Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (35 page)

I
NSULIN
C
OMA

In the 1920s, doctors in England, France, and particularly the Soviet Union dealt with the acute excitement states of catatonic and manic patients by trying to keep them in a continuous state of sleep, accomplished through the use of hypnotics. It was a short stumble to go from induced continuous sleep to induced temporary coma.

In 1933 in Vienna, insulin shock treatment—by means of hypoglycemic comas—was introduced by Manfred Sakel, who claimed to be a direct descendant of Moses Maimonides, the twelfth-century rabbi, physician, and philosopher. Insulin shock was the first treatment method ever to be directed at schizophrenia, the most common and most hopeless illness among mental patients in institutions.
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Shock treatment came about through a chain of serendipitous events when Sakel was working as an assistant physician at the Lichterfelde Sanitorium in Berlin. Sakel accidentally administered an overdose of insulin to one of his morphine-addicted patients who also happened to be diabetic. The level of glucose—the main source of energy for the brain—in the patient's blood dropped so severely that a mild coma ensued. Upon recovery, “the patient's mind, until then completely befogged, was absolutely clear,” and his craving for morphine had subsided. Emboldened, Sakel gave insulin overdoses to other drug addicts and, in 1930, published a report on his successes.

Again by accident, he gave a significant overdose of insulin to a drug addict who also happened to be psychotic, putting him into a deep coma. When the patient came out of it, Sakel thought he detected signs of mental improvement. Had he stumbled on a new approach? Confirming by experiments in animals—conducted, according to Sakel, in his kitchen—that such comas could be controlled by prompt injections of glucose, Sakel began inducing deep comas in schizophrenics. He relocated to Vienna and, after five years of work, announced his insulin shock cure before the Vienna Medical Society in November 1933. The psychiatric world initially found the results incredible, but soon specialists came from all over the world to observe the treatment and results directly. Sakel's reputation grew with his shock treatment of Vaslav Nijinsky, the famous ballet dancer who was stricken with schizophrenia. For the first time, Nijinsky was able to leave the sanitarium where he had been confined since 1919. Nevertheless, he spent the last thirty-two years of his life in an insane asylum.

Ardently espoused and publicized by Sakel, particularly after he fled to the United States in 1936, two years before the Nazis came to power in Austria, insulin shock treatment was widely adopted. The reports of its success were exaggerated, received enthusiastically by the popular press, and not critically analyzed by the psychiatry profession.

Foster Kennedy, professor of neurology at the Cornell Medical School and Bellevue Hospital, celebrated the victory over traditional psychoanalysis, in the preface to the 1938 American edition of Sakel's work: “In Vienna, at least one man had revolted from the obsession that only psychological remedies could benefit psychological ills…. We shall not again be content to minister to a mind diseased merely by philosophy and words.” This tribute must have offered some balm to the wound incurred when Sakel's application for membership in the psychoanalytically dominated American Psychiatric Association was initially refused. A report by an American adherent of Sakel detailing early clinical experience with insulin-coma therapy at Bellevue Hospital was published in a neurology journal after being rejected by psychiatry journals.

Doctors induced a state of unconsciousness in their patients by administering overdoses of insulin. The patient would go into convulsions and then, anywhere from thirty minutes to several hours later, be brought out with glucose administered through a stomach tube or intravenously. There were impressive results in patients in the early stages of schizophrenia who were treated with a series of as many as fifty of these hypoglycemic comas over six to ten weeks. Some patients were fully cured of their psychotic symptoms, while others saw only temporary improvement. Complications of the procedure were not widely publicized. The death rate for the treatment averaged about 6 per 1,000. Death occurred when a patient could not be revived from the coma. Nonfatal brain damage occurred in about 8.5 cases out of 1,000.

Insulin shock treatment was a turning point in psychiatry. For the first time in medical history, there was real hope for the mentally ill. It transformed mental institutions from exclusively custodial facilities to centers of treatment and rehabilitation. But it certainly was not without its drawbacks.

Extensive studies in 1939–40 showed that most patients did not derive long-term benefit from insulin shock treatments, although some did sustain a slight improvement. Interest in the procedure declined in the 1940s and disappeared with the introduction of modern drugs in the 1950s.

