Biotechnology and Society

1. Biotechnology and Society Chapter 14

2. Keep In Mind • Recombinant DNA is DNA that has been artificially created by incorporating DNA from 2 or more sources into a single recombinant molecule • Biotechnology • The use of recombinant DNA technology to produce commercial goods and services

3. Recombinant DNA • Originally used to transfer foreign genes into bacteria so that researchers could clone large quantities of specific genes in order to study: • gene organization • gene function • gene regulation

4. Human Proteins Can Be Made in Animals • Transgenic • The transfer of genes between species • Transgenic organism • An organism that has received a gene from another species by means of recombinant DNA technology

5. Biotechnology now used… • to make pharmaceutical products in genetically altered plants &animals • to produce new varieties of agricultural plants & animals • to generated animal models for the study of human diseases • to diagnose & treat diseases • to prepare DNA profiles used in forensic applications and in other fields

6. Biopharming: Making Medical Molecules in Animals and Plants • Genetic engineering is used to manufacture human proteins in bacteria and cell lines from higher organisms (such animals and plants) • These proteins are used in treating human diseases • Examples: Blood clotting factors for hemophiliacs, insulin for diabetics • Provides a constant supply, uncontaminated by disease-causing agents (in the early 1980’s, 60% of hemophiliacs became HIV positive due to receiving contaminated blood serum)

7. Pompe Disease • Pompe disease • An inability to make α-glucosidase (GAA) • Treated by enzyme replacement therapy • Transgenic animals produce human GAA • Transgenic female rabbits produce human GAA enzyme in their milk • The enzyme is purified from collected milk and given to patients intravenously (also use hamsters!)

8. More on Biopharming • Crop plants such as corn and bananas are being investigated as sources of edible vaccines • Trials of a vaccine against bacterial diarrhea - eating uncooked potatoes • Future? Hepatitis & diphtheria vaccines in bananas?

9. Genetically Modified Foods • Genetically modified organisms (GMOs) • A term referring to transgenic plants or animals • 60% to 70% of foods in US supermarkets contain some transgenic plant material • Products made from corn, soybeans, cottonseed and canola oils most commonly contain transgenic ingredients

10. 14.2 Genetically Modified Foods Artificial selection has been used by farmers for years to improve yield & nutritional value of their crops. (modern corn to ancestral maize) Today… • Gene transfer into crop plants confers resistance to herbicides, insect pests, and plant diseases • Also used to increase the nutritional value of foods (such as vitamin A)

11. Herbicide Resistance & Bt crops • Herbicide-resistant crops (resistant to broad-spectrum herbicides) • herbicides kill all plants in the field except the crops & the herbicides break down quickly in the soil • Bt crops carry a bacterial gene that produces a toxin; insects eat part of the plant, the toxin is released in the gut of the insect –DIE BUG!! • Farmers use less pesticide & herbicide – save money, protect environment!

12. Transgenic Crops Used to Enhance Nutrition • Vitamin A deficiency is a serious health issue in over 70 countries (primarily in Asia) • ~500,000 children become permanently blind every year due to Vitamin A deficiency in their diets • Golden rice increases vitamin A • Genes from daffodils, corn, and bacteria allow the rice to produce beta-carotene (Vitamin A precursor)

13. Concerns About Genetically Modified Organisms • Are foods containing new proteins safe to eat? • Is it safe to eat food carrying part of a viral gene that switches on transgenes? • Will pesticide-resistant insects develop? • Will disease-causing bacteria acquire antibiotic-resistance genes used as markers?

14. 14.3 Transgenic Animals as Models of Human Diseases Mouse models of human diseases • Transfer of disease-causing human genes into mice creates transgenic organisms that are used to • produce an animal with symptoms that mirror those in human • study the development & progress of the diseases and • test the effects of drugs and other therapies as methods of treating these disorders

15. Huntington Disease Mice as Models • HD mice are extremely useful as models of human neurodegenerative disorders • Used to study the progressive destruction of brain structures in early disease stages • Used to link changes in brain structure with changes in behavior • Used to screen drugs to improve symptoms or reverse brain damage

16. Transferring Genes into Mammals To make a transgenic HD mouse… • copies of the mutant HD gene were cloned into vectors • the vectors carrying the HD gene were microinjected into the nucleus of a fertilized mouse eggs • the eggs were implanted into surrogate mothers who gave birth to transgenic mice with the mutant HD gene

17. 14.4 Testing for Genetic Disorders • Genetic testing • Used to determine if someone has a genotype for a genetic disorder or is a carrier • Identifies individuals with a particular genotype • Usually a matter of choice to be tested • Genetic screening • Systematic search for individuals in a population where there is a risk for a particular disorder (in other words – everyone in the population is tested • Often is mandated by law

18. Four Types of Testing Programs • Newborn screening • Carrier testing • Prenatal testing • Presymptomatic (predictive) testing

