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.

Origins of the Concept of Hereditary Load

“[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 became institutionalized in Germany when in 1917, Rüdin was appointed director of the Department of Genealogical and Demographic Studies in the newly established German Institute for Psychiatric Research. The studies performed in Rüdin’s institute showed that morbidity risks for certain relatives of the mentally ill were often rather meager: for example, the morbidity risks of nephews and nieces of schizophrenics ranged from ∼1.5 to 3.5%. Nevertheless, “according to the circumstance, it is not the real [numbers] which should be the measure of the matter;” the key point to be considered, it was claimed, was that the nephews’ and nieces’ figures were several times greater than the ones in the general population (Walker 1929, p. 120; similarly, Kattentidt 1926, p. 305). Throughout the 1920s, German psychiatrists were therefore instructed to advise their patients not to procreate, and also to warn potential marriage partners not to marry into “sick” families, by conveying to their audiences the relative dangers, and not the absolute ones, to their future progeny. The comparison to a control group of healthy persons, which Diem had used to show that heredity was not as powerful as it was previously thought, was now used for the exact opposite purpose—to boost the hereditary danger attributed to the mentally ill.

Making the Load Palpable

While Belastung is a noun, the adjectives belastend (bestowing Belastung, active voice) and belastet (receiving the Belastung—burdened/loaded, passive voice) convey the notion of a process. In pre-Mendelian literature, the active role was assigned to belastenden Faktoren or Momenten, embodied in and made apparent through the sick relatives of the proband, who were responsible for making him belastet; though at the same time, a person could be belastet by his own mental illness. Following the Mendelian revolution, an individual could also be belastet if he (or she) was suspected of carrying a defective (recessive) hereditary factor; in such a case, the “burden” was laid on the individual by his own genetic endowment. At the same time, one ill person continued to make the entire clan into a loaded (belastet) one.

Hereditary load also had an implied epidemic nature, which found its clearest expression in the domain of diagrammatic representation. While acknowledging that individual pedigrees were not to be relied upon for the analysis of hereditary patterns, “because each pedigree is only a particular realization in the game of dice of heredity and in itself proves nothing,” (Rüdin 1916, p. III), psychiatrists nevertheless continued to chart pedigrees for analytical, illustrative, documentation, communication, and propaganda purposes. The infectious nature of heredity was magnified due to certain conventions relevant to the charting of such medical pedigrees, particularly common among (but far from unique to) German psychiatrists. First, as one psychiatrist admitted, “our chart includes, naturally, only the psychotic and psychopathic members of the family with the necessary connecting links” (Lange 1925, p. 330). In other words, it was customary to omit healthy individuals from pedigrees. In addition, all the healthy siblings in a family were often depicted jointly using a single denotation (circle/square) encompassing the number of such siblings, while at the same time each and every “sick” sibling was denoted separately (e.g., Bateson 1909; Goddard 1912; Tornow and Weinert 1942, and see Figure 1). Reviewing an article for publication, the eugenicist Fritz Lenz accordingly recommended “the substantial contraction of pedigrees,” both “by omitting whole branches” as well as by, “drawing together siblings with a single number in their circle.” (MPG Archive, Dept. III Rep. 86B Nr. 3, Lenz to Verschuer, 30.12.31) This graphical reduction of information was not part of a deliberate attempt to give exaggerated weight to the impact of heredity; the fact of omission was often either stated explicitly or otherwise disclosed. Obviously, no pedigree could contain all of the (infinite) genealogical details about a person or a family; choices had to be made, and they included giving minimal or no room for data that was considered insignificant—in this case, data on healthy relatives.

Still, the net effect of the condensing of data on healthy family members was that the salience of the sick ones became 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 at pedigrees, one is always attracted to the black spots, because they make themselves noticeable in the most unpleasant manner. Little or nothing at all is said on the healthy elements” (Strohmayer 1908, p. 480). Furthermore, charts, once drawn, became autonomous reference points and evidence in and of themselves for the magnitude of heredity. For example, the official commentary to the German sterilization law of July 1933 used several pedigrees to describe the hereditary nature of different hereditary defects, such as schizophrenia. The commentary authors did not try to hide the fact that only part of the familial data were represented; in one caption they clearly stated that, “[o]nly the sick and the psychopaths, as well as the healthy [persons] linking them, are depicted.” This did not prevent the authors, however, from observing, “[o]ne sees in all pedigrees the full contamination (Durchseuchung) of families with ill persons.” (Gütt et al. 1933, p. 41, 43) When healthy persons were not drawn, such a contamination was not only visible—it was inevitable, an artificial construct of the method of representation itself.

From Advice to Coercion: When Reducing Hereditary Load Became Official State Policy

The notion of hereditary load was especially useful for promoting eugenic (or, in the case of Germany, “racial-hygienic”) agendas because of its multiple connotations. For example, at the end of a talk given to the members of the Society of Gynecologists in Munich in 1930, psychiatrist Hans Luxenburger exclaimed that, “[o]ur nation and the future of our culture cannot tolerate for long the present load (Belastung) of the mentally-ill.” The mentally ill individual was, “like a parasite, draining strength from the financial and mental powers of his surroundings, creating stress on the social and financial standards of his siblings.” According to Luxenburger, any measure that would check the procreation of the mentally ill should be considered. “A radical eugenic measure would therefore be a continuous, unmerciful hospitalization of all the hereditary mentally ill, eventually in big colonies, where they would build a state within state.” Such a measure was rejected as unfeasible, due to the contemporary financial situation. Furthermore, a retreat to medieval techniques, which, in the eyes of Luxenburger, resembled the practices of “certain Negro tribes” who send their mentally ill to an island in the hope that they would be eaten by crocodiles, was inappropriate. “Even if our entire period suffers from the jabbering of humanitarianism (Humanitätsdudelei)… this humanitarianism is a degenerate child, but still a child of a great Ethos;” and so, therapy should be offered to the “defective.” (Luxenburger 1930, esp. p. 242, 254).

Luxenburger’s repeated references to the financial aspects of the problem of the mentally ill were far from exceptional. Eugenic activists openly argued over the magnitude of the economic burden the weak laid upon society. A long discussion held in 1932 at the Prussian Health Council revolved around the load placed on society by schizophrenics, the feeble-minded, psychopaths, criminals, and alcoholics; its final result was a proposal for a voluntary sterilization law (Die Eugenik im Dienste der Volkswohlfahrt 1932).

And so, the term Belastung proved to be useful for eugenicists and policy-makers alike, precisely because it functioned simultaneously at various levels of “biological” organization—genetic, individual, familial, and communal—and in various domains—economic, biological, social, and national. The fact that Belastung simultaneously threatened the individual, his family, and the community at large also meant that whenever prophylaxis was considered, it required intervention on all three levels: that of the individual, the family, and the entire people. The steps taken to reduce these multiple loads accelerated once Hitler assumed power, on January 30, 1933. In July that year, the Law for the Prevention of Hereditarily Diseased Offspring was passed. Two weeks prior to the passing of the law, Interior Minister Wilhelm Frick stressed to a professional committee of eugenicists that, the “extremely heavy load on our nation of taxes, social levies and payments” necessitated that the burden of the “inferiors and anti-socials” be reduced (Frick 1933, p. 9–10; see also Helmut 1933, p. 29). Hence from January 1934, German citizens with mental or physical defects began to face hereditary tribunals that decided whether or not they should be sterilized. Reducing the overall (hereditary, economic, social, and national) burden was the stated reason for the sterilization campaign, and the Belastungsstatistics of Rüdin’s school supplied the scientific rational for the imperative of sterilization. According to current estimates, hereditary courts discussed ∼436,000 cases between 1934 and 1945, and their decisions led to the sterilization of roughly 300,000 individuals (Benzenhöfer and Ackermann 2015). Furthermore, during World War II, >70,000 mentally and physically handicapped were murdered by starvation, lethal injections, and gassing in the Nazi “euthanasia” program (Proctor 1988; Burleigh 1994).

Although it was individuals who were sterilized and murdered, in the view of eugenicists, the root of the problem of Belastung, the reason for the constantly growing burden, or what we may call the unit of selection, was not any specific individual, but those individuals’ malignant genetic components. These were the source of burden, which doctors, psychiatrists, and eugenicists made it their goal to extinguish. In an article on the meaning of the term, “hereditary load” published in 1935, Luxenburger therefore stressed that, “it is not the disease as such that burdens, but its hereditary basis, not the phenotype, but the genotype, not the timely, transitory, changeable, but the lasting, essentially constant, unchangeable. The trait, the disease, is only the indicator, [whereas] the substance of the load is [hereditary] disposition.” (Luxenburger 1935) The corollary, according to Luxenburger, was that anyone carrying pathological recessive dispositions was by definition, belastet. The fact that the sterilization law enabled the sterilization only of those who actually manifested diseases, but not of healthy carriers, was accordingly bemoaned by eugenicists (Gütt et al. 1936, p. 60). To hamper the transmission of recessive ailments, and to ensure the reproductive isolation of those deemed of lesser genetic value, healthy carriers of bad genes also had to abstain from procreating, and eugenicists hoped to achieve that end if not by sterilization than through intensive public propaganda and marriage counseling.

Muller’s 1950 “Our Load of Mutations”

How is all of this relevant to Muller’s 1950 “Our Load of Mutations?” According to the narrative favored by geneticists, it isn’t. In the existing accounts (e.g., Brues 1969; Crow 1970, 1992; Carlson 1981; Whitlock and Davis 2011), Muller’s notion of “genetic load” stemmed, first and foremost, from his concerns over the long-term hazards of radiation. As Muller saw it, every mutant gene induced was effectively a time-bomb, or hidden mine, that could explode in later generations (Muller 1950, p. 168; Carlson 1981, chap. 22, 24), and Muller was relentless in calling for restraint in the use of X-rays, especially in the field of medicine, where radiation diagnosis and therapy had been applied extensively. After winning the 1946 Nobel prize for his discovery of the effects of radiation on mutagenesis, Muller was in a particularly favorable position to speak out, and be heard, on these issues. Scientifically, Muller based his ideas on several precedents: (1) C. H. Danforth’s (1923) address to the 2nd International Congress of Eugenics, where it was shown that the number of deleterious mutation of any given severity reaches an equilibrium in the population; (2) R. A. Fisher’s (1923, 1930) and J. B. S. Haldane’s (1927, 1937) works on the relations between mutations, selection and fitness; (3) Muller’s (1927) own experiments and those of his student in Moscow, J. J. Kerkis, who demonstrated that X-rays caused an increase in the number of detrimental (and not only lethal) mutations, as well as (4) the realization (argued forcefully also by S. G. Levit) of the partial dominance of disorder-causing mutations, formerly presumed to be completely recessive. To judge by Muller’s own account, as well as by that of his student and biographer, Elof A. Carlson, it was these intellectual insights, coupled by his commitment to reducing the negative effects of radiation, that provided the background and motivation for Muller’s analysis of “Our Load of Mutations.”

Such a depiction, I argue, is partial at best. It marginalizes Muller’s well-documented, life-long commitment to the eugenic cause. It also fails to note Muller’s later admission that one of his goals in writing the paper was, indeed, to induce people to think eugenically (Paul 1987, p. 328). It therefore overlooks the fact that Muller’s radiation anxieties, genuine as they were, also provided a socially acceptable context through which he could convey his eugenic ideas to the post-WWII world. Most importantly, however, the primary association of “Our Load of Mutations” with the fear of radiation and several prior writings on evolution ignores the content of the 1950 paper itself, select parts of which will now be highlighted.

According to Muller (1950), the relaxation of natural selection in modern society would “ultimately lead to an ever greater heaping up of mutant genes.” His description of the consequences is worth quoting at length: “There would be no limit to this short of the complete loss of all of the genes or their degradation into utterly unrecognizable forms, differing chaotically from one individual of the population to another. Our descendants’ natural biological organization would in fact have disintegrated and have been replaced by complete disorder. Their only connections with mankind would then be the historical one… it would in the end be far easier and more sensible to manufacture a complete man de novo… than to try to refashion into human form those pitiful relics which remained.” (p. 146–147).

In such a horrendous future world, the only way that those who would have been “sure failures under primitive conditions” could survive would be through continuous medical care. Muller does not address directly the resulting accumulating financial burden on society, although the point had long been familiar to him. For example, in his 1932 talk on, “The Dominance of Economics over Eugenics,” he mentioned the, “economic and psychological burden” that imbeciles laid on their fellow men, along with the burdens imposed on mothers wishing to bring up children. A better, socialist-oriented economic system, he then argued, could reduce the latter burden and allow for healthy families to foster larger number of offspring (Muller 1933). In his 1950 paper he does not refer to these elements directly, although he does introduce economic language by calling his contemporary generation a “debtor generation.” Present-day generations are debtors because they apply ameliorative practices, thus reducing selection pressures and allowing mutant genes to propagate and therefore “transfer to [their] descendants a price of detriment which the latter must eventually pay in full.” (Muller 1950, p. 147) Thus, with an abundance of inherited defects, in future generations, “instead of people’s time and energy being mainly spent in the struggle with external enemies… they would be devoted chiefly to the effort to live carefully, to spare and to prop up their feebleness, to sooth their inner disharmonies and, in general, to doctor themselves as effectively as possible. For everyone would be an invalid, with his own special familial twists.” (p. 146).

Importantly, there was no doubt in Muller’s mind that disorders were familial in nature (“familial twists”), because, contrary to prior beliefs, mutant detrimental states were not completely recessive but partially dominant; they were also idiosyncratic in their effects. Taken together, their unique patterns of inheritance could be observed directly in certain families and differed from those characteristics in others; this could indeed explain doctors’ experiences that pathologies tended to run in families (p. 169–170). Thus, Muller was able to adhere to an old principle of eugenic thinking—that of “familial taint”—even within the larger framework of population genetics.

To face the genetic challenge, Muller suggested that those of poorer genetic quality would cease to reproduce, and, possibly, those with better mental talents gain priority in reproduction (the latter point was only hinted at in his 1950 paper, and made much more forcefully in other works, see below). Muller nevertheless insisted that such a solution must be voluntary: “not by means of decrees and orders from authorities, but through the freely exercised volition of the individuals concerned, guided by their recognition of the situation and motivated by their own desire to contribute to the human benefit in the ways most effective for them” (p. 150). In the hoped-for regime of, “intelligently directed selection… individuals having the largest number of mutant genes are systematically chosen for elimination.” (Elimination here seems like an unfortunate slip of the pen; what Muller meant was the elimination of reproduction, not of the individuals themselves). (p. 152)

Muller therefore intended that “the most heavily loaded fraction” of the population would voluntarily cease to reproduce. What specific kind of load was he referring to? Contrary to what could have been understood throughout most of his paper, toward the conclusion Muller conceded that his primary concern was not physical or physiological disabilities, but mental ones. Muller wanted to see an increased breeding of those with “greater intellectual capacity, and along with it kindlier natural feelings,” both of which were genetically grounded and were “the greatest biological needs of all humanity.” Unfortunately, also with relation to these traits, “there is reason to conclude that selection has greatly relaxed under modern conditions” (p. 165; Muller did not substantiate this statement with any reference).

