National Institutes of Health (U.S.) Division of R.

Report of program activities : National Institutes of Health. Division of Research Resources (Volume 1975) online

. (page 32 of 34)
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form will provide a record of not only glassware issued, but items of glass-
ware ordered, and some indication of how well the Unit is meeting the demand
for glassware. The percentage of each item ordered and supplied by size and
type of glassware should provide useful data.

A workload measurement study was conducted in the Unit this year with the help
of the Management Analysis office, to calculate new average processing times
for individual types of glassware. As a result of this study, several workload
improvement recommendations were made and are being implemented. As a prelim-
inary step, a large glassware drying unit, which is no longer required, was
removed to create space for installation of a proposed conveyor system to be
adapted to the M-2 washer. This conveyor system should reduce the manual
handling of glassware baskets as they are filled and transported to the machine
for washing.

7. Animal Biologies Production

Domestic turkeys and ducks were utilized in small numbers to produce normal
blood and antisera for specific research projects.

The canine blood donor colony, which consists of 258 dogs, produced 3, 500 units
(1 unit = 500 ml) of blood.

Biologies production from ungulate animals is about the same as during FY 1974-
Projected production includes 14-00 liters of ungulate blood for the year. The
size of the ungulate herd being maintained for all purposes increased from 550
to 610 during FY 1975.


8. Genetic Repository and New Animal Models Program

VRB rodent colonies were designated as a World Health Organization
collaborating center in recognition of the importance of this collection of
animal models for biomedical research. The one other collaborating center
designated was the Laboratory Animal Center of the Medical Research Council
of Great Britain. The director of that center served as a consultant to VRB
during a WHO sponsored visit this year.

A committee of the National Research Council studied the VRB small animal
program. It concluded that the repository effort should be separately
financed through management funding and not supported by inflating the price
for animals. About $500,000 was determined to be the annual cost for
maintaining the repository.

A Catalogue of NIH Rodents was published and distributed to about 257 NIH
investigators and 765 researchers and specialists in animal science worldwide.
It describes characteristics of the over 100 strains and stocks of rodents and
rabbits maintained. In addition to supplying animals for intramural investi-
gators, breeding nuclei from these colonies serve as a resource for the
international biomedical research community as many of the stocks, strains, and
substrains are not available elsewhere. Over 300 investigators were provided
with litters of inbred animals to start colonies. This is a twofold increase
over FY 1974- вАҐ Also, several hundred noninbred animals were provided as
breeding stock. Several commercial producers were also provided with breeding
stock. Requests were particularly numerous for the rat with diabetes insipidus
and hypertension, inbred NZB and NZW mouse strains, and inbred guinea pigs.

A program to assist investigators in obtaining new animal models to meet
previously unfilled research needs continued. In some instances, new strains
of existing laboratory animals exhibiting unique physiological or anatomic
characteristics were used. In others, animals having characteristics
required in a particular research problem were adapted from nature. New models
are hysterectomy derived and foster nursed or hand nursed prior to introduction
into the NIH colonies. Twelve new strains were added to the repository at
the request of NIH investigators. They are:

Mice Rats European Giant Hamster

BALB/eCRN WFU/CrN Guinea Pig


Dwarf (dw) SHRSP/A3N PCA (passive cutaneous

Motheaten (me) Corpulent (cp) anaphylaxis)

Dystrophic-2 ( dy-2 )

BDL-ky (kyphoscoliosis)

9. Experimental Surgery, X-ray, and Related Activities
a. Building 14E and 28 Facilities

The surgical facilities are primarily available to B/I/RD investigators;
however, surgery was frequently performed by staff veterinarians assigned to


the Section at the specific request of investigators. Assistance to
investigators was provided in anesthesiology, surgical support, diagnostic
radiology and postoperative care of animals.

The number of surgical procedures stabilized at approximately 800 per year and
the facilities were used at maximum capacity. An increase of 10 percent is
projected next year since the Surgery Unit relocated from Building 28 to 14-E
and will provide more surgical space. The Surgery Unit maintains a 500-milli-
amperage radiographic unit with fluoroscopy which adds an improved service for
research and clinical support to laboratory animal medicine.

b. Animal Center Ungulate Surgery

Activities in ungulate surgery declined. Projects utilizing sheep for
intrauterine fetal surgery have ceased. Surgery was utilized for porcine skin
transplantation procedures, collection of fetal pig serum, and to treat a
variety of clinical conditions. Miniature swine breeding is continuing to
develop four inbred lines of immunologically distinct animals. Five sows
produced progeny this year.

