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                  Case Study: Gene, gene cloning and biotechnology
Key Concept:

    Overview of Gene and Nucleic Acids
    Structure of DNA, DNA Sequences and Restriction Enzyme
    Introduction of Gene Cloning, Genetic Engineering and Biotechnology
    Ethnical, social and economical issues in Biotechnology and Gene Therapy

Materials Preparation:

    Prior to the class, search information, such as news articles relating to gene, gene
     cloning and biotechnology.

Suggested activities:

1.   Have a class discussion about genes. Explain that genes are inherited from parents
     and are important because they determine much about behavioral, mental, and
     physical traits. Every gene contains a DNA (deoxyribonucleic acid) code that gives
     the cell instructions about how to make specific proteins. These proteins form the
     basis for the structural framework of life.


2.   Encourage students to discuss on the following:
     1.   Issues on the new genetic research – students may write their ideas on a large
          sheet of newsprint, discuss cloning animals, using DNA in criminal
          investigations, or gene therapy for some types of genetic diseases and cancer.
     2.   Issues on biotechnology, gene cloning and genetic engineering. For example,
          the technology may allow a 60-year-old woman to have a baby. Is that a
          positive or negative outcome? Consider its ramifications.

3.   It took scientists 277 attempts to clone a normal, healthy sheep (Dolly). But what
     happened to the other 276 sheep? Encourage students to research these previous
     attempts and ask them to think about the consequences of cloning.

4.   Have students brainstorm the risks and benefits associated with biotechnology. For
     example, the removal of hemophilia or other serious disorders from the gene pool is
     a benefit because people would no longer suffer from a chronic condition. An
     example of a risk is going too far in selecting the genetic makeup of future children.

     Possible risks:

          Selection of the genetic makeup of future children. This practice may give
           people the power to control some personal traits, such as having blond hair or
           being tall. Taken to an extreme, this could eliminate some traits.
          Using biotechnology before exploring other options, particularly in
           reproductive medicine. For example, technology enables scientists to implant
           an egg from one woman into the uterus of another. But it may not be a good
           idea to use this technique before trying less extreme techniques first.


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    Possible benefits:

         Eliminating genetic diseases. For example, geneticists think it may be possible
          to eliminate genetic diseases such as Tay-Sachs through careful and
          methodical screening programs.
         Screening unborn babies. This refers to screening for genetic disorders either
          before a pregnancy takes place or in the early months of a pregnancy. More
          information would give prospective parents more options in dealing with their
          infants’ problems.
         Treating diseases. For example, scientists are working on ways to insert cells
          from embryos into cancerous cells as a way to stop the growth of cancer.

 Reference:
1. http://www.accessexcellence.org/AE/AEPC/BE02/gentest/fail15.html? Cloning
     Genetic Science Learning Center “Teacher resources” –
     (http://gslc.genetics.utah.edu/teachers/)
2. Biotechnology – (www.zoo.ufl.edu/PCB3063/biotech handout.pdf)
3. Molecular Genetics –
     (http://fig.cox.miami.edu/~cmallery/150/gene/mol_gen.old.htm)
4. Cloning Fact Sheet –
     (http://www.ornl.gov/sci/techresources/Human_Genome/elsi/cloning.shtml#whatis)
5. What is Biotechnology – (www.aitc.ca/bc/media/BioTechS1.pdf)
6. Biotech Kids Carnival – (http://www.swmed.edu/stars/resources/stock02/Riddle.doc)
7. AACAES : Educators : Science Activities –
     (http://www.uga.edu/discover/educators/environmental_science/activities/qcc34.ht
     ml) / (http://www.uga.edu/discover/educators/applied_bio_chem_2/all/all10.html)
8. Isolation DNA – (http://fog.n4h.org/f33.htm)
9. A Feast For Our Future –
     (http://www.accessexcellence.org/AE/AEPC/WWC/1992/transgenic_food.html)


   Prepare notes and questions to be discussed before the session:

     Level of difficulties:
     [1] Prior concepts
     [2] Essential concepts
     [3] Big and global concepts




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1.   Discovery of inheritance [1]

                        The mechanism of inheritance was discovered by Gregor Mendel
                        (1822-1884), an Austrian monk who crossed different pea plants
                        and noted the manner in which different characteristics of coloring,
                        of seed appearance, of length of stem were developed. This led to
                        the proposal of “the Mendelian laws of inheritance.” However, he
                        did not know the factors responsible for inheritance.


