Slide 1 - North Carolina Association for Biomedical Research by yaosaigeng


									NCABR Rx for Science Literacy
The What, Where, How and Why of Health
Science Research

November 10, 2011

Michael C. Humble, PhD

Program Administrator
Division of Extramural Research and Training (DERT)
National Institute of Environmental Health Science (NIEHS)
National Institutes of Health (NIH)
Dept of Health & Human Services (DHHS)

                                                             The National Institute of Environmental Health Sciences
                                                             The National Institutes of Health
 NIH consists of 27 Institutes and Centers

NHLBI                                                                                   NINR

NCCAM                                                                                  NIEHS
          NCI                                                                NIAMS

   CIT                                                                               NIDA

                   NEI                                              NIMH

          CC                                                                 NIDDK

                               NLM                  NINDS
                 NHGRI                                               NIDCR
  NCMHD                                                                              NIBIB
                         NIA                                NIDCD
                                NIAAA             NICHD

 FIC       CSR                                                             NCRR         NIGMS

                                     = Extramural only
      Hamilton, MT

                             NIA, NIDA
                             Baltimore, MD

NIDDK                        NIH
Phoenix, AZ                  Bethesda, MD
                             Bethesda, MD

                     Raleigh/Durham, NC
                     Raleigh/Durham, NC
 Rx for Science Literacy

The What, Where, How and
  Why of Health Science

Unit 1 – Biomedical Research

Unit 2 – Care and Use of Animals in
         Biomedical Research

Unit 3 – Challenges to Biomedical Research

Unit 4 – Other Issues in Science
 Unit 1 – Biomedical Research

Chapter 1 - What is Science

Chapter 2 - What is Biomedical Research

Chapter 3 - Biomedical Research Methods

Chapter 4 - Benefits of Biomedical Research
What is Science?
 Unit I-1: What is Science?

"Science is a continuous stream of ideas
  that are constantly being reshaped,
  added to, subtracted from and built

Science is always evolving.
  What is Science? (Continued)
Basic science is the foundation of biomedical
  research. Introducing the concepts of critical
  thinking and inquiry-based learning will provide
  students with the tools they need to solve

These tools are important whether students
  eventually pursue careers in science or vote on
  public policy issues based on scientific and
  technological research advances.
     How to Think Like a Scientist
•   Anyone can think like a scientist!

•   BE CURIOUS — look around and ask questions about things! Why is the
    sky blue? How do amoebas eat? How can I get energy from the sun?

•   BE SKEPTICAL — don't always believe the first thing you hear. Look for
    MANY possible explanations, see which facts support which explanations,
    and then pick the best one. Do you believe in UFOs? Bigfoot?

•   BE FLEXIBLE — even after you've found one explanation, keep looking!
    Sometimes you can find an even better one later. Don't be afraid to give up
    old ideas for new ones, as long as they’ve passed the skepticism test!

•   These three brain exercises add up to what is called CRITICAL
    THINKING...what scientists do all the time!
              How to Act Like a Scientist
Once you're in the habit of thinking like a scientist, it's a simple matter to APPLY it to real life.

You can use the same logical four-step approach that scientists do -- the SCIENTIFIC METHOD.

OBSERVATION — carefully watching something around us — in the environment, in animals, or in
   ourselves-in an objective way.

HYPOTHESIS — an educated guess explaining what you are observing, or how to change what you
   are observing.

EXPERIMENT — testing your hypothesis by designing and carrying out an experiment. Part of
   designing an experiment is determining what measurements, or data, you will take to compare the
   experimental and control groups. The measurements you choose should be repeatable by
   someone else as well as relevant as a predictor. t's important to gather enough data and have a
   sufficient number of subjects in each group. The scientist often uses a branch of mathematics
   called statistics to calculate whether the difference between the groups was significant.

CONCLUSION — judging on the basis of your experiment if your hypothesis is right or wrong. Your
   conclusion usually falls into one of two categories:
   CORRELATION — two things that tend to happen together.
   CAUSE-EFFECT — one thing or event actually causes the other to happen.

