The river

I never knew my Dad’s father. He died in 1950 during radical chest surgery, a last-ditch attempt to contain the tuberculosis that was killing him. Born in 1900, he was one of eleven surviving offspring of parents who farmed family land in the hills settled by their pioneer forebears. They were a hardworking, enterprising family who built their home from timber on the property, along with a sawmill, a store, and a school. The sons and daughters left the farm to become railroad telegraphers, carpenters, nurses, and teachers but returned every summer for their mother’s birthday. I met many of them at reunions that continued into the 21stcentury.

In the late 1960’s, researchers at the National Cancer Institute (NCI) studied the family for clues to chronic lymphocytic leukemia (CLL), which had developed in three of the eleven siblings. NCI doctors examined seven of the eight still living and sent questionnaires to the next generation, including my Dad. Years later, I found the published study in MEDLINE. It described immune abnormalities in several of the apparently healthy siblings, as well as in the three with CLL and another with severe arthritis. The authors suggested that these could be different manifestations of an inherited immune defect—perhaps a recessive trait inherited from both parents, who were second cousins.

Fraumeni et al. Familial chronic lymphocytic leukemia. Ann Int Med, 1969

Well before genetics was a science, thousands of years of agriculture offered ample evidence for the passage of traits from one generation to the next. Charles Darwin’s longest book, The Variation of Animals and Plants Under Domestication, may have inspired his half-cousin Francis Galton to study the heredity of human traits, from height to mental ability. Galton conceived of twin studies to separate the influences of inherited and environmental influences and is credited with the expression “nature versus nurture.” He also coined the term “eugenics,” which is now associated mostly with the misguided social application of genetic theories.

Wedgwood-Darwin-Galton pedigree, Eugenics Education Society, 1909.

Common 19th-century diseases such as pellagra and tuberculosis were suspected of being hereditary because they so often occurred in multiple family members. Darwin, familiar with the effects of inbreeding on plants and animals, worried that marriage to his first cousin, Emma Wedgwood, had contributed to their daughter’s early death from tuberculosis. Two of their ten children died in infancy and of the six who eventually married, three had no children. Scientific speculation on the Darwin pedigree continues to this day.

Well after Koch’s 1882 discovery of the tubercle bacillus, heredity was considered a potentially important factor in tuberculosis. The Medical Record, a New York weekly medical journal, in 1903 published the following thoughts in an article titled “Some Questions on Heredity”:

“Pathologists assert, and seemingly with absolute justification for their assertion, that tuberculosis is not directly an inherited disease but that it is always the result of infection. We all recognize that the most we can say, certainly about pulmonary tuberculosis, so far as heredity is concerned, is that the lessened resistance to the attacks of the tubercle bacillus may be inherited.”

The author then suggested that hereditary factors could play a role in extra-pulmonary tuberculosis and might help explain why some people recovered spontaneously. He added:

“It is often observed in families that certain diseases develop at corresponding periods in the life of parent and offspring. This not infrequently extends through several generations. Tuberculosis is a notable example of this. The widespread prevalence of tuberculosis adds to the difficulty of arriving at definite conclusions, in regard to the part which heredity plays.”

The “white plague” was on the upswing in Western Europe when my Dad’s ancestors departed in 1740 for the American colonies.  Tuberculosis mortality is thought to have peaked around 1800, then declined 10-fold during the 19th century for reasons that can only be conjectured today. The first antibiotic to cure tuberculosis, streptomycin, became available for clinical use in the late 1940’s; although too late to save my grandfather, its discovery earned the 1952 Nobel Prize in medicine. Resistance to streptomycin emerged quickly, but so did effective new antimicrobials. Deaths from tuberculosis dropped precipitously.

Estimated trend in tuberculosis mortality, Western Europe 1740-1985.

Population-level trends in infectious diseases, including tuberculosis, are influenced by characteristics of the human population, the environment, and the pathogen—the epidemiologic triangle. A change in any one of these “causes” affects the apparent contribution of the others. For example, before the bacterial cause of tuberculosis was known, treatment focused on the environment: sanatoriums provided fresh air and a healthy diet. When some patients responded but others didn’t, suspicion turned to human factors, including inherited susceptibility. When antimicrobial treatment became routine, pathogen characteristics—especially drug resistance—became the focus of public health investigations.

While my Dad’s father, mother, and sister were in the sanatorium, he and his brother were sent to the country. All his life, my Dad took pleasure in remembering those months on the family farm on the New River, surrounded by aunts, uncles, and cousins. His mother and sister recovered completely in the sanatorium. Could an inherited immune defect have tipped the balance in his father’s case?

In later years, long after the NCI study was done, several more of my grandfather’s siblings developed CLL. Family members wondered whether chest X-rays, once used for routine tuberculosis screening, might have played a role; however, CLL is “one of the few malignant conditions never linked to radiation.” No more cases occurred in the next generation, which is now well beyond the age at which CLL usually appears. Perhaps a rare, recessive trait came to light and then faded into the genetic background. Perhaps something else particular to that time and place found a footing in the family that grew up there but has now dispersed.

The farm was sold in the 1960’s to a businessman who wanted to mine titanium from the sands. His venture never materialized and after the national Wild and Scenic Rivers Act passed in 1968, the riverbank became Federal property. Early plans called for the family home to become a museum of pioneer life but eventually the house fell victim to vandalism, rain, and neglect.

The New River isn’t really new but ancient, perhaps 300 million years old. People have lived along its banks for only the last 10,000 years and European settlers only for the last few hundred. Farming there has now gone the way of hunting and gathering, and the railroad, which once carried away the area’s timber and coal, is barely running. The best way to visit the place today is to put a boat in the water at the New River Gorge national river recreation area. That’s what we will do when we carry my Dad’s ashes to the place he loved most.

New River, 2002, by Tom Brown.

 

 

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