                        For details, visit:
                        Gregor Mendel –
                        (http://www.accessexcellence.org/RC/AB/BC/Gregor_Mendel.html)

                        (Photo adapted from:
                        http://tidepool.st.usm.edu/crswr/103inheritance.html
                        http://www.uwinnipeg.ca/~simmons/cm1503/mendel.htm)




     In the early twentieth century, it became clear
     the factors were something called “genes”
     which were found in chromosomes in the
     nucleus of a cell. [Now, it is known that genes
     are made up of deoxyribonucleic acid (DNA)
     packaged in compact units in chromosomes.
     One strand of DNA, approximately 3 meters
     long, contains many genes. All these genes
     give instructions for how to make and operate
     the parts in our body.]                         (Photo adapted from:
                                                     http://www.toyama-
                                                     mpu.ac.jp/ph/yakka/research/p3.html)
2.   Gene and nucleic acids

    In 1869, Friedrich Miescher, a German chemist, found a “new” class of acid substance from
     pus cells (also salmon sperm heads) that was not carbohydrate, lipid, or protein. (At that
     time, organic substances were classified into these three broad groups.) Since the substance
     was isolated from nuclei, it was later named nucleic acid.

    In around 1910, it was found that nucleic acid contained two purines adenine (A) and
     guanine (G), and two pyrimidines, thymine (T) and cytosine (C), all in equimolar amounts.
     These are called bases.


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    In the mid twentieth century, both circumstantial and direct evidence suggested the role of
     deoxyribonucleic acid (DNA) in heredity. It is now known that DNA is the genetic material
     except in the case of certain viruses which do not contain DNA. In such viruses the genetic
     information is contained in ribonucleic acid (RNA).

    All nucleic acids contain three components: a base and a sugar with a phosphate attached to
     it. RNA differs from DNA in two major aspects: (a) RNA contains uracil instead of
     thymine, and (b) the sugar is a ribose instead of a deoxyribose.

    Now it is clear that a gene is a DNA sequence. A gene is a linear sequence of DNA that
     contains all information necessary for the production of a protein and different types of
     RNA.

     In human, there are 46 chromosomes (22 pairs of autosomal chromosomes and 2 sex
     chromosomes, X and Y). They house almost 3 billion base pairs of DNA that contains
     about 30,000 - 40,000 protein-coding genes. The coding regions make up less than 5% of
     the genome (the function of the remaining DNA is not clear) and some chromosomes have
     a higher density of genes than others.


3.   Structure of DNA [1]

     In 1953, Wilkins, MHF and associates               O
                                                                P
                                                                        OH

     based on their x-ray diffraction (a            -
                                                        O               O                                                                   HO
                                                                        H2C
     technique that enable molecular                                                    O               T               A
                                                                                                                                        O
     biologists to construct the 3-dimensional                  O               O
                                                                                                                                            CH2
                                                                                                                                                            -
                                                                                                                                                    O           O
     structure of a molecule) study proposed                -
                                                                        P
                                                                                                                                                        P
                                                                O               O
                                                                                                                                                    O
     that a DNA molecule contained helical                                      H2C
                                                                                                                                                            O
                                                                                            O                   G               C
     chains, like a twisted ladder. In the same                                                                                             O
                                                                                                                                                CH2
     year, Watson JD and Crick FHC, based                               O           O
                                                                                                                                                        O           -
                                                                                                                                                                        O
                                                                                P
     on     their    and    other     scientists’                   -
                                                                        O           O
                                                                                                                                                        O
                                                                                                                                                            P
                                                                                                                                                                    O
     biochemical findings, proposed the                                             H2C
                                                                                                O           C               G
                                                                                                                                                O
     double-helix model of DNA in which A                                                                                                               CH2
                                                                                O       O                                                                                   -
     paired specifically with T, and G with C.                                      P
                                                                                                                                                            O                   O
                                                                            -
                                                                                O       O                                                                           P
     The means that the two strands are                                                 H2C
                                                                                                                                                            O               O
                                                                                                                    A               T
     complimentary and that the nucleotide                                                          O
                                                                                                                                                    O
                                                                                                                                                            CH2
     sequence on one strand determines that                                             HO                                                                      O
                                                                                                                                                                                    -
                                                                                                                                                                                        O
     on the other.                                                                                                                                                      P
                                                                                                                                                            OH                      O