Correlation can be established through observation. You just need to notice two things always seem to
    occur together. Cause-effect is tougher to establish. Once you've noticed two things occurring,
    you need to TEST to see if they are actually linked to each other. Cause-effect is a better predictor
    than correlation.
Activity – How Observant are You?
Without looking, answer the following questions:

1.    Without looking down, what color socks are you wearing today?
2.    When you fold your arms, which arm do you put on top?
3.    When you clasp your hands in front of you, which thumb is on
4.    Which direction does Lincoln face on a penny?
5.    How many sides does a pencil have?
6.    What color is the top light on a traffic light?
7.    How many sides does a stop sign have?
8.    In the kitchen or bathroom sink, which side of the faucet is the hot
      water knob on?
9.    Without looking back at your neighbor, what color shirt are they
10.   What color was the pen in my pocket?
                         Great "Truths"
At various times in history, scientist "knew" these things:

4,000 B.C. The moon is eaten once each month by a large invisible beast.
1400 A.D. Diseases are caused by evil spirits that inhabit a body.
1500        Flies develop spontaneously from rotten meat.
1800        Tyrannosaurus Rex walked vertically and dragged its tail.
1900        The Apatosaurus and brontosaurus are two different dinosaurs.
1970        Saturn is the only planet with rings around it.
1980        Eating eggs makes your cholesterol levels rise.
1985        Pandas are bears.
1995        Human Genome Project begins and estimates that human
                chromosomes carry about 100,000 genes.
1999        The Y2K Bug will shut the world down
                             Great "Truths"
These are our explanations for Great "Truths" today:

•   The moon darkens each month because the angle between the Earth, Moon and Sun changes.
•   Diseases are caused by microscopic agents ("germs"), such as bacteria, viruses, protozoa and
•   Flies lay their eggs in rotten meat and hatch.
•   Tyrannosaurus Rex leaned forward and its tail balanced it, but it didn't touch the ground.
•   Apatosaurus and brontosaurus are the same species.
•   Uranus and Jupiter also have rings.
•   Some people's cholesterol levels stay the same or go down even if they eat eggs.
•   Pandas are genetically between bears and raccoons.
•   The human genome has at most 25,000 genes — and 95 percent of our genome is the same as
    the chimpanzee.
•   Great efforts to prevent the Y2K "bug" seemed to work, since very few computer systems crashed
    on January 1, 2000.

What do we know today that will make scientists 500 years from now laugh?
  Activity – What is a Scientist?
Make a list of adjectives and/or nouns that
 come to mind when you think of science or

Draw a picture of a scientist.
  Activity – What is a Scientist?
Typical Responses:

smart                white lab coats
eccentric            chemicals
wild looking hair    test tubes
male                 microscopes
glasses              rockets
Activity – What is a Scientist?
  Activity – What is a Scientist?
Follow-up Questions:

Can women be scientists?
Can black or Hispanic people be scientists?
Do scientists have babies?
Do some scientists have pets? Go on vacation?
 Watch TV? Go to the movies? Do scientists
 always work indoors?
Do scientists always work during the daytime?
Activity – Think Creatively

A scientist needs to think creatively
  and see new solutions to old
         Activity – Think Creatively
  How would your students solve the following problems?
1. You have five pieces of tissue paper in the palm of your hand. You
   need to drop them one at a time into a bowl, but you can only use
   that one hand ... HOW COULD YOU DO IT?

2. You have a sheet of newspaper. Can you place it on the floor in
   such a way that you and a friend can both stand on it, but no matter
   how hard you try, your friend cannot touch you?