19. Newborn Screening in the US • Newborn screening tests infants within 48 to 72 hours after birth for a variety of genetically controlled metabolic disorders • All states require newborns to be tested • Most states screen for 3 to 8 disorders (ex: PKU & galactosemia) • New methods can scan for 30 to 50 disorders

20. Carrier Testing for Genetic Disorders • Carrier testing searches for heterozygotes that may be at risk of producing a child with a genetic disorder • Done on family members, or cultural groups, with a history of a genetic disorder such as sickle cell anemia or cystic fibrosis

21. Prenatal Testing for Genetic Disorders Prenatal testing tests a fetus for genetic disorders (e.g. cystic fibrosis, Tay Sacs, ) or chromosome abnormalities (e.g. Down syndrome) In most cases, testing is done only when there is a family history or some other indication, like advanced maternal age, points to risk for the fetus having a genetic disorder

22. Methods of Prenatal Testing Risks to mother & fetus include • Amniocentesis can be done after the 15th week of development • risk of miscarriage: 0.5% to 1% • Chorionic villus sampling (CVS) is usually done at 10 to 12 weeks of development • risk of miscarriage: 1% to 3%

23. Prenatal Testing Can Diagnose Sickle Cell Anemia Recombinant DNA-based prenatal testing can detect genetic disorders that cannot otherwise be detected before birth • Sickle-cell beta globin genes have a distinctive pattern of banding on a Southern blot • Normal gene: Two small fragments • Sickle gene: One large fragment

24. Prenatal Testing using Recombinant DNA Recombinant DNA-based prenatal testing can detect genetic disorders that cannot otherwise be detected before birth; techniques include… Southern blot analysis testing can be done on blastomeres from in vitro fertilization, before embryo is implanted polar body biopsy before egg is fertilized in vitro

25. Presymptomatic Testing Can Be Done for Some Genetic Disorders • Presymptomatic testing (predictive testing) identifies some individuals who will develop adult-onset genetic disorders; ex:

26. Genetics in Society: Who Owns a Genetic Test? • Families of children with Canavan disease, a rare and fatal disorder, started a foundation to obtain tissue samples and funding for research • The research hospital patented the gene and charged participating families for the test • After a lawsuit, the hospital was allowed to continue to license the test and collect royalties

27. 14.5 DNA Microarrays in Genetic Testing • Testing for a wide range of genetic disorders is possible using DNA chips (microarrays), which can hold thousands of genes • http://learn.genetics.utah.edu/content/labs/microarray/ • DNA microarray • A series of short nucleotide sequences placed on a solid support (such as glass) that have several different uses

28. Uses of Microarray Technology • Detecting mutant genes • Individuals who will develop late-onset genetic disorders such as polycystic kidney disease (PCKD) and Huntington disease • Individuals at risk for disorders such as diabetes • Detecting differences in the pattern of gene expression in normal and cancerous cells

29. Microarray Testing • Each field of the microarray contains a unique sequence of single-stranded DNA • Test DNA and normal DNA are converted to single strands, tagged with fluorescent dyes, and hybridized to the chip • Each result has a different color • Normal alone is green; mutant alone is red • Both together are yellow; a blank field is black

30. 14.6 DNA Profiles & DNA Fingerprints as Tools for Identification • DNA profiles (& DNA fingerprints) use variations in the length of short repetitive DNA sequences (STRs = short tandem repeats) to identify individuals with a high degree of accuracy and reliability http://www.teachersdomain.org/asset/tdc02_int_creatednafp2/ • This method is used in many areas, including law enforcement, biohistory, conservation, and the study of human populations

31. DNA Profiles Can Be Made from Short Tandem Repeats (STRs) • STRs range from 2 to 9 base pairs in length • CCTTCCCTTCCCTTCCCTTCCCTTCCCTTC contains six repeats of the CCTTC sequence • Repeat numbers vary between individuals • A unique profile can be produced by analyzing several STRs in a DNA sample • In the US, a standard set of 13 STRs (CODIS) is used to prepare a profile

32. DNA Profiles Are Used in the Courtroom • Analysis of DNA profiles combines probability theory, statistics, and population genetics to estimate how frequently an allele combination is found in a population • Population frequencies for STRs are multiplied together to produce an estimate

33. Genetic Journeys: Death of a Czar • Forensics and several types of DNA evidence were used to confirm that bones discovered in 1991 belonged to Czar Nicholas Romanov II, his wife, and three of their five children

34. 14.7 Social and Ethical Questions about Biotechnology • Applications of recombinant DNA technology have developed faster than societal consensus, public policy, and laws governing its use • Efforts to inform legislators, members of the legal and medical profession, and the public often have lagged behind its commercial use • A balanced approach requires education and debates on risks and benefits

35. Keep In Mind • The uses of biotechnology have produced unresolved ethical issues