| PERSPECTIVES

Caution, Overload: The Troubled Past of Genetic Load

Amir Teicher1 Department of History, Tel Aviv University, Israel 6997801 ORCID ID: 0000-0002-6890-2073 (A.T.)

KEYWORDS genetic load; history; eugenics; psychiatry; radiation; population genetics

REOCCUPATION with “genetic load” seems to be on the Dowbiggin 1985, p. 191). In mid nineteenth-century France, Prise again, fueled by the new opportunities that full hu- the notion that heredity, and in particular morbid heredity, man genome sequencing provides (e.g., Simons et al. 2014; was the underlying cause of a variety of nervous and mental Lynch 2016a; Stewart et al. 2017; Verduijn et al. 2017). The disorders, was already becoming widespread. Even though fear of the ultimately devastating effect that the accumula- there was no precise understanding of the mechanism gov- tion of deleterious mutations would have on the future of erning hereditary transmission at the time, the fact of herita- humanity was articulated nearly 70 years ago by Hermann bility itself seemed undeniable, and apparently could explain J. Muller in a 1950 seminal paper, Our Load of Mutations. why, in certain families, social, medical, and psychological Four decades later, in his 50 Years of Genetic Load: An Odyssey, deviations were so abundant. These ideas received their Bruce Wallace (1991) recounted how the concept of genetic clearest expression in Bénédict Augustin Morel’s Treatise on load had evolved in the twentieth century, and traced its the Physical, Intellectual and Moral Degeneracy of the Human origins further back to J. B. S. Haldane’s 1937, The Effect of Race (Morel 1857). For Morel, degeneracy was a process of Variation on Fitness. This paper by Haldane, wrote Wallace, progressive mental, physical, and moral deterioration from “marks the origin of the genetic load concept.” Both points of one generation to the next, whose initial impetus may have departure, however—Muller (1950) as well as Haldane been external (poor nutrition, urban living conditions, ner- (1937)—furnish a history of the concept “genetic load” that vous strain from industrial work, and alcohol) but whose in- utterly ignores its eugenic roots, manifested most clearly in fluence was inherited and whose ultimate result was the the concept’s German predecessor: erbliche Belastung.To production of imbeciles and the annihilation of entire familial properly assess the meaning and complexities of the concept stocks. of genetic load, as well as its potential social implications, it is The same idea was also developed by other contemporary vital that we acknowledge these scientific and cultural ori- thinkers, in and outside of France (reviewed in Chamberlin gins, some of whose trajectories are still pertinent today. 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 Origins of the Concept of Hereditary Load that, “degenerates are not always criminals, prostitutes, an- “[T]oday we possess numerous examples, not only of trans- archists and pronounced lunatics; they are often authors and mission but as well of hereditary accumulation of morbid artists,” the Hungarian-born doctor and social critic Max predisposition [to mental anomalies].” These are the words Nordau characterized all fin-de-siècle “decadent” cultural of L. F. E. Renaudin, Director of the mental asylum at fashions as expressions of moral and social degeneracy. Maréville, in his 1854 Medical Psychological Studies on Men- Nordau defined degeneracy as “a morbid deviation from an tal Alienation (Renaudin 1854, p. 33, translation following original type. This deviation, even if, at the outset, it was ever so slight, contained transmissible elements of such a nature Copyright © 2018 by the Genetics Society of America that anyone bearing in him the germs becomes more and more doi: https://doi.org/10.1534/genetics.118.301093 incapable of fulfilling his functions in the world; and mental Manuscript received May 1, 2018; accepted for publication May 22, 2018. fi 1Address for correspondence: Department of History, Tel Aviv University, Tel Aviv, progress, already checked in his own person, nds itself Israel 6997801. E-mail: [email protected] menaced also in his descendants.” (Nordau 1895, p. vii, 16).

