Volume 44 (3)
Introduction pp 185-186
Diversity in animal experimentation can
assume a number of different meanings depending on the experiences of
laboratory animal veterinarians and the justifications of scientists for doing
any experiment. Usually technical
differences between studies are more commonly thought of as confounders rather
than behavioral and physiological disparities, phenomena that cannot be easily controlled
in or out of the lab. One of the
greatest challenges in prospective humane study design is dealing with the
assumptions that all animal experiments can be easily controlled. Even though our profession has designed
strategies for dealing with animal care in the era of genetic manipulations, we
now face a time when phenotypic evaluation of chimers, clones, and models are
produced by targeted mutation. Some
programs face competing needs between agricultural production and agricultural
research. Field and agricultural
veterinarians may face unique challenges while working in nonconventional
programs that are more research-oriented, especially in studies with
genetically engineered livestock that are phenotypically altered and may have
to be returned to an animal society.
This issue is a collection of different perspectives and guidelines
regarding the care and use of animals outside the customary laboratory setting.
A. A type of memo one sends to a primary
investigator
B. A behavioral composite
C. A record or display obtained by ultrasonic
scanning
D. A graph in which values found in a
statistical study are represented by lines or symbols placed horizontally or
vertically, to indicate frequency distribution
E. A tabulation of the leukocytes present in a
blood sample
1. An ethogram is B – a behavioral composite. C is a sonogram, D is a histogram, E is a leukogram.
Ethical Issues Concerning Animal Research Outside the Laboratory pp. 187-190
SUMMARY: Unique ethical issues can be associated with
research outside of the typical lab setting (i.e. clinical research,
agricultural research, field studies).
The IACUC must ensure that ethical standards are met in the conduct of any
kind of animal research. Three reasons
that research outside of the lab pose unique ethical issues are 1) nature of
animals being studies, 2) number of additional factors that must be included in
the moral deliberations, and 3) nature of the review and oversight
process.
1) Animals Used in Research: In order
to address animal welfare issues adequately, one must consider the different
nature and needs of different animals.
An animal’s welfare should be determined by the match between an
animal’s needs and interest and the treatment that animal receives. Because the vast majority of research
animals have been purpose-bred and most likely would not survive in the wild,
we may not have violated an our ethical duty by confining them to the
laboratory. Field research raises unique
moral challenges. The most obvious is
causing pain or distress. Trapping and
handling of wild animals, even if conducted in a way where no physical harm is
done, can still cause fear, anxiety, and frustration in animal subjects. Thus the question of how often traps will be
checked and how the animals will be handled are relevant to the ethics of a
field research project. There are
concerns that agricultural research may be driven by production concerns at the
expense of welfare and ethics. Research
conducted in typical agricultural settings can generate serious ethical issues
because many common agricultural practices are not attuned to the physiological
and behavioral needs and interests that underlie an animal’s welfare.
2) Other Factors: Additional factors
impacting on ethical issues include environment, animal owners, and the general
public. In the case of wildlife, the
potential impact on species and ecosystem must be considered as we have a moral
obligation to protect and preserve both individual species and the
environment. Clinical research must
consider the moral obligations to animal owners. Veterinarians have an obligation to provide the highest standard
of care, yet this obligation can pose obstacles in clinical research requiring
a control group. The process of
informed consent must be carefully scrutinized by the IACUC. Autonomy and malfeasance are 2 other
principles that protect human research subjects. Autonomy as it applies to clinical animal research allows owners
free and informed choices.
Nonmalfeasance requires an absence of any sort of fraud or harmful
deceit, as well as avoiding harm to the animal. Sham surgery in a control group in a clinical setting would
therefore constitute malfeasance. The
effect of research on the general public must also be considered. Other effects are related more to general
perceptions.
3) Role of the IACUC: Most of the
burden of ensuring ethical animal research falls on the IACUCs. The expertise of IACUC members should
accommodate the needs of the relevant species and the type of research being
conducted outside of the lab.
Procedures on which IACUCs rely for monitoring research may also need to
be modified as research outside of the lab affords fewer opportunities for
monitoring the ethical treatment of animals.
Questions have recently been raised about how adequately IACUC members
are trained or informed of their responsibilities towards laboratory
research. The additional complications
of research outside of the lab intensify these concerns by adding an additional
level of complexity to IACUC duties and by increasing the need for training.
1. What types of research occur outside of
the customary laboratory setting?
2. Name 3 principles that protect human
research subjects?
3. Which laws, regulations, and guidelines
are applicable if farm animals are involved with biomedical research? Is livestock production research regulated
in a similar manner?
1. Clinical research, research in
agricultural settings, or field studies; each form may be designed to study
either physiological or behavioral questions.
