Caution, Overload: The Troubled Past of Genetic Load

PREOCCUPATION with “genetic load” seems to be on the rise again, fueled by the new opportunities that full human genome sequencing provides (e.g., Simons et al. 2014; Lynch 2016a; Stewart et al. 2017; Verduijn et al. 2017). The fear of the ultimately devastating effect that the accumulation of deleterious mutations would have on the future of humanity was articulated nearly 70 years ago by Hermann J. Muller in a 1950 seminal paper, Our Load of Mutations. Four decades later, in his 50 Years of Genetic Load: An Odyssey, Bruce Wallace (1991) recounted how the concept of genetic load had evolved in the twentieth century, and traced its origins further back to J. B. S. Haldane’s 1937, The Effect of Variation on Fitness. This paper by Haldane, wrote Wallace, “marks the origin of the genetic load concept.” Both points of departure, however—Muller (1950) as well as Haldane (1937)—furnish a history of the concept “genetic load” that utterly ignores its eugenic roots, manifested most clearly in the concept’s German predecessor: erbliche Belastung. To properly assess the meaning and complexities of the concept of genetic load, as well as its potential social implications, it is vital that we acknowledge these scientific and cultural origins, some of whose trajectories are still pertinent today. “[T]oday we possess numerous examples, not only of transmission but as well of hereditary accumulation of morbid predisposition [to mental anomalies].” These are the words of L. F. E. Renaudin, Director of the mental asylum at Maréville, in his 1854 Medical Psychological Studies on Mental Alienation (Renaudin 1854, p. 33, translation following Dowbiggin 1985, p. 191). In mid nineteenth-century France, the notion that heredity, and in particular morbid heredity, was the underlying cause of a variety of nervous and mental disorders, was already becoming widespread. Even though there was no precise understanding of the mechanism governing hereditary transmission at the time, the fact of heritability itself seemed undeniable, and apparently could explain why, in certain families, social, medical, and psychological deviations were so abundant. These ideas received their clearest expression in Bénédict Augustin Morel’s Treatise on the Physical, Intellectual and Moral Degeneracy of the Human Race (Morel 1857). For Morel, degeneracy was a process of progressive mental, physical, and moral deterioration from one generation to the next, whose initial impetus may have been external (poor nutrition, urban living conditions, nervous strain from industrial work, and alcohol) but whose influence was inherited and whose ultimate result was the production of imbeciles and the annihilation of entire familial stocks. The same idea was also developed by other contemporary thinkers, in and outside of France (reviewed in Chamberlin and Gilman 1985; Pick 1989). In Italy, for example, Cesare Lombroso related “born” criminal behavior to degeneracy; impressed by Lombroso’s writings, and under the impression that, “degenerates are not always criminals, prostitutes, anarchists and pronounced lunatics; they are often authors and artists,” the Hungarian-born doctor and social critic Max Nordau characterized all fin-de-siècle “decadent” cultural fashions as expressions of moral and social degeneracy. Nordau defined degeneracy as “a morbid deviation from an original type. This deviation, even if, at the outset, it was ever so slight, contained transmissible elements of such a nature that anyone bearing in him the germs becomes more and more incapable of fulfilling his functions in the world; and mental progress, already checked in his own person, finds itself menaced also in his descendants.” (Nordau 1895, p. vii, 16). The concept of degeneration was also popular in the Anglo-Saxon world (e.g., Talbot 1898). In America, studies on “social degenerate” families (the Jukes, the Ishmaels, the Kallikaks) and investigation into degenerate heredity by such prominent scientists as Charles B. Davenport and Henry H. Goddard, ostensibly furnished the links between crime, poverty, alcoholism, and mental deviancy, and helped frame social problems as inherently biological ones (see discussions by Rafter 1988 and Carlson 2001). To counter the looming degeneration of human germplasm, some form of counter-regeneration was needed. The British polymath Francis Galton, Charles Darwin’s half-cousin, proposed the term “eugenics” to define the means and methods to be mobilized for taking control over human evolution and for redirecting it toward a better path, whether by checking the reproduction of those deemed less fit, or by boosting the propagation of those who were of higher quality. Throughout this period, when French, American, and British scholars wanted to address the nature of degeneracy or hereditary processes, they spoke quite generally of hereditary transmission, hereditary particles (Darwin’s “gemmules”) or even accumulating hereditary influences or “taint.” Disregarding religious- and economic-related contexts, they did not yet use in any systematic fashion the term hereditary “load” or “burden.” Their German-speaking counterparts, however, did. The term Belastung in German is