Brave
New Pharmacy
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Clinicians, meanwhile, are assembling a list of 1,500 patients being treated for
depression, whose varying responses to medication will be carefully documented.
Eventually the clinical data will be combined with the genetic studies. Says
Herskowitz: "It's interesting to see the changes to the cell, but what you really
want to know is how someone with that change would respond differently to
Prozac, or to an anticancer compound. That's more elaborate, which is why this
clinical aspect is exciting stuff."
Promising as all these projects seem, they're really only the first stage of the
revolution in genomics-based drug discovery. The ultimate payoff of genomics
will be a drug resulting from an entirely novel, as yet undiscovered class of
compounds. And that will come about only when scientists have assembled a road
map laying out not just the functions of individual genes but the dizzyingly
complex network of enzyme reactions, receptor interactions and protein-binding
patterns that result - not just the building blocks of human life, in short, but the
entire working machine. "When we understand that in great, gory detail, we'll be
someplace," says Alfred Gilman, a pharmacologist at the University of Texas
Southwestern Medical Center at Dallas and winner of the 1994 Nobel Prize for his
work on cellular signaling mechanisms.
Gilman and some 50 investigators at 20 different universities have banded
together to form the Alliance for Cellular Signaling, whose goal is to trace the
maze of chemical pathways in working cells and then use that knowledge to
create a "virtual cell" inside a computer. This electronic cell will, in theory, allow
researchers to test potential drugs for safety and effectiveness with much less
need to resort to mouse, monkey or human subjects. Says Gilman: "You'll be able
to take a library of millions of hypothetical chemical compounds and let the
computer watch them interact with the theoretical models of drug targets. It will
be a fantastic drug-discovery engine for the future."
The task, he admits, is extraordinarily daunting. A typical cell has perhaps 50
different receptors, and the cell doesn't pay attention to just one receptor at a
time. "How," asks Gilman, "does it know how to interpret the signal from one
hormone when it's listening to 45 other ones at the same time? How does the
whole signaling system work as a network? That's what we want to find out."
Leading-edge genomics firms aren't waiting until all the answers are in.
Companies like Myriad Pharmaceuticals in Salt Lake City, Utah, Human Genome
Sciences in Rockville, Md., and the British company GlaxoSmithKline, along with
dozens of others, are moving equally aggressively to plumb the genome for
whatever secrets it's ready to reveal.
For its part, Millennium - both on its own and in collaboration with its partners
- has identified 121 potential targets, developed 17 drugs currently being tested
in animals and moved six drugs into Phase I human trials, four into Phase II and
one into Phase III. Says company ceo Mark Levin: "We're going to understand the
mechanism of diseases much better, so eventually, obesity, asthma and
schizophrenia will be seen not as single diseases but as a subset of 10 to a dozen
conditions. That means breakthrough products that have better efficacy and
therefore more value to patients than the drugs we have today."
The drugs will have more value for drugmakers as well. With its largely
automated, computer-driven searches for new medicines and the cost saving
from tightly targeted human trials, Millennium chief technology officer Mike
Pavia estimates, the company can cut the cost of developing a new medicine from
about $500 million to $200 million while shaving the development time from
more than 10 years down to six or seven. These savings, the firm hopes, will
translate into pure profit for investors.
That same hope is echoed by dozens of other companies that have jumped into the
race to perfect genome-based drugs - and nobody seems to doubt that it will
eventually happen. While the genomics revolution hasn't touched most of our
lives yet, the day when it will may not be far off. "When it starts to happen, it will
happen quickly," predicts Adrian Hobden, president of Myriad Pharmaceuticals.
"There will be a few brave pioneers who believe in it, and the vast majority will
carry on as they've done before. Then over five years it will become an accepted
standard of care, and everyone will be doing it."
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January 15, 2001
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COVER
STORIES
MEDICINE:
The Future of Drugs
Now that our dna has been decoded, the search for better, faster and more
effective medications begins in earnest
THE
LABS: Inside the Brave New Pharmacy
At a leading genomics company, the star of the show is a robot
DISEASES:
The Search for Cures
For AIDS, cancer, mental illness, obesity, Alzheimer's, etc.
Antibiotics:
The microbes are winning
Delivery:
Beyond pills and needles
Natural remedies:
Turning poisons into potions
Recreational
drugs: What comes after K and ecstasy?
THE
YEAR IN MEDICINE: An A-to-Z guide
T
H E A R T S
CINEMA:
East meets West
in a film with universal appeal
Robert de Niro and Ben Stiller team up in a funny
farce
Three generations of Ralph Fiennes in Sunshine
MUSIC:
Erykah Badu's new CD has soul and guts
TRAVELER'S
ADVISORY
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