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     Some basic features of DNA and RNA

     DNA
          a double stranded helix
          “rungs’ in the ladder of the helix joined together by hydrogen bonds
          phospodiester linkages between 5’ & 3’ ends of nucleotides; 5’ 3’ direction
          contains deoxyribose sugar
          contains A, T, C, G nucleotides
          found in the nucleus of cells; some is found in the mitochondria

     RNA
          primarily a single stranded molecule
          linked by the same type of phosphodiester bonds that join DNA together; 5’ 3’
           direction
          contains ribose sugar
          contains A, U, C, G nucleotides
          3 types of RNA – messenger, ribosomal & transfer (mRNA, rRNA, tRNA)
          found in the cytoplasm; however it is manufactured in the nucleus, so some is found
           there

     Most naturally occurring DNA molecules are so long that to determine the sequence of the
     whole molecule in one operation would be unthinkable. For example, there are about 4 x
     106 base pairs in the entire genetic content of Escherichia coli (E. coli), an intestinal
     bacterium.

     (For detail about DNA, genes and chromosomes visit: Tour of the Basic
     (http://gslc.genetics.utah.edu/units/basics/tour/)

4.   DNA sequencing [2,3]

     In order to decode the secret information stored in a DNA molecule, it is necessary to find
     out the sequence of bases in it. Because DNA is such a long molecule, how do we know
     where is the head? Where is the tail? Fortunately, there are restriction endonucleases which
     cleave DNA at specific base sequence they recognize, hence named restriction enzymes. An
     endonuclease is a pair of DNA scissors that catalyzes (hydrolytic) cleavage of a DNA
     molecule at specific base sequence.

     For example, HaeIII, a restrict enzyme, cleaves in the middle of the
     sequence …..GG↓CC….. and no where else. BamHI makes a cut at G↓GATCC and PstI at
     CTGCA↓G. Whenever this sequence occurs, this enzyme will make a cut. At present,
     hundreds of restriction enzymes have been isolated and many of them are commercially
     available. By using different enzymes (or enzyme combinations), we can obtain pieces of
     shorter DNA fragments. By arranging these fragments, we can deduce the base sequence in
     a DNA molecule.




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5.   Why do bacteria produce restriction enzymes? [2,3]

     Restriction enzymes are found in a wide variety of microorganisms and play vital defense
     role in bacterial cells. We know that viruses can infect a bacterial cell, if the cell contains a
     set of restriction enzymes that cut up foreign viral DNA into pieces and destroy it as soon as
     it enter the cell. The entry of such DNA would be “restricted.” Bacterial cells contain
     special chemically modified DNA to prevent the attack on the host DNA.

6.   What is polymerase chain reaction (PCR)? [1,2]

     DNA polymerase is an enzyme that is able to replicate a DNA molecule in the cell nucleus.
     Replication of DNA requires DNA polymerase, a primer and nucleotides. PCR is a
     technique that is designed based on the DNA replication in cells to amplify the number of
     copies of a specific DNA sequence (or a gene) through cycles of denaturation (breaking the
     helix into separate chains) and replication in a test tube.

     Kary Banks Mullis was the inventor of PCR. For his invention of the PCR method, he won
     The Nobel Prize in Chemistry 1993. PCR is a key technique in molecular biology and
     biomedical fields that permits the analysis of any pieces of a short sequence of DNA
     without having to clone it. Before the invention of PCR, amplifying of genes or DNA was
     done in bacteria, and took weeks. But now with PCR, it takes only a few hours.

     Three steps are involved in a PCR. These 3 steps are repeated for 35 or 45cycles. The cycles
     are done in a machine called PCR machine or a thermo-cycler, which rapidly heats and
     cools the test tubes containing the reaction mixture.

     The 3 steps for one cycle take place at different temperatures and they are:

     1.   Denaturation:

          At 94°C, heat breaks the hydrogen bonds and the double-stranded DNA melts and
          opens into single-stranded DNA.

     2.   Annealing:

          At 54°C, hydrogen bonds form between the "primer" and the single-stranded DNA
          from samples. Primer is a short single-stranded DNA with known sequence designed
          by scientists to amplify a particular gene. The single-stranded DNA from samples is a
          template that provides the pattern to be copied. Since the number of primers is more
          than that of the long complimentary strand of the DNA, primers form hydrogen bonds
          with the single-stranded DNA from samples more easily than the long complimentary
          strand .We call this step as annealing.