3. You accidentally drop a ping pong ball into a hole in the ground. The
   hole is too deep for you to reach in and grab it. How could you get it

4. Can you tip a glass of water over without spilling it?

5. Can you empty a glass of water without touching it or the table it's
Unit I-2: What is Biomedical
Biomedical research is the area of
  science devoted to:

 the study of the processes of life;

 the prevention and treatment of disease;

 and the genetic, lifestyle and environmental
 factors related to disease and health.
Biomedical (health science) research
 can be divided into three highly
 interdependent yet broad

    1) basic research
    2) applied research
    3) clinical research
                Basic Research
• Basic research is research conducted to increase
  fundamental knowledge and understanding of the
  physical, chemical and functional mechanisms of life
  processes and disease.

• It is not directed to solving any particular biomedical
  problem in humans or animals.

• This type of research often involves observing,
  describing, measuring and manipulating natural systems.

• It provides the building blocks upon which other types of
  research are based.
              Applied Research
• Applied research is directed toward specific objectives,
  such as development of a new drug, treatment or surgical

• It involves the application of existing knowledge, much of
  which is obtained through basic research, to a specific
  biomedical problem.

• Applied research can be conducted with animals, with non-
  animal methods such as computer models or tissue
  cultures, and with humans.

• Behind most every health advance lies years of applied
                   Clinical Research
•   Information gained through basic and applied research often leads to
    potential treatments to prevent or cure disease.

•   Once all other forms of study and testing have taken place, scientists look to
    clinical research to test potential drugs and treatments in humans.

•   This research builds upon that done in the basic and applied research
    stages. However, clinical research is not always the end. Often, it leads
    back to the lab, where further research is done. It is this interdependence
    that at times makes science seem so complex.

•   Clinical research takes place in a hospital or other clinical setting for health
    care and directly applies to the prevention, diagnosis or treatment of a
    specific disease in the individual or group of individuals, or to the
    rehabilitation of the patient.

•   Clinical research includes a broad variety of activities, and there are many
    areas of study. These areas include human clinical trials, psycho social and
    behavioral research, and disease control research.
Unit I-3: Biomedical Research
• Biomedical research is a complex process. Rather than a simple
  "lab-to-patient" scenario, it employs a wide variety of methods to
  develop new treatments and cures. This section presents a brief
  description of some of the major types of methods being used

• While each of the methods provides valuable information, they
  are highly interdependent. As a result, researchers today must
  cooperate more than ever before. The lessons in this section
  are designed to introduce some of the basic methods of
  biomedical research and to provide some hands-on activities for
  student research.
Biomedical Research Methods
• Chemical       • Non-human animal
• Mathematical
                 • Clinical trials
• Computer
  Simulations    • Epidemiological
• In Vitro
          Chemical Methods
• Often used when developing vaccines,
  prescription drugs and vitamins
• Analytical chemistry tests
• Antibody tests
• Can detect substances and measure potency
• Pros - can simplify, reduce number of animals
• Cons - often too simple
  Mathematical and Computer
• Has been used to test a structure’s
  “activity” within an organism
• Predict biological response
• Analyze chemical structure of new drugs
• Pros - Increase speed and efficiency, can
  extrapolate data, use less animals
• Cons - Can’t generate data- only process
  information given, hardware very
           In Vitro Methods
• “In glass” - cell cultures – artificial
• Pros - Can study single effect without
  interference, less expensive, less time.
• Cons - Difficult to maintain cultures, can’t
  duplicate complex reactions
      Non-human Methods

• Uses animals as models for humans (in
• Pros - ethical replacement for humans,
  provides whole biological system
• Cons - controversy using animals,
  expensive, animals aren’t identical to
      Human Clinical Trials

• Actual use of drug or treatment on
• Pros - Gives precise data on drug or
  treatments effectiveness
• Cons - Lengthy, some risk for
Human Clinical Studies
    Epidemiological Studies
• Another type of human study
• Examine the occurrence and distribution of
  disease in a population