2. Informed consent, autonomy,
nonmalfeasance.
3. Although the Animal Welfare Act, the Federation of Animal Sciences Societies’ guide, and the Public Health Service Policy are applicable if farm animals are involved in biomedical research, livestock production research is not so regulated.
Regulatory Issues Surrounding the Use of Companion Animals in Clinical Investigations, Trials and Studies pp. 191-196
This article reviews the pertinent regulations and guidelines that apply to the use of companion animals in clinical trial situations such as those used for vaccine or drug testing or development of new treatment protocols. Although there are some overlapping guidelines and regulations between clinical trials and preclinical animal research in the laboratory setting, clinical trials are often subject to additional guidelines and regulations with which laboratory animal practicioners may not be familiar. The number of federal agencies that may potentially be involved with animal research is significantly greater than with human clinical trials which are primarily regulated by only the Department of Health and Human Services (DHHS). In contrast, animal studies may be subject to oversight by a variety of federal agencies depending on the type of testing being done: US PHS Policy (if funded by NIH), the USDA Virus-Serum-Toxin Act (vaccine testing), the FDA Federal Food, Drug, and Cosmetic Act (drugs, devices, feeds and feed additives) and the EPA Federal Insecticide, Fungicide, and Rodenticide Act (flea and tick products).
One issue of concern regarding the use of companion animals in clinical trials is informed consent. The procedures for obtaining informed consent in animal clinical trials are based on those for human clinical research and can be found in the 1976 Belmont Report (NCPHS 1976). The consent form must clearly discuss how new the procedure/technique or drug really is, it must state the chances that the animal will not benefit and it must state the probability and nature of anticipated adverse effects. The form must be written in appropriate lay terminology.
Clinical trials involving drugs are primarily subject to regulation by the FDA’s Center for Veterinary Medicine which reviews Investigational New Animal Drug applications (INADs) and New Animal Drug applications (NADAs). The reporting and investigation of adverse drug effects is of great concern and specific guidelines set forth by the FDA address procedures which must be followed including clinical examination of the animals, collection of clinical pathology and histopathology data and necropsy data when applicable. The guidelines which are specifically followed by investigators participating in companion animal clinical drug trials include sections 511 and 512 of the Federal Food Drug and Cosmetic Act (FFDCA) as defined in the CFR Title 21. The FFDCA does not duplicate the Animal Welfare Act (AWA) and the regulations found in CFR Title 21 require compliance with the AWA regulations. The FDA requires the use of monitors during clinical trials that support INADs and NADAs. The monitors are responsible for overseeing the study protocol and implementing quality assurance measures. The monitor must be an unbiased person and must maintain regular contact with the investigator and must visit the study site to review records and documentation.
Vaccine development is regulated by the Virus-Serum-Toxin Act of 1913 (amended 1985). The USDA’s Center for Veterinary Biologics oversees the safety and efficacy of marketed animal vaccines in the U.S. The Center issues licensing, testing, and permit requirements and procedures and provides licenses for production facilities and reviews production methods and labels. Most vaccine trials are still done in a typical research setting and thus do not use companion animals and are subject to the usual regulations that apply to the use of animals in research. Increased concern regarding the safety of vaccines has lead to increased postmarketing surveillance of vaccine reactions.
Questions:
1) True or False: In veterinary clinical trials, CFR Title 21 supercedes the Animal Welfare Act regulations.
