Realised by jl assi ous sama Mini projet d’anglais Mai 2002 Contents o Introduction o What is genetic engineering? o genetic engineering and plants o Genetic engineering and cloning animals o Genetic and current curing applications o Dangers of genetic engineering o Genetic engineering and religion o Conclusion Introduction Genetics is a relatively new area of study. Since the times of the Greeks and Romans, scientists and commoners alike have speculated about inheritance and the resemblances shared between family members, but it was not until the nineteenth century that any legitimate and scientifically based hypotheses were formed. It was in the unlikely realm of a monastery that an Austrian monk by the name of Gregor Mendel touched off the genetic revolution with some seemingly innocent experiments with pea plants. By breeding several generations of peas and recording his findings, Mendel found that each seed contained both hidden and obvious information about its genetic traits.
He referred to these traits as dominant and recessive. Although Mendel’s information proved vital to the start of genetic research, the mechanism of this genetic inheritance was not yet understood. It was not until 1953 that two men named James Watson and Francis Crick discovered the double helix model of DNA, which was found to be the carrier of all of a human’s genetic information. They found that each rung of a DNA ladder consisted of nucleotides. The arrangements of these nucleotides determines which traiwhichts are expressed. Portions of DNA together made up a gene stood for an inherited trait.
... egg, combine their genetic information and a new life is created with the traits from its parents. Genetic engineering is isolating and removing ... of organisms for the next one hundred years following Mendel's discoveries. These early studies concluded that each ... a desired gene from a strand of DNA. In genetic engineering, many ...
These genes made up a chromosome. In an normal human cell there are twenty-three pairs of chromosomes. There were four nucleotide bases that could be present in any given DNA strand: Adenine, Thymine, Cytosine, and Guanine. There are twenty naturally occurring amino acids which are the building blocks of all protein structures in our bodies. That is the mechanism which determines who we are. Scientists are continuing to unravel the mysteries of DNA, which is folded in coiled strands 500 times finer than those of a spider web, but yet are almost six feet long when unfolded.
And with knowledge has come the ability to apply that knowledge in many areas such as farming and medicine in order to cure some dangerous diseases like cancer, emphysema or cystic fibrosis In this work we will deal with the most important applications of genetic engeneering: its definition, its application in the farming field in order to obtain better fruits and vegetables and bigger harvest, its current application for curing people, its relation with cloning and we will quote the example of the famous cloned sheep Dolly, its dangers and some probable solutions and finally we will deal with genetic engeneering specially cloning from a religious corner because this issue has created, during the latest years, a big controversy and the opinions are still different about this subject This subject is bigger than being illustrated by a small mini project because genetic engeneering has still more and more to achieve for the good of the mankind and has so a promising future… o What is genetic engineering? Basic biology: We find it mixed in our food on the shelves in the supermarket — genetically engineered soybeans and maize. We find it growing in a plot down the lane, test field release sites with genetically engineered rape seed, sugar beet, wheat, potato, strawberries and more. There has been no warning and no consultation.
It is variously known as genetic engineering, genetic modification or genetic manipulation. All three terms mean the same thing, the reshuffling of genes usually from one species to another; existing examples include: from fish to tomato or from human to pig. Genetic engineering (GE) comes under the broad heading of biotechnology. But how does it work? If you want to understand genetic engineering it is best to start with some basic biology. What is a cell? A cell is the smallest living unit, the basic structural and functional unit of all living matter, whether that is a plant, an animal or a fungus. Some organisms such as amoebae, bacteria, some algae and fungi are single-celled – the entire organism is contained in just one cell.
... to financial matters. One of the most contentious uses of genetic information is its potential use by insurance companies to determine whether ... the understanding of how a human gene dictates what a cell does in the body. This knowledge of human genetics and ... knowledge of how genes affect the specific tasks of different cells in the human body. The study of this interaction is ...
Humans are quite different and are made up of approximately 3 million cells – (3, 000, 000, 000, 000 cells).
Cells can take many shapes depending on their function, but commonly they will look like a brick with rounded comers or an angular blob – a building block. Cells are stacked together to make up tissues, organs or structures (brain, liver, bones, skin, leaves, fruit etc. ).
In an organism, cells depend on each other to perform various functions and tasks; some cells will produce enzymes, others will store sugars or fat; different cells again will build the skeleton or be in charge of communication like nerve cells; others are there for defence, such as white blood cells or stinging cells in jelly fish and plants. In order to be a fully functional part of the whole, most cells have got the same information and resources and the same basic equipment.