C
HEMICALLY
I
NDUCED
C
ONVULSIONS

Based on observations made during autopsies on the brains of epileptics and schizophrenics, neuropathologist Ladislaus von Meduna in Budapest came to believe that there were differences in the nerve cells between the two and formulated the theory that epileptics would not suffer from schizophrenia. In other words, he believed schizophrenia and epilepsy were biologically exclusive diseases. In 1934 he began treating schizophrenia patients with Metrazol, a modified version of camphor, which is derived from laurel and has a long history of causing seizures.
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It caused considerable pain at the injection site, but this was not the worst of its effects. The induced epileptic fit was a particularly
distressing procedure because it evoked terrible fright in a patient as he felt himself seized by a powerful, all-encompassing force.

While somewhat useful in treating schizophrenia, Metrazol was found a few years later in the United States to be most effective against depression. By 1940 almost all major mental institutions had it among their treatments, but within a few years it was replaced by electroconvulsive therapy.

A T
RULY
S
HOCKING
A
PPROACH
: ECT

The third major convulsive treatment, electroshock, was introduced in Rome by physicians Ugo Cerletti and Lucio Bini in 1938. Long interested in the possibility of inducing convulsions with electricity, they had been concerned about the safety of the procedure in humans. Cerletti wrote, “The idea of submitting man to convulsive electric discharges was considered utopian, barbaric and dangerous: in everyone's mind was the spectre of the ‘electric chair.’” This fear was not unfounded, since their initial animal experiments often resulted in death. When Bini, working as the electrotechnician, realized that the electrodes originally placed in the mouth and anus resulted in the electric current passing through the heart and stopping it, he changed their position to the sides of the head and none of the animals died.

Later, on a visit to one of Rome's slaughterhouses, Cerletti and Bini observed that pigs were stunned into unconsciousness by electric shocks applied to both sides of the head before having their throats cut. After this visit, they began conducting numerous experiments on dogs by applying an electric current through the skull and inducing convulsions and then modified the technique for its use in man for depression and schizophrenia.

Their first hapless human subject was a thirty-nine-year-old schizophrenic found wandering around the Rome train station by the police. During a phase of convulsions, an individual typically suspends breathing temporarily and may turn blue—a condition called cyanosis—from the lack of oxygen. Following this first experience in a human, Cerletti described their alarm:

We watched the cadaverous cyanosis of the patient's face…it seemed to all of us painfully interminable. Finally, with the first stertorous breathing and the first clonic spasm, the blood flowed better not only in the patient's vessels but also in our own. Thereupon, we observed with the most intensely gratifying sensation the characteristic gradual awakening of the patient “by steps.” He rose to sitting position and looked at us calm and smiling, as though to inquire what we wanted of him. We asked: “What happened to you?” He answered: “I don't know. Maybe I was asleep.” Thus occurred the first electrically produced convulsion in man, which I at once named electroshock.”
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After eleven applications of electroconvulsive therapy (ECT), the patient lost his notions of persecution and hallucinations, and was discharged from the clinic a month later and returned to his work as an engineer.

ECT was widely adopted and replaced chemically induced epileptic fits. It was recognized as an almost specific treatment for not only recent but also long-standing severe depressions, and is still used today in drug-resistant depression. Sylvia Plath's fictionalized account of an ECT session in
The Bell Jar
(1963) uses analogy to portray the feeling of loss of self: “A great jolt drubbed me till I thought my bones would break and the sap fly out of me like a split plant.”
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Better anesthetics and chemical relaxants have made ECT less traumatic.

32

Ice-Pick Psychiatry

Surgical approaches were adopted in the 1920s at a few medical centers on the rationale that certain disordered organs underlay mental illnesses. Some endocrine glands were cut away, but the most bizarre rationale in the United States was surgery to eliminate the presumed sources of infection in the body that released toxins affecting the brain: besides removal of teeth and tonsils, resections of the stomach, colon, cervix, and uterus were undertaken.
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This was germ theory gone mad.