2) True or False: Study monitors are required by the USDA
3) True or False: Most vaccine trials are conducted in clinical (non-research laboratory) settings
4) True or False: Flea and tick products are regulated by the EPA
Answers:
1) False, CFR Title 21 requires full compliance with the Animal Welfare Act regulations
2) False, the FDA requires the use of study monitors in clinical trials done in animals to support INADs and NADAs
3) False, Most vaccine trials are done in research laboratory settings
4) True, flea and tick products are regulated by the EPA in accordance with the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA 1996)
Assessment of Pain in Dogs: Veterinary Clinical Studies pp. 197-205
Summary: This is a review article which describes the current state of veterinary clinical pain studies in dogs and the application of computer-assisted behavioral analysis. It serves the purposes of tying public expectations and awareness to investigations of chronic pain syndromes in pet animals and determining whether animals suffer the same pain syndromes found in humans. Most common models for acute pain have included experimental (using heat or pressure) and clinical (traumatic) pain; most often they evaluate the effects of surgical trauma on pet animals. A common surgical procedure--ovariohysterectomy (OHE)-is considered a relatively standardized source of moderate soft tissue pain, making it suitable for clinical studies of analgesia. Pain behaviors may be invoked by several mechanisms: physical impairment due to pathology, protective, expression of pain or a learned response (coping strategy) to reduce pain. Experience of pain is highly variable across individuals, even when identical stimuli are applied under identical environmental conditions. Further, subjective assessments of observable behavior may vary among species depending on the observer. Pain rating scales are endless. Several (3) have been patterned on similar instruments developed for use in humans. Scales described in veterinary studies include: 1) verbal ordinal 3- to 5-point scales [use descriptors none, mild, moderate and severe], 2) numerical (ordinal) rating scales [4- to 10-point scale], 3) categorized numerical rating scales with ordinal ranking of individual behaviors within 3 to 7 categories [0-2 points assigned for various behaviors within a category (categories may include vocalization, movement, respiratory pattern and posture)], and 4) visual analog scales (VAS) All of these scales are characterized by reliance on subjective evaluation of behaviors, and the subjective nature of these instruments is revealed by the presence of significant variability of pain scores between observers, for which there can be many reasons, even when properly conducted. Patient evaluation criteria scale descriptors have not been clearly defined. Nonlinearity also surfaces as a problem in clinical evaluation of humans. In an effort to improve on the ordinal scale, behavioral and physiological observations have been refined into several general categories and assigned a weighted score within each. An example used is the Melbourne Pain Scale (MPS) which has 6 broad categories that have been divided into 3 or more levels assigned a different numerical weight, has 2 observers, and utilizes videotaped footage of interactions between the dog and the other observer. Maximum number of possible points awarded by the scale is 27. The highest mean score for an OHE was 8.0, which only underscores the difficulty of interpretation of the scale and the differences between live evaluations and working off a videotape. The purpose of the videotape was to validate and capture movement data from the animals being observed. Effects measured from animals receiving surgery that were significant included: 1) a reduction in the amount of time spent near the front of the cage, 2) total distance traveled, and 3) the average speed of movement. The administration of carprofen had no identifiable effect. Similar correlations are being made with animals on an outpatient basis, where owners administered analgesics and coded behaviors. They are still carrying on the study at veterinary hospitals for Evaluation of pain behavior in animals; it is believed that this can be accomplished by frequency analysis of objectively coded behaviors.Questions???1. Define ethology.2. List the pain rating scales that have been used to evaluate behavior in surgical procedures performed on canines.3. True or False ??? Similar effects on behavior of anesthesia, surgery and analgesia demonstrate significant effects of these manipulations on plasma cortisol concentration.4. What is the most obvious limitation of the VAS pain scale?Answers !!!1. Ethology: objective evaluation of behavior2. Pain rating scales: verbal, numerical, categorized numerical, visual analog scales (VAS) or a combination of two or more of these scales3. True4. significant interobserver variability
Agricultural (Nonbiomedical) Animal Research Outside the Laboratory: A Review of Guidelines for Institutional Animal Care and Use Committees pp. 206-210
The purpose of this article was to review the guidelines that apply to agricultural animals that are used in agricultural research settings. The Animal Welfare Act does not specifically include livestock and poultry used in agricultural research settings while the Guide for the Care and Use of Laboratory Animals addresses agricultural research that is funded by the U.S. Public Health Service. Currently the most comprehensive set of guidelines concerning the use of agricultural animals for agricultural research and teaching can be found in the Federation of Animal Science Societies (FASS) publication Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching (the Ag Guide). While the Ag Guide provides general guidelines for establishing institutional policies, health care standards and husbandry protocols, it has no regulatory authority unlike the Guide or the Animal Welfare Regulations. The USDA has adopted the Ag Guide (animal care policy 29) to provide guidance regarding the care and use of farm animals in biomedical research settings. Specific examples of the AWA farm animal exemption can be found in the USDA APHIS animal care policy 26. Portions of the Ag Guide have also been adopted as standards for the use of agricultural animals in biomedical and agricultural research by the Association for the Accreditation and Assessment of Laboratory Animal Care International (AAALAC).
Some areas that can present unique challenges when working in an agricultural setting include inspection, repair and maintenance of physical facilities, disaster preparation planning, and recruitment and training of animal care staff. With respect to the IACUC, the author notes that the committee should include scientists, caretakers and/or veterinarians that are familiar with livestock and/or poultry management practices. Other IACUC concerns include the use of standard agricultural practices (dehorning, castration, beak-trimming, etc.), animal welfare assessment (behavior, appearance, performance/productivity), biosecurity, social environment and investigator qualifications. The author also notes that some agricultural research projects may require more intense veterinary care and emphasizes that staffing should be adequate enough to prevent overburdening a single veterinarian which may require the hiring of additional relief or consulting veterinarians or additional veterinary technical staff.
