Happy President’s Day. I wrote this medical history paper in conjunction with my research for my two books about FDR. This is the first time it has ever been published. I hope you find will enjoy reading it as much as I did writing it.
When Franklin D. Roosevelt was born on January 30, 1882, medical science was also in its infancy. The therapeutic arsenal was little more than herbs, leeches, blood-letting and toxic purging. The average life expectancy was forty years. Infectious diseases regularly ravaged the population. Wartime casualties from disease and wound infection far outnumbered those from bullets, cannon and swords. Effective treatment was a half century away.
At the turn of the twentieth century, cutting-edge scientific research was little more than trial and error, best exemplified by the work of Paul Ehrlich, a German physician who worked in the fields later known as hematology, immunology, and antimicrobial chemotherapy.[i] With the support of his assistant, Sahachiro Hata, Ehrlich tested hundreds of compounds containing highly toxic arsenic and discovered in 1909 that the 606th compound he tested, arsphenamine, was effective against a bacteria similar to the one that caused the dreaded sexually transmitted disease, syphilis.[ii] “606” proved to have acceptable side effects in human trials and was marketed to the public in 1910 as Salvarsan. While it was highly toxic and technically challenging to administer,[iii] Salvarsan was far safer and more effective than previous therapy using mercury salts. An improved version, neosalvarsan, was released in 1911 and became the world’s most widely prescribed drug until the advent of penicillin therapy in the nineteen forties.
Ehrlich popularized the concept of “magic bullets,” chemicals injected into the body to fight specific bacteria. His biopic, “Dr. Ehrlich’s Magic Bullet,” was released In 1940, by Warner Brothers with Edward G. Robinson in the title role. The controversial word “syphilis” was permitted be used, but the film left out any reference to Ehrlich’s Jewish heritage (and Robinsin’s), so as not to offend Nazi German audiences.[iv]
The era of what was then called “chemotherapy” began in 1932 when the antibacterial effects of sulfonamides were pioneered by German bacteriologist and pathologist Gerhard Domagk, director of Bayer's Institute of Pathology and Bacteriology, a division of IG Farben, the world’s leading innovator in organic chemistry and the world’s largest manufacturer of chemicals and pharmaceuticals.[v] Ehrlich had observed that certain chemical dyes colored some bacteria but not others and Domagk surmised that these substances might also selectively kill bacteria without harming other cells. He performed experiments on mice that demonstrated the red dye prontosil was effective against the virulent streptococcus bacteria and used it to treat his daughter, saving her arm from amputation. French researchers later discovered the active drug was sulfanilamide, a breakdown product of the body’s metabolism of prontosil.
On December 17, 1936, the New York Times ran a front-page story entitled “Young Roosevelt Saved by New Drug,” reporting that Franklin D. Roosevelt Jr. had been cured of a potentially fatal bacterial throat infection. As a result, the popularity of “sulfa” drugs rose considerably in America. While sulfa often had dramatic curative effects and had been used safely as a tablet and powder, in June 1937 a salesman for the S.E. Massengill Co. in Bristol, Tennessee, reported a demand for a liquid form of the drug. The company's chief chemist and pharmacist, Harold Cole Watkins, found that sulfanilamide could be dissolved in diethylene glycol (commonly employed today as anti-freeze). Watkins tested the mixture for flavor, appearance, and fragrance of the compound and found it satisfactory. Unaware of the solvent’s profound kidney and liver toxicity, the company sent out over six hundred shipments of it. During September and October 1937 “elixir sulfanilamide” was responsible for more than 100 deaths in 15 states.
With the New Deal social reform in the nineteen thirties came the realization that the Food and Drugs Act of 1906 was obsolete, but bitter disagreement arose as to what should replace it. By 1937 congressional action had stalled but gained enough momentum in 1938 after the elixir sulfonamide debacle to pass the Federal Food, Drug, and Cosmetic Act, which remains the basis for FDA pharmaceutical regulation.
