HGP BENEFITS
In just a single year, 2010, genomics-enabled industries generated more than $3.7 billion in federal taxes,
and $2.3 billion in state and local taxes. In other words, governments at every level in the U.S. received
more income in one year than was invested by the federal government ($5.6 billion in 2010 dollars) during
the 13 years of the Human Genome Project.
Cash is good, but that is not the only (or even the most important) payoff. The medical and scientific
visionaries who planned the Human Genome Project more than two decades ago could clearly see how
genomics would ultimately advance medicine. And today, we are starting to see that vision become a
reality.
Medical advances in the diagnosis and treatment of cancer will be realized first. After all, cancer is
basically a genomic disease. Already, doctors can better categorize some cancers by examining the
constellation of genomic changes in an individual tumor rather than simply establishing the anatomical
origins of that tumor; this refined categorization will often lead to more appropriate treatment. For example,
patients with metastatic melanoma who carry a mutation in BRAF kinase respond dramatically well to
treatment with vemurafenib, a BRAF-kinase inhibitor. But this treatment option only works for patients
with that mutation.
Genomic findings are also beginning to guide treatments for other common diseases. For example, the
blood thinner clopidogrel is widely prescribed to prevent platelets from binding inappropriately and causing
strokes or heart attacks. For this drug to work, the liver must first convert it into an active form. Some 30
percent of the population, however, carries a gene variant that compromises the liver's ability to activate
clopidogrel; in these individuals, the drug does not work as effectively. Making the clinical picture even
more complicated, a different variant heightens the effectiveness of clopidogrel, creating a rather small
therapeutic window that doctors must identify empirically.
To help establish the right dose of clopidogrel for a patient, doctors can now test the patient's genome for
relevant variants. In doing so, an appropriate dose of clopidogrel or a more expensive medication that does
not require activation can be prescribed. Testing the patient's genome first can make the treatment more
effective by minimizing the risk of prescribing the wrong dose.
Other exciting clinical genomic advances involving the study of rare diseases were reported earlier this
year. For example, the Human Genome Sequencing Center at the Baylor College of Medicine discovered a
rare mutation in California twins that explained their mysterious, but increasingly life-threatening
neuromuscular symptoms. Through whole-genome sequencing, the group identified three genomic variants
in the twins, and further narrowed down the cause to a mutation in a single gene — sepiapterin reductase
— that disrupted a cellular pathway that produces three neurotransmitters (dopamine, serotonin and
noradrenalin). This discovery led to the immediate treatment with both dopamine and serotonin, which
dramatically reversed the twin's symptoms.
Similar rare mutations have been discovered through genomic analyses performed by the National
Institutes of Health (NIH) Undiagnosed Diseases Program. As one example, several members of a
Kentucky family suffered from severe, symptomatic calcification that narrowed their leg arteries so
severely that they could only walk a few blocks without pain. Genomic analyses led to the discovery of a
single mutation in a gene, NT5E, involved in calcium metabolism. Pinpointing the genetic cause has
suggested several therapeutic approaches to the family's condition that NIH physicians are now developing.
While the list of examples where genomic analyses are providing answers or new therapeutic approaches to
vexing clinical problems is growing, much basic research remains to be done to ensure a productive
implementation of genomics for clinical care. For example, a large number of genome-wide association
studies have shown that many genetic variants contributing to medical conditions are outside of the proteincoding regions of our DNA, for example in the regions of the genome that regulate gene activity. A
tremendous amount of work remains to be done to establish how these variants contribute to disease.
And the field will need to work on pragmatic clinical problems as well, such as establishing how to get
important genomic information into electronic medical records (in anticipation of electronic medical
records becoming universal) and how to establish robust medical informatics tool that healthcare providers
can readily use to interpret the genomic information about individual patients.
This is a remarkable time. We can now clearly see the outlines of the impact that genomics will have on
medical care, as well as some of the challenges that remain. There is little doubt that the predicted benefits
of the Human Genome Project, originally envisioned more than 25 years ago, are beginning to arrive —
both economically and clinically.