Butter
Before butter
During butter
After butter
"60 bucks is pretty good for 3 seconds"
Save the music
Look hard over my shoulder.
This guy knows his audience. He just didn't have the right equipment.
(For those who can't see - he was playing "the drums" with two water bottles.)
Right near berklee college of music. Sent from my Verizon Wireless BlackBerry
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Moment of zen
I found a great place to study in the middle of the city. Sent from my Verizon Wireless BlackBerry
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Fw: OK, who was trying to get out early today?
This is what I do at work. Distract people.
GAVIN MCGRATH • L.E.K. CONSULTING
28 State Street, 16th Floor • Boston, MA 02109
----- Forwarded by Gavin McGrath/LEK on 07/10/2008 04:36 PM -----
| Dan Schorr/LEK
07/10/2008 04:33 PM |
|
| Gavin McGrath/LEK
07/10/2008 04:18 PM |
|
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My favorite part of the Park
L.E.K. goes to Fenway. The view from our seats.
Sent from my Verizon Wireless BlackBerry
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Life science is taking a new road
This is a very readable article that does a good job of explaining the
shift in life science from symptom-therapeutic to root biology as
viewed through the lens of Prozac's development.
Heavy. -G
************************************************
From Sunday's Boston Globe Ideas section:
Head fake: How Prozac sent the science of depression in the wrong direction
By Jonah Lehrer | July 6, 2008
PROZAC IS ONE of the most successful drugs of all time. Since its
introduction as an antidepressant more than 20 years ago, Prozac has
been prescribed to more than 54 million people around the world, and
prevented untold amounts of suffering.
But the success of Prozac hasn't simply transformed the treatment of
depression: it has also transformed the science of depression. For
decades, researchers struggled to identify the underlying cause of
depression, and patients were forced to endure a series of ineffective
treatments. But then came Prozac. Like many other antidepressants,
Prozac increases the brain's supply of serotonin, a neurotransmitter.
The drug's effectiveness inspired an elegant theory, known as the
chemical hypothesis: Sadness is simply a lack of chemical happiness.
The little blue pills cheer us up because they give the brain what it
has been missing.
There's only one problem with this theory of depression: it's almost
certainly wrong, or at the very least woefully incomplete. Experiments
have since shown that lowering people's serotonin levels does not make
them depressed, nor does it does not make them depressed, nor does it
worsen their symptoms if they are already depressed.
In recent years, scientists have developed a novel theory of what
falters in the depressed brain. Instead of seeing the disease as the
result of a chemical imbalance, these researchers argue that the
brain's cells are shrinking and dying. This theory has gained momentum
in the past few months, with the publication of several high profile
scientific papers. The effectiveness of Prozac, these scientists say,
has little to do with the amount of serotonin in the brain. Rather,
the drug works because it helps heal our neurons, allowing them to
grow and thrive again.
In this sense, Prozac is simply a bottled version of other activities
that have a similar effect, such as physical exercise. They aren't
happy pills, but healing pills.
These discoveries are causing scientists to fundamentally reimagine
depression. While the mental illness is often defined in terms of its
emotional symptoms - this led a generation of researchers to search
for the chemicals, like serotonin, that might trigger such distorted
moods - researchers are now focusing on more systematic changes in the
depressed brain.
"The best way to think about depression is as a mild neurodegenerative
disorder," says Ronald Duman, a professor of psychiatry and
pharmacology at Yale. "Your brain cells atrophy, just like in other
diseases [such as Alzheimer's and Parkinson's]. The only difference
with depression is that it's reversible. The brain can recover."
Given the prevalence of depression - more than 16 percent of people
will suffer from a major depressive episode at some point in their
lives - a more accurate scientific understanding of the disease is of
immense value. In fact, this research is already being used to develop
more effective treatments for the mental illness, some of which are
currently in clinical trials.
The progress exemplifies an important feature of modern medicine,
which is the transition from a symptom-based understanding of a
disease - depression is an illness of unrelenting sadness - to a more
detailed biological understanding, in which the disease is categorized
and treated based on its specific anatomical underpinnings.
In the 19th century, the "fever" was a common medical illness. Of
course, doctors now realize that a fever is merely a common symptom of
many different diseases, from the flu to leukemia.
Likewise, when Richard Nixon declared a "War on Cancer" in 1971,
scientists largely defined cancer in terms of its most tangible
characteristic: uncontrolled growth leading to a tumor. As a result,
every cancer was treated with the same blunt tools. Over time, of
course, scientists have discovered that cancer is not a single disease
with a single biological cause. Breast cancer, for instance, can be
triggered by a wide variety of genes and environmental risk factors.