The era of psychosurgery was introduced by António Egas Moniz in 1938.
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A Portuguese aristocrat, Egas Moniz held the chair of professor of neurology at the Faculty of Medicine in Lisbon from 1911 and, for many years, pursued a second career as a politician. He was briefly ambassador to Spain in 1917, before becoming minister of foreign affairs and leading the Portuguese delegation at the Paris Peace Conference. He was a celebrated neurologist who pioneered cerebral angiography, the process of X-ray examination of the pattern of arteries in the brain by injecting radiopaque solutions via its feeding vessels. He used this knowledge to develop a method of diagnosing and localizing brain tumors by visualization of abnormalities in the arterial pattern. In 1927 he announced these results.

“G
AGE
W
AS
N
O
L
ONGER
G
AGE
”

The frontal lobes of the brain, regions just behind the forehead and in the front of the motor areas, had long been considered the “silent lobes,” since they lack the easily identifiable sensory and motor areas of other parts of the brain. This medical terra incognita began to be mapped with much help from the famous case of Phineas Gage.

In 1848 Gage was a twenty-five-year-old railway construction foreman who was highly respected by his men for his judgment and competence. One of his major tasks was overseeing the blasting of rock to lay new tracks. The detonation was prepared in a series of steps: drill the hole in the rock, fill it halfway with explosive powder, insert a fuse, tamp in a layer of sand to direct the explosion inward, and finally light the fuse. But on this fateful day, Gage was distracted for a critical second. Thinking that the man working with him had already inserted the sand, he began tamping the powder directly with his specially designed iron bar. A spark ignited the powder, and the explosion hurtled the three-and-a-half-foot-long tamping iron right through his head, specifically through his frontal lobe, carrying off about half a cupful of brains with it.

Poor Phineas survived for thirteen years but was never the same. He became reckless, profane, stubbornly willful, and lost any concept of the future, yet was unaware of the changes to himself. To his friends, “Gage was no longer Gage.”
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Gage's case was the first reported instance of loss of intellectual and behavioral function from damage to the frontal lobes.

In 1861 Paul Broca, the French surgeon and anthropologist, attributed the higher functions of the brain to the frontal lobes, the part of Gage's brain that had been largely destroyed: “The majesty of the human is owing to… judgment, comparison, reflection, invention, and above all the faculty of abstraction…. The whole of these higher faculties constitute the intellect.”
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Further understanding was advanced by observation of soldiers in World War I who had suffered frontal-lobe damage from gunshot wounds. These were characterized by personality changes without damage to any vital body process.

The frontal lobes are the most recently evolved part of the
nervous system. They execute all higher-order purposeful behavior. They are crucial in focusing on a goal, developing plans to reach it, and monitoring the extent to which it is accomplished. The frontal lobes free man from fixed routines of behavior and cognition, and allow for imagination, judgment, and identity. With the loss of such functions, an individual loses himself, loses his “soul,” and is indifferent to or ignorant of this loss.

Egas Moniz was sixty-one when he attended the 1937 London conference at which two American physiologists from Yale University reported the results of surgically removing the frontal lobes of chimps. Before the operation, the chimps had been adept at solving certain types of puzzles, but they were also excitable. Afterwards, they were unable to solve any problem involving extensive use of short-term memory or integration of data over time. Yet they were placid and imperturbable. Egas Moniz was particularly impressed with the elimination of “frustrational behavior”—angry, impatient actions in situations of frustration—in the animals and decided to try the method on humans with anxiety states or “disturbing” social behavior. Within the next year, without conducting experiments on animals to test the safety of the procedure, he performed lobotomy—or leucotomy, as he called it—on twenty patients. (The term “leucotomy” is composed of two segments derived from the Greek:
leuco-,
referring to the white matter of the brain, and
-tome,
meaning knife.) Egas Moniz claimed that he was scientifically basing his work on an anatomical concept derived from Ramón y Cajal. In truth, however, his speculations were poorly constructed and served merely as an ill-conceived rationalization for his surgery. His University of Lisbon colleague who held the chair of psychiatry labeled them “pure cerebral mythology.”
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