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.

     

THE MUSICAL SURGEON: THEODORE BILLROTH

     One of the great figures of 19^th century medicine was Theodor Billroth, a skilled, inventive surgeon and a consummate musician. His accomplishments are too numerous to fit into a short essay but even a few comments will reveal his great breadth.

     Billroth was born on the island of Rügen, Prussia. His father, a Lutheran minister, died when he was five. Theodor took to music at an early age, but after a gymnasium education he was induced, for monetary reasons, to study medicine rather than music. He

Theodor Billroth (Nat Library of Medicine)

obtained his medical degree in Berlin followed by a period of study in Vienna. On return to Berlin he received an appointment as surgical assistant to the famous Bernhard von Langenbeck at Berlin University. Here, in addition to practicing surgery, he immersed himself in pathology, publishing on polyps, testicular tumors, the spleen, and other topics. In 1860 he was tapped for a professorship of surgery at the University of Zürich, where he published a textbook on surgical pathology and was the first to publish “total” results of operations, including complications and mortality rates. In 1867 he was called to Vienna as professor of surgery at the famous Vienna General Hospital (Allgemeine Krankenhaus). Here he remained until his death in 1894. Lacking experience in battle surgery he volunteered at field hospitals in the Franco-Prussian war, developing triage techniques and principles of ambulance service. He took an

                                        "Theodor Billroth Operating" by Adalbert Seligman, painted between 1880-90 (Wikipedia)
                                          Notice the resemblance to "The Gross Clinic" by Thomas Eakins painted years earlier.
                                    Notice also the gowns but no gloves or masks, lighting by sunlight, and open drop anesthesia.
         According to the artist the operation is a neurotomy for trigeminal neuralgia. The artist and the Duke of Bavaria (who enjoyed attending)                                                                                       are depicted in the audience. The painting was found forgotten in a closet at the Surgical Clinic in 1963 (LITMED:    http://medhum.med.nyu.edu/view/10332 ) 

interest in wound infections, developed important new operations,  published a surgical text, and authored numerous articles. His students went on to professorships in university centers around the world.

     One of his famous operations became known as “Billroth I”. Two of Billroth’s assistants had worked on dogs to see if partial gastric resection was feasible, and especially to learn whether gastric juice would dissolve an anastomosis. So he was ready when in January, 1881, a 43 year-old woman, Therese Heller, presented with over 3 months of regurgitation and vomiting. A tumor was easily felt through her wasted abdominal wall. Under chloroform, using Lister’s antiseptic principles (except the spray), and after washing the stomach with 14 liters of warm water, a horizontal incision exposed the moveable, apple-

Frau Heller's Excised Pyloric Tumor
(Billroth, T. Clinical Surgery: Extracts from
the Reports of Surgical Practice, 1860-76. Eng Trans, 1881.
New Sydenham Soc., Hathi Trust)

sized, pyloric tumor, which was resected. The greater curvature of the stomach was narrowed and a residual opening sutured to the duodenum. The operation lasted 1½ hours. Postoperatively Frau Heller had little pain and almost no fever. She took sour milk, then a soft diet, and finally beefsteak. She had no intravenous fluid or antibiotics. She died 4 months later from metastatic disease and with an intact anastomosis. It was the first successful partial gastric resection, after which the field developed rapidly.

     While in Zürich Billroth took time to indulge his musical interests. Already accomplished on the piano and violin, he taught himself the viola and became part of a quartet. He was taken on as a music critic by the local paper, Neuen Zürcher Zeitung. After an uncomplimentary review of the Zürich Symphony he was fired, but rehired when the orchestra musicians protested that they needed expert criticism to maintain good quality. In Zürich he met Johannes Brahms twice, once hosting him as a guest in his home. He surprised Brahms by recognizing his compositional ability before the public had appreciated him.

     Musical theory fascinated Billroth so much that later in life he attempted a complicated manuscript, combining science and esthetics, to explain what made a person “musical”.

