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600 NATURE | VOL 418 | 8 AUGUST 2002 | www.nature.com/nature

The remarkable successes of modernbiomedical research stem from acombination of factors: talented scientistshave enjoyed an intellectual climate thatencourages innovation and excellence, and they have received growing fundingsupport from public and private sources.W. Maxwell Cowan, who died on 30 June,will be remembered for his outstandingcontributions relating to each of these factors. He was a renownedneuroanatomist who charted fundamentalaspects of brain circuitry anddevelopment. He helped to shape modern neuroscience as an integrated yet interdisciplinary field, not leastthrough his editorship of several journals.In the last decade of his working life, hemoved onto a broader stage at the Howard Hughes Medical Institute(HHMI), where he orchestrated theexpansion of its support for research.

For more than a century,neuroanatomists have worked to decipher the fabulously complex neuralcircuitry that underlies brain function.Progress has depended on a succession of methodological advances for analysingaxonal pathways with increasing precisionand sensitivity. Cowan entered this field onmoving in 1953 to Oxford, UK, from SouthAfrica, where he had studied underRaymond Dart, the discoverer of the earlyprehuman fossil Australopithecusafricanus.

At Oxford, Cowan carried out doctoralresearch under Wilfrid LeGros Clark, aleading neuroanatomist. Cowan and hiscolleagues (most notably T. P. S. Powell)used the then new silver-staining methodsbased on axonal degeneration to chart theconnections of many different brainstructures, particularly those involving the thalamus, hypothalamus andhippocampus. Although the ‘degeneration’methods had serious technical limitations,these observations formed the basis formuch of our current understanding ofbrain circuitry.

In 1966, Cowan moved to theUniversity of Wisconsin and, two yearslater, to St Louis, to head the Departmentof Anatomy at Washington UniversitySchool of Medicine — where we now work.Around this time, discoveries in otherlaboratories revealed that neurons have aspecialized transport system for conveyingmaterials between their cell bodies andsynaptic terminals. Cowan recognized thatif tracer molecules were piggybacked ontothis system, many of the drawbacks of

degeneration-based methods for tracingneuronal pathways could be circumvented.He and his colleagues introduced a methodfor injecting radioactive amino acids intospecific sites in the brain, to reveal thedistribution of labelled proteins thatunderwent anterograde transport (that is,from neuronal cell bodies to their axonalterminations). This was a key step inlaunching modern neuroanatomy, whichnow uses a variety of tracers —transported in an anterograde, retrogradeor bidirectional manner — to reveal howneurons connect with one another.Increasingly widespread application ofthese methods at Washington Universityand elsewhere generated a revolution inneuroanatomy in the 1970s.

An advantage of the tracer-basedmethod was its applicability to thedeveloping brain, which is notoriouslydifficult to study with the classicaldegeneration methods. Over the next 20 years, much of Cowan’s research wasdirected at questions of how connectionsform and are refined during development,and how they can be modified in the adult.He also explored factors that influenceneuronal survival, inspired by his longfriendship with Viktor Hamburger, whose own studies of cell death duringdevelopment led to the identification ofnerve growth factor and other agents thatcontrol the growth of neurons.

In the late 1960s, an identity crisis wasbrewing in brain research — the numberof neuroscientists was increasing rapidly,yet they were typically scattered across

departments of anatomy, physiology,biology and pharmacology. Neurosciencedid not exist as a generally recognized field of investigation or of graduatetraining. Over the ensuing two decades,Cowan was prominent in helping to launchand define neuroscience as a broad yetintegrated discipline. He took overeditorship of the faltering Journal ofComparative Neurology in 1969, reviving it as a major neuroscience journal. Heattracted a diverse group of scientists to his department, renamed it theDepartment of Anatomy andNeurobiology, and led it to pre-eminenceas a centre of interdisciplinaryneuroscience research. An infamousfeature that he instituted was the Saturdaymorning seminar series, where fullattendance was expected.

In 1980, Cowan moved to the SalkInstitute, where he served as vice-presidentfrom 1982 to 1986. The talented younginvestigators in his laboratory continuedto produce striking results, butincreasingly his time was occupied withadministration. He became the inauguraleditor of The Journal of Neuroscience in1982 and led it to prominence. Hisrecruitment, in 1984, to the MedicalAdvisory Board of the HHMI gave him awider arena in which to exercise hisscientific and organizational talents totheir fullest effect.

The HHMI is the largest privatesupporter of biomedical research in theUnited States, and his advice helped bringneuroscience into the portfolio ofprogrammes sponsored by the institute. In 1988, he became vice-president andchief scientific officer of the HHMI, andover the subsequent 12 years played apivotal role in shaping the institute’sscientific agenda. During this period, thenumber of HHMI-supported investigatorsmore than doubled, as did the number of academic institutions at which they are located.

Cowan’s depth of knowledge ofneuroscience was legendary. Equallyimpressive was his voracious appetite forlearning about the full breadth of researchactivities supported by the HHMI. Cowanwas a masterly communicator, equallyeffective at holding the attention ofscientific experts and a lay audience. He has left an indelible stamp on the field of modern neuroscience and on the broader realm of biomedical research. David C. Van Essen and Joseph L. Price

David C. Van Essen and Joseph L. Price are in theDepartment of Anatomy and Neurobiology,Washington University School of Medicine, 660 S. Euclid, St Louis, Missouri 63110-1093, USA.e-mail: vanessen@v1.wustl.edu

Obituary

W. Maxwell Cowan (1931–2002)

A founder of modernneuroscience, and a guiding hand inbiomedical research

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