Making Personalized Medicine a Reality

September 13, 2008 by

Dr. Ken Buetow, BIG Health Catalyst

Existentialists posit that “Existence precedes essence…  reality is existence”.   A loose paraphrase would be “You are what you do”.  BIG Health took its first steps this week and in the process made Personalized Medicine that much closer to becoming a reality.

A core confederation of “do-ers”, individuals committed to actualizing the 21st Century Biomedical System necessary for Personalized Medicine, convened this week.   This novel collection of stakeholders representing the different dimensions of this new ecosystem – providers, consumers, government, academia, research, advocacy, industry – shared their needs and offered their capabilities.

What was truly impressive was the collection of “boots on the ground” activities and networks that the participants shared as potential resources that could be joined to create the ecosystem.  The energy was palpable and the enthusiasm was infectious.

Perhaps most important was the overall commitment to action.  The group rolled up its collective sleeves and began framing specific projects that it could undertake.  One key area for further exploration was centered on “virtual clinical research”.  There was much enthusiasm for assembling the unique components of the ecosystem to demonstrate new models for clinical research; models that connect the care delivery system with the research enterprise.  

The group also identified developing a “Learning Health Care System” as another focal point.  This project will explore how the primary observations that occur in clinical encounters could be repurposed to improve care outcomes and assess quality of care.

This initial meeting represents the first wave of the “pebble in the pond”.  The wave is already expanding to include more interested parties and these early participants are already reaching out to other constituencies that will join the expanding circle.  They will bring additional ideas and candidate projects.  Join us in our action-oriented, existential “leap of faith” in making Personalized Medicine a reality

The Need to do Something Different.

September 5, 2008 by

Dr. Ken Buetow, BIG Health Catalyst

One definition of insanity is doing the same thing over and over again and expecting different results. One may then fairly question the sanity of the biomedical enterprise – stuck by complex forces in existing paradigms we continue to hope for new outcomes such as personalized medicine.

Time Magazine has just published an article “He Won His Battle With Cancer” , outlining the challenges cancer presents to the biomedical community. It quotes Senator Kennedy from the June Senate hearings as saying “We need to integrate our current fragmented and piecemeal system of addressing cancer. Front and center in our current system are the troubling divisions that separate research, prevention and treatment”.

The Time article makes a strong call to do something different. It focuses on the new “Stand Up to Cancer” (SU2C) advocacy group that proposes supporting a model for research where cross-institutional, multi-disciplinary teams work on time delimited projects designed to produce specific deliverables.

The BIG Health Consortium will personify the “do something different” call as a “boots on the ground” group committed to exploring novel approaches. It will join the disconnected pieces observed by Senator Kennedy into a 21st Century Biomedical System. Like the approach of SU2C it will attempt to break down the barriers that slow the discovery process and translation to care by joining individuals, organizations, and institutions that want to demonstrate the reality of personalized medicine.

Crazy? No more than doing nothing.

The End of a Beginning in Personalized Medicine

September 4, 2008 by

Dr. Ken Buetow, BIG Health Catalyst

The first manuscript reporting results for The Cancer Genome Atlas (TCGA) was published today in the advanced, on-line addition of Nature.  TCGA is a 3-year pilot project of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) whose goal is to increase our comprehensive understanding of the molecular basis of cancer.  The TCGA team describes the discovery of a complex collection of molecular alterations in glioblastoma multiforme (GBM) that have potential implications for the diagnosis and treatment.  GBM is the most common form of brain cancer in adults affecting 21,000 people annually.

The paper describes previously unknown high frequency mutations for NF1, ERBB2, and PIK3R1 and confirms previous mutational findings in PTEN, RB1, EGFR, and PIKC3A.  It implicates three pathways: the CDK/cyclin/CDK inhibitor/RB pathway, the p53 pathway, and the RTK/RAS/PI3K pathway as the target of molecular alterations in over 80% of GBMs.

These findings, whose true biologic and clinical significance will only be known over time, are of immediate significance in two ways.  First, this novel integration of multidimensional molecular data provides a rare systematic view of cancer.  It is breath taking to see the diversity of molecular mechanisms that generate this single cancer type.  Multiple genes, disrupted by multiple mechanisms (mutations, deletions, amplifications, and epigenetic alterations) interacting through multiple pathways.  However, through this team approach, in a matter of months the cancer community has learned what might have otherwise taken years. What would have been separate observations in different labs in separate papers measuring different molecular dimensions all requiring additional studies to understand the interactions are all seen in concert, simultaneously.  WOW!

