Biotechnology and Society

1. Biotechnology and Society Prof. Arnaldo Ferreira

2. Keep In Mind • Biotechnology is an outgrowth of recombinant DNA technology • Biotechnology • The use of recombinant DNA technology to produce commercial goods and services

3. 14.1 Biopharming: Making Medical Molecules in Animals and Plants • Genetic engineering is used to manufacture proteins used in treating human diseases • Examples: Blood clotting factors, insulin • Provides a constant supply, uncontaminated by disease-causing agents • These proteins are made in bacteria, cell lines from higher organisms, animals, and plants

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. 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 • Human GAA produced in transgenic hamster cells

6. 14.2 Genetically Modified Foods • 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) • Genetically modified organisms (GMOs) • A term referring to transgenic plants or animals

7. Genetically Modified Foods • 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

8. Transgenic Crops Used to Enhance Nutrition • Golden rice increases vitamin A • Genes from daffodils, corn, and bacteria

9. 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?

10. Keep In Mind • Many crop plants have been genetically modified

11. 14.3 Transgenic Animals as Models of Human Diseases • Transfer of disease-causing human genes creates transgenic organisms that are used to study the development of human diseases and the effects of drugs and other therapies as methods of treating these disorders

12. HD 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

13. Transferring Genes into Mammals • Microinjection of fertilized eggs

14. 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 • Genetic screening • Systematic search for individuals in a population who have certain genotypes • Tests general populations that may have a low frequency for a disorder

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

16. 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 • New methods can scan for 30 to 50 disorders

17. Carrier and Prenatal Testing Screen for Genetic Disorders • Carrier testing searches for heterozygotes that may be at risk of producing a defective child • Done on family members or cultural groups with a history of a genetic disorder such as sickle cell anemia or cystic fibrosis • Prenatal testing tests a fetus for genetic disorders (e.g. cystic fibrosis) or chromosome abnormalities (e.g. Down syndrome)

18. Methods of Prenatal Testing • Amniocentesis can be done after the 15th week of development • Chorionic villus sampling (CVS) is usually done at 10 to 12 weeks of development

19. 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

20. Prenatal Genetic Diagnosis (PGD) Can Test Embryos for Genetic Disorders • Testing can be done on blastomeres from in vitro fertilization, before embryo is implanted • Blastomere • Cell in early stages of embryonic development

21. Polar Body Biopsy • In a woman heterozygous for an X-linked disorder, the X chromosome with the mutant allele segregates into a polar body or an oocyte

22. Prenatal Testing is Associated with Some Risks • Risks for mother and fetus • Infection, hemorrhage, fetal injury, and spontaneous abortion • Risk of miscarriage • Amniocentesis: 0.5% to 1.0% • CVS: 1% to 3%

23. Cystic Fibrosis: Testing For 25 Mutationsin Different Ethnic Groups • With over 1,500 mutations identified, it is not possible to test for all cases

24. Presymptomatic Testing Can Be Done for Some Genetic Disorders • Presymptomatic testing (predictive testing) identifies some individuals who will develop adult-onset genetic disorders • Huntington disease • Polycystic kidney disease (PCKD)

25. 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

26. Keep In Mind • Genetic disorders can be diagnosed using biotechnology

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 • 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. Reading a Microarray Field • The tumor-suppressor gene p53

31. 14.6 DNA Profiles as Tools for Identification • DNA profiles use variations in the length of short repetitive DNA sequences to identify individuals with a high degree of accuracy and reliability • This method is used in many areas, including law enforcement, biohistory, conservation, and the study of human populations

32. DNA Fingerprints • Minisatellites • Nucleotide sequences 14 to 100 base pairs long organized into clusters of varying lengths; used in the construction of DNA fingerprints • DNA fingerprint • Detection of variations in minisatellites used to identify individuals

33. DNA Profiles • Short tandem repeats are now used routinely instead of minisatellites, and DNA profile has replaced the term DNA fingerprint • Short tandem repeat (STR) • Short nucleotide sequences 2 to 9 base pairs long organized into clusters of varying lengths • DNA profile • STR pattern used to identify individuals

34. 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

35. 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

36. Analyzing DNA Profiles • One suspect matches the crime scene evidence

37. Keep In Mind • DNA profiles are based on variations in the copy number of DNA sequences

38. Other Uses for DNA Profiles • Two littermates, one a pure Shih Tzu, the other a mixed breed

39. 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

40. 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

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