THE FIRST WESTERN MEDICAL SCHOOL

   

     In the decades after the American Revolution the “west” meant anything on the Pacific side of the Appalachian Mountains. A forested area of western Virginia was called the Transylvanian Colony, near which, in Lexington, a small Transylvania Seminary served as an educational center. In 1792 most of the area moved into the newly-formed state of Kentucky and 7 years later the Seminary merged with a rival school, the Kentucky Academy, to become Transylvania University. It included a law and medical

Transylvania Colony circa 1792 (Wikipedia)

school and earned Lexington the label “the Athens of the West”. Henry Clay, later a well-known senator, taught in the law school. The medical school had a faculty of two, Dr. Frederick Ridgely and Dr. Samuel Brown. Ridgely had been schooled in Philadelphia and served in the Revolutionary Army, while Brown had studied medicine at Edinburgh. Instruction was mainly out of their homes, with no anatomical dissections and few medical students. In 1815, however, a major overhaul began, led by the prominent and feisty surgeon, Benjamin Winslow Dudley.  

Benjamin Dudley (Wikipedia)

  

     Dudley had been apprenticed to Dr.  Ridgely. He then earned an MD degree at the University of Pennsylvania Medical School after 2 winter seasons of lectures (standard at the time). There he met 2 men important to him in later life: Daniel Drake and William Richardson. He headed for  Paris where he studied surgery with Dominique Jean Larrey, the famous surgeon who served Napoleon’s army. In London he studied with John Abernathy and Astley Cooper, both excellent surgeons, and passed the exams for admission to the Royal College of Surgeons. He was the most educated surgeon in the “west” and was appointed professor of anatomy and surgery at the Transylvania Medical School. He became famous for doing over 200 lithotomies with about a 2% mortality, unheard of at the time and possibly related to his habit of washing all his instruments with boiled water. He also published on numerous other conditions.

     Dudley recruited other talented faculty. The most important catch was Daniel Drake, appointed professor of materia medica. Drake, born in New Jersey, grew up in a log cabin in the small

Daniel drake (Wikipedia)

settlement of Mays Lick, Kentucky, where danger of Indian attacks still lurked. At age 15, barely literate, the boy was apprenticed to a Cincinnati practitioner, Dr. Goforth, who granted him a “diploma” after 4 years. Goforth was an enlightened physician for his time and introduced vaccination to Cincinnati. Drake then studied one year (1805-6) at the U of Penn under Benjamin Rush, completing his second year in 1816, gaining him an MD degree. He was bookish, read widely, and built a successful practice in Cincinnati. When Dudley offered him a professorship in materia medica and medical botany in Lexington he took it. He enjoyed teaching and the students consistently rated his lectures as the best.

     A third faculty member appointed was William Richardson, an acquaintance from U of Penn days. He had only completed one

William Richardson (from Hathi Trust)

semester at Penn and practiced obstetrics. He became professor of midwifery at Transylvania U. Two other new appointments, James Overton as Professor of “Theory and Practice” and James Blythe as Professor of Chemistry, filled out the new faculty by 1817.

     There was strife from the start. In 1818 Dudley and Richardson fought a duel. Dudley shot Richardson in the groin, severing an artery. Dudley then saved him by pressing on the artery until it could be tied. They continued to work together but it is unclear how harmoniously.

     Drake, to escape tensions, moved back to Cincinnati after one year, resumed his practice, and founded his own medical school, the Medical College of Ohio. He studied and wrote on diseases of the Ohio Valley and later taught once more at Transylvania U. He is regarded as a founder of western medicine.

     In the same year as the duel, the Kentucky legislature appropriated money for an upgrade of Transylvania U. The trustees hired Horace Holley, a Unitarian minister from Boston, as president. Holley quickly transformed the University. He enlisted Charles Caldwell from the University of Pennsylvania as dean of the medical school, who traveled to Europe to acquire scientific apparatus and especially books, the start of a fine library. There being no separate medical building, Dudley built an amphitheater onto his own house for dissections and surgical instruction. Cadavers were procured by graverobbing or sometimes by the use of deceased slaves. Other classes were held in the main building until a separate building was erected in 1839. In 1828 the respected quarterly, The Transylvania Journal of Medicine, was launched.

     The school soon began to be affected by the steamboat age. Louisville and Cincinnati, both on the Ohio River, grew rapidly as Lexington, farther from navigable rivers, remained more static. A medical school opened in Louisville, galvanizing the Lexington legislature to appropriate more money. A new medical building went up and

(from The History of the Medical Department of Transylvania University)

another team went to Europe for more books and equipment. The new library was praised as the finest in the west and among the finest anywhere. Nathan Smith (see blog of 8/12/16) and Elisha Bartlett, famous names at the time, taught there and the school flourished through the 1840s. But the schools in Louisville and Cincinnati gained in size and in 1850 several of the Transylvania faculty opened a new medical school, the Kentucky Medical School, in Louisville, to compete. Eventually, in 1860, the Transylvania medical school closed, and the new one in Louisville merged with the University of Louisville in 1908. Transylvania U eventually became the University of Kentucky.

     The Transylvania U medical school had a short but illustrious life, easily comparable to eastern schools and responsible for training most of the practitioners of the early west.