Second, but perhaps of greater significance, this multidimensional information is available in an integrated fashion to biomedical community NOW!  By going to the caBIG Cancer Molecular Analysis Portal that integrates and shares the data –, one can examine and judge for one’s self the assertions made in the manuscript.  Alternatively, a researcher can perform their own in-silico experiments.  This first manuscript will likely be the first of many significant finding drawn from this incredibly rich data resource

Of course the real challenge laid bare is how do we translate these findings into next generation interventions?  The BIG Health Consortium’s 21st Century platform for discovery and translation provides one possible solution.

BIG Health – A Consortium to Realize 21st Century Personalized Medicine

September 1, 2008 by

Dr. Ken Buetow, BIG Health Catalyst

In the spirit of full disclosure, it is important to let you know, up front – I’m a true believer! I believe, without equivocation, that our individual molecular topography holds the key to understanding disease and driving health. This belief today corresponds to many related health agendas – personalized medicine, molecular medicine, information based medicine. I don’t think it is worth getting hung up on the label.


I’ve spent 30 years in the trenches in pursuit of this vision. The seeds of my “faith” were planted when I encountered my first genetics class as an undergraduate. The die was cast for me when I took my senior internship with the Medical Genetics group at Indiana University. This group was making pioneering effort to create a genetic map of human chromosome 1. From the perspective of a completely sequenced human genome, it is difficult to grasp how audacious a goal that was at the time. My first “leap of faith” occurred later that year. I decided to pursue a career in human genetics. A genuinely concerned senior member of the experimental genetics community reacted in horror and told me in no uncertain terms I was throwing away my professional career – “Nothing of importance has ever come from human genetics, nothing ever will…”.


It was clear from the onset that the genetic endeavor in humans was very different from other genetics. It required big databases, powerful statistics, and fast computers. It also required a team of scientists from across all of biomedicine. No single individual could assemble the resources necessary to address all the challenges. All the disciplines contributed a novel insight. This was brought home to me as I traveled during my senior internship with a very talented clinician to the homes of study participants identified through his practice, collecting biospecimens for laboratory characterization and collecting family history information for statistical analysis using cutting edge computer technology.


The changes in laboratory, statistical, and computer technology that have occurred between that summer and now are breathtaking – cost-efficient, genome-wide genetic characterization, laptop computers with computational capacity that dwarfs the mainframe and mini-computers I used that summer, the internet, the world wide web – WOW! Biomedicine has embraced and exploited them all to give us a remarkable perspective of our molecular landscape. I am always thankful that I grew up with these emerging technologies. I’ve had 30 years to master them as they matured with me. I am amazed that today’s young scientists master these technologies in such short periods of time.


One place we have not seen this transformation is in how we as a community conduct biomedicine. We continue to apply existing organizational models. The conduct of studies is as labor intensive as it was 30 years ago. We have used computers to automate old business practices rather than enable completely new approaches. The information from individual health encounters is not accessible to providers or to those developing next generation prevention or treatment strategies. To quote the Secretary of Health and Human Services Michael Leavitt, we have a “health care sector, not a system”.


Progress in moving from bench to bedside has always been slower than we “true believers” have hoped and projected. Molecularly-based, personalized medicine is not a reality. We are seeing incremental change occurring by diffusion using tried and true practices that have weathered the test of time. The change will happen we are advised. We are the envy of the world in our US efforts in biomedicine. These things just take time. I am counseled patience.


It is hard to be patient. The urgency of the moment is particularly evident in my field, cancer, where over 1.3 million individuals will receive a diagnosis of cancer and over 500,000 will die of this disease this year. We have to try something different!


The BIG Health Consortium is that something different. BIG Health’s mission is to

demonstrate – in real settings, in real time – the essential unity of research and care and to model a 21st Century approach to biomedicine, one in which clinical care, clinical research, and scientific discovery are linked to achieve personalized medicine and improved clinical outcomes. It is a new biomedical ecosystem that joins the sectors of biomedicine into a synergistic whole. It leverages information technology as “electronic glue” (the BIG in BIG Health stands for Biomedical Informatics Grid – technology to interconnect the various parts of the biomedical community through semantic interoperable infrastructure).


BIG is just the tip of the iceberg. 21st Century medicine requires new organizational approaches that embrace our capacity to work digitally. As Nicholas Negroponte suggests in “Being Digital”, as we transition from atoms to bits the limitations of time and space disappear. Just as technology has permitted us the capacity to look inside a cancer cell, today’s new information technology permits us to reconsider traditional organizational structure and conventions. The BIG Health Consortium will leverage these new approaches as we set out creating our virtual community.


The BIG Health Consortium is a coalition of stakeholders who want to create a 21st Century biomedical ecosystem to address the challenges and opportunities of 21st Century personalized medicine. It will be exciting to see what happens when we bring together “true believers” from across all sectors of biomedicine. WATCH THIS SPACE!