William Horner Andrews (1887-1953)- first professor of physiology at Onderstepoort.

W H Andrews qualified as a veterinarian in London in 1908 and was recruited soon after, in 1909, by Sir Arnold Theiler to join the staff of the newly established veterinary laboratory at Onderstepoort. After initial studies on the treatment of trypanosomosis and on snake venoms he was deployed by Theiler in 1911 to start research on lamsiekte (botulism)at a field station on the farm Kaffraria near Christiana, where he met and married his wife Doris. After a stint as Captain in the SA Veterinary Corps during World War I he succeeded D T Mitchell as head of the Allerton Laboratory in 1918, where he excelled in research on toxic plants, inter alia identifying Matricaria nigellaefolia as the cause of staggers in cattle. When the Faculty of Veterinary Science was established in 1920 he was appointed as the first Professor of Physiology. After the graduation of the first class in 1924, and due to health problems, he returned to the UK, first to the Royal Veterinary College and then to the Weybridge Veterinary Laboratories of which he became Director in 1927. After his retirement in 1947 he returned to South Africa as a guest worker at Onderstepoort where he again became involved in teaching physiology when Prof. Quin unexpectedly died in 1950. Andrews died in Pretoria in 1953 and was buried in the Rebecca Street Cemetery.

History of bluetongue research at Onderstepoort.

Research on this economically important disease of ruminants, especially sheep, which had been named bluetongue by farmers in the 19th century, has been part and parcel of the activities at Onderstepoort ever since its establishment in 1908 and therefore covers a full century of the OVI's existence. In view of Onderstepoort's centenary celebration a brief overview of this research is given in terms of the historic milestones which influenced and guided global research on this and other viral diseases of animals.

Detection of Maedi-Visna virus antibodies using a single fusion transmembrane-core p25 recombinant protein ELISA and a modified receiver-operating characteristic analysis to determine cut-off values.

The core p25 and transmembrane (TM) genes of Maedi-Visna virus (MVV) were cloned individually into the pGEX-2T expression vector. Both proteins were expressed as a combined fusion protein in frame with glutathione S-transferase (GST). The purified recombinant antigens (GST-TM and GST-TM-p25) were used to develop a MVV ELISA. A preliminary assessment of the diagnostic potential of the recombinant antigens (GST-TM and GST-TM-p25) was made by testing the antigens against 46 seropositive and 46 seronegative sheep and comparing the results with a commercial p25 ELISA kit. A two-graph receiver operating characteristic (TG-ROC) analysis program was used to interpret the data. The GST-TM-p25 ELISA was more sensitive than the commercial assay which is based on the p25 antigen alone and more specific than the GST-TM ELISA.

The role of veterinary research laboratories in the provision of veterinary services.

Veterinary research laboratories play an essential role in the provision of veterinary services in most countries. These laboratories are the source of new knowledge, innovative ideas and improved technology for the surveillance, prevention and control of animal diseases. In addition, many laboratories provide diagnostic and other services. To ensure the optimal integration of various veterinary activities, administrators must understand the functions and constraints of research laboratories. Therefore, a brief discussion is presented of the following: organisational structures methods for developing research programmes outputs of research scientists and how these are measured the management of quality assurance funding of research. Optimal collaboration can only be attained by understanding the environment in which a research scientist functions and the motivational issues at stake.

Biotechnology, viral oncogenesis and jaagsiekte.

A brief description is given of the discovery of retroviral and cellular oncogenes and of their putative role in oncogenesis. Attempts to apply the biotechnological techniques that were so successful in the study of other retroviruses to the newly-discovered jaagsiekte retrovirus are briefly reviewed.

A scanning and transmission electron microscopy study of jaagsiekte lesions.

A scanning electron microscopy (SEM) and transmission electron microscopy (TEM) study was made of lesions from acute, experimentally induced cases of jaagsiekte. In the SEM study tumour cells were easily identified by the abundant microvilli on their peripheral surface. The SEM study gave further insight into the development of lesions and the spatial relationship of cells involved in jaagsiekte. TEM revealed that the tumour cells were in a state of rapid protein synthesis and had many characteristics in common with other malignant cells.

