Human Chorionic Gonadotropin
(hCG) was a fascinating hormone to study in 1970, partly because
not much was known about its behavior or makeup. Scientists
did know that the human body secretes hCG only during pregnancy
or during certain kinds of cancers. If they could find a way
to precisely measure the hormone, they would have a reliable
tumor marker, as well as a way to identify problems with a pregnancy.
NCI’s Roy Hertz was studying a cancer called choriocarcinoma
at the time. In this disease, patients exhibited tumors that
secreted hCG. The clinicians wanted a way to test blood samples
reliably for the presence of hCG so that they could track the
tumor during treatment.
JV: We knew that the bioassay that was used for monitoring
the amount of hormone they were measuring was very crude, very
insensitive, but it was better than anything else we had at
that time. So we needed another way of measuring the hCG in
the presence of a finite amount of LH [luteinizing hormone].
JV: While we were doing this, we had no idea of the
impact on early pregnancy detection, abnormal pregnancy detection.
In ectopic pregnancy, the levels of hCG usually start falling
and they don’t rise as high as they do within a normal
pregnancy.
However, measuring precise levels of hCG is exactly what the
bioassays of the mid-twentieth century and the immunoassays
of the 1960s could not do. The best test they had in 1970 was
an immunoassay that could measure hCG but could not distinguish
between hCG and luteinizing hormone (LH), another of the human
gonadotropins that shares its biological characteristics.
GB: Griff and I spoke. “Wouldn’t it be
great to develop a new assay for hCG.” At that time Judy
Vaitukaitis was immunizing rabbits with subunits of hCG and
harvesting antibodies.
Vaitukaitis was working at separating the subunits of hCG and
determining their biological function and characteristics. In
1970 and 1971 she worked on generating an antibody that would
be specific to the beta-subunit of hCG and that could therefore
be used in a radioimmunoassay—so called because the process
used radioactive labels in the immunoassay—and would not
cross-react with other hormones in the body. In 1972, she found
it. The first rabbit to produce the antibody was called “SB6”
and became the baseline for future experiments.
JV: We were looking at structure-function studies
of human chorionic gonadotropin. Was there biologic activity
in the isolated subunit? What was it about the molecule that
was responsible for the unique immunologic and biologic activity?
Then we realized that the biologic effect of the hormone resided
in the beta unit of hCG. So in doing these structure-function
studies to understand where the immunologic and biologic specificity
resided, it became obvious that you could really take advantage
of the relative specificity of the antiserum.
JV: It was critical for [NICHD’s] John Robbins
to be involved with this because he had the immunology background.
Actually, we tried two doses of immunogen [to make the antibody],
10 and 50 micrograms, and so the animal that had the first dose
of 50 micrograms of immunogen was labeled SB6, since it was
the sixth rabbit. There were five rabbits immunized with 10
micrograms, and we were told they would never make antibody
at 10. I said, “Let’s see.” We went down subsequently
to 2 and showed it would respond at that, too. So the first
animal that was immunized with 50 micrograms, SB6, became the
classic antiserum that had the best relative specificity that
was used for years, and we provided it all over the place.
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Griff Ross and Judith Vaitukaitis discuss
their research, c. 1971. |
