DANGER IN THE BITTERROOT VALLEY:

EARLY STRUGGLES WITH SPOTTED FEVER

     One of America’s most idyllic spots, the Bitterroot Valley, nestled between two mountain ranges in southwest Montana, seemed a healthy place. Lewis and Clark, passing through the Valley, and native-American peoples living there did not

Bitterroot Valley today (Wikipedia)

manifest unusual illness. After the Civil War settlers moved in, felling thousands of trees in the western side of the Valley to feed a burgeoning lumber industry. Scrub vegetation, populated with small mammals, replaced the trees. By the 1880s scattered cases of a “spotted fever” were reported, usually fatal, most coming from the west side of the Valley, and most showing recent tick bites. Between 1895 and 1902 64 people died out of 88 with the disease.    

     In 1902 two investigators from the University of Minnesota, Louis Wilson and William Chowning, suggested the wood tick as a vector and found organisms in the blood of victims they believed were a type of Pyroplasma, similar to that causing Texas cattle fever, another tick-transmitted disease. The notion of insects transmitting disease was popular. In the previous 25 years mosquito transmission of filaria, malaria, and yellow fever, and tick transmission of Texas cattle fever had all been discovered.

     Getting rid of ticks, though, by burning brush and killing animal hosts didn’t reduce the disease incidence. Other

Howard Ricketts,
martyr to typhus (Wikipedia)

investigators cast doubt on the tick theory, adding confusion, until the arrival of Howard Ricketts and William King. They were able in 1906 to infect guinea pigs and to prove that ticks transmitted the disease. Ricketts also thought he saw tiny microorganisms he believed were the disease agents but could not culture them. Stymied by an interruption of funding, Ricketts left for Mexico to study typhus (another spotted fever). He perished in Mexico, tragically, from that very disease.

     Ricketts had recommended learning more about wood tick habits, enticing Robert Cooley, Montana State entomologist, to step in. Cooley employed Willard King and Clarence Birdseye (who later founded the frozen food industry), both field biologists, to collect ticks and wild animals for study. The work was hazardous. Their lab was set up in an old two-room log cabin in which one man had died of

Cabin and tent of Cooley's team, Bitterroot Valley
(National Library of Medicine)

spotted fever. The yard, full of ticks, was burned, then sprayed with kerosene (a tick repellant), and the team slept in tents around the cabin. As they worked collecting animals and ticks they wore high shoes, with tight kerosene-soaked khaki leggings above them, and doused their outer clothing with kerosene. They stripped and inspected each other for ticks every two hours. Somehow they remained healthy.

     The team demonstrated a 2-year cycle from egg to adult tick and showed that adults fed primarily on large domesticated animals. As a result dipping centers were set up to “de-tick” farm and domestic animals. But, related to poor dipping agents and bureaucratic infighting, the program foundered and spotted fever (now called Rocky Mountain spotted fever) claimed more victims.

     What about the supposed causative agent, Pyroplasma? No one else could find it. S. Burt Wolbach, a young Harvard pathologist, saw tiny intracellular organisms, particularly in vascular endothelial cells, that he could not grow and which he named Dermatocentroxenus rickettsii, in honor of Ricketts (later renamed Rickettsia rickettsii). They were a new type of organism that grew only in cells, the details of which had to await further developments in technology.

     In the era before antibiotics the main strategy against infectious diseases was vaccination, and so it was with the spotted fever.

Roscoe Spencer (National Library
of Medicine)

Roscoe Spencer, a US Public Health Service physician, and Ralph Parker, a Montana entomologist, working in an abandoned two-story brick schoolhouse in Hamilton (in the Valley) in the 1920s, discovered that injecting material into guinea pigs from ground-up infected ticks, sterilized with formalin and phenol, could produce an imperfect but substantial immunity. Spencer developed this into a commercial vaccine.

     Vaccine production was a cumbersome process. Each year’s supply required collection of 30-40,000 adult ticks to feed on 4 to 6,000 rabbits and 20-30,000 guinea pigs. The adult ticks were fed on rabbits, then collected for egg laying. The hatched larvae were fed on newly infected rabbits, dropped off, and molted into nymphs. The nymphs fed on more rabbits (400/rabbit), were

Brick schoolhouse where original vaccine work
was done (National Library of Medicine)

collected, dried with hair dryers, and kept at 22 degrees C to molt into adults. The adults were stored at near freezing levels for 6-12 months (to enhance vaccine efficiency), after which they were warmed up and fed on guinea pigs. Swollen with blood, they were emulsified in a Waring blender with formalin, phenol, and saline. Finally, after storage, further dilution, and purification, the vaccine was ready, and was accepted by residents.

