CK-12 Biology I - Honors

by CK-12 Foundation

  There are many applications of genetic information, including applications in medicine and agriculture. The applications of genetics to forensic science have become one of the most important aspects of the criminal justice system. And of course, these applications raise many ethical questions. These applications and questions will be the focus of this lesson.

  Applications of DNA Technology: Medicine

  As discussed in the first lesson of this chapter, the Human Genome Project has opened up many applications to take advantage of what we know about our genome in order to help us. Many of these applications are medically related. Others will be legally related. And yet still other uses of DNA technology include those in agriculture and the food sciences.

  Understanding and curing genetic diseases is the ultimate goal of human geneticists. As discussed in the Human Genetics chapter, gene therapy is the insertion of a new gene into an individual’s cells and tissues to treat a disease, replacing a mutant disease-causing allele with a normal, non-mutant allele. Of course, the findings of the Human Genome Project are significant in determining the disease-causing alleles.

  In the 1920s, there was no known way to produce insulin, which was needed by people to remove excess sugar from the bloodstream. People with diabetes either lack insulin, produce low levels of insulin, or are resistant to insulin, and thus they may need external insulin to control blood glucose levels. This problem was solved, at least temporarily, when it was found that insulin from a pig’s pancreas could be used in humans. This method was the primary solution for diabetes until recently. The problem with insulin production was raised again: there were not enough pigs to provide the quantities of insulin needed. Scientists needed to devise another way. This led to one of the biggest breakthroughs in recombinant DNA technology: the cloning of the human insulin gene.

  By methods discussed in the first lesson in this chapter, the specific gene sequence that codes for human insulin was introduced into the bacteria E. coli. The transformed gene altered the genetic makeup of the bacterial cells, such that in a 24 hour period, billions of E. coli containing the human insulin gene resulted, producing human insulin to be administered to patients.

  Though the production of human insulin by recombinant DNA procedures is an extremely significant event, many other aspects of DNA technology are beginning to become reality. In medicine, modern biotechnology provides significant applications in such areas as pharmacogenomics, genetic testing (and prenatal diagnosis), and gene therapy. These applications use our knowledge of biology to improve our health and our lives. Many of these medical applications are based on the findings of the Human Genome Project.

  Pharmacogenomics

  Currently, millions of individuals with high cholesterol take a similar type of drug. You may know of people who take a medicine to help with their cholesterol levels. However, these drugs probably work slightly differently in many of those people. In some, it lowers their cholesterol significantly; in others it may lower it only moderately; and in some, it may have no effect at all. Why the difference? Because of the genetic background of all people. Pharmacogenomics, a combination of pharmacology and genomics (the study of the genome) that refers to the study of the relationship between pharmaceuticals and genetics, may explain and simplify this problem.

  Pharmacogenomics is the study of how the genetic inheritance of an individual affects his or her body’s response to drugs. In other words, pharmacogenomics will lead to the design and production of drugs that are adapted to each person’s genetic makeup.

  Pharmacogenomics will result in the following benefits:

  Development of tailor-made medicines. Using pharmacogenomics, pharmaceutical companies will be able to create drugs based on the proteins, enzymes and RNA molecules that are associated with specific genes and diseases. These tailor-made drugs promise not only to maximize the beneficial effects of the medicine, but also to decrease damage to nearby healthy cells.

  More accurate methods of determining appropriate drug dosages. Knowing a patient’s genetics will enable doctors to determine how well his or her body can process and metabolize a medicine. This will allow doctors to prescribe the proper levels of the medicine, allowing the medicine to have optimal results.

  Improvements in the drug discovery and approval process. Once the genes and proteins associated with a disease are known, the discovery of new medicines will be made easier using these genes and proteins as targets for the medicine. In addition to creating much more beneficial medicines, this could significantly shorten the drug discovery process.

  Better vaccines. Safer vaccines can be designed and produced by organisms transformed with DNA sequences from an antigen. These vaccines will trigger the immune response without the risks of infection. They will be capable of being engineered to carry several strains of pathogen at once, combining several vaccines into one.

  Genetic Testing and Prenatal Diagnosis

  Let's propose a hypothetical situation: unfortunately, your family is predisposed to develop a genetic disease. You and your spouse want to have a baby, but you want to know the likelihood of the child developing the disease.

  This scenario could happen to anyone. As we learn more and more about disease causing genes, it will become easier to test for mutations in those genes. Currently, is there any way to determine if a baby will develop a disease due to a known mutation? Is it possible to screen for a mutation in a developing baby? Yes.

  Genetic testing involves the direct examination of DNA sequences. A scientist scans, by any number of methods, a patient’s DNA for mutated sequences. Genetic testing can be used to:

  Diagnose a disease.

  Confirm a diagnosis.

  Provide information about the course of a disease.

  Confirm the existence of a disease.

  Predict the risk of future development of a disease in otherwise healthy individuals or their children.

  Identify carriers (unaffected individuals who are heterozygous for a recessive disease gene).