A cell belonging to higher organisms (e. g. plant or animal) is composed of: o a cell MEMBRANE enclosing the whole cell. (Plant cells have an additional cell wall for structural reinforcement. ) o many ORGANELLES, which are functional components equivalent to the organs in the body of an animal e. g.
for digestion, storage, excretion. o a NUCLEUS, the command centre of the cell. It contains all the vital information needed by the cell or the whole organism to function, grow and reproduce. This information is stored in the form of a genetic code on the chromosomes, which are situated inside the nucleus. Chromosomes means “coloured bodies” (they can be seen under the light microscope, using a particular stain).
They look like bundled up knots and loops of a long thin thread.
Chromosomes are the storage place for all genetic – that is hereditary – information. This information is written along the thin thread, called DNA. “DNA” is an abbreviation for deoxyribo nucleic acid, a specific acidic material that can be found in the nucleus. The genetic information is written in the form of a code, almost like a music tape. To ensure the thread and the information are stable and safe, a twisted double stranded thread is used – the famous double helix. When a cell multiplies it will also copy all the DNA and pass it on to the daughter cell.
... Why is confidentiality critical when managing information? Section 3 – Understand the purpose of producing documents that are fit for ... purpose of agreeing objectives and deadlines when researching information. If possible, refer to specific examples from research ... the benefits to businesses (and others) of using information technology for doing work tasks? Spreadsheet provides accurate calculation ...
The totality of the genetic information of an organism is called genome. Cells of humans, for example, possess two sets of 23 different chromosomes, one set from the mother and the other from -the father. The DNA of each human cell corresponds to 2 meters of DNA if it is stretched out and it is thus crucial to organise the DNA in chromosomes, so as to avoid knots, tangles and breakages. The length of DNA contained in the human body is approximately 60, 000, 000, 000 kilometres.
This is equivalent to the distance to the moon and back 8000 times! The information contained on the chromo-somes in the DNA is written and coded in such a way that it can be understood by almost all living species on earth. It is thus termed the universal code of life. In this coding system, cells need only four symbols (called nucleotides) to spell out all the instructions of how to make any protein. Nucleotides are the units DNA is composed of and their individual names are commonly abbreviated to the letters A, C G and T These letters are arranged in 3-letter words which in turn code for a particular amino acid. The information for how any cell is structured or how it functions is all encoded in single and distinct genes. A Gene is a certain segment (length) of DNA with specific instructions for the production of commonly one specific protein.
The coding sequence of a gene is, on average about 1000 letters long. Genes code for example for insulin, digestive enzymes, blood clotting proteins, or pigments. How does a cell know when to produce which protein and how much of it? In front of each gene there is a stretch of DNA that contains the regulatory elements for that specific gene, most of which is known as the promoter. It functions like a “control tower,” constantly holding a “flag” up for the gene it controls. Take insulin production (which we produce to enable the burning of the blood sugar).
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When a message arrives in the form of a molecule that says, ‘more insulin”, the insulin control tower will signal the location of the insulin gene and say “over here.” The message molecule will “dock in” and thus activate a “switch” to start the whole process of gene expression.
How does the information contained in the DNA get turned into a protein at the right time? As, each gene consists of 3 main components: a “control tower” (promoter), an information block and a polyA signal element. If there is not enough of a specific protein present in the cell, a message will be sent into the nucleus to find the relevant gene. If the control tower recognises the message as valid it will open the “gate” to the information block. Immediately the information is copied – or transcribed – into a threadlike molecule, called RNA. RNA is very similar to DNA, except it is single stranded. After the copy is made, a string of up to 200 “A”-type nucleotides – a polyA tail – is added to its end.
This process is called poly-adenylation and is initiated by a polyA signal located towards the end of the gene. A polyA tail is thought to stabilise the RNA message against degradation for a limited time. Now the RNA copies of the gene leave the nucleus and get distributed within the cell to little work units that translate the information into proteins. No cell will ever make use of all the information coded in its DNA. Cells divide the work up amongst one other – they specialise. Brain cells will not produce insulin, liver cells will not produce saliva, nor will skin cells start producing bone.
If they did, our bodies could be chaos! The same is true for plants: root cells will not produce the green chlorophyll, nor will the leaves produce pollen or nectar. Furthermore, expression is age dependent: young shoots will not express any genes to do with fruit ripening, while old people will not usually start developing another set of teeth (exceptions have been known).