Radiographic procedures increased from 250 exposures in FY 1974 to 420.

10. Experimental Animal Holding

a. Primates

Renovations for Phases II and Illof Building 14D will be awarded to contractors
before the end of FY 1975, and estimated completion date is 12 months after the
award date. This renovation is a joint program between DRS and BoB which will
provide a centralized research primate holding facility. The new renovations
are designed to permit infectious disease studies, provide a safe working
environment for personnel, and minimize cross-infection among primates. The
total capacity of the facility, including the conventional primate facilities
of Phase I renovations, will establish one of the largest primate research
facilities in the country with a maximum primate population of ever 1900

b. Large Laboratory Animals

The research holding facilities of Building 28 has increased its scope of
research support by greater diversity of animal species including: dogs, cats,
miniature swine, goats, sheep, and other large laboratory animals. In addition,
new collaborative DRS research programs with NCI and NHLI were initiated.
Continued use of a contract to hold dogs off the Bethesda campus allowed
improved utilization of space for studies requiring constant investigator
attention. The atherogenic diet study in dogs in Building 14E will relocate
to Building 28.

The population of research animals in this facility averages approximately 360
per month. Additional research animals, requiring only infrequent investi-
gator manipulation, are maintained on contract. This has permitted a more
suitable animal density population per kennel to achieve better animal care


management. Recent renovations of two large animal wards in Building 28
significantly improved animal welfare, and improved the research environment
and employee working conditions.

11. Animal Nutrition

VRB-developed, open formula rations continue to be used throughout the NIH.
Purchase arrangements were made through competitive contracts for three new
open formula rations; autoclavable rations for rats and mice, rabbits and
guinea pigs. Based on current prices, the open formula rations purchased under
competitive contracts cost 36 percent less than the closed formula rations
purchased under noncompetitive contracts. When this price differential is
applied to the open formula feeds purchased under competitive instead of
noncompetitive contracts, an apparent savings of approximately $115,000 will
be realized by NIH during the contract year.

The NIH, open formula ration for conventionally reared rats and mice was
adopted as a standard reference ration by committees of the American Institute
of Nutrition and the National Research Council.

The proximate nutrient, calcium, and phosphorous concentrations in NIH contract
animal feeds were monitored. This information is useful in demonstrating to
investigators the variation in nutrient concentrations among production batches
of a given ration.

The contract to conduct nutrient analyses on experimental rations was expanded
to include assays for various feed contaminants. At least one sample collected
from all animal feeds purchased under NIH contracts has been assayed for heavy
metals and pesticide residues. To date, the concentrations of these potential
contaminants have been either undetectable or within acceptable ranges.

An open formula, autoclavable ration containing 18 percent crude protein is
being fed to SPF production colonies of rats and mice on a trial basis. There
has been no apparent decrease in the reproductive performance of animals fed
this ration as compared to animals fed a commercial ration containing 24 "
percent crude protein. Similar results were obtained under experimental

12. Animal Health

a. VRB Animal Health Problems

A pinworm eradication program was initiated in conventional mouse production
colonies. Piperazine was proportioned into the drinking water continuously
for a one-month period while the buildings were being disinfected with an
iodophor to destroy pinworm ova. Following this, treatment was alternated
every other week and untreated, helminth-free sentinal animals placed in the
rooms were monitored to determine whether total eradication was achieved.
Plans were made to use dichlorvos to treat a mite infestation discovered in
inbred mouse production colonies.


