Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (52 page)

3. J. McLean, “The discovery of heparin,”
Circulation
19 (1959): 75–78.

4. S. Sherry, “The origin of thrombolytic therapy,”
American College of Cardiology
14 (1989): 1085–92.

5. In another example of prematurity in discovery, dicumarol had been previously synthesized in 1903, albeit in impure form, and then promptly ignored. K. P. Link, “The anticoagulant from spoiled sweet clover hay,”
Harvey Lectures
34 (1943–44): 162–207.

6. Warfarin is from the acronym of the Wisconsin Alumni Research Foundation, which funded his research, and “arin” from coumarin. K. P. Link, “The discovery of dicumarol and its sequels,”
Circulation
19 (1959): 97–107.

7. L. Craven, “Acetyl salicylic acid: Possible preventive of coronary thrombosis,”
Annals of Western Medicine and Surgery
4 (1950): 95–99.

8. J. R. Vane, “Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs,”
Nature: New Biology
231 (1971): 230–35.

Part IV:
The Flaw Lies in the Chemistry, Not the Character:
Mood-Stabilizing Drugs, Antidepressants, and
Other Psychotropics

C
HAPTER
30: It Began with a Dream

1. Benedict Carey, “Most Will Be Mentally Ill at Some Point, Study Says,”
New York Times,
June 7, 2005. Article based on a series of four papers in the June 2005 issue of
Archives of General Psychiatry.

2. Ken Johnson, senior vice president of Pharmaceutical Research and Manufacturers of America (PHARMA), letter to the editor,
New York Times,
September 23, 2005.

3. Almost at the same time as Loewi's investigations began to become known, Walter Bradford Cannon in Harvard was carrying out experiments about a possible transmitter at sympathetic nerve endings. Eventually this was identified as noradrenaline.

4. Otto Loewi, “An autobiographical sketch,”
Perspect Bio Med
4 (1960): 17.

C
HAPTER
31: Mental Straitjackets: Shocking Approaches

1. Elliot S. Valenstein,
Great and Desperate Cures: The Rise and Decline of Psychosurgery and Other Radical Treatments for Mental Illness
(New York: Basic Books, 1986).

2. J. Wagner von Jauregg, “Über den Einwirkung fieberhafter Erkrankungen auf Psychosen,”
Jahrbücher für Psychiatrie und Neurologie
7 (1887): 94–131.

3. The name of this clinical investigator changed with the times. He was born Julius Wagner, but when in 1883 his father, an Austrian government official, was granted the title “Ritter von Jauregg,” he became Wagner von Jauregg. He took the hyphenated name “Wagner-Jauregg” when titles of nobility were abolished after the dissolution of the Hapsburg Empire in 1918. It was with this name that in 1927 he was awarded the Nobel Prize in Medicine, the only psychiatrist to be honored with this achievement. His work laid the foundation for the belief in an organic physical view of mental disorders.

4. A curious episode brought this physician and Sigmund Freud into a professional encounter. After World War I, it was alleged that Austrian military doctors in Wagner von Jauregg's psychiatric clinic had used cruel treatments on soldiers who had been suspected of malingering. The condition known as “shell shock” was not well understood, and the idea was to make electric shock treatments so disagreeable that the soldiers would prefer to return to the front. The strength of the current used on readmissions was increased to such an unbearable point that death and suicides resulted. In 1920 the Austrian military authorities appointed a commission to investigate, one of whose members was Freud, a former school-mate of Wagner von Jauregg's. The latter was personally exonerated. According to Freud's biographer, Ernest Jones, Freud emphasized the distinction between a doctor's primary responsibility to the patient and the demand of the military authorities that the doctor's chief duty is to return soldiers to active duty promptly. Freud's observation was condemned as unpatriotic by the commission. Ernest Jones,
The Last Phase: 1919–1939,
vol. 3 of the
Life and Work of Sigmund Freud
(New York: Basic Books, 1953–57), 21–22.

5. Manfred J. Sakel, “A new treatment of schizophrenia,”
Am J Psychiatry
84 (1934): 1211–14.

6. Ladislaus J. Meduna, “Versuche über die biologische Beeinflussung des Ablaufes der Schizophrenie: Camphor und Cardiazolkrämpfe,”
Zeitschrift für die gesamte Neurologie und Psychiatrie
152 (1935): 235–62.

