506 
HEMATOLOGY 
When, however, initial transfusions are fol- 
lowed by one or more additional transfusions at 
intervals of several days or weeks, the reactions 
can be severe.^^'^ Such reactions are almost al- 
ways due to isoimmune antibodies engendered 
as a result of the initial transfusions or arising 
as a consequence of vaccination with homolo- 
gous tissue vaccines. Failure to elicit reactions 
on initial transfusions cannot be attributed to 
the absence of naturally occurring isoanti- 
bodies. On the contrary, most J-negative cattle, 
R-negative sheep and A-negative pigs manifest 
the equivalent isoantibodies. And I understand 
(personal communication. Dr. J. W. Templeton, 
this Conference) some A-negative dogs mani- 
fest anti-A. But, in contrast with anti-A and 
anti-B of man, the titers of these natural anti- 
bodies are generally low, and most of the anti- 
bodies act much better as hemolysins than they 
do as agglutinins, thereby indicating that em- 
bolism due to in vitro clumping of red cells is 
less likely to occur. Moreover, in the case of 
anti-J, anti-R and anti-A there is usually abun- 
dant soluble blood group substances in the 
plasma and tissues of those animals possessing 
the equivalent antigens and these soluble sub- 
stances bind with the antibodies and prevent 
them from reaching the red cells. 
There is, as far as I am aware, no blood 
group locus in cattle, dogs, pigs, sheep and 
horses which functions also as a major histo- 
compatibility locus, like for example, the H-2 
loci of mice. Consequently, none of the antigenic 
markers on the red cells of those species is use- 
ful as an indicator of histocompatibility. 
The problems associated with transfusion re- 
actions and the rejection of tissue grafts and 
organ transplants can be circumvented by using 
cattle twins. Most dizygotic cattle twins, and 
higher zygotic multiples, come to share each 
other's hematopoietic tissues as a result of cho- 
rionic vascular anastomosis. ^ They are tolerant 
not only to each others blood but also to grafts 
of each other's skin.^ Therefore, they should 
also be tolerant to transplants of each other's 
organs. Monozygotic twins are, of course, just 
as useful, if not more so, for such experiments, 
but they occur much less frequently than chi- 
meric cattle twins. 
Blood typing can be used to diagnose chi- 
meric and monozygotic twins. Likewise, when 
twins reject allografts of each other's skin it is 
clear that they cannot be chimeric or monozy- 
gotic. In view of the ease of diagnosis, either by 
blood typing or skin grafting, it comes as a sur- 
prise that such twins are not in greater demand 
for experimental surgery and organ transplan- 
tation. 
Chimeric twins also occur in sheep but their 
rarity precludes their extensive use in medical 
research.^'^" 
SOME FIRSTS IN ANIMAL BLOOD TYPING 
In addition to the discovery, by blood typing, 
of chimeric twins and higher chimeric multiples 
in cattle and sheep, there are other firsts for an- 
imal blood typing which are often overlooked in 
treatises on blood groups in man. 
One of those firsts relates to the initial dis- 
covery of isoantigenic determinants. Although 
Landsteiner is often credited with the discovery 
of the ABO blood groups of man in 1900, and 
did in fact observe isoagglutination when he 
mixed the serum of certain persons with the red 
cells of others, the first description of the exist- 
ance of isoantigenic determinants in any species 
was set forth by Ehrlich and Morgenroth.^^^ 
They injected individual goats intraperitoneally 
with rather large quantities of pooled, laked 
blood of other goats and then sampled the in- 
jected goats at regular intervals for the appear- 
ance of isolysins and autolysins. Although no 
autolysins were detected, isolysins did appear, 
some arising as early as two or three days and 
others only after several weeks. Each of the 
isoimmune antisera was of a different specific- 
ity, as ascertained by testing them with a panel 
of goat and sheep red cells. The authors men- 
tioned four different isolysins (A, B, C and D) 
and, in a subsequent note,^^'' Ehrlich pointed 
out that altogether 13 specificities were defined. 
He concluded, therefore, that red blood cells 
possess a large number of receptors (i.e., isoan- 
tigenic determinants) which probably belong to 
hundreds of different types, but it was not until 
some 40 years later that the real significance of 
his remarks could be appreciated. 
That 1900 paper by Ehrlich and Morgenroth 
was of particular significance in two ways. It 
