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Nearly half of all U.S. adults, nearly 117 million individuals, are living with one or more chronic health conditions. This has become the age of chronic disease, and achieving better outcomes depends on developing tools for research and clinical care that efficiently and accurately address the complex diseases we face today.
A century ago, chronic diseases caused less U.S. mortalities, compared to influenza, pneumonia and other infectious diseases, which struck quickly and often at a young age. In 1900, the average life expectancy in the U.S. was just 47 years. Today, that number is nearly 80. Our longevity is no longer determined by our ability to dodge or defeat infectious disease, but by a complex combination of genetic and environmental factors that lead to chronic health conditions including cancer, diabetes and heart disease.
The increase in our life expectancy is an impressive achievement for our health care system, as well as a threat to its stability. As Americans live longer, our health care consumption increases. The share of U.S. gross domestic product dedicated to health care spending rose to 16% in 2008 from just 9% in 1980. It’s critical that we improve our ability to manage the costs of these chronic conditions, or ideally, to prevent them in the first place.
Progress in reducing the frequency and burden of these conditions can be accelerated with the development of highly predictive diagnostic tests that accurately forecast the health conditions a person is genetically predisposed to developing. Due to the complex interaction of genetic factors, along with environmental influences to describe one’s phenotype, scientific research is increasingly demonstrating that genotypic information alone is insufficient to wholly describe a patient’s health status; rather it’s imperative to complement genotypic state with phenotypic information by measuring a patient’s proteome, metabolome and microbiome. This information will be key to identifying preventative measures that are best suited for each individual so we can improve both the length and quality of life.
This is the promise of personalized or precision medicine, and realizing its potential for routine clinical care requires us to make significant progress on two very difficult tasks simultaneously. The first is to greatly expand our understanding of which panels of biomarkers indicate risk for a particular disease. The second is to translate the growing catalogue of biomarker panels into reliable diagnostics that can fit seamlessly into physician workflows.
Mass spectrometry, combined with genetic testing, is our best chance to be successful at both tasks. It’s the bridge between the basic science of disease and the development of clinical diagnostics. It’s the most powerful analytical tool for measuring the proteome, metabolome and microbiome.
For both the researchers seeking to identify new biomarkers and the physicians eager to leverage that information for care in real-world clinical settings, the early tools developed for analyzing human specimens aren’t powerful enough to digest the volume and complexity of biologic information that’s key to biomarker panel discovery and diagnostics development.
Existing methods are capable of testing a sample for only a few analytes at one time. Given the incredible complexity of our biochemical make-up, which requires us to look at proteomics, metabolomics, lipidomics and microbiomics, testing for individual analytes provides a limited set of information, artificially limiting our understanding of phenotypic status.
Mass spectrometry’s power to transform research and diagnostic use is rooted in its capacity to test the same sample for an entire panel of biomarkers in a single pass, or—once an assay has been discovered—to test numerous samples for the same biomarkers. Equally as important, mass spectrometry is a highly selective and sensitive tool, which is critical to achieving the specificity and confident quantitative measurement that is required to discover and test for biomarkers.
For instance, tissue imaging pathology is an area where mass spectrometry may be particularly useful. Traditional methods are slow and subjective to user interpretation: Two different pathologists may interpret the same image of a stained tissue sample vastly differently. Mass spectrometry can deliver the tissue’s molecular fingerprint—and its status as healthy or diseased—in a single screen with consistent chemical objectivity.
The utility of mass spectrometry is already demonstrated in real-world clinical practice across a number of areas. For example, mass spectrometry is used to test for early metabolism risks in each of the approximately four million live births that take place in the U.S. each year. The screening examines hundreds of analytes, something unfeasible with traditional diagnostic methods. Mass spectrometry is also used in immunosuppressant drug monitoring following organ transplants to ensure a patient receives the appropriate dosage and doesn’t experience an overly compromised immune system. The specificity and sensitivity mass spectrometry delivers makes it uniquely suited to perform these diagnostic tasks.
For clinical researchers, mass spectrometry has the potential to accelerate the rate of biomarker discovery and broaden our knowledge of how our genetic code and environment interact. Instead of being limited to searching for less than a handful of analyte measures during each screening of a sample, research can use a mass spectrometer to measure as many as 50 analytes simultaneously. The analysis will also be more precise than traditional methods, which will also speed the research process.
A visionary use of mass spectrometry is the iKnife, or Intelligent Knife, which is a tool in development to analyze a human sample in real-time during surgery. During an operation to remove cancerous tissue, surgeons can be unsure of exactly where the diseased tissue ends and healthy tissue begins. The result is that healthy tissue is sometimes excised during the surgery, or worse, parts of a tumor are missed and a follow up operation must be scheduled to remove the remaining malignant tissue.
The conceptual stage iKnife, based on rapid evaporative ionization mass spectrometry (REIMS) technology, integrates with a standard electrosurgical tool, collecting and analyzing the resulting smoke to instantly determine the status of the excised tissue. The ability of mass spectrometry to quickly and accurately determine the status of human tissue has the potential to one day transform surgical interventions.
The potential impact of mass spectrometry has supported a growing number of pioneers in the space. Waters, city, state, co-founded the National Phenome Centre at Imperial College London. Plans are underway to partner with other institutions to create a network of phenome centers with locations across the globe. The networks’ discoveries, and the work of researchers and clinicians across the medical profession, will help realize the potential for mass spectrometry to help transform health care.
Innovation in diagnostics that leads to personalized medicine ranks among the most challenging tasks facing the health care community. Mass spectrometry is the most promising tool to achieving the goal of providing each individual with the health care that best fits their unique biochemical makeup.
