Biotechnology and Society

Chapter 14

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

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 organizationgene functiongene regulation

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

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

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)

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!)

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?

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

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)

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!

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)

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?

14.3 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 humanstudy the development & progress of the

diseases and test the effects of drugs and other therapies as

methods of treating these disorders

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

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

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

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 (ex: PKU

& galactosemia)

• New methods can scan for 30 to 50 disorders

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

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

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%

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 Testing using Recombinant DNA

Recombinant DNA-based prenatal testing can detect genetic disorders that cannot otherwise be detected before birth; techniques include…

Southern blot analysistesting can be done on blastomeres from in vitro

fertilization, before embryo is implantedpolar body biopsy before egg is fertilized in vitro

Presymptomatic Testing Can Be Done for Some Genetic Disorders

Presymptomatic testing (predictive testing) identifies some individuals who will develop adult-onset genetic disorders; ex:

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

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

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

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 reliabilityhttp://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

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

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