When the first draft of the human genome was released at the beginning of this century, it was hailed as an achievement that would allow us to understand "what it means to be human."
Many enthusiastic observers at the time believed that the sequencing of the human genome would soon open the door to a future of personalized medicine where therapies are tailored to each person's genetic profile.
More than 17 years have passed since this historic announcement and many of the promises of the "genomic revolution" have yet to be realized. In our ongoing efforts to understand the basic science underlying complex diseases, we have found that the corresponding genetic associations are extremely difficult to decipher.
While it is certainly true that human genomic data has yielded a treasure of biomedical information, unfortunately, the dream of personalized medicine remains largely unmet.
However, there is a success story to be celebrated.
The first draft of the human genome took 10 years and more than $2 billion to complete. Today, a human genome can be sequenced in just two weeks for approximately $2,000.
One result of this rapid technological advancement is that genome analysis has moved out of the laboratory and into the home. There are now several companies that will do a sequence scan of your DNA for roughly $200. You simply fill a tube with saliva, mail it back to the company, and within six weeks your data is available to view.
In addition to showing if you have (or carry) a range of genetic diseases, the results can provide insights into hereditary information. It is not uncommon, for example, for people to learn details about their ethnic or geographic origins that contradict stories they've been told about their ancestry.
In addition to these sequencing services, there are now about a dozen free genome analysis services. Individuals who use a sequencing service such as 23andMe can then upload their results to a website such as GEDMatch.com to get their own genetic analysis.
GEDMatch has an amazing array of libraries against which to compare your personal data. Below is a view of one person's Chromosome 5 using the "paleo" library from GEDMatch which shows one's genetic origins from among a Paleolithic population.
The above scan is along the length of the chromosome. The blue region shows DNA inherited from Baltic hunter-gathers; the orange region is inherited from Mediterranean farmers; and the red region is inherited from Anatolian farmers.
There are many different genetic libraries from which to choose and therein lies the problem. It's like deciding on how to classify a book based on a comparison with a specific library. If I scanned a freshmen physics book against a children's library, it might be classified very strangely because it lies outside of the library.
Yet, these tools put a great deal of power and knowledge into the hands of the general population.
Becky Blanchard '90, Ph.D., is the Executive Director of Clinical Pharmacogenomics and Operations at Merck. She recently had her genome typed using 23andMe. Unlike most people, Dr. Blanchard has the scientific expertise to analyze her personal genetic data on her own.
She observed a deleterious gene variant in her profile that indicates the anti-platelet drug clopidogrel (Plavix) would not only be an ineffective form of treatment for her, but might even be harmful, since ineffective antiplatelet therapy may lead to life threatening cardiovascular events.
Since Becky has this particular gene variant, this means that, at a minimum, her mother is also a carrier. With her mother about to be treated with clopidogrel, Becky was able to speak with the physician and successfully talk him out of prescribing this drug to her mother based on the information she had learned.
When we think of genetic counseling, we usually think of concerns of parents for their offspring, but this example illustrates that genetic insights may also be used by a child to inform treatment of their parent.
Earlier this year, Kinney Drugs began piloting a pharmacogenetic testing program in six of its Vermont stores. The program includes a pharmacist consultation to learn how patients respond to more than 200 medications in 53 drug classes for conditions ranging from acid reflux to diabetes to depression.
Through the application of pharmacogenomics, providers can examine a patient's genetic make-up to help determine the medication and drug doses that are likely to work best. The program (named "Rxight") was developed by a company called MD Labs, meaning Kinney did not require an advanced research team to bring this product to market, a factor that helps keep costs for the service more reasonable for patients.
Despite the slow advances in other applications of human genomics, these examples illustrate how real progress is being made in pharmacogenomics. Why is that? I believe it is because pharmacogenomics deals with intrinsically simpler phenomena than most complex diseases.
Pharmacogenomics focuses on the body's ability to adsorb, distribute, metabolize, and eliminate drugs. While these are complicated processes, many of them are tied to specific enzymes working as a single entity. These enzymes are not completely independent of the various controlling networks, but I suspect they are more independent than complex diseases which are typically built upon an intricate web of gene regulatory, signaling, and metabolic networks.
If this logic is true, pharmacogenomics should continue to advance rapidly and have a major impact on the practice of medicine.
Regardless of how quickly or how far pharmacogenomics moves into the mainstream, there is no doubt that we will be seeing an increasing amount of genetic data being accessed by the general public. As people explore their heredity, they will be mining medical data to inform them of their health conditions. And they will be pushing the health care establishment to become more conversant with this information.
I have recently joined this group of genetic explorers. The readout that appears above is from my own 23andMe data. I told my wife that I would rather be a Mediterranean farmer then a Baltic hunter-gatherer. Sounds like a more idyllic life!