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The History and Future of Personalized Medicine

October 27, 2014

Many of us in the genetics and genomics community think that this a golden age for our work. During the last thirty years or so, it has become apparent that genetics plays a very important role in virtually all aspects of human health and disease.

The completion of the human genome sequence at the beginning of this century promised that the use of genetic and genomic tools in understanding the basis for disease and in providing novel approaches to care would become available. It was anticipated that genetic and genomic testing would allow accurate diagnosis of disease, determine the prognosis for the patients with disease, and help physicians make the most optimal choices about how to treat their patients.

This promise launched the era of Personalized Medicine. Several academic institutions embraced this concept. In Boston, Harvard Medical School and Partners HealthCare (the parent organization for several major hospitals in Massachusetts including the Brigham and Women’s Hospital and the Massachusetts General Hospital) launched a new center designated the Harvard Partners Center for Genetics and Genomics (HPCGG), and I had the privilege of being its first Scientific Director.

HPCGG wished to promote personalized medicine and decided that one way to accomplish that goal was to provide a forum for review of the advances in personalized medicine, in all of its facets, and to discuss ways in which the field can be advanced and have an impact on patient care. This vision was shared by a few other organizations including Edward Abrahams of the Personalized Medicine Coalition and Marcia Kean of Feinstein Kean Healthcare. Together we launched the annual Personalized Medicine Conference.

We have always felt that to advance personalized medicine, business had to embrace the concept and find value in investing in this enterprise. To promote that goal, we were joined by Regi Herzlinger, Richard Hamermesh and their many colleagues at Harvard Business School.

In 2014, we are celebrating the tenth anniversary of the Conference as well as the anniversary of the birth of the Personalized Medicine Coalition. The past decade has witnessed many exciting new developments in personalized medicine: the significant reduction in the cost of DNA sequencing and related technologies; the use of these technologies for an unprecedented rate of discovery of human disease genes; a near universal acceptance of the importance of genetics and genomics in drug development, especially for cancer; the levels of investment in personalized medicine companies; recognition of the importance of personalized medicine by professional societies; and the deep involvement by the administrative and legislative bodies in the U.S. and throughout the world.

There have been exciting moments such as the passage of the Genetic Information Non-discrimination Act; the successful launch and execution of whole exome and whole genome sequencing to understand diseases such as cancer and several childhood disorders of unknown etiology; and the development of novel drugs and therapies based on the genetic constitution of individuals or tumors. There are frustrations around the lack of certainty about regulation and reimbursement — but such is progress!

The tenth anniversary of the Personalized Medicine Conference, to be held on the campus of Harvard Medical School November 12-13, 2014, will again bring together leaders from many different areas of personalized medicine and promises to provide a lively forum for exchange of ideas. I personally welcome the opportunity to again host this meeting in November and look forward to seeing you and greeting you there.


The Personalized Medicine Conference is an annual two-day event co-hosted and presented by Partners HealthCare Personalized Medicine, Harvard Business School, and Harvard Medical School in association with the American Association for Cancer Research and Personalized Medicine Coalition. 

For more information and to register for the 10th Annual Personalized Medicine Conference, please visit http://www.personalizedmedicineconference.org.

Personalized Medicine Community Gathers in Boston for the Ninth Year to Share Insights and Innovation from the Field

October 29, 2013

Personalized Medicine was an emerging field of medicine in 2005 when we first held what was to become an annual event, our personalized medicine conference. The importance of personalized medicine was given a boost by the then U.S. Secretary of Health and Human Services, Michael Leavitt, who said in January 2005, “I believe we are moving into a remarkable and powerful new era in medicine and particularly in prescription drugs.  I’d refer to it as an era of personalized medicine.” Since then many different names have been given to this approach to medicine. They include “Precision Medicine”, “Genomic Medicine”, “Genetic Medicine”, “Individualized Medicine”, and “P4 Medicine” to name a few.

This year, we gear up for our 9th Annual Personalized Medicine Conference on November 6th and 7th, in Boston, arguments can be made about what name adequately describes the enterprise in which genetic and genomic information informs us about a person’s risk for human disease; about a clear diagnosis on which treatments depend; about prognosis for a disease such as cancer; about genetic variants in an individual patient that may determine that person’s ability to metabolize a particular chemical entity; about genetic and genomic changes that might inform physicians about the appropriate therapeutic approach; and about many other aspects of health and medicine where genetics may play a role. Some people in the scientific community contend that the use of such a diversity of names for the same enterprise is natural and reflects the evolution of the field. What we cannot ignore is the direction that the science is leading us – toward precision diagnosis and treatment of disease at the molecular level.

