Having one's genome sequenced and analyzed is now faster and cheaper than ever. Whereas in 2001 the cost of sequencing an individual genome — made up of 3.1 billion base pairs that code for 25,000 genes — was $2.3 billion, in 2012 the cost has dropped to about $2,700. Sequencing takes about three weeks, analysis one week using a high-powered computer. At the time of the Human Genome Project, these steps took years.
Given these advances in time and expense, has personalized medicine progressed to the point where it makes sense for more people to have their individual genomes sequenced and analyzed? Dr. Ronald Crystal, chairman of the Department of Genetic Medicine, addressed this question and many others related to personalized medicine at his Medicine Grand Rounds presentation "What Do You Want to Know About Your Genome?" on March 6 in Uris Auditorium.
Dr. Crystal approached the issue of genomic testing by sharing the results of one specific experience — his own.
"As doctors, we need to ask ourselves about the role of genomic testing today in the care of our patients and also understand how to respond to patients when they ask us about this," Dr. Crystal told the audience of physicians, students and scientists. "I wanted to see what this type of testing could tell me about my health as a way of extrapolating to others."
Dr. Crystal's genome was sequenced at Weill Cornell's Qatar Genomics Core, directed by Dr. Joel Malek in the Department of Genetic Medicine. Others in the department involved in the project were assistant professor Dr. Jason Mezey and postdoctoral associate Dr. Juan Rodriguez-Flores.
After making the decision to go ahead with the testing, Dr. Crystal admitted to some trepidation.
"Making your genome public carries risks," he said. "There are issues of privacy and of insurance coverage. In today's digital age, once information is out in the public domain, it is out there forever. Do you really want the world to know if you are homozygous for Alzheimer's?" (Dr. Crystal is not).
While the U.S. government provides some protection against the abuse of genetic information through the Genetic Information Nondiscrimination Act of 2008, this act prohibits the use of genetic information only in health insurance and employment; it does not apply to life, long-term care, disability insurance or the U.S. military.
In addition, there is the issue of "genetic anxiety" that can result when someone learns that he or she is at risk for a certain disease. A person also might discover something about his or her ancestry or paternity that might have been better left untouched. And, by revealing one's own genetic makeup, the genome of the family is also inadvertently revealed.
The results of sequencing Dr. Crystal's genes revealed both the strengths and weaknesses of genomic testing today.
Where genomics is strong is in tying risk to specific ancestry-related diseases. Dr. Crystal's genes confirmed some of what he already knew — that his ancestry was European (on his mother's side) and Russian (on his father's side). But they also revealed something he didn't know — that his ancestors had a strong presence in northern Europe — in countries like Denmark, Sweden and Finland (he even learned of a very distant relationship to a Viking who may have lived in the 800s). From this ancestry Dr. Crystal discovered that he carried a recessive gene for an extremely rare (100 cases worldwide) and always fatal (by ages two to four) congenital disease that was spawned in this part of the world, a fact that may be relevant for his son if chooses to have children.
"Genomics testing can tell you a great deal about where a person comes from, which could be helpful in understanding diseases related to geography," Dr. Crystal said.
Does understanding a person's genome today give doctors a meaningful way to assess disease risk? Yes and no. Where genes are linked to diseases in a purely Mendelian way — as occurs in cystic fibrosis, lysosomal storage disorders and Huntington's — or where there is high penetrance of the genetic variant, disease risk is clear. What is going to take a lot of effort is understanding the genes responsible for complex, multigenic diseases such as heart disease, type 2 diabetes, hypertension and obesity. For these diseases, doctors currently still must resort to the same advice they have been offering their patients for years: Don't smoke, don't do drugs, drink in moderation, eat healthily, maintain normal weight and exercise.
Pharmacogenomics, whose goal is to define the genetic determinants of drug metabolism, efficacy and toxicity, holds the key and the promise to personalized medicine. Many strides are being made in this area, with some meaningful applications already in the clinic. Much depends on making more progress in the ability to analyze the results of sequencing the genome.
"Having the ability to personalize drugs to individuals is the holy grail of genomic medicine," Dr. Crystal said.
In his case, Dr. Crystal learned that he had genetic variants that would put him at risk if he took the antiplatelet drug clopidogrel — used to prevent strokes and heart attacks; and, if he had to take the anticlotting drug warfarin, it would have to be a low dose.
How can Weill Cornell and NewYork-Presbyterian contribute to advances in the field of genome-based personalized medicine?
"In the end, this must be a collaboration," Dr. Crystal said. "Clinicians, lab researchers, those working in computational genomics, in public health, basic biologists, educators and translational scientists — everyone has to pull together. There is much to be done before we can unlock the promise of genomics and personalized medicine."