A FAMOUS NAVAL HOSPITAL:

HASLAR

 

         By the mid-eighteenth century, Britain had established colonies around the world. To protect the new possessions and maintain the trade routes that rendered the colonies profitable required an expanded navy. Larger ships, into which hundreds of crewmen were crowded in close quarters, sailed ever-longer routes far from land. Though the seamen’s diet, measured in calories and meat content, was richer that that found in most homes at the time, it did not included perishable fruits or vegetables.

         The diet rendered the crews susceptible to scurvy, brought on by the lack of vitamin C, and the killer of more men than combat wounds and other diseases combined. Crowding also permitted infectious diseases to flourish. Among the latter, typhus was the most common, though smallpox and yellow fever appeared intermittently.

         In the early years of naval expansion, the sick arriving in a port were placed in homes, lodging houses, or small private hospitals contracted to care for them. Such a system, however, failed. Fraud was rampant; the host facilities padded the bills and provided minimum care. Alcohol was traded for clothing and the few contract doctors available were often busy with private patients. Faced with over 15,000 men yearly invalided ashore, the Navy decided to build substantial hospitals to provide better care. The largest, Haslar Hospital, went up across the bay from Plymouth, home of the Navy’s principal docks.

         Originally designed as a large four-sided building around a large square central court, only three sides were constructed to allow more ventilation. The central portion was primarily for

Plan of Haslar Hospital (from Tait, History of Haslar Hospital)

administrative functions (the administration was civilian) and the side wings featured double pavilions three stories high and separated by a small, aerated area. The building opened in 1754, allowing accommodation for 1200 patients, and was the largest brick building in England and perhaps in Europe. Lighting was by gas, replaced by electricity in 1905. Water closets were installed at the end of each ward, and sewage emptied into Portsmouth Harbor via a nearby creek. Wells supplied fresh water. The first chief physician was James Lind, a civilian at the time.

James Lind (Wikipedia)

         Lind was a Scot who learned surgery as an apprentice and went to sea as a surgeon’s mate at age 23. While serving in the Channel Fleet he conducted his famous trial of remedies for scurvy, noting that the most effective curative was juice from lemons and oranges. He then left the Navy to earn an MD degree at Edinburgh, entered private practice, and found time to write A Treatise on Scurvy, published in 1753, in which he detailed his success with citrus juice to prevent scurvy. Strangely, though, Lind did not emphasize citrus juice for the treatment of scurvy, believing it to have other causes. Lind held the post at Haslar until 1783, succeeded by his son.

         By the time of the American revolt against England, Haslar held 2100 patients, making it four times the size of Guy’s Hospital in London. Not all seamen wanted to be there. Many had been impressed into service out of prisons or poorhouses and frequently escaped during the night or had alcohol smuggled in. To discourage desertion, bars were put on the windows, a wall twelve feet high surrounded the hospital, and guards patrolled outside. Yet in1794, 226 still managed to escape. Nursing care was unreliable, with alcohol often bartered for clothing, and sometimes nurses or attendants coaxed sick patients into willing their property over. Mortality overall was substantial. In 1780, 909 deaths were recorded.

         The few doctors assigned to the hospital were allowed to engage private practice and when needed might be miles away with a patient. Only after 1797, was private practice forbidden. At first, surgeons operated without anesthesia on the wards, but after patients objected a separate operating room was installed. Surgeries were infrequent, however, until the arrival of anesthesia in the 1850s.

         In the early days, scurvy and typhus were the most common medical problems in the hospital. Typhus most commonly broke out on a ship after men from jails or from other ships carrying typhus were put aboard as crewmembers. Most medical men considered it “contagious,” not recognizing the role of the louse in its

Thomas Trotter (Wikipedia)

transmission. Thomas Trotter, appointed Physician to the Hospital in 1793, improved hygiene enormously. New patients were bathed (as before), shaved, their hair cut short, and given clean clothes. Thereafter they were washed daily and given twice-weekly changes of hospital gowns, which undoubtedly helped prevent new typhus cases. Trotter halted the treatment of bleeding for fevers and supplied a rich diet, speeding recovery. By this time, the value of fruits and vegetables for scurvy was evident. Trotter also revised the administrative structure, pleaded for more personnel to attend the sick, and recommended that the Navy take over the previous civilian administration.

