A commentary on pharmacogenomics: what can it do?
Forty years ago when I was in high school, genetic testing and genetic manipulation generally involved farmers, livestock, and crops. We knew that certain families in Pennsylvania and Minnesota were prone to genetic disorders. We also knew about Woody Guthrie, Lou Gehrig, four- and five-leafed clover, and the genetic defects of people who survived the atomic bombs of Hiroshima and Nagasaki. I never imagined then that I would run a genomics company that is able to determine an individual's genetic ancestry, potentially identify an individual who left his DNA at a crime scene, or differentiate a drug responder from a nonresponder.
Since our company is one of the first to launch a genetic heritage product into the marketplace. ANCESTRYbyDNA for genealogy and DNAWitness for forensics, I ask myself: How can I convince others that even though we do not yet understand all of the ramifications of pharmacogenomic testing, population structure, and genetic heritage, we will make it safer to test and, by understanding test results, we will move forward to face today's challenge of treating and maybe curing diseases?
What pharmacogenomics means--and what it does not--is a legitimate concern about which members of the pharmaceutical industry and the healthcare market should be aware and be willing to take time to explain. Regulators from Capitol Hill to local communities can have a dramatic impact upon the emerging field of pharmacogenomics. Points of view based upon scientific discovery or knowledge (or not) must be addressed head-on and dealt with in a straightforward manner. Reporters have asked me why National Institutes of Health researchers (some of whom head genetic research groups) think that determining an individual's genetic heritage is a trivial exercise, and that our DNAPrint testing is a sham and should be banned. While many good arguments exist as to why pharmacogenomics should be avoided, these are strong criticisms from eminent scientists in the fields of genetics and population structure--the very fields we believe hold keys to unlocking the origins of a vast majority of diseases afflicting humankind.
The FDA (U.S. Food and Drug Administration) adopted an opinion on pharmacogenomic testing as it relates to new drug approval and published this landmark document in November 2003. Our FDA and similar government bodies across the globe are chartered with one very important mission: to protect patients from harm derived from toxic medicines, poor quality control, or deceptive practices. This first rational position written by FDA regulators demonstrates just how important our government believes improving drug response and personalized medicine is.
Pharmaceutical executives, researchers, physicians, and medical professionals have an opportunity through knowledge of a patient's genetic heritage to change the way drugs are developed, approved, regulated, and used to treat illnesses. Linking a drug, such as Herceptin, to a genetic disorder and having the FDA approve it is a tremendous stride. The pharmaceutical industry has an even more profound opportunity to further develop drugs for genetic ancestors that are often hidden under an individual's physical appearance.
Medicines work differently in different peoples. The most recent example is the discovery of a gene passed down to Russians vis-a-vis the Mongolian invaders. The Mongols apparently liked their drink--fermented mare's milk--which required a particular enzyme for digestion. When Mongols mingled with European tribes--who derived their preferred alcoholic drink from grapes and various fruits, grains, or honey--this inherited Mongol enzyme eventually afflicted millions of Russians. Although they do not look "Mongolian," the Russian inheritors of that particular Mongolian gene are unable to process ethanol derived from fruit or potatoes, thus proving more susceptible to the disease of alcoholism. On the other hand, many Mongolian people express the phenotypic descriptors of the Mongolian race, yet, if given a drink of Russian vodka, are very capable of drinking it and not turning into an alcoholic. Population structure and genetic inheritance has absolutely nothing to do with the Russian or the Mongolian "races" but everything to do with genetic ancestry.
When we conduct clinical trials focusing on African-Americans or Hispanics, what are we testing? Genetic heritage is a component of race, but not all of the descriptors we use for race are inherent in our genes. We have genes for eye color, hair color, height, weight, skin shade, and other phenotypic descriptors. We have a series of identifiers that we call ancestry informative markers (or AIMs) that span the entire human genome. These markers can be linked to the four major subcontinental groups from which all humans evolved (based on our current understanding of human evolution): subSaharan African, East Asian, European, and Native American. We have been able to link these markers to such fundamental information as drug metabolism.
We know that phenotypic descriptors, such as high blood pressure, are linked to inherited genetic traits, not an individual's race. Appearance is as deceptive and elusive as the mystery of life itself. We know that prostate cancer among African-Americans is not linked to an individual who says he is African-American and appears to be an African-American but is linked to the gene he inherited from subSaharan Africans. We know that statins and the negative or positive response to statin treatment is linked to genetic ancestry. And we certainly know that among Russians, alcoholism can most likely be linked to an invading East-Asian army's genetic make-up. Identifying these inherited descriptors--along with learning whether we can or cannot absorb or metabolize certain fundamental compounds--can be used to alleviate pain and suffering.
We are working on our first pharmacogenomic product (our first target is Taxol), in conjunction with the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and should be able to predict, with 95% accuracy, whether or not a cancer patient responds to a particular medication. Although our company's research in pharmaceutical prediction has not yet met our company's standards for a product launch nor our internal FDA standards for discussions with the U.S. government, we are highly encouraged by our discoveries, as are the doctors and scientists at Moffitt and their patients with whom we have talked.
Our company code of ethics, like many others, speaks not only to our corporate behavior but also to our determination to root out and end any abuse of our science, products, or technology. We are mindful of our responsibility and very much aware that our research and products can be misused. It is similar to the discovery of any compound for treatment of a disease: There are always associated side effects, lethal to some patients. Although we hope to minimize or reduce side effects, their elimination--while probably unlikely--remains a worthy aspiration.
Always teetering on the edge of the abyss (where we could plunge into a quagmire of despair and misuse), science, discovery, and invention can also help us leap across the abyss to a new horizon. The same drive that carries us today helped our ancestors cross the frozen Bering Sea or migrate up from Africa and settle the continents. Every day scientists, doctors, and healthcare workers stride toward a greater knowledge of disease over the "frozen tundra" of genetic testing.
Richard Gabriel is CEO and president of DNAPrint, Sarasota, FL. He completed Suffolk University's Executive MBA Program, Boston, MA, and received his BS in chemistry from Ohio Dominican College, Columbus, OH. He served with the U.S. Army's 82nd Airborne Division from 1967 to 1970.
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|Publication:||Medical Laboratory Observer|
|Date:||Mar 1, 2005|
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