Transmission of jaagsiekte (ovine pulmonary adenomatosis) by means of a permanent epithelial cell line established from affected lungs.

An epithelial cell line, designated JS-15,4, has been established in culture from jaagiekte lesions and subcultured in vitro for almost 2 years. It exhibits morphological and other features of transformed cells and has been shown by electron microscopy to consist of type B ovine alveolar epithelial cells. Jaagiekte was successfully transmitted to 3 new-born lambs by the intratracheal injection of cells following immunosuppressive treatment with either anti-thymocyte immunoglobulin alone or combined with anti-macrophage immunoglobulin. Incubation periods as short as 10 weeks were recorded. Evidence was also obtained that natural transmission may result from the inhalation of viable cells.

Immunosuppression in new-born lambs.

A novel technique, based on cytotoxicity-neutralization, was developed for the in vitro titration of anti-sheep lymphocyte and anti-sheep macrophage sera. The titres obtained for a number of antisera were compared with those found in an agglutination assay. Anti-lymphocyte sera with a high cytotoxicity-neutralization titre very effectively suppressed the number of circulating lymphocytes in the peripheral blood of treated new-born lambs, thus indicating in vivo immunosuppressive activity.

Presence of Herpesvirus ovis DNA sequences in cellular DNA from sheep lungs affected with jaagsiekte (pulmonary adenomatosis).

To investigate further the possible involvement of Herpesvirus ovis in the aetiology of jaagsiekte, the kinetics of reassociation of viral DNA and DNA isolated from tumour tissue as well as from cell cultures derived from it were studied. Although DNA-DNA hybridization could be demonstrated in 2 cases of jaagsiekte, no correlation was found between the presence of Herpesvirus ovis genome sequences and the occurrence of the disease.

The localization of a Mason-Pfizer monkey virus-related antigen in jaagsiekte tumour tissue and cell lines.

Mason-Pfizer monkey virus-related antigen was detected in 3 out of 5 jaagsiekte lungs examined using a direct immunoperoxidase staining technique with anti-MPMV p27 serum. Most of the antigen was localized in the alveolar lumina of the lesions. The reaction was further characterised on immune blots and found to involve a protein with a molecular mass of 29 000 daltons (JSRV p29). JSRV p29 antigen was also detected in 2 jaagsiekte cell lines.

The morphology and morphogenesis of jaagsiekte retrovirus (JSRV).

Jaagsiekte retrovirus ( JSRV ) was recently shown to be the aetiological agent of jaasiekte (ovine pulmonary adenomatosis). The morphogenesis of JSRV was studied in jaagsiekte tumour tissue. Intracytoplasmic particles, often associated with centrioles, were found in tumour cells. JSRV budded from tumour cells with a complete core which appeared to mature during the budding process. Extracellular particles were found in the alveolar lumen. Immature extracellular particles were rare. Mature extracellular JSRV was membrane-bound and had a slightly eccentric nucleoid with an electron-dense perinucleoidal space. In negatively stained preparations of JSRV the envelope was covered with spikes. JSRV is morphologically distinct from all known retroviruses.

Demonstration of growth-inhibitory as well as growth-stimulatory factors in medium conditioned by lung lavage cells stimulated with a chemotactic factor secreted by jaagsiekte tumour cells.

Both growth-inhibitory and growth-stimulatory factors were detected in vitro in medium from chemotactically stimulated cultures of lung lavage cells. The macrophage component of the lavage cells was found to produce a growth stimulatory factor that was replaced by a growth inhibitory factor following chemotactic factor stimulation.

Production of a macrophage chemotactic factor by cultured jaagsiekte tumour cells.

The increase of alveolar macrophages in jaagsiekte sheep lungs is not caused by excessive surfactant production but is due to a chemotactic factor secreted by the tumor cells. This factor has a molecular mass in the region of 13 kilodaltons, is stable at 56 degrees C but labile at 100 degrees C and, being sensitive to proteases, indicates that it is a small protein molecule.

The effect of a natural maedi-visna virus infection on the productivity of South African sheep.