         The Navy did assume responsibility for the hospital and introduced a teaching program aimed at medical problems peculiar to shipboard life. Courses in new subjects, such as bacteriology, were introduced. Anesthesia allowed a more active surgical service. The hospital, over time, cared for casualties from the Napoleonic wars, the Crimean War, and both World Wars. The country’s first blood bank opened there in 1940. The National Health Service took over the site in 2007 and closed it in 2009. The hospital now contains flats for retirees. Over 10,000 bodies are believed to be buried on the grounds. Forensic scientists have recently examined a few skeletal remains and documented osseous signs of scurvy, once a persistent threat to a seaman’s life.

 

Modern view of the hospital, showing a guard tower (Wikipedia)

SOURCES:

 

William Tait, A History of Haslar Hospital, 1906; Griffin & Co.

Kenneth J. Carpenter, The History of Scurvy and Vitamin C, 1986; Cambridge Univ Press.

Bryan Vale and Griffith Edwards, Physician to the Fleet: The Life and Times of Thomas Trotter. 2011; Boydell Press, Woodbridge.

James Lind, A Treatise on the Scurvy, 3^rd ed. 1772; London.

Eric Birbeck, “Royal Naval Hospital Haslar: Paragon of Nautical Medicine.” The Grog Ration 5 (2): 2-5, 2010.

Eric Birbeck, “The Royal Hospital Haslar: from Lind to the 21^st century.” The James Lind Library, accessible at: https://www.jameslindlibrary.org/articles/the-royal-hospital-haslar-from-lind-to-the-21st-century/

 

 

                     THE VIBRANT LIFE AND TRAGIC DEATH OF

RENÉ FAVALORO

 

            René Favaloro, an Argentinian cardiac surgeon, is best known to the world as the “father” of coronary artery bypass surgery. His life in medicine, however, ranges well beyond cardiac surgery.

         René was born in La Plata, Argentina, in 1923, the son of an artisan carpenter of Sicilian origin. After medical school and internship in La Plata, he decided on a career in surgery. But he declined a residency when he was required to sign a declaration of allegiance to the Peronist party. Coincidentally, a letter came from an uncle in a remote village in the Pampa asking him to fill in while the local doctor was absent for medical treatment. René accepted and traveled to Jacinto Aráuz, a village in flat, desolate land whose inhabitants, mainly of German descent, labored at raising livestock and farming in barren land with unpredictable weather conditions. The previous doctor soon died, and René brought in his brother,

René Favaloro (Wikipedia)

recently graduated from medical school, to set up a more modern clinic. They expanded their area of activity, acquired used X-ray equipment, medical books and journals, a reliable automobile, and materials for local and spinal anesthesia. They taught midwives to be nurses and others to educate villagers about hygiene, clean water, and ways to stay healthy. Cesarian sections, gallbladder surgery, hernia repair, and many other procedures became possible. He tabulated the blood types of all the residents, thus establishing a “mobile blood bank” in case of emergencies. René married and built a house, but after twelve years of hard work and little vacation, decided to broaden his horizons. He wanted to study thoracic surgery.

         His old professor of surgery, José María Mainetti, encouraged him to go to the Cleveland Clinic. René took some quick English lessons and flew north. George Crile, one of the Clinic's founders, greeted him and referred him to the cardiac surgery service under Dr. Donald Effler. Effler found that Favaloro had not passed any U.S. exams and spoke halting English and told him he could work only as an unpaid aid. Using modest savings, René carried out aid duties and earned enough confidence to be allowed to scrub in on operations. He learned English, crammed every night to pass the National and State Board exams, and was accepted as a cardiac surgery resident. 

The timing was propitious. A brilliant cardiologist at the Cleveland Clinic, Mason Sones, was the first to use a rapid frame motion picture camera to photograph dye in the coronary arteries and clearly demonstrate obstructive lesions. Favaloro worked with Sones

Mason Sones with Favaloro (Wikimedia Commons)

intensively and before long tried bypassing the lesions using a saphenous vein graft. The coronary artery bypass graft (CABG), as the procedure was called, replaced the less effective Vineberg operation (implanting a mammary artery in the myocardium) and became a favored operation worldwide. Favaloro justifiably earned many honors, especially for his rigorous collection of data to establish the value of the procedure. 