As I reflect on the past nine years, some aspects of personalized medicine have changed rapidly and others are relatively unchanged. One of the biggest and most exciting changes involves the growing commitment of drug developers to the development of targeted therapies. At the beginning of the 21st century, there were only a few drugs that could be considered “targeted” therapies. Now, in cancer, for example, the development of such targeted therapies is becoming the norm because many of these drugs have few adverse effects and the response rates of patients, whose tumors have the molecular target for the drugs, are very high compared to other non-targeted therapies. We can find similar “personalized” approaches to treatment in the areas of infectious disease, cardiovascular disease and other areas.

Today, much of personalized medicine is fueled by new technologies related to DNA and RNA sequencing. It has been estimated that the cost of sequencing has dropped by a factor of 100 from the beginning of this century. The amount of DNA or RNA required to sequence whole genomes has also been reduced by orders of magnitude and there are now technologies in development that promise to sequence single molecules of DNA in a matter of few hours. As the technologies improve and associated costs decline, the benefits of genome sequencing become more apparent. It is easy to imagine a not-too-distant future when people around the world have their genome sequenced as part of the standard of care. Despite present concerns about the cost to analyze all of these genomic data, I am certain that newer algorithms will enable us to automate much of the analytical and interpretive processes to propel us toward a new level of understanding regarding the prevention and treatment of disease.

As the science evolves and entrepreneurs continue to innovate, we are faced with new challenges.

Open and informed discussions about issues related to personalized medicine are critical for better understanding of the successes, failures and promises of this relatively young medical enterprise. Our Conference in Boston provides one such forum and we hope that you will be able to join us.

The future of medicine is before us.

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Harvard Medical School, Harvard Business School and the Partners HealthCare System in Boston will convene the 9th Annual Personalized Medicine Conference on the campus of Harvard Medical School this November 6 and 7. As has been the practice since the Conference’s inception, this year’s meeting is in association with the Personalized Medicine Coalition (PMC). For the first time, we also welcome the participation of the American Association for Cancer Research (AACR), a member driven organization that has been dedicated for more than a hundred years to promoting cancer research and cancer care, as a co-convener.

For more information and to register for the 9th Annual Personalized Medicine Conference, please visit www.personalizedmedicineconference.org.

The 8th Annual Personalized Medicine Conference

November 14, 2012

On November 28th and 29th, Partners HealthCare, Harvard Medical School, and Harvard Business School will host the 8th Annual Personalized Medicine Conference in Boston. As has been customary since the conference began, the meeting is also the venue at which the Personalized Medicine Coalition presents its leadership award. This year, it will go to Randy Scott, Ph.D., a founder and former CEO of Genomic Health, Inc.

During the past seven years, we have seen many changes in personalized medicine. Much of the excitement about personalized medicine continues to be driven by the ever decreasing cost of sequencing DNA and RNA. Whole genome sequencing, estimated to cost a billion dollars or more at the beginning of the century has gone down to a few thousand dollars, and the so called $1,000 genome is not too far behind. All in all, the 20,000 or so genes of the human genome only add up to less than two percent of the genome. If the sequencing cost is directly proportional to the size of DNA that is being sequenced, the cost of sequencing all genes should one day be no more $100. We are not quite there yet, but the rapid decline in costs is fueling the evolution of personalized medicine.

There is also a rapid evolution in our understanding of the genes and genomes of many organisms, including humans. Understanding how a normal gene functions and how changes in it (mutations) alter the cellular function is increasing at a rapid pace. As a result, sequencing whole genomes, whole exomes (all of the coding portions of genes), and subsets of genes for medical purposes is becoming ever more common. The fruits of all of these exciting developments are evident in many specialties of medicine but especially in prenatal testing, diagnosis of newborn and pediatric disorders, and cancer.

This year’s conference will highlight the genomic advances in science and medicine, and how they are being applied to diagnose and treat many disorders. The rapid development of technology also raises many questions about the clinical utility of these advances; about the policy and regulatory issues around what, when, who, and how to regulate; and about how the costs are reimbursed.