At the outset of World War II, a powdered form of sulfanilamide was standard in battlefield first-aid kits for the treatment of open wounds and a tablet was used to fight intestinal infections. Though it was relatively safe, Sulfa had significant limitations. It was inactive against other types of virulent bacteria, in particular staphylococcus, and in the presence of pus. It was also prone to cause allergic reactions and side effects such as skin rashes, fever, nausea, vomiting, and mental confusion. The remarkable ability of bacteria to mutate was not yet recognized and overuse began to render the drug less effective. Its use declined following the introduction of penicillin in 1943.
FDR was treated at least once with sulfa drugs in late February 1943, most probably for infection in the left maxillary or frontal sinus.
“The Dr. was with him, just finished treating his sinus. The Dr. turned him over to me, as nurse,” wrote FDR’s “closest companion” Daisy Suckley in her diary. “It is the P.’s fourth day in bed, & he still feels somewhat miserable though his fever has gone. Last Tuesday, without any warning, he felt ill at about noon. He lay on his study sofa & slept ‘til 4.30, when he found he had a temp. of 102. The Dr. found it was a toxic poisoning, but they can’t ascribe it to anything they know of. On Wednesday they gave him 4 doses of a sulpha (sic) drug – from which he will have to recover.” [vi]
Roosevelt’s most important assistant, Marguerite LeHand, was cured of a severe heart valve infection (bacterial endocarditis) by sulfa in August 1941 but unfortunately a severe career-ending stroke caused by the infection permanently rendered her unable to speak or use her right side.[vii]
Winston Churchill was treated for pneumonia with sulfa in 1943. A well-manicured myth was manufactured by the British press that he was given penicillin, in order to connect him to the popular hero, Alexander Fleming. But the Prime Minister later publicly declared he was saved by “admirable M&B”—a sulfa drug manufactured in England by May & Baker Ltd.[viii]
Sulfa drugs made little difference on battlefield wounds but played a major role in controlling outbreaks of dysentery among Allied troops in the South Pacific[ix], and again during a meningitis outbreak at British military bases. “Acute respiratory diseases, including influenza, pneumonia, bronchitis and other diseases, had killed almost 50,000 U.S. soldiers in World War I. During World War II, with twice as many men and women in uniform, only 1,265 died.”
The Miracle Drug
Scotsman Alexander Fleming became interested in anti-microbial therapy while performing laboratory experiments in a French hospital during World War I, where he observed the high rate of death in soldiers from overwhelming infections. Of the ten million soldiers who died, nearly half succumbed to bacterial infections, often after relatively minor injuries. Fleming concluded that the widespread use of topical wound disinfectants such as carbolic acid was useless and set out to find another “magic bullet” to control bacterial infection. In 1921, he found a substance in human tears and sputum that had a mild anti-bacterial effect and named it “lysozyme.” Fleming spent a good portion of the remainder of his career trying to characterize its chemical structure and efficacy. It was probably Fleming’s random trial and error search for animal and vegetable substances that contain lysozyme that caused him to stumble upon the penicillium mold.
Eric Lax’s exquisitely researched 2005 book, The Mold in Dr. Florey’s Coat, The Story of the Penicillin Miracle, explodes the well-worn story of how Fleming discovered penicillin on a contaminated bacterial culture after returning to his laboratory from a vacation. To Fleming’s credit, though, he did recognize the potential of the mold to kill bacteria, performed a few primitive animal safety experiments and published his observations in a vague, poorly worded article in the British Journal of Experimental Pathology in June 1929 which is now considered foundational in the history of medicine.[x] Fleming’s diminutive and self-deprecating manner failed to impress any of his colleagues. He wrote a second paper on penicillin in 1932, but by 1935 was still unable to isolate and purify the mold and lost interest in it.