     The Vienna that greeted Billroth was a major cultural center, where compositions of Johann Strauss, Liszt, Bruckner, Dvorak, and Robert Schumann were bringing audiences to their feet. Brahms was already resident there and he and Billroth formed a close friendship, often joined by the music critic Eduard Hanslick in extended conversations on music. Brahms came to appreciate Billroth’s musical judgment so much that he often tried out compositions in Billroth’s home, which had a sumptuous music room, before public performances. The two men carried on an extensive correspondence, largely about music.

Johannes Brahms, c 1872 (Wikipedia)

     Both men were disciplined workers, but in many ways they were not alike. Billroth was well educated, outgoing, gracious, and fond of social gatherings. Brahms had been born in poverty in a Hamburg slum. His father was a fiddler in local bars who taught him the violin and piano. Young Johannes had been forced to play piano in similar bars and in brothels to earn money. His education was self-acquired, he was more introverted, and could be rude or gruff with others. His friendship with Billroth was warm, however, and he sought Billroth’s opinions on many occasions.

     Shortly before Billroth’s death Brahms happened to see a letter from Billroth to Hanslick, mentioning that he, Brahms, was often abrupt and discourteous to others, “like Beethoven”, and

House of Brahms' Birth, destroyed in WW II
(Wikipedia)

hampered by the poverty of his youth and his lack of education. Brahms and Billroth continued to correspond, but their relationship thereafter was cooler. Billroth died 2 years later of heart failure, and Brahms died 3 years after that of liver disease. Both were honored by large funeral processions and both were buried in the Central Cemetery in Vienna, not far from the graves of Beethoven, Schubert, and a monument to Mozart.

     Billroth was a great surgical innovator and an inspiring teacher. He emphasized the importance of research for surgery and introduced the fashion of surgical statistics, along with 5-year survival rates, into surgical literature. He was also an accomplished and insightful musician with a refined esthetic sensibility. Brahms was his primary sounding board and major link to the world of music.

SOURCES:

Rutledge, R H. “A Musical Friendship: Billtorh and Brahms”. 2007; J Surg Education 64: 57-60.

Rutledge, R H. “In Commemoration of Theodor Billroth on the 150^th Anniversary of his Birth”. 1979; Surgery 86: 672-93.

Ellis, Harold. Famous Operations. 1984; Harwal Publishing. pp29-35.

Wangensteen, Owen. The Rise of Surgery.  1978; Univ of Minnesota Press. pp 142-57.

McLaren, N and Thorbeck, R. “Little-Known Aspect of Theodor Billroth’s Work: His Contribution to Musical Theory”. 1997; World J Surg 21: 569-71.

Buklijas, T “Surgery and National Identity in Late Nineteenth-Century Vienna”. 2007; Stud Hist Philos Biomed Sci 38: 756-74.

    

Billroth, T. Clinical Surgery: Extracts from the Reports of Surgical Practice, 1860-76. Eng Trans, 1881. New Sydenham Soc. pp 502-5.

Hemmeter, J C. “Theodor Billroth, Musical and Surgical Philosopher. A Biography and a Review of his Work on Psycho-physiological Aphorisms on Music”. 1900; Bull J Hopkins Hosp. 11: 297-317.

Nagel, M, Schober, K-L, Weiss, G. Theodor Billroth: Chirurg und Musiker. 1994; Regensburg.

VENEREAL DISEASE AND COMPULSION

     In the spring of 1916 the Mexican revolutionary Pancho Villa raided the town of Columbus, New Mexico, setting off a small war with the U.S. After General Pershing chased him back to Mexico numerous American troops remained encamped on the Mexican border. Saloons and brothels appeared almost instantly and the venereal disease rate among the troops soared, reaching close to 30%. As rumors of the “debauched” scene drifted out, Secretary of War Baker dispatched Raymond Fosdick, a

Raymond Fosdick (Wikicommons)

Progressive and social reformer, to investigate, and he confirmed the news. Baker ordered stricter discipline, which helped, somewhat.