But how could those with reduced intellect and inferior moral genetic endowment be led to cease their own reproduction of their own free will? Why would the less-perceptive and less-caring persons sacrifice their reproductive capacities for the benefit of their fellow citizens? Muller’s answer was that, “for the voluntary adoption by people in general of a course of such wisdom, and so different from that now followed, a deep-seated change in mores would be necessary.” (p. 150) It was the geneticists’ duty to show the way, and they should, “be prepared for a long uphill struggle.” The task was a daunting one because the average man “will be inclined to give priority to his immediate concerns, the interests of which will often (at least under existing mores) run counter to those of the seemingly immaterial abstractions conjured up by the geneticist.” Therefore, only, “after the processes and consequences of genetic change throughout the ages have been vividly visualized and dramatized for people in general from their early years on through their later developments, can we expect the arguments, calculations and recommendations of geneticists to take on sufficiently concrete meaning for the average man.” (p. 163).

We do not know if Muller was familiar with the German term Belastung, even though, given his acquaintance with some of its most vocal protagonists (including Ernst Rüdin, whom he met and heard in eugenic conferences), his deep interest in eugenics [“the leitmotif of Muller’s life,” as his biographer aptly put it; see Carlson (1981), p. 393], and his perfect control of the German language, it seems most unlikely that he never encountered the term one way or the other. But even if Muller did not know the German concept of Belastung, it is apparent that he shared its underlying eugenic premises: the fear of looming degeneration, the familial nature of (mental) diseases, the criticism of inadequacy of the prevailing moral values, and the need to visualize and dramatize the results of genetic studies.

Muller maintained these views also in later years. In a 1961 paper in Science, as part of his attempt to promote his “genius sperm-bank” initiative, he lamented the fact that, “the term eugenics has been in such disrepute… that few responsible students of evolution or genetics have dared to contaminate themselves by mentioning it.” (Muller 1961, p. 643) Muller’s frustration was evident throughout the paper; he remarked that “nonconformists [like himself] may at times have moral standards superior, in a longer perspective, to those of the majority who condemn them.” And he fantasized about a society where the gifted would be encouraged—and receive state aid for that purpose—to raise more children, whereas “persons less well-endowed [would] choose, of their own accord, situations in life that would encourage them to expend their energies in other pursuits than reproduction.” (p. 645). True, Muller vehemently opposed, and publicly denounced, Nazi eugenics, as well as the American eugenic movement, for their racism, crudity, and compulsory nature. He advocated social and economic equality as necessary preconditions for any attempt to voluntarily apply eugenic measures. But he never truly gave up his hopes to refashion society along genetic principles; as he saw it, “the odious perversions of the subject should not blind us longer to a set of hard truths… that cannot be permanently ignored or denied without ultimate disaster.” (Muller 1961, p. 643)

From “Our Load of Mutations” to the Present

Although Muller introduced (into English, at least) the term “genetic load,” he did not strictly define it, mathematically or otherwise. He also fluctuated freely between the terms “load” and “burden” as well as between genetic, phenotypic, mutational, and individual loads. All of these issues were picked up by his followers and opponents, who thoroughly explored the term’s various mathematical and experimental implications. Genetic load was defined by James F. Crow (1958) as the proportional decrease in the mean fitness of a population, compared to an ideal, optimal genotype. Furthermore, different types of genetic load were defined and studied, such as mutation load, segregation/balanced load, recombination-, maternal-fetal incompatibility-, migration-, substitutional-, and drift-load (see a useful summary in Crow 1970). Thus, throughout the two decades that followed the publication of Muller’s paper, genetic load became, “a major preoccupation of population geneticists” (Wallace 1970, p. vii).

These scientific developments led to a substantial change in the meaning and connotations of the term itself. In some of the newly defined “loads,” novel mutations and their heterozygous carriers were characterized as having higher fitness than the original, wild-type homozygotes. Consequently, genetic load gradually evolved from an inherently negative concept to a neutral one and even to include a beneficial component and aspect—indeed, a “sine qua non for evolution,” as had been suggested by Haldane already in 1937 (Haldane 1937; Crow 1970, p. 173). This neutral, or even beneficial, understanding of “load” sounded paradoxical: the choice of terminology itself no longer seemed appropriate. “In view of the normal connotations of “load” another word might have been more apt,” commented George R. Fraser in 1962 (Fraser 1962, p. 387); similarly, in 1969, physical anthropology professor Alice M. Brues noted that, “[i]t would seem advisable, in the interests of good sense and adequate communication, that… the vernacular words should be replaced by obviously specialized ones which will mislead no one into believing that he understands their meaning when in fact he does not.” She suggested “viability polymorphism” as an alternative (Brues 1969).

