4.7. The animal house facility
Establishment of animal house in 1977 was another example
of the foresight of the NTI. It is a well established fact that experiments
in animal models have contributed significantly to the battle against
human TB right from the discovery of tubercle bacilli by Robert Koch in
the year 1889. The necessity of the animal house at NTI was felt just
after the establishment of its bacteriology section when the sputum samples
in large number started arriving from the research field areas. In 1962
a proposal was submitted to the GOI for creation of an animal house114.
It took about 15 years before Central Public Works Department (CPWD) could
hand over the building to NTI. Just after its establishment, a scientific
meting was held under the chairmanship of Dr NK Menon, Director, NTI.
It was attended by Dr BNM Barua, Adviser in TB, Dr K Padmanabha Rao, former
Senior Bacteriologist and Dr N Naganathan, Jr Bacteriologist of NTI, who
chalked out the plans for future experiments in laboratory animals and
their utility in TB control. Later in October 1979 when Dr KN Tandon,
Veterinarian joined the Institute, the breeding wing of the animal house
became operational with the procurement of initial stock of three guinea
pigs, six rabbits and four hamsters from Indian Institute of Science (IISc),
Bangalore. In May 1981, Dr Naganathan, with the assistance of Dr Tandon,
Veterinarian initiated the experimental work on a modest scale in the
northern wing of animal house which was cardoned off with suitable modifications
and installation of essential equipments like autoclave and incinerator.Verysoon,
Dr Tandon left NTI but preliminary experimental work which included standardisation
of techniques in getting familiarised with the experimental procedures
and finding out the suitability of a particular laboratory animal as animal
model for TB, continued. It was decided that the albino guinea pig is
ideal for this purpose. The breeding of other animals was discontinued
thereafter. Subsequently, full-fledged research projects involving guinea
pigs for animal experimentations were started. Prof. Donald W Smith of
University of Wisconsin Madison, USA along with Dr GVJ Baily, Director
played a key role in the above policy making decisions. Dr VK Challu joined
as Veterinarian in June 1983. This further strengthened the activities
of animal house. The highlights of some of the studies is briefly described
as under :
The Institute entered the 21st year with a happy
augury; the animal house commenced its activities. No doubt it has
started humbly, yet there is no denying the fact that new dimensions
are going to be added to our research in the near future.
Editorial, NTI Newsletter 1980, Vol 17/3
Dr. N. Naganathan Jr. Bacteriologist
Between 1982 and 1986, a study on significance of virulence of tubercle
bacilli in animal model was conducted. This revealed isolation of high
virulent tubercle bacilli from TB meningitis patients cerebrospinal fluid
in contrast to cavitory pulmonary TB patients sputum, where majority of
them excreted low virulent tubercle bacilli115. In another study carried
out between 1985 and 1988, isolates of M.tb from the urine and sputum
of pulmonary TB patients were found to differ in their virulence, phage
type and drug sensitivity pattern in a significant number of cases116.
This prompted for further investigations to understand the key events
in the pathogenesis of TB leading to the development of cavitory lesions.
Low virulent character of tubercle bacilli termed as south Indian
variant was interestingly found to remain unchanged during eight
years of animal passage from 1984 to 1992 in albino guinea pig animal
model117. Experiments on evaluation of protective effect of BCG and role
of environmental mycobacterial infection was also initiated. This was
followed by improvisation for assessing the virulence of tubercle bacilli
in animal model by a quantitative measurement which would be reproducible
in different laboratories irrespective of the investigators 118,119.
Animal experiments carried out in the institute have
also been assisting other research organisations in evaluating new antigens,
preparation of immunotherapeutic agents and new antigenic preparations.
Currently, experiments carried out at the institute involved T-cell proliferative
response to M.tb sonicate and protective efficacy of (plasmid DNA encoding
recombinant protein)/vector DNA; testing of coded purified mycobacterial
antigen against challenge with high virulent bacilli; behaviour of INH
drug resistant tubercle bacilli, etc. During the later part of 1990s,
techniques and procedures for the immunological studies involving animal
experimentation have been standardised in collaboration with the scientists
from Centre for Genetic Engineering, IISc, Bangalore.
In 1998, the animal house was redesignated as Animal
Model Research Unit (AMRU). The necessity arose not due to change in its
functions but because of worldwide movement of environment and animal
protection. Another ongoing collaborative study involving animal experiments
is on Regulation of gyrase gene expression, invivo function of DNA
gyrase and effect of gyrase expression on virulence of virulent related
genes a long term project on structure function mechanism
of action and regulation of DNA gyrase from mycobacteria has already been
initiated at IISc, Bangalore.
The establishment of bio-safety level III facility also
known as P-3 facility at AMRU, utilising the unique low dose aerosol infection
system is under progress. Prof Donald W Smith of Wisconsin university
on the eve of his retirement gifted the P-3 laboratory equipment to NTI.
This facility will help in carrying out studies in human beings aimed
at better understanding of the key events of TB pathogenesis and the effective
and innovative interventions to win over the TB problem. With introduction
of low dose aerosal infection system, the infection produced in animal
model will reflect very closely to TB infection caused in human beings.
It will also help in reducing the number of animals used for the research.
Besides invitro experiments will continue as complimentary methods.