• Pros - Can study effect of humans
  exposed to disease

• Cons - Difficult to detect cause and effect,
  hard to have control groups
 Activity – Itchy Sleep Disease
• There is a new disease called "itchy sleep"
  that affects children.
• The "itchy sleep" disease causes children
  to become very sleepy but as they try to
  fall asleep, they become itchy all over.
• Scientists have discovered that mice can
  catch the disease as well.
        Activity – Itchy Sleep Disease

 Topics for Discussion:
1. What was the same about the groups?
2. What was the purpose of giving different
3. Why didn't the "mice" in the control group
  receive any medicine?
4. How did the scientists know their mice got
  better? (Talk about the importance of
  observation in the research process.)
      Human Clinical Trials
Human clinical trials are a very important
  component of the biomedical research process
  and are most often used in developing
  prescription drugs.

Even after a promising new drug has undergone
  extensive laboratory research and testing,
  scientists still need actual human data from
  controlled studies to answer two key questions:

1. Is the drug biologically active in humans?
2. Is it safe in humans?
      Human Clinical Trials
There are three major phases of clinical trials that begin after
a pharmaceutical firm files an Investigational New Drug (IND)
application with the U.S. Food and Drug Administration
(FDA). In the IND, a pharmaceutical firm shows the results of
laboratory testing and explains how the drug is made.

In Phase I clinical trials, researchers determine a drug's
interaction with the human system, including how it is
absorbed, distributed, metabolized and excreted, and the
likely duration of its therapeutic effect. This phase involves a
small number of healthy volunteers and takes approximately
one year.
     Human Clinical Trials
Phase II trials use controlled tests that help determine a
drug's effectiveness. These studies involve 100 to 300
volunteer patients. Simultaneous animal and human tests are
also conducted at this stage as researchers continue to
assess the safety of the drug. This phase takes
approximately two years.

Phase III trials are conducted to confirm the results of earlier
efficacy tests and further identify any adverse reactions.
Clinical testing at this point is extensive, involving 1,000 to
3,000 volunteer patients in medical clinics and hospitals. This
phase takes approximately three years.
     Human Clinical Trials
After human clinical trials are completed, firms file a New
Drug Application (NDA) with the FDA.

The NDA is a comprehensive statement of the information

•drug structure
•the scientific rationale and purpose of the drug therapy
•pre-clinical animal and other laboratory study results
•all human clinical testing results
•drug formulation and production details
•and the company's proposed labeling

This takes approximately two and one-half years to complete.
Human Clinical Trials
Activity – Cholera and the Scientific Method

  Students act as epidemiologists and
    use the scientific method to track the
    contamination source.
Activity – You Choose the Test!
     Unit I-4: Benefits of
    Biomedical Research
• Biomedical research has led to
  tremendous advances in quality of life,
  therapeutic drugs, diagnostic tools,
  vaccine production, and workplace

• Everyone, in some way, has been
  touched by the results.
Activity – Did You or Will You Ever?
1. Drink tap water?
2. Have a dog?
3. Have a cat?
4. Fertilize your lawn?
5. Drink milk?
6. Eat a hamburger?
7. Call Poison Control?
8. Receive a vaccination?
9. Take an antibiotic for an infection such as strep throat or an ear
10. Eat eggs?
11. Observe an endangered species at a zoo?
12. Eat bacon or North Carolina barbecue?
13. See a guide dog?
14. Have a relative over the age of 45?
15. Take medicine?
16. Know anyone with diabetes who needs to take insulin?
 Activity – Did You or Will You Ever?

Count the number of times you answered yes.

12- 14   You and biomedical research are inseparable
9 - 11   You are affected
7-8      Take it or leave it
5-6      Would not miss it
0-4      Bio-what?
            Activity – Did You or Will You Ever?
1. Drink tap water?
      Chemicals and agricultural runoff add to contaminants in our water supply. Biomedical research continues to
    identify and to study what these contaminants might do to human health.

2. Have a dog?
    A vaccine for rabies in dogs was developed in the 1880s by a biomedical researcher, Louis Pasteur.

3. Have a cat?
    A vaccine for cats has been developed for the fatal feline leukemia virus.

4. Fertilize your lawn?
    Research continues to expand knowledge about the health effects of agricultural products for those who
    manufacture these chemicals as well as consumers who use them.