SOURCES CONSULTED:

Wright, John D. Transylvania: Tutor to the West. 1975; University Press of Kentucky.

Juettner, Otto. Daniel Drake and his Followers. 1909; Harvey Publishing Co.

Wright, James R. “Early History of Transylvania Medical College” 2019; Clin Anat 32: 489-500.

Peter, Robert. The History of the Medical Department of Transylvania University. 1905; John P Morton & Co, Louisville.

Flexner, James Thomas. “Genius on the Ohio: Daniel Drake”, chapter in Doctors on Horseback. 1937; Viking Press. pp 165-234.

    

A CONTROVERSIAL NOBEL PRIZE

     Few would dispute that Nobel Prizes in the sciences are seldom mistakenly awarded. Occasionally, but only occasionally, the prize has been viewed later as inappropriate. One such instance was the award made to Dr. Johannes A. G. Fibiger, in 1926, for his work showing that intestinal worms could cause cancer. Fibiger’s conclusions eventually proved invalid but his research and life story are worth reviewing.

     Fibiger was born in Denmark in 1867. He received his medical degree from the University of Copenhagen and later studied

Johannes Fibiger (Wikipedia and National
Library of Medicine)

bacteriology in Germany. At the age of 33 he was named director of the Institute of Pathological Anatomy at the University of Copenhagen, a post he held until his death 28 years later.

     In 1907 Fibiger noticed stomach tumors in wild rats and on sectioning found small roundworms inside the growths. He learned that the worms, which he named Spiroptera carcinoma (now called Gongylonema neoplastica), were common in cockroaches, existing as a larval form in their muscles. He fed cockroaches infected with larvae to rats and produced stomach tumors, though feeding adult worms produced none. He reported the results in 1913 and the work was considered a breakthrough. However, criticisms of the report came quickly, centered mainly around whether the histology was consistent with cancer. Fibiger reported metastases in some rats but again the histology was disputed. Other workers could not easily duplicate the findings.

     In 1926 Fibiger and Katsusaburo Yamagiwa (who had induced cancer by painting coal tar on rabbit ears) were considered jointly for the Nobel Prize in medicine. No decision could be reached, however, and the prize was postponed. It was finally given to

Nobel Prize medal (Wikipedia)

Fibiger alone in 1927. The 1927 prize was awarded at the same time to Julius Wagner-Jauregg for his discovery of the helpful effect of malaria in treating tertiary syphilis (also considered a mistake by some). The staff at the Karolinska Institute, that awards the prize, commented on Fibiger’s work that “It was thus shown authoritatively not that cancer is always caused by a worm, but that it can be provoked by an external stimulus. For this reason alone, the discovery was of incalculable importance.” In his acceptance speech Fibiger acknowledged that helminthes occupied “only a modest place among the causes of neoplasms among humans”, adding that physical and chemical influences and “endogenic and exogenic” factors all played a role.

     How did the Nobel committee make the decision to award Fibiger the prize? Several seasoned pathologists had agreed with Fibiger’s histologic diagnosis of cancer, though today it would be considered hyperplasia (non-cancerous excessive growth). Cancer was known to be more common in certain occupations, such as chimney sweepers, chemical factory workers, and after radiation exposure but laboratory attempts at cancer production had generally been unsuccessful, Katsusaburo’s work being an exception. Thus the work was considered a step forward. Doubters and critics of Fibiger’s work remained, however.

     In 1937 it was shown that vitamin A-deficient diets could lead to similar changes in stomach linings. Fibiger’s rats were probably fed a vitamin A-deficient diet of bread (made without milk or egg) and water. In 1952, Hitchcock and Bell repeated

Plate from Fibiger's study of rat tumors (Hathi
Trust.  Click image to enlarge)

Fibiger’s experiments using rats on and off a vitamin A-deficient diet and produced stomach lesions resembling those of Fibiger’s animals (the original slides were studied). They concluded that vitamin A deficiency was necessary for the hyperplasia-inducing effect of the worms.

     Fibiger made another contribution to medicine, perhaps a more important one from today’s perspective. In 1896-7, before his cancer work and while working as a junior physician in Copenhagen, he carried out a clinical trial of an antiserum against diphtheria developed by Behring and Kitasato. (Fibiger had studied earlier under Koch and Behring.) Antiserum trials were successful in animals, but in humans had yielded uncertain results. Fibiger devised a randomized trial whereby children admitted on alternate days were treated alternately with conventional means (painting the throat with silver nitrate or tar oil) or conventional means plus antiserum. The study lasted one year. Eight of 239 in the serum group and 30 out of 245 in the control group died (the epidemic had a fairly low mortality rate). 60% developed serum sickness. The X² test, developed two years later, would have shown a p-value of 0.0003.

     This is believed to be the first controlled therapeutic trial using randomization. Fibiger consciously sought to “eliminate completely the play of chance and the influence of subjective judgment”. He realized the value of large numbers of subjects to eliminate chance variations and the value of long duration of study to eliminate seasonal variations in severity/mortality.

     The study had one immediate effect - an immediate boost in demand for serum. Surprisingly, the technique of random allocation did not catch on rapidly. Excepting a few small trials, generally with scanty details on technique, it took a major British Medical Research Council trial of streptomycin against tuberculosis in 1948 to put the technique on the map.