      The toll was heavy. In the process three laboratory workers died of spotted fever. Others, including Spencer, Parker, and a third all developed tularemia, a tick-born disease originally discovered in Tulare County, California (they survived). Spencer, depressed, was transferred back east. The head of the tick-rearing room resigned, and Parker carried on as chief in a new, safer laboratory building.

     The tick-based vaccine continued to be produced by the Rocky Mountain laboratory until 1948 when it was replaced by an egg yolk-derived vaccine and the advent of antibiotics. There is no vaccine available today. The laboratory continues as a part of the National Institute of Allergy and Infectious Diseases/NIH.

     Once considered a localized disease, Rocky Mountain spotted fever has been found throughout much of the U.S., primarily in the central eastern and mid-western states. Its history could be said to have had a “rocky” beginning, with false starts and at least three martyrs.

SOURCES:

Harden, Victoria. Rocky Mountain Spotted Fever: History of a Twentieth Century Disease. 1990; J Hopkins Univ. Press.

Price, Ester. Fighting Spotted Fever in the Rockies. 1948; Naegele Printing Co. Helena.

Ricketts, H. “The Transmission of Rocky Mountain Spotted Fever by the bite of the Wood Tick (Dermacentor occidentalis). 1906; JAMA 47: 358.

Spencer, R and Parker, R. “Rocky Mountain Spotted Fever: Vaccination of Monkeys and Man. 1925; Public Health Reps 41: 2159-67.

Wolbach, S B. “Studies on Rocky Mountain Spotted Fever”. 1919; J Med Research 41:3.

THE FIRST BRAINWAVE RECORDINGS

     When we want to know if someone is “legally dead” we look at the brain waves – the electroencephalogram. This sophisticated diagnostic tool also helps diagnose a wide range of other neurologic problems, especially seizure disorders. The first electroencephalograms (EEGs), however, were performed for another purpose.

     The first to record human brain electrical activity was Hans Berger, a professor of Psychiatry at the University of Jena,

Hans Berger (Wikipedia)

Germany. Berger, born in 1873, was the son of a physician and grandson of a celebrated poet, Friedrich Rüchert. Without finishing university studies he enlisted in the military, after which he decided on a medical career. On receiving his degree he was taken on as assistant to Otto Biswanger, Professor of Psychiatry at Jena, who was working on general paresis (tertiary syphilis of the central nervous system), a common problem in mental hospitals of the time. In the 1890s, though, Berger veered off into other realms: the relation of mind and matter and the conservation of energy in the brain.

     The principle of conservation of energy had been established during the nineteenth century, and some investigators sought to apply these principles to the brain. The Viennese neuropsychiatrist Theodor Meynert, for example, felt that when energy is expended

Theodor Meynert (Wikipedia)

in an area to produce a thought or action, an equivalent energy must be transferred from another part. Meynert and a colleague, Alfred Lehmann, surmised that energy was distributed around through changes in blood flow, regulated from centers deeper in the brain. Brain energy could be in the form of heat, electrical energy, or “psychic” (mental) energy, all derived from chemical (nutritional) sources. 

     These ideas were attractive to Berger. He believed in an interaction between “mind and brain”, as opposed to another school, led by John Hughlings Jackson, a British neurologist, that insisted on a separation between brain physiology and psychologic processes. Berger's challenge was to demonstrate how the interaction happened. He started by measuring local blood flows as a marker for energy changes. He studied patients who had undergone brain surgery and were left with holes in the cranium, over which the brain was covered only with dura mater and skin. By placing small plethysmographs onto these gaps he measured changes in pressure after mental stimuli (light, sounds, thoughts) as a gauge of local blood flow. He noted increases in flow with pleasant sensations and decreases with unpleasant ones. Although interesting, the work was fraught with technical difficulties. These studies, however, were the forerunners of the ubiquitous functional MRI scans of today that demonstrate changes in regional blood flow in response to mental phenomena.

     He then tried measuring brain temperatures during brain surgery and recorded changes on emerging from anesthesia, during arithmetic calculations, etc. Though he generated much data, nothing meaningful came of it. So he turned to looking at electrical energy. Berger applied pairs of tiny electrodes under the  scalp, first in patients with cranial defects (later flat electrodes over intact skull). He used a sensitive string galvanometer made for EKG, moving later to more sensitive Siemens oscilloscopes. 

From Berger's first publication. Top line is EEG from 2 leads on scalp of 36 year-old bald male, placed
 fore and aft. Second line is EKG, third line is clock at 1/10 second intervals.

     Various stimuli, such as opening the eyes to bright light, produced different patterns, as previously seen in animals. He viewed seizures as an example of the consumption of all available brain energy, thus explaining the sleep that followed a seizure. He identified the basic alpha and beta wave patterns, though his interpretations have been modified.