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     3.   Extension:

          After the annealing, the enzyme polymerase attaches to this double-stranded structure
          and starts copying the template. At 72°C, the polymerase works best.

     PCR is widely used in the biochemistry and molecular biology research, DNA
     fingerprinting and DNA sequencing.

     For animation of PCR in the Internet, visit:
     i. RT-PCR Methodology –
          (http://www.bio.davidson.edu/courses/Immunology/Flash/RT_PCR.html)
     ii. PCR animated – (http://users.ugent.be/~avierstr/principles/pcrani.html
     iii. Internet Resources –
          (http://www.woodrow.org/teachers/esi/2002/Biology/Projects/p3/pcrinternet.htm)

7.   What is gene cloning? [1]

     A clone is a population of organisms that are genetically the same as they are derived from a
     single ancestor. For example, all of the bacteria in a colony on a culture plate are clones
     because they were derived from a single bacterium. To clone a gene generally means to use
     organisms to generate, through genetic engineering techniques, many copies of the specific
     gene in question or interest.

     Reference:
     i.   Gene Cloning – (http://www.lsic.ucla.edu/ls3/tutorials/gene_cloning.html)
     ii. Gene Cloning (animation) – (http://croptechnology.unl.edu/download.cgi)
     iii. Human Cloning –
          (http://www.bbc.co.uk/science/genes/gene_safari/clone_zone/human_cloning.shtml)

8.   How is a gene cloned? [2]

     First, with the help a restrict enzyme, one can isolate a DNA sequence containing a gene.
     Next, is to insert the gene into a vector (a carrier that would carry the gene into a host cell).
     The most commonly used vectors are plasmids or bacteriophages because they can replicate
     independently in a host cell, usually a bacterium like E.coli..

     Gene Cloning Animation –
     (http://www.mybiology.com/archive_movies/dna_tech_movies.htm)

9.   Since one can make copies of a DNA fragment by PCR, why do we still need to clone a
     gene? [2,3]

     PCR can only make copies of a small DNA fragment, but a gene is a very large fragment.
     So, it would be very difficult (or inefficient) when compared to what a cell can accomplish.
     Imagine if one wishes to obtain a large quantity of a particular protein (enzyme), one can
     simply insert the gene into bacteria to generate many copies of the gene. Also, they would
     do protein synthesis and we can collect the protein of interest later.


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         PCR Animation:
            http://www.lsic.ucla.edu/ls3/tutorials/gene_cloning.html
            http://www.people.virginia.edu/~rjh9u/pcranim.html
            http://www.abpischools.org.uk/resources/poster-series/pcr/pcranim.asp
            http://www.rvc.ac.uk/Extranet/DNA_1/7_PCR.htm
            http://www.mybiology.com/archive_movies/dna_tech_movies.htm

    10. What is genetic engineering? [1]

         By definition, genetic engineering is a scientific alteration of the structure of genetic
         material in a living organism. It involves the production and use of recombinant DNA and
         has been employed to create bacteria that synthesize insulin and other human proteins.
         Therefore, genetic engineering is a process that alters the genetic makeup of an organism.
         This technique provides remarkable opportunities to make a large quantity of protein,
         insulin for example, and to develop new medical procedures to treat diseases. In addition to
         revolutionizing some medical treatments, genetic engineering has much impact on food
         production, fuel industries, mining and pollution control. It has been said, the effects of
         genetic engineering to biotechnology is similar to microchips to information technology.

         Reference:
         i.   Say no to genetic engineering –
              (http://www.greenpeace.org/international/campaigns/genetic-engineering)
         ii. Genetic engineering and its danger –
              (http://online.sfsu.edu/~rone/GEessays/gedanger.htm)
         iii. Genetic Engineering – look ma! no math! –
              (http://www.eurekascience.com/ICanDoThat/gen_eng.htm)
         iv. Human Cloning and Genetic Engineering – (http://www.biofact.com/cloning/)

    11. What is biotechnology? [1]

         Biotechnology is the application of biological principles, organisms and products to
         perform specific industrial or manufacturing processes. Some economists define it as the
         use of biological organisms for commercial ends. Biotechnology is not a new technology;
         brewing of beer, fermentation of wine, and production of cheese is almost as old as human
         civilization. In brewing, carbohydrates from a variety of agricultural products (rice, wheat,
         potato, etc) are subjected to fermentation usually by yeast to produce alcohol. Soy sauce has
         been produced by microbial fermentation of soybean for hundred of years.

