Looking for a sign: ASU biomarker research
October 29, 2012
ASU's biomarker research seeks to diagnose disease before symptoms appear
Biomarkers research initiatives seek to diagnose disease before symptoms appear
Editor's note: This article appeared in the Fall edition of ASU Magazine
by Christopher Vaughan
Imagine a future in which sensors constantly monitor your vital signs, sending that data to your smartphone and computer for your review, and sending it to your health providers.
You may feel just a bit under the weather, but your physicians will see that your blood pressure is elevated and that your exercise has declined. Perhaps they also see a certain troubling molecule showing up in your saliva, collected daily by an instrument that monitors a number of chemical changes, that points to an increasing insulin insufficiency.
In this imagined future scenario, the doctors may take proactive steps – including perhaps scheduling an office visit where they review the records of among others your immune status, your genetic profile, potentially your whole genome, and MRI images. Through a blood test, they determine what proteins are being made by your cells, see signs that the insulin-producing cells in your pancreas are under assault by a virus, and prescribe a drug that targets a specific abnormal protein found in your blood. This drug has been shown to specifically cure this disease in people with your specific genetic profile. They also adjust your other medications and your exercise plan based on data from previous months in order to return your blood pressure and protein levels to normal levels. In a few days you are back in top shape and feeling much better, with the interventions prescribed preventing what could have become a major health problem.
In this future, one of the major advances facilitating the capability to treat health issues long before they are pernicious comes from the physicians’ ability to understand changes in genetic information (mutations) that cause many diseases. These abnormal proteins and other chemicals in the blood are called “biomarkers.” New drugs and diagnostics, directed specifically at these abnormal molecules, will allow doctors to craft a treatment plan that is tailor-made for your body.
ASU researchers who study biomarkers view them as keys to understanding the complex, dynamic interactions between all the cells in the human body.
“Biomarkers are signals that tell you about underlying normal and abnormal biological activity,” says Anna Barker, who came from a leadership position at the National Cancer Institute (NCI) to the university to become director of ASU’s Transformative Healthcare Networks and co-director of the Complex Adaptive Systems Initiative.
The research is intriguing, perhaps groundbreaking, in terms of its potential impact on how medicine is practiced, but it is still a young field. Barker points out that there are very few biomarkers that currently have Food and Drug Administration (FDA) approval to be used as a part of clinical therapy.
“The biomarkers that we have are the first generation of an effort to develop and use drugs in a more rational way,” Barker said. For instance, there are certain biomarkers that the FDA insists must be present before certain drugs are used: in order to use the anti-cancer drug Gleevec, physicians must show that particular gene defects are present, and a certain melanoma drug can only be used if there are alterations to a gene called BRAF.
The hunt for biomarkers is a major focus of biomedical research today. George Poste, Regents’ Professor, Del E. Webb Chair in Health Innovation and co-director of the Complex Adaptive Systems Initiative, stated last year in an article he wrote for the journal Nature that in 2011, scientists published more than 150,000 papers claiming the discovery of thousands of new biomarkers.
ASU Biochemistry Professor Joshua LaBaer, M.D., sees an ambitious future for the area, one in which biomarkers of all sorts are at the center of the health care universe. LaBaer, one of the nation’s leading experts in protein biomarkers, explains that although the term biomarkers traditionally has meant the molecular or genetic landmarks, when he talks about biomarkers he is talking about much more.
“To me, a biomarker is any biological measurement that can be predictive of a biological state,” said LaBaer, who is director of the Biodesign Institute’s Virginia G. Piper Center for Personalized Diagnostics. “It could be blood pressure, body temperature or the amount of lipid in the blood. It could even be X-ray or MRI images.”
Understanding and monitoring these markers of underlying biological states in an intelligent and comprehensive way, researchers say, can transform all aspects of health care.
One of the many advocates of this view is Rick Myers, chairman of the Arizona Board of Regents. Previous to his appointment Myers was chief operating officer of the Critical Path Institute, a Tucson-based independent nonprofit institute dedicated to bringing scientists from the FDA, industry and academia together to improve the path for innovative new drugs, diagnostic tests and devices to reach patients in need.