     During this work Berger became secretive, working alone, avoiding discussions of his ideas with colleagues and in his lectures. His diaries indicate a depressive state of mind, frequent discouragement and insecurity. Finally, in 1929, after about 5 years of work, he published what is now a “classic” paper: “On the Human Encephalogram” (Über das Elektrenkephalogramm des Menschen), coining the new term “encephalogram” in the paper. Other papers followed.

     The work was received with some apathy in Germany, but was picked up by others, especially by Edgar Douglas Adrian at

Edgar Douglas Adrian (Wikipedia)

Cambridge, who was recording electrical impulses from individual axons (and who won a Nobel Prize in 1932). Adrian expanded the EEG work, opening it to the wider scientific community, and making Berger well known outside Germany.

     Berger fell in love with a laboratory technician before WWI, a Baroness - Ursula von Bülow, whom he married despite the social difference between them. He was called away during WWI as a psychiatrist near the Western front, but had few duties. Over time he was promoted and became a  professor and director of the Neurology and Psychiatric Clinic at  Jena University. He is described as an excellent diagnostician, but made almost no close friends and was considered “shy, reticent, and inhibited” by a colleague (Ginzberg).

University of Jena about 1910 (Wikipedia)

     As Nazism penetrated Germany in the 1930s the University of Jena was affected. Berger did not like the Nazis, did not join the party, and any papers he gave abroad had to be censured. But it has been recently reported that Berger accepted a position on the Erbsgesundheitgericht, the Court for Eugenics, in Jena. Nazi Germany had passed several eugenics laws, allowing for the sterilization of persons with various categories of neurologic and psychiatric diseases, such as dementia, deafness, multiple sclerosis, alcoholism, etc. Methods included tubal ligations, vasectomies, and radiation of gonads. Berger served on two levels of the regional Court, passing judgment on cases for sterilization during 1938.    

     On reaching age 65 that year he took mandatory University retirement and left the Court. His previous congestive heart failure worsened and he became more depressed. A final diary entry speaks of despair, sleepless nights, brooding, self accusations, and includes,"...I yearningly wished for my early end"(Gloor). Ten days later he committed suicide by hanging.

SOURCES:

Gloor, P. "Hans Berger and the Discovery of the 

      Electroencephalogram". Electroencephalography and Clinical 

      Neurophysiology, 1969, Suppl 28, pp 1-36.

Ginzberg, R. “Three Years with Hans Berger: A Contribution to  

      His Biography. J Hist Med and Allied Sci. 1949, pp 361-71.

Millett, D. “Hans Berger: From Psychic Energy to the EEG”. 

       Perspectives in Biol and Med, 2001. 44(4): 522-42.

Berger, H. “Über das Elektroenkephalogramm des Menschen”. 

       1929; Arch Psych und Nervenkrankeiten, 87: 527-70.

Zeidman, LA, et al. “New Revelations About Hans Berger, Father  

       of the Electroencephalogram (EEG), and his Ties to the Third 

        Reich”. 2014; J Child Neurology 29(7): 1002-1010.

Finger, S. Minds Behind the Brain: A History of the Pioneers and   

        their Discoveries. 2000, Oxford U. Press.

PROHIBITION AND THE PRESCRIPTION OF ALCOHOL

     In January, 1919, a bewildered nation woke up to a hard fact: the eighteenth Constitutional Amendment had just been ratified, prohibiting the manufacture, sale, transportation, importation, or exportation (but not possession) of alcoholic products “for beverage purposes”. In one year it would take effect. Those who could afford it quickly stocked up on booze (this included outgoing President Woodrow Wilson and incoming President Warren Harding). Those on the lower economic scale made do with cheaper, sometimes dangerous, substitutes.

Poster for popular Prohibition song (Wikipedia)

     Since the Amendment applied to intoxicating liquors “for beverage purposes”, doctors (and patients) immediately asked about consuming liquor as a medicine. Wasn’t this permitted? In fact, physicians frequently prescribed whiskey, wine, or beer for health reasons. Perhaps more important, was not the prohibition of prescribing alcoholic liquors interference in the practice of medicine by Congress?

     Congressman Andrew Volstead, chairman of the Judiciary Committee, headed the drafting of the “Volstead Act”, to create rules for enforcement of the Amendment. “Intoxicating” beverages were defined as containing over 0.5% alcohol. Regarding physicians (Sect. 7), they could prescribe

Andrew Volstead (Wikipedia)

alcoholic beverages if they believed “that the use of such liquor...is necessary and will afford relief to [the patient] from some known ailment”.