  Perform prenatal diagnostic screening.

  Perform newborn screening.

  Consultations with human geneticists and genetic counselors are an important first step in genetic testing. They will most likely prescribe some sort of prenatal screening (see the Human Genetics chapter). Prenatal screening (also known as prenatal diagnosis or testing) is the testing for diseases or conditions in a fetus or embryo before it is born. Methods may involve amniocentesis or chorionic villus sampling to remove fetal cells. DNA can be isolated from these cells and analyzed. If the mutation that results in the phenotype is known, that specific mutation can be tested, either through restriction fragment length polymorphism analysis or, more likely, through PCR and DNA sequence analysis. As it is the baby’s DNA that is being analyzed, the analysis will determine if the developing baby will have the mutation and develop the phenotype, or not have the mutation. Parents can then be informed of the probability of the baby developing the disease.

  In human genetics, preimplantation genetic diagnosis (PIGD) is genetic analysis performed on embryos prior to implantation. PIGD is considered an alternative to prenatal diagnosis. Its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that the baby will be free of the disease in question. In PIGD, in vitro fertilization is used to obtain embryos for analysis. DNA is isolated from developing embryos prior to implantation, and specific genetic loci are screened for mutations, usually using PCR based analysis. Embryos that lack the specific mutation can then be implanted into the mother, thereby guaranteeing that the developing baby will not have the specific mutation analyzed for (and thus not have the disease associated with that mutation).

  Applications of DNA Technology: Agriculture

  Biotechnology has many other useful applications besides those that are medically related. Many of these are in agriculture and food science. These include the development of transgenic crops - the placement of genes into plants to give th
e crop a beneficial trait. Benefits include:

  Improved yield from crops.

  Reduced vulnerability of crops to environmental stresses.

  Increased nutritional qualities of food crops.

  Improved taste, texture or appearance of food.

  Reduced dependence on fertilizers, pesticides and other agrochemicals.

  Production of vaccines.

  Improved Yield from Crops

  Using biotechnology techniques, one or two genes may be transferred into a crop to give a new trait to that crop. This is done in the hope of increasing its yield. However, these increases in yield have proved to be difficult to achieve. Current genetic engineering techniques work best for single gene effects - that is traits inherited in a simple Mendelian fashion. Many of the genetic characteristics associated with crop yield, such as enhanced growth, are controlled by a large number of genes, each of which just has a slight effect on the overall yield. There is, therefore, still much research, including genetic research, to be done in this area.

  Reduced Vulnerability to Environmental Stresses

  Crops are obviously dependent on environmental conditions. Drought can destroy crop yields, as can too much rain or floods. But what if crops could be developed to withstand these harsh conditions? Biotechnology will allow the development of crops containing genes that will enable them to withstand biotic and abiotic stresses. For example, drought and excessively salty soil are two significant factors affecting crop productivity. But there are crops that can withstand these harsh conditions. Why? Probably because of that plant's genetics. So biotechnologists are studying plants that can cope with these extreme conditions, trying to identify and isolate the genes that control these beneficial traits. The genes could then be transferred into more desirable crops, with the hope of producing the same phenotypes in those crops.

  Thale cress (Figure below), a species of Arabidopsis (Arabidopsis thaliana), is a tiny weed that is often used for plant research because it is very easy to grow and its genome has been extensively characterized. Scientists have identified a gene from this plant, At-DBF2, that confers resistance to some environmental stresses. When this gene is inserted into tomato and tobacco cells, the cells were able to withstand environmental stresses like salt, drought, cold and heat far better than ordinary cells. If these preliminary results prove successful in larger trials, then At-DBF2 genes could help in engineering crops that can better withstand harsh environments. Researchers have also created transgenic rice plants that are resistant to rice yellow mottle virus (RYMV). In Africa, this virus destroys much of the rice crops and makes the surviving plants more susceptible to fungal infections.

  Figure 10.7

  Thale cress.

  Increased Nutritional Qualities of Crops

  Maybe you’ve heard over and over that eating beans is good for you. True? Well, maybe. But what if it were possible to increase the nutritional qualities of food? One would think that would be beneficial to society. So, can biotechnology be used to do just that? Scientists are working on modifying proteins in foods to increase their nutritional qualities. Also, proteins in legumes and cereals may be transformed to provide all the amino acids needed by human beings for a balanced diet.

  Improved Taste, Texture or Appearance of Food

  Have you ever gone to the grocery store, bought some fruit and never gotten around to eating it? Maybe you haven’t, but I bet your parents have. Modern biotechnology can be used to slow down the process of spoilage so that fruit can ripen longer on the plant and then be transported to the consumer with a still reasonable shelf life. This is extremely important in parts of the world where time from harvest to the consumer may be longer than in other areas. In addition to improving the taste, texture and appearance of fruit, it will also extend the usable life of the fruit. As the world population grows and grows, this may become a fairly important issue. Extending the life of fruit can expand the market for farmers in developing countries due to the reduction in spoilage. This has successfully been demonstrated in the tomato. The first genetically modified food product was a tomato which was transformed to delay its ripening. Researchers in Indonesia, Malaysia, Thailand, Philippines and Vietnam are currently working on delayed-ripening papayas.

