Chapter 10: Biotechnology

1. Chapter 10: Biotechnology Part 3

2. Genetic Engineering • Genetic engineering is a process performed in a laboratory in which deliberate changes are introduced into an individual’s genome. • A gene from one species or even genus can be transferred into another species (or genus), creating a transgenic organism. • A gene from a species may also be removed, altered, and then re-inserted into the same species. • In either case, a genetically modified organism (GMO) is the result.

3. Genetically Modified microorganisms • Bacteria and yeast are the most common GMOs. • This is because they contain the metabolic “machinery” to produce desired organic molecules (such as proteins), yet their DNA is easy to modify. • Many bacteria and yeast have been modified to produce medically important molecules. • For example, since 1982, transgenic E. coli has been producing human insulin for diabetics. • Before this, diabetics had to use animal insulin and many suffered allergic reactions. • Slight gene modifications of the human insulin gene in E. coli has also allowed scientists to produce both fast-acting and slow-release human insulin.

4. Genetically modified microorganisms • The food industry has also taken advantage of genetically modified microorganisms. • Cheese traditionally produced using an extract from calf stomachs containing the enzyme, chymotrypsin. • Today, however, genetically modified bacteria produce this enzyme for use in cheese-making. • Other enzymes that are being produced by GMOs that are being used in the food industry include enzymes that improve the taste and clarity of beer and fruit juices and enzymes that slow the staling of bread. • **Explain your own example of a genetically modified microorganism (bacterium, yeast) that has not been discussed in this presentation or your textbook. What was the purpose/benefit of creating this microorganism?

5. Genetically modified microorganisms Fluorescence microscopy image of bacteria which have been genetically engineered to produce the green fluorescent protein. The amount of protein produced by each bacterium is under the control of a genetic circuit. Mathematical analysis of naturally occurring circuits as well as the engineering of artificial gene circuits is a rapidly expanding area of research at the interface of physics and biology. Metabolix has already developed a process that uses genetically engineered yeast to produce plastics. DuPont has developed a kind of bacteria that turns out polyesters. Several companies are developing organisms that will yield larger quantities and higher concentrations of ethanol for automobile fuel.

6. Designer plants • Plants can be genetically modified in several different ways. • One way involves using the bacterium Agrobacterium tumefaciens. • Agrobacterium tumefaciens is a bacterium that infects many plants including peas, beans, potatoes, and other important food crops. • Naturally, Agrobacterium tumefaciens carries a plasmid that causes tumors to form on infected plants. • However, scientists have genetically modified this plasmid by removing the tumor-inducing gene and inserting desired genes. • Then, a plant cell in infected with this modified bacterium. Whole plants can be grown from these infected cells. • The plants that are grown from these infected cells do not form tumors but, instead, produce desired products such as natural pesticides that make the plant more resistant to devastating plant diseases and pests.

7. Designer plants • Genes can also be transferred into plants by electric or chemical shocks, or by blasting the plant tissues with DNA-coated pellets. • These genetically modified plants may also be engineered so that they have double the yield of their unmodified counterparts. • Some crops are also genetically modified so that they contain genes that make them more resistant to environmental disturbances such as severe droughts like those in Africa. • **Explain your own example of a genetically modified plant that has not been discussed in this presentation or your textbook. What was the purpose/benefit of creating this plant?

8. Why designer plants? • The human population is rapidly growing at a rate faster than food production can keep up. • Irrigation leaves mineral and salt residues in soils. • Tilled soil erodes, allowing topsoil to be eroded away. • Runoff clogs rivers and fertilizers on crops allows algae to overgrow so that it suffocates fish. • Pesticides used on crops can harm human, animals, and beneficial insects.

9. Why designer plants? • Use of genetically modified crops may allow use to reduce our dependence upon and use of harmful pesticides and fertilizers. • They may also allow us to reduce the amount of land we have to cultivate, preserving some of that land for wildlife and reducing our impact on the landscape and the environment, while still feeding our ever-growing population. • Higher yielding GM crops can help us to produce enough food to feed all of the people of the world. • In addition, genetically modified crops may help people that rely on agriculture for food and income in drought-stricken, impoverished regions of the world.

