WORLD OF MICROBIOLOGY AND IMMUNOLOGY Elion, Gertrude Belle183•
in a particular medium and thus migrate toward the negative
end of the matrix. In another solution, the same protein might
carry a negative charge and migrate toward the positive end of
the matrix. For each protein there is an isoelectric point related
to a pH characteristic for that protein where the protein mole-
cule has no net charge. Thus, by varying pH in the matrix,
additional refinements in separation are possible.
The advent of electrophoresis revolutionized the meth-
ods of protein analysis. Swedish biochemist Arne Tiselius
was awarded the 1948 Nobel Prize in chemistry for his pio-
neering research in electrophoretic analysis. Tiselius studied
the separation of serum proteins in a tube (subsequently
named a Tiselius tube) that contained a solution subjected to
an electric field.
Sodium dodecyl sulfate (SDS) polyacrylamide gel
electrophoresis techniques pioneered in the 1960s provided a
powerful means of protein fractionation (separation).
Because the protein bands did not always clearly separate
(i.e., there was often a great deal of overlap in the protein
bands) only small numbers of molecules could be separated.
The subsequent development in the 1970s of a two-dimen-
sional electrophoresis technique allowed greater numbers of
molecules to be separated.
Two-dimensional electrophoresis is actually the fusion
of two separate separation procedures. The first separation
(dimension) is achieved by isoelectric focusing (IEF) that sep-
arates protein polypeptide chains according to amino acid com-
position. IEF is based on the fact that proteins will, when
subjected to a pH gradient, move to their isoelectric point. The
second separation is achieved via SDS slab gel electrophoresis
that separates the molecule by molecular size. Instead of broad,
overlapping bands, the result of this two-step process is the for-
mation of a two-dimensional pattern of spots, each comprised
of a unique protein or protein fragment. These spots are subse-
quently subjected to staining and further analysis.
Some techniques involve the application of radioactive
labels to the proteins. Protein fragments subsequently obtained
from radioactively labels proteins may be studied my radi-
ographic measures.
There are many variations on gel electrophoresis with
wide-ranging applications. These specialized techniques
include Southern, Northern, and Western blotting. Blots are
named according to the molecule under study. In Southern
blots, DNA is cut with restriction enzymes then probed with
radioactive DNA. In Northern blotting, RNA is probed with
radioactive DNA or RNA. Western blots target proteins with
radioactive or enzymatically tagged antibodies.
Modern electrophoresis techniques now allow the iden-
tification of homologous DNA sequences and have become an
integral part of research into genestructure, gene expression,
and the diagnosis of heritable and autoimmune diseases.
Electrophoretic analysis also allows the identification of bac-
terial and viral strains and is finding increasing acceptance as
a powerful forensic tool.See also Autoimmunity and autoimmune diseases;
Biochemical analysis techniques; ImmunoelectrophoresisEElion, Gertrude BelleLION, GERTRUDEBELLE(1918-1999)
American biochemistGertrude Belle Elion’s innovative approach to drug discovery
advanced the understanding of cellular metabolismand led to
the development of medications for leukemia, gout, herpes,
malaria, and the rejection of transplanted organs.
Azidothymidine (AZT), the first drug approved for the treat-
ment of AIDS, came out of her laboratory shortly after her
retirement in 1983. One of the few women who held a top post
at a major pharmaceutical company, Elion worked at
Wellcome Research Laboratories for nearly five decades. Her
work, with colleague George H. Hitchings, was recognized
with the Nobel Prize for physiology or medicine in 1988. Her
Nobel Prize was notable for several reasons: few winners have
been women, few have lacked the Ph.D., and few have been
industrial researchers.
Elion was born on January 23, 1918, in New York City,
the first of two children, to Robert Elion and Bertha Cohen.
Her father, a dentist, immigrated to the United States from
Lithuania as a small boy. Her mother came to the United
States from Russia at the age of fourteen. Elion, an excellent
student who was accelerated two years by her teachers, grad-
uated from high school at the height of the Great Depression.
As a senior in high school, she had witnessed the painful death
of her grandfather from stomach cancer and vowed to become
a cancer researcher. She was able to attend college only
because several New York City schools, including Hunter
College, offered free tuition to students with good grades. In
college, she majored in chemistry.
In 1937, Elion graduated Phi Beta Kappa from Hunter
College with a B.A. at the age of nineteen. Despite her out-
standing academic record, Elion’s early efforts to find a job as
a chemist failed. One laboratory after another told her that
they had never employed a woman chemist. Her self-confi-
dence shaken, Elion began secretarial school. That lasted only
six weeks, until she landed a one-semester stint teaching bio-
chemistryto nurses, and then took a position in a friend’s lab-
oratory. With the money she earned from these jobs, Elion
began graduate school. To pay for her tuition, she continued to
live with her parents and to work as a substitute science
teacher in the New York public schools system. In 1941, she
graduated summa cum laude from New York University with
a M.S. degree in chemistry.
Upon her graduation, Elion again faced difficulties find-
ing work appropriate to her experience and abilities. The only
job available to her was as a quality control chemist in a food
laboratory, checking the color of mayonnaise and the acidity
of pickles for the Quaker Maid Company. After a year and a
half, she was finally offered a job as a research chemist at
Johnson & Johnson. Unfortunately, her division closed six
months after she arrived. The company offered Elion a new
job testing the tensile strength of sutures, but she declined.
As it did for many women of her generation, the start of
World War II ushered in a new era of opportunity for Elion. As
men left their jobs to fight the war, women were encouraged
to join the workforce. “It was only when men weren’t avail-womi_E 5/6/03 2:12 PM Page 183