     The very next year the U.S. military began preparing for war in Europe. The War Department formed the Commission on Training Camp Activities (CTCA), headed by Fosdick, to help keep STIs out of the military training camps. The goal was to create a wide perimeter around the camps, devoid of bars and brothels, encourage sporting and recreational facilities, and provide education about STIs with graphic lectures, pamphlets, and movies.

     But male-female contacts flourished anyway and the VD rate remained high. As a stopgap measure “chemical prophylaxis” was provided for recruits recently exposed: first urinate, then wash the genitals, follow with a mercury bichloride rinse, then an injection of protargol (a silver-albumin compound) into the urethra to be held for five minutes, then expelled. It seemed to be effective for gonorrhea prevention.

     Meanwhile, another group, the Committee on Protective Work for Girls (CPWG), headed by the social worker Maude Miner, was formed to patrol around bases, befriend nearby women, and try and talk them out of meeting recruits. This also had little impact, persuading the CTCA to turn to more repressive measures, initiating a dark chapter in public health history. Detention became the watchword.

     Subdivisions of the CTCA worked with Law Enforcement personnel. They approached young women found near training camps and, if suspicious, hauled them off for an examination for venereal disease. If any was found they were incarcerated for treatment. For syphilis this meant several weeks.

     State governments, fearful of losing lucrative military camps, cooperated in the effort by passing laws for the arrest of women “reasonably suspected” of having VD. In many cases there was no habeas corpus, bail, or legal recourse for arrested women. By March 1918, 32 states had passed such laws. Rockefeller money went into the CTCA. President Wilson allocated $250,000 for establishing “detention homes” where the women were held and treated (to keep them out of prisons), and states provided others. Congress passed the Chamberlain-Kahn bill authorizing one million dollars for the same purpose, though the money went for maintenance of existing ones. The homes were often pretty shabby. Many of the detainees were given IQ tests, part of the nascent eugenics movement seeking to sterilize mental defectives. Over 18,000 women were incarcerated in federally funded institutions, some of whom did not have VD. The total number incarcerated is estimated at 30,000 or more.

     A recent book describes the ordeal of Nina McCall, an 18-year-old woman in St. Louis, Michigan, thought to have been fraternizing with soldiers at a nearby base. Confronted with a choice of being quarantined in her house with a sign outside saying she had venereal disease or entering a treatment facility, she opted for the latter. She was treated for gonorrhea and syphilis

August von Wassermann

in a “detention hospital” – a former contagious disease hospital. Once inside she could not leave until treatment was complete, about 2 ½ months in her case.

     A cacophony of public opinions on venereal disease provided a backdrop. Many still saw it as a moral issue, preaching education and abstention. Others advocated legally regulated prostitution near camps, with regular inspection of women by doctors to weed out those with disease (This was done in Nashville and Memphis during the Civil War). Many, especially women’s groups, complained, rightly but in vain, that detaining women and suppressing prostitution implied that men had little responsibility for passing on infections. If women were to be arrested, why not

Poster for film on Paul Ehrlich played by
Edward G Robinson (Wikipedia)

men? In the military soldiers were seldom disciplined even though acquiring VD was a punishable offence. Strangely, condoms were seldom emphasized, partly because they were seen as an inducement for “loose behavior” and partly to avoid antagonizing the Catholic Church.

     Medically, progress had been made with VD. In the first decade of the twentieth century the spirochete causing syphilis was

Fritz Schaudinn (Wikipedia)

discovered by Schaudinn and Hoffmann, and August von Wasserman developed his serologic test for syphilis. In the next decade Paul Ehrlich’s lab discovered compound 606 (Salvarsan), then Neosalvarsan, both arsenicals, usually used with mercury, for treatment of syphilis. Side effects of arsenicals were significant and dose regimens unstandardized. Many underwent treatment for months. Urethral silver

remained the treatment for gonorrhea.

     After WWI most of the detention activities ceased as training camps dissolved and funding evaporated. Important too was a public reaction against detentions and the compromise of civil rights. Raymond Fosdick eventually became president of the Rockefeller Foundation. The US Public Health Service, filling the postwar void, assumed a greater role in STI prevention and education.

SOURCES:

Stern, Scott. The Trials of Nina McCall. 2018; Beacon Press.

Brandt, Allan. No Magic Bullet: A social History of Venereal Disease in the United States since 1980. 1985; Oxford Univ Press.

Parascandola, John. Sex, Sin, and Science: A history of Syphilis in America. 2008; Praeger Press.

Sartin, J S, Perry, H O. “From Mercury to Malaria to Penicillin: The History of the Treatment of Syphilis at the Mayo Clinic-1916-1955”. J Amer Acad Dermatology 1995; 32:255-61.

Kampmeier, R H. “Venereal Disease in the United States Army: 1775-1900”. Sexually Transmitted Dis 1982; 9(2): 100-03.

Kampmeier, R H. “The Continuous Treatment of Early Syphilis by Arsphenamine and Heavy Metals”. Sexually Transm Dis 1981; 8: 224-6.

Brown, MT and Fee, E. “Raymond D. Fosdick (1883-1972): Ardent Advocate of Internationalism” Am J Public Health. 2012; 102(7): 1285.

    

    

FLU SHOTS 100 YEARS AGO

     Just for fun I decided recently to peek at the contents of the JAMA from 100 years ago. As you might expect several articles dealt with medical problems of WWI soldiers and several with the 1918 influenza epidemic, also roaring through the military. What caught my eye, though, was the attention paid to influenza vaccines.

     Influenza was believed by many to be caused by “Pfeiffer’s bacillus”, a small

Richard Pfeiffer (Wikipedia)

fastidious rod now considered to be the bacterium Hemophilus influenzae. However, because Pfeiffer, a protégé of the great bacteriologist Robert Koch, could not produce the illness in animals, and because the bacillus turned up in other conditions and in normal throats, proof of its causative role remained elusive. Brushing aside these uncertainties, however, influenza vaccines hit the market rapidly and were aggressively promoted.

     The power of vaccination was well known by then and several, such as smallpox, rabies, and typhoid, were available. William Park, director of New York City Health Dept’s

William Park (Wikipedia)

laboratories, who had already made diphtheria antitoxin and vaccine, made a three-dose influenza vaccine from Pfeiffer’s bacillus, widely used in the military and by industrial employees. A professor of bacteriology at Tufts Medical School, Timothy Leary (not the marijuana guy), made another one, used in state custodial institutions and on the private market. At the University of Pittsburg Medical School a vaccine was created from 13 different strains of Pfeiffer bacillus (employed by the Red Cross), at Tulane still another, and in New York a private physician, Horace Greeley, made his from a cocktail of 17 strains.

      But was Pfeiffer’s bacillus really the cause of influenza? More studies generated more uncertainty. Pneumococci and streptococci were now turning up in greater numbers in sputum and lung samples than Pfeiffer’s bacillus. Based on this, Edward Rosenow of the Mayo Clinic made a vaccine from five different respiratory tract bacteria, including

Preparing Rosenow vaccine at Chicago Public Health Lab (from A Report on
the Epidemic of Influenza in Chicago, 1918. Courtesy National Library of Medicine)

pneumococci and streptococci. It was distributed to the upper Midwest and manufactured by the City of Chicago, where over 500,000 doses were produced.

     Could all these vaccines be effective? Most reports said they were, but sensible readers realized that was impossible. Study design had been faulty in all but one case,

George McCoy (NIH Almanac)

said William Park of New York and George McCoy of the US Public Health Service in an important article. And that one exception failed to show any protective effect. The missteps, they said, were giving vaccines without randomization, using too few subjects, and starting the studies well after an epidemic begins. Park and McCoy each performed their own studies, Park with employees of the Metropolitan Life Insurance Co. and McCoy with inmates of a “state institution for the insane” in California. Both studies began before the flu hit their subjects, both ensured comparable study and control groups, and both employed the Rosenow vaccine. Neither study showed any protective effect, thus setting important precedents for future vaccine trials. (True randomization and blinding of experimenters were later developments. The first such trial was in 1943, evaluating a remedy for the common cold.)

