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The Journal of Nervous and Mental Disease • Volume 197, Number 1, January 2009
The Scientific Contributions of Paul D. MacLean
John D. Newman, PhD,* and James C. Harris, MD†
Abstract: Paul D. MacLean, a leading brain scientist of the 20th century, died
on December 26, 2007. We review his life as a scientist and highlight some of
his most important research contributions.
Key Words: Limbic system, triune brain.
(J Nerv Ment Dis 2009;197: 3–5)
December 26, 2007 marked the passing of Paul D. MacLean one
of the leading brain scientists of the 20th century and a
long-time member of this Journal’s Editorial Board (Fig. 1). In a
remarkably long and productive career, he established the parame-
ters for investigating the evolution and functioning of the emotional
brain and set the stage for current research in affective and social
neurosciences. He is best known for identifying and naming the
limbic system in 1952, but this was only the beginning of his
research contributions. In 1990, nearly 40 years later, he summa-
rized his lifetime of research in his magnum opus, The Triune Brain
in Evolution (MacLean, 1990; hereafter “TB”). There he discussed
the ramiﬁcations of the limbic system concept and his subsequent
ﬁndings on brain evolution and behavior culminating in his proposal
of a new brain model he called “the Triune Brain.” His research has
altered our view of Homo sapiens and our understanding of brain
evolution and behavior. Words cannot capture Paul MacLean’s
elegance as a scientist, compassion as a human being and his impact
in inspiring others. Those who spent time with him appreciated these
MacLean’s Work in Historical Perspective
MacLean’s contributions have impacted evolutionary biol-
ogy, neuroethology, clinical neuroscience, neurology, psychiatry,
and the social sciences. He posed 2 critical research questions that
are pertinent to each of these ﬁelds: (1) “where do subjective
emotional experiences reside in the brain?” and (2) “is the functional
circuitry of the brain inherited in the evolution of vertebrates and, if
so, how did these circuits evolve?” He was particularly interested in
the evolution of the family, writing “the evolution of the limbic
system is the history of the evolution of mammals, whereas the
history of the evolution of mammals is the history of the evolution
of the family (TB, p. 247).”
MacLean helped establish an approach to neuroscience es-
sentially unknown in the United States at the time he began his
research. In Europe, the ﬁeld of neuroethology had arisen with
*Laboratory of Comparative Ethology, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, NIH, Poolesville, Maryland, and
†Departments of Psychiatry and Behavioral Sciences and Pediatrics, The
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Supported in part by the Intramural Research Program of the NIH and NICHD.
Send reprint requests to John D. Newman, PhD, Laboratory of Comparative
Ethology, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, Poolesville, MD 20837. E-mail:
Copyright © 2009 by Lippincott Williams & Wilkins
primary focus on nonmammalian models. Still, in Zurich, Swit-
zerland, W. R. Hess and his coworkers, using electrical brain
stimulation of indwelling electrodes in cats, were mapping out areas
in the hypothalamus and other parts of the diencephalon from which
coordinated species-typical aggressive and fear-like behavior could
be elicited. MacLean visited the Zurich laboratory in 1956, but did
not refer to the work that came out of that laboratory in his own
publications. Subsequently, with Detlev Ploog, he developed a
laboratory environment where species-typical behavior could be
studied in a primate, the squirrel monkey (MacLean, 1962). Ploog
set up his own laboratory, the Department of Primate Behavior, at
the Max Planck Institute for Psychiatry in Munich. There, he
focused in large measure on squirrel monkey vocal behavior and its
underlying mechanisms (e.g., Ploog, et al., 1975). MacLean returned to
the United States initiating his own research on brain and behavior. His
approach was clearly ethological and he emphasized the importance of
preparing an ethogram, an inventory of the behavior of a species that
thoroughly describes its behaviors and organizes them into categories.
He was particularly interested in identifying behavioral master routines
and subroutines. Although he never used the term ‘neuroethology,’
MacLean was clearly an important early pioneer in this ﬁeld.
