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Genetic engineering - an overview
(a) Microbes as medicine factories Many conditions, such as diabetes and retarded growth, result from the body not producing enough of a particular protein. As a result, many people with these conditions depend on drugs to provide the proteins. These proteins, such as human hormones and growth factors, are often only present in tiny quantities even in healthy bodies. Before 1980 these proteins were very hard to come by -- they were either not available at all or were painstakingly purified from animal organs or human cadavers. But in less than 20 years, the production of human protein by genetically engineered microbes has led to a number of new medicines for use in human health. Insulin used to be extracted from the pancreas of pigs and cows and, although the animals' hormones are similar to human insulin, a number of diabetics developed allergies. Human insulin was the first drug to be genetically engineered (produced by recombinant DNA technology). The drug was approved for therapy by the American Food and Drug Administration (FDA) in 1982 and became available in New Zealand shortly after that. Most of New Zealand's 14,000 diabetics now depend on insulin genetically engineered in bacteria. Hard on the heels of GE insulin came human growth hormone for the treatment of children with retarded growth. This effective therapy was hampered by the need to use the human protein - animal substitutes do not work. Before gene technology, the hormone had to be isolated from the pituitary glands of dead people and was sometimes contaminated by the agent causing the human equivalent of mad cow disease or Creutzfeldt-Jacob syndrome. Another GE protein, erythropoietin (EPO), was introduced in New Zealand in the early 1990s for treating anaemia associated with kidney failure. This protein is normally made by the kidneys and is responsible for producing the red blood cells. Patients with kidney failure previously needed regular blood transfusions, but can now make enough of their own red blood cells by using the GE product. Interferons are small proteins that help regulate the immune system. They, too, are produced in very small amounts in a healthy body. Several GE human interferons are now available in New Zealand to treat a number of cancers and some cases of multiple sclerosis. New GE blood proteins have freed haemophiliacs of the risks of blood borne-diseases contracted through blood transfusions or contaminants in human blood. The number of GE-produced drugs so far available in New Zealand is still comparatively small, but hundreds are being developed worldwide and are likely to enter New Zealand within a few years. Most of these drugs are produced by recombinant DNA technology in bacteria, yeast cells, or mammalian cells in culture. In recent, years, scientists have looked into the possibility of using live domestic animals, such as cows, as 'pharmaceutical factories'. DNA 'signals' can restrict a gene's 'expression' (the synthesis of the corresponding protein product) to certain tissues such as mammary gland. This makes it possible to use living animals engineered to produce human proteins in their milk. In these cows, the gene for the human protein is introduced in combination with a tissue-specific 'promoter'. The promoter is a gene sequence, which acts as an on/off switch for the translation of the gene and ensures that the foreign gene is expressed only in the mammary glands. In New Zealand, the Environmental Risk Management Authority (ERMA), which regulates the use of gene technology, has approved two such experiments. A Scottish company has been given permission to develop a flock of 10,000 sheep genetically engineered to produce the human protein alpha-1-antitrypsin in their milk, for the purpose of preparing enough protein to use in tests of treating patients with cystic fibrosis and emphysema. In another experiment, scientists at the Crown Research Institute AgResearch are breeding a flock of 200 cows with the human gene for myelin, which is being investigated as a possible treatment for multiple sclerosis. In addition to GE drugs, a number of genetically engineered vaccines are used in New Zealand. In their simplest form, vaccines immunise people by exposing them to an attenuated form of virus or bacteria. The exposure to this harmless or mild version of disease prompts a person's immune system to build up an arsenal of defence mechanisms against the pathogen, so that the body is well prepared in case the real thing ever strikes. In some cases, it has been found that exposure not to the whole organism but to a single protein from its coat or shell provokes an immune response. Here GE has proved a valuable tool. The most widely used GE vaccine is that for hepatitis B, a highly contagious blood-borne virus that causes liver inflammation and cancer. There are 350 million carriers of the disease worldwide, and more than a million people die from liver cancer each year. But immunisation can prevent hepatitis B. In 1980, the gene coding for a protein from the shell of the hepatitis B virus was cloned and, seven years later, the U.S. Food and Drug Administration approved a GE vaccine. Several other GE vaccines against diseases, such as diphtheria and tetanus, have been developed and are in use worldwide. In New Zealand, another field of research focuses on non-infectious diseases such as asthma or psoriasis, a debilitating skin-flaking disease. Researchers are also using 'naked' DNA instead of protein to generate an immune response. As genes can be transferred from one cell to another, medical researchers are hoping that one day they will be able to correct genetic defects. This approach may be useful where the disorder is caused by a defect in a single gene. The main targets for corrective gene therapy are stem cells, which are found in the bone marrow and which can repopulate the entire blood and immune system. So far, very few of the hundreds of attempts at gene therapy have worked. Most of the successful trials have involved children with sever combined immune-deficiency syndrome (SCID). Some attempts have achieved only a temporary improvement, but could not maintain ongoing expression of the transplanted gene. Many questions remain about the possible long-term effect of the viral DNA used to transport the new gene into position. Multigene disorders such as cancer, diabetes and atherosclerosis account for about half of all gene therapy trials. Some have shown promise in clinical trials, but none are currently in use in clinical practice as the risks and benefits are still too poorly understood. The prospect of gene therapy, particularly the idea of corrective gene therapy of embryos and germ-line cells, has raised a number of complex ethical issues and social concerns about informed consent and the possible abuse of genetic information by employers and insurance companies. (e) Engineering medicine into foods A typical example of how food could deliver health-promoting ingredients is 'golden rice', a GE variety of rice that has been modified to produce (-carotene, a precursor of vitamin A. Rice is a staple in many developing countries and the golden variety could provide a source of vitamin A for millions of children who suffer from a deficiency. It could also help to combat blindness, which can happen when the diet is short of vitamin A. Researchers at the Boyce Thompson Institute for Plant Research in the United States have been working on a genetically-modified banana that produces an antigen found in the outer coat of the hepatitis B virus. Such a fruit could potentially be used in developing countries to immunise children against hepatitis B for just a few cents per dose, compared to the current cost of $100-$200 per dose. In theory, any fruit that is eaten raw could be engineered to vaccinate against a whole range of diseases. The current testing of modified foods (or, in fact, of any GMO) is so strict that it might help to solve health problems. For example, in an attempt to engineer soybeans to improve their nutritional balance of amino acids, scientists inserted a gene from brazil nuts. Because the nuts were known to cause allergies in some people, the protein was tested for such reactions. When it became clear that the specific protein concerned was indeed the component responsible for the allergies, the soybean trials were stopped and this knowledge can now be used to eliminate the allergen from the nuts themselves. The Environmental Risk Management Authority (ERMA) regulates the introduction of any new GMOs, whether they are created for research or for commerce. ERMA operates under the Hazardous Substances and New Organisms Act, which requires every project resulting in a genetically modified organism to go through a rigorous approval process. Drugs are controlled by the Medicines Act, which protects the public against any false claims and ensures that high standards of safety and information are met. Each pharmaceutical product undergoes lengthy trials and clinical tests to establish an optimum dose, efficacy, benefits and risks. The use of each drug is monitored. |
