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20th Century Eugenics and the Risks of Modern Genetic Interventions

by Michaela B. Reinhart, 2023 Medical Fellow

The vast strides in the field of medical genetics since the Human Genome Project have created unparalleled opportunities to prevent and address disabling genetic diseases. The potential for misuse of genetic therapies necessitates remembrance and recognition of atrocities committed against people with disabilities by the eugenics movement of the early 20th century. Past perpetrators’ motivations and methods warn of the risk of misappropriating these rapidly advancing technologies. Within the field of genetics, the still-limited knowledge of the complexity should protect against similar crimes in the future.

The interest in hereditary traits in the late 19th and early 20th centuries gave way to eugenics, the desire to manipulate the population’s gene pool. Nazi Germany conflated genetic principles with racial differences, promoting “racial hygiene” for the superior “Aryan race.” In 1929, many German physicians formed the National Socialist German Medical Association within the Nazi Party to define the scientific foundation of Nazi health policy. To form a “purer” and “healthier” German body, they initially targeted those with medical differences such as psychiatric disorders, genetic malformations, epilepsy, and congenital blindness. Their operation would expand to target Jewish, Roma and Sinti, and Afro-German populations, among others, deemed inferior to the “Aryan race.” Starting in the early 1930s, they used pseudoscience to justify forced sterilizations of vulnerable populations. With Adolf Hitler’s appointment to chancellor in 1933, these efforts became official policy, the Law for Prevention of Hereditarily Diseased Offspring. Under Nazi direction, this law led to forced sterilization of about 400,000 people.1 

Forced sterilization set the foundation for mass murder through the institution of “euthanasia” programs to purge the population. In 1939, after receiving a request from a German man for permission to kill his deformed son, Hitler appointed his personal physician Dr. Karl Brandt and head of staff Philipp Bouhler to develop a program to kill children with “lives unworthy of living.” The subsequently formed Reich Committee for the Scientific Registration of Serious Hereditary and Congenitally Based Illnesses required midwives and doctors to report children with deformities. Forms describing the children were then judged by three officials (two physicians and one judge from the Nazi party) who would determine if each child would live or die. They sent 5,000 children to clinics where the victims either starved to death or died from lethal injections.1,2 

This program of mass murder extended to adults under the T-4 Program, named after the Berlin headquarters address Tiergartenstrasse 4, that targeted individuals with psychiatric disorders and disabilities. Hitler wrote an informal directive empowering Brandt and Bouhler to allow “those suffering from illnesses deemed to be incurable may be granted a mercy death.”1 He further backdated the note to the date of Germany’s invasion of Poland to correlate this initiative with that of the war.1 The program had a similar method of evaluating institutionalized patients and sending them to killing centers. There, they experimented with methods of mass murder to improve efficiency, notably establishing the use of carbon monoxide gas for asphyxiation en masse. Those in the program would then send letters to families stating false causes of death.The program killed approximately 200,000-300,000 people deemed an excessive burden to the Reich and its desired growth.1,2

Having seen how systematized eugenics can decimate multiple populations in Nazi Germany, the role of eugenics takes a more personal approach today, though it continues to operate within the healthcare system. The use of in vitro fertilization (IVF) allows for selection of embryos without pathogenic genetic variants harbored by their parents, and progress in pre-implantation gene editing makes the option of customizing progeny evermore real. While the use of this technology has allowed couples to avoid having children suffer from devastating illnesses such as Tay Sachs disease, the question of the modern definition of “lives unworthy of living,” if it exists at all, arises. The most glaringly obvious difference in this approach as opposed to that of Nazi Germany, of course, is intention: preventing occurrence of disease rather than extermination of those with disease. Limitations of scientific knowledge in the use of these technologies, both to prevent and treat disease, help curb the implications of these values for now. However, the risk of “designer babies” who undergo extensive gene editing for socially desirable traits–beyond avoiding pathology–still exists. As many children will continue to have these diseases, whether they harbor new pathogenic variants or their parents opt to naturally conceive, clinicians have a duty to preserve respect for persons with disease and disability, actively avoiding their devaluation.

Recognition of the place of IVF and gene editing within the healthcare system is essential in safeguarding their ethical implementation. Nazi efforts to exterminate children and adults with undesirable traits succeeded within a governmental framework supported by many German physicians. The current systematic approach to modern reproductive options for those carrying pathogenic genetic variants is vulnerable to analogous prejudices. Standard care for couples identified as carriers of genetic disease is to offer counseling on IVF as a future reproductive option. Gene editing may become standard, as well, as the technology develops and becomes part of routine care for disease. Patients should know all of their options, and clinicians should help them to make the best decisions for themselves and their reproductive plans. Throughout prenatal counseling, clinicians should remain aware that they have a responsibility to ensure that their personal preferences and biases do not influence their patients. Clinicians should remain cognizant of the requests and guidance of governing bodies, healthcare institutions, professional organizations, and other stakeholders to avoid systemic prejudices that may harm vulnerable groups.  Society’s attributing a diminished quality of life to people with disabilities lays at the root of stigma around disease and disability. Within Nazi Germany, a person’s worth was tied to their ability to contribute to the Reich. Those with genetic disorders, especially ones with neurodevelopmental delays or malformations, were targeted for extermination. A review of victims’ files shows people with Down syndrome and features reminiscent of many other genetic syndromes such as Fragile X syndrome, 22q11.12 microdeletion syndrome, and Noonan syndrome. Cases also described birth injuries that likely led to hypoxic ischemic encephalopathy or cerebral palsy.3 Nazis decided these individuals had “lives unworthy of living” and failed to recognize their inherent value as people. 