MacLean was aware of Paul Broca’s (Broca, 1878) observation
that the ‘limbic lobe,’ so named because it surrounds the brainstem, is
common to the brains of all mammals. He was intrigued with James
Papez’s (Papez, 1937) proposal that emotional experience is based on
connections linking the hypothalamus with the limbic lobe (MacLean,
1993) and visited Papez to discuss his observations with neurological
patients. MacLean’s curiosity about subjective emotional experience
arose from his earlier work with people with psycho-motor epilepsy
whose symptoms included emotional feelings and viscerosomatic
symptoms (MacLean, 1949). Seeking to account for sensations in-
volved in the visual, olfactory, and auditory auras associated with these
seizures, he reasoned that the external sensory apparatus must have
access to the brain circuits where seizures arose and that cortical
association pathways could potentially connect visual, auditory, and
somatic neocortical areas with the hippocampal gyrus. MacLean am-
pliﬁed and reconceptualized Papez’s proposal and suggested that a
circuit consisting of the limbic lobe and its major connections in the
forebrain—the hypothalamus, amygdala, and septum—constituted a
“visceral brain” (MacLean, 1949). Seeking greater clarity, he intro-
duced the term “limbic system” (MacLean, 1952) soon afterward. He
wrote that emotional feelings elude “the grasp of the intellect” (Ma-
cLean, 1949 p. 348) because their origins lie in evolutionary primitive
structures preventing their communication in verbal terms. He wrote
that this underlying neurobiology provides a clue to understanding the
difference between what we feel and what we know (MacLean, 1993).
His research focus on the limbic system led to the establishment of the
Section on Limbic Integration and Behavior at the National Institute of
Mental Health (NIMH). Subsequently, with the creation of the new
NIMH Laboratory of Brain Evolution and Behavior on a rural farm
owned by the NIH near Poolesville, Maryland, MacLean, as laboratory
chief, expanded his research. There he studied brain mechanisms
underlying behavior in animal models under semi-natural conditions.
Newman and Harris The Journal of Nervous and Mental Disease • Volume 197, Number 1, January 2009
FIGURE 1. Paul D. MacLean. Photo by Alex MacLean.
At the Laboratory of Brain Evolution and Behavior, MacLean
embarked on a series of experiments on the effects of targeted brain
lesions on species-typical behavior in lizards (Greenberg, et al.,
1979), and squirrel monkeys (MacLean, 1978), and the role of
limbic cortex on play and maternal behavior in hamsters (Murphy,
et al., 1981). These studies resulted in his triune brain proposal ﬁrst
fully enunciated in his Hinck’s Memorial Lecture in 1969 (Ma-
cLean, 1973). Tracing brain evolution from reptiles to mammals, he
established that the reptilian forebrain, characterized by greatly
enlarged basal ganglia, resembles the striatopallidal complex of
mammals. Later, describing forebrain structures in an evolutionary
context, MacLean coined the term “protoreptilian formation,” or
“R-complex,” in describing the striatal complex, locating it at the
base of the forebrain in reptiles, birds, and mammals (TB, p. 15).In
the triune brain model he reconceptualized the limbic system as the
In enunciating his triune brain proposal from an evolutionary
perspective, MacLean wrote (1967, p. 375): “There are those who
argue that one has no right to apply behavioral observations on
animals to human affairs, but they may be reminded that man has
inherited the basic structure and organization of 3 brains, 2 of which
are quite similar to those of animals. They evolved somewhat like a
house to which wings and superstructure are added. Despite their
great disparity in structure and chemistry, all 3 must function
together. Man’s brain of oldest heritage is basically reptilian. It
forms the matrix of the brain stem and comprises much of the
so-called reticular system, midbrain, and basal ganglia. Superim-
posed on the reptilian is a structure inherited from lower mammals.
It consists of the 2 oldest forms of cerebral cortex together with
related nuclei of the brain stem. As it is common to the brains of all
mammals, 1 might refer to it as the paleomammalian brain [limbic
brain]. Superimposed on the old mammalian brain and appearing
late in evolution is a more elaborate form of cortex called neocortex
which, together with its associated nuclei of the brain stem, reaches
the most advanced stage of development in man and overshadows
the rest of the brain. It can be characterized as neomammalian in
structure and organization.” Accompanying this text is the now-
famous ﬁgure (Fig. 2), showing in schematic side view the 3 basic
types of brains that MacLean proposed as man’s inheritance.