All in all, gene regulation is very specific to the environment in which the cell finds itself and is also linked to the developmental stages of an organism. So fl want the leaves of poppy plants to produce the red colour of the flower petals I will not be able to do so by traditional breeding methods, despite the fact that leaf ells will have all the genetic information necessary. There is a block that prevents he leaves from going red. This block may be caused by two things: o The “red” gene has been permanently shut down and bundled up thoroughly in all leaf cells.
... genes with correct information into the DNA of the cells that contain malfunctioning genes. Adding genes in this way is called gene insertion. The added genetic information allows these cells ... Human Gene Therapy "To much of the general public, genetic engineering is a vague notion of high tech manipulation of plants and animals. Its ...
Thus the information cannot be accessed any more. o The leaf cells do not need the colour red and thus do not request RNA copies of this information. Therefore no message molecule is docking at the “red” control tower to activate the gene. against its own will. We Of course – you might have guessed – there is a trick to fool the plant and make it turn red can bring the red gene in like a Trojan horse, hidden behind the control tower of a different gene. But for this we need to cut the genes up and glue them together in a different form.
And here genetic engineering begins Genetic engineering: Genetic engineering (GE) is used to take genes and segments of DNA from one species, e. g. fish, and put them into another species, e. g. tomato. To do so, GE provides a set of techniques to cut DNA either randomly or at a number of specific sites.
Once isolated one can study the different segments of DNA, multiply them up and splice them (stick them) next to any other DNA of another cell or organism. GE makes it possible to break through the species barrier and to shuffle information between completely unrelated species; for example, to splice the anti-freeze gene from flounder into tomatoes or strawberries, an insect-killing toxin gene from bacteria into maize, cotton or rape seed, or genes from humans into pig. Yet there is a problem – a fish gene will not work in tomato unless I give it a promoter with a “flag” the tomato cells will recognise. Such a control sequence should either be a tomato sequence or something similar. Most companies and scientists do a shortcut here and don’t even bother to look for an appropriate tomato promoter as it would take years to understand how the cell’s internal communication and regulation works.
In order to avoid long testing and adjusting, most genetic engineering of plants is done with viral promoters. Viruses – as you will be aware – are very active. Nothing, or almost nothing, will stop them once they have found a new victim or rather host. They integrate their genetic information into the DNA of a host cell (such as one of your own), multiply, infect the next cells and multiply. This is possible because viruses have evolved very powerful promoters which command the host cell to constantly read the viral genes and produce viral proteins. Simply by taking a control element (promoter) from a plant virus and sticking it in front of the information block of the fish gene, you can get this combined virus / fish gene (known as a “construct’) to work wherever and whenever you want in a plant.
... affected with Tay-Sachs Disease. Tay-Sachs Disease is a recessive genetic disorder which contains harmful ... quantities of fatty substances called Ganglioside GM2 which harms the nerve cells ... in the brain. This disease ...
This might sound great, the drawback though is that it can’t be stopped either, it can’t be switched off. The plant no longer has a say in the expression of the new gene, even when the constant involuntary production of the “new” product is weakening the plant’s defences or growth. And furthermore, the theory doesn’t hold up with reality. Often, for no apparent reason, the new gene only works for a limited amount of time and then “falls silent.” But there is no way to know in advance if this will happen. Though often hailed as a precise method, the final stage of placing the new gene into a receiving higher organism is rather crude, seriously lacking both precision and predictability.
The “new” gene can end up anywhere, next to any gene or even within another gene, disturbing its function or regulation. If the “new” gene gets into the “quiet” non-expressed areas of the cell’s DNA, it is likely to interfere with the regulation of gene expression of the whole region. It could potentially cause genes in the “quiet” DNA to become active. Often genetic engineering will not only use the information of one gene and put it behind the promoter of another gene, but will also take bits and pieces from other genes and other species.
Although this is aimed to benefit the expression and function of the “new” gene it also causes more interference and enhances the risks of unpredictable effects. How to get the gene into the other cell? : There are different ways to get a gene from A to B or to transform a plant with a “new” gene. A VECTOR is something that can carry the gene into the host, or rather into the nucleus of a host cell. Vectors are commonly bacterial plasmids or viruses (a).
Another method is the “SHOTGUN TECHNIQUE” also known as “bio-ballistics,” which blindly shoots masses of tiny gold particles coated with the gene into a plate of plant cells, hoping to land a hit somewhere in the cell’s DNA (b).