5. Drink milk?
    Milk is fortified with vitamin D, which research has shown is necessary for proper absorption of calcium salts and
    their deposition (placement) in bone.

6. Eat a hamburger?
    Vaccines for cattle diseases, such as hoof-and-mouth disease, were developed by scientists.

7. Call Poison Control?
    Information is provided to those calling about the potentially toxic effects of such things as household products,
    fertilizers, etc. and, if appropriate, further treatment is recommended.

8. Receive a vaccination?
    North Carolina requires children to be vaccinated against several diseases before school entry. These vaccines
    are the result of biomedical research. They include polio, diphtheria (whooping cough), measles, mumps and
              Activity – Did You or Will You Ever?
9. Take an antibiotic for an infection such as strep throat or an ear infection?
    Alexander Fleming's studies provided evidence that penicillin was a potent antibacterial agent.

10. Eat eggs?
     Vaccines for a number of chicken diseases (no, not chicken pox) have been developed thanks to biomedical

11. Observe an endangered species at a zoo?
     Embryo transfer techniques are being used to increase populations of endangered species.

12. Eat bacon or North Carolina barbecue?
    A vaccine for "scours," a disease that kills piglets, was made possible by genetic engineering.

13. See a guide dog?
    Behavioral studies made possible the training of dogs used to aid the blind and deaf.

14. Have a relative over the age of 45?
    At the turn of the century the average life span was about 45 years. Thanks to improved sanitation, nutrition and
    biomedical research, the average life expectancy has increased to about 73 years of age.

15. Take medicine?
     All prescription and nonprescription medicines sold in the United States are first tested in at least two species of

16. Know anyone with diabetes who needs to take insulin?
     Insulin isolated from animal pancreas (the organ that makes insulin for humans and other mammals) was used for
     decades to keep people with diabetes alive. Now, thanks to biomedical research and biotechnology techniques,
     most people with diabetics take insulin produced by cells that carry the human insulin gene. These cells are grown
     in giant vats on a commercial scale.
    What Difference Has Biomedical Research
             Made to Human Health?
•   There isn't a day that goes by that medical research doesn't affect our lives.

•   And in many cases, it is our own awareness that has made the difference.

•   The public's awareness of healthy lifestyle choices has helped reduce
    mortality rates and has become the best medicine in preventing needless
    disease and disabilities.

•   Think about the childhood diseases generations of children won't have
    because of vaccines. Measles — mumps — chicken pox — polio. Vaccines
    save millions of lives.

•   For the most part we don't think about medical research until we're sick.
    Then we want the cure, in a bottle, at the drug store, and for a low price.
    However, that will only happen through medical research, and that requires
    an investment — an investment that saves lives and money.
What Difference Has Biomedical Research Made to Human Health?

  •   Treatments for:
       –   Heart Disease
       –   Cancer
       –   Diabetes

  •   Protective Vaccines
       –   Polio Vaccine
       –   Chicken Pox
       –   Hepatitis

  •   Development of Treatments like:
       –   Fluoride
       –   Penicillin and Other Antibiotics
       –   Cyclosporine and Other Anti-Rejectiton Drugs
       –   Monoclonal Antibodies

  •   Surgical and Other Artificial Devices
       –   Angioplasty
       –   Organ Transplantation
             •   Heart
             •   Kidney
             •   Liver
             •   Corneas
             •   Bone Marrow
 What Difference Has Biomedical Research
          Made to Animal Health?
Benefits for Animals:
• Artificial joints for dogs with hip displace
• Cancer treatments
• Embryo transfer techniques to improve breeding
• Chemotherapy
• Feline leukemia research
• Genetic research for inherited diseases in pedigreed animals
• Heart disease treatment
• Nutrition research for pet food
• Orthopedic surgery & rehabilitation techniques for horses
• Tooth and gum disease research
• Treatment for parasites (heartworm, hookworm)
• Vaccines for livestock and poultry
• Vaccines for pet diseases (rabies, distemper, parvo virus, infectious
• Antibiotics
• Anesthesia
Unit 2 – Care and Use of Animals
     in Biomedical Research


