Revolutionizing and personalizing global health
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.
"Every generation needs a new revolution." ThomasJefferson's words are poignant and timely, as we sit on the cusp of an urgentlyneeded revolution to transform health on a personalized and global scale.
While we are buoyed by some extraordinary scientific andmedical breakthroughs in recent years, we are mindful that most common diseasesstill cannot be effectively treated by existing therapies. Many cancers,including breast, lung, colon and prostate, are incurable once they havemetastasized, while heart disease and stroke remain leading causes ofmortality. Based on the current trajectory, cancer and type 2 diabetes willdouble by 2030, while Alzheimer's disease will triple by 2050. Consequently,these and other rising non-communicable diseases are on track to wreak havocwith most economies—and most families.
Environmental factors such as obesity and exposure topollutants are having a growing impact on our health, and left unchecked, willoutpace our ability to innovate cost effective solutions. These issues arecompounded with the impact of aging in most developed and many developingcountries. The largest global health study ever conducted (Lancet, Dec. 2012) showed that despite the fact that people areliving 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 diseasepredisposition; (2) personalized treatments that are safe and efficacious; (3)the actual prevention of disease; and (4) affordable healthcare that does notcripple global economies. While daunting, these goals are attainable, thanks tothe culmination of decades of research in genomics, epigenomics, proteomics andother fields, yielding an unprecedented understanding of diseases as complex ascancer, as well as mechanistic insight into environmental factors that impacthealth. Broadly, the new transformative disciplines fall into six keycategories.
(1) Genomic analysis
Next-generation sequencing (NGS) has transformed ourunderstanding of many diseases, especially cancer. Thanks to NGS, we understandcancer to be a disparate collection of molecular diseases and should be treatedaccordingly. NGS is increasingly being incorporated into clinical trials, andmay eventually be a routine stratification tool. Arguably the most impactful application ofNGS is in the clinic, in life-critical situations such as guiding treatment forcancer patients and identifying rare disease-causing mutations in newborns.Translating NGS from a research platform to a clinically useful tool has beenpossible thanks to a dramatic shift in cost and efficiency, as well as keyancillary technologies that enable efficient extraction of DNA fromdiminishingly small tumor samples.
Coming swiftly upon the heels of NGS is the field ofepigenomics, which has grown exponentially over the past decade. Thanks to agrowing suite of analytical tools that can measure DNA methylation, histoneacetylation and microRNA expression in high throughput, we have the ability toassess the molecular effect of specific environmental factors on the epigenome,and link this to phenotype and disease causation. In the past year alone, wehave seen a wealth of evidence supporting an environmental link with diseasessuch as cancer, types 1 and 2 diabetes, allergies, asthma and many others. Weare also learning about the direct molecular link between nutrition and energymetabolism, and the effect on epigenetics and ultimately disease.
Using new innovative technologies to understand the directmolecular influence of our environment on health is a significant step towardsfiguring out how to stop—and ideally reverse—the imminent explosion ofnon-communicable diseases.
(2) Biomarkers andcompanion diagnostics
An important consequence of genomics and other 'omicanalyses has been the discovery and validation of a large, growing number ofclinically useful biomarkers and biosignatures. The impact of these on clinicalpractice has been profound and swift, ranging from their inclusion in virtuallyall clinical trials from the outset, through to their use in the clinic fordiagnosing patients and guiding treatment to ensure optimal safety andefficacy. The greatest impact thus far has been in the field of cancer, wherethe analysis of a patient's tumor biomarkers is increasingly becoming standardof care.