What is a plasmid? PLASMIDS can be found in many bacteria and are small rings of DNA with a limited number of genes. Plasmids are not essential for the survival of bacteria but can make life a lot easier for them. Whilst all bacteria – no matter which species – will have their bacterial chromosome with all the crucial hereditary information of how to survive and multiply, they invented a tool to exchange information rapidly. If one likens the chromosome to a bookshelf with manuals and handbooks, and a single gene to a recipe or a specific building instruction, a plasmid, could be seen as a pamphlet. Plasmids self-replicate and are thus easily reproduced and passed around.
Plasmids often contain genes for antibiotic resistance. This type of information which can easily be passed on, can be crucial to bacterial strains which are under attack by drugs and is indeed a major reason for the quick spread of antibiotic resistance. o Genetics and plants: The advance of the introduction of genetic engineering in farming: Farming was revolutionized with the introduction of new equipment such as tractors and ploughs. By crossbreeding the farmers are able to get rid of unwanted characteristics and while keeping the ones that they desire. However, genetic engineering holds the next great change for this industry. Perhaps the most widespread influence of genetic manipulation on farming techniques will be in the plant world.
Plants are naturally more susceptible to genetic manipulation than animal cells. Why? Because for many species a whole adult plant can be generated from a only single cell grown in tissue culture! Controlling and predicting the outcome of inserting foreign genes into only a single cell is easier than when dealing with a whole organism. This transfer of characteristics makes better functioning crops. One example of this is the “Flavor Save” tomato, which seems to have overcome the problem that grocery stores have with the ripening season; this genetically engineered tomato has a longer shelf life as the ripe phase lasts significantly longer before the rotting begins.
However, even with this extra longevity there are some negative side effects that must be worked out. An example of this is a decline in the quality of taste, which would definitely outweigh the benefits of a long shelf life! Here are some examples of “new” plants that are being developed: wheat, cotton and soybeans that are resistant to the herbicides that farmers use to control weeds, and strains of corn, cotton, and potatoes that resist invasion by dangerous insects. Other advances in genetic engineering have made it possible to decrease the need for fertilizer by breeding plants that produce their own form of efficient fertilizers. Farmers are looking for a greater crop yield while having to plant fewer crops. These are only a few of the many advances and prospects that genetic engineering holds for agriculture. Genetically modified organisms in agriculture: A genetically modified organism, or GMO, is any life form which has been subjected to genetic engineering.
In other words, it is an organism into which a gene has been artificially introduced or from which a gene has been artificially removed. The purpose of this is to introduce new traits into such an organism, be it a bacterium, a plant or an animal. The gene, such as one which would confer disease resistance to a crop, could be derived from any organism and this is where the novelty, and the power, of the technique come in. Normally new traits are acquired by conventional breeding and selection, and would thus be limited to organisms capable of fertilizing each other. This is therefore normally to members of the same species. In the production of GMOs, such specie barriers are overcome.
However, this is not to imply that we are capable of creating monsters in the laboratory! Whereas breeding and selection is a rather hit-or-miss affair and it might take many generations to achieve the desired results, genetic engineering is an extremely precise technique and only the gene (s) required to achieve a given trait is introduced. What is the value of GMOs to agriculture? Let us first consider crops. Some of the most significant improvements are in the production of plants resistant to insect, bacterial and fungal infections. The most prevalent in use, both here and abroad, is resistance to herbivorous insects due to a highly specific toxin. The gene for the toxin is derived from a soil bacterium and the toxin has no effect on mammals or non-target insects. Another trait in commercial use is resistance to herbicides or weed killers.
In South Africa about 2% of the current yellow maize crop is planted with GMOs resistant to maize borers. Other GMOs of interest to agriculture include bacteria with improved nitrogen fixing abilities, crops with improved yields, fruit with increased shelf life, and animals with leaner meat production. It is estimated that the benefits that accrued to farmers in the USA due to transgenic crops in 1997 amounted to $366 million. Example of a world- known corporation practising genetic engeneering: All over the world many farming corporations have introduced the genetic manipulation in their working methods because it brings for them many advances and benefits. For many farmers hoping for a haelthy harvest, the best place to turn is “Monsanto Corp”, which is one of the world’s leading biotechnology companies and a pioneer in genetically engineered seeds.
Monsanto has been incorporating herbicide and pest resistance into everything from canola to corn. Monsanto is selling two basic varieties of genetically-modified seeds: “Roundup Ready” seeds that have been genetically modified to withstand a heavy soaking with Monsanto’s best-selling herbicide, Roundup (glyphosate).
