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Commentary: Precision medicine is not just about genetic testing
Standing before the U.S. Congress at this year’s State of the Union address, President Barack Obama held up precision medicine as one of the most promising scientific breakthroughs that can enhance our quality of life.
Most healthcare experts agree. Leveraging science and technology to prevent and treat diseases based on our individual biological makeup is a potentially transformative approach that will enable us to deliver healthcare more effectively and efficiently than we ever thought possible.
The president dedicated more than words to advance the science; he committed $215 million in additional funding for the National Institutes of Health as part of the growing investment to “give all of us access to the personalized information we need to keep ourselves and our families healthier.” This is an exciting development for those of us who have spent our careers developing technology and analytical methods to advance patient care.
Seeing the whole picture
The key to precision medicine is finding the biological, environmental and lifestyle determinants that lead to variations in how people develop diseases and respond to treatments. Decoding our genetic makeup gives us significant clues in predicting disease risk, but it is just one part of the equation. Genetics is our starting position. The trajectory of our health depends on other variables, such as diet, exercise and other environmental factors.
The phenome, or the interaction between genetics and environment, is what determines a person’s likelihood of developing specific diseases. A common example of this interaction is type 2 diabetes. Some people are born more susceptible to developing the condition than others, but eating and exercise habits will eventually determine whether that probability turns into a reality for most patients. As many have explained, “genetics loads the gun, but our environment pulls the trigger.”
Research on the human genome must be complemented by studies of the phenome to produce a more complete view of patient health. While our genetics are determined at birth and remain static throughout our lives, our phenome represents the current state of our biological condition. It is a real-time reflection of how the choices we make—or the exposures we experience—are interacting with our genetic predispositions. Importantly, our phenome often changes far in advance of an actual health condition materializing, giving us an early warning system for preventing illness.
Understanding both parts of this equation can also translate to more precise diagnostics that more accurately measure patient health. Patients are typically encouraged to keep key biomarker levels within a certain range that studies have shown to be safe for the average patient, when it comes to disease risk. But there is likely a high variance from patient to patient on what level is safe or acceptable. Genetics can determine what range each of us should fall within, and phenotype analysis can tell us if other factors are influencing the appropriate range. This is the idea behind precision medicine: We should evaluate patients against their own health status, not against a general population average.
All of us are likely familiar with the timeless debate over whether we are products of nurture or nature; when it comes to our health, the answer is both.
Making phenome analysis possible
Understanding the variables that determine patient health is just the first step. Accurately and efficiently measuring the molecular-level changes that determine our health is more difficult. This is where liquid chromatography-mass spectrometry (LC-MS) shines as uniquely suited to conduct complex analyses that can accelerate the rate of biomarker discovery and broaden our knowledge of how genetic codes and environmental factors interact.
The information we need to understand the biochemical processes that lead to disease is contained within thousands of analytes—the various biological substances studied in health sciences. When understood, they describe the circumstances that lead to heightened risk or onset for conditions like cancer, diabetes and heart disease.
An immunoassay, traditionally considered the gold standard for biochemical tests, is an effective and inexpensive method for studying one analyte in one sample at time. It struggles, however, to measure multiple analytes from a single sample using a single method. As a result, it is too costly and time intensive to measure the massive numbers of analytes that reveal the full range of molecular-level attributes of a patient.
LC-MS stands alone in its ability to complete such types of multiplexed analyses that measure multiple analytes in a single pass. It is capable of driving multiple proteomics, metabolomics and lipidomics studies, and it is highly selective and sensitive. Aside from its limited analytic capacity, a common issue with immunoassay is its reliance on correctly engineered antibodies to ensure accuracy. LC-MS provides greater accuracy that leads to more reliable information regarding how molecular-level changes can reveal current and future health conditions.
The technology is also making great strides in accessibility. Originally perceived to be too complicated and too costly to integrate into many bioscience laboratories, mass spectrometers have become intuitive and automated so they can fit seamlessly into researchers’ workflow. While the upfront costs associated with LC-MS are greater, the number of simultaneous tests that mass spectrometers can perform translates to a lower cost per test than traditional methods.
Over the last few years, LC-MS has become more powerful, accurate and accessible for those developing new diagnostics to discover the roots of common conditions and new therapeutics to treat those conditions.
Harmonizing the data
The emergence of LC-MS has led to an explosion of data analysis capabilities that will speed our understanding of health and the biological basis of disease. Our growing research capacity has highlighted the need for standardization to allow labs from around the world to pool their data and further accelerate the timeline for new discoveries. If each research group works in isolation, we will miss out on the benefits of collaboration and fail to collect data from the large patient populations required to achieve meaningful results.
Metabolomics is an example of a field that has been the subject of terrific and voluminous research for a number of labs in the United States and abroad using LC-MS. While the earliest efforts have been focused on advancing the science of metabolomics, we are reaching a stage where it is necessary to start standardizing core methods and comparing data across patients and labs.
The National Phenome Centre at Imperial College London, which is supported by Waters’ equipment and technical support, is working to develop standard methods that can be used across institutions. This is a major challenge that, if done successfully, will allow us to manage and assemble data in ways that can be mined for deeper understanding of the biological traits that can lead to precision medicine.
From ‘sick care’ to healthcare
A greater appreciation for how to predict and prevent health conditions will allow us to redesign our approach to health care so that it prevents illnesses. Every part of our current healthcare system—from medical training to financial incentives—is primarily designed to address health conditions after they occur. The overwhelming percentage of healthcare spending is dedicated to therapeutics instead of diagnostics. This is one reason why we as a population far outlive our good health.
Precision medicine is our best opportunity to break the mold. While much of bioscience research will remain focused on identifying how to treat illnesses according to our individual differences, the real transformative effect of this emerging field will be in shifting the emphasis to early detection and prevention.
From biomarker discovery research, phenomics and translational research through to clinical diagnostic solutions, at Waters, we are proud to partner with the biomedical community to make breakthrough scientific discoveries and translate them into healthcare solutions.
And we are excited because the growing commitment of the health policy and research communities to precision medicine—combined with the expanding capabilities of LC-MS and related analytical techniques and methods—will soon deliver new clinical tools to improve the prevention, diagnosis and treatment of disease.
Jeff Mazzeo is senior director of health sciences at Waters Corp.
For 50 years, Waters Corp. has developed innovative analytical science solutions to support health and science research discoveries, operations, performance and regulatory compliance—providing researchers investigating complex diseases with analytical tools to help make breakthrough discoveries, as well as the tools required to translate these discoveries into improved healthcare solutions, which is an end goal of precision medicine.