         Since the early 1970’s, biotechnology has received a significant boost from the introduction
         of a number of powerful new techniques known collectively as genetic engineering. These
         techniques allow biological scientists to alter the genetic structure of organisms by adding
         new genes/removing some existing genes that allow the organism to perform new functions.
         Genetic engineering together with other ways of manipulating and using biological
         organisms has provided new opportunities with profound implications for a wide range of
         commercial activities, from agriculture to pharmaceuticals, chemicals, food and industrial
         to processing, and mining.

         Reference:
          Biotech Timeline - (http://www.ncbiotech.org/biotech101/timeline.cfm)
          Biotech – (http://bioweb.wku.edu/courses/BIOL115/Wyatt/Biotech/Biotech2.htm)
          Food Biotechnology - http://ific.org/food/biotechnology/index.cfm


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12. Applications of biotechnology in medicine [3]

     One type of diabetes (insulin-dependent diabetes) is due to lack of insulin. Insulin acts on
     certain cells (e.g. muscle cells) in our body to increase the entry of glucose into them and
     this lowers the level of glucose in the blood. Insulin-dependent diabetes is treated by regular
     injections of controlled amounts of insulin that serve to bring the insulin levels in the blood
     to normal. This treatment requires a large quantity of insulin. The demand for insulin is
     increasing rapidly because of the steady increase in diabetic patients. Until recently, the
     supply was obtained from the pancreas (an organ that produces insulin) of cows or pigs.
     This involves tedious isolation procedures. Moreover, if the insulin is contaminated, this
     could be life threatening. Pharmaceutical companies saw the potential of this large and
     lucrative market and attempted to produce insulin less costly and more efficiently.

     Some medical products of genetic engineering
      Product                       Application and production source
      Human insulin                 Therapy for diabetics; produced by E. coli*
      Interferon (alpha)            Possible treatment for cancer and viral diseases; produced
                                    by E. coli
      Hepatitis B vaccine           Prevent hepatitis B; produced by certain yeast that carries a
                                    fragment of hepatitis virus gene
      Taxol                         Plant product used for treatment for ovarian cancer;
                                    produced by E. coli
      Human growth factor           Correct growth defects in children; produced by E. coli
      Relaxin                       Ease childbirth; produced by E. coli
     (*E. coli is used to make most of these products because it is much less harmful and can
     readily culture in a laboratory.)

     Biotechnology can also be applied to cure diseases, and the procedure is known as gene
     therapy. Gene therapy is a biotechnological technique for correcting defective genes with
     healthy genes.

     For more information about gene therapy, visit:
     http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml#whatis

13. Application of biotechnology in agriculture [3]

     Development of higher-yield crops, particularly rice and wheat, to satisfy the nutrition
     needs of people of the less developed countries and to feed an ever-growing world
     population had been put into action for many decades. The first wave of high-yield crops
     came about through traditional cross breeding method – using knowledge gained from
     Mendelian genetics to identify and select strains of crops that exhibit desirable
     characteristics. However, there are still some disadvantages in the use of high-yield crops.
     They generally required more fertilizer, more pesticide and herbicide treatments and better
     irrigation. In short, more costly. Today, biotechnology has been applied to identify, select
     and create strains that are more resistant to insects and drought and even strains that can
     produce more nutrients (vitamins).


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     Some medical products of genetic engineering
      Product                 Application and production source
      Ice-minus bacteria      Lacks normal protein product that initiates undesirable ice
                              formation on plants; produced by P. syringae
      Insect toxin producing Has toxin-producing gene inserted from B. thuringiensis;
      bacteria                toxin kills root-eating insects that ingest bacteria
      B. thuringiensis cotton Plans have toxin-producing gene from B. thuringiensis;
      and corn                toxin kills insects that eat plants
      Pork and beef growth Improve weight gain in pigs and cattle; produced by E. coli
      hormones
      Cellulase               Enzymes that degrade cellulose (a complex carbohydrate
                              that is very difficult to digest) to make animal feedstocks:
                              produced by E. coli