But as Crow wrote in 1970, “[a]lthough it might have been better to choose a word with fewer emotional overtones, it has now become too widely used to change” (Crow 1970, p. 173). Interestingly, Crow’s view that the term could not be replaced fit comfortably with his position in what was then called the classical/balance controversy. On the “classical” side of the debate were those, like Muller and Crow, who assumed there was usually one optimal allele for any given locus and that, by favoring this allele over all others, selection produced uniformity and homozygosity. The “balance” camp, led by Theodosius Dobzhansky and Bruce Wallace, argued that selection actually favored versatility, hence heterozygosity, a view which became all the more plausible with the growing evidence of great amounts of neutral and nearly neutral mutations in genomes (Lewontin 1974; Beatty 1987). The controversy reflected directly on the notion of load. Thus unlike Crow, Dobzhansky and Wallace not only debated different parts of the theory of genetic load but also repeatedly protested the terminology itself, which implied variation to be itself a burden (Paul 1987, p. 328–329).

Throughout this debate, “genetic load” altered many of its earlier meanings. The concept of load as used in German and eugenic literature and, to some extent, also in Muller’s paper, characterized individuals and families within society and the 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; and it was linked with higher reproduction rates—often, it was precisely the fact that the mentally infirm purportedly produced more children than the “valuable” citizens that stressed the dreadfulness associated with their load. In its new form, the concept of load was theoretical at base, used mainly to devise population-genetic models for changes in frequencies of genotypes (and not phenotypes), disassociated from actual individuals or diseases, and almost by definition linked with reduced reproduction rate, or fitness. As stated above, according to this conception, load was not necessarily harmful. At least for those who belonged to the “balance” camp, like Wallace, genetic load was a poor measure for ascertaining the well-being of a population, not correlated with lower fitness, and, generally speaking, “not… particularly useful in pondering the status of a given population at a given moment nor in predicting its future” (Wallace 1968, p. 267–280).

Measured against these developments from the 1950s and 1960s, Michael Lynch’s recently published concerns (2016a) about “Our Future Genetic Load” may be considered a step backward, if only for its directing the concept of load back to its earlier, exclusively negative, eugenically laden, meaning. Lynch evaluates current findings on deleterious genetic mutations to reach a dim conclusion on the ultimate effects of reducing selection pressures. Worried about the future of the human gene pool, he sees it as his duty to “to highlight the fact that long-term, population-genetic issues merit recognition and discussion” (Lynch 2016b, p. 826). Like Muller’s questioning of the “existing mores,” Lynch also wants us to rethink “today’s ethical imperative for maximizing individual reproductive potential and longevity independent of genetic background” (Lynch 2016a, p. 869). The basic contours of Lynch’s argument are also not very different from those of Muller and earlier eugenicists (relaxation of natural selection + deficient ethical principles that prevent us from addressing the problem = inevitable, catastrophic future degeneration). If, however, we wish to promote a fruitful discussion on “our future genetic load,” we must not content ourselves with looking straight at the genetic prospects of the future; we must take into consideration also the human realities of the not-so-recent past. For that purpose, in addition to arguing over the validity of some of Lynch’s claims (Roth and Wakeley 2016; Lynch 2016b), some historical perspective is appropriate. As shown above, preoccupation with genetic load did not begin in 1950 and as a result of atomic-energy related anxieties, but had deep pre-1945 eugenic roots, meanings, connotations and implications. To evaluate the potential damage of genetic load, these, too, must be acknowledged.

Acknowledgments

I thank Eva Jablonka, Snait Gissis, Adam Wilkins, Sarah Mandel, and four anonymous reviewers for their instructive criticism on earlier drafts of this paper.

Footnotes

Literature Cited