An outbreak of Tyzzer's disease occurred in C-wing rabbits early in the year.
Tylosin in the drinking water was found to be therapeutically effective, stopping
the outbreak after only 20 deaths. A major epizootic may have been averted
since the C-wing rabbits have been free of the disease and are probably highly
susceptible. Inasmuch as the causative agent is a spore former, it is considered
likely that it will gain entrance into the colony again. The indirect fluor-
escent antibody technique has been used in preliminary studies of the natural
history of the disease and to demonstrate antigenic similarities between the
causative agent in rabbits and the agent recently isolated from horses.
Because of shortcomings of this method for serologic survey work, several
antigens are being tested in the development of a complement fixation test.
As more is learned about the antigens, hopefully, the preparation of a vaccine
will become possible.

Although Tylosin was effective in treating C-wing rabbits for Tyzzer's disease,
its use appeared to precipitate a severe outbreak of enterocecocolitis which
resulted in 108 deaths in one month. Enterocecocolitis has been present in
C-wing rabbits for several years, causing an average of about 20 deaths per
month. Culture results have indicated that it is caused by imbalances of
intestinal microflora, particularly overgrowth of E. coli, which may be stimu-
lated by the use of certain antibiotics such as Tylosin. It is postulated
that these cesarian-derived rabbits are "too clean" and that additional
bacteria are needed to broaden the intestinal microflora to provide effective
competition for E. coli . For this reason, attempts were made to acquire
specific pathogen-free rabbits from other sources to act as microfloral donors.
Two attempts failed. The rabbits from one source had coccidiosis and those
from another source were infected with Bordetella bronchi septica .

The barrier-maintained mouse colony suffered its worst recorded outbreak of
hemothorax. The outbreak lasted 2 months. All strains of mice were affected,
and virtually all males over the age of 6 months were lost. As previously
described, this disease appears to be a noninfectious condition of male mice
characterized by myocarditis and prolonged clotting time. The cause of the
sporadic outbreaks is not known. It has been postulated that some noxious
substance, which secondarily increases the mouse's requirement of vitamin K,
periodically finds its way into the ration. Supplemental vitamin K was added
to the diet of the barrier mice but, unfortunately, this was at about the time
the outbreak was subsiding so that the effect was impossible to evaluate.
A beneficial effect was suggested, however, by the finding that only a few
scattered hemothorax fatalities occurred in the 9 months since the supplemental
vitamin K was started. The results of a recent pilot study indicate that the
disease can be reproduced by feeding mice excessive vitamin A, which is known
to increase the mouse and rat requirements for vitamin K.

The incidence of Johne's disease in goats increased. Fecal culturirg for
Mycobacterium paratuberculosis in the goat herd was continued during FY 1975.
The incidence of Johne's disease declined from 21 cases in 1972 to two in 1973
and rose to five in 1974. Culturing will be continued indefinitely on a semi-
annual basis. The disease is considered difficult to eradicate since the
causative organism is relatively stable in the environment and its detection in
animals incubating the disease is laborious. Goats may incubate the disease
for several years before fecal cultures reveal the causative agent. Current


information indicates that Johne's disease is endemic in Maryland and that
anyone buying goats on the open market will, in time, purchase animals with
the disease.

The monkey breeding facility at Perrine, Florida, experienced an outbreak of
progressive debilitating disease characterized by alopecia, acneform dermatitis,
facial edema, squamous metaplasia in palpebral glands, hypertropic gastritis
and death. Many of the clinical and histopathologic findings are compatible
with hypovitaminosis A which, in rhesus monkeys receiving adequate amounts of
dietary vitamin A, points to the possibility of toxic exposure to chlorinated
hydrocarbons. Preliminary chromatographic analysis of tissue specimens from
affected monkeys indicatesthat the toxic substance may be polychlorinated
biphenyls (PCB's). PCB's are known to be rapidly toxic for rhesus monkeys in
very low dose, 2 ppm in feed, and to produce similar lesions to those occurring
in the Perrine monkeys.

Brucellosis testing is now performed annually in the swine and goat herds and
in the sheep flock. All new acquisitions are tested during the quarantine
period. No new cases were observed.

