Medicine by Mechanism


[we interrupt this diatribe to look at precision medicine]

I am alerted by the JAMA network to an editorial, Ushering Hypertension Into a New Era of Precision Medicine by Theodore A. Kotchen, MD; Allen W. Cowley Jr, PhD; Mingyu Liang, MB, PhD,JAMA. Published online January 14, 2016. doi:10.1001/jama.2015.18359

It is not appalling, like many current publications about the future of medicine.  It discusses two popular ideas – precision medicine, and epigenomics.  What makes it appalling and a bit terrifying is its application to the coming trend in medicine, which is not described accurately as Precision Medicine. Rather, it is Large-Animal Herd Veterinary Medicine.  And you are a member of the herd.

 In 2011, the US National Research Council introduced a more expansive and comprehensive concept of precision medicine, based on the assumption that an individual’s genomic and epigenomic determinants will enable the personalization of appropriate preventive and therapeutic interventions. Recently articulated by President Obama and endorsed by the National Institutes of Health (NIH), the Precision Medicine Initiative is intended to develop new approaches for detecting, measuring, and analyzing a wide range of biomedical information, including molecular, genomic, cellular, clinical, behavioral, physiological, and environmental parameters. NIH has recently announced new funding opportunities for precision medicine research initiatives.

 Current efforts in precision medicine focus primarily, often exclusively, on genome sequences. This approach is likely to be productive for congenital disorders and diseases such as cancer, for which a small number of genome sequence variations appear to play a major role in individual patients. Oncology is currently a focus of the Precision Medicine Initiative because of the prevalence of cancer, the recognition of unique genomic signatures of an increasing number of cancers, and the potential benefit of genetically targeted therapies.

Epigenomics is the study of epigenetic marks on a genome or near-genome scale. Epigenomes capture the biological influence of environmental and lifestyle factors in a quantifiable and analyzable molecular form. Epigenetic dysregulation has emerged as a hallmark of several complex pathologies, including hypertension, other cardiovascular disease risk factors (eg, smoking, diabetes, aging), cardiovascular disease, and all-cause mortality.

Several challenges contribute to the difficulty of identifying the epigenetic determinants of hypertension and cardiovascular disease. Specific environmental exposures may be difficult to identify and quantify and may have small effects. There is also the potential for reverse causality. Because of its lability, blood pressure is a difficult phenotype to accurately assess. Further, hypertension may not be a discrete phenotype. Based on epidemiologic evidence and results of clinical trials, definitions of hypertension, prehypertension, and targets for blood pressure control have useful clinical relevance. However, as articulated by Pickering more than half a century ago: “…the practice of making a sharp division between normal and pathologically high pressure is entirely arbitrary and is in the nature of artifact. Essential hypertension represents the upper end of a distribution curve showing continuous variation, with no definite evidence of two populations.”

In augmenting the science of medicine, these approaches bring great promise, and should be continued.  There is no argument against the science of medicine, but in the manner of its implementation.

In our society, we have turned more strongly towards the principle of the person-as-object.  It is the hallmark of 20th century thinking, and has brought about some of the worst mistakes of that century.  Facts obtained by epigenetic analysis and “individualization of treatment” must remain instrumental in nature.  The approach can never supplant the actuality of treatment; rather, their relevance lies in their validity when applied to a particular patient for a particular treatment.

Efficiency of a treatment must always remain defined by its effect when applied by a human in the care of another.  All else is ancillary – it is an implication and none other.

Into whose hands do we deliver the power of epigenomic studies?  To the patient?   To the doctor?  Or to the faceless corporation that can reap a profit from it?  To whom does the herd belong?

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