     What did physicians really think about prescribing alcohol? The AMA sent questionnaires out to 53,900 physicians and received answers from 58%, representing 21.5% of all MDs in the country. The primary question was whether the respondent considered whiskey, beer, or wine “a necessary therapeutic agent in the practice of medicine” (following language in the Volstead Act). For whiskey, 51% said yes, 32% for wine, and 26% for beer. Whiskey was used most commonly in pneumonia, influenza, other acute infectious diseases and diseases of old age. Beer was recommended for lactation, convalescence, debility, etc. Urban MDs prescribed more alcohol than rural ones. Several commented on seeing adverse effects from moonshine brews, and many felt that alcohol prescriptions should be placed in the same category as narcotics, controlled under the Harrison Act.

Prescription for whiskey, 1924. "Use as directed" is written (Wikipedia)

     Instead of a survey, Dr. Charles Rosewater quoted from recent literature. William Osler wrote in his 1906 text: “I should be sorry to give up the use of alcohol in the severer forms of enteric fever and pneumonia.” Abraham Jacobi, the “father of pediatrics”, wrote in 1918: “Cases of young children in sepsis would improve immediately when 3 ounces of whiskey was increased in one day to 12 ounces.” He also noted that alcohol “need not make you strong, but it makes you feel strong.” Many other professors advocated alcohol in their writings.

     Volstead planned a “Supplemental Prohibition Bill” to prohibit beer prescriptions and narrow other alcohol uses. This brought matters to a head. The Prohibition Commissioner in Washington (under the Treasury Dept) was bombarded with requests from physicians to prescribe beer. He deferred to the Attorney General, Mitchell Palmer, who issued the opinion that the Volstead Act did not apply to medicinal uses, including the prescription of beer. He stated that physicians should determine what type and what quantity of alcoholic beverage was prescribed. Then he left office as the new Harding administration moved in.

     Volstead, head of the Judiciary Committee, and the drys, were not to be thwarted. Believing that non-alcoholic beer would do just as well, they pushed ahead with the Supplementary Bill. Alcoholic liquors could be prescribed if they did not exceed 24% alcohol, prescriptions did not exceed 100 per month per doctor or one pint per 10 day period per patient. Beer was out. The Act (known as the Willis-Campbell Act) passed by a large majority. A vocal opponent was Senator Henry Cabot Lodge who fumed over the attack of Congress on the autonomy of the physician. The press generally seconded him. 

Budweiser ad for alcohol-free beer (Wikipedia)

     The medical community’s response also focused on government intrusion. Samuel Lambert, dean of Columbia University’s medical school and leader of a group of prominent physicians opposed to the Act, sued Edward Yellowley, Prohibition Director in New York City, claiming interference with medical practice. The court ruled for Lambert, saying that since the Act allowed prescription of some alcoholic beverages, excluding beer was arbitrary and contrary to the sense of the Volstead Act. In the first appeal the decision was unanimously reversed, the court deferring to the legislature. The doctors appealed to the U.S. Supreme Court, but by a 5/4 decision they lost. The decision resembled that of Jacobson v Massachusetts (see last month’s blog) in that the Court deferred to the legislature, noting that regulating medicine fell under the “necessary and proper” clause of the Constitution. “There is no right to practice medicine which is not subordinate to the police power of the States, and also to the power of Congress to make laws necessary and proper for carrying into execution the Eighteenth Amendment” is a quote from the Lambert opinion.

     Lambert v Yellowley was the first instance in which congressional legislation regulating medical practice was enacted in opposition to the medical community. It would not be the last.  

SOURCES:

Appel, Jacob. “Physicians are not Bootleggers: The Short, Peculiar  

       Life of the Medicinal Alcohol Movement.” 2008; Bull Hist Med. 

       82: 355.

“The Referendum on the Use of Alcohol in the Practice of 

       Medicine: Final Report”. 1922; JAMA 78: 210.

“Lay Comment on Alcohol Resolution”. JAMA 1922, 79:63-4.

Gage, Beverly. “Just What the Doctor Ordered”. Smithsonian 

        Magazine, April 1, 2005.

Lambert v Yellowley opinion, found at:

     https://www.law.cornell.edu/supremecourt/text/272/581

Rosewater, Charles. “Alcohol as Medicine: Abstracts from the 

        Writings of Eminent Authorities” 1919. J Med Soc New  

        Jersey; 16: 274.

Okrent, Daniel. Last Call: The Rise and Fall of Prohibition. 2010;

          Scribner.

THE RIGHT TO VACCINATE

     In 1901-2, a wave of smallpox swept through the northeastern U.S., from which Boston suffered particularly. To control the accelerating epidemic the Boston Health Department, among other measures, instituted compulsory vaccination. Squads were dispatched to poorer areas to vaccinate tenants in cheap

Smallpox victim, 4th day of eruption

apartments and lodging houses. Many received the vaccine against their will, as did many whose employers had required it. Massachusetts law authorized compulsory vaccination when a city deemed it appropriate, and refusal of vaccination carried a $5 fine. Exemptions for schoolchildren, but not for adults, were obtainable with a physician’s signature (often granted freely).

     Close to 85% of Boston inhabitants took the vaccine. Many refused, however, usually from fear of side effects and complications. The newly formed Massachusetts Anti-Compulsory Vaccine Society (MACVS), along with other anti-vaccination groups, led the opposition. The MACVS, which included some physicians, contended that compulsion constituted an infringement on personal liberty, though the group understood the risk of smallpox.

     Fears of side effects were not without grounds. The vaccine didn’t always take, children with certain skin disorders developed generalized vaccinia, vaccination sites developed erysipelas, and stories circulated of deep ulcerating lesions at vaccination sites. Most alarming were verified cases of tetanus after vaccination.

     Vaccine manufacture was not yet standardized. Jenner’s

Edward Jenner (unknown artist, Wikipedia)

original cowpox virus had been lost. New vaccines, derived from cowpox or from smallpox inoculated into cattle whose lymph was harvested, found acceptance. Preservation of vaccine lymph was another problem. Person-to-person transfer of vaccine assured some purity but lost favor after cases surfaced of syphilis transmission by that route. Lymph directly from cows could carry bacterial contamination. Glycerin was tried as an antiseptic and preservative, but it worked slowly and inactivated virus along with bacteria. Use of dried lymph on ivory “points” could also carry

Ivory "points". Dry vaccine on the tips was scratched into
the skin. (Wellcome Library)

bacteria. And vaccination techniques varied from doctor to doctor. All these variables contributed uncertainty to vaccination results.

     The epidemic had two important consequences.

     The first grew out of fears of vaccination sequelae. Clusters of tetanus cases had emerged in Camden, NJ and Philadelphia, with smaller numbers from other sites. Suspicion fell on contaminated glycerinated vaccine, though full proof was lacking. The lymph was usually harvested in a barn, a good source for tetanus contamination. When the Massachusetts State Board of Health mentioned it might make its own vaccine the larger manufacturers lobbied the U.S. government to introduce licensing instead, to assure quality in established manufacturers (and keep them in business). The result was passage by Congress of the Biologics Control Act in 1902, authorizing the Laboratory of Hygiene, part of the Public Health and Marine Hospital Service (and later to become the NIH), to establish standards and issue licenses to producers of biologics. This Act was the first step in biologics regulation and was a forerunner to the 1906 Pure Food and Drug Act.

     The second important consequence of the epidemic was a legal one. Anti-vaccinationists sought a test case to challenge the Massachusetts compulsory vaccination law. Reverend Henning Jacobson, who had refused vaccination, was arrested and fined $5 and appealed his case to the State Supreme Court. Jacobson was minister to the Swedish Lutheran Church in Cambridge, a small congregation of 364 members. His arguments centered on possible ill effects of the vaccine, and he sought protection under the fourteenth amendment (prohibition against depriving a citizen of life, liberty, or property without due process of law).

     The State Supreme Court held against Jacobson, arguing that the compulsion law was constitutional, the result of deliberation by the legislature, and established to protect the general public. Jacobson appealed his case to the U.S. Supreme Court.   

     John Marshall Harlan (born into a slaveholding family and later known for his defense of black civil rights) wrote the 7-2 Supreme Court opinion. It too recognized that in the public interest there

John Marshall Harlan (Wikipedia)

were necessary restrictions on individual freedom. The Court declined to interfere with properly deliberated State legislation, but did suggest that refusal of vaccination was allowed if the health of the individual indicated a likelihood of harm. The Jacobson v Massachusetts decision, thinking of the public interest, was cited later in upholding a Virginia law authorizing forced sterilization of inmates of a State institution for mentally retarded, thus establishing the basis for sterilization programs elsewhere.

     How relevant is the Jacobson v Massachusetts decision today? There’s no space here for that, but it is discussed in the American J Public Health, 2005, in the light of changes in the nature of infectious diseases and civil rights legislation.

SOURCES:

Walloch, Karen L. The Antivaccine Heresy. 2015. U of Rochester   

     Press.

McFarland, Joseph. “Tetanus and Vaccination: A Study of 95 

     Cases of the   Complication. Lancet, 1902, Sept 13, pp 730-5

Willson, Robert N. “An Analysis of 52 Cases of Tetanus 

     FollowingVaccinia, with Reference to the Source of Infection”.  

