oCtoBeR 2010 - American Association for Clinical Chemistry

P4 Medicine on the Horizon
future of medicine, continued from page 1
paradigm that incorporates analysis of vast
data inputs to consider the complexity of
biological systems and their responses to
wellness and disease, in aggregate and for
individual patients. “Medicine has become
an informational science, and my view of
medicine is one that is information-based
and data-driven,” he explained. “In the future,
each patient will be surrounded by a
virtual cloud of billions of data points and
the question will be, how can we use that
complexity to find parameters for wellness
that are unique to each individual?” Hood
is co-founder of the Institute for Systems
Biology (ISB), a research institute dedicated
to the integration of technology, computation,
biology, and medicine.
Hood believes the P4 approach—predictive,
personalized, preventive and participatory
medicine—will drive the health-
care system in the 21st Century, and he sees
it as nothing short of revolutionary. “Many
people don’t understand technology, but
it’s what drives all of science. That’s why
the advance of science is often thought of
as being terribly incremental—and that’s
true when technology isn’t changing too
rapidly. But today it’s changing enormously
quickly. We’re seeing exponentially higher
throughput, more accurate data, and costs
being driven down,” he explained.
A Mere Drop of Blood
Hood envisions that within 10 years, most
everyone will have had a complete genomics
analysis run at a reasonable cost. This
information will enable a data mining of
sorts that will provide a clear picture of
health and disease for each individual, effectively
shifting the focus of medicine
from disease to wellness. On top of that, he
sees a time when biannually, patients will
provide a one-drop blood sample from
which about 2,500 protein measurements
will be taken, and these also will be used to
assess health as opposed to disease for 50
major organ systems.
If this seems pretty far removed from
today, Hood pointed to several projects
ISB has underway that are planting seeds
to achieve the P4 medicine model. Scientists
at ISB recently completed an entire
genome sequence for a family of four. This
effort identified 230,000 new rare variants
within the family and enabled investigators
to create a precise recombinant map. “That
gave us exactly the haplotypes of the parental
chromosomal regions that conjoin
together to make up the chromosomes of
the children,” he explained. “What was fascinating
is that about 70 percent of these
recombinations fell in hotspots of recombination,
and that has important implications
for genetics.”
ISB researchers also have been studying
prion disease in mice, analyzing its behavior
as a network from a state of wellness
through neuronal degeneration. The first
set of analyses involved nearly 50 million
data points. “This required creation of
entirely new computational and integrative
methods for dealing with a significant
amount of data,” said Hood. The researchers
also employed subtractive biological
analyses to address “absolutely overwhelming”
signal-to-noise problems. Hood believes
this type of analysis can help investigators
understand how biological networks
become perturbed, and to eventually develop
interventions to modify disease progression
in humans.
In addition, ISB scientists have a goal to
create within the next few years mass spectrometry
assays for about 20,000 human
proteins. Already they have developed such
assays for 97% of yeast proteins, according
to Hood.
Overcoming the Skeptics
ISB is beginning to tie the themes of its
work together in a pilot project with Ohio
State University Medical Center. “With
lung cancer we plan to develop very early
diagnostic markers and be able to stratify
patients into different types so we can
match them with appropriate drugs,”
Hood explained. “In wellness, we hope to
develop molecular and cellular parameters
for evaluating each individual’s wellness
status and use that to optimize behaviors to
achieve greater wellness.”
This effort will be essential to moving
the P4 medicine paradigm forward, according
to Hood. “Scientists are trained to
be inherently skeptical, cynical, and conservative,
and they don’t feel comfortable with
new ideas, so you just have to overwhelm
leroy hood, md, phd, says the emergence of p4 medicine will revolutionize
the healthcare system in the 21st century.
James Thomson, vmd, phd, presented his research on human-produced
pluripotent stem cells and potential medical applications.
them with success,” he observed.
As P4 medicine gains ground—an
eventuality about which Hood is utterly
confident—it will transform the entire
healthcare landscape. “This will force every
sector of healthcare to rewrite business
plans in major ways,” he predicts. Laboratories
will be part of this sweeping change.
“My own feeling is that specialty diagnostic
companies will emerge that have finetuned
technologies that enable us to do
what can’t be done today. There’ll be real
opportunity for economic advances for
these new companies,” said Hood.
Stem Cell Therapy Coming of Age
Pioneering stem cell researcher Thomson
gave a compelling presentation about developments
in and the promise of stem
cell research in transforming medicine.
The first scientist to isolate and culture
an embryonic stem (ES) cell line in 1998,
Thomson is the John D. MacArthur professor
and director of regenerative biology at
the Morgridge Institute for Research at the
University of Wisconsin.
In 2007, his lab made history again by
deriving eight new cell lines from human
skin cells aided by four transcription factors.
Like ES cells, these induced pluripotent
stem (iPS) cells are capable of differentiating
into any of the 220 cell types in the
human body and proliferating indefinitely.
However, they do not carry the same ethical,
legal, or political controversies that surround
ES cells.
A Profound Change
The remarkable achievement of creating
ES and iPS cell lines will open wide the
doors of scientific discovery in ways that
can’t even be foreseen right now, Thomson
predicted. A comparable situation existed
with the advent of recombinant DNA research
in the 1970s. “Everyone knew that
DNA was really important, but no one
got the details right. We thought gene
therapy was going to be easy, and we’re 30
to 40 years into it now and there’s no gene
therapy to speak of. It profoundly changed
everything, but the specifics were not accurate,”
he observed.
Thomson also suggested that the breakthroughs
made by his and other labs would
pick up the pace of discovery in the field.
“A relatively small number of genes allowed
us to do this, and it’s clear the work
has implications beyond making the functional
equivalent of human embryonic
stem cells,” he indicated. “My sense is that
things are going to move forward even
faster now.”
Many Challenges Ahead
Even as the field advances rapidly, Thomson
cautioned that a number of challenges
still need to be worked out for both ES and
iPS cell-based transplantation therapy. For
example, researchers need to be able to reliably
make the type of cells of interest, such
as neurons or hematopoietic cells. Concerns
exist as well about whether stem cells
introduced into a patient’s body can provoke
an immune rejection response.
In 2009, Thomson’s lab tackled a key
safety concern associated with viral vectors,
the method he used initially to deliver
genes into skin cells in order to make iPS
cells. The concern was that iPS cells created
by this approach carried residual genetic
material that could have triggered
mutations in the induced cells. However,
Thomson successfully used plasmids to
introduce genetic material into the target
cells. These circles of DNA that can replicate,
but lack the complexity and efficiency
of chromosomal DNA, can be engineered
to introduce genetic material into cells and
then be subsequently eliminated, thereby
creating a line of iPS cells free of exotic genetic
material. “We believe this was the first
time human-induced pluripotent stem
cells have been created that are completely
free of vector and transgene sequences,”
said Thomson. “It’s another important step
along the way toward developing cells in
sufficient quantity and quality to explore
the possibility of human therapeutic use.”
Edging Towards Everyday Use
As Thomson’s lab continues its groundbreaking
work, he looks forward to the
practical application of stem cell therapy in
areas such as drug discovery and regenerative
medicine. The hope is that stem cells
can improve the drug development process
by helping researchers identify candidate
compounds that are likely to be effective
in specific patients. “If you already know
See future of medicine, continued on page 4
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