Michael Cummings

David Reisman • University of South Carolina

Biotechnology and Society

Chapter 14

Biotechnology

Biotechnology • The use of recombinant DNA technology to produce

commercial goods and services• Chp13 discussed how DNA from different organisms

could be combined to create specific DNA molecules with the ability to grow in various types of cells. (1970’s)• Now, recombinant DNA technology is making a direct

impact on our everyday lives.• This has generated unresolved ethical issues.

Biotechnology

…in this chapter

1. Pharmaceutical products made in transgenic plants and animals

2. Use of stem cells to treat disease

3. GMOs

4. Use of animals that model human diseases

5. Use of DNA in forensics and other fields

14.1 Biopharming: Making Human Proteins in bacteria, cells, and animals Before biotechnology insulin, growth hormone, blood-clotting

factors were isolated from animals and/or human blood donations—often contaminated with HIV or hepatitis virus , some patients had a negative reaction to the animal protein.

As of 1982 insulin production utilized bacteria that were engineered to make human insulin—pure and reliable.

Blood-clotting factors made in hamster cells using recombinant DNA technology began in 1990s

Some Products Made by Recombinant DNA Technology

Table 14-1, p. 314

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

Human proteins made in animals

Use recombinant DNA technology to express a human protein in the mammary glands of a cow, sheep, goat, (rabbits and hamsters used in early experiments) then patients drink the milk from these transgenic animals

• For enzyme-replacement therapy as in Pompe disease• Blood-clotting factors for hemophiliacs• Collagen• Antibodies (vaccines)

Large Scale Synthesis of Human GAA-Pompe disease

Fig. 14-3, p. 315

Rather than using an entire animal, only animal cells are used to make a recombinant protein for medical use.

The Use of Transgenic Plants

Gene transfer into crop plants can result in the production of human proteins

• Lower costs• Easier to grow• Using corn to make human collagen:

http://www.inpharm.com/news/161608/us-team-make-human-biocollagen-plants

14.2 Using Stem Cells to Treat Disease

Embryonic stem cells: from the inner cell mass of early embryos. These cells are pluripotent and can form many different cell types.

Fig. 14-4a, p. 316

Inner cell mass

Additional Classes of Stem Cells

Adult Stem cells: recovered from bone marrow or other organs. Can develop into a limited number of mature cells, thus are considered multipotent.

Induced plutipotent stem cells (iPS): adult cells reprogrammed by transferring several master control genes into the nucleus. They behave similar to embryonic stem cells.

Generation of Induced Puripotent Stem Cells

Stem cell Based Therapies may Treat many Diseases Can be used to replace defective cells

Table 14-2, p. 317

Stem cell Based Therapy for the Treatment of Burns

Fig. 14-8, p. 318

iPS cells from patients with specific disorders Producing induced pluripotent stem cells from

individuals with genetic diseases provides a way to study disease processes, scanning drug candidates for safety and effectiveness, or application to regenerative medicine

Examples include:• Huntington’s disease• Gaucher disease• Type I juvenile diabetes

14.3 Genetically Modified Foods

Transgenic plants are often referred to as either genetically modified organisms (GMOs) or genetically modified (GM) plants

Often more widely accepted in the US than in other nations.

Most likely over half of the food items you consumed today contained an ingredient from a GMO. 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

Fig. 14-9a, p. 319

Foreign gene incorporated into a Ti plasmid

Chromosomes inside plant-cell nucleus

Bacterial chromosome

The foreign gene is transferred into a plant cell. It becomes incorporated into one of the plant’s chromosomes.1

Fig. 14-9b, p. 319

The plant cell grows and divides. Some of the descendant cells give rise to embryos that might go on to develop into mature, genetically engineered whole plants, as below.

Embryo

2

Transgenic Crop Plants can be made Resistant to Herbicides and Disease

Fig. 14-10, p. 320

Transgenic Crop Plants can be made to Enhance the Nutritional Value of Foods Golden rice contains increased levels of

vitamin A

Fig. 14-11, p. 320

Genetically Modified Crops Approved in the US

Table 14-3, p. 320

Some 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?

Can insect resistance genes be transferred to weeds or wild plants?

Can these plants have an unforeseen detrimental effect on the ecosystem?

Will pesticide-resistant insects develop?

14.4 Transgenic Animals as Models of Human Diseases Transgenic mice are a common model system

Transfer of disease-causing human genes into mice creates mice that are used to study the development of human diseases and the effects of drugs and other therapies

Transferring Genes into Mammals

Microinjection of fertilized eggs

Fig. 14-12, p. 322

Mouse model for Huntington’s Disease (HD)

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

Some Human Diseases Studied in Animal Models

Table 14-4, p. 323

DNA Profiles

Originally, minisatellites were used to make a DNA fingerprint, now STRs are used to create a DNA profile

Short tandem repeat (STR) • Short nucleotide sequences 2 to 9 base pairs long

found throughout the human genome that 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 (for more info see:

http://www.fbi.gov/about-us/lab/codis/codis-and-ndis-fact-sheet)

A Sample DNA Profile from a Family

DNA Profiles Are Used in the Forensics and Criminal Justice System DNA profiles are used in more than 10,000 criminal

cases per year.

Analysis of DNA profiles combines probability theory, statistics, and population genetics to estimate how frequently an allele combination is found in a population to calculate the probability that a single person will have that combination

Fig. 14-14, p. 324

Siz

e re

fere

nce

Co

ntr

ol

DN

A

Siz

e re

fere

nce

Vic

tim

Su

spec

t 1

Su

spec

t 2

Fem

ale

cell

s

Sem

en

Siz

e re

fere

nce

Bo

yfri

end

Co

ntr

ol

DN

A

Co

ntr

ol

DN

AS

ize

refe

ren

ce

A DNA profile from a criminal case

(Electrophoresis gel of PCR products)

Exploring Genetics: 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 who were killed during the Russian Revolution

p. 325

14.6 Social and Ethical Questions about Biotechnology

Applications of recombinant DNA technology have developed faster than public policy, legislation, and social norms

Some issues that have arisen include:• Should genetically modified foods be labeled?• How much do animals suffer when used to make human

proteins or used in disease models?• Who should have access to genetic information obtained from

genetic testing?• Should we test for diseases for which there is no cure yet?