Questions:
1) True or False: The Guide for the Care and Use of Laboratory Animals (The Guide) provides detailed information regarding the use of agricultural animals in agricultural research and teaching.
2) What does FASS stand for?
3) Which of the following agencies have adopted portions of the FASS Ag Guide to address standards of care for agricultural animals in both agricultural and biomedical research settings?
a) USDA
b) FDA
c) AAALAC
d) a and b
e) a and c
Answers:
1) False, The Guide covers the use of agricultural animals in biomedical research settings but does not provide details concerning their use in agricultural research settings.
2) Federation of Animal Science Societies
3) e) both the USDA and AAALAC have adopted portions of the Ag Guide
Behavioral Evaluation of the Psychological Welfare and Environmental Requirements of Agricultural Research Animals: Theory, Measurement, Ethics, and Practical Implications pp. 211-221
Agricultural animals are used in a variety of research endeavors including human focused biomedical research, development of biomedical and pharmaceutical products, agricultural production research and study of the welfare of food production species. This article explores the theory, psychological welfare, and environmental requirements for the psychological well being of these species, especially pigs and poultry. Further discussions address the design of experimental research incorporating considerations for psychological research. Relevant points are included below.
1. Animal welfare must include consideration of scientific evidence, philosophical values and economic considerations. The concept of what constitutes an individual animal’s welfare remains a point of contention between scientific and philosophical studies. Animal emotion and distress are subjective emotional states proposed and described by neurophysiologists and ethologists. These emotional states do not lend easily to scientific observations, thus are not directly open to scientific measurement. Therefore, aspects that may impact these emotional states, such as of husbandry, are difficult to correlate to animal well-being.
2. Motivational behavior occurs when an animal performs an instrumental response to obtain a reward or escape or avoid punishment. Such measures can provide an observable correlate of subjective states, and may enable an objective measure of the importance an animal places on gaining or avoiding a particular stimulus.
3. The preference test is the simplest measure of an animal’s choice. They are valuable as a first step in understanding animal priorities because they are practical, relatively easy to perform and highly externally valid when animals are tested in environments that mirror the animal’s normal housing. The limitation of the preference test is it is difficult to determine if the animal is choosing between two valued commodities, or the lesser of the two evils.
4. Consumer demand research uses techniques adapted from human microeconomics. It measures the animals demand for a resource (example food) by determining how the animal’s behavior changes when increasing “costs” are imposed on access or utilization of the resource. Demand studies are powerful indicators of animal priorities, and may be used to measure a wide range of resources. However, demand studies utilize complex apparatus and require careful consideration of methodology, lengthy animal training periods and extensive time. They are particularly useful when paired with physiologic parameter measures.
5. Behaviors performed in the absence of eliciting stimuli that have been termed “vacuum behaviors”. These behaviors are strong intrinsic behaviors that require a particular resource for the performance of the behavior. They closely resemble normal behavior sequences, but when performed without the stimuli, suggest a need to perform the behavior, and the lack of stimuli constitutes a behavioral deprivation. Triggers can be husbandry related such as dust or litter for poultry dust bathing. Observations of wild animals in their natural habitat can provide predictive indications of stimuli that have implications for welfare.
6. Stereotypic behavior (repetitive, invariant, non-functional behavior) draws much attention to the animal welfare issues. Speculations indicate this may reflect an inappropriate environment or that the welfare of the animal is compromised. Sterotypies can occur temporarily and may be modified by simple environmental enrichment. Note that stereotypy within a group shows notable individual variation and thus may increase uncontrolled variation in data that relies on the flexibility of response.
7. Good practice requires the critical evaluation of all research for potential costs and benefits. Ethical and methodological considerations can be included in experimental design, and the results of these practices reflected in journal reports to help amass documentation of “best practice”.
Simple changes in the research or farm environment in terms of enrichment, information searches and consideration of welfare in experimental design can increase rewards for both scientific knowledge and animal welfare. Professional scientific advise on psycho logic welfare is available from a wide range of resources such as AWIC, SCAW and UFAW. Great progress and understanding of ag animal welfare has been made in incorporating animal welfare knowledge into experimental design, housing and husbandry. and the best practice should be incorporated to reflect these advances to peers and the public. Simple straightforward solutions are available.
QUESTIONS:
ANSWERS:
Demands for Rhesus Monkeys in Biomedical Research: A Workshop Report pp. 222-238
There is a current shortage in certain nonhuman primate models. The two components of the NIH, the Office of AIDS Research (OAR) and National Center for Research Resources (NCRR) are taking a lead role in addressing the issue of shortages of NHPs. In conjunction with this, the NCRR & OAR convened a panel to discuss the following:
1. Specific demands for rhesus & determine rhesus availability and limitations
2. Identify other NHP models (besides Indian origin rhesus) used for biomedical research
3. Put forth recommendations to alleviate the demands on rhesus
Speakers invited to talk addressed the following concerns relative to the NHP species they represented:
-What diseases do they model?