Chapter 1 – Student Surveys

Chapter 2 – Why Use Animals

Chapter 3 – Advances Based on Animal Research

Chapter 4 – Numbers and Species of Animals Used

Chapter 5 – Care of Research Animals
Unit II-1: Student Surveys
Surveys of young people have shown a
 lack of understanding about the
 tremendous care that animal care
 technicians and scientists deliver to
 animals used in research.

This chapter is designed to increase
 young people's awareness of the care
 and treatment such animals receive.
Unit II-2: Why Use Animals?
In research, animals are used to learn more
  about biological systems and the illnesses
  that afflict human beings and other animals.
They serve as surrogates for humans in
  obtaining information that cannot be gained
  in any other way.

The reference sheets in this chapter provide
  information on animal models used for
  biomedical research.
                Most Commonly Used Animal Models
       Animal             System/Condition                                            Why Is It Studied?

       Cats      Auditory                    Like man, cats have a very well-developed hearing
                                             system and brain mechanisms for hearing. They can
                                             be trained to respond to many behavioral cues given
                                             through auditory stimuli. Cats also experience
                                             naturally occurring hearing defects and are susceptible
                                             to environmentally induced defects, as is man.
Primates         Immune                      Primates possess striking immunological similarities to
                                             humans. They are susceptible to similar diseases and
                                             often react to the same infectious agents as humans.
Dogs             Cardiovascular              A dog's cardiovascular system is structured quite
                                             similarly to man. They suffer from many inherited
                                             cardiovascular defects that affect man. Because they
                                             possess inherited defects nearly identical to those seen
                                             in humans, hematology, the study of the blood, is also
                                             practiced using dogs.
Dogs             Endocrine                   Dogs naturally experience diabetes, as do humans.
                                             Diabetes can also be easily induced in dogs to aid
                                             research. In addition, dogs share other diabetes-
                                             induced deficits, such as glaucoma, that occur in man.
Mice             Aging                       Mice age 30 times more rapidly than humans, with
                                             several body systems declining with age in the same
                                             manner as those in humans. Genetic composition and
                                             environmental conditions can be precisely and easily
                                             duplicated and controlled, a vital consideration in
                                             interpreting data.
Rats             Aging                       Rats are available in a number of purpose-bred strains
                                             and have been the focus of intensive physiological and
                                             biochemical research. Rats show major, spontaneously
                                             developing, age-related damage in most major systems
                                             of the body that are commonly seen in humans.
                                             However, in rats these deficits occur faster and are
                                             easily studied during a rats lifetime.
Unit II-3: Advances Based on
        Animal Research
Virtually all major medical advances have
  involved research with animals.
Animal models provide a ready mechanism for
  the screening and evaluation of new drugs
  prior to human clinical trials.
Researchers must discover not only what the
  drug does to the body, but also what the body
  does to the drug.
The information provided in this chapter looks at
  some major biomedical advances and the
  animal models that were used.
Without Animal Research…
•   Polio would kill or cripple thousands of unvaccinated children and adults this year.
•   Some of the 50 to 60 percent of newborns who develop jaundice each year would develop cerebral palsy, now preventable through phototherapy.
•   Most of the nation's 580,000 insulin-dependent diabetics wouldn't be insulin dependent. They would be dead.
•   The U.S. would experience 1.5 million cases of rubella... over 400 times the current annual incidence of the disease.
•   65 million Americans would be at risk of death from heart attack, stroke or kidney failure for lack of medication to control their high blood pressure.
•   The 200,000 arthritics who each year receive hip replacements would be confined to wheelchairs.
•   Without cataract surgery, more than a million people would lose their vision in at least one eye. Eighty percent of all persons 65 or older will need cataract
    surgery in at least one eye.
•   Death would be a certainty for the more than 16,000 patients in the United States who receive kidney transplants each year. An additional 63,000 patients are
    in need of this operation.
•   There would be no kidney dialysis to extend the lives of the more than 453,000 victims of end-stage renal disease.
•   Chemotherapy would not be able to save the children who now survive acute lymphocytic leukemia.
•   Hundreds of thousands of people disabled by stroke and head injury would not benefit from rehabilitation techniques developed in animals.
•   New surgical procedures to repair congenital heart defects would have to be abandoned or tried for the first time on children.
•   A cure for diabetes would be beyond reach.
•   The number and variety of medications that keep HIV infections under control would not be available.
•   There would be no hope of finding a safe and effective vaccine against AIDS.
•   Development of techniques that may help restore function to paralyzed victims of spinal cord injuries would not continue.
•   The 30,000 young Americans with cystic fibrosis would have little hope of a normal lifespan.
•   The 350,000 people with multiple sclerosis, including 4,500 in North Carolina, would lose the promise of new treatments for the symptoms of this degenerative
•   Thousands of schizophrenics would be institutionalized because of lack of understanding of the disease and its treatment.
•   Methods to prevent many cancers would never be found, since theories about genetic and environmental causative factors cannot be tested in humans.
•   Improvement of hearing through electronic stimulation of the inner ear might never benefit any of the 20 million hearing-impaired Americans.
•   It would be too dangerous to test breakthrough products such as artificial blood, which show promise for saving the lives of critically injured accident victims.
•   Researchers would be unable to clarify the cause of Alzheimer's disease. Without that knowledge, the prognosis for the 4 million Alzheimer's victims would
    remain bleak. Almost 58,000 North Carolinians are affected by Alzheimer's disease.
•   The development of urgently needed new drugs to treat heart disease, cancer and a host of other diseases would be severely curtailed.
 Activity – Human and Animal
Health Has Come A Long Way