And a group of seeds implanted with a Bt gene, which produces a pesticidal toxin in every cell of the resulting plant. Caterpillars that eat any part of suchaplant will die, at least until the whole caterpillar population develops “resistance ” to the BT toxin Within the U. S. , genetically altered crops are rapidly coming into widespread use.
In 1995, no genetically-modified crops were grown for commercial sale. Three years later, in 1998, 73 million acres of genetically-modified crops were grown worldwide, more than 50 million acres of them in the U. S. To allow this rapid change to occur with a minimum of foods do not need to be labeled, thus depriving consumers of the opportunity to make an informed choice in the grocery store. You cannot refuse to buy what you cannot identify. It is presently estimated that ‘some 30, 000 items in U.
S. grocery stores already contain genetically modified organisms. Monsanto has announced that soon, 100% of U. S. soybeans (60 million acres) will be genetically modified.
Of particular concern is Monsanto’s latest genetic technique called the Developed with taxpayer money by the U. S. Department of Agriculture but patented by a Mississippi-based seed company that Monsanto has recently purchased, terminator technology is a genetic technique that renders the seeds of crops sterile after one or two years. This assures that Monsanto ” seeds cannot be illegally saved and re-planted year after year. o Genetic engineering and cloning animals: How is cloning related to genetic engineering? Genetic engineering (or bioengineering) is a general term referring to any alteration of an organism’s genes for practical purposes. Cloning is one aspect of genetic engineering, the part that allows scientists to use a variety of methods to duplicate copies of already existing organisms or genetic material.
But the term “genetic engineering” is much broader, encompassing a wide range of procedures designed to alter genetic material, not only copying genes, but in some cases, making completely new proteins. Dolly the famous cloned sheep: From all appearances Dolly looks like a very ordinary lamb. Yet the extraordinary way she was born has not only has made her the most famous sheep on the planet, but has ignited widespread curiosity, amazement and debate over cloning and genetic technology On February 27, 1997, the world learned that Dolly was a clone. Guided by Ian Wilmot and colleagues from the Roslin Institute in Scotland, they announced that they had succeeded in giving birth to a sheep that had originated from a cell taken from an adult sheep.
This made her the identical twin of a sheep that was six years older! Just as amazing is the fact that she has no father. Although there were some who doubted that the procedure had been reported accurately, subsequent cloning successes with other animals (i. e. cattle, mice) have proven the power of the technology. Mother sheep with baby lamb Cloned animals meet early deaths: Cloned animals may indeed die young suggests the first direct study of their lifespan, carried out by Japanese researchers on mice.
Cloning involves removing the nucleus from an egg and replacing it with the nucleus of a donor cell. Many of these “nuclear transfer” embryos never develop or miscarry. Even after birth some clones die. But many cloning scientists argue that the few survivors can be perfectly normal.
They suggest that some effects of cloning are not apparent in the days, weeks or even years after birth. “It is very probable that, at least for some populations of clones, some unpredictable defects will appear in the long run,” the say. The debate over the health of clones and how they age has swung one way and then the other. In November 2001, US biotech company Advanced Cell Technology reported the cloning of two dozen apparently healthy cloned cows. But in January, the first mammal cloned from an adult cell, was reported to have prematurely developed arthritis. the first cloned animal died after only 311 days and, by day 800, 10 (83 per cent) of the animals were dead.
In contrast, only three (23 per cent) of the controls died during the same period. The dead clones showed high rates of pneumonia, liver disease, cancer and a lower level of antibody production, suggesting they had an immune system defect. the scientists are now trying to pinpoint the precise cause of death and repeat the experiment with more animals. o Genetic engineering and current curing applications: Gene therapy: An area that holds great promise upon completion of the Human Genome Project (HGP) is human gene Therapy (HGT), which focuses on treating inherited diseases.
Most often, these diseases are caused by gene abnormalities that produce non-functioning proteins or enzymes, thus causing the pathology of the disease. Ever since scientists discovered that there was a connection between inherited diseases and gene abnormalities, the idea of correcting the disease at its source fascinated many researchers. In essence, gene therapy involves replacing, manipulating or supplementing faulty genes in somatic or germ-line cells with functional genes in order to cure a disease. To date, researchers have primarily targeted somatic cells with the intent being solely to correct the problem for the individual, thus avoiding the ethics and additional constraints involved in germ-line gene modifications. Probability Every thing in genetics is random The recombinant DNA which contains all human ‘s Genetic information human genetic Diseases: Already, approximately 4000 human genetic diseases are known including such diseases as hemophilia B, coronary artery disease, ADA-SCID, glycogen and lysosomal storage diseases such as mucopolysaccharidosis, phenylketonuria (PKU), Duchenne Muscular Dystrophy (DMD), and Limb-Girdle Muscular Dystrophy (L GMD), Alzheimer’s disease, Parkinson’s disease, cystic fibrosis, and atherosclerosis. Increased risks for certain cancers have also been linked to inherited gene abnormalities such as breast and ovarian cancer, lung cancer, brain cancer, and malignant melanoma.
