A 10th Anniversary Reading List

It comes as no surprise that The Age of Personalized Medicine Blog isn’t alone in recognition of this momentous anniversary for the human genome sequencing. Many are eager to discuss the ramifications of this milestone, which is serving in some way as a litmus test for the potential of the genome, and the revolution its sequencing is expected to bring. Some are celebrating the successes we’ve achieved in personalized medicine in only one decade; others are impatient for the arrival of more significant advances; and some are skeptical that we will ever get there.

As you might see at any milestone, a lively debate is taking place.  I remain convinced that personalized medicine is not only achievable, it is also changing the way medicine is practiced here and now, and is laying the groundwork for more successes in the future.  See The Case for Personalized Medicine for some of those examples.

In the April issue of Nature, referencing his decade-old predictions on the adoption and implementation of personalized medicine, Francis Collins remarked, “It is fair to say that all of these predictions have come true, with some caveats that offer important lessons about the best path forward for genomics and personalized medicine. The promise of a revolution in human health remains quite real.”[i] The primary challenge as we look to the future is that we ensure that the lessons we have learned thus far—both from successes and “dead-ends”—are applied in our continued efforts to achieve this revolution.

We’ve summarized below some of the recent coverage related to the anniversary.  I invite you to take a look at what others have written, and contribute to the conversation by letting us know what you think.

New York Times

The New York Times recently ran a series of articles and an editorial on the human genome at ten.  The first article A Decade Later, Genetic Map Yields Few New Cures discusses how additional research has revealed that the genetic roots of disease are extremely complex, making the development of effective target therapies a greater challenge than was originally anticipated. The second article, Awaiting the Genome Payoff, shows that researchers and drug companies are investing heavily and still maintain hope for genomic medicine.  The article points to examples Merck, Bristol-Meyers Squibb, Genentech, Human Genome Sciences and other companies that are using molecular targets to transform their drug development process. The articles prompted a number of Letters to the Editor, including one from Leon E. Rosenberg of Princeton University and Huntington F. Willard of Duke University Institute for Genome Sciences and Policy.  In their letter, they noted, “Scientific discoveries have always been separated from their clinical contributions, not by 10 years, but usually by 25 or more.  This has been true for every major improvement in health care…The genome’s secrets will accrue to the benefit of sick as well as healthy people, but not overnight.”

Reuters

Last week, Reuters published an article entitled Ten Years On, Genomic Revolution Only Just Starting.  Andrew Witty, Chief Executive Officer of GlaxoSmithKline, echoed the sentiment reflected in the title, “The great mistake everybody made was thinking that the decoding of the genome would somehow yield a drug. It’s got nothing to do with yielding a drug – it’s got everything to do with yielding a whole array of components and ways of looking at a problem which, together with other things, will yield drugs. It’s going to take time.”

For a more comprehensive status check from Reuters, read their report A Golden Age of Genomics? A Decade after the Human Genome Was Decoded, Cures Are on the Horizon.

Nature

In April, Nature published an issue dedicated entirely to The Human Genome at Ten which included editorials from the two men who led the charge in the draft sequencing of the human genome in 2000 – Francis Collins, then head of the Human Genome Project, and Craig Venter, then head of Celera Genomics. When the issue was released, Nature conducted an online survey of its readers probing the question “What did the human genome sequence mean to you?” Last week, they published the results of the survey, as well as an analysis of the findings in the article Science after the Sequence. While the general consensus is that the true revolution of the human genome is still taking shape, many agree that “it has transformed the professional lives of scientists, inspiring them to tackle new biological problems and throwing up some acute new challenges along the way.”