Students construct a timeline
  showing biomedical achievements
  for a specific time period.
   Unit II-4: Numbers and Species of
               Animals Used
Most people are not aware that more
 than 90 percent of the animals used in
 biomedical research are rats and mice.

These reference sheets and the lesson
 plan contained in this chapter provide
 accurate numbers of the various types
 of animal models used in biomedical
               Did you know that:
•   Ninety-five percent of all animals used in medical research are rats, mice or
    other rodents specifically bred for research.

•   Valid and useful scientific findings are obtainable only when research animals
    are healthy and protected from undue stress.

•   Federal regulations prohibit both animal abuse and the use of sick, injured or
    distressed animals as research subjects.

•   The majority of animal studies use medical techniques similar to those used on
    humans. They involve little or no pain for the animals.

•   Humans are also often used as research subjects.

•   Research animals are carefully selected to ensure that only the number and
    species essential to each research project is used.

•   Most research animals are bred specifically for that purpose.
       What Kinds of Animals are used for

Primates (Monkeys)               Less than 0.5%

Cats                             Less than 0.5%

Dogs                             Less than 0.5%

Rabbits, Guinea Pigs, Hamsters   Less than 3.3%

Rats & Mice                      More than 90%
 Unit 3 – Challenges to Biomedical

Chapter 1 – Critical Thinking

Chapter 2 – Animal Research: Issues and Answers

Chapter 3 – Transgenic Animals

Chapter 4 – Therapeutic vs. Reproductive Cloning:
            Scientific Realities, Public Controversy
Unit III-3: Transgenic Animals

transgenic animals -- species that carry
  one or more genes from another
Unit III-3: Transgenic Animals

scientists around the world can now
  create customized transgenic animals
  for their own research

Many species are used, including sheep,
 goats, cows, chickens, pigs, mice,
 rabbits, rats, chickens, and fish
 Unit III-3: Transgenic Animals

