Insulin is a hormone produced in the body by the pancreas; its main role is to cause cells to take up glucose from the blood thus regulating its level. The history of the discovery of insulin is an interesting one, albeit involving the death of a pack dogs.

In 1889, the physicians Oscar Minowski and Joseph von Mering removed the pancreas from a dog to test its assumed role in digestion. Several days after the dog’s pancreas was removed, it was noticed that there was a swarm of flies feeding on the dog’s urine. On testing the urine they found that there was an unusually high sugar content, establishing for the first time a relationship between the pancreas and diabetes mellitus.  In 1901, it was established that the diabetes was caused by the destruction of a part of the pancreas called the Islets of Langerhans. These islets had been identified by Paul Langerhans whilst a medical student in 1869. 

We now know that what the islets were producing was insulin, but this proved difficult to isolate. Nicolae Paulescu a professor of physiology in Bucharest was the first one to succeed and published his work in 1921. Use of his techniques was patented in Romania , but no clinical use resulted.  At almost the same time, Canadian Frederick Banting hypothesised that the reason for the difficulties was that some of the other products of the pancreas, digestive enzymes, were destroying the islet secretions before they could be extracted.  In the summer of 1921 he was supplied with a laboratory, Charles Best, a medical student assistant, and ten more dogs.  The idea was to ligate the dog’s pancreatic ducts; the pancreatic secretions would then pool in the pancreas, but the digestive elements would be reabsorbed leaving the islets.  It was found that an extract from these islets was able to keep a pancreatectomized dog alive all summer as the extract lowered the level of sugar in the blood. 

Efforts continued by Banting and Best to purify the extracted insulin enough to allow administration to humans, which was underway by late 1921; commercial quantities were available by 1923.  Banting received the Nobel Prize for his work, although controversially Paulescu was not recognised.

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In the sadly now departed spirit of have-a-go experimentalism, the newly discovered insulin was then tried out on patients suffering with illnesses for which no treatment was known. In Berlin , between 1928 and 1931, Dr. Manfred Sakel used insulin to reduce the unpleasant symptoms of patients undergoing opiate withdrawal. With insulin, they became calm, gained weight, and were much more cooperative.  When the dose of insulin was high, the patient went into stupor; after such events, the patients were less argumentative, less hostile, and less aggressive. 

Noting these results, Sakel moved to Vienna , and was assigned to treat patients with schizophrenia.  He further investigated the benefits of insulin, and reported that when the patients developed stupor or coma, they lost their psychotic thoughts.  His experience was reported to the Vienna Medical Society in January 1933, and by May 1936, favorable reports of the benefits of insulin coma therapy in schizophrenia from 22 countries were presented at a major meeting of the Swiss Psychiatric Society.

The German name for the treatment was ‘Insulin-shock-behandlung’. Translated into English, the phrase became ‘insulin-shock-treatment’.  Sakel interpolated the word ‘shock’ to emphasize his belief that the essential element of ICT was the lowered blood pressure, sweating, increased heart rate, and increased breathing rate that resulted from the stresses produced.  It was later understood that, that the medical shock aspects were not important to the treatment results, and any benefit was mostly likely due to the insulin induced coma.  Insulin coma therapy was regarded as a specific treatment for schizophrenia, and was probably the first in this regard.

Essentially the treatment involved a large dose of insulin which lowered the patient’s blood glucose enough to produce a coma.  This would be maintained for one to three hours and terminated by either tube feeding or intravenous glucose.  A course of treatment could include up to 60 comas.  Serious side effects were common, and a mortality of at 1-10% could be expected depending on the standard of the clinic and physical state of the patient.  Epileptic seizures could occur during the beginning stages of treatment, roughly 45–100 minutes into the procedure, but before the onset of the comatose state.  Seizures occurring during the coma were more dangerous, requiring immediate interruption of the procedure and coma termination, and were often followed by delayed recovery or severe hypotension.  Complications would also occur from the unconsciousness reaching excessive depths and that the coma would not end despite the administration of feeding or glucose.   Administrators would monitor the patient’s vital signs, to determine the level of danger.   

Despite these risks, insulin coma treatment was rapidly taken up throughout Europe and many specialized treatment units were built.  It is worth remembering that at this time there were no effective treatments for psychotic disorders and that the physical effects of prolonged psychosis were also severe, such that it was felt at the time that the risks were worth taking.  Indeed there was a great improvement in the morale of patients and staff because of the belief that this dramatic treatment could cure symptoms of the most serous psychiatric disorders. 

There were always some doctors who doubted the efficacy of insulin coma treatment.  Their doubts were reinforced by a controlled trial by Acker and Oldham (1962) who found that, in patients with schizophrenia, insulin coma was no more effective than a similar period of unconsciousness induced by barbituates.  It may be that the treatment had a tranquillising effect on patients by inducing brain damage through the prolonged deprivation of the brain cells of glucose, as suggested in a journalist Robert Whitaker’s book Mad in America*. It was also a very dramatic procedure, with patients being put into a long coma, and then re-awoken quite suddenly by the injection of glucose. This raises the possibility that coma therapy may have owed its perceived effect to a placebo effect, and a result of the drama of the whole procedure.