A cohort study was conducted in order to measure the effect of the chronic indurative lymphocytic mastitis caused by the South African strain of maedi visna virus (MVV) on the pre-weaning growth of lambs born either of naturally infected or uninfected ewes kept under similar conditions. Fifty naturally infected ewes as well as another 40 from a maedi-visna-free source to be used as control animals, were purchased and kept in separate flocks which were managed in a similar way. All the ewes were of the same breed and 3-4 years old. During the adaptation period, and through the mating, pregnancy and lactation periods they were periodically monitored for the presence of MVV serum antibodies. The lambs were weighed at birth and thereafter every 2 weeks until the age of 90 days, when they were weaned. The ewes were then slaughtered, and their udders examined histologically and the number of lymphocytic follicles were counted and assessed. Although the calculated values indicated a correlation between the number of follicles in the udder and the reduction in the growth rate of the lambs, this was not statistically significant. Similarly, despite higher counts of lymphoid follicles in the udders of sero-positive ewes as compared to those that were sero-negative and the lower ewe productivity indexes in infected ewes, no statistically significant differences were found in the indexes of ewes in different follicle categories.

The serological relationship of herpesvirus ovis to other herpesviruses and its possible involvement in the aetiology of jaagsiekte.

Cross-neutralization studies showed that 3 different isolates of herpesvirus ovis from cell cultures derived from the lungs of sheep suffering from jaagsiekte were not only identical but were also related to similar isolate made in Scotland. No relationship, however, could be established between herpesvirus ovis and common bovine or equine herpesviruses. Antibodies to herpesvirus ovis were present in roughly 70% of all animals tested and no evidence was obtained for the involvement of the virus in the aetiology of jaagsiekte. On the other hand, the absence of antibodies in sheep sera from Iceland as well as the other data obtained in this study did not exclude involvement of the virus in jaagsiekte.

Transplantation of cultured jaagsiekte (sheep pulmonary adenomatosis) cells into athymic nude mice.

Epithelial cells of the 15.4 line, which were originally established from the adenomatous lung of a jaagsieke case and which had been cultured in vitro for 22 generations, were injected subcutaneously into athymic nude mice. A slow-growing tumour which soon became cystic was established in each case. The cysts rapidly increased in size as a result of the accumulation of a slightly turbid secretion containing aggregates of tumour cells which rapidly refilled the cysts after the fluid had been withdrawn. Cultures were readily re-established from these cells and a chromosomal analysis proved that the tumor consisted of sheep cells. An epithelial cell lining, very similar to that found in the adenomatous lung alveoli of typical jaagsiekte, could be demonstrated histologically.

Aetiology of jaagsiekte: transmission by means of subcellular fractions and evidence for the involvement of a retrovirus.

Jaagsiekte (ovine pulmonary adenomatosis) was transmitted to new-born lambs by inoculation of the microsomal fraction of a cytoplasmic extract of cultured tumour cells or tumour tissue. Various treatments of the biologically active fraction were carried out to differentiate between various classes of possible aetiological agents. The results obtained suggested the involvement of a membrane-associated RNA containing virus. Reverse transcriptase activity dependent on Mg++ was subsequently demonstrated in these extracts and in lung exudate, and was shown to be associated with particles banding at a density 1,175 in sucrose gradients. These characteristics, as well as the appearance of the particles in the electron microscope, are similar to those reported for Type B and Type D retroviruses. Serial transmissions of jaagsiekte over a number of years, using cytoplasmic extracts and purified virus, strongly suggest that this virus is the aetiologic agent of jaagsiekte.

Aetiology of jaagsiekte: experimental transmission to lambs by means of cultured cells and cell homogenates.

Studies on the transmission of jaagsiekte (ovine pulmonary adenomatosis) both by subinoculation of cells of known sex and by cell homogenates into male and female lambs are reported. The results obtained indicate a thymocyte-dependent rejection of male cells in female recipients in contrast to the successful transplantation of male cells in male animals and female cells in both sexes. This suggests the presence of a surface antigen determined by the gamma-chromosome in the tumour cells. A second mechanism of transmission, dependent on the transformation of the recipient's cells, was demonstrated by 2 cases of heterologous transplantation and confirmed by inoculation of cellular homogenates.