is introduced into the
plant genome
•
the plants are grown and harvested
Example: Japanese research team developed rice that can deliver a
cholera vaccine by genetically altering it to include DNA that codes for
part of the protein of a cholera bacterium (thus initiating an immune
response!)
Drug Delivery by
Nanoparticles
Reading page 125-126
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are manufactured through nanotechnology
1-100 nanometres in diameter, small enough to pass through a cell
membrane
made of a double layer of phospholipids so that they mimic the plasma
membrane
are used to deliver toxic drugs directly to target cells (such as tumour
cells) reducing the chance of affecting healthy cells
three compounds are attached to a dendrimer to be used in cancer
treatment:
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The drug methotrexate (to kill the cancer)
Five molecules of folic acid, a vitamin (attractive to cancer cells!)
A fluorescent stain (allows assessment and monitoring of the process)
Tasks
Quick Check 17-21
Tasks
Biochallenge
Chapter Review