14. Application of biotechnology in fuel production [3]

     The availability of energy reserves is getting lower and lower these days. Oil and coal are
     more and more expensive. Countries without energy reserves have to spend a lot of their
     national incomes to purchase energy. Some countries are actively exploring ways to find
     alternative fuels to satisfy the demands, and some turn to biotechnology. One of the success
     stories is the National Programme in Brazil launched in 1974. In Brazil, the most abundant
     material was and still is sugar cane. Much of the sugar cane plant is disposed as waste after
     sugar extraction. These leftovers are fermented to produce alcohol. In 1996, 14.5 billion
     liters, or about 46 percent of the global total ethanol was produced using this procedure.
     Some of alcohol produced is used to fuel cars and commercial vehicles.

15. Estimated worldwide biotechnological markets in 2000 [3]
             Market sector                 US$ (In millions)
             Energy                        15,392
             Foods                         11,912
             Chemicals                     9,936
             Health care (pharmaceuticals) 8,544
             Agriculture                   8,048
             Metal recovery                4,304
             Pollution control             96

     Source: (http://www.accessexcellence.org/RC/AB/IE/Biotech_Industry_Review.html)
     Some ethnical, social and economical issues in biotechnology
     As science continues to push the spectrum of biotechnological possibilities further,
     economic profit for participating sectors and vast improvements in the quality of life for all
     certainly await. However, before the benefits of applying such technology can be realized,
     many scholars insist that the ethical, social and environmental consequences of altering the
     natural genetic code must be thoroughly understood. Some of issues are briefly considered
     below:




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16. Positive and negative issues in food biotechnology [2,3]

     (a)   Positive issues

           With a genetically improved seed, farmers have the ability to reduce expenses, obtain
           higher crop yields, use less pesticide, produce a more nutritious, better tasting crop,
           and provide a longer shelf life and better shipping properties.

           For example, in an era when millions of people starve in third-world countries
           because they cannot produce enough food to sustain life, biotechnology offers a hope
           for the future. It has been hypothesized that in the future, modified seeds will allow
           third-world farmers to continually grow food in areas with poor soil or irrigation by
           developing crops that more efficiently absorb nutrients, also reducing the need for
           costly fertilizers. Biotechnology could also help prevent disease and malnutrition in
           the third-world by producing more healthful crops.

           As a specific example, a strain of "golden rice" that contains high levels of iron and
           beta carotene could be available within a few years, holding uncountable benefit for
           the more than 100 million children who suffer from Vitamin A deficiency.
           Furthermore, research is already in progress on developing fruits and vegetables that
           could distribute life-saving vaccines simply through easily distributed, locally grown
           crops. These are some positive aspects of food biotechnology.

     (b)   Negative issues

           On the other hand, the general public concerns about human allergic reactions to
           altered food, the environment and the use of animal genes in plants. Take allergic
           reaction as an example, the risk of potential allergens (substances causing allergic
           reactions) in a genetically modified food is of particular concern because of the
           possibility of transferring a gene that causes allergic reactions to a new food source,
           without the consumer's knowledge of the transfer. If a gene from a food that
           commonly causes allergic reactions, like in shellfish or peanuts, is inserted into a food
           where people would not expect to find such allergens, then the food could potentially
           harm the consumer. Although regulatory authorities closely monitor its safety, will
           food on the market with said characteristics be labeled; with the information fully
           disclosed to consumers?

           Another common critique of food biotechnology concerns the environmental risks
           involved in producing genetically altered foods. Would growing of the genetically
           modified plant harm the surrounding soil, water, animals or other plants? Also, plants
           and animals with clones genes may grow faster and they may upset the balanced
           ecosystem and reduce the biodiversity.

           Lastly, many consumers are concerned about their health when eating new sources of
           food. Not to mention that some vegetarians “hate” eating genetically modified plants
           with an animal gene.



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17. What is gene therapy? [2,3]

     First discovered in the middle of the 1970’s researchers were able to isolate certain genes
     from DNA. During the 1980’s the term gene therapy came about and propelled research
     further.

     Gene therapy is a technique where the genes causing a defect are themselves substituted by
     “correct” genes in the patient to cure a disease. At birth, each of us receives a set of
     chromosomes that contain the genes that code for our personality, appearance, and long
     term-health. When one of those genes has a mutation or flaw in the DNA structure it can
     lead to disease. Some diseases related to genetic inheritance are diabetes, sickle cell anemia,
     and some cancers. With gene therapy we can eliminate these diseases before they even
     show their first symptom.

