Introduction to “The Beginnings of Systematic Studies of the Genetics of Schizophrenia: 1916–1933”

We here want to introduce this special issue of Schizophrenia Bulletin by providing some background about the history of psychiatric genetics before 1910, the choice of the 5 papers here examined, the methodology we used in writing these papers, the relevance for contemporary psychiatric genetics and a background on our approach to the relationship of the authors of these papers to the eugenic, racist policies of the German National Socialists that led to the large-scale involuntary sterilization of the mentally ill, and the K-4 program of wide-scale murder of mentally ill and handicapped children and adults and the Holocaust. We recommend that interested individuals read the 5 papers in order as this will help them see the historical progression of the methods and results in this early phase of psychiatric genetics research. To appreciate the papers reviewed in this special issue, it is helpful to understand the status of the field of psychiatric genetics circa 1910, before the first important papers based on the rediscovery of Mendel’s work in 1900. K.S.K. has recently written a review paper covering this literature “The Pre-History of Psychiatric Genetics: 1780-1910”,1 which can be consulted by readers interested in this topic. Briefly, in the 19th century, far and away the most common data point used in the psychiatric genetic investigation was a statement in an asylum record of the presence or absence of a “hereditary burden” for the patient, a term broadly congruent with what we might now call a “positive family history.” However, its use was complicated by the fact that across different hospitals, different groups of relatives were included (eg, direct ancestors only, eg, parents and grandparents or direct + collateral including aunts/uncles and potentially siblings), and different conditions were considered as affected (narrowly defined insanity, more broadly defined mental illness, alcoholism, eccentricities, epilepsy, etc.). Few of these relatives were ever personally examined by the alienist recording this information. Common topics of interest at that time included the relationship between a heredity burden and the sex of the patient, the recurrence of episodes of insanity, and the degree of homogeneity versus heterogeneity of transmission of mental illnesses in families.1,2 No formal theories of hereditary transmission were ever examined as the first detailed application of both the biometrical school of Galton and Pearson and Mendelian theory to insanity were not published until the first and second decades of the 20th century.3–8 We selected 5 papers for translation and commentary, all of which are of substantial historical import in the history of genetic studies of dementia praecox (schizophrenia). Each came from individuals working at, or collaborating with, the Genealogic-Demographic Department at the German Research Institute for Psychiatry in Munich. They were published in German from 1916 to 1933 and have not been previously translated into English. The first 3 are of historical importance because each represented the first systematic studies using modern statistical and clinical methodologies of rates of psychiatric disorders in siblings,6 offspring,9 and nieces/nephews10 of probands with dementia praecox. Furthermore, Rüdin’s sibling study6 pioneered a range of key methodological features of future family studies. The fourth was the first twin study of dementia praecox using modern methods,11 which began a major subspeciality of twin research within the broader field of psychiatric genetics. The fifth was the first well-powered study to examine the genetic homogeneity of the schizophrenia syndrome12 and stimulated multiple further inquiries addressing the same question. We took the same approach to all 5 papers. After selection by K.S.K., A.K. would develop a first draft translation that would travel back and forth with K.S.K. until both were clear about the best translations and the meaning of the technical and statistical terms. K.S.K. would then draft a commentary of the paper and A.K. a brief biography of the author from available historical sources that would be integrated into the final manuscript. These papers were submitted to Schizophrenia Bulletin, sent out for review by Will Carpenter, and we revised them all in response to the concerns of reviewers. In working on these papers, we were keenly aware of the prior controversies around this body of work because several of these authors, especially Rüdin and Hoffmann, were active supporters of the Racial Ideology of the German National Socialists (NAZIs) who came to power in 1933—the year of publication of the last of our papers (The actions of some of our authors, who supported, and gave scientific credence, to Nazi racial policies, including, without doubt, large scale forced sterilizations, represent serious ethical crimes. However, it is worth noting that there is no evidence that Rüdin and his associates conducted their research in, what was for their time, an unethical manner or that subjects in their studies were directly harmed through their participation. To the best of our knowledge, Rüdin and his colleagues collected personal information on the relatives of dementia praecox probands and relatives by traveling around Bavaria, interviewing individuals, reviewing hospital records and by correspondence with relatives, physicians, hospitals, and other officials to gather more information on their subjects. Therefore, the ethical questions raised about the work examined in this special issue are different from those concerning the direct medical experiments with human subjects conducted by the