Biology Reference
In-Depth Information
demystifying disease for the benefit of the individual, as
well as dealing with the societal opportunities and chal-
lenges created by this revolution in medicine.
A key component of P4 medicine is the 'activated'
(continually informed patients possessing the knowledge,
skill and confidence necessary to manage their health and
healthcare and that of their families) and 'networked'
(patients connected with other patients and other members
of their community, working together to enhance personal
and community wellbeing) patients
[56]
.Theconvergence
of systems approaches to wellness and disease with acti-
vated and networked patients will result in a P4 medicine
that integrates discovery science with clinical practice and
health management by networked and activated patients.
This integration will generate the virtual clouds of billions
of data points for each patient (
Figure 23.3
). Analyses of
this data cloud will decipher the 'network of networks' for
each patient and lead to discoveries and the optimization
of wellness and disease emerging from relevant patient
social networks. P4 medicine is now pioneering some-
thing that never existed before
social opportunities and challenges that inevitably will
arise from these new relationships. Here is a 10-year
glimpse into the envisioned future of the 4 Ps.
Predictive. In 10 years nearly everyone will have his or
her genome sequenced. 'Actionable genetic variants'
e
those whose identification opens the door to a course of
action that will improve physical health or relieve anxiety
for the individual
will drive forward the acceptance of
the complete genome sequence as a part of the individual's
medical record. While most of the medically relevant
variation catalogued to date occurs in the coding regions of
genes, it is becoming clear that variations in non-coding
regions, copy number, structural variations, and other
features of chromosomal architecture play a role in disease
etiology. We believe that complete genome sequencing
should be done in families. Family sequencing enables the
correction of a significant fraction of the DNA sequencing
errors, thus generating very accurate sequences. It also
provides a deep understanding of the one-dimensional
organization of the many genetic variants in the chromo-
somes of each individual (this is denoted haplotype deter-
mination) (
Figure 23.8
), thereby enormously facilitating
the discovery of disease genes or loci. We have identified
more than 300 of these actionable variants and many more
are being identified with every passing year. Indeed, every
person's genome will be reviewed yearly for new action-
able variants
e
actionable understand-
ings of disease and wellness as a continuum of network
states unique in time and space to each individual human
being that can be perturbed by various means, including
butbynomeans im tedtodrugs,torestoreand
maintain health.
These databases of patient information and social
networks will provide physicians and other healthcare
providers with the information they need to deliver care
tailored to the circumstances of each individual. We are
beginning to see this in the case of certain cancers, where
the DNA sequencing of the tumors provides insights
into the mutations in signal transduction pathways that
inform the choice of therapy for the individual patient
[57,
58]
. In addition, data from clinical encounters, and from
networked patients and consumers actively involved in
managing their health and that of their families, will
provide millions of data points that will enable systems
biologists to decipher signal from noise in complex bio-
logical networks. These data will be funneled to scientific
research centers and emerging health information compa-
nies to fuel large-scale studies. Eventually 100 000s or even
millions of patients' data on physiological, cellular, and
molecular markers will be used to increasingly demystify
disease and quantify wellness by augmenting the relevant
biological signals.
An exciting new cycle of accelerating biomedical
innovation will emerge as systems-medicine discoveries
are routed back to patients and consumers, thereby gener-
ating more data to fuel further advances in actionable
insights into individual biological systems. P4 medicine
includes novel techniques and paradigms for facilitating
new relationships between scientists, care providers,
patients and consumers, as well as for dealing with the
e
and these will provide powerful insights to
optimize the wellness of the individual. The genomes of
individuals will provide an investment in individual infor-
mation that will permit a yearly optimization of wellness
for the rest of the person's life.
P4 medicine is making blood a window for assessing
health and disease. Organ-specific proteins found in the
blood will be analyzed in a longitudinal manner across the
individual's life (
Figure 23.7
). Within 10 years, we envision
a hand-held device that can prick your finger, take a fraction
of a droplet of blood and quantify several thousand organ-
specific proteins in 5 minutes. This device will permit the
health or impairment status for each of your major 50 organ
systems to be followed in a longitudinal manner over time
[41]
. Moreover, these 'microfluidic protein assays' will
permit hundreds of millions of patients to be analyzed
routinely, e.g., biannually. Thus transitions from health to
disease may immediately be identified and acted upon. The
organ-specific blood fingerprints will allow us to stratify
diseases into their distinct subtypes (for an impedance
match against proper therapies) and to follow the
progression of a disease. In the future different drugs will
be effective against different stages of a disease. In addi-
tion, organ-specific blood protein fingerprints will enable
one to analyze the responses of multiple organs to a given
disease
e
and thereby extend the analysis of the 'networks
of networks' from DNA, molecules and cells to organs
(
Figure 23.4
). Finally, organ-specific blood protein will
e