18. Positive and negative aspects in gene therapy [2,3]

     (a)   Positive aspects

           The positive aspect of gene therapy is that it can wipe out genetic disease before they
           can begin and eliminate suffering for future generations. Gene therapy is also a good
           technique for diseases not researched yet. All of us carry defected genes and may not
           know it. Gene therapy is a “medicine” for the future since it can control or eliminate
           hereditary diseases.

           In reality, every human carries nearly six defective genes. However, most of us do not
           suffer any harmful effects from our defective genes because we carry two copies of
           nearly all genes, one given to us by our mother and the other from our father.
           Fortunately in most cases, one normal gene is sufficient to avoid all the symptoms of
           disease. Nonetheless, about one in ten people has, or will develop at some later stage,
           an inherited genetic disorder, and approximately 2,800 specific conditions are known
           to be caused by defects (mutations) in just one of the patient’s genes. Some single
           gene disorders are quite common, for example, cystic fibrosis is found in one out of
           every 2,500 babies born in the Western World.

           At present, the method of choice for delivering genes into cells uses the natural ability
           of viruses to deliver genetic material to cells. (Viruses have evolved a way of
           encapsulating and delivering their genes to human cells in a pathogenic manner.)
           Scientists have tried to take advantage of this capability and manipulate the virus
           genome to remove disease-causing genes and insert therapeutic genes. Currently, gene
           therapy has only been approved to treat a limited number of diseases, including
           adenosine deaminase in the US. Nonetheless, despite the low level of approved
           treatments available today, many attempts are concentrating on applying gene therapy
           to treat Parkinson’s disease, Huntington’s disease, thalassaemia, sickle cell anemia,
           leukemia, autism and liver cancer. The future for gene therapy appears bright, as cures
           for many of the most human diseases stand ready to be discovered.
           (http://www.duke.edu/web/mms190/biotech/environmental.html)



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                                                                      Trial Version

Reference:
 Living with a genetic disorder –
     (http://www.nature.ca/genome/03/d/10/03d_14_e.cfm)
 Human Gene Therapy –
     (http://www.ndsu.nodak.edu/instruct/mcclean/plsc431/students/zhou.html
 BIO. "Biotechnology in Perspective." Washington, D.C.: Biotechnology Industry
     Organization, 1990.

(b)   Negative aspects

      Despite promising evidence about the benefits of gene therapy, many hurdles must be
      overcome before applying gene therapy effectively to treat diseases. Some of them are
      due to procedural and/or methodological difficulties.

     Short-lived nature of gene therapy
      Before gene therapy can become a permanent cure for genetic diseases, the inserted
      DNA in target cells must remain functional and the cells containing the inserted DNA
      must be long-lived and stable. However, the rapidly dividing nature of many cells
      prevents gene therapy from achieving any long-term benefits.

     Immune response
      Anytime a foreign object is introduced into human tissues, it may stimulate the
      immune system to generate antibodies to remove them, and this reduces gene therapy
      effectiveness.

     Problems with viral vectors
      Viruses are employed as the carriers in most gene therapy studies, and some potential
      problems associates with this method are: toxicity, immune and inflammatory
      responses, and gene control and targeting issues. In addition, there is always the fear
      that the viral vector, once inside the patient, may recover its ability to cause disease.

     How can one control the expression? The number of genes incorporated? The amount
      of protein synthesized?

     Multigene disorders
      A number of diseases, such as heart disease, high blood pressure, Alzheimer’s disease,
      arthritis, cancer, mental illness and diabetes, are caused by the combined effects of
      variations in many genes. In all these cases, no one gene has the sole yes/no power to
      say whether a person has a disease or not. It is likely that more than one genetic defect
      is required before the disease is manifest, and a number of genes may each make a
      subtle contribution to a person's susceptibility to a disease; genes may also affect how
      a person reacts to environmental factors. Unraveling these complexed and
      complicated networks of events will undoubtedly be a challenge for some time to
      come.