Penicillin therapy could not have come about without the combined effort of three brilliant scientists: an Australian, a Jewish refugee from Nazi Germany and an Englishman, in partnership with American wartime ingenuity and largesse.[xi]
Australian Howard Florey early on distinguished himself as a highly motivated and exceptional student. After entering Adelaide University Medical School in 1916, his skills soon eclipsed those of his professors as he dedicated his life to medical research. Also a talented athlete, Florey graduated first in his class in 1921 and was awarded a Rhodes Scholarship.[xii] He emigrated to England, entered the highly competitive Magdalen School at Oxford, and soon came under the wing of iconic neurophysiologist Charles Sherrington.[xiii] Though he never lost his typically Australian irreverence and informality, Florey was awarded the prestigious John Lucas Walker Studentship at Cambridge and began work in the fields of physiology and experimental pathology, under the mentorship of the celebrated immunologist Henry Roy Dean. Florey published four papers within a year and was awarded a Rockefeller Foundation fellowship to study in the United States, where he became recognized as the “rough colonial genius.” Upon his return to England, Florey became the Huddersfield Lecturer in Special Pathology at Cambridge, Fellow of Gonville and Caius College of Cambridge University and director of its medical research studies. In 1931 he was appointed Professor and Chairman of Pathology at Sheffield University and, in May 1935, ascended to the pinnacle of his field as Chairman of Pathology at Oxford. Florey was convinced that the science of bacteriology “will not go very well without a very big injection of chemistry.” In an effort to bring new life to the stodgy and conservative Dunn School of Pathology, [xiv] he began a search for a biochemist to supplement his staff.
Ernst Boris Chain emigrated from Nazi Germany in April 1933 and soon landed a position at London’s University College Hospital Medical School Department of Chemical Pathology. He was just twenty-nine when he came to Oxford to join Florey in September 1935 at the recommendation of his mentor, Nobel laureate biochemist, Sir Frederick Hopkins.[xv] Chain’s outstanding intellect, histrionic personality and artistic temperament were intertwined with a complicated psyche, best defined today as bipolar, at times crossing into paranoid hypochondriasis. It was fueled by frustration over his inability to bring his mother and sister out from Nazi persecution.[xvi] Chain’s exceptional skills and ebullient personality helped to overcome the rampant anti-semitism of pre-war Britain. As many men and women of high intellect, Chain was a polymath and had chosen a career in science despite great skill as a concert pianist. His autocratic style reflected his German education and he soon distinguished himself at Oxford with elegant studies of the biochemical effects of snake venom on the nervous system.
The last piece of the penicillin puzzle was Norman Heatley, a native Englishman who came to Cambridge in 1929 to study natural sciences and biochemistry. Heatley was also a protégé of Frederick Hopkins. His doctoral thesis at the Dunn School, “The Application of Microchemical Methods to Biological Problems” laid out a previously unexplored enabling technology of microanalysis of organic substances that caught the eye of Chain, who brought him to Oxford, funded by a three year grant to investigate carbohydrate metabolism in cancerous tumors. Heatley’s technical skills in micromanipulation and microdissection were unrivaled. While their personalities and styles were often diametrically opposed, Florey and Chain’s innovative brilliance and Heatley’s superior technical expertise became a powerful force of scientific progress. In 1998, Professor Henry Harris, who succeeded Florey at Oxford, succinctly stated “Without Fleming, no Chain or Florey; without Chain no Florey; without Florey no Heatley; without Heatley, no penicillin.”[xvii]
From the outset of his tenure at Oxford, Florey’s major roadblock was funding. The purse strings of the British Medical Research Council (MRC) were extremely tight. Additionally, England would soon be drawn into an expensive, existential war with Germany. Florey turned to his old benefactor, the Rockefeller Foundation, for help and asked for a grant to develop “the chemical aspect of pathology.” On June 26, 1936, a modest stipend was approved to assist in support of “the progressive wing of the British scientific community.” Never in history has grant money been awarded with so much reward for humanity. With Heatley’s assistance, Florey and Chain continued their investigation on tumor metabolism only to reach a dead end after finding no difference from normal tissue.