Personalized medicine is not just an American issue. Many nations of the world are developing strategies to implement personalized medicine in their own countries, and a number of those efforts will be featured at the conference. Professor Richard Hamermesh of the Harvard Business School and Norman Selby of Perseus LLC developed a business case on companion diagnostics that promises to be thought provoking and, based on previous years’ experience, a highlight of the conference.

Please join us at the end of November and participate in the dialog about how personalized medicine is evolving and what its implications are for your health and that of all peoples of the world.

Register online at www.personalizedmedicineconference.orgFollow the conversation online at @HarvardPMConf and #PMConf.

Welcome to Personalized Medicine: Impacting Healthcare

November 17, 2010

At this morning’s opening session of the Sixth Annual Personalized Medicine Conference, I welcomed conference participants with a quote from Charles Dickens to describe the current environment in personalized medicine:

“It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness….”

There are many that believe we are experiencing the “best of times” in personalized medicine as the field has experienced continued growth and is being implemented in clinical practice. There are others who believe personalized medicine has over-promised and under-delivered. Certainly the theme of this year’s event, Personalized Medicine: Impacting Healthcare, will explore the progress that has been made in the past six years since the conference first began. The representation at this year’s event from across stakeholders in the biopharmaceutical industry, commercial entities, research and academia, and policymakers are a reflection of the groundswell taking place to make personalized medicine a reality.

Nevertheless, to demonstrate the lively debate on the issue, I asked those attending the conference to share their opinion on whether the field of personalized medicine is achieveing its mission, and via an audience response system, received the following feedback:

  • 26.4% believe personalized medicine is being achieved at a satisfactory rate
  • 67% believe personalized medicine is being achieved too slowly
  • 6.6% had no opinion

But what do you think? Use the poll below to share your response.

Innovation Along the Path to Personalized Medicine (Part II)

August 26, 2010

In my previous entry, I discussed how the Human Genome Project has served as the foundation for additional research that has produced new insights into the genomic basis of disease and resulted in new tools and reagents that continue to generate new discoveries. Every endeavor—even those that may not result in a significant leap in technology or a new targeted drug therapy for patients—has contributed to our knowledge and understanding of the vastness and diversity of our genome, and is propelling us toward the reality of personalized medicine. Indeed, there are examples across disease areas of how personalized medicine is improving our ability to detect, prevent, and treat disease. 

Personalized medicine informs our understanding of disease origin

In the past and perhaps in much of today’s practice of medicine, diagnosis and treatment decisions are based upon observations within a clinical setting.  However, it is becoming increasingly clear that clinical features alone are not sufficient for diagnostic or treatment decision purposes.  Some good examples include:

  • Hypertrophic cardiomyopathy (HCM) is a relatively common disorder characterized by an adult onset hypertrophy of the heart muscle sometimes more genes. 
  • Noonan syndrome, a childhood disorder that has many manifestations was considered to be one clinically defined entity, but is now understood to be a disease resulting from the mutations in any one of ten or more different genes.
  • Adult macular degeneration is an important cause of blindness in older individuals and genetic variants in a particular gene have been identified to be responsible.

Today, many clinicians would not make a diagnosis of these and many other disorders until the patient’s DNA is tested.  Having a more comprehensive picture of the underlying cause of the disease can lead to earlier, more accurate diagnosis, more informed treatment decisions, and better outcomes for patients.

Personalized medicine informs our understanding of disease risk

As we understand the role of specific genetic and genomic variants in the human population, it will become possible to assess the relative risk and absolute risk of individuals for particular diseases. Having such a risk assessment can allow for the development of prevention or postponement strategies for a specific disorder. As an example, our ability to detect individuals at high risk for cardiovascular disease through testing for lipid levels has had and continues to have a major impact on heart disease incidence in the United States and elsewhere in the world.  With seventy-five cents of every healthcare dollar going to the treatment of preventable chronic disease, prevention and early interventions for our most common and treatable chronic illnesses could save a significant amount of money and result in better health outcomes across the country.