translated as strain, load, or burden. When accompanied by the adjective, erblich (hereditary) this term was often used to refer to mentally ill individuals in one’s family circle or community. Throughout the nineteenth century, German psychiatrists made repeated attempts to assess the relative significance of heredity in the causation of mental abnormalities (see Gausemeier 2015). In 1895, for example, an assistant at the Burghölzli psychiatric clinic in Zurich by the name of Jenny Koller turned “hereditary load” into her direct object of inquiry. Koller (1895) not only offered a detailed analysis of the frequencies of different mental disorders in the families of 370 asylum patients, but also compared these results to a control group of (reportedly) healthy individuals; this was a true methodological novelty at the time. Ten years later, another scholar from the same institute, Otto Diem, published an additional massive study on the degree of Belastung of both mentally ill and healthy individuals. Diem (1905) stated with dissatisfaction that, “[i]t has evolved into an actual dogma that hereditary load is the most important cause of mental and nervous diseases.” Diem’s own results indicated, ironically, that healthy individuals were almost as hereditarily loaded as the ill. This latter fact, he thought, proved that mental problems might just as well disappear; they could be inherited, but they did not have to be. Therefore, he argued, hereditary load ceased to be a Damoclean sword which threatened any person who was unfortunate enough to have a distant, mentally ill ancestor (Diem 1905, p. 216–218, 358–360). The rise of Mendelian genetics introduced a new concept that slightly altered the characterization of Belastung, namely, the fact of recessivity. Early attempts to apply Mendelian reasoning to the psychiatric domain indicated that most mental diseases were recessive and that, even when dominant factors were involved, the more severe mental aberrations were caused by recessive variants (Davenport 1908; Rüdin 1911; Lenz 1912, p. 597). When it came to hereditary load, however, the concept of recessivity also enabled, at least in theory, the narrowing down of the idea of familial burden to only those members of a family who really carried harmful hereditary factors. “Every individual, in whose family circle… mental illness appeared, was termed ‘belastet,’” recalled psychiatrist Ernst Wittermann in 1913, referring to pre-Mendelian times. He explained, however, that Mendelian theory supported a distinction between homozygous individuals, who were free from a certain recessive disease (DD), and heterozygous carriers (DR). As long as Belastung continued to be a familial concept, Wittermann (1913) argued, the two types remained indistinguishable, despite the fact that only the second type of individuals (DR) were truly belastet. The mid 1910s saw the establishment of a novel kind of analysis of hereditary relations in German psychiatry. The limitations of simple Mendelian schemes were already becoming apparent, and psychiatrist Ernst Rüdin, greatly assisted by Wilhelm Weinberg (better known today for the Hardy-Weinberg equilibrium), developed innovative methods to assess the hereditary risk that the mentally ill posed to their relatives (Weinberg 1912, 1913a,b, 1929; Rüdin 1916; see also Just 1920; Crow 1999). The new statistical toolbox, which quickly acquired international recognition and some of whose results are considered robust to this day, was officially referred to under the heading, “empirical hereditary prognosis” (Rüdin 1933), but was often labeled simply as “statistics of load” (Belastungsstatistik). Different scholars published the results of their studies on the “load” of the “average population” with respect to various mental disorders, and evaluated the chances that children, siblings, or even nephews or nieces of the mentally ill would manifest mental deviances (Kattentidt 1926; Schulz 1927, 1931; Luxenburger 1928; Brugger 1929; Panse 1935). As in the case of the American eugenics movement, the underlying agenda informing these works was that families with members displaying mental illnesses—and not only the mentally ill themselves—needed to be socially isolated and their reproduction stemmed. The calculation of morbidity risk for nephews and nieces of a disease sufferer (Schulz 1926; Hoffmann 1928; Banse 1929; Walker 1929) were seen as an effective measure for deterring healthy individuals from marrying not only the mentally ill themselves, but also their brothers and sisters. This research program in when in Rüdin was of the of and Studies in the German for The studies in that morbidity for certain relatives of the mentally ill were often for example, the morbidity of nephews and nieces of from to to the it is not the which be the measure of the the to be it was was that the and were the ones in the p. p. Throughout the German psychiatrists were to their not to and also to potential not to into families, by to their the relative and not the to their future The to a control group of healthy which Diem had used to that heredity was not as as it was thought, was used for the the hereditary to the mentally ill. 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