Ralph Snyderman

ORIGINAL SOURCE

My interest in personalized health care began approximately a dozen years ago when as Chancellor for Health Affairs at Duke University, I realized that emerging sciences and technologies were creating medical capabilities never before known. Through the power of genomics, proteomics, metabolomics, systems biology, and bioinformatics, one could begin to predict an individual’s risk for diseases, define the exact mechanism of the disease and develop targeted therapies specifically for the patient. I was enamored with the power of science to provide better solutions than the current reactive approach of treating disease events long after chronic disease has begun. As I thought more about personalized health care, however, it became obvious that while solutions from research were important, they were not sufficient for the prevention and treatment of complex diseases which require addressing personal and societal issues as well. Moreover, scientific advances might be decades off, and we could use currently available tools now until better ones become available.

This past weekend I had a striking reminder of how powerful biomedical research can be in eliminating dreaded human diseases. I attended the Annual Joint Meeting of the American Society for Clinical Investigation (ASCI) and Association of American Physicians (AAP) in Chicago to present the Kober Medal to my close friend, Dr. Robert J. Lefkowitz, a giant in biomedical research who has contributed much to our current knowledge of how receptors work. Immediately following the presentation of his medal was the delivery of talks by Drs. Brian Drucker and Charles Sawyers, this year’s recipients of the Stanley J. Korsmeyer Award. Drs. Drucker and Sawyers received this award for their groundbreaking work in developing targeted therapies for the treatment of Chronic Myelogenous Leukemia (CML), a previous fatal disease that now has a 90% cure rate. Their work is but one example of the power of basic biological research leading to applications that entirely change the face of a disease and provides a prime example of its value in fostering the personalization of care.

CML had been a uniformly fatal disease with peak instances in people in their 40s. Research going back to 1960 identified a characteristic morphologic abnormality in the white blood cells of affected patients. This abnormality was shown to be due to the translocation of parts of two chromosomes resulting in a “Philadelphia chromosome” named as such because the discoverers were at the University of Pennsylvania in Philadelphia. Subsequent research identified the specific abnormality of this translocation as being the increased expression of a protein termed BCR-ABL, a tyrosine kinase involved in the development and progression of CML. The line of research identifying BCR-ABL as the cause of CML actually began in the earlier part of the 20th Century through the discovery that certain leukemias in mice were caused by viruses and one was associated with the over expression of BCR-ABL. This research accelerated rapidly in the last ten years to lead to a miraculous therapeutic triumph. Drs. Drucker and Sawyers became aware of a drug termed Imatinib (Gleevac) that specifically inhibited the BCR-ABL tyrosine kinase. In collaboration with scientists at Novartis, Drucker and Sawyers demonstrated the ability of Imatinib to inhibit the BCR-ABL enzyme in animals as well as in the cells of individuals with CML. In a subsequent series of brilliant experiments and clinical trials, Imatinib was shown to induce remission in patients with CML. Importantly, in the small percentage of individuals that relapsed after Imatinib treatment, they showed that the cause was a mutation in the BCR-ABL protein that rendered the drug unable to block its activity. Through the development of additional inhibitors of this tyrosine kinase, even more effective therapies were developed. Importantly, the field of cancer therapy is being revolutionized by research leading to the identification of the enzymes that are associated with the growth of different cancers. Treatment is already being targeted to each individual’s needs by using drugs specifically directed at their abnormality. I can think of no better example of personalized medicine as it relates to finding the right drug for the right individual.

The Korsmeyer Award and the purpose of the ASCI/AAP are to foster physician-led biomedical research and such research plays a fundamental role in the evolution of personalized health care. I think of advances in personalized health care as having a pull and a push. The pull comes from the needs of the individual to improve their health, minimize preventable diseases, and specifically target what they need to attain the best state of health. A push comes from the capabilities made available by science and biomedical research discoveries that provide tools to meet the needs of the individual. Biomedical research provides a more precise understanding of the molecular basis of diseases and the creation of targeted therapies. It is important that we understand this bi-directional dynamic of the pull and push. The needs of the individuals provide the market for the best capabilities to address them — a pull. Science and technology provides specific capabilities to address them — a push. In complex chronic diseases, solutions provided by science and technology cannot alone solve all the problems patients face, but they can play a vital part in the solution.

As we envision the development of better models of personalizing health care, we must never forget the vital role played by biomedical research in providing critical tools to address an individual’s specific health needs.