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Brain Projects
to Reap Dividends for Neurotech Firms
by James Cavuoto, editor
In much the same way that the biotechnology and pharmaceutical industries
have benefited from the ambitious efforts to map the human genome,
work underway at several private corporations and research institutions
to map the functional connections of the human nervous system may
well prove fruitful for the neurotechnology industry. While our
understanding of biological processes active at the molecular and
subcellular levels have advanced profoundly over the last two decades,
progress at deciphering exactly how the central nervous system effects
specific sensory, motor, and cognitive functions has been much more
restrained.
This shortcoming in scientific understanding has hampered much of
the effort to build useful neural prostheses and stimulation devices.
For example, manufacturers of deep-brain stimulation systems have
spent years exploring precise regions of the subthalamic nucleus
to stimulate for most effective treatment of Parkinsons disease
and essential tremors. Researchers working on motor prostheses have
been hampered by their inability to trace neural connections from
motor cortex to spinal cord, to specific muscle fibers. And development
teams working on visual prosthesis projects would benefit greatly
from a better understanding of the precise neural pathways involved
with visual perception and scene analysis. Manufacturers of neurodiagnostic
systems would also benefit greatly from an enhanced store of knowledge
about brain activity corresponding to specific neurological and
psychological disorders. Further, just identifying connections presents
an incomplete view of nervous system functions, as connections can
be excitatory, inhibitory, state-dependent, and change their magnitude
over time.
One of the first efforts at cataloging the functional connections
within the brain was the Project Brain initiative at the University
of Southern California, headed by Michael Arbib with funding from
the National
Institutes of Mental Health. The project endeavored to create
a collection of distributed neuroscience databases to which multiple
researchers could contribute data at the molecular, subcellular,
cellular , network, or systems level.
In 1999, NIMH issued four neuroinformatics program announcements
for its Human Brain Project with the goal of bringing together neuroscientists,
computer scientists, engineers and mathematicians working on models
of the human brain. Among the institutions that secured funding
is Caltech, for a neuronal database derived from its Genesis simulator.
The Caltech team, headed by James Bower, has built a set of software
tools written in Java called Modelers Workbench, which allows users
on the Internet to search for and visualize different nervous system
components.
Another modeling database, ModelDB, is maintained by the developers
of the neural simulation package NEURON (Michael Hines and Ted Carnevale
at Yale and John W. Moore at Duke), and is designed to enable scientists
to contribute data and models, and simplify implementation of models
by users.
George Mason University also received funding for its software package
L-Neuron, which compiles topographical and morphological information
about dendritic branches in an effort to construct virtual neurons
that are anatomically indistinguishable from actual neurons. In
still another NIMH-funded project, Anders Dale at Massachusetts
General Hospital is building a two-dimensional map of the human
cerebral cortex in an effort to develop a surface-based coordinate
system.
On the commercial side, Neurome,
Inc. of La Jolla, CA is developing a series of quantitative
databases of nervous system attributes at the molecular, gene, cellular,
and circuit level. The company, founded in 2000 by Scripps Research
Institute scientists Floyd Bloom and Warren Young, along with John
Morrison from Mount Sinai School of Medicine, has as clients several
pharmaceutical and biotechnology companies looking to discover gene
targets useful in treating brain-based diseases. The founders received
$9 million in funding from a team of private biotech investors including
Digital Gene Technologies and Elan Pharmaceuticals. Scripps and
Mount Sinai also received shares in the venture.
Neurome management is pursuing an ambitious goal: Nothing
less than a complete understanding of the role and function of each
structure of the human brainfrom cognition to appetite, from
learning to motor function, from memory to sleep. Neurome
has developed a suite of technology tools to help them collect data
on the architecture and functions of brain structures. These include
NeuroZoom, a computer-aided extraction, imaging, and analysis tool;
BrainArchive, an electronic brain atlas of structure and circuitry
data, and MiceSlice, a standardized method of preparing brain sections.
Another technology firm constructing models of the nervous system
is Physiome Sciences of Princeton,
NJ. The company has developed a series of biological modeling tools,
including an In-Silico Cell software architecture that
helps researchers visualize and simulate signaling networks such
as ion channels in a neuronal cell. Physiome has entered into an
alliance with IBM in which Physiome will use the computer firms
supercomputing technology and IBM will license Physiomes biological
modeling technology.
While there is a great deal of current interest in genomic and proteomic
approaches to cataloging nervous system function, both pharmaceutical
and device companies in the neuro space are dependent on efforts
to understand the nervous system at higher levels of organization.
This is particularly the case for neurological diseases and disorders
such as stroke or spinal cord injury that cannot readily be cured
with the discovery of a single drug, gene target, or protein. Treatment
of more complex neurological and psychiatric disorders will undoubtedly
require a rich store of knowledge of which nervous system components
are involved with specific functions or dysfunctions, whether the
ultimate treatment is with drugs, cell therapies, or neurotechnology
devices. While the current efforts at mapping the human neurome
may not have attracted as much attention as the human genome project,
the implications could very well be just as great.
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