-What are the similarities/dissimilarities to rhesus & humans?
-What is their availability? Are they endangered?
-Are there importing problems?
-Are there animal husbandry issues?
-Are there specific pathogen concerns?
Summary of
recommendations
Rhesus macaques are in short supply in the US, for at least the next 5-10 years, panel supports developing alternative NHP models.
Common reagents needed that can be used across species
Cross species comparisons of vaccines & challenges
Cynos are susceptible to SIV/DeltaB670 and can be used for SIV pathogenesis studies & therapy, pig-tailed macaques can be used for microbicide studies & Chinese rhesus are available for use.
Establishing national resource centers devoted to certain species that are good models, like the African green monkey.
Support breeding of species with biomedical uses (cynos & baboons).
Diversify the National Primate Research Centers (NPRCs) and encourage the use of alternative species.
Can use these species for infectious disease, immunology, genetics & aging.
Increase research in basic sciences
Websites & scientific conferences.
g. Develop comprehensive national primate plan
Meet the needs of US scientists by forging relationships with source countries
h. Expand breeding of rhesus and enhance
access to NHPs
Rhesus is indispensable to some types of research, develop partnerships with other countries.
-Address issues with transportation
i. Address critical need of
adequate facilities
Facilities are needed for:
Breeding
Experimental use & quarantine
i.
Recognize the need
for long-term planning & stable funding
Chronic shortages of funds jeopardizes current programs
WORKSHOP
PRESENTATIONS
Session 1: Rhesus resource needs, availability, limitations
Overview of NCRR-supported rhesus
resources
NCRR supports the 8 national primate research centers (NPRCs)
25,000 NHPs, 15,000 rhesus & 4,000 baboons, breeding programs are expanding.
SPF colonies. Being expanded by 6 grants awarded by NCRR for rhesus & pigtailed macaques. Takes 5 years to start producing, more grants are to be awarded.
NIH grantees survey. 13,000 NHPs were used for NIH research in 1999, 65% were rhesus. Scientists outlined a need for: more breeding of NHPs, more availability of NHPs, NHPs should be available to scientists outside of NPRCs, increase publicity for NPRCs, and increase funding or reduce cost of NHP resources.
Overview of specific monkey needs
for AIDS research
Model to study AIDS developed by injecting sooty mangabey or African green SIV into rhesus would mimic AIDS in people. At the time, rhesus were available because they had been bred for polio vaccine research. Scientists needed a single model system of a certain type of monkey & virus stock to compare results to conduct vaccine research. A better approach, however, would be to develop methodologies that would be comparable across species, like some commercially available immunological reagents.
Vaccine research made the demand for macaques grow. In fact, they used so many macaques they had to get them from commercial resources.
Macaques used for AIDS research represent less than half used for all biomedical research, and the demand is expected to grow esp for transplantation & bioterrorism.
Some solutions:
-Use pigtailed & bonnet macaques for microbiocide research
-Compile across species databases for viral & immunologic parameters
-Compare across species, look for alternatives, find primary & secondary animals for disease research
Session 2: Alternative Macaque Models for AIDS Research
PIGTAILED MACAQUES
-Scientists have learned that viral load is not an absolute predictor of survival in trials with SIV-infected pigtailed macaques.
-Scientists are also encouraged to consider which type of SIV virus they are using as well as what type of monkey,…because this will improve efficiency of infection.
-In regards to CD-4 cell depletion, often our monkey models do not mimic human infections.
INDIAN VS. CHINESE
RHESUS MACAQUES
-Most NHP SIV challenges are conducted IV even though most human acquire the disease from mucosal contact.
-The NIAID Division of AIDS is developing a NHP lentiviral natural history database in order to help standardize which SHIV virus evolved with which animal to aid scientists.
-Chinese macaques are susceptible to SIVmac & certain SHIV, they are cheaper and more readily available than Indian. Indian rhesus SIV infection does not necessarily mimic human infection because the disease develops faster & the viral load is 1000 times higher in Indian rhesus vs. human.
-Researchers have also found viral loads for humans & Chinese rhesus were more similar than viral loads when compared to Chinese vs. Indian & Indian vs. human.
INDIAN VS. CHINESE
RHESUS MACAQUES II.
-Variation within Indian or Chinese is as great as variation between these populations!
-Some studies have shown no difference between these two groups when IV & intravaginal tests were performed, and have seen that viral titers can be highly variable among Indian rhesus especially.