     JAMA 1902; 19:1222-31.

American J Pub Health 2005, 95(4); 571-590. (3 articles on the 

      historyand significance of Jacobson v Massachusetts)

Liebenau, Jonathan. Medical Science and Medical Industry: The

      Formation of the American Pharmaceutical Industry. 1987. J 

      Hopkins U Press. (covers relation of tetanus to contaminated 

      vaccine, and 1902 Act)

MEDICINE IN THE TIME OF FRANKENSTEIN

     Exactly two hundred years ago, in 1818, one of the world’s great bestsellers, Frankenstein, hit the London bookstores. The

Mary Shelly, by Richard Rothwell (Wikipedia)

author of the book, anonymous at first, turned out to be a woman, Mary Shelly.

     In the story a Swiss youth, Victor Frankenstein, while studying chemistry and physiology in Germany, asks himself “whence…did the principle of life proceed?”. His discoveries led him to create a living being out of an assembly of body parts. He learns later that his creation has intelligence, language, and emotions, and is so alone in the world that he begs Frankenstein to create a female companion. I won’t go further, but the story is germane in today’s world of cloning, genetic engineering, and intelligent robots.

     In a preface to the 1831 edition Shelly writes, “The event on which this fiction is founded has been supposed, by Dr. [Erasmus] Darwin and some of the physiological writers of Germany, as not of impossible occurrence”. In another paragraph she mentioned experiments by Darwin on “vermicelli” that had been induced to move. She probably meant vorticella, a bell-shaped ciliated protozoan, to which Darwin restored motion after adding water to its dehydrated state.

     Restoration of life was on her mind.

     Erasmus Darwin, grandfather of Charles Darwin, was arguably the most prominent physician in England at the time. He had an

Erasmus Darwin, by Joseph Wright (Wikipedia)

extensive practice in and around Lichfield in the Midlands and was famous for his diagnostic and prognostic skills, his kindly manner, and his broad scientific interests. He was a founder of the famous “Lunar Society”, a collection of business and scientifically oriented men who exerted wide influence in British Enlightenment thought. Darwin penned two works that probably influenced Shelly, Zoonomia and The Temple of Nature.

     In the preface to Zoonomia Darwin laments that scientists (to use a modern word) too often thought of laws of the body in terms of mechanics and chemistry, forgetting that the “spirit of animation” was its essential characteristic. He defines “sensorium” as consisting of the brain, nerves, muscles, sensory organs and “the living principle, or spirit of animation, that resides throughout the body”. The “living principle” was an ethereal spirit or fluid residing in the brain, nerve, and muscle tissues that was necessary for motion, or for life itself. It flowed through nerves in a poorly defined way. The idea was championed by the Swiss scholar, Albrecht von Haller, and was not new with Darwin. The vorticella that regain life appear in The Temple of Nature, briefly.

     In 1791 Luigi Galvani, a professor in Bologna, startled the scientific world by

Luigi Galvani, artist unknown (Wikipedia)

publishing the summary of a decade of work on effects of electricity in biological subjects, showing that nerves conducted an electric “fluid”. He showed as well that the charge did not spread beyond nerve channels because of their insulating sheath of lipid material. The idea of electrical “fluid” conduction by nerves eventually replaced the ethereal fluid. For human experiments Galvani’s nephew, John Aldini, raced to the scaffold immediately after executions. “On the first application of the process to the face the jaw of the deceased criminal began to quiver, and the adjoining muscles were horribly contorted, and one eye was actually opened. In the subsequent part of the process the right hand was raised and clenched and the legs and thighs were set in motion. It appeared…as if the wretched man was on the eve of being restored to life.”(Med Phys J, 9:195, 1803) The journal editor indicates that this technique might be useful in reviving victims of “apparent death” by drowning or asphyxiation. The idea of reviving the recently dead was certainly considered feasible.

     In Shelly’s novel the only sentence that describes bringing the creature to life is, “…I collected the instruments of life around me that I might infuse a spark of being into the lifeless thing that lay at my feet” (italics mine). Presumably electricity played a role, but the text is vague.

     Electricity, or “Galvinism”, became popular as a treatment for all sorts of diseases and conditions. Tingling or outright shocks were something a patient could feel, after all. Conditions treated ranged from blindness and deafness to urinary calculi, insanity, and, of course, various forms of muscular paralysis. Treatment

devices and techniques proliferated, though were rarely properly evaluated.