As with genomics, the successful transition of biomarkers,companion diagnostics and personalized medicine into mainstream clinicalpractice is contingent on analytical tools that are accurate, robust,efficient, scalable, cost-effective and that extract very large amounts ofinformation from exceedingly small clinical samples. Automation is key toaddressing the issues of efficiency, reproducibility, scale and cost, ascompanies transition their diagnostic assays from small scale to commerciallaunch. As samples become smaller and less invasive, the ability to multiplex,measuring multiple biomarkers simultaneously, is critical for maximizinginformation and enabling accurate diagnosis. Consequently, multiplexedplatforms 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 ablood draw, and thus are more amenable to routine screening. While it is wellestablished that the measurable presence of CTCs in blood is correlated withpoor prognosis for various solid tumor types, the clinical utility of thisapproach has been limited by the poor sensitivity of the assay, providinglittle clinically actionable information. In recent years, progress inmicrofluidics and engineering has produced a new generation of CTC platformsthat are tenfold more sensitive than earlier versions, and allow isolation ofsingle cells for various omics analyses. One near-term benefit will be tests togauge 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 andpathology
One important tenet of disease diagnosis and treatmentcontinues to be biological contextual and heterogeneity information, as theseprovide clinically informative data that is lost with most omics technologies,which typically use isolated homogenized samples. The continued strong growthin histopathology highlights the importance of direct biomarker visualizationand contextual analysis. Multiplexing provides another important dimension,maximizing clinically relevant information from each precious tumor sample.
Preclinical in-vivoimaging continues to be one of the most critical enabling technologies intranslational medicine, allowing non-invasive longitudinal studies to track theimpact of therapeutic candidates in animals. The importance of thesetechnologies is underscored by the fact that many approved drugs were validatedpreclinically using them, including Pfizer's Sutent and Lyrica, Roche'sZelboraf and Novartis' Zometa.
Building on the success of in-vivo imaging, the same fluorescence-based imaging technologiesare being translated to human surgery, whereby they enable surgeons tovisualize precisely cancer tissues in real-time during surgery, and excise theoptimal amounts of tissue. Intraoperative imaging promises significant benefitsin cancer, reducing repeat surgeries as well as the risk of tumor spread fromnon-excised cancerous tissue.
(4) Targeted smallmolecules, therapeutics and vaccines
The availability of genomic information has transformed ourability to design and optimize targeted small-molecule drugs and biologics thatcan treat patients more safely and effectively. This is further enhanced bylayering in biomarkers and companion diagnostics, oftentimes enabling treatmentof diseases that were hitherto untreatable or that were not economicallyviable, such as orphan diseases including many life-threatening cancers thataffect very small numbers of patients.
Underpinning the successful development of these noveltreatments has been the fusion of information from many disruptive tools thatspan 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 tothe most useful tools is their ability to seamlessly translate from bench toclinic across the "in-vitro to in-vivo to human bridge"—the greatdivide that separates clinical success and failure. This is especially true forcancer research, where many promising in-vitroand preclinical candidates have failed when tested in humans.
(5) Cellular systems
One of the greatest objectives in medicine is treating theunderlying cause, rather than just the symptoms. Regenerative medicine,although slow to start, is now gaining traction, with a growing number of stemcell therapies in late-stage clinical trials spanning a wide range of acute andchronic diseases. While still in relative stealth mode, regenerative medicineshould not be underestimated, particularly for addressing the impact ofage-related disease and thereby bending the healthcare cost curve.
Cardiovascular disease and neurological disorders, whichincrease exponentially with age, can potentially be addressed using stem celltherapies, as evidenced by very encouraging clinical progress on multiplefronts. As with small-molecule and biologic therapeutics, innovativetranslational tools that span the in-vitroto in-vivo to human continuum havebeen critical for establishing the safety and efficacy of these potent cellulartreatments.
The aforementioned technologies and disciplines aregenerating mind-boggling amounts of data at an accelerating pace. The finalcritical piece that fuses all of these data and helps leverage the tremendouspower of this information is bioinformatics. As the complexity and volume ofdata continue to rise, bioinformatics is emerging as one of the cornerstones ofpersonalized medicine, from enabling discovery and development of noveltreatments and diagnostics to facilitating collection, analysis andinterpretation of data that ultimately helps an individual patient.
The convergence of biological information with theavailability of a formidable collection of disruptive and innovative tools thatenable personalized medicine leads me to believe that we now have the means toaffordably improve health through better diagnosis, treatment and prevention. Moreover,the scalability of these tools combined with the rapid dissemination ofinformation means that the benefits in improved health will likely have aglobal impact.
E. Kevin Hrusovsky wasappointed president of life sciences and technology at PerkinElmer Inc. inNovember 2011 following the company's acquisition of Caliper Inc., whereHrusovsky had served as CEO since July 2003. Prior to that, he served as CEO ofZymark Corp. He received a B.S. degree in mechanical engineering from OhioState University and an M.B.A. degree from Ohio University.