Yalow, Rosalyn Sussman WORLD OF MICROBIOLOGY AND IMMUNOLOGY608•
load and teaching duties, she took some extra undergraduate
courses to increase her knowledge. While in graduate school
she also met Aaron Yalow, a fellow student and the man she
would eventually marry. The pair met the first day of school
and wed about two years later on June 6, 1943. Yalow received
her master’s degree in 1942 and her doctorate in 1945. She
was the second woman to obtain a Ph.D. in physics at the
University.
After graduation the Yalows moved to New York City,
where they worked and eventually raised two children,
Benjamin and Elanna. Yalow’s first job after graduate school
was as an assistant electrical engineer at Federal
Telecommunications Laboratory, a private research lab. Once
again, she found herself the sole woman as there were no other
female engineers at the lab. In 1946, she began teaching
physics at Hunter College. She remained a physics lecturer
from 1946 to 1950, although by 1947, she began her long
association with the Veterans Administration by becoming a
consultant to Bronx VA Hospital. The VA wanted to establish
some research programs to explore medical uses of radioac-
tive substances. By 1950, Yalow had equipped a radioisotope
laboratory at the Bronx VA Hospital and decided to leave
teaching to devote her attention to full-time research.
That same year, Yalow met Solomon A. Berson, a physi-
cian who had just finished his residency in internal medicine
at the hospital. The two would work together until Berson’s
death in 1972. According to Yalow, the collaboration was a
complementary one. In Olga Opfell’s Lady Laureates,Yalow
is quoted as saying, “[Berson] wanted to be a physicist, and I
wanted to be a medical doctor.” While her partner had accu-
mulated clinical expertise, Yalow maintained strengths in
physics, math, and chemistry. Working together, Yalow and
Berson discovered new ways to use radioactive isotopes in the
measurement of blood volume, the study of iodine metabo-
lism, and the diagnosis of thyroid diseases. Within a few years,
the pair began to investigate adult-onset diabetes using
radioisotopes. This project eventually led them to develop the
groundbreaking radioimmunoassay technique.
In the 1950s, some scientists hypothesized that in adult-
onset diabetes, insulin production remained normal, but a liver
enzyme rapidly destroyed the peptide hormone, thereby pre-
venting normal glucose metabolism. This contrasted with the
situation in juvenile diabetes, where insulin production by the
pancreas was too low to allow proper metabolism of glucose.
Yalow and Berson wanted to test the hypothesis about adult-
onset diabetes. They used insulin “labeled” with^131 iodine (that
is, they attached, by a chemical reaction, the radioactive iso-
tope of iodine to otherwise normal insulin molecules.) Yalow
and Berson injected labeled insulin into diabetic and non-dia-
betic individuals and measured the rate at which the insulin
disappeared.
To their surprise and in contradiction to the liver
enzyme hypothesis, they found that the amount of radioac-
tively labeled insulin in the blood of diabetics was higher than
that found in the control subjects who had never received
insulin injections before. As Yalow and Berson looked into
this finding further, they deduced that diabetics were forming
antibodies to the animal insulin used to control their disease.These antibodies were binding to radiolabeled insulin, pre-
venting it from entering cells where it was used in sugar
metabolism. Individuals who had never taken insulin before
did not have these antibodies and so the radiolabeled insulin
was consumed more quickly.
Yalow and Berson’s proposal that animal insulin could
spur antibody formationwas not readily accepted by immu-
nologists in the mid–1950s. At the time, most immunologists
did not believe that antibodies would form to molecules as
small as the insulin peptide. Also, the amount of insulin anti-
bodies was too low to be detected by conventional immuno-
logical techniques. Yalow and Berson set out to verify these
minute levels of insulin antibodies using radiolabeled insulin
as their marker. Their original report about insulin antibodies,
however, was rejected initially by two journals. Finally, a
compromise version was published that omitted “insulin anti-
body” from the paper’s title and included some additional data
indicating that an antibodywas involved.
The need to detect insulin antibodies at low concentra-
tions led to the development of the radioimmunoassay. The
principle behind RIA is that a radiolabeled antigen, such as
insulin, will compete with unlabeled antigen for the available
binding sites on its specific antibody. As a standard, various
mixtures of known amounts of labeled and unlabeled antigen
are mixed with antibody. The amounts of radiation detected in
each sample correspond to the amount of unlabeled antigen
taking up antibody binding sites. In the unknown sample, a
known amount of radiolabeled antigen is added and the
amount of radioactivity is measured again. The radiation level
in the unknown sample is compared to the standard samples;
the amount of unlabeled antigen in the unknown sample will
be the same as the amount of unlabeled antigen found in the
standard sample that yields the same amount of radioactivity.
RIA has turned out to be so useful because it can quickly and
precisely detect very low concentrations of hormones and
other substances in blood or other biological fluids. The prin-
ciple can also be applied to binding interactions other than that
between antigen and antibody, such as between a binding pro-
tein or tissue receptor site and an enzyme. In Yalow’s Nobel
lecture, recorded in Les Prix Nobel 1977,she listed more than
100 biological substances—hormones, drugs, vitamins,
enzymes, viruses, non-hormonal proteins, and more—that
were being measured using RIA.
In 1968, Yalow became a research professor at the Mt.
Sinai School of Medicine, and in 1970, she was made chief of
the Nuclear Medicine Service at the VA hospital. Yalow also
began to receive a number of prestigious awards in recogni-
tion of her role in the development of RIA. In 1976, she was
awarded the Albert Lasker Prize for Basic Medical Research.
She was the first woman to be honored this laurel—an award
that often leads to a Nobel Prize. In Yalow’s case, this was
true, for the very next year, she shared the Nobel Prize in phys-
iology or medicine with Andrew V. Schally and Roger
Guillemin for their work on radioimmunoassay. Schally and
Guillemin were recognized for their use of RIA to make
important discoveries about brain hormones.
Berson had died in 1972, and so did not share in these
awards. According to an essay in The Lady Laureates, shewomi_Y 5/7/03 9:15 AM Page 608