large-scale studies that compare old-school approaches, where “you give the same drug to all people and hope for the best,” to the new targeted therapies.

Vaccinations represent an area of
drug therapy traditionally associated
with the CDC. But as Khoury says,
different people react differently to
vaccines. “If you’re able to find the
people at risk for side effects, you
give them a different vaccine or don’t
give them a vaccine at all,” he says.
And where one vaccine might not
be effective, you might be able to go
with a second or third choice. “You
can tailor the vaccine… to the indi-
How is the movement to tailor thera-
pies to an individual’s genetic makeup
changing the pharmaceutical industry?
It’s a field where Khoury says research
follows “blockbuster drugs that can
help the greatest number of people
with the fewest side effects. As indus-
try develops them, a lot of them look
promising early on but have a high side-
effects rate and get discarded through
the manufacturing process.” But by eval-
uating genetic markers, pharmaceutical
companies may be able to isolate which
groups of people benefit and which
have side effects, resulting in an array
of useful drugs that might otherwise be
discarded.

“Pharmacogenomics holds the promise of a different way of looking at the developmental pathways of drugs,” says Khoury, though whether industry chooses to embrace this new paradigm remains to be seen. “At the end of the day,” he says, “if you try to segment the population into smaller and smaller subgroups, until you have only 10 people who will benefit from the drug, then the

incentive may not be the same from an industry perspective.”

How It Works

How do our genes influence our health? Michael Olivier, Ph.D., co-director of the Wisconsin Center of Excellence in Genomics Science in Milwaukee, offers this explanation: “Our large genome contains about

25,000 genes, all of which need to be
turned off or on in tightly controlled
and coordinated fashion for our cells
and our body to function normally.
When this regulation no longer works,
things go wrong in our body, ultimately
leading to a variety of diseases.”
If our health reflects how the switch-
es are set, what might flip them to the
wrong position? “Groups of proteins
that bind to DNA sequences near these
genes either activate a particular gene or
turn it off,” says Olivier. Unfortunately,
there is no clear schematic showing how
the switches should be set for maximum
human functioning or where exactly
to set all the proper switches within
an individual’s genome if things aren’t
right. The 25,000 genes, says Olivier,
are interpreted differently by different
cell types; that is to say, the brain and
the liver, as well as cells at different ages
(embryo, newborn, adult), have different
interpretations. As a result, evaluating
how the regulatory proteins operate is
complicated and difficult. “Currently,”
he says, “we have no comprehensive
technology that lets us investigate what
proteins regulate our genome at any
time and make it function normally (in
health) or abnormally (in disease).”
Developing such technology is a goal
of the Wisconsin Center. Olivier says,
“Any researcher could identify all the
proteins that bind to the entire genome
at any given time. If that approach was
feasible, you could, for example, ask
how this set of proteins is different in a
normal heart or in the heart of a patient
with heart disease and at what genes
proteins bind differently.”
With knowledge of how and where
proteins differ, medical experts could
use what is already known about how
the gene (or sets of genes) in question
influences heart development or func-
tion. “Once that becomes clear,” says
Olivier, “you could then try and inter-
fere (alter) the binding of proteins to
these genes to make it look like [it does]
in a normal heart, thus helping to cor-
rect the abnormal function.”
How might researchers create tech-
nology to understand the proteins that
bind to the genome? Says Olivier, you
would need to do multiple steps: