50 whys to look for genes: 13. Genetics is “the future of medicine”

[A] deeper understanding of the fundamental mechanisms of life promises to lead to an era of molecular medicine, with precise new ways to prevent, diagnose, and treat disease.  National Human Genome Research Institute report, Genetics: The Future of Medicine.

(Google “genetics promise medical treatment” and many similarly confident statements can be found.)

Phenylketonuria (PKU) is the poster child for genetic medicine.

A single measurable genetic factor can be detected at birth by a biochemical test. Severe cognitive impairment can be averted if the appropriate environmental factor—an adhered-to special diet with reduced levels of the amino acid phenylalanine—is present…


However, as Paul’s history of PKU screening describes, the certainty of severe cognitive impairment has been replaced by a chronic disease with a new set of problems (Paul 2000, Paul and Brosco 2013, 111ff). For example, although screening of newborns became routine quite rapidly during the 1960s and 70s in the United States, in many states there remains an ongoing struggle to secure health insurance coverage for the expensive special diet. It can be hard to enlist family and peers to support individuals with PKU staying on the diet through adolescence and into adulthood. Math deficits common among individuals with PKU make diet calculations difficult…

Likewise, the apparent simplicity of the genetic factor presumes control over the varying degrees of dietary modification needed by different individuals. Screening has improved over time so that false positives—individuals said to have PKU but needing no special diet—are rare (Sweetman 2001). Yet differences remain among individuals with PKU because hundreds of mutations have been identified in the PAH gene; any individual with PKU may have one pair of mutations out of hundreds of thousands of possible pairs. Efforts are underway to classify mutations as mild, moderate, or severe and as responsive to the drug BH4, which allows a higher-protein diet. Tailoring the dietary modification will require acceptance and application of the diagnostic classification of mutations, secondary screening to place individuals in the right category, and maintenance of the appropriately calibrated diet despite the issues noted in the previous paragraph and some new ones—access to BH4 and keeping individuals who take it from going off the special diet altogether, which is not medically recommended (Paul and Brosco 2013, 108-109). Conversely, when individuals with PKU are not differentiated, this presumes that the medical and health insurance system can withstand any pushback from individuals with PKU or their families about the lack of more personalized treatment.

To acknowledge heterogeneity is not simply to promote more refined genetics-based diagnosis. It can also mean getting involved at a variety of points that shape the PKU life course, such as support groups for individuals and families, campaigns for insurance coverage for the special diet, counseling, or paid family leave. As we consider more recent lines of research on measurable genetic and environmental factors underlying human traits, the case of PKU can serve to remind us to examine the actions possible or proposed on the basis of what is known if one takes into account the possibility of heterogeneity in the genetic and environmental factors.


The quotes above (except the first) are from pages 131-2 in Taylor, Peter J. (2014) Nature-Nurture? No: Moving the Sciences of Variation and Heredity Beyond the Gaps.

Paul, D. B. (2000). “A double-edged sword.” Nature 405: 515.

Paul, D. B. and J. P. Brosco (2013). The PKU Paradox: A Short History of a Genetic Disease. Baltimore: Johns Hopkins University.

Sweetman, L. (2001). “Newborn screening by tandem mass spectrometry: Gaining experience.” Clinical Chemistry 47(11): 1937-1938.


(Introduction to this series of posts)

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