By the late nineteen thirties, Fleming’s work on penicillin had been forgotten. It was only resurrected after Chain, at Florey’s urging, performed an extensive literature review and the words “antibacterial action of Penicillium” caught his attention in the title of Fleming’s 1929 article. Penicillin’s cryptic chemical structure and its potency against staphylococcus focused the team’s sights directly on Fleming’s mold. Working with an American Rhodes Scholar, Leslie A. Epstein, Chain also confirmed Fleming’s suspicion that lysozyme was an enzyme but also found it useless against bacteria that cause serious human disease. [xviii]
World events would soon to play a role in the success of the project. In 1939, Heatley’s original three-year grant was coming to an end and he successfully applied for a Rockefeller grant to send him to Denmark to work with an esteemed biochemist. Just before he was set to depart, on September 1, Nazi Germany invaded Poland. Travel abroad became problematic and Heatley remained at Oxford, turning his efforts to Penicillin.
With Britain literally fighting for its life against Nazi Germany, Florey’s team forged ahead on an austerity budget. The Rockefeller Foundation again stepped up in late 1939 and provided a grant of the equivalent of twenty-thousand American dollars over three years. Fleming had never been able to solve the problem of producing the mold in sufficient quantities for further research. Heatley’s expertise carried the day, devising a system of producing a modest amount of the mold to facilitate Chain’s research. A simple experiment disproved Fleming’s contention that “penicillium” was an enzyme, or indeed a protein at all!
In August 1940, the Oxford team published results from their experiments on mice that demonstrated penicillin’s safety and efficacy against a variety of pathogens, most importantly Clostridium Perfringens, the bacterium that caused gas gangrene, an infection responsible for the deaths of hundreds of thousands of soldiers during World War I. After a safety trial on a women dying of cancer, the first patient treated in Britain was a constable who had been stricken in early 1941 with a deadly staphyloccal infection after a seemingly trivial injury of being scratched by a rose. After a dramatic response to the drug, he relapsed and died when the drug supply ran out, despite a heroic effort of recovering and re-infusing the unabsorbed portion from his urine.[1]
Using precious Rockefeller money, Florey and Heatley set out for America in July 1941 to inform the American government and pharmaceutical companies of their work and to solicit their support and expertise to produce the drug. Their first stop was Washington D.C. where they met with Florey’s old friend from his previous visit to America, Dr. A.N. Richards, who was now director of the Committee for Medical Research (CMR), a division of the Office of Scientific Research and Development (OSRD), that had been established by President Roosevelt under the aegis of Vannevar Bush, the president of M.I.T. Richards immediately recognized the importance penicillin could play on the welfare of soldiers in the battlefield and elevated its development to a priority rivaled only by one other critical OSRD project, the atomic bomb!
A more efficient means of growing the mold was desperately needed. The seminal event in the Penicillin story came in August 1941. Florey and Heatley were referred by Dr. Robert Thom, America’s pre-eminent authority in the study of fungi, to Percy A. Wells,[xix] an administrator of the Department of Agriculture with an interest in fermentation. Wells dispatched the team to the government funded Northern Regional Research Laboratory in Peoria, Illinois, which had the latest fermentation equipment. With the infusion of $2,700,000, progress towards the reality of widespread treatment with Penicillin accelerated to breakneck speed.