     Fibiger died the year after his prize was awarded. He had given up working with parasites and was working on coal tar painting to induce cancer. He was a member of numerous prestigious societies, was well-regarded by his colleagues as a careful researcher, and probably would have changed his mind about the stomach tumors as new evidence accumulated. He worked at a time when knowledge of cancer and histology was still patchy. Unfortunately he entered a blind alley, a hazard threatening many an investigator.

SOURCES

Stolley, PD and Lasky, T. “Johannes Fibiger and His Nobel Prize for the Hyposthesis that a Worm Causes Stomach Cancer”. 1992; Ann Internal Med 116: 765.

Bullock, FD and Rohdenburg, GL. “Experimental ‘Carcinomata’ of Animals and their Relation to True Malignant Tumors. 1917; J Cancer Research 3: 227.

 Fibiger, J. “On Spiroptera Carcinomata and their Relation to True Malignant Tumors; with Some Remarks on Cancer Age” 1919; J Cancer research 4: 367.

 Hitchcock, CR and Bell, ET. “Studies on the Nematode Parasite, Gongylonema neoplasticum (Spiroptera neoplasticum), and Avitaminosis A in the Forestomach of Rats: Comparison with Fibiger’s Results. 1952; J National Cancer Institute 12: 1345.

Hróbjartsson, A, et al. “The Controlled Clinical Trial Turns 100 Years: Fibiger’s Trial of Serum Treatment of Diphtheria” 1998; BMJ 317: 1243.

Nobel web site: https://www.nobelprize.org/prizes/medicine/1926/fibiger/biographical/. His biography and acceptance speech are both there.

    

    

VIEWING BONES THROUGH TELESCOPES

   by Roy Meals MD

     Probably primitive man's curiosity markedly increased soon after he stood up and started walking on just his feet. He could both peek into caves and drop back onto all fours to peer down badger holes. Looking into his family’s mouths and ears soon followed. Many generations later his progeny developed metal tubes and glimpsed human interiors through all of our natural orifices. Lighting, however, was always an issue, and the torch that satisfactorily illuminated the cave was poorly accepted by early patients in the proctology clinic. FIGURE 1

     This changed in 1879 with Edison’s invention of the incandescent light bulb. Just seven years later, two German doctors were lighting up bladders with a tiny bulb on the end of a steel tube through which they squinted. Heat from the bulb and risk of breakage, however, posed problems. Nonetheless, enterprising doctors began poking holes in the skin and exploring the bladder, abdomen, and chest with lighted tubes. In 1912, Severin Nordentoft, a Danish doctor, extended this concept to the knee and coined the word “arthroscopy” (joint-view). Multiple investigators from the world around then refined and continue to refine the technique.  

     Prior to antibiotics, tuberculosis, especially in the knee, occupied much of orthopedists’ time. This was particularly so in Japan, where squatting and kneeling have long been cultural imperatives. In 1918 Doctor Kenji Takagi began using a bladder scope to examine tuberculous knees. His idea was to develop early treatment that would preclude the awkward outcome of an entirely stiff knee. Over the next 20 years he designed and tested 12 versions of arthroscopes that were progressively smaller in diameter and that incorporated better optical systems. None of them, however, were entirely practical. 

     After World War II, Takagi’s student, Masaki Watanabe, took up the banner and continued to make design improvements. In 1957, Watanabe presented a color movie describing his work, first to an international orthopedic meeting in Spain and then to major European and North American orthopedic groups on his way home to Japan. The response was tepid at best.

     Undaunted, Watanabe pressed on. The twenty-first version finally provided an adequate view and good focus even though it necessitated grinding each lens by hand. By 1958 this version became the world’s first production arthroscope, but breakage of the incandescent bulb on the end of the tube continued to be problematic. Watanabe began to receive international visitors interested in learning his technique; but when they returned home, began using it, and reported their results, collegial criticism, even ridicule, prevailed.

     In 1967 the twenty-second version, for the first time, incorporated a novel fiber optic cable. Now the hot, fragile light bulb could be 6 - 10 feet away from the operative field and transmit “cold light” into the knee joint via thousands of bundled glass threads.

     Watanabe developed at least three more versions to further address the conflicting goals of better illumination and visualization vs. smaller diameter scopes that could probe the deepest recesses of small joints. His final version was less than 1/12^th of an inch in diameter—about the diameter of a coat hanger wire.  Later came miniaturized television cameras that could be attached to the arthroscope. A video monitor in the operating room displayed the images. Now residents, nurses, and students no longer had to stare at the back of the surgeon’s head as he squinted into an eyepiece attached to a narrow tube. Patients, when awake, could watch too, and a video recording of the event later allowed their families untold hours of viewing pleasure. Well, maybe minutes.

     Along with further advances in arthroscopic instrument and in scope design, international interest began to grow. At first, every procedure was merely diagnostic and was followed immediately by a large incision and exploration of the joint under direct vision to treat whatever pathology the arthroscope had revealed.

     Tiny nippers and shavers, first manual and then also powered, began to allow for arthroscopic treatment as well as diagnosis. Current techniques and instruments even allow the surgeon to place and tie sutures inside a joint. Such minimally invasive surgery allows for faster and more complete rehabilitation. Because the knee joint is large, the innovations started there, but now orthopedists also routinely apply these techniques to the shoulder, elbow, wrist, hip, and ankle joints.      Undoubtedly our caveman ancestors, torches and clubs in hand, would be pleased to know where their curiosity for peering into holes has led. FIGURE 2

Sources:

Jackson RW: A history of arthroscopy. Arthroscopy 2010; 26 (1): 91–103

Spaner SJ, Warnock GL: A brief history of endoscopy, laparoscopy, and laparoscopic surgery. J Laparoendosc Adv Surg Tech A. 1997;7(6):369-73.

Treuting R: Minimally invasive orthopedic surgery: arthroscopy. Ochsner J 2000; 2(3): 158–163.

ALBERT NEISSER AND HUMAN EXPERIMENTATION

     Medical experimentation on humans has a long and sometimes depressing history, brought into high relief by experiences in Germany and Japan during WWII. After the war numerous papers, declarations, and laws emerged, coalescing into a more definitive approach to human experimentation. Long before the war, though, the case of Albert Neisser aroused great interest in Germany and gave birth to what is thought to be the first governmental guidelines for human experimentation.

     Albert Neisser was born in 1855 in a small Silesian town to a physician father. He studied medicine at the pretigious Breslau University Medical School (where Robert Koch had given his demonstration of the cause of anthrax in 1876, probably while Neisser was there). After obtaining his MD degree he joined the Breslau University Dermatology Clinic. 

Albert Neisser (National Library of Medicine)

     Dermatology, in those days, dealt with venereal diseases, including gonorrhea. Bacteriology, the new, popular science, induced Neisser to seek a bacterial cause for gonorrhea. He had learned microbiology at Breslau and was familiar with Abbe’s condenser and oil immersion techniques, new in the 1870s, that improved the resolution of microscopic images. At the age of 24, using the latest microscopic equipment, he discovered, in urethral discharges, the paired cocci that bear his name (Neisseria gonorrhea), and cultured them shortly afterward – an important discovery.

     After a trip to Norway to work with Armauer Hansen on leprosy, that ended in a priority dispute, Neisser returned to Germany and rose to head the Breslau dermatology clinic after his chief died. Neisser was impressed with the recent demonstrations by Behring and Kitasato of the healing effects of antiserum in cases of diphtheria. He wondered if serum from people with syphilis, made cell-free for purity, could provide similar “passive immunization” against the disease. First he injected subcutaneously serum from a patient with early syphilis into four female patients, aged 10 to 24. None developed syphilis. Next, using cell-free serum from patients with syphilis in various stages, he injected up to 30cc intravenously into four prostitutes, aged 17 to 20. They all developed syphilis. None had given informed consent.

     News of the experiments reached the press, creating an uproar. Neisser wrote a statement defending his work, suggesting also that that the latter four women contracted syphilis because they were prostitutes and not because of his serum injections. Similar experiments were done by other physicians, and he was supported by the majority of his colleagues though one, the psychiatrist Albert Moll, who was writing a book on physicians’ ethics, spoke out against him. Neisser was fined by the Royal Disciplinary Court - because he had not obtained the patients’ consent, not because of questionable science.

     The Prussian Parliament took up the case and sought an opinion from the Scientific Medical Office of Health. Rudolf Virchow, Emil von Behring, and other prominent physicians were on the panel. Lawyers were also consulted. In 1900 the Minister for Religious, Educational, and Medical affairs issued a directive. All medical interventions other than for diagnosis or treatment were prohibited if the subject was a minor or not competent, or if consent was not obtained after proper explanation of possible negative consequences. All research interventions had to be authorized by the medical director of the institution and all details had to be documented in the medical record. The directive was not legally binding.

     Evidently similar cases subsequently came to light and in 1931, in the context of an overall reform of criminal law in Germany, the national government issued “guidelines for new therapy and human experimentation”. These guidelines distinguished between experimental new treatments and experiments intended to extend knowledge but without therapeutic benefit. In both cases minors and incompetents were excluded, and consent from a properly informed and autonomous subject was required for any experiment. The only exception was if a new treatment were desired in urgent cases and immediate consent was impossible. Experimentation on dying patients was prohibited and animal experimentation should precede that on humans. Exploitation of financial or social needs was prohibited. The physician’s special responsibilities in clinical trials should be emphasized in medical teaching. A form of institutional review board was discussed but the review and oversight function was left with the medical director. The complete guidelines (translated) are found at: file://localhost/Users/john/Documents/ history of medicine & science/ethics,GERMAN GUIDELINES ON HUMAN EXPERIMENTATION 1931.webarchive. They are believed to be the first such guidelines issued by a government. They were not annulled during the Nazi era but were certainly ignored. 

Fritz Schaudinn, co-discoverer with E. Hoffmann
of Treponema Pallidum
(National Library of Medicine)

     Neisser turned to monkeys for further syphilis research and moved to Java where monkeys were abundant. He clarified several aspects of syphilis, including showing 

Erich Hoffmann, co-discoverer of Treponema
Pallidum (Wellcome Library)

inability to arrest the disease by removal of the primary chancre (a common belief at the time), or to immunize monkeys. He published a book summarizing the work. While he was in Java the causative Treponema pallidum was discovered and on his return he and his assistants worked with August Wasserman to develop the Wasserman test (1906). 

August Wassermann (Wikipedia)

     Neisser took an increasing interest in public health aspects of venereal disease, advocating public health clinics and regulation of prostitution, all at a time when these subjects were seldom discussed in public. He died in 1931 from complications after surgery for bladder stone.

      Neisser’s career encompassed much of modern knowledge of syphilis. His one irresponsible experiment brought the issue of human experimentation into the German public arena, where the first governmental guidelines for human experimentation were formulated, well before similar rules existed in the United States.

 SOURCES:

Vollmann, J and Winau, R. “Informed Consent in Human Experimentation before the Nuremberg Code” 1996: BMJ 313: 1445-7

Oriel, J. “Eminent Venereologists, 1. Albert Neisser” 1989; Genitourin Med 65: 229-234.

Ligon, B L. “Albert Ludwig Sigesmund Neisser: Discoverer of the Cause

of Gonorrhea” 2005; Semin Pediatr Infect Dis 16: 336-41.

 Benedek, T G. “Case Neisser: Experimental Design, the Beginnings of Immunology, and Informed Consent” 2014; Perspect Biol Med 57(2): 249-67.

USHER PARSONS AND NAVAL MEDICINE IN

THE WAR OF 1812

     “The most outstanding naval surgeon in the War of 1812” is a generous tribute to a man who helped shape U.S. naval medicine. Who was he?

     His name is Usher Parsons, born in Maine in 1788. His father was a farmer and merchant, apparently with little money. After primary schooling through age 12 Usher worked clerking in stores, then at age 19 was apprenticed to a local doctor, attended anatomy lectures and read medical texts. Realizing he was still not well educated he studied Latin and Greek, then, in 1811, won an apprenticeship with Dr. John Warren, the founder of Harvard

Usher Parsons (National Library of Medicine)

 Medical School. The following year he was licensed by the Mass. Medical Society. After an unsuccessful try at private practice, knowing that war had come, he sought a commission in the Navy.

     The War of 1812 was in large part a naval war. When the United States declared war on England, the fledgling United States had almost no navy. President Madison, intending to invade Canada, built a naval force on the Great Lakes to support army troops. Two ships, the Lawrence and the Niagra, both 20-ton brigs (2-masted vessels), and numerous smaller vessels were constructed on Lake Erie. Parsons was assigned as surgeon’s mate to the Lawrence, named after the James Lawrence who had uttered the cry, “don’t give up the ship”.

     Three levels of medical personnel served on naval ships at the time: surgeon, surgeon’s mate, and the “loblolly boy”. The surgeon was responsible for the overall health of the ship, and duties included inspection of food and water, care of patients (and keeping records of care), surgeries when needed, and maintaining stores of medicines and instruments. The surgeon’s mate, having less education and experience, assisted in surgery (generally to restrain the patient) and performed routine patient care in sickbay (generally located forward on the gun deck in an empty gun space called a “bay”). The loblolly boy, named for a thick porridge (“loblolly”) doled out to sailors, fed and nursed patients, and performed leeching, cupping, and other duties.  

      The Lawrence engaged two British vessels. Moving in close it was severely damaged by the opposing ships and was saved only after the Niagra, holding off for unclear reasons, was finally brought in to defeat the British ships.

The dismasted center ship is the Lawrence, the large ship to the right is the Niagra, and the small craft is carrying
Commodore Perry to bring the Niagra into the battle.  British ships are on the left.
(Lithograph by J P Newell, courtesy Library of Congress) click on image to enlarge

     Wounds received by navy men were varied. Cannonball hits caused some injuries, but smaller shot and canister caused many more. A cannonball hit to a ship’s hull would send splinters flying inside the vessel, inflicting serious wounds, and if it hit at the waterline would open a hole to let water in. Sharpshooters were posted in the rigging to pick off men on enemy decks. The wounded were usually cared for in a room below waterline, to avoid shot and splinters.

     On the Lawrence the surgeon was ill, and Parsons took over. The wounded were carried to the wardroom (mess room for midlevel officers), a roughly 10 to 12 square foot room just above the water line. Occasional cannonballs sailed through as Parsons worked feverishly. He had no time for the usual amputations and simply applied tourniquets and pressure bandages to stop bleeding. The only immediate surgery, he noted in an account in the New England Journal of Medicine and Surgery, was when a “division was made in a small portion of flesh, by which a dangling limb that annoyed the patient was hanging to the body.” He labored until midnight to “administer opiates and preserve shattered limbs in a uniform position”. At dawn the next day he carried out the necessary amputations (no anesthesia), followed by treating fractures, dislocations, and superficial wounds. Out of about 100 men fit for duty, 21 were dead and 63 wounded.

     The next day he boarded the Niagra, whose surgeon he found ill in bed, with “hands too feeble to execute the dictates of a feeling heart,” and cared for the wounded. The number of wounded from both ships was 96, of whom only 3 later died, an extraordinary recovery rate for the times. Parsons cites three reasons: the wounded were kept on deck for two weeks, inhaling lots of fresh air; they were well fed with meat, vegetables, and eggs; and finally, they possessed “the happy state of mind which victory occasioned.” Pretty good results for someone freshly out of an apprenticeship and little practical experience.

The first book of Usher Parsons
(Hathi Trust)

     After the war Parsons earned his MD from Harvard and studied in Europe at Navy expense. Subsequent naval voyages took him to the tropics, the Middle East, and Europe, where he met many notables in science and medicine. From France he wrote, “Larrey’s manner of operating is pleasing…He is humane and solacing in his behavior to patients, differing in this respect very much from Dupuytren, whose behavior to them is savage.”¹ He later taught anatomy at Dartmouth and helped found the medical school at Brown University. He resigned his commission in 1823, opened a practice in Providence, and penned numerous papers. In 1824 he published Sailor’s Physician, a short handbook of naval medicine that recommended citrus fruits for scurvy and Peruvian bark for intermittent fever. The book later evolved into an important work: Physician for Ships, that went through at least 4 editions and was a

Section on sea-sickness from Physician for Ships, 3rd edition. (Hathi Trust) Click on image to enlarge.

leading text for naval doctors through the Civil War. Parsons, married to the sister of Oliver Wendell Holmes, died in 1868.

     Usher Parsons was a talented man who helped bring modern medicine to a fledgling American Navy.

     This essay was kindly reviewed and improved by Andre Sobocinski, Historian, Bureau of Medicine and Surgery, U.S.Navy.

    [1] Dominique Larrey was Napoleon’s prized army surgeon. Guillaume Dupuytren was the gifted chief of surgery at the Hôtel Dieu-Hospital in Paris.

SOURCES:

Cushman, P. “Usher Parsons MD” N Y State J Med 1971; 71(24): 2891-4.

Cushman, P. “Naval Surgery in the War of 1812”. N Y State J Med 1972; 72(14): 1881-7.

Pleadwell, F L. “Usher Parsons (1788-1868), Surgeon, United States Navy”, 1922; United States Naval Med Bull 17: 423-60.

Daughan, George. 1812: The Navy’s War. 2011. Basic Books.

Goldowsky, S J. Yankee Surgeon: The Life and Times of Usher Parsons. 1988.

To subscribe to the blog, send an email to gfrierson@gmail.com.

    

     

EINSTEIN TO DEBAKEY:

EVOLUTION OF ANEURYSM SURGERY

     Albert Einstein had a pain in his belly, not a new one, but worsening. Admitted to Brooklyn Jewish Hospital in December of 1948, his white hair defying gravity, he underwent surgery and was found to have a grapefruit-sized aneurysm of the aorta (an expanding section of the body’s major artery) that threatened to rupture. The surgeon, Rudolph Nissen, wrapped a piece of

Albert Einstein (Wikipedia)

polyethene cellophane around the visible part of the aneurysm, considering it too dangerous to raise the vessel for a full wraparound. Polyethene had irritant properties that caused a fibrous thickening of the aneurysm wall, hopefully strengthening it enough to prevent a rupture. Einstein recovered uneventfully and returned to work in Princeton, N.J.

     Though he had intermittent pains he did well until April, 1955, when he was readmitted with severe abdominal pain. Now a huge mass extending from the left lower rib cage to the pelvic brim pulsated visibly. It was his aneurysm, greatly enlarged and again in imminent danger of rupturing. Surgery was offered, this time to resect the aneurysm and replace it with a section of aorta from a cadaver. Einstein refused, saying it was time to go and “I will do it elegantly”. He expired five days later, and at autopsy a ruptured aneurysm was the reason. Did the cellophane wrapping prolong Einstein’s life? Based on statistics at the time, probably yes.   

    Fifty-one years after Einstein’s death, on New Year’s Eve of 2006, another celebrity of the scientific world had a similar problem. Dr. Michael DeBakey, age 97, suffering a fierce chest pain, diagnosed the pain as a dissecting aortic aneurysm. He

Michael DeBakey (Wikipedia)

would know, as he had operated on hundreds, maybe thousands, of aneurysms over the years. Dr. DeBakey refused hospitalization but consented to a CT scan, which confirmed a dissecting aneurysm of the ascending aorta (saccular enlargement due to a tear of the inner lining of the aorta, just above the heart, in danger of rupture and internal bleeding). He declined hospital admission and, pale and unsteady, gave a lecture three days later, followed by a luncheon. He grew weaker, ate little, and was finally admitted to Methodist Hospital, Houston, on Jan 23, where another scan showed “dangerous” enlargement of the aneurysm. His physicians advised surgery in spite of his age, but, like Einstein, DeBakey said no. By Feb. 9, with the aneurysm still expanding, DeBakey had lost consciousness. His surgeons, though, still felt he had a chance with surgery.

