Revolutionizing and personalizing global health
"Every generation needs a new revolution." Thomas Jefferson's words are poignant and timely, as we sit on the cusp of an urgently needed revolution to transform health on a personalized and global scale.
While we are buoyed by some extraordinary scientific and medical breakthroughs in recent years, we are mindful that most common diseases still cannot be effectively treated by existing therapies. Many cancers, including breast, lung, colon and prostate, are incurable once they have metastasized, while heart disease and stroke remain leading causes of mortality. Based on the current trajectory, cancer and type 2 diabetes will double by 2030, while Alzheimer's disease will triple by 2050. Consequently, these and other rising non-communicable diseases are on track to wreak havoc with most economies—and most families.
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
Next-generation sequencing (NGS) has transformed our understanding of many diseases, especially cancer. Thanks to NGS, we understand cancer to be a disparate collection of molecular diseases and should be treated accordingly. NGS is increasingly being incorporated into clinical trials, and may eventually be a routine stratification tool. Arguably the most impactful application of NGS is in the clinic, in life-critical situations such as guiding treatment for cancer patients and identifying rare disease-causing mutations in newborns. Translating NGS from a research platform to a clinically useful tool has been possible thanks to a dramatic shift in cost and efficiency, as well as key ancillary technologies that enable efficient extraction of DNA from diminishingly small tumor samples.
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.
(2) Biomarkers and companion diagnostics
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
One important tenet of disease diagnosis and treatment continues to be biological contextual and heterogeneity information, as these provide clinically informative data that is lost with most omics technologies, which typically use isolated homogenized samples. The continued strong growth in histopathology highlights the importance of direct biomarker visualization and contextual analysis. Multiplexing provides another important dimension, maximizing clinically relevant information from each precious tumor sample.
Preclinical in-vivo imaging continues to be one of the most critical enabling technologies in translational medicine, allowing non-invasive longitudinal studies to track the impact of therapeutic candidates in animals. The importance of these technologies is underscored by the fact that many approved drugs were validated preclinically using them, including Pfizer's Sutent and Lyrica, Roche's Zelboraf and Novartis' Zometa.
Building on the success of in-vivo imaging, the same fluorescence-based imaging technologies are being translated to human surgery, whereby they enable surgeons to visualize precisely cancer tissues in real-time during surgery, and excise the optimal amounts of tissue. Intraoperative imaging promises significant benefits in cancer, reducing repeat surgeries as well as the risk of tumor spread from non-excised cancerous tissue.
(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.
Underpinning the successful development of these novel treatments has been the fusion of information from many disruptive tools that span a broad range of platforms, from molecular and cellular assays, NGS, high-throughput biomarker analysis, preclinical imaging to "high-context" multiplexed immunohistochemical tissue imaging. A critical feature common to the most useful tools is their ability to seamlessly translate from bench to clinic across the "in-vitro to in-vivo to human bridge"—the great divide that separates clinical success and failure. This is especially true for cancer research, where many promising in-vitro and preclinical candidates have failed when tested in humans.
(5) Cellular systems
One of the greatest objectives in medicine is treating the underlying cause, rather than just the symptoms. Regenerative medicine, although slow to start, is now gaining traction, with a growing number of stem cell therapies in late-stage clinical trials spanning a wide range of acute and chronic diseases. While still in relative stealth mode, regenerative medicine should not be underestimated, particularly for addressing the impact of age-related disease and thereby bending the healthcare cost curve.
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.
E. Kevin Hrusovsky was appointed president of life sciences and technology at PerkinElmer Inc. in November 2011 following the company's acquisition of Caliper Inc., where Hrusovsky had served as CEO since July 2003. Prior to that, he served as CEO of Zymark Corp. He received a B.S. degree in mechanical engineering from Ohio State University and an M.B.A. degree from Ohio University.