Innovation Along the Path to Personalized Medicine (Part I)

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.