     As related by the noted physician-journalist Lawrence Altman, who knew DeBakey well, the family gave permission to operate, but the anesthesiologists of the hospital refused to anesthetize him, feeling they would be looked upon as aiding his death. Another anesthesiologist, an old colleague, was brought in. Heated discussions that included doctors, lawyers, and hospital

Methodist Hospital, Houston (Wikipedia)

administrators dragged into the evening. Complicating the issue were a note saying that he did not want surgery and a signed “do not resuscitate” order, both in DeBakey’s chart. But Mrs. DeBakey and the doctors, all long-time colleagues, felt that the situation had changed enough to make these wishes inapplicable. The ethics committee of the hospital was summoned to an emergency meeting at about 10PM. After an hour of inconclusive deliberation Mrs. DeBakey, waiting outside, burst into the room shouting that her husband would die if nothing were done soon. The ethics committee agreed to the surgery at 11 PM. No minutes were taken of the meeting.

     The operation lasted seven hours, with DeBakey placed on a bypass pump and his body temperature lowered. The aortic tear was resected and replaced with a Dacron graft, an operation DeBakey had pioneered himself years earlier. After a prolonged and “stormy” course, including dialysis, he recovered enough to resume work. One year after surgery he could walk unassisted but preferred a motorized scooter, on which he raced up and down hospital corridors. His mind remained clear. He said later that he was happy that his wish to avoid surgery was ignored. He passed away in July of 2008, cause not mentioned. The cost of his care was estimated at over $1 million. 

Aorta showing two aneurysms, a large one in
the thoracic portion and another, sectioned in two,
in the lower aorta (from Clinical Lectures on the Principles
and Practice of Medicine, by John H Bennett, 1860)

     Michael DeBakey was born in Louisiana of Lebanese immigrant parents and attended the Tulane School of Medicine. In WWII he helped develop Auxiliary Surgical Groups that provided surgical care close to the front lines, a predecessor of the MASH units of the Korean and Vietnam wars. He subsequently built the small Baylor College of Medicine department of surgery into a large, advanced, surgical training center and helped pioneer many innovative procedures, especially in cardiovascular surgery. He was also instrumental in forming the National Library of Medicine.

     In 1952 DeBakey did his first aortic aneurysm resection, replacing the aortic segment with cadaver aorta, the same operation offered to Einstein in 1955. Cadaver aortas were in short supply, however, and a synthetic material was sought. Nylon and related materials were tried but did not work well. One day DeBakey, looking for nylon in a store, was offered a new material, Dacron. Trying it in dogs, he found it performed well, and Dacron soon became the standard for aorta surgery. The gap between the surgeries of Einstein and DeBakey covers this period of major progress in aortic surgery.

     The debates around DeBakey’s surgery at age 97 clearly reflect today’s struggles over defining what is reasonable treatment for patients in advanced age, a problem all too common as our population grows older.

SOURCES:

Cohen, J R and Graver, M. “The Ruptured Abdominal Aortic Aneurysm of Albert Einstein.” 1990; Surg, Gyn, Obst 170 (5): 455-8.

L Altman. “The Man on the Table was 97 but He Devised the Surgery”. New York Times Dec 25, 2006.

L Altman. “Michael DeBakey, 99, Rebuilder of Hearts, Dies”. New York Times July 13, 2008.

Chunn, C F. “Treatment of Aneurysms by Polyyethene Wrapping”. Ann Surg 1954; 139:  751-9.

DeBakey, M E. “The National Library of Medicine: Evolution of a Premier Information Center”. JAMA 1991; 266: 1252-8.

Morris, Thomas. The Matter of the Heart: A History of the Heart in Eleven Operations. 2017; St. Martin’s Press. Chap. 3.

“The Michael E. DeBakey Papers”. Profiles in Science, National Library of Medicine. Online at: https://profiles.nlm.nih.gov/ps/retrieve/Narrative/FJ/p-nid/322

WILLEM EINTHOVEN AND THE FIRST

ELECTROCARDIOGRAMS

     Is there electricity in heart muscle?  No one knew until, by accident, two German scientists, Köllicker and Müller, in 1856, saw that when the end of a frog’s sciatic nerve was mistakenly laid on top of a living frog’s heart, every heartbeat caused a twitch in muscle attached to the nerve. In subsequent years the anatomic pathways conducting current through the heart were mapped out, laying the groundwork for further study.

     The knowledge was fascinating, but could a recording of the feeble electrical activity help people with heart disorders? Yes, as it turned out.    

     The first recording in a human appears to have been done by Alexander Muirhead at St. Bartholomew’s Hospital in 1869 or 1870. He used something called a Thompson siphon recorder, an instrument made to record telegraph messages and based on movements of a wire coil between two magnets. Muirhead left medicine, however, to become a telegraph engineer. Next was

Auguste Waller (Wellcome Library)

Auguste Waller, son of Augustus Waller, who discovered “Wallerian degeneration” (degeneration of a nerve fiber distal to the site of injury). Waller placed a capillary electrometer, a thin, capillary-like tube enclosing a column of mercury topped by sulfuric acid, on the human chest. The electricity of the heart passed through the tube, moving the mercury level up and down, the motion recorded by strong light passing through a magnifier to a moving film. Response time was slow and the recordings not very sensitive. (See figure 1) Waller did not foresee much clinical use for his device.