Stigmatization of disability remains today–both in the public and among healthcare professionals. These biases devalue individuals with diseases or disabilities, best explained by the disability paradox. This paradox serves as the basis of a social model of disability by describing the gap between a disabled person’s experience and public perception of their experience: people with disabilities, in comparison to those without disability, consistently have more positive attitudes regarding their own quality of life and those of other persons with disabilities. Having meaningful relationships with family and friends, as well as the ability to work, largely contributes to this positive view.4 The majority of family members with disabled children also rate their own quality of life highly despite the unique challenges that come with raising children with disabilities.5,6,7 Through this review of positive experiences among people with disabilities, this social model of disability then holds that the disabling of impaired people comes from society’s view of them. Despite having a functional limitation (impairment), a significant component of disability comes from limited opportunities to participate equally.8 Thus society places “disability” onto impaired people by not making reasonable accommodations and viewing them as limited. This ableist mindset leads to the view that disabled people have a poorer quality of life than most disabled perceive in their own experience. Subsequently, systematized barriers arise from this bias.

The disability paradox highlights the risk of introducing generalized assumptions into protocols or even law regarding genetic-based interventions. The U.S. Supreme Court case Buck v. Bell (1927) illustrates the impact of this subjectivity in Justice Oliver Wendell Holmes, Jr. statement that “Three generations of imbeciles are enough,” justifying forced sterilization of “feeble-minded and socially inadequate” people to prevent further offspring.9 This case followed a wave of interest in eugenics in the United States, as well as multiple European countries, at the beginning of the 20th century.2 The push for removing the “feeble-minded” stemmed from a lack of appreciation for their inherent value, as well as a desire to erase those who acted outside of the social norm. These biases remain today. Iezzoni, et al. (2021) assessed in a survey of 714 practicing physicians that 82.4% of them thought people with significant disability have worse quality of life and many expressed concern about their ability to care for them.10 By placing patients within the physician’s value system, then, the physicians feed into the disability paradox. However, some of these negative views appear to stem more from fear of or anxiety about not providing adequate care for patients with disabilities rather than a judgment of the patients themselves.10,11 These statistics are worrying as they suggest implicit and explicit biases in the care of people with disabilities. Despite these social limitations, expanded medical genetics knowledge, in some cases, has likely had a protective effect for people with disabilities as better understanding of the etiology of disease contributes to better treatments and approaches to support their needs.

The rudimentary understanding of genetic disorders in the early to mid-20th century led to the nonsensical pseudoscience of “feeble-mindedness.” A.H. Estabrook’s testimony in Buck v. Bell attempted to use Mendelian genetics to explain intellectual disability:

Where feeble-mindedness if found in two strains, the two strains meeting, feeblemindedness will show up in one-fourth of the children. Where feeble-mindedness is found in one parent, that is, and only in the strain – that is, the other parent being normal but coming from a strain where there is feeble-mindedness, one-half of the children will be feeble-minded.9

Estabrook describes Mendelian autosomal recessive inheritance of intellectual disability, and, while some disorders associated with intellectual disabilities are inherited as a recessive trait traceable through generations, his methodology fails to address the many disorders with complex inheritance. A pathogenic variant in a gene, including those of Mendelian inheritance, may have variability in its expression (extent of disease) and variability of penetrance among family members (whether the same change in a gene will cause disease at all in different people). For example, Xlinked adrenoleukodystrophy, a disease classically associated with progressive neurologic deficits in childhood, may present in childhood, adolescence, or adulthood with different physical findings among family members.12 The resulting diversity of presentation makes prediction of outcome based on the variant of the gene alone impossible. Expression of genes is now known to have many modifiers too, including epigenetic alterations that affect how a gene is expressed (if at all), environmental effects, and the influence of other genes on the expression of one gene (polygenic traits), among others. The complexity of inheritance and expression makes manipulation of the genome more difficult than appreciated in earlier generations, which serves as a protective factor in misusing gene editing for whichever traits society may deem desirable at a given time.