During his time at the Cleveland Clinic, he was still mindful of the lagging state of surgery in his native city and wanted no less than to bring the Cleveland Clinic to La Plata. At the height of his fame, he resigned his position at the Clinic, moved to La Plata in June of 1971, and began to assemble a cardiac institute. As Chief of Cardiac Surgery at the Clinica Güemes Hospital, he and his brother put together, in 1975, the Favaloro Foundation, a nonprofit organization devoted to cardiology and cardiac surgery. Tragically, René’s brother died in an accident one year later and René helped raise his four children, two of whom became physicians. In 1978 an eight-story building was donated to the Foundation as a research institute. Two years later, René performed the first cardiac transplant in Argentina and established a teaching unit in the hospital. 

René's worldwide reputation helped him raise funds for a new institute that combined cardiology, teaching, and research into one unit: The Institute of Cardiology and Cardiovascular Surgery. It resembled the National Heart, Lung, and Blood Institute in the U.S. and opened in 1992 as part of the Favaloro Foundation. It was a nonprofit entity, providing care to all, regardless of ability to pay. About 25% of surgical patients had no insurance. By the seventh year, the Institute had trained at least 400 cardiologists and cardiac surgeons for work throughout South America and beyond.

Planet Heart (Corazón Planetario), by Gyula Kosice, at the Favaloro Foundation 
(Wikimedia Commons)

Outside his medical work, René was an active member of the National Commission on the Disappearance of Persons, a group investigating the tragedies of thousands of “disappeared” citizens during the military Junta regime. He took an interest in Argentina’s history and wrote two books on the life of its founding father, San Martín. He wrote a book on his life as a country doctor and another on his life at the Cleveland Clinic. His favorite fictional character was said to be Don Quixote, and many friends felt his entire life resembled a quixotic quest.

Maintaining a nonprofit foundation requires money, and when times were prosperous the Institute received adequate funds. However, in the late 1900s Argentina’s finances fell into serious trouble. The usual subsidies from government and private agencies dried up. René struggled with the Institute’s increasing debt, but to no avail. Letters to the government went unheeded. In desperation, on July 29, 2000, at the age of 77, René shook the conscience of Argentina to the core when he pointed a revolver to his chest and ended his life. He left a long letter detailing his accomplishments in his home country and the corruption he was surrounded with. He said a goodbye to his family and ordered that his body be cremated and his ashes scattered in the hills near Jacinto Aráuz, where he had labored for twelve years as a rural physician.

Public outrage helped the Favaloro Foundation survive the crisis and René would be happy to know that the Foundation now is a major cardiac center in Argentina, as he dreamed it would be.

 

SOURCES:

 

Captur, Gabriella, “Memento for René Favaloro.” Texas Heart Institute Journal 2004; 31(1): 47-60.

Favaloro, René, “Landmarks in the Development of Coronary Bypass Surgery.” Circulation 1998; 98(5): 466-78.

Favoloro suicide letter, available at:    https://web.archive.org/web/20160305021334/http://www.avizora.com/publicaciones/biografias/textos/textos_f/0013_favaloro_rene_anexo_01.htm

Fye, Bruce, Caring for the Heart: Mayo Clinic and the Rise of Specialization, 2015; Oxford Univ Press, pp 315-342.

Rubenstein, Robyn, et al, “René Gerónimo Favaloro (1923-2000): A Man Who Struggled with Matters of the Heart.” American Surgeon, January 2018, 7-11.

Favaloro, R, Recuerdos de un Médico Rural, 2^nd edition, Editorial Sudamericana, 2018.

Favaloro, R, De la Pampa a Los Estados Unidos, digital edition, Random House, 2012.

"Argentina Searches it Soul over a Suicide," New York Times, August 7, 2000.

 

 

         

        IMMUNOLOGICAL CAPITAL IN NEW ORLEANS

 

                Much has been written about the impact that disease has on the course of human affairs. Typhus, for example, decimated Napoleon’s army as it retreated from Russia. Plague ravaged Europe in the fourteenth century to such an extent that the population dropped by about one third. Malaria and cholera have crippled military campaigns. Influenza killed millions toward the end of the Great War.

                One more disease deserves mention: yellow fever. In 1802, when Napoleon sent an army to St. Dominique (now Haiti) to put down a revolution, yellow fever carried off so many troops that the effort failed. After the failed invasion, Napoleon decided to sell the French possessions in America to the new United States. Thomas Jefferson, suddenly responsible for the management of the Louisiana Purchase, acted to bring it and its most important city, New Orleans, under American governance. He filled the various administrative offices with men to whom he owed political favors.