Waller's Mercury Column Tracings
Fig 1: Lower tracing is EKG, middle one is chest wall vibrations from heart beat,
and upper one counts time (From J Physiol 1887; 8: 229-34, Hathi Trust))

     For the transition to modern electrocardiography we owe thanks to a Dutchman, Willem Einthoven. Einthoven was born in 1860 in the Dutch East Indies, where his father was a military physician. He was educated in Holland after his father died and

Willem Einthoven (Wellcome Library)

received his medical degree at the University of Utrecht. With the help of his professor of physiology, Franz Donders (who made important advances in ophthalmology), Einthoven became professor of physiology at Leiden University in 1886, at age 26. Stimulated by Donders, he began to record electric currents from the human heart, employing the same mercury column used by Waller. Einthoven, however, was also a self-taught mathematician and devised formulas to extrapolate the sluggish EKG pattern into a more readable and remarkably accurate form. (See figure 2)

Fig 2. Upper tracing by Einthoven is from mercury column. Lower one is derived mathematically
from the upper, with PQRST labelling applied (from Arch ges Phys 1885; 60:101-23, Hathi Trust))

He also changed the lettering of the deflections to PQRST from the ABCD used by Waller, apparently following a mathematical convention for labeling curved forms. He experimented with leads placed in various combinations, ending up with the 3 conventional leads used today. The leads were obtained by submerging a hand or foot in a jar of electrolyte solution.

     Einthoven’s lab was located in an old building adjacent to a cobblestone street. Vibrations from horse-drawn wagons passing by outside frustrated his work with the electrometer. Digging a hole 10-15 feet deep and fortifying it with rocks did not help.

      As a way out, Einthoven took advantage of a new instrument invented by a Frenchman, Clement Ader, called a string galvanometer. Ader placed a thin metal wire, 20 microns thick, between 2 magnets, to record wiggles as a tiny current passed through. This ingenious man had devised the first stereo apparatus and gave the first stereo renditions of the Paris Opera. He also was the first to fly a motorized plane, uncontrolled (the Wright brothers' was controlled), and later wrote a popular book on aviation.

     Einthoven took the galvanometer a step further, using a string of only 2.1 micron diameter. The string was made by placing a piece of quartz on the rear end of an arrow attached to a crossbow.

Schematic of Einthoven's string galvanometer. String is vertically
placed between 2 magnets. A microscope and light pass through
horizontally to project onto film (Einthoven, 1906, Hathi
Trust))

The quartz was heated to near-liquid state and the arrow fired. The thin, floating, thread left behind was coated delicately with silver before use. Using a strong arc light, a 600-power magnifier, and sensitive rolling film, Einthoven recorded amazingly accurate tracings. They corresponded well to the renditions he had calculated from the coarse mercury tube records. Einthoven called his recordings “electrokardiograms”, soon 

Lead one EKG, string galvanometer, published 1906 (Einthoven, 1906, Hathi Trust)
The high quality is remarkable

shortened to “EKG”. Before long he was able to publish on various rhythm disturbances, including heart block, atrial fibrillation, and the like (see Figure). 

Atrioventricular block (Einthoven, 1906, Hathi Trust)

     Einthoven’s apparatus was so large it could not be transported to a hospital, but the Cambridge Scientific Instrument Company learned how to manufacture a moveable version. One of the company’s founders, Horace Darwin, youngest son of Charles Darwin, negotiated with Einthoven to put galvanometers on the market, giving Einthoven a percentage of the sales. Clinical

Subject with hands in jars of electrolyte
solution as leads (Einthoven, 1906, Hathi Trust)

electrocardiography was born.  

     For his discoveries Einthoven was awarded the Nobel Prize in 1924, a prize worth $40,000 dollars at the time. Feeling that he could not have won the prize without the help of his now-retired lab assistant, Van der Woerd, Einthoven wished to share the prize. He found that the former assistant had died but was survived by 2 sisters, living frugally in an almshouse. Einthoven awarded half of his prize to the sisters.

     When the Queen of Holland learned of Einthoven’s award she offered to replace his old building with a new, modern structure with a fine laboratory. Einthoven declined the building, asking instead for money to hire another assistant and purchase new research equipment. The Queen obliged.

     Einthoven was described as a generous, graceful, man of simple tastes, who spoke 3 languages, and was instrumental in maintaining good international scientific relations over the years, not an easy task through the World War One period. His contribution to cardiology speaks for itself.

SOURCES

Cooper, J. “Electrocardiography 100 Years Ago”. NEJM 1986; 315: 461-4.

Ershler, I. “Einthoven – The Man”. Arch Int Med 1988; 148: 453-5.

Burnett, J. “The Origins of the Electrocardiograph as a Clinical Instrument” Medical History Suppl 5, 1985; 53-76.

Waller, A. “A Demonstration on Man of Electromotive Changes Accompanying the Heart’s Beat”. J Physiol 1887; 8: 229-34.

Einthoven, W. “Über die Form des Menschlichen Electrocardiogramms”. Arch gesamte Physiol 1895; 60:101-23.

Einthoven, W. “Über das Normale Menschliche Electrokardiogramm und über die capillar-electrometrische Untersuchung Einige Herzkranken” Arch gesamte Physiol 1900; 80: 139-60.

Einthoven, W. “Über das Normale Menschliche Electrokardiogramm und über die capillar-electrometrische Untersuchung Einige Herzkranken” Arch gesamte Physiol 1900; 80: 139-60.

Acierno, L J. The History of Cardiology. 1994; Parthenon Publishing.