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                                                                           Trial Version

     In conclusion, due to a lack of conclusive evidence proving that genetic treatment has
     produced therapeutic benefits, the future of gene therapy is still highly skeptical at present.
     While the scientists made much progress in DNA technologies in food, medicine and
     energy, perhaps the most important obstacle for further advancement in genetic technology
     is to overcome its social and ethical implications. Each requires personal thought and
     reflection to determine one’s opinion.

     Some ethical and social issues are:
     1.   Do we understand the risks and limitations of genetic technology? Would you trust the
          assessment (or testing) of your doctor or a reputable scientist?
     2.   Where is the line between medical treatment and enhancement?
     3.   If you had your DNA sequence analyzed by a scientist, who owns and controls your
          genetic information? Would you agree if he/she supplied it to an insurance company,
          your (future) employer, or the police?
     4.   Should genetic testing be performed when no therapeutic treatment is available?
     5.   Are GM foods and other products safe to humans and the environment?
     6.   How will these technologies affect developing nations' dependence on the developed
          countries?
     7.   In 1997, the European Commission found it difficult to ignore scientific evidence that
          crops produced through biotechnology are indeed safe. The European Farm
          Commissioner Franz Fischler approved an application to market gene-modified corn
          produced in the United States in Europe, but it must fulfill some labeling conditions.
          Do you think this requirement is reasonable and adequate?
     For more information, visit http://www.fb.org/views/focus/fo97/fo0106.html.
Reference
1. Biotechnology Online - (http://www.biotechnologyonline.gov.au/)
2. Ethical, Legal, and Social issues –
    (http://www.ornl.gov/sci/techresources/Human_Genome/elsi/elsi.shtml)
3. Gene watch – (http://www.genewatch.org/)
4. Introduction to nucleic acids and application to infectious disease detection -
    (http://www.accessexcellence.org/RC/AB/BA/dnaintro/index.html)
5. Debate over GM products and biotechnology -
    (http://www.ornl.gov/sci/techresources/Human_Genome/publicat/hgn/v12n1/06gmpr
    oducts.shtml)
6. Gene therapy for cancer: questions and answers -
    (http://cis.nci.nih.gov/fact/7_18.htm)
7. Gene therapy in simple terms –
    (http://kidshealth.org/parent/system/medical/gene_therapy.html)
8. Scientific issues and social concerns –
    (http://www.dnapolicy.org/genetics/transfer.jhtml;$sessionid$4I4DCIQAACY4WCQ
    BAT3RVQQ)
9. Explain “What is a gene?” “Gene therapy” in simple terms –
    (http://kidshealth.org/kid/talk/qa/what_is_gene.html)
10. Basics on genes and genetic disorders –
    (http://kidshealth.org/teen/your_body/health_basics/genes_genetic_disorders.html)
11. Molecular Genetics –
    (http://www.kensbiorefs.com/MolecularGen.html#anchor194140)
12. Using Genomics – (http://www.nature.ca/genome/index_e.cfm)
See also the block on “Stem cells and their applications”
Animation:
1. Tour of the Basics – (http://gslc.genetics.utah.edu/units/basics/tour/)’
2. DNA Workshop – (http://www.pbs.org/wgbh/aso/tryit/dna/#)


                                                                                         14
                                                      Trial Version

      Local news [3]
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                                           digest 46
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          者》




                                                                 15
                                         Trial Version

Glossary
English                 Chinese
Autism                  孤獨症
Autosomal               常染色體的
Bacteriophage           噬菌體
Biotechnology           生物工程學
Chromosomes             染色體
Denaturation            改變本質
Deoxyribonucleic acid   去氧核糖核酸(簡稱 DNA)
Diabetics               糖尿病
DNA Fingerprinting      DNA 指紋術
Enzyme                  酵
Ethanol                 乙醇,酒精
Fermentation            發酵
Gene Cloning            基因複製
Gene therapy            基因治療
Genes                   遺傳因子
Genetic Engineering     遺傳工程
Genetic research        基因研究
Hemophilia              血友病
Hepatitis B vaccine     B 型肝炎疫苗
Herbicide               除草劑
Inflammation            發炎
Inheritance             遺傳
Mendelian               孟德爾遺傳定律的
Mutation                變種
Nucleic acid            核酸
Parkinson’s disease     帕金森氏病
Pesticide               殺蟲劑
Replication             複製
Ribonucleic acid        核醣核酸
Sickle cell anemia      鐮狀細胞性貧血
Slaughterhouses         屠殺場
Trait                   特徵




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