Personalized medicine informs our understanding of disease treatment

Another area where genomics has had a great impact is in the area of pharmacogenomics.  Although for many years clinicians and researchers alike have known that not all drugs are equally effective in all individuals, the molecular basis for these differences has not been well understood.  This is changing very dramatically.  Pharmacogenomics is the study of how genetic variation affects a patient’s response to a treatment.  In cancer, for example, we now know that the molecular changes that cause the progression of particular types of cancer are very complex.  In turn, organ-based treatment approaches are not completely adequate.  In non small-cell lung cancer (NSCLC) some tumors have mutations that result in the activation of epidermal growth factor receptor (EGFR) and these tumors are exquisitely sensitive to treatment with some oral inhibitors of EGFR function.  Other NSCLC tumors have mutations in a gene called K-RAS a protein that acts downstream from the action of EGFR and tumors with this mutation do not respond to EGFR inhibitors.  Yet other NSCLC tumors are now known to have to overexpress Her2/Neu and treatment of these tumors with an inhibitor of Her2/Neu may be warranted.  In other lung tumors a gene called Met is amplified and treatment with Met inhibitors (under development) may be warranted.  Yet others have a novel translocation called EML-ALK4 and a drug that inhibits the fusion product appears very promising.  This is but one example of a tumor type where patient stratification is becoming critical for making appropriate clinical decisions.  Having a better understanding of how patients will respond to a drug based on their genetic makeup can lead to more optimal treatment choices, reduced side effects, and overall better patient outcomes.

The use of personalized medicine is beginning to impact many disease areas, and there is evidence that it is already improving the outcomes for patients at a reduced cost to society.  In our current status of healthcare where the costs are increasing at a pace that cannot be sustained by our economy, personalized medicine, illuminated by our ever-increasing understanding of the complexity of the human genome, shines as a beacon for solving some of the most important problems in our fight against disease.

Innovation Along the Path to Personalized Medicine (Part I)

August 24, 2010

Ten years ago, Bill Clinton and Tony Blair made a joint announcement that an international consortium had completed the draft sequence of the human genome.  The following year, papers describing the mapping and sequencing of the human genome were published by the public effort and a biotech company, appearing in Nature and Science respectively.  These were indeed, historic events as scientific innovation led us to decipher our genetic blueprint.  This year, we can mark this occasion by taking stock of what advances have occurred since the genome sequence and how its discovery continues to inform our understanding of medicine and influence medical care.

Diversity of the human genome

The International HapMap project was among the first to build on the initial sequencing of the human genome, and sought to achieve greater understanding of the diversity of the genome. What we discovered is that every human being has approximately the same amount of genetic information.  The similarities in the sequence of DNA, among all populations in the world, illustrate just how similar we are at the genetic level and put a spotlight on our common origins.  But there are differences among us.  If we compare the DNA of any two individuals their sequence would differ in approximately one out of every thousand nucleotides.  Some of these changes occur in coding sequences and others in non-coding regions of the genome. Some of these changes are certainly benign and others are certainly important and result in the diversity of the individuals.  Much research remains to uncover the connection between our genetic makeup and health and disease.  A large catalog of the genetic differences among individuals and populations is now publicly available and continues to grow, feeding researchers’ need for this valuable data to inform their work.

Genomic basis of disease

One of the reasons for launching the human genome effort was to provide the tools and reagents for rapid identification of the human genes and their variants responsible for human health and disease.  For example, a large number of genes important in Mendelian disorders have already been identified.  There is a large body of evidence that many common disorders such as cancer, diabetes, autoimmune disorders, and psychiatric disorders also have a strong genetic contribution.  Building on years of scientific effort, researchers have revealed strong associations between specific genetic variants in the human populations and their susceptibility to human disease.  Despite periodic criticisms of the genomic approaches and their cost, it is clear that genetic approaches are opening new doors to our understanding of human health and disease.  These efforts will continue.

Decreasing cost of whole genome sequencing

An important driver of the genomic revolution is the rapid reduction in the cost of DNA sequencing.  Many estimates indicate that the description of the first human genome sequence cost about three billion dollars.  In 2010 several commercial entities are offering human DNA sequence and sometimes its interpretation for less than $10,000.  This is close to five orders of magnitude in the reduction of the cost of sequencing and it is anticipated that this cost would go down by one or two orders of magnitude to $1,000 and perhaps even $100 in the not too distant future.  By any measure, this cost reduction has to be considered nothing short of phenomenal and a tribute to human ingenuity in its efforts to advance scientific discovery.

Advent of personalized medicine

What has been the impact of all these genomic developments on medicine?  Identification of genes involved in disease and how loss of function, alteration of function, or acquisition of new functions in the gene products are providing clues to our understanding of the molecular etiology and molecular pathology of disease.  Such information is critical for prediction of disease susceptibility, progression, and therapeutic response on an individual level.  The use of genetic and genomic information for diagnosis, prognosis and treatment decisions is called personalized medicine and it is gaining greater traction in medical practice.