Scientists are already or will soon be targeting these diseases for treatment with HGT. Various requirements exist before effective gene therapy can be accomplished. The primary requirement is the ability to isolate the faulty protein or enzyme that causes the disease. Next, the correct sequence for the fully functional protein must be determined or known — this is one area in which the completion of the HGP will facilitate and expedite gene therapeutic options. Once the functional protein sequence is known, the fundamental challenge of gene therapy, targeting and delivering the gene to the affected cells, must be overcome. Either an ex vivo or in vivo approach may be used, but both have their shortcomings.
Ex vivo vs. In vivo Gene Therapy: The ex vivo approach involves removing the targeted cells from the patient and genetically modifying them in the laboratory. Sometimes, hematopoietic stem cells or macrophages may be transfected and used to deliver the gene to the targeted cells. These genetic modifications may involve electroporation in which electric currents are used to create transient pathways to insert the gene into the cell.
More commonly used gene transfer vehicles are vectors, either plasmids or viruses. Next, the cells which contain the gene of interest are selected and injected back into the patient [Figure 1 ]. This approach works well for diseases involving free floating cells like those of the immune system that can be isolated rather easily. However, for diseases that affect the organs, the targeted cells are much more difficult to isolate without causing loss of organ function.
For diseases that affect specific organs, an in vivo approach involving viral vectors is used to target genes to particular areas of the body. The gene of interest is incorporated into the chosen virus. By removal of genes required for replication and transfection, the virus is crippled to minimize the normal disease pathology of the virus. Once the virus is prepared, the chosen dosage, or viral titer, is administered to the individual.
The route of administration is chosen with the goal of concentrating the viral particles in the area of greatest disease pathology. Many different routes are used to administer the adenovirus for gene therapy. Likewise, if the muscles lack the functioning protein, as is the case in Duchenne’s and Limb-Girdle Muscular Dys trophies, then an intramuscular injection may be given (go to Delivering Therapeutic Genes to Muscles).
Figure 1: the first human gene Therapy Highlights of Gene Therapy: On September 14, 1990, one of the first successes for human gene therapy was realized using an ex vivo approach. A girl who had a mutation in the gene which encoded the enzyme adenosine deaminase (ADA) developed severe combined immunodeficiency disease (SCID).
The ADA enzyme is required to break down excess deoxy adenosine, which is toxic at high levels particularly to T-cells and B-cells.
As depicted above in Figure 1, the gene encoding the correct enzyme was cloned into a viral vector, which was then incubated with T-lymphocytes isolated from the patient and then injected back into the patient. One year after receiving gene therapy, the child no longer required isolation as her immune system had recovered enough that she was able to attend public school taking off no more days due to illness then her classmates. Now, ten years later, there is hope of using gene therapy to treat a variety of diseases including the possibility of preventing full blown AIDS by keeping HIV-1 in a latent stage. Currently, combination antiretroviral therapy is used to control HIV-1 replication, but the virus still maintains a reservoir in CD 4+ T lymphocytes. To keep the virus in its latent form, the patient must be committed to long-term antiretroviral therapy, which is unpleasant to say the least. Yet, noncompliance means progression to full blown AIDS.
The tat gene product is a key target for intervening in the HIV life cycle, as Tat interacts with the tat activation response element (TAR) sequence thus acting in a trans fashion to activate all HIV genes. Tat also stimulates production of certain cytokines, which in turn promote HIV replication. Recently, Li et al. at the University of Pennsylvania Medical School, Division of Immunologic and Infectious Diseases used the antitat gene to inhibit tat expression and also inhibit production of tumor necrosis factor- alpha (TNF-a).
The antitat gene is perfect from the therapeutic standpoint for several reasons [see Figure 2 ]. First, antitat expression is regulated by Tat, so antitat is not produced in uninfected cells.