                Before long, however, his appointees expressed reluctance to accept the new jobs. Their predecessors were dying of yellow fever. The fever season lasted from June to the end of October or early November and the mortality among the newcomers hovered around fifty percent. A new book, Necropolis: Disease, Power, and Capitalism in the Cotton Kingdom, by the Stanford historian Kathryn Olivarius, relates the dominance that yellow fever exerted on the rhythm of life in New Orleans during the antebellum years and the importance of “immunological capital.”

                The city, by all accounts, was filthy. Local government, controlled by the planter and merchant class, funded the most meager civic improvements possible. Sewage was virtually absent. Cesspools stank in the summer. Butchers slaughtered animals in the street and left the carcasses behind. Diseases of poor sanitation were common. All this was in spite of the predominant medical opinion that yellow fever was not contagious but arose from the miasmas produced during hot months. Travelers were astonished at the nonchalance of the inhabitants living among such foulness, stench, and, in the summer, death. Newspapers and publications, on the contrary, ignored the truth and painted the city as healthful and prosperous.

                Importantly, there were fortunes to be made in New Orleans (mainly on the backs of slaves) and new immigrants kept coming from both the United States and from Europe. Young, optimistic arrivals often felt they could weather a bout of the fever and then, being immune, seek greater opportunity. A man was much more likely to be hired after surviving yellow fever, especially in a job with long-term prospects. Surviving “yellow jack” is how he earned his “immunological capital.” Immunity to yellow fever was a ticket to a social and business world of privilege that tended to exclude those who had not crossed this threshold. An immune person could rise in business, hold office, be a member of clubs and associations, buy life insurance more easily, and even marry the daughter of a father who rejected any nonimmune suiter. It was common for employers and insurance companies to ask for a doctor’s certificate verifying immunity to yellow fever. The doctor, of course, had no laboratory test or visible sign to buttress his opinion. He relied on the patient’s history, focusing especially on how long the individual had lived in the city.

                It was almost a universal belief that the black population had a natural, inborn, immunity to yellow fever. Doctors believed it too. For slaves born in Africa that may have been partially true since they grew up in a yellow fever environment. But slaves and free blacks born in the United States were as susceptible as anyone else. Planters, of course, knew the truth. They lost slaves to the fever during epidemics, sometimes in large numbers, seeing it as a cost of business. Slaves known to have survived yellow fever commanded higher prices.

                Some residents profited from the epidemics. Doctors, for instance, charged a higher “yellow fever rate” during epidemics. They often became wealthy enough to invest in a plantation or slaves, prospects that attracted more doctors to town. Gravediggers, usually blacks, charged higher rates during outbreaks. Even so, they were often overwhelmed. Undertakers, coffin makers, pharmacists, and irregular practitioners all did well during epidemics. Residents of French and Spanish background usually called on French-trained physicians, who tended to prescribe baths, rest, and hydration. American-trained doctors, in contrast, were more aggressive, employing generous purges, copious bleeding, and blistering. Medical care for poor people was more haphazard. Charity Hospital, founded back in 1736, was overloaded with patients and lacked the money for decent nursing, bathing, and even adequate diet. Numerous private charities and the Catholic Church filled the gap for the poor as best they could. Irregular practitioners, even Voodoo doctors, were also active.

                The deadliest yellow fever epidemic in antebellum New Orleans came in 1853. Up to 1000 people a week were dying and an estimated 10% of the city population (of 120,000) perished, even as newspapers reported on everything except the epidemic. Amazingly, the deaths and misery of that terrible outbreak still failed to persuade the city to establish a permanent health department or a quarantine regimen. The filth, stench, and repeated yellow fever tragedies continued until the Civil War, when Union forces under General Butler cleaned up the city and enforced a quarantine. Yellow fever cases dropped dramatically, paradoxically reinforcing the general belief that the disease arose from filth and miasmas. It took a massive epidemic in 1878 to finally convince New Orleans to institute definitive measures. Mosquito transmission was not confirmed until 1900.

 

                                     A MIRACLE DRUG, MAYBE

       She was known only as Mrs. G, a twenty-seven-year-old woman with debilitating rheumatoid arthritis that largely confined her to a bed and chair existence. Grasping at straws, she had already undergone a trial of streptomycin, based on theories of an infectious cause for her arthritis, without any improvement. In July 1948, she journeyed to the Mayo Clinic after hearing about a possible new approach to the disease: inducing jaundice.