  Reduced Dependence on Fertilizers, Pesticides and Other Agrochemicals

  There is growing concern regarding the use of pesticides in agriculture. Therefore, many of the current commercial applications of modern biotechnology in agriculture are focused on reducing the dependence of farmers on these chemicals. For example, Bacillus thuringiensis (Bt) is a soil bacterium that produces a protein that can act as an insecticide, known as the Bt toxin. But it is a protein, not a foreign chemical. Could this protein be used in crops instead of pesticides? Traditionally, an insecticidal spray has been produced from these bacteria. As a spray, the Bt toxin is in an inactive state and requires digestion by an insect to become active and have any effect. Crop plants have now been engineered to contain and express the genes for the Bt toxin, which they produce in its active form. When an insect ingests the transgenic crop, it stops feeding and soon thereafter dies as a result of the Bt toxin binding to its gut wall. Bt corn is now commercially available in a number of countries to control corn borer (a lepidopteran insect like moths and butterflies), which is otherwise controlled by insecticidal spraying.

  Figure 10.8

  Kenyans examining genetically modified insect resistant transgenic Bt corn.

  In addition to insects, weeds have also been a menace to farmers - just ask anyone with a garden how much they hate weeds. They can quickly compete for water and nutrients needed by other plants. Sure, farmers can use herbicides to kill weeds, but do these chemicals also harm the crops? Can biotechnology help with this issue? Some crops have also been genetically engineered to acquire tolerance to the herbicides - allowing the crops to grow, but killing the weeds. But the lack of cost effective herbicides with a broad range of activity - that do not harm crops - is a problem in weed management. Multiple applications of numerous herbicides are routinely needed to control the wide range of weeds that are harmful to crops. And at times these herbicides are being used as a preventive measure – that is, spraying to prevent weeds from developing rather than spraying after weeds form. So these chemicals are being added to crops. This practice is followed by mechanical and/or hand weeding to control weeds that are not controlled by the chemicals. Crops that are tolerant of herbicides would obviously be a tremendous benefit to farmers (Figure above). The introduction of herbicide tolerant crops has the potential to reduce the number of chemicals needed during a growing season, thereby increasing crop yield due to improved weed management and decreased harm to the crops.

  In 2001, 626,000 square kilometers of transgenic crops were planted. Seventy-seven percent of the transgenic crops were developed for herbicide tolerance in soybean, corn, and cotton, 15% were Bt crops for insect resistance, and 8% were developed with genes for both insect resistance and herbicide tolerance in cotton and corn.

  Production of Vaccines in Crop Plants

  Many little children hate shots. And many children in parts of the world do not even have access to vaccines. But what if these vaccines were available in an edible form? Modern biotechnology is increasingly being applied for novel uses other than food. Banana trees and tomato plants have been genetically engineered to produce vaccines in their fruit. If future clinical trials prove successful, the advantages of edible vaccines would be enormous, especially for developing countries. The transgenic plants could be grown locally and cheaply. Edible vaccines would not require the use of syringes, which, in addition to being unpleasant, can be a source of infections if contaminated.

  Applications of DNA Technology: Animal Cloning

  DNA technology has proved very beneficial to humans. Transgenic animals are animals that have incorporated a gene from another species into their genome (Figure below). They are used as experimental models to perform phenotypic tests with genes whos
e function is unknown, or to generate animals that are susceptible to certain compounds or stresses for testing purposes. Other applications include the production of human hormones, such as insulin. Many times these animals are rodents, such as mice, or fruit flies (Drosophila melanogaster). Fruit flies are extremely useful as genetic models to study the effects of genetic changes on development.

  Figure 10.9

  GloFish: the first genetically modified animal to be sold as a pet. GloFish are transgenic zebrafish transfected with a natural fluorescence gene.

  But transgenic animals just have one novel gene. What about a whole new genome? It could be argued that human cloning is one of the techniques of modern biotechnology. It involves the removal of the nucleus from one cell and its placement in an unfertilized egg cell whose nucleus has either been deactivated or removed. Theoretically this would result in an individual genetically identical to the donor. Of course, there are many ethical issues associated with human cloning. But animal cloning is arguably a different story.

  In February 1997, Ian Wilmut and his colleagues at the Roslin Institute announced the successful cloning of a sheep named Dolly from the mammary glands of an adult female (Figure below). Dolly was the first mammal to be cloned from an adult somatic cell. The cloning of Dolly made it apparent to many that the techniques used to produce her could someday be used to clone human beings. This resulted in tremendous controversy because of its ethical implications. After cloning was successfully demonstrated by Dolly's creators, many other large mammals, including horses and bulls, were cloned. Cloning is now considered a promising tool for preserving endangered species.