The Acker and Oldham study was published about the same time that chlorpromazine was introduced and both factors lead to a rapid decline in the use of insulin coma treatment.  It should be said though that some controlled studies did not exclude the efficacy of insulin treatment in certain circumstances and a number of workers continued to maintain that it was effective**.  Recent experimental studies have shown that insulin administration causes changes in the release of monoamine neurotransmitters, suggesting a possible mechanism of action**.

Links:

The Insulin Treatment of Schizophrenia From An Introduction to Physical Methods of Treatment in Psychiatry (First Edition) by William Sargant and Eliot Slater (1944, Edinburgh, E & S Livingstone).

A History of Shock Therapy in Psychiatry by Renato M.E. Sabbatini, director of the Center for Biomedical Informatics and Chairman of Medical Informatics of the Medical School of the State University of Campinas Brazil

Drug Treatments in Modern Psychiatry: A History of Delusion Dr Joanna Moncrieff Senior lecturer UCL UK

A Brilliant Madness PBS minisite about Nobel Prize winning schizophrenia sufferer John Nash.  In the same site Dr. Max Fink, the head of the insulin coma unit at the Hillside Hospital in Glen Oaks, Queens, New York from 1952 to 1958 writes about the treatment

Wikipedia on insulin shock therapy

* I haven’t read this, Joanna Moncrieff, Senior Lecturer in Social and Community Psychiatry UCL and chair of the Critical Psychiatry Network cites it in the above presentation.  He’s a journalist though, so I can’t shake the suspicion that he’s making it up.

**Source Shorter Oxford Textbook of Psychiatry by Michael Gelder, Richard Mayou and Philip Cohen Oxford 2001 pg 648.  They don’t cite a source.

This is the first in an occasional series of posts examining aspects of psychiatric practice which have given shrinks a bad name. As always comments and suggestions are welcome and if you can think of a candidate then let me know.

Anyone who has seen the film ‘One Flew Over the Cuckoo’s Nest’ will remember McMurphy’s fate; having tried to strangle Nurse Ratched and subsequently restrained, he comes back to the ward where Chief Bromden discovers that he has been given a lobotomy. Previously sparky and defiant, he appears subdued and submissive.

Evidence for the use of surgical techniques, such as trepanation of the skull, in people has been found from skulls dating from the middle ages. Famously Phineas Gage underwent a non-surgical lobotomy following an accident during railroad construction. His subsequent personality change played a role in the understanding of the localisation of brain function.

Neurosurgery for psychiatric problems was introduced in modern times by the Portuguese neurologist Egas Moniz and his neurosurgical colleague Almeida Lima, when in 1935 they sought to damage connections to and from the frontal lobes in patients with symptoms of mental disorders. At this time there were no effective therapies for these conditions and the surgery was received positively, Moniz receiving the 1949 Nobel prize for medicine. Moniz’s technique was to drill holes in the skull and inject alcohol into the frontal lobes.

Walter Freeman and James Watts in America modified Moniz’s operative technique and introduced the standard prefrontal leucotomy, which is what we are normally referring to when we say ‘prefrontal lobotomy’. This however required trained neurosurgeons and Freeman was concerned that this restriction would mean that those patients who needed the procedure most, those in asylums, would not be able to access it. As a result he developed the transorbital lobotomy, a terrifying technique whereby a pick like instrument was driven through the thin bone at the top of the eye socket and into the brain at which stage it was blindly manipulated. This procedure could be undertaken anywhere, without surgical training; beforehand the patient was rendered unconscious by electroshock. Dr Freeman was a showman, who would occasionally like to show off in front of an audience of doctors by lobotomizing both sides of a patient at the same time. Dr Freeman alone peformed over 3,000 lobotomies during his career, the results of which, due to its imprecision, were very variable.

Overall between 1936 and 1961 50,000 patients underwent surgery in the United States and about 10,000 in the United Kingdom. No controlled studies were performed and many people who received this treatment did not have a mental health disorder. It is stated that about 20 per cent of patients with schizophrenia and between one-half and two-thirds of patients with affective disorder derived who underwent the procedure derived some benefit. There was a very high mortality (up to 4%), as well as severe abulia and amotivation (up to 4%), personality change (up to 60%), and postoperative epilepsy (up to 15% – all figures for success and side effects are from the Oxford Textbook of Psychiatry). Due to a lack of other effective treatments these were accepted by many psychiatrists as worthwhile risks.

The use of surgery declined rapidly following the introduction of antipsychotic and antidepressant medication during the late 1950s. Since then, neurosurgery has only been used for severe treatment-resistant affective, obsessional, and anxiety disorders. These operations are used only rarely there having been, on average, no more than 20 operations a year in the United Kingdom over the last 20 years.

Howard Dully, one of Dr Freeman’s youngest patients has written a book about his experiences called My Lobotomy (which I haven’t read), the subject of this Observer article

Dr Elliot Valenstein has written a book called Great and Desperate Cures!: Rise and Decline of Psychosurgery and other Radical Treatments for Mental Illness. (Which I haven’t read either)

Jack El-Hai has written a biography of Walter Freeman. I have read this, and it’s very interesting and detailed. It’s called The Lobotomist: A maverick medical genius and his tragic quest to rid the world of mental illness