Because doctors can look beyond the superficial similarities of the
symptoms - all tumors are not created equal - they are able to tailor
their treatments to the specific disease.
Neuroscience is only beginning to catch up. Thanks to a variety of new
experimental tools, such as brain scanners and DNA microarrays,
researchers are now refining their understanding of mental illness. In
many instances, this means recategorizing disorders, so that patients
are no longer diagnosed solely in terms of their most obvious
symptoms.
"We used to think there was only one kind of anemia," says Arturas
Petronis, a scientist at the University of Toronto who investigates
the underlying causes of schizophrenia. "But now we know there are at
least 15 different kinds. We'll likely learn the same thing about many
mental illnesses."
. . .
One of the first cracks in the chemical hypothesis of depression came
from a phenomenon known as the "Prozac lag." Antidepressants increase
the amount of serotonin in the brain within hours, but the beneficial
effects are not usually felt for weeks.
This led neuroscientists to wonder if something besides serotonin
might be responsible. Duman, for instance, began to study a class of
proteins known as trophic factors, which help neurons grow and
survive. Trophe is Greek for nourishment; what sunlight and water do
for trees, trophic factors do for brain cells. Numerous studies had
shown that chronic stress damages the brain by suppressing the release
of trophic factors. In a series of influential papers published
earlier this decade, Duman demonstrated that the same destructive
hallmark is seen in depression, so that our neurons are deprived of
what they need.
"The mental illness occurs when these stress mechanisms in the brain
spiral out of control," he says.
Once that happens, the brain begins to shut itself down, suppressing
all but the most essential upkeep. Not only do neurons stop growing,
but the brain seems to stop creating new cells. A 2003 study, led by
Columbia University neuroscientist Rene Hen, found that when the birth
of new brain cells was blocked with low doses of radiation in
"depressed" rats, antidepressants stopped working.
A recent study by Italian researchers, published in the journal
Science, helps to reveal another mechanism by which antidepressants
reverse the damage of depression. The scientists were interested in
seeing if fluoxetine, the active ingredient of Prozac, could increase
the potential of brain cells in the adult rat. They studied animals
with severe cases of "lazy eye," a condition characterized by poor
vision in one eye due to underdevelopment of the visual cortex. The
scientists showed that fluoxetine gave brain cells the ability to take
on new roles and form new connections, which erased the symptoms of
the disorder.
"The drug appears to make brain cells quite young," says Jose
Vettencourt, a lead author. The scientists are currently repeating the
experiment with humans, raising the possibility that fluoxetine will
soon be used to treat lazy eye and related conditions.
"Even five years ago, this would have seemed like a very strange
idea," Vettencourt says.
Duman's lab has demonstrated, in a paper published earlier this year,
that physical exercise seems to stimulate the same regenerative
pathways. Mice given access to running wheels not only showed reduced
anxiety and stress, but also increased levels of the same trophic
factors activated by antidepressants. When the activity of these
trophic factors was blocked, the benefits of exercise disappeared. The
mice stayed stressed, even when they were allowed to run on their
wheel.
It is jarring to think of depression in terms of atrophied brain
cells, rather than an altered emotional state. It is called
"depression," after all. Yet these scientists argue that the name
conceals the fundamental nature of the illness, in which the building
blocks of the brain - neurons - start to crumble. This leads, over
time, to the shrinking of certain brain structures, like the
hippocampus, which the brain needs to function normally.
In fact, many scientists are now paying increased attention to the
frequently neglected symptoms of people suffering from depression,
which include problems with learning and memory and sensory deficits
for smell and taste. Other researchers are studying the ways in which
depression interferes with basic bodily processes, such as sleeping,
sex drive, and weight control. Like the paralyzing sadness, which
remains the most obvious manifestation of the mental illness, these
symptoms are also byproducts of a brain that's literally withering
away.
"Depression is caused by problems with the most fundamental thing the
brain does, which is process information," says Eero Castren, a
neuroscientist at the University of Helsinki. "It's much more than
just an inability to experience pleasure."
This new scientific understanding of depression also offers a new way
to think about the role of drugs in recovery. While antidepressants
help brain cells recover their vigor and form new connections, Castren
says that patients must still work to cement these connections in
place, perhaps with therapy. He compares antidepressants with anabolic
steroids, which increase muscle mass only when subjects also go to the
gym.
"If you just sit on your couch, then steroids aren't going to be very
effective," he says. "Antidepressants are the same way: if you want
the drug to work for you, then you have to work for the drug."
Jonah Lehrer is an editor at large at Seed magazine and the author of
"Proust Was a Neuroscientist." He is a regular contributor to Ideas.
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