Quite by accident, a more virulent strain of Fleming’s mold, penicillium notatum, was found growing on a rotting cantaloupe at a local Illinois market, and a far better culture medium to grow it was discovered in a plentiful by-product of corn starch production, corn-steep liquor. Wartime urgency facilitated a waiver of anti-trust laws, permitting the pharmaceutical industry to share their expertise. In December 1941, pharmaceutical giants Merck and Squibb signed on to lead American penicillin production. Pfizer, then a small company with unique expertise in fermentation in the manufacture of Vitamin C, joined them in September 1942. Under the direction of their vice-president, John L. Smith, whose sixteen-year old daughter had died of an infection, Pfizer went all in and opened the first commercial deep fermentation plant in February 1943 in Brooklyn, New York. By 1944 Pfizer was producing half of America’s penicillin.[xx]
The first patient was treated for streptococcal septicemia with penicillin produced by Merck on March 14, 1943, using half of the total supply produced at the time. By the end of the year, the new antibiotic was being tested on soldiers wounded in North Africa. It was also used unsuccessfully on the daughter of FDR’s secret service agent, Charles Fredericks, in early November [xxi]. Penicillin also found widespread demand for treating syphilis and previously resistant forms of gonorrhea, which had become dangerously epidemic in the military. By D-Day in June 1944, it was being widely used to treat troops for infections, both in hospitals and in the field. Conservatively, 100,000 soldiers benefited from penicillin treatment in the European Theater between D-Day and the final German surrender. It also saved thousands of lives during the last year of combat in the Pacific.[xxii] As a direct result of the efforts of the War Production Board, by June 1945 a staggering thirty tons, over 646 billion units per year, were being produced. The drug was not widely available to the American public until 1946.
News of a new “miracle drug” began leaking into the press as early as 1943, long before the supply was available to treat more than a select few patients. Howard Florey tried futilely to discourage raising the hopes of the public, but Fleming, first carefully, then overtly began fueling the fire, even though he bore little if any of the responsibility for the drug’s development. The Oxford group that had done all the heavy lifting soon fell prey to a mountain of publicity and Fleming became lionized for a discovery he had abandoned a decade earlier, including the prestigious cover article of Time magazine on May 15, 1944 over the caption “His penicillin will save more lives than we can spend.” Florey was not mentioned until the last half of the article. Chain’s name appeared only once. Fortunately, the Nobel committee knew better and awarded the 1945 prize in Physiology or Medicine jointly to Fleming as the discoverer and both Florey and Chain for developing the drug. Heatley, whose technical expertise was responsible for getting penicillin across the finish line, was shut out.
On July 20, 1944 Adolf Hitler suffered burns and abrasions when a bomb planted by one of his officers exploded in a bunker where he was meeting with staff. According to molecular biologist Milton Wainwright in his 2004 article “Hitler’s Penicillin,”[xxiii] the Fuhrer was treated with life-saving penicillin, most probably obtained from captured American soldiers. German soldiers were not so fortunate, dying of battlefield wound infections at twenty times the rate of the Allies.[xxiv]
In February 1945, after the Yalta conference, President Roosevelt stopped at Great Bitter Lake, near Cairo, to meet with the “three kings,” Farouk of Egypt, Haile Selassie of Ethiopia and Ibn Saud of Saudi Arabia, who famously stonewalled any attempt to discuss Jewish immigration to Palestine. After striking out on the diplomatic front, the conversation turned to more mundane matters. Ibn Saud became more amicable and “betrayed a lively interest in personal things – guns, planes and particularly penicillin.” Presidential physician Ross McIntire wrote in his 1946 memoir “I was summoned together with the (Saudi) royal physician; and finding they held the drug in almost superstitious esteem as a miracle worker, I presented them with 500,000 units out of the ship’s store. ”[xxv] While Roosevelt also gifted Saud an airplane and his spare wheelchair, curing the venereal disease of the Saudi royal court was, by far, his greatest diplomatic success.