CYNOMOLGUS MACAQUES
-Researchers found there were no significant differences between Indian rhesus macaques, Chinese rhesus macaques, and cynomolgus macaques at 1,2 & 8 months post vaginal infection with SIV/DeltaB670, a primary isolate of SIV.
Session 2: Alternative Old World Primate Models for
Non-AIDS research
CYNOMOLGUS MACAQUES (Macaca fascicularis)
|
GENERAL
CONSIDERATIONS |
Smaller than rhesus, M=5kg, F=2.5kg. From Indonesia & Malaysia, live 20 years. Usually B-virus positive, less susceptible to TB than rhesus. Absorb dietary cholesterol better than rhesus, vervets, baboons, humans. |
|
AVAILABILITY &
COST |
Current prices are $750 to $2000, large numbers have been imported but future availability from countries of origin is uncertain. |
|
RESEARCH AREAS/MODELS |
Readily adapt to industrialized-type human diets, vulnerable to chronic diseases of humans |
|
Cancers of repro
tract |
Breast & uterine in relation to estrogen exposure (models human condition of estrogen exposure causing breast & uterine cancer), and phytoestrogen health food supplements |
|
Cardiovascular
disease |
Atherosclerosis and coronary function are studied to decide the role of dietary cholesterol, stress, repro hormones |
|
Diabetes |
At least 1% of cynos spontaneously develop type 2 diabetes, having elevated blood glucose, fructosamine, glycated hemoglobin, & triglyceride |
|
Drug abuse |
Cocaine & alcohol abuse in relation to social interaction |
|
Osteoporosis |
Estrogen deficiency causes rapid bone loss, similar to humans. |
|
Repro function |
Have a menstrual cycle similar to that of humans, not seasonal breeders, subordinates in small social groups become estrogen-deficient similar to psychogenic amenorrhea in people |
|
Other disease |
Depression, TB, AIDS |
PIGTAILED MACAQUES (Macaca nemestrina)
|
GENERAL CONSIDERATIONS |
Most originated from Sumatra, Kalimantan or Borneo. Malaysia, Burma, Thailand & Vietnam. Omnivorous, size of a rhesus, more tractable than rhesus, most herpes-B positive, TB is a concern. |
|
AVAILABILITY &
COST |
Washington & Yerkes NRPC have pigtailed macaques, breeding colonies are needed to support increased use of this NHP |
|
RESEARCH
AREAS/MODELS |
|
|
Infectious disease |
AIDS, particularly HIV-1, HIV-2 and numerous SHIVs. |
|
Reproductive
physiology |
Pronounced tumescence and detumescence. 28 day menstrual cycle, vagina is human-like in flora, pH and epithelial thickness. |
BABOONS (Papio sp.)
|
GENERAL
CONSIDERATIONS |
DNA between macaques & baboons 98-99% identical Chimp & human are 98-99% identical 5 subspecies: Olive baboon (Tanzania & Kenya) Red baboon (West Africa) Yellow baboon (Tanzania) Hamadryas baboon (Ethiopian, Somalia & Arabian peninsula) |
|
AVAILABILITY &
COST |
Readily available from SW NPRC Transportation from Africa is a problem Cost from SW NPRC is $3500-5000 |
|
QUICK FACTS |
0.8-0.85 live births per year/female Single male can service 20-40 females Females weigh 10-20 kg Males weigh 20-40 kg |
|
ADVANTAGES TO
BABOONS |
Hardy to environmental conditions Gene map is farther along than rhesus or vervet Size=larger is better for surgery Do not carry herpes B, resistant to TB |
|
DISADVANTAGES TO
BABOONS |
Size=larger, stronger cages and more dose if used for tox |
|
RESEARCH
AREAS/MODELS |
|
|
Aging |
SW NPRC has 200-300 pedigreed & genotyped 16+ year old baboons |
|
Alcoholic liver
disease |
Proved that alcohol, not poor diet is the cause |
|
Cardiovascular |
Genetics of blood cholesterol control & atherosclerosis |
|
Developmental
biology |
Embryology, teratology, dental development, lung disease, infant nutrition |
|
Diabetes |
Type 2 develop spontaneously |
|
Genetics |
Baboon chromosomes are remarkably similar to humans |
|
Hypertension |
Develop naturally or induced by renal artery stenosis |
|
Infectious disease |
Chagas disease (T. cruzi), shistosomiasis, periodontal disease & dental caries |
|
Neonatology |
Reboons (cross between rhesus male and female baboon) are born prematurely |
|
Neurobiology |
Drug abuse, epilepsy, etc. |
|
Obesity |
Spontaneous obesity |
|
Osteoporosis |
Some baboons develop disease similar to humans, some are resistant to it |
|
Reproduction |