Urolithiasis was diagnosed in 12 goats (wethers) and six sheep (wethers).
Three of the cases were fatal. The disease is thought to be associated with
the exclusive feeding of grain concentrates, and may also be related to
mycoplasma infections.

b. B/I/D Animal Health Problems

No large-scale epizootics such as mouse pox occurred in the B/I/D' s this year.
Examples of lesser problems included the occurrence of cervical lymphadenopathy
in rats purchased on contract from a VRB contractor. The rats showed facial
edema and failed to sustain Walker carcinomas. Autopsies on animals on the
day of arrival in the laboratory revealed tracheitis and pronounced
peritracheal lymphadenopathy. Pasteurella pneumotropica was isolated from the
lymph nodes in six of eight animals cultured. The commercial colony was found
to be serologically positive for Sendai virus, which is reported to augment the
pathogenicity of P. pneumotropica infections. The company that produced the
rats was required to correct the problem.

Assistance was extended to the B/I/D 's also in the form of participation in
collaborative research of several types, including hepatitis A & B trans-
mission studies and studies of the effects of thymus- and bone marrow-derived
lymphocytes on the pathogenesis of autoimmune disease In NZB mice.

13. Animal Disease Investigation Service

The Animal Disease Investigation Service answered 182 calls for assistance
from the B/I/D' s, or approximately the same number as last year. These
involved consultative, diagnostic, and therapeutic activities. Animal species
encountered were varied; including rodents, rabbits, primates, carnivores, and
miscellaneous feral animals. The complexity of the calls also varied and
involved all Institutes. Ninety-four of the investigations required supple-
mental pathology exams, 38 required microbiologic testing and 30 utilized


clinical pathology tests. This service has been extremely well received by
B/I/D investigators. The service continues to be mutually beneficial to
investigators and to the VRB professional staff.

D. Problems

Problems of animal disease are referred to in Part II, C, 12, a and b.

It now appears that the program initiated in 1968 to hysterectomy derive
foundation colonies for all mouse and rat strains and stocks may not result,
as expected, in the issuance of strictly pathogen-free animals to investigators.
Although VRB barrier colonies remain uncontaminated for periods beyond expecta-
tion, the production colonies in conventional facilities were reinfested with
internal and external parasites. Whether this was due to inadequate decontam-
ination of facilities or a recontamination by a flourishing resident feral
rodent population in the Building 14 - 28 complex is undetermined. Perhaps the
design, construction, location, state of repair, and age of the buildings
housing the present rodent colonies make it unrealistic to expect maintenance
of a totally pathogen-free status of rodents following hysterectomy derivation.
The facilities for rodent production are not barriers and are in close proximity
to quarters for primates, sheep, and carnivores. Nonetheless, the effort to
produce pathogen-free rodents will continue.

Some General Schedule (GS) Biological Laboratory Technicians working in the
barrier are being paid less than some Wage Grade (WG) animal caretakers in
conventional colonies performing less technically skilled work. The conversion
of these employees to GS pay scale has worked to their disadvantage because of
large WG pay increases. General Schedule technicians in the gnotobiotics unit
and professional services staff, as well as the barrier, are inadequately
compensated compared to WG employees. Unless the situation is corrected,
recruitment of qualified employees into these areas will become impossible.
Employees presently assigned these jobs are becoming interested in leaving or
returning to WG animal caretaker positions.

E. Program Plans

Consideration will be given to requesting approval to establish a committee to
advise VRB whether strains warrant being added to or dropped from the genetic
repository, as recommended by the NRC committee reviewing NIH rodent activities.

A computerized record keeping system is being developed by VRB personnel and
the DRS management analysts. Primary emphasis is on collection of data on
rodent breeding performance. Mating and mortality data will also be collected.

An expanded program of genetic monitoring is necessary to provide adequate
safeguards for the integrity of inbred strains. A routine testing program
involving test matings, histocompatability testing, and mandible analysis will
be established.

Present obsolete cages for rabbits and guinea pigs will be replaced as soon
as funding is available and an acceptable design tested. The evaluation of


a semiautomated cage for rabbits continues and plastic cages for guinea pig
harems are being tested.

The disease surveillance program for the rodent colonies must be enhanced to
ensure prompt detection of disease through VRB monitoring. The effort to free
all rodent strains and stocks of disease through hysterectomy derivation will
continue. Methods will be developed for applying this practice to guinea pigs
and rabbits. This requires a cooperative effort in areas of nutrition,
microbiology, and genetics.

