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In addition to leading TSRI's Department of Neuropharmacology,
Bloom is currently serving as the president of the American
Association for the Advancement of Science (AAAS), a position
he moved into after working for several years as editor-in-chief
of Science, the flagship publication of the AAAS. As his last
duty in that position, he will open the AAAS annual meeting
and give the president's lecture in February 2003.
Somebody who doesn't know Bloom could assume that today,
after a distinguished career that has taken him from Yale
to the National Institutes of Mental Heath to The Salk Institute
and finally to TSRI 20 years ago, he might be at a place in
his career where he would be mostly looking back.
He's not.
In fact, Bloom is looking forward to the truly great challenges
that await neuroscientists in the 21st century. For much is
yet to be discovered about the brain.
"The brain uses well over half of the genome," says Bloom.
By most recent estimates, there are around 40,000 genes in
the human genome, which means that the brain uses about 20,000
genes. "If you look for brain-specific molecules in all the
books [in the library], you won't find 2,000," Bloom says.
"That's how much further we have to go."
Identifying the Genes that Predispose
"The real trick now," says Bloom, "is to figure out the genetic
vulnerability factors for the major illnesses that we don't
have effective ways to treat—such as schizophrenia, depression,
drug abuse, and alcoholism."
There is no question that having particular genes predisposes
you to certain conditions and there are probably other factors
that can turn a vulnerability into a susceptibility. For instance,
if your identical twin has bipolar disorder, your chances
of having the disorder as well may be 100-fold higher than
any average person on the street. There are very strong genetic
susceptibility factors, but the question is, what are they?
"That's where [neuroscientists] are at now—the discovery
of many of the genes we didn't even know existed and how they
are affected in the genomes of people with diagnosed mental
illness," says Bloom.
Part of the problem may be that many mental illnesses, like
bipolar disorder, are multifactorial—they result from
a combination of several interacting factors from genes and
the environment.
The story, of course, does not stop with the identification
of genes. Basic science can go on to describe the expression,
regulation, and localization of these genes—both in "normal"
and in pathological states—and relate these microscopic
observations to macroscopic effects, such as behaviors and
mental conditions.
Bloom, in fact, pioneered the microscopy of neurons and
neurotransmitters decades ago in order to complete molecular
descriptions of neuronal function. In order to figure out
which neurotransmitters were important for which neurological
processes, he had to figure out where they were in the brain
and to develop methods that allowed him to see these neurotransmitters
with light microscopes and through electron microscopy. Once
he accomplished this, he was able to see the synapses that
had the chemicals of interest and thus identify, categorize,
map, and perturb genes essential for important functions in
the brain.
Bloom also pioneered the use of molecular biology in neuroscience.
In the 1980s Bloom, in collaboration with Professor J. Gregor
Sutcliffe of TSRI's Department of Molecular Biology, used
recombinant DNA technology to identify unknown gene products
expressed selectively in the brain—by isolating thousands
of mRNAs from brain tissue and cloning and sequencing the
ones that were not detectable in the liver or kidney.
Bloom now is devoted to devising systems of computer-assisted
tools to collect, collate, organize and analyze the multidimensional
data sets that characterize modern neuroscience research.
He focuses much of his time at TSRI on maintaining a laboratory
that specializes in quantitative microscopy—observations
of neurons and neurotransmitters with light microscopes. The
laboratory is funded as part of the large Interacademic Neuroscience
Consortium Center Grant, which is sponsored by the NIH and
led by his colleague George Koob.
"My laboratory is largely a core function for members of
the department and other collaborators," says Bloom.
This work grew out of the TSRI Alcohol Research Center,
of which Bloom was administrative leader in the early 1990s.
The center pioneered the use of animal models to analyze human
drug self-administration and later expanded to involve all
of the disciplines of the neurosciences, with the department's
faculty developing similar models for psychostimulants (amphetamine
and cocaine) and for opiates (morphine, heroin).
The Story of the Brain
The story of the brain is not just one of tissues and cells,
but of bodies and behaviors—encompassing everything from
the identification of genes relevant to the brain and basic
questions of their regulation and function to the broadest
measures of how these genes affect behavior. It covers everything
from the development of neurons in the embryo to the degeneration
of neurons in old age; from the expression of genes to the
expression of behavior; and from mechanism to treatment of
diseases.
Bloom once described the field of neurosciences as including
"virtually any activity that contributes to an understanding
of the biological basis of mental activity, regardless of
species, in health or disease." Interdisciplinary approaches
naturally lend themselves to such a broad field, and collaboration
has always been the norm in the neurosciences. Today, it is
becoming a necessity.
Where once the story a neuroscientist told would take the
reader from cells to circuits to function, now the same neuroscientist
must weave a more elaborate tale: from genes to proteins to
chemicals to cells to neurons to circuits to function to behavior
in complex eukaryotic—indeed, human—life.
"It requires that you combine anatomy, chemistry, physiology,
pharmacology, behavioral science," says Bloom, "and now, molecular
biology and computer science."
With this more extensive set of disciplines grows not only
the number of observations that may be relevant for a particular
story, but the number of specialists who need to be involved
to tell it well.
"Virtually everybody in the department is collaborating
with someone else in the department," he says.
And that is exactly where he likes the department to be.
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