10. Designer plants

11. Designer plants: the controversy • The most commonly planted GMO crops include corn, sorghum, cotton, soy, canola, and alfalfa that genetically modified to be resistant to the herbicide glyphosate. • Instead of having to till the soil to get rid of weeds, farmers can spray their crops with this herbicide, which will kill weeds but not the crops. • However, weeds are developing resistance to this herbicide so that spraying it does no good. • In addition, the engineered gene is also appearing in wild plants and non-engineered crops, indicating that transgenes can do escape in to the environment as a result of being transferred from GM plants to non-GM plants by pollen carried by the wind or by insects.

12. Biotech barnyards • The first genetically modified animals were mice. • Today these mice are very common and are invaluable in research. • As discussed earlier in this chapter, we have discovered the function of many human genes by “knocking-out” their counter-parts in mice. • Also, genetically modified mice serve as a model for use to study many human diseases such as diabetes. • Researchers can knock-out the genes that control glucose metabolism in a strain of mice and study the effects of these knockouts.

13. Biotech barnyards • Researchers have also created genetically modified animals that make proteins that have medical and industrial significance. • For example, transgenic goats have been created that produce proteins that are used to treat cystic fibrosis, heart attacks, and blood clotting disorders. • Transgenic goats have also been created that produce humanized milk. • Specifically, these goats’ milk contains lysozyme, an antibacterial human protein that can prevent infants and children in developing countries from suffering from diarrheal diseases. • In addition, researchers are engineering goats to produce milk containing spider silk (for producing fabrics), rabbits that produce a human protein (interleukin-2) to treat immune disorders, goats that produce heart healthy milk, pigs that are low fat, sheep that are extra large, and the list goes on and on. • **Explain your own example of a genetically modified animal that has not been discussed in this presentation or your textbook. What was the purpose/benefit of creating this animal?

14. Biotech barnyards

15. Knockout cells and organ factories • Animals could be the new source of organs for transplantation into humans. • Millions of people suffer with organs and tissues that are damaged beyond repair. • 80,000 people are on the waiting for an organ transplant at any one time. • Because human organs are in such high demand and such short supply, human organ trafficking has become a common problem. • Since pig organs are about the same size as human organs, pigs could serve as a source of organs for humans if we could rid the pig organs of their cell surface proteins that identify them as foreign to the human immune system. • Researchers have produced genetically modified pigs that lack these cell surface proteins in order to prevent human immune system rejection upon transplantation. • Transplantation of pig organs into humans is called xenotransplantation. • The major concern about this practice is that it could lead to pig viruses crossing the species barrier and infecting humans. • This is of major concern since evidence suggests that some of the worst viral outbreaks have occurred when animal viruses cross over into humans (for example, AIDS).

16. Genetically modified humans:Getting better • We are aware of over 15,000 genetic disorders. • Collectively, they are responsible for 20 to 30 percent of infant deaths every year, half of all mentally impaired patients, and one fourth of all hospital admissions. • They also cause age-related disorders including cancer, Parkinson’s disease and diabetes. • Although drugs and other treatments can minimize the symptoms of these disorders, gene therapy is the only cure. • Gene therapy is the transfer of recombinant DNA into an individual’s body cells, with the intent to correct a genetic defect or treat a disease. • The transfer of the recombinant DNA is done by viruses or by lipid clusters. • These vectors are able to insert an unmutated gene into an individual’s DNA to do the job not being done by a mutated gene.

17. Genetically modified humans:getting better • Gene therapy is now being used to treat genetic disorders such as cystic fibrosis, hemophilia A, certain types of cancer, as well as diseases of the eye, the ear, and the immune system. • In a specific example, a gene therapy for cystic fibrosis has been developed in which researchers genetically modify a flu virus by removing the gene that causes it to be pathogenic and inserting an unmutated gene into the virus. • The CF patient then breathes in the genetically modified flu virus. • The virus infects the lungs cells, inserting the unmutated gene into the DNA of the patient’s lung cells, causing the functional protein to be produced that allows the proper transport of chloride ions and water across the lung epithelial tissues. • However, this gene therapy is only a temporary solution, since the body’s immune system recognizes the viral DNA as foreign and destroys it, causing this therapy to last only about 6 months after treatment.