7. Ugo Cerletti, “Electroshock Therapy,” in
The Great Physiodynamic Therapies in Psychiatry,
ed. Arthur M. Sackler et al. (New York: Hoeber, 1956), 91–120.

8. Sylvia Plath,
The Bell Jar
(1963; London: Faber and Faber, 1966), 151.

C
HAPTER
32: Ice-Pick Psychiatry

1. Andrew Scull,
Madhouse: A Tragic Tale of Megalomania and Modern Medicine
(New Haven: Yale University Press, 2005).

2. Baptized António Caetano de Abreu Freire, he was also christened with the name Egas Moniz, after a twelfth-century Portuguese patriot who had fought against the Moors and from whom his family descended. Later, this was the name he adopted.

3. J. M. Harlow, “Recovery from the passage of an iron bar through the head,”
Publication of the Massachusetts Medical Society
2 (1868): 327–47.

4. P. P. Broca, “Sur le volume et la forme du cerveau suivant les individus et suivant les races,”
Bulletin de la Société Anthropologique
2 (1861): 301–21.

5. Egas Moniz had been nominated twice for a Nobel Prize for cerebral angiography, but did not win. He was a proud and ambitious man, “dominated,” as he said, “by the desire to reach something new in the scientific world.” He prided himself on his persistence, and in this regard a historian's assessment is illuminating: “He had the ability to pick important problems but did not attack them with great originality or creativity. His problem solving was characterized by trial and error, persistence and a willingness to take risks.” Valenstein,
Great and Desperate Cures,
82–83.

6. Egas Moniz, “How I Succeeded in Performing the Prefrontal Leucotomy,” in
The Great Physiodynamic Therapies in Psychiatry,
ed. Arthur M. Sackler et al. (New York: Hoeber, 1956), 131–37.

7. William Sargant,
The Unquiet Mind
(London: Heinemann, 1967), 71.

8. Walter Freeman and James W. Watts,
Psychosurgery: Intelligence, Emotion, and Social Behavior Following Prefrontal Lobotomy for Mental Disorders
(Springfield, Ill.: C. C. Thomas, 1942).

9. Jack El-Hai,
The Lobotomist
(Hoboken, N.J.: John Wiley, 2005).

10. William Arnold,
Shadowland
(New York: McGraw-Hill, 1978).

11. Most lobotomies were done in state hospitals, and many others in medical school hospitals and Veterans Administration hospitals. Only about 6 percent were done in private hospitals.

12. A full-length feature film on lobotomy,
A Hole in One,
was made in 2004 by Richard Ledes, a first-time director. It is based on the archives of Walter Freeman, kept at George Washington University, and the 1953 Annual Report of the New York State Department of Mental Hygiene. Randy Kennedy, “A Filmmaker Inspired by Lobotomy,”
New York Times,
April 29, 2004.

13. Sargant,
The Unquiet Mind,
36.

14. Quoted in J. Wortis, “In Memoriam, Manfred Sakel, M.D., 1900–1957,”
Am J Psychiatry
115 (1958–59): 287–88.

C
HAPTER
33: Lithium

1. John F. J. Cade, “The Story of Lithium,” in
Discoveries in Biological Psychiatry,
ed. Frank J. Ayd and Barry Blackwell (Philadelphia: Lippincott, 1970), 219.

2. A missed opportunity for the earlier discovery of the antimanic properties of lithium occurred in the 1870s. S. Weir Mitchell, a neurologist, introduced lithium bromide, straight from photography, in the treatment of epilepsy or mental exertion with insomnia from overwork. He found the lithium salts superior to other bromides, and came breathtakingly close to attributing its “more rapid and intense” hypnotic effects to lithium itself: “This result must have been due to some more sure or speedy action of this salt (lithium) because the other bromides failed.” Yet he fixed on the value of the bromide of lithium. Anne E. Caldwell, “History of Psychopharmacology,” in
Principles of Psychopharmacology,
ed. William G. Clark and Joseph del Giudice, 2nd ed. (New York: Academic Press, 1978), 22–23.

