After 40 years practicing Internal Medicine I remain perplexed by the challenges of really bringing help to a patient that is consistent with the commitment: First do no harm. Easier said than done. Why? The most conscientious among us has been responsible for a medical complication such as an adverse drug event.

Not surprising given the variation in human beings, the mayhem of packed schedules, paperwork and documentation, tightening protocols, safety nets and standards of care notwithstanding.

Personalizing care remains out of reach as witnessed by the annual surging rate of adverse drug events.

Yet there is a bright spot. The genetics of human disease and treatment is now a reality.

But bringing clinical genetics into everyday practice is difficult for reasons well known to doctors. Clinical integration of the genetics of disease has not been robustly integrated into medical training. Obtaining a reasonable comfort level is just a lot of work.

In most cases, the first and best genetic test is a good family history, a routine part of every comprehensive patient evaluation, but hey, who has time for that when the average patient encounter is measured in minutes.

Indeed, when I was responsible for the Genetic Cancer Center at Florida Hospital Cancer Institute we could spend days to weeks tracking down important family history to support a diagnosis or identify a risk dwelling deep within a family’s DNA.

Here are a few important ideas.

Disease risk genetic testing (DNA sequencing) is not generally diagnostic, only predictive (relative risk). This applies to both germ line (inheritable) and somatic (non-inheritable mutations) and includes both single gene and polygenic disorders. Mitochondrial disorders are part of this.

Pharmaco-genetics is a sequencing analysis that does provide a definite (non-relative risk) base of information on how a given individual will react to a variety of drugs (Black Box warnings).

Genetic science is providing a variety of non-sequencing diagnostic and therapeutic opportunities based on gene expression such as HER2 and estrogen/progesterone (found on the actual tumor and not in nuclear DNA) status in breast cancer for example.

In addition chromosomal analysis for problems like Down and Turner Syndrome is readily available.

What is relative risk? Simply a number compared to the baseline risk that exists in large patient populations largely determined by epidemiology. For example if the lifetime risk of prostate cancer is 16 percent that is a relative risk of 1. If a group of prostate cancer relevant gene loci are interrogated and various Single Nucleotide Polymorphisms are found that double the relative risk to 2, the lifetime risk of prostate cancer is now 32 percent. That gets my attention justifying more aggressive prostate assessments. Prostate cancer is polygenic.

One of the concerns about this type of testing for “common diseases” as a component of personalized medicine is that common diseases are as above often polygenic and the result of multiple minor genetic variants as well as a witch’s brew of environmental, nutritional and social issues. This is very different from the impact of a potent inheritable autosomal dominant gene like BRCA which when present as a heterozygote increases breast cancer risk by over 40 percent. If a homozygote mutation is present, risk goes up to over 80 percent (a 7 -8 fold increase).

Personalized care can be guided by informed relative risk assessment but the truth is the biggest benefit accrues to a small percentage of cancer patients such as the victims of aggressive inherited germ line mutations such as BRCA and the Lynch Syndrome (colorectal cancer) amounting to 10 percent or less of cancer victims. These familial disease families are able to be helped by genetic counseling more than are those with common every day issues that are the result of a large number of non-inherited interacting minor gene variants and the patient environment. (This would include non-BRCA breast cancer)

After being immersed in relative risk issues as director of a large cancer institute’s genetic cancer center, I believe the real promise of clinical genetics for personalized medicine resides in pharmaco-genetics and the ability to predict adverse drug events.

Your +/- 40,000 genes are fairly stable except for the mostly unimportant somatic mutations that accumulate as we age and are part of the wear and tear on our DNA. But I said mostly, since virtually all cancers result from a tedious process of mutation accumulation spanning years in most cases and nudged along by lifestyle choices such as smoking. That said, the body’s ability to metabolize drugs tends to be defined very early and remains fairly stable unless one destroys their liver with drugs and alcohol.

So while some mutations are inheritable and some are not, the fact is we’re born with or slowly accumulate our troubling mutations. How they are expressed is another long story. A prudent alert physician can change the course of a patient’s life by providing patients with personal knowledge of their liver’s ability to metabolize drugs through pharmaco-genetics.

With countless adverse drug events and over 100,000 deaths annually from ADEs, it is a problem that physicians should attack. Reviewing our prescribing habits is a good start. But if we want to practice personalized medicine we have some amazing tools to help us with the ADE problem. We have pharmaco-genetics to provide patients with protection never before available!

Pharmaco-genetics studies the metabolism of the enzyme systems that manage drugs. Simply put it is a drug effect test.

If one does not detoxify a drug or metabolize it normally a standard dose can result in an over dose. If one metabolizes a drug faster than usual the intended and desired effect may never be realized. Some drugs need conversion from one form to another e.g. codeine’s conversion to morphine to relieve pain.

The use of pharmaco-genetics as part of a personalized medicine practice provides patients a life-long safety net for future treatments. Established labs that provide physicians and patients clinically relevant information should do your pharmaco-genetics. Such information should be in the EHR just as allergies are noted. Pharmaco-genetics can truly help us realize the promise of personalized medicine.

John G. Langdon, M.D., FACP is the chief medical strategist for New Wave Biosciences, Inc. For over 40 years he has held leadership positions in clinical (Internal Medicine), academic and socioeconomic medical institutions. New Wave Biosciences is a medical device support team that partners with innovative developers of new medical technologies that have the potential to be major assets in healthcare and the practice of medicine. Dr. Langdon’s e-mail is jlangdon@newwavebio.com