     That a filterable agent might be the cause of influenza had occurred to only a few people during the pandemic. One was Charles Nicolle, winner of the Nobel Prize for his discovery of the louse as the vector of epidemic typhus. He reported transmission of flu to monkeys and humans with submicroscopic filtrates of sputum from flu sufferers. Eventually he and others with similar ideas were proven to be correct, paving the way for modern flu vaccines.

      

     HAPPY HOLIDAYS TO ALL, AND DON’T FORGET YOUR FLU SHOT!

    

SOURCES:

Eyler, John M. “The State of Science, Microbiology, and Vaccines Circa 1918”. Public Health Reports. 2010 suppl 3; 125: 27-36.

McCoy, G W. “Pitfalls in Determining the Prophylactic or Curative Value of Bacterial Vaccines” Public Health Reports 1919; 34(22): 1193-5.

Sholly, A I and Park, W H. “Report on the Vaccination of 1536 Persons Against Respirtory Diseases, 1919-20.” J Immunology1921; 6: 103-16.

McCoy, G W and Murray, V B. “The Failure of a Bacterial Vaccine as a Prophylactic Against Influenza” 1918; JAMA 71(24):1997.

Nicolle, Charles and Lebailly, Charles. “Recherches Expérimentales sur la Grippe” Annales de l’Institut Pasteur 1919; 33: 395-402.

Bhatt, Arun. “Evolution  of Clinical Research: A History Before and Beyond James Lind” Perspect Clin Res 2010; 1(1): 6-10.

Bike Spokes and a Wrong Turn Advance

Fracture Treatment

by

Roy Meals MD

     Gavriil Ilizarov, a Pole, attended medical school in Crimea and Kazahkstan during World War II and then, without any practical training, was posted to Kurgan, Siberia. This war-torn region was 1200 miles east of Moscow, far away from any established center of advanced understanding. The area was rife with wounded soldiers suffering from nonhealing, infected fractures.

     With vast need, limited resources, and no preconceptions to restrain him, Ilizarov developed an external fixation frame, which would support a tibia fracture, for instance, during healing. As others had done before, he placed pins perpendicular to the bone on both sides of the fracture site and left the pins protruding through the skin.  He then attached the pins to each other with longitudinally aligned threaded rods—the external fixator.

     By 1955, Ilizarov had become chief of trauma and orthopedics at his Siberian outpost. Because resources remained scarce, he used bicycle

Gavril Ilizarov (photo by Dr. Bernd-Dietmar
Parteke, posted on Wikipedia)

spokes for the bone-penetrating pins in his external fixators. The spokes were flimsy compared to the stout quarter-inch-diameter pins previously employed; but when tensioned, the spokes met the need and did so with minimal soft tissue injury. Ilizarov compared the complete construct to that of a bicycle wheel, where the bone was the fully-stabilized hub. The “rims” were metal rings encompassing the limb at several levels above and below the injury site, and the tensioned wires passing from hub to rim (bone to rings) were bicycle spokes. Once the spokes and rings were in place, the rings were secured to one another with the threaded rods.

   The aim of the external fixation was to hold the fractured bone ends firmly against each other. Without any motion at the fracture site, the bone-producing cells, osteoblasts, could begin to bridge the gap. This was problematic, however, when the gap was large, because osteoblasts can “jump” only so far, across a stream but not across a chasm. Ilizarov used a wrench to make daily, tiny adjustments of the rings on the threaded metal rods and could thereby slowly draw the bone ends together and close the gap. He showed the nurses how to perform this at home to close the fracture gap in almost imperceptible increments over weeks.