Genetics, Vol. 210, 747–755 November 2018 747 The concept of degeneration was also popular in the reasoning to the psychiatric domain indicated that most men- Anglo-Saxon world (e.g., Talbot 1898). In America, studies on tal diseases were recessive and that, even when dominant “social degenerate” families (the Jukes, the Ishmaels, the factors were involved, the more severe mental aberrations Kallikaks) and investigation into degenerate heredity by such were caused by recessive variants (Davenport 1908; Rüdin prominent scientists as Charles B. Davenport and Henry H. 1911; Lenz 1912, p. 597). When it came to hereditary load, Goddard, ostensibly furnished the links between crime, however, the concept of recessivity also enabled, at least in poverty, alcoholism, and mental deviancy, and helped frame theory, the narrowing down of the idea of familial burden to social problems as inherently biological ones (see discussions only those members of a family who really carried harmful by Rafter 1988 and Carlson 2001). To counter the looming hereditary factors. “Every individual, in whose family circle... degeneration of human germplasm, some form of counter- mental illness appeared, was termed ‘belastet,’” recalled regeneration was needed. The British polymath Francis psychiatrist Ernst Wittermann in 1913, referring to pre- Galton, Charles Darwin’s half-cousin, proposed the term “eu- Mendelian times. He explained, however, that Mendelian the- genics” to define the means and methods to be mobilized for ory supported a distinction between homozygous individuals, taking control over human evolution and for redirecting it who were free from a certain recessive disease (DD), and toward a better path, whether by checking the reproduction heterozygous carriers (DR). As long as Belastung continued of those deemed less fit, or by boosting the propagation of to be a familial concept, Wittermann (1913) argued, the two those who were of higher quality. Throughout this period, types remained indistinguishable, despite the fact that only when French, American, and British scholars wanted to ad- the second type of individuals (DR) were truly belastet. dress the nature of degeneracy or hereditary processes, they The mid 1910s saw the establishment of a novel kind of spoke quite generally of hereditary transmission, hereditary analysis of hereditary relations in German psychiatry. The particles (Darwin’s “gemmules”) or even accumulating he- limitations of simple Mendelian schemes were already reditary influences or “taint.” Disregarding religious- and becoming apparent, and psychiatrist Ernst Rüdin, greatly economic-related contexts, they did not yet use in any sys- assisted by Wilhelm Weinberg (better known today for the tematic fashion the term hereditary “load” or “burden.” Hardy-Weinberg equilibrium), developed innovative meth- Their German-speaking counterparts, however, did. The ods to assess the hereditary risk that the mentally ill posed term Belastung in German is translated as strain, load, or to their relatives (Weinberg 1912, 1913a,b, 1929; Rüdin burden. When accompanied by the adjective, erblich (hered- 1916; see also Just 1920; Crow 1999). The new statistical itary) this term was often used to refer to mentally ill indi- toolbox, which quickly acquired international recognition viduals in one’s family circle or community. Throughout the and some of whose results are considered robust to this nineteenth century, German psychiatrists made repeated at- day, was officially referred to under the heading, “empirical tempts to assess the relative significance of heredity in the hereditary prognosis” (Rüdin 1933), but was often labeled causation of mental abnormalities (see Gausemeier 2015). In simply as “statistics of load” (Belastungsstatistik). Different 1895, for example, an assistant at the Burghölzli psychiatric scholars published the results of their studies on the “load” clinic in Zurich by the name of Jenny Koller turned “heredi- of the “average population” with respect to various mental tary load” into her direct object of inquiry. Koller (1895) not disorders, and evaluated the chances that children, siblings, only offered a detailed analysis of the frequencies of different or even nephews or nieces of the mentally ill would mani- mental disorders in the families of 370 asylum patients, but fest mental deviances (Kattentidt 1926; Schulz 1927, 1931; also compared these results to a control group of (reportedly) Luxenburger 1928; Brugger 1929; Panse 1935). healthy individuals; this was a true methodological novelty at As in the case of the American eugenics movement, the the time. Ten years later, another scholar from the same in- underlying agenda informing these works was that families stitute, Otto Diem, published an additional massive study on with members displaying mental illnesses—and not only the the degree of Belastung of both mentally ill and healthy indi- mentally ill themselves—needed to be socially isolated and viduals. Diem (1905) stated with dissatisfaction that, “[i]t their reproduction stemmed. The calculation of morbidity has evolved into an actual dogma that hereditary load is risk for nephews and nieces of a disease sufferer (Schulz the most important cause of mental and nervous diseases.” 1926; Hoffmann 1928; Banse 1929; Walker 1929) were seen Diem’s own results indicated, ironically, that healthy individ- as an effective measure for deterring healthy individuals from uals were almost as hereditarily loaded as the ill. This latter marrying not only the mentally ill themselves, but also their fact, he thought, proved that mental problems might just as brothers and sisters. This research program became institu- well disappear; they could be inherited, but they did not have tionalized in Germany when in 1917, Rüdin was appointed to be. Therefore, he argued, hereditary load ceased to be a director of the Department of Genealogical and Demographic Damoclean sword which threatened any person who was un- Studies in the newly established German Institute for Psychi- fortunate enough to have a distant, mentally ill ancestor (Diem atric Research. The studies performed in Rüdin’s institute 1905, p. 216–218, 358–360). showed that morbidity risks for certain relatives of the men- The rise of Mendelian genetics introduced a new concept tally ill were often rather meager: for example, the morbidity that slightly altered the characterization of Belastung, namely, risks of nephews and nieces of schizophrenics ranged from the fact of recessivity. Early attempts to apply Mendelian 1.5 to 3.5%. Nevertheless, “according to the circumstance,

748 A. Teicher it is not the real [numbers] which should be the measure of contraction of pedigrees,” both “by omitting whole branches” the matter;” the key point to be considered, it was claimed, as well as by, “drawing together siblings with a single number was that the nephews’ and nieces’ figures were several times in their circle.” (MPG Archive, Dept. III Rep. 86B Nr. 3, Lenz to greater than the ones in the general population (Walker Verschuer, 30.12.31) This graphical reduction of information 1929, p. 120; similarly, Kattentidt 1926, p. 305). Through- was not part of a deliberate attempt to give exaggerated out the 1920s, German psychiatrists were therefore in- weight to the impact of heredity; the fact of omission was structed to advise their patients not to procreate, and also often either stated explicitly or otherwise disclosed. Obvi- to warn potential marriage partners not to marry into “sick” ously, no pedigree could contain all of the (infinite) genea- families, by conveying to their audiences the relative dangers, logical details about a person or a family; choices had to and not the absolute ones, to their future progeny. The com- be made, and they included giving minimal or no room for parison to a control group of healthy persons, which Diem data that was considered insignificant—in this case, data on had used to show that heredity was not as powerful as it healthy relatives. was previously thought, was now used for the exact opposite Still, the net effect of the condensing of data on healthy purpose—to boost the hereditary danger attributed to the family members was that the salience of the sick ones became mentally ill. heightened, and pedigrees became increasingly laden with ill persons. The impact was both visual and analytical. One psychiatrist admitted as early as 1908 that, “[w]hen looking Making the Load Palpable at pedigrees, one is always attracted to the black spots, be- While Belastung is a noun, the adjectives belastend (bestowing cause they make themselves noticeable in the most unpleas- Belastung, active voice) and belastet (receiving the Belastung— ant manner. Little or nothing at all is said on the healthy burdened/loaded, passive voice) convey the notion of a pro- elements” (Strohmayer 1908, p. 480). Furthermore, charts, cess. In pre-Mendelian literature, the active role was assigned once drawn, became autonomous reference points and evi- to belastenden Faktoren or Momenten, embodied in and made dence in and of themselves for the magnitude of heredity. For apparent through the sick relatives of the proband, who were example, the official commentary to the German sterilization responsible for making him belastet; though at the same time, law of July 1933 used several pedigrees to describe the he- a person could be belastet by his own mental illness. Follow- reditary nature of different hereditary defects, such as schizo- ing the Mendelian revolution, an individual could also be phrenia. The commentary authors did not try to hide the fact belastet if he (or she) was suspected of carrying a defective that only part of the familial data were represented; in one (recessive) hereditary factor; in such a case, the “burden” was caption they clearly stated that, “[o]nly the sick and the laid on the individual by his own genetic endowment. At the psychopaths, as well as the healthy [persons] linking them, same time, one ill person continued to make the entire clan are depicted.” This did not prevent the authors, however, into a loaded (belastet) one. from observing, “[o]neseesinallpedigreesthefullcon- Hereditary load also had an implied epidemic nature, tamination (Durchseuchung) of families with ill persons.” which found its clearest expression in the domain of diagram- (Gütt et al. 1933, p. 41, 43) When healthy persons were matic representation. While acknowledging that individual not drawn, such a contamination was not only visible—it pedigrees were not to be relied upon for the analysis of was inevitable, an artificial construct of the method of repre- hereditary patterns, “because each pedigree is only a partic- sentation itself. ular realization in the game of dice of heredity and in itself proves nothing,” (Rüdin 1916, p. III), psychiatrists neverthe- From Advice to Coercion: When Reducing Hereditary less continued to chart pedigrees for analytical, illustrative, Load Became Official State Policy documentation, communication, and propaganda purposes. The infectious nature of heredity was magnified due to cer- The notion of hereditary load was especially useful for pro- tain conventions relevant to the charting of such medical moting eugenic (or, in the case of Germany, “racial-hygienic”) pedigrees, particularly common among (but far from unique agendas because of its multiple connotations. For example, to) German psychiatrists. First, as one psychiatrist admitted, at the end of a talk given to the members of the Society “our chart includes, naturally, only the psychotic and psycho- of Gynecologists in Munich in 1930, psychiatrist Hans pathic members of the family with the necessary connecting Luxenburger exclaimed that, “[o]ur nation and the future of links” (Lange 1925, p. 330). In other words, it was custom- our culture cannot tolerate for long the present load (Belastung) ary to omit healthy individuals from pedigrees. In addition, of the mentally-ill.” The mentally ill individual was, “like a all the healthy siblings in a family were often depicted jointly parasite, draining strength from the financial and mental using a single denotation (circle/square) encompassing the powers of his surroundings, creating stress on the social number of such siblings, while at the same time each and and financial standards of his siblings.” According to Luxen- every “sick” sibling was denoted separately (e.g., Bateson burger, any measure that would check the procreation of the 1909; Goddard 1912; Tornow and Weinert 1942, and see mentally ill should be considered. “A radical eugenic measure Figure 1). Reviewing an article for publication, the eugeni- would therefore be a continuous, unmerciful hospitalization cist Fritz Lenz accordingly recommended “the substantial of all the hereditary mentally ill, eventually in big colonies,

The Troubled Past of Genetic Load 749 Figure 1 Pedigree of cataract. Healthy siblings are depicted using a single denotation with the number of siblings in the middle, leading to a visual over- loading of the pedigree with ill individuals. Source: Bateson 1909.

where they would build a state within state.” Such a measure Hence from January 1934, German citizens with mental or was rejected as unfeasible, due to the contemporary financial physical defects began to face hereditary tribunals that de- situation. Furthermore, a retreat to medieval techniques, cided whether or not they should be sterilized. Reducing the which, in the eyes of Luxenburger, resembled the practices overall (hereditary, economic, social, and national) burden of “certain Negro tribes” who send their mentally ill to an was the stated reason for the sterilization campaign, and the island in the hope that they would be eaten by crocodiles, Belastungsstatistics of Rüdin’s school supplied the scientific was inappropriate. “Even if our entire period suffers from the rational for the imperative of sterilization. According to cur- jabbering of humanitarianism (Humanitätsdudelei)... this rent estimates, hereditary courts discussed 436,000 cases humanitarianism is a degenerate child, but still a child of a between 1934 and 1945, and their decisions led to the great Ethos;” and so, therapy should be offered to the “de- sterilization of roughly 300,000 individuals (Benzenhöfer fective.” (Luxenburger 1930, esp. p. 242, 254). and Ackermann 2015). Furthermore, during World War II, Luxenburger’s repeated references to the financial aspects .70,000 mentally and physically handicapped were mur- of the problem of the mentally ill were far from exceptional. dered by starvation, lethal injections, and gassing in the Eugenic activists openly argued over the magnitude of the Nazi “euthanasia” program (Proctor 1988; Burleigh 1994). economic burden the weak laid upon society. A long discus- Although it was individuals who were sterilized and mur- sion held in 1932 at the Prussian Health Council revolved dered, in the view of eugenicists, the root of the problem of around the load placed on society by schizophrenics, the Belastung, the reason for the constantly growing burden, or feeble-minded, psychopaths, criminals, and alcoholics; its fi- what we may call the unit of selection, was not any specific nal result was a proposal for a voluntary sterilization law (Die individual, but those individuals’ malignant genetic compo- Eugenik im Dienste der Volkswohlfahrt 1932). nents. These were the source of burden, which doctors, psy- And so, the term Belastung proved to be useful for eugen- chiatrists, and eugenicists made it their goal to extinguish. In icists and policy-makers alike, precisely because it functioned an article on the meaning of the term, “hereditary load” pub- simultaneously at various levels of “biological” organization— lished in 1935, Luxenburger therefore stressed that, “it is not genetic, individual, familial, and communal—and in various the disease as such that burdens, but its hereditary basis, domains—economic, biological, social, and national. The fact not the phenotype, but the genotype, not the timely, tran- that Belastung simultaneously threatened the individual, his sitory, changeable, but the lasting, essentially constant, family,andthecommunityatlargealsomeantthatwhen- unchangeable. The trait, the disease, is only the indicator, ever prophylaxis was considered, it required intervention [whereas] the substance of the load is [hereditary] disposition.” on all three levels: that of the individual, the family, and (Luxenburger 1935) The corollary,according to Luxenburger, the entire people. The steps taken to reduce these multiple was that anyone carrying pathological recessive dispositions loads accelerated once Hitler assumed power, on January 30, was by definition, belastet. The fact that the sterilization law 1933. In July that year, the Law for the Prevention of Heredi- enabled the sterilization only of those who actually mani- tarily Diseased Offspring was passed. Two weeks prior to the fested diseases, but not of healthy carriers, was accordingly passing of the law, Interior Minister Wilhelm Frick stressed to a bemoaned by eugenicists (Gütt et al. 1936, p. 60). To ham- professional committee of eugenicists that, the “extremely per the transmission of recessive ailments, and to ensure the heavy load on our nation of taxes, social levies and payments” reproductive isolation of those deemed of lesser genetic necessitated that the burden of the “inferiors and anti-socials” value, healthy carriers of bad genes also had to abstain from be reduced (Frick 1933, p. 9–10; see also Helmut 1933, p. 29). procreating, and eugenicists hoped to achieve that end if not

750 A. Teicher by sterilization than through intensive public propaganda limit to this short of the complete loss of all of the genes or and marriage counseling. their degradation into utterly unrecognizable forms, differing chaotically from one individual of the population to another. Our descendants’ natural biological organization would in Muller’s 1950 “Our Load of Mutations” fact have disintegrated and have been replaced by complete How is all of this relevant to Muller’s 1950 “Our Load of disorder. Their only connections with mankind would then be Mutations?” According to the narrative favored by geneti- the historical one... it would in the end be far easier and cists, it isn’t. In the existing accounts (e.g., Brues 1969; more sensible to manufacture a complete man de novo... Crow 1970, 1992; Carlson 1981; Whitlock and Davis than to try to refashion into human form those pitiful relics 2011), Muller’s notion of “genetic load” stemmed, first and which remained.” (p. 146–147). foremost, from his concerns over the long-term hazards of In such a horrendous future world, the only way that those radiation. As Muller saw it, every mutant gene induced was who would have been “sure failures under primitive condi- effectively a time-bomb, or hidden mine, that could explode tions” could survive would be through continuous medical in later generations (Muller 1950, p. 168; Carlson 1981, care. Muller does not address directly the resulting accumu- chap. 22, 24), and Muller was relentless in calling for re- lating financial burden on society, although the point had straint in the use of X-rays, especially in the field of medicine, long been familiar to him. For example, in his 1932 talk on, where radiation diagnosis and therapy had been applied ex- “The Dominance of Economics over Eugenics,” he mentioned tensively. After winning the 1946 Nobel prize for his discov- the, “economic and psychological burden” that imbeciles laid ery of the effects of radiation on mutagenesis, Muller was in a on their fellow men, along with the burdens imposed on particularly favorable position to speak out, and be heard, on mothers wishing to bring up children. A better, socialist- these issues. Scientifically, Muller based his ideas on several oriented economic system, he then argued, could reduce the precedents: (1) C. H. Danforth’s (1923) address to the 2nd latter burden and allow for healthy families to foster larger International Congress of Eugenics, where it was shown that number of offspring (Muller 1933). In his 1950 paper he does the number of deleterious mutation of any given severity not refer to these elements directly, although he does intro- reaches an equilibrium in the population; (2) R. A. Fisher’s duce economic language by calling his contemporary gener- (1923, 1930) and J. B. S. Haldane’s (1927, 1937) works on ation a “debtor generation.” Present-day generations are the relations between mutations, selection and fitness; (3) debtors because they apply ameliorative practices, thus re- Muller’s (1927) own experiments and those of his student in ducing selection pressures and allowing mutant genes to Moscow, J. J. Kerkis, who demonstrated that X-rays caused an propagate and therefore “transfer to [their] descendants a increase in the number of detrimental (and not only lethal) price of detriment which the latter must eventually pay in mutations, as well as (4) the realization (argued forcefully full.” (Muller 1950, p. 147) Thus, with an abundance of also by S. G. Levit) of the partial dominance of disorder- inherited defects, in future generations, “instead of people’s causing mutations, formerly presumed to be completely re- time and energy being mainly spent in the struggle with ex- cessive. To judge by Muller’s own account, as well as by that ternal enemies...they would be devoted chiefly to the effort of his student and biographer, Elof A. Carlson, it was these to live carefully, to spare and to prop up their feebleness, to intellectual insights, coupled by his commitment to reducing sooth their inner disharmonies and, in general, to doctor the negative effects of radiation, that provided the back- themselves as effectively as possible. For everyone would ground and motivation for Muller’s analysis of “Our Load of be an invalid, with his own special familial twists.” (p. 146). Mutations.” Importantly, there was no doubt in Muller’s mind that Such a depiction, I argue, is partial at best. It marginalizes disorders were familial in nature (“familial twists”), because, Muller’s well-documented, life-long commitment to the eu- contrary to prior beliefs, mutant detrimental states were not genic cause. It also fails to note Muller’s later admission that completely recessive but partially dominant; they were also one of his goals in writing the paper was, indeed, to induce idiosyncratic in their effects. Taken together, their unique people to think eugenically (Paul 1987, p. 328). It therefore patterns of inheritance could be observed directly in certain overlooks the fact that Muller’s radiation anxieties, genuine families and differed from those characteristics in others; this as they were, also provided a socially acceptable context could indeed explain doctors’ experiences that pathologies through which he could convey his eugenic ideas to the tended to run in families (p. 169–170). Thus, Muller was able post-WWII world. Most importantly, however, the primary to adhere to an old principle of eugenic thinking—that of association of “Our Load of Mutations” with the fear of radi- “familial taint”—even within the larger framework of popu- ation and several prior writings on evolution ignores the con- lation genetics. tent of the 1950 paper itself, select parts of which will now be To face the genetic challenge, Muller suggested that those highlighted. of poorer genetic quality would cease to reproduce, and, According to Muller (1950), the relaxation of natural se- possibly, those with better mental talents gain priority in lection in modern society would “ultimately lead to an ever reproduction (the latter point was only hinted at in his greater heaping up of mutant genes.” His description of the 1950 paper, and made much more forcefully in other works, consequences is worth quoting at length: “There would be no see below). Muller nevertheless insisted that such a solution

The Troubled Past of Genetic Load 751 must be voluntary: “not by means of decrees and orders from premises: the fear of looming degeneration, the familial na- authorities, but through the freely exercised volition of the ture of (mental) diseases, the criticism of inadequacy of the individuals concerned, guided by their recognition of the sit- prevailing moral values, and the need to visualize and dra- uation and motivated by their own desire to contribute to the matize the results of genetic studies. human benefit in the ways most effective for them” (p. 150). Muller maintained these views also in later years. In a In the hoped-for regime of, “intelligently directed selection... 1961 paper in Science, as part of his attempt to promote his individuals having the largest number of mutant genes are “genius sperm-bank” initiative, he lamented the fact that, systematically chosen for elimination.” (Elimination here “the term eugenics has been in such disrepute... that few seems like an unfortunate slip of the pen; what Muller meant responsible students of evolution or genetics have dared to was the elimination of reproduction, not of the individuals contaminate themselves by mentioning it.” (Muller 1961, themselves). (p. 152) p. 643) Muller’s frustration was evident throughout the pa- Muller therefore intended that “the most heavily loaded per; he remarked that “nonconformists [like himself] may at fraction” of the population would voluntarily cease to repro- times have moral standards superior, in a longer perspective, duce. What specific kind of load was he referring to? Contrary to those of the majority who condemn them.” And he fanta- to what could have been understood throughout most of his sized about a society where