        The chief of the rheumatology service at the Mayo Clinic was Philip Hench. He had founded and directed the first rheumatology

Philip Hench (Wikipedia)

service at the Clinic. An alert clinician, Hench noticed that the pain and immobility of rheumatoid arthritis sometimes improved for weeks to months in patients who were jaundiced from various causes (except hemolysis). Sensing a treatment opportunity, he infused bilirubin in large doses into patients and even transfused blood from jaundiced individuals, but with little or no improvement (1938). Noticing that pregnancy also helped rheumatoid arthritis in women, Hench transfused blood from pregnant women and administered female hormones, but without success. Some women even deliberately became pregnant again, hoping to make permanent the improvement in pain and stiffness.

This time Hench gave Mrs. G, and another patient, lactophenin, a substance that induced jaundice. But Mrs. G never turned yellow, though her companion did, and was released from the study. She refused to leave, however, badgering the Mayo doctors for another possible therapy. 

Based on the jaundice and pregnancy results, Hench had proposed a “substance X” present in the blood in these conditions that rendered rheumatoid arthritis potentially reversible. Since it appeared not to be a sex hormone or released from the liver, attention turned to the adrenal cortex. During WWII, research on extracts from the adrenal cortex had accelerated. Rumors proliferated that German scientists had isolated a substance from the adrenal cortex that increased tolerance to oxygen deprivation in fighter pilots and that submarines were transporting large quantities of bovine adrenal

Edward Kendall (Wikipedia)

glands from Argentina to Germany. Edward Kendall, at the Mayo Clinic, who had already isolated thyroxine and glutathione, and a Swiss chemist, Tadeusz Reichstein, had both isolated compound E from the adrenal cortex in 1936. The procedures were laborious and the quantities small. Because compound E, unlike other isolates, kept adrenalectomized rats alive and might be valuable for stressed pilots, the U.S. prioritized efforts to synthesize it.

       Mrs. G’s pleas for another treatment touched Hench. He turned to Edward Kendall, who had isolated compound E, who persuaded Merck, the owner of the scarce

Tadeusz Reichstein (Wikipedia)

substance, to release 5 grams for use. Hench, not optimistic about the outcome, left the trial to two younger rheumatologists working on the service, Charles Slocum and Howard Polley. 

       Mrs. G received the first of twice daily injections of 50 mg of compound E on September 21. By the 23^rd she felt better and by the 24^th she was walking around and doing light exercise. By the 28^th she went shopping for three hours, saying “I have never felt better in my life.” Hench, stunned, was about to leave for London at this critical moment to give the prestigious Heberden Lecture. He swore everyone involved to complete secrecy until he returned. On the way to London, he detoured to New York to meet with Merck executives to swear them to secrecy and to obtain more of the scarce compound E.

       Meanwhile, Mayo doctors tried compound E (soon to be called cortisone) on more patients, including some with lupus and other rheumatic diseases, with equally startling results. Merck, before publicizing such extraordinary findings, wanted the security of involving experts beyond the Mayo group. Hench coaxed a group of five prominent rheumatologists from around the country to come to Rochester. One of them, Dr. Richard Freyberg, from New York’s Hospital for Special Surgery, recalled the event years later. Hench had turned his large house into a clinic, complete with X-ray viewers, microscopes, and movie projectors, and plenty of food. Two patients were examined carefully, then injected once with 300 mg of cortisone. Over the next three days the same miraculous transformation from an almost immobile status to a freely moving one amazed the onlookers. Back home, the experts tried it on their own patients, with the same astonishing results, but always with relapses after the cortisone ceased. 

       The rheumatologists reported their findings at the International Congress of Rheumatology. One of them, Walter Bauer from

Nobel Medal, showing a figure gathering water from a spring 
to help an ailing young woman (Wikipedia)

Harvard, recalling Boston’s ether story, declared, “Gentlemen, this is no humbug.” During the Congress, however, Hench received a phone call alerting him to side effects that were to mar cortisone’s reputation. In particular, Mrs. G had become bloated, developed a moon-like face, lost bone density, and suffered a depression and psychosis so serious she was transferred to a locked psychiatric ward. After recovery, she refused to take cortisone ever again. She died in 1954 of pulmonary edema during a course of ACTH in Indiana. 