“Anything that you can measure and represents some aspect of underlying health can be sent to a central repository,” Myers said. “Once you do that, it can have an effect on personal health, it can be applied in drug development, medical device development, or public health.”
Keith Lindor, M.D., who last year left his post as dean of the Mayo Medical School in Rochester, Minn., to become ASU’s executive vice provost for its Health Solutions initiative and dean of the university’s new College of Health Solutions, is a big supporter of biomarker research.
“These programs have the potential to change the way we manage diseases such as cancer as we move further along the path to truly targeted therapies,” Lindor says. “This approach may allow us to deliver ever more effective therapies targeted at the specific molecular abnormalities without all the side effects that occur with our older, non-specific cytotoxic approaches.”
Biomarker research also is performed by Deirdre Meldrum, a senior scientist at the Biodesign Institute and director of the Center for Biosignatures Discovery Automation. Meldrum’s team uses instruments to monitor ongoing changes in the body and spot the signs that provide an early warning for nearly all diseases and disorders. These signals provide useful information about a person’s health status and the automated approach attempts to determine which information is predictive of disease and what intervention can put people on a path to better health.
To accomplish the ambitious goal of achieving a future where medicine is personalized, the biomarkers field has to overcome a few challenges. For example, it can be difficult to confirm that certain biomarkers are indeed excellent indicators of a particular biological state. The perfect biomarker exhibits both specificity (low false positives) and sensitivity (low false negatives)—it is present only in very specific circumstances, and tests are very accurate in spotting it when present. But the real world is much messier, according to researchers.
Even if such specific and sensitive biomarkers exist, finding them is difficult because the statistical analysis necessary to verify good biomarkers can be tricky and misleading.
“My statistician friends say that the data will say anything if you torture it long enough,” says Dr. Carolyn Compton, current CEO of the Critical Path Institute. “From the FDA perspective, there is an enormous need for standardizing terminology and the methods you use to evaluate biomarkers. We need a way to measure and evaluate biomarkers that is highly reliable and based on firm science.”
Nobel Laureate Lee Hartwell, chief scientist at the Biodesign Institute’s Center for Sustainable Health, looks at the thousands of new potential biomarkers discovered every year and sees a lack of business incentive as the problem.
“In the last decade, we have seen an enormous increase in the performance of technologies to look at all kinds of molecules, which on paper should lead to an increased ability to diagnose disease, but it has not,” he says. “The problem is that commercial companies won’t invest in finding out which of those biomarkers really work and which ones don’t” because of lack of return on investment for verifying which ones are good. Hartwell therefore has decided to focus on creating a process for large-scale screening of those thousands of biomarkers and verifying which ones are actually valuable.
While at NCI, Barker worked closely with the FDA to define bottlenecks in biomarker development for cancer and design new approaches to qualify and validate them in patients. She is currently using her experience to explore with a number of local organizations how Arizona could play a key role in enabling biomarker development, and ultimately personalized medicine as a whole.
“This is a complex problem that will require a solid knowledge base and experienced network of experts to make significant progress. I’m optimistic that we can assemble a unique network to tackle the problem,” Barker stated.
When biomarker research moves into the practical application phase, the opportunities to improve human health are enormous.
“Biomarkers that can predict who should receive a drug versus who will not benefit will remove an enormous amount of the waste from the system,” says Barker. “In addition, the cost of developing a new drug, currently estimated at a billion dollars or more, could decrease significantly, as currently most drugs fail because we can’t identify the patients who are likely to benefit.”
Myers pointed out that biomarker-related advances that could reduce or eliminate hospital stays have the potential to help control medical costs.“Healthcare spending in the United States was $2.6 trillion in 2010 and almost three-quarters of that was spent on chronic diseases,” Myers says. “Managing people with chronic diseases and keeping them out of the hospital can dramatically lower the cost of health care.”
ASU’s researchers will play a leadership role as biomarker research advances and realizes the potential inherent in personalized medicine, said Sethuraman Panchanathan, senior vice president in the Office of Knowledge Enterprise Development.
“If we really want to bring health costs down, we will have to keep people healthier,” said Panchanathan. ”We have to spot problems early and intervene quickly with personalized, targeted therapies. Biomarker research by ASU and its partners will have a big role in making that approach possible nationally.”
Media contact:Joe Caspermeyer