A further complicating factor in attempting to remove genetic disease within the eugenic context of a healthier population is the ongoing mutation rate of DNA replication in the process of gamete (egg and sperm) formation. The estimated mutation rate in DNA replication is 10-4-10-6 per gene in each generation, translating to a rate of nucleotide substitution of 1 in 108 per generation, or 30 nucleotide mutations in each gamete.13 Typically, substitutions are not in clinically meaningful locations, but some of these substitutions occur within gene coding regions or regions that affect gene expression and can cause disease. Unless the entire genome is sequenced in an embryo–and every pathogenic variant to exist in the population is known (which is not the case)–genetic disease cannot be completely avoided. Moreover, mutations can occur shortly after fertilization in a subset of cells, which leads to only some bodily tissues being affected by disease – a concept known as mosaicism. Currently, it is impossible to know the DNA sequence of every cell in every tissue, so mosaicism can be difficult to detect, depending on which tissues are affected. Combine these factors with the principles of variable expressivity and penetrance, as well as modifiers of gene expression, and the eugenic objective of removing any source of genetic disease is futile.

Because genetic diseases will persist despite early interventions, it is necessary for the clinician to appreciate the value of the individual with a genetic disorder. An examination of the Nazi extermination of disabled people, or the US and European history of forced sterilization, within a legal context shows the extreme of risk of assigning value to another’s lived experience. While the emergence of genetic technologies can reduce the burden of devastating disease on future children and families, the necessity remains to draw a line between therapeutic intervention and interventions for socially desirable traits. Clinicians must balance their duty and ability to prevent disease with humility regarding their own social biases and stilllimited knowledge of genetics.

Michaela B. Reinhart was a 2023 FASPE Medical Fellow. She is a pediatric geneticist completing a fellowship in medical biochemical genetics and mitochondrial disorders.

Notes

  1. Bergen, D. L. (2009). War and genocide. United States: Rowman & Littlefield Publishers.
  2. Grodin MA, Miller EL, Kelly JI. The Nazi Physicians as Leaders in Eugenics and “Euthanasia”: Lessons for Today. Am J Public Health. 2018 Jan;108(1):53-57. doi: 10.2105/AJPH.2017.3041203. Gedenkort-T4. Opferbiografien. German Parity Welfare Association. (2023). https://www.gedenkortt4.eu/biografien 
  3. Albrecht G, Devlieger P. The disability paradox: high quality of life against all odds. Social Science & Medicine. 1999;48(8):977-988. doi: 10.1016/S0277-9536(98)00411-0
  4. Boehm, TL, Carter, EW. Family Quality of Life and Its Correlates Among Parents of Children and Adults With Intellectual Disability. Am J Intellect Dev Disabil. 1 March 2019;124(2):99–115.doi: 10.1352/1944-7558-124.2.99
  5. Fairfax, A., Brehaut, J., Colman, I. et al. A systematic review of the association between coping strategies and quality of life among caregivers of children with chronic illness and/or disability. BMC Pediatr. 2019;19,215. doi:10.1186/s12887-019-1587-3.
  6. Correia RA, Seabra-Santos MJ. “I Would Like to Have a Normal Brother but I’m Happy with the Brother That I Have”: A Pilot Study About Intellectual Disabilities and Family Quality of Life From the Perspective of Siblings.” Journal of Family Issues. 2022 Dec;43(12):3148-3167. doi:10.1177/0192513X211042845
  7. Anastasiou D, Kauffman JM. The Social Model of Disability: Dichotomy between Impairment and Disability. Journal of Medicine and Philosophy. 2013;38:441-459. doi: 10.2105/AJPH.2017.304120
  8. Buck v. Bell. 274 U.S. 200 (1927)
  9. Iezzoni LI, Rao SR, Ressalam J, Bolcic-Jankovic D, Agaronnik ND, Donelan K, Lagu T, Campbell EG.Physicians' Perceptions Of People With Disability And Their Health Care. Health Aff (Millwood). 2021 Feb;40(2):297-306. doi: 10.1377/hlthaff.2020.01452
  10. Satchidanand, N, Gunukula, SK, Lam, WY, McGuigan, D, New, I, Symons, AB, Withiam-Leitch, M, Akl, EA. Attitudes of Healthcare Students and Professionals Toward Patients with Physical Disability. American Journal of Physical Medicine & Rehabilitation. 2012;91(6): 533-545. doi:1097/PHM.0b013e3182555ea4
  11. Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, van Trotsenburg ASP, Mochel F, Sevin C, Regelmann MO, Tritos NA, Halper A, Lachmann RH, Davison J, Raymond GV, Lund TC, Orchard PJ, Kuehl JS, Lindemans CA, Caruso P, Turk BR, Moser AB, Vaz FM, Ferdinandusse S, Kemp S, Fatemi A, Eichler FS, Huffnagel IC. International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach. Neurology. 2022 Nov 22;99(21):940-951. doi: 10.1212/WNL.0000000000201374
  12. Johnston, HR, Keats, BJB, Sherman, SL. 12 - Population Genetics, Editor(s): Pyeritz, RE, Korf, BR, Grody, WW. Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics (Seventh Edition), Academic Press, 2019: 359-373. doi: 10.1016/B978-0-12-812537-3.00012-3.