Similar side effects from cortisone in others shattered the euphoria of the doctors and their arthritic patients. In the end, cortisone, used safely, offered little benefit over aspirin. Only the later introduction of prednisone provided a safer alternative.

       In 1950, two years after Mrs. G received her first dose of cortisone, the Nobel Prize in physiology or medicine was awarded to Hench, Kendall, and Reichstein. 

Was the Nobel prize premature? Maybe, since cortisone proved to be a disappointment. On the other hand, its use led to improved steroids and opened vast new avenues of research, considerably improving the lives of those with rheumatic diseases.

 

SOURCES:

Rooke, Thom, The Quest for Cortisone. Michigan State University Press, 2012.

 

Burns, C M, “The History of Cortisone Discovery and Development.” 2016; Rheum Dis Clin North Am 42: 1-14.

 

Warner, M E, “Witness to a Miracle: The Initial Cortisone Trial: An Interview with Richard Freyberg, MD.” 2001; Mayo Clin Proc 76: 529-32.

 

Hench, P S, “Effect of Spontaneous Jaundice on Rheumatoid (atrophic) Arthritis.” Brit Med J 1938; Aug 20: 394-8. 

 

Benedek, T G, “History of the Development of Corticosteroid Therapy.” 2011; Clin Experim Rheumatol 29(Suppl 68): S5-S12.

       

       

       

       

       

         

       

         FURTHER TALES OF ANGINA: 

A REMEDY AT LAST

 

         Last month’s essay outlined the first descriptions of angina pectoris and its relation to coronary artery disease. William Jenner was probably the first to notice the association of the syndrome with calcification of the coronary arteries. He withheld publication of his findings to avoid frightening his friend and former teacher, John

Caleb Parry (Wikipedia)

Hunter. In 1799, Jenner’s colleague, Caleb Parry, a physician in Bath, published a monograph on angina in which he reveals the story of Jenner’s discovery, details three more cases that show diseased coronary arteries at autopsy, and unfortunately confuses the picture by adding syncope as an accompanying symptom in some cases. 

         Osler, in his 1892 textbook, called angina a rare disease, reiterating its rarity in a series of lectures published in 1897. Regarding the cause of anginal chest pain, Osler noted that hardened coronary arteries are

William Osler (Wikipedia)

found in many cases with no angina, making it uncertain what actually caused the pain. He listed three main possibilities: a neuralgia of the cardiac nerves, a cramp in the heart muscle, or an extreme tension in ventricular walls (or in the associated nerves) caused by dilatation of the heart from insufficiency of coronary blood flow.

         Treatment since Heberden’s time and until the late 19^th century consisted in administration of spirits, plasters, bleeding (to relieve “plethora”), and sometimes opiates or chloroform. Removing a few ounces of blood often prevented recurrent attacks for a short period, probably related to a lower blood pressure. Details of the physiology involved, however, were far from clear. 

         Nitroglycerin, the “modern” treatment for angina pectoris, originated, strangely enough, in homeopathic practice. 

         Dr. Samuel Hahnemann, a well-trained German physician, began the homeopathy movement in 1796. It was based on his idea

Sanuel Hahnemann (Wikipedia)

that if the effects of a drug caused symptoms resembling those of a particular disease, then small doses of that medication would counteract the action of the same disease – “like cures like.” The idea proved attractive and, possibly because patients avoided the traditional bleeding and purging, the practice of homeopathy grew. 

         The chief founder and organizer of homeopathy in America was Constantin Hering. Born and educated in medicine in Germany, Hering was asked by a professor, while training in Leipzig, to write an essay against homeopathy. But when he studied the works of Hahnemann, he became a convert. He landed in America after a shipwreck near the New England coast. He decided to stay, opened a homeopathy practice in Philadelphia, and was instrumental in founding the first school of homeopathy in America. He devoted much time to “proving” medications. Proving was a method, initiated by Hahnemann, by which medications were tested systematically on

Constantin Hering (National Library of Medicine)

humans to observe and record their effects. It was perhaps the first such evaluation of items in the pharmacopeia, an advance over methods of regular physicians.