18. Genetically modified humans:getting better • In a more permanent example, a gene therapy has been developed for the severe immune disorder, SCID-X1. • SCID-X1 is a genetic disorder caused by a mutation in the IL2RG gene, which codes for a receptor for an immune signaling molecule. • Children who are affected by the genetic disorder are able to survive only in germ-free isolation tents because they cannot fight infections. • In 1998, a virus was used to insert unmutated copies of the IL2RG gene into bone marrow cells from 11 boys affected by SCID-X1. Bone marrow cells were used because bone marrow is responsible for producing blood cells, including white blood cells, which make up a major part of the body’s immune system. • The genetically modified cells were then inserted back into the children. • Within a few months, 10 of the 11 boys were able to leave their isolation tents permanently because the genetically modified virus used for this gene therapy was able to repair the boys’ immune systems.

19. Genetically modified humans:getting better

20. Geneticallt modified humans:getting better

21. Genetically modified humans:getting worse • Manipulating a gene within a living human is very unpredictable even when we know the gene’s sequence and where it is located within the genome. • The very gene therapy that was used to make an individual better can actually take his or her life when unpredictable side effects occur. • For example, in the SCID-X1 gene therapy trial, 3 of the 11 boys developed a type of bone marrow cancer called leukemia and one of them died. • Cancer as a result of gene therapy occurs because the the virus inserted its DNA into a location in the patient’s DNA that caused an interruption of genes that are responsible for the control of cell division. • In another example, an 18 year old boy had a rare deficiency of a liver enzyme caused by a genetic mutation. • This liver enzyme helps to break down ammonia, which is a by-product of the break down of proteins in the body. • The young man’s health had been fairly stable as long as he remained on a low-protein diet. • In 1999, he volunteered to participate in a gene therapy trial for his disorder. • He suffered an allergic reaction to the viral vector used in the trial and four days later, his vital organs shut down and he died.

22. Genetically modified humans:getting perfect • The idea of selecting the most desirable trait is called eugenics. • This idea, though harmless sounding enough, has been used as a justification for some of the most horrific events in history, including the genocide of 6 million Jews during World War II. • Most people would agree that it’s ok to use gene therapy to improve the lives of or even cure individuals suffering from genetic disorders. • But where do we stop? • Is it ok use genetic modification to have a child with enhanced learning ability, improved memory, bigger muscles, or longer lives? • Mice have already been genetically engineered to have traits such as these. Why not humans?

23. Genetically modified humans:getting perfect • Creating gene therapies and cures might not be very profitable for companies involved in this research, but getting paid to ensure that parents have their “perfect” child might. • Would you be willing to pay to ensure that your child would be tall or blue-eyed, have super human strength or intelligence? • How many people do you know who would be willing to pay for a treatment that might help them permanently lose weight? • Would you be willing to pay for a cuter smarter baby? A less aggressive child or one who would definitely grow up to be heterosexual? • MANY parents would. • Where do we draw the line or can we? • The question today is not how would we do this because we already know how. The only question today is how do we choose the traits that are ok to manipulate?

24. Genetically modified humans:getting there • Some people insist that we should never genetically modify anything. • They feel that, when it comes to genetic modification, we are on a “slippery slope” that may not only irreversibly damage us but also our entire biosphere. • Has our ability to tinker with genetics surpassed our ability to understand the impact of our tinkering? • What are we missing out on if we don’t take these risks? • Do we have the right to impose the consequences of taking these risks on those people who choose not to take them?

25. Drawing lines • **Consider all of the types of genetic modification we have discussed and ways that we can perform these techniques. If you could draw a line to restrict genetic modification, where would you draw it and why? Would you draw the line at all? Explain.