YALE JOURNAL OF BIOLOGY AND MEDICINE 80 (2007), pp.159-163. Copyright © 2007. ESSAY Why Some People Prefer Pickle Juice: The Research of Dr. Richard P. Lifton Peter M. Gayed Yale University School of Medicine In this essay, the author interviews Dr. Richard P. Lifton and examines the use of genomics throughout his studies on the molecular pathophysiology of hypertensive and hypotensive diseases. To date, Dr. Lifton has identified 10 different gene mutations that result in severe hypertension and another 10 that result in severe hypotension. Dr. Richard Lifton has seen patients who crave nothing more than pickle juice. “Another favorite snack is a salted lemon,” reports Lifton, a Howard Hughes Medical Investigator and chairman of the Depart- ment of Genetics at Yale. His professional career has been devoted to understanding the complexities governing salt retention and blood pressure, in which dietary prefer- ences play a role. So far, Lifton counts 10 different genes and gene mutations that re- sult in severe hypertension and another 10 that result in severe hypotension. “Examining the extremes has revealed a lot about the way our bodies regulate blood pressure,” explains Lifton. Remark- ably, these genes and their products all con- verge on a single, powerful regulator of blood pressure: renal salt retention. When the kidneys are unable to excrete salt, water is retained in the blood. “When too much water is retained,” Lifton says, “blood pres- sure goes up.” The converse is also true: When too much salt is excreted in the urine, water is lost, and the result is hypotension. The chronically hypotensive body tries to compensate in many ways, and one of those ways is manifested by a craving for salty products — and what better than pickle juice? The idea that the body might respond to hypotension by increasing its salt intake made good sense and was supported by re- ports that the most hypotensive members of an affected family also ingested the most salt. What remained unclear to scientists and clinicians, however, was the primary organ responsible for salt retention and salt wasting. “To address this problem,” Lifton wrote in a 2002 review, “our group has taken a genetic approach to the understand- ing of hypertension in humans, using the paradigm of positional cloning,” which re- lies on knowing the approximate location of a gene thought to be involved with a par- ticular disease phenotype [1]. During the lab’s many chromosomal walks, Lifton and his colleagues have re- vealed the molecular pathophysiology of an impressive number of diseases affecting salt †Abbreviations: PHA, pseudohypoaldosteronism; ENaC, epithelial sodium channel; GRA, glucocorticoid-remediable aldosteronism; SSCP, single-strand conformational polymor- phism; MR, mineralocorticoid receptor. 159