Roosevelt himself had been treated with penicillin by 1945, complaining to labor advisor Anna Rosenberg in early March that his “penicillin rash” was keeping him awake. [xxvi] The rash was extensive and persisted until his death on April 12th as confirmed by embalmer, Hayden Snoderly, who noted FDR’s corpse to be “covered with blisters”.[xxvii]
Another Magic Bullet
Tuberculosis has been the scourge of civilization since prehistoric times, known as pththisis, the white plague and “consumption” for the way its victims slowly wasted away. At the time of Roosevelt’s birth the disease was widely believed to be hereditary. Less than two months later, in a famous lecture on March 24th 1882, Robert Koch demonstrated the causative agent of the disease to be the slow-growing mycobacterium tuberculosis. Significant progress was made in preventing the disease in 1908 with an early form of immunotherapy using BCG[xxviii], a vaccine from denatured tubercle bacilli discovered by and named after two French physicians Albert Calmette and his assistant Camille Guerin, while working at the Pasteur Institute of Lille.[xxix]
The seminal breakthrough in the treatment of tuberculosis is credited to Selman Waksman, who emigrated to central New Jersey in 1910 from what is now Ukraine. His life-long interest in soil biology eventually resulted in the isolation of substances with activity against bacteria that he called “antibiotics.” His interest was piqued by the discoveries of Sulfa and Penicillin as well as the need for drugs to treat resistant bacterial disease. Waksman began studying microbial antagonism using soil impregnated with tubercle bacilli. With his graduate student, Albert Schatz, as senior author, [xxx] he published a series of papers in 1944 after purifying an aminoglycoside[xxxi] from Streptomyces Griseus he called streptomycin, the first therapeutic agent to be successfully employed against tuberculosis. Waksman partnered with veterinarian William Feldman and lung specialist H. Corwin Hinshaw of the Mayo clinic foundation in Rochester, Minnesota, where a model for therapeutic research with the drug using guinea pigs had been established.[xxxii] He also tapped the immense resources of Merck Pharmaceuticals in nearby Rahway, New Jersey.
Tuberculosis decimated Roosevelt’s inner circle. Future brain-truster Raymond Moley had to curtail his early career to enter a sanatorium. Secretary Grace Tully required frequent prolonged absences from work for treatment throughout the nineteen thirties. The disease killed Margaret “Rabbit” Durand, Louis Howe’s and, after his death, James Roosevelt’s personal secretary in 1941 as well as press secretary and member of Roosevelt’s most inner circle of advisors, Marvin McIntyre, in 1943. Secretary of State Cordell Hull was long rumored to be stricken with the disease but more probably had a non-infectious lung problem known as sarcoidoisis that forced his retirement in late 1944. First Lady Eleanor Roosevelt succumbed to tuberculosis in 1962 after an incorrect diagnosis subjected her to treatment with steroids that activated a previously dormant infection. Interestingly, the fatal infection was resistant to both streptomycin and a newer therapeutic agent, isoniazid[xxxiii], proving it had been acquired no earlier than 1952.[xxxiv]
While there is no evidence that FDR had tuberculosis, a strong circumstantial case can be made that he was treated with streptomycin for one of his many infections.[xxxv] Contrary to the popular myth that FDR’s medical care was suboptimal, he and those in his inner circle were always provided the most cutting-edge therapies, which would have included the most recently developed antibiotics, in this case, perhaps, making history as the first to experience an untoward side-effect of streptomycin. The first human treatment with the drug occurred on November 20, 1944, at the Mayo Clinic. By early 1945, Roosevelt was noticeably hearing impaired at press conferences. [xxxvi] The first published report of streptomycin’s notorious propensity for causing deafness due to damage to the nerves of the ear did not appear until two months after Roosevelt’s death.[xxxvii]
[1][1] Bud. Robert, Penicillin: Triumph and Tragedy, Oxford 2007, p. 32.
[i] Ehrlich also devised a precursor to the technique known as gram staining, that enhanced the capability to distinguish between different types of blood cells and bacteria. Most bacteria can be divided into two categories with distinct biochemical differences, those that absorb the blue dye are “gram positive” and those that do not “gram negative”.