the gifted would be encouraged— paper, toward the conclusion Muller conceded that his pri- and receive state aid for that purpose—to raise more children, mary concern was not physical or physiological disabilities, whereas “persons less well-endowed [would] choose, of their but mental ones. Muller wanted to see an increased breeding own accord, situations in life that would encourage them to of those with “greater intellectual capacity, and along with it expend their energies in other pursuits than reproduction.” kindlier natural feelings,” both of which were genetically (p. 645). True, Muller vehemently opposed, and publicly grounded and were “the greatest biological needs of all hu- denounced, Nazi eugenics, as well as the American eugenic manity.” Unfortunately, also with relation to these traits, movement, for their racism, crudity, and compulsory nature. “there is reason to conclude that selection has greatly relaxed He advocated social and economic equality as necessary pre- under modern conditions” (p. 165; Muller did not substan- conditions for any attempt to voluntarily apply eugenic mea- tiate this statement with any reference). sures. But he never truly gave up his hopes to refashion society But how could those with reduced intellect and inferior along genetic principles; as he saw it, “the odious perversions moral genetic endowment be led to cease their own repro- of the subject should not blind us longer to a set of hard duction of their own free will? Why would the less-perceptive truths... that cannot be permanently ignored or denied with- and less-caring persons sacrifice their reproductive capacities out ultimate disaster.” (Muller 1961, p. 643) for the benefit of their fellow citizens? Muller’s answer was that, “for the voluntary adoption by people in general of a From “Our Load of Mutations” to the Present course of such wisdom, and so different from that now fol- lowed, a deep-seated change in mores would be necessary.” Although Muller introduced (into English, at least) the term (p. 150) It was the geneticists’ duty to show the way, and “genetic load,” he did not strictly define it, mathematically or they should, “be prepared for a long uphill struggle.” The task otherwise. He also fluctuated freely between the terms “load” was a daunting one because the average man “will be in- and “burden” as well as between genetic, phenotypic, muta- clined to give priority to his immediate concerns, the interests tional, and individual loads. All of these issues were picked of which will often (at least under existing mores) run up by his followers and opponents, who thoroughly explored counter to those of the seemingly immaterial abstractions the term’s various mathematical and experimental implica- conjured up by the geneticist.” Therefore, only, “after the tions. Genetic load was defined by James F. Crow (1958) as processes and consequences of genetic change throughout the proportional decrease in the mean fitness of a population, the ages have been vividly visualized and dramatized for compared to an ideal, optimal genotype. Furthermore, differ- people in general from their early years on through their later ent types of genetic load were defined and studied, such as developments, can we expect the arguments, calculations mutation load, segregation/balanced load, recombination-, and recommendations of geneticists to take on sufficiently maternal-fetal incompatibility-, migration-, substitutional-, concrete meaning for the average man.” (p. 163). and drift-load (see a useful summary in Crow 1970). Thus, We do not know if Muller was familiar with the German throughout the two decades that followed the publication of term Belastung, even though, given his acquaintance with Muller’s paper, genetic load became, “a major preoccupation some of its most vocal protagonists (including Ernst Rüdin, of population geneticists” (Wallace 1970, p. vii). whom he met and heard in eugenic conferences), his deep These scientific developments led to a substantial change interest in eugenics [“the leitmotif of Muller’s life,” as his in the meaning and connotations of the term itself. In some of biographer aptly put it; see Carlson (1981), p. 393], and the newly defined “loads,” novel mutations and their hetero- his perfect control of the German language, it seems most zygous carriers were characterized as having higher fitness unlikely that he never encountered the term one way or the than the original, wild-type homozygotes. Consequently, ge- other. But even if Muller did not know the German concept of netic load gradually evolved from an inherently negative Belastung, it is apparent that he shared its underlying eugenic concept to a neutral one and even to include a beneficial

