PIONEERS AND PATHFINDERS
Kurt Stern (1909-2003)
S. Gerald Sandler, Noga Manny, and Eilat Shinar
Solutions to problems in biology almost invari-
ably lead to as many, and sometimes more, new
questions that are left unanswered by the newly
acquired information. The discovery that maternal
isosensitization to the Rh factor is the most
frequent cause of hemolytic disease of the
newborn was no exception to this maxim.
— Kurt Stern, 1956
1
I
N 1943, PHILIP LEVINE reported the unex-
plained and intriguing observation that women
were more likely to form Rh antibodies (anti-D) if
they lacked natural isoagglutinins (anti-A, -B) to
their offspring’s red blood cells, when compared
with women who had such isoagglutinins. By
1956, other scientists had confirmed Levine’s
observation, but the mechanism(s) by which
ABO isoagglutinins inhibited the formation of Rh
antibodies was not known. Leading scientists
proposed various hypotheses. Sir Robert Fisher
suggested that ABO-incompatible offspring were
aborted more frequently, decreasing the chance
of maternal immunization. Alexander Wiener
proposed that there was competition between A
or B antigens and Rh antigens, resulting in
unfavorable conditions for forming Rh antibodies.
Robert Race and Ruth Sanger suggested that
maternal ABO isoagglutinins caused rapid destruc-
tion of incompatible fetal red blood cells entering
the maternal circulation, reducing their chance to
stimulate maternal Rh antibodies.
Kurt Stern, then Director of the Blood Center,
Mount Sinai Medical Research Foundation, and
Associate Professor of Pathology at the Chicago
Medical School, applied to the National Institutes
of Health for a grant to elucidate the scientific
basis for Levine’s observation. His application
was approved and the results of his research are
now the foundation of our present understanding
of Rh immunoprophylaxis. As an immunologist,
Stern approached the problem of Rh hemolytic
disease of the newborn by studying the inter-
action of ABO and Rh antigens in men and,
thereby, separated the immunological from the
maternal-fetal interactions. Together with Israel
Davidsohn, Professor and Chairman of the
Department of Pathology, and Lillian Masaitis,
his research technician, Stern injected Rh-positive
red cells into 39 male subjects. For 17 subjects,
the Rh-positive red cells were ABO-compatible;
for 22, the red cells were ABO-incompatible. Ten
of the 17 subjects receiving ABO-compatible red
cells formed Rh antibodies, but only 2 of the
22 receiving ABO-incompatible RBCs formed
Rh antibodies. Stern published his findings in
1956, concluding that the effect of ABO on
abortion (or conception) was excluded and that
bat present, it seems to us that rapid elimina-
tion of antigen from the host is a highly prob-
able explanation for the low incidence and
low levels of Rh antibodies in Rh-negative per-
sons who are injected with Rh-positive, ABO-
incompatible blood.Q
1
Stern followed up with a second study designed
to bfurnish some insight into the mechanism(s) of
interference of ABO-incompatibility with Rh sen-
sitization, and also some tentative generalizations
concerning factors influencing immune responses
to red cell isoantigens.Q
2
He tested the hypoth-
esis that rapid coating of ABO-incompatible
Rh-positive red cells inhibited the of formation of
Rh antibodies by Rh-negative subjects by injecting
8 group A, Rh-negative subjects with group
A, Rh-positive red cells that had been coated in
vitro with anti-A. Five group A Rh-negative
Transfusion Medicine Reviews, Vol 20, No 1 (January), 2006: pp 80-8380
From the Departments of Pathology and Medicine, George-
town University Medical Center, Washington, DC; Department
of Blood Bank, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel; and Blood Services, Magen David Adom, Tel
Hashomer, Israel.
Address reprint requests to S. Gerald Sandler, MD,
Department of Laboratory Medicine, Georgetown University
Hospital, 3800 Reservoir Road, N.W., Washington, DC 20007.
E-mail: sandlerg@gunet.georgetown.edu
0887-7963/05/$ – see front matter
n 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.tmrv.2005.08.008