Furthermore, it inhibits Tat protein by binding it and blocking its translation from mRNA. Finally, it is an RNA based approach so little or no immune response to eliminate transfected cells is mounted. There is potential for AIDS inhibition as their results show increased survival rates in peripheral blood mononuclear cells and T lymphocytes infected with the antitat gene. Overall, those patients expressing the antitat gene had reduced HIV-1 replication. Figure 2: protection of latently infected cells by antitat gene therapy. Prospective Enhancements in Gene Therapy as a Result of Human Genome Project: In order for Human Gene Therapy to reach its full potential, a clearer understanding of the intricate interactions that occur as a result of gene expression must be realized.
Although the deciphering of the human genome is the first step to better understanding this intricate process, gene therapy will benefit greatly from its completion. First, the similarities and differences among DNA binding domains will be known which will allow greater specificity when determining which rheostatic inducing molecule should be used to control expression of gene therapeutic products. Second, the sequence of the genes will improve understanding of the function of their products. Thus, additional diseases that are currently classified as “idiopathic” may be classified as genetic diseases due to additional cellular pathways that are influenced by faulty or non-existent gene products.
The greatest challenge now in gene therapy involving viral vectors is evading the immune system. Once the human genome is sequenced, questions begged by numerous immune reactions, what triggers them, how can we control them, will be answered. These discoveries will provide the tool gene therapists need to successfully implant and maintain long-term expression of targeted genes. Furthermore, a better understanding of cellular uptake mechanisms will abet additional methods of transecting cells. For example, synthetic, non-viral, non-biological reagents may be used to deliver genes to cells, which may be an additional way to avoid the immune system. Likewise, improved understanding of cell adhesion may provide the key to inducing transfected hematopoietic stem cells or macrophages to home to tissues requiring therapy.
Finally, the technology and databases that have been developed to sequence the entire human genome and the automation of various processes that has resulted will greatly reduce the cost of gene therapy research and the end cost to the treated individual. The completion of the Human Genome Project is definitely the springboard that will propel discoveries in various aspects of biomedical research, especially human gene therapy. o Dangers of genetic engineering: What is wrong with genetic engineering? Genetic Engineering is a test tube science and is prematurely applied in food production. A gene studied in a test tube can only tell what this gene does and how it behaves in that particular test tube. It cannot tell us what its role and behaviour are in the organism it came from or what it might do if we place it into a completely different species. Genes for the colour red placed into petunia flowers not only changed the colour of the petals but also decreased fertility and altered the growth of the roots and leaves.
Salmon genetically engineered with a growth hormone gene not only grew too big too fast but also turned green. These are unpredictable side effects, scientifically termed pleiotropic effects. We also know very little about what a gene (or for that matter any of its DNA sequence) might trigger or interrupt depending on where it got inserted into the new host (plant or animal).
These are open questions around positional effects. And what about gene silencing and gene instability? How do we know that a genetically engineered food plant will not produce new toxins and allergenic substances or increase the level of dormant toxins and allergens? How about the nutritional value? And what are the effects on the environment and on wild life? All these questions are important questions yet they remain unanswered. Until we have an answer to all of these, genetic engineering should be kept to the test tubes.
Biotechnology married to corporations tends to ignore the precautionary principle but it also ignores some basic scientific principles. Fundamental weakness of the concept: o Imprecise Technology-A genetic engineer moves genes from one organism to another. A gene can be cut precisely from the DNA of an organism, but the insertion into the DNA of the target organism is basically random. As a consequence, there is a risk that it may disrupt the functioning of other genes essential to the life of that organism.
o Side Effects-Genetic engineering is like performing heart surgery with a shovel. Scientists do not yet understand living systems completely enough to perform DNA surgery without creating mutations which could be harmful to the environment and our health. They are experimenting with very delicate, yet powerful forces of nature, without full knowledge of the repercussions o Widespread Crop Failure-Genetic engineers intend to profit by patenting genetically engineered seeds. This means that, when a farmer plants genetically engineered seeds, all the seeds have identical genetic structure.
As a result, if a fungus, a virus, or a pest develops which can attack this particular crop, there could be widespread crop failure o Threatens Our Entire Food Supply-Insects, birds, and wind can carry genetically altered seeds into neighboring fields and beyond. Pollen from transgenic plants can cross-pollinate with genetically natural crops and wild relatives. All crops, organic and non-organic, are vulnerable to contamination from cross-pollinatation. – Health hazard: o No Long-Term Safety Testing-Genetic engineering uses material from organisms that have never been part of the human food supply to change the fundamental nature of the food we eat. Without long-term testing no one knows if these foods are safe. o Toxins-Genetic engineering can cause unexpected mutations in an organism, which can create new and higher levels of toxins in foods.
o Allergic Reactions-Genetic engineering can also produce unforeseen and unknown allergens in foods. o Decreased Nutritional Value-Transgenic foods may mislead consumers with counterfeit freshness. A luscious-looking, bright red genetically engineered tomato could be several weeks old and of little nutritional worth. o Antibiotic Resistant Bacteria-Genetic engineers use antibiotic-resistance genes to mark genetically engineered cells. This means that genetically engineered crops contain genes which confer resistance to antibiotics.