Although transgenic techniques are applicable to many species,
   mice are more commonly used for research than other
   transgenic animals for several reasons:
• They reproduce quickly.
• They are small animals and therefore easily housed.
• Their genetic makeup is better understood than other
• Their lifespan is 2-3 years, allowing researchers to follow
   disease processes from infancy to old age over a relatively
   short time.
• Moreover, numerous strains of inbred mice -- where all
   members of one strain have exactly the same genetic makeup -
   - are available commercially.
Making a Transgenic Mouse
   Model for Leukemia
                               What is leukemia?
                               Leukemia – a cancer involving blood cells

RBCs carry oxygen to tissues                                             White blood cells help fight infection
throughout the body

                                       Platelets help form blood clots
                                       that control bleeding

           In people with leukemia, the bone marrow produces abnormal white blood
           cells. At first, leukemia cells function almost normally. In time, they may
           crowd out normal white blood cells, red blood cells, and platelets, making it
           hard for blood to do its work.
                         Gene Structure
                     Promoter      Coding Region   Termination Sequence
 How to Produce a Transgenic Animal

The first step in producing a
 transgenic animal is to construct
 the transgene, which is the DNA
 to be transferred into the animal.
  How to Produce a Transgenic Animal

What should the transgene do?
To model leukemia, we want to create and add a gene that will cause the bone
   marrow to make too many white blood cells

Promoter: should enable gene expression only in the tissue of interest, the bone
          example: globin gene promoter

Gene: should be a gene that causes cell proliferation
          example: ras oncogene

Termination Sequence: something unique that can be “traced,” perhaps a viral
   sequence that would not normally be found in the organism
          example: SV-40 polyadenylation sequence
zeta globin
 promoter     v-Ha-ras   SV40 Poly A
                  Tg.AC Transgene

        zeta globin
         promoter                 v-Ha-ras                SV40 Poly A

EcoR1           HincII/BamH1                       Xba1                 EcoR1

                           Mutations in v-Ha-ras
               Codon 12                            Codon 59
          glycine      arginine              alanine      threonine
    How to Produce a Transgenic Animal

For a transgene to be incorporated into all of the cells of an organism, it
      must be introduced at the single-cell embryo stage. The following
      method is used to produce transgenic mice:

•     Female mice are given hormones so that they superovulate
      (produce a large number of eggs).
•     They are mated.
•     Hours later, single-cell embryos are removed from the females.
•     Using a microscope and a microinjecter, scientists inject each
      embryo with copies of the transgene.

•     These eggs are then transferred to surrogate mothers of the same
      strain who have been treated with hormones so that the eggs can
      implant and grow.
 How to Produce a Transgenic Animal

Scientists can determine if the mice in the litter have the gene by
     analyzing a small piece of each mouse’s tail when it is eight
     to 10 days old, using a technique called polymerise chain
     reaction (PCR). Millions of copies of a gene can be made in a
     few hours.

Mice that carry the transgene are observed for any indication that
     the presence of the transgene has affected the animal.
 Characteristics of the Tg.AC Transgenic
              Mouse Model

• location of transgene
  – insertion on chromosome 11
  – 10+ copies
• mice were not overly susceptible to
• mice were susceptible to skin cancer
• transgene expression is inducible in the
   Potential Use of the Tg.AC Transgenic
               Mouse Model

• opportunity to identify the molecular
  mechanisms that associate with the biology of
  the induced tumor response

• chemical evaluation for human risk assessment
Unit 4 – Other Issues in Science


  Chapter 1 – Careers in Biosciences

  Chapter 2 – Genetics Primer
I fully realize that I have not succeeded in
   answering all of your questions … Indeed; I feel
   that we have not answered any of them
   completely. The answers we have found only
   serve to raise a new set of questions, which only
   lead to more problems, some of which we
   weren’t even aware were problems.

To sum it all up … In some ways I feel we are as
  confused as ever, but I believe we are confused
  on a higher level, and about more important

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