Edelman, Gerald M. WORLD OF MICROBIOLOGY AND IMMUNOLOGY176•
methods of breaking immunoglobulins into smaller units that
could more profitably be studied. Their hope was that these
fragments would retain enough of their properties to provide
insight into the functioning of the whole.
Porter became the first to split an immunoglobulin,
obtaining an “active fragment” from rabbit blood as early as- Porter believed the immunoglobulin to be one long con-
tinuous molecule made up of 1,300 amino acids—the building
blocks of proteins. However, Edelman could not accept this
conclusion, noting that even insulin, with its 51 amino acids,
was made up of two shorter strings of amino acid chains work-
ing as a unit. His doctoral thesis investigated several methods
of splitting immunoglobulin molecules, and, after receiving
his Ph.D. in 1960 he remained at Rockefeller as a faculty
member, continuing his research.
Porter’s method of splitting the molecules used
enzymesthat acted as chemical knives, breaking apart amino
acids. In 1961 Edelman and his colleague, M. D. Poulik suc-
ceeded in splitting IgG—one of the most studied varieties of
immunoglobulin in the blood—into two components by using
a method known as “reductive cleavage.” The technique
allowed them to divide IgG into what are known as light and
heavy chains. Data from their experiments and from those of
the Czech researcher, Frantisek Franek, established the intri-
cate nature of the antibody’s “active sight.” The sight occurs at
the folding of the two chains, which forms a unique pocket to
trap the antigen. Porter combined these findings with his, and,
in 1962, announced that the basic structure of IgG had been
determined. Their experiments set off a flurry of research into
the nature of antibodies in the 1960s. Information was shared
throughout the scientific community in a series of informal
meetings referred to as “Antibody Workshops,” taking place
across the globe. Edelman and Porter dominated the discus-
sions, and their work led the way to a wave of discoveries.
Still, a key drawback to research remained. In any nat-
urally obtained immunoglobulin sample a mixture of ever so
slightly different molecules would reduce the overall purity.
Based on a crucial finding by Kunkel in the 1950s, Porter and
Edelman concentrated their study on myelomas, cancers of the
immunoglobulin-producing cells, exploiting the unique nature
of these cancers. Kunkel had determined that since all the cells
produced by these cancerous myelomas were descended from
a common ancestor they would produce a homogeneous series
of antibodies. A pure sample could be isolated for experimen-
tation. Porter and Edelman studied the amino acid sequence in
subsections of different myelomas, and in 1965, as Edelman
would later describe it: “Mad as we were, [we] started on the
whole molecule.” The project, completed in 1969, determined
the order of all 1,300 amino acids present in the protein, the
longest sequence determined at that time.
Throughout the 1970s, Edelman continued his research,
expanding it to include other substances that stimulate the
immune system, but by the end of the decade the principle he
and Poulik uncovered led him to conceive a radical theory of
how the brain works. Just as the structurally limited immune
system must deal with myriad invading organisms, the brain
must process vastly complex sensory data with a theoretically
limited number of switches, or neurons.
Rather than an incoming sensory signal triggering a pre-
determined pathway through the nervous system, Edelman
theorized that it leads to a selectionfrom among several
choices. That is, rather than seeing the nervous system as a rel-
atively fixed biological structure, Edelman envisioned it as a
fluid system based on three interrelated stages of functioning.
In the formation of the nervous system, cells receiving
signals from others surrounding them fan out like spreading
ivy—not to predetermined locations, but rather to regions
determined by the concert of these local signals. The signals
regulate the ultimate position of each cell by controlling the
production of a cellular glue in the form of cell-adhesion mol-
ecules. They anchor neighboring groups of cells together.
Once established, these cellular connections are fixed, but the
exact pattern is different for each individual.
The second feature of Edelman’s theory allows for an
individual response to any incoming signal. A specific pattern
of neurons must be made to recognize the face of one’s grand-
mother, for instance, but the pattern is different in every brain.
While the vast complexity of these connections allows for
some of the variability in the brain, it is in the third feature of
the theory that Edelman made the connection to immunology.
The neural networks are linked to each other in layers. An
incoming signal passes through and between these sheets in a
specific pathway. The pathway, in this theory, ultimately deter-
mines what the brain experiences, but just as the immune sys-
tem modifies itself with each new incoming virus, Edelman
theorized that the brain modifies itself in response to each new
incoming signal. In this way, Edelman sees all the systems of
the body being guided in one unified process, a process that
depends on organization but that accommodates the world’s
natural randomness.
Dr. Edelman has received honorary degrees from a
number of universities, including the University of
Pennsylvania, Ursinus College, Williams College, and others.
Besides his Nobel Prize, his other academic awards include
the Spenser Morris Award, the Eli Lilly Prize of the American
Chemical Society, Albert Einstein Commemorative Award,
California Institute of Technology’s Buchman Memorial
Award, and the Rabbi Shai Schaknai Memorial Prize.
A member of many academic organizations, including
New York and National Academy of Sciences, American
Society of Cell Biologists, Genetics Society, American
Academy of Arts and Sciences, and the American
Philosophical Society, Dr. Edelman is also one of the few
international members of the Academy of Sciences, Institute
of France. In 1974, he became a Vincent Astor Distinguished
Professor, serving on the board of governors of the Weizmann
Institute of Science and is also a trustee of the Salk Institute
for Biological Studies. Dr. Edelman married Maxine
Morrison on June 11, 1950; the couple have two sons and one
daughter.See alsoAntibody and antigen; Antibody formation and kinet-
ics; Antibody, monoclonal; Antibody-antigen, biochemical
and molecular reactions; Antigenic mimicrywomi_E 5/6/03 2:12 PM Page 176