WIL Research Labs School Name Presenter Name Biomedical Research and Animals

WIL Research LabsSchool Name

Presenter Name

Biomedical Researchand Animals

WIL Research Laboratories, Inc. 2

Biomedical Research

History of Legislation Evolution of Animal Research Medical Advances from Animals


Paracelsus

Phillipus Aureolus Theophrastus Bombast von Hohenheim

Concept of Dose-Response

“All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy.”


Early Acts 1902 Biologics Act

10 Children Died Contaminated Diphtheria Toxins

1906 Pure Food and Drug Act USDA Bureau of Chemistry Poison Squads Prohibited Misbrandings Post-Facto Convictions Only

1911 Sherley Amendments Prohibited False Therapeutic Claims


Lash Lure®

1933 Eyelash Dye “Lash Lure®” p-phenylenediamine Sensitize external ocular tissues Corneal Ulceration 17 Women Blinded One Death


Minimata Disease Mercury Waste from Acetaldehyde

Production Methyl Mercury 1956 - Discovered Chisso Corporation Minimata Bay, Japan Effects 1966 - Release Stopped


Thalidomide 1950s - Morning Sickness 1960 FDA Review Frances Kelsey Tingling Extremities ~12K Cases Eurasia, Canada Phocomelia 1962 - Banned Worldwide Animal Studies Revised Data Requirements


DES


Medical Advances

Treatments War on Cancer Heart Disease Current Research


Early 1900s

Pellagra treatment developed using monkeys, dogs

Rickets treatment developed using dogs

Cardiac catheterization developed using dogs, rabbits


1920s

Discovery of thyroxin utilized many species

Discovery of insulin using dogs


1930s

Tetanus vaccine developed using horses

Anticoagulants were developed using cats

Modern anesthesia developed using dogs


1940s Rheumatoid arthritis treatments

developed using rabbits and monkeys Antibiotics tested on many species Streptomycin used in treating TB,

pneumonia, typhoid, and spinal meningitis developed using chickens, guinea pigs

Diphtheria vaccines developed using horses

Whooping cough vaccine created using rabbits, guinea pigs

Discovery of Rh Factor


1950s

Polio vaccine developed using rabbits, monkeys, rodents

DNA discovered using rats, mice Chlorpromazine and other

tranquilizers developed using rats, rabbits, monkeys

Chemotherapy techniques developed using monkeys, rabbits, rodents


1960s

Rubella vaccine developed using monkeys

Lithium developed for human manic-depressives using rats, guinea pigs

Antipsychotics, antidepressants developed using rats, mice


1970s Measles vaccine created using many

species

Hansen’s Disease cure developed using armadillos, monkeys

Coronary artery bypass surgery developed in dogs


1980s

Organ transplant techniques advanced using dogs, sheep, cows, swine

Antirejection Drugs

Gene therapy


1990s

Isolation of AIDS Virus

Laparoscopic Techniques

Gene Therapy for Cystic Fibrosis

Breast Cancer Links


War on Cancer

Chemotherapeutics Radiotherapy

Chemoprevention


Heart Disease

1923 - First Human Open-Heart Surgery

Heart Valve Replacement 1953 - First Heart-Lung Machine

600,000 People/Year 1950s - Cardiac Pacemaker 1970 - Balloon Angioplasty

200,000 People/Year


Current Research Multiple Sclerosis Muscular Dystrophy Cerebral Palsy Sickle-Cell Anemia Parkinson’s Disease ALS Alzheimer’s Disease AIDS


Toxicology Defined

A science that deals with poisons and their effect and with the problems involved (as clinical, industrial or legal)


Government Internationally Mandated Safety Testing

Pharmaceuticals Environmental Chemicals Workplace Chemicals Household Chemicals Cosmetics Food Animal Medicine


Environmental Chemicals EPAEPA MAFFMAFF

Pesticides PCBs Petroleum Solvents Lead


Developmental Toxicology

Maternal Toxicity In Utero Exposure

Death, Malformation, Growth Retardation, Functional Deficit

Malformations Variations Historical Control


Reproductive Toxicology Gonadal Function, Estrous Cyclicity,

Mating Behavior, Conception, Gestation, Parturition, Lactation, Weaning, Offspring Growth and Development

Two-generation study F0 - Prior to Mating and through Breeding

F1- In Utero through Breeding

F2- Cumulative Effects


Statistical Requirements

vs.


In-Vitro Assays

Screens Limited Acceptability

Poor correlation with in-vivo tests Skin 2/Corrositex Whole-Animal Test


Department of Agriculture Animal Welfare Act (AWA)

Animal and Plant Health Inspection Service (APHIS)

Regulatory Enforcement and Animal Care (REAC)


Animal Welfare Act (9 CFR 1-4)

All Research Facilities Using Live Animals Except: Birds, Rats, Mice

Registration, Identification, Records Prohibits Use of Stolen Animals Attending Veterinarian Minimum Standards of Care Exercise, Socialization


IACUC Membership

A doctor of veterinary medicine At least one public member

Not affiliated with institution Not a laboratory animal user Not immediate family of an employee

At least one practicing scientist involved with laboratory animals

One nonscientific member


IACUC Inspections

Facility Review Required by law every six months Review animal areas Review activity areas (e.g., necropsy)

Surprise Inspections Conducted at least monthly Observe animal procedures


Animal Activism

Animal Welfare v. Animal Rights 1992 - Animal Enterprise Protection Act

Federal Crime to cause damage in excess of $10,000

“A rat is a pig is a dog is a boy.” Ingrid Newkirk


Animal Sources

Tightly Regulated by USDA

Controlled Source

Purpose-Bred

Transgenic Models


Research Facilities Standard Operating Procedures Environmental Concerns

Temperature Humidity Lighting

Caging Construction Size Maintenance

Waste Disposal


Animal Husbandry

Feeding Watering Sanitation Separation Veterinary Care


Mice Hold gently, but firmly Grasp tail near base for removal from cage Scruff Hold (Grasp skin at base of neck,

tail held between fourth and fifth fingers Clear Plastic Restraint Devices

When additional restraint is required Adjustable Size Easily Sanitized


Rats Hold firmly, but without excessive

pressure Gasp tail near base for removal from

cage Hold around thorax, just behind

forelimbs Tail and/or hindlimbs may be restrained

if necessary Monitor breathing to ensure it is

unrestricted Clear Plastic Restraint Devices


Rats

Teeth can become malaligned: must be trimmed because they grow throughout life

Take care to prevent sloughing of tail

Group house to aid in acclimation to automatic water system


Guinea Pigs Hold firmly, but without excessive

pressure Hold around pectoral girdle, with thumb

and forefingers directly behind forelimbs Support hindquarters Easy to handle due to docile nature and

limited agility Prone to wandering off working surfaces Prone to vocalization during handling


Rabbits Gentle but firm manual restraint Use scruff hold while supporting back

and hindquarters Tuck rump under arm or support back in

crook of arm for thorough examination Allow rabbit to tuck head in crook of arm Never restrain by grasping the ears Hindquarters support prevents injury to

animal and handler Avoid loud or sudden sounds


Canine Exercise

Mandated by the AWA By group and sex Use anteroom Clean room between rounds, prevent

exposure to contaminated excreta


Ruminants Safety

Horns Hooves

Manual Restraint Mechanical Restraint

Cages Slings Head Gates

Chemical Restraint


Nonhuman Primates

Why nonhuman primates? Socialization Enrichment Safety Training

Serology PPE

Documents

WIL Research Labs School Name Presenter Name Biomedical Research and Animals