Nazis, largely in concentration camps in World War II. Such studies were designed to cause serious harm and often death in the subjects, among the best studied examples being examinations of the effects of high-altitude and hypothermia. For relevant discussions of these issues, see references13,14). The papers reviewed in this special issue sit at an intersection of 2 different history disciplines with distinct orientations and goals. Up until now, their study has been largely conducted within the context of the social history of German Nazi ideology or what has sometimes been termed “Holocaust Studies.” This is an important and informative line of inquiry that has many points of relevance to the current and future relationship between the science of genetics and a range of critical social and ethical issues. However, it is not the focus of our approach. Rather, we review these studies mainly as historians of science and specifically as historians of psychiatric genetics. These articles deserved such a treatment because of their importance in the history of our field. It is also a history we are well qualified to write. K.S.K., often with the help of A.K., has written widely in the history of psychiatric genetics (eg,1,2,8,15–24) and has, through decades of work as an active psychiatric genetic researcher, gained substantial experience in the relevant genetic methodologies. By contrast, neither of us can claim deep expertise in the history of Nazi ideology in Germany, for example, through the study of primary sources, although we have tried to inform ourselves through careful reading of secondary sources. The crucial question that arises—what should be the relationship between these two historical perspectives on this body of work? We suggest that 3 main positions have evolved. The first posits that the ethical crimes revealed by historical analysis of at least some of the participants, especially Rüdin and Hoffmann, are so egregious that any study and publication of their scientific work or those of their close colleagues’ inevitability rehabilitates them. This, in turn, dishonors the millions of individuals who suffered and were murdered as a result of the Nazi racial policies they supported and should therefore be forbidden. We do not ascribe to this position. We also do not accept what might be seen as an ancillary postulate to this position. That is, it might be claimed that because some of the scientific results we review were used to support eugenic-racist policies, including forced sterilization and murder, then ipso facto, the science itself must be flawed. This is simply not true. Rüdin was a strong eugenicist and later Nazi supporter. Yet, his 1916 family study is viewed by others25,26 as well as us, as introducing important and innovative methodologies into psychiatric genetics. To be plainer, the historical record does not suggest that the moral qualities of individual scientists are necessarily closely related to the quality of their science. Bad people can do good science and vice-versa. A second perspective argues that the history of science should entirely take precedence and need not consider the historical and social context in which the scientific work was done regardless of potential ethical concerns involved. While this approach is likely appropriate for the large body of history of science, we would argue that this is not the case here. The perversion of genetic theory and research by the National Socialists was of such magnitude that to ignore it is to risk inadequately educating future generations about the dangers of the mis-use of human genetics. So, in these articles, we try to take a middle ground. While our major focus remains their scientific findings, we provide background material about the involvements of each of our authors with various aspects of Nazi ideology. It is important for readers to understand that according to our research, our 4 authors varied widely in their support and enthusiasm for Nazi racial theories. They do not present us with a uniform picture of the relationship between psychiatric genetic investigations in Germany between the Word Wars and eugenic and Nazi racial policies. We do hope our readers will come away both with a new interest in the fascinating history of the genetics of schizophrenia and the many conceptual, diagnostic, and statistical issues it confronted. Many times, we hope that readers will see early phases of debates that remain central in current psychiatric genetics in the 2020s, a century after some of our papers were written. We also hope that they will see this story as a cautionary tale—about the possible misuses of genetic findings. Many possible lessons might be learned. Among the most basic might be to always be cautious, and acknowledge the limitations of our findings, to oppose those who make unrealistic claims for reasons of potential financial or academic gains and to work with patients and the public to explain the implications and limitations of our science. In this and other ways, genetics researchers have an obligation to try to reduce the chances of negative unintended consequences of their work through open discussion and increased understanding. Finally, for those who want to pursue further the issues about the approach to the study of this period of genetics research, we provide references that express a range of opinions on this topic.25,27–37 This supplement is sponsored by Professor Kenneth S. Kendler MD. The authors have declared that there are no conflicts of interest in relation to the subject of this study. The concept of this paper and the first draft was developed by K.S.K. Both authors reviewed and revised the first draft.

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