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Revolutionizing and personalizing global health
April 2013
SHARING OPTIONS:
Environmental factors such as obesity and exposure to
pollutants are having a growing impact on our health, and left unchecked, will
outpace our ability to innovate cost effective solutions. These issues are
compounded with the impact of aging in most developed and many developing
countries. The largest global health study ever conducted (Lancet, Dec. 2012) showed that despite the fact that people are
living longer, they are doing so in poor health. For every year of longer life,
only 9.5 months are in good health, while the rest are in a diminished state,
and the numbers get progressively worse for people aged 50 and up.
This leaves us with the quadruple challenge of finding (1)
improved diagnosis/screening for early-stage detection and disease
predisposition; (2) personalized treatments that are safe and efficacious; (3)
the actual prevention of disease; and (4) affordable healthcare that does not
cripple global economies. While daunting, these goals are attainable, thanks to
the culmination of decades of research in genomics, epigenomics, proteomics and
other fields, yielding an unprecedented understanding of diseases as complex as
cancer, as well as mechanistic insight into environmental factors that impact
health. Broadly, the new transformative disciplines fall into six key
categories.
(1) Genomic analysis Coming swiftly upon the heels of NGS is the field of
epigenomics, which has grown exponentially over the past decade. Thanks to a
growing suite of analytical tools that can measure DNA methylation, histone
acetylation and microRNA expression in high throughput, we have the ability to
assess the molecular effect of specific environmental factors on the epigenome,
and link this to phenotype and disease causation. In the past year alone, we
have seen a wealth of evidence supporting an environmental link with diseases
such as cancer, types 1 and 2 diabetes, allergies, asthma and many others. We
are also learning about the direct molecular link between nutrition and energy
metabolism, and the effect on epigenetics and ultimately disease.
Using new innovative technologies to understand the direct
molecular influence of our environment on health is a significant step towards
figuring out how to stop—and ideally reverse—the imminent explosion of
non-communicable diseases.
An important consequence of genomics and other 'omic
analyses has been the discovery and validation of a large, growing number of
clinically useful biomarkers and biosignatures. The impact of these on clinical
practice has been profound and swift, ranging from their inclusion in virtually
all clinical trials from the outset, through to their use in the clinic for
diagnosing patients and guiding treatment to ensure optimal safety and
efficacy. The greatest impact thus far has been in the field of cancer, where
the analysis of a patient's tumor biomarkers is increasingly becoming standard
of care.
As with genomics, the successful transition of biomarkers,
companion diagnostics and personalized medicine into mainstream clinical
practice is contingent on analytical tools that are accurate, robust,
efficient, scalable, cost-effective and that extract very large amounts of
information from exceedingly small clinical samples. Automation is key to
addressing the issues of efficiency, reproducibility, scale and cost, as
companies transition their diagnostic assays from small scale to commercial
launch. As samples become smaller and less invasive, the ability to multiplex,
measuring multiple biomarkers simultaneously, is critical for maximizing
information and enabling accurate diagnosis. Consequently, multiplexed
platforms are becoming increasingly important in personalized cancer medicine.
In the field of cancer, circulating tumor cells (CTCs)
represent a paradigm-shifting biomarker. CTCs are "liquid biopsies" based on a
blood draw, and thus are more amenable to routine screening. While it is well
established that the measurable presence of CTCs in blood is correlated with
poor prognosis for various solid tumor types, the clinical utility of this
approach has been limited by the poor sensitivity of the assay, providing
little clinically actionable information. In recent years, progress in
microfluidics and engineering has produced a new generation of CTC platforms
that are tenfold more sensitive than earlier versions, and allow isolation of
single cells for various omics analyses. One near-term benefit will be tests to
gauge a patient's response to a targeted therapy in days rather than weeks,
giving physicians vital time to adjust and find the optimum therapy.
(3) Imaging and
pathology
(4) Targeted small
molecules, therapeutics and vaccines
The availability of genomic information has transformed our
ability to design and optimize targeted small-molecule drugs and biologics that
can treat patients more safely and effectively. This is further enhanced by
layering in biomarkers and companion diagnostics, oftentimes enabling treatment
of diseases that were hitherto untreatable or that were not economically
viable, such as orphan diseases including many life-threatening cancers that
affect very small numbers of patients.
Cardiovascular disease and neurological disorders, which
increase exponentially with age, can potentially be addressed using stem cell
therapies, as evidenced by very encouraging clinical progress on multiple
fronts. As with small-molecule and biologic therapeutics, innovative
translational tools that span the in-vitro
to in-vivo to human continuum have
been critical for establishing the safety and efficacy of these potent cellular
treatments.
The aforementioned technologies and disciplines are
generating mind-boggling amounts of data at an accelerating pace. The final
critical piece that fuses all of these data and helps leverage the tremendous
power of this information is bioinformatics. As the complexity and volume of
data continue to rise, bioinformatics is emerging as one of the cornerstones of
personalized medicine, from enabling discovery and development of novel
treatments and diagnostics to facilitating collection, analysis and
interpretation of data that ultimately helps an individual patient.
The convergence of biological information with the
availability of a formidable collection of disruptive and innovative tools that
enable personalized medicine leads me to believe that we now have the means to
affordably improve health through better diagnosis, treatment and prevention. Moreover,
the scalability of these tools combined with the rapid dissemination of
information means that the benefits in improved health will likely have a
global impact.
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