Obvious perineal changes during cycle, used for pregnancy, endometriosis, conception |
|
Transplantation |
Xenotransplantation from pigs |
AFRICAN GREEN MONKEYS
(Chlorocebus aethiops)
|
GENERAL
CONSIDERATIONS |
Aka Vervet Originate from sub-saharan Africa with populations introduced to St. Kitts, Nevis, & Barbados Sexual maturity: M3-4 years, F 2-3 years Produce one infant per year, gestation 165 days Carry African green SIV (SIV-agm), Cercopithecine herpes virus-2 (SA-8), and Marburg, do not carry herpes B. Caribbean vervets free of most diseases |
|
AVAILABILITY &
COST |
Readily available from import from the Caribbean, Large colonies at New Iberia, UCLA/VA, Wake Forest, U of Texas-Austin Cost is $1000-$2000 |
|
ADVANTAGES TO AGMs |
Low cost, do not carry B virus, can be housed in same caging as rhesus, genetically homogenous |
|
RESEARCH
AREAS/MODELS |
|
|
Cell Biology |
Green monkey kidney cells used for cell bio & physiology |
|
AIDS |
Used more in Germany |
|
Behavior |
Maternal, developmental, communication, aggression, impulsivity, etc. |
|
Cardiovascular/pulmonary |
Atherosclerosis, heart disease, COPD |
|
Diabetes |
Develop type 2 diabetes |
|
Genetics |
Alcohol preference & anxiety, map of the vervet genome is underway |
|
Neurobiology |
Parkinson’s disease, neural development |
Session 4: Alternative New World Primate Models for
Non-AIDS Research
OVERVIEW OF NEW WORLD
PRIMATES
|
GENERAL
CONSIDERATIONS |
Not as closely related to humans as old world monkeys, but very suitable for studying certain diseases. Central & South America |
|
AVAILABILITY |
Most South American countries have banned importation, squirrel monkeys and marmosets are bred at US colonies Need for increased supply |
|
CARE & HANDLING |
Need routine & regular handling, generally hardy if habituated to procedures and have good housing |
|
ADVANTAGES TO NWMs |
Small size means more economic to feed & house Do not carry B virus |
|
DISADVANTAGES TO
NWMs |
Limited availability Small size means limited blood collection & not good for surgery |
SQUIRREL MONKEYS (Saimiri sciureus)
|
GENERAL
CONSIDERATIONS |
Bolivian squirrel monkey, S. boliviensis boliviensis is the best biomedical research model, and is most of Alabama’s colony (largest in US) S. oerstedii is only endangered squirrel monkey Before they were banned, 3000 per year were being imported |
|
SCIENTIFIC DEMAND |
1400 papers published in last few years Very good for drug studies because they are small |
|
AVAILABILITY &
COST |
Alabama has 115 live births per year, only 60-70 are used for research, rest are replacement breeders. Working with Bolivia to be allowed import permits |
|
QUICK FACTS |
Seasonally polyestrus, only ovulate for 3 months per year, gestation 150 days, females produce 0.65 offspring/year, breeding starts at 2.5-3 years old, housed in harems with 1-2 males per group, harbor Herpesvirus saimiri 1 & 2, which infect other NWMs and cause lymphoma, no transmission to humans, no B virus |
|
RESEARCH
AREAS/MODELS |
|
|
Aging |
Calorie restricted diets |
|
CNS |
Brain/body weight ratio is similar to humans |
|
Creutzfeldt-Jakob
Disease (CJD) |
Susceptible to all spongiform encephalopathies, develops 20-22 months after inoculation, shorter than rhesus |
|
Genetics |
Satellite markers are available, maternal pedigrees are being developed |
|
Leishmania &
Chagas |
10% from South America are naturally infected with T. cruzi & squirrels develop fibrous cardiomyopathy |
|
HTLV1 |
Persistent viremic state, vaccine development |
|
Malaria |
1-2M people die from malaria, 300-500M develop the disease. Squirrel monkeys can be infected with Plasmodium falciparum & P. vivax which are human malarias. Other NHPs are in great demand for malaria vaccine research |
|
Parkinson’s Disease |
MPTP neurotoxin has been developed for Parkinson’s in squirrel monkeys |
|
Peridontal disease |
Naturally prevalent |
|
Pelvic organ
prolapse |
Incidence increases with age, parity, infant weights |
OWL MONKEYS (Aotus trivirgatus & nancymae)
|
GENERAL
CONSIDERATIONS |
Aotus nancymae (Peruvian red-necked owl monkey) species making up the nation’s largest colonies of owl monkeys. Pair monogamously, which necessitates large breeding colonies |
|
