Animal Experiments: Can We Do Better

1
Animal Experiments Can We Do Better?

• Aysha Akhtar M.D., M.P.H.
• Physicians Committee for Responsible Medicine
  (PCRM)

2
Uses of Animals Safety Testing
3
Uses of Animals Basic Research
4
Uses of Animals Education
5
Concerns with Animal Experiments

• Ethical
• Medical/Scientific

6
Ethical Concerns with Animal Experiments

• Animal Welfare Act
• Rats and mice not covered
• Provides minimal protection
• Rarely enforced

7
Ethical Concerns with Animal Experiments

• Stress during routine laboratory procedures

8
Ethical Concerns with Animal Experiments

• Psychological
• distress
• Stereotypic behaviors
• Witnessing effect

9
Ethical Concerns with Animal Experiments

• Pain and suffering

10
Ethical Concerns with Animal Experiments

• Waste of resources
• and time

11
Ethical Concerns with Animal Experiments

• Misplaced hope

12
Ethical Concerns with Animal Experiments

• Inaccurate Results
• TGN 1412 multiple organ failure
• Vioxx heart failure
• Rezulin liver failure
• Selacryn liver failure
• Eraldin blindness

13
Examples of Animal Experiments

• Stroke experiments-Columbia University
• Spinal cord injury experiments-OSU, NYU
• Visual deprivation-M.I.T-March of Dimes Funded

14
Historical Perspectives in Human Research Ethics

• 1947Nazi Trials
• 1960s Jewish Chronic Disease Hospital Case, NY
• 1956-1971 Willowbrook State School, NY.
• 1930s-1972 US Syphilis Study. Tuskegee, AL.

15
Parallels ?

• Vulnerable populations
• Subjects considered inferior
• Research considered vital

16
Scientific Concerns with Animal Research

• Fundamental Tenet of Medical Research
• For a research model/method to work, it must be
  predictive of human physiology and disease

17
Problems With Animal Experiments

• Artificiality of laboratory-induced diseases
• Differences in anatomy
• Differences in physiology

18
Comparison of Neuroanatomy
19
Comparison of Neuroanatomy
20
Why Animal Experiments Fail Differences in
Anatomy

• The human cortex has 10X the surface area of that
  of the rhesus monkey
• Substantially larger prefrontal cortex in humans
• Differences in size and locations of functional
  areas
• Specific brain regions not present in monkeys

21
Why Animal Experiments FailDifferences in
Physiology

• Homologous areas in brain differ in function
• Number of synapses per neuron
• humans 6000-10,000 monkeys2000-6000
• Differences in neurotransmitter distribution
• Differential expression of genes

22
Why Animal Experiments Fail Artificiality of
Animal Models

• For an effective model, 3 conditions must be met
• Full understanding of the animal model
• Full understanding of the human disease
• The above two cases must be substantially
  congruent in all important respects
• David F. Horrobin, MD, PhD Nature Reviews Drug
  Discovery. 2003 2 151-154

23
Humanized Animals Are they Effective?
24
Why Animal Experiments Fail

• Even minor differences in physiology and anatomy
  can lead to profound differences in disease
  pathology and treatment effectiveness

25
Animal Models ? Human Disease

• The history of cancer research has been a history
  of curing cancer in the mouse. We have cured mice
  of cancer for decades, and it simply didnt work
  in humans
• Dr. Richard Klausner, Director of the National
  Cancer Institute 1998.

26
Animal Models ? Human Disease

• Stroke
• HIV/AIDS
• Spinal Cord Injury

?
?
?
27
Animal Experiments in Stroke

• Number of treatments effective in animal stroke
  models gt700
• Number of these treatments tested in human
  clinical trials gt150
• Number of these that have proven effective for
  humans 0
• Macleod MR (2004, 2005)

28
Animal Experiments in HIV/AIDS

• Number of HIV/AIDS vaccines that have been
  proven in effective in animals (including
  chimps) and tested in clinical trials gt50
• Number of these vaccines found effective in
  humans 0
• Bailey J. Biogenic Amines 2005.

29
Animal Experiments in Spinal Cord Injury

• Results of Methylprednisolone (MP) for treatment
  of acute spinal cord injury
• Cats mostly positive
• Dogs mostly positive
• Rats mostly negative
• Mice all negative
• Monkey positive
• Rabbit equivocal
• Sheep negative
• Humans?

30
Animal Experiments in Spinal Cord Injury
Differences in Pathology Among Species

• Cavity Size after Injury
• Mice v. small central cavity
• Rats large central cavity
• Hamsters v. large central cavity
• Cavity Size over Time
• Mice diminishes over time
• Rats remains same over time
• Hamsters increases over time

31
Animal Experiments in Spinal Cord Injury
Differences Within Species

• Genetic Expression After Injury

32
Fundamental Tenet of Medical Research

• For a research model/method to work, it must be
  predictive of human physiology and disease

33
LD50 of LSD
Intravenous Route The Merck Index, 11th Edition
34
LD50 of Sodium Monofluroactetate

• Tasmania Dept. Food Agriculture
• http//www.dpiw.tas.gov.au/internnsf/WebPages/RPIO
  -4ZM7CX?openSpeciesSusceptibilit

35
Comparison of Animal Tests to In Vitro Tests

• Multicenter Evaluation of In Vitro Cytotoxicity
  Tests (MEIC)
• Study
• Compared animal tests to human cell line tests
  evaluating toxicity of 50 chemicals
• Results
• Accuracy of in vitro tests 83
• Accuracy of animal tests 59
• Voskoglou-Nomikos T, et al Clinical Cancer
  Research 2003 9 4227-4239.

36
Animal Experiments Fail the Predictive Test

• Currently, nine out of ten experimental drugs
  fail in clinical studies because we cannot
  accurately predict how they will behave in people
  based on laboratory and animal studies."
• Comment by Secretary Mike Leavitt, U.S.
  Department of Health and Human Services,
• Jan 2006

37
What Will We Use if We Dont Test on Animals?

• Epidemiological studies
• Computer modeling
• Human cell and tissue culture
• Post-mortem studies
• Genetic microarrays
• Human non-invasive studies
• Clinical Trials

38
Summary

• Unethical
• Ineffective
• Wastes resources
• Human harms
• Human based tests more accurate

39
Thank You

• For more information on animal experiments and
  non-animal research methods, please visit
• www.pcrm.org