[ii] The causative agent, Treponema Pallidum, had only recently been isolated in 1905 by dermatologist Erich Hoffmann and zoologist Fritz Schaudinn. A year later bacteriologist August von Wasserman developed a test that still carries his name to diagnose its presence in humans.
[iii] Due to the difficulty of dissolving it in water, a large amount needed to be infused, sometimes bringing about the loss of an arm.
[iv] Robinson was also Jewish. For details, see: https://en.wikipedia.org/wiki/Dr._Ehrlich%27s_Magic_Bullet
[v] IG Farben is notoriously remembered for also producing a cyanide-based insecticide, Zyklon B, the primary agent of mass extermination in the Nazi gas chambers during World War II.
[vi] Diary of Daisy Suckley, February 27, 1943
[vii] Smith, Kathryn, The Gatekeeper, Touchstone, 2014, p. 245
[viii] Richard Conniff, Penicillin: Wonder Drug of World War II. Military History, July 2013
[ix] Hager, Thomas, The Demon Under the Microscope
[x] Fleming, A. On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzae, Br J of Exp Pathol. V. 10 (3) 226-236
[xi] Bud, R. Penicillin. Triumph and Tragedy. Oxford University Press, 2007. p. 29 (Chapter 2, footnote 14)
[xii] Rhodes Scholarships are awarded for a combination of excellence in academics and athletics
[xiii] Sherrington coined the terms neuron and synapse. His classic 1904 book, The Integrative Action of the Nervous System, is the foundational work for the science of neurophysiology.
[xiv] that had previously been administered by Georges Dreyer
[xv] Hopkins is best known for his research on vitamins.
[xvi] Both eventually died in a concentration camp.
[xvii] From: The Mold in Dr. Florey’s Coat: The Story of the Penicillin Miracle by Eric Lax, New York, Henry Holt, 2005, Chapter 6
[xviii] The research added valuable information about the chemical nature of the bacterial cell wall.
[xix] Penicillin: the Wonder Drug of World War II by Richard Conniff in Military History Magazine, July 3, 2017 see: http://www.historynet.com/penicillin-wonder-drug-world-war-ii.htm
[xx] Bud, pp 44-45.
[xxi] Suckley Diary, November 7, 1943. From Closest Companion, p. 252
[xxii] Conniff
[xxiii] Wainright, M. Perspectives in Biology and Biochemistry 47:2 Spring 2004 189-98
[xxiv] Conniff
[xxv] McIntire, White House Physician p. 231.
[xxvi] Gunther, J. Roosevelt in Retrospect Harper & Bros; (1950) 365
[xxvii] F. Haden Snoderly: hand-written memoir of Franklin Roosevelt’s autopsy, private collection
[xxviii] Bacille Calmette Guerin
[xxix][xxix] Bacille Calmette-Guerin (BCG) is still in use today
[xxx] The lack of proper credit for the discovery eventually resulted in contentious litigation whereupon Schatz was awarded a percentage of the royalties from the patent. See: http://microbiologymatters.com/?p=1206
[xxxi] an aminoglyside is a naturally occurring substance that is a combination of a complex sugar and nitrogen
[xxxii][xxxii] Spink, Wesley. Infectious Diseases. Prevention and Treatment in the Nineteenth and Twentieth Centuries. University of Minnesota Press, 1978. p 108-09
[xxxiii] this suggests that the infection was acquired after 1946 see: Lerner
[xxxiv] see: https://en.wikipedia.org/wiki/Isoniazid
[xxxv] Lomazow, S. Was Franklin Delano Roosevelt treated with Streptomycin? J Med Biogr 2010 Feb;18(1):61.
[xxxvi] Press conference with Ross McIntire, New York Times, 21 January 1945
[xxxvii] Hinshaw, HC, Feldman, WH. Streptomycin in treatment of clinical tuberculosis: a preliminary report. Proceedings of the Staff of the Mayo Clinic 1945; 20: 545