An effort will be made to survey requirements of investigators for rodents
beyond the capability of in-house production and to initiate new contracts to
meet these needs where possible, using VRB colonies as the genetic base.

Studies to define the major nutrient requirements of different species and
strains of inbred rodents will continue. Efforts will continue to develop
open formula rations purchasable through advertised contracts to replace closed
formula rations purchased through negotiated, sole source contracts.

It is expected that the Carnivore Unit will be reorganized before the end of
FY 1975; canine long-term holding will replace random source dog activities.
A canine socialization program was initiated and will be developed for
continuing application to colony reared dogs. Continued expansion of the
canine breeding colony by purchase of quality dogs from outside sources will
be pursued. Contract production of purebred foxhound puppies (approximately
500/year) will be continued into and beyond FY 1976. Plans are being developed
to create outdoor housing space for growing puppies. This program will permit
purebred production to expand by 200-300 per year.

The dairy goat and burro breeding herds will be expanded during FY 1976. About
15 jennies will be bred in FY 1975 and are expected to foal in the spring of
FY 1976.

Health surveillance of ungulate herds and flocks will be expanded and
intensified during FY 1976. Emphasis will be placed on identification and
containment of equine diseases because of implementation of a burro breeding

Further definition of the blood groups of dogs in the canine donor and
breeding colonies will be undertaken when "typing" anitsera becomes available
from outside sources.

Contract primate breeders will have been supplied all necessary breeding
stock before the end of FY 1975. Thereafter, efforts will be directed toward
supplying the contractors with replacement rhesus breeding stock on a
continuing basis. Animal Center programs will be readjusted in order to
provide holding space for young monkeys produced by contractors.

Improvement of leased property, consisting of some 200 acres of pasture and
several buildings adjacent to the Animal Center will provide space for
programs utilizing sheep, swine, and burros. Partial improvement of a pole
barn and installation of fences enclosing about 4-0 acres will permit expansion


of sheep activities (100-200 head) early in FY 1976. Expansion of swine
breeding/holding activities is anticipated late in FY 1976 with the erection
of a temporary farrowing/holding structure.

Within the limits of current manpower restrictions and space limitations,
continued efforts will be made to expand or improve automation of media
production. Continually increasing demands for bacteriologic media in plates
require the development or purchase of improved automated equipment for this
area of production. Quality control procedures will be expanded to focus
more emphasis on those aspects of bacteriologic media production which can be
monitored with limited space and personnel.

The possibility of using automatic data processing methods for inventory and
ordering of supplies will be explored. The shortages of various items of
supply make more efficient inventory and ordering methods mandatory if
production slowdowns are to be avoided.

A survey is being conducted by PEB to determine costs associated with the
current methods for regeneration of the large mixed bed deionizers. Items
monitored will include water usage per day, cost of caustic soda and hydro-
chloric acid for regeneration, and labor costs. Consideration will be given
to the possibility of contracting for this service, automating the present
equipment, or continuing the present manual system of regeneration.

The possibility of replacing the outdated cage and rack washers in the Clinical
Center cagewashing unit is being explored. The proposed consolidation of the
NCI animal rooms in the B corridor adjacent to the cagewashing unit is expected
to increase the workload on existing equipment and personnel. Purchase of new
equipment is recommended as the expense of upgrading existing equipment, due
to its age, is uneconomic.

F. . Publications

Bacher, J.D. and Potkay, S. : Intussception of the Small Intestine (ileum):
What is your diagnosis? J. Amer. Med. Assoc , 164: 1135-1136, 1974-

Ganaway, J.R.: Bacterial, mycoplasma, rickettsial disease. In Wagner, J.
and Manning, P. (ed. ): Biology of the Guinea Pig . New York, N.Y., Academic
Press, in press.

Ganaway, J.R. : Bacterial Zoonoses of Laboratory Animals. In Melby, E.C., Jr.
and Altman, N.H. (ed.): CRC Handbook of Laboratory Animal Science , Vol. II.
Cleveland, 0., CRC Press, 1974, pp. 243-257.

Online LibraryNational Institutes of Health (U.S.) Division of RReport of program activities : National Institutes of Health. Division of Research Resources (Volume 1975) → online text (page 32 of 34)