In his next entry, Dr. Kucherlapati will continue the discussion of how the Human Genome Project has served as an important driver on our path to personalized medicine, and will offer examples of how genomic medicine is already having an impact on the diagnosis, prevention, and treatment of some diseases.

Personalized Medicine: The Time is Now

November 16, 2009

Five years ago the Harvard-Partners Center for Genetics and Genomics, an organization that was a joint enterprise of Harvard Medical School and Partners HealthCare in Boston, held a conference on Personalized Medicine (PM).  As the subtitle of that first meeting, “Promises and Prospects,” indicated, the conference sought to examine the status of personalized medicine and to bring together different stakeholders in this emerging field. 

A newly founded organization, the Personalized Medicine Coalition (PMC), joined the effort.  The PM conference in 2005 focused on the scientific and medical basis of PM.  Two themes emerged from that meeting.  One was that a conference organized by a not-for-profit organization, together with an entity whose mission is to educate different societal constituencies about different facets of PM, was a welcome addition.  The second theme to come out of that meeting was that the implementation of personalized medicine requires collaborations between academic medical centers, government and its regulatory agencies, businesses, pharmaceutical companies, payers, doctors and patients. 

Personalized medicine has evolved significantly during the past five years.  In 2005 few people knew about PM and some who did know about it felt that it represented a futuristic view of medicine that may be implemented in 10-15 years.  In the ensuing years there has been a significant change in the awareness and attitude about PM.  Many influential people in the national administration and Congress have embraced PM as an important component of healthcare future.  President Obama, while he was a Senator, introduced PM legislation in the Senate.  Michael Leavitt, while he was the Secretary of HHS, embraced PM, and the current Secretary, Kathleen Sebelius, is very supportive. 

Many pharmaceutical executives are speaking of the importance of personalized medicine in their drug development efforts.  An electrifying moment in our 2007 conference was a talk by John Lechleiter, the current CEO of Eli Lilly, championing how a pharmaceutical company can develop excellent drugs based on the principles of PM while maintaining profitability.  Today most, if not all, pharmaceutical companies are developing many drugs based on these principles.  

At that first meeting in 2005 the payer community did not believe that PM was ready for implementation and there was inadequate evidence to support payer attention.  We are pleased that since then examples of personalized medicine and their success have caught the attention of payers and that this is an important topic in the boardrooms and executive offices.

A major development during the past five years is the development and availability of technologies that enable rapid and low cost DNA sequencing.  In 2003 when the first human genome sequence was completed it was estimated to have cost nearly two billion dollars.  A few months ago a company announced that it has sequenced human genome for less than $10,000 a genome.  Many believe that the $1,000 genome is just around the corner.  This cost of sequencing has important implications for diagnostics and handling the large data sets. 

It also has implications for consumer genetics companies that raised excitement in some quarters and concerns in others.  Several thought leaders argue that the involvement of consumers in healthcare decisions augurs well for our future and the consumer genetics companies have the potential to predict and therefore prevent disease in our population.  The role of information technologies in medicine in general and personalized medicine in particular cannot be overemphasized.  It is important to assess the current status and future of all these features.

Based on the feedback from that first meeting all of the subsequent meetings have been a collaborative effort between the Center, now renamed the Partners HealthCare Center for Personalized Genetic Medicine (PCPGM), Harvard Medical School and the Harvard Business School.  The PMC continues to be an active partner in these meetings.  Past conferences attracted speakers and participants from many walks of life and the discussions inside and the outside the conference auditorium have been lively. 

This year we are hosting the 5th annual Personalized Medicine Conference.  It is going to bring together the largest group ever to celebrate the discoveries and success stories of personalized medicine and explore new ways to bring the power of PM to our healthcare.  We believe that the implementation of personalized medicine will result in better outcomes for the patient population at a reduced cost to the society.  Such implementation would indeed revolutionize the practice of medicine.

This year’s meeting is attracting a more diverse audience than previous years and we expect that there will be many interesting discussions at the meeting.  We welcome you to our conference.  I am sure you will find something of interest at our meeting.  It is also a great opportunity to meet new people.

By Raju Kucherlapati, Ph.D., Paul C. Cabot Professor of Genetics, Professor of Medicine, Harvard Medical School


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