     One confused nurse, however, kept turning the wrench the wrong way, repeatedly distracting the bone ends rather than drawing them together. To Ilizarov’s surprise when he saw an X-ray of the patient weeks later, the slowly expanding gap was filling in with new bone. The bone-forming cells had been toiling happily, unaware that their task was ever-expanding.

     Other surgeons had lengthened limbs through external distraction but had always filled the gap in the lengthened bone with bone graft taken from elsewhere in the body, typically the pelvic rim. This necessitated additional surgery to harvest the graft and risked the development of donor site pain, disfigurement, and disability. Sometimes the gap in a bone was too big for even the largest possible bone graft to span it.

     In an ah-ha moment Ilizarov realized that by moving the bone ends apart ever so slowly (less than a sixteenth of an inch a day in six evenly spaced intervals), new bone would fill in the gap on its own. (Yank on taffy and it snaps in half. Pull on it gently and it stretches.) This slow movement between bone ends could allow lengthening of bones that had healed too short and also could correct angular and rotational deformities of fractures that had healed with misalignment. (Twist taffy slowly, it twists.) Ilizarov applied the technique widely, and his patients called him “the magician from Kurgan.” Nonetheless, the medical establishment in Moscow considered Ilizarov a quack and discounted his growing achievements and reputation.

     This began to change when Russian high jumper Valeriy Brumel injured his leg in a motorcycle accident in 1965, a year after winning the Olympic gold medal. Following 3 years of multiple and unsuccessful operations in Moscow to heal the injury, Brumel traveled to Kurgan for treatment. He recovered sufficiently to high jump 6 feet 9 inches, which was 7 inches off his world record but still quite respectable for somebody who had been hobbled by injury for years.

     Regardless of his success in treating Brumel, Ilizarov’s contributions did not receive the recognition they deserved. This was even though his center in the 1970s grew to 24 operating rooms, 168 physicians, and around 1000 beds—by far the largest orthopedic center in the world.

     Then in 1980, an Italian adventurer sought Ilizarov’s help after European doctors had given up hope of ever producing a sound leg. The mountaineer had broken his leg 10 years previously and was left with an unhealed fracture with an inch of shortening. After Ilizarov achieved bone healing and lengthening, the grateful patient called Ilizarov “the Michelangelo of Orthopedics.” On return to Europe, the patient’s result astounded the Italian doctors, who then invited Ilizarov to speak at a European fracture conference in 1981. Ilizarov gave three lectures, the first time he had presented his material outside the Soviet Union. At the end he received a 10-minute standing ovation.

                   

     In subsequent years, others have refined Ilizarov’s external fixator hardware and technique. Now many limbs with unhealed fractures, shortening, and angular or rotational deformities have been spared amputation beginning with that one patient who turned the wrench the wrong way. Anybody could do that, but Ilizarov recognized the implications and appreciated that the wrong way might be the right way. 

Sources:

Abdel‐Aal, A. M. (2006). Ilizarov Bone Transport for Massive Tibial Bone Defects. Orthopedics. 29(1):70‐74.

Aronson, J. e. (1989). The histology of distraction osteogenesis using different external fixators. Clinical Orthopaedics and Related Research. 241:106‐116.

Codivilla, A. (1904). On the means of lengthening, in the lower limbs, the muscles and tissues which are shortened through deformity. Am J Orthopedic Surgery, 2:353.

Smith, D N., Harrison. M H M. (1979) The correction of Angular Deformities of Long Bones by Osteotomy‐Osteoclasis. The Journal of Bone and Joint Surgery. 61‐B(4):410-4.

Spiegelberg B, Parratt T, Dheerendra SK, Khan WS, Jennings R, Marsh DR. (2010). "Ilizarov principles of deformity correction". Annals of the Royal College of Surgeons of England. 92 (2): 101–5.

Svetlana Ilizarov (2006). "The Ilizarov Method: History and Scope". In S. Robert Rozbruch and Svetlana Ilizarov. Limb Lengthening and Reconstruction Surgery. Boca Raton, CRC Press.