New England Journal of Medicine

The New England Journal of Medicine has also embarked on a series dedicated to genomic medicine in recognition of the anniversary. The series began in May with an editorial from Harold Varmus, who was recently nominated by President Obama to serve as the director of the National Cancer Institute. NEJM also published  Genomic Medicine — An Updated Primer  which offers a crash course in DNA, RNA, SNPs, GWAS, and all the “-omics” in between.  The series continued in June as NIH Director Francis Collins and FDA Commissioner Margaret Hamburg described the scientific and regulatory structure, and the strides that FDA and NIH are making, that will illuminate The Path to Personalized Medicine. Collins and Hamburg note, “Together, we have been focusing on the best ways to develop new therapies and optimize prescribing by steering patients to the right drug at the right dose at the right time.” And indeed, efforts such as the NIH-funded Clinical and Translational Sciences Award program, FDA’s Voluntary Genomic Data Submission program, and the recently announced FDA-NIH collaboration offer just a few examples of the agencies’ confidence that personalized medicine is not only achievable, but represents the best path forward in providing optimal patient care. 

Now that you’ve taken a look at what others have to say, please let us know what you think about this milestone and the accomplishments in science, business and policy over the last decade.   

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[i] Collins, Francis. “Has the Revolution Arrived?” Nature 464, 674-675 (1 April 2010).

Health IT to the Rescue: Managing Data in the Age of Genomics

The 10^th anniversary of the drafted human genome, released by the Human Genome Project in 2000, is a milestone for personalized medicine.  Our mantra – “get the right intervention to the right patient at the right time” – all but mandates the roll-out of genomic information in clinical practice.  As we come closer to the goal of the $1,000 genome, I can now imagine a world in which an individual genomic profile allows us to tailor cancer treatment to a patient’s personal situation. In the next decade, genomics will provide us with the opportunity to refine treatment planning so that we use drugs when they are going to work, spare patients unnecessary side effects, and avoid wasting precious time, emotional resources, or funds on drugs that are unlikely to be effective.  Even intimately personal decisions, such as how to preserve fertility, can be elucidated by and based on genomic data mixed with an understanding of effectiveness and toxic risk.  

Coexisting with excitement at the possibilities of genomically-guided personalized medicine is a pervasive angst.  The profusion of new information can be daunting.  How will I know all of the relevant inputs into decision-making in the era of personalized medicine?  How will I balance multiple important factors for each patient, without a roadmap or algorithm for this new type of clinical decision-making?  In personalized medicine, when treatment choices rely on unique genomic data for each patient, the quantity of potential data points to be factored into any single clinical decision boggle the mind.  How can I intelligently coordinate and consider all of this data?

Recent progress in health information technology (HIT) and in advancing our country’s data infrastructure provide hope that technology may come to the rescue, saving us from a morass of data and helping us make sense of the new plethora of information.  The Human Genome Project yielded vast amounts of data; its completion required development of interoperable data, novel statistical methods, and new HIT systems.  These same tools can also help us use genomic information, as well as rapidly increasing bodies of clinical and research evidence, to inform decision-making.  Genomically-guided biomarkers and predictive tests will help generate personalized information, but tools will be needed to help clinicians understand and use the resulting data, integrated with myriad other personal data types like blood chemistries, clinical exam findings, pre-existing toxic exposures over a life-time, and patient reported concerns. The development of personalized clinical decision support tools and prediction models, tailored and designed for efficient use at the point of care, will assist us in connecting the dots between the promise of The Human Genome Project and the vision of personalized medicine. May this 10^th anniversary energize us to move from theory to action, and to strive for ever more finely individualized care that optimizes outcomes for our patients.

The Age of Personalized Medicine Celebrates the 10th Anniversary of the Human Genome Project

On June 26, 2000, Francis Collins and J. Craig Venter announced the completion of the draft sequence of the human genome. Although it would be another three years until the project was complete, the event was nothing short of history-making, and has been foundational in the pursuit of personalized medicine.  This year marks the 10^th anniversary of that landmark achievement, and indeed there is much to celebrate. And while remarkable achievements have ensued, the promised revolution in our understanding and approach to treating disease is still just beginning.

At the White House event where Dr. Collins and Dr. Venter made their announcement, then President Bill Clinton made bold predictions of its import. “Genome science will have a real impact on all our lives—and even more, on the lives of our children. It will revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases.”