These genes may be picked up by bacteria which may infect us. o Problems Cannot Be Traced-Without labels, our public health agencies are powerless to trace problems of any kind back to their source. The potential for tragedy is staggering. o Side Effects can Kill-37 people died, 1500 were partially paralyzed, and 5000 more were temporarily disabled by a syndrome that was finally linked to tryptophan made by genetically-engineered bacteria. Environmental Hazards: o Increased use of Herbicides-Scientists estimate that plants genetically engineered to be herbicide-resistant will greatly increase the amount of herbicide use. Farmers, knowing that their crops can tolerate the herbicides, will use them more liberally.
o More Pesticides-GE crops often manufacture their own pesticides and may be classified as pesticides by the EPA. This strategy will put more pesticides into our food and fields than ever before. o Ecology may be damaged-The influence of a genetically engineered organism on the food chain may damage the local ecology. The new organism may compete successfully with wild relatives, causing unforeseen changes in the environment. o Gene Pollution Cannot Be Cleaned Up-Once genetically engineered organisms, bacteria and viruses are released into the environment it is impossible to contain or recall them. Unlike chemical or nuclear contamination, negative effects are irreversible.
DNA is actually not well understood. 97% of human DNA is called ^3 junk^2 because scientists do not know its function. The workings of a single cell are so complex, no one knows the whole of it. Yet the biotech companies have already planted millions of acres with genetically engineered crops, and they intend to engineer every crop in the world. The concerns above arise from an appreciation of the fundamental role DNA plays in life, the gaps in our understanding of it, and the vast scale of application of the little we do know. Even the scientists in the Food and Drug administration have expressed concerns.
Some probable solutions: As we have seen genetic engineering is at the same time profitable (in some fields like farming medicine… ) and dangerous so in order to be safe and far from its hazards we should: – Avoid genetically engineered (GE) food, currently in products containing soya and maize. – Buy organic products – Demand clear choice and non-GE products from your supermarket – Read up on the issue. – Join a local environmental group and campaign against GE crops and GE food. o Genetic engineering and religion: The universe is created by God. It is not merely “nature.” It belongs to God, not human beings.
Because God created them, animals have intrinsic value. They exist first of all in relation to God, before any considerations of their value and use to humans. Humans, however, have a special place, being both a part of creation and also over it. Humans are uniquely the bearers of God’s image. Two expressions of the relationship are found in the opening chapters of Genesis. For centuries the emphasis was in strong terms of dominion or subduing from Genesis.
In recent years belated recognition of the environmental damage we have caused has led to a recovery of second picture, in the gentler language of working and caring for a garden. The relationship of humans to God’s creation has been expressed most often in Calvin’s notion of the steward. God gives humans a special duty both to develop the natural world – and hence the use of technology – but also to take care of it – which puts limits on our activities. Stewardship means that humankind is answerable not merely to future human generations, but to God, the divine owner, for how we have looked after his estate. Alongside this Ruth Page introduced the notion of companionship, to reflect that we are also fellow creatures in a shared creation. Thus while God puts animals under human subjugation for a wide variety of uses, they are still God’s creatures first, and humans will have to give an account to God for their care of them.
Old Testament injunctions such as “Do not muzzle an ox when it is treading out the grain”, “Do not boil a kid goat in its mother’s milk.” imply that wider principles of relationship set restraints on human uses Commercial animal production by selective breeding would be allowed, but not to every degree possible. Limits are exceeded when this is taken as an end in itself, or if it becomes so dominated by a functional view of the animal under pressures of economic efficiency that wider principles of God’s creation are overridden. The case of poultry production has shown that when taken to such degrees that harms, distortions, disablement or impairment of function begin to emerge, a good end would have been taken too far. o Conclusion: With increased knowledge of genetics we have a greater understanding of the principles underlying selective breeding. This was further enhanced by the development of gene transfer from one species to another.
Research is developing bacteria to produce human interferon, growth hormone, cytokines, and a large variety of important complex compounds for the treatment of diseases. The advantages of genetic engineering outlay the disadvantages, but care has to be taken at all times.