         Hering was aware of nitroglycerin. An Italian chemist, Ascanio Sobrero (whose face was scarred from an explosion and who knew Alfred Nobel), first synthesized nitroglycerin in 1847 while seeking a better explosive than the available “gun cotton.” Hering “proved” nitroglycerin as early as 1849 and noted that small doses on the tongue rapidly produced throbbing headaches and a rapid pulse, effects Sobrero had also noted. He gave the name “glenoin” to nitroglycerin and, in diluted doses, it became a treatment for headaches and sometimes palpitations. Occasionally it produced an oppressive feeling or even pain in the chest, but it was never promoted for angina, which homeopaths agreed was a rare condition.

         In England, homeopaths were also using glenoin. A British regular physician, Alfred Field, obtained the substance from a homeopathic chemist and reported, in 1858, a single case of a woman with angina-like chest pains who was relieved by nitroglycerin. Others with varied non-chest pains also had relief. The first to use it specifically for angina pectoris was William Murrell, a physician at the Royal Hospital for Diseases of the Chest. He had worked under Burton-Sanderson, one of England’s finest physiologists, and Sydney Ringer (of Ringer’s solution) and was thus trained in experimental techniques. Having read the papers of Sobrero and Field, Murrell made a 1% solution of nitroglycerin and placed a small amount on his tongue. He noted a headache and a sudden bounding of his pulse, so forceful that, just as a patient had entered his office, “I hardly felt steady enough to perform percussion” and, “The pen I was holding was violently jerked with every beat of the heart.” He took nitroglycerine many more times and began to administer it to others, recording pulse, symptoms, and the like. 

         Murrell was aware that the effects of nitroglycerine resembled those of amyl nitrate, an inhaled substance first described as a treatment for angina in 1867. In 1879, he published his experiments

Murrell's first article on nitroglycerine.

with nitroglycerin in a series of four articles, showing that its effects were similar to amyl nitrate but with faster onset of action and longer duration. As an attempt to prevent angina, he gave it as a small tablet to take four times a day. The frequency of anginal attacks in three patients tested diminished, as did the intensity. However, one patient found it easier to simply take a nitroglycerine tablet on the tongue when an attack came on, after which he obtained quick relief. This use of a former homeopathic remedy became the standard approach to managing angina up to the present time. Few medical remedies have enjoyed such a long life.

 

SOURCES:

Fye, B, “Nitroglcerin: a homeopathic remedy.” 1986; Circulation 73: 21-9.

 

Murrell, W, “Nitroglycerine as a remedy for angina pectoris.” 1879; Lancet v 1, 80-81, 113-15, 151-2, 225-7.

 

Osler, W, Lectures on Angina Pectoris and Allied States. 1897; Appleton & Co., New York.

 

Eastman, A M, Life and Reminiscences of Dr. Constantine Hering. 1917; reprint from The Hahnemannian Monthly, 1917, privately printed.

 

Field, A G, “Toxical and medicinal properties of nitrate of oxide of glycyl.” 1858; Med Times Gazette 16: 291.

 

       TALES OF ANGINA

 

            The oppressive chest pains induced by exertion, known as angina pectoris, have plagued sufferers for centuries. Even the hearts of ancient Egyptian mummies have revealed calcified coronary arteries, an anatomical change that restricts blood flow to the heart muscle that is the usual cause of angina. A full description of anginal pain, recognizing it as a distinct entity to be distinguished from other chest complaints, was first made by William Heberden in an address to the Royal College of Physicians in 1768. The address was published four years later in the Medical Transactions of the Royal Society of Physicians and in the periodical, Critical Review or Annals of Literature, a popular magazine aimed at an educated readership that frequently published medical news.

         Heberden describes angina in the following words: “Those who are afflicted with it are seized, while they are walking, and more

Article by Heberden in Medical
Transactions. (Hathi Trust)

particularly when they walk soon after eating, with a painful and most disagreeable sensation in the breast, which seems as if it would take their life away if it were to increase or continue: the moment they stand still, all this uneasiness vanishes. In all other respects the patients are at the beginning of this disorder perfectly well, and in particular, have no shortness of breath, from which it is totally different.” Heberden adds that he and another physician, whom he discussed the matter with, both noticed a high frequency of sudden deaths within a short time after the onset. Heberden speculated on some sort of “strong spasm” beneath the sternum as the cause of pain, not mentioning heart disease.