3. Questions about the large doses of lithium salts used in the guinea pigs have since been raised, and some have even conjectured that the lassitude and docility of the animals may have been due to lithium toxicity. The question as to why manic urine appeared to be “more toxic” was never answered.

4. Cade, “The Story of Lithium,” 220.

5. John F. J. Cade, “Lithium salts in the treatment of psychotic excitement,”
Med J Aust
3 (1949): 349–52.

6. M. Schou, N. Juel-Nielsen, E. Stromgren, and H. Voldby, “The treatment of manic psychoses by the administration of lithium salts,”
J Neurol Neurosurg Psychiatry
17 (1954): 250–60.

7. Lithium, the lightest of all solid elements, has an atomic number of three. Its atomic structure is relatively simple. The nucleus comprises three or four neutrons and three protons. Two of three electrons occur in an inner shell, while one remaining electron occupies a distant outer shell from which it is readily lost. It is this that is the major determinant of the element's chemical properties. Nevertheless, the precise mode of its action as a mood-stabilizing agent remains unknown. It is thought likely that it inhibits norepinephrine uptake into nerve endings.

C
HAPTER
34: Thorazine

1. H. Laborit, “Sur l'utilisation de certains agents pharmacodynamiques à action neuro-végétative en periode pré- et postopératoire,”
Acta Chirurgica Belgica
48 (1949): 485–92.

2. H. Laborit, P. Huguenard, and R. Alluaume, “Un nouveau stabilisateur végétatif (le 4560 RP),”
Presse Méd
60 (1952): 206–8.

3. Deniker's presentation of these findings at the Fiftieth French Congress of Psychiatry and Neurology in Luxembourg at the end of July 1952 was not particularly auspicious. It was scheduled at the end of the last session of the week.

4. Caldwell, “History of Psychopharmacology,” 30.

5. Quoted in Judith P. Swazey,
Chlorpromazine in Psychiatry
(Cam-bridge, Mass.: MIT Press, 1974), 157.

6. F. Labhardt, “Die Largactiltherapie bei Schizophrenien und anderen psychotischen Zustanden,”
Schweiz Arch Neurol Psychiat
73 (1954): 309–38.

C
HAPTER
35: Your Town, My Town, Miltown!

1. Frank M. Berger, “Anxiety and the Discovery of the Tranquilizers,” in
Discoveries in Biological Psychiatry,
ed. Frank J. Ayd and Barry Blackwell (Philadelphia: Lippincott, 1970), 115–29.

2. F. M. Berger, “The pharmacological properties of 2-methyl-2-
n-
propyl-1.3-propanediol dicarbamate (Miltown), a new interneuronal blocking agent,”
J Pharmacol Exp Ther
112 (1954): 413–23.

3. Frank M. Berger (interview), “The Social Chemistry of Pharmacological Discovery: The Miltown Story,”
Social Pharmacology
2 (1988), 189–204.

4. “‘Ideal’ in Tranquility,”
Newsweek,
October 29, 1956, 63.

C
HAPTER
36: Conquering the “Beast” of Depression

1. These depths have been movingly related in the novelist William Styron's true account of his own descent into a crippling and suicidal depression: “I felt an immense and aching solitude. I could no longer concentrate during those afternoon hours, which for years had been my working time, and the act of writing itself, becoming more and more difficult and exhausting, stalled, then finally ceased. There were also dreadful, pouncing seizures of anxiety. One bright day on a walk through the woods with my dog I heard a flock of Canada geese honking high above trees ablaze with foliage; ordinarily a sight and sound that would have exhilarated me, the flight of birds caused me to stop, riveted with fear, and I stood stranded there, helpless, shivering, aware for the first time that I had been stricken by no more pangs of withdrawal but by a serious illness whose name and actuality I was able finally to acknowledge. Going home, I couldn't rid my mind of the line of Baudelaire's dredged up from the distant past, that for several days had been skittering around at the edge of my consciousness: ‘I have felt the wind of the wing of madness.’” William Styron,
Darkness Visible: A Memoir of Madness
(New York: Random House, 1990), 46.