The systems above, the genomes below

In medicine, it is often said the exceptions are the rule and atypical presentations of diseases are typical. However, diagnoses are also often preceded by typical symptoms, accompanied by diseases, and succeeded by other symptoms and diseases. There are patterns in these journeys and they often follow consistent trajectories.  A heart attack is announced by chest pain but tracks with a history of smoking, diabetes, high cholesterol, and obesity. Lung cancer is heralded by a persistent cough or shortness of breath but is correlated with a longstanding history of smoking. “Type 2” diabetes is signaled by excessive thirst or fatigue but is related to obesity and is succeeded by renal failure or retinopathy. In fact, these patterns are replicated across patients because they involve the mechanistic “how” of the underlying disease process, and therefore, serve as diagnostic signals. The differential diagnosis  and medical decision making begins after an immediate history is taken in the context of existing histories. 

Generally, each person presenting to the clinician has four relevant histories. First, there is the “history of present illness (HPI)” which describes the patient’s symptoms. Ideally, it is  a chronological description of the trajectory of the patient’s present illness from the first sign and symptom to the present. Second,  the “past medical history (PMH)” which represents a list of prior  illnesses, surgeries, injuries, and treatments. Third, the “social history” addresses the potentially clinically relevant  familial, occupational, and recreational aspects of the patient’s personal life. Alcohol, tobacco and drug use as well as workplace exposures  or home risk factors including diet, exercise, and sleep are included in this section. Last, there is the “family history” which is a review of diseases which may be hereditary and place the patient at risk. The hereditary data represented by the family history serves as a proxy to our cultural and  evolutionary history. 

Although all four histories are represented in the EHR,  the quality and the perceived value of these histories is markedly different. Whereas the HPI and PMH are documented, interpreted, and curated extensively, the social and family histories are at best represented as cursory, self-described, intake forms. For example, where is the genotypic variation in salt retention associated with an equatorial physiology that leads to a higher prevalence of hypertension in historically equatorial human’s represented in the medical note? Where is the higher risk of diabetes and obesity associated with the thrifty genotype or the thrifty phenotype – improved energy efficiency adaptations for energy-poor environments that are maladaptive in an energy-rich environment – represented in the medical note? How are the pillars of health and disease in the modern world – sleep, diet, exercise, alcohol, and smoking – captured in the medical record? At best, crude proxies such as intake surveys and demographics are used to capture the family and social history and they lack depth or detail. This chasm in social and family history data and knowledge leaves a chasm in our understanding . By one estimate, social determinants of health and genetics account for 90% of health outcomes such as premature death.

The headline and prevalent diseases of modernity – diabetes, cardiovascular disease, cancer, and neurodegenerative diseases – have thus far been resistant to medical interventions because their causes are multifactorial and predominantly reside in the systems above – social – or in the genome below – family history – and the non-linear interplay of the two (future essay). They involve processes that have been optimized and integrated over millions of years of evolution, and thus, incredibly resistant to alteration or tinkering. In order to “solve” these diseases, it will require a multi-pronged approach including an evolutionary framework in order to understand of the etiological “why.” The historian Will Durant stated, “the present is the past rolled up for action, and the past is the present unrolled for understanding.” However, as Santiago Ramon y Cajal said,  “nature seems unaware of our intellectual need for convenience and unity, and very often takes delight in complication and diversity.” Evolutionary and social pasts are often not unrolled to see but require probing, experimentation, varied perspectives, and creative conceptual frameworks. The potential payoff of this inquiry could be informed action that would lead to more effective prevention strategies accompanied by perspicacious prognostications and precise treatments. 

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