Kathryn Paige Harden


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Annotated by:
Trachtman, Howard

Primary Category: Literature / Nonfiction

Genre: Treatise

Summary:

The Graduate is a movie classic from what seems like a bygone era. It is accompanied by great music by Simon and Garfunkel and has one of the most famous one-word lines in cinema history. When Benjamin Braddock is wandering aimlessly around the pool at a graduation party thrown in his honor, a friend of his parents asks him what he plans to do with his post-collegiate life. Another family friend jumps in and volunteers, “Plastics.” There are many who will also give a one-word answer to any medical school graduate searching for a career – Genetics.

In this important new book,  Kathryn Harden provides staunch support for the key role of genetics in health, disease, and in human well-being. She provides a remarkably clear primer on genetics in accessible language. Harden begins with statistical issues like the normal distribution and Bayesian priors. In her capable intellectual hands, she uses analogies that effectively move the teaching agenda forward. With recipes as a framing image for genetics, she demonstrates the relationship between the coding material in the DNA nucleotide sequence and the actual building blocks, namely the proteins that do the heavy lifting inside cells. Concepts like genetic recombination, linkage disequilibrium, and monogenic versus polygenic disorders are introduced and make perfect sense. She then builds on this foundation to consider genome-wide association studies (GWAS) which represent the powerful tool that has been introduced to explore the relationship between genetic endowment and health. That is where things start getting complicated.

When people think of medical genetics, they usually have classical Mendelian disorders in mind. They are caused by mutations in a single gene that disrupts a protein pivotal to normal health. Examples are sickle cell disease, hemophilia A, or muscular dystrophy. However, many health problems like hypertension that are associated with significant global disease burden are polygenic. This means that they are caused by less dramatic mutations in a number of genes that in the aggregate lead to the disease.  Harden details how quantitative assessment of the contribution of these minor variations in a large array of discrete genes enables the formulation of polygenic risk scores (PRS) for these conditions. These measures provide estimates of susceptibility to developing other polygenic conditions like obesity, cardiovascular disease, and diabetes.

As a psychologist, Harden’s work focuses on the application of PRS to non-medical aspects of human behavior such as impulsivity, attentiveness, job satisfaction, and executive function. The waters remain relatively calm until Harden’s fellow psychologists venture into the realm of educational achievement and lifetime income status. Harden methodically reviews relevant studies that have been done with siblings, twins, adoptees, and family trios. She dissects them and highlights when investigators have misinterpreted their data. There is a steady drumbeat of data, almost too much at times. But the overall consensus that emerges is that PRS and other measures of heritability continue to show a genetic component for these psychosocial outcomes in large population studies. The challenge that Harden raises is how to incorporate this knowledge about genetics into a better understanding of these aspects of human behavior and if and how to address abnormal manifestations.

Questions remain concerning how genetics “causes” these changes and how to interpret the findings. What is determinative? Is it genetics i.e., nature, or is it all environment i.e., nurture? There are those, like Harden, who advocate for thoughtful analysis and utilization of all the GWAS data. She highlights the difference between use of PRS to assess outcomes within populations versus between populations. In sharp contrast, there are others who resist  the introduction of genetics into psychology. Pointing to the sordid history of eugenics and its degeneration into the creation of racial hierarchies, the opponents of the Harden’s work dismiss it as unscientific at best and destructive at worst. Harden makes a compelling case for the validity of the science and a spirited defense of the thoughtful use of genetics dismiss it as unscientific at best and morally repugnant at worst.

Harden provides a strong defense of the science and statistical methods and offers a spirited argument that without acknowledging the role of genetics in human achievement, society will be unable to thoughtfully address inequalities and restore balance. Her work touches on many other pressing issues including human autonomy, agency, freewill and the role of government intervention. She outlines a social agenda that acknowledges the importance of genetics as a contributing factor. But it incorporates a recognition that its distribution in the population is solely a matter of luck and does not serve as the basis for a hierarchy of human worth. I leave it to readers to judge for themselves the validity of her proposals, but her commitment to making this world a better place is not in question.

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