Today, the list of targeted therapies and treatments is growing, and over 200 product labels recommend genetic testing or point to the influence of genetic variation on drug response or safety. All of these discoveries have been guided by an ever-increasing understanding of the molecular underpinnings of disease and the genetic predisposition of the patients they affect.

The Human Genome Project required an investment of over $3 billion and 13 years to complete. Today, enabled by innovation in high-speed sequencing technology, the $1000 genome appears to be within reach. With these advances, genomic sequencing has made its way out of the lab and into the hands of clinicians and consumers. Genetic tests are available to guide treatment decisions in the clinic for drugs like Selzentry® (maraviroc) for the treatment of HIV and Tarceva® (erlotinib) for the treatment of lung cancer, and direct-to-consumer genetic tests that can provide information about an individual’s predisposition for some health conditions are also on the rise. As these tests become increasingly available, we must work to ensure that they are scientifically grounded, and that they are supported by the appropriate policy and regulatory framework to govern them and protect patient interests.

These examples are the tip of the iceberg when it comes to the accomplishments, challenges, and opportunities that have succeeded the Human Genome Project.  In the coming weeks, leaders and visionaries from across the personalized medicine landscape will share their perspectives on the impact of the Human Genome Project, and how it continues to reverberate in our efforts to align policy, science, and clinical care to enable personalized medicine.

I invite you to join in the discussion. As the conversation unfolds this month, please share your thoughts about where the Human Genome Project has brought us, and the path that lies ahead.

Why Rare Disease Research Matters

The Progeria Research Foundation (PRF) was formed 11 years ago to find the cause, treatment, and cure for Progeria.  Progeria is a rare, fatal genetic condition characterized by an appearance of accelerated aging in children.  All children with Progeria die of heart attack or stroke by an average age of 13 years.  In 2003, the genetic mutation that causes Progeria was discovered on the Lamin A gene.

Progeria is one of the rarest known diseases. With a reported incidence of about one in 4-8 million newborns, there are only 65 known children currently living with Progeria worldwide.  When my son Sam was diagnosed 12 years ago, we turned to research and literature for more information.  There was nothing, and so, with my husband, sister, friends, colleagues, and other family members, we formed PRF to help drive research. 

Over the last 10 years, PRF has made significant strides impacting policy (PRF was instrumental in securing language in the Children’s Health Act of 2000 that mandates the National Institutes of Health to report on its plan for supporting children with Progeria); establishing research partnerships (The PRF Genetics Consortium identified the gene that causes Progeria less than 10 months after its formation in 2002); and driving the search for potential treatments and a cure (clinical trials for potential treatments are underway). 

The research over the last several years has helped us uncover a tremendous amount about Progeria and progerin, the protein caused by the genetic mutation.  At the same time, this research may help us better understand heart disease, the number one cause of death in the United States, as well as the process of aging.  As it turns out, we all produce a little bit of progerin, and the amount of progerin in our bodies increases with age.  But how much progerin does each person have and how does it differ among patient sub-populations?  Understanding more about Lamin A and progerin could lead to insights and treatments for patient sub-populations suffering from cardiovascular disease. 

That, to me, is exactly why scientific research in rare diseases is so important.  When we started our research in Progeria, we had no idea that the investigation of a disease that impacts a few children could potentially impact many. 

Now PRF is funding clinical trials and studying multiple treatment possibilities for Progeria, while continuing to examine the similarities between children with Progeria and people experiencing “normal” aging and heart disease.  I look forward to sharing the results of those studies with you in the coming months, and to continuing research that will benefit children with Progeria, as well as other sub-sets of patients. 

Stay tuned to The Age of Personalized Medicine Blog next week for an update from Audrey Gordon, the executive director of PRF, on exciting developments discussed at our recent scientific workshop, and the collaborations that have helped to advance research in Progeria from bench to bedside.

Leslie Gordon is Medical Director of the Progeria Research Foundation