752 A. Teicher component and aspect—indeed, a “sine qua non for evolu- the status of a given population at a given moment nor in tion,” as had been suggested by Haldane already in 1937 predicting its future” (Wallace 1968, p. 267–280). (Haldane 1937; Crow 1970, p. 173). This neutral, or even Measured against these developments from the 1950s and beneficial, understanding of “load” sounded paradoxical: the 1960s, Michael Lynch’s recently published concerns (2016a) choice of terminology itself no longer seemed appropriate. about “Our Future Genetic Load” may be considered a step “In view of the normal connotations of “load” another word backward, if only for its directing the concept of load back to might have been more apt,” commented George R. Fraser in its earlier, exclusively negative, eugenically laden, meaning. 1962 (Fraser 1962, p. 387); similarly, in 1969, physical an- Lynch evaluates current findings on deleterious genetic mu- thropology professor Alice M. Brues noted that, “[i]t would tations to reach a dim conclusion on the ultimate effects of seem advisable, in the interests of good sense and adequate reducing selection pressures. Worried about the future of the communication, that... the vernacular words should be human gene pool, he sees it as his duty to “to highlight the replaced by obviously specialized ones which will mislead fact that long-term, population-genetic issues merit recogni- no one into believing that he understands their meaning tion and discussion” (Lynch 2016b, p. 826). Like Muller’s when in fact he does not.” She suggested “viability polymor- questioning of the “existing mores,” Lynch also wants us to phism” as an alternative (Brues 1969). rethink “today’s ethical imperative for maximizing individual But as Crow wrote in 1970, “[a]lthough it might have been reproductive potential and longevity independent of genetic better to choose a word with fewer emotional overtones, it background” (Lynch 2016a, p. 869). The basic contours of has now become too widely used to change” (Crow 1970, Lynch’s argument are also not very different from those of p. 173). Interestingly, Crow’s view that the term could not Muller and earlier eugenicists (relaxation of natural selection + be replaced fit comfortably with his position in what was then deficient ethical principles that prevent us from addressing called the classical/balance controversy. On the “classical” the problem = inevitable, catastrophic future degeneration). side of the debate were those, like Muller and Crow, who If, however, we wish to promote a fruitful discussion on “our assumed there was usually one optimal allele for any given future genetic load,” we must not content ourselves with locus and that, by favoring this allele over all others, selection looking straight at the genetic prospects of the future; we produced uniformity and homozygosity. The “balance” camp, must take into consideration also the human realities of the led by Theodosius Dobzhansky and Bruce Wallace, argued not-so-recent past. For that purpose, in addition to arguing that selection actually favored versatility, hence heterozygos- over the validity of some of Lynch’s claims (Roth and Wakeley ity, a view which became all the more plausible with the 2016; Lynch 2016b), some historical perspective is appropri- growing evidence of great amounts of neutral and nearly ate. As shown above, preoccupation with genetic load did not neutral mutations in genomes (Lewontin 1974; Beatty 1987). begin in 1950 and as a result of atomic-energy related anxi- The controversy reflected directly on the notion of load. Thus eties, but had deep pre-1945 eugenic roots, meanings, con- unlike Crow, Dobzhansky and Wallace not only debated dif- notations and implications. To evaluate the potential damage ferent parts of the theory of genetic load but also repeatedly of genetic load, these, too, must be acknowledged. protested the terminology itself, which implied variation to be itself a burden (Paul 1987, p. 328–329). Acknowledgments Throughout this debate, “genetic load” altered many of its earlier meanings. The concept of load as used in German and I thank Eva Jablonka, Snait Gissis, Adam Wilkins, Sarah eugenic literature and, to some extent, also in Muller’s paper, Mandel, and four anonymous reviewers for their instructive characterized individuals and families within society and the criticism on earlier drafts of this paper. dangers that they constituted to their own progeny, relatives, and society; it referred directly and specifically to phenotypes defined as harmful to one’s own health and social surrounding; Literature Cited and it was linked with higher reproduction rates—often, it was fi Banse, J., 1929 Zum problem der Erbprognosebestimmung. 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As stated above, accord- und der Sterilisationen nach der Gesetz zur Verhütung erbkranken ing to this conception, load was not necessarily harmful. Nachwuchses. Kontur, Münster. At least for those who belonged to the “balance” camp, like Brues, A. M., 1969 Genetic load and its varieties. Science 164: 1130–1136. https://doi.org/10.1126/science.164.3884.1130 Wallace, genetic load was a poor measure for ascertaining the Brugger, C., 1929 Zur Frage einer Belastungsstatistik der well-being of a population, not correlated with lower fitness, Durchschnittsbevölkerung. Z. gesamte Neurol. Psychiatr. 118: and, generally speaking, “not...particularly useful in pondering 459–488. https://doi.org/10.1007/BF02892924

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