Electrotherapy apparatus. The columns are of alternating silver and zinc discs in 
dilute HCL, creating a current (Voltaic pile). The wires lead to a metal clamp on 
the head. (London Medical and Physical J. 7: 528-40, 1802)

     It is probable that Mary’s husband, Percy, influenced her thought. Though primarily a poet Percy was intensely interested in science, and Mary remembered accompanying him to a public lecture on Galvinism. A close friend and mentor of Percy was Dr. James Lind, a cousin of the James Lind associated with scurvy. Percy’s Lind was widely traveled and corresponded with several intellectuals of the day. His library was said to resemble an alchemist’s lab and he was probably the model for Frankenstein’s chemistry professor. Lind undoubtedly guided Percy’s reading.

     The “spirit of animation” as a concept lasted for a while but inevitably gave way to developments in chemistry and physiology later in the century. Electrotherapy suffered a similar decline. Mary Shelly’s novel has never been out of print, however, and is perhaps more pertinent today than it was in her time.

SOURCES

Simili, R. “Two Special Doctors: Erasmus Darwin and Luigi Galvani”, in The Genius of Erasmus Darwin, Smith and Arnott, eds. 2005; Ashgate.

Pfeiffer, CJ. The Art and Practice of Western Medicine in the Early Nineteenth Century. 1985, McFarland & Co.

Finger, S. Origins of Neuroscience. 1994; Oxford U Press.

Goulding, C. “The Real Doctor Frankenstein?”. J Roy Soc Med 2002; 95: 257-9.

Bresadola, M. “Medicine and Science in the Life of Luigi Galvani” Brain Res Bull 1998; 46(5): 367-80.

Medical and Physical Journal 1803; 9: 195 (on Aldini’s experiments)

Darwin, E. Zoonomia (1794), Section II,2.  and The Temple of Nature (1804), p 36.

    

    

    

     

DR. ALOIS ALZHEIMER

     In November 1901 Mrs. August D., age fifty-one, was admitted to the Asylum for the Insane and Epileptic in Frankfurt am Main with advanced dementia. Her husband, a railway clerk, had been aware of her deterioration for about eight months.  The senior

Auguste D, Alzheimer's original case
(Wikipedia)

physician of the Asylum, Dr. Alois Alzheimer, saw this as an unusual case and examined her in detail. In time, Mrs. Auguste D's problem would make the name Alzheimer a household word.

     Alois Alzheimer was born in Marktbreit, Germany, not far from Würzburg. Son of a notary, he received his secondary education at a gymnasium, then studied medicine in Berlin, Würzburg, and

Alois Alzheimer (Wikipedia)

Tübingen. He was an enthusiastic fraternity member and while fencing sustained a large gash over his left face. Since then he only allowed photographs from his right side. He took an interest in histology, having studied under the pioneer histologist Alfred von Kölliker,  and in  neuro-psychiatry, seeking an organic basis for mental illness. He obtained a position at the above-mentioned Asylum in Frankfurt, working under Dr. Emil Sioli.

 Emil Sioli was an early advocate of “open therapy” – substituting relaxing warm baths for restraints and using activities such as crafts and gardening as therapy in a time when almost no helpful medicines were available. Alzheimer was soon joined by

Franz Nissl (Wikipedia)

Franz Nissl, already known for his development of a neuron stain. He and Alzheimer became life-long friends and colleagues. They worked together on many histologic projects (usually at night, after clinical duties), published extensively, and both became recognized authorities in neuropathology.

     In 1892 Wilhelm Erb (of Erb’s paralysis) asked Alzheimer to travel to North Africa to care for a wealthy patient. The patient died en route to Europe but his widow, Cecilie, was taken with Alzheimer and eventually proposed to him. They were married in 1894 and lived happily until her relatively sudden death of unknown cause seven years later. 

     Alzheimer moved briefly to Heidelberg and in 1903 accepted a position under the famous psychiatrist Emil Kraepelin at the Royal Psychiatric Clinic in Munich. Since Kraepelin could not find funds for him Alzheimer, now wealthy, worked for no remuneration (imagine that today!). He built a large laboratory, mainly at his own expense. His genial personality and modern lab attracted excellent scientists such as Hans Creutzfeldt, Alfonse Jakob, and Frederik Lewey (Lewey bodies). Alzheimer published on histologic findings in alcoholism, epilepsy, and mental retardation, and was promoted to “chief physician”, finally earning a modest salary.

      About one third of patients in mental hospitals at the time suffered from general paresis. Most female patients were prostitutes and among males military officers, salesmen, and firefighters predominated. Priests were rarely afflicted. Syphilis was suspected as the cause but the evidence was circumstantial. To teach at the University of Munich Alzheimer had to submit a Habilitation thesis. He had studied 320 cases at autopsy over seven years and selected 26 for the thesis. The work,

Inflammatory thickening of pia mater in paresis
(from Alzheimer, Reference 5, Hathi Trust)

published in 1904, was considered a landmark paper. The very next year the treponema of syphilis was discovered by Fritz Schaudinn and Erich Hoffmann, and the year after that Wassermann announced a diagnostic test for syphilis.

