Personalizing Medicine for the Future
While personalized medicine is emerging as one of the most promising approaches to medicine nationally, the field already has a distinguished tradition and grounding at Penn State College of Medicine.
Consider that our first Dean, George Harrell, M.D., established Penn State as the first College of Medicine to have a Humanities Department, promoting the idea that students should learn the art along with the science of medicine – or, as he called it, “hearts and handbags.”
And Elliot Vesell, M.D., Evan Pugh professor emeritus and founding chair of the Department of Pharmacology, is widely considered to be one of the pioneers of personalized medicine. As early as 1967, Dr. Vesell published groundbreaking research identifying environmental and genetic factors that caused large variations in how individuals respond to drugs.
What exactly is personalized medicine? Essentially, it is an approach to medical care that is based on identifying the factors that affect an individual’s health, while recognizing that many diseases are expressed differently in each patient.
“Building on our understanding of the human genome and an increasing awareness of individual differences in disease processes and responses to treatment, personalized medicine aims to tailor health care to the individual, based on a number of factors – biological, environmental, and behavioral – that affect that individual’s health,” said Harold L. Paz, Medical Center CEO, Penn State’s senior vice president for health affairs, and dean of the College of Medicine.
But it’s not just about treating disease. Personalized medicine also offers a way to enhance prevention and early diagnosis, tailoring strategies for good health by considering an individual’s risk factor and needs.
It is has been nearly a decade since the human genome sequencing was completed. Personalized medicine takes the results of this work and makes the next leap forward – offering the potential to tailor therapies to an individual at the right time, in the right dose.
“It took us that long to find out what the gene was telling us,” said Daniel A. Notterman, M.D., M.A., vice dean for research and graduate studies who also serves as associate vice president for health sciences research and Professor of Pediatrics, Biochemistry and Molecular Biology. “We can now design experiments to learn how differences in biologic properties, metabolism, and environmental exposure affect one’s risk of acquiring disease and their response to drugs or surgery.”
The evolution of electronic health records reaps additional rewards. “We now have increasing computational ability to combine biological data with highly textured clinical information,” he added.
Personalized medicine is making its most significant impact now in specialized areas such as oncology, though this approach will eventually diffuse into everyday practice.
Currently, gene mutations associated with particular cancers helps dictate which therapy will be most effective for an individual patient. For example, the FDA-approved drug Zelboraf provides a significant response in most patients with a particular tumor mutation. But for patients whose tumors do not have that particular mutation, the drug is not effective.
The same holds true for patients with estrogen receptor-positive breast cancer. Genetic tests help dictate which therapy should be pursued and how aggressively. Practitioners can also currently genotype patients before prescribing the blood thinner Coumadin to determine the right dosage.
But when will personalized medicine become the norm? Dr. Notterman, who worked with colleagues to develop the Penn State Hershey Institute for Personalized Medicine, says that most physicians will see major changes in practice within a decade. He predicts that “what is esoteric now will become routine clinical practice.”
“The fundamentals of treating a person will not change. Physicians will continue to use physical examination, routine lab tests, and their knowledge of human disease to assess risk and treat their patients,” Dr. Notterman said.
“But it is an evolution in approach, of using more and more detailed genomic and metabolic tests to produce greater specificity in diagnosis and treatment,” he added. “Ultimately, we will be able to provide a diagnosis that respects each patient as a unique individual.”
As a teaching institution, the College of Medicine must prepare future practitioners for these changes. “We’ll have to train students much more on using the basic science they learned and incorporating genetics into their daily clinical practice,” Dr. Notterman said. “Their training has to include an appreciation of genomics and the underpinnings of disease.”
A ribbon-cutting ceremony for the new Institute is slated for late spring or summer.
The College recently named the Institute’s inaugural director, James R. Broach, Ph.D., an internationally respected figure in the field of genomics who will lead the growth of personalized medicine at Penn State. A basic researcher who has been continuously funded by the National Institutes of Health for 35 years, Dr. Broach also serves as chair of the Department of Biochemistry and Molecular Biology at Penn State Hershey.
“This was an opportunity to put into practice what we all know is likely to be the future of medicine,” he said. “It was an offer I simply couldn’t refuse.”
Prior, Dr. Broach served as associate chair of Princeton University’s Department of Molecular Biology, as associate director of the Lewis-Sigler Institute for Integrative Genomics (2001-2008) and as co-founder and director of research for Cadus Pharmaceuticals (1992-99).
As he explains it, the new Institute for Personalized Medicine will consist of three arms:
• A biorepository to collect (with consent) and store patient samples (hundreds of thousands of samples from the clinics and hospital)
• Genomic resources with tools and tests for genetic testing and analysis
• Bioformatics to connect patient outcomes with genotypes.
“It will be incumbent on us to package the data we can generate in a way that makes it easy for clinicians to incorporate it into their treatment regimen,” Dr. Broach said. “This is information that should inform the treatment of a patient throughout his or her life – not only in response to disease, but in developing methods to prevent disease.”
Early on, the Institute will focus on two or three disease states – most likely cancer, diabetes, and obesity – for sponsored research. But as Dr. Broach explains “The resources are there for other investigators to use the patient samples and genomic tools to explore their own particular disease interests.”
As he sees it, the new Institute for Personalized Medicine is a combined repository, tool kit, and research effort. The biggest challenge right now is in raising money to support the Institute’s work and identifying talent. “Once we get a good kick start, we will be in the position to obtain additional funding from federal sources like NIH.”
Dr. Notterman is equally confident. “We’ve always worked hard to integrate basic science into our clinical practice,” he said. “While other academic health systems will develop efforts related to personalized medicine, ours will be uniquely successful due to our history and ability to collaborate between the College of Medicine and Medical Center.”
He added, “Hershey was there in the beginning. We intend to refine the principles that Elliot laid down to help us care for our patients. It’s all about better, more predictable, more efficient care for people.”
Dr. Broach said, “As a basic researcher all my life, I recognize the tools that are becoming readily applicable to human health. Seeing that transition – from model organisms to application to existing patients – is really quite exciting.”
“Personalized medicine will revolutionize the practice of medicine as much as the discovery of antibiotics or the germ theory of disease,” he added. “That’s our goal – to make that come true.”
Recommended reading: “Towards Precision Medicine” published by the National Research Council (http://www.nap.edu/openbook.php?record_id=13284&page=R1)