Veterinary Microbiology, 1 (1976) 3 2 3 - 3 2 6 323 Elsevier Scientific Pubhshing Company, Amsterdam - Printed in The Netherlands

Introductory remarks to the session on transmission

F. W. Schmidt

Veterinary Institute of the University of G~ttingen,

Groner Landstr. 2, 3400 G~ttingen, Federal Republic of Germany

Since the very beginning of research in bovine leukemia

the question of its transmissibility has been discussed. Al-

ready Siedamgrotzky described in 1878 his epidemiological

observation of bovine leukosis spreading slowly from East-

Prussia to the West and most of the following reports on

epidemiology seemed to support the idea of bovine leukemia

being an infectious and transmissible disease.

Very soon it was tried to answer this question by experi-

ments, beginning with Knuth and Volkmanns transmission ex-

periments in 1916. Instead of listing all experiments done

in the past, I will just try to summarize the results of the

laborious work, which has been put into experimental trans-

mission studies during the past 60 years and especially to

discuss some of the difficulties, which had to be and still

have to be dealt with while conducting such experiments.

If one would try to cite all bovine transmission experi-

ments reported this list would at least contain 320 animals -

calves and adult cattle - used up to 1974. In 117 animals

the transmission of the disease has been successful in one

way or the other by parenteral injection of

i. cellular material from leukotic donors

(blood, leukocytes, tumor suspensions)

2. cellfree material from leukotic donors or in-vitro-cultures

(serum or plasma, supernatant from leukocyte cultures)

Transmissions also occured after feeding of raw milk or colo-

strum from leukotic dams to calves, by housing leukotic cattle

with "normal" animals. Other experiments show the possibility

of a vertical, diaplacental transmission from the leukotic

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dam to the fetus.

It is not easy to gather and evaluate all data on trans-

mission experiments with accuracy because of the enormous

variety of different techniques and materials used. Also,

difficulties arise in interpreting the results obtained.

All this laborious and expensive work was done at a time,

when the definition of the status "leukosis" was difficult to

give. The first experiments almost showed a iOO per cent

"takes". Was it the availability of more aggressive, more in-

fectious material or recipients more susceptible in those

early experiments or was it because the parameters for the

interpretation of the results obtained were too crude? Which

parameters have been used? Mainly the clinical development of

tumorous leukosis, then hematological and histopathological

criteria. Today, we know that these criteria cannot be con-

sidered as a i00 % reliable and reproducible detection system.

The clinical phase of leukosis in the bovine may develop very

late during the course of the experiment or not at all, but

still other criteria like hematological or virological tests

would indicate a positive transmission. Histology in the early

phase of leukosis may fail to show any specific alterations

and hematological changes might not occur at all as shown from

some experiments and epidemiological findings in the field.

Even if all three criteria - clinical, histological, and hema-

tological - indicate negative results, still the experimental

animal might show the presence of C-type particles and pro-

duction of antibodies.

The difficulties concerned with the factor time are for

example demonstrated by the milk and colostrum transmission

experiment done by Weinhold and Straub.

In 1968 they reported negative results in 15 head of cat-

tle,which were raised on colostrum and milk from leukotic cows

after an observation period of 4 years. From their cautious

interpretation was taken that "no evidence for the presence

of a leukemogenic agent in colostrumor milk could be obtain-

ed."

In 1971, three years later, they could report, that only

4 out of the remaining ii animals still showed normal lympho-

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cyte values. One had already died because of tumorous leuko-

sis, the others showed persistent lymphocytosis of varying

degrees.

Difficulties also arise because of genetic heterogeneity?

In murine and avian leukosis research it is well established

that it is essential to use genetically defined recipients in

transmission experiments. Graffi mentions the lack of inbred

strains of mice as one of the reasons responsible for the con-

siderable difficulties to be overcome in experimental studies

of murine leukemia. He states: "Not until inbred strains of

mice with a high incidence of spontaneous leukemia became

available, could experimental studies on this disease be per-

formed with any consistency. Consistent and reproducible

transmission of leukemia in mice by graft of leukemic celis

actually became possible only after the development of inbred

lines of mice." (Graffi, 1972)

The genetic heterogeneity in bovine species probably ex-

plains the fact, that in most transmission experiments only

a few recipients develop at least some symptoms of leukosis.

In our own experience this amounts to about 30 per cent of

the inoculated animals.

The difficulties mentioned are only a few which encounter

those concerned with transmission experiments in the bovine

species. The question remains, what can be done to minimize

some of them in the future and expecially to standardize the

procedures, thus facilitating the interpretation of results

of different working groups.

In the late sixties an international committee met at the

University of Pennsylvania to determine what would be con-

sidered as experimental requirements and criteria for trans-

mission experiments. Recommendations were set up which in-

cluded the selection of donors and recipients in transmission

experiments. At that time no reliable detection system had

been available which could be used for identification of for

example "animal free of infection" or which could be used as

objective criterion in the interpretation of test results.

During the last years considerable progress has been made

in detection of bovine C-type leukemia virus as causative

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agent and the identification of viral antigens as well as

antibodies. In view of the recommendations given by the com-

mittee the new virological and immunological results in my

opinion should lead to new recommendations to be considered

in future transmission experiments.

This workshop-conference and the establishment of a common

CEC-program for research on bovine leukosis gives us the op-

portunity to combine and harmonize our efforts, as Dr. Ben-

dixen already pointed out in his lecture on future epidemio-

logical research. Especially in the field of transmission ex-

periments with its high investment of labor, time and last not

least money, standardization of procedures and criteria would

help to fully utilize the small number of test animals usually

available.

(References on request from the author)