          William Heberden was one of the most sought-after physicians in London. Born in 1710 to an innkeeper, his early schooling was at a grammar school that emphasized the Classics. He entered St. John’s College at Cambridge at the age of

William Heberden (Wikipedia)

fourteen, obtained a Bachelor of Arts degree four years later, followed by further study and a medical degree after another eleven years. He taught physic and materia medica for several years at Cambridge and later opened a practice in London. He was a careful observer, taking extensive clinical notes that coalesced eventually into a book: Commentaries on the History and Cure of Disease. His description of digitorum nodi (Heberden’s nodes) appears there. He was a founder of the journal, Medical Transactions, published by the Royal College of Physicians. 

He was conservative regarding the multiplicity of medicines at the time, naming only Peruvian bark for ague, mercury for syphilis, sulfur for the itch (probably scabies), and opium as specific remedies. His broad education and gentle manner attracted many friends and patients, especially from the sphere of literature, such as Samuel Johnson, who dubbed him “ultimus Romanorum,” the last of our learned physicians. He was a friend of Benjamin Franklin, who persuaded him to write a pamphlet on the prevention of smallpox by variolation (inoculation of smallpox virus, a technique used prior to vaccination with cowpox-derived virus), which Franklin published in America on his own press in 1759. The pamphlet was distributed free of charge, the cost being absorbed by Franklin and Heberden. 

         One of Heberden’s patients suffering from angina had willed his body to be dissected when he died. Heberden asked the famous surgeon and anatomist, John Hunter, to perform the autopsy. Helping

Edward Jenner (Wikipedia)

him was Edward Jenner, his 23-year-old pupil in surgery. They found no particular cause of death. Fourteen years later, Jenner, now in practice in the town of Berkeley, autopsied a patient of his with angina pectoris who had died suddenly. While making a transverse section of the heart, Jenner’s knife encountered something hard and gritty. As he wrote to a colleague, Caleb Perry, he looked up at the old and crumbling ceiling, “…conceiving that some plaster had fallen down. But on a further scrutiny, the real cause appeared: the coronaries were become bony canals.” Jenner, sensing that the “bony canals” impaired cardiac circulation and might cause anginal pains, was anxious to publish his finding but hesitated. He had kept in close touch with John Hunter and knew that Hunter himself was having anginal pains. He worried that publication of the idea would have distressed his old mentor and friend.

Knowing Heberden was Hunter’s physician, Jenner wrote to him. He observed that patients with angina had a substantial layer of fat around the heart, and, “as these vessels lie quite concealed in that

John Hunter, by John Jackson (Wikipedia)

substance, is it possible this appearance has been overlooked?” He felt certain that the coronary arteries of Heberden’s previous case had not been examined and he feared that if Hunter learned of his theory of hardened arteries, “it may deprive him of the hope of a recovery.” Heberden agreed that it was best not to publish the findings as Hunter’s anginal attacks sometimes came when he was agitated.

Sadly, a few years later, in 1793, after a dispute at a hospital board meeting, Hunter suddenly collapsed and died. At autopsy, his coronary arteries were “in the state of bony tubes, which were with difficulty divided by the knife,” consistent with Jenner’s speculations.

Edward Jenner later achieved fame with the discovery of the immunizing effect of cowpox against smallpox. He had suppressed his seminal discovery of the hardened arteries in anginal patients out of concern for a friend, a generous act. Heberden and Jenner had opened the way to the study of coronary circulation and its relation to angina pectoris and myocardial infarction. Effective therapies were not to emerge, however, for many years. 

 

SOURCES:

Acierno, Louis J, The History of Cardiology. Parthenon Publishing Group, 1994.

 

Fisk, Dorothy, Dr. Jenner of Berkeley. Heinemann, 1959.

 

Finger, Stanley, Doctor Franklin’s Medicine. University of Pennsylvania Press, 2006.

 

Hart, F D, “William Heberden, Edward Jenner, John Hunter, and angina pectoris.” J Medical Biography, 1995; 3(1): 56-8.

 

Heberden, W, “Some Account of a Disorder of the Breast.” Medical transactions / Royal College of Physicians. 1772; v. 2: 59-67.

 

Heberden, W, Commentaries on the History and Cure of Diseases. London, 1802.

 

Beasley, A W, “A Story of Heartache: The Understanding of angina pectoris in the Pre-surgical Period.” J Royal Coll Physicians Edinb 2011; 41: 361-5.