The Early History of Autism Research: John K. Darby, MD

The early history of research in autism is marked by a paucity of neuropathological studies. In agreement with Descartes dualist theory mental disorders were attributed to the mind and thus were thought to lack a structural substrate in the brain. Even as late as the 1960’s and 70’s few psychiatric institutions promoted autopsying their patients. Still, those who died within a psychiatric institution were examined by a medical examiner (coroner) whose mandate was to establish cause of death, nothing more. Seldom was an autopsy done by a specialist (neuropathologist) or pursued by microsocopic examination.

There were few exceptions to the distancing of psychiatry and neuropathology. Wilhelm Griesinger (1817-1868) who headed an institution for the mentally handicapped in Germany was a firm believer that mental conditions were brain conditions. His famous quote was: “Psychiatry and neuropathology are not merely two closely related fields; they are but one field in which only one language is spoken and the same laws rule”. However, despite these exceptions, the whole of psychiatry distanced itself from neurobiological investigations thus leaving the field open to psychoanalytical ruminations. It did not help that throughout the early years of research people who had an interest in the condition had to wrestle their way through confusing terminology. Before and even after Kanner’s description published articles variously referred to autism as childhood psychosis, dementia praecoccisima, dementia infantilis, or childhood schizophrenia. Many early descriptions of autism thus lay hidden under the diagnosis of mental retardation or epilepsy.

Two decades after Kanner made his initial description of autism, Bernard Rimland reviewed the medical literature to find only one autopsied case with some scant information. By 1997 Isabel Rapin indicated that there were less than 30 brains with detailed postmortem examination (Rapin, 1999). The numbers rose slightly over the next decade. In a review by Palmen the total number of reported cases was 40 (Palmen et al., 2004).

The most comprehensive review of the early neuropathological literature of autism was performed by John Darby during his tenure as Director for Research and Education at the Scott and White Hospital and Clinic in Texas. Darby reviewed the available literature (an annotated bibliography of over 1,700 references) and held correspondence with many higher academic institutions. The result of his perusal gave rise to a series of 33 cases, 29 of which had been previously reported in the literature (Darby, 1976).

The cases in Darby’s series varied tremendously in regards to clinical presentation and tissue availability. Gross examination of the brains was unremarkable. Under the microscope the most common reported finding was that of “cerebral lipidosis”. The term made reference to the accumulation of the pigment lipofuscin, also known as the “wear and tear” pigment of the brain. (Note: A recent report by Lopez-Hurtado and Prieto in 2008 revealed a significantly increased number of pigmented neurons in autistic patients. The authors believed their findings were consistent with accelerated neuronal death or increased oxidative metabolism).

The arrow indicates the accumulation of a golden brown pigment (lipofuscin) in a neuron.

Darby (1976) concluded that the variability he observed in clinical presentation suggested that autism was the expression of a number of disorders. Many years after the fact he published a letter to the editor of the American Journal of Psychiatry entitled: “Autism Syndrome as a Final Common Pathway of Behavioral Expression for Many Organic Disorders” (Darby and Clark, 1992). The espoused concept reminds us of a similar proposal by Bellak (1958) who claimed a “final common pathway” to the nature of schizophrenia wherein a variety of insults were somehow funneled to provide a similar set of manifestations.

A few other authors contributed isolated efforts, primarily as case reports in the 1970’s and 1980’s. The new era was to be ushered by the neuropathological studies of Margaret Bauman and Tom Kemper in the mid 1980’s. However, the lessons from Darby and other early investigators were valuable and can be summarized as:

1) There is an inherited tendency to autism as shown by pairs of siblings within case reports.
2) Idiopathic autism comprises the majority of reported cases, but so-called secondary autism is common. Genetic conditions, especially tuberous sclerosis, have always been recognized as a common cause of secondary autism.
3) Gross examination of the brain is almost always normal.
4) Early investigators questioned some pathological findings as artifacts, e.g. prolonged postmortem intervals.

Jon Darby received his medical degree from the University of Texas-Southwestern in 1967. In the same year, he received a National Foundation Merit Award to study Congenital Birth Defects. From 1990 till present he has been a Consultant in Neuropsychiatry for Agnes State Hospital in San Jose, California. According to PubMed Dr. Darby’s contribution to autism in 1976 was his first effort at a publication. The same is considered a classic within the field of autism research.


Bellak, L. (1958). Schizophrenia: a review of the syndrome. New York: Logos Press.

Darby, J. K.. Neuropathologic aspects of psychosis in children. Journal of Autism and Childhood Schizophrenia, 6, 339¬¬–352, 1976.

Darby, J.K., Clark, L. Autism syndrome as a final common pathway of behavioral expression for many organic disorders. AJP 149(1):146, 1992.

López-Hurtado, E., Prieto, J. J. A microscopic study of language-related cortex in autism. American Journal of Biochemistry and Biotechnology, 4, 130–145, 2008.

Palmen, S. J., Van Engeland, H., Hof, P. R., Schmitz, C. Neuropathological findings in autism. Brain, 127, 2572–2584, 2004.

Rapin, I. Autism in search of a home in the brain. Neurology, 52, 902–904, 1999.

4 responses to “The Early History of Autism Research: John K. Darby, MD

  1. Before Bauman and Kemper, don’t forget there was Williams et al., I believe it was who autopsied four brains and found abnormalities in the cerebellum. I think this was the start of a number of studies of postmortem brains and scans that found cerebellar abnormalities.


  2. Thank you for the comment. Williams reported his findings in 1980. As you said they were based on 4 patients. One of the reported patients with autism had phenylketonuria and another one probably had Rett’s syndrome. Also from the series, 1 of the brains had been perfused (for embalming) which should have prevented comparisons to other subjects. Gross and microscopic findings overall were negative. Another early author was Coleman (1985) who attempted the first report on cell counts. It was only 1 autistic patient and he probably had hypotensive ischemic damage to his brain. Although a lot of effort went to both series the results remain doubtful because of flaws in study design and patient selection.

    As an aside I will tweet your book today again. My main problem is not having a Kindle to read it on, but hope to get an app to allow me to do so in my computer (if one exists). Good luck and thank you for your support.


  3. thanks for your support and tweet. You can download the kindle app from Amazon for free. Though I don’t know exactly how to do it, since I have a kindle, but I think you can contact amazon or go to their website and download it for either a computer or smart phone.


  4. Pingback: What Is Loss Of Proteostasis? - The Hallmarks Of Ageing Series - Gowing Life·

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