     Back at the Asylum in Frankfurt, Auguste D. was deteriorating, and died in April, 1906. Alzheimer received her brain in Munich and on examination he found plagues, fibrillary tangles, and a paucity of neurons.

     Dr. Alzheimer presented the case of Auguste D. at a lecture in November, 1906, during a meeting of the Southwest German Psychiatrists. Much of the meeting was taken up with criticisms of Freud’s theory of the sexual basis for hysteria. Alzheimer’s paper, despite numerous illustrations, provoked no discussion. It was published the following year (1907) without illustrations in a German journal of psychiatry and “psycho-forensic” medicine. Alzheimer asked a coworker, Dr. Gaetano Perusini, to watch for similar cases at the Clinic, and after three more turned up the four were published in a serial work on the histology and histopathology of the cerebral cortex edited by

Plaque and fibrils seen by Alzheimer
(from Reference 6, Hathi Trust)

 Alzheimer and Franz Nissl. Three years later Emil Kraepelin, in the eighth edition of his popular psychiatry textbook, formally named the disorder “Alzheimer’s disease”. 

     Before long other reports drifted in, and eventually the gap between “pre-senile” dementia and the dementia of old age (“senile dementia”) narrowed. Today the disease is referred to as dementia of the Alzheimer type or Alzheimer’s dementia. The advancing age of the population plus a few cases in celebrities such as Rita Hayworth and Ronald Reagan have assured the disorder a prominent place in the public eye.

     In 1912, at the age of 48, Alzheimer was appointed full professor of psychiatry in Breslau, a prestigious post. Unfortunately his health began to fail shortly after and he died in 1915 of kidney failure.

     Was Alzheimer really the first to characterize the pathology

Oskar Fischer (Wikipedia)

of early dementia? In the journal Brain, 2009, Michel Goedert writes about Oskar Fischer, a Czech investigator at the now defunct German University in Prague, who made almost simultaneous observations. In 1907 – the same year as Alzheimer’s first publication on dementia, he reported on 16 cases of senile dementia (called “presbyophrenia” by him), 12 of whom had neuritic plaques and neurofibrils. Later papers of 1910 and 1912 enlarged the findings. The plaques were, in fact, often called “Fischer’s

Plaque and fibrils by Fischer
(from Reference 7, Hathi Trust)

plaques”, and "presbyophrenic dementia" and "Alzheimer’s disease" were terms used interchangeably for several years.  While Fischer felt that the plaques and fibrils were important in causing dementia, Alzheimer, mentioning Fischer, was less convinced of the causative role of plaques.

     Fischer, being Jewish, was eventually let go from the German University and perished in a concentration camp. After the war communism ruled in Czechoslovakia and the German University was never reopened. It is not surprising that Fischer’s name was forgotten until Dr. Goedert rescued him from archives in Prague.

    

SOURCES

1. Maurer, K and Maurer U, Alzheimer: The Life of a Physician and the Career of a Disease (Eng trans) 2003; Colombia Univ Press, NY.

2. Maurer K, et al, “Auguste D and Alzheimer’s Disease” 1997; Lancet 349:1546-9.

3. Goedert, M and Ghetti, B, “Alois Alzheimer: His Life and Times”. 2007; Brain Pathology 17: 57-62.

4. Goedert, M. “Oskar Fischer and the Study of Dementia” 2009; Brain 132: 1102-11.

5. Alzheimer, A. “Histologische Studien zur Differentialdiagnose der progressiven Paralyse” (Histologic studies in the differential

diagnosis of general paresis). 1904; Histologische und

Histopathologische Arbeiten. F Nissl, ed. 1: 1-297.

6. Alzheimer, A, “Über eigenartige Krankheitsfälle des späteren Alters”1911; Zeitschr für die gesamte Neurologie u Psychiatrie 4: 356-85.

7. Fischer, O. “Miliare Nekrosen mit drusigen Wucherungen der

Neurofibrillen, eine regelmässige Veränderung der Hirnrinde bei

seniler Demenz” (Miliary necroses with plaque-like growths in the

neurofibrils, a regular alteration of the cerebral cortex in senile

dementia) Monatsschrift Psychiatrie und Neurologie 1907; 22:36-    

72.

8. Perusini, G, “Über klinisch und histologisch eigenärtige psychische Erkrankungen des späteren Lebensalters”. 1909; in Histologische und Histopathologische Arbeiten. F Nissl, A Alzheiner, eds. 3: 297-351.