AVAILABILITY &
COST |
Extremely limited supply, export is banned |
|
QUICK FACTS |
Only nocturnal simian primate, nonseasonal breeding, gestation 150 days, sexual maturity is 2-2.5 years of age, give birth to one young every 13 months, live as monogamous pairs. |
|
RESEARCH AREAS |
Best model for human malaria, esp P. falciparum |
OVERVIEW OF TAMARINS
& MARMOSETS (Family Callithrichidae)
|
GENERAL
CONSIDERATIONS |
Range in size, but are exceptionally small. Produce more than one young at a time, and share blood supply, produce hematopoietic chimeras, proven useful in some research on autoimmune diseases. |
|
QUICK FACTS |
Cooperative breeding groups, older offspring take care of the young of a breeding pair |
|
ADVANTAGES OF
MARMOSETS & TAMARINS |
Unusually fertile, produce 1.5-2.8 young per year |
|
RESEARCH AREAS |
Aging & transplantation/immunology |
TAMARINS
|
GENERAL
CONSIDERATIONS |
Four species important in biomedical research: Cotton-top tamarin (Sanguinus
oedipus) Saddleback tamarin
(Sanguinus fusicolis) Moustache tamarin (Sanguinus
mystax) White-lipped tamarin (Sanguinus labiatus) Indiginous to south america from Panama to Amazon |
|
AVAILABILITY &
COST |
One remaining captive colony at New England NPRC |
|
RESEARCH
AREAS/MODELS |
|
|
Colitis and colon
cancer |
Defining natural history & pathology, examine role of environmental factors, E coli & new helicobacters species as playing |
|
Hepatitis &
viral oncology |
GBV has been studied in S. labiatus & S. mustax and is an excellent model for human hep C. Has been used to test potential antiviral compounds & screening test for hepC |
|
COMPARISON WITH
MARMOSETS |
Common marmosets is a better animal model because they are available & fecund |
MARMOSETS
|
GENERAL
CONSIDERATIONS |
One genus Callithrix Atlantic coastal forest species C. aurita & C. flaviceps, C. penicillata, C. jacchus, C. kuhli,
C. geoffroyi Amozonian species C.
argentata, humeralifer, C. emiliae. C. jacchus is only one important for biomedical research. Primate of choice in Europe, but not suitable for AIDS research |
|
AVAILABILITY &
COST |
Several commercial suppliers in Europe & US |
|
QUICK FACTS |
Social groups with parental care of infants done by the adult males & females in the group. Should not be singly housed. Gestation 145 days, twins produced every 6 months, mature at 1.5 years old, live 12-14 years. |
|
ADVANTAGES OF
MARMOSETS |
Need little floor space, prefer vertical space. Tractable & responsive, economical, great reproductive capacity |
|
DISADVANTAGES OF
MARMOSETS |
Historical data is lacking on tox outcomes of drug studies, inflammatory bowel disease plagues this species, 12-14 years |
|
RESEARCH
AREAS/MODELS |
|
|
Adrenal dysfunction |
Adrenals have a fetal zone at birth, then a inner zone that is poorly developed in adulthood, new insights into molecular regeneration |
|
Aging |
Maintain bone mass during estrogen depletion |
|
Behavior |
Marmosets fail to rear young offspring, even though they are socialized with their parents, can be neglectful & abusive |
|
Infectious disease |
Human herpes simplex susceptible |
|
Multiple sclerosis |
Immunized against human nerve tissue & develop MS |
|
Neurobiology |
Smooth cerebrum & small brain but can complete two-step puzzle tasks Can sit in MRI & PET scanners without sedation |
|
Obesity |
Model for viral induced apidosity, a problem in 10% of humans |
|
Parkinson’s |
MPTP has been used |
|
Reproduction |
Transgenic marmosets, male contraception & female social regulation. |
Questions:
1. What do the following acronyms stand for?
a. OAR
b. NCRR
c. NPRC
2. What type of SIV-virus are cynos susceptible to which maymake them good AIDS-disease models?
3. Name the following genus and species.
a. Pigtailed macaque
b. Olive baboon
c. African green monkey
d. Bolivian squirrel monkey
e. Red-necked owl monkey
f. Common marmoset
Answers:
1. a. Office of AIDS Research
b. National Center for Research Resources
c. National Primate Research Center
2. SIV/DeltaB670
3.
a. Macaca nemestrina
b. Papio anubis
c. Chlorocebus aethiops
d. Saimiri boliviensis boliviensis
e. Callithrix jacchus
There are many more questions I could write but this is a pretty exhaustive summary!