The Family and the Brain
MacLean’s appreciation of the importance of family-related
behavior in the evolution of the mammalian brain became a major
theme in his later writings. He summarized this research in his Adolph
Meyer lecture to the American Psychiatric Association in Toronto,
Canada in 1982 (MacLean, 1985). MacLean cited evidence that the
thalamo-cingulate division of the limbic system was unique to mam-
mals, hence it followed that this structure would mediate behaviors that
were either unique to mammals, or, at the very least, largely absent in
infra-mammalian vertebrates. These behaviors included play, nurs-
ing and maternal care, and audiovocal mother-infant communi-
cation (the separation or isolation cry). Two classic papers
examined his hypotheses about the brain and family life. One
(Murphy, et al., 1981) showed that hamsters deprived from birth
of their neocortex, but sparing limbic cortex, retained both
playfulness when young and maternal care as adults, but that play
was disrupted if the limbic cortex was damaged. A later study
(MacLean and Newman, 1988), involving lesions placed in
midline frontolimbic cortex of adult squirrel monkeys, showed
that such lesions largely eliminated production of the adult form
of the “isolation peep,” which in infants serves as the species-
speciﬁc infant cry.
MacLean’s Views on Medical Education and the
Future of Psychiatry
MacLean spoke widely about the implication of brain evolu-
tion and behavior, addressing educators on the importance of pro-
viding an education that took into account the evolution of our
FIGURE 2. From the frontispiece to MacLean, 1990.
© 2009 Lippincott Williams & Wilkins 4
The Journal of Nervous and Mental Disease • Volume 197, Number 1, January 2009 Paul D. MacLean
species). He expressed concern that the present emphasis in psychi-
atry on ﬁnding a chemical cure for every condition could lead to
patients being “manipulated like machines.” As an antidote to this,
he proposed an evolutionary psychiatry (MacLean, 1985) whose
domain is the subjective self. He proposed that “evolutionary psy-
chiatry will focus on the integrated function of the still evolving
brain (MacLean, 1985).” MacLean emphasized the importance of
empathy as a mark of integrated brain functioning in brain evolution
(Harris, 2003). MacLean concluded a paper on the evolution of
audiovocal communication on an optimistic note (MacLean, 1988):
“Judged by human behavior, it was as though there were a directed
evolution towards the development of a concern not only for the
feelings and future welfare of human beings, but also for all living
It remains to be seen the extent to which MacLean’s work
will continue to stimulate further research and if his ideas will be put
into practice. It was his hope that a national “brain library” be
established to facilitate comparative study. Such a library has come
into being (http://nmhm.washingtondc.museum/collections/neuro/
neuro.html). It is ironic however, that MacLean’s own extensive col-
lection of brain histology is not part of the museum’s collections,
having been discarded during the last days before closing of his
laboratory at the NIH Animal Center (R. Gelhard, personal communi-
Several symposia have been held to honor MacLean. One,
held in Boston in 1999, resulted in an edited volume of papers whose
contributors were familiar with MacLean’s work (Cory and Gardner,
2002). Subsequently, a special satellite symposium to the Interna-
tional Behavioral Neuroscience Society’s annual meeting held in
Capri, Italy was devoted to MacLean. This led to a special issue of
Physiology and Behavior with papers from attendees, along with
additional invited contributions. The preface to that issue (Lambert
and Gerlai, 2003) contained a ﬁtting expression of appreciation to
MacLean and his work: “A special thanks is extended to this
amazing scientist for opening the door to social and evolutionary
neuroscience so that today’s scientists and practitioners can embark
on many paths to understand more about the brain in its natural
context” (p. 342).
A collection of MacLean’s papers and correspondence is
available at the National Library of Medicine in Bethesda, MD. A
ﬁnding aid to the collection is available at http://nlm.nih.gov/hmd/
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Greenberg N, MacLean PD, Ferguson JL (1979) Role of the paleostriatum in
species-typical behavior of the lizard (Anolis carolinensis). Brain Res. 172:
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© 2009 Lippincott Williams & Wilkins 5