J. Moor-Jankowski

Blood Groups of Apes and Monkeys: I. The A‐B‐O Blood Groups in Baboons

Saliva and serum from 124 baboons have been tested for A‐B‐H specificity. All the baboons were secretors and could be classified into one of the three groups, A, B, and AB; there were no baboons of group O. Occasional seeming contradictions to the Landsteiner rule, namely, baboons with A in the saliva and anti‐A in the serum were shown to be due to two different kinds of serological specificity of A, one shared by saliva and red blood cells and designated as As and the other peculiar to red cells alone and designated as Ac. Baboons of groups A and AB have only As, and so can produce antibodies of specificity anti‐Ac‐ A similar explanation accounts for previous observations of occasional spider monkeys with B in the saliva and anti‐B in the serum. Analysis of population data and family material indicates that the A‐B‐O groups are inherited by allelic genes in baboons as in man.

Human‐Type Blood Factors in Gibbons, with Special Reference to the Multiplicity of Serological Specificities of Human Type M Blood

The human‐type blood groups of 20 gibbons of subspecies Hylobates lar lar and of four gibbons of subspecies Hylobates lar pileatus have been determined. Differences in distribution of the ABO blood groups and MN types were observed for the two subspecies, but all 24 gibbons were of Rh‐Hr type RhGi. All the animals also lack both factors I and i. By absorption experiments anti‐M reagents were shown to contain antibodies of at least three distinct M specificities; one M specificity is shared by all gibbon red cells, a second is absent from all gibbon red cells, while a third is shared only by gibbons red cells of type (M)Gi and type (MN)Gi. The theoretical and practical significance of the multiplicity of M factors in human M blood are pointed out.

The V‐A‐B Blood Group System of Chimpanzees: A Paradox in the Application of the 2 × 2 Contingency Test

Using population genetics it was demonstrated that two newly discovered blood factors of chimpanzee blood, Ac and Bc, and the blood factor Nv detected by Vicia graminea lectin, belong to the same blood group system, designated the V‐A‐B blood group system. In a study of 60 chimpanzees, all eight of the theoretically possible phenotypes were encountered. By gene frequency analysis, it was demonstrated that five of the eight possible genes postulated by the genetic theory of multiple allelic genes occurred among these 60 animals. A suitable nomenclature has been formulated which incorporates the facts observed.

Blood groups of apes and monkeys--their practical implications for experimental medicine.

A report at the 1967 convention of the American Society of Clinical Pathologists deals with the effect of A-B-0 blood group incompatibility on rehal homotransplantation in man. Among 24 patients, there were 12 who received kidneys of a donor of an incompatible A-B-0 blood group and who did poorly, compared with those who received A-B-0 compatible grafts. Thus, the patients who received the blood group incompatible grafts were deprived of a number of months of life. The point is that this type of human experimentation has become unnecessary because analogous experimentation can be carried out in nonhuman primates. It has been firmly established that apes have A-B-0 blood groups very similar serologically to the A-B-0 groups of man.2 To be sure, in Chimpanzees only blood groups 0 and A exist, while gibbons have group A, group B, and group AB, but not group 0. t Still, in chimpanzees one could compare the results of transplants of group A kidneys to group 0 chimpanzees with those of transplants between chimpanzees of compatible blood groups, while other combinations could be tested in gibbons. Experimentation in primate animals has been facilitated by newly developed methods for handling and maintenance even of the powerful chimpanzees. The U. S. Air Force has pioneered in this area, as will be demonstrated by the presentation of the Holloman Air Force Base g r o ~ p . ~ * ~ Comparable experiments, moreover, can be carried out in baboons, which have the advantage of convenient size, easy handling, and relatively low cost, as will be shown here by the presentation from our Laboratory for Experimental Medicine and Surgery in Primates of the New York University Medical Center.5 While red cells of baboons are not agglutinable by anti-A,

Seroprimatology of chimpanzees: blood-group distribution as a "racial" characteristic.

anti-B, or anti-]ti reagents, blood groups analogous to the human A-B-0 blood groups are readily demonstrable by tests on saliva and serum! as shown in TABLE 1. Thus, experiments such as the kidney transplantation experiments in man can now be done in baboons, chimpanzees, and gibbons, and the results extrapolated to man much more readily than experiments carried out in nonprimate animals. Actually, homotransplantation experiments with organs have been carried out in baboons for a number of years in the laboratory of Dr. John Haglin, who will report some of his results here. Presently, a large series of kidney transplantations in baboons is being carried out at the Stellenbosch University, South Africa, by Dr. Gerald F. Murphy, of Johns Hopkins Hospital, Baltimore, Md., and by Dr. Gerald S. Johnston, of Walter Reed Army Hospital, Washington, D.C., who will here present his earlier results on rhesus monkeys and his more recent findings on

MAINTENANCE AND HANDLING OF PRIMATE ANIMALS FOR MEDICAL RESEARCH

Significant differences in the distribution of human-type and simian-type blood groups have been demonstrated in chimpanzees classified into subspecies or races on the basis of morphological traits. The differences in chimpanzees are analogous to racial differences in the distribution of blood groups in man.

Simian Blood Groups Another Blood Group System, C‐E‐F, in Chimpanzees

When planning our facilities four years ago, we did not start with any existing design, but we established a list of requirements specifically suited for the use of primate animals in medical research. Thus, our animal rooms, cages, and working methods were developed on the basis of our experience and knowledge of primate animals and on the needs of medical researchers, under the most humane conditions for animal maintenance and handling. The list of requirements for functional and efficient housing of primates for medical research are as follows: 1. Easy accessibility of the animal for handling. 2. Greatest possible visibility of the animal in the cage for purposes of observation. 3. Optimal size of animal rooms, which are self-contained to prevent the spread of possible infections between animal rooms. 4. Maintenance methods that would limit spread of possible infections among animals within the self-contained animal rooms. 5. Variation of housing methods in conformity with the variable behavior and living habits of various primate species, without, however, lending anthropomorphic traits to primate animals. 6. Flexibility of housing space that would be amenable to low-cost transformations whenever required by experimental protocols. 7. Highest possible efficiency and automation to eliminate routine and repititious unskilled and semiskilled tasks in order to keep labor costs down, and to attract superior research-oriented personnel. 8. Overall economy in housing, equipment, and operation, based on careful analysis of all costs. Emphasis has been placed on achieving maximum research results per dollar of expenditure.

THE LABORATORY FOR EXPERIMENTAL MEDICINE AND SURGERY IN PRIMATES

Of eight chimpanzees which completed the course of immunization with red cells of other chimpanzees, five responded by producing antibodies of two different specificities previously not encountered and designated anti‐Ec and anti‐Fc, respectively. Serological and statistical evidence is presented indicating that the blood factors Ec and Fc detected by these antisera, together with the blood factor Cc previously described, define a blood group system designated the C‐E‐F system. Th C‐E‐F system is thus the second blood group system, not counting the human‐type A‐B‐O system, to be identified in chimpanzees.

A “New” Simian‐Type Blood Factor, Lc, Associated with the C‐E‐F Blood Group System of Chimpanzees

The unique importance of non-human primates for medical research has been demonstrated most strikingly to our generation by the virtual eradication of poliomyelitis by vaccines prepared in monkey tissues and controlled through bioassays in monkeys. The initial discovery that, ultimately, led to the development of the vaccines now in use, was made as early as the beginning of this century, when in 1909 Karl Landsteiner and E. Popper demonstrated the transmission of poliomyelitis from man to monkeys and apes. However, Landsteiner’s desire to expand and continue his investigations was frustrated by the unavailability of primate animals for extensive immunological research because of the high costs involved. More than a generation later, experiments with blood of rhesus monkeys led to the discovery of the Rh factor by Landsteiner and Wiener in 1937, and resulted in one of the most important advances in preventive perinatal medicine, better understanding of human blood grouping and genetics, and spectacular expansion of transfusion therapy during the last quarter of a century. Despite these great scientific and therapeutic advances, which resulted directly from the use of non-human primates in biomedical research, the availability of apes and monkeys for experimental use remained severely restricted until the most recent times. The difficulties inherent to the use of these animals derived mainly from the lack of ready availability of properly conditioned animals, compounded by the lack of qualified personnel and of methods of maintenance and handling, including mechanical and pharmacological restraint. These problems could not be solved in small colonies of animals maintained by single investigators for their own studies. The methods of husbandry and handling of primate animals are different from those developed relatively earlier for experiments with small rodents, rabbits, cats, and dogs. Therefore, the protagonists of the use of primate animals for research purposes soon realized the need of establishing larger colonies in order to develop specialized husbandry and handling principles. Dr. Robert Yerkes did pioneering work on great apes, beginning in the early 1930’s. In the Soviet Union in 1927, a primate colony for biomedical research was established in Shukumi, Crimea. Dr. Gertrude van Wagenen at Yale has been engaged in long-range study on primate reproduction. An experimental monkey colony was established on an uninhabited island off Puerto Rico under US. government sponsorship before the second World War. However, the greatest advances in availability and use of non-human primates in research began in the early 1960’s with the advent of the N.1.H.-supported Primate Research Centers program, and through the programs of the National Cancer Institute, carried out on large

THE USE OF APES and MONKEYS FOR THE INVESTIGATION OF THE HUMAN BLOOD GROUPS

A new blood factor Lc of chimpanzee red cells has been defined with two isoimmune sera. The blood factor Lc is the seventh blood factor associated with the chimpanzee C‐E‐F blood group system which is the counterpart of the human Rh‐Hr system.