Biotechnology and SocietyBiotechnology and Society

Prof. Arnaldo FerreiraProf. Arnaldo Ferreira

Keep In Mind

Biotechnology is an outgrowth of recombinant DNA technology

Biotechnology • The use of recombinant DNA technology to

produce commercial goods and services

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

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

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

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

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

Transgenic Crops Used to Enhance Nutrition

Golden rice increases vitamin A• Genes from daffodils, corn, and bacteria

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?

Keep In Mind

Many crop plants have been genetically modified

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

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

Transferring Genes into Mammals

Microinjection of fertilized eggs

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

Four Types of Testing Programs

Newborn screening

Carrier testing

Prenatal testing

Presymptomatic (predictive) testing

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

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)

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

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

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

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

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%

Cystic Fibrosis: Testing For 25 Mutationsin Different Ethnic Groups

With over 1,500 mutations identified, it is not possible to test for all cases

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)

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

Keep In Mind

Genetic disorders can be diagnosed using biotechnology

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

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

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

Reading a Microarray Field

The tumor-suppressor gene p53

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

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

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

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

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

Analyzing DNA Profiles

One suspect matches the crime scene evidence

Keep In Mind

DNA profiles are based on variations in the copy number of DNA sequences

Other Uses for DNA Profiles

Two littermates, one a pure Shih Tzu, the other